gebhart/patrepeval huggingface dataset:
Heat-labile proteases in molecular biology applications (2001)

Thermolabile proteases were identified in three Gram-negative psychrotrophic bacteria. The protease from the psychrotrophic strain A9 was purified and its application to common molecular biology techniques was demonstrated. Heat-stable molecular biology enzymes (Taq polymerase and PvuII) were digested by a heat-labile protease, which was then inactivated by a mild heat treatment. The clear benefit of using heat-labile proteases arises in situations where further reactions may be accomplished without an intermediate purification step, thereby saving time and avoiding the possibility of product loss.
Nuclear factor-kappaB activity correlates with growth, angiogenesis, and metastasis of human melanoma cells in nude mice. (2000)

The purpose of this study was to determine the role of nuclear factor (NF)-kappaB/relA activity in the induction of angiogenesis and production of metastasis by human melanoma cells. Highly metastatic melanoma variant cells expressed high levels of constitutive NF-kappaB activity. Transfection of highly metastatic human melanoma variant cells with a dominant-negative mutant inhibitor of nuclear factor-kappaB alpha (Ikappabeta alpha) expression vector (Ikappabeta alphaM) decreased the level of constitutive NF-kappaB activity, inhibited s.c. tumor growth, and prevented lung metastasis in nude mice. Furthermore, the slow-growing s.c. tumors formed by the IkappaB alphaM-transfected cells exhibited a decrease in microvessel density (angiogenesis), which correlated with a decrease in the level of interleukin-8 expression. Collectively, these results demonstrate that NF-kappaB/reLA activity significantly contributes to tumorigenicity, angiogenesis, and metastasis of human melanoma cells implanted in nude mice.
tRNA 5′-end repair activities of tRNA His guanylyltransferase (Thg1)-like proteins from Bacteria and Archaea (2010)

The tRNA(His) guanylyltransferase (Thg1) family comprises a set of unique 3'-5' nucleotide addition enzymes found ubiquitously in Eukaryotes, where they function in the critical G(-1) addition reaction required for tRNA(His) maturation. However, in most Bacteria and Archaea, G(-1) is genomically encoded; thus post-transcriptional addition of G(-1) to tRNA(His) is not necessarily required. The presence of highly conserved Thg1-like proteins (TLPs) in more than 40 bacteria and archaea therefore suggests unappreciated roles for TLP-catalyzed 3'-5' nucleotide addition. Here, we report that TLPs from Bacillus thuringiensis (BtTLP) and Methanosarcina acetivorans (MaTLP) display biochemical properties consistent with a prominent role in tRNA 5'-end repair. Unlike yeast Thg1, BtTLP strongly prefers addition of missing N(+1) nucleotides to 5'-truncated tRNAs over analogous additions to full-length tRNA (k(cat)/K(M) enhanced 5-160-fold). Moreover, unlike for -1 addition, BtTLP-catalyzed additions to truncated tRNAs are not biased toward addition of G, and occur with tRNAs other than tRNA(His). Based on these distinct biochemical properties, we propose that rather than functioning solely in tRNA(His) maturation, bacterial and archaeal TLPs are well-suited to participate in tRNA quality control pathways. These data support more widespread roles for 3'-5' nucleotide addition reactions in biology than previously expected.
Differential expression of neurotrophin receptors during renal development (1993)

Early kidney differentiation is driven by local cell-cell interactions. The metanephrogenic mesenchyme stimulates the epithelial ureter bud to grow and branch, whereas the ureter bud stimulates the mesenchyme to convert into a new epithelium. These interactions may be dependent on local growth factors and their receptors. We studied the expression of receptors for nerve growth factors during kidney development. Expression of the low- and high-affinity receptors was cell-type specific. The low-affinity NGF receptor was found in the uninduced mesenchyme at early developmental stages, but in the glomerular podocytes at later developmental stages. In contrast, the high-affinity trkB receptor was found in the cortical mesenchyme cells that will differentiate into stroma. The trkC receptor was found only weakly expressed and in a few parts of the collecting ducts. The role of these receptors and c-ros, a receptor-type kinase expressed on the tip of the ureter bud, was studied by modified antisense oligonucleotides. However, we found that both sense, antisense and nonsense phosphorothioate oligonucleotides inhibited mouse and rat embryonic kidney development in vitro. The oligonucleotides appeared to be toxic for rodent embryonic kidneys in the experimental conditions that we used. Moreover, oligonucleotides did not penetrate well into the epithelial sheets in the organ cultures. We conclude that studies with phosphorothioate antisense oligonucleotides in organ cultures of embryonic kidneys should be interpreted with caution. Our current data do not allow us to not assign a function for the low- or high-affinity NGF receptors or c-ros in kidney development.
Modeling of heteroduplex formation during PCR from mixtures of DNA templates. (1992)

