gebhart/patrepeval huggingface dataset:
Diagnosis of ABCB11 gene mutations in children with intrahepatic cholestasis using high resolution melting analysis and direct sequencing (2014)

Intrahepatic cholestasis represents a heterogeneous group of disorders that begin during childhood, most commonly manifesting as neonatal cholestasis, and lead to ongoing liver dysfunction in children and adults. For children, inherited pathogenic factors of cholestasis have gained increasing attention owing to the rapid development of molecular biology technology. However, these methods have their advantages and disadvantages in terms of simplicity, sensitivity, specificity, time required and expense. In the present study, an effective, sensitive and economical method is recommended, termed high-resolution melting (HRM) analysis and direct sequencing, based on general polymerase chain reaction, to detect mutations in disease‑causing genes. As one type of inherited intrahepatic cholestasis, progressive familial intrahepatic cholestasis type 2 (PFIC2) is caused by pathogenic mutations in the ABCB11 gene, HRM was used to detect mutations in the ABCB11 gene in the present study, and the diagnosis for PFIC2 was made by comprehensive analysis of genetic findings and clinical features. Furthermore, the characteristics of mutations and single nucleotide polymorphisms (SNPs) in the ABCB11 gene were elucidated. A total of 14 types of mutations/polymorphisms were identified in 20 patients from mainland China, including six missense mutations (p.Y337H, p.Y472C, p.R696W, p.Q931P, p.D1131V and p.H1198R), one nonsense mutation (p.R928X) and seven SNPs (p.D36D/rs3815675, p.F90F/rs4148777, p.Y269Y/rs2287616, p.I416I/rs183390670, p.V444A/rs2287622, p.A865V/rs118109635 and p.A1028A/rs497692). Five mutations were novel. The majority of the mutations were different from those detected in other population groups. A total of 4/20 patients (1/5) were diagnosed to be PFIC2 by combining genetic findings with the clinical features. Polymorphisms V444A and A1028A, with an allele frequency of 74.5 and 67.2%, respectively, were highly prevalent in the mainland Chinese subjects. No differences were found between the patients with cholestasis and the control subjects. Efficient genetic screening facilitates the clinical diagnosis of genetic disorders. The present study demonstrated that HRM analysis was efficient and effective in detecting mutations and expanded the known spectrum of ABCB11 gene mutations.
Anatomy of the infrapatellar branch in relation to skin incisions and as the basis to treat neuropathic pain by cryodenervation. (2015)

Based on our findings, the surgeon can localize the unbranched main nerve. Compared with the current practice, our approach should allow for a lower impact on tissues and should facilitate complete pain relief through a single cryodenervation. Furthermore, we propose that the lateral parapatellar skin incision is an acceptable alternative surgical approach in knee replacement surgery because it is associated with the lowest risk of damage to the infrapatellar branch.
Nutritional and Functional Characteristics of Whey Proteins in Food Products (1998)

Whey proteins are well known for their high nutritional value and versatile functional properties in food products. Estimates of the worldwide production of whey indicate that about 700,000 tonnes of true whey proteins are available as valuable food ingredients. Nutritional and functional characteristics of whey proteins are related to the structure and biological functions of these proteins. During recent decades, interest has grown in the nutritional efficacy of whey proteins in infant formula and in dietetic and health foods, using either native or predigested proteins. This paper focuses attention on the differences and similarities in composition of human and bovine milks with reference to infant formula. More desirable milk protein composition for consumption by humans is obtained by the addition of lactoferrin and more specific fractionations of proteins from bovine milk. Optimization of heating processes is important to minimize the destruction of milk components during fractionation and preservation processes. Some functional characteristics of whey proteins are discussed in relation to their properties for application in food products. Information obtained from functional characterization tests in model systems is more suitable to explain retroactively protein behavior in complex food systems than to predict functionality.
Role of Raf in Vascular Protection from Distinct Apoptotic Stimuli (2003)

