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Sandrock, Kirstin, Karin Kurnik, Stephan Ehl, Christoph Bidlingmaier, Lea Nakamura, Nina Rombach, Sophie Schäfer, and Barbara Zieger. "Patients with Hermansky-Pudlak Syndrome Show Various Phenotypes Caused by Novel Mutations,." Blood 118, no. 21 (November 18, 2011): 3286. http://dx.doi.org/10.1182/blood.v118.21.3286.3286.
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Abstract Abstract 3286 Background: Hermansky-Pudlak syndrome (HPS) is a rare autosomal recessive disorder causing oculocutaneous albinism, bleeding disorder and ceroid lipofuscinosis. Platelets from HPS patients are characterized by impaired secretion of dense (δ)-bodies (CD63). Neutropenia and susceptibility to recurrent infections were exclusively observed in HPS2 patients so far. There are eight known human HPS genes (HPS1-HPS8), each leading to a particular clinical HPS subtype (HPS1-HPS8). Patients/Results: The patients show a typical HPS phenotype concerning oculocutaneous albinism and bleeding symptoms. In vivo-, in vitro bleeding time and platelet aggregometry analyses revealed impaired platelet function. We identified HPS3 in two Turkish brothers and HPS2 in a girl from the United Emirates. Both brothers with HPS3 demonstrated absence of platelet δ-granule secretion measured by flow cytometry analysis. A novel 1 bp-deletion in the HPS3 gene was identified in both brothers. In addition, one brother with HPS3 demonstrated psychomotoric retardation. MRI scan revealed cranial gliosis. Interestingly, array-CGH analysis revealed a 0.7 Mb deletion on chromosome 17 which had not been identified in the other brother and which seems to have caused the cranial gliosis. The girl with HPS2 suffered from life-threatening bleeding after tonsillectomy leading to severe asphyxia, resuscitation and finally, to mental retardation. Flow cytometry analysis demonstrated impaired platelet δ-granule secretion with a typical pattern for HPS2. CD63 expression was already increased on resting platelets, but there was only little increase after thrombin stimulation. Interestingly, only a NK-CD107 partial degranulation defect was diagnosed. So far, clinical symptoms of immunodeficiency are not obvious. Molecular genetic analyses revealed a novel 2 bp-deletion in the last exon of HPS2 leading to a frameshift and a prolonged altered protein. The location of the deletion at the very C-terminal end may prevent a complete loss of the HPS2 protein leading to a less pronounced severity of immunodeficiency as in other HPS2 patients. Conclusion: Patients with oculocutaneous albinism should be investigated for increased clinical bleeding symptoms. In case of increased bleeding symptoms, analyses of primary hemostasis should be initiated to confirm HPS. Using flow cytometry analyses HPS2 can be distinguished from the other subtypes of HPS. Molecular genetic investigations should be performed to differentiate the various subtypes of HPS which is important for therapy and prognosis. The HPS3 patient`s mental retardation seemed to be caused by an additional deletion. The identification of the molecular genetic defect helps to understand the patients` various clinical phenotypes. Disclosures: Zieger: Novo Nordisk: Research Funding.
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Rosenblum, Sara, and Liat Gafni-Lachter. "Handwriting Proficiency Screening Questionnaire for Children (HPSQ–C): Development, Reliability, and Validity." American Journal of Occupational Therapy 69, no. 3 (April 8, 2015): 6903220030p1. http://dx.doi.org/10.5014/ajot.2015.014761.
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Ciciotte, Steven L., Babette Gwynn, Kengo Moriyama, Marjan Huizing, William A. Gahl, Juan S. Bonifacino, and Luanne L. Peters. "Cappuccino, a mouse model of Hermansky-Pudlak syndrome, encodes a novel protein that is part of the pallidin-muted complex (BLOC-1)." Blood 101, no. 11 (June 1, 2003): 4402–7. http://dx.doi.org/10.1182/blood-2003-01-0020.
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Abstract Hermansky-Pudlak syndrome (HPS) is a disorder of organelle biogenesis affecting 3 related organelles—melanosomes, platelet dense bodies, and lysosomes. Four genes causing HPS in humans (HPS1-HPS4) are known, and at least 15 nonallelic mutations cause HPS in the mouse. Where their functions are known, the HPS-associated proteins are involved in some aspect of intracellular vesicular trafficking, that is, protein sorting and vesicle docking and fusion. Biochemical and genetic evidence indicates that the HPS-associated genes encode components of at least 3 distinct protein complexes: the adaptor complex AP-3; the HPS1/HPS4 complex; and BLOC-1 (biogenesis of lysosome-related organelles complex-1), consisting of the proteins encoded at 2 mouse HPS loci, pallid (pa) and muted (mu), and at least 3 other unidentified proteins. Here, we report the cloning of the mouse HPS mutation cappuccino (cno). We show that the wild-type cno gene encodes a novel, ubiquitously expressed cytoplasmic protein that coassembles with pallidin and the muted protein in the BLOC-1 complex. Further, we identify a frameshift mutation in mutant cno/cno mice. The C-terminal 81 amino acids are replaced with 72 different amino acids in the mutant CNO protein, and its ability to interact in BLOC-1 is abolished. We performed mutation screening of patients with HPS and failed to identify any CNO defects. Notably, although defects in components of the HPS1/HPS4 and the AP-3 complexes are associated with HPS in humans, no defects in the known components of BLOC-1 have been identified in 142 patients with HPS screened to date, suggesting that BLOC-1 function may be critical in humans.
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Wang, Zhao-Xia, Yi-Hui Liu, Yi Dong, Ya-Li Li, Tie-Yu Tang, and Liang-Liang Fan. "Whole-Exome Sequencing Identified a Novel Homozygous Frameshift Mutation of HPS3 in a Consanguineous Family with Hermansky-Pudlak Syndrome." BioMed Research International 2021 (September 24, 2021): 1–7. http://dx.doi.org/10.1155/2021/4535349.
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Hermansky-Pudlak syndrome (HPS) is a rare genetic disorder with an autosomal recessive inherited pattern. It is mainly characterized by deficiencies in lysosome-related organelles, such as melanosomes and platelet-dense granules, and leads to albinism, visual impairment, nystagmus, and bleeding diathesis. A small number of patients will present with granulomatous colitis or fatal pulmonary fibrosis. At present, mutations in ten known genetic loci (HPS1–11) have been identified to be the genetic cause of HPS. In this study, we enrolled a consanguineous family who presented with typical HPS phenotypes, such as albinism, visual impairment, nystagmus, and bleeding diathesis. Whole-exome sequencing and Sanger sequencing were applied to explore the genetic lesions of the patient. A novel homozygous frameshift mutation (NM_032383.5, c.1231dupG/p.Aps411GlyfsTer32) of HPS3 was identified and cosegregated in the family members. Furthermore, real-time PCR confirmed that the mutation decreased the expression of HPS3, which has been identified as the disease-causing gene of HPS type 3. According to ACMG guidelines, the novel mutation, resulting in a premature stop codon at amino acid 442, is a pathogenic variant. In summary, we identified a novel mutation (NM_032383.5, c.1231dupG/p.Aps411GlyfsTer32) of HPS3 in a family with HPS. Our study expanded the variant spectrum of the HPS3 gene and contributed to genetic counseling and prenatal genetic diagnosis of the family.
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Bastida, Jose Maria, Sara Morais, Veronica Palma-Barqueros, Rocio Benito, Nuria Bermejo, Mutlu Karkucak, Maria Trapero-Marugan, et al. "Ten New Cases of Hermansky-Pudlak Syndrome in the Iberian Peninsula: Identification of Novel Genetic Variants in HPS3, HPS4, HPS6 and DTNBP1 Associated with Significant Clinical Complications." Blood 132, Supplement 1 (November 29, 2018): 1147. http://dx.doi.org/10.1182/blood-2018-99-112968.
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Abstract Introduction Hermansky-Pudlak syndrome (HPS) is an inherited platelet disorder characterized by bleeding diathesis, oculocutaneous albinism (OCA) and, sometimes, serious clinical complicationssuch as immunodeficiency, granulomatous colitis, and/or pulmonary fibrosis. Heterogeneous clinical symptoms and a large number of possible genetic culprits (10 HPS genes, >120 exons) complicate an unequivocal diagnosis of HPS. This study aimed to assess the clinical and platelet phenotype in ten patients with suspected HPS, and to identify the underlying genetic defects. Methods Ten patients from six families (F1 and F3 were Spanish, F2 was Turkish and F4, F5 and F6 were Portuguese) presenting with OCA (confirmed by skin biopsy) and bleeding diathesiswere included. Bleeding was evaluated by ISTH-BAT score. Phenotyping included, in patients with fresh blood samples available, platelet aggregation and ATP release, flow cytometry (FC), 14C-serotonin uptake and whole-mount electron microscopy (EM). Patients DNA was analyzed using two different targeted panels by high throughput sequencing (HTS). Sequence variants classification was performed according to ACMP recommendations. Results Patient characteristics are summarized in table 1. In F1, that had no history of consanguinity, there were two affected sisters. Patients 1 (P1) had several episodes of gastrointestinal bleeding (GI), which was attributed to granulomatous colitis. F2 is a consanguineous Turkish family, were P3 had severe rectal bleeding, requiring colectomy combined with ileostomy surgery. Pathological examination of the colon was reported as non-granulomatous colitis. Her older sister (P4) had exhibited dyspnea and shortness according to diffuse bilateral pulmonary fibrosis (BPF) diagnosis. In F3, P5 had been referred with acute GI bleeding secondary to angiodysplasia. In the non-consanguineous F4, HPS was first confirmed in P6, who showed blonde hair, nystagmus and low visual acuity; his older sister was diagnosed with HPS later, at the age of 56 years old (P7), because her OCA was masked using dark brown hair-coloring products. In P8, born from a non-consanguineous family (F5), HPS was suspected early in life, four months of age, upon recognition of OCA, nystagmus, deep visual deficiency and exotropia with compensatory torticollis. Lastly, in the consanguineous Portuguese family (F6), the two affected children (P9 and P10) had also showed a horizontal and torsional nystagmus and reduced visual activity. P10 also suffered from epilepsy and mild development delay. In phenotyping studies, the Spanish patients (P1, P2, P5) showed impaired platelet aggregation to mild agonists and reduced platelet dense granules by FC and EM. No platelet studies could be performed in F2. In Portuguese patients (F4, F5 and F6), the ATP release studies demonstrated a dense granule deficiency (Table 1). Molecular diagnosis was achieved, as a first-line approach, by means of HTS gene panels that revealed: a) F1 (P1 & P2) a homozygous deletion c.2054delC (p.P685L fs17*) in exon 13 of the HPS4, which had been previously reported in one Asian patient who showed BPF; b) F2 (P3 & P4): anovel missense homozygousvariant c.272T>C (p.L91P) in exon 4 of the HPS4. Remarkably, the phenotype of the two Turkish sisters was different, with one having had severe GI bleeding requiring colectomy, and the other had developed BPF. C) F3 (P5): a novel heterozygous variant c.2464C>T (p.R822*) in exon 13 of the HPS3 was detected; d) F4 (P6 & P7) and F5 (P8): here a nonsense variant c.307C>T (p.Q103*) was identified in exon 5 of the DTNBP1, which was previously reported in a Portuguese patient. E) F6 (P9 & P10): these patients carried a novel five base pair duplication in the single exon of HPS6, c.60_64dup (p.L22R fs*33). Conclusions This study reports 10 new HPS patients, which demonstrates the heterogeneous nature of this syndrome and the complex phenotype-genotype correlations. The novel HTStechnology has facilitated the molecular diagnosis of HPS in these patients. Among the underlying molecular pathology, we identified a novel p.L91P variant in HPS4 that is associated with a severe clinical phenotype. Funding Gerencia Regional de Salud (GRS 1647/A/17), Fundación Séneca (19873/GERM/15), Instituto de Salud Carlos III (ISCIII, PI17/01966, PI17/01311,CB15/00055), Grupo de trabajo SETH and Instituto de Investigación Biomédica de Salamanca (IBSAL, IBY17/00006). Table Table. Disclosures No relevant conflicts of interest to declare.
