gebhart/patrepeval huggingface dataset:
DISTINCT EXPRESSION OF TRANSFORMING GROWTH FACTOR‐β RECEPTOR SUBTYPES ON VASCULAR SMOOTH MUSCLE CELLS FROM SPONTANEOUSLY HYPERTENSIVE RATS AND WISTAR‐KYOTO RATS (1995)

1. We investigated the characteristics and expression of transforming growth factor-beta (TGFbeta) receptor subtypes on vascular smooth muscle cells (VSMC) from spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats. 2. TGFbeta binding assays revealed that VSMC from SHR showed higher number and affinity of TGFbeta receptors than cells from WKY rats. 3. The affinity labelling with [125I]-TGFbeta1 revealed the presence of TGFbeta receptor subtypes with molecular sizes of 280, 85, 70 and 60kDa on VSMC from both strains at high cell density. The abundance of the 85kDa receptor subtype was greater in VSMC from SHR than cells from WKY rats. The 85kDa receptor subtype was not detected on VSMC from both strains at low cell density. 4. These results suggest distinct expression of TGFbeta receptor subtypes on VSMC from SHR and WKY rats, which may account for the exaggerated proliferative response of VSMC from SHR to TGFbeta.
Application of RFID Technology for In-House Drug Management System (2012)

RFID based technology plays an important role in healthcare environments by providing a better drug management system by overcoming the current challenges associated with it. In this aspect, we have developed an in-house drug management system by employing RFID technology. This system is based on tracking of medicine such as regular as well as emergency medicine by the users with or without RFID tag. A prototype has been demonstrated in small scale by assigning HF RFID tags to users and by employing RFID reader along with camera and web based system to track the users. It is observed that this prototype shows excellent performance by providing proper management of medicine in homecare. The main advantage of our system is that it can be applicable to all types of users irrespective of their age, education, with or without tags. It can also be useful for tracking all type of medicines such as regular and emergency medicines. The details about the prototype have been presented.
Injection site reactions after subcutaneous oligonucleotide therapy (2016)

Oligonucleotides (ONs) are short fragments of nucleic acids, currently being investigated as therapeutic agents. When administered subcutaneously (sc), ONs cause a specific local reaction originating around the injection site, such as erythema, itching, discomfort and pain, including more severe manifestations such as ulceration or necrosis. These injection site reactions (ISRs) are common, but rather poorly described in the literature. With this review, we aim to provide an overview on the extent of the problem of ISRs, based on reported incidence. A structured literature search was performed to identify reported incidence and clinical features of ISRs which yielded 70 manuscripts that contained information regarding ISRs. The data from literature was combined with data on file available at our institution. All sc administered ONs described in the literature lead to the occurrence of ISRs. The percentage of trial subjects that developed ISRs ranged from 22 to 100% depending on ON. The majority of ONs caused ISRs in more than 70% of the trial subjects. The severity of the observed reactions varied between different ONs. Occurrence rate as well as severity of ISRs increases with higher doses. For chemistry and target of the compounds, no clear association regarding ISR incidence or severity was identified. All ONs developed to date are associated with ISRs. Overcoming the problem of ISRs might add greatly to the potential success of sc-administered ONs. Knowledge of these skin reactions and their specific immunostimulatory properties should be increased in order to obtain ONs that are more suitable for long-term use and clinically applicable in a broader patient population.
Adiposity Elevates Plasma MCP-1 Levels Leading to the Increased CD11b-positive Monocytes in Mice (2003)

Obesity is currently considered as an epidemic in the western world, and it represents a major risk factor for life-threatening diseases such as heart attack, stroke, diabetes, and cancer. Taking advantage of DNA microarray technology, we tried to identify the molecules explaining the relationship between obesity and vascular disorders, comparing mRNA expression of about 12,000 genes in white adipose tissue between normal, high fat diet-induced obesity (DIO) and d-Trp34 neuropeptide Y-induced obesity in mice. Expression of monocyte chemoattractant protein-1 (MCP-1) mRNA displayed a 7.2-fold increase in obese mice as compared with normal mice, leading to substantially elevated MCP-1 protein levels in adipocytes. MCP-1 levels in plasma were also increased in DIO mice, and a strong correlation between plasma MCP-1 levels and body weight was identified. We also showed that elevated MCP-1 protein levels in plasma increased the CD11b-positive monocyte/macrophage population in DIO mice. Furthermore, infusion of MCP-1 into lean mice increased the CD11b-positive monocyte population without inducing changes in body weight. Given the importance of MCP-1 in activation of monocytes and subsequent atherosclerotic development, these results suggest a novel role of adiposity in the development of vascular disorders.
Factor VIIa-catalyzed activation of factor X independent of tissue factor: its possible significance for control of hemophilic bleeding by infused factor VIIa (1990)