We have investigated the capability of PCR to amplify a specific locus from each template in a mixture of allelic DNAs. Modeling experiments employed a 300-bp HOX2B segment as target and utilized, as distinct template "alleles," genomic DNAs from 1 human and from 2 chimpanzees known to differ in sequence at the target. Two modes were used: (1) mixtures of PCR products that had been previously amplified individually from a single template and (2) PCR amplification en masse from composite human/chimpanzee genomic DNA templates. Products generated by either mode were separated by denaturing gradient gel electrophoresis (DGGE). Detection of a "trace" allele mixed with a "dominant" one was possible by simple ethidium bromide staining of the gel up to a sensitivity of 1 part in 20. A balanced mixture was represented by 5:5 and 4:3:3 mixtures of allelic PCR products or genomic templates; an uneven mixture of dominant and trace alleles, by 9:1 and 8:1:1 mixtures. For 5:5, two homoduplex bands and two heteroduplex bands of equal intensity were generated. For 9:1, the trace homoduplex disappears whereas the two heteroduplexes are easily visible. For 8:1:1, four heteroduplexes and one homoduplex were observed; homoduplexes and heteroduplexes formed from the trace alleles were not visible. These experiments demonstrate that PCR can amplify mixed allelic templates in direct proportion to the stoichiometric fraction of each template. Trace species are captured as heteroduplexes with the most abundant species and are clearly displaced on denaturing gradient gels from the dominant homoduplex species. Our analytical studies can be applied to analysis of sequence variants in DNA collected from cancerous or infected tissues.(ABSTRACT TRUNCATED AT 250 WORDS)
Antibodies that activate β2 integrins can generate different ligand binding states (1995)

A human erythroleukemic cell line (K562) that does not normally express beta 2 integrins has been transfected with the genes encoding these integrins. The resulting cell lines show minimal background adhesion but can be stimulated to bind to appropriate substrates when activated with either of two different antibodies to CD18. The two antibodies appear to generate different ligand binding states in LFA-1 such that different members of the ICAM family are recognized. Antibody-activated complement receptor type 3 and p150,95-transfected cells bind protein-coated surfaces, although they require slightly different activation conditions for optimal binding.
O4‐09‐03: Ttp488: From futile to fast track (2015)

TTP488 is an oral antagonist of the Receptor for Advanced Glycation Endproducts (RAGE), which was evaluated in a 18-month Phase 2 study in mild to moderate AD patients. Study treatment was discontinued, and the development of TTP488 was halted, when a pre-specified analysis met futility criteria. However, when protocol-specified analyses were executed as originally planned, it was evident that the study had reached its primary endpoint, contrary to the futility analysis predictions. To examine the risks of futility analysis and the precautions that should be taken when executing and interpreting these analyses. Futility analysis was performed on a snapshot of dynamic data, using descriptive statistics only. At study completion and final database lock, pre-specified primary ITT analysis (using ANCOVA with MI) was on the ADAS-cog11. Four pre-specified supportive analyses (MMRM, LOCF, completers, GEE) and a post hoc on-treatment analysis based on the presence of drug in plasma were also employed. Contrary to the futility analysis, ITT analysis demonstrated a decreased decline in ADAS-cog at 18 months (delta=3.1, p=0.008), relative to placebo, in the group initially randomized to low dose TTP488. This was confirmed by all 4 pre-specified supportive analyses. The benefit of the drug was also confirmed in the “on-treatment” analyses. There were no differences between treatment groups in the incidence of adverse events, except for psychiatric disorders, which occurred less frequently in the group treated with TTP488 (nominal p=0.04). The results of the ITT analysis, and the observed beneficial effects on psychiatric adverse events of special interest for AD patients, justify further investigation of low dose TTP488 in Phase 3 trials in patients with mild AD. TTP488 has been granted Fast Track Status by FDA and is entering Phase3 under a Special Protocol Agreement. Futility analyses in AD trials may be misleading and argue for conducting the full analysis plan even when futility criteria are met. Futility analysis should reflect standards of robustness similar to those supporting final conclusions, particularly when discontinuation of study medication is considered in the absence of safety concerns. Trial registration: ClinicalTrials.gov identifier NCT00566397.
QUERCUS (FAGACEAE) IN THE UTAH FLORA (1986)

