gebhart/patrepeval huggingface dataset:
Stem Cell–like Glioma Cells Promote Tumor Angiogenesis through Vascular Endothelial Growth Factor (2006)

Malignant gliomas are highly lethal cancers dependent on angiogenesis. Critical tumor subpopulations within gliomas share characteristics with neural stem cells. We examined the potential of stem cell-like glioma cells (SCLGC) to support tumor angiogenesis. SCLGC isolated from human glioblastoma biopsy specimens and xenografts potently generated tumors when implanted into the brains of immunocompromised mice, whereas non-SCLGC tumor cells isolated from only a few tumors formed secondary tumors when xenotransplanted. Tumors derived from SCLGC were morphologically distinguishable from non-SCLGC tumor populations by widespread tumor angiogenesis, necrosis, and hemorrhage. To determine a potential molecular mechanism for SCLGC in angiogenesis, we measured the expression of a panel of angiogenic factors secreted by SCLGC. In comparison with matched non-SCLGC populations, SCLGC consistently secreted markedly elevated levels of vascular endothelial growth factor (VEGF), which were further induced by hypoxia. In an in vitro model of angiogenesis, SCLGC-conditioned medium significantly increased endothelial cell migration and tube formation compared with non-SCLGC tumor cell-conditioned medium. The proangiogenic effects of glioma SCLGC on endothelial cells were specifically abolished by the anti-VEGF neutralizing antibody bevacizumab, which is in clinical use for cancer therapy. Furthermore, bevacizumab displayed potent antiangiogenic efficacy in vivo and suppressed growth of xenografts derived from SCLGC but limited efficacy against xenografts derived from a matched non-SCLGC population. Together these data indicate that stem cell-like tumor cells can be a crucial source of key angiogenic factors in cancers and that targeting proangiogenic factors from stem cell-like tumor populations may be critical for patient therapy.
Laryngotracheitis in Chickens: Infection Studies and the Efficacy of a Tissue-Culture Vaccine in Chicks less than Four Weeks Old (1989)

Challenge studies using the standard National Veterinary Services Laboratory laryngotracheitis (LT) challenge virus (Log 10(6.7) EID50 per ml) were conducted to assess the presence of maternal protection in chicks of various ages (1, 7, 14, 21, and 28 days). Chicks from vaccinated and unvaccinated breeders were challenged by intratracheal inoculation. Chicks of all these ages irrespective of origin were susceptible to infection. Similarly derived chicks were vaccinated by eyedrop with a commercially available tissue-culture vaccine. Chicks vaccinated at 21 and 28 days were adequately protected from challenge (77-94% protection), whereas less than 60% of chicks vaccinated at 1, 7, or 14 days were protected.
Engineering interchain disulfide bonds into conserved framework regions of Fv fragments: improved biochemical characteristics of recombinant immunotoxins containing disulfide-stabilized Fv (1994)

Using molecular modeling technology, we have recently identified two positions in conserved framework regions of antibody Fv fragments (Fvs) that are distant from CDRs, and potentially can be used to make recombinant Fv fragments in which the unstable VH and VL heterodimer is stabilized by an interchain disulfide bond inserted between structurally conserved framework positions. A disulfide bond has been introduced at one of these positions, VH44-VL105, and shown to stabilize various Fvs that retain full binding and specificity. Recombinant immunotoxins, e.g. B3(dsFv)-PE38KDEL in which this disulfide-stabilized Fv moiety is connected to a truncated form of Pseudomonas exotoxin (PE; PE38KDEL) which contains the translocation and ADP ribosylation domains, are indistinguishable in binding and specificity from its single-chain immunotoxin counterparts. We have now analyzed the alternative position, (VH111-VL48), predicted by the modeling methodology, for disulfide stabilization of mAb B3(Fv) by producing a recombinant immunotoxin with such disulfide-stabilized (ds) Fv. This immunotoxin was also very active and retained full specificity to B3 antigen-positive cells. However, it was 2- to 3-fold less active than the VH44-VL105 dsFv-molecule. We also tested various biochemical features of VH44-VL105 and VH111-VL48 dsFv immunotoxins and compared them with the corresponding single-chain immunotoxin. We found the dsFv immunotoxins were more stable in human serum and more resistant to thermal and chemical denaturation than the single chain (sc) Fv immunotoxin. Because dsFv immunotoxins and dsFvs have full activity and specificity and improved stability, they may be more useful than scFv immunotoxins as therapeutic and diagnostic agents.
An antibiotic-binding motif of an RNA fragment derived from the A-site- related region of Escherichia coli 16S rRNA (1996)