Raf kinases have been linked to endothelial cell survival. Here, we show that basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) differentially activate Raf, resulting in protection from distinct pathways of apoptosis in human endothelial cells and chick embryo vasculature. bFGF activated Raf-1 via p21-activated protein kinase-1 (PAK-1) phosphorylation of serines 338 and 339, resulting in Raf-1 mitochondrial translocation and endothelial cell protection from the intrinsic pathway of apoptosis, independent of the mitogen-activated protein kinase kinase-1 (MEK1). In contrast, VEGF activated Raf-1 via Src kinase, leading to phosphorylation of tyrosines 340 and 341 and MEK1-dependent protection from extrinsic-mediated apoptosis. These findings implicate Raf-1 as a pivotal regulator of endothelial cell survival during angiogenesis.
TNF Recruits TRADD to the Plasma Membrane But Not the trans -Golgi Network, the Principal Subcellular Location of TNF-R1 (1999)

The subcellular localization of TNF-R1 to the Golgi apparatus, initially observed in endothelial cells, has been confirmed using transfection of bovine aortic endothelial cells with a human TNF-R1 expression plasmid. The subcellular interactions of TNF-R1 and the TRADD (TNFR-associated death domain protein) adaptor protein have been analyzed in the human monocyte cell line U937 and the human endothelial cell line ECV304 by confocal immunofluorescence microscopy and by Western blot analysis of fractionated cell extracts. In untreated cells, in which TNF-R1 is found on the cell surface but principally localizes to the trans-Golgi network, TRADD is concentrated in the cis- or medial-Golgi region, but separates from the Golgi during cell fractionation. Coimmunoprecipitation studies have shown that TRADD binds to TNF-R1 within 1 min of TNF treatment in a cell fraction-containing plasma membrane. This association is followed by a gradual dissociation, which is prevented if receptor-mediated endocytosis is inhibited by hypertonic medium. In contrast, no association is detected between TRADD and TNF-R1 in the Golgi in response to exogenous TNF at any time examined. These results suggest that although TNF-R1 is predominantly a Golgi-associated protein and TRADD also localizes to the Golgi region, exogenous TNF causes TRADD to bind to TNF-R1 only at the plasma membrane.
Randomized, Placebo- and Active-Controlled Crossover Study of the Safety and Efficacy of THVD-102, a Fixed-dose Combination of Oxybutynin and Pilocarpine, in Subjects With Primary Focal Hyperhidrosis. (2017)

THVD-102 was generally well-tolerated. Both THVD-102 and oxybutynin 7.5 mg twice daily were effective in treating PFH. THVD-102 was associated with significantly reduced dry mouth compared to oxybutynin. <em>J Drugs Dermatol. 2017;16(2):127-132.</em>.
Recent Progress in Diazirine‐Based Photoaffinity Labeling (2008)

Abstract As a result of recent developments in molecular biology, the investigation of biofunctional machinery at ligand‐accepting interfaces has become one of the challenging and important subjects in the post‐genome field. The technique of photoaffinity labeling has become increasingly appreciated as a powerful methodology for this purpose. This microreviewfocuses on the synthesis of 3‐phenyl‐3‐(trifluoromethyl)diazirine, one of the most promising photophores, and its application to biomolecules.(© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2008)
A study of instruction cache organizations and replacement policies (1983)

Instruction caches are analyzed both theoretically and experimentally. The theoretical analysis begins with a new model for cache referencing behavior—the loop model. This model is used to study cache organizations and replacement policies. It is concluded theoretically that random replacement is better than LRU and FIFO, and that under certain circumstances, a direct-mapped or set associative cache may perform better than a full associative cache organization. Experimental results using instruction trace data are then given. The experimental results are shown to support the theoretical conclusions.
Vaccine Therapy in NHL: Future Promises and Current Limitations (2003)

Recent advances in genomics are revealing new molecular targets for vaccination strategies in cancer, and unraveling the immune pathways that must be activated. Initially, work focused on idiotypic antigen expressed by the clonal immunoglobulin (Ig) of B-cell tumors. This involved assembling the encoding V(H) and V(L) genes as single-chain Fv (scFv), which has been fused to Fragment C (FrC) of tetanus toxin to enhance recognition and response. The fusion gene induces strong anti-idiotypic protection against lymphoma in experimental models, and is now in clinical trials with encouraging results emerging. This principle of fusing a pathogen-derived sequence is widely applicable. A coat protein from a potato virus substituted for the FrC sequence has also been found to be capable of promoting anti-tumor immunity. The current design is effective in inducing anti-idiotypic (Id) antibody and CD4+ T-cell attack. For intracellular tumor antigens expressed as MHC Class I-associated peptides, a design consisting of a gene encoding a single domain of FrC linked to a candidate peptide sequence has been developed. This induces fast cytotoxic T-cell attack on peptide-expressing tumor cells. Injection of DNA appears safe and clinical trials will test the efficacy of this approach, and probably lead to improvements in these flexible vaccines.
Endothelin-1 and angiotensin-II stimulate delayed mitogenesis in cultured rat aortic smooth muscle cells: evidence for common signaling mechanisms. (1994)