(Uploaded by Plazi from the Biodiversity Heritage Library) No abstract provided.
Inhibitory Effects of the Gastrin Receptor Antagonist (L-365,260) on Gastrointestinal Tumor Cells (1991)

A selective gastrin receptor (GR) antagonist, L-365,260 is bound to the GR on AR42J cells with a potency 7.5-fold less than G17 (50% inhibitory concentration [IC50] G17, 6 x 10(-9) mol/l; IC50 L365-260, 4.5 x 10(-8) mol/l). G17 is mitogenic for AR42J cells, as assessed by 75Se-selenomethionine uptake and L-365,260 at concentrations of 2.5 x 10(-6) mol/l and 2.5 x 10(-7) mol/l, (55X and 5.5 X the dose required to displace 50% 125I G17, respectively), and reduced optimal G17 stimulated mitogenesis in 75% of experiments. The basal growth of two human colon cancer cell lines, LoVo and C146 was reduced by L-365,260 (2.5 x 10(-7) mol/l) after 5 days of treatment to 44% and 64% of the control, respectively. However, inhibition was followed by a rebound of growth to control levels. The growth of AR42J xenografts in nude mice was increased by administration of G17 (10 micrograms/mouse/d, P less than 0.027). This increase was blocked by coadministration of oral L-365,260 (5 mg/kg/d, P less than 0.034). L-365,260 could be an important therapeutic agent in slowing the growth of GR-positive, G17-sensitive gastrointestinal tumors.
Interference of mRNA Function by Sequence-specific Endoribonuclease PemK (2004)

In Escherichia coli, programmed cell death is mediated through the system called "addiction module," which consists of a pair of genes encoding a stable toxin and a labile antitoxin. The pemI-pemK system is an addiction module present on plasmid R100. It helps to maintain the plasmid by post-segregational killing in E. coli population. Here we demonstrate that purified PemK, the toxin encoded by the pemI-pemK addiction module, inhibits protein synthesis in an E. coli cell-free system, whereas the addition of PemI, the antitoxin against PemK, resumes the protein synthesis. Further studies reveal that PemK is a sequence-specific endoribonuclease that cleaves mRNAs to inhibit protein synthesis, whereas PemI blocks the endoribonuclease activity of PemK. PemK cleaves only single-stranded RNA preferentially at the 5' or 3' side of the A residue in the "UAH" sequences (where H is C, A, or U). Upon induction, PemK cleaves cellular mRNAs to effectively block protein synthesis in E. coli. The pemK homologue genes have been identified on the genomes of a wide range of bacteria. We propose that PemK and its homologues form a novel endoribonuclease family that interferes with mRNA function by cleaving cellular mRNAs in a sequence-specific manner.
Clinical Significance of α II-Spectrin Breakdown Products in Cerebrospinal Fluid after Severe Traumatic Brain Injury (2007)

Following traumatic brain injury (TBI), the cytoskeletal protein alpha-II-spectrin is proteolyzed by calpain and caspase-3 to signature breakdown products. To determine whether alpha -II-spectrin proteolysis is a potentially reliable biomarker for TBI in humans, the present study (1) examined levels of spectrin breakdown products (SBDPs) in cerebrospinal fluid (CSF) from adults with severe TBI and (2) examined the relationship between these levels, severity of injury, and clinical outcome. This prospective case control study enrolled 41 patients with severe TBI, defined by a Glasgow Coma Scale (GCS) score of < or =8, who underwent intraventricular intracranial pressure monitoring. Patients without TBI requiring CSF drainage for other medical reasons served as controls. Ventricular CSF was sampled from each patient at 6, 12, 24, 48, 72, 96, and 120 h following TBI and analyzed for SBDPs. Outcome was assessed using the Glasgow Outcome Score (GOS) 6 months after injury. Calpain and caspase-3 mediated SBDP levels in CSF were significantly increased in TBI patients at several time points after injury, compared to control subjects. The time course of calpain mediated SBDP150 and SBDP145 differed from that of caspase-3 mediated SBDP120 during the post-injury period examined. Mean SBDP densitometry values measured early after injury correlated with severity of injury, computed tomography (CT) scan findings, and outcome at 6 months post-injury. Taken together, these results support that alpha -II-spectrin breakdown products are potentially useful biomarker of severe TBI in humans. Our data further suggests that both necrotic/oncotic and apoptotic cell death mechanisms are activated in humans following severe TBI, but with a different time course after injury.
Multilevel and mixed-domain simulation of analog circuits and systems (1996)

