gebhart/patrepeval huggingface dataset:
Measurement of Isoketal Protein Adducts by Liquid Chromatography-Electrospray Ionization/Tandem Mass Spectrometry (2003)

Oxidative stress has been increasingly implicated in the pathogenesis of a wide variety of diverse human diseases. Free radical damage to lipids, proteins, and DNA may all contribute to the pathogenesis of disease. We have recently discovered a series of highly reactive γ-ketoaldehydes that are formed by rearrangement of bicyclic endperoxide intermediates in the isoprostane (IsoP) pathway of free radical-mediated peroxidation of arachidonic acid (1), which we now term isoketals (IsoKs) (2) (Fig. 1). IsoKs rapidly react with the ε-amine of lysyl residues on proteins to form Schiff base, lactam, and hydroxylactam adducts (1,3,4) (Fig. 2). The rapidity with which IsoKs adduct to proteins exceeds that of other known reactive products of lipid peroxidation, e.g., 4-hydroxynonenal, by orders of magnitude (1). Adduction of proteins frequently leads to altered protein function (5–8). This in turn can lead to cellular dysfunction, which may be causally linked to the pathogenesis of disease processes.
Megakaryocytes Contribute to the Bone Marrow-Matrix Environment by Expressing Fibronectin, Type IV Collagen, and Laminin (2013)

Megakaryocytes associate with the bone marrow vasculature where they convert their cytoplasm into proplatelets that protrude through the vascular endothelium into the lumen and release platelets. The extracellular matrix (ECM) microenvironment plays a critical role in regulating these processes. In this work we demonstrate that, among bone marrow ECM components, fibronectin, type IV collagen, and laminin are the most abundant around bone marrow sinusoids and constitute a pericellular matrix surrounding megakaryocytes. Most importantly, we report, for the first time, that megakaryocytes express components of the basement membrane and that these molecules contribute to the regulation of megakaryocyte development and bone marrow ECM homeostasis both in vitro and in vivo. In vitro, fibronectin induced a threefold increase in the proliferation rate of mouse hematopoietic stem cells leading to higher megakaryocyte output with respect to cells treated only with thrombopoietin or other matrices. However, megakaryocyte ploidy level in fibronectin-treated cultures was significantly reduced. Stimulation with type IV collagen resulted in a 1.4-fold increase in megakaryocyte output, while all tested matrices supported proplatelet formation to a similar extent in megakaryocytes derived from fetal liver progenitor cells. In vivo, megakaryocyte expression of fibronectin and basement membrane components was upregulated during bone marrow reconstitution upon 5-fluorouracil induced myelosuppression, while only type IV collagen resulted upregulated upon induced thrombocytopenia. In conclusion, this work demonstrates that ECM components impact megakaryocyte behavior differently during their differentiation and highlights a new role for megakaryocyte as ECM-producing cells for the establishment of cell niches during bone marrow regeneration.
Differential regulation of Ca2+/calmodulin-dependent enzymes by plant calmodulin isoforms and free Ca2+ concentration (2000)

Multiple calmodulin (CaM) isoforms are expressed in plants, but their biochemical characteristics are not well resolved. Here we show the differential regulation exhibited by two soya bean CaM isoforms (SCaM-1 and SCaM-4) for the activation of five CaM-dependent enzymes, and the Ca2+ dependence of their target enzyme activation. SCaM-1 activated myosin light-chain kinase as effectively as brain CaM (Kact 1.8 and 1.7nM respectively), but SCaM-4 produced no activation of this enzyme. Both CaM isoforms supported near maximal activation of CaM-dependent protein kinase II (CaM KII), but SCaM-4 exhibited approx.12-fold higher Kact than SCaM-1 for CaM KII phosphorylation of caldesmon. The SCaM isoforms showed differential activation of plant and animal Ca2+-ATPases. The plant Ca2+-ATPase was activated maximally by both isoforms, while the erythrocyte Ca2+-ATPase was activated only by SCaM-1. Plant glutamate decarboxylase was activated fully by SCaM-1, but SCaM-4 exhibited an approx. 4-fold increase in Kact and an approx. 25% reduction in Vmax. Importantly, SCaM isoforms showed a distinct Ca2+ concentration requirement for target enzyme activation. SCaM-4 required 4-fold higher [Ca2+] for half-maximal activation of CaM KII, and 1.5-fold higher [Ca2+] for activation of cyclic nucleotide phosphodiesterase than SCaM-1. Thus these plant CaM isoforms provide a mechanism by which a different subset of target enzymes could be activated or inhibited by the differential expression of these CaM isoforms or by differences in Ca2+ transients.
Reduction of CWR22 prostate tumor xenograft growth by combined tamoxifen-quercetin treatment is associated with inhibition of angiogenesis and cellular proliferation (2004)

