gebhart/patrepeval huggingface dataset:
The Cellular Protein Level of Parkin Is Regulated by Its Ubiquitin-like Domain (2003)

Parkin is a ubiquitin-protein isopeptide ligase (E3) involved in ubiquitin/proteasome-mediated protein degradation. Mutations in the parkin gene cause a loss-of-function and/or alter protein levels of parkin. As a result, the toxic build-up of parkin substrates is thought to lead to autosomal recessive juvenile Parkinsonism. To identify a role for the ubiquitin-like domain (ULD) of parkin, we created a number of hemagglutinin (HA)-tagged parkin constructs using mutational and structural information. Western blotting and immunocytochemistry showed a much stronger expression level for HA-parkin residues 77-465 (without ULD) than HA-parkin full-length (with ULD). The deletion of ULD in Drosophila parkin also caused a sharp increase in expression of the truncated form, suggesting that the function of the ULD of parkin is conserved across species. By progressive deletion analysis of parkin ULD, we found that residues 1-6 of human parkin play a crucial role in controlling the expression levels of this gene. HA-parkin residues 77-465 showed ubiquitination in vivo, demonstrating that the ULD is not critical for parkin auto-ubiquitination; ubiquitination seemed to cluster on the central domain of parkin (residues 77-313). These effects were specific for the ULD of parkin and not transfection-, toxic-, epitope tag-, and/or vector-dependent. Taken together, these data suggest that the 76 most NH(2)-terminal residues (ULD) dramatically regulate the protein levels of parkin.
Repression and activation of arginine transport genes in Escherichia coli K 12 by the ArgP protein (1999)

In Escherichia coli K 12, arginine modulates the functioning of the arginine transport system. Cells grown in the presence of arginine show a 60 % reduction in the active incorporation of radioactive arginine. This regulation of arginine transport is independent of the regulation of arginine biosynthesis. Previously, a mutant was isolated with a 90 % reduction of arginine transport. The mutation affected also the transport of ornithine and lysine. It was mapped and assigned to a locus named argP at minute 65 of the E. coli linkage map. Genetic studies showed that in argP/argP+ merodiploids, the mutated argP allele is dominant. The argP+ gene was cloned and sequenced. Analysis of the sequenced gene revealed that it is identical with iciA, an E. coli gene that encodes an inhibitor of chromosomal initiation of replication in vitro. The sequence analysis of the mutated argP gene identified a single mutation that led to the substitution of proline for serine in the C-terminal domain of the ArgP protein. This protein has homology with a large group of prokaryotic regulatory proteins known as the LysR family. Proteins from this family have been shown to function as transcriptional regulators. Here, it is shown that the ArgP protein activates the formation of the ArgK protein, an ATP-binding protein essential for the operation of the arginine transport system. In the presence of l-arginine, ArgP inhibits its own synthesis.
Morphologic Analysis of Tissue-Expander Shape Using a Biomechanical Model (1993)

Using a biomechanical model designed to reproduce the forces exerted by the soft tissues of the chest wall, the contours created by several currently available round as well as anatomically shaped tissue expanders were evaluated. Parameters that describe expander shape were defined, the most useful of which proved to be the point of maximal projection and the percentage of upper pole deformity. Direct comparison of seven different expanders with respect to these variables revealed the anatomically shaped expanders to offer improved contours over traditional round designs. Continuing modifications in expander design should focus on lowering the point of maximal projection and minimizing the upper pole deformity.
Thrombotic Microangiopathies (2002)

This article reviews the substantial progress made in understanding the thrombotic microangiopathies. The mechanisms of both thrombotic thrombocytopenic purpura and the hemolytic–uremic syndrome are considered.
Thioredoxin increases the proliferation of human B-cell lines through a protein kinase C-dependent mechanism. (1994)

