Articoli di riviste: "I-701"

1

Lee, Tsung Hung. "Ecological patterns of distribution on gradients of elevation and species diversity of snakes in southern Taiwan". Amphibia-Reptilia 26, n. 3 (2005): 325–32. http://dx.doi.org/10.1163/156853805774408522.

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AbstractThe study was conducted in southern Taiwan, along a road traversing the study area from 287 to 1680 m a.s.l. from May to October 2003 to investigate the distribution patterns and species diversity of the snakes. A total of 69 individual snakes belonging to 16 species were recorded. The Shannon's index and evenness index of the full study area were 2.4337 and 0.8777, respectively. Moreover, evenness index was 401 to 700 m > 1001 to 1300 m > 701 to 1000 m > 1301 to 1600 m altitudinal zone. The Shannon's index, DMG, and the reciprocal form of the Berger-Parker index (1/d) were 1001 to 1300 m > 401 to 700 m > 701 to 1000 m > 1301 to 1600 m altitudinal zone. Thirty-seven snakes were found in natural forest, 12 in plantation forest, 8 in secondary forest, and 12 in agricultural lands. I concluded that the highest species richness and diversity are found in mid-altitudinal mountains in southern Taiwan.

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2

Agnelli, Giancarlo, Benilde Cosmi, Cinzia Renga, Fiorella Federici, Giuseppe G. Necil, Georges Houin e Francesco Gianese. "Human Pharmacokinetics and Pharmacodynamics of MF 701 Dermatan Sulfate Administered by Continuous Intravenous Infusion". Thrombosis and Haemostasis 64, n. 02 (1990): 256–59. http://dx.doi.org/10.1055/s-0038-1647296.

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SummaryThe pharmacokinetics and haemostatic effects of MF 701 dermatan sulfate (DS) administered by i. v. infusion were studied in 11 healthy volunteers. Each subject received 0.6 mg kg-1 h-1 MF 701 for 10 h. DS plasma concentrations were measured by a chromogenic assay based on the catalysis of thrombin inhibition by HCII. DS plasma levels followed a single compartment pharmacokinetic model, with a half-life of 1.28 ± 0.46 h, a plasma clearance of 2.75 ± 0.46 1/h and a volume of distribution of 4.92 ± 1.36 1 (means ± SD). Steady-state was reached 3 to 6 h after infusion started. The maximal DS plasma concentration was 16.4 ± 5.7 μg/ml. Maximal APTT prolongation over pre-infusion values was 42 ± 7%; TCT performed with bovine and human thrombin was prolonged by 16 ± 7% and 83 ± 35% respectively. No anti-IIa or anti-Xa activities were detected by chromogenic tests. The treatment was well tolerated. The pharmacokinetics of MF 701 infusion are consistent with those previously described after i. v. bolus administration. The infusion of MF 701 allows fast achievement and steady maintenance of elevated DS plasma concentrations.

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Tavera, Luz, Stefanie Schalm, John Campbell, Jian Guo, Clare Medendorp, Maxine Chen, Faris Albayya et al. "Abstract 3328: Antitumor activity of BLU-945 and BLU-701 as single agents and in combination in EGFR L858R-driven models of NSCLC". Cancer Research 82, n. 12_Supplement (15 giugno 2022): 3328. http://dx.doi.org/10.1158/1538-7445.am2022-3328.

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Abstract BACKGROUND: Lung cancer is the leading cause of cancer death globally. EGFR mutations are the most common genomic drivers of non-small cell lung cancer (NSCLC), occurring in ~17% and up to 50% of Caucasian and Asian patients, respectively, with exon 19 deletions (ex19del) and L858R substitutions being the most prevalent activating EGFR mutations (EGFRm). Outcomes have improved in patients with EGFR-driven NSCLC since the introduction of EGFR tyrosine kinase inhibitors (TKIs); however, treatment resistance almost inevitably occurs. It has been reported that patients harboring the EGFR L858R mutation, who represent 3.4% of lung adenocarcinoma cases in North America and 23% in Asia, have poorer outcomes than those with EGFR ex19del, suggesting a significant unmet need in this population. BLU-945 and BLU-701 are investigational, reversible, selective, and orally available TKIs optimized for use as single-agent or combination therapy to effectively suppress activating and on-target resistance EGFR mutants while sparing WT EGFR, and have the potential to treat or prevent central nervous system metastases. In vivo studies previously demonstrated the antitumor activity of BLU-945 against EGFR L858R/T790M and EGFRm/T790M/C797S mutants, and BLU-701 against EGFR ex19del and EGFRm/C797S mutants. Because EGFR L858R-driven NSCLC constitutes a large population of patients who may not be receiving the same benefit from third-generation (3G) TKIs as those with EGFR ex19del, studies were conducted to evaluate the antitumor activity of BLU-945 and BLU-701, as single agents and in combination, in preclinical NSCLC tumor models driven by L858R in the absence of the T790M mutation. METHODS: The in vivo antitumor activities of BLU-945 and BLU-701, as single-agents or in combination, were evaluated in 2 EGFR L858R-driven patient-derived xenograft (PDX) subcutaneous tumor models and in an engineered EGFR L858R/C797S-driven Ba/F3 cell line-derived xenograft (CDX) subcutaneous tumor model. RESULTS: Oral daily administration of single-agent BLU-945 and single-agent BLU-701 resulted in sustained tumor regression in 2 PDX models of EGFR L858R NSCLC. Compared with single agents in an EGFR L858R/C797S Ba/F3 CDX tumor model, combination of BLU-945 with BLU-701 resulted in marked antitumor activity and prolonged tumor regression. CONCLUSION: The in vivo antitumor activities of BLU-945 and BLU-701 in preclinical tumor models suggest that both BLU-945 and BLU-701 have the potential to be used in patients with EGFR L858R-driven NSCLC, including those who are treatment naïve or previously treated with 3G TKI. Combining BLU-945 and BLU-701 may enable coverage of frequent on-target resistance mechanisms, including the EGFR C797S mutation, in addition to the common L858R activating mutation. Citation Format: Luz Tavera, Stefanie Schalm, John Campbell, Jian Guo, Clare Medendorp, Maxine Chen, Faris Albayya, Tom Dineen, Zhuo Zhang, Maria Iliou, Ebby Job, Nisha Perez, Yoav Timsit, Scott Wardwell, Katie McGinn, Richard Woessner, Chiara Conti. Antitumor activity of BLU-945 and BLU-701 as single agents and in combination in EGFR L858R-driven models of NSCLC [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3328.

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4

Spira, Alexander I., David R. Spigel, D. Ross Camidge, Adrianus De Langen, Tae Min Kim, Koichi Goto, Yasir Y. Elamin et al. "A phase 1/2 study of the highly selective EGFR inhibitor, BLU-701, in patients with EGFR-mutant non–small cell lung cancer (NSCLC)." Journal of Clinical Oncology 40, n. 16_suppl (1 giugno 2022): TPS9142. http://dx.doi.org/10.1200/jco.2022.40.16_suppl.tps9142.

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TPS9142 Background: Although 3rd-generation tyrosine kinase inhibitors (TKIs), such as osimertinib, are highly effective in front-line metastatic EGFR-mutated ( EGFRm) NSCLC, treatment resistance ultimately occurs, including the emergence of the on-target C797X mutation for which there are no approved TKIs. BLU-701 is an investigational, reversible, brain-penetrant, wildtype-sparing oral TKI with nanomolar potency on common activating (exon 19 deletion and L858R) and C797X resistance mutations (Tavera L et al. AACR 2022). BLU-701 has shown promising preclinical data, including antitumor central nervous system (CNS) activity that may improve patient outcomes. Additionally, combining BLU-701 with standard of care therapies may provide enhanced disease control across multiple lines of treatment, including against heterogenous tumors, in patients with EGFRm NSCLC. Methods: HARMONY (NCT05153408) is an ongoing, global phase 1/2, open-label, first-in-human study designed to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and antitumor activity of BLU-701 as a monotherapy or in combination with osimertinib or platinum-based chemotherapy in patients with EGFRm NSCLC. Key inclusion criteria include patients ≥18 years of age with metastatic EGFRm NSCLC; Eastern Cooperative Oncology Group performance status 0–1; and previous treatment with ≥1 EGFR-targeted TKI. Patients in the phase 2 monotherapy part must harbor an EGFR C797X resistance mutation (locally assessed). Key exclusion criteria are tumors harboring EGFR T790M mutations, EGFR exon 20 insertions, or other known driver alterations, including KRAS, BRAF V600E, NTRK1/2/3, HER2, ALK, ROS1, MET, or RET. Phase 1 primary endpoints are maximum tolerated dose, recommended phase 2 dose (RP2D), and safety. The phase 2 primary endpoint is overall response rate (ORR) by RECIST 1.1. Secondary endpoints include ORR (phase 1), duration of response, and PK/PD (phase 1 and phase 2); disease control rate, progression-free survival, overall survival, antitumor CNS activity, and safety (phase 2). The phase 1 dose escalation will adopt a Bayesian optimal interval design. Patients will be enrolled into 3 treatment cohorts: part 1A (n≈40–80; BLU-701), part 1B (n≈35; BLU-701 + osimertinib), and part 1C (n≈18; BLU-701 + carboplatin and pemetrexed). Patients in the phase 2 dose expansion (n≈24) will be treated at the RP2D of BLU-701 as monotherapy. Patients may receive treatment until disease progression, unacceptable toxicity, or other discontinuation criteria are met. Enrollment in this study has started, and sites will be open across North America, Europe, and Asia. Clinical trial information: NCT05153408.

