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Dellaoui, Hafsa, Abdelkrim Berroukche, Bakhta Bouzouira, Narimen Taibi, Mohamed Zouidi, and Belkacem Belatbi. "Effects of Myrtus communis leaf extracts on CdCl2-induced metabolic disturbance in male wistar rats." South Asian Journal of Experimental Biology 9, no. 5 (January 1, 2020): 185–92. http://dx.doi.org/10.38150/sajeb.9(5).p185-192.
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Cadmium (Cd) is widespread in the environment. Cd toxicity targets liver and renal tissues and generates oxidative stress. Medicinal plants produce antioxidants scavenging reactive oxygen species (ROS) and chelate heavy metals. This study aimed to investigate the preventive effects of Myrtus communis leaves hydro-methanol extract (HME) and aqueous extract (AE) on Cdinduced toxicity. The experiments were carried out, during 30 days, on male rats; GR1 (controls), GR2 treated with CdCl2 (18 mg/kg), GR3 co-treated with HME (1 g/kg) and Cd (18 mg/kg), GR4 co-treated with AE (1 g/kg) and Cd (18 mg/kg), GR5 with HME and GR6 with AE. Cd induced changes in biochemical parameters (transaminases, urea, creatinine and blood sugar)related to hepato renal function, increased tissue mortification and decreased animals’ body weight. While the treatment animals, with M. communis leaves (HME) or (AE), regulated blood sugar levels. Hepatic steatosis and loss of glomeruli were particularly induced either by Cd or a co-treatment with Cd and plant extracts. M. communis extracts (HME and EA) can regulate blood sugar levels and prevent cadmium accumulation.
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Kumar Barman, Barun, and Karuna Kar Nanda. "Uninterrupted galvanic reaction for scalable and rapid synthesis of metallic and bimetallic sponges/dendrites as efficient catalysts for 4-nitrophenol reduction." Dalton Transactions 44, no. 9 (2015): 4215–22. http://dx.doi.org/10.1039/c4dt03426k.
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Here, we demonstrate an uninterrupted galvanic replacement reaction (GRR) for the synthesis of metallic (Ag, Cu and Sn) and bimetallic (Cu–M, MAg, Au, Pt and Pd) sponges/dendrites by sacrificing the low reduction potential metals (Mg in our case) in acidic medium.
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Chia, Gek-Ling, and Chong-Keang Lim. "Counting 2-circulant graphs." Journal of the Australian Mathematical Society. Series A. Pure Mathematics and Statistics 39, no. 2 (October 1985): 270–81. http://dx.doi.org/10.1017/s1446788700022527.
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AbstractAlspach and Sutcliffe call a graph X(S, q, F) 2-circulant if it consists of two isomorphic copies of circulant graphs X(p, S) and X(p, qS) on p vertices with “cross-edges” joining one another in a prescribed manner. In this paper, we enumerate the nonisomorphic classes of 2-circulant graphs X(S, q, F) such that |S| = m and |F| = k. We also determine a necessary and sufficient condition for a 2-circulant graph to be a GRR. The nonisomorphic classes of GRR on 2p vertices are also enumerated.
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Liu, Jinquan, Xiaofei Li, Pooya Saffari, Qichao Liang, Ling Li, and Weizhong Chen. "Developing a Polypropylene Fabric, Silica Fume, and Redispersible Emulsion Powder Cementitious Composite for Dynamic Water Environment." Polymers 11, no. 1 (December 30, 2018): 47. http://dx.doi.org/10.3390/polym11010047.
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In the dynamic water environment, grouting requires a material with higher strength and anti-washout performance to prevent groundwater inrush. This study aims to develop a dynamic water slurry by mixing polypropylene fiber (PP fiber), silica fume (SF) and the polymer material of redispersible emulsion powder (REP) to the Portland cement. Towards this aim, a series of tests, including strength, gel time, bleeding rate, fluidity, and anti-washout, were conducted to evaluate the effects of SF, PP fiber, and REP on the slurry properties. The test results show that: (1) SF displays significant effects on strength, gel time, fluidity, and bleeding rate of cement slurry. Differently, PP fiber mainly affects the stress–strain behavior of the slurry and can improve the ductility significantly. (2) By mixing SF and fiber simultaneously, the slurry strength can increase by about 30%, and its strain can extend by more than 70%. Meanwhile, the composite slurry possesses great anti-washout properties at a low flow velocity (v ≤ 0.4 m/s), and the grouting retention rate (GRR) can reach up to 98.7%. However, the GRR decreases to a maximum value of 31.3% when v = 0.6 m/s. (3) By mixing the REP into the fiber-SF composite slurry, the GRR can further increase, reaching more than 60% even when v = 0.6 m/s. As a result, the developed fiber-SF cementitious composite slurry, which when mixed with REP, presents a favorable performance in the dynamic water environment.
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Rosen, RL, KD Winestock, G. Chen, X. Liu, L. Hennighausen, and DS Finbloom. "Granulocyte-macrophage colony-stimulating factor preferentially activates the 94-kD STAT5A and an 80-kD STAT5A isoform in human peripheral blood monocytes." Blood 88, no. 4 (August 15, 1996): 1206–14. http://dx.doi.org/10.1182/blood.v88.4.1206.bloodjournal8841206.
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Granulocyte-macrophage colony-stimulating factor (GM-CSF) induces immediate effects in monocytes by activation of the Janus kinase (JAK2) and STAT transcription factor (STAT5) pathway. Recent studies have identified homologues of STAT5, STAT5A, and STAT5B, as well as lower molecular weight variants of STAT5. To define the activation of the STAT5 homologues and lower molecular weight variant in human monocytes and monocytes differentiated into macrophages by culture in macrophage- CSF (M-CSF), we measured the GM-CSF induced tyrosine phosphorylation of STAT5A, STAT5B, and any lower molecular weight STAT5 isoforms. Freshly isolated monocytes expressed 94-kD STAT5A, 92-kD STAT5B, and an 80-kD STAT5A molecule. Whereas 94-kD STAT5A was clearly tyrosine phosphorylated and bound to the enhancer element, the gamma response region (GRR), of the Fc gamma RI gene, substantially less tyrosine phosphorylated STAT5B bound to the immobilized GRR element. Macrophages lost their ability to express the 80-kD STAT5A protein, but retained their ability to activate STAT5A. STAT5A-STAT5A homodimers and STAT5A- STAT5B heterodimers formed in response to GM-CSF. Therefore, activation of STAT5A predominates compared to STAT5B when assayed by direct immunoprecipitation and by evaluation of bound STATs to immobilized GRR. Selective activation of STAT5 homologues in addition to generation of lower molecular isoforms may provide specificity and control to genes expressed in response to cytokines such as GM-CSF.
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MOSQUERA CUESTA, HERMAN J. "A WHITE DWARF-NEUTRON STAR RELATIVISTIC BINARY MODEL FOR SOFT GAMMA-RAY REPEATERS." International Journal of Modern Physics D 14, no. 09 (September 2005): 1473–84. http://dx.doi.org/10.1142/s0218271805007024.
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A scenario for soft gamma-ray repeaters (SGRs) is introduced in which gravitational radiation reaction (GRR) effects drive the dynamics of an ultrashort orbital period X-ray binary embracing a high-mass donor white dwarf (WD) to a rapidly rotating low magnetized massive neutron star (NS) surrounded by a thick, dense and massive accretion torus. Driven by GRR, over timescales of ΔTrep~ 10 years, the binary separation reduces, the WD overflows its Roche lobe and the mass transfer drives unstable the accretion disk around the NS. As the binary circular orbital period is a multiple integer number (m) of the period of the WD fundamental mode,37the WD is since long pulsating at its fundamental mode; and most of its harmonics, due to the tidal interaction with its NS orbital companion. Hence, when the powerful irradiation glows onto the WD; from the fireball ejected as part of the disk matter slumps onto the NS, it is partially absorbed. This huge energy excites other WD radial (p-mode) pulsations.34,35After each mass-transfer episode the binary separation (and orbital period) is augmented significantly1,5due to the binary's angular momentum redistribution. Thus a new adiabatic inspiral phase driven by GRR reaction starts which brings the binary close again, and the process repeats after a time span ΔTrep. This model allows to explain most of SGRs observational features: their recurrent activity, energetics of giant superoutbursts and quiescent stages, and particularly the intriguing subpulses discovered by BeppoSAX,10which are suggested here to be overtones of the WD radial fundamental mode (see the accompanying paper).31
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Bratton, Eric L., Zikun Lin, Fridolin Weber, Milva G. Orsaria, Ignacio F. Ranea-Sandoval, and Nathaniel Saavedra. "Gravitational-Wave Instabilities in Rotating Compact Stars." Galaxies 10, no. 5 (August 30, 2022): 94. http://dx.doi.org/10.3390/galaxies10050094.
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It is generally accepted that the limit on the stable rotation of neutron stars is set by gravitational-radiation reaction (GRR) driven instabilities, which cause the stars to emit gravitational waves that carry angular momentum away from them. The instability modes are moderated by the shear viscosity and the bulk viscosity of neutron star matter. Among the GRR instabilities, the f-mode instability plays a historically predominant role. In this work, we determine the instability periods of this mode for three different relativistic models for the nuclear equation of state (EoS) named DD2, ACB4, and GM1L. The ACB4 model for the EoS accounts for a strong first-order phase transition that predicts a new branch of compact objects known as mass-twin stars. DD2 and GM1L are relativistic mean field (RMF) models that describe the meson-baryon coupling constants to be dependent on the local baryon number density. Our results show that the f-mode instability associated with m=2 sets the limit of stable rotation for cold neutron stars (T≲1010 K) with masses between 1M⊙ and 2M⊙. This mode is excited at rotation periods between 1 and 1.4 ms (∼20% to ∼40% higher than the Kepler periods of these stars). For cold hypothetical mass-twin compact stars with masses between 1.96M⊙ and 2.10M⊙, the m=2 instability sets in at rotational stellar periods between 0.8 and 1 millisecond (i.e., ∼25% to ∼30% above the Kepler period).
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Pannier, Diane, Antoine Adenis, Emmanuelle Tresch-Bruneel, Emilie Bogart, Farid El Hajbi, Eric Dansin, Nuria Kotecki, et al. "Paclitaxel once weekly (wP) combined with fixed dose of oral metronomic cyclophosphamide (OMC): A dose-escalating phase I trial." Journal of Clinical Oncology 35, no. 15_suppl (May 20, 2017): e14015-e14015. http://dx.doi.org/10.1200/jco.2017.35.15_suppl.e14015.
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e14015 Background: OMC, as continuous administration of low doses of chemotherapy acts as direct cytotoxic as well as antiangiogenetic agent. wP also induces antiangiogenic effects in mouse models. The aims of this trial were to determine the recommended Phase 2 dose (RP2D) of wP given in combination with OMC, and estimate activity and safety of the combination. Methods: Methods This is a single-center, phase 1 trial. Patients (pts) > 18 years with refractory metastatic cancers were eligible if no standard curative measures existed. Paclitaxel was administered IV weekly (D1, D8, D15; D1 = D28) in combination with a fixed dose of OMC (50mg x2/day). A 3+3 design was used for Dose-Escalation of wP (40 mg/m² to 75 mg/m²), followed by an expansion cohort at RP2D. The primary endpoint was the dose-limiting toxicity (DLT), defined as grade > 3 non-hematological or grade 4 hematological toxicity (NCI-CTCAE v4.0) occurring in the first 28 days, or any toxicity leading to a dose reduction. Results: 28 pts (18 in dose-escalation phase and 10 in expansion cohort) were included between May 2011 and December 2013. The sex ratio was 2:1, the median age was 54.5 (range, 26-67); the most common primary tumors were colorectal cancers (n = 9), sarcomas (n = 4), Head & Neck (n = 3). 16/18 pts enrolled in the dose-escalation phase were evaluable for DLT. DLT occurred in 0/3, 1/6 (neuropathy), 0/3 and 2/4 pts (hematological toxicity) at dose 40, 60, 70 and 75 mg/m² of wP, respectively. The RP2D of wP was 70 mg/m2; 1/10 pts in the expansion phase had an hematological DLT. At RP2D (n = 14), the maximal grade of adverse events (AE), regardless of causality, was Gr2 in 3 pts, Gr3 in 7 pts, Gr4 in 3 pts and Gr5 in 1 pt; the maximal grade of treatment-related AE was Gr1 in 1 pt, Gr2 in 8 pts, Gr3 in 3 pts and Gr4 in 1 pt (no AE in 1 pt). At RP2D, the median PFS was 2.8 mo and Growth Modulation index was ≥1.33 in 4/14 pts (29%). There was 1 objective response (1/14; 7%): 1 pt with lung adenocarcinoma achieved a partial response. Conclusions: The combination of OMC and wP resulted in an acceptable safety profile. Further evaluation of this combination with wP at 70mg/m² could be warranted in a phase 2 trial. Clinical trial information: NCT01374620.