Thioredoxin (Trx) catalyzes thiol-disulfide oxidoreductions. We and others recently showed that human Trx could function as an autocrine growth factor for human lymphoid cells immortalized by the human T-lymphotrophic virus type I or the Epstein-Barr virus. Here we report that reduced Trx from Escherichia coli generated by NADPH and thioredoxin reductase increases the proliferation of an Epstein-barr virus(+)-B cell line 1G8, which constitutively produces low amounts of human Trx. This proliferative effect involved the activation of protein kinase C through its translocation to the membrane. Staurosporin and calphostin C, two inhibitors of protein kinase C, but not of H8, a protein kinase A inhibitor, were able to block Trx-dependent proliferation. The addition of Trx to 1G8 cells resulted in the formation of inositol 1,4,5-triphosphate and sn-1,2-diacylglycerol by a phosphoinositide-specific phospholipase C, as well as increased free calcium concentration. Diacylglycerol showed a biphasic increase; the first phase, corresponding to an early peak (30 s) of inositol 1,4,5-triphosphate and a second larger, prolonged phase. The second phase was inhibited by propranolol, a specific inhibitor of phosphohydrolase, indicating that it is most likely derived from phosphatidylcholine hydrolysis by the sequential action of phospholipase D and phosphatidic acid phosphohydrolase. Our data suggest that enhanced phosphoinositide-specific phospholipase C activity induced by the dithiol form of Trx in 1G8 cells is associated to protein kinase C activation, and thus plays a role in the permanent growth of Epstein-Barr virus-infected B cells.
Dietary marine algae maintains egg consumer acceptability while enhancing yolk color (1998)

A drum-dried docosahexaenoic acid (DHA; C22:6n-3) enriched marine microalgal product (MA) was investigated as a n-3 fatty acid (n-3 FA) source in laying hen diets. Hen diets were supplemented with 2.4 or 4.8% MA. Eggs were analyzed for yolk color following 4 wk of feeding as well as weekly for 4 wk. Egg flavor was evaluated by consumer panelists. Feeding MA significantly (P < 0.01) increased yolk a* values in a dose response manner as early as 1 wk post-MA feeding. Consumer panelists found n-3 FA enriched eggs as acceptable as typical eggs. These data suggest that dietary MA is useful for enhancing yolk n-3 FA and color while maintaining consumer acceptability of the resulting egg product.
Synthesis and antitubercular activity of N-(2-naphthyl)glycine hydrazide analogs (1989)

N-(2-Naphthyl)glycine hydrazide analogues were synthesized and tested for possible in vitro antitubercular activity. N-(2-Naphthyl)alanine hydrazide (3), N-methyl-N-(2-naphthyl)glycine hydrazide (5), N-(6-methoxy-2-naphthyl)glycine hydrazide (7), and 3-(2-naphthylamino)butyric acid hydrazide (23) showed potent inhibitory action against Mycobacterium tuberculosis H37Rv in Youman's medium at concentrations ranging from 0.5 to 10.0 micrograms/mL. These compounds showed significant inhibitory action against isonicotinic acid hydrazide and streptomycin-resistant strains of M. tuberculosis. N-(6-Quinolyl)glycine hydrazide (18) and 3-(2-quinolylamino)butyric acid hydrazide (24), which are bioisosteres of compounds 1 and 23, showed loss of antitubercular activity at low concentrations.
Helium-implanted silicon: A study of bubble precursors (1999)

The interaction of helium atoms with the radiation damage imparted to (100) silicon single crystal by He+ implantation at 5×1015 cm−2, 20 keV, and liquid–nitrogen temperature is investigated by means of various complementary techniques during and after thermal treatments. Thermal programmed desorption was used to study the dissociation kinetics of helium from the defects and to plan suitable heat treatments for the other techniques. The helium profiles were determined by 8 MeV N2+15 elastic recoil detection, quantitative data on damage were obtained by channeling Rutherford backscattering spectrometry, double crystal x-ray diffraction, and positron annihilation spectroscopy. Isothermal treatments at 250 °C produce first helium redistribution and trapping in vacancy-like defects, rather than helium desorption from traps. The process is thermally activated with an effective activation energy, dispersed in a band from 1.1 to about 1.7 eV. For higher temperature treatments (2 h at 500 °C) the traps are almost emptied and at 700 °C all vacancy-like defects are annealed out. No bubbles or voids are observed by transmission electron microscopy, either in the as-implanted or in annealed samples.
Analysis of an inversion within the human beta globin gene cluster (1985)

We have cloned and sequenced the DNA from two regions of the defective beta-globin gene cluster from a patient with Indian A gamma delta beta thalassaemia, and confirmed the complex and unusual pattern of rearrangement involving two separate deletions (0.8 kb and 7.5 kb) the inversion of the 15.5 kb segment separating them, as previously proposed from gene mapping studies [1]. All four breakpoints occur within the transcribed region of the globin genes and at one junction are found six nucleotides of unknown origin. This unique rearrangement results in enhanced expression of the upstream fetal gene, and is therefore is pertinent to the localisation of any putative control region involved in the coordinate expression of fetal and adult genes.
Ibrutinib: an evidence-based review of its potential in the treatment of advanced chronic lymphocytic leukemia (2013)