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Spira, Alexander I., David R. Spigel, D. Ross Camidge, Adrianus De Langen, Tae Min Kim, Koichi Goto, Yasir Y. Elamin et al. "A phase 1/2 study of the highly selective EGFR inhibitor, BLU-701, in patients with EGFR-mutant non–small cell lung cancer (NSCLC)." Journal of Clinical Oncology 40, n. 16_suppl (1 giugno 2022): TPS9142. http://dx.doi.org/10.1200/jco.2022.40.16_suppl.tps9142.

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Abstract (sommario):

TPS9142 Background: Although 3rd-generation tyrosine kinase inhibitors (TKIs), such as osimertinib, are highly effective in front-line metastatic EGFR-mutated ( EGFRm) NSCLC, treatment resistance ultimately occurs, including the emergence of the on-target C797X mutation for which there are no approved TKIs. BLU-701 is an investigational, reversible, brain-penetrant, wildtype-sparing oral TKI with nanomolar potency on common activating (exon 19 deletion and L858R) and C797X resistance mutations (Tavera L et al. AACR 2022). BLU-701 has shown promising preclinical data, including antitumor central nervous system (CNS) activity that may improve patient outcomes. Additionally, combining BLU-701 with standard of care therapies may provide enhanced disease control across multiple lines of treatment, including against heterogenous tumors, in patients with EGFRm NSCLC. Methods: HARMONY (NCT05153408) is an ongoing, global phase 1/2, open-label, first-in-human study designed to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and antitumor activity of BLU-701 as a monotherapy or in combination with osimertinib or platinum-based chemotherapy in patients with EGFRm NSCLC. Key inclusion criteria include patients ≥18 years of age with metastatic EGFRm NSCLC; Eastern Cooperative Oncology Group performance status 0–1; and previous treatment with ≥1 EGFR-targeted TKI. Patients in the phase 2 monotherapy part must harbor an EGFR C797X resistance mutation (locally assessed). Key exclusion criteria are tumors harboring EGFR T790M mutations, EGFR exon 20 insertions, or other known driver alterations, including KRAS, BRAF V600E, NTRK1/2/3, HER2, ALK, ROS1, MET, or RET. Phase 1 primary endpoints are maximum tolerated dose, recommended phase 2 dose (RP2D), and safety. The phase 2 primary endpoint is overall response rate (ORR) by RECIST 1.1. Secondary endpoints include ORR (phase 1), duration of response, and PK/PD (phase 1 and phase 2); disease control rate, progression-free survival, overall survival, antitumor CNS activity, and safety (phase 2). The phase 1 dose escalation will adopt a Bayesian optimal interval design. Patients will be enrolled into 3 treatment cohorts: part 1A (n≈40–80; BLU-701), part 1B (n≈35; BLU-701 + osimertinib), and part 1C (n≈18; BLU-701 + carboplatin and pemetrexed). Patients in the phase 2 dose expansion (n≈24) will be treated at the RP2D of BLU-701 as monotherapy. Patients may receive treatment until disease progression, unacceptable toxicity, or other discontinuation criteria are met. Enrollment in this study has started, and sites will be open across North America, Europe, and Asia. Clinical trial information: NCT05153408.

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Agnelli, Giancarlo, Benilde Cosmi, Paolo Di Filippo, Valeria Ranucci, Franca Veschi, Mauro Longetti, Cinzia Renga et al. "A Randomised, Double-Blind, Placebo-Controlled Trial of Dermatan Sulphate for Prevention of Deep Vein Thrombosis in Hip Fracture". Thrombosis and Haemostasis 67, n. 02 (1992): 203–8. http://dx.doi.org/10.1055/s-0038-1648413.

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SummaryDermatan sulphate (MF 701) is a natural glycosaminoglycan that catalyses thrombin inhibition by heparin cofactor II. The aim of the study was to evaluate the efficacy and safety of MF 701 for prevention of deep vein thrombosis (DVT) in patients with hip fracture. A randomised, double-blind, placebo-controlled design was used to assess two dose regimens of MF 701 in two consecutive study phases. Treatment was started within 48 h from the trauma and continued for 14 days for non-operated patients or until the 10th postoperative day. Bilateral mandatory venography was used to assess the end-point. Eighty patients were included in the first phase (40 MF 701, 40 placebo). MF 701, 100 mg IM b. i. d., did not reduce incidence of DVT from that on placebo and did not induce any bleeding. In the second phase 126 patients were included, with a randomisation ratio of 2:1 (84 MF 701, 300 mg IM b.i.d., 42 placebo). Bilateral venography was obtained for 110 patients. The incidence of DVT was 64% (23/36) in the placebo group and 38% (28/74) in the MF 701 group (p = 0.01; odds ratio [OR] = 0.34, 95% confidence limits [CL] = 0.15-0.80); proximal DVTs were 42% (15/36) and 20% (15/74), respectively (p = 0.02; OR = 0.36, CL = 0.15-0.89). No significant differences were found in haemorrhagic complications (2.4% in each group), blood loss from drains, blood transfusions, haemoglobin and haematocrit values. This study is the first demonstration that dermatan sulphate is a clinically effective antithrombotic agent without bleeding effects. It also provides evidence of the biological role of heparin cofactor II.

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Bertsche, Ute, Christopher Weidenmaier, Daniel Kuehner, Soo-Jin Yang, Stefanie Baur, Stefanie Wanner, Patrice Francois, Jacques Schrenzel, Michael R. Yeaman e Arnold S. Bayer. "Correlation of Daptomycin Resistance in a ClinicalStaphylococcus aureusStrain with Increased Cell Wall Teichoic Acid Production and d-Alanylation". Antimicrobial Agents and Chemotherapy 55, n. 8 (23 maggio 2011): 3922–28. http://dx.doi.org/10.1128/aac.01226-10.

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ABSTRACTCell wall thickening is a common feature among daptomycin-resistantStaphylococcus aureusstrains. However, the mechanism(s) leading to this phenotype is unknown. We examined a number of cell wall synthesis pathway parameters in an isogenic strain set ofS. aureusbloodstream isolates obtained from a patient with recalcitrant endocarditis who failed daptomycin therapy, including the initial daptomycin-susceptible parental strain (strain 616) and two daptomycin-resistant strains (strains 701 and 703) isolated during daptomycin therapy. Transmission electron microscopy demonstrated significantly thicker cell walls in the daptomycin-resistant strains than in the daptomycin-susceptible strain, a finding which was compatible with significant differences in dry cell weight of strain 616 versus strains 701 to 703 (P< 0.05). Results of detailed analysis of cell wall muropeptide composition, the degree of peptide side chain cross-linkage, and the amount of the peptidoglycan precursor, UDP-MurNAc-pentapeptide, were similar in the daptomycin-susceptible and daptomycin-resistant isolates. In contrast, the daptomycin-resistant strains contained less O-acetylated peptidoglycan. Importantly, both daptomycin-resistant strains synthesized significantly more wall teichoic acid (WTA) than the parental strain (P< 0.001). Moreover, the proportion ofd-alanylated WTA species was substantially higher in the daptomycin-resistant strains than in the daptomycin-susceptible parental strain (P< 0.05 in comparing strain 616 versus strain 701). The latter phenotypic findings correlated with (i) enhancedtagAanddltAgene expression, respectively, and (ii) an increase in surface positive charge observed in the daptomycin-resistant versus daptomycin-susceptible isolates. Collectively, these data suggest that increases in WTA synthesis and the degree of itsd-alanylation may play a major role in the daptomycin-resistant phenotype in someS. aureusstrains.

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Decker, Todd, Daniel Fister e Rachel Jones. "The 701 Articles of American Music: A Quantitative Study of Forty Years of Scholarship". American Music 40, n. 4 (1 dicembre 2022): 424–32. http://dx.doi.org/10.5406/19452349.40.4.02.