A small RNA derived from the decoding region of Escherichia coli 16S rRNA can bind to antibiotics of aminoglycosides (neomycin and paromomycin) that act on the small ribosomal subunit [Purohit,P. and Stern,S. (1994) Nature, 370, 659-662]. In the present study, the P-site subdomain was removed from this decoding region RNA to construct a 27mer RNA (designated as ASR-27), which includes the A-site-related region (positions 1402-1412 and 1488-1497) of 16S rRNA. Footprint experiments with dimethyl sulfate as a chemical probe indicated that the ASR-27 RNA can interact with the neomycin family in the same manner as the decoding region RNA. A mutagenesis analysis of the ASR-27 RNA revealed that paromomycin binding of ASR-27 involves the C1407.G1494 and C1409-G1491 base pairs, and the internal loop comprising A1408 and the nucleotides in positions 1492-1493, located between the two C.G base pairs. In addition, a G or U in position 1495, and base pairing between positions 1405 and 1496 are also involved. These structural features were found in a viral RNA element, the Rev-binding site of human immunodeficiency virus type-1, which may explain why neomycin can bind to this viral RNA.
The synaptic muscle‐specific kinase (MuSK) complex: New partners, new functions (2005)

The muscle-specific kinase MuSK is part of an agrin receptor complex that stimulates tyrosine phosphorylation and drives clustering of acetylcholine receptors (AChRs) in the postsynaptic membrane at the vertebrate neuromuscular junction (NMJ). MuSK also regulates synaptic gene transcription in subsynaptic nuclei. Over the past few years, decisive progress has been made in the identification of MuSK effectors, helping to understand its function in the formation of the NMJ. Similarly to AChR, MuSK and several of its partners are the target of mutations responsible for diseases of the NMJ, such as congenital myasthenic syndromes. This minireview will focus on the multiple MuSK effectors so far identified that place MuSK at the center of a multifunctional signaling complex involved in the organization of the NMJ and associated disorders.
The Acid-Inducible asr Gene in Escherichia coli : Transcriptional Control by the phoBR Operon (1999)

Escherichia coli responds to external acidification (pH 4.0 to 5.0) by synthesizing a newly identified, approximately 450-nucleotide RNA component. At maximal levels of induction it is one of the most abundant small RNAs in the cell and is relatively stable bacterial RNA. The acid-inducible RNA was purified, and the gene encoding it, designated asr (for acid shock RNA), mapped at 35.98 min on the E. coli chromosome. Analysis of the asr DNA sequence revealed an open reading frame coding for a 111-amino-acid polypeptide with a deduced molecular mass of approximately 11.6 kDa. According to computer-assisted analysis, the predicted polypeptide contains a typical signal sequence of 30 amino acids and might represent either a periplasmic or an outer membrane protein. The asr gene cloned downstream from a T7 promoter was translated in vivo after transcription using a T7 RNA polymerase transcription system. Expression of a plasmid-encoded asr::lacZ fusion under a native asr promoter was reduced approximately 15-fold in a complex medium, such as Luria-Bertani medium, versus the minimal medium. Transcription of the chromosomal asr was abolished in the presence of a phoB-phoR (a two-component regulatory system, controlling the pho regulon inducible by phosphate starvation) deletion mutant. Acid-mediated induction of the asr gene in the Delta(phoB-phoR) mutant strain was restored by introduction of the plasmid with cloned phoB-phoR genes. Primer extension analysis of the asr transcript revealed a region similar to the Pho box (the consensus sequence found in promoters transcriptionally activated by the PhoB protein) upstream from the determined transcription start. The asr promoter DNA region was demonstrated to bind PhoB protein in vitro. We discuss our results in terms of how bacteria might employ the phoB-phoR regulatory system to sense an external acidity and regulate transcription of the asr gene.
Expression of three UDP-N-acetyl-alpha-D-galactosamine:polypeptide GalNAc N-acetylgalactosaminyltransferases in adenocarcinoma cell lines. (1997)