The vasoactive peptides endothelin-1 (ET-1) and angiotensin-II (AII) have been implicated in chronic hypertension and may play important roles in related vascular diseases such as restenosis and atherosclerosis. Using a rat aortic smooth muscle (RASM) cell model, both ET-1 and AII induced concentration-dependent delayed increases in DNA synthesis relative to that in the serum-deprived controls. Stimulation of DNA synthesis was maximal at 100 nM for each peptide. All treatment of RASM cells resulted in a greater mitogenic effect (4- to 7-fold) than that observed for ET-1 (3-fold). When added in the presence of AII, ET-1 had a supplemental effect on DNA synthesis (5- to 10-fold above control). Although RASM cells expressed both ETA and AT1 receptors, radioligand binding experiments indicated that approximately 10-fold as many AT1 receptors as ETA receptors were present. In signal transduction studies, ET-1 and AII each elicited concentration-dependent increases in the intracellular Ca2+ concentration. ET-1 and AII also stimulated phosphoinositide metabolism and phosphorylation of a specific substrate for protein kinase-C. The release of total inositol phosphates in response to ET-1 and AII was concentration dependent and inhibited by the ETA receptor-selective antagonist BQ-123 and the AT1 receptor-selective antagonist losartan, respectively. In addition, tyrosine phosphorylation of 120- and 75-kilodalton proteins as well as the mitogen-activated protein kinases p44mapk and p42mapk was observed within 5 min of the addition of either ET-1 or AII. Taken together, these data indicate that ET-1 and AII may promote smooth muscle cell growth through common intracellular signaling mechanisms.
A novel viral 2,3-sialyltransferase (v-ST3Gal I): transfer of sialic acid to fucosylated acceptors (2000)

The substrate specificity of an alpha2,3-sialyltransferase (v-ST3Gal I) obtained from myxoma virus infected RK13 cells has been determined. Like mammalian sialyltransferase enzymes, the viral enzyme contains the characteristic L- and S-sialyl motif sequences in its catalytic domain. Analysis of the deduced amino acid sequences of cloned sialyltransferases suggests that v-ST3Gal I is closely related to mammalian ST3Gal IV. v-ST3Gal I catalyzes the transfer of sialic acid from CMP-NeuAc to Type I (Galbeta1-3GlcNAcbeta) II (Galbeta1-4GlcNAcbeta) and III (Galbeta1-3GalNAcbeta) acceptors. In addition, the viral enzyme also transfers sialic acid to the fucosylated acceptors Lewis(x) and Lewis(a). This substrate specificity is unlike any sialyltransferases described to date, though it is most comparable with those of mammalian ST3Gal IV enzymes. The products from reactions with fucosylated acceptors were characterized by capillary zone electrophoresis, (1)H-NMR spectroscopy and mass spectrometry. They were shown to be 2,3-sialylated Lewis(x) and 2,3-sialylated Lewis(a), respectively.
Spin-Dependent Tunneling in Self-Assembled Cobalt-Nanocrystal Superlattices (2000)

Self-assembled devices composed of periodic arrays of 10-nanometer-diameter cobalt nanocrystals display spin-dependent electron transport. Current-voltage characteristics are well described by single-electron tunneling in a uniform array. At temperatures below 20 kelvin, device magnetoresistance ratios are on the order of 10%, approaching the maximum predicted for ensembles of cobalt islands with randomly oriented preferred magnetic axes. Low-energy spin-flip scattering suppresses magnetoresistance with increasing temperature and bias-voltage.
Effect of Laparoscopy on the Immune System (2004)