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Moka, Nagabhishek, Dong Chen, Chen Han, Kevin J. O'Brien, Sara Haroutinian, Laryssa Huryn, Wendy Introne, et al. "Novel Hermanksky-Pudlak Syndrome Type 6 Missense Variant Associated with Subclinical Oculocutaneous Albinism and Mild Bleeding." Blood 132, Supplement 1 (November 29, 2018): 1153. http://dx.doi.org/10.1182/blood-2018-99-109829.
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Abstract Qualitative disorders of platelets are often missed at clinical evaluation. Hermansky-Pudlak (HPS) syndrome is a rare genetic metabolic disorder with subtype specific clinical associations most prevalent in Puerto Rico with strong link to consanguinity. HPS is usually associated with albinism, visual impairment and a qualitative platelet dysfunction due to absence of dense granules. Ceroid accumulation can be associated with inflammatory bowel disease, pulmonary fibrosis and kidney disease. Ten variants have been described with types 1, 2 and 4 associated with severe disease whilst type 3, 5 and 6 is associated with mild disease. Little is known about types 7, 8, 9 and 10. A Caucasian adult female presented with a history of intermittent episodes of severe bleeding. She carried the diagnosis of probable von Willebrand's disease at presentation. This particular patient did not respond to cryoprecipitate infusion but bleeding stopped secondary to infusion of normal platelets, a clue to a platelet storage disorder. Hence she was re-investigated for a bleeding disorder and initial coagulation testing identified abnormal platelet aggregation and amplitude pattern to epinephrine. She was subsequently evaluated with platelet transmission electron microscopy and platelet flow cytometry at the Mayo Clinic Hematopathology. Platelet TEM showed complete absence of dense granules and a normal flow cytometry. HPS was suspected and initial genetic studies identified a variant genetic abnormality. Further studies were done at the NIH. Classical clinical features of HPS like nystagmus, and ocular albinism was not identified at initial neurological and ophthalmologic examination. But more detailed evaluation revealed subclinical oculocutaneous albinism. Genome wide SNP analysis showed regions of homozygosity including HPS 1 and HPS 6; deletions were not identified in these genes. Full length HPS1 transcript was amplified by PCR of genomic DNA. Targeted next-generation sequencing identified a novel homozygous missense variant [c.383T>C (p.V128A)] in HPS6. Reduced HPS6 mRNA levels were found in the patient's skin fibroblasts compared to cells from patients with HPS-1 and normal control cells. HPS6 protein expression in the patient's cells was also low and approximately 60% lower than that of normal cells. HPS is a rare platelet storage disorder that can often be missed. Platelet aggregation tests need to be followed up by platelet TEM and genetic testing to definitively diagnose this condition. Further work up has defined a new missense variant by SNP analysis, next generation sequencing and fibroblast culture. It is important to identify the subtype of HPS, because certain subtypes of HPS (HPS 1, 2 and 4) have clinical manifestations like progressive pulmonary fibrosis. Identification of the platelet storage disorder also helps in management of the bleeding diathesis. Disclosures No relevant conflicts of interest to declare.
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Mayer, Jutta, Thomas Huhn, Michael Habeck, Karin Denger, Klaus Hollemeyer, and Alasdair M. Cook. "2,3-Dihydroxypropane-1-sulfonate degraded by Cupriavidus pinatubonensis JMP134: purification of dihydroxypropanesulfonate 3-dehydrogenase." Microbiology 156, no. 5 (May 1, 2010): 1556–64. http://dx.doi.org/10.1099/mic.0.037580-0.
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2,3-Dihydroxypropane-1-sulfonate (DHPS) is a widespread intermediate in plant and algal transformations of sulfoquinovose (SQ) from the plant sulfolipid sulfoquinovosyl diacylglycerol. Further, DHPS is recovered quantitatively during bacterial degradation of SQ by Klebsiella sp. strain ABR11. DHPS is also a putative precursor of sulfolactate in e.g. Ruegeria pomeroyi DSS-3. A bioinformatic approach indicated that some 28 organisms with sequenced genomes might degrade DHPS inducibly via sulfolactate, with three different desulfonative enzymes involved in its degradation in different organisms. The hypothesis for Cupriavidus pinatubonensis JMP134 (formerly Ralstonia eutropha) involved a seven-gene cluster (Reut_C6093–C6087) comprising a LacI-type transcriptional regulator, HpsR, a major facilitator superfamily uptake system, HpsU, three NAD(P)+-coupled DHPS dehydrogenases, HpsNOP, and (R)-sulfolactate sulfo-lyase (SuyAB) [EC 4.4.1.24]. HpsOP effected a DHPS-racemase activity, and HpsN oxidized (R)-DHPS to (R)-sulfolactate. The hypothesis for Roseovarius nubinhibens ISM was similar, but involved a tripartite ATP-independent transport system for DHPS, HpsKLM, and two different desulfonative enzymes, (S)-cysteate sulfo-lyase [EC 4.4.1.25] and sulfoacetaldehyde acetyltransferase (Xsc) [EC 2.3.3.15]. Representative organisms were found to grow with DHPS and release sulfate. C. pinatubonensis JMP134 was found to express at least one NAD(P)+-coupled DHPS dehydrogenase inducibly, and three different peaks of activity were separated by anion-exchange chromatography. Protein bands (SDS-PAGE) were subjected to peptide-mass fingerprinting, which identified the corresponding genes (hpsNOP). Purified HpsN converted DHPS to sulfolactate. Reverse-transcription PCR confirmed that hpsNOUP were transcribed inducibly in strain JMP134, and that hpsKLM and hpsNOP were transcribed in strain ISM. DHPS degradation is widespread and diverse, implying that DHPS is common in marine and terrestrial environments.
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Gu, Cheng Long, Ai Juan Gu, Guo Zheng Liang, and Li Yuan. "Modified Phenolic Resins Based on Hyperbranched Polysiloxane with Improved Thermal Stability and Flame Retardancy." Advanced Materials Research 430-432 (January 2012): 264–72. http://dx.doi.org/10.4028/www.scientific.net/amr.430-432.264.
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A novel modified phenolic (PF) resin with high performance was developed, which was prepared by hybranched phenyl polysiloxane (HPSi) synthesized by our research group with PF resin. The effect of the incorporation of HPSi into PF resin on typical performance of HPSi/PF resins were systemically discussed. Results show that the incorporation of HPSi can not only effectively promote the thermal properties, but also improve the flame retardancy. For example, in the case of the modified PF resin with 10wt% HPSi, initial decompose temperature (Tdi) of HPSi is at about 405°C, which is 18°C more than that of neat PF resin at the heating rate of 10°C/min; its char yield at 800°C increases from 68.9% to 76.2% at the heating rate of 10°C/min. What’s more, HPSi10/PF resin has the maximum LOI value, which is 14.6% more than that of neat PF resin. The novel modified PF resin with improving integrated properties exhibits great potential to be used for many cutting-edges fields.
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Tse, William T., Livana Soetedjo, Timothy Lax, Lei Wang, and Patrick J. Kennedy. "Obligatory Asymmetric Cell Division Regulates Self-Renewal In Hematopoietic Progenitor/Stem Cells." Blood 116, no. 21 (November 19, 2010): 571. http://dx.doi.org/10.1182/blood.v116.21.571.571.
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Abstract Abstract 571 Asymmetric cell division, a proposed mechanism by which hematopoietic progenitor/stem cells (HPSC) maintain a balance between self-renewal and differentiation, has rarely been observed. Here we report the surprising finding that cultured mouse primary HPSC routinely generate pairs of daughter cells with 2 distinct phenotypes after a single round of cell division. Mouse bone marrow cells were cultured on chamber slides in the presence of stem cell factor (SCF). BrdU was added overnight to label dividing cells, and the cells were examined by immunofluorescence microscopy on day 2–4 of culture. In each BrdU+c-Kit+ divided cell doublet, c-Kit was invariably expressed in only 1 of the 2 daughter cells. In contrast, the other daughter cell was negative for c-Kit but positive for the asymmetric cell fate determinant Numb and mature myeloid markers Mac1, Gr1, M-CSFR and F4/80. Similarly, in each BrdU+Sca1+ cell doublet, 1 daughter cell was positive for the stem cell markers Sca1, c-Kit, CD150 and CD201, whereas the other cell was negative for these markers but positive for Numb and the mature myeloid markers. Analysis of 400 such doublets showed that the probability of HPSC undergoing asymmetric division was 99.5% (95% confidence interval 98–100%), indicating that asymmetric division in HPSC is in fact not rare but obligatory. In other model systems, it has been shown that activation of the atypical protein kinase C (aPKC)-Par6-Par3 cell polarity complex and realignment of the microtubule cytoskeleton precede asymmetric cell division. We asked whether similar steps are involved in the asymmetric division of HPSC. We found that c-Kit receptors, upon stimulation by SCF, rapidly capped at an apical pole next to the microtubule-organizing center, followed by redistribution to the same pole of the aPKC-Par6-Par3 complex and microtubule-stabilizing proteins APC, β-catenin, EB1 and IQGAP1. Strikingly, after cell division, the aPKC-Par6-Par3 complex and other polarity markers all partitioned only into the c-Kit+/Sca1+ daughter cell and not the mature daughter cell. The acetylated and detyrosinated forms of stabilized microtubules were also present only in the c-Kit+/Sca1+ cell, as were the Aurora A and Polo-like kinases, 2 mitotic kinases associated with asymmetric cell division. To understand how c-Kit activation triggers downstream polarization events, we studied the role of lipid rafts, cholesterol-enriched microdomains in the cell membrane that serve as organization centers of signaling complexes. These are enriched in phosphatidylinositol 4,5-bisphosphate and annexin 2, putative attachment sites for the aPKC-Par6-Par3 complex. We found that SCF stimulation led to coalescence of lipid raft components at the site of the c-Kit cap, and treatment with a wide range of inhibitors that blocked lipid raft formation abrogated polarization of the aPKC-Par6-Par3 complex and division of the c-Kit+/Sca1+ cells. Because obligatory asymmetric division in cultured HPSC would prevent a net increase in their number, we sought a way to bypass its mechanism. We tested whether inhibition of protein phosphatase 2A (PP2A), a physiological antagonist of aPKC, would enhance aPKC activity and promote self-renewal of HPSC. Treatment of cultured HPSC with okadaic acid or calyculin, 2 well-characterized PP2A inhibitors, increased the percent of c-Kit+/Sca1+ cells undergoing symmetric division from 0% to 23.3% (p<0.001). In addition, small colonies comprised of symmetrically dividing cells uniformly positive for Sca1, c-Kit, CD150 and CD201 were noted in the culture. To functionally characterize the effect of PP2A inhibition, mouse bone marrow cells were cultured in the absence or presence of PP2A inhibitors and transplanted into irradiated congenic mice in a competitive repopulation assay. At 4–8 weeks post-transplant, the donor engraftment rate increased from ∼1 in mice transplanted with untreated cells to >30% in mice transplanted with PP2A inhibitor-treated cells. This dramatic increase indicates that PP2A inhibition can effectively perturb the mechanism of asymmetric cell division and promote the self-renewal of HPSC. In summary, our data showed that obligatory asymmetric cell division works to maintain a strict balance between self-renewal and differentiation in HPSC and pharmacological manipulation of the cell polarity machinery could potentially be used to expand HPSC for clinical use. Disclosures: No relevant conflicts of interest to declare.
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Ostrovsky, Olga, Polina Baryakh, Yan Morgulis, Margarita Mayorov, Nira Bloom, Katia Beider, Avichai Shimoni, Israel Vlodavsky, and Arnon Nagler. "The HPSE Gene Insulator—A Novel Regulatory Element That Affects Heparanase Expression, Stem Cell Mobilization, and the Risk of Acute Graft versus Host Disease." Cells 10, no. 10 (September 23, 2021): 2523. http://dx.doi.org/10.3390/cells10102523.