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Meierovich, Boris E. "Guessing the Riddle of a Black Hole." Universe 6, no. 8 (August 7, 2020): 113. http://dx.doi.org/10.3390/universe6080113.
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A static structure of matter, extremely compressed to the state of a Bose–Einstein condensate by its own gravitational field, is considered. Instead of the widely spread restriction detgik<0, I used a weaker condition of regularity: all invariants of gik are finite. This makes it possible to find regular static solutions to Einstein equations for a spherically symmetric distribution of matter with no restriction on total mass. In these regular static solutions, the metric component grr changes its sign twice: grr(r)=0 at r=rg and at r=rh>rg. The signature of the metric tensor is changed to (+,+,−,−) within the spherical layer rg<r<rh. Though the gravitation dominates at extremely high density, I assume that it does not violate the exchange interaction of elementary particles of the Standard Model. The found regular static solution to Einstein equations, having no limitation on mass, pretends to describe the state of a black hole to which the gravitational collapse leads. The features of a collapsed black hole, its internal composition depending on total mass and the relation with surrounding dark matter, are considered. An astrophysical application: The pressure balance at the interface between a black hole and dark matter determines the plateau velocity of a galaxy rotation curve as a function of the black hole mass. The plateau velocity is inversely proportional to the black hole mass. The speed of rotation of a star at the periphery of a galaxy is proportional to the square root of the black hole mass (direct attraction to the center) and inversely proportional to the mass of the same black hole (as the influence of dark matter). For a condensate of massive bosons in the Standard Model, the direct attraction to the black hole and the influence of dark matter are equal if the black hole mass is about M˜ ∼ 4.24×1037 g. In galaxies with black hole masses M≳M⊙=1.989×1033 g (like UMa: NGC 3726 and UMa: NGC 3769 of the Ursa Major cluster), the motion of stars is driven by dark matter. Their rotation curves should have a well-defined plateau. On the contrary, in galaxies with black hole masses M>>M˜ (like in our Milky Way with the black hole mass M=8.6×1039 g), the motion of stars is regulated by the black hole in the center. Dark matter does not play a significant role in our Milky Way Galaxy.
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Niyomrattanakit, Pornwaratt, Pakorn Winoyanuwattikun, Santad Chanprapaph, Chanan Angsuthanasombat, Sakol Panyim, and Gerd Katzenmeier. "Identification of Residues in the Dengue Virus Type 2 NS2B Cofactor That Are Critical for NS3 Protease Activation." Journal of Virology 78, no. 24 (December 15, 2004): 13708–16. http://dx.doi.org/10.1128/jvi.78.24.13708-13716.2004.
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ABSTRACT Proteolytic processing of the dengue virus polyprotein is mediated by host cell proteases and the virus-encoded NS2B-NS3 two-component protease. The NS3 protease represents an attractive target for the development of antiviral inhibitors. The three-dimensional structure of the NS3 protease domain has been determined, but the structural determinants necessary for activation of the enzyme by the NS2B cofactor have been characterized only to a limited extent. To test a possible functional role of the recently proposed Φx3Φ motif in NS3 protease activation, we targeted six residues within the NS2B cofactor by site-specific mutagenesis. Residues Trp62, Ser71, Leu75, Ile77, Thr78, and Ile79 in NS2B were replaced with alanine, and in addition, an L75A/I79A double mutant was generated. The effects of these mutations on the activity of the NS2B(H)-NS3pro protease were analyzed in vitro by sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of autoproteolytic cleavage at the NS2B/NS3 site and by assay of the enzyme with the fluorogenic peptide substrate GRR-AMC. Compared to the wild type, the L75A, I77A, and I79A mutants demonstrated inefficient autoproteolysis, whereas in the W62A and the L75A/I79A mutants self-cleavage appeared to be almost completely abolished. With exception of the S71A mutant, which had a k cat/K m value for the GRR-AMC peptide similar to that of the wild type, all other mutants exhibited drastically reduced k cat values. These results indicate a pivotal function of conserved residues Trp62, Leu75, and Ile79 in the NS2B cofactor in the structural activation of the dengue virus NS3 serine protease.
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Roberts, G. P. "Characterization of the antigens recognized by two monoclonal antibodies reactive with basal-layer keratinocytes of human epidermis." Biochemical Journal 299, no. 3 (May 1, 1994): 659–64. http://dx.doi.org/10.1042/bj2990659.
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Two monoclonal antibodies, GR3 and GR4, reactive with the basal-layer keratinocytes of human epidermis, were derived by immunization of Balb/c mice with glycoproteins isolated from cultured keratinocytes by lectin-affinity chromatography. Immunoprecipitation of Triton X-100 extracts from human keratinocytes metabolically labelled with D-[1-14C]glucosamine revealed that GR3 recognized a major glycoprotein with migration properties identical with those of a glycoprotein (reduced form M(r) 126,000) which was previously shown to be implicated in intercellular adhesion [Roberts and Brunt (1985) Biochem J. 232, 67-70]. In their unreduced forms the antigens recognized by GR3 and GR4 both migrated as two bands with M(r) values of 118,000 and 147,000. Comparison of 125I-labelled glycoproteins immunoprecipitated by GR3, GR4 and integrin antibodies revealed that, under reducing conditions, the major band immunoprecipitated by both GR3 and GR4 co-migrated with the alpha 3 and beta 1 integrin chains. In addition the immunoprecipitate obtained with GR4 contained an additional band co-migrating with the alpha 2 integrin chain. Sequential immunoprecipitation studies with GR3, GR4 and integrin antibodies confirmed that GR3 is directed against the alpha 3 integrin chain, whereas GR4 is directed against the beta 1 chain. These studies also indicate that some of the alpha 2 integrin chains on keratinocytes may be associated with a beta-chain not recognized by the antisera against the beta 1 integrin chain used in this study.
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Fumoleau, Pierre, Florence Dalenc, Audrey Mailliez, Corinne Veyret, Jacques Bonneterre, Cecile Guillemet, Sylvie Zanetta, et al. "Phase I dose escalation study of oral lapatinib in combination with docetaxel in patients with HER2-positive locally advanced or metastatic breast cancer (LAMBC): Initial safety and tolerability results." Journal of Clinical Oncology 31, no. 15_suppl (May 20, 2013): e11529-e11529. http://dx.doi.org/10.1200/jco.2013.31.15_suppl.e11529.
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e11529 Background: Previous studies evidenced that the combination docetaxel (D) (75 mg/m²) + lapatinib (L) (1,250 mg/d) is well tolerated in heavily pretreated HER2-positive metastatic breast cancer patients (pts) in association with systematic G-CSF. This phase I study was conducted to assess safety, optimal tolerated regimen (OTR) and clinical activity of D + L in naïve treatment pts with HER-2 positive LAMBC without primary use of growth factor. Methods: Women with HER2+ LAMBC, naïve of treatment for advanced or metastatic disease, ECOG PS 0-2, were eligible for this study. Pts received once daily oral dosing of L with intravenous D on day 1 of every 3 week cycle. Initial dose was D (75 mg/m²) + L (1,250 mg/d) escalating up to D 100 mg/m² and L 1,500 mg/d until the Maximal Tolerated Dose (MTD) was reached. An expansion cohort of 6 pts was treated at the OTR level. Primary use of G-CSF was not permitted. Results: From Aug 2008 to Nov 2011, 17 pts were enrolled: median age 54.4 years [34.6-77], 59% were PS 0. All patients have metastatic disease with lung (29,4%), bone (41,2%), liver (76.5%) and lymph nodes (35.3%) metastasis. 7 pts received previously chemotherapy in adjuvant setting, 5 pts hormonotherapy and 7 pts radiotherapy. All but two pts were evaluable for dose limiting toxicities (DLT). 1 DLT/6 pts (FN) was observed at dose level (DL) 1 (D 75 mg/m² + L 1,250 mg/d) and 2 DLT/3 pts (gr 3 diarrhoea; gr4 neutropenia >7 d) at DL2 (D 75 mg/m² + L 1,500 mg/d). Only one DLT (FN) was observed in expansion cohort at OTR (D 75 mg/m² + L 1,250 mg/d; 6 pts). Over all C1, other significant toxicities (% pts) included gr4 neutropenia 53%, gr3 transaminase increase 6%, gr2 skin rash 36%, gr2 nausea/vomiting 18%, gr2 diarrhoea 12%, gr2 stomatitis 12%, gr2 hand-foot syndrome 6%; no decrease of cardiac function occurred. Conclusions: OTR for D and L was 75 mg/m² once every 3 weeks and 1,250 mg once daily respectively. This study demonstrates that this combination could be administered without systematic use of G-CSF in non pretreated pts with LAMBC. Additional safety data and preliminary evidence of activity are anticipated to be available at the time of presentation. Clinical trial information: NCT01044485.
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Taglia, Lauren, Damien Matusiak, Kristina A. Matkowskyj, and Richard V. Benya. "Gastrin-releasing peptide mediates its morphogenic properties in human colon cancer by upregulating intracellular adhesion protein-1 (ICAM-1) via focal adhesion kinase." American Journal of Physiology-Gastrointestinal and Liver Physiology 292, no. 1 (January 2007): G182—G190. http://dx.doi.org/10.1152/ajpgi.00201.2006.
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Gastrin-releasing peptide (GRP) and its receptor (GRPR) act as morphogens when expressed in colorectal cancer (CRC), promoting the assumption of a better differentiated phenotype by regulating cell motility in the context of remodeling and retarding tumor cell metastasis by enhancing cell-matrix attachment. Although we have shown that these processes are mediated by focal adhesion kinase (FAK), the downstream target(s) of GRP-induced FAK activation are not known. Since osteoblast differentiation is mediated by FAK-initiated upregulation of ICAM-1 (Nakayamada S, Okada Y, Saito K, Tamura M, Tanaka Y. J Biol Chem 278: 45368–45374, 2003), we determined whether GRP-induced activation of FAK alters ICAM-1 expression in CRC and, if so, determined the contribution of ICAM-1 to mediating GRP's morphogenic properties. Caco-2 and HT-29 cells variably express GRP/GRPR. These cells only express ICAM-1 when GRPR are present. In human CRC, GRPR and ICAM-1 are only expressed by better differentiated tumor cells, with ICAM-1 located at the basolateral membrane. ICAM-1 expression was only observed subsequent to GRPR signaling via FAK. To study the effect of ICAM-1 expression on tumor cell motility, CRC cells expressing GRP, GRPR, and ICAM-1 were cultured in the presence and absence of GRPR antagonist or monoclonal antibody to ICAM-1. CRC cells engaged in directed motility in the context of remodeling and were highly adherent to the extracellular matrix, only in the absence of antagonist or ICAM-1 antibody. These data indicate that GRP upregulation of ICAM-1 via FAK promotes tumor cell motility and attachment to the extracellular matrix.
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de Moffarts, Brieuc, Nathalie Kirschvink, Emmanuelle van Erck, Tatiana Art, Joël Pincemail, and Pierre Lekeux. "Assessment of the oxidant–antioxidant blood balance in a field exercise test in Standardbredand eventing horses." Equine and Comparative Exercise Physiology 2, no. 4 (November 2005): 253–61. http://dx.doi.org/10.1079/ecp200567.
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AbstractThe aim of this study was to determine which oxidant–antioxidant blood markers are of interest for a field exercise test (ET) performed on a racetrack. Healthy Standardbred horses (S: n = 12) and healthy eventing horses (E: n=12) were investigated. Exercise was monitored by measuring velocity (V), heart rate (HR), and plasma lactate (LA). Whilst maximal LA did not differ (11.8±0.88 mmol l−1), maximal V (S: 12.3±0.17 m s−1versus E: 11.1±0.24 m s−1, P<0.05) and final HR (S: 222±1 versus E: 203±8 beats min−1, P<0.05) were significantly different between groups. Venous blood was collected at rest (R) prior to ET and the following oxidant–antioxidant markers were determined: uric acid (UA), ascorbic acid (AA), α-tocopherol (Vit E), vitamin A (Vit A), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione (reduced: GSH and oxidized: GSSG), glutathione redox ratio (GRR), copper (Cu), zinc (Zn) and selenium (Se), oxidized proteins (Protox), lipid peroxides (Pool), antioxidant capacity of water-soluble components (ACW) and antioxidant capacity of lipid-soluble components (ACL). The following markers were further determined 15 min (E15) after the ET: UA, ACW, AA, GSH, Protox, Pool, ACL. Standardbreds had significantly higher concentrations of ACW, GSH, ACL and Protox, whilst Se, Zn and SOD were significantly lower than in eventing horses. Exercise induced a significant increase in ACW and UA. GSH decreased in eventing horses and Pool significantly decreased in both horse groups. This study describes a field ET of high intensity for Standardbred and eventing horses, which could be performed by all animals tested. By sampling blood at rest and at E15, changes of the hydrophilic antioxidant defence were partially assessed, whereas no interpretable changes of the lipophilic antioxidants and of oxidation markers (Protox, Pool) could be detected.