Infusing factor VIIa (FVIIa) has been reported to control bleeding in hemophilic patients with factor VIII (FVIII) inhibitors. This is difficult to attribute to an enhanced FVIIa/tissue factor (TF) activation of factor X, since in vitro studies suggest that infusion of FVIIa should neither increase substantially the rate of formation of FVIIa/TF complexes during hemostasis (Proc Natl Acad Sci USA 85:6687, 1988) nor bypass the dampening of TF-dependent coagulation by the extrinsic pathway inhibitor (EPI) (Blood 73:359, 1989). Partial thromboplastin times have also been reported to shorten after infusion of FVIIa. The experiments reported herein establish that shortening of partial thromboplastin times after adding FVIIa to hemophilic plasma in vitro stems from an FVIIa-catalyzed activation of factor X independent of possible trace contamination of reagents with TF. Experiments in purified systems confirmed that FVIIa can slowly activate factor X in a reaction mixture containing Ca2+ and phospholipid but no source of TF. The rate of activation was sufficient to account for the shortening of partial thromboplastin times observed. EPI, which turned off continuing FVIIa/TF activation of factor X, was unable to prevent continuing FVIIa/phospholipid activation of factor X. Because circulating plasma contains only a trace, if any, free FVIIa, such a reaction could never occur physiologically. However, infusing FVIIa creates a nonphysiologic circumstance in which a continuing slow FVIIa/phospholipid catalyzed activation of factor X could conceivably proceed in vivo unimpeded by EPI. Such a mechanism of factor X activation might compensate for an impaired factor IXa/FVIIIa/phospholipid activation of factor X during hemostatis, and therefore control bleeding in a hemophilic patient.
Los derechos fundamentales y la Constitución a los veinticinco años (2018)

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Engineering Corynebacterium glutamicum for isobutanol production (2010)

The production of isobutanol in microorganisms has recently been achieved by harnessing the highly active 2-keto acid pathways. Since these 2-keto acids are precursors of amino acids, we aimed to construct an isobutanol production platform in Corynebacterium glutamicum, a well-known amino-acid-producing microorganism. Analysis of this host's sensitivity to isobutanol toxicity revealed that C. glutamicum shows an increased tolerance to isobutanol relative to Escherichia coli. Overexpression of alsS of Bacillus subtilis, ilvC and ilvD of C. glutamicum, kivd of Lactococcus lactis, and a native alcohol dehydrogenase, adhA, led to the production of 2.6 g/L isobutanol and 0.4 g/L 3-methyl-1-butanol in 48 h. In addition, other higher chain alcohols such as 1-propanol, 2-methyl-1-butanol, 1-butanol, and 2-phenylethanol were also detected as byproducts. Using longer-term batch cultures, isobutanol titers reached 4.0 g/L after 96 h with wild-type C. glutamicum as a host. Upon the inactivation of several genes to direct more carbon through the isobutanol pathway, we increased production by approximately 25% to 4.9 g/L isobutanol in a pycldh background. These results show promise in engineering C. glutamicum for higher chain alcohol production using the 2-keto acid pathways.
Modeling of organic thin film transistors of different designs (2000)

We report on modeling of direct current (DC) characteristics of organic pentacene thin film transistors of different designs. Our model incorporates a gate-voltage dependent mobility and highly nonlinear drain and source contact series resistances. The contact nonlinearities are especially pronounced in bottom source and drain contact thin film transistors. The model successfully reproduced both below- and above-threshold characteristics of top source and drain contact and bottom source and drain contact organic pentacene thin film transistors.
Lebrikizumab in moderate-to-severe asthma: pooled data from two randomised placebo-controlled studies (2015)