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The HPSE gene encodes heparanase (HPSE), a key player in cancer, inflammation, and autoimmunity. We have previously identified a strong HPSE gene enhancer involved in self-regulation of heparanase by negative feedback exerted in a functional rs4693608 single-nucleotide polymorphism (SNP) dependent manner. In the present study, we analyzed the HPSE gene insulator region, located in intron 9 and containing rs4426765, rs28649799, and rs4364254 SNPs. Our results indicate that this region exhibits HPSE regulatory activity. SNP substitutions lead to modulation of a unique DNA-protein complex that affects insulator activity. Analysis of interactions between enhancer and insulator SNPs revealed that rs4693608 has a major effect on HPSE expression and the risk of post-transplantation acute graft versus host disease (GVHD). The C alleles of insulator SNPs rs4364254 and rs4426765 modify the activity of the HPSE enhancer, resulting in altered HPSE expression and increased risk of acute GVHD. Moreover, rs4426765 correlated with HPSE expression in activated mononuclear cells, as well as with CD3 levels and lymphocyte counts following G-CSF mobilization. rs4363084 and rs28649799 were found to be associated with CD34+ levels. Our study provides new insight into the mechanism of HPSE gene regulation and its impact on normal and pathological processes in the hematopoietic system.
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Kiener, Sarah, Alexandra Kehl, Robert Loechel, Ines Langbein-Detsch, Elisabeth Müller, Danika Bannasch, Vidhya Jagannathan, and Tosso Leeb. "Novel Brown Coat Color (Cocoa) in French Bulldogs Results from a Nonsense Variant in HPS3." Genes 11, no. 6 (June 9, 2020): 636. http://dx.doi.org/10.3390/genes11060636.
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Brown or chocolate coat color in many mammalian species is frequently due to variants at the B locus or TYRP1 gene. In dogs, five different TYRP1 loss-of-function alleles have been described, which explain the vast majority of dogs with brown coat color. Recently, breeders and genetic testing laboratories identified brown French Bulldogs that did not carry any of the known mutant TYRP1 alleles. We sequenced the genome of a TYRP1+/+ brown French Bulldog and compared the data to 655 other canine genomes. A search for private variants revealed a nonsense variant in HPS3, c.2420G>A or p.(Trp807*). The brown dog was homozygous for the mutant allele at this variant. The HPS3 gene encodes a protein required for the correct biogenesis of lysosome-related organelles, including melanosomes. Variants in the human HPS3 gene cause Hermansky–Pudlak syndrome 3, which involves a mild form of oculocutaneous albinism and prolonged bleeding time. A variant in the murine Hps3 gene causes brown coat color in the cocoa mouse mutant. We genotyped a cohort of 373 French Bulldogs and found a strong association of the homozygous mutant HPS3 genotype with the brown coat color. The genotype–phenotype association and the comprehensive knowledge on HPS3 function from other species strongly suggests that HPS3:c.2420G>A is the causative variant for the observed brown coat color in French Bulldogs. In order to clearly distinguish HPS3-related from the TYRP1-related brown coat color, and in line with the murine nomenclature, we propose to designate this dog phenotype as “cocoa”, and the mutant allele as HPS3co.
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Laukner, Anna, Laura Truchet, Georgi Manukjan, Harald Schulze, Ines Langbein-Detsch, Elisabeth Mueller, Tosso Leeb, and Alexandra Kehl. "Effects of Cocoa Genotypes on Coat Color, Platelets and Coagulation Parameters in French Bulldogs." Genes 12, no. 7 (July 19, 2021): 1092. http://dx.doi.org/10.3390/genes12071092.
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A nonsense variant in HPS3, c.2420G>A or p.Trp807*, was recently discovered as the cause for a brown coat color termed cocoa in French Bulldogs. Here, we studied the genotype–phenotype correlation regarding coat color in HPS3 mutant dogs that carried various combinations of mutant alleles at other coat color genes. Different combinations of HPS3, MLPH and TYRP1 genotypes resulted in subtly different shades of brown coat colors. As HPS3 variants in humans cause the Hermansky–Pudlak syndrome type 3, which in addition to oculocutaneous albinism is characterized by a storage pool deficiency leading to bleeding tendency, we also investigated the phenotypic consequences of the HPS3 variant in French Bulldogs on hematological parameters. HPS3 mutant dogs had a significantly lowered platelet dense granules abundance. However, no increased bleeding tendencies in daily routine were reported by dog owners. We therefore conclude that in dogs, the phenotypic effect of the HPS3 variant is largely restricted to pigmentation. While an effect on platelet morphology is evident, we did not obtain any indications for major health problems associated with the cocoa coat color in French Bulldogs. Further studies will be necessary to definitely rule out very subtle effects on visual acuity or a clinically relevant bleeding disorder.
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Armstrong, Alison J., Hal Hansen, and Roger Gauthier. "Development of a Model for Evaluating High Performance Sport Centers in Canada." Journal of Sport Management 5, no. 2 (July 1991): 153–76. http://dx.doi.org/10.1123/jsm.5.2.153.
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A theory based model was developed for the evaluation of high performance sport centers (HPSCs) in Canada. The model was developed according to de Groot’s (1969) four-phase interpretative-theoretical methodology. The phases of exploration, analysis, classification, and explanation guided the collection of current program evaluation literature and information on the nature of the HPSC program and its past evaluation practices. Appropriate evaluation models from the literature were assessed with respect to the HPSC program’s nature, and a single theoretical-integrative model was developed with corresponding guidelines for HPSC evaluation. The model is described with reference to (a) the role of evaluation at each stage of the HPSC life cycle, (b) the evaluators and decision makers, (c) utilization of the evaluation information, and (d) a general format for guiding the responsible national sport organizations through the important process of evaluation.
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Blomqvist, Stefan, Shahnaz Amiri, Patrik Rohdin, and Louise Ödlund. "Analyzing the Performance and Control of a Hydronic Pavement System in a District Heating Network." Energies 12, no. 11 (May 30, 2019): 2078. http://dx.doi.org/10.3390/en12112078.
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A hydronic pavement system (HPS) is an alternative method to clear snow and ice, which avoids the use of salt, sand, and fossil fuel in conventional snow clearance, and minimizes the risk of accidents. The aim is to analyze the performance of different control strategies for a 35,000 m2 HPS utilizing heat from a district heating and cooling (DHC) system. The key performance indicators are (1) energy performance of the HPS, and (2) primary energy use, (3) electricity production and (4) greenhouse gas (GHG) emissions from the DHC system. The methodology uses a simulation model of the HPS and an optimization model of the DHC system. Three operational strategies are analyzed: A reference scenario based on the current control strategy, and scenarios where the HPS is shut down at temperatures below −10 °C and −5 °C. The study shows that the DHC return temperature is suitable for use. By operational strategies, use during peak demand in the DHC system can be avoided, resulting in reduced use of fossil fuel. Moreover, the energy use of the HPS could be reduced by 10% and the local GHG emissions by 25%. The study emphasizes that the HPS may have positive effects on global GHG emissions, as it enables electricity production from renewable resources.
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Marais, Evelyn, Gerard Jacobs, and Deirdre M. Holcroft. "Postharvest Irradiation Enhances Anthocyanin Synthesis in Apples But Not in Pears." HortScience 36, no. 4 (July 2001): 738–40. http://dx.doi.org/10.21273/hortsci.36.4.738.
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`Cripps' Pink' apples (Malus ×domestica Borkh.) subjected to 72 hours of postharvest irradiation developed a better red blush with high pressure sodium (HPS) (hue angle 56.5°) than with UV-B plus incandescent (UVB+I) lamps (hue angle 70.7°). Only HPS lamps were used in subsequent experiments. The increase in red color (hue angle decrease of 14.9°) in `Braeburn' apples held at -0.5 °C for 8 weeks prior to treatment was smaller than in fruit stored for 4 weeks (hue angle decrease of 23°). No increase in color or anthocyanin concentration was observed in `Forelle' pears (Pyrus communis L.) that were similarly treated. `Forelle' pears were harvested with or without attached stem and leaves to determine whether precursor availability restricted postharvest color development. Fruit were irradiated with HPS at 20/20 °C and 20/6 °C (day/night) for 168 hours. The absence of leaves hastened the decrease in hue angle, but this was due to yellowing and not to development of red blush. Since `Forelle' pears showed no response to light after harvest, two fully red cultivars, Bon Rouge and Red Anjou, were irradiated with HPS lamps for 72 hours. Hue angle was not affected by irradiation. Thus, anthocyanin synthesis was stimulated by postharvest irradiation with HPS lights in apples, but not in pears.
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Zhang, Ying, Bolong Huang, Gan Luo, Tu Sun, Yonggang Feng, Yucheng Wang, Yanhang Ma, et al. "Atomically deviated Pd-Te nanoplates boost methanol-tolerant fuel cells." Science Advances 6, no. 31 (July 2020): eaba9731. http://dx.doi.org/10.1126/sciadv.aba9731.
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The methanol crossover effect in direct methanol fuel cells (DMFCs) can severely reduce cathodic oxygen reduction reaction (ORR) performance and fuel efficiency. As a result, developing efficient catalysts with simultaneously high ORR activity and excellent antipoisoning methanol capability remains challenging. Here, we report a class of Pd-Te hexagonal nanoplates (HPs) with a Pd20Te7 phase that simultaneously overcome the activity and methanol-tolerant issues in alkaline DMFC. Because of the specific arrangement of Pd atoms deviated from typical hexagonal close-packing, Pd-Te HPs/C displays extraordinary methanol tolerance with high ORR performance compared with commercial Pt/C. DFT calculations reveal that the high performance of Pd-Te HPs can be attributed to the breakthrough of the linear relationship between OOH* and OH* adsorption, which leaves sufficient room to improve the ORR activity but suppresses the methanol oxidation reaction. The concurrent high ORR activity and excellent methanol tolerance endow Pd-Te HPs as practical electrocatalysts for DMFC and beyond.
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Nikoshvili, Linda, Elena S. Bakhvalova, Alexey V. Bykov, Alexander I. Sidorov, Alexander L. Vasiliev, Valentina G. Matveeva, Mikhail G. Sulman, Valentin N. Sapunov, and Lioubov Kiwi-Minsker. "Study of Deactivation in Suzuki Reaction of Polymer-Stabilized Pd Nanocatalysts." Processes 8, no. 12 (December 15, 2020): 1653. http://dx.doi.org/10.3390/pr8121653.
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This work is addressed to the phenomenon of catalyst deactivation taking place during the repeated uses in the reaction of Suzuki-Miyaura (S-M) cross-coupling, which is widely applied in industry for C-C bond formation. Ligandless catalysts based on Pd(0) NPs supported on hyper-cross-linked polystyrene (HPS) of two types (non-functionalized and bearing tertiary amino groups) were studied in a model S-M reaction between 4-bromoanisole and phenylboronic acid. Synthesized catalysts were shown to be highly active under mild reaction conditions. HPS allows stabilization of Pd(0) NPs and prevents their agglomeration and detectable Pd leaching. However, the loss of catalytic activity was observed during recycling. The deactivation issue was assigned to the hydrophobic nature of non-functionalized HPS, which allowed a strong adsorption of cross-coupling product during the catalyst separation procedure. A thorough washing of Pd/HPS catalyst by hydrophobic solvent was found to improve to the big extent the observed catalytic activity, while the replacement of non-functionalized HPS by a one containing amino groups increased the catalyst stability at the expense of their activity.
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Ostrovsky, Olga, Ania Hava Grushchenko Polaq, Katia Beider, Rita Mayorov, Avichai Shimoni, Israel Vlodavsky, and Arnon Nagler. "Functional rs4693608 SNP is Located into Strong Hpse Gene Intron Enhancer and Thereby Influences to the Ability of Nuclear Proteins Binding and Activity of This Enhancer in Broad Number of Hematological Cell Lines and ALL/AML Primary Samples." Blood 128, no. 22 (December 2, 2016): 3934. http://dx.doi.org/10.1182/blood.v128.22.3934.3934.
