gebhart/patrepeval huggingface dataset:
Anti-infectives : recent advances in chemistry and structure-activity relationships (1997)

Part 1 Advances in antibacterials/antibiotics: the glycopeptide story - how to kill the deadly superbugs, D.H. Williams et al design and synthesis of novel oxazolidinones active against multidrug-resistant bacteria, M.R. Barbachyn et al from the Michael reaction to the clinic, J.C. Barriere and J.M. Paris the synthesis of salinomycin, R.C.D. Brown and P. Kocienski inhibition of protein export in bacteria - the signalling of a new role for beta-lactams, A.E. Allsop et al synthetic studies toward complex polyether macrolides of marine origin, S.D. Burke et al trinems - synthesis and antibacterial activity of a new generation of antibacterial beta-lactams, S. Biondi new concepts of inhibition of penicillin sensitive enzymes, P. Pfleiger et al design, synthesis and studies of new antibacterial, antifungal and antiviral agents, M.J. Miller et al. Part 2 Advances in antifungals: the chemistry of azole antifungals - fluconazole and beyond, S.D.A. Street tubulins - a target for antifungal agents, D.W. Hollomon et al cell-wall active antifungals and emerging targets, N.H. Georgopapadakou strobilurin analogues as inhibitors of mitochondrial respiration in fungi, J.M. Clough et al advances in the chemistry of novel broad-spectrum orally active azole antifungals - recent studies leading to the discovery of SCH56592, A.K. Saksena et al. Part 3 Advances in antivirals: 4'-thio-2'-deoxyribonucleosides, their chemistry and biological properties - a review, R.T. Walker the invention and development of CRIXIVAN(R) - an HIV protease inhibitor, B.D. Dorsey et al design, synthesis and evaluation of some novel nucleotides and inhibitors of HIV, C. McGuigan et al an overview of TSAO-T derivatives, a peculiar class of HIV-1 specific RT inhibitors, M.-J. Camarasa et al new sialidase inhibitors for the treatment of influenza, P.W. Smith et al viral proteinases as targets for inhibitors in viruses other than HIV-1, J.S. Mills design, synthesis and testing of inhibitors of viral cysteine proteinases, S. Frormann et al nucleosides with a six-membered carbohydrate moiety - structural requirements for antiviral activity, P. Herdewijn.
Spatially Varying Material Properties of the Rat Caudal Intervertebral Disc (2006)

The average equilibrium Young's modulus may be dependent on short-range ultrastructural organization. Spatially varying material properties within the intervertebral disc may be caused by orientation of fiber bundles in the different regions of the anulus fibrosus. The fiber bundles are better able to resist compressive loads when oriented parallel rather than perpendicular to the loading direction. At equilibrium, the anulus fibrosus also appears to have a shielding effect independent of the material filling up the nucleus pulposus space.
Wideband Stacked Rectangular Dielectric Resonator Antenna at 5.2 GHz (2012)

This paper presents a design of stacked rectangular dielectric resonator antenna (RDRA) with wide bandwidth, in the range of 13.56 % is described. The antenna exploits two low-Q modes with overlapping bandwidths to achieve a wide continuous bandwidth. This is achieved using low-permittivity DRA volume placed on high permittivity DRA volume. The antenna consists of dielectric constant of 10 and 32, stacked vertically to obtain improved bandwidth as compared to the conventional RDRA. A 50 Î© microstrip line is used in the proposed antenna as a feeding mechanism. Physical parameters of stacked RDRA have been optimized by extensive simulations using Ansoft HFSS. The parameters of antenna are 17x7x4.56 <i>mm</i><SUP>3</SUP> with grounded substrate size: 80x50 <i>mm</i><SUP>2</SUP>. The prototype is fabricated. Measured and simulated results are both in good agreement. The prototype antenna designed to operate in band from 5.0 to 5.7 GHz with measured gain at 5.2 GHz resonant frequency. The proposed antenna is suitable for wireless local area networks (WLAN) applications in 5 GHz frequency band (in the frequency range 5.15-5.35 GHz and 5.5-5.7 GHz). This stacked RDRA exceeds the bandwidth requirements for IEEE 802.11a WLAN applications within a required VSWR. Parametric studies of the stacked DRA are presented.
Serum matrix metalloproteinases -2, -9 and tissue inhibitors of metalloproteinases -1, -2 in lung cancer--TIMP-1 as a prognostic marker. (2000)

