gebhart/patrepeval huggingface dataset:
Alternative sources of gametes: reality or science fiction? (2000)

Although great progress has been made in both the investigation and treatment of infertility, a considerable number of patients still fail to conceive. Spermatogenic failure and/or oocyte ageing appear to be responsible for a large proportion of cases. The use of donor gametes may bring legal, ethical and even social problems of acceptance that can discourage infertile couples from the donor route. Fortunately, emerging reproductive technologies and preliminary results from animal experiments provide some hope for alternative sources of gametes through which these infertile patients can finally conceive their own genetic child. In conjunction with intracytoplasmic sperm injection (ICSI), fertilization of human oocytes with immature sperm precursors, e.g. spermatids and even secondary spermatocytes, has resulted in healthy babies. Pregnancies have also resulted from the use of spermatids derived from in-vitro spermatogenesis. In the mouse, even primary spermatocytes appear able to participate in normal embryogenesis. In view of the possibility for transplantation and even xenotransplantation of spermatogonia to a host testis in animals, a similar use of human male stem cells might provide an attractive source for the treatment of males with arrested spermatogenesis, as well as male cancer patients. Transplantation of somatic cell nuclei and their haploidization within oocytes may prove to be a practical way of eradicating age-related aneuploidy and so constitute an innovative source of healthy oocytes. Most importantly, however, the safety of the procedures described here needs to be proven before their application to the human arena. Finally, we discuss the implications of cytoplasmic quality and of genetic imprinting in the context of these manipulations.
The PspA Protein of Escherichia coli Is a Negative Regulator of ς 54 -Dependent Transcription (2000)

In Eubacteria, expression of genes transcribed by an RNA polymerase holoenzyme containing the alternate sigma factor sigma(54) is positively regulated by proteins belonging to the family of enhancer-binding proteins (EBPs). These proteins bind to upstream activation sequences and are required for the initiation of transcription at the sigma(54)-dependent promoters. They are typically inactive until modified in their N-terminal regulatory domain either by specific phosphorylation or by the binding of a small effector molecule. EBPs lacking this domain, such as the PspF activator of the sigma(54)-dependent pspA promoter, are constitutively active. We describe here the in vivo and in vitro properties of the PspA protein of Escherichia coli, which negatively regulates expression of the pspA promoter without binding DNA directly.
Role of Matrix Metalloproteinases in Photoaging and Photocarcinogenesis (2016)

Matrix metalloproteinases (MMPs) are zinc-containing endopeptidases with an extensive range of substrate specificities. Collectively, these enzymes are able to degrade various components of extracellular matrix (ECM) proteins. Based on their structure and substrate specificity, they can be categorized into five main subgroups, namely (1) collagenases (MMP-1, MMP-8 and MMP-13); (2) gelatinases (MMP-2 and MMP-9); (3) stromelysins (MMP-3, MMP-10 and MMP-11); (4) matrilysins (MMP-7 and MMP-26); and (5) membrane-type (MT) MMPs (MMP-14, MMP-15, and MMP-16). The alterations made to the ECM by MMPs might contribute in skin wrinkling, a characteristic of premature skin aging. In photocarcinogenesis, degradation of ECM is the initial step towards tumor cell invasion, to invade both the basement membrane and the surrounding stroma that mainly comprises fibrillar collagens. Additionally, MMPs are involved in angiogenesis, which promotes cancer cell growth and migration. In this review, we focus on the present knowledge about premature skin aging and skin cancers such as basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and melanoma, with our main focus on members of the MMP family and their functions.
A Phase I Dose-Finding Study of the Novel Toll-like Receptor 8 Agonist VTX-2337 in Adult Subjects with Advanced Solid Tumors or Lymphoma (2014)

VTX-2337 is clinically well tolerated and biologically active with a predictable pharmacokinetic profile. Suitable doses for testing in combination studies were identified. Phase II placebo-controlled studies of VTX-2337 in combination with doxorubicin in ovarian cancer, and in combination with platinum chemotherapy, 5 FU, and cetuximab in head and neck cancer have been initiated (NCT #01666444 and NCT#01836029).
Nitric oxide synthesis inhibition alters rat cutaneous wound healing (2006)