Integrated circuit design has evolved to the stage where large, complex, analog and digital functionalities are implemented on a single chip or as an integrated chip set. Besides the mixed signal nature of the designs, the analog sections also include continuous-time and discrete-time components. Thus, for analysis of these integrated modules, all encompassing simulation capabilities are required that address, not only transient analysis of mixed analog-digital circuits, but frequency domain analysis as well. In this paper, we present mechanisms for multilevel and mixed-domain simulation of analog systems tied in with mixed analog-digital simulation. We then describe the implementation in the form of an open-ended and expandable simulation framework, iMACSIM. A simulation backplane is used to provide a general event-processing and scheduling framework that ties together the various algorithms necessary for simulation of various classes of circuits in different analysis regimes.
Molecular mechanisms of angiogenesis: fibroblast growth factor signal transduction (1995)

The fibroblast growth factors are a family of structurally related polypeptides that are mitogenic for a broad range of cell types as well as mediators of a wide spectrum of developmental and pathophysiological processes in vivo and in vitro. The fibroblast growth factor family presently consists of nine distinct members. Indeed, the FGF prototypes FGF-1 (acidic) and FGF-2 (basic) are well described as modifiers of angiogenesis. The absence of a signal sequence to direct their secretion and their ability to traffic to the nucleus are unique structural features that may be relevant to the regulation of their activities. The FGF receptor family consists of four transmembrane receptor tyrosine kinases. Each of these receptors give rise to multiple isoforms as a result of alternative splicing of their mRNAs. The significance of these multiple isoforms is not fully understood; however it is known that alternative splicing in the extracellular domain of these receptors results in altered ligand binding specificities. In addition, alternative splicing in the cytoplasmic domain results in isoforms with increased oncogenic potential. This review will describe recent insights into the pathways used for the regulation of FGF secretion and cellular trafficking as well as signaling by FGFRs.
The genome sequence of the colonial chordate, Botryllus schlosseri (2013)

Botryllus schlosseri is a colonial urochordate that follows the chordate plan of development following sexual reproduction, but invokes a stem cell-mediated budding program during subsequent rounds of asexual reproduction. As urochordates are considered to be the closest living invertebrate relatives of vertebrates, they are ideal subjects for whole genome sequence analyses. Using a novel method for high-throughput sequencing of eukaryotic genomes, we sequenced and assembled 580 Mbp of the B. schlosseri genome. The genome assembly is comprised of nearly 14,000 intron-containing predicted genes, and 13,500 intron-less predicted genes, 40% of which could be confidently parceled into 13 (of 16 haploid) chromosomes. A comparison of homologous genes between B. schlosseri and other diverse taxonomic groups revealed genomic events underlying the evolution of vertebrates and lymphoid-mediated immunity. The B. schlosseri genome is a community resource for studying alternative modes of reproduction, natural transplantation reactions, and stem cell-mediated regeneration. DOI:http://dx.doi.org/10.7554/eLife.00569.001.
Exosomes derived from miR-122-modified adipose tissue-derived MSCs increase chemosensitivity of hepatocellular carcinoma (2015)

The findings suggest that the export of miR-122 via AMSC exosomes represents a novel strategy to enhance HCC chemosensitivity.
Endothelial Injury in a Transforming Growth Factor β–Dependent Mouse Model of Scleroderma Induces Pulmonary Arterial Hypertension (2013)

In this study, we replicated key features of systemic sclerosis-related PAH in a mouse model. Our results suggest that pulmonary endothelial cell injury in a genetically susceptible mouse strain triggers this complication and support the underlying role of functional interplay between TGFβ and VEGF, which provides insight into the pathogenesis of this disease.
Comparison of viable cell counts and fluorescence in situ hybridization using specific rRNA-based probes for the quantification of human fecal bacteria (2000)

