gebhart/patrepeval huggingface dataset:
G Protein Pathways (2002)

The heterotrimeric guanine nucleotide-binding proteins (G proteins) are signal transducers that communicate signals from many hormones, neurotransmitters, chemokines, and autocrine and paracrine factors. The extracellular signals are received by members of a large superfamily of receptors with seven membrane-spanning regions that activate the G proteins, which route the signals to several distinct intracellular signaling pathways. These pathways interact with one another to form a network that regulates metabolic enzymes, ion channels, transporters, and other components of the cellular machinery controlling a broad range of cellular processes, including transcription, motility, contractility, and secretion. These cellular processes in turn regulate systemic functions such as embryonic development, gonadal development, learning and memory, and organismal homeostasis.
Piezoresistance Effect in Germanium and Silicon (1954)

Uniaxial tension causes a change of resistivity in silicon and germanium of both $n$ and $p$ types. The complete tensor piezoresistance has been determined experimentally for these materials and expressed in terms of the pressure coefficient of resistivity and two simple shear coefficients. One of the shear coefficients for each of the materials is exceptionally large and cannot be explained in terms of previously known mechanisms. A possible microscopic mechanism proposed by C. Herring which could account for one large shear constant is discussed. This so called electron transfer effect arises in the structure of the energy bands of these semiconductors, and piezoresistance may therefore give important direct experimental information about this structure.
Production of CFTR-null and CFTR-ΔF508 heterozygous pigs by adeno-associated virus–mediated gene targeting and somatic cell nuclear transfer (2008)

Progress toward understanding the pathogenesis of cystic fibrosis (CF) and developing effective therapies has been hampered by lack of a relevant animal model. CF mice fail to develop the lung and pancreatic disease that cause most of the morbidity and mortality in patients with CF. Pigs may be better animals than mice in which to model human genetic diseases because their anatomy, biochemistry, physiology, size, and genetics are more similar to those of humans. However, to date, gene-targeted mammalian models of human genetic disease have not been reported for any species other than mice. Here we describe the first steps toward the generation of a pig model of CF. We used recombinant adeno-associated virus (rAAV) vectors to deliver genetic constructs targeting the CF transmembrane conductance receptor (CFTR) gene to pig fetal fibroblasts. We generated cells with the CFTR gene either disrupted or containing the most common CF-associated mutation (DeltaF508). These cells were used as nuclear donors for somatic cell nuclear transfer to porcine oocytes. We thereby generated heterozygote male piglets with each mutation. These pigs should be of value in producing new models of CF. In addition, because gene-modified mice often fail to replicate human diseases, this approach could be used to generate models of other human genetic diseases in species other than mice.
Tolerance and immunity to MUC1 in a human MUC1 transgenic murine model. (1998)

The human epithelial mucin, MUC1, is a large transmembrane glycoprotein that is expressed on most simple epithelia. It is overexpressed and aberrantly glycosylated on many human epithelial tumors, including more than 90% of human breast cancers. MUC1 is of interest as an immunotherapy target because patients with breast, ovarian, and pancreatic cancers have T lymphocytes in their tumor-draining lymph nodes that can be induced to recognize and lyse MUC1-expressing tumor cells. We have produced a transgenic mouse model that expresses the human MUC1 molecule on an inbred C57Bl/6 background to investigate the effect of endogenous expression of MUC1 on the ability of mice to generate antitumor immunity to MUC1-expressing tumors. Transgenic mice expressed the human transgene in a pattern and level consistent with that observed in humans. Transgenic mice were tolerant to stimulation by MUC1 as evidenced by the ability of MUC1-expressing tumor cells to grow in these mice, whereas MUC1-expressing cells were eliminated from wild-type mice. Moreover, transgenic mice immunized with MUC1 peptides failed to exhibit immunoglobulin class switching to the IgG subtypes. These data suggest that endogenous expression of MUC1 protein by MUC1 transgenic mice induces T-cell tolerance to stimulation by MUC1. The transgenic mice will provide a useful model to investigate the mechanisms that regulate immunological tolerance to tumor antigens and will facilitate the investigation of anti-MUC1 immunotherapy formulations.
Expression of a cloned Bacillus thuringiensis delta-endotoxin gene in Bacillus subtilis (1989)