The levels of mRNA expression of three UDP-N-acetyl-alpha-D-galactosamine:polypeptide GalNAc N-acetylgalactosaminyltransferases (GalNAc-transferases) were quantified for human adenocarcinoma cell lines from pancreas, colon, stomach, and breast. Two of the GalNAc-transferases, GalNAc-T1 and GalNAc-T2, were expressed constitutively and at low levels in most or all cell lines examined. A third GalNAc-transferase, GalNAc-T3, was differentially expressed. Well-differentiated adenocarcinoma cell lines expressed high levels and moderately differentiated cell lines expressed lower levels of GalNAc-T3. Cell lines classified as poorly differentiated failed to express GalNAc-T3 mRNA at levels that could be detected by Northern blot analysis. Differential expression of the GalNAc-T3 protein was confirmed in these cell lines by Western blotting. We propose that glycosylation in tumor cell lines may be regulated in part by differential expression of GalNAc-transferases, and we suggest that GalNAc-T3 gene expression may be a molecular indicator of differentiated adenocarcinoma.
Obstetrical endoscopy (1999)

Fetoscopy has been reintroduced in fetal diagnosis and therapy, as a result of instrumental innovations. It has been suggested that fetoscopy be used to guide endoscopic operations on the fetus, but this application is still in the experimental phase. Its use for surgical interventions on the placenta, umbilical cord, and to a lesser extent the fetal membranes, could be called 'obstetrical' endoscopy. Nd:YAG laser coagulation of chorionic plate vessels for feto-fetal transfusion syndrome is the most common operation carried out today. Survival rates of 60% or more have recently been reported on both sides of the Atlantic Ocean. Neurological morbidity does not exceed 6%, which compares favorably with serial amnioreductions and may become the most important incentive for performing the operation. A randomized trial comparing both therapies as a next step is being proposed. Fetoscopy has also been used for cord ligation, but because of the complexity of the operation and the high risk for preterm prelabor rupture of the membranes, other alternatives have been investigated. Most experience has been gathered with bipolar cord occlusion, a procedure which can be performed under ultrasound guidance. The instrumental considerations and potential complications of fetoscopy are discussed.
Use of Piezoresistive Materials in the Measurement of Displacement, Force, and Torque (1957)

The use of piezoresistive materials as strain gauges and in the measurement of displacement, force, and torque is discussed generally. A torsional transducer which has been constructed from n-type germanium is described, and the experimentally obtained voltage-torque characteristic given.
Multiple Splicing Defects in an Intronic False Exon (2000)

Splice site consensus sequences alone are insufficient to dictate the recognition of real constitutive splice sites within the typically large transcripts of higher eukaryotes, and large numbers of pseudoexons flanked by pseudosplice sites with good matches to the consensus sequences can be easily designated. In an attempt to identify elements that prevent pseudoexon splicing, we have systematically altered known splicing signals, as well as immediately adjacent flanking sequences, of an arbitrarily chosen pseudoexon from intron 1 of the human hprt gene. The substitution of a 5' splice site that perfectly matches the 5' consensus combined with mutation to match the CAG/G sequence of the 3' consensus failed to get this model pseudoexon included as the central exon in a dhfr minigene context. Provision of a real 3' splice site and a consensus 5' splice site and removal of an upstream inhibitory sequence were necessary and sufficient to confer splicing on the pseudoexon. This activated context also supported the splicing of a second pseudoexon sequence containing no apparent enhancer. Thus, both the 5' splice site sequence and the polypyrimidine tract of the pseudoexon are defective despite their good agreement with the consensus. On the other hand, the pseudoexon body did not exert a negative influence on splicing. The introduction into the pseudoexon of a sequence selected for binding to ASF/SF2 or its replacement with beta-globin exon 2 only partially reversed the effect of the upstream negative element and the defective polypyrimidine tract. These results support the idea that exon-bridging enhancers are not a prerequisite for constitutive exon definition and suggest that intrinsically defective splice sites and negative elements play important roles in distinguishing the real splicing signal from the vast number of false splicing signals.
Cis-acting regulatory elements controlling temporal and organ-specific activity of nopaline synthase promoter (1989)

