gebhart/patrepeval huggingface dataset:
Transcriptome regulation and chromatin occupancy by E2F3 and MYC in mice (2016)

E2F3 and MYC are transcription factors that control cellular proliferation. To study their mechanism of action in the context of a regenerating tissue, we isolated both proliferating (crypts) and non-dividing (villi) cells from wild-type and Rb depleted small intestines of mice and performed ChIP-exo-seq (chromatin immunoprecipitation combined with lambda exonuclease digestion followed by high-throughput sequencing). The genome-wide chromatin occupancy of E2F3 and MYC was determined by mapping sequence reads to the genome and predicting preferred binding sites (peaks). Binding sites could be accurately identified within small regions of only 24 bp-28 bp long, highlighting the precision to which binding peaks can be identified by ChIP-exo-seq. Forty randomly selected E2F3- and MYC-specific binding sites were validated by ChIP-PCR. In addition, we also presented gene expression data sets from wild type, Rb-, E2f3- and Myc-depleted crypts and villi within this manuscript. These represent comprehensive and validated datasets that can be integrated to identify putative direct targets of E2F3 and MYC involved in the control of cellular proliferation in normal and Rb-deficient small intestines.
The Family of the Small Leucine-Rich Proteoglycans: Key Regulators of Matrix Assembly and Cellular Growth (1997)

The focus of this review is on conceptual and functional advances in our understanding of the small leucine-rich proteoglycans. These molecules belong to an expanding gene class whose distinctive feature is a structural motif, called the leucine-rich repeat, found in an increasing number of intracellular and extracellular proteins with diverse biological attributes. Three-dimensional modeling of their prototype protein core proposes a flexible, arch-shaped binding surface suitable for strong and distinctive interactions with ligand proteins. Changes in the properties of individual proteoglycans derive from amino acid substitutions in the less conserved surface residues, changes in the number and length of the leucine-rich repeats, and/or variation in glycosylation. These proteoglycans are tissue organizers, orienting and ordering collagen fibrils during ontogeny and in pathological processes such as wound healing, tissue repair, and tumor stroma formation. These properties are rooted in their bifunctional character: the protein moiety binding collagen fibrils at strategic loci, the microscopic gaps between staggered fibrils, and the highly charged glycosaminoglycans extending out to regulate interfibrillar distances and thereby establishing the exact topology of fibrillar collagens in tissues. These proteoglycans also interact with soluble growth factors, modulate their functional activity, and bind to cell surface receptors. The latter interaction affects cell cycle progression in a variety of cellular systems and could explain the purported changes in the expression of these gene products around the invasive neoplastic cells and in regenerating tissues.
INDUCTION OF SPECIFIC TOLERANCE BY INTRATHYMIC INJECTION OF RECIPIENT MUSCLE CELLS TRANSFECTED WITH DONOR CLASS I MAJOR HISTOCOMPATIBILITY COMPLEX (1994)

Induction of tolerance to allogeneic MHC antigens has been a goal in the field of transplantation because it would reduce or eliminate the need for generalized immunosuppression. Although encouraging results have been obtained in experimental models by exposing recipient thymus to donor cells before transplantation, donor cells are not typically available at that time, and the donor antigens responsible for the effect are poorly defined. In the present study, thymic tolerance was demonstrated without using donor cells. Recipient thymus was injected before transplantation with autologous myoblasts and myotubes that were genetically modified to express allogeneic donor-type MHC class I antigen. Donor-specific unresponsiveness was induced to a completely MHC-disparate liver transplant and to a subsequent donor-type cardiac allograft, but not a third-party allograft. In vitro, recipient CTL demonstrated a 10-fold reduction in killing of donor cells, but not of third-party cells. Our results demonstrate: (1) that recipient muscle cells can be genetically engineered to induce donor-specific unresponsiveness when given intrathymically, and (2) transfected recipient cells expressing only donor MHC class I antigen can induce tolerance to a fully allogeneic donor.
Manipulation of Adenovirus Vectors (2003)