Combination chemotherapy is increasingly practiced for the treatment of malignant prostate cancers. The aim of this study was to evaluate the in vivo efficacy of combined tamoxifen and quercetin in prostate tumor xenografts. Severe combined immune deficient (SCID) mice inoculated with CWR22 prostate tumor cells were treated with either tamoxifen (10 mg/kg/week), quercetin (200 mg/kg/day) or combined tamoxifen-quercetin for 28 days. Tamoxifen or quercetin alone exhibited a moderate antitumor activity. Tamoxifen decreased the Ki-67 index by 52.4%, reduced the vascular endothelial growth factor (VEGF) 121 and VEGF165 mRNA by 18.6 and 21.8%, respectively, and suppressed the blood vessel formation, while quercetin modulated the expression and phosphorylation of cdc-2 and cyclin B1, and inhibited the Ki-67 index by 66.0%. Combined tamoxifen-quercetin effectively delayed the appearance of tumors, inhibited the final tumor volume by 73.3% and reduced the endpoint tumor weight by 67.1% (p<0.05). The Ki-67 index, VEGF121, VEGF165 mRNA and microvessel density (MVD) were decreased by 66.9, 22.1, 40.1 and 59.0%, respectively, by the combined treatment. These findings indicate that tamoxifen inhibits CWR22 prostate tumor by modulating the angiogenesis and its antineoplastic effects can be potentiated by combined use with quercetin.
Neuromuscular function impairment is not caused by motor neurone loss in FALS mice (1996)

DOMINANT mutations of human Cu/Zn superoxide dismutase (SOD1) are found in about 20% of patients with familial amyotrophic lateral sclerosis (FALS). A transgenic mouse model of FALS (FALSG93A mice) has been generated by overexpression of a mutated form of SOD1. Using electromyography we first show that FALSG93A mice suffer from motoneurone dysfunction similar to that observed in ALS patients and fullfill Lambert's criteria for ALS. We also showed that FALSG93A mice demonstrate a massive loss of functional motor units starting at 47 days of age. Impairment of motor neurone function preceeds by 6 weeks the onset of apparent clinical signs (shaking, tremor) and the beginning of motor neurone loss. Neuromuscular deficits in FALS mice do not result from motoneuronal cell death but rather from loss of axonal integrity.
Managing Distributed Systems with Smart Subscriptions (2000)

We describe an event-based, publish-and-subscribe system based on using “smart subscriptions ” to recognize weakly structured events. We present a hierarchy of subscription languages (propositional, predicate, temporal and agent) of increasing expressability and computational complexity, and several algorithms (Sig, Memo, Lattice, Compile and RETE) for efficiently recognizing event matches. We have applied this system to implementing and managing distributed applications
Characterization of synaptogyrin 3 as a new synaptic vesicle protein (2004)

Synaptogyrins comprise a family of tyrosine-phosphorylated proteins with two neuronal (synaptogyrins 1 and 3) and one ubiquitous (cellugyrin) isoform. Previous studies have indicated that synaptogyrins are involved in the regulation of neurotransmitter release. Synaptogyrin 1 is a synaptic vesicle protein; cellugyrin, by contrast, is absent from synaptic vesicles. In an effort to further characterize the synaptogyrin family, we studied the distribution of the synaptogyrin 3 protein in the nervous system. Subcellular fractionation and immunoprecipitation of synaptic vesicles from mouse brain showed that synaptogyrin 3 is associated with synaptic vesicles and that synaptogyrins 1 and 3 can reside on the same synaptic vesicle. Immunofluorescent staining of cultured hippocampal neurons confirmed the synaptic localization of synaptogyrin 3. Analysis of the relative distributions of synaptogyrins 1 and 3 in mouse brain revealed a more restricted expression pattern for synaptogyrin 3 compared to the ubiquitous distribution of synaptogyrin 1. Strong synaptogyrin 3 labeling was observed in the mossy fiber region of the hippocampus, substantia nigra pars reticulata, pallidum, and deep cerebellar nuclei. By comparison, the striatum and reticular and ventral posterolateral thalamic nuclei, which all showed synaptogyrin 1 labeling, contained significantly less synaptogyrin 3. Finally, we used in situ hybridization experiments to correlate synaptogyrin 3 mRNA in cell bodies with synaptogyrin 3 protein at synapses. Altogether, our data indicate that neuronal synaptogyrins are differentially expressed protein isoforms that may represent functionally distinct populations of synapses and/or synaptic vesicles.
Physiological IgM Class Catalytic Antibodies Selective for Transthyretin Amyloid (2014)