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Abstract Introduction: Heparanase (HPSE) is an endo-glucuronidase degrading heparan sulfate and playing important roles in angiogenesis, tumor metastasis, inflammation and autoimmunity. The enzyme also regulates histone methylation by binding to target gene regulatory regions. Our previous studies indicated that HPSE gene SNP rs4693608 significantly correlated with the expression level of heparanase among healthy persons. Furthermore, the rs4693608 SNP showed significant association with i) the risk of acute and extensive chronic GVHD, ii) HPSE gene expression both before and after chemotherapy administered as pre-hematopoietic stem cell transplantation conditioning, iii) the time of neutrophils and platelets recovery and iv) HPSE gene expression after lipopolysaccharide (LPS) treatment. Other studies revealed correlations between rs4693608 and sinusoid obstruction syndrome, and with bone morbidity and outcome of multiple myeloma. Methods: In the present study we cloned 440bp fragment of the HPSE gene (intron 2) that includes rs4693608 SNP using Pgl4.26 minimal promoter vector. Reporter activity of luciferase was detected in U937, KG1, K562, RPMI8226, and CAG cell lines. In addition, nuclear protein extracts from a broad range of malignant cell lines as well as from primary samples of patients with acute myeloid (AML) and lymphatic (ALL) leukemia and normal healthy individuals were subjected to binding to 30bp oligonucleotides probe representing the enhancer region of either the A allele or the G allele of rs4693608 SNP by EMSA (electrophoretic mobility shift assay). Results:Our results indicate that the 440bp fragment of the HPSE gene exhibits enhancer activity in both the sense and antisense directions of the HPSE gene. Relative luciferase activity was higher in constructs with antisense direction of the enhancer. Moreover, constructs that included the allele G revealed elevated level of luciferase activity in comparison to constructs that included the A allele. Analysis of healthy control samples using EMSA identified gel shift bands for both allelic probes. However, the affinity of the complex to the G allele probe was significantly higher in comparison to the A allele probe (Fig.1A). The DNA-protein complexes were shifted significantly more in malignant cell lines and primary leukemic samples as compared to normal control samples (Fig.1A). Moreover, there were additional nuclear-protein complexes that bind to the A allele probe (Fig.1B). Notably, at least 5 different DNA-protein complexes connected to allele A were found. In order to identify them we used bioinformatics analysis to predict proteins in the DNA/protein complex, followed by super-shift assay. At least three proteins were identified: β-glucocorticoid receptor, Yin Yang1 (YY1) transcription factor, and CCAAT/enhancer-binding protein-α (C/EBPα), which are part of this structured nuclear protein-binding complex (Fig.1B-C). Conclusions: The study demonstrated that HPSE rs4693608 SNP is located in a strong enhancer. A to G alteration leads to a different enhancer activity as a result of unique DNA-protein complex which binds to DNA regulatory elements in the enhancer. The composition of the DNA-protein complex which binds to the G allele, shifted similarly in all cell lines and primary leukemic samples but not in normal samples. At least 5 different variations of DNA-protein complexes connected to allele A were found, including β-glucocorticoid receptor, YY1 and C/EBPα. Precise identification of the specific proteins that bind to the unique enhancer region will allow modification of the enhancer activity that accelerates the expression of HPSE and thereby influences downstream processes. Disclosures No relevant conflicts of interest to declare.
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Burkova, N. V., O. P. Kirichuk, E. V. Romanchuk, V. A. Davankov, V. N. Postnov, and S. I. Kuznetsov. "Changes in plasma spectral characteristics during the in vitro contact of human venous blood with granulated sorbents." Almanac of Clinical Medicine 46, no. 8 (December 31, 2018): 772–77. http://dx.doi.org/10.18786/2072-0505-2018-46-8-772-777.
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Rationale: During hemosorption procedures, it is important to investigate not only the sorption and activation characteristics of hemocontact agents, but also to assess the effect of sorbents on the parameters of blood homeostasis. The intensity of hemolysis can be judged by the degree of changes in optical density of blood plasma at wavelengths corresponding to the peak absorption of hemoglobin (414, 544 and 577 nm).Aim: To assess the effect of three granular sorbents (SKT-6A, HPS, Silochrome C-120) contacting human venous blood in vitro on changes in plasma spectral characteristics.Materials and methods: The blood contact was modeled at bench conditions with the use of donated blood at rotating mode. Blood samples were drawn before the experiment and after 5, 20, 40, and 60 minutes. Spectroscopic assessment was performed in the visible light range (300–700 nm) with UNICO 2802(S) spectrophotometer.Results: The interaction of the SKT-6A sorbent with blood resulted in a 17.3% decrease in the plasma optical density at a wavelength of 540 nm, compared to baseline, as soon as at 5 minute of the experiment (p < 0.05). The decline in optical density imposed by the blood contact with HPS ranged from 2.6 to 12.1% (p < 0.05) during the observation period. The sorption activity of SKT-6A and HPS prevailed over their lytic properties. On the contrary, the percentage change in the optical density of the Silochrome C-120 sorbent during its blood contact increased from 25.6 to 38.3% (p < 0.05), indicating that this sorbent was inducing hemolysis. The sorbents tested can be arranged as follows according to their ability to induce hemolysis during their contact with blood: HPS < SKT-6A < Silochrome C-120.Conclusion: The tested SKT-6A and HPS sorbents can be used as blood-contact agents for the low volume hemoperfusion. The HPS agent seems to be the most promising for routine clinical use. The Silochrome C-120 sorbent requires some chemical modifcation to improve its properties of hemocompatibility.
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Gavrilovskaya, Irina N., Elena E. Gorbunova, and Erich R. Mackow. "Andes Virus Infection of Lymphatic Endothelial Cells Causes Giant Cell and Enhanced Permeability Responses That Are Rapamycin and Vascular Endothelial Growth Factor C Sensitive." Journal of Virology 86, no. 16 (June 13, 2012): 8765–72. http://dx.doi.org/10.1128/jvi.00817-12.
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Hantaviruses primarily infect endothelial cells (ECs) and nonlytically cause vascular changes that result in hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS). Acute pulmonary edema during HPS may be caused by capillary leakage and failure of lymphatic vessels to clear fluids. Uniquely regulated lymphatic ECs (LECs) control fluid clearance, although roles for lymphatics in hantavirus disease remain undetermined. Here we report that hantaviruses productively infect LECs and that LEC infection by HPS causing Andes virus (ANDV) and HFRS causing Hantaan virus (HTNV) are inhibited by αvβ3integrin antibodies. Although αvβ3integrins regulate permeabilizing responses directed by vascular endothelial growth factor receptor 2 (VEGFR2), we found that only ANDV-infected LECs were hyperpermeabilized by the addition of VEGF-A. However, VEGF-C activation of LEC-specific VEGFR3 receptors blocked ANDV- and VEGF-A-induced LEC permeability. In addition, ∼75% of ANDV-infected LECs became viable mononuclear giant cells, >4 times larger than normal, in response to VEGF-A. Giant cells are associated with constitutive mammalian target of rapamycin (mTOR) activation, and we found that both giant LECs and LEC permeability were sensitive to rapamycin, an mTOR inhibitor, and VEGF-C addition. These findings indicate that ANDV uniquely alters VEGFR2-mTOR signaling responses of LECs, resulting in giant cell and LEC permeability responses. This suggests that ANDV infection alters normal LEC and lymphatic vessel functions which may contribute to edematous fluid accumulation during HPS. Moreover, the ability of VEGF-C and rapamycin to normalize LEC responses suggests a potential therapeutic approach for reducing pulmonary edema and the severity of HPS following ANDV infection.
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Mahtouk, Karene, Dirk Hose, Thierry Reme, Michael Hundemer, Michel Jourdan, Eric Jourdan, Veronique Pantesco, et al. "Heparanase Influences Expression and Shedding of Syndecan-1, and Its Expression by the Bone Marrow Environment Is a Bad Prognostic Factor in Multiple Myeloma." Blood 108, no. 11 (November 16, 2006): 3502. http://dx.doi.org/10.1182/blood.v108.11.3502.3502.
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Abstract The heparan sulfate (HS) proteoglycan (PG) syndecan-1 plays a major role in multiple myeloma (MM), in part by concentrating HS-binding growth factors on the surface of MM cells (MMC). The function of HSPG is regulated by extracellular enzymes that modulate the structure of HS-chains. One such enzyme is heparanase (HPSE), an endo-glucuronidase that cleaves HS chains at only a few sites, resulting in fragments of 10–20 sugar units long that are biologically active. Using Affymetrix microarrays and real-time RT-PCR, we showed that the gene encoding HPSE was expressed by 11/19 myeloma cell lines (HMCLs). In HSPE-positive HMCLs, syndecan-1 mRNA expression and production of soluble syndecan-1, unlike expression of membrane syndecan-1, were significantly increased. Downregulation of HPSE by HPSE-siRNA resulted in a decrease of syndecan-1 mRNA expression and soluble syndecan-1 production, without affecting membrane syndecan-1. Contrary to HMCLs, HPSE was expressed in only 4/39 primary MMC samples at a low level, whereas it was highly expressed in 36/39 whole bone marrow (WBM) microenvironment samples. In the latter, HPSE was expressed at a median level in polynuclear cells and T cells, at high level in monocytes and osteoclasts, and it was not expressed in BM stromal cells. In order to investigate the connection of clinical parameters with HPSE gene expression, 30/39 myeloma patients treated with high dose chemotherapy and autologous stem cell transplantation where classified into two groups: 15 patients with the lowest or the highest HPSE expression in the WBM. The HPSEhigh group had an increased percentage of patients with elevated C-reactive protein and β2-microglobulin. According to the international staging system (ISS), the HPSEhigh group included a significant higher frequency of patients with stage III MM and a lower frequency of patients with stage I MM. HPSEhigh patients had a shorter event free survival (EFS) (p=.017) and overall survival (OAS) (p=.023) than HPSElow patients. Classifying these 30 patients into two groups according to HPSE expression in MMC did not yield to any EFS or OAS significant differences between the two groups. Altogether, those data provide evidence that HPSE not only modulate syndecan-1 activity through the cleavage of HS chains but also regulates syndecan-1 mRNA expression and shedding. We report for the first time that the expression of a gene in the BM, i.e. HSPE, is an indicator of poor prognostic for MM patients. Therefore, HPSE inhibitors like PI-88, which is currently in clinical trial, will be of interest for the treatment of patients with MM.
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Alshawaf, Abdullah J., Ana Antonic, Efstratios Skafidas, Dominic Chi-Hung Ng, and Mirella Dottori. "WDR62 Regulates Early Neural and Glial Progenitor Specification of Human Pluripotent Stem Cells." Stem Cells International 2017 (2017): 1–9. http://dx.doi.org/10.1155/2017/7848932.
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Mutations in WD40-repeat protein 62 (WDR62) are commonly associated with primary microcephaly and other developmental cortical malformations. We used human pluripotent stem cells (hPSC) to examine WDR62 function during human neural differentiation and model early stages of human corticogenesis. Neurospheres lacking WDR62 expression showed decreased expression of intermediate progenitor marker, TBR2, and also glial marker, S100β. In contrast, inhibition of c-Jun N-terminal kinase (JNK) signalling during hPSC neural differentiation induced upregulation of WDR62 with a corresponding increase in neural and glial progenitor markers, PAX6 and EAAT1, respectively. These findings may signify a role of WDR62 in specifying intermediate neural and glial progenitors during human pluripotent stem cell differentiation.
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KIM, JI-MIN, SEUNG-KI KWOK, JI HYEON JU, HO-YOUN KIM, and SUNG-HWAN PARK. "Reactive Hemophagocytic Syndrome in Adult Korean Patients with Systemic Lupus Erythematosus: A Case-Control Study and Literature Review." Journal of Rheumatology 39, no. 1 (December 15, 2011): 86–93. http://dx.doi.org/10.3899/jrheum.110639.
