gebhart/patrepeval huggingface dataset:
Three-Dimensional Cell Culture-Based Screening Identifies the Anthelmintic Drug Nitazoxanide as a Candidate for Treatment of Colorectal Cancer (2015)

Because dormant cancer cells in hypoxic and nutrient-deprived regions of solid tumors provide a major obstacle to treatment, compounds targeting those cells might have clinical benefits. Here, we describe a high-throughput drug screening approach, using glucose-deprived multicellular tumor spheroids (MCTS) with inner hypoxia, to identify compounds that specifically target this cell population. We used a concept of drug repositioning-using known molecules for new indications. This is a promising strategy to identify molecules for rapid clinical advancement. By screening 1,600 compounds with documented clinical history, we aimed to identify candidates with unforeseen potential for repositioning as anticancer drugs. Our screen identified five molecules with pronounced MCTS-selective activity: nitazoxanide, niclosamide, closantel, pyrvinium pamoate, and salinomycin. Herein, we show that all five compounds inhibit mitochondrial respiration. This suggests that cancer cells in low glucose concentrations depend on oxidative phosphorylation rather than solely glycolysis. Importantly, continuous exposure to the compounds was required to achieve effective treatment. Nitazoxanide, an FDA-approved antiprotozoal drug with excellent pharmacokinetic and safety profile, is the only molecule among the screening hits that reaches high plasma concentrations persisting for up to a few hours after single oral dose. Nitazoxanide activated the AMPK pathway and downregulated c-Myc, mTOR, and Wnt signaling at clinically achievable concentrations. Nitazoxanide combined with the cytotoxic drug irinotecan showed anticancer activity in vivo. We here report that the FDA-approved anthelmintic drug nitazoxanide could be a potential candidate for advancement into cancer clinical trials.
Therapeutic applications of carbon monoxide-releasing molecules (2005)

Carbon monoxide (CO), which is formed in mammalian cells through the oxidation of haem by the enzyme haem oxygenase, actively participates in the regulation of key intracellular functions. Emerging evidence reveals that an increased generation of haem oxygenase-derived CO plays a critical role in the resolution of inflammatory processes and alleviation of cardiovascular disorders. The authors have identified a novel class of substances, CO-releasing molecules (CO-RMs), which are capable of exerting a variety of pharmacological activities via the liberation of controlled amounts of CO in biological systems. A wide range of CO carriers containing manganese (CORM-1), ruthenium (CORM-2 and -3), boron (CORM-A1) and iron (CORM-F3) are currently being investigated to tailor therapeutic approaches for the prevention of vascular dysfunction, inflammation, tissue ischaemia and organ rejection.
Changes in Breast Density Associated With Initiation, Discontinuation, and Continuing Use of Hormone Replacement Therapy (2001)

These results indicate that breast density changes associated with HRT are dynamic, increasing with initiation, and decreasing with discontinuation.
Comparative Pharmacology of Site Directed Antithrombin Agents. Implication in Drug Development (1995)

Beside the direct inhibition of thrombin and its regulatory functions, many of the newer antithrombin agents produce several additional effects, unrelated to their anticoagulant actions. Synthetic peptide inhibitors are capable of producing fibrinolytic compromise by virtue of their actions on fibrinolytic enzymes such as t-PA, plasmin, urokinase and protein Ca. In addition, the low molecular weight arginine-containing peptides are also known to produce hemodynamic and hemostatic deficits. The designs of the ongoing clinical trials are largely empirical because of the non-availability of valid pharmacologic and toxicologic data on thrombin inhibitors. In contrast to heparin, none of the thrombin inhibitors produce endogenous release of tissue factor pathway inhibitor (TFPI) in the experimental and clinical settings. These observations suggest that beside the direct inhibition of thrombin, these agents also produce multiple additional effects that can significantly contribute to their pharmacologic and toxicologic profile.
T-cell redirecting bispecific antibodies targeting BCMA for the treatment of multiple myeloma (2020)