The LUTE study was registered under NCT01545440 and the VERSE study under NCT01545453 at http://www.clinicaltrials.gov.
La stratification thermique et chimique des lacs Kivu Édouard et Ndalaga (Congo Belge) (1938)

(1938). La stratification thermique et chimique des lacs Kivu Edouard et Ndalaga (Congo Belge) SIL Proceedings, 1922-2010: Vol. 8, No. 3, pp. 51-68.
Senolytic drugs: from discovery to translation (2020)

Senolytics are a class of drugs that selectively clear senescent cells (SC). The first senolytic drugs Dasatinib, Quercetin, Fisetin and Navitoclax were discovered using a hypothesis-driven approach. SC accumulate with ageing and at causal sites of multiple chronic disorders, including diseases accounting for the bulk of morbidity, mortality and health expenditures. The most deleterious SC are resistant to apoptosis and have up-regulation of anti-apoptotic pathways which defend SC against their own inflammatory senescence-associated secretory phenotype (SASP), allowing them to survive, despite killing neighbouring cells. Senolytics transiently disable these SCAPs, causing apoptosis of those SC with a tissue-destructive SASP. Because SC take weeks to reaccumulate, senolytics can be administered intermittently - a 'hit-and-run' approach. In preclinical models, senolytics delay, prevent or alleviate frailty, cancers and cardiovascular, neuropsychiatric, liver, kidney, musculoskeletal, lung, eye, haematological, metabolic and skin disorders as well as complications of organ transplantation, radiation and cancer treatment. As anticipated for agents targeting the fundamental ageing mechanisms that are 'root cause' contributors to multiple disorders, potential uses of senolytics are protean, potentially alleviating over 40 conditions in preclinical studies, opening a new route for treating age-related dysfunction and diseases. Early pilot trials of senolytics suggest they decrease senescent cells, reduce inflammation and alleviate frailty in humans. Clinical trials for diabetes, idiopathic pulmonary fibrosis, Alzheimer's disease, COVID-19, osteoarthritis, osteoporosis, eye diseases and bone marrow transplant and childhood cancer survivors are underway or beginning. Until such studies are done, it is too early for senolytics to be used outside of clinical trials.
Time-resolved scattering investigations of brome mosaic virus microcrystals appearance (2002)

The behavior of brome mosaic virus in solution as a function of physico-chemical conditions has already been characterized by Small Angle X-ray Scattering studies. The most striking result was that the precipitates induced by the addition of polyethylene glycol were in fact made of microcrystals. This result was reinvestigated on the ID2 beamline at ESRF (Grenoble, France) to determine whether there was an amorphous state before the organized one, and measure the necessary period of latency for the microcrystals to form. The stopped-flow device associated to the high brilliance of the beamline enabled us to characterize the growth of the diffraction peaks as a function of time.
The herpes simplex virus 1 gene for ICP34.5, which maps in inverted repeats, is conserved in several limited-passage isolates but not in strain 17syn+ (1990)

In a previous study, it was reported that herpes simplex virus 1 (HSV-1) strain F contains a transcribed open reading frame situated in the inverted repeats of the L component between the terminal a sequence and the open reading frame that encodes the alpha 0 gene (J. Chou and B. Roizman, J. Virol. 57: 629-637, 1986). By means of an antibody to repeats of the trimer Ala-Thr-Pro predicted to be specified by the open reading frame, it was shown that the open reading frame specifies a protein (M. Ackermann, J. Chou, M. Sarmiento, R. A. Lerner, and B. Roizman, J. Virol. 58: 843-850, 1986). This open reading frame is absent from the reported sequence of HSV-1(17)syn+ (D. J. McGeoch, M. A. Dalrymple, A. J. Davison, A. Dolan, M. C. Frame, D. McNab, L. J. Perry, J. E. Scott, and P. Taylor, J. Gen. Virol. 69: 1531-1574, 1988; L. J. Perry and D. J. McGeoch, J. Gen. Virol. 69: 2831-2846, 1988). To define the extent of variability in this open reading frame, we compared the sequences of the ICP34.5-encoding open reading frames of the genomes of three strains characterized by limited passage in cell culture with that of the HSV-1(17)syn+ strain. Furthermore, to establish unambiguously that the antibody to the Ala-Thr-Pro repeats reacts with the product of this open reading frame, we inserted a short sequence that encodes a known epitope in frame at the 5' terminus of the coding domain. Our results indicate that with minor variations, the open reading frame is conserved in the three HSV-1 genomes analyzed but not in HSV-1(17)syn+. Thus, two strains contain an inserted amino acid and one strain, isolated from a case of human encephalitis, lacks a seven-amino-acid sequence. The recombinant virus carrying the foreign epitope expressed a slightly slower-migrating protein which reacted with both the rabbit polyclonal antibody to the Ala-Thr-Pro trimer repeats and the monoclonal antibody to the inserted epitope. The implications of the results are discussed.
Stromelysin is an activator of procollagenase. A study with natural and recombinant enzymes (1987)