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Objective.To determine the characteristics of hemophagocytic syndrome (HPS) in adult Korean patients with systemic lupus erythematosus (SLE).Methods.We reviewed the medical records of 1033 adult patients with SLE for a recent 14-year period and identified 15 patients who had developed HPS. Forty-two age- and sex-matched patients with SLE admitted for other manifestations were included as disease controls. Features of HPS in these patients were analyzed.Results.Reactive HPS occurred from some distinct causes during the course of SLE. HPS was associated with SLE in 11 patients (4 at onset of SLE and 7 at SLE flare), infection in 3 patients (2 bacterial infection; 1 viral infection), and drug use (azathioprine) in 1 patient. Common clinical features included fever (93.3%), hepatomegaly (60.0%), and splenomegaly (60.0%). Steroid pulse therapy (46.7%), immunosuppressants (46.7%), and intravenous immunoglobulin (46.7%) were frequently used for treatment of HPS. One patient (6.7%) died. Compared with SLE patients without HPS, those with HPS showed a higher SLEDAI score (p = 0.003) and lower levels of plasma leukocytes (p < 0.001), hemoglobin (p = 0.013), and platelets (p < 0.001) as well as a higher serum C-reactive protein level (p = 0.039) and a lower serum albumin level (p = 0.004).Conclusion.HPS was observed in 1.5% of adult Korean patients with SLE. The occurrence of HPS was most frequently associated with the SLE disease activity. Profound pancytopenia, a high SLEDAI score, and notable changes in the level of acute-phase reactants can be the characteristics of SLE patients with HPS.
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Kapylou, Andrei, Vladimir Urbanovich, and Vladimir Kukareko. "High pressure sintering of TiB2 ceramics at different temperatures." Processing and Application of Ceramics 2, no. 1 (2008): 9–12. http://dx.doi.org/10.2298/pac0801009k.
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In this paper the effect of high-pressure sintering (HPS) temperature on the microstructure, physical and mechanical properties of TiB2 ceramics has been investigated. Initial TiB2 powder with the average particle size of 5 ?m was sintered in a modified high-pressure anvil-type apparatus under static pressure of 4 GPa in the temperature range of 1400-1800?C. It is shown that HPS allows preparing full-dense TiB2 ceramics with fine-grained structure. The density of samples rises with increasing the sintering temperature up to 1800?C while the maximal microhardness is observed on samples prepared in the temperature range of 1500-1600?C. XRD analysis has shown that this fact is connected with an increase of the level of internal stresses in these samples.
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Li, Shi Gang, and Yong Qi Zhang. "Characterization and Antitumor Activity of a Glucan Structure-Activity Relationship Analysis." Advanced Materials Research 726-731 (August 2013): 47–49. http://dx.doi.org/10.4028/www.scientific.net/amr.726-731.47.
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A water-soluble polysaccharide named as HPS-1 was isolated from the roots of Hedysarum polybotrys Hand.-Mazz by hot water extraction, anion-exchange and gel-permeation chromatography and tested for its antitumor activity. Its structural characteristics were investigated by FTIR, HPLC, NMR spectroscopy, GLCMS, methylation analysis, Periodate oxidation and Smith degradation. Based on the data obtained, HPS-1 was found to be an α- (14)-D-glucan, with a single α-D-glucose at the C-6 position every nine residue, on average, along the main chain. The glucan has a weight-average molecular weight of about 9.4×104 Da. MTT assay revealed that HPS-1 significantly inhibited the proliferation of Human hepatocellular carcinoma HEP-G2 cells and human gastric cancer MGC-803 cells in vitro, indicating HPS-1 could have a possible cancer therapeutic potential.
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Waghmare, Swapnil Gorakh, Azadeh Mohagheghi Samarin, Roman Franěk, Martin Pšenička, Tomáš Policar, Otomar Linhart, and Azin Mohagheghi Samarin. "Oocyte Ageing in Zebrafish Danio rerio (Hamilton, 1822) and Its Consequence on the Viability and Ploidy Anomalies in the Progeny." Animals 11, no. 3 (March 22, 2021): 912. http://dx.doi.org/10.3390/ani11030912.
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Fish egg quality can be markedly influenced by the oocyte age after ovulation. In this study, we examined the duration of oocyte ageing in the zebrafish (Danio rerio) and whether prolonged ageing is associated with the incidence of ploidy anomalies in the resulting embryos. Oocytes were incubated in vitro for 6 h post-stripping (HPS) at 26 °C and fertilized at 2-h intervals. Meanwhile, for eggs fertilized immediately after stripping, the fertilization, embryo survival, and hatching rates started at ~80%; these rates decreased to 39%, 24%, and 16%, respectively, for oocytes that had been stored for 4 h (p ˂ 0.05), and there was an almost complete loss of egg viability at 6 HPS. Furthermore, almost 90% of the embryos derived from 6-h aged oocytes died prior to hatching, and all larvae originating from 4- and 6-h aged oocytes showed malformations. The proportion of ploidy abnormal embryos was significantly greater at 4 HPS (18.5%) than at either 0 or 2 HPS (4.7% and 8.8%, respectively). The results revealed that zebrafish oocytes retained their fertilization potential for up to 2 h after stripping at 26 °C and indicated the contribution of post-ovulatory oocyte ageing in the occurrence of ploidy anomalies in the resulting embryos.
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Chen, Junjun, Liting Cheng, Zefeng Wang, Zhuo Liang, Ruiqing Dong, Fei Hang, Jieruo Chen, et al. "Comparison of efficacy and safety of His-Purkinje system pacing versus cardiac resynchronisation therapy in patients with pacing-induced cardiomyopathy: protocol for a randomised controlled trial." BMJ Open 11, no. 8 (August 2021): e045302. http://dx.doi.org/10.1136/bmjopen-2020-045302.
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IntroductionRecent studies have shown that the His-Purkinje system pacing (HPSP) can achieve electrocardiomechanical synchronisation, and thus improve cardiac function. For patients with pacing-induced cardiomyopathy (PICM) who should be treated with pacemaker upgrade, the HPSP is a viable alternative to cardiac resynchronisation therapy (CRT). However, no randomised controlled trial has been performed to evaluate the efficacy and safety of HPSP in patients with PICM. The present study compared the efficacy and safety of HPSP with that of traditional CRT in the treatment of patients with PICM.Methods and analysisThis study is a single-centre, randomised controlled non-inferiority trial. This trial was carried out at the cardiac centre of Beijing Anzhen Hospital. A total of 46 patients with PICM who needed pacemaker upgrade treatment between January 2022 and December 2023 will be enrolled in this study. Patients will be randomised into an investigational group (HPSP) and a control group (CRT) at a 1:1 ratio. The primary outcome is the duration of QRS complex (QRS width), and the secondary outcomes are NT-proBNP (N terminal pro B type natriuretic peptide), C reactive protein, the number of antibiotics used, left ventricular ejection fraction, end systolic volume, end diastolic volume, the hospitalisation duration, the incidence of postoperative infection, pacemaker parameters (threshold, sensing and impedance), the 6-minute walking test, and quality of life (36-Item Short Form Survey scale), all-cause mortality, cardiovascular death, heart failure-related rehospitalisation rate, other rehospitalisation rates, major complication rates and procedure costs.Ethics and disseminationThis study has been approved by the Beijing Anzhen Hospital Medical Ethics Committee (No. 2020043X).Trial registration numberChinese Clinical Trial Registry (ChiCTR2000034265).
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Leonardos, Evangelos D., Xiao Ma, Jason Lanoue, and Bernard Grodzinski. "Leaf and whole-plant gas exchange and water-use efficiency of chrysanthemums under HPS and LEDs during the vegetative and flower-induction stages." Canadian Journal of Plant Science 99, no. 5 (October 1, 2019): 639–53. http://dx.doi.org/10.1139/cjps-2018-0245.
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The effects of light quality on photosynthesis and transpiration of chrysanthemums during the vegetative and flowering stages are not known. Leaf and whole-plant CO2 and H2O exchanges of chrysanthemums during long-day (LD) and short-day (SD) photoperiods were measured under varying intensity levels of high-pressure sodium (HPS) and different monochromatic and multicolour light-emitting diode (LED) lights. All light sources induced leaf photosynthesis effectively, including green and orange LEDs. During both LD and SD, HPS, white, and notably orange light produced high rates of photosynthesis, whereas blue light had the lowest rates. In addition, there were only subtle changes in the response of leaf functions to light quality during flowering induction. Diurnal patterns of whole-plant net C exchange rate were similar under HPS and two commercial LED lights, one red–blue (RB) and one red–white (RW), during both LD and SD. The RB and RW LED lights were as effective at maintaining whole-plant C gain during the day as traditional HPS lights. However, in comparison to HPS, the RB and RW LEDs increased whole-plant transpiration and decreased water-use efficiency (WUE). A decrease in WUE under these LEDs was not evident from the leaf measurements, which emphasizes the importance of examining responses to light quality at the whole-plant level as well and not at the leaf level alone. In commercial production, the wavelength of supplementary lighting may heavily influence WUE and subsequent nutrient uptake, and ultimately growth and quality of cut flower crops.
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Richardson-Calfee, L. E., J. W. Day, W. T. Witte, and D. C. Fare. "Effects of Extended Photoperiod and Light Quality on Growth of Carpinus caroliniana, Fagus grandifolia and Gymnocladus dioicus Seedlings." Journal of Environmental Horticulture 19, no. 4 (December 1, 2001): 171–74. http://dx.doi.org/10.24266/0738-2898-19.4.171.
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Abstract Although Carpinus caroliniana (American hornbeam), Fagus grandifolia (American beech), and Gymnocladus dioicus (Kentucky coffeetree) have considerable landscape merit, they are not readily available in nurseries. Little research has been conducted on the cultural preferences of these species during nursery production. This study tested the effects of light quality and extended photoperiod on these species. Container-grown seedlings were subjected to three light treatments: 18-hour photoperiod using high pressure sodium lights (HPS), 18-hour photoperiod using incandescent lights (INC), and natural light and daylength (NAT). After 14 weeks, stem height of F. grandifolia seedlings was greatest for HPS light and least for NAT light. After 8 and 12 weeks, light source had no impact on stem heights of C. caroliniana. In 1997, stem height and caliper of G. dioicus were greatest using HPS light. In a repeat of the G. dioicus, experiment in 1998, HPS and INC light treatments resulted in greater stem height, caliper, and shoot and root dry weight compared to NAT treatment. The increase in height of seedlings under the HPS and INC treatments compared to the NAT treatments resulted from a greater number of seedlings that produced a second flush of growth under the HPS and INC treatments.
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Zhu, Li Hui, Guang Jie Shao, Yi Xiong Liu, and Dave Siddle. "Spark Plasma Sintering and Hot Pressing Sintering of Nanocrystalline WC-10CO-0.8VC." Materials Science Forum 534-536 (January 2007): 1229–32. http://dx.doi.org/10.4028/www.scientific.net/msf.534-536.1229.
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WC-10Co-0.8VC nanocrystalline powders were sintered by spark plasma sintering (SPS) and hot pressing sintering (HPS), and the microstructure and properties were compared. Results show that, sintered at 1300°C, the sample prepared by SPS for only 3 minutes has higher density than that prepared by HPS for 60 minutes. SEM and SPM observation shows SPS at 1200°C has a more uniform and finer microstructure, and most of the WC grains are smaller than 100nm. It has a relative density of 95.1%, HV30 of 1887, and KIC of 11.5 MPam1/2. If a suitable sintering parameter is chosen, SPS is a promising consolidation technique to prepare nanocrystalline WC-10Co-0.8VC with improved properties.
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Sun, Yuyao, Jinfeng Wang, and Jing Xie. "Performance Optimizations of the Transcritical CO2 Two-Stage Compression Refrigeration System and Influences of the Auxiliary Gas Cooler." Energies 14, no. 17 (September 6, 2021): 5578. http://dx.doi.org/10.3390/en14175578.