B-cell maturation antigen (BCMA)-targeting bispecific antibodies and bispecific T-cell engagers (BiTEs) redirect T-cells to BCMA-expressing multiple myeloma (MM) cells. These MM cells are subsequently eliminated via various mechanisms of action including the release of granzymes and perforins. Several phase 1, dose-escalation studies show pronounced activity of BCMA-targeting bispecific antibodies, including teclistamab, AMG420 and CC-93269, in heavily pretreated MM patients. Cytokine release syndrome is the most common adverse event, which can be adequately managed with tocilizumab or steroids. Several clinical trials are currently evaluating combination therapy with a BCMA-specific bispecific antibody, based on preclinical findings showing that immunomodulatory drugs or CD38-targeting antibodies enhance the activity of bispecific antibodies. In addition, bispecific antibodies, targeting other MM cell surface antigens (i. e. GPRC5D, CD38 and FcRH5), are also evaluated in early phase clinical trials. Such bispecific antibodies, targeting other antigens, may be given to patients with low baseline BCMA expression, disease with substantial heterogeneity in BCMA expression, following prior BCMA-targeted therapy, or combined with BCMA bispecific antibodies to prevent development of antigen escape.
Dynamics of the holes in human erythrocyte membrane ghosts. (1982)

Osmotic lysis of human erythrocytes creates in each membrane a single large hole which subsequently contracts to a size determined largely by the buffer, typically 7-140 A in radius. Cations, but not anions, stimulated the rate and extent of hole size reduction with simple saturation behavior; the potency of Ca2+ exceeded M&+, which greatly surpassed Na+. The hole size was minimal at pH 5.5. Hole size change was greatly accelerated by increasing temperature between 0 and 50 “C. Whatever its size, the hole radius was stable to 21-2 A over several days at 0 “C. Cationic amphipaths such as chlorpromazine promoted hole closure in a salt-dependent fashion, while anionic amphipaths such as 2,4-dinitrophenolate or hexanoate opposed hole closure. Hole size thus appears to be determined by a balance between the force expanding the hole (electrostatic repulsion among anionic groups on the membrane) and the force driving hole closure (perhaps the hydrophobic effect of the lipid/ water interface at the hole perimeter and/or membrane elasticity). Hole size was initially completely reversible; however, the extent to which holes were able to expand and contract gradually diminished in parallel until the oles became fixed at an ambient size. The rate of this process increased directly with temperature, pH, and the presence of hexanol, and inversely with cation concentration. A 30% reduction in membrane cholesterol greatly accelerated the loss of hole sealing. Glutaraldehyde at 0.5 l ~ l ~ (0.005%) blocked hole closure (but not hole expansion) without cross-linking membrane proteins significantly. Once lost, the ability to expand hole size could be regenerated by osmotically stressing sucrosefilled ghosts. We infer that hole size dynamics. reflect metastable configurations of the membrane bilayer which can be reversibly altered, dissipated, and restored by experimental manipulations. Applications of the hemolytic hole as a continuously tunable molecular filter are suggested.
Akt Signaling--Linking Membrane Events to Life and Death Decisions (1997)

Many growth factors exert their effects on cells by simulating intracellular kinases, which add phosphate groups to proteins. Two reports on p. 661 and p. 665 of this week's issue implicate the oncogenic kinase Akt in IGF-1-mediated neuronal survival (Dudek et al .) and show how lipids can regulate the activity of Akt (Franke et al .). In his Perspective, Hemmings discusses these results and several other recent reports about Akt and its unique mode of activation by phospholipids.
Standard compatible extension of H.263 for robust video transmission in mobile environments (1997)

In this paper we address the problem of robust video transmission in error prone environments. The approach is compatible with the ITU-T video coding standard H.263. Fading situations in mobile networks are tolerated and the image quality degradation due to spatio-temporal error propagation is minimized utilizing a feedback channel between transmitter and receiver carrying acknowledgment information. In a first step, corrupted group of blocks (GOB's) are concealed to avoid annoying artifacts caused by decoding of an erroneous bit stream. The GOB and the corresponding frame number are reported to the transmitter via the back channel. The encoder evaluates the negative acknowledgments and reconstructs the spatial and temporal error propagation. A low complexity algorithm for real-time reconstruction of spatio-temporal error propagation is described in detail. Rapid error recovery is achieved by INTRA refreshing image regions (macroblocks) bearing visible distortion. The feedback channel method does not introduce additional delay and is particularly relevant for real-time conversational services in mobile networks. Experimental results with bursty bit error sequences simulating a Digital European Cordless Telephony (DECT) channel are presented with different combinations of forward error correction (FEC), automatic repeat on request (ARQ), and the proposed error compensation technique, Compared to the case where FEC and ARQ are used for error correction, a gain of up to 3 dB peak signal-to-noise ratio (PSNR) is observed if error compensation is employed additionally.
Age-Related Macular Degeneration and Smoking (1996)