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Yeh, K., C. Hsu, C. Hsu, C. Lin, Y. Shen, S. Wu, T. Chiou, Y. Chao, and A. Cheng. "Phase II study of cetuximab plus weekly cisplatin and 24-hour infusion of high-dose 5-fluorouracil and leucovorin for the first-line treatment of advanced gastric cancer." Journal of Clinical Oncology 27, no. 15_suppl (May 20, 2009): 4567. http://dx.doi.org/10.1200/jco.2009.27.15_suppl.4567.
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4567 Background: Cisplatin-HDFL regimen, using weekly 24-hour infusions of cisplatin and high-dose 5-fluorouracil (5-FU) and leucovorin, is commonly used in Taiwan for patients with advanced gastric cancer (GC), showing an overall response rate of approximately 60% (95% CI: 45%-76%) [J Clin Oncol (Suppl) 2006; 24(18S): A14063 ]. We have demonstrated that cetuximab is cytotoxic to human GC cells, and has a chemosensitizing effect for cisplatin and 5-FU in GC cells [Proc AACR 2006; 47: A1233]. Methods: All patients had pathologically confirmed metastatic/ recurrent chemonaive GC, at least 1 measurable lesion, a fasting serum triglyceride level > 70 mg/dl, WHO PS 0/1/2, adequate hepatic, renal, and bone marrow functions. Cetuximab 400 mg/m2 was given as 2h infusion, initially (i.e., D1 of cycle 1); and followed by weekly 1h infusion of 250 mg/m2 (i.e., D8, D15, D22 of cycle 1, and D1, D8, D15, D22 of cycle 2). Cisplatin 35 mg/m2 was given as a 24h infusion, admixing with 5-FU 2,000 mg/m2 and leucovorin 300 mg/m2 (HDFL), D1, D8. A 24h infusion of HDFL was given on D15. Cycles were repeated every 28 days, and response evaluation was performed every 2 cycles & at the end of protocol treatment. The primary end-point was confirmed objective response rate (RR) by RECIST. Results: Between Dec. 2005 and Nov. 2008, 35 patients (M:19, F:16) with a median age of 56 (40–74) were enrolled and evaluable for response assessment. The overall RR was 68.6% (51–83%, 95% C.I.) with 1 CR and 23 PRs. Among a total of 269 cycles (median: 7, range: 2 to 22+ cycles) given, Gr3/4 neutropenia, infection, and hepatic toxicity developed in 6.0%, 4.8%, and 0.74% of 269 cycles, respectively. Two patients have developed acute hepatitis B flare-up among seven HBsAg (+) carriers, and were well controlled by lamivudine. Gr1, Gr2, and Gr3 acne- like rashes have developed in 57.1%, 31.4%, 5.7%; and Gr1, Gr2, Gr3 paronychia have developed in 40.0%, 8.6%, and 2.9% of 35 patients, respectively. Median PFS (range: 3 to 22+ months) and median OS (range: 3 to 35+ months) was11.0 and 14.5 months, respectively. Conclusions: Cetuximab plus infusional cisplatin-HDFL is a highly effective regimen with low toxicity and favourable survival in the first-line treatment of advanced GC. No significant financial relationships to disclose.
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Farahi, Sara, Parviz Shishehbor, and Alireza Nemati. "Bisexual and oedipal reproduction of Macrocheles muscaedomesticae (Acari, Macrochelidae) feeding on Musca domestica (Diptera, Muscidae) eggs." Acarologia 58, no. 2 (March 15, 2018): 430–41. http://dx.doi.org/10.24349/acarologia/20184251.
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Macrocheles muscaedomesticae (Scopoli) is a predatory mesostigmatic mite that inhabits different manure microhabitats and preys mostly on housefly (Musca domestica L.) eggs. When a virgin female colonizes a new manure substrate, it produces male offspring through parthenogenesis (arrhenotoky); when her sons reach maturity, oedipal mating takes place and the female begins to produce bisexual offspring. In order to examine the consequence of oedipal reproduction on population development, we designed two separate experiments to compare life history traits and life table parameters of oedipal versus bisexual cohorts of M. muscaedomesticae, using the age-stage, two sex life table method. Experiments were conducted at 28 +/- 1 °C, using a photoperiod of 14:10 (L: D) h, and 65 +/- 5% relative humidity, with housefly eggs used to feed mites. Mean adult female longevity was 38.63 days, and fecundity 128.51 offspring under bisexual reproduction, and 37.48 days and 68.23 offspring under oedipal reproduction. In the bisexual cohort, the intrinsic rate of increase (rm), the finite rate of increase (λ), the net reproduction rate (R0), the gross reproductive rate (GRR) and the mean generation time (T) of M. muscaedomesticae were 0.2938 d-1, 1.3415 d-1, 54.216 offspring/individual, 77.7 offspring/individual and 13.5885 days, respectively. Because only male eggs were produced during the first 5.62 days (on average) of the oviposition period in the oedipal cohort, it was theoretically incorrect to compute the population parameters using the survival and fecundity values for this group, even though bisexual reproduction did occur after this period. Our findings determined that the effect of oedipal reproduction could be correctly defined and analyzed by using the age-stage, two-sex life table method. Our results demonstrated that virgin females are able to produce and copulate with their sons (oedipal mating), which then allows those females to produce both sexes. This reproductive system can enable this valuable natural enemy to considerably extend its distribution potential.
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PINHEIRO, G., and R. CHAN. "RADIATING GRAVITATIONAL COLLAPSE WITH SHEARING MOTION AND BULK VISCOSITY REVISITED." International Journal of Modern Physics D 19, no. 11 (September 2010): 1797–822. http://dx.doi.org/10.1142/s0218271810018050.
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A new model is proposed to collapsing stars consisting of an anisotropic fluid with bulk viscosity, radial heat flow and outgoing radiation. In a previous paper one of us has introduced a time-dependent function into the grr, besides the time-dependent metric functions gθθ and gϕϕ. The aim of this work is to generalize this previous model by introducing bulk viscosity and comparing it to the non-viscous collapse. The behavior of the density, pressure, mass, luminosity and the effective adiabatic index is analyzed. Our work is also compared to the case of a collapsing fluid with bulk viscosity of another previous model, for a star with 6 M⊙. The pressure of the star, at the beginning of the collapse, is isotropic, but due to the presence of the bulk viscosity the pressure becomes more and more anisotropic. The black hole is never formed because the apparent horizon formation condition is never satisfied, in contrast to the previous model where a black hole is formed. An observer at infinity sees a radial point source radiating exponentially until it reaches the time of maximum luminosity, and suddenly the star turns off. This is in contrast to the former model where the luminosity also increases exponentially, reaching a maximum and decreases thereafter until the formation of the black hole. The effective adiabatic index diminishes due to the bulk viscosity, thus increasing the instability of the system, in both models, in the former paper as well as in this work.
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Ovsyannikova, O., L. P. Ananyeva, L. Garzanova, O. Koneva, S. Glukhova, M. Starovoytova, O. Desinova, and R. Shayakhmetova. "AB0455 MODIFICATION OF PROGNOSIS INTERVALS WAS DERIVED BY THE DISCRIMINATION FUNCTION FOR SSc-ILD PATIENTS." Annals of the Rheumatic Diseases 80, Suppl 1 (May 19, 2021): 1254.2–1255. http://dx.doi.org/10.1136/annrheumdis-2021-eular.3627.
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Background:Systemic sclerosis (SSc) is a multisystem autoimmune disease. Pulmonary alterations are the major cause of mortality in SSc. SSc-ILD has heterogeneous disease progression: many patients will have a chronic, indolent course while others may develop progressive, life-threatening disease.Objectives:To assess prognosis intervals for pts with SSc-ILD.Methods:It was a longitudinal study involving 140 pts with SSc-ILD. The mean age was 46.7±13.9years, females 82%, SSc duration 6.2±5.8 years, diffuse subset - 54%. The mean duration of follow up was 73,2±27,8 months. Clinical, laboratory, and immunologic data were collected on all patients.Based on analysis of discrimination function the equation of prognosis was developed. The equation is 3.14GGO (ground glass opacities) + 0,7 index EScSG – 1,326 FVC - 0,1 the maximum daily dose of glucocorticoids + 0,136 Gamma globulins + 1.066 CYP – 1.075 DLCO ≤ 5,8. Value of equation of prognosis to 5.8 corresponds to stabilization or good prognosis and value after 5.8 corresponds to poor prognosis. The equation of prognosis had 86% sensitivity and 56% specificity. The cut-off point 4.7 was represented 65% sensitivity and 67% specificity. The prognosis intervals were following: value of equation to 4.7 corresponds to good prognosis; value from 4.8 to 5.8 corresponds to stabilization and value after 5.8 corresponds to poor prognosis.Results:Pts were distributed into groups depending on results of discrimination function: 14 pts (10%) - zone of good prognosis; 8 pts (6%) - zone of stabilization and 118 (84%) - zone of poor prognosis. We have decided to join pts from zone good prognosis and zone stabilization into united group (U-group) - 22 pts (16 %).Table 1.Comparative characteristics of the groupsParametersGroup 1 (n=14)Group 2(n=8)U-Group(n=22)Group 3(n=118)Age years45,4±16,450,2±15,847,2±1647,5±13P>0,05GenderMale3(21%)1(12,5%)4(18%)21(18%)Female11(79%)7(87,5%)18(82%)97(82%)P>0,05Limited form8(57%)2(35%)10(46%)54(46%)Diffuse form6(43%)6(75%)12(54%)64(54%)P>0,05Duration of disease years6,8±7,65±4,26,2±6,46,5±5,7p>0,05CRP mg/ml10±108,5±10,69,4±10,412,6±23,9p>0,05ESR mm/h16,7±13,117,4±21,917±16,323,5±16,7p>0,05ANA-hep-2525±322*420±190487±281*774±430*p: Gr1 vs Gr3 =0,038; Gr2 vs Gr3=0,02; Gr1,2 vs Gr3 =0,032a-Scl-70 u/ml59,9±82,7*67±94,5116±93**62,5±85* **p: Gr1 vs Gr3 =0,03; Gr1,2 vs Gr3 =0,013Ejection fraction(EF)(%)67,3±5,3*65,5±6,166,7±5,5**63±6,8* **p: Gr1 vs Gr3 =0,02; Gr1,2 vs Gr3 =0,017PAP mm hg31,6±5,832,4±9,331,9±736,4±14p>0,056MWT m(6 Minute walk test)490±110477±104485±104430±100p>0,05The age, SSc duration, gender proportion and SSc forms, were similar in the all groups (p>0,05). In the study mean dates of ANF-hep-2, a-Scl-70 were significantly lower and EF was significantly higher in groups 1 and U-group than in group 3. In groups 1,2 and U-group the mean levels of ESR, CRP, PAP were lower and value of 6MWT were higher than mean levels in group 3 accordingly. So separately group 2 didn’t have significant differences with group 1 and 3.Conclusion:In the study we didn’t find any correlation between meanings of group 2 and groups 1,3 but the meanings of group 1 and U-group have had the same correlation. It would be rational to highlight only one zone of prognosis before and after 5,8.Disclosure of Interests:None declared.
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Razumnikova, O. M. "Age- and Individual Specificity of Training Visual Short-term Spatial Memory." Experimental Psychology (Russia) 15, no. 1 (2022): 4–18. http://dx.doi.org/10.17759/exppsy.2022150101.
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Cognitive training is known to increase the plasticity of the brain’s neural networks and reduce the expectation of cognitive dysfunction during aging. However, opinions differ regarding the age, individual and time range of the training efficiency. Thus, the aim of the work was to clearing the temporal dynamics of changes in the short-term visual spatial memory of older people in comparison with young people and the dependence on its baseline level. The study involved 65 people of retirement age (M = 65.8; SD = 7.5 years) (GR1) and 92 university students (M = 20.1; SD = 1.4 years) (GR2). To determine the spatial memory, we used a modified “Visual Patterns Test” technique posted on the website psytest.nstu.ru. After a lecture on the methods of formation and implementation of cognitive resources, the study participants were asked to carry out memory training in a free mode at home in order to achieve a consistently maximum result. It is shown that by significantly lower values of short-term visual spatial memory in GR1 than in GR2 in the first testing session, to increase its efficiency, GR1 requires more than 80 sessions of training during some months, while GR2 requires 20 sessions during one-two weeks. The achievement of maximum memory indices occurs faster at its initially high values; however, the effect of training in the first sessions is more pronounced in persons with low memory values, regardless of age. It can be concluded that the effectiveness of spatial memory training at the initial stages is determined by the learning potential, and the realization of the compensatory resources of the brain, whereas the achievement of a result comparable to the young in the elderly is determined by the high level of executive control of behavior, which ensures long-term memory training.