Abstract: Chronic lymphocytic leukemia (CLL) is a heterogeneous disease with a variable course, and remains an incurable disease. Frequent relapses and eventual resistance to fludarabine characterize symptomatic CLL and portends a dismal prognosis for patients. Growing evidence has shown that signaling pathways such as the B cell receptor and NFkB are implicated in the survival and proliferation of the CLL cells which are ultimately associated with persistence of the disease. The Bruton’s tyrosine kinase pathway regulates downstream activation of the B cell receptor and has emerged as an attractive target. Ibrutinib inhibits the Bruton’s tyrosine kinase pathway, and consequently induces apoptosis of B cells. Phase I and II studies have shown impressive response rates with an excellent safety profile in patients with refractory/relapsed CLL and elderly treatment-naïve CLL patients. This paper reviews the preclinical and clinical data for ibrutinib when used in the treatment of CLL. Recent studies showing the benefit of combination therapy using ibrutinib, monoclonal antibodies, and chemoimmunotherapy are also discussed. Keywords: ibrutinib, B-cell receptor, chronic lymphocytic leukemia, Bruton’s tyrosine kinase
Comparative Study of Kallikrein-Like Serine Proteinases from Rat Submandibular Glands (1996)

The present investigation describes the comparative properties, particularly the substrate specificity of three kallikrein-like serine proteinases (I, II and III) purified from rat submandibular gland extract (Bedi, G.S., Prep. Biochem. 22,67-81, 1992). The physico-chemical and immunological properties of three proteinases were compared by Western blot analysis, immunodiffusion, immuno-electrophoresis, amino terminal sequence analysis, molecular weight determination and isoelectric focusing. Detailed substrate specificity of these proteinases was determined using chromogenic substrates, synthetic peptides and native proteins. The chromogenic substrate tosyl-gly-pro-arg-pNA was hydrolyzed preferentially by Proteinase I. The replacement of pro at the P2 position with bulky hydrophobic residues phe and leu completely abolished the hydrolysis by Proteinase I. The hydrolysis of the chromogenic substrates by Proteinase II was also affected by the amino acid residue present at the P2 position in the order of pro > gly > val > leu > phe. Neither Proteinase I nor Proteinase II hydrolyzed substrates in which arg was replaced with lys at the P1 position. Proteinase III was reactive against all the chromogenic substrates with arg or lys at the P1 position. Synthetic polypeptides T-kinin-leu and insulin B chain were resistant to cleavage by both Proteinase I and II and were cleaved specifically at arg-X peptide bond by Proteinase III. Tonin-like activity of Proteinase II was confirmed by cleavage of the angiotensin 1-14 at phe-his linkage to generate two fragments DRVYIHPF and HLLVYS respectively. All three proteinases cleaved human high molecular weight kininogen but only Proteinase III could cleave T-kininogen. Proteinase III was also reactive towards human and bovine fibronectin, fibrinogen and gelatin. Several other salivary and serum proteins were resistant to cleavage by these proteinases. Although the three enzymes are immunologically related, they differ with respect to size, isoelectric point, amino terminal sequence and inhibition profile.
Clinical, Virologic, and Immunologic Effects of Combination Therapy with Ribavirin and Isoprinosine in HIV-Infected Homosexual Men (1990)

We evaluated the clinical, immunologic, and virologic effects of oral treatment with ribavirin and isoprinosine for up to 3 months in asymptomatic, HIV-culture-positive homosexual men. Fifteen consecutive men received isoprinosine 4 g/day (1 g q.i.d.), and 800 (9 men) or 1,200 mg/day (6 men) of ribavirin. Five men in each ribavirin dosage group completed at least 2 months of treatment. No unexpected toxicities were observed. Eight minor HIV-related events occurred in six men while on study. All men remained HIV-positive, and time to positive culture decreased by at least 4 days in three men from each treatment group. Serum p24 levels did not change in two men who were p24 antigenemic and received 800 mg/day of ribavirin. Treatment was associated with a generalized lymphopenia affecting all lymphocyte subsets including CD4, which was partially reversible 1 month after stopping treatment. Most of the men remained anergic on DTHS skin testing. No improvements were noted in in vitro lymphoproliferative responses to antigens or in NK cell activity (which decreased significantly in the 1,200 mg/day ribavirin group). Although well tolerated at the doses employed, the combination of ribavirin and isoprinosine produced an unexpected generalized lymphopenia and did not exhibit HIV-suppressive or immunorestorative effects.
5‐Lipoxygenase and anandamide hydrolase (FAAH) mediate the antitumor activity of cannabidiol, a non‐psychoactive cannabinoid (2007)