The results provide evidence for a dose-response relationship between smoking and AMD, particularly in persons with the neovascular form of the disease.
The Split Bregman Method for L1-Regularized Problems (2009)

The class of L1-regularized optimization problems has received much attention recently because of the introduction of “compressed sensing,” which allows images and signals to be reconstructed from small amounts of data. Despite this recent attention, many L1-regularized problems still remain difficult to solve, or require techniques that are very problem-specific. In this paper, we show that Bregman iteration can be used to solve a wide variety of constrained optimization problems. Using this technique, we propose a “split Bregman” method, which can solve a very broad class of L1-regularized problems. We apply this technique to the Rudin–Osher–Fatemi functional for image denoising and to a compressed sensing problem that arises in magnetic resonance imaging.
Resistant Hypertension (2002)

Although resistant hypertension affects a minority of all hypertensives, this group continues to experience disproportionately high cardiovascular event rates despite newer antihypertensive agents. Hypertension represents an imbalance of hemodynamic forces within the circulation, usually characterized by elevated systemic vascular resistance. We studied the utility of serial hemodynamic parameters in the selection and titration of antihypertensive medication in resistant hypertensive patients using highly reproducible noninvasive measurements by thoracic bioimpedance. Resistant hypertension patients (n=104) were randomized to drug selection based either on serial hemodynamic (HD) measurements and a predefined algorithm or on drug selection directed by a hypertension specialist (SC) in a 3-month intensive treatment program. Blood pressure was lowered by intensified drug therapy in both treatment groups (169+/-3/87+/-2 to 139+/-2/72+/-1 mm Hg HD versus 173+/-3/91+/-2 to 147+/-2/79+/-1 mm Hg SC, P<0.01 for systolic and diastolic BP), using similar numbers and intensity of antihypertensive medications. Blood pressures were reduced further for those treated according to hemodynamic measurements, resulting in improved control rates (56% HD versus 33% SC controlled to </=140/90 mm Hg, P<0.05) and incremental reduction in systemic vascular resistance measurements. Although the number of patients taking diuretics did not differ between groups, final diuretic dosage was higher in the hemodynamic cohort. Our results demonstrate superior blood pressure control using a treatment algorithm and serial hemodynamic measurements compared with clinical judgment alone in a randomized prospective study. Our measurements of thoracic fluid volume support occult volume expansion as a mediator of antihypertensive drug resistance and use of impedance measurements to guide advancing diuretic dose and adjustment of multidrug antihypertensive treatment.
Transfected Leishmania expressing biologically active IFN-gamma (1993)

Infection of susceptible BALB/c mice with Leishmania major leads to progressive infection with the failure to expand and activate Th1 CD4+ T cells that elaborate IFN-gamma, a critically implicated cytokine for control of disease. We used the recently described capacity to express foreign genes in trypanosomatids to introduce into Leishmania the murine IFN-gamma gene on a drug-selectable plasmid under the constitutive control of intergenic tubulin sequences. Several clones of L. major were established and demonstrated to contain IFN-gamma DNA and IFN-gamma RNA that was appropriately trans-spliced with the Leishmania-specific leader sequence, and to secrete IFN-gamma into the media. The secreted IFN-gamma was biologically active as assessed by up-regulation of class II MHC Ag and induction of macrophage nitric oxide synthase activity in a macrophage cell line. Infection of nude mice with IFN-gamma-containing organisms resulted in significantly slower progression of disease as compared to infection with organisms containing the empty plasmid, suggesting that biologically important activation of infected macrophages might be occurring in vivo. Infection of genetically susceptible BALB/c mice, however, did not impede the expansion of Th2 cells and the inexorable progression of disease. Despite the demonstration of increased levels of IFN-gamma transcription in vivo, induction of nitric oxide synthase in macrophages and expression of Ly-6, and IFN-gamma-inducible Ag, on CD4+ lymphocytes could not be shown. In all cases, organisms recovered from tissue amastigotes contained the IFN-gamma plasmid and secreted active IFN-gamma. The data confirm earlier studies that IFN-gamma alone is not sufficient to impede activation and maturation of Th2 cells in susceptible mice, even when targeted directly to the infected cell.
Diagnostic efficacy of random albumin creatinine ratio for detection of micro and macro-albuminuria in type 2 diabetes mellitus (2016)