The immunoreactive protein for the tissue inhibitor of the metalloproteinase (TIMP)-1 and -2 as well as for the matrix metalloproteinase (MMP)-2 and -9 was quantified from the sera/plasma of 90 lung cancer patients and 20 control subjects with enzyme linked immunoassays (ELISA) using specific monoclonal antibodies. Free MMP-2 and that bound to the inhibitor, the MMP-2/TIMP-2 complex were measured separately using different ELISAs. For the detection of MMP-9, TIMP-1 and TIMP-2, the total protein was measured to quantify both free and complex forms. Serum protein levels for TIMP-1, TIMP-2 and the MMP-2/TIMP-2 complex differed significantly in patients with lung cancer when compared to controls. TIMP-1 levels were found to be higher in lung cancer than in controls, whereas TIMP-2 and MMP-2/TIMP-2 complex levels were lower in lung cancer than in the sera of the control subjects. High TIMP-1 (> 300 ng/ml) or MMP-9 (> 30 ng/ml) correlated to poor cumulative survival in lung cancer patients (log rank P < 0.05). High TIMP-1 indicated a poor prognosis, especially in squamous cell cancer and in NSCLC patients with stage III: 66% and 70%, respectively, of the patients with low TIMP-l serum levels survived for more than one year, when only 25% and 20%, respectively, of the patients with high serum levels for TIMP-1 protein survived at that time. 56% of lung cancer patients with a plasma MMP-9 level < 30 ng/ml survived for 12 months when only 31% of the lung cancer patients with high MMP-9 plasma levels survived for more than one year. Also this difference was significant (log rank analysis, P < 0.05). Our results suggest that the factors of the metalloproteinase system might be important in lung cancer progression. TIMP-1 as well as MMP-9 could serve as prognostic markers, and their values could be investigated in the follow-up of lung cancer patients when selecting patients for systemic chemotherapy or other treatment modalities.
Targeting PDGF Signaling in Carcinoma-Associated Fibroblasts Controls Cervical Cancer in Mouse Model (2008)

The authors discuss a new study of a paracrine regulatory circuit centered on PDGF receptor signaling in cancer-associated fibroblasts and pericytes of a mouse model of cervical carcinoma.
Nanowire single-photon detector with an integrated optical cavity and anti-reflection coating (2006)

We have fabricated and tested superconducting single-photon detectors and demonstrated detection efficiencies of 57% at 1550-nm wavelength and 67% at 1064 nm. In addition to the peak detection efficiency, a median detection efficiency of 47.7% was measured over 132 devices at 1550 nm. These measurements were made at 1.8K, with each device biased to 97.5% of its critical current. The high detection efficiencies resulted from the addition of an optical cavity and anti-reflection coating to a nanowire photodetector, creating an integrated nanoelectrophotonic device with enhanced performance relative to the original device. Here, the testing apparatus and the fabrication process are presented. The detection efficiency of devices before and after the addition of optical elements is also reported.
Foveal and parafoveal contrast suppression are different: Mechanisms revealed by the study of healthy aging (2016)

Visual contextual effects enable inference regarding neural mechanisms of cortical function, principally because of similarities between the stimulus properties influencing human perception and those modifying primate visual cortical neural responses. Most neurophysiology assesses nonfoveal cellular function and circuitry, while most human studies are foveal. Here we use parafoveal stimuli to measure center-surround perception of contrast in older and younger adults. We measure the influence of both near and far surround because neurophysiology demonstrates different circuitry for these areas. Contrast suppression from the near surround was reduced in older observers, while that from the far surround was intact. Our results are consistent with reduced intracortical inhibition with age and normal extrastriate feedback. Interestingly, in the same older observers, foveal surround suppression of contrast was strengthened relative to younger adults, demonstrating a clear distinction between foveal and parafoveal center-surround behavior. We assume that underlying alterations in cortical neurotransmitter levels with age should not differ substantially between the areas of visual cortex representing foveal and near foveal regions. Consequently, our results suggest regional differences in center-surround circuitry. That older adults have varied contextual effects of visual contrast as a function of retinal eccentricity suggests complex effects of aging on scene and object perception.
Comparative studies of oncostatin M expression in the tissues of adult rodents (2005)

Oncostatin M (OSM), a member of the interleukin-6 family of cytokines, is thought to be expressed mostly by activated T-lymphocytes and monocytes in adult animals. However, here we report specific constitutive tissue expression of OSM in the pancreas, kidney, testes, spleen, stomach, and brain, but not liver or lung, of three adult rodent species.
New approaches for inhibiting HIV integrase: a journey beyond the active site. (2009)

Integrase (IN) inhibitors have proven to be highly beneficial in the treatment of HIV infection. The recently approved inhibitor, raltegravir, the phase III clinical trials compound elvitegravir, and all other agents reported to be in clinical trials bind to the active site of IN and share the same mechanism of action. There is a high probability for the development of cross resistance among these compounds. Therefore, drugs targeting alternative mechanisms and binding sites on IN are desired. Two potential sites for inhibiting the enzyme have been disclosed recently. The first site is located in the catalytic core domain and is used by the enzyme to bind the host protein lens epithelium-derived growth factor. The second site was identified by the selective covalent trapping of pyridoxal phosphate to the C-terminal domain of the enzyme. The targeting of these sites as a potential novel approach for inhibiting HIV IN is reviewed.
AN IMPLICIT ONE-DIMENSIONAL TWO-PHASE COMPRESSIBLE FLOW SOLVER FOR PIPELINES (2002)