The latent forms of stromelysin and collagenase from human gingival fibroblasts were purified to homogeneity. These latent proenzymes underwent serial small reductions in Mr upon activation by treatment with either 4-aminophenylmercuric acetate or trypsin. Similar shifts in Mr and activation kinetics were observed upon identical treatments of either recombinant prostromelysin or procollagenase. Prostromelysin showed a lag between activation and Mr fall, suggesting an initial activation by conformational change. Collagenase activity was enhanced up to 12-fold by either natural or recombinant stromelysin in the presence of trypsin or 4-aminophenylmercuric acetate. Stromelysin caused a further apparent decrease in the Mr of procollagenase. Since these important connective-tissue-degrading enzymes are usually co-ordinately produced by cells, a cascade mechanism is proposed in which collagenase is activated by stromelysin.
Purification of recombinant C-reactive protein mutants (1992)

C-reactive protein (CRP) is an evolutionarily conserved protein, a component of the innate immune system, and an acute phase protein in humans. In addition to its raised level in blood in inflammatory states, CRP is also localized at sites of inflammation including atherosclerotic lesions, arthritic joints and amyloid plaque deposits. Results of in vivo experiments in animal models of inflammatory diseases indicate that CRP is an anti-pneumococcal, anti-atherosclerotic, anti-arthritic and an anti-amyloidogenic molecule. The mechanisms through which CRP functions in inflammatory diseases are not fully defined; however, the ligand recognition function of CRP in its native and non-native pentameric structural conformations and the complement-activating ability of ligand-complexed CRP have been suggested to play a role. One tool to understand the structure-function relationships of CRP and determine the contributions of the recognition and effector functions of CRP in host defense is to employ site-directed mutagenesis to create mutants for experimentation. For example, CRP mutants incapable of binding to phosphocholine are generated to investigate the importance of the phosphocholine-binding property of CRP in mediating host defense. Recombinant CRP mutants can be expressed in mammalian cells and, if expressed, can be purified from the cell culture media. While the methods to purify wild-type CRP are well established, different purification strategies are needed to purify various mutant forms of CRP if the mutant does not bind to either calcium or phosphocholine. In this article, we report the methods used to purify pentameric recombinant wild-type and mutant CRP expressed in and secreted by mammalian cells.
Dynamically discovering likely program invariants (2000)

This dissertation introduces dynamic detection of program invariants, presents techniques for detecting such invariants from traces, assesses the techniques' efficacy, and points the way for future research. 
Invariants are valuable in many aspects of program development, including design, coding, verification, testing, optimization, and maintenance. They also enhance programmers' understanding of data structures, algorithms, and program operation. Unfortunately, explicit invariants are usually absent from programs, depriving programmers and automated tools of their benefits. 
This dissertation shows how invariants can be dynamically detected from program traces that capture variable values at program points of interest. The user runs the target program over a test suite to create the traces, and an invariant detector determines which properties and relationships hold over both explicit variables and other expressions. Properties that hold over the traces and also satisfy other tests, such as being statistically justified, not being over unrelated variables, and not being implied by other reported invariants, are reported as likely invariants. Like other dynamic techniques such as testing, the quality of the output depends in part on the comprehensiveness of the test suite. If the test suite is inadequate, then the output indicates how, permitting its improvement. Dynamic analysis complements static techniques, which can be made sound but for which certain program constructs remain beyond the state of the art. 
Experiments demonstrate a number of positive qualities of dynamic invariant detection and of a prototype implementation, Daikon. Invariant detection is accurate—it rediscovers formal specifications—and useful—it assists programmers in programming tasks. It runs quickly and produces output of modest size. Test suites found in practice tend to be adequate for dynamic invariant detection.
Stereo matching using belief propagation (2003)