Performance of RACR was comparable to 24 hour UAE assay particularly in excluding renal damage in T2DM.
Studies on Modification of Surface Properties in Polycarbonate (PC) Film Induced by DC Glow Discharge Plasma (2011)

The polycarbonate film (PC) surface was treated using glow discharge low-pressure air plasma. The modified surface was characterized by contact angle, FTIR, XRD, AFM, and XPS analysis. The surface-modified samples were further investigated using T-peel test for technical applications. The surface energy of the sample was estimated by measuring contact angle. The results show that, after plasma treatment, the root mean square (RMS) roughness of PC film was gradually increased with exposure time. Plasma treatment modified the chemical composition of the polymer surface and it made the surface to be highly hydrophilic. It was found that the air plasma treatment increases the polar component of PC film.
Influenza virus M2 protein ion channel activity stabilizes the native form of fowl plague virus hemagglutinin during intracellular transport (1994)

The influenza A/fowl plague virus/Rostock/34 hemagglutinin (HA), which is cleaved intracellularly and has a high pH threshold (pH 5.9) for undergoing its conformational change to the low-pH form, was expressed from cDNA in CV-1 and HeLa T4 cells in the absence of other influenza virus proteins. It was found, by biochemical assays, that the majority of the HA molecules were in a form indistinguishable from the low-pH form of HA. The acidotropic agent, ammonium chloride, stabilized the accumulation of HA in its native form. Coexpression of HA and the homotypic influenza virus M2 protein, which has ion channel activity, stabilized the accumulation of HA in its pH neutral (native) form, and the M2 protein ion channel blocker, amantadine, prevented the rescue of HA in its native form. These data provide direct evidence that the influenza virus M2 protein ion channel activity can affect the status of the conformational form of cleaved HA during intracellular transport.
The anemone, Nematostella vectensis, in Britain: considerations for conservation management (1997)

1. The starlet sea anemone, Nematostella vectensis, is a small edwardsiid anemone found in sheltered brackish habitats on the Atlantic and Pacific coasts of North America and on the south and east coasts of England. 2. On eastern Atlantic coasts, this anemone is limited to relatively few sites and has consequently been listed in the IUCN Invertebrate Red Data Book as ‘vulnerable’, receives protection in Britain under The Wildlife and Countryside Act, and is short listed in the UK Biodiversity Action Plan. As detailed information on the ecology of the species is lacking, informed management of existing populations and habitats is difficult. 3. The current distribution in England is outlined, together with a description of habitat characteristics and a list of associated species. 4. The importance of salinity and water flow in determining the occurrence and spatial/temporal patterns of distribution of the species is demonstrated. 5. Population change at three English south coast sites is described and the patterns interpreted in terms of seasonal changes in food availability, salinity and temperature. 6. Although females develop ovaries and are capable of sexual reproduction, males are absent from all south coast populations of N. vectensis and it is concluded that populations at these sites produce all offspring asexually. 7. It is suggested that the species may have been introduced to Europe from North America, though clarification awaits the genetic study of existing populations. © 1997 John Wiley & Sons, Ltd.
Selective non-ablative wrinkle reduction by laser (2000)

In conclusion, the treatment modality described may be a new approach to the treatment of wrinkles.
Idiopathic Pulmonary Fibrosis: Spectrum of High-Resolution CT Findings (2005)