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Nozad-Bonab, Zahra, Mir Jalil Hejazi, Shahzad Iranipour, Mehdi Arzanlou, and Antonio Biondi. "Lethal and sublethal effects of synthetic and bio-insecticides on Trichogramma brassicae parasitizing Tuta absoluta." PLOS ONE 16, no. 7 (July 30, 2021): e0243334. http://dx.doi.org/10.1371/journal.pone.0243334.
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The tomato leaf miner (TLM), Tuta absoluta (Meyrick), is an invasive tomato pest found worldwide. Sustainable control strategies aimed at increasing biological control approaches and decreasing chemical inputs are required, due to the tendency to develop insecticide resistance. In this study, the lethal and sublethal effects of four chemical insecticides (abamectin, indoxacarb, chlorantraniliprole, and spinosad) and the sublethal effects of the entomopathogenic fungus Metarhizium anisopliae (Metschnikoff) on a widespread TLM egg parasitoid, Trichogramma brassicae Bezdenko, were estimated. Concentration mortality response bioassays enabled the estimation of lethal concentrations of the tested insecticides for the parasitoids, with chlorantraniliprole having the lowest LC50 and indoxacarb the highest. The LC25 and LC50 of the tested insecticides on the TLM were sprayed on eggs and then offered at three time intervals to the parasitoids. The fertility and other life table parameters of the individuals emerging from the treated eggs were estimated. All of the chemical insecticides, but not the fungus, had harmful effects on T. brassicae. The insecticide applications caused a 3.84–5.17 times reduction in the net reproductive rate (R0) compared with the control. No parameters were affected by spraying the fungus in the 0h treatment, but effects were recorded at 24 and/or 48h, except for the gross reproduction rate (GRR). The value of the intrinsic rate of increase (rm) also decreased to 0.528–0.617 after the insecticide treatments. The doubling time (DT) increased in all treatments compared to the control. Nevertheless, the generation time (T) was only very slightly affected. In addition, in the combination experiments, M. anisopliae showed a remarkable synergism with T. brassicae in controlling TLM eggs. These results indicate that low levels of lethal effects on key biological control agents should be considered in the choice of insecticides to be included in sustainable TLM control packages.
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Wright, Cynthia J., and Shelley W. Linens. "Patient-Reported Efficacy 6 Months After a 4-Week Rehabilitation Intervention in Individuals With Chronic Ankle Instability." Journal of Sport Rehabilitation 26, no. 4 (July 2017): 250–56. http://dx.doi.org/10.1123/jsr.2016-0044.
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Objective:To track the patient-reported efficacy of a 4-wk intervention (wobble board [WB] or resistance tubing [RT]) in decreasing symptoms of chronic ankle instability (CAI) at 6 mo postintervention (6PI) as compared with immediately postintervention (IPI).Design:Randomized controlled trial.Participants:Fourteen of 21 participants (66.7%) responded to an electronic 6-m follow-up questionnaire (age 19.6 ± 0.9 y, height 1.63 ± 0.18 m, weight 70.5 ± 16.3 kg; 2 male, 12 female; 5 WB, 9 RT). All participants met CAI criteria at enrollment, including a history of ankle sprain and recurrent episodes of giving way.Interventions:Participants completed either RT or WB protocols, both 12 sessions over 4 wk of progressive exercise. WB sessions consisted of five 40-s sets of clockwise and counterclockwise rotations. RT sessions consisted of 30 contractions against resistance tubing in each of 4 ankle directions.Main Outcome Measurements:Patient-reported symptoms of “giving way” preintervention and at 6PI, global rating of change (GRC) frequencies at IPI and 6PI, and resprains at 6PI were reported descriptively. Changes in global rating of function (GRF) and giving way were compared using Wilcoxon tests, while GRC was compared with Fisher exact test.Results:All participants reported giving way preintervention, only 57.1% reported giving way at 6PI. Resprains occurred in 21.4% of participants. Giving-way frequency (P = .017), but not GRF or GRC (P > .05), was significantly different at IPI vs 6PI.Conclusions:Simple 4-wk interventions maintained some but not all improvements at 6PI. At least 42.9% of participants would no longer meet the current study’s CAI inclusion criteria due to a reduction in giving way.
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MOUSAVI, Mahdieh, Youbert GHOSTA, and Nariman MAROOFPOUR. "Insecticidal activity and sublethal effects of Beauveria bassiana (Bals.-Criv.) Vuill. isolates and essential oils against Aphis gossypii Glover, 1877 (Hemiptera: Aphididae)." Acta agriculturae Slovenica 115, no. 2 (June 10, 2020): 463. http://dx.doi.org/10.14720/aas.2020.115.2.1306.
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<p>The cotton aphid, <em>Aphis gossypii</em> Glover, 1877, is a polyphagous species and one of the most important pests of cucumber crops in Iran. In this study, virulence of three <em>Beauveria bassiana </em>(Bals.-Criv.) Vuill isolates, IRAN 108, IRAN 429C and LRC 137, as well as insecticidal activity of two essential oils extracted from <em>Matricaria chamomilla</em> L. and <em>Cuminum cyminum </em>L. were evaluated against adult stage of <em>A. gossypii </em>under laboratory conditions. The data for life table were analyzed using the age-stage, two-sex life table theory. Results showed that all isolates were pathogenic on aphid, but their virulence was varied in different isolates. The lowest calculated LC<sub>50</sub> was belonged to IRAN 429C (3.9 × 10<sup>4</sup>conidia ml<sup>-1</sup>). The lowest LT<sub>50</sub> was obtained at concentration of 10<sup>8</sup> and 10<sup>7</sup> conidia ml<sup>-1</sup> for IRAN 429C (2.9 and 3.55 days, respectively). <em>M. chamomilla</em> essential oil had the lowest LC<sub>50</sub> and LT<sub>50</sub> values (19 µl l<sup>-1</sup> air and 11.4 h), respectively. Longevity and population growth parameters, including the intrinsic rate of increase (<em>r<sub>m</sub></em>), gross reproduction rate (<em>GRR</em>), net reproductive rate (<em>R</em><sub>0</sub>), generation time (<em>T</em>) and finite rate of population increase (<em>λ</em>), were affected negatively by both agents. According to the results obtained in this study, both entomopathogenic fungi and essential oils could be used as an alternative to chemical insecticides in aphid IPM programs.</p>
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Link, Brian K., Michael D. Taylor, John M. Brooks, Elizabeth A. Chrischilles, Ming Lin, Kara Wright, Lucy Pan, and Julie M. Vose. "Correlates of Treatment Intensity for Initial Management of Follicular Lymphoma (FL) in the United States: Report from the National Lymphocare Study (NLCS)." Blood 110, no. 11 (November 16, 2007): 2612. http://dx.doi.org/10.1182/blood.v110.11.2612.2612.
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Abstract FL is incurable with standard therapy, with no consensus on best initial management strategy. Two critical choices - deferral of initial therapy and use or not of anthracyclines - are often “individualized” per clinical circumstances. To date, no data exist regarding whether ‘disease-specific’, ‘patient-specific’, or ‘disease/patient-independent’ characteristics influence these two critical choices for initial therapy. The NLCS is the first prospective observational study in the US designed to assess FL baseline characteristics, prognosis, treatment choices, and clinical outcomes. We utilized this database to correlate the above characteristics with initial therapeutic choices regarding deferral of therapy and use of anthracyclines in pts with FL. NLCS enrolled pts with FL diagnosed within 6 months with no prior lymphoma history. Data collected included demographics, histology, staging, prognostic evaluation, therapy, response, relapses and death. As NLCS is an observational study, no prescribed treatment regimen or intervention is required. Therapy was considered deferred if none was administered within 3 months of diagnosis. Univariate and multivariate analyses were performed. 2254 pts with FL grades 1–3 were enrolled from 237 sites throughout the US from March 2004–January 2007. Median age was 61, 52% were female, and 90% were Caucasian. Grade distribution was 47% 1, 31% 2, and 22% 3. Stages were: I: 18%; II: 15%; III: 30%, and IV: 36%. Initial therapy was deferred in 18%. This frequency varied widely among subgroups defined by disease-, patient-, and provider-specific factors. Among disease-specific factors, strongest association was with grade (Gr1 24%, Gr2 15%, Gr3 9% {p<0.0001}), and with lesser, but still significant, correlation with FLIPI (low 22%, int 20%, hi 10% {p<0.0001}) and stage. Patient-specific factors associated with therapy deferral included age (<60 14%, 60–74 19%, >75 24% {p=0.0004}) and gender (F 20%, M 16% p=0.04}), but not ethnicity. Disease/patient-independent characteristics associated with therapy deferral included geographic region (South/West 14%, Midwest 18%, Northeast 29% {p <0.0001}) and lowest deferral rates with lowest oncologist density, but not academic vs. community treatment site. Initial management included anthracyclines in 34% of all FL pts. Among disease-specific factors, stronger association was with grade (Gr1 21%, Gr2 35%, Gr3 61% {p < 0.0001}), than FLIPI (low 31%, int 34%, hi 39% {p=0.01}). Patient-specific factors associated with anthracycline use included age (<60 41%, 60–74 33%, >75 14% {p<0.0001}) and gender (F 31%, M 37% p=0.0025}), but not ethnicity. Disease/patient-independent characteristics associated with anthracycline use included geographic region (South/West 39%, Midwest 32%, Northeast 21% {p<0.0001}), but not academic vs. community treatment site. As expected, disease-specific characteristics predict intensity of initial management of FL patients with histologic grade a stronger predictor than FLIPI scores. However, lower treatment intensity was also found for factors less clearly predictive of clinical outcome including Northeast location of treating physician and increased density of oncologists. It will be important to evaluate how groups with lower treatment intensity fare when outcome data mature.
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Daniele, Gennaro, Malcolm Ranson, Montserrat Blanco-Codesido, Emma Jane Dean, Krunal Jitendrakumar Shah, Matthew Krebs, Andre Brunetto, et al. "Phase I dose-finding study of golvatinib (E7050), a c-Met and Eph receptor targeted multi-kinase inhibitor, administered orally QD to patients with advanced solid tumors." Journal of Clinical Oncology 30, no. 15_suppl (May 20, 2012): 3030. http://dx.doi.org/10.1200/jco.2012.30.15_suppl.3030.
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3030 Background: Golvatinib is a highly potent, small molecule ATP-competitive inhibitor of the c-Met receptor tyrosine kinase and multiple members of the Eph receptor family as well as c-Kit and Ron, based on isolated kinase assays. Golvatinib showed preclinical evidence of anti-tumor activity. This phase 1 study was performed to determine the MTD, safety, PK, PD and preliminary activity of golvatinib. Methods: Patients (pts) with advanced solid tumors, ECOG PS 0-1, ≥ 18 years (yrs) and adequate organ function were eligible. Golvatinib was administered orally, once daily (QD), continuously. Blood samples for PK and PD analysis were collected at multiple time-points. Mandatory tumor biopsies for PD analysis were taken pre and post Cycle 1 in an expanded MTD cohort. Results: 34 pts (M/F: 21/13; median age 63.5yrs [range 32-78]) were treated at 6 dose levels: 100, 200, 270, 360, 450 and 400 mg. Tumor types were colorectal (n=15), lung (n=4), renal (n=4), esophageal (n=2), melanoma (n=2) and others (n=7). Three DLTs were observed: Gr3 GGT and alkaline phosphatase (n=1; 200mg) and repeated Gr2 (n=1) and Gr3 (n=1) fatigue, both at 450mg. The MTD was determined to be 400 mg QD. Frequently occurring adverse events ([AEs]; all grades) were fatigue: 68% (Gr3: 15%), diarrhea: 65%, nausea: 62%, vomiting: 53%, decreased appetite: 47% (Gr3: 9%), ALT increase: 38% and AST increase: 23%. No Gr4 AEs were observed. Best response was stable disease in 6 pts lasting >84 days. PK showed high variability and plasma concentration increased with dose. The Cmax was reached within a median time of 4 hours. Plasma PD analysis showed an increase in soluble c-Met and Ang 2 levels after golvatinib treatment. Tumor PD analysis in 5 pts at 400 mg demonstrated a baseline elevated MET gene copy number, with c-Met overexpression and post treatment decline in phospho(p)-c-Met expression in 1 pt; post-treatment decline in p-c-Met in a 2nd pt, and post-treatment decline in p-ERK in a 3rd pt. Conclusions: Golvatinib at an MTD of 400 mg QD has manageable toxicity. Preliminary PD analysis demonstrated evidence of c-Met target modulation. Further evaluation will continue in phase 2 combination studies.
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Mirabell, I. F. "Microquasars and ULXS: Fossils of GRB Sources." International Astronomical Union Colloquium 194 (2004): 14–17. http://dx.doi.org/10.1017/s0252921100151735.