Surgery induces alterations in local and systemic immune responses. These changes appear to be associated with an increase in postoperative morbidity. Minimally invasive techniques are considered to improve the preservation of immune function compared with open surgery and may therefore be beneficial for patient recovery. As laparoscopic techniques are increasingly used in abdominal surgery, more research has focussed on the immunologic consequences of these techniques. Nevertheless, the changes that occur in response to trauma are still not completely understood. The immunologic benefits of laparoscopic surgery are the most obvious for minor surgical procedures such as cholecystectomy and antireflux surgery. For more complex procedures such as colorectal surgery for cancer, the benefits are not immediately obvious. Although laparoscopic surgery for colorectal malignancies may be associated with higher survival rates and lower recurrence rates because of improved immune function, it has also been related to high incidences of port-site metastases. Reviews in the literature have now shown that incidences of port-site metastases are comparable to incidences of wound metastases after open surgery. However, it will be necessary to wait for the long-term results of randomized, clinical trials to provide further clarification of how immune function is altered after laparoscopic and open surgery for colorectal cancer.
ALCAT1 is a polyglycerophospholipid acyltransferase potently regulated by adenine nucleotide and thyroid status (2008)

Acyl-CoA:lysocardiolipin acyltransferase-1 (ALCAT1) catalyzes acylation of lysocardiolipin back to cardiolipin, an important step in cardiolipin remodeling. The present study reports the catalytic properties of ALCAT1 in vitro and its regulation by thyroid hormone status in mouse liver and heart. Recombinant ALCAT1 expressed in Sf9 cells preferred basic pH conditions and did not require divalent cations or integrity of the subcellular membrane for its enzymatic activity. Recombinant ALCAT1 was potently inhibited by ADP and ATP, but not by adenosine nucleotide analogs or other nucleotides, such as UTP and GTP, suggesting that ALCAT1 does not require ATP hydrolysis for its enzyme activity. In addition to cardiolipin, ALCAT1 also catalyzed acylation of other members of the polyglycerophospholipid family, including phosphatidylglycerol, a precursor for cardiolipin synthesis, and bis(monoacylglycero)phosphate, a structural isomer of lysophosphatidylglycerol and a metabolic intermediate of cardiolipin. These findings suggest that ALCAT1 plays a role in the remodeling of other polyglycerophospholipids. In support of a regulatory role of ALCAT1 in cardiolipin remodeling in response to oxidative stress, ALCAT1 expression in liver and heart was significantly downregulated in mice with hypothyroidism and upregulated in mice treated with thyroid hormone, which is known to stimulate mitochondrial activity, oxidative stress, and cardiolipin remodeling.
Pre-decoding mechanism for superscalar architecture (2002)

A predecoding mechanism for superscalar processors that is necessary to issue instructions to plural functional units is described. Using a predecoding mechanism, a processor can issue instructions without increasing the cycle time or the branch penalty. The predecoder decides which functional unit should execute an instruction during a cache miss and refill. A special tag, the call predecode tag, is generated by the predecoder. This tag is saved with instructions to an instruction cache memory. The processor fetches instructions with the predecode tag and issues instructions controlled by the predecode tag. Using this mechanism, fast cycle times, comparable to those of RISC processors, are attained.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Effects of Arginine Vasopressin on Oxygenation and Haemodynamics during One-Lung Ventilation in an Animal Model (2008)