Conventional cultivation and fluorescence in situ hybridization (FISH) using 16S rRNA-based probes were compared for the enumeration of human colonic bacteria. Groups of common intestinal anaerobic bacteria were enumerated in slurries prepared From fecal samples of three healthy volunteers. To introduce variation between the samples, they were incubated for 48 h in batch culture (anaerobic) fermenters at 37 degrees C, and pure cultures of Bifidobacterium infantis, Clostridium perfringens, or Lactobacillus acidophilus were added. Samples were taken from the fermenters at different times. Total anaerobes, bifidobacteria, bacteroides, clostridia, and lactobacilli were enumerated by both plating and FISH. The results showed that plate counts of total anaerobes, bifidobacteria, lactobacilli and bacteroides were approximately ten-fold lower than the corresponding FISH counts, Numbers of clostridia were higher using the plating method, probably because the clostridia probe used in FISH analyses was designed to only detect part of the genus Clostridium. The introduced variation in the methods could be detected by both methods and was comparable. (C) 1999 Federation of European Microbiological Societies. Published by Elsevier Science B.V. All rights reserved.
Cell-Free DNA in Metastatic Colorectal Cancer: A Systematic Review and Meta-Analysis (2017)

Reliable prognostic markers could help to guide patients and treating physicians regarding the relevance and choice of systemic therapy. Small fragments of circulating cell-free DNA (cfDNA) can be measured in a simple blood sample. This report presents the first meta-analysis of the prognostic value of total cfDNA measurement in patients with metastatic colorectal cancer. Data from 1,076 patients confirmed that patients with the lowest pre-treatment levels of cfDNA had a significantly higher chance of longer survival than those with higher levels. Cell-free DNA analysis can also be used for detection of tumor-specific mutations, and hold potential as a valuable tool in colorectal cancer treatment.
Roles of Brevibacterium linens and yeasts on the development of volatile flavour substances in Limburger cheese (1970)

本実験ではリンブルガーチーズより分離した酵母の一般的性質ならびに揮発性風味物質の生産性について調べた.チーズ中の酵母は熟成開始後急速に増加し,熟成20日付近で最高となり,以後漸減の傾向を示した.これら酵母はCandida mycodermaとDebaryomyces kloeckeriの2菌株に同定され,熟成全般を通じてC. mycodermaが優勢であった.これら酵母の一般的性質ならびに全脂乳培地において生産した揮発性風味物質は次のとおりである.(1) 分離した二種の酵母とも食塩濃度により著しくその生育が影響されたが,C. mycodermaは3%の食塩濃度に,またD. kloeckeriは7%の濃度にそれぞれ耐え得ることを認めた.また,両酵母ともかなり強い蛋白分解性を有し,さらにクエン酸の生産性に顕著に富んでいることを認めた.(2) 量的な差はあるが両酵母とも硫化水素,各種揮発性脂肪酸および各種揮発性カルボニル化合物を生成することを認めた.Brev. linensにより生産される揮発性物質は全般的にみて酵母の場合に比べ,量的にも種類的にも多く,リンブルガー風味出現に欠くべからざる役割を演じていることは言うまでもないが,酵母もまた,それに対し重要な役割を果しているものと考えられた.酵母の顕微鏡写真撮影に多大の御便宜を下された信州大学農学部助教授 松尾信一博士に御礼申し上げます.本報告の要旨は日本畜産学会第56回大会で発表した.
Vascular Targeted Nanoparticles for Imaging and Treatment of Brain Tumors (2006)

This study reveals the versatility and efficacy of the multifunctional nanoparticle for the targeted detection and treatment of cancer.
Efficacy of SIV/DeltaB670 glycoprotein-enriched and glycoprotein-depleted subunit vaccines in protecting against infection and disease in rhesus monkeys (1991)

Immunization with an inactivated whole-virus vaccine is highly effective in preventing lentivirus infection. The viral protein(s) essential to the induction of protective responses, however, have not been identified. To define the role of virion components in the induction of protective immunity, we evaluated the efficacy of glycoprotein-enriched and glycoprotein-depleted simian immunodeficiency virus (SIV) subunit vaccines prepared by lentil-lectin affinity chromatography of gradient-purified virions using the immunization and challenge regimen previously found successful with an inactivated whole-virus vaccine. Infection was determined by successful recovery of virus, the induction of SIV-specific antibody responses, and infection of naive recipients by inoculation with lymph-node-derived lymphocytes from the vaccinates. Immunization with the glycoprotein-enriched preparation prevented infection in two out of four monkeys, whereas the glycoprotein-depleted vaccine failed to prevent infection in all four vaccinates tested. However, the glycoprotein-depleted vaccine appeared to moderate the progression of SIV-induced disease compared with non-immunized infected control monkeys inoculated with the same challenge dose. These data suggest that subunit vaccines containing sufficient quantities of viral glycoproteins can protect against SIV infection, whereas subunit vaccines composed predominantly of viral core proteins cannot. The development of effective vaccines against HIV infection should include studies on the optimum presentation of the viral envelope glycoproteins to produce long-term broadly protective immune responses.