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AbstractGamma-ray bursts (GRBs) of long duration probably result from the core-collapse of massive stars in binary systems. After the collapse of the primary star the binary system may remain bound leaving a microquasar or ULX source as remnant. In this context, microquasars and ULXs are fossils of GRB sources and should contain physical and astrophysical clues on their GRB-source progenitors. Here I show that the identification of the birth place of microquasars can provide constrains on the progenitor stars of compact objects, and that the runaway velocity can be used to constrain the energy in the explosion of massive stars that leave neutron stars and black holes. The observations show that the neutron star binaries LS 5039, LSI +61°303 and the low-mass black hole GRO J1655-40 formed in energetic supernova explosions, whereas the black holes of larger masses (M ≥ 10 M⊙) in Cygnus X-l and GRS 1915+105 formed promptly, in the dark or in underluminous supornovao. The association with clusters of massive stars of the microquasar LSI +61°303 and the magnetars SGR 1806-20 and SGR 1900+14, suggest that very massive stars (M ≥ 50 M⊙) may -in some cases- leave neutron stars rather than black holes. The models of GRB sources of long duration have the same basic ingredients as microquasars and ULXs: compact objects with accretion disks and relativistic jets in binary systems. Therefore, the analogies between microquasars and AGN may be extended to the sources of GRBs.
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Bonnet, Christophe, Thierry Lamy, Christophe Fruchart, Steven Le Gouill, Katharina Gunzer, Thomas Gastinne, Fabrice Jardin, et al. "Ibrutinib in Association with R-DHAP/Ox for Patients with Relapsed/Refractory B-Cell Lymphoma: Preliminary Results of the Biblos Phase Ib Lysa Study." Blood 128, no. 22 (December 2, 2016): 5384. http://dx.doi.org/10.1182/blood.v128.22.5384.5384.
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Abstract Background: Ibrutinib is a first-in-class selective, irreversible inhibitor of Bruton's tyrosine kinase (BTK) approved for the treatment of patients with relapsed or refractory (R/R) mantle cell lymphoma (MCL) and R/R chronic lymphocytic leukemia. In heavily pretreated MCL, in monotherapy, an ORR of 68% was observed in a phase II study (Wang, 2013). Toxicity is mainly hematological and gastrointestinal. Safety profiles for combination of ibrutinib with R-CHOP or R-benda are acceptable and these combinations are under evaluation in phase III randomized studies (Younes, 2014; Maddocks 2015). We present here preliminary data of a phase Ib study evaluating the safety and tolerability of ibrutinib in association with R-DHAP or R-DHAOx for patients with B-cell lymphoma after first or second treatment failure who are candidates for autologous stem cell transplantation (ASCT). Patients & methods: Eligible patients were planned to receive 3 cycles, given every 21 days, of rituximab 375 mg/m² on day 1, dexamethasone 40 mg on days 1 to 4, cytarabine 2 g/m² bid on day 2 and cisplatin 100 mg/m² on day 1 (R-DHAP) or oxaliplatin 130 mg/m² on day 1 (R-DHAOx) in association with escalating doses of ibrutinib. The starting dose (dose level 1, DL1) was 420 mg/day on days 1 to 21. The dose-variation scheme followed a traditional "3+3" design (DL-1: 280 mg/day on days 1 to 21; DL2: 560 mg/day on days 1 to 21). Dose-limiting toxicities (DLT) were considered during the first cycle. DLT were defined as: non-hematological toxicity grade (Gr) 3-4 excluding alopecia, diarrhea and/or nausea/vomiting and/or fatigue/asthenia for less than 7 days; any Gr ≥ 2 hemorrhagic events; any Gr≥ 1 intracranial hemorrhage and any Gr≥ 4 hematological toxicity lasting more than 7 days. Results: Between May 2014 and July 2015, 25 patients have been treated (R-DHAP: 13, 1 non evaluable for DLT; R-DHAOx: 12). In the DL1 cohort (420 mg/day), DLTs assessed as related to ibrutinib were observed in 3/6 patients receiving R-DHAOx (Gr3 cutaneous eruption, Gr3 febrile neutropenia and prostatic infection, Gr4 thrombocytopenia) and in 3/6 patients receiving R-DHAP (Gr4 cutaneous eruption, Gr4 thrombocytopenia and Gr4 sepsis). According to protocol, ibrutinib dose was decreased to 280 mg/day. Thirteen patients were treated at DL-1 with 1 patient experiencing DLT in each cohort (1/6 evaluable patients in R-DHAP group: Gr4 thrombocytopenia and Gr4 gastric hemorrhage, Gr3 atrial fibrillation; 1/6 patient in R-DHAOx group: Gr3 epigastric pain). Six (50%) patients treated with ibrutinib at the dose of 420 mg and 10 (77%) of those treated at the dose of 280 mg received more than 80% of the planned dose before ASCT. All 25patients experienced one or more adverse events (AE). Diarrhea occurred in 8% of patients. All 25 patients presented Gr3-4 hematological adverse events (neutropenia: 17 patients, including 7 with febrile neutropenia; thrombocytopenia: 25). Three patients presented serious hemorrhagic events. Four patients developed cutaneous eruptions (all of them received prophylactic sulfamethoxazole-trimethoprim). There was 1 death attributable to cardiac toxicity (assessed as unrelated to ibrutinib). Nine patients discontinued ibrutinib (7 due to toxicities, including DLTs, and 2 due to patient's decision). Response to treatment (Cheson 2007 criteria) is currently evaluable in 16 patients (64%). Fourteen responded to the treatment: 8 CR (50%) and 6 PR (37%). Stem cells were harvested in 16 patients and all of them underwent ASCT (CD34+ cells > 3.0x106/kg in 94% of the collected patients after one sole apheresis). Conclusion: Our preliminary result show thatthe DHAP/Ox plus ibrutinib (administered continuously from D1-21) regimen led to several dose-limiting toxicities. Because the dose of 280 mg might be insufficient to improve the quality of response, the protocol was amended in October 2015 in order to change the schedule of Ibrutinib. A new escalation phase using ibrutinib only from day 5 to day 18 is currently ongoing. Pharmacokinetics analyses are also performed. Disclosures Bonnet: JANSSEN: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; SERVIER: Membership on an entity's Board of Directors or advisory committees; ROCHE: Membership on an entity's Board of Directors or advisory committees. Karlin:takeda: Consultancy; amgen: Consultancy, Honoraria; janssen-cilag: Consultancy, Honoraria; celgene: Consultancy, Honoraria; Bristol: Consultancy. Dupuis:janssen: Honoraria; ABBVIE: Membership on an entity's Board of Directors or advisory committees. Salles:Roche/Genentech: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Gilead: Honoraria, Research Funding; Mundipharma: Honoraria.
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Yeh, K., C. Hsu, Y. Lu, C. Hsu, S. Kuo, C. Huang, Y. Shen, C. Hsiao, C. Yang, and A. Cheng. "Phase II study of sequential non-cross-resistant chemotherapy using weekly 24-hour infusion of cisplatin, high-dose 5-fluorouracil and leucovorin (P-HDFL) followed by weekly docetaxel and irinotecan (DI) for recurrent or metastatic gastric cancer: an interim analysis." Journal of Clinical Oncology 24, no. 18_suppl (June 20, 2006): 14063. http://dx.doi.org/10.1200/jco.2006.24.18_suppl.14063.
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14063 Weekly 24-hour infusion of high-dose 5-FU and leucovorin (HDFL)-based regimens are highly effective for advanced gastric cancer (AGC). Although the response rate has been improved, the overall survival (OS) was not significantly prolonged. To prolong the OS, we designed a sequential chemotherapy strategy incorporating non-cross-resistant docetaxel and irinotecan (DI). All patients had patho/cytologically confirmed recurrent/metastatic chemonaive AGC, at least 1 measurable lesion, a fasting serum triglyceride level > 70 mg/dl, adequate hepatic, renal, and marrow functions. Induction regimen was P-HDFL (cisplatin 35 mg/m2, i.v. 24-hr, D1, 8; 5-FU 2600 mg/m2 and leucovorin 300 mg/m2, i.v. 24-hr, D1, 8, 15; every 4 wks), and consolidation regimen was weekly DI (docetaxel 30–35 mg/m2/wk, i.v. 30-min, then irinotecan 60–70 mg/m2/wk, i.v. 30-min, D1, 8, 15; every 4 wks). Patients with inferior conditions (prior Gr4 neutropenia or Gr3/4 infection, poor marrow reserve with delayed hemogram recovery, poor nutritional status or ileus) started with dose-modified DI (D: 30, I: 60 mg/m2/wk). For CR patients by P-HDFL, 3 cycles of DI were given; and for PR or SD patients, DI was continued till 2 cycles after CR, disease progression, or unacceptable toxicities. Between Jun. 2000 and Dec. 2005, 23 patients were enrolled (M:11, F:12) with a median age of 52 (37–68). Total 114 cycles (median: 6, range: 2–8) of P-HDFL were given. Overall RR was 60.9% (38–80%, 95% C.I.) with 3 CRs and 11 PRs. Gr3/4 toxicities: neutropenia (14%), infection (4.4%), thrombocytopenia (1.6%), diarrhea (5%), and vomiting (7%). Gr1/2 hand-foot syndrome was noted in 11% of cycles. Patients with CR, PR, and SD were treated with weekly DI regimen. Total 59 cycles (median: 4, range: 1–10) of weekly DI were given. Gr3/4 toxicities: neutropenia (30.5%), infection (13%), thrombocytopenia (2%), and diarrhea (17%). Median OS of the whole intent-to-treat group is 18 months (3 to 62+), and median OS of 14 responders of P-HDFL is 20 months (7 to 62+). This sequential non-cross-resistant strategy is very effective for prolongation of OS in advanced AGC. No significant financial relationships to disclose.
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Carethers, John M. "GRG Profiles: John M. Carethers." Digestive Diseases and Sciences 61, no. 6 (February 5, 2016): 1429–35. http://dx.doi.org/10.1007/s10620-016-4058-9.
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Holst, J. J., S. Knuhtsen, C. Orskov, T. Skak-Nielsen, S. S. Poulsen, and O. V. Nielsen. "GRP-producing nerves control antral somatostatin and gastrin secretion in pigs." American Journal of Physiology-Gastrointestinal and Liver Physiology 253, no. 6 (December 1, 1987): G767—G774. http://dx.doi.org/10.1152/ajpgi.1987.253.6.g767.
Full textAbstract:
By immunohistochemistry, nerve fibers containing gastrin-releasing polypeptide (GRP)-like immunoreactivity were identified close to the somatostatin (SS)-producing cells of the gastric antral mucosa. We, therefore, studied the possible role of GRP in the control of antral SS secretion by use of isolated perfused pig antrum with intact vagus nerve supply. Electrical stimulation of the vagus nerves at 4 Hz increased the antral release of GRP up to 10-fold and increased SS output 2- to 3-fold. Atropine at 10(-6) M had no effect on these responses. Intra-arterial GRP increased SS secretion significantly at 10(-10) M and eightfold at 10(-8) M, whereas gastrin secretion was stimulated significantly at 10(-11) M and maximally at 10(-10) M and inhibited at 10(-8) M. Preperfusion with a GRP antagonist ([D-Arg1,D-Pro2,D-Trp7,9,Leu11]substance P) or Fab fragments of antibodies against GRP abolished the effects of vagus stimulation on gastrin and somatostatin output. Gastrin in concentrations up to 10(-7) M was without effect on SS secretion. We conclude that electrical stimulation of the vagus nerves increases antral SS gastrin secretion and that GRP is a likely transmitter.
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Rajkumar, S., M. Loganathan, and R. Venkatesh. "Optimization of NaCl based spray corrosion test process parameters of heat treated hybrid metal matrix composites." Bulletin of the Chemical Society of Ethiopia 36, no. 4 (August 30, 2022): 903–14. http://dx.doi.org/10.4314/bcse.v36i4.15.
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ABSTRACT. Aluminium hybrid metal matrix composites (AHMMCs) have widely employed in aerospace, transportation, and automotive applications since for their excellent mechanical qualities and high corrosion resistance. In this research, Al8079 is selected as a matrix material. The titanium diboride (TiB2) is selected as hard reinforcement and molybdenum disulfide (MoS2) is used as soft reinforcement. The Al8079/15 wt.% TiB2/x wt.% MoS2 (x = 0, 2.5, 5 and 7.5) HMMCs are fabricated by using stir casting. The composites are heat treated under T6 condition. The density and micro hardness tests are conducted. The optimization on NaCl based spray corrosion test process parameters is done using grey relational analysis (GRA). The selected input process parameters are Al8079/15 wt.% TiB2/wt.% MoS2 (x = 0, 2.5 and 5), pH value of NaCl solution (x = 6, 9 and 12), hang time (x = 24, 48, and 72 h) and pressure (x = 0.7, 0.9 and 1.1 kg/cm2). The selected response parameters are micro hardness, mass loss and wear loss. The L9 Taguchi design is used for optimization. The wear test is conducted at the constant speed of 0.5 m/s, loading rate of 20 N and the sliding distance of 1000 m. The percentage of improvement of GRG from initial setting to experimental is 10.4%.