The entire coding region of the Bacillus thurigiensis HD73 crystal protein gene was subcloned from plasmid pJWK20 into the integration vector pUG2-15. This plasmid expresses chloramphenicol resistance when integrated into the Bacillus subtilis chromosome in the outH locus near the recE region. The correct molecular organization of the integrated plasmid was verified by hybridization to Southern blots of chromosomal DNA digests. Production of the toxic crystal protein was monitored at different time points during the life cycle of B. subtilis. Toxicity assays against Anagasta (Ephestia) larvae, direct electron microscopy crystal detection, and immunoblotting assays proved that the expression of the gene in B. subtilis is time regulated and restricted mainly to the sporulation stage. RNase protection experiments defined the transcription initiation start point and the transcription timing. All tests were made in a strain containing one to three copies of the integrated plasmid and in a strain subjected to an amplification regimen.
C-Reactive Protein and Other Circulating Markers of Inflammation in the Prediction of Coronary Heart Disease (2004)

C-reactive protein is a relatively moderate predictor of coronary heart disease. Recommendations regarding its use in predicting the likelihood of coronary heart disease may need to be reviewed.
Immunotherapy of tumors with vaccine based on quail homologous vascular endothelial growth factor receptor-2 (2003)

The breaking of immune tolerance of "self-antigens" associated with angiogenesis is an attractive approach to cancer therapy by active immunity. We used vascular endothelial growth factor receptor-2 (VEGFR-2) as a model antigen to explore the feasibility of the immunotherapy with a vaccine based on a xenogeneic homologous protein. To test this concept, we prepared a quail homologous VEGFR-2 protein vaccine (qVEGFR) based on quail VEGFR-2. At the same time, a protein vaccine based on the corresponding ligand-binding domain of mouse self-VEGFR-2 (mVEGFR) was also prepared and used as a control. We found that immunotherapy with qVEGFR was effective at protective and therapeutic antitumor immunity in several solid and hematopoietic tumor models in mice. Autoantibodies against mouse VEGFR-2 (Flk-1) were identified by Western blot analysis and enzyme-linked immunosorbent assay (ELISA). Anti-VEGFR antibody-producing B cells were detectable by ELISPOT. Endothelial deposition of immunoglobulins developed within tumor. VEGF-mediated endothelial cell proliferation was inhibited in vitro by immunoglobulins from qVEGFR-immunized mice. Antitumor activity was caused by the adoptive transfer of the purified immunoglobulins. Antitumor activity and production of autoantibodies against Flk-1 could be abrogated by the depletion of CD4+ T lymphocytes. Angiogenesis was apparently inhibited within the tumors, and the vascularization of alginate beads was also reduced. No marked toxicity was found in the immunized mice. The observations may provide a vaccine strategy for cancer therapy through the induction of autoimmunity against the growth factor receptor associated with angiogenesis in a cross-reaction with single xenogeneic homologous protein.
A second visual rhodopsin gene,rh1-2, is expressed in zebrafish photoreceptors and found in other ray-finned fishes (2016)

Rhodopsin (rh1) is the visual pigment expressed in rod photoreceptors of vertebrates that is responsible for initiating the critical first step of dim-light vision. Rhodopsin is usually a single copy gene; however, we previously discovered a novel rhodopsin-like gene expressed in the zebrafish retina, rh1-2, which we identified as a functional photosensitive pigment that binds 11-cis retinal and activates in response to light. Here, we localized expression of rh1-2 in the zebrafish retina to a subset of peripheral photoreceptor cells, which indicates a partially overlapping expression pattern with rh1 We also expressed, purified and characterized Rh1-2, including investigation of the stability of the biologically active intermediate. Using fluorescence spectroscopy, we found the half-life of the rate of retinal release of Rh1-2 following photoactivation to be more similar to that of the visual pigment rhodopsin than to the non-visual pigment exo-rhodopsin (exorh), which releases retinal around 5 times faster. Phylogenetic and molecular evolutionary analyses show that rh1-2 has ancient origins within teleost fishes, is under similar selective pressure to rh1, and likely experienced a burst of positive selection following its duplication and divergence from rh1 These findings indicate that rh1-2 is another functional visual rhodopsin gene, which contradicts the prevailing notion that visual rhodopsin is primarily found as a single copy gene within ray-finned fishes. The reasons for retention of this duplicate gene, as well as possible functional consequences for the visual system, are discussed.
AlN thin films with controlled crystallographic orientations and their microstructure (1987)