L-NAME-treated animals presented delayed wound contraction, alterations in collagen organization, and neoepidermis thickness. The inhibition of NO synthesis increased mast cell migration 7 days after wounding, but decreased 21 days after wounding. Volume density of vessels was decreased in L-NAME-treated animals, 21 days after lesion. Surface density of vessels was frequently smaller in L-NAME-treated animals than in controls. CONCLUSIONS; The blockade of NO synthesis impaired cutaneous wound healing, acting in early and late phases of wound repair.
Effect of Immunization With Homologous LDL and Oxidized LDL on Early Atherosclerosis in Hypercholesterolemic Rabbits (1996)

Although the existence of an immune response against modified lipoproteins in atherosclerosis has been observed in experimental animals as well as in humans, the precise pathophysiological relevance of these findings remains unclear. In this study we determined the effect of an immunization with homologous LDL and copper-oxidized LDL on the formation of atherosclerotic plaque in hypercholesterolemic rabbits. Immunizations were performed at the start of a cholesterol-rich diet and 3 weeks later. After 16 weeks, antibodies against oxidized LDL had developed in rabbits given hypercholesterolemic diet alone, but the titers were increased by twofold in rabbits immunized with oxidized LDL as well as in rabbits immunized with LDL, suggesting that the LDL had also become oxidized during the preparation and/or immunization procedure. Immunization with LDL and oxidized LDL reduced atherosclerotic lesions in the proximal aorta by 74% ( P &lt;.05) and 48% ( P =NS), respectively. The cellular composition of the lesions was not affected by the immunizations. These results support the hypothesis that an immune response against modified LDL has a protective effect against the development of early atherosclerotic lesions.
Outcome Prediction in Patients with Glioblastoma by Using Imaging, Clinical, and Genomic Biomarkers: Focus on the Nonenhancing Component of the Tumor (2014)

Patients with high rCBVNER and NER crossing the midline and those with high rCBVNER and wild-type EGFR mutation showed poor survival. In multivariable survival models, however, rCBVNER provided unique prognostic information that went above and beyond the assessment of all NER imaging features, as well as clinical and genomic features.
A Structured Self-attentive Sentence Embedding (2017)

This paper proposes a new model for extracting an interpretable sentence embedding by introducing self-attention. Instead of using a vector, we use a 2-D matrix to represent the embedding, with each row of the matrix attending on a different part of the sentence. We also propose a self-attention mechanism and a special regularization term for the model. As a side effect, the embedding comes with an easy way of visualizing what specific parts of the sentence are encoded into the embedding. We evaluate our model on 3 different tasks: author profiling, sentiment classification, and textual entailment. Results show that our model yields a significant performance gain compared to other sentence embedding methods in all of the 3 tasks.
Identification ofMycobacterium tuberculosisRNAs synthesized in response to phagocytosis by human macrophages by selective capture of transcribed sequences (SCOTS) (1999)

A widely applicable, positive cDNA selection method was developed to identify RNAs synthesized by Mycobacterium tuberculosis in response to phagocytosis by cultured human primary macrophages. cDNAs for sigE and sigH (alternative sigma factors), aceA (isocitrate lyase), ponA (class I penicillin-binding protein), pks2 (polyketide synthase), uvrA (UvrABC endonuclease), and ctpV (putative cation transporter) were obtained from macrophage-grown bacteria. cDNAs for ORFs Rv3070, Rv3483c, Rv0903c (encoding a putative bacterial two-component transcriptional activator), and Rv0170 of the mce1 virulence operon also were obtained from phagocytized bacilli. cDNAs for these genomic regions were not obtained from approximately 1, 000-fold more bacteria grown in laboratory broth. Methods described here, which have identified M. tuberculosis genes expressed in response to host interaction, will allow the study of gene expression in a variety of microorganisms, including expression resulting from interaction with human tissues in natural disease states.
Protein-Sized Quantum Dot Luminescence Can Distinguish between "Straight", "Bent", and "Kinked" Oligonucleotides (1995)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTProtein-Sized Quantum Dot Luminescence Can Distinguish between "Straight", "Bent", and "Kinked" OligonucleotidesRahina Mahtab, Jessica P. Rogers, and Catherine J. MurphyCite this: J. Am. Chem. Soc. 1995, 117, 35, 9099–9100Publication Date (Print):September 1, 1995Publication History Published online1 May 2002Published inissue 1 September 1995https://doi.org/10.1021/ja00140a040RIGHTS & PERMISSIONSArticle Views655Altmetric-Citations170LEARN 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 InReddit PDF (979 KB) Get e-Alerts Get e-Alerts
Inactivation of the acid labile subunit gene in mice results in mild retardation of postnatal growth despite profound disruptions in the circulating insulin-like growth factor system (2000)