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To optimize the performance of the transcritical CO2 two-stage compression refrigeration system, the energy analysis and the exergy analysis are conducted. It is found that higher COP, lower compression power, and less exergy destruction can be achieved when the auxiliary gas cooler is applied. Moreover, the discharge temperature of the compound compressor (HPS) can be reduced by decreasing the temperature at the outlet of the auxiliary gas cooler (Tagc,out). When the Tagc,out is reduced from 30 to 12 °C, the discharge temperature of the compound compressor (HPS) can be decreased by 13.83 °C. Furthermore, the COP and the exergy efficiency can be raised by enhancing the intermediate pressure. Based on these results, the optimizations of system design and system operation are put forward. The application of the auxiliary gas cooler can improve the performance of the transcritical CO2 two-stage compression refrigeration system. Operators can decrease the discharge temperature of the compound compressor (HPS) by reducing the Tagc,out, and increase the COP and the exergy efficiency by enhancing the intermediate pressure.
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Palombaro, Kerstin M., Jill D. Black, Robin L. Dole, Sidney A. Jones, and Alexander R. Stewart. "Civic-Mindedness Sustains Empathy in a Cohort of Physical Therapy Students: A Pilot Cohort Study." Journal of Patient Experience 7, no. 2 (March 19, 2019): 185–92. http://dx.doi.org/10.1177/2374373519837246.
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Background: Empathy is critical to patient-centered care and thus is a valued trait in graduate health-care students. The relationship between empathy and civic-mindedness in health professions has not previously been explored. Objectives: (a) To determine whether significant differences occurred on the Jefferson Scale for Empathy–Health Professions Student Version (JSE-HPS) and Civic-Minded Professional scale (CMP) and its subscales across the curriculum, (b) to explore a potential relationship between civic-mindedness and empathy in a cohort of graduate physical therapy (PT) students at regular intervals, and (c) to explore the predictive ability of civic-mindedness on empathy scores. Methods: This study was a convenience sample of a cohort of 48 PT students who completed both the JSE-HPS and the CMP at 4 points of a service-learning intensive curriculum. Statistical analysis included descriptive statistics, a Friedman’s analysis of variance with Wilcoxon signed-ranks post hoc testing, and Spearman correlations with stepwise linear regressions. Results: Statistically significant differences were not found for the JSE-HPS. Civic-Minded Professional scores increased across the curriculum. The JSE-HPS, the CMP, and various CMP subscales were significantly correlated. The JSE-HPS pretest scores were predictive of the year 1 and 2 posttest JSE-HPS scores. Conclusion: This study’s findings indicate that service-learning and the resulting development of civic-mindedness supports empathy. Programs could use JSE-HPS pretests to identify individual graduate students need for empathy mentorship upon program entrance or as one admission criterion.
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Stone, P. C., A. Kalpakidou, C. Todd, J. Griffiths, V. Keeley, K. Spencer, P. Buckle, D. Finlay, V. Vickerstaff, and R. Z. Omar. "The Prognosis in Palliative care Study II (PiPS2): A prospective observational validation study of a prognostic tool with an embedded qualitative evaluation." PLOS ONE 16, no. 4 (April 28, 2021): e0249297. http://dx.doi.org/10.1371/journal.pone.0249297.
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Background Prognosis in Palliative care Study (PiPS) models predict survival probabilities in advanced cancer. PiPS-A (clinical observations only) and PiPS-B (additionally requiring blood results) consist of 14- and 56-day models (PiPS-A14; PiPS-A56; PiPS-B14; PiPS-B56) to create survival risk categories: days, weeks, months. The primary aim was to compare PIPS-B risk categories against agreed multi-professional estimates of survival (AMPES) and to validate PiPS-A and PiPS-B. Secondary aims were to assess acceptability of PiPS to patients, caregivers and health professionals (HPs). Methods and findings A national, multi-centre, prospective, observational, cohort study with nested qualitative sub-study using interviews with patients, caregivers and HPs. Validation study participants were adults with incurable cancer; with or without capacity; recently referred to community, hospital and hospice palliative care services across England and Wales. Sub-study participants were patients, caregivers and HPs. 1833 participants were recruited. PiPS-B risk categories were as accurate as AMPES [PiPS-B accuracy (910/1484; 61%); AMPES (914/1484; 61%); p = 0.851]. PiPS-B14 discrimination (C-statistic 0.837) and PiPS-B56 (0.810) were excellent. PiPS-B14 predictions were too high in the 57–74% risk group (Calibration-in-the-large [CiL] -0.202; Calibration slope [CS] 0.840). PiPS-B56 was well-calibrated (CiL 0.152; CS 0.914). PiPS-A risk categories were less accurate than AMPES (p<0.001). PiPS-A14 (C-statistic 0.825; CiL -0.037; CS 0.981) and PiPS-A56 (C-statistic 0.776; CiL 0.109; CS 0.946) had excellent or reasonably good discrimination and calibration. Interviewed patients (n = 29) and caregivers (n = 20) wanted prognostic information and considered that PiPS may aid communication. HPs (n = 32) found PiPS user-friendly and considered risk categories potentially helpful for decision-making. The need for a blood test for PiPS-B was considered a limitation. Conclusions PiPS-B risk categories are as accurate as AMPES made by experienced doctors and nurses. PiPS-A categories are less accurate. Patients, carers and HPs regard PiPS as potentially helpful in clinical practice. Study registration ISRCTN13688211.
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Steiner, Marcelo Luis, Thérèse Rachell Theodoro, Shirley Gimenez Garcia, Ana Maria Amaral Antonio Mader, Luciano de Melo Pompei, Maria Aparecida da Silva Pinhal, and César Eduardo Fernandes. "Is the Expression of the Components of the Carotid Matrix of Rats Influenced by Estrogen, Progestin and Tibolone?" Revista Brasileira de Ginecologia e Obstetrícia / RBGO Gynecology and Obstetrics 41, no. 07 (July 2019): 449–53. http://dx.doi.org/10.1055/s-0039-1693681.
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Objective To analyze the effects of estrogen alone or in combination with progestogens and tibolone (TIB) on the expression of the extracellular matrix metalloproteinases 2 and 9 (MMP-2 and MMP-9), of perlecan, and of heparanase (HPSE) of the vascular walls of the carotid arteries. Methods A total of 30 250-day-old ovariectomized Wistar rats were orally treated for 5 weeks with: a) 1 mg/kg of estradiol benzoate (EB); b) EB + 0.2 mg/kg of medroxyprogesterone acetate (MPA); c) EB + 0.2mg/kg of norethisterone acetate (NETA); d) EB + 2 mg/kg of dydrogesterone (DI); e) 1 mg/kg of TIB; f) placebo (CTR). Following treatment, the expression of mRNA for MMP-2, MMP-9, and HPSE was analyzed by real-time polymerase chain-reaction (PCR), and the expression of MMP-2, of MMP-9, of tissue inhibitor of metalloproteinase 2 (TIMP-2), and of perlecan was quantified by immunohistochemistry in the carotid arteries. Results The groups showed significant differences on mRNA HPSE expression (p = 0.048), which was higher in the EB, EB + MPA, and TIB groups. There was no statistically significant difference in mRNA MMP-2 or MMP-9 expression. The immunohistochemical expression of MMP-2, of TIMP-2, of MMP-9, of HPSE, and of perlecan showed no differences between groups. Conclusion Estradiol alone or associated with MPA and TIB treatment can increase mRNA HSPE expression of the walls of the carotid arteries in ovariectomized rats.
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Herrala, Annakaisa, Riitta Kurkela, Katja Porvari, Ritva Isomäki, Pirkko Henttu, and Pirkko Vihko. "Human prostate-specific glandular kallikrein is expressed as an active and an inactive protein." Clinical Chemistry 43, no. 2 (February 1, 1997): 279–84. http://dx.doi.org/10.1093/clinchem/43.2.279.
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Abstract A polymorphism in the human prostate-specific glandular kallikrein (hKLK2) gene was described by direct sequencing (by PCR) of genomic DNAs isolated from prostatic cancer tissue, benign prostatic hyperplasia tissue, and blood leukocyte specimens. Results showed two forms of human prostate-specific glandular kallikrein protein (hK2), a consequence of a change from C to T at base 792 in the hK2 coding region. Producing the two forms as recombinant proteins in insect cells demonstrated that Arg226-hK2 (CC genotype) is an active protein and Trp226-hK2 (TT genotype) is inactive. Polymorphism studies of 36 patients with prostatic diseases identified only 1 with the TT genotype. The same kind of polymorphism was not detected in the human prostate-specific antigen (hKLK3) gene. Arg226-hK2 possessed only trypsin-like enzyme activity, whereas recombinant human prostate-specific antigen (hPSA) had only chymotrypsin-like activity. Monoclonal and polyclonal antibodies raised against hPSA purified from seminal plasma detected both active and inactive hK2. Thus, because inactive as well as stable hK2 protein may be present, a lack of trypsin-like activity in hPSA standards is not enough to confirm that the materials are free of hK2 contamination.
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Yoo, Dong-Lim, and Seung-Woo Lee. "634 Effects of Light Sources for Light Period Extension on Growth and Fowering in Statice." HortScience 35, no. 3 (June 2000): 507A—507. http://dx.doi.org/10.21273/hortsci.35.3.507a.
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This experiment was conducted to investigate the effects of artificial light sources for light period extension on growth and flowering of statice `Sophia' and `Early Blue'. The seeds were sown on 10 June in a plug tray with 128 plugs. The seedlings were grown at the highland (800 m above sea level) for 50 days, and transplanted on 30 July in 20-cm-diameter plastic pots. High-pressure sodium lamps (HPS) (220V, 400W), incandescent lamps (Il) (220V, 200W), and fluorescent lamps (Fl) (220V, 40W) for day length extension (16-h photoperiod) as compared with short day (8-h photoperiod) were tested. HPS gave the greatest photosynthetically active radiation (PAR), but Fl did the smallest. HPS or Fl as compared with Il showed high ratio of red/far-red light. The leaves of plant grown under HPS were effective for light absorbance and chlorophyll contents. HPS promoted photosynthesis as much as light period extension, while more respiration than photosynthesis occurred under Fl affected by low PAR. Long day condition as light period extension hastened flowering of statice, and HPS or Il were more effective than Fl on flowering among artificial light sources tested. The light compensation and saturation points of statice were 50 and 500 μmol·m–2·s–1, respectively. Photosynthesis hastened at high temperature, but amount of photosynthesis at vegetative stage showed much higher than flowering stage under the condition below 20 °C These results indicated that day length extension with HPS increased productivity and quality for cut flower of statice at the highland in Korea.
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Deng, Li, Xie, Wu, Wang, Yu, Li, and Zheng. "Heat Pipe Thermal Management Based on High-Rate Discharge and Pulse Cycle Tests for Lithium-Ion Batteries." Energies 12, no. 16 (August 15, 2019): 3143. http://dx.doi.org/10.3390/en12163143.
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A battery thermal management system (BTMS) ensures that batteries operate efficiently within a suitable temperature range and maintains the temperature uniformity across the battery. A strict requirement of the BTMS is that increases in the battery discharge rate necessitate an increased battery heat dissipation. The advantages of heat pipes (HPs) include a high thermal conductivity, flexibility, and small size, which can be utilized in BTMSs. This paper experimentally examines a BTMS using HPs in combination with an aluminum plate to increase the uniformity in the surface temperature of the battery. The examined system with high discharge rates of 50, 75, and 100 A is used to determine its effects on the system temperature. The results are compared with those for HPs without fins and in ambient conditions. At a 100 A discharge current, the increase in battery temperature using the heat pipe with fins (HPWF) method is 4.8 °C lower than for natural convection, and the maximum temperature difference between the battery surfaces is 1.7 °C and 6.0 °C. The pulse circulation experiment was designed considering that the battery operates with a pulse discharge and temperature hysteresis. The depth of discharge is also considered, and the states-of-charge (SOC) values were 0.2, 0.5, and 0.8. The results of the two heat dissipation methods are compared, and the optimal heat dissipation structure is obtained by analyzing the experimental results. The results show that when the ambient temperature is 37 °C, differences in the SOC do not affect the battery temperature. In addition, the HPWF, HP, and natural convection methods reached stable temperatures of 40.8, 44.3, and the 48.1 °C, respectively the high temperature exceeded the battery operating temperature range.