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Downing, J. R., S. A. Shurtleff e C. J. Sherr. "Peptide antisera to human colony-stimulating factor 1 receptor detect ligand-induced conformational changes and a binding site for phosphatidylinositol 3-kinase". Molecular and Cellular Biology 11, n. 5 (maggio 1991): 2489–95. http://dx.doi.org/10.1128/mcb.11.5.2489-2495.1991.

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A peptide antiserum (anti-A) directed to the intracellular, juxtamembrane region (residues 552 to 574) of the human colony-stimulating factor 1 receptor (CSF-1R) precipitated only ligand-activated, native receptors from solution but bound to unstimulated forms after their denaturation. Two peptide antisera (anti-KI1 and -KI2), directed to residues 679 to 700 and 701 to 721, respectively, in the CSF-1R kinase insert (KI) domain and including mapped sites of ligand-induced phosphorylation at Tyr-699 and Tyr-708, bound at least 80% of the receptor molecules expressed in either CSF-1-stimulated or unstimulated cells. Immune complexes formed with anti-KI1, anti-A, or a peptide antiserum to the CSF-1R carboxyl terminus (anti-C-ter) coprecipitated CSF-1R complexed to a phosphatidylinositol 3-kinase (PtdIns 3-K) from CSF-1-stimulated cells, whereas anti-KI2 serum did not. In an in vitro assay, binding of CSF-1R to PtdIns 3-K required receptor tyrosine phosphorylation but not CSF-1R-mediated phosphorylation of the lipid kinase, and the association was specifically blocked by anti-KI2 or antibodies to phosphotyrosine. Neither anti-KI1, anti-A, nor anti-C-ter serum inhibited binding. We conclude that (i) only a minority of ligand-activated receptors form a stable complex with PtdIns 3-K in vivo, (ii) efficient binding of the lipid kinase requires receptor tyrosine phosphorylation within the CSF-1R KI domain, and (iii) a region within the KI domain defined by residues 701 to 721 at least partially overlaps the PtdIns 3-K binding site.

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Downing, J. R., S. A. Shurtleff e C. J. Sherr. "Peptide antisera to human colony-stimulating factor 1 receptor detect ligand-induced conformational changes and a binding site for phosphatidylinositol 3-kinase." Molecular and Cellular Biology 11, n. 5 (maggio 1991): 2489–95. http://dx.doi.org/10.1128/mcb.11.5.2489.

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A peptide antiserum (anti-A) directed to the intracellular, juxtamembrane region (residues 552 to 574) of the human colony-stimulating factor 1 receptor (CSF-1R) precipitated only ligand-activated, native receptors from solution but bound to unstimulated forms after their denaturation. Two peptide antisera (anti-KI1 and -KI2), directed to residues 679 to 700 and 701 to 721, respectively, in the CSF-1R kinase insert (KI) domain and including mapped sites of ligand-induced phosphorylation at Tyr-699 and Tyr-708, bound at least 80% of the receptor molecules expressed in either CSF-1-stimulated or unstimulated cells. Immune complexes formed with anti-KI1, anti-A, or a peptide antiserum to the CSF-1R carboxyl terminus (anti-C-ter) coprecipitated CSF-1R complexed to a phosphatidylinositol 3-kinase (PtdIns 3-K) from CSF-1-stimulated cells, whereas anti-KI2 serum did not. In an in vitro assay, binding of CSF-1R to PtdIns 3-K required receptor tyrosine phosphorylation but not CSF-1R-mediated phosphorylation of the lipid kinase, and the association was specifically blocked by anti-KI2 or antibodies to phosphotyrosine. Neither anti-KI1, anti-A, nor anti-C-ter serum inhibited binding. We conclude that (i) only a minority of ligand-activated receptors form a stable complex with PtdIns 3-K in vivo, (ii) efficient binding of the lipid kinase requires receptor tyrosine phosphorylation within the CSF-1R KI domain, and (iii) a region within the KI domain defined by residues 701 to 721 at least partially overlaps the PtdIns 3-K binding site.

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Goldstein, Rebecca L., Ana Goyos, Chi-Ming Li, Petra Deegen, Pamela Bogner, Alexander Sternjak, Oliver Thomas et al. "AMG 701 induces cytotoxicity of multiple myeloma cells and depletes plasma cells in cynomolgus monkeys". Blood Advances 4, n. 17 (4 settembre 2020): 4180–94. http://dx.doi.org/10.1182/bloodadvances.2020002565.

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Abstract Multiple myeloma (MM) is a hematologic malignancy that is characterized by the accumulation of abnormal plasma cells (PCs) in the bone marrow (BM). Patient outcome may be improved with BiTE (bispecific T-cell engager) molecules, which redirect T cells to lyse tumor cells. B-cell maturation antigen (BCMA) supports PC survival and is highly expressed on MM cells. A half-life extended anti-BCMA BiTE molecule (AMG 701) induced selective cytotoxicity against BCMA-expressing MM cells (average half-maximal effective concentration, 18.8 ± 14.8 pM), T-cell activation, and cytokine release in vitro. In a subcutaneous mouse xenograft model, at all doses tested, AMG 701 completely inhibited tumor formation (P < .001), as well as inhibited growth of established tumors (P ≤ .001) and extended survival in an orthotopic MM model (P ≤ .01). To evaluate AMG 701 bioactivity in cynomolgus monkeys, a PC surface phenotype and specific genes were defined to enable a quantitative digital droplet polymerase chain reaction assay (sensitivity, 0.1%). Dose-dependent pharmacokinetic and pharmacodynamic behavior was observed, with depletion of PC-specific genes reaching 93% in blood and 85% in BM. Combination with a programmed cell death protein 1 (PD-1)–blocking antibody significantly increased AMG 701 potency in vitro. A model of AMG 701 binding to BCMA and CD3 indicates that the distance between the T-cell and target cell membranes (ie, the immunological synapse) is similar to that of the major histocompatibility complex class I molecule binding to a T-cell receptor and suggests that the synapse would not be disrupted by the half-life extending Fc domain. These data support the clinical development of AMG 701.

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Cortés, Donald Arguedas. "Necrosis Pancreatic Infectious Virus does not block 701-STAT1 (α/β) tyrosine in Oncorhynchus mykiss (‎Salmoniformes: ‎Salmonidae)." Repertorio Científico 22, n. 2 (8 giugno 2020): 1–11. http://dx.doi.org/10.22458/rc.v22i2.2788.

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ABSTRACT: Necrosis Pancreatic Infectious Virus does not block 701-STAT1 (α/β) tyrosine in Oncorhynchus mykiss (‎Salmoniformes: ‎Salmonidae). Introduction: Infectious pancreatic necrosis virus (IPNV) is a pathogen important that affects predominantly salmonids. The type I interferon alpha system has a crucial role in the first line of defense against IPNV infection. IFN-I(α) activation triggers the signaling pathway JAK-STAT, binding to their receptors results in the rapid phosphorylation of STATs a critical step for the nuclear translocation to induce the interferon stimulated genes (ISGs). The relationship between infectivity level of IPNV strain and pathway signaling of IFN is yet poorly understood. Objective: our purpose was to investigate if the IFN-I(α) signaling pathway is affected by IPNV strains of different infectivity levels. Methods: We used two IPNV isolated (VR-299 and Sp) to infect RTG-2 cells. Total RNA was isolated using the commercial kit for determine to VP2 expression and ISGs using qRT-PCR. Western Immunoblotting analysis was carried out for determine the 701 STAT1(α/β) phosphorylation into infected cells. Results: Hence, a higher virulence strain is not associated with a greater blocking effect for interferon signaling. Furthermore, the activation of Y701-STAT1 (α/β) was significantly increased in serotype Sp virus infected cells compared with serotype VR-299 virus infected cells, indicating that IPNV inhibits IFN signaling pathway. Conclusions: As concluded, IPNV does not block the phosphorylation of 701-tyrosine STAT1 (α/β) stimulated by IFN-I(α), contrary to other RNA viruses.

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Wang, Yan, Ying Tian, Bin Jiang, Jeffery Weiser e Hao Shen. "Streptococcus pneumoniae specific Th17 memory immunity provides cross protection against invasive pneumococcal diseases in mice. (IRC9P.701)". Journal of Immunology 192, n. 1_Supplement (1 maggio 2014): 191.2. http://dx.doi.org/10.4049/jimmunol.192.supp.191.2.