Adenoviruses have been isolated from a large number of different species (mammalian and fowl) and over 100 different serotypes have been reported, some 43 of them human. The human adenoviruses, particularly types 2, 5, and 12, have been the most extensively characterized, and these viruses have served as valuable tools in the study of the molecular biology of DNA replication, transcription, RNA processing, and protein synthesis in mammalian cells. Seeref. 1 for a general review.
A low temperature wafer-level hermetic MEMS package using UV curable adhesive (2004)

In order to lower the packaging cost and resolve the process complexity of MEMS fabrications, a new wafer-level post-process hermetic package using UV curable adhesive bonding is introduced for MEMS applications. The UV curable adhesive is cured through UV light exposure without any additional heating, suitable for packaging the devices with temperature sensitive materials or processes. A Pyrex 7740 glass is micromachined and used as a protection cap substrate with microcavities which is spin-coated with the adhesive, aligned, and bonded with a device substrate to form the package after the UV curing. Finally, electrical contact pads expose and die separation are done simultaneously by dicing. Two different monitoring devices, dew point sensor and capacitive accelerometer are built to evaluate the package strength and hermeticity. After dicing operation, no structure damage or stiction phenomenon is found in the packaged capacitive accelerometer. Furthermore, no moisture condensation is observed in the package with 190 /spl mu/m bonding width after 150 minutes boil water immersion. The acceleration test results indicate the package can survive more than 3 weeks at 25/spl deg/C, 100% RH (relative humidity) working environment.
Selective Electrochemical Removal of Protecting Groups in Nucleotide Synthesis (1979)

Selective removal of an ester group from the completely protected nucleoside 3′-phosphate (2) by electrochemical reduction solves a serious problem of nucleotide synthesis. Reaction (2) → (3) requires a potential of −0.5 V; (2) → (1) can be accomplished by acid hydrolysis. At −1.2 V the remaining ester groups are removed from (1).
Basic materials physics of transparent conducting oxides (2004)

Materials displaying the remarkable combination of high electrical conductivity and optical transparency already from the basis of many important technological applications, including flat panel displays, solar energy capture and other opto-electronic devices. Here we present the basic materials physics of these important materials centred on the nature of the doping process to generate n-type conductivity in transparent conducting oxides, the associated transition to the metallic (conducting) state and the detailed properties of the degenerate itinerant electron gas. The aim is to fully understand the origins of the basic performance limits of known materials and to set the scene for new or improved materials which will breach those limits for new-generation transparent conducting materials, either oxides, or beyond oxides.
Development of PCR Assays for Species- and Type-Specific Identification of Pasteurella multocida Isolates (1998)

Genomic subtractive hybridization of closely related Pasteurella multocida isolates has generated clones useful in distinguishing hemorrhagic septicemia-causing type B strains from other P. multocida serotypes. Oligonucleotide primers designed during the sequencing of these clones have proved valuable in the development of PCR assays for rapid species- and type-specific detection of P. multocida and of type B:2 in particular. This study demonstrated that the primer pair designed from the sequence of the clone 6b (KTT72 and KTSP61) specifically amplified a DNA fragment from types B:2, B:5, and B:2,5 P. multocida and that the primers KMT1T7 and KMT1SP6 produced an amplification product unique to all P. multocida isolates analyzed. It was also shown that PCR amplification performed directly on bacterial colonies or cultures represents an extremely rapid, sensitive method of P. multocida identification.
Polyvalent Display and Packing of Peptides and Proteins on Semiconductor Quantum Dots: Predicted Versus Experimental Results (2010)

Quantum dots (QDs) are loaded with a series of peptides and proteins of increasing size, including a <20 residue peptide, myoglobin, mCherry, and maltose binding protein, which together cover a range of masses from <2.2 to approximately 44 kDa. Conjugation to the surface of dihydrolipoic acid-functionalized QDs is facilitated by polyhistidine metal affinity coordination. Increasing ratios of dye-labeled peptides and proteins are self-assembled to the QDs and then the bioconjugates are separated and analyzed using agarose gel electrophoresis. Fluorescent visualization of both conjugated and unbound species allows determination of an experimentally derived maximum loading number. Molecular modeling utilizing crystallographic coordinates or space-filling structures of the peptides and proteins also allow the predicted maximum loadings to the QDs to be estimated. Comparison of the two sets of results provides insight into the nature of the QD surface and reflects the important role played by the nanoparticle's hydrophilic solubilizing surface ligands. It is found that for the larger protein molecules steric hindrance is the major packing constraint. In contrast, for the smaller peptides, the number of available QD binding sites is the principal determinant. These results can contribute towards an overall understanding of how to engineer designer bioconjugates for both QDs and other nanoparticle materials.
Atelectasis Causes Alveolar Injury in Nonatelectatic Lung Regions (2006)

