gebhart/patrepeval huggingface dataset:
Identification of granzyme A isolated from cytotoxic T‐lymphocyte‐granules as one of the proteases encoded by CTL‐specific genes (1986)

A serine esterase called granzyme A, which is specifically expressed in cytolytic lymphocytes has been characterized. It is a disulfide-linked dimer and exhibits a trypsin-like specificity cleaving best after Arg. N-terminal sequence analysis revealed that granzyme A is identical to a protease recently predicted from a cloned CTL-specific gene.
Chemical composition and biological activity of the essential oil obtained from Bupleurum marginatum (Apiaceae) (2009)

The essential oil of B. marginatum exhibited a promising anti-inflammatory activity along with strong cytotoxicity against many cancer cells (CCRF-CEM and HepG2) mediated through induction of apoptosis, and this in-vitro activity make its local traditional uses rational. However, its limited antimicrobial activity indicates that a combination with other drugs is essential for effective use. Further selectivity testing is required to evaluate the effect of the oil against normal cells.
Apurinic Endonuclease Activity in Adult Gliomas and Time to Tumor Progression after Alkylating Agent-Based Chemotherapy and after Radiotherapy (2004)

Our data suggest that Ap endo activity mediates resistance to alkylating agents and radiation and may be a useful predictor of progression after adjuvant therapy in a subset of gliomas.
In Vitro Synthesis of Hyaluronan by a Single Protein Derived from Mouse HAS1 Gene and Characterization of Amino Acid Residues Essential for the Activity (2000)

HAS1 was expressed as a FLAG-tagged HAS1 fusion protein in COS-1 cells. This recombinant protein was extracted with CHAPS (3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonic acid) from the membrane fraction and purified by anti-FLAG affinity chromatography and subsequent SDS-polyacrylamide gel electrophoresis. A protein solubilized from the one single band on the gel was able to synthesize hyaluronan when incubated with UDP-GlcNAc and UDP-GlcA as donor substrates without any further additions. The detergent-solubilized and purified HAS1 protein, however, exhibited quite different kinetic properties from the membrane-bound protein. When assayed under the reconstitutive conditions where the reaction mixture was layered onto the buffer containing high concentration of CHAPS, the activity was enhanced and the kinetic properties became similar to those of the membrane-bound protein. In addition, a HAS1 gene product by an in vitro transcription/translation system also showed HAS1 activity under the reconstitutive conditions. To our surprise, when incubated with UDP-GlcNAc alone, the protein was found to synthesize chito-oligosaccharide. Taking advantage of these enzyme reaction properties, active sites on the protein involved in for hyaluronan and chito-oligosaccharide synthesis were characterized. Site-directed mutagenesis induced in the cytoplasmic central loop domain of the protein revealed that several amino acid residues conserved among those domains of various proteins of a HAS family were essential for both hyaluronan and chito-oligosaccharide syntheses but one of them was not for chito-oligosaccharide synthesis. The substitutions that caused partial or severe loss of the activity gave no significant changes of the K(m) values of the mutated proteins, suggesting that no conformational or other indirect changes were involved in the effect. Taken together, the results suggest that the HAS1 protein alone is able to synthesize hyaluronan and different amino acid residues on the cytoplasmic central loop domain are involved in transferring GlcNAc and GlcA residues, respectively.
3D Proximal Tubule Tissues Recapitulate Key Aspects of Renal Physiology to Enable Nephrotoxicity Testing (2017)