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Abstract Pneumonia caused by Streptococcus pneumoniae (Sp) remains a leading cause of serious illness and numerous deaths in children and elderly worldwide. Current pneumococcal vaccine is effective in preventing colonization by inducing serotype-specific antibodies. However, there is an increasing prevalence of infection by serotype strains not included in the vaccine; this highlights the need for a universal vaccine that protects against all serotypes. In current study, we found that mice intranasal immunized with Sp were protected against challenge with a different serotype Sp strain and cleared bacteria from the lung by day 2 post-challenge, and exhibited less apoptosis and tissue damage in lung. Sp infection in lung resulted in a tremendous CD4+T cell expansion and activation that consisted of mostly IL-17 producing Th17 cells but also IFNγ producing Th1 cells. Adoptive transfer of T cells from Sp immunized mice provided cross protection with a dominant Th17 recall response in the lung from donor CD4+ memory T cells. Furthermore, adoptive transfer of Sp specific CD4+ memory T cells provided cross protection against pneumonia and bacteremia, which can be blocked by IL-17 neutralizing antibody and transfer Sp memory CD4+ T cells from IL-17 knockout mice. Our results suggest that Sp memory Th17 cells played a key role in providing broad protective immunity against invasive Sp infection in a serotype independent manner.

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Lucarelli, Sonia, e Roberto Menotti. "LE RELAZIONI INTERNAZIONALI NELLA TERRA DEL PRINCIPE". Italian Political Science Review/Rivista Italiana di Scienza Politica 32, n. 1 (aprile 2002): 31–82. http://dx.doi.org/10.1017/s0048840200029920.

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IntroduzioneA distanza di molti anni, è tuttora difficile contestare la famosa affermazione di Stanley Hoffmann secondo la quale le Relazioni Internazionali (Ri) sono una disciplina americana (Hoffmann 1977). Basti notare che larghissima parte degli articoli pubblicati su riviste di Ri americane o europee oggi sul mercato sono scritti da autori americani (Wæver 1998, 696-701), che la storia degli sviluppi teorici della disciplina è raccontata soprattutto in riferimento a dibattiti teorici (i Great Debates) che solo raramente si svolgono in Europa continentale (J⊘rgensen 2000), e infine che le tendenze quanto a citazioni e adozione di teorie prodotte altrove rivelano un rapporto fortemente sbilanciato tra le Ri americane e quelle europee continentali.

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Symeonides, S. N., A. Skolariki, N. R. M. Haris, Z. Boh, M. Myers, E. M. Oelmann, J. D. Bloss, R. Plummer e S. P. Blagden. "455MO NUC-7738 in patients with advanced solid tumours: Phase I results from the NuTide:701 phase I/II study". Annals of Oncology 33 (settembre 2022): S745—S746. http://dx.doi.org/10.1016/j.annonc.2022.07.584.

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Sharma, Yamini, e Harminder Singh. "Effects of Par on Plant Spacing in Relation to Yield Efficiency in Peach". Bangladesh Journal of Botany 50, n. 3 (29 settembre 2021): 701–7. http://dx.doi.org/10.3329/bjb.v50i3.55851.

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Effects of PAR in relation with plant spacing in peach cultivar ‘Shan-i-Punjab’ during the year 2013-14 and 2014-15 were evaluated. The trees were trained to 4 different training systems and each system consisted of 2 spacings viz., 5 × 3 m and 5 × 2 m. Daily PAR was recorded at morning, midday and evening and it was found that irrespective of planting distance maximum light interception was recorded at midday hours. Plants spaced at 5 × 3m received more light inside the canopy during full day which directly influenced number of fruits per tree, number of picking, fruiting density, yield efficiency, relative pattern of fruit maturity whereas, fruit yield per hectare was maximum in 5 × 2 m. Bangladesh J. Bot. 50(3): 701-707, 2021 (September)

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Ye, Ding-Wei, Jian Zhang, Hua Yang, Jin Yang, Tongsen Zheng, Hongmei Sun, Xuechao Wan, Ge Lan, Guilan Sun e Xiao Zhang. "Phase 1 dose escalation of SYS6002 (CRB-701), a next-generation nectin-4 targeting antibody drug conjugate (ADC)." Journal of Clinical Oncology 42, n. 4_suppl (1 febbraio 2024): 622. http://dx.doi.org/10.1200/jco.2024.42.4_suppl.622.

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622 Background: Linker-conjugation of an ADC is a key feature in optimizing highly active and well tolerated agents. For maximal intra-tumoral delivery, linkers need to be highly stable in the systemic circulation yet allow for eﬃcient drug release at the target site. SYS6002 (CRB-701) is a next generation Nectin-4 ADC that makes use of third-generation conjugation technology designed to overcome dose-limiting toxicities observed with the commonly approved linker-payload system involved in agents like enfortumab vedotin (EV). Non-clinically, SYS6002 demonstrates preferential internalization-mediated payload release and a longer half-life than EV. It is being explored in dose escalation on a Q3W schedule, with a view to reducing free-MMAE related toxicities and increasing clinical convenience. Methods: The dose escalation/Ph I trial SYS6002-011 spanned 6 dose groups (0.2, 0.6, 1.2, 1.8, 2.7 & 3.6 mg/kg) utilizing Bayesian Optimal Interval (BOIN) design with accelerated titration. The trial is evaluating the safety and tolerability of SYS6002 (CRB-701) to determine the Maximum Tolerated Dose (MTD) and/or the Phase II dose in patients with advanced solid tumors who have failed or were intolerant to standard treatment. Patients were enrolled based on Nectin-4 staining. Beyond determining safety and tolerability, the pharmacokinetic (PK) and preliminarily anti tumor activity of SYS6002 (CRB-701) were assessed. Results: Patients enrolled to-date range from 37-76 years, with 69% of patients being female. Disease indications included metastatic urothelial cancer (mUC), cervical cancer, triple-negative breast cancer (TNBC) and colorectal cancer (CRC), having failed a median of 4 prior therapies. All six dose cohorts have been enrolled, with 0.2-2.7 mg/kg cohorts progressing without DLTs and a maximum patient follow up of 10mo. SYS6002 (CRB-701) was well tolerated with most adverse events of Grade 1/2 in severity. Treatment related adverse events of grade 1/2 occurring >20% included corneal epithelial lesions, hematauria, hypertriglyceridemia, hyponatremia, proteinurea, anaemia and dry eye. Of note, the frequency of skin rash and peripheral neuropathy were both 0%. Across the dose escalation cohorts SYS6002 (CRB-701) demonstrated approximately dose-proportional PK and limited accumulation, a longer ADC half-life and a lower free-MMAE conc relative to EV at similar dose levels. Anti tumor responses across multiple doses were observed, with the first confirmed stable disease at 0.6mg/kg and the first confirmed partial response, whose sum of diameters of target lesions decreased by 60% at 1.2 mg/kg. Conclusions: SYS6002 (CRB-701) was well tolerated in escalation, and relative to EV demonstrates early signs of a differentiated safety and PK (longer half-life and lower free-MMAE) profile. Continued development of SYS6002 (CRB-701) as both a monotherapy and in combination are planned. Clinical trial information: SYS6002-001 .

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Croce, Roberta, Tomas Morosinotto, Janne A. Ihalainen, Agnieszka Chojnicka, Jacques Breton, Jan P. Dekker, Rienk van Grondelle e Roberto Bassi. "Origin of the 701-nm Fluorescence Emission of the Lhca2 Subunit of Higher Plant Photosystem I". Journal of Biological Chemistry 279, n. 47 (24 agosto 2004): 48543–49. http://dx.doi.org/10.1074/jbc.m408908200.

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Marshall, John L., Hedy Kindler, John Deeken, Pankaj Bhargava, Nicholas J. Vogelzang, Naiyer Rizvi, Taina Luhtala et al. "Phase I trial of orally administered CEP-701, a novel neurotrophin receptor-linked tyrosine kinase inhibitor". Investigational New Drugs 23, n. 1 (gennaio 2005): 31–37. http://dx.doi.org/10.1023/b:drug.0000047103.64335.b0.

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Prince, H. M., D. George, A. Patnick, M. Mita, P. Atadja, M. Dugan, D. Butterfoss, K. Culver, H. S. Burris e J. Beck. "701 POSTER Phase I study of oral LBH589 in advanced solid tumours and non-Hodgkin's lymphoma". European Journal of Cancer Supplements 5, n. 4 (settembre 2007): 107. http://dx.doi.org/10.1016/s1359-6349(07)70500-1.

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Chan, Emily, Daniel Mulkerin, Mace Rothenberg, Kyle D. Holen, A. Craig Lockhart, James Thomas e Jordan Berlin. "A phase I trial of CEP-701 + gemcitabine in patients with advanced adenocarcinoma of the pancreas". Investigational New Drugs 26, n. 3 (24 gennaio 2008): 241–47. http://dx.doi.org/10.1007/s10637-008-9118-3.