It has been recently reported that cannabidiol (CBD), a non-psychoactive cannabinoid, is able to kill glioma cells, both in vivo and in vitro, independently of cannabinoid receptor stimulation. However, the underlying biochemical mechanisms were not clarified. In the present study, we performed biochemical analysis of the effect of CBD both in vivo, by using glioma tumor tissues excised from nude mice, and in vitro, by using U87 glioma cells. In vivo exposure of tumor tissues to CBD significantly decreased the activity and content of 5-lipoxygenase (LOX, by approximately 40%), and of its end product leukotriene B4 ( approximately 25%). In contrast cyclooxygenase (COX)-2 activity and content, and the amount of its end product prostaglandin E2, were not affected by CBD. In addition, in vivo treatment with CBD markedly stimulated ( approximately 175%) the activity of fatty acid amide hydrolase (FAAH), the main anandamide-degrading enzyme, while decreasing anandamide content ( approximately 30%) and binding to CB1 cannabinoid receptors ( approximately 25%). In vitro pre-treatment of U87 glioma cells with MK-886, a specific 5-LOX inhibitor, significantly enhanced the antimitotic effect of CBD, whereas the pre-treatment with indomethacin (pan-COX inhibitor) or celecoxib (COX-2 inhibitor), did not alter CBD effect. The study of the endocannabinoid system revealed that CBD was able to induce a concentration-dependent increase of FAAH activity in U87 cells. Moreover, a significantly reduced growth rate was observed in FAAH-over-expressing U87 cells, compared to wild-type controls. In conclusion, the present investigation indicates that CBD exerts its antitumoral effects through modulation of the LOX pathway and of the endocannabinoid system, suggesting a possible interaction of these routes in the control of tumor growth.
Low Precision Neural Networks using Subband Decomposition (2017)

Large-scale deep neural networks (DNN) have been successfully used in a number of tasks from image recognition to natural language processing. They are trained using large training sets on large models, making them computationally and memory intensive. As such, there is much interest in research development for faster training and test time. In this paper, we present a unique approach using lower precision weights for more efficient and faster training phase. We separate imagery into different frequency bands (e.g. with different information content) such that the neural net can better learn using less bits. We present this approach as a complement existing methods such as pruning network connections and encoding learning weights. We show results where this approach supports more stable learning with 2-4X reduction in precision with 17X reduction in DNN parameters.
Boosting Tumor-Specific Immunity Using PDT (2016)

Photodynamic therapy (PDT) is a cancer treatment with a long-standing history. It employs the application of nontoxic components, namely a light-sensitive photosensitizer and visible light, to generate reactive oxygen species (ROS). These ROS lead to tumor cell destruction, which is accompanied by the induction of an acute inflammatory response. This inflammatory process sends a danger signal to the innate immune system, which results in activation of specific cell types and release of additional inflammatory mediators. Activation of the innate immune response is necessary for subsequent induction of the adaptive arm of the immune system. This includes the priming of tumor-specific cytotoxic T lymphocytes (CTL) that have the capability to directly recognize and kill cells which display an altered self. The past decades have brought increasing appreciation for the importance of the generation of an adaptive immune response for long-term tumor control and induction of immune memory to combat recurrent disease. This has led to considerable effort to elucidate the immune effects PDT treatment elicits. In this review we deal with the progress which has been made during the past 20 years in uncovering the role of PDT in the induction of the tumor-specific immune response, with special emphasis on adaptive immunity.
Complex image theory-revisited (1991)

A quasi-historical sketch of complex image theory for low-frequency electromagnetic fields is presented from a personal perspective. Studies using complex image theory, on launching TM (transverse magnetic) modes into the Earth-ionosphere waveguide from a horizontal insulated cable, grounded at the end points, are described. Subsequent implementation and further development of the concept by other authors is summarized.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Self‐Assembled Monolayers on Gold Nanoparticles (1996)