KEY WORDS: Reinforcement, Stir casting, Optimization, GRA, NaCl
Bull. Chem. Soc. Ethiop. 2022, 36(4), 903-914.
DOI: https://dx.doi.org/10.4314/bcse.v36i4.15
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Gawin, A. Z., J. N. Baraniuk, J. D. Lundgren, and M. Kaliner. "Effects of gastrin-releasing peptide and analogues on guinea pig nasal mucosal secretion." American Journal of Physiology-Lung Cellular and Molecular Physiology 264, no. 4 (April 1, 1993): L345—L350. http://dx.doi.org/10.1152/ajplung.1993.264.4.l345.
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The effects of gastrin-releasing peptide (GRP), bombesin, GRP-(1–16) and GRP-(21–27) on guinea pig nasal mucosal secretion were studied in vivo. GRP, bombesin, and GRP-(21–27) induced significant secretion of total protein, albumin, and alkaline phosphatase. GRP induced significant secretion at lower concentrations (10(-11) and 10(-10) M) than were required for bombesin and GRP-(21–27) (10(-7) M). GRP-(1–16) did not stimulate secretion, indicating that the COOH-terminal region of GRP contained the secretagogic principle. Capsaicin, a stimulant of nociceptive sensory nerves, stimulated GRP release into nasal secretions. These data suggest that GRP is present in guinea pig nasal mucosa and that the COOH-terminal region of GRP may regulate mucosal macromolecule secretion.
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Huang, Jie, Gui-Zhen Chen, Sagheer Ahmad, Yang Hao, Jin-Liao Chen, Yu-Zhen Zhou, Si-Ren Lan, Zhong-Jian Liu, and Dong-Hui Peng. "Genome-Wide Identification and Characterization of the GRF Gene Family in Melastoma dodecandrum." International Journal of Molecular Sciences 24, no. 2 (January 9, 2023): 1261. http://dx.doi.org/10.3390/ijms24021261.
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Growth-regulating factor (GRF) is a kind of transcription factor unique to plants, playing an important role in the flowering regulation, growth, and development of plants. Melastoma dodecandrum is an important member of Melastomataceae, with ornamental, medicinal, and edible benefits. The identification of the GRF gene family in M. dodecandrum can help to improve their character of flavor and continuous flowering. The members of the GRF gene family were identified from the M. dodecandrum genome, and their bioinformatics, selective pressure, and expression patterns were analyzed. The results showed that there were 20 GRF genes in M. dodecandrum. Phylogenetic analysis showed that the 71 GRF genes from M. dodecandrum, Arabidopsis thaliana, Camellia sinensis, and Oryza sativa can be divided into three clades and six subclades. The 20 GRF genes of M. dodecandrum were distributed in twelve chromosomes and one contig. Furthermore, the gene structure and motif analysis showed that the intron and motif within each clade were very similar, but there were great differences among different clades. The promoter contained cis-acting elements related to hormone induction, stress, and growth and development. Different transcriptomic expression of MdGRFs indicated that MdGRFs may be involved in regulating the growth and development of M. dodecandrum. The results laid a foundation for further study on the function and molecular mechanism of the M. dodecandrum GRF gene family.
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Kusano, K., H. Gainer, J. F. Battey, Z. Fathi, and E. Wada. "Receptor-activated currents in mouse fibroblasts expressing transfected bombesin receptor subtype cDNAs." American Journal of Physiology-Cell Physiology 265, no. 4 (October 1, 1993): C869—C876. http://dx.doi.org/10.1152/ajpcell.1993.265.4.c869.
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BALB/c 3T3 cells do not normally express receptors for bombesin-like peptides [bombesin (Bn), gastrin-releasing peptide (GRP), and neuromedin B (NmB)]. Transfection of BALB/c 3T3 cells with complementary DNA-encoding GRP receptors or NmB receptors leads to stable expression of functional GRP receptors (GRP Rt) or NmB receptors (NmB Rt), respectively, which are coupled to cell membrane ion channels. Whole cell current analysis using patch electrodes shows that the activation of these newly expressed receptors induces cation conductance increases, most frequently a Ca(2+)-activated plasma membrane K+ conductance. The dose-response (peak-current) relations of both transfected receptor subtypes were sigmoidal and exhibited threshold activation concentration in the picomole range and the saturation of responses to higher concentrations than 10(-8) M. The GRP Rt responded about equally to GRP, NmB, and Bn when compared at equimolar levels, despite their known difference in binding affinity for the three peptides (GRP, Bn > NmB). In contrast, for the NmB Rt, the NmB was more potent than GRP or Bn. Among four GRP/Bn-receptor antagonists tested, the [D-Phe6]Bn(6-13) ethyl ester suppressed GRP Rt responses at low concentrations (10(-7) M). N-acetyl-GRP-(20-26) amide, [Leu13-psi(CH2NH)-Leu14]Bn, and [D-Arg1,D-Phe5,D-Trp7,9,Leu11]substance P also blocked GRP Rt responses but at higher concentrations (10(-5) M). However, at these concentrations, these four antagonists had little effect on NmB Rt responses, thereby showing a specificity of these antagonists for the GRP receptors.
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Jimeno, Antonio, Patricia LoRusso, Robert Matthew Strother, Jennifer Robinson Diamond, Leah Plato, Anne Younger, Wells A. Messersmith, et al. "Phase I study of REGN421 (R)/SAR153192, a fully-human delta-like ligand 4 (Dll4) monoclonal antibody (mAb), in patients with advanced solid tumors." Journal of Clinical Oncology 31, no. 15_suppl (May 20, 2013): 2502. http://dx.doi.org/10.1200/jco.2013.31.15_suppl.2502.
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2502 Background: Dll4, a Notch receptor ligand, may have a role in tumor angiogenesis and is an emerging anticancer target. REGN421 (R) is a fully human IgG1mAb that binds human Dll4 and disrupts Notch-mediated signaling. Methods: Primary objectives of the dose escalation (3+3 design) trial were to determine safety and a recommended phase II dose (RP2D) of R in patients (pts) with advanced cancer. R was given IV at doses of 0.25, 0.5, 1, 2 and 4mg/kg every 3 weeks (Q3W) or 0.75, 1, 1.5, and 3mg/kg every 2 weeks (Q2W). Secondary objectives were PK, immunogenicity, and antitumor activity. Results: 53 pts (M/F=22/31, ECOG 0/1=18/35) were enrolled; 31 pts were treated Q3W at doses of 0.25 - 4 mg/kg; 22 pts were treated Q2W at doses of 0.75 - 3 mg/kg. Two DLTs occurred: Grade 3 (Gr3) nausea (0.5mg/kg Q3W) and Gr3 abdominal pain (1 mg/kg Q2W). A maximum tolerated dose was not reached on either schedule. Grade 3/4 AEs occurred in 29 pts; nausea, abdominal pain, dyspnea, hypoxia, and hypertension (HTN) were reported in ≥ 5%. Most frequent treatment related AEs were fatigue (30%), headache (26%), HTN (26%), and nausea (15%). Six treatment related SAEs (all reversed off treatment) were reported in 4 patients: BNP increase (0.25mg/kg, Gr1), troponin I increase (4mg/kg, Gr3), right ventricular dysfunction (1.5mg/kg, Gr3), left ventricular dysfunction (3mg/kg, Gr3) and 2 events of pulmonary HTN (1.5mg/kg, Gr 3, and 3mg/kg Gr3). Laboratory abnormalities (≥ Gr3) were neutropenia (3) and anemia (2), and elevated ALP (7), ALT (3), bilirubin (3), AST (2), and decreased albumin (1). Anti-tumor activity included 2 PRs (NSCLC BAL-type with a beta-catenin mutation and ovarian cancer [OvCa]), and 16 pts with SD (3 pts had SD > 6 months). Two of 8 pts with OvCa had CA125 responses. R had non-linear target-mediated PK without accumulation. The half-life of R at 3mg/kg Q2W was 7 days. No immunogenicity was observed. Conclusions: REGN421 had an acceptable safety profile, and RP2Ds of 4mg/kg Q3W and 3mg/kg Q2W. Responses and prolonged SD were noted in OvCa pts and other solid tumors. Dose escalation has concluded and disease specific expansion cohorts are ongoing. Clinical trial information: NCT00871559.
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Jiang, Jun, Shichang Xiao, Shu Yan, Jianpeng Xiao, and Ximing Xu. "Glycyrrhizae Radix et Rhizoma Processed by Sulfur Fumigation Damaged the Chemical Profile Accompanied by Immunosuppression and Liver Injury." BioMed Research International 2020 (February 6, 2020): 1–11. http://dx.doi.org/10.1155/2020/5439853.
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Glycyrrhizae Radix et Rhizoma (GRER) has been used as a medicinal plant and dietary supplements for its beneficial effect in immunomodulatory effects. Sulfur fumigation (SF) processing was widely used in the storage and maintenance of Chinese medicine because of its convenience and cheapness. However, the disadvantage of SF has been reported, but the systematic study of SF on GRER was deficient. In this paper, the active ingredients, sulfur-fumigated products, immunomodulatory effect, and liver injury of SF-GRER were studied. After SF, the liquiritin decreased from 4.49 ± 0.03 mg/g to 3.94 ± 0.08 mg/g (P<0.01). Compared with the NSF-GRER group, the SF-GRER group showed a decreased immunoregulation in the thymus index, spleen index, and serum IL-6 and SOD levels (P<0.05). After 2 weeks of continuous intragastric administration of SF-GRER in healthy mice, the level of serum aspartate aminotransferase (AST) significantly increased (P<0.05) and the area of liver lesion significantly increased compared with the NSF-GRER (P<0.05) group. The sulfonated products (m/z, 631.13) corresponding to liquiritin apioside (m/z, 551.17) and isoliquiritin apioside (m/z, 551.17) were screened out in SF-GRER by using UPLC-Orbitrap-MS. The sulfonated products provided in this paper were discovered for the first time and could be powerfully applied for the identification of SF-GRER. SF destroyed the chemical composition of GRER, inhibited immunoregulation, and induced liver injury. The feasibility of this processing method needs to be reconsidered.
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Du Four, Stephanie, Sofie Wilgenhof, Amelie Clementine Seghers, Johnny Duerinck, and Bart Neyns. "Ipilimumab in patients with melanoma brain metastases, a single-center experience in an expanded access program." Journal of Clinical Oncology 30, no. 15_suppl (May 20, 2012): e19027-e19027. http://dx.doi.org/10.1200/jco.2012.30.15_suppl.e19027.
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e19027 Background: patients (pts) diagnosed with melanoma brain metastases (MBM) have a poor prognosis with conventional treatment options. Ipilimumab (IPI) is a CTLA-4 blocking monoclonal antibody with established activity in patients (pts) with pretreated advanced melanoma. Methods: observational study on the clinical outcome of melanoma pts with a prior diagnosis of MBM among pts treated with IPI (3 mg/kg q3wks x4, allowing for retreatment after a PFS of >24 wks) in an expanded access program at a single center. Results: among the 50 pts who initiated IPI treatment between April 2010 and May 2011, 16 pts had been diagnosed with MBM. Only 1 pt had a solitary MBM, all other pts had > 3 MBM. Baseline characteristics for pts with- and without MBM: M/F 8/8 vs. 20/14; mAge 44- vs. 50y; BRAF V600-mut/wt 10/6 vs 19/15; stage IV-M1c/-a&b 16/0 vs 31/3; WHO-PS 0-1/2 9/7 vs 30/4; LDH >ULN 10/6 vs 23/11; CRP >ULN 10/6 vs 20/14; ALC<1000/mm³ 3/13 vs 11/23. All pts were pretreated with DTIC; 3 pts with stereotactic (stRT), 7 pts with WBRT, and 2 pts with WBRT followed by a stRT boost; 4 pts had no prior therapy for MBM. 7/16 pts with- vs. 24/34 pts without MBM completed IPI-treatment; 3/16 pts with- vs 8/34 pts without MBM had IPI-retreatment. Adverse events were managed following established guidelines and were generally mild/reversible (<20% pts gr3-, none gr4/5) and similar in pts with- or without MBM at the exception of symptomatic radiation necrosis of the brain (RNB) observed in 3 pts (1x gr2, 2x gr3). Following surgery (1pt), and corticotherapy (3pts) all pts recovered their RNB related symptoms. Best objective tumor response (BOR) by RECIST outside the CNS in pts with- vs without MBM was 1PR vs. 1CR/2PR/4SD; according to the immune-related response criteria: 3PR vs. 1CR/2PR/7SD. After a median follow-up of 18 months, 32 pts have died (11/16 with- vs. 21/34 without MBM). The probability for OS was not significantly different for pts with- or without MBM (HR .76 [95%CI 0.36-1.59]; p: .475 by Log-Rank test). Conclusions: in our single-center experience with IPI for pts with advanced melanoma treated in an EAP, the probability for OS for patients with a prior history of MBM was not significantly different from pts without a prior history of MBM.