These data support the notion that lung injury associated with atelectasis involves trauma to the distal airways. We provide topographic and biochemical evidence that such distal airway injury is not localized solely to atelectatic areas, but is instead generalized in both atelectatic and nonatelectatic lung regions. In contrast, alveolar injury associated with atelectasis does not occur in those areas that are atelectatic but occurs instead in remote nonatelectatic alveoli.
Near-Infrared Imaging of Dental Decay at 1310 nm (2010)

In this review paper we present an overview of our research which has shown that dental enamel manifests high transparency in the near-infrared (NIR) and suggests that NIR light at 1310 nm is ideally suited for the imaging of carious lesions on proximal and occlusal tooth surfaces. NIR-sensitive imaging systems with broadband light sources centered at 1310 nm were used to acquire NIR images of lesions in extracted teeth and proximal lesions in vivo. Stains and noncalcified plaque are not visible in the NIR, enabling better discrimination of defects, cracks, and demineralized areas. Carious lesions were visible in the NIR with high contrast and can be viewed from multiple surfaces to aid in diagnosis. These studies indicate that NIR imaging may offer significant advantages over the conventional visual, tactile, and radiographic caries-detection methods.
Fluorescence (FISH) and chromogenic (CISH) in situ hybridisation in prostate carcinoma cell lines: comparison and use of virtual microscopy (2008)

Chromogenic in situ hybridisation (CISH) has become an attractive alternative to fluorescence in situ hybridisation (FISH) due to its permanent stain which is more familiar to pathologists and because it can be viewed using light microscopy. The aim of the present study is to examine reproducibility in the assessment of abnormal chromosome number by CISH in comparison to FISH. Using three prostate cell lines--PNT1A (derived from normal epithelium), LNCAP and DU145 (derived from prostatic carcinoma), chromosomes 7 and 8 were counted in 40 nuclei in FISH preparations (x100 oil immersion) and 100 nuclei in CISH preparations (x40) by two independent observers. The CISH slides were examined using standard light microscopy and virtual microscopy. Reproducibility was examined using paired Student's t-test (P<0.05). Reproducibility between observers was good for both FISH and CISH. No significant differences in chromosome count were seen between the techniques. Chromosomes 7 and 8 showed disomic status for each cell line except LNCAP, which proved to be heterogeneous (disomic/aneusomic), particularly for chromosome 8. Virtual microscopy proved to be easy to use and gave no significant differences from standard light microscopy. These results support the hypothesis that there is no significant difference between FISH and CISH techniques.
Inhibitory effects of octreotide on renal and glomerular growth in early experimental diabetes in mice (2002)

It was recently discovered that the streptozotocin (STZ)-diabetic mouse model is characterised by GH hypersecretion in contrast to the STZ-diabetic rat, the former thus mimicking the changes in GH in human type 1 diabetes. Inhibition of circulating and renal IGF-I by long-acting somatostatin analogues reduces renal and glomerular growth and urinary albumin excretion in diabetic rats. The aim of the present study was to examine renal and glomerular growth in early experimental diabetes in mice along with changes in the GH/IGF-I axis following treatment with the somatostatin analogue octreotide. Balb/C(a) mice were randomised into non-diabetic controls, placebo-treated and octreotide-treated diabetic (50 microg/day) mice and examined 7 and 14 days after induction of diabetes. There was no effect of octreotide treatment on body weight, glycaemic control or food intake. However, octreotide treatment significantly inhibited renal and glomerular growth by the end of the study period when compared with placebo treatment. In addition, octreotide prevented an increase in kidney IGF-I by day 7. GH hypersecretion was observed in the diabetic groups but octreotide treatment reduced GH levels compared with placebo treatment by day 14. No significant differences in serum or kidney IGF-binding protein-3 levels were observed between placebo- and octreotide-treated diabetic mice. In conclusion, this new diabetic mouse model mimicking human type 1 diabetes is characterised by GH hypersecretion and the somatostatin analogue octreotide is able to prevent renal and glomerular growth, probably mediated through changes in circulating GH and local kidney IGF-I levels.
GARP Is Regulated by miRNAs and Controls Latent TGF-β1 Production by Human Regulatory T Cells (2013)