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Sun, Nai-Yun, Suresh Kumar, Amber Weiner, Yoo Sun Kim, Arnulfo Mendoza, Rosa Nguyen, Reona Okada et al. "Abstract 6573: Targeting DLK1, a Notch ligand, with an antibody-drug conjugate in adrenocortical carcinoma". Cancer Research 84, n. 6_Supplement (22 marzo 2024): 6573. http://dx.doi.org/10.1158/1538-7445.am2024-6573.

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Abstract Adrenocortical carcinoma (ACC) is an aggressive and rare endocrine malignancy with poor prognosis. First-line therapy (adrenolytic agent mitotane in combination with chemotherapy) for recurrent and metastatic ACC has limited efficacy and there are no approved second-line therapies. Antibody-drug conjugates (ADCs) are an emerging immunotherapeutic class in which a cytotoxic payload is directed to tumor cells via antibodies to cell surface proteins. As Notch ligands, such as DLL3, are ADC targets in neuroendocrine cancers, we screened for expression of Notch ligands in ACC. Among Notch ligands (DLL1, DLL3, DLK1, JAG1, JAG2), DLK1 (delta-like non-canonical Notch ligand 1) was the most highly expressed. Moreover, ACC had the near highest expression of DLK1 across all TCGA tumors likely because this ligand is of adrenal origin (with limited expression in other normal tissues apart from the pituitary gland and ovaries). By immunohistochemistry, we verified DLK1 to be expressed, at variable levels, in 97% of ACC tumors (n=30/31). We then tested a DLK1-directed antibody-drug conjugate (ADCT-701; DLK1-PBD), consisting of a humanized anti-DLK1 monoclonal antibody coupled to DNA damaging pyrrolobenzodiazepine (PBD) dimers (SG3199; drug-to-antibody ratio~1.8) via a cleavable linker in ACC pre-clinical models. ADCT-701 exhibited potent, nanomolar cytotoxicity in DLK1-expressing ACC cell lines and ACC patient-derived short-term organoid cultures. ADCT-701 cytotoxicity was dependent on DLK1 expression as DLK1 knockout and DLK1 overexpression abrogated and facilitated cytotoxicity, respectively. Mechanistically, ADCT-701 induced cytotoxicity through DLK1 dependent receptor-mediated internalization and DNA damage (γH2AX) as well as apoptosis (annexin V/PI positive cells, cleaved PARP, and cleaved caspase-3). In vivo studies showed that ADCT-701 was highly effective against DLK1-positive ACC xenografts and PDX models with durable anti-tumor activity. Our pre-clinical data demonstrate DLK1 as an important therapeutic target in ACC and support an upcoming phase I clinical trial of ADCT-701 in patients with neuroendocrine tumors including ACC (NCT06041516). Citation Format: Nai-Yun Sun, Suresh Kumar, Amber Weiner, Yoo Sun Kim, Arnulfo Mendoza, Rosa Nguyen, Reona Okada, Yves Pommier, Dan Martinez, Jennifer Pogoriler, Sharon Diskin, John Maris, Jaydira Del Rivero, Nitin Roper. Targeting DLK1, a Notch ligand, with an antibody-drug conjugate in adrenocortical carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6573.

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Azarine Nuratna Shafa e Endang Pandamdari. "PEMBERIAN GANTI KERUGIAN PEMBANGUNAN JALAN TOL DI KABUPATEN OGAN ILIR". Reformasi Hukum Trisakti 5, n. 1 (1 febbraio 2023): 56–63. http://dx.doi.org/10.25105/refor.v5i1.15423.

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In order to implement the supply of fair and appropriate compensation during land acquisition for the public benefit, the implementation of compensation must be founded on land acquisition principles. The question being addressed is whether or not the compensation being granted for the construction of Phase I of the Simpang Indralaya-Muara Enim Toll Road in Ogan Ilir Regency is appropriate or not in light of the principles of land acquisition, as well as whether the provisions of the cassation decision No. 701 K/Pdt/2021 regarding the compensation being granted are appropriate or not in light of those principles. Normative legal research is the research method used to address the issues in the study, and analytical descriptive, secondary data kinds are the research's nature and making judgments based on deductive reasoning. The study's findings demonstrate that the provision of compensation for the Phase I Simpang Indralaya-Muara Enim Toll Road in Ogan Ilir Regency is not in accordance with the principles of agreement and openness, and the contents of the appeal decision number 701 K/Pdt/2021 regarding the provision of compensation strengthen the decision of the Kayuagung district court number 39/Pdt.G/2020/PN Kag which is not in accordance with the principles of agreement on land acquisition.

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MORISHITA, YOSHIKAZU, SHIGERU CHIBA, EIJI TSUKUDA, TAKEO TANAKA, TATSUHIRO OGAWA, MOTOO YAMASAKI, MAYMUMI YOSHIDA, ISAO KAWAMOTO e YUZURU MATSUDA. "RES-701-1,a novel and selective endothelin type B receptor antagonist produced by Streptomyces sp. RE-701. I. Characterization of producing strain, fermentation, isolation, physico-chemical and biological properties." Journal of Antibiotics 47, n. 3 (1994): 269–75. http://dx.doi.org/10.7164/antibiotics.47.269.

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Luna-Yolba, Raquel, Justine Marmoiton, Véronique Gigo, Xavier Marechal, Emeline Boet, Ambrine Sahal, Nathalie Alet et al. "Disrupting Mitochondrial Electron Transfer Chain Complex I Decreases Immune Checkpoints in Murine and Human Acute Myeloid Leukemic Cells". Cancers 13, n. 14 (13 luglio 2021): 3499. http://dx.doi.org/10.3390/cancers13143499.

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Oxidative metabolism is crucial for leukemic stem cell (LSC) function and drug resistance in acute myeloid leukemia (AML). Mitochondrial metabolism also affects the immune system and therefore the anti-tumor response. The modulation of oxidative phosphorylation (OxPHOS) has emerged as a promising approach to improve the therapy outcome for AML patients. However, the effect of mitochondrial inhibitors on the immune compartment in the context of AML is yet to be explored. Immune checkpoints such as ectonucleotidase CD39 and programmed dead ligand 1 (PD-L1) have been reported to be expressed in AML and linked to chemo-resistance and a poor prognosis. In the present study, we first demonstrated that a novel selective electron transfer chain complex (ETC) I inhibitor, EVT-701, decreased the OxPHOS metabolism of murine and human cytarabine (AraC)-resistant leukemic cell lines. Furthermore, we showed that while AraC induced an immune response regulation by increasing CD39 expression and by reinforcing the interferon-γ/PD-L1 axis, EVT-701 reduced CD39 and PD-L1 expression in vitro in a panel of both murine and human AML cell lines, especially upon AraC treatment. Altogether, this work uncovers a non-canonical function of ETCI in controlling CD39 and PD-L1 immune checkpoints, thereby improving the anti-tumor response in AML.

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Alsaadi, Mohamad, e Ahmet Erkliğ. "Mode-I interlaminar fracture of aramid and carbon fibers reinforced epoxy matrix composites at various SiC particle contents". Materials Testing 63, n. 10 (1 ottobre 2021): 913–18. http://dx.doi.org/10.1515/mt-2021-0020.

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Abstract The Mode-I interlaminar fracture characteristics of aramid fabric andcarbon fabric reinforced epoxy composites along with the influence of SiC particle content were explored. Double cantilever beam (DCB) tests were performed in accordance with ASTM D 5528 for the purpose of examining the behavior of Mode-I delamination. The results showed that, the adhesion strength of an SiC particle within an aramid/ epoxy composite system was better than that within a carbon/epoxy composite system. The highest values of Mode-I fracture toughness of an aramid fabric/epoxy specimen and a carbon fabric/epoxy specimen were 1391 J × m-2 and 701 J × m-2 with SiC particle contents of 10 wt.-% and 5 wt.-%, respectively. The micrographs from optical and scanning electron microscopes verified the enhancements of Mode-I interlaminar fracture toughness behavior.

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Zhang, Ouqi. "Discussions on Behavior of Bolted Joints in Tension". Journal of Mechanical Design 127, n. 3 (24 novembre 2004): 506–10. http://dx.doi.org/10.1115/1.1867513.

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It is known that the behavior of real axisymmetric bolted joints in tension is much more complicated than that the conventional theory describes. Phenomenon conflicting with the theory prediction was observed in experimental and finite element analysis [Kwiatkowski, J. K., Winnicki, L. A., and Krzyspiak, A., 1986, “Stress Analysis of Bolted Tensile End Plate Connections,” Rozprawy Inzynierskie Eng. Trans., 34, pp. 113–137; Webjörn, J., 1988, “Die Moderne Schraubenverbindung,” VDI-Z, 130, pp. 76–78; Grosse, I. R., and Mitchell, L. D., 1990, “Nonlinear Axial Stiffness Characteristics of Bolted Joints,” ASME J. Mech. Des., 122, pp. 442–449; Gerbert, G., Bastedt, H., 1993, “Centrically Loaded Bolt Joints,” ASME J. Mech. Des., 115, pp. 701–705]. Recently, a new analytical model of bolted joints was presented [Zhang, O., and Poirier, J. A., 2004, “New Analytical Model for Axisymmetric Bolted Joints,” ASME J. Mech. Des., 126, pp. 721–728], based on which some discussions are further made in this note.