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Whitman, Catherine, Royal Heins, Arthur Cameron, and William Carlson. "Effects of Temperature, Photoperiod, and Light Quality on Flowering in Several Herbaceous Perennial Species." HortScience 30, no. 4 (July 1995): 771D—771. http://dx.doi.org/10.21273/hortsci.30.4.771d.
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The influence of low temperatures on Campanula carpatica `Blue Clips' and Lavandula angustifolia `Munstead' flowering was determined; plants were stored at 5C for several weeks and forced under 9-h photoperiods with a 4-h night interruption (NI). C. carpatica, L. angustifolia, and Asclepias tuberosa were forced under NI at five temperatures (15–27C) and time to flower under each treatment was calculated. Flower number and size were reduced at highest temperatures. The effectiveness of cool-white fluorescent (CWF), high-pressure sodium (HPS), incandescent (I), and metal halide (MH) lights in inducing flowering in C. carpatica and Coreopsis lanceolata `Early Sunrise' was compared. Lighting was delivered as a 7-h daylength extension with PPF ranging from 0.05–2.0 μmol·m–2·s–1. Minimum irradiances above which all C. carpatica flowered were approximately 0.14, 0.12, 0.1, and 0.17 μmol·m–2·s–1, respectively. C. lanceolata under CWF displayed irregular flowering throughout the range of intensities used. Under HPS and MH, minimum irradiances for 100% flowering were 0.37 and 1.0 μmol·m–2·s–1, respectively, with sporadic flowering at lower intensities. Under I light, all C. lanceolata exposed to 0.12 μmol·m–2·s–1 or more flowered.
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Randall, Wesley C., and Roberto G. Lopez. "Comparison of Supplemental Lighting from High-pressure Sodium Lamps and Light-emitting Diodes during Bedding Plant Seedling Production." HortScience 49, no. 5 (May 2014): 589–95. http://dx.doi.org/10.21273/hortsci.49.5.589.
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Annual bedding plant seedlings or plugs are considered high quality when they are compact, fully rooted transplants with a large stem caliper and high root dry mass. Greenhouses in northern latitudes rely on supplemental lighting (SL) from high-pressure sodium lamps (HPS) during winter months to achieve high-quality, finished plugs. Light-emitting diodes (LEDs) offer higher energy efficiencies, a long operating life, and precise waveband specificity that can eliminate wavebands not considered useful. Seedlings of Antirrhinum, Catharanthus, Celosia, Impatiens, Pelargonium, Petunia, Tagetes, Salvia, and Viola were grown at 21 °C under a 16-hour photoperiod of ambient solar light and SL of 100 μmol·m−2·s–1 from either HPS lamps or LED arrays with varying proportions (%) of red:blue light (100:0, 85:15, or 70:30). Height of Catharanthus, Celosia, Impatiens, Petunia, Tagetes, Salvia, and Viola was 31%, 29%, 31%, 55%, 20%, 9%, and 35% shorter, respectively, for seedlings grown under the 85:15 red:blue LEDs compared with those grown under HPS lamps. Additionally, stem caliper of Antirrhinum, Pelargonium, and Tagetes was 16%, 8%, and 13% larger, respectively, for seedlings grown under the 85:15 red:blue LEDs compared with seedlings grown under HPS lamps. The quality index (QI), a quantitative measurement of quality, was similar for Antirrhinum, Catharanthus, Impatiens, Pelargonium, and Tagetes grown under LEDs and HPS lamps. However, it was significantly higher for Petunia, Salvia, and Viola under 85:15, 70:30, and 100:0 red:blue LEDs than under HPS lamps, respectively. These results indicate that seedling quality for the majority of the species tested under SL from LEDs providing both red and blue light was similar or higher than those grown under HPS lamps.
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Backhaus-Ricoult, M., and Yu G. Gogotsi. "Identification of oxidation mechanisms in silicon nitride ceramics by transmission electron microscopy studies of oxide scales." Journal of Materials Research 10, no. 9 (September 1995): 2306–21. http://dx.doi.org/10.1557/jmr.1995.2306.
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Additive-free HIPSN and Y2O3 + Al2O3-doped HPSN are oxidized in air in the temperature range from 1300 to 1500 °C. TEM, SEM, EDS, and XRD are used to analyze the composition and microstructure of the oxide scales in order to determine the oxidation mechanisms. HIPSN exhibits excellent resistance to oxidation in air at temperatures up to 1480 °C due to the formation of a protective silica (cristobalite) scale. No formation of Si2N2O and oxygen-enriched β'-Si3N4 under the silica layer is observed for materials densified without additives. Oxidation rates of additive-containing HPSN are more important due to the formation of a viscous aluminosilicate phase, which easily penetrates along the grain boundaries in the material. Silicon nitride grains in contact with the viscous phase first become enriched in aluminum and oxygen and are then dissolved in the glassy phase. No Si2N2O intermediate layer is formed. The finding of the decisive role of the aluminosilicate in the oxidation process allows one to explain inconsistencies observed in the oxidation kinetics of silicon nitride ceramics. Effects of sintering additives, WC contamination and temperature on the oxidation mechanisms, and structure of oxide scales are discussed.
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Takamori, Hiroyuki, and John W. Fisher. "Tests of Large Girders Treated To Enhance Fatigue Strength." Transportation Research Record: Journal of the Transportation Research Board 1696, no. 1 (January 2000): 93–99. http://dx.doi.org/10.3141/1696-12.
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Two large-scale fatigue test studies of plate girders are reported on. One study involved a series of coverplated bridge girders with small fatigue cracks that were retrofitted in 1976 as described in NCHRP Report 206. The second study involved plate girders fabricated from HPS-485W (HPS-70W) steel with welded attachments. The Category E’ coverplated beams that were removed from the I-95 Yellow Mill Pond Bridge in 1997 had been retrofitted in 1976 by either air hammer peening or gas tungsten arc (GTA) remelting. All details had small fatigue cracks at the time of retrofit. No further fatigue cracking was observed at the coverplate ends after 20 years of service and an estimated 56 million truck passages. The beams were tested at a stress range of 69 MPa (10 ksi). Cracks developed from the root of the transverse end weld and propagated through the weld throat. The fatigue resistance of the treated weld toe details improved to Category C except for one GTA-remelted detail, which exceeded Category D. Another study was carried out on large-scale HPS-485W plate girders with as-welded and ultrasonic-impact treatment (UIT) details. UIT was applied to the weld toe of transverse stiffeners welded to the web and flanges (Category C) and to coverplated ends (Category E’). The as-welded details cracked at their expected fatigue resistance. The UIT transverse stiffeners improved to Category B fatigue resistance, whereas the UIT coverplated details improved to Category C fatigue resistance.
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Kim, Jung-Hyun, Jeeyoung Kim, Woo Jin Kim, Yung Hyun Choi, Se-Ran Yang, and Seok-Ho Hong. "Diesel Particulate Matter 2.5 Induces Epithelial-to-Mesenchymal Transition and Upregulation of SARS-CoV-2 Receptor during Human Pluripotent Stem Cell-Derived Alveolar Organoid Development." International Journal of Environmental Research and Public Health 17, no. 22 (November 13, 2020): 8410. http://dx.doi.org/10.3390/ijerph17228410.
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Growing evidence links prenatal exposure to particulate matter (PM2.5) with reduced lung function and incidence of pulmonary diseases in infancy and childhood. However, the underlying biological mechanisms of how prenatal PM2.5 exposure affects the lungs are incompletely understood, which explains the lack of an ideal in vitro lung development model. Human pluripotent stem cells (hPSCs) have been successfully employed for in vitro developmental toxicity evaluations due to their unique ability to differentiate into any type of cell in the body. In this study, we investigated the developmental toxicity of diesel fine PM (dPM2.5) exposure during hPSC-derived alveolar epithelial cell (AEC) differentiation and three-dimensional (3D) multicellular alveolar organoid (AO) development. We found that dPM2.5 (50 and 100 μg/mL) treatment disturbed the AEC differentiation, accompanied by upregulation of nicotinamide adenine dinucleotide phosphate oxidases and inflammation. Exposure to dPM2.5 also promoted epithelial-to-mesenchymal transition during AEC and AO development via activation of extracellular signal-regulated kinase signaling, while dPM2.5 had no effect on surfactant protein C expression in hPSC-derived AECs. Notably, we provided evidence, for the first time, that angiotensin-converting enzyme 2, a receptor to mediate the severe acute respiratory syndrome coronavirus clade 2 (SARS-CoV-2) entry into target cells, and the cofactor transmembrane protease serine 2 were significantly upregulated in both hPSC-AECs and AOs treated with dPM2.5. In conclusion, we demonstrated the potential alveolar development toxicity and the increase of SARS-Cov-2 susceptibility of PM2.5. Our findings suggest that an hPSC-based 2D and 3D alveolar induction system could be a useful in vitro platform for evaluating the adverse effects of environmental toxins and for virus research.
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Trainor, Deirdre, James Tolley, Carl LaCerte, Barbara Gaynor, Toddy Sewell, Melinda Jazdzewski, Augusto Lois, and Frank Gonzales. "Quantitative Gene Expression Assays without Target Amplification." JALA: Journal of the Association for Laboratory Automation 8, no. 2 (April 2003): 30–33. http://dx.doi.org/10.1016/s1535-5535-04-00247-3.
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Evaluating changes in gene expression is essential when identifying and validating new drug targets, however, the methods used to measure transcription are laborious, time-consuming and expensive ( e.g., RT-PCR, microarray or northern blot). High Performance Signal Amplification (HPSA™) gene expression assays quantitate particular mRNA targets directly in cell lysate samples using DNA probe hybridization and fluorescent signal amplification. The assay format eliminates the need for RNA purification prior to testing and does not require RT-PCR amplification. The HPSA™ protocol involves three steps carried out at 37°C in 96- or 384-well plates, making the technique amenable to automation. Cellular mRNA levels are quantitated relative to a standard curve consisting of purified in vitro RNA transcripts derived from cDNA clones. Assay sensitivity is in the low attomole range and can detect mRNA expressed at twenty copies per cell. A number of HPSA™ assays have been developed for cytokine, housekeeping and cytochrome P450 messages. Gene induction profiles were monitored in cell lines or peripheral blood mononuclear cells (PBMC) treated with activators such as phorbol 12-myristate-13-acetate (PMA), ionomycin or phytohemagglutinin (PHA). Recent validation studies demonstrated IL-9 mRNA induction in primary cultures of T-cells treated with PMA and anti-CD3. Similar testing with PBMCs showed significant IL-13 mRNA induction after 48 hours of treatment with PMA, thymosin and staphylococcal enterotoxin. Cytokine STATE® panels are being constructed according to functional categories such as innate or adaptive immunity to better characterize changes in transcription patterns during an immune response. The HPSA™ gene expression assays offer a rapid and convenient alternative to more cumbersome, expensive methods.
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Moog, Philipp, Rahmin Schams, Alexander Schneidinger, Arndt F. Schilling, Hans-Günther Machens, Ektoras Hadjipanayi, and Ulf Dornseifer. "Effect of Hypoxia Preconditioned Secretomes on Lymphangiogenic and Angiogenic Sprouting: An in Vitro Analysis." Biomedicines 8, no. 9 (September 20, 2020): 365. http://dx.doi.org/10.3390/biomedicines8090365.