GARP is a transmembrane protein present on stimulated human regulatory T lymphocytes (Tregs), but not on other T lymphocytes (Th cells). It presents the latent form of TGF-β1 on the Treg surface. We report here that GARP favors the cleavage of the pro-TGF-β1 precursor and increases the amount of secreted latent TGF-β1. Stimulated Tregs, which naturally express GARP, and Th cells transfected with GARP secrete a previously unknown form of latent TGF-β1 that is disulfide-linked to GARP. These GARP/TGF-β1 complexes are possibly shed from the T cell surface. Secretion of GARP/TGF-β1 complexes was not observed with transfected 293 cells and may thus be restricted to the T cell lineage. We conclude that in stimulated human Tregs, GARP not only displays latent TGF-β1 at the cell surface, but also increases its secretion by forming soluble disulfide-linked complexes. Moreover, we identified six microRNAs (miRNAs) that are expressed at lower levels in Treg than in Th clones and that target a short region of the GARP 3' UTR. In transfected Th cells, the presence of this region decreased GARP levels, cleavage of pro-TGF-β1, and secretion of latent TGF-β1.
Factor Xa inhibitors: today and beyond. (2003)

Serine proteases play an important role in thrombogenesis, the process that leads to blood clotting and conditions such as heart attack, stroke and other cardiovascular disorders. In the coagulation network, the activation of various serine proteases facilitates the formation of the serine protease Factor Xa, which plays a central role in the process of coagulation and platelet activation. Factor Xa is an essential component of the prothrombinase complex, from which thrombin is formed, which then directly leads to fibrin clot formation. Thus, the inhibition of Factor Xa and its generation is an important strategy in the development of new antithrombotic drugs.
Dietary fish oil inhibits Δ6‐desaturase activity in vivo (1998)

Abstract Liver Δ6‐desaturase activity was determined in mice which were made deficient in (i) n‐6 and n‐3 polyunsaturated fatty acids (PUFA), (ii) n‐6 PUFA, or (iii) arachidonic acid (AA). Initially, the mice were subjected to two cycles of a fasting (1 d)/refeeding (2–3 d) protocol in which they were refed an essential fatty acid‐deficient (EFAD) diet during the refeeding period. This 1‐wk fasting/refeeding protocol, referred to as F/R EFAD, produced a rapid and substantial decline in tissue n‐3 and n‐6 PUFA and a corresponding increase in n‐9 fatty acids, notably oleic acid and Mead acid (20:3n‐9). Combined liver Δ6‐desaturase/elongase/Δ5‐desaturase activities in vivo were quantified by measuring the conversion of 14 C‐linoleic acid (LA) to 14 C‐AA in mouse liver. Although F/R EFAD caused, as expected, a substantial decline in liver AA and LA content, the conversion of 14 C‐LA to 14 C‐AA was the same in these mice as in chow‐fed controls (approximately 33–34%). Subsequent refeeding of F/R EFAD mice with an EFAD diet, supplemented with corn oil, restored tissue n‐6 PUFA levels without altering the conversion of 14 C‐LA to 14 C‐AA. In contrast, refeeding with an EFAD diet, supplemented with fish oil, inhibited 14 C‐LA to 14 C‐AA conversion by 78%. Significantly, inhibition of conversion of 14 C‐LA to 14 C‐AA was maintained in F/R EFAD mice that were subsequently fed an EFAD diet supplemented with a 1:1 mixture of fish oil/corn oil. This latter protocol yielded a unique liver fatty acid composition in which AA was selectively depleted, whereas LA and the n‐3 PUFA were increased. The data suggest that dietary n‐3 C 20–22 PUFA negatively regulate the in vivo synthesis of n‐6 PUFA at the level of the Δ6‐desaturase.
Improving the Judicial System to Handle Computer Crime (2007)