Insulin-like growth factors (IGFs) I and II are important regulators of cell proliferation and differentiation. After birth, plasma IGFs, representing mostly liver-derived IGFs, circulate in ternary complexes of 150 kDa consisting of one molecule each of IGF, IGF-binding protein (IGFBP) 3, and an acid labile subunit (ALS). Onset of ALS synthesis after birth is the primary factor driving the formation of ternary complexes. Capture of IGFs by ALS is thought to allow the development of a plasma reservoir without negative effects such as hypoglycemia and cell proliferation. To evaluate the importance of ALS and ternary complexes, we have created mice in which the ALS gene has been inactivated. The mutation was inherited in a Mendelian manner, without any effects on survival rates and birth weights. A growth deficit was observed in null mice after 3 weeks of life and reached 13% by 10 weeks. This modest phenotype was observed despite reductions of 62 and 88% in the concentrations of plasma IGF-I and IGFBP-3, respectively. Increased turnover accounted for these reductions because indices of synthesis in liver and kidney were not decreased. Surprisingly, absence of ALS did not affect glucose and insulin homeostasis. Therefore, ALS is required for postnatal accumulation of IGF-I and IGFBP-3 but, consistent with findings supporting a predominant role for locally produced IGF-I, is not critical for growth. This model should be useful to determine whether presence of ALS is needed for other actions of liver-derived IGF-I and for maintenance of homeostasis in presence of high circulating levels of IGF-II.
Levetiracetam has an activity‐dependent effect on inhibitory transmission (2012)

LEV exerts a qualitatively similar, frequency-dependent effect on both IPSCs and EPSCs. The much shorter latency for IPSC reduction is consistent with the greater levels of spontaneous inhibition in brain slices, supporting the hypothesis that vesicular uptake is necessary for the entry of LEVs into terminals. The vesicular entry of LEV resembles the cell entry pathways for tetanus and botulinum neurotoxins, but is unique for small, neuroactive drugs. Although the reduction of IPSC trains by LEV initially seems counterintuitive for an antiepileptic drug, there are multiple reasons that disruption of γ-aminobutyric acid (GABA) release could ultimately attenuate pathologic discharges.
Term rewriting with traversal functions (2003)

Term rewriting is an appealing technique for performing program analysis and program transformation. Tree (term) traversal is frequently used but is not supported by standard term rewriting. We extend many-sorted, first-order term rewriting with traversal functions that automate tree traversal in a simple and type-safe way. Traversal functions can be bottom-up or top-down traversals and can either traverse all nodes in a tree or can stop the traversal at a certain depth as soon as a matching node is found. They can either define sort-preserving transformations or mappings to a fixed sort. We give small and somewhat larger examples of traversal functions and describe their operational semantics and implementation. An assessment of various applications and a discussion conclude the article.
Laminin-332 Is a Substrate for Hepsin, a Protease Associated with Prostate Cancer Progression (2008)