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O’Dwyer, Colm. "From the President: ECS United". Electrochemical Society Interface 33, n. 2 (1 giugno 2024): 7. http://dx.doi.org/10.1149/2.002242if.

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It gives me great pleasure to write to you for the first time since becoming ECS President. I assumed the role following the 245th ECS Meeting in San Francisco, CA, which I certainly hope you attended. That amazing event featured 49 symposia with 439 sessions presenting more than 2,290 talks, 3,022 abstracts, and 701 posters by authors from 68 countries. Of these, 575 were invited talks, 25 ECS award and keynote talks, and 1,240 student abstracts, 842 oral talks, and 388 posters! If you were unable to attend, complete coverage of the meeting’s highlights and key moments is forthcoming in the next edition of Interface. I would like to share with you my vision as President of this esteemed Society, and what I see are the main challenges and opportunities facing ECS in the year ahead.

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Gibbons, Patti. "Freda Matassa. Museum Collections Management: A Handbook. London: Facet Publishing, 2011. 258p. ISBN 978-1-85604-701-2. $110." RBM: A Journal of Rare Books, Manuscripts, and Cultural Heritage 13, n. 1 (1 marzo 2012): 66–69. http://dx.doi.org/10.5860/rbm.13.1.371.

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Writing from the United Kingdom, Freda Matassa prepared her textbook Museum Collections Management: A Handbook as a text for museum professionals and students in British classrooms, yet the clearly laid out information is equally relevant to a range of different types of cultural heritage institutions outside England. In the first part of her book, Matassa covers big-picture issues and defines the scope of collection management, before introducing day-to-day collection management activities in the second part of the text. Her treatment covers the full scope of collection management including registrarial responsibilities as well as physical collection care duties.As a central . . .

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Obadić, Alka. "Administrativne prepreke s kojima se suočavaju mala i srednja poduzeća na području zapošljavanja". Ekonomski pregled 69, n. 2 (17 aprile 2018): 163–87. http://dx.doi.org/10.32910/ep.69.2.4.

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Mala i srednja poduzeća imaju ključnu ulogu u europskom gospodarstvu, ali istovremeno su suočena s mnogo većim administrativnim poteškoćama u svojem poslovanju u usporedbi s velikima. Postojeća rigidnost na tržištu rada još više je otežala njihov položaj prilikom kreiranja novih radnih mjesta. Upravo stoga cilj ovog rada bio je provjeriti postoje li između različitih grupa malih i srednjih poduzeća značajne razlike u opterećenosti administrativnim poslovima na području zapošljavanja? Rezultati istraživanja pokazuju kako Hrvatska u usporedbi s drugim zemljama Europske unije (EU) još uvijek obiluje rigidnostima i ima relativno strogo tržište rada. Primarno istraživanje provedeno u Hrvatskoj obuhvatilo je konačni uzorak od 701 malog i srednjeg poduzeća. Rezultati istraživanja pokazali su da većina malih i srednjih poduzeća (54%) najvećom administrativnom preprekom na području regulacije tržišta rada smatra prečeste izmjene propisa vezane uz poslovanje. Na temelju provedenog istraživanja zaključeno je da postoje značajne razlike između različitih grupa (broj zaposlenih, pravno-organizacijski oblik i sektor) malih i srednjih poduzeća u pogledu broja ključnih administrativnih prepreka na području zapošljavanja, koje najviše percipiraju mikro poduzeća i obrtnici koji razvijaju svoju djelatnost u području tercijarnog sektora.

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Doberstein, SK, e TD Pollard. "Localization and specificity of the phospholipid and actin binding sites on the tail of Acanthamoeba myosin IC". Journal of Cell Biology 117, n. 6 (15 giugno 1992): 1241–49. http://dx.doi.org/10.1083/jcb.117.6.1241.

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We used bacterially expressed beta-galactosidase fusion proteins to localize the phospholipid binding domain of Acanthamoeba myosin IC to the region between amino acids 701 and 888 in the NH2-terminal half of the tail. Using a novel immobilized ligand lipid binding assay, we determined that myosin I can bind to several different acidic phospholipids, and that binding requires a minimum of 5 mol% acidic phospholipid in a neutral lipid background. The presence of di- and triglycerides and sterols in the lipid bilayer do not contribute to the affinity of myosin I for membranes. We confirm that the ATP-insensitive actin binding site is contained in the COOH-terminal 30 kD of the tail as previously shown for Acanthamoeba myosin IA. We conclude that the association of the myosin IC tail with acidic phospholipid head groups supplies much of the energy for binding myosin I to biological membranes, but probably not specificity for targeting myosin I isoforms to different cellular locations.

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MINAMI, Masaharu, Katsunari OOZONO e Hiroyuki ISHIGAKI. "701 Study on Metal Seal for Vacuum Use". Proceedings of Conference of Chugoku-Shikoku Branch 005.2 (2000): 201–2. http://dx.doi.org/10.1299/jsmecs.005.2.201.

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Genet, Jean-Philippe. "Anne Hudson éd., English Wyclifflte Sermons, Oxford, Clarendon Press, « Some Oxford English Texts », 1983, vol. I, IX-701 p." Annales. Histoire, Sciences Sociales 42, n. 1 (febbraio 1987): 142–43. http://dx.doi.org/10.1017/s0395264900075156.

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Garey, Kevin W., Khurshida Begum, Chenlin Hu, Weiqun Wang, Chris Lancaster, Anne J. Gonzales-Luna, Caroline Loveall, M. Jahangir Alam e Michael Silverman. "701. An Open-label Phase 2a Study of Ibezapolstat, a Unique Gram-positive Selective Spectrum (GPSS) Antibiotic, for Patients with Clostridioides difficile Infection". Open Forum Infectious Diseases 8, Supplement_1 (1 novembre 2021): S451. http://dx.doi.org/10.1093/ofid/ofab466.898.

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Abstract Background Ibezapolstat, a DNA polymerase IIIC inhibitor, currently in Phase 2 clinical development for treatment of C. difficile infection (CDI). Its unique mechanism of action targets low G+C content Gram-positive bacteria primarily Firmicutes including C. difficile. Phase I healthy volunteer results demonstrated a favorable microbiome profile suggestive of an anti-recurrence effect. The purpose of this study was to report clinical outcomes, pharmacokinetics, and microbiome changes from this Phase 2a clinical study and to continue to test for anti-recurrence microbiome properties. Methods Ibezapolstat 450 mg was given twice daily for 10 days to patients with mild-moderate CDI defined as diarrhea plus a positive C. difficile toxin test. Test of cure was evaluated at day 12 and sustained clinical cure at day 38. Stool samples were evaluated for C. difficile cultures and microbiome changes. Results Ten subjects (female: 50%) aged 50 ±15 years were enrolled. All ten subjects experienced a clinical cure by the test of cure visit at day 12 and all 10 subjects experienced a sustained clinical cure at the day 38 visit. Ibezapolstat was well tolerated with 1 adverse event (nausea) probably related to drug. Ibezapolstat systemic exposure was minimal with no plasma level reaching 1 ug/mL any time during therapy. Ibezapolstat colonic concentrations averaged 400 ug/g stool at day 3 and greater than 1,000 ug/g by day 10 of dosing. Six of the seven available baseline stool samples grew toxigenic C. difficile of various ribotypes including RT078-226 and RT014-020 (Ibezapolstat MIC range: 0.25-1 ug/mL). Follow-up cultures were no growth starting from day 3 stool cultures. Microbiome changes included overgrowth of Actinobacteria and/or Firmicute phylum species while on therapy. Conclusion Favorable clinical efficacy and safety results were observed in ibezapolstat patients with CDI including 100% clinical cure and sustained clinical cure. These results begin to validate our approach to ibezapolstat development in that the favorable microbiome effects seen in healthy Phase 1 volunteers may be predictive of beneficial patient outcomes, including low rates of recurrence. These results support the continued clinical development of ibezapolstat. Disclosures Kevin W. Garey, Pharm.D., M.S., FASHP, Summit Therapeutics (Research Grant or Support) Michael Silverman, MD, Acurx Pharmaceuticals (Consultant)

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AKIYAMA, Daisuke, Akira MATSUMOTO e Naoki SEKIYA. "701 Manufacture of a micro pressure sensor using MEMS technology". Proceedings of Yamanashi District Conference 2007 (2007): 177–78. http://dx.doi.org/10.1299/jsmeyamanashi.2007.177.