Regulatory elements controlling temporal and organ-specific expression of the nopaline (nos) gene were identified by analyzing deletion mutants of the promoter. As observed in cultured cells, the TATA box element was required for efficient promoter function and the 29 bp upstream promoter region between -130 and -101 was necessary for the nos promoter activity in various vegetative organs. This 29 bp region includes ten nucleotides of a potential Z-DNA-forming sequence (Z element) and eight nucleotides of a repeated element (b element). Duplication of b elements significantly enhanced the promoter strength, revealing the importance of the element in all plant organs. Unlike the results in the cultured cells, however, deletion of the b element or CCAAT box region completely inactivated the promoter function in regenerated organs. Therefore, it appears that transcription initiation is more tightly controlled in differentiated plant cells than in cultured cells.
Alterations of Sarcoplasmic Reticulum Proteins in Failing Human Dilated Cardiomyopathy (1995)

Levels of SR proteins involved in calcium binding and release are unchanged in failing dilated cardiomyopathy. In contrast, protein levels of calcium ATPase involved in SR calcium uptake are reduced in the failing myocardium. Moreover, SR calcium ATPase is decreased relative to its inhibitory protein, phospholamban.(ABSTRACT TRUNCATED AT 250 WORDS)
Click to Fit:  Versatile Polyvalent Display on a Peptidomimetic Scaffold (2005)

We describe an efficient protocol to effect multisite conjugation reactions to oligomers on solid-phase support. Sequence-specific N-substituted glycine "oligopeptoids" were utilized as substrates for azide-alkyne cycloaddition reactions. Diverse groups, including nucleobases and fluorophores, were conjugated at up to six positions on peptoid side chains with yields ranging from 88 to 96%. This strategy will be broadly applicable for generating polyvalent displays on peptides and other scaffolds, allowing precise control of spacing between the displayed groups.
A TALE of Two Nucleases: Gene Targeting for the Masses? (2011)

Genome editing appears poised to enter an exciting new era. Targeted double-stranded breaks due to custom restriction enzymes are powerful nucleating events for the induction of local changes in the genome. The zinc finger nuclease (ZFN) platform established the potential of this approach for the zebrafish, but access to high quality reagents has been a major bottleneck for the field. However, two groups recently report successful somatic and germline gene modification using a new nuclease architecture, transcription activator-like effector nucleases (TALENs). TALEN construction is simpler, potentially more reliable, and in the few cases examined, shows fewer off-target effects than corresponding ZFNs. TALENs promise to bring gene targeting to the majority of zebrafish laboratories.
Automatic Training Data Cleaning for Text Classification (2011)

Supervised text classification algorithms rely on the availability of large quantities of quality training data to achieve their optimal performance. However, not all training data is created equal and the quality of class-labels assigned by human experts may vary greatly with their levels of experience, domain knowledge, and the time available to label each document. In our experiments, focused label validation and correction by expert journalists improved the Micro and Macro-F1 scores achieved by Linear SVMs by as much as 14.5% and 30% respectively, on a corpus of professionally labeled news stories. Manual label correction is an expensive and time consuming process and the classification quality may not linearly improve with the amount of time spent, making it increasingly more expensive to achieve higher classification quality targets. We propose ATDC, a novel evidence-based training data cleaning method that uses training examples with high-quality class labels to automatically validate and correct labels of noisy training data. A subset of these instances are then selected to augment the original training set. On a large noisy dataset with about two million news stories, our method improved the baseline Micro-F1 and Macro-F1 scores by 9% and 13% respectively, without requiring any further human intervention.
Origin of the TEM-beta-lactamase gene found on plasmids (1975)