C-axis oriented AlN thin films, or AlN 〈001〉, are normally obtained by various reactive deposition methods. We have found the AlN thin films with orientations other than 〈001〉 can be prepared by controlling rf sputter deposition conditions. Three different orientations, 〈001〉, 〈102〉, and 〈101〉, were independently grown and verified by x-ray diffraction. A factor controlling the growth habit is discussed. A cross-sectional transmission electron microscopy/scanning transmission electron microscopy technique with microdiffraction was used to study microstructure of the film. It is found that the AlN thin film is grown in a columnar structure and individual columnar grains were verified to be single crystalline.
[Analysis of the nucleotide sequence of a fragment (92-100%) of the CELO avian adenovirus genome]. (1993)

The nucleotide sequence of 92-100% of the adenovirus CELO (FAV1), strain Phelps, genome has been determined. The computer analysis of the sequences revealed a ClaI site methylated by m*Ecodam. A recognition site for XbaI and two sites for PstI, not found in the corresponding genome of CELO, strain Ote, have been determined. Three extensive (more than 100 amino acid residues) open reading frames exist, coding for the polypeptides with molecular weights of 31.5, 19.3 and 14.5 kD (276, 178 and 128 amino acids, respectively). Some shorter open reading frames have been detected as well within the sequences studied.
Efficient Synthesis of Narrowly Dispersed Brush Polymers via Living Ring-Opening Metathesis Polymerization of Macromonomers (2009)

Various macromonomers (MMs) were efficiently synthesized through the copper-catalyzed “click” coupling of a norbornene moiety to the chain end of poly(methylacrylate), poly(t-butylacrylate), and polystyrene that were prepared using atom transfer radical polymerization. Ring-opening metathesis polymerization (ROMP) of these MMs was carried out using the highly active, fast-initiating ruthenium catalyst (H2IMes)(pyr)2(Cl)2RuCHPh in THF at room temperature. ROMP of MMs was found to be living with almost quantitative conversions (>90%) of MMs, producing brush polymers with very low polydispersity indices of 1.01−1.07 and high Mn’s of 200−2600 kDa. The efficient ROMP of such MMs provides facile access to a variety of brush polymers and overcomes previous difficulties in the controlled polymerization of MMs. Atomic force microscopy of the brush polymer products revealed extended, wormlike shapes as a result of significant steric repulsion of densely grafted side chains.
Double-antigen sandwich time-resolved immunofluorometric assay for the detection of anti-hepatitis C virus total antibodies with improved specificity and sensitivity (2008)

Current anti-hepatitis C virus (HCV) antibody screening immunoassays are routinely based on an indirect format. Although their use for anti-HCV antibody detection has achieved a very high specificity and sensitivity, false-positive results are still a problem especially among populations with a low prevalence of HCV infection. One strategy to obviate this problem is to adapt the assay from an indirect format to a double-antigen sandwich one to further improve its specificity. In this study, a double-antigen sandwich time-resolved immunofluorometric assay (DAS-TRIFMA) has been developed to detect total anti-HCV antibodies based on biotin-streptavidin interaction. For comparison, 1025 samples were analysed by the DAS-TRIFMA and three indirect anti-HCV antibody detection methods. For samples with discordant results, PCR-ELISA and Inno-LIA were employed as supplementary assays to analyse the presence of HCV antibodies. With regard to the 1025 clinical samples, the overall concordance between the DAS-TRIFMA and the three indirect methods was 99.41, 98.93 and 98.93 % for Ortho ELISA 3.0, WAT ELISA and I-TRIFMA, respectively. The specificity/sensitivity of the DAS-TRIFMA, Ortho HCV ELISA 3.0, WAT HCV ELISA and I-TRIFMA were 100/99.09, 99.34/98.18, 99.23/97.27 and 99.01 %/98.18 %, respectively. The DAS-TRIFMA was able to detect HCV antibodies at a concentration about 1/10 of that detectable by indirect methods. From the obtained results and their comparison, it is concluded that the DAS-TRIFMA is a more specific and reliable method for screening anti-HCV antibodies, and weakly positive S/Co values by the DAS-TRIFMA were more predictive of HCV infection than those by indirect methods.
Role of Foxp3-positive Tumor-infiltrating Lymphocytes in the Histologic Features and Clinical Outcomes of Hepatocellular Carcinoma (2012)