Hepsin, a cell surface protease, is widely reported to be overexpressed in more than 90% of human prostate tumors. Hepsin expression correlates with tumor progression, making it a significant marker and target for prostate cancer. Recently, it was reported that in a prostate cancer mouse model, hepsin up-regulation in tumor tissue promotes progression and metastasis. The underlying mechanisms, however, remain largely uncharacterized. Hepsin transgenic mice displayed reduced laminin-332 (Ln-332) expression in prostate tumors. This is an intriguing cue, since proteolytic processing of extracellular matrix macromolecules, such as Ln-332, is believed to be involved in cancer progression, and Ln-332 expression is lost during human prostate cancer progression. In this study, we provide the first direct evidence that hepsin cleaves Ln-332. Cleavage is specific, since it is both inhibited in a dose-dependent manner by a hepsin inhibitor (Kunitz domain-1) and does not occur when catalytically inactive hepsin is used. By Western blotting and mass spectrometry, we determined that hepsin cleaves the beta3 chain of Ln-332. N-terminal sequencing identified the cleavage site at beta3 Arg(245), in a sequence context (SQLR(245) LQGSCFC) conserved among species and in remarkable agreement with reported consensus target sequences for hepsin activity. In vitro cell migration assays showed that hepsin-cleaved Ln-332 enhanced motility of DU145 prostate cancer cells, which was inhibited by Kunitz domain-1. Further, hepsin-overexpressing LNCaP prostate cancer cells also exhibited increased migration on Ln-332. Direct cleavage of Ln-332 may be one mechanism by which hepsin promotes prostate tumor progression and metastasis, possibly by up-regulating prostate cancer cell motility.
Regulation of Sucrose-6-Phosphate Hydrolase Activity in Streptococcus mutans : Characterization of the scrR Gene (1998)

Previous results have implicated an important role for the enzyme IIScr, the sucrose-specific permease, in the transport of sucrose by cariogenic Streptococcus mutans. The product of the scrB gene, sucrose-6-phosphate hydrolase (Suc-6PH), is required for the metabolism of phosphorylated sucrose. The results from the utilization of scrB::lacZ fusions in S. mutans GS-5 have suggested that sucrose-grown cells have higher levels of scrB gene expression than do cells grown with glucose or fructose. Northern blot analysis of scrB transcripts has also confirmed the relative strengths of expression as sucrose>glucose>fructose. Immediately downstream from the scrB gene, an open reading frame with homology to regulatory proteins of the GalR-LacI family as well as to ScrR proteins from several other bacteria has been identified. In addition, this gene appears to be transcribed in the same operon as scrB. Inactivation of this gene, scrR, did not alter the relative expression of the scrB gene in the presence of sucrose or fructose but did increase SUC-6PH levels in the presence of glucose to that observed with sucrose. Furthermore, the S. mutans ScrR homolog appears to bind to the scrB promoter region as determined from the results of gel shift assays. These results suggest that the scrR gene is involved in the regulation of scrB, and likely scrA, expression. However, it is not clear whether sucrose acts as an inducer of expression of these genes or, alternatively, whether glucose and fructose act as repressors.
Proteolytic specificity of plasmin on bovine αs1‐Casein (1993)

Abstract The proteolytic specificity of plasmin (fibrinolysin, E. C. 3.4.21.7, from bovine plasma) on bovine αs1‐casein was determined in solution in 50 mM ammonium bicarbonate buffer, pH 8.4, at 37°C. Peptides, isolated by reverse‐phase high performance liquid chromatography on a C18 column or by electroblotting from urea‐polyacrylamide gel electrophoretograms, were identified from their amino acid sequence and mass. The principal plasmin cleavage sites were found at Arg22‐Phe23, Arg90‐Tyr91, Lys102‐Lys103, Lys103‐Tyr104, Lys105‐Val106, Lys124‐Glu125 and Arg151‐Gln152. The initial cleavage sites and the order of production of small (pH 4.6‐soluble) peptides suggest that αs1‐casein was cleaved initially towards the centre of the molecule.
Living Carbocationic Polymerization of Isobutylene with Blocked Bifunctional Initiators in the Presence of Di-tert-butylpyridine as a Proton Trap (1992)