This paper describes the use of a fully compressible two-phase flow model for the simulation of pipeline flows. The model is capable of dealing with a wide range of flow regimes, and is unconditionally well posed for transient computations. Applications described include both horizontal and vertical two-phase flows, air-water sedimentation flows and a two-phase shock tube problem. In all of these tests, good agreement is obtained with experimental or analytical solutions. Results simulating the rapid pressure surges encountered during the emergency shutdown of exit valves are also provided for two-phase pipeline flows. The use of advanced numerical methods, coupled with a fast implicit solver, enables accurate solutions to be obtained with considerably reduced computing times when compared with explicit schemes. The code developed here is capable of dealing with general equations of state (EOS) for each phase, and results are described using both an equivalent perfect and stiffened EOS for the liquid phase.
Intensity of Infection in AIDS-Associated Cryptosporidiosis (1993)

A fluorescent monoclonal anti-Cryptosporidium antibody was used to count the oocysts in stools of 12 AIDS patients with chronic cryptosporidiosis. Oocyst excretion was present throughout the day in all 12 patients. Stool-to-stool variation in oocyst concentration was within one order of magnitude. Small variations were also found in daily mean oocyst concentration and total daily oocyst excretion in 3 patients who had multiple 24-h stool collections. However, there was a large patient-to-patient variation in mean oocyst concentration (from < 5.0 x 10(3) to 9.2 x 10(5) oocysts/mL) and 24-h total oocyst excretion (from < 6.0 x 10(6) to 1.2 x 10(9) oocysts/day). There was a significant correlation between oocyst excretion and numbers of Cryptosporidium organisms seen on small bowel biopsy. Oocyst excretion was reduced in 4 patients treated with paromomycin, but diarrhea improved only in the 2 patients with high initial oocyst excretion.
Survival determinants in extensive-stage non-small-cell lung cancer: the Southwest Oncology Group experience. (1991)

We analyzed the 2,531-patient Southwest Oncology Group extensive-stage non-small-cell lung cancer (ENSCLC) data base from 1974 to 1988 to (1) assess the interactions of host- or tumor-related prognostic factors and therapy using Cox modeling and recursive partitioning and amalgamation (RPA) to determine whether each independently predicts outcome, and (2) use RPA to define prognostic subsets with different survival potentials. Good performance status (PS), female sex, and age greater than or equal to 70 years were significant independent predictors in a Cox model applied to the entire population. In a second Cox model for patients with good PS enrolled on recent studies, hemoglobin level greater than or equal to 11.0 g/dL, normal lactate dehydrogenase (LDH), normal calcium, and a single metastatic site were significant favorable factors. The use of cisplatin was an additional independent predictor of improved outcome in both Cox models after adjustments for year of accrual and all prognostic variables. The favorable effect of cisplatin was observed in each of six RPA-derived subgroups from the entire population. A second RPA of 904 patients from recent trials (nearly all received cisplatin-based therapy) resulted in three distinct prognostic subsets based on PS, age, hemoglobin, and LDH; greater than or equal to 1-year survivals were 27%, 16%, and 6% (P less than .0001). The best survival occurred for patients with a good PS who had a hemoglobin level greater than or equal to 11 g/dL and who were older than 47 years. This analysis suggests that although several factors were independent variables in the Cox models, three important prognostic subgroups were easily defined through RPA. Together with other analyses, our results suggest the need to modify the stage IV category in NSCLC.
PIB: A Score to Select Sorafenib Treatment Candidates for Hepatocellular Carcinoma in Resource-Limited Settings (2018)

El Carcinoma Hepatocelular es la segunda causa de muerte relacionada con cáncer en el mundo. Sorafenib, un inhibidor de tirosina quinasa, permanece en el estandar de la prescripción a pacientes con carcinoma hepatocelular avanzado o inoperable. Usando información de la red de investigación en hígado en Sud América (1336 casos de carcinoma hepatocelular) se creó un sistema de pronóstico costo-efectividad para ayudar a identificar a los pacientes con probabilidad del beneficio de sobrevivencia con el tratamiento con sorafenib.
Widespread Distribution in Pathogenic Bacteria of Di-Iron Proteins That Repair Oxidative and Nitrosative Damage to Iron-Sulfur Centers (2008)