Peptide bond-hydrolyzing catalytic antibodies (catabodies) could degrade toxic proteins, but acquired immunity principles have not provided evidence for beneficial catabodies. Transthyretin (TTR) forms misfolded β-sheet aggregates responsible for age-associated amyloidosis. We describe nucleophilic catabodies from healthy humans without amyloidosis that degraded misfolded TTR (misTTR) without reactivity to the physiological tetrameric TTR (phyTTR). IgM class B cell receptors specifically recognized the electrophilic analog of misTTR but not phyTTR. IgM but not IgG class antibodies hydrolyzed the particulate and soluble misTTR species. No misTTR-IgM binding was detected. The IgMs accounted for essentially all of the misTTR hydrolytic activity of unfractionated human serum. The IgMs did not degrade non-amyloidogenic, non-superantigenic proteins. Individual monoclonal IgMs (mIgMs) expressed variable misTTR hydrolytic rates and differing oligoreactivity directed to amyloid β peptide and microbial superantigen proteins. A subset of the mIgMs was monoreactive for misTTR. Excess misTTR was dissolved by a hydrolytic mIgM. The studies reveal a novel antibody property, the innate ability of IgMs to selectively degrade and dissolve toxic misTTR species as a first line immune function.
Enhancing protein stability with extended disulfide bonds (2016)

Disulfide bonds play an important role in protein folding and stability. However, the cross-linking of sites within proteins by cysteine disulfides has significant distance and dihedral angle constraints. Here we report the genetic encoding of noncanonical amino acids containing long side-chain thiols that are readily incorporated into both bacterial and mammalian proteins in good yields and with excellent fidelity. These amino acids can pair with cysteines to afford extended disulfide bonds and allow cross-linking of more distant sites and distinct domains of proteins. To demonstrate this notion, we preformed growth-based selection experiments at nonpermissive temperatures using a library of random β-lactamase mutants containing these noncanonical amino acids. A mutant enzyme that is cross-linked by one such extended disulfide bond and is stabilized by ∼9 °C was identified. This result indicates that an expanded set of building blocks beyond the canonical 20 amino acids can lead to proteins with improved properties by unique mechanisms, distinct from those possible through conventional mutagenesis schemes.
Pakistan. (2001)

The potential of biotechnology in Pakistan was formally recognized in 1981, when a course on recombinant DNA technology was organized by the Nuclear Institute for Agriculture and Biology (NIAB), Faisalabad. NIAB is one of three agricultural centres of the Pakistan Atomic Energy Commission. The training workshop asked the government of Pakistan to develop a national centre of biotechnology and genetic engineering. The Ministry of Education later approved the creation of a Centre of Excellence in Molecular Biology (CEMB), to be built on the campus of Punjab University. The National Institute for Biotechnology and Genetic Engineering (NIBGE) was approved in 1986. The aims of the institute are to develop, adopt and apply innovative modern research in agriculture, industry, health and the environment. Agriculture is the backbone of Pakistan's economy, contributing 25% to gross domestic product (GDP). About 68% of the people depend on agriculture for their livelihood, engaging about 50% of the country's workforce.
Phosphorylation of Vitronectin by Casein Kinase II (1998)