A sequence of deoxyribonucleic acid of 2.7 times 10-6 to 3.3 times 10-6 daltons which includes the TEM beta-lactamase gene is present on the small plasmid RSF 1030 (R-Amp). This same sequence is present on plasmid derivatives that have received a translocation of deoxyribonucleic acid specifying the TEM beta-lactamase and is also present on naturally occurring plasmids of the F1, F11, N, X, O, I, C, and W incompatibility groups that do not specify ampicillin resistance or specify O-type beta-lactamases.
Injectable Collagenase Clostridium Histolyticum for Dupuytren's Contracture (2009)

Collagenase clostridium histolyticum significantly reduced contractures and improved the range of motion in joints affected by advanced Dupuytren's disease. (ClinicalTrials.gov number, NCT00528606.)
History and development of radiation-protective agents (2009)

Over the years, extensive experimental studies of radiation-protective agents have enhanced our knowledge of radiation physics, chemistry, and biology. However, translation of agents from animal testing to use in various scenarios, such as prophylactic adjuncts in radiotherapy or post-exposure treatments for potential victims of radiation accidents/incidents, has been slow. Nevertheless, a number of compounds are now available for use in a variety of radiation situations. These include agents approved by the U.S. Food and Drug Administration for use in reducing exposure to internal radionuclides (Prussian blue, calcium diethylenetriamene pentaacetate (DTPA) and zinc DTPA, potassium iodide) and amifostine for alleviating xerostomia associated with radiotherapy. Consensus groups have also recommended other therapies such as granulocyte colony-stimulating factor for radiation-induced neutropenia. The variety of prophylactic and therapeutic agents in the research pipeline includes those that are naturally-occurring with low toxicity, provide a long window of protection, protect normal tissue while sensitising tumours, or act via receptors and modulate biological processes such as induction of genes responsible for radioresistance. The search for agents that protect against acute and late effects of ionising radiation injury will undoubtedly continue into the future and influence other areas of radiation research.
Macromolecular engineering of polyactones and polyactides. 12. Study of the depolymerization reactions of poly(.epsilon.-caprolactone) with functional aluminum alkoxide end groups (1993)

peer reviewed
The assembly of integrin adhesion complexes requires both extracellular matrix and intracellular rho/rac GTPases. (1995)

Interaction of cells with extracellular matrix via integrin adhesion receptors plays an important role in a wide range of cellular: functions, for example cell growth, movement, and differentiation. Upon interaction with substrate, integrins cluster and associate with a variety of cytoplasmic proteins to form focal complexes and with the actin cytoskeleton. Although the intracellular signals induced by integrins are at present undefined, it is thought that they are mediated by proteins recruited to the focal complexes. It has been suggested, for example, that after recruitment to focal adhesions p125FAK can activate the ERK1/2 MAP kinase cascade. We have previously reported that members of the rho family of small GTPases can trigger the assembly of focal complexes when activated in cells. Using microinjection techniques, we have now examined the role of the extracellular matrix and of the two GTP-binding proteins, rac and rho, in the assembly of integrin complexes in both mouse and human fibroblasts. We find that the interaction of integrins with extracellular matrix alone is not sufficient to induce integrin clustering and focal complex formation. Similarly, activation of rho or rac by extracellular growth factors does not lead to focal complex formation in the absence of matrix. Focal complexes are only assembled in the presence of both matrix and functionally active members of the rho family. In agreement with this, the interaction of integrins with matrix in the absence of rho/rac activity is unable to activate the ERK1/2 kinases in Swiss 3T3 cells. In fact, ERK1/2 can be activated fully by growth factors in the absence of matrix and it seems unlikely, therefore, that the adhesion dependence of fibroblast growth is mediated through the ras/MAP kinase pathway. We conclude that extracellular matrix is not sufficient to trigger focal complex assembly and subsequent integrin-dependent signal transduction in the absence of functionally active members of the rho family of GTPases.