The spectrum of HRCT manifestations varies from typical findings that allow confident diagnosis to atypical patterns mimicking other diseases, including predominance of ground-glass opacity, consolidation, nodules, and atypical distribution of lesions.
Delaunay's mesh of a convex polyhedron in dimension d. application to arbitrary polyhedra (1992)

Abstract This paper presents a method for creating a Delaunay triangulation connected to a set of specified points. The theoretical aspect is recalled for an arbitrary dimension and the method is discussed in order to derive a practical approach, valid for dimensions 2 and 3, which is simple, robust and well adapted to computation. Convex polyhedral and arbitrary polyhedral situations are introduced.
Micromechanics via x-ray assisted processing (1994)

The application potential of micromechanics is very large and falls into very-large-scale-integration-like markets such as magnetic recording and electromechanical components and application specific markets such as surgery tools and sensors. Many of these markets cannot now be addressed because cost effective fabrication technology is not now available to fabricate the required highly complex devices. Idealized fabrication tools must address three dimensional processing with tolerances in the 100 ppm range and must extend over a large material base. They must do that with some integrated circuit-cofabrication compatibility in a cost effective manner. There is a premium for tools which can handle large structural heights with small critical dimensions. X-ray assisted processing can satisfy some of the requirements of the idealized tool. X-ray assisted processing started with the basic LIGA process in Germany. This process can be extended by merging it with surface micromachining and assembly. The current versions of LIGA and LIGA-like processing are restricted in performance by photoresist strain which is typically found in thick photoresist processes. Photoresist strain can and has been reduced significantly by introducing solvent bonded photoresist application procedures which are followed by precision milling and polishing. This extends allowed photoresist thicknesses to heights in the centimeter range. Exposure via synchrotron generated x-ray fluxes and subsequent developing has produced structures with structural heights to 1 cm. This implies that x-ray assisted processing does not only play a major role in micromechanical fabrication but also in precision engineering. This statement is further supported by results that indicate that multiple x-ray mask processes are feasible and that plastic parts can be fabricated by direct x-ray exposure over large surface areas without injection molding. Test vehicles for x-ray assisted processing at the University of Wisconsin fall into two categories: modular micromechanical building blocks such as gear boxes and novel sensors such as high speed magnetic micromotors.
Induction of the differentiated phenotype in human colon cancer cell is associated with the attenuation of subcellular tyrosine phosphorylation. (1995)

In the present study we have determined membrane, cytosolic, and cytoskeleton-associated tyrosine protein kinase (TPK) activity in human colon cancer cell lines exposed to (i) the differentiation-promoting agents sodium butyrate and 8-chloro-cyclic-adenosine 3',5'-monophosphate (8-Cl-cAMP), (ii) tyrphostins, specific TPK inhibitors, or (iii) differentiation-inducing culture manipulations. Treatment of human colon cancer cell lines, LS 174T, COLO 205, and SW620, with sodium butyrate and 8-Cl-cAMP or tyrphostins AG-30 and AG-34, significantly attenuated TPK activity concomitantly with an increase in the activity of alkaline phosphatase, an enzymatic marker of intestinal cell differentiation. The differentiated phenotype induced in Caco-2 and HT-29 colon cancer cells by culture manipulation was associated with a significant decrease in cytoskeleton-associated TPK activity and marked activity of alkaline phosphatase (AP). Electron microscopy and freeze-fracturing analysis of HT-29 cells showed that the gradual transition from the undifferentiated to the differentiated phenotype resulted in the acquisition of a distinct polarized morphology. Immunocytochemical phosphotyrosine analysis of cultured SW620 cells showed positive staining mostly localized in zones of focal contacts. A marked reduction in phosphotyrosine staining with notable changes in cell morphology was observed in SW620 cells exposed to tyrphostins. Cumulatively, the present results indicate that the induction of the differentiated phenotype in colon cancer cells is associated with a marked decrease in TPK activity and tyrosine phosphorylation.
El debate empieza ahora: a propósito de "Precios de subsistencias, salarios nominales y niveles de vida en Castilla la Vieja. Palencia, 1751-1861", de Javier Moreno (2001)

Standars of living, real wages, agrarian capitalism, unequality