The cell adhesion protein vitronectin (Vn) was previously shown to be the major target in human blood for an extracellular protein kinase A, which is released from platelets upon their physiological stimulation with thrombin and also prevails as an ectoenzyme in several other types of blood cells. Because plasma Vn was shown to have only one protein kinase A phosphorylation site (Ser378) but to contain approximately 3 mol of covalently bound phosphate, and because human serum and blood cells were shown to contain also a casein kinase II (CKII) on their surface, we studied the phosphorylation of Vn by CKII attempting to find out whether such phosphorylation modulates Vn function, an acid test for its having a physiological relevance. Here we show (i) that the CKII phosphorylation of Vn has a Km of 0.5-2 microM (lower than the Vn concentration in blood, 3-6 microM), (ii) that it is targeted to Thr50 and Thr57, which are vicinal to the RGD site of Vn, and (iii) that the phosphorylation of Thr57 facilitates the phosphorylation of Thr50. The maximal stoichiometry of the CKII phosphorylation of plasma Vn was found to be low, which, in principle, could be due to its partial prephosphorylation in vivo. However, for the detection of a functional modulation, we needed a comparison between a fully phosphorylated Vn (at Thr57 and Thr50) and a nonphosphorylated Vn. Therefore, we expressed Vn in a baculovirus system and show (i) that the CKII phosphorylation of wt-Vn enhances the adhesion of bovine aorta endothelial cells; (ii) that the double mutant T50E/T57E (in which the neutral Thr residues are replaced by the negatively charged Glu residues considered analogs of Thr-P) has a significantly enhanced capacity to promote cell adhesion and to accelerate cell spreading when compared with either wild-type Vn or to the neutral T50A/T57A mutant; and (iii) that, at least in the case of bovine aorta endothelial cells, the T50E/T57E mutant exhibits an enhanced adhesion, which seems to be due to an increased affinity toward the alphav beta3 Vn receptors.
Usefulness of Optometric services in the Eyecare Profession: Ophthalmologists Perspective. (2019)

Purpose: The objective of the study was to evaluate ophthalmologists' views regarding the usefulness of optometric services in the eye care profession in Pakistan. Methods: Data was gathered by a self-designed questionnaire. All the data was entered and analyzed using Statistical Package for Social Science (SPSS Version 20.0). A total of 105 ophthalmologists participated in this study. Results: Eighty-one percent of ophthalmologists had the view that optometric services were useful in the eye care profession. Their services included the management of uncooperative patients, retinoscopy, cycloplegic refraction, glaucoma co-management, refraction, and diagnosis of other eye conditions. The majority of participants had a positive opinion about the behavior of optometrists with their patients, their communication, retinoscopy, skills of managing uncooperative patients and cycloplegic skills respectively. Ninety percent of ophthalmologists agreed that the role of optometrists was very important in achieving goals of vision 2020. Mixed responses were obtained for their contact lens practices.  Most of them were neutral about the diagnostic skills of optometrists. Above 60% of participants replied that optometrists had good glaucoma referrals. According to the ophthalmologists' perspective, there was a need for enhancement in clinical skills. Ninety percent of participants agreed that optometrists were an integral part of an eye care team and they felt difficulty in managing OPD’s and patients in the absence of optometrists. Conclusions: Ophthalmologists considered different optometric services, very useful for the community and eye care profession. The study showed that optometrists were performing their duties very well. Optometrists provide high-quality services that were greatly accepted and appreciated by patients, health professionals, and the community.         Key Words: optometrists, ophthalmologists, perspective, usefulness, services, Enhanced services scheme (ESS).
Developmental Milestones (2016)

• On the basis of observational studies (level C), preterm birth is a leading cause of neurodevelopmental disabilities in children, and the degree of neurodevelopmental disability is inversely correlated with gestational age at birth. When comparing performance of preterm children to developmental norms, “corrected age” or age from due date rather than birth date should be used for the first 24 to 36 months. • On the basis of observational studies (level C), clinicians should pay specific attention to sensory function in children born preterm because the incidence of visual and hearing impairments is higher in preterm than term children. Due to the elevated risk of cognitive and behavioral disabilities, clinicians caring for children born preterm should be vigilant when performing developmental assessments to improve outcomes. • On the basis of observational studies (level C), early identification of developmental delays allows for referral to therapeutic services, and children referred for early intervention are more likely to make gains in developmental milestones.
Glucosidase Inhibitors for Treatment of HIV-1 Infection (1992)

The HIV-1 envelope protein is a glycoprotein composed of 120 kD and 41 kD subunits. It contains 30-38 potential asparagine-linked glycosylation sites which have been shown to play a role in CD4 binding, virus uptake, and cytopathogenicity. Several inhibitors of oligosaccharide attachment or modification have been tested. An agent which inhibits glucosidases, N-butyl deoxynojirimycin was found to inhibit HIV-1 and SIVmac infectivity, and is currently in clinical trials.
Köhler illumination and brightness measurement with lanthanum hexaboride cathodes (1979)