Due to its exposure to high concentrations of xenobiotics, the kidney proximal tubule is a primary site of nephrotoxicity and resulting attrition in the drug development pipeline. Current pre-clinical methods using 2D cell cultures and animal models are unable to fully recapitulate clinical drug responses due to limited <i>in vitro</i> functional lifespan, or species-specific differences. Using Organovo's proprietary 3D bioprinting platform, we have developed a fully cellular human <i>in vitro</i> model of the proximal tubule interstitial interface comprising renal fibroblasts, endothelial cells, and primary human renal proximal tubule epithelial cells to enable more accurate prediction of tissue-level clinical outcomes. Histological characterization demonstrated formation of extensive microvascular networks supported by endogenous extracellular matrix deposition. The epithelial cells of the 3D proximal tubule tissues demonstrated tight junction formation and expression of renal uptake and efflux transporters; the polarized localization and function of P-gp and SGLT2 were confirmed. Treatment of 3D proximal tubule tissues with the nephrotoxin cisplatin induced loss of tissue viability and epithelial cells in a dose-dependent fashion, and cimetidine rescued these effects, confirming the role of the OCT2 transporter in cisplatin-induced nephrotoxicity. The tissues also demonstrated a fibrotic response to TGFβ as assessed by an increase in gene expression associated with human fibrosis and histological verification of excess extracellular matrix deposition. Together, these results suggest that the bioprinted 3D proximal tubule model can serve as a test bed for the mechanistic assessment of human nephrotoxicity and the development of pathogenic states involving epithelial-interstitial interactions, making them an important adjunct to animal studies.
PV Power Injection and Active Power Filtering With Amplitude-Clamping and Amplitude-Scaling Algorithms (2007)

This paper presents a half-bridge single-phase two-wire (1phi2W) photovoltaic (PV) inverter system that can perform both active power filtering and real power injection. In the proposed system, it needs only two active switches, reducing cost significantly. In addition, output current of the inverter can be controlled to prevent switches from exceeding their current ratings. Thus, power rating of the inverter can be effectively used and power quality can be improved. For controlling inverter output current, an amplitude-clamping algorithm and an amplitude-scaling algorithm are proposed, which can determine inverter current command without needs of complicated calculation. Simulations and experimental results have verified the feasibility of the proposed PV inverter system and the two current control algorithms
Three outbreaks of yersinia pseudotuberculosis infection. (1988)

Three outbreaks of Yersinia pseudotuberculosis infection during 1982 to 1984 in Okayama Prefecture, Japan are described. In outbreak A, Yersinia pseudotuberculosis a causal organism was detected in 16 patients (serotype 5A). The latent period of the infection was 2 to 20 days estimating, from time of ingesting food suspected of being contaminated and onset of the illness. Outbreak B and C occurred in remote mountain areas. In outbreak B, Yersinia pseudotuberculosis bacilli were detected in the feces of 35 out of 276 people (serotype 4B in 34 stools, 2C and 4B in one stool). In outbreak C, 12 children became sick; one of the 4 patients whose stools were examined, showed an organism belonging to serotype 4B. The inhabitants in the area of outbreak B and C took unchlorinated mountain stream and well water for drinking. After the outbreak B and C, we examined water and wild animals fecea in these areas for the bacilli. As a result, they were detected in 3 out of 51 water samples (serotype 4A in one, 6 in 2 samples) and 2 out of 57 wild animal fecal samples (serotype 2C in 2 samples) in B area, and 4 out of 33 water samples (serotype 4A in 2, 4B in 2 samples) in C area.
The Synthesis of the 2-Amino-3-(3-indolyl)-butyric Acids (β-Methyltryptophans) (1957)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTThe Synthesis of the 2-Amino-3-(3-indolyl)-butyric Acids (β-Methyltryptophans)H. R. Snyder and Donald S. MattesonCite this: J. Am. Chem. Soc. 1957, 79, 9, 2217–2221Publication Date (Print):May 1, 1957Publication History Published online1 May 2002Published inissue 1 May 1957https://pubs.acs.org/doi/10.1021/ja01566a050https://doi.org/10.1021/ja01566a050research-articleACS PublicationsRequest reuse permissionsArticle Views705Altmetric-Citations63LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
The Role of Spirituality in Living with Disabilities (2005)

Abstract This paper reviews the existing literature on the role of spirituality in the experiences of people with disabilities as well as parents of children with disabilities. Spirituality appears to provide meanings, inner strength, peace, and hope to both groups of individuals. In addition, many experience self-transformation through living with disability, becoming more mature and compassionate. Future research is needed to explore the deeper role of spirituality to expand and deepen our understanding of the core nature of spirituality in living with disabilities. There is also a need for research on how to integrate spirituality into the practice of working with individuals with disabilities as well as families of children with disabilities.
An Efficient Stereoselective Synthesis of Penaresidin A from (E)-2-Protected Amino-3,4-unsaturated Sulfoxide (2009)