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Marx, Angela N., Megumi Kai, Min Fu, Hope E. Murphy, Jie S. Willey, Huiming Sun, Angela Alexander, et al. "Abstract P4-06-09: A phase 1b study of neratinib with THP in metastatic and locally advanced breast cancer, and phase II study of THP followed by AC in HER2 + primary inflammatory breast cancer (IBC), and neratinib with taxol followed by AC in HR+/HER2- IBC." Cancer Research 83, no. 5_Supplement (March 1, 2023): P4–06–09—P4–06–09. http://dx.doi.org/10.1158/1538-7445.sabcs22-p4-06-09.
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Abstract Background: The pathologic complete response (pCR) rate in inflammatory breast cancer (IBC) patients is worse than in non-IBC patients; new drug combinations are warranted to improve pCR rates across all IBC molecular subtypes. Based on our preclinical data, we added neratinib to standard neoadjuvant chemotherapy in both HER2+ (synergy) and HER2-/hormone receptor (HR)+ (high frequency of ERBB2 mut) untreated IBC, as a single-center, non-randomized phase I/II trial. Patients and Method: This study enrolled three cohorts: Cohort I phase Ib (C1P1B), Cohort I Phase II (C1P2) and Cohort II (C2). In C1P1B to determine the recommended phase 2 dose (RP2D), we enrolled patients with HER2+ metastatic or locally advanced breast cancer. Patients received paclitaxel/trastuzumab/pertuzumab (THP) + neratinib x 4 cycles (up to 8 cycles per physician’s discretion). For C1P2 and C2, we enrolled Stage III – IV primary IBC patients. In C1P2, patients with HER2+ IBC received neratinib (RP2D) combined with THP x 4 cycles followed by doxorubicin/cyclophosphamide (AC) x 4 cycles. Per stage I design, 11 patients were enrolled with plan to enroll 20 more patients in Stage II if at least 6 had a pCR. In C2, patients with HER2-/HR+ IBC received neratinib 200 mg/day combined with paclitaxel x 4 cycles followed by AC x 4 cycles. Stage I design planned for enrollment of 16 patients with enrollment of 15 more patients on stage II, if at least 2 Stage I patients had pCR. In all three cohorts, patients initiated prophylactic anti-diarrheal medication (loperamide & budesonide) with the first dose of neratinib. Results: From 2018 to 2022, thirty-four patients were enrolled and treated (n=4 C1P1B, n=14 C1P2, n=16 C2). In C1P1B, observed DLTs (dose limiting toxicities) were Grade (Gr) 2 Diarrhea, n=2 (50%); Gr3 diarrhea, n=2 (50%); 2 patients had a serious adverse event (SAE); 3 patients (55%) had Gr2 nausea. The RP2D was established at 80 mg/day (dose level 0). For patients in C1P2, the most frequently occurring adverse events (AEs) included Gr2 Alopecia, n=14 (100%); Gr2&3 Diarrhea, n=14 (100%); Gr2/3 Nausea, n=12 (86%); Gr2/3 Anemia, n=7 (50%); Gr2/3 Fatigue, n=8 (57%); Gr2/3 Hypokalemia, n=6 (57%); and Gr2/3 Neutrophil count decreased, n= 7 (50%). 6 patients had an SAE. Of the first 11 patients, 5 (46%) had pCR, 1 (9%) RCB-1, 1 (9%) RCB-II and 1 (9%) RCB-III. Three patients stopped study treatment for toxicity (27%), were non-evaluable and replaced. Of these, one had RCB-III (33.3%), one progression of disease (PD) (33.3%), and one came off study for toxicity (33.3%). Rather than replacing additional non-evaluable patients, the study was closed to new patient accrual. In C2, the most frequently occurring AEs were Gr2 diarrhea, n=7(44%); Gr3 diarrhea, n=8 (50%); Gr2 alopecia, n=14 (88%); Gr2/3 Anemia, n=10 (63%); Gr2/3 Nausea, n=7 (44%); Gr2/3 Neutropenia, n= 7 (44%). 3 patients had an SAE. Of 16 patients in this cohort, 1 had pCR (6%), 5 RCB-II (31%), 4 RCB-III (25%), 3 came off study for toxicity (19%) and 3 had PD (19%). C2 also closed to new patient accrual given the high toxicity profile. Conclusion: The addition of neratinib did not improve the pCR rate in HER2+ or HER2-/HR+ subtypes of IBC, and increased toxicities were observed. The trial closed to new patient entry March 2022. However, some patients achieved significant response. Biomarker analysis is ongoing. Evaluable participants will continue long-term follow-up per protocol. Acknowledgments: This study is supported by PUMA Biotechnology. Citation Format: Angela N. Marx, Megumi Kai, Min Fu, Hope E. Murphy, Jie S. Willey, Huiming Sun, Angela Alexander, Roland L. Bassett, Gary J. Whitman, H. T. Carisa Le-Petross, Miral Patel, Banu K. Arun, Sausan Abouharb, Parijatham S. Thomas, Carlos H. Barcenas, Nuhad K. Ibrahim, Vicente Valero, Naoto T. Ueno, Rachel M. Layman, Bora Lim, Wendy Woodward, Anthony Lucci. A phase 1b study of neratinib with THP in metastatic and locally advanced breast cancer, and phase II study of THP followed by AC in HER2 + primary inflammatory breast cancer (IBC), and neratinib with taxol followed by AC in HR+/HER2- IBC [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-06-09.
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Guo, Y. S., L. Mok, C. W. Cooper, G. H. Greeley, J. C. Thompson, and P. Singh. "Effect of gastrin-releasing peptide analogues on gastrin and somatostatin release from isolated rat stomach." American Journal of Physiology-Gastrointestinal and Liver Physiology 253, no. 2 (August 1, 1987): G206—G210. http://dx.doi.org/10.1152/ajpgi.1987.253.2.g206.
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A differential biological potency of bombesin (BBS), compared with its mammalian counterpart gastrin-releasing peptide (GRP), has been reported in several biological systems in rodents. In the present study we have examined the relative potency of BBS, GRP-(1-27) (GRP-L), and GRP-(14-27) (GRP-S) on the release of gastrin and somatostatin (SRIF) from the isolated perfused rat stomachs. Male rats were fasted overnight and the stomachs perfused via the celiac artery. Increasing doses of BBS, GRP-L, and GRP-S were perfused for 15 min each and the effluent collected for measurement of gastrin and SRIF. The release of gastrin and SRIF in response to the GRP analogues was biphasic, with a peak increase occurring within the first 5 min, followed by a sustained increased secretion. The release of gastrin in response to 10(-10)-10(-9) M concentrations of the peptides was strongest with GRP-S (1.5-2.0 times higher than that released by BBS and GRP-L), although at higher concentrations (10(-8) M), the response to all three analogues was similar. The release of SRIF, on the other hand, was significantly higher in the presence of BBS compared with that in response to GRP-S, while GRP-L was ineffective. These studies indicate that the biological potency of BBS compared with its mammalian counterpart, GRP, is different on the two cell populations [gastrin (G) and SRIF (D)].
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PANSKY, ANDREAS, ANDREAS DE WEERTH, ELIZAVETA FASLER-KAN, JEAN-LOUIS BOULAY, MARTINA SCHULZ, SYLVIA KETTERER, CRISTIN SELCK, CHRISTOPH BEGLINGER, TAMMO VON SCHRENCK, and PIUS HILDEBRAND. "Gastrin Releasing Peptide-Preferring Bombesin Receptors Mediate Growth of Human Renal Cell Carcinoma." Journal of the American Society of Nephrology 11, no. 8 (August 2000): 1409–18. http://dx.doi.org/10.1681/asn.v1181409.
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Abstract. Bombesin-like peptides typically act as neurotransmitters along the brain-gut axis and as growth factors in various human tissues. The present study demonstrates the expression of gastrin releasing peptide (GRP)-preferring bombesin receptors in human renal cell carcinoma but not in normal kidney tissue. The expression of GRP receptors was characterized at the mRNA level by reverse transcription-PCR, as well as at the protein level by binding of 125I-[Tyr4] bombesin to membranes prepared from tumor tissue (Kd 0.3 nM) and healthy kidney tissue from the same four patients. GRP receptors were also demonstrated in four human kidney carcinoma cell lines (A-498, CAKI-1, CAKI-2, and ACHN). The effects of bombesin/GRP agonists and/or antagonists on growth were investigated in vitro on CAKI-2 cells, which expressed large amounts of GRP receptors. Cell numbers stimulated by 10% fetal calf serum were significantly stimulated by interleukin-1β (control) and GRP-7 (10-7 M), both in the range of 136 to 148%; addition of the GRP receptor antagonist acetyl-GRP(20-27) (10-6 M) completely reversed this effect. Bombesin alone (10-6 M) significantly stimulated CAKI-2 cells (129%) cultured with 0.5% fetal calf serum, whereas another antagonist, D-Phe6,Leu13,(CH2NH)Leu14 bombesin(6-14) (1 μM), alone did not inhibit growth, thus excluding an autocrine mechanism. These results indicate for the first time that malignant transformation of human kidney tissue into renal cell carcinoma is accompanied by novel expression of GRP receptors. Bombesin-like peptides might act as mitogens in these carcinomas, and they might be useful as diagnostic or therapeutic tools such as tumor imaging or internal radiotherapy.
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Lan, Guang-Xuan, Jun-Jie Wei, Ye Li, Hou-Dun Zeng, and Xue-Feng Wu. "The Stellar-mass Function of Long Gamma-Ray Burst Host Galaxies." Astrophysical Journal 938, no. 2 (October 1, 2022): 129. http://dx.doi.org/10.3847/1538-4357/ac8fec.
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Abstract Long gamma-ray bursts (GRBs) have been discussed as a potential tool to probe the cosmic star formation rate (SFR) for a long time. Some studies found an enhancement in the GRB rate relative to the galaxy-inferred SFR at high redshifts, which indicates that GRBs may not be good tracers of star formation. However, in these studies, the GRB rate measured at any redshift is an average over all galaxies at that epoch. A deep understanding of the connection between GRB production and environment also needs to characterize the population of GRB host galaxies directly. Based on a complete sample of GRB hosts, we constrain the stellar-mass function (SMF) of GRB hosts, and examine redshift evolution in the GRB host population. Our results confirm that a strong redshift evolution in energy (with an evolution index of δ = 2.47 − 0.89 + 0.73 ) or in density ( δ = 1.82 − 0.59 + 0.22 ) is needed in order to account for the observations. The GRB host SMF can be well described by the Schechter function with a power-law index ξ ≈ −1.10 and a break mass M b,0 ≈ 4.9 × 1010 M ⊙, independent of the assumed evolutionary effects. This is the first formulation of the GRB host SMF. The observed discrepancy between the GRB rate and the galaxy-inferred SFR may also be explained by an evolving SMF.
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Nishi, S., Y. Seino, J. Takemura, H. Ishida, M. Seno, T. Chiba, C. Yanaihara, N. Yanaihara, and H. Imura. "Vagal regulation of GRP, gastric somatostatin, and gastrin secretion in vitro." American Journal of Physiology-Endocrinology and Metabolism 248, no. 4 (April 1, 1985): E425—E431. http://dx.doi.org/10.1152/ajpendo.1985.248.4.e425.
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The effect of electrical stimulation of the vagus nerves on the release of immunoreactive gastrin-releasing peptide (GRP), gastrin, and somatostatin was investigated using the isolated perfused rat stomach. Electrical stimulation (10 Hz, 1 ms duration, 10 V) of the peripheral end of the subdiaphragmatic vagal trunks produced a significant increase in both GRP and gastrin but a decrease in somatostatin. The infusion of atropine sulfate at a concentration of 10(-5) M augmented GRP release and reversed the decrease in somatostatin release in response to vagal stimulation to an increase above basal levels. However, the gastrin response to vagal stimulation was not affected by atropine. The infusion of hexamethonium bromide at a concentration of 10(-4) M significantly suppressed GRP release but did not affect gastrin secretion in response to vagal stimulation. On the other hand, the somatostatin response to vagal stimulation was completely abolished by hexamethonium. These findings lead us to conclude that the intramural GRP neurons might play an important role in the regulation of gastrin as well as somatostatin secretion and that somatostatin secretion may be controlled not only by a cholinergic inhibitory neuron but also by a noncholinergic, e.g., peptidergic stimulatory neuron, both of which may be regulated through preganglionic vagal fibers via nicotinic receptors. In addition, because the infusion of 10(-7) M GRP suppressed the somatostatin secretion, we suggest that either GRP should be excluded from the list of candidates for the noncholinergic stimulatory neurotransmitter for somatostatin secretion or that there are different mechanisms of action for endogenous and exogenous GRP.
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Naus, Krzysztof, and Piotr Szymak. "Using Interchangeably the Extended Kalman Filter and Geodetic Robust Adjustment Methods to Increase the Accuracy of Surface Vehicle Positioning in the Coastal Zone." Applied Sciences 13, no. 4 (February 6, 2023): 2110. http://dx.doi.org/10.3390/app13042110.