The role of Foxp3-positive regulatory T cells (Foxp3 Tregs) in suppression of antitumoral immune response is well documented in patients with cancer. However, it is not known whether Foxp3 Tregs are associated with specific clinicopathologic characteristics of hepatocellular carcinoma (HCC). The aims of the present study were: (1) to investigate the relationship between Foxp3 Tregs and histologic differentiation, Edmondson-Steiner (ES) nuclear grade, vascular invasion, and pathologic stage of HCC in patients undergoing surgery for their disease; and (2) to evaluate any Foxp3 Treg-defined difference in the risk for tumor recurrence or death. The study sample included 131 histologic sections of HCC. The number of tumor-infiltrating CD3, CD8, and Foxp3 lymphocytes was assessed by immunohistochemistry. An increased Foxp3:CD3 ratio was associated with more poorly differentiated HCC (P=0.0016) and higher ES nuclear grade (P=0.0407). An increased Foxp3:CD8 ratio was also associated with poorer differentiation (P=0.0044), higher ES nuclear grade (P=0.0179), recurrence (P=0.0183), decreased overall survival (hazard ratio=1.153; 95% confidence interval, 1.019-1.304; P=0.0235), and decreased disease-free survival (hazard ratio=1.138; 95% confidence interval, 1.016-1.273; P=0.0249). Tumor size and type of surgery (surgical resection) were associated with decreased disease-free survival on univariate analysis but not on multivariate analysis. In conclusion, a higher concentration of tumor-infiltrating Foxp3 Tregs in HCC is associated with higher grade and poorly differentiated tumors and signifies an unfavorable prognosis.
AspergillusEnzymes Involved in Degradation of Plant Cell Wall Polysaccharides (2001)

Degradation of plant cell wall polysaccharides is of major importance in the food and feed, beverage, textile, and paper and pulp industries, as well as in several other industrial production processes. Enzymatic degradation of these polymers has received attention for many years and is becoming a more and more attractive alternative to chemical and mechanical processes. Over the past 15 years, much progress has been made in elucidating the structural characteristics of these polysaccharides and in characterizing the enzymes involved in their degradation and the genes of biotechnologically relevant microorganisms encoding these enzymes. The members of the fungal genus Aspergillus are commonly used for the production of polysaccharide-degrading enzymes. This genus produces a wide spectrum of cell wall-degrading enzymes, allowing not only complete degradation of the polysaccharides but also tailored modifications by using specific enzymes purified from these fungi. This review summarizes our current knowledge of the cell wall polysaccharide-degrading enzymes from aspergilli and the genes by which they are encoded.
Autotaxin, a Secreted Lysophospholipase D, Is Essential for Blood Vessel Formation during Development (2006)

Autotaxin (ATX), or nucleotide pyrophosphatase-phosphodiesterase 2, is a secreted lysophospholipase D that promotes cell migration, metastasis, and angiogenesis. ATX generates lysophosphatidic acid (LPA), a lipid mitogen and motility factor that acts on several G protein-coupled receptors. Here we report that ATX-deficient mice die at embryonic day 9.5 (E9.5) with profound vascular defects in yolk sac and embryo resembling the Galpha13 knockout phenotype. Furthermore, at E8.5, ATX-deficient embryos showed allantois malformation, neural tube defects, and asymmetric headfolds. The onset of these abnormalities coincided with increased expression of ATX and LPA receptors in normal embryos. ATX heterozygous mice appear healthy but show half-normal ATX activity and plasma LPA levels. Our results reveal a critical role for ATX in vascular development, indicate that ATX is the major LPA-producing enzyme in vivo, and suggest that the vascular defects in ATX-deficient embryos may be explained by loss of LPA signaling through Galpha13.
Remembrance of Professor David Gregory (2001)