In a case of arterial hypotension during one-lung ventilation, haemodynamic support may be required to maintain adequate mean arterial pressure. Arginine vasopressin, a potent systemic vasoconstrictor with limited effects on the pulmonary artery pressure, has not been studied in this setting. Twelve female pigs were anaesthetised and ventilated and arterial, central venous and pulmonary artery catheters were inserted. A left-sided double lumen tube was placed via tracheostomy and one-lung ventilation was initiated. The animals were in the left lateral position, with the left lung ventilated and right lung collapsed. Respiratory and haemodynamic values were recorded before and during a continuous infusion of arginine vasopressin sufficient to double the mean arterial pressure. The arginine vasopressin caused a decrease in cardiac output (3.8+/-1.1 vs. 2.7+/-0.7 l/min, P <0.001) and mixed-venous oxygen tension (39.1+/-5.8 vs. 34.4+/-5 mmHg, P=0.003). Pulmonary artery pressure was unchanged (24+/-2 vs. 24+/-3 mmHg, P=0.682). There was no effect of the arginine vasopressin on arterial oxygen tension (226+/-106 vs. 231+/-118 mmHg, P=0.745). However, there was a significant decrease in shunt fraction (28.3+/-6.2 vs. 24.3+/-7.8%, P=0.043) and a significant proportional increase in perfusion of the ventilated lung (78.8+/-9.5 vs. 85.5+/-7.9%, P=0.036). In our animal model of one-lung ventilation, doubling mean arterial pressure by infusion of arginine vasopressin significantly affected global haemodynamics, but had no influence on systemic arterial oxygen tension.
<title>Effect of laser mask repair-induced residue and quartz damage in sub-half-micrometer DUV wafer processes</title> (1995)

In this paper, the effect of laser ablation induced carbon residue and quartz damage near the mask repair region in a sub-half-micron DUV wafer printing process is discussed. In the study, we found that the laser ablation induced carbon residue and quartz damage during a clean-up process of a clear intrusion mask defect repair could cause both phase and transmission errors near the repaired region. As a result, the printing characteristics of the resist in the repaired region are different than that of the defect-free region, especially at defocus conditions. At zero defocus, the resist critical dimension (CD) difference between the repaired and defect-free regions is mainly determined by the repair edge error and the amount of transmission loss which is due to the quartz damage and carbon residue in the clear mask region. At positive defocus, the repaired region tends to print narrower than that of defect-free region and vice versa for the negative defocus conditions. This phenomenon is the result of quartz damage induced phase error in the clear mask area near the repair. This quartz damage induced effect is more pronounced at 0.25 micrometer regime than that of 0.4 micrometer regime. In the study, we also compared wafer level results of laser repaired features to that of focused ion beam repaired features to identify the carbon residue and quartz damage induced effects in the laser repair. Our simulations also predicted the above observed experimental results.
Functional Annotation, Genome Organization and Phylogeny of the Grapevine (Vitis vinifera) Terpene Synthase Gene Family Based on Genome Assembly, FLcDNA Cloning, and Enzyme Assays (2010)

The highly expanded VvTPS gene family underpins the prominence of terpenoid metabolism in grapevine. We provide a detailed experimental functional annotation of 39 members of this important gene family in grapevine and comprehensive information about gene structure and phylogeny for the entire currently known VvTPS gene family.
Monoclonal antibodies to immunodeterminants of lipoteichoic acids (1984)

Murine hybrid cell lines producing monoclonal antibodies directed against determinants present on lipoteichoic acids were generated. Hapten inhibition studies showed that one group of monoclonal antibodies was inhibited by deacylated cardiolipin, and the second group was inhibited by kojibiose. Thus, antibodies directed against the polyglycerophosphate chain, which is common to the lipoteichoic acids of many gram-positive species, and against the streptococcal group D antigen were obtained.
Therapeutic proteins : methods and protocols (2005)

With the completion of the human genome, the number of protein-based drug candidates has increased dramatically, along with the need to find methods for producing these proteins on a scale large enough to meet demand without compromising the authenticity of the final product. In Therapeutic Proteins: Methods and Protocols, world-class researchers share their innovative and proven techniques for the production of therapeutic proteins downstream of the discovery stage. The methods use a variety of sources for producing therapeutic proteins, including bacterial and yeast expression systems, and insect and mammalian cells, and then cover the purification of the resulting protein using both state-of-the-art and traditional methods, such as those sourced from plasma. Additional chapters offer methods for the characterization of therapeutic proteins throughout the production process, along with methods and strategies for viral inactivation and protein formulation. The protocols follow the successful Methods in Molecular Biology™ series format, each offering step-by-step laboratory instructions, an introduction outlining the principles behind the technique, lists of the necessary equipment and reagents, and tips on troubleshooting and avoiding known pitfalls. Authoritative and highly practical, Therapeutic Proteins: Methods and Protocols offers both novice and experienced researchers the latest innovative, readily reproducible techniques, as well as helpful commentaries on the development and production of therapeutic proteins, ranging from their expression to actual formulation