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Ramtani, S., e M. Zidi. "Damaged-Bone Adaptation Under Steady Homogeneous Stress". Journal of Biomechanical Engineering 124, n. 3 (21 maggio 2002): 322–27. http://dx.doi.org/10.1115/1.1467918.

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In this work an extension of the adaptive-elasticity theory is proposed in order to include the contribution of bone microdamage as a stimulus. Some aspects of damaged-bone tissue adaptation, brought about by a change of the daily loading history, are investigated. In particular, under the assumption of a small strain approximation and isothermal conditions, the solution of the remodeling rate equation for steady homogeneous stress is discussed and the damage effect upon the remodeling time constant is shown. The result is both theoretical and numerical, based on a recent theory of internal damaged-bone remodeling (Ramtani, S., and Zidi, M., 1999, “Damaged-Bone Remodeling Theory: Thermodynamical Approach,” Mechanics Research Communications, Vol. 26, pp. 701–708. Ramtani, S., and Zidi, M., 2001, “A Theoretical Model of the Effect of Continum Damage on a Bone Adaption Model,” Journal of Biomechanics, Vol. 34, pp. 471–479) and motivated by the works of Cowin, S. C., and Hegedus, D. M., 1976, “Bone Remodeling I: Theory and Adaptive Elasticity,” Journal of Elasticity, Vol. 6, pp. 471–479 and Hegedus, D. H., and Cowin, S. C., 1976, “Bone Remodeling II: Small Strain Adaptive Elasticity,” Journal of Elasticity, Vol. 6, pp. 337–352.

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FUJIO, Tadashi. "701 Variety of the Materials of the Mechanical Engineering No.3". Proceedings of Yamanashi District Conference 2010 (2010): 188–89. http://dx.doi.org/10.1299/jsmeyamanashi.2010.188.

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Dejong, David N., e Charles H. Whiteman. "Modeling Stock Prices without Knowing How to Induce Stationarity". Econometric Theory 12, n. 4 (ottobre 1996): 739–40. http://dx.doi.org/10.1017/s0266466600007027.

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In “Modeling Stock Prices without Knowing How to Induce Stationarity” (1994, Econometric Theory 10, 701–719), we used posterior-odds calculations to evaluate restrictions imposed by a present-value model of stock prices across the equations of a VAR representation of stock prices and dividends. The results we reported are tainted by the omission of two factors: the Jacobians induced by the mapping of our priors over VAR parameters β into the restricted sample spaces relevant under hypotheses H2-H4 (hence, tainting our calculations of p(Hi|y,X) in (22) for i = 2–4), and an integrating constant needed in calculating the unrestricted probability p(Hi|y,X) in (22). Table 1 reports our revised calculations, which differ substantively from those reported previously.

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Mendoza, E. T., J. A. Jimenez e J. Mateo. "A coastal storms intensity scale for the Catalan sea (NW Mediterranean)". Natural Hazards and Earth System Sciences 11, n. 9 (15 settembre 2011): 2453–62. http://dx.doi.org/10.5194/nhess-11-2453-2011.

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Abstract. A 5-class intensity scale for wave storms in the Catalan coast is presented. This has been done by analysing a storm data set which comprises 5 buoys during the period 1988/2008. The obtained classification improves the former proposal of Mendoza and Jiménez (2008) by better resolving spatial and temporal variability in wave storms in the area. The obtained classification reflects the increase in wave storm properties as the storm category increases. Because the selected classification parameter was the energy content which implicitly contains Hs and storm duration, this variable was used to define class limits; class I storms (24–250 m2 h), class II storms (251–500 m2 h), class III (501–700 m2 h), class IV storms (701–1200 m2 h) and class V storms (>1200 m2 h). The energy content variable was also used as proxy for induced hazards; the observed increase in energy content for higher classes reflected a significant increase in the intensity of the potential hazards. Lastly, the dominant synoptic situation for wave storms along the Catalan coast was the presence of a Mediterranean cyclone although a direct correspondence on cyclone's intensity over the western Mediterranean with wave energy content was not found.

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OKUMOTO, Yasuhisa, Masayuki BOOKA e Kazuki Ohta. "701 Study on Muscle Load at Joystick Operation of Electric Wheelchair". Proceedings of Conference of Chugoku-Shikoku Branch 2009.47 (2009): 229–30. http://dx.doi.org/10.1299/jsmecs.2009.47.229.

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Tucak Junaković, Ivana, Sanja Broz Tominac e Vesna Vašiček. "Physical and Other Activities in the Community as Support for Active and Healthy Aging". Suvremena psihologija 26, n. 1 (2023): 31–45. http://dx.doi.org/10.21465/2023-sp-261-03.

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Glavni cilj provedenog istraživanja bio je utvrditi koliko su starije osobe u Hrvatskoj fizički aktivne i zainteresirane za druge vrste rekreativnih aktivnosti u zajednici te individualne ili grupne hobije. Istraživanje je provedeno u okviru projekta SENIOR 2030, nositelja Matice umirovljenika Hrvatske. Anketni upitnik primijenjen je pomoću telefonskog intervjua na kvotnom uzorku od 701 starije osobe u dobi od 65 i više godina iz različitih dijelova Hrvatske, reprezentativnom prema spolu i regiji, prema Popisu stanovništva iz 2011. godine. Glavni je nalaz da je većina ispitanih starijih osoba (90%) bila u nekom obliku fizički aktivna tijekom posljednjih 5 godina, a kao glavne vrste aktivnosti navode šetnju i rad u vrtu. Ipak, svaka deseta ispitana osoba nije bila fizički aktivna i to prvenstveno iz zdravstvenih razloga. Interes za aktivnosti općenito je visok jer je 86% sudionika izjavilo da je zainteresirano za neku vrstu aktivnosti i hobija. Interes je najveći za šetnju i boravak u prirodi te druženje s prijateljima. Iako je svijest o važnosti različitih aktivnosti za zdravlje dosta visoka, 54% ispitanih osoba navodi da ne bi sudjelovale u besplatnim rekreacijskim grupama ili aktivnostima kada bi one bile organizirane u njihovim mjestima. Fizički aktivne osobe te one općenito zainteresirane za različite hobije i aktivnosti u zajednici češće su pripadnici mlađih dobnih podskupina. Zbog dokazanih pozitivnih učinaka fizičke aktivnosti te različitih oblika participacije u zajednici na zdravo i aktivno starenje, nužno je i dalje educirati ljude o važnosti takvih aktivnosti za preveniranje degenerativnih procesa starenja i poboljšanje kvalitete života u starijoj dobi te olakšati uključivanje starijih osoba u različite organizirane aktivnosti u zajednici.

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42

HASHINO, Satoshi, e Sho YAMADA. "701 Study on Ultrasonic Mouse for the elderly and handicapped". Proceedings of Yamanashi District Conference 2009 (2009): 180–81. http://dx.doi.org/10.1299/jsmeyamanashi.2009.180.

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Vagapova, Elmira, Maxim Kozlov, Timofey Lebedev, Karina Ivanenko, Olga Leonova, Vladimir Popenko, Pavel Spirin, Sergey Kochetkov e Vladimir Prassolov. "Selective Inhibition of HDAC Class I Sensitizes Leukemia and Neuroblastoma Cells to Anticancer Drugs". Biomedicines 9, n. 12 (6 dicembre 2021): 1846. http://dx.doi.org/10.3390/biomedicines9121846.

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The acquired resistance of neuroblastoma (NB) and leukemia cells to anticancer therapy remains the major challenge in the treatment of patients with these diseases. Although targeted therapy, such as receptor tyrosine kinase (RTK) inhibitors, has been introduced into clinical practice, its efficacy is limited to patients harboring mutant kinases. Through the analysis of transcriptomic data of 701 leukemia and NB patient samples and cell lines, we revealed that the expression of RTK, such as KIT, FLT3, AXL, FGFR3, and NTRK1, is linked with HDAC class I. Although HDAC inhibitors have antitumor activity, they also have high whole-body toxicity. We developed a novel belinostat derivative named hydrazostat, which targets HDAC class I with limited off-target effects. We compared the toxicity of these drugs within the panel of leukemia and NB cell lines. Next, we revealed that HDAC inhibition with hydrazostat reactivates NTRK1, FGFR3, ROR2, KIT, and FLT3 expression. Based on this finding, we tested the efficacy of hydrazostat in combination with RTK inhibitor imatinib. Additionally, we show the ability of hydrazostat to enhance venetoclax-induced apoptosis. Thus, we reveal the connection between HDACs and RTK and describe a useful strategy to overcome the complications of single-agent therapies.