An efficient, modular, asymmetric synthesis of penaresidin A is disclosed. A beta-protected amino-gamma,delta-unsaturated sulfoxide was prepared by stereoselective addition of the lithio anion of (R)-methyl p-tolyl sulfoxide to an unsaturated sulfinylimine. The pendant sulfoxide group was used as an intramolecular nucleophile to functionalize an alkene regio- and stereoselectively to furnish a bromohydrin, which was employed as the key intermediate in the preparation of the azetidine subunit of penaresidin A. The stereogenic centers of the side chain were introduced by a regioselective opening of an epoxide. Julia-Kocienski olefination was used to couple the azetidine and side chain subunits. The methodology disclosed herein is also useful for the synthesis of ribo- and arabino-phytosphingosines and compounds possessing the amino alcohol moiety.
Experimental Generation of SNP Haplotype Signatures in Patients with Sickle Cell Anaemia (2010)

Phased haplotypes yield more information than the individual marker genotypes. Procedures such as the one described here would therefore benefit genetic mapping and functional studies as well as diagnostic procedures where the identity or parental origin of short genetic fragments is of importance.
The Reactivity of the 5-Hydroxy-5,6-dihydrothymidin-6-yl Radical in Oligodeoxyribonucleotides (2005)

Hydroxyl radical can be induced from Fenton reaction or gamma radiolysis of water. It can add preferentially to the C5 position of thymidine to give the 5-hydroxy-5,6-dihydrothymidin-6-yl radical. In this report, we examined the independent generation and reactivity of this radical in oligodeoxyribonucleotides (ODNs). Our results showed that the major products originated from this radical in single- and double-stranded ODNs were thymidine glycol, 5-hydroxy-5,6-dihydrothymidine, thymidine, and abasic site lesion. A cross-linking lesion, where the C6 of 5-hydroxy-5,6-dihydrothymidine and the C8 of its neighboring guanine are covalently bonded, could be induced from the independently generated radical in dinucleoside monophosphate and trinucleoside diphosphates. The formation of this type of cross-link product in duplex ODNs from either the independently generated radical or gamma irradiation was near or below the detection limit of the LC-MS/MS method that we used.
Hepcidin as a therapeutic tool to limit iron overload and improve anemia in β-thalassemic mice (2010)

Excessive iron absorption is one of the main features of β-thalassemia and can lead to severe morbidity and mortality. Serial analyses of β-thalassemic mice indicate that while hemoglobin levels decrease over time, the concentration of iron in the liver, spleen, and kidneys markedly increases. Iron overload is associated with low levels of hepcidin, a peptide that regulates iron metabolism by triggering degradation of ferroportin, an iron-transport protein localized on absorptive enterocytes as well as hepatocytes and macrophages. Patients with β-thalassemia also have low hepcidin levels. These observations led us to hypothesize that more iron is absorbed in β-thalassemia than is required for erythropoiesis and that increasing the concentration of hepcidin in the body of such patients might be therapeutic, limiting iron overload. Here we demonstrate that a moderate increase in expression of hepcidin in β-thalassemic mice limits iron overload, decreases formation of insoluble membrane-bound globins and reactive oxygen species, and improves anemia. Mice with increased hepcidin expression also demonstrated an increase in the lifespan of their red cells, reversal of ineffective erythropoiesis and splenomegaly, and an increase in total hemoglobin levels. These data led us to suggest that therapeutics that could increase hepcidin levels or act as hepcidin agonists might help treat the abnormal iron absorption in individuals with β-thalassemia and related disorders.
Basic fibroblast growth factor enhances axonal sprouting after cortical injury in rats (1999)