Abstract The polymerization of isobutylene (IB) has been studied using 5-tert-butyl-1,3-dicumyl-chloride, 5-tert-butyl-1,3-dicumyl-methyl ether, and 5-tert-butyl-1,3-dicumyl-acetate initiators in the absence and presence of 2,6-di-tert-butylpyridine (DTBP) as a proton trap. It is demonstrated that living polymerization can be achieved in the IB/initiator/TiCl4/methylchloride-n-hexane (40:60 v:v)/DTBP/-80°C system, and that polymers with close to a Poisson molecular weight distribution can be obtained in the presence of a proton trap in concentrations only slightly higher than the concentration of protic impurities in the system. The polymerization rate is a first-order function of the monomer concentration and is not affected by the excess amount of DTBP added, which indicates that the living nature of the polymerization is not due to carbocation stabilization.
An Appeal to Medical Journal Editors: The Need for a Full Description of Laboratory Methods and Specimen Handling in Clinical Study Reports (2012)

We, the editors of the laboratory medicine journals, urge our colleagues in the International Committee of Medical Journal Editors (ICMJE)1 to adopt and enforce the following requirements for clini...
Genetic Analysis and Complete Primary Structure of Microcin L (2004)

Escherichia coli LR05, in addition to producing MccB17, J25, and D93, secretes microcin L, a newly discovered microcin that exhibits strong antibacterial activity against related Enterobacteriaceae, including Salmonella enterica serovars Typhimurium and Enteritidis. Microcin L was purified using a two-step procedure including solid-phase extraction and reverse-phase C(18) high-performance liquid chromatography. A 4,901-bp region of the DNA plasmid of E. coli LR05 was sequenced revealing that the microcin L cluster consists of four genes, mclC, mclI, mclA, and mclB. The structural gene mclC encoded a 105-amino-acid precursor with a 15-amino-acid N-terminal extension ending with a Gly-Ala motif upstream of the cleavage site. This motif is typical of the class II microcins and other gram-positive bacteriocins exported by ABC transporters. The mclI immunity gene was identified upstream of the mclC gene and encodes a 51-amino-acid protein with two potential transmembrane domains. Located on the reverse strand, two genes, mclA and mclB, encoded the proteins MclA and MclB, respectively. They bear strong relatedness with the ABC transporter proteins and accessory factors involved in the secretion of microcins H47, V, E492, and 24. The microcin L genetic system resembles the genetic organization of MccV. Furthermore the MccL primary structure has been determined. It is a 90-amino-acid peptide of 8,884 Da with two disulfide bridges. The N-terminal region has significant homologies with several gram-positive bacteriocins. The C-terminal 32-amino-acid sequence is 87.5% identical to that of MccV. Together, these results strongly indicate that microcin L is a gram-negative class II microcin.
Upstream promoter element of the human metallothionein-IIA gene can act like an enhancer element. (1985)

Initiation of transcription by RNA polymerase II in eukaryotes is strongly increased by cis-acting genetic elements, known as activators or enhancers. Enhancers, first detected in simian virus 40 (SV40), were subsequently also found to control the expression of several cellular genes. The human metallothionein-IIA (hMT-IIA) gene, although inducible by heavy metals and glucocorticoids, is widely expressed in most cell types in the absence of inducers. Here we show that the high basal level of transcription of the hMT-IIA gene is due to the presence of an enhancer element within the hMT-IIA promoter region. The structural and functional organization of this cellular enhancer element in two direct repeats is strikingly similar to that of the enhancer element of SV40. This suggests a possible functional and evolutionary relationship between enhancers and upstream promoter elements.
Pathogenesis of the anemia of chronic disease: A cytokine‐mediated anemia (1995)

The anemia found in patients with chronic infectious, inflammatory and neoplastic disorders, known as the anemia of chronic disease (ACD), is one of the most common syndromes in medicine. A characteristic finding of the disorders associated with ACD is increased production of the cytokines which mediate the immune or inflammatory response, such as tumor necrosis factor, interleukin 1 and the interferons. All the processes involved in the development of ACD can be attributed to these cytokines, including shortened red cell survival, blunted erythropoietin response to anemia, impaired erythroid colony formation in response to erythropoietin and abnormal mobilization of reticuloendothelial iron stores. Improved understanding of the role played by cytokines in the pathogenesis of ACD may lead to the development of more specific therapy for this syndrome.