Abstract Self‐assembled monolayers (SAMs) of n ‐alkanethiolates on gold, silver, and copper have been intensively studied both as model organic surfaces and as modulators of metal surface properties. Sensitivity restrictions imposed by monolayer coverage and the low surface area of planar metal substrates, however, limit the characterization of these films in molecular terms to surface enhancement techniques. As a result, key aspects such as film dynamics and alkyl chain ordering remain ill‐defined. The characterization of the thermal behaviour of SAMs is important not only for the design of stable, well‐ordered organic superlattices, but also for the fundamental understanding of the factors that drive molecular interactions in two dimensions. Phase properties in SAMs have been addressed here through the synthesis of gold nanoparticles of 20–30 Å in diameter and fully covered with alkylthiol chains. These thiolmodified gold nanoparticles with large surface areas have enabled the monolayer film structure to be uniquely characterized by transmission FT‐IR spectroscopy, NMR spectroscopy, and differential scanning calorimetry. Our studies reveal that for long‐chain thiols (≥ C 16 ), the alkyl chains exist predominantly in an extended, all‐ trans ordered conformation at 25°C. Furthermore, calorimetry, variable temperature transmission FT‐IR spectroscopy, and solid‐state 13 C NMR studies have established that a cooperative chain melting process occurs in these alkylated metal colloids. How this arises is not immediately evident, given the relation between the extended chain conformation and the geometry of the spherical nanoparticles. Transmission electron microscopy (TEM) reveals that adjacent gold particles are separated by approximately one chain length; this suggests that chain ordering arises from an interdigitation of chains on neighboring particles. The thermotropic behavior is sensitive to the alkyl chain length and chain packing density. The alkylated nanoparticles can thus serve as a highly dispersed analogue to the much‐studied planar SAMs.
Both α- and β-calcitonin gene-related peptides are present in plasma, cerebrospinal fluid and spinal cord in man (1989)

The presence of both alpha- and beta-calcitonin gene-related peptide (CGRP) was demonstrated by oxidation and by CNBr cleavage in extracts of plasma, cerebrospinal fluid and spinal cord in man. This was achieved by the use of both CNBr cleavage and oxidation of the methionine residue present in the human beta-CGRP molecule. This study demonstrates that around 50% of CGRP immunoreactivity in plasma, cerebrospinal fluid and spinal cord is not alpha-CGRP, but corresponds to beta-CGRP-like activity. Furthermore, experiments with CNBr also suggest the presence of another methionine-containing CGRP-like peptide in all three extracts.
Cyclic loading of anchor‐based rotator cuff repairs: Confirmation of the tension overload phenomenon and comparison of suture anchor fixation with transosseous fixation (1997)

Previous experimental studies of failure of rotator cuff repair have involved single pull to ultimate load. Such an experimental design does not represent the cyclic loading conditions experienced in vivo. We created 1 x 2 cm rotator cuff defects in 16 cadaver shoulders, repaired each defect with three Mitek-RC suture anchors (Mitek Surgical Products, Inc, Westwood, MA) using simple sutures of No. 2 Ethibond, and cyclically loaded the repairs by a servohydraulic materials test system actuator at physiological rates and loads (rate of 33 mm/s, load 180 N). A progressive gap was noted in each specimen, for a 100% rate of failure of the repairs. The central suture always failed first and by the largest magnitude, confirming tension overload centrally. One specimen exhibited combined bone and tendon failure, but the other 15 specimens failed through the tendon. Overall, the repairs failed to 5 mm and 10 mm at an average of 61 cycles and 285 cycles, respectively. Half the specimens were less than 45 years of age and had a 5-mm and 10-mm failure at an average of 107 and 478 cycles, respectively. The other half were over 45 years of age and failed to 5 mm and 10 mm at an average of 17 and 91 cycles, respectively, indicating more rapid failure of the rotator cuff tendons in the older group, and this was statistically significant (P < or = .02). Comparison of suture anchor fixation in this study with transosseous bone tunnel fixation in a previous cyclic loading study at this institution indicates that bone fixation by suture anchors is significantly less prone to failure than bone fixation through bone tunnels (P = .0008). Changing the bone fixation from bone tunnels to suture anchors effectively transferred the weak link from bone to tendon.