The trophic factors responsible for initiating and guiding the outgrowth of axons have proven to be elusive throughout most of this century. Entorhinal cortex injury, which denervates the hippocampal formation of rats, induces axonal sprouting by several surviving hippocampal afferents and results in a significant elevation of growth factors, one of which is basic fibroblast growth factor (bFGF). The possibility that bFGF may regulate lesion-induced hippocampal sprouting was examined by making i.v. bFGF infusions into rats with unilateral entorhinal lesions. Basic FGF treatment significantly increased sprouting by the cholinergic septodentate pathway. Thus, the increase in bFGF following central nervous system injury may signal its role in the regulation of injury-related axonal remodeling of a cholinergic pathway.
Basal membrane heparan sulphate proteoglycan expression during wound healing in human skin (1997)

Heparan sulphate proteoglycans (HSPGs) are integral components of the basement membrane (BM) in various tissues. HSPGs are important in the assembly and structure of the BM, and their putative functions include regulation of basement membrane permeability, binding of growth factors, and a role in cellular adhesion. In this study the expression of HSPG was examined during wound healing in human skin, using monoclonal antibodies (MAbs) that recognize the HSPG core protein and two different heparan sulphate (HS) epitopes, and the dynamics of HSPG expression were investigated in relation to epidermal cellular proliferation and permeability of the BM. Healing of excisional wounds in healthy volunteers was studied from day 0 up to 1 year. Intact human skin showed strong continuous staining of the dermo-epidermal BM and the vascular BM with all MAbs. Up to day 4 after wounding, staining for HSPG was absent under the ingrowing epidermis, with any of the MAbs, indicating that no complete BM was present. From day 7 onwards, the BM of the neo-epidermis showed positive staining for the HSPG core protein and a low sulphated HS epitope, and after day 14, the staining intensity was similar to normal skin. The staining patterns of these HSPG epitopes were similar to that of laminin. The staining pattern with a MAb against an epitope in the highly sulphated part of HS was found to be distinct from the other BM markers studied. This epitope was absent under the neo-epidermis up to 2 months after wounding. One year after wounding, the epitope was found to be present again. We observed that only in the time period between 2 months and 1 year had the epidermis normalized with respect to the number of cycling cells and the absence of high molecular weight plasma proteins. These findings suggest a correlation between normalization of epidermal proliferation, BM permeability, and regeneration of BM HS. It is proposed that complete BM maturation following skin wounding is a slow process and may account for the epidermal abnormalities that persist for a considerable period of time after wound healing.
The neurofibromatosis 2 tumor suppressor protein interacts with hepatocyte growth factor-regulated tyrosine kinase substrate (2000)

The neurofibromatosis 2 tumor suppressor protein schwannomin/merlin is commonly mutated in schwannomas and meningiomas. Schwannomin, a member of the 4.1 family of proteins, which are known to link the cytoskeleton to the plasma membrane, has little known function other than its ability to suppress tumor growth. Using yeast two-hybrid interaction cloning, we identified the HGF-regulated tyrosine kinase substrate (HRS) as a schwannomin interactor. We verified the interaction by both immunoprecipitation of endogenous HRS with endogenous schwannomin in vivo as well as by using bacterially purified HRS and schwannomin in vitro. We narrowed the regions of interaction to include schwannomin residues 256-579 and HRS residues from 480 to the end of either of two HRS isoforms. Schwannomin molecules with a L46R, L360P, L535P or Q538P missense mutation demonstrated reduced affinity for HRS binding. As HRS is associated with early endosomes and may mediate receptor translocation to the lysosome, we demonstrated that schwannomin and HRS co-localize at endosomes using the early endosome antigen 1 in STS26T Schwann cells by indirect immunofluorescence. The identification of schwannomin as a HRS interactor implicates schwannomin in HRS-mediated cell signaling.
Peginesatide for the treatment of anemia due to chronic kidney disease – an unfulfilled promise (2016)