An aperture illumination system such as a Köhler system offers the ability to illuminate an electron probe system with the peak brightness from an electron source. It also provides an object with an ideal step-function current distribution. This paper describes results obtained using Köhler illumination on a short focal length final lens SEM. Application of the SEM to brightness measurement is discussed at some length. Examples of overall probe performance for scanning transmission electron microscopy, low-loss surface microscopy, and microfabrication are also given.
Solar Flash Desalination Under Hydrostatically Sustained Vacuum (2009)

A new desalination scheme has been proposed. The system consists of a saline water tank, a concentrated brine tank, and a fresh water tank placed on ground level plus an evaporator and a condenser located several meters above the ground. The evaporator-condenser assembly, or flash chamber, is initially filled with saline water that later drops by gravity, creating a vacuum above the water surface in the unit without a vacuum pump. The vacuum is maintained by the internal hydrostatic pressure balanced by the atmospheric pressure. The ground tanks are open to the atmosphere, while the flash chamber is insulated and sealed to retain both heat and vacuum. A theoretical simulation of the proposed model was carried out using a detailed model built by employing the fundamental physical and thermodynamic relationships to describe the process and was complimented by reliable empirical correlations to estimate the physical properties of the involved species and the operational parameters of the proposed system. The simulation results show that running the system at higher flash temperatures with a fixed flash chamber size will result in faster vacuum erosion leading to less overall evaporation.
Electrochemical hydrogen storage alloys and batteries fabricated from Mg containing base alloys (2023)

An electrochemical hydrogen storage material comprising: (Base Alloy).sub.a M.sub.b where, Base Alloy is an alloy of Mg and Ni in a ratio of from about 1:2 to about 2:1, preferably 1:1; M represents at least one modifier element chosen from the group consisting of Co, Mn, Al, Fe, Cu, Mo, W, Cr, V, Ti, Zr, Sn, Th, Si, Zn, Li, Cd, Na, Pb, La, Mm, and Ca; b is greater than 0.5, preferably 2.5, atomic percent and less than 30 atomic percent; and a+b=100 atomic percent. Preferably, the at least one modifier is chosen from the group consisting of Co, Mn, Al, Fe, and Cu and the total mass of the at least one modifier element is less than 25 atomic percent of the final composition. Most preferably, the total mass of said at least one modifier element is less than 20 atomic percent of the final composition.
Management of infection by the Zika virus (2016)

A panel of national experts was convened by the Brazilian Infectious Diseases Society in order to organize the national recommendations for the management of zika virus infection. The focus of this document is the diagnosis, both clinical and laboratorial, and appropriate treatment of the diverse manifestations of this infection, ranging from acute mild disease to Guillain-Barré syndrome and also microcephaly and congenital malformations.
Optical Gratings Coated with Thin Si3N4 Layer for Efficient Immunosensing by Optical Waveguide Lightmode Spectroscopy (2012)

New silicon nitride coated optical gratings were tested by means of Optical Waveguide Lightmode Spectroscopy (OWLS). A thin layer of 10 nm of transparent silicon nitride was deposited on commercial optical gratings by means of sputtering. The quality of the layer was tested by x-ray photoelectron spectroscopy and atomic force microscopy. As a proof of concept, the sensors were successfully tested with OWLS by monitoring the concentration dependence on the detection of an antibody-protein pair. The potential of the Si3N4 as functional layer in a real-time biosensor opens new ways for the integration of optical waveguides with microelectronics.
Search algorithms for software-only real-time recognition with very large vocabularies (1993)

This paper deals with search algorithm for real-time speech recognition. We argue that software-only speech recognition has several critical advantages over using special or parallel hardware. We present a history of several advances in search algorithms, which together, have made it possible to implement real-time recognition of large vocabularies on a single workstation without the need for any hardware accelerators. We discuss the Forward-Backward Search algorithm in detail, as this is the key algorithm that has made possible recognition of very large vocabularies in real-time. The result is that we can recognize continuous speech with a vocabulary of 20,000 words strictly in real-time entirely in software on a high-end workstation with large memory. We demonstrate that the computation needed grows as the cube root of the vocabulary size.