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This paper presents a study to evaluate the comparative positioning accuracy of Surface Vehicle (SV) using Dead Reckoning (DR), Geodetic Least-Squares Adjustment (GLSA), Geodetic Robust Adjustment (GRA), and External Kalman Filter (EKF) methods. This involved simulating the results of navigational measurements subject to errors (including gross errors) used to position the SV swimming along a given trajectory in the vicinity of three beacons. We showed an apparent increase in the SV positioning accuracy, from approximately 9 m of Root Mean Square (RMS) obtained by DR and GLSA methods, to approximately 2 m (RMS), achieved using GRA and EKF methods. We also showed that, by interchanging GRA and EKF methods, it is still possible to increase the positioning accuracy of the SV up to 1.14 m (RMS). However, such an interchange should occur after the experimentally determined limit of the mean error of the position coordinates estimated by the GRA method has been exceeded.
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Kalantari, Zeinab, Sohrab Rahvar, and Alaa Ibrahim. "Fermi-GBM Observation of GRB 090717034: χ 2 Test Confirms Evidence of Gravitational Lensing by a Supermassive Black Hole with a Million Solar Mass." Astrophysical Journal 934, no. 2 (July 29, 2022): 106. http://dx.doi.org/10.3847/1538-4357/ac7da9.
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Abstract Gravitational lensing of gamma-ray bursts (GRBs) can provide an opportunity to probe the massive compact objects in the universe at different redshifts. We have discovered two consecutive pulses in the light curve of GRB 090717034, with the same temporal profile and different count rate, separated by a time interval, which is identified as a gravitationally lensed candidate in the Fermi-GBM GRB catalog. Here, we use the χ 2 minimization method to investigate the similarity of the temporal profile variability of the two pulses as a gravitationally lensed GRB candidate. We find the magnification factor and the time delay between two pulses to minimize the χ 2 function. Then, we perform a Monte Carlo simulation on a sample of mock lensed GRBs and compare the χ 2 of the lensed GRB candidate with the simulation, which confirms this candidate with 1σ confidence level. Assuming that GRB 090717034 is lensed by a pointlike object, the redshifted lens mass is about M L (1 + z) = (4.839 ± 1.148) × 106 M ⊙. The lens of this GRB is a candidate for a supermassive black hole along the line of sight to the GRB.
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Aliev, A. A., and A. N. Inyushkin. "THE EFFECTS OF GASTRIN-RELEASING PEPTIDE MICROINJECTIONS INTO THE PRE-BOTZINGER COMPLEX ON THE RESPIRATORY PARAMETERS OF RATS." Vestnik of Samara University. Natural Science Series 18, no. 6 (June 9, 2017): 167–73. http://dx.doi.org/10.18287/2541-7525-2012-18-6-167-173.
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In the article, the results of investigation of the respiratory effects of gastrinreleasing peptide microjections into the pre-Botzinger complex are presented. It was found that microinjections of neuropeptide induced an increase in respiratory rate, tidal volume, amplitude of diaphragm and external intercostal muscles bursting activity. The statistically significant respiratory responses observed when 10^-5 M of GRP was used, while 10^-8 M of GRP appeared to be sub-threshold and didn’t alter the breathing pattern and activity of inspiratory muscles. The suggested mechanisms of action of GRP at the level of pre-Botzinger complex are discussed.
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Nuhu, Habila, Suhairul Hashim, Muneer Aziz Saleh, Mohamad Syazwan Mohd Sanusi, Ahmad Hussein Alomari, Mohamad Hidayat Jamal, Rini Asnida Abdullah, and Sitti Asmah Hassan. "Soil gas radon and soil permeability assessment: Mapping radon risk areas in Perak State, Malaysia." PLOS ONE 16, no. 7 (July 28, 2021): e0254099. http://dx.doi.org/10.1371/journal.pone.0254099.
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In this study geogenic radon potential (GRP) mapping was carried out on the bases of field radon in soil gas concentration and soil gas permeability measurements by considering the corresponding geological formations. The spatial pattern of soil gas radon concentration, soil permeability, and GRP and the relationship between geological formations and these parameters was studied by performing detailed spatial analysis. The radon activity concentration in soil gas ranged from 0.11 to 434.5 kBq m−3 with a mean of 18.96 kBq m−3, and a standard deviation was 55.38 kBq m−3. The soil gas permeability ranged from 5.2×10−14 to 5.2×10−12 m2, with a mean of 5.65×10−13 m2. The GRP values were computed from the 222Rn activity concentration and soil gas permeability data. The range of GRP values was from 0.04 to 154.08. Locations on igneous granite rock geology were characterized by higher soil radon gas activity and higher GRP, making them radon-prone areas according to international standards. The other study locations fall between the low to medium risk, except for areas with high soil permeability, which are not internationally classified as radon prone. A GRP map was created displaying radon-prone areas for the study location using Kriging/Cokriging, based on in situ and predicted measured values. The GRP map assists in human health risk assessment and risk reduction since it indicates the potential of the source of radon and can serve as a vital tool for radon combat planning.
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Johnson, Sam T., Grace M. Golden, John A. Mercer, Brent C. Mangus, and Mark A. Hoffman. "Ground-Reaction Forces during Form Skipping and Running." Journal of Sport Rehabilitation 14, no. 4 (November 2005): 338–45. http://dx.doi.org/10.1123/jsr.14.4.338.
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Context:Form skipping has been used to help injured athletes progress to running. Because little research has been done on form-skipping mechanics, its justification as a progression to running exercises is unclear.Objective:To compare ground-reaction forces (GRF) during form skipping and running in healthy subjects at clinically relevant speeds, 1.75 m/s and 3.83 m/s, respectively.Design:Dependentttests (α= .05).Setting:Sports-injury research center.Participants:9 male college athletes (age 20 ± 1.33 years, mass 848.4 ± 43.24 N, height 1.80 ± 0.07 m).Main Outcome Measures:Average (Fzavg) and maximum (Fzmax) vertical GRF and (Fy) braking impulse were compared.Results:FzavgandFzmaxwere greater during running than during form skipping (P< .05). Braking impulses were not different (P> .05).Conclusions:It appears thatFz, but not theFy, GRF might explain why form skipping might be an appropriate progression to running.
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Mazzali, P. A., E. Pian, F. Bufano, and C. Ashall. "Modelling of SN 2013dx associated with the low-redshift GRB130702A points to diversity in GRB/SN properties." Monthly Notices of the Royal Astronomical Society 505, no. 3 (June 7, 2021): 4106–19. http://dx.doi.org/10.1093/mnras/stab1594.
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ABSTRACT The properties of the broad-lined Type Ic supernova (SN) 2013dx, associated with the long gamma-ray burst GRB 130702A at a redshift z = 0.145, are derived via spectral modelling. SN 2013dx was similar in luminosity to other GRB/SNe, with a derived value of the mass of 56Ni ejected in the explosion of ≈0.4 M⊙. However, its spectral properties suggest a smaller explosion kinetic energy. Radiation transport models were used to derive a plausible mass and density distribution of the SN ejecta in a one-dimensional approximation. While the mass ejected in the explosion that is obtained from the modelling (Mej ≈ 9 M⊙) is similar to that of all other well-studied GRB/SNe, the kinetic energy is significantly smaller (EK ∼ 1052 erg). This leads to a smaller EK/Mej ratio, ≈1051 erg/M⊙, which is reflected in the narrower appearance of the spectral lines. While the low EK does not represent a problem for the scenario in which magnetar energy aids powering the explosion and the nucleosynthesis, it is nevertheless highly unusual. SNe Ic with similar EK have never been seen in coincidence with a GRB, and no well-observed GRB/SN has shown similarly low EK and EK/Mej.
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Zheng, Tian-Ci, Long Li, Le Zou, and Xiang-Gao Wang. "X-ray flares raising upon magnetar plateau as an implication of a surrounding disk of newborn magnetized neutron star." Research in Astronomy and Astrophysics 21, no. 12 (December 1, 2021): 300. http://dx.doi.org/10.1088/1674-4527/21/12/300.
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Abstract The X-ray flares have usually been ascribed to long-lasting activities of the central engine of gamma-ray bursts (GRBs), e.g., fallback accretion. The GRB X-ray plateaus, however, favor a millisecond magnetar central engine. The fallback accretion can be significantly suppressed due to the propeller effect of a magnetar. Therefore, if the propeller regime cannot resist the mass flow onto the surface of the magnetar efficiently, the X-ray flares raising upon the magnetar plateau would be expected. In this work, such peculiar cases are connected to the accretion process of the magnetars, and an implication for magnetar-disc structure is given. We investigate the repeated accretion process with multi-flare GRB 050730, and give a discussion for the accretion-induced variation of the magnetic field in GRB 111209A. Two or more flares exhibit in the GRB 050730, 060607A and 140304A; by adopting magnetar mass M = 1.4 M ⊙ and radius R = 12 km, the average mass flow rates of the corresponding surrounding disk are 3.53 × 10−4 M ⊙ s−1, 4.23 × 10−4 M ⊙ s−1, and 4.33 × 10−4 M ⊙ s−1, and the corresponding average sizes of the magnetosphere are 5.01 × 106 cm, 6.45 × 106 cm, and 1.09 × 107 cm, respectively. A statistic analysis that contains eight GRBs within 12 flares shows that the total mass loading in single flare is ∼ 2 × 10−5 M ⊙. In the lost mass of a disk, there are about 0.1% used to feed a collimated jet.
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Kalantari, Zeinab, Alaa Ibrahim, Mohammad Reza Rahimi Tabar, and Sohrab Rahvar. "Imprints of Gravitational Millilensing on the Light Curve of Gamma-Ray Bursts." Astrophysical Journal 922, no. 1 (November 1, 2021): 77. http://dx.doi.org/10.3847/1538-4357/ac1c06.
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Abstract In this work, we search for signatures of gravitational millilensing in gamma-ray bursts (GRBs) in which the source−lens−observer geometry produces two images that manifest in the GRB light curve as superimposed peaks with identical temporal variability (or echoes), separated by the time delay between the two images. According to the sensitivity of our detection method, we consider millilensing events due to point-mass lenses in the range of 105 − 107 M ⊙ at lens redshift about half that of the GRB, with a time delay on the order of 10 s. Current GRB observatories are capable of resolving and constraining this lensing scenario if the above conditions are met. We investigated the Fermi/GBM GRB archive from the year 2008 to 2020 using the autocorrelation technique and found one millilensed GRB candidate out of 2137 GRBs searched, which we use to estimate the optical depth of millilensed GRBs by performing a Monte Carlo simulation to find the efficiency of our detection method. Considering a point-mass model for the gravitational lens, where the lens is a supermassive black hole, we show that the density parameter of black holes (ΩBH) with mass ≈ 106 M ⊙ is about 0.007 ± 0.004. Our result is one order of magnitude larger compared to previous work in the lower mass range of 102 − 103 M ⊙, which gave a density parameter ΩBH ≈ 5 × 10−4, and recent work in the mass range of 102 − 107 M ⊙, which reported ΩBH ≈ 4.6 × 10−4. The mass fraction of black holes in this mass range to the total mass of the universe would be f = ΩBH/Ω M ≈ 0.027 ± 0.016.
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Forner-Cordero, Isabel, Fabianne Furtado, Juan Cervera-Deval, and Arturo Forner-Cordero. "Ground reaction force patterns during gait in patients with lower limb lymphedema." Acta Fisiátrica 23, no. 4 (December 29, 2016): 201–7. http://dx.doi.org/10.11606/issn.2317-0190.v23i4a137673.
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Although gait problems have been reported in patients with lower limb lymphedema (LLL), the gait pattern (GP) changes have not been documented yet. However, it is possible that patients with LLL show abnormal GP that can be related to biomechanical complications related to osteoarthritis or falls affecting the quality of life. Ground reaction force analysis during gait allows objective assessment of the patients and it can be used to plan a rehabilitation approach. Objective: To analyze the GRF during gait in patients LLL. Methods: An experimental descriptive study was realized with twenty-three LLL patients, both unilateral and bilateral and classified as moderate and severe, participated in the experiments. The patients walked on a force plate while the three ground reaction force (GRF) components, vertical, mediolateral (M-L) and anteroposterior (A-P), under their feet were recorded and analyzed. Results: In the patients with unilateral lymphedema, either moderate or severe, the vertical GRF components of the affected limb were similar to the sound one and also resembling those found in healthy adults. The M-L GRF was smaller in the non-affected side. In patients with bilateral lymphedema gait speed was significantly slower. More interestingly, the vertical GRF pattern was flat, not showing the typical 2-peak shape. Finally, the large M-L forces found suggest gait stability problems. Conclusions: The patients showed abnormal GRF patterns, including compensation with the non-affected leg. The GRF variability was higher in the patients with severe unilateral lymphedema. Bilateral lymphedema results in lower A-P forces. Stance phase duration was longer in patients with bilateral and severe lymphedema