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YAMADA, Hiroyuki, Mika IMORI, Rui KAWACHI e Nagahisa OGASAWARA. "701 Compressive Deformation Behavior of Expand Polymer Materials Having Rib Structure". Proceedings of Yamanashi District Conference 2011 (2011): 186–87. http://dx.doi.org/10.1299/jsmeyamanashi.2011.186.

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Pudełko, Judyta. "Obecność anioła w opowiadaniu o najeździe Sennacheryba na Jerozolimę w Syr 48,21". Biblical Annals 9, n. 2 (11 marzo 2019): 269–84. http://dx.doi.org/10.31743/biban.4204.

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Księgi biblijne przedstawiają wydarzenia z historii biblijnego Izraela interpretując je w kluczu teologicznym. Dotyczy to również opisu najazdu króla Asyrii Sennacheryba na Judę i Jerozolimę w 701 r. przed Chr. Konfrontacja ta znalazła nawet odzwierciedlanie w źródłach asyryjskich, które podkreślają potęgę Asyrii. Jednak przekaz biblijny uwidacznia niezwykłą interwencję Boga, który w tajemniczy sposób ocalił swój lud. Był to przekaz tak istotny, iż został przedstawiony w Starym Testamencie aż cztery razy: 2 Krl 19,35; 2 Krn 32,21; Iz 37,21 oraz Syr 48,21. Przekazy biblijne tłumaczą ocalenie Jerozolimy interwencją Boga, który działa poprzez swojego „posłańca” – anioła. Najpóźniejszy opis tego wydarzenia w Syr 48,21 wraz z kontekstem sugeruje własną interpretację tego wydarzenia. Anioł, przez którego Bóg działa w obronie swojego ludu może być zidentyfikowany w prorokiem Izajaszem, który ogłasza Boże orędzeie ocalenia, jako odpowiedź na modlitwę ludu.

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Hawkes, Jane, Éamonn Ó Carragéain e Ross Trench-Jellicoe. "John the Baptist and the Agnus Dei: Ruthwell (and Bewcastle) Revisited". Antiquaries Journal 81 (settembre 2001): 131–53. http://dx.doi.org/10.1017/s0003581500072176.

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The identity of the figure with a lamb carved on the upper stone of the Anglo-Saxon cross at Ruthwell, Dumfriesshire, was interpreted by Paul Meyvaert (in 1982 and 1992), as an apocalyptic image of the Deity instead of John the Baptist. Close inspection of the panel, however, makes it difficult to accept such an explanation. Instead, an adaptation of the early Christian images of the Baptist is proposed, and it is argued that the details of the panel are best understood in the light of the introduction of the Agnus Dei chant into the Mass by Pope Sergius I (687–701), and of biblical commentary which saw the Baptist himself as an apocalyptic figure associated with the Lamb, the paschal sacrifice, commemorated each day in the Mass.

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UÇAR, Erdem. "Altun Yaruq Sudur’un Berlin Versiyonundan Neşredilmemiş Yeni Parçalar (Tegzinç II, III, VIII ve IX’a Ait Parçalar)". Journal of Old Turkic Studies 7, n. 1 (27 gennaio 2023): 200–233. http://dx.doi.org/10.35236/jots.1235667.

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Altun Yaruq Sudur is a sūtra which belongs to Old Turkic-Mahāyāna Buddhism. The text includes the essence and philosophy of Buddhism, as well as legends and rituals of Buddha. The sūtra was translated from Chinese to Uighur by Šiŋko Šäli Tutuŋ. Old Turkic translation has a lot of manuscripts. Among these, the nearly complete manuscript is preserved in the archive of the Institute of Oriental Manuscripts of the Russian Academy of Sciences (IOM RAS) in St. Petersburg, but there are many more manuscripts and fragments in the Berlin-Brandenburg Academy of Sciences Turfan collection. In this article, some unpublished fragments are edited. Finally, I discuss Old Turkic word yaqčırtdur- which probably occurs for the first time in U 2546 (T II 701) during the Old Turkic period.

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48

Collin, Jean-Paul, Pablo Gaviña, Jean-Pierre Sauvage, André De Cian e Jean Fischer. "Synthesis and Structural Characterization of Copper(I) and Copper(II) Complexes with an Ambivalent Phenanthroline-Type Ligand". Australian Journal of Chemistry 50, n. 10 (1997): 951. http://dx.doi.org/10.1071/c97106.

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The new phenanthroline ligand 2-(p-methoxyphenyl)-9-(5′-methylpyridin-2′-yl)-1,10-phenanthroline L has been synthesized and shown to form four-coordinate CuI(L)2 (1) and six-coordinate CuII(L)2 (2) complexes. Their structures have been determined by X-ray crystallography: (1) C50H38CuN6O2.BF4, triclinic, space group P -1, a12·924(3), b 14·567(4), c 12·649(3) Å , α 105·57(2), β 107·68(2), γ 104·00(2)°; (2) C50H38CuN6O2.2PF6, monoclinic, space group P 21/c, a 17·701(5), b 19·285(5), c 14·93(4) Å, β 98·20(2)°. In solution, cyclic voltammetry measurements indicate for the copper(I) and copper(II) complexes a very fast rearrangement of the pyridine substituent with the change of the oxidation state. Surprisingly, the X-ray data show two different coordination modes for the ligand around the copper(I) ion, the 1,10-phenanthroline nucleus being either mono- or bi-dentate. In solution, since the 1H n.m.r. spectra obtained even at several temperatures display only one set of signals, it is proposed that a fast equilibrium takes place between two coordination modes of the phenanthroline

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Basinger, Nicholas T., Katherine M. Jennings, Erin L. Hestir, David W. Monks, David L. Jordan e Wesley J. Everman. "Phenology affects differentiation of crop and weed species using hyperspectral remote sensing". Weed Technology 34, n. 6 (18 agosto 2020): 897–908. http://dx.doi.org/10.1017/wet.2020.92.

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AbstractThe effect of plant phenology and canopy structure of four crops and four weed species on reflectance spectra were evaluated in 2016 and 2017 using in situ spectroscopy. Leaf-level and canopy-level reflectance were collected at multiple phenologic time points in each growing season. Reflectance values at 2 wk after planting (WAP) in both years indicated strong spectral differences between species across the visible (VIS; 350–700 nm), near-infrared (NIR; 701–1,300 nm), shortwave-infrared I (SWIR1; 1,301–1,900 nm), and shortwave-infrared II (SWIR2; 1,901–2,500 nm) regions. Results from this study indicate that plant spectral reflectance changes with plant phenology and is influenced by plant biophysical characteristics. Canopy-level differences were detected in both years across all dates except for 1 WAP in 2017. Species with similar canopy types (e.g., broadleaf prostrate, broadleaf erect, or grass/sedge) were more readily discriminated from species with different canopy types. Asynchronous phenology between species also resulted in spectral differences between species. SWIR1 and SWIR2 wavelengths are often not included in multispectral sensors but should be considered for species differentiation. Results from this research indicate that wavelengths in SWIR1 and SWIR2 in conjunction with VIS and NIR reflectance can provide differentiation across plant phenologies and, therefore should be considered for use in future sensor technologies for species differentiation.

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Herrera-Sobek, María. "Gloria Anzaldúa: Place, Race, Language, and Sexuality in the Magic Valley". PMLA/Publications of the Modern Language Association of America 121, n. 1 (gennaio 2006): 266–71. http://dx.doi.org/10.1632/003081206x129800.

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The Rio Grande Valley, also known as the Magic Valley, is situated in the southeastern tip of Texas, circumscribed on the east by the Gulf of Mexico and on the south by the Rio Grande and the Mexican borderlands. Here, among the tall, green, swaying palm trees, the short, squatty mesquite trees, and the endless rows of verdant agricultural fields, Gloria Anzaldúa grew up in the 1940s and 1950s. The Magic Valley has produced a series of distinguished scholars, poets, and novelists, including Rolando Hinojosa-Smith, the Saldivar clan (Sonia Saldivar-Hull, Ramon Saldivar, and José Saldivar), Américo Paredes, and of course Anzaldúa. Although I do not claim the same stature as the above luminaries, I too grew up in the Rio Grande Valley in the 1940s and 1950s, in a tiny town called Rio Hondo, population 701, which is but a few miles from Hargill, Texas, where Anzaldúa was born (1942) and raised. It is from this personal perspective, of one who grew up in the rich farmlands of the Magic Valley and experienced the economic and sociohistorical context of the era, that I propose to discuss Anzaldúa's Borderlands / La Frontera: The New Mestiza (1987). Specifically, I focus on the sense of place, race, language, and sexuality that characterized the area and Anzaldúa's brilliant insights in the narrative she wove and reconfigured in the pages of Borderlands.

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