The Board and Staff of the Maine Law Review dedicate this issue to the memory of Professor David Doliver Gregory, who passed away on December 9, 2000. The Maine legal community and the University of Maine School of Law mourn the loss of our beloved teacher, advocate, and friend. In the collective memory of his students, Professor Gregory will always be remembered for the Socratic genius that he employed so effectively in class; his keen wit, often accompanied by a knowing smile and a twinkle in his eyes; his passion for ferreting out seemingly elusive legal principles; and his compassion and warmth for those he instructed. Perhaps above all, Professor Gregory will be recalled as the archetypal Law Professor that he was. He was the rarest of educators, someone who taught us how to challenge ourselves intellectually, and who demonstrated both in his life and in his teaching that the law not only reaches all facets of society but also touches upon the most fundamental and important aspects of human existence itself. On January 17, 2001 hundreds of his colleagues and students gathered at the First Parish Church in Portland, Maine to celebrate Professor Gregory's life. What follows are the remembrances delivered at the memorial service and two tributes from professional colleagues that give a picture of his life in the courtroom and the classroom.
Atlas of Functional Histology (1999)

SECTION 1 Chapter 1 The Cell Chapter 2 Blood Chapter 3 Epithelial Cells Chapter 4 Support and connective tissues Chapter 5 Muscle Chapter 6 Nervous tissue and CNS SECTION 2 Chapter 7 Circulatory system Chapter 8 Skin Chapter 9 Skeletal tissues Chapter 10 Immune system Chapter 11 Respiratory system Chapter 12 Oral/salivary system Chapter 13 Gastrointestinal tract Chapter 14 Major gut glands Chapter 15 Urinary system Chapter 16 Endocrine system Chapter 17 Female Chapter 18 Male Chapter 19 Special senses Lookalikes
Early Detection of Systemic Degos Disease (DD) or Malignant Atrophic Papulosis (MAP) May Increase Survival (2010)

Purpose: Our experience successfully treating MAP led us to investigate means of early detection of gastrointestinal involvement. Methods: Literature search via PubMed using the words Malignant Atrophic Papulosis, Degos Disease, endoscopy, laparoscopy and laparotomy. The process resulted in a total of 200 articles that were further analyzed regarding diagnostic procedures. Eleven cases were identified in which endoscopy was performed. Results of endoscopy and laparotomy in our patient with MAP were compared to those in the literature. Results: MAP is a rare thrombo-occlusive vasculopathy that can affect multiple organ systems. The small bowel is the most common internal organ involved, with repeated microperforations that lead to death. We successfully treated a 17 year old male who survived small bowel microperforations. Two months prior to his presentation with acute abdomen, colonoscopy showed patchy erythematous mucosa with central clearing at the sigmoid, rectosigmoid colon and splenic flexure. Endoscopy demonstrated mild acute gastritis. At laparotomy, innumerable classical lesions (0.3-0.5) cm papules with central pearly hue and erythematous border) were seen. He rapidly responded and has had sustained response to infusions of eculizumab, an inhibitor of C5 activation, which stops C5a (anaphylatoxin) production and halts C5b-9 tissue deposition. In virtually all prior reports, those with systemic disease die. GI involvement occurs 60% of the time, usually one to three years after the skin lesions first appear. The skin and GI lesions look very similar both grossly and on histology. Literature review (9 out of the 11 endoscopies performed had endoscopic changes) led us to strongly believe that very commonly there are endoscopic changes prior to or simultaneous to catastrophic bowel perforation. Conclusion: Guidelines for evaluation of MAP have not been established. In patients with an acute abdomen, findings at laparatomy are always striking, while endoscopic changes might be subtle. Eculizumab may dramatically change the prognosis for MAP, making early detection more critical. Endoscopic evaluation is warranted in all patients with skin lesions. In both the literature and in our own case, endoscopic evaluation may reveal pearly-rose patches with hyperemic rim in the mucosa. Findings are most commonly seen in the small bowel, especially jejunum, but can involve any part of the gastrointestinal lumen. Laparoscopy could be a more sensitive diagnostic tool. An open label study of eculizumab in MAP is being developed.