The case of peginesatide illustrates the difficulties in detecting rare sADRs in trials with limited patient populations and the need for improved pharmacovigilance after marketing approval. However, the need for simpler drug production methods as a result of non-dependence on recombinant DNA techniques and mammalian cell lines remains. Lessons learned during the scientific development of peginesatide can be used in developing other drugs.
gp130 and c-Kit signalings synergize for ex vivo expansion of human primitive hemopoietic progenitor cells. (1995)

gp130, a signal-transducing receptor component of interleukin 6 (IL-6), associates with an IL-6 and IL-6 receptor (IL-6) complex and transduces signals. To examine the role of gp130 signaling in the expansion of human hemopoietic progenitor cells, we tested the effects of a recombinant soluble human IL-6 receptor (sIL-6R) and/or IL-6 in combination with other cytokines on purified human umbilical cord blood CD34+ cells, using methylcellulose clonal assay and suspension culture in the presence or absence of serum. A combination of sIL-6R and IL-6 (sIL-6R/IL-6), but not sIL-6R or IL-6 alone, was found to dramatically stimulate expansion of hemopoietic progenitor cells as well as CD34+ cells in the presence of stem cell factor. Significant generation of multipotential hemopoietic progenitors over a period of 3 weeks in suspension culture and efficient formation of colonies, especially multilineage and blast cell colonies, in methylcellulose assay supplemented with a combination of sIL-6R/IL-6 together with stem cell factor were observed in serum-containing and serum-free culture. Addition of anti-gp130 monoclonal antibodies or anti-IL-6R monoclonal antibodies to the above cultures dose-dependently inhibited the expansion of progenitor cells in suspension culture and also completely blocked the formation of multilineage colonies in methylcellulose culture. These findings demonstrated that the significant expansion of human primitive hemopoietic progenitors could be achieved with the gp130 and c-Kit signalings initiated by the sIL-6R/IL-6 complex in the presence of stem cell factor and suggested the possible application of this method for ex vivo expansion of CD34+ cells for bone marrow transplantation.
Interstrand Cross-Links:  A New Type of γ-Ray Damage in Bromodeoxyuridine-Substituted DNA (2005)

Interstrand cross-links (ICL) represent one of the most toxic types of DNA damage for dividing cells. They are induced both by natural products (e.g., psoralens + UVA) and by several chemical agents, some of which are used in chemotherapy (e.g., carboplatin and mitomycin C). Although repair mechanisms exist for interstrand cross-links, these lesions can induce mutations, chromosomal rearrangements, and cell death. Here, we report, for the first time, the formation of ICL by gamma-rays in brominated DNA. It is well established that the radiosensitization properties of bromodeoxyuridine (BrdUrd) result primarily from the electrophilic nature of the bromine, making it a good leaving group and leading to the irreversible formation of a uridinyl radical (dUrd(*)) or uridinyl anion (dUrd-) upon addition of an electron. We observe that the radiolytic loss of the bromine atom is greatly suppressed in double-stranded compared to single-stranded DNA. We have used a model DNA containing a bulge, formed by five mismatched bases, and have observed a linear dose-response for the formation of strand breaks on the single-stranded regions of both the brominated strand and the opposite nonbrominated strand. Surprisingly, we have observed the formation of interstrand cross-links exclusively in the mismatched region. Thus, we propose that the radiosensitization effects of bromodeoxyuridine in vivo will almost certainly be limited to single strand regions such as found in transcription bubbles, replication forks, mismatched DNA, and possibly the loop region of telomeres. Our results suggest that interstrand cross-links may contribute to the radiosensitization effects of BrdUrd. These findings may have profound implications for the clinical use of bromodeoxyuridine as a radiosensitizer, as well as for the development of targeted radiosensitizers.
Autism and Our Intestinal Microbiota (2015)

Microbial products, released into the bloodstreams of mammals including humans, cross the blood-brain barrier and influence neurodevelopment. They can either promote or alleviate neurological disorders including autism spectrum disorders (ASD). This editorial describes how our microbiota influence our feelings, attitudes and mental states with particular reference to ASD.
No association of age-related maculopathy susceptibility protein 2/HtrA serine peptidase 1 or complement factor H polymorphisms with early age-related maculopathy in a Chinese cohort. (2013)

The association of ARMS2/HTRA1 and CFH SNPs in early ARM was not detected in our cohort. The findings in the current study indicated that the effects of ARMS2/HTRA1 and CFH in early ARM could be much lower compared to those in AMD.