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Hypoxia Preconditioned Plasma (HPP) and Serum (HPS) are two blood-derived autologous growth factor compositions that are being clinically employed as tools for promoting tissue regeneration, and have been extensively examined for their angiogenic activity. As yet, their ability to stimulate/support lymphangiogenesis remains unknown, although this is an important but often-neglected process in wound healing and tissue repair. Here we set out to characterize the potential of hypoxia preconditioned secretomes as promoters of angiogenic and lymphangiogenic sprouting in vitro. We first analysed HPP/HPS in terms of pro- (VEGF-C) and anti- (TSP-1, PF-4) angiogenic/lymphangiogenic growth factor concentration, before testing their ability to stimulate microvessel sprouting in the mouse aortic ring assay and lymphatic sprouting in the thoracic duct ring assay. The origin of lymphatic structures was validated with lymph-specific immunohistochemical staining (Anti-LYVE-1) and lymphatic vessel-associated protein (polydom) quantification in culture supernatants. HPP/HPS induced greater angiogenic and lymphatic sprouting compared to non-hypoxia preconditioned samples (normal plasma/serum), a response that was compatible with their higher VEGF-C concentration. These findings demonstrate that hypoxia preconditioned blood-derived secretomes have the ability to not only support sprouting angiogenesis, but also lymphangiogenesis, which underlines their multimodal regenerative potential.
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Manaenkov, Oleg V., Olga V. Kislitsa, Ekaterina A. Ratkevich, and Mikhail G. Sulman. "MAGNETICALLY RECOVERABLE POLYMER CATALYST FOR CELLULOSE HYDROGENOLYSIS." IZVESTIYA VYSSHIKH UCHEBNYKH ZAVEDENII KHIMIYA KHIMICHESKAYA TEKHNOLOGIYA 63, no. 2 (February 8, 2020): 59–63. http://dx.doi.org/10.6060/ivkkt.20206302.6062.
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A new type of Ru-containing magnetically recoverable catalyst based on a polymer matrix of hypercrosslinked polystyrene (HPS) for the reaction of the hydrogenolysis of microcrystalline cellulose to ethylene and propylene glycol (EG and PG) is proposed. The catalyst is synthesized sequentially in two stages. At the first stage, by means of thermal decomposition of iron (III) salts in the presence of polyols, magnetite particles (Fe3O4) are formed in the pores of the HPS. At the second stage, Ru-containing nanoparticles of the active phase of the catalyst are synthesized on the surface of Fe3O4/HPS. Samples of the original HPS, Fe3O4/HPS and Ru-Fe3O4/HPS were characterized using various physicochemical methods. In particular, it was shown that the synthesized samples of catalysts have a high specific surface area (450 - 750 m2/g, depending on the magnetite content), retain the micro-mesoporous nature of the original polymer, and have a high saturation magnetization (4.0 ± 0.5 emu /g), which makes them easy to separate from the reaction mass by an external magnetic field. According to the results of transmission electron microscopy (TEM), the average diameter of the nanoparticles of the active phase Ru was 2.0 ± 0.5 nm. The hydrogenolysis of cellulose to glycols was carried out under the following conditions: 255 °C; 60 bar H2; 55 min; 0.3 g of cellulose; 0.07 g of catalyst 3% Ru-Fe3O4/HPS; 30 ml of H2O; 0.07 g of Ca(OH)2. Under these conditions, the selectivities for EG and PG were 22.6 % and 20.0 %, respectively. The degree of cellulose conversion reaches 100 %. The catalyst showed good stability under hydrothermal reaction conditions, is easily separated from the reaction mass by an external magnetic field, and can be used in the processes of cellulose-containing biomass conversion.
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Huizing, Marjan, Rangaprasad Sarangarajan, Erin Strovel, Yang Zhao, William A. Gahl, and Raymond E. Boissy. "AP-3 Mediates Tyrosinase but Not TRP-1 Trafficking in Human Melanocytes." Molecular Biology of the Cell 12, no. 7 (July 2001): 2075–85. http://dx.doi.org/10.1091/mbc.12.7.2075.
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Patients with Hermansky-Pudlak syndrome type 2 (HPS-2) have mutations in the β3A subunit of adaptor complex-3 (AP-3) and functional deficiency of this complex. AP-3 serves as a coat protein in the formation of new vesicles, including, apparently, the platelet's dense body and the melanocyte's melanosome. We used HPS-2 melanocytes in culture to determine the role of AP-3 in the trafficking of the melanogenic proteins tyrosinase and tyrosinase-related protein-1 (TRP-1). TRP-1 displayed a typical melanosomal pattern in both normal and HPS-2 melanocytes. In contrast, tyrosinase exhibited a melanosomal (i.e., perinuclear and dendritic) pattern in normal cells but only a perinuclear pattern in the HPS-2 melanocytes. In addition, tyrosinase exhibited a normal pattern of expression in HPS-2 melanocytes transfected with a cDNA encoding the β3A subunit of the AP-3 complex. This suggests a role for AP-3 in the normal trafficking of tyrosinase to premelanosomes, consistent with the presence of a dileucine recognition signal in the C-terminal portion of the tyrosinase molecule. In the AP-3–deficient cells, tyrosinase was also present in structures resembling late endosomes or multivesicular bodies; these vesicles contained exvaginations devoid of tyrosinase. This suggests that, under normal circumstances, AP-3 may act on multivesicular bodies to form tyrosinase-containing vesicles destined to fuse with premelanosomes. Finally, our studies demonstrate that tyrosinase and TRP-1 use different mechanisms to reach their premelanosomal destination.
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Hettler, Cameron, William W. Sullivan III, and James Dickens. "Characterization of Annealed HPSI 4H-SiC for Photoconductive Semiconductor Switches." Materials Science Forum 717-720 (May 2012): 301–4. http://dx.doi.org/10.4028/www.scientific.net/msf.717-720.301.
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Annealing of high purity semi-insulating (HPSI) 4H-SiC is investigated as a method to improve bulk photoconductive semiconductor switches through recombination lifetime modification. Five samples of HPSI 4H-SiC were annealed at 1810 °C for lengths of time ranging from 3 to 300 minutes. The recombination lifetime of the unannealed and annealed samples was measured using a contactless microwave photoconductivity decay (MPCD) system. The MPCD system consists of a 35 GHz continuous microwave probe and a tripled Nd:YAG pulsed laser. The recombination lifetime was increased from 6 ns, as received, up to 185 ns by annealing for 300 minutes. To experimentally verify switch improvements, identical switches from unannealed and annealed material were fabricated and tested at low voltage. The unannealed device generated a 15 ns pulse with a 2 ns rise-time. The annealed device conducted for upwards of 300 ns with a comparable 2 ns rise-time. The increased recombination lifetime resulted in lower on-state resistance and increased energy transfer.
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Zeman, Miroslav, Marek Vecka, František Perlík, Barbora Staňková, Robert Hromádka, Eva Tvrzická, Jakub Širc, Jakub Hrib, and Aleš Žák. "Pleiotropic effects of niacin: Current possibilities for its clinical use." Acta Pharmaceutica 66, no. 4 (December 1, 2016): 449–69. http://dx.doi.org/10.1515/acph-2016-0043.
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Abstract Niacin was the first hypolipidemic drug to significantly reduce both major cardiovascular events and mortality in patients with cardiovascular disease. Niacin favorably influences all lipoprotein classes, including lipoprotein[a],and belongs to the most potent hypolipidemic drugs for increasing HDL-C. Moreover, niacin causes favorable changes to the qualitative composition of lipoprotein HDL. In addition to its pronounced hypolipidemic action, niacin exerts many other, non-hypolipidemic effects (e.g., antioxidative, anti-inflammatory, antithrombotic), which favorably influence the development and progression of atherosclerosis. These effects are dependent on activation of the specific receptor HCA2. Recent results published by the two large clinical studies, AIM-HIGH and HPS2-THRIVE, have led to the impugnation of niacin’s role in future clinical practice. However, due to several methodological flaws in the AIM-HIGH and HPS2-THRIVE studies, the pleiotropic effects of niacin now deserve thorough evaluation. This review summarizes the present and possible future use of niacin in clinical practice in light of its newly recognized pleiotropic effects.
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Orita, Izumi, Hiroya Yurimoto, Reiko Hirai, Yutaka Kawarabayasi, Yasuyoshi Sakai, and Nobuo Kato. "The Archaeon Pyrococcus horikoshii Possesses a Bifunctional Enzyme for Formaldehyde Fixation via the Ribulose Monophosphate Pathway." Journal of Bacteriology 187, no. 11 (June 1, 2005): 3636–42. http://dx.doi.org/10.1128/jb.187.11.3636-3642.2005.
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ABSTRACT Pyrococcus horikoshii OT3, a hyperthermophilic and anaerobic archaeon, was found to have an open reading frame (PH1938) whose deduced amino acid sequence of the N-terminal and C-terminal halves showed significant similarity to two key enzymes of the ribulose monophosphate pathway for formaldehyde fixation in methylotrophic bacteria, 3-hexulose-6-phosphate synthase (HPS) and 6-phospho-3-hexuloisomerase (PHI), respectively. The organism constitutively produced the encoded protein and exhibited activity of the sequential HPS- and PHI-mediated reactions in a particulate fraction. The full-length gene encoding the hybrid enzyme, the sequence corresponding to the HPS region, and the sequence corresponding to the PHI region were expressed in Escherichia coli and were found to produce active enzymes, rHps-Phi, rHps, or rPhi, respectively. Purified rHps-Phi and rHps were found to be active at the growth temperatures of the parent strain, but purified rPhi exhibited significant susceptibility to heat, suggesting that thermostability of the PHI moiety of the bifunctional enzyme (rHps-Phi) resulted from fusion with HPS. The bifunctional enzyme catalyzed the sequential reaction much more efficiently than a mixture of rHps and rPhi. These and other biochemical characterizations of the PH1938 gene product suggest that the ribulose monophosphate pathway plays a significant role in the archaeon under extreme environmental conditions.
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Lozynska, L. Y., A. Plawski, M. R. Lozynska, I. Vytvytskyi, R. Y. Lozynskyi, N. Prokopchuk, and B. Tretiak. "VARIANT OF RARE HERMANSKY — PUDLAK SYNDROME ASSOCIATED WITH GRANULOMATOUS COLITIS: DIAGNOSTICS, CLINICAL COURSE AND TREATMENT." Experimental Oncology 40, no. 1 (March 22, 2018): 73–78. http://dx.doi.org/10.31768/2312-8852.2018.40(1):73-78.
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Aim: To study the relationship between the genotype and the phenotype in the patients with Hermansky — Pudlak syndrome (HPS) associated with granulomatous colitis; to monitor clinical course of the disease for adequate treatment, cancer surveillance and genetic counseling. Materials and Methods: The diagnosis of HPS is established by physical examination, chest X-ray, computed tomography, endoscopic examination with biopsy, and laboratory tests, including histology, baseline laboratory blood, urine and feces tests, determination of ASCA-C and ANCA antibodies using an ELISA. Molecular genetic testing for HPS gene mutations, R702W, G908R, L1007fs and P268S mutations in NOD2 gene, and TaqI variant of the VDR gene were carried out. Results: We report 2 cases of HPS from unrelated families. Both were complicated by inflammatory bowel disease with pathologic features of Crohn’s disease refractory to antibiotics and corticosteroids. One patient (family 1) with Ashkenazi Jewish ancestry had pathogenic variant of the HPS-4 gene in exon 8, mutation P268S of NOD2 genes and “Tt” genotype of TaqI variant of the VDR gene. Another patient (family 2) carried two mutations P268S and G908R of NOD2 gene, and had a large paraovarian cyst diagnosed. No consistent success with the standard medical therapy, used for treating granulomatous colitis, associated with HPS, in presented cases was achieved. Patients needed surgical interventions at a young age and a long-term surveillance of the probable development of tumors and other complications. Azathioprine at 2 mg/kg/day and mesalazine 3 g/day were used with some positive effect for prevention of Crohn’s disease postoperative recurrence. Conclusion: The occurrence of perianal lesions, the histopathological findings and the results of the molecular genetic analysis confirmed the mutations P268S and G908R of NOD2 gene in these cases suggest that HPS was truly associated with Crohn’s disease variant with early onset and severe course. The search for the molecular causes of the disease in some individuals may help in the development of new therapeutic and surgical approaches, as well in the improvement of understanding of premalignant inflammatory conditions in a large bowel.