Expression of two genes of unknown function, Staphylococcus aureus scdA and Neisseria gonorrhoeae dnrN, is induced by exposure to oxidative or nitrosative stress. We show that DnrN and ScdA are di-iron proteins that protect their hosts from damage caused by exposure to nitric oxide and to hydrogen peroxide. Loss of FNR-dependent activation of aniA expression and NsrR-dependent repression of norB and dnrN expression on exposure to NO was restored in the gonococcal parent strain but not in a dnrN mutant, suggesting that DnrN is necessary for the repair of NO damage to the gonococcal transcription factors, FNR and NsrR. Restoration of aconitase activity destroyed by exposure of S. aureus to NO or H2O2 required a functional scdA gene. Electron paramagnetic resonance spectra of recombinant ScdA purified from Escherichia coli confirmed the presence of a di-iron center. The recombinant scdA plasmid, but not recombinant plasmids encoding the complete Escherichia coli sufABCDSE or iscRSUAhscBAfdx operons, complemented repair defects of an E. coli ytfE mutant. Analysis of the protein sequence database revealed the importance of the two proteins based on the widespread distribution of highly conserved homologues in both gram-positive and gram-negative bacteria that are human pathogens. We provide in vivo and in vitro evidence that Fe-S clusters damaged by exposure to NO and H2O2 can be repaired by this new protein family, for which we propose the name repair of iron centers, or RIC, proteins.
Selective Inhibition of a Regulatory Subunit of Protein Phosphatase 1 Restores Proteostasis (2011)

Many biological processes are regulated through the selective dephosphorylation of proteins. Protein serine-threonine phosphatases are assembled from catalytic subunits bound to diverse regulatory subunits that provide substrate specificity and subcellular localization. We describe a small molecule, guanabenz, that bound to a regulatory subunit of protein phosphatase 1, PPP1R15A/GADD34, selectively disrupting the stress-induced dephosphorylation of the α subunit of translation initiation factor 2 (eIF2α). Without affecting the related PPP1R15B-phosphatase complex and constitutive protein synthesis, guanabenz prolonged eIF2α phosphorylation in human stressed cells, adjusting the protein production rates to levels manageable by available chaperones. This favored protein folding and thereby rescued cells from protein misfolding stress. Thus, regulatory subunits of phosphatases are drug targets, a property used here to restore proteostasis in stressed cells.
Peptides in Melanoma Therapy (2012)

Peptides derived from tumor associated antigens can be utilized to elicit a therapeutically effective immune response against melanoma in experimental models. However, patient vaccination with peptides - although it is often followed by the induction of melanoma- specific T lymphocytes - is rarely associated with tumor response of clinical relevance. In this review I summarize the principles of peptide design as well as the results so far obtained in the clinical setting while treating cutaneous melanoma by means of this active immunotherapy strategy. I also discuss some immunological and methodological issues that might be helpful for the successful development of peptide-based vaccines.
Rational Design and Simple Chemistry Yield a Superior, Neuroprotective HDAC6 Inhibitor, Tubastatin A (2010)

Structure-based drug design combined with homology modeling techniques were used to develop potent inhibitors of HDAC6 that display superior selectivity for the HDAC6 isozyme compared to other inhibitors. These inhibitors can be assembled in a few synthetic steps, and thus are readily scaled up for in vivo studies. An optimized compound from this series, designated Tubastatin A, was tested in primary cortical neuron cultures in which it was found to induce elevated levels of acetylated alpha-tubulin, but not histone, consistent with its HDAC6 selectivity. Tubastatin A also conferred dose-dependent protection in primary cortical neuron cultures against glutathione depletion-induced oxidative stress. Importantly, when given alone at all concentrations tested, this hydroxamate-containing HDAC6-selective compound displayed no neuronal toxicity, thus, forecasting the potential application of this agent and its analogues to neurodegenerative conditions.
LDPC Codes Based on Latin Squares: Cycle Structure, Stopping Set, and Trapping Set Analysis (2007)

It is well known that certain combinatorial structures in the Tanner graph of a low-density parity-check (LDPC) code exhibit a strong influence on its performance under iterative decoding. These structures include cycles, stopping/trapping sets, and parameters such as the diameter of the code. In general, it is very hard to find a complete characterization of such configurations in an arbitrary code, and even harder to understand the intricate relationships that exist between these entities. It is, therefore, of interest to identify a simple setting in which all the described combinatorial structures can be enumerated and studied within a joint framework. One such setting is developed in this paper, for the purpose of analyzing the distribution of short cycles and the structure of stopping and trapping sets in Tanner graphs of LDPC codes based on idempotent and symmetric Latin squares. The parity-check matrices of LDPC codes based on Latin squares have a special form that allows for connecting combinatorial parameters of the codes with the number of certain subrectangles in the Latin squares. Subrectangles of interest can be easily identified, and in certain instances, completely enumerated. This study can be extended in several different directions, one of which is concerned with modifying the code design process in order to eliminate or reduce the number of configurations bearing a negative influence on the performance of the code. Another application of the results includes determining to which extent a configuration governs the behavior of the bit-error rate curve in the waterfall and error-floor regions