This paper asked professionals in the legal system to evaluate the current state and effectiveness of laws to identify and deter computer crime. Responses were evaluated with a formal structural equation model. The results generally show that legal professionals believe potential jurors have minimal knowledge of computer crime issues. More importantly, they also believe that judges have little knowledge or experience. A similar lack of knowledge by defense attorneys indicates that it could be difficult for a person accused of computer related infractions to find adequate representation. On the other hand, more experienced participants do not believe computer laws present an effective deterrent to computer crime. The bottom line is that all levels of the legal profession will need more education and training in aspects of computer security laws.
Prostate-specific membrane antigen antibody drug conjugate (PSMA ADC): A phase I trial in metastatic castration-resistant prostate cancer (mCRPC) previously treated with a taxane. (2012)

4662 Background: The abundant expression of prostate specific membrane antigen (PSMA) type II transmembrane glycoprotein on prostate cancer cells provides a rationale for antibody therapy. PSMA ADC, a fully humanized antibody to PSMA linked to the potent antitubulin agent monomethyl auristatin E (MMAE), binds PSMA and is internalized within the prostate cancer cell where cleavage by lysosomal enzymes and releases free MMAE, causing cell cycle arrest and apoptosis. We report results from an ongoing phase 1 dose escalation study of PSMA ADC in subjects with taxane-refractory mCRPC. Methods: Eligibility requirements include progressive mCRPC following taxane-containing chemotherapy and ECOG status of 0 or 1. PSMA ADC was administered by IV infusion Q3W for up to 4 cycles. Adverse events, pharmacokinetics (PK), PSA, circulating tumor cells, clinical disease progression and immunogenic response to PSMA ADC were assessed. Serum PSMA ADC and total antibody were measured by ELISA, and free MMAE was measured by LC/MS/MS.The dosing cohorts range from 0.4 mg/kg to 2.8 mg/kg, with dose escalation continuing. Results: 40 subjects have been dosed in nine dose levels (0.4, 0.7, 1.1, 1.6, 1.8, 2.0, 2.2, 2.5, 2.8 mg/kg). To date, PSMA ADC has been well tolerated with the most commonly seen adverse events being anorexia and nausea, and the most common laboratory abnormalities being reversible hematologic parameters and liver function tests. Antitumor activity has been manifested as reductions either in PSA or circulating tumor cells in the higher dose cohorts. Exposure to PSMA ADC increased with dose and was ~1,000-fold greater than MMAE exposure. Similar PK metrics were observed after the first and third doses. Dosing at the 2.8 mg/kg cohort is continuing and an MTD has not yet been reached. Conclusions: PSMA ADC is generally well tolerated in subjects with mCRPC, previously treated with taxane in doses up to 2.8 mg/kg. Antitumor activity at higher dose levels has been observed. The MTD has not yet been reached and enrollment is ongoing at higher dose levels.
The Ca2+-binding Proteins S100A8 and S100A9 Are Encoded by Novel Injury-regulated Genes (2001)

To gain insight into the molecular mechanisms underlying cutaneous wound repair, we performed a large scale screen to identify novel injury-regulated genes. Here we show a strong up-regulation of the RNA and protein levels of the two Ca(2+)-binding proteins S100A8 and S100A9 in the hyperthickened epidermis of acute murine and human wounds and of human ulcers. Furthermore, both genes were expressed by inflammatory cells in the wound. The increased expression of S100A8 and S100A9 in wound keratinocytes is most likely related to the activated state of the keratinocytes and not secondary to the inflammation of the skin, since we also found up-regulation of S100A8 and S100A9 in the epidermis of activin-overexpressing mice, which develop a hyperproliferative and abnormally differentiated epidermis in the absence of inflammation. Furthermore, S100A8 and S100A9 expression was found to be associated with partially differentiated keratinocytes in vitro. Using confocal microscopy, both proteins were shown to be at least partially associated with the keratin cytoskeleton. In addition, cultured keratinocytes efficiently secreted the S100A8/A9 dimer. These results together with previously published data suggest that S100A8 and S100A9 are novel players in wound repair, where they might be involved in the reorganization of the keratin cytoskeleton in the wounded epidermis, in the chemoattraction of inflammatory cells, and/or in the defense against microorganisms.