In this paper, we formulate the stereo matching problem as a Markov network and solve it using Bayesian belief propagation. The stereo Markov network consists of three coupled Markov random fields that model the following: a smooth field for depth/disparity, a line process for depth discontinuity, and a binary process for occlusion. After eliminating the line process and the binary process by introducing two robust functions, we apply the belief propagation algorithm to obtain the maximum a posteriori (MAP) estimation in the Markov network. Other low-level visual cues (e.g., image segmentation) can also be easily incorporated in our stereo model to obtain better stereo results. Experiments demonstrate that our methods are comparable to the state-of-the-art stereo algorithms for many test cases.
The Brain Parenchyma Is Permissive for Full Antitumor CTL Effector Function, Even in the Absence of CD4 T Cells (2000)

Abstract Effective antitumor immune responses against cerebral malignancies have been demonstrated in several models, but precise cellular function of specific effector cells is poorly understood. We have explored this topic by analyzing the MHC class I-restricted T cell response elicited after implantation of HLA-CW3-transfected P815 mastocytoma cells (P815-CW3) in syngeneic mice. In this model, tumor-specific CTLs use a distinctive repertoire of TCRs that allows ex vivo assessment of the response by immunophenotyping and TCR spectratyping. Thus, for the first time in a brain tumor model, we are able to directly visualize ex vivo CTLs specific for a tumor-expressed Ag. Tumor-specific CTLs are detected in the CNS after intracerebral implantation of P815-CW3, together with other inflammatory cells. Moreover, despite observations in other models suggesting that CTLs infiltrating the brain may be functionally compromised and highly dependent upon CD4 T cells, in this syngeneic P815-CW3 model, intracerebral tumors were efficiently rejected, whether or not CD4 T cells were present. This observation correlated with potent ex vivo cytotoxicity of brain-infiltrating CTLs, specific for the immunodominant epitope CW3170–179 expressed on P815-CW3 tumor cells.
Load-Pull Analysis of Outphasing Class-E Power Amplifier (2007)

In this paper, we discuss a load-pull analysis technique to charaterize the efficiency performance of class-E amplifier in an outphasing power combining scheme. Class-E amplifier has the potential to deliver high efficiency. Class-E amplifier is not an ideal current or voltage source as is required for the traditional analysis of outphasing structures. It requires a phase modulated input signal and has a non-linear transfer characteristic which is a function of load impedance. Here we define an operating load locus based on the load-pull analysis which can be used to predict the non-linear transfer function, efficiency, output power, input drive phase and many other factors associated with the outphasing class-E amplifier. This scheme could also be used to characterize any amplifier class in an outphasing structure.
The Antiparasitic Clioquinol Induces Apoptosis in Leukemia and Myeloma Cells by Inhibiting Histone Deacetylase Activity (2013)

The antiparasitic clioquinol (CQ) represents a class of novel anticancer drugs by interfering with proteasome activity. In the present study, we found that CQ induced blood cancer cell apoptosis by inhibiting histone deacetylases (HDACs). CQ accumulated the acetylation levels of several key proteins including histone H3 (H3), p53, HSP90, and α-tubulin. In the mechanistic study, CQ was found to down-regulate HDAC1, -3, -4, and -5 in both myeloma and leukemia cells. Computer modeling analysis revealed that CQ was well docked into the active pocket of the enzyme, where the oxygen and nitrogen atoms in CQ formed stable coordinate bonds with the zinc ion, and the hydroxyl group from CQ formed an effective hydrogen bond with Asp-267. Moreover, co-treatment with CQ and zinc/copper chloride led to decreased Ac-H3. Furthermore, CQ inhibited the activity of Class I and IIa HDACs in the cell-free assays, demonstrating that CQ interfered with HDAC activity. By inhibiting HDAC activity, CQ induced expression of p21, p27, and p53, cell cycle arrest at G1 phase, and cell apoptosis. This study suggested that the HDAC enzymes are targets of CQ, which provided a novel insight into the molecular mechanism of CQ in the treatment of hematological malignancies.