gebhart/patrepeval huggingface dataset:
Tilted-Plane Optical Processor (1972)

A new optical system concept for processing data from synthetic-aperture radars is described. The optical systems are multilens, anamorphic telescopes including spherical and cylindrical lenses. The new method has as its basis two well-known properties of lenses: (a) the longitudinal magnification of an imaging system is equal to the square of the lateral magnification; and (b) a telescope provides an image with magnification independent of the object position.
Nature of linkage and mode of action of methotrexate conjugated with antitumor antibodies: implications for future preparation of conjugates. (1988)

The binding of methotrexate (MTX) to IgG in conjugates was examined by studies on a direct MTX conjugate with a monoclonal antibody (aMM46) to mouse mammary tumor MM46 cells and corresponding irrelevant antibody and normal gamma-globulin conjugates, all prepared by the active ester method with MTX N-succinimidyl ester (MTX-OSu). The binding was examined in terms of effects on the potency and selectivity of the cytotoxic activity of the aMM46 conjugate. The results obtained supported the following conclusions: (a) MTX-OSu reacts not only with the amino group of IgG to give an amide bond, but also with another group(s) to give a less stable bond(s) such as an ester bond; (b) in contrast to the amide bond-linked MTX, which is taken up by the cells by endocytic internalization, a substantial portion of the MTX linked by an ester or other less stable bond(s) is released from the conjugates extracellularly and enters the cells by the MTX active transport system, as revealed by the inhibitory effect of thiamine pyrophosphate on the cytotoxicity; (c) this MTX linked by a less stable bond(s) that causes nonspecific cytotoxicity can be removed by treatment with hydroxylamine; (d) the overall cytotoxicity of aMM46-MTX decreased on removal of this less stably linked MTX, suggesting that the lysosomal degradation of the conjugate carrying amide bond-linked MTX to liberate MTX derivatives of low molecular weight is insufficient; (e) the liberation of low-molecular-weight substances in the lysosomes is probably more important for efficient entry of active substances into the cytosol, than for inhibition of the activity of dihydrofolate reductase, because after hydroxylamine treatment, the amide bond-linked MTX showed greater decrease in drug cytotoxicity than in inhibitory activity against dihydrofolate reductase; (f) in combination with hydroxylamine treatment, insertion between MTX and IgG of a linkage capable of ready cleavage in lysosomes deserves exploitation as a method for making potent conjugates with less nonspecific activity.
Radical cystectomy for high risk patients with superficial bladder cancer in the era of orthotopic urinary reconstruction (1995)

Pathologic upstaging to muscle-invasive or metastatic tumors occurs in one third of highly selected patients with clinically superficial bladder cancer who have had radical cystectomy, half of whom have extravesical disease. Survival is significantly decreased in this group of upstaged patients. With the alternative of orthotopic urinary diversion available to most men and women requiring cystectomy, radical cystectomy should be considered a viable alternative to continued conservative measures for selected patients with aggressive superficial bladder tumors.
Efficient cell surface expression of class II MHC molecules in the absence of associated invariant chain. (1986)

The intracytoplasmic forms of class II (or Ia) major histocompatibility complex heterodimers are associated with a third glycoprotein, termed the invariant chain (Ii). This specific interaction has led to the view that Ii plays a necessary role in the assembly, intracellular transport, and/or membrane insertion of Ia molecules. To test this hypothesis directly, we have transfected complementary DNA clones that encode murine class II alpha and beta chains into cells that do not express any endogenous Ii messenger RNA (mRNA) (COS-7 and BALB/c 3T3 cells). After DNA-mediated gene transfer, significant cell surface expression of Ia was observed in transient expression assays using COS-7 cells and a stable expression system using BALB/c 3T3 cells. Furthermore, the total levels of class II alpha and beta mRNA were similar in Ii- cells (transfected BALB/c 3T3) and in Ii+ cells (B cell hybridoma) that expressed nearly identical amounts of surface Ia, suggesting that the efficiency of Ia expression was equivalent in the two cell types and, therefore, independent of Ii. These results indicate that the physiologic role for Ii is not simply to mediate membrane expression of Ia molecules, and that alternative hypotheses concerning the true function of this molecule need to be considered.
Alpha7 Neuronal Nicotinic Receptor: A Pluripotent Target for Diseases of the Central Nervous System (2014)

Twenty years ago the alpha7 nicotinic acetylcholine receptor (nAChR) was thought to be vestigial with little biological relevance, but in recent years it has emerged as a functional target with ubiquitous localization and biological roles. In the last decade more than two thousand manuscripts have been published unraveling the multi-dimensional complexity of this target, the heterogeneity of its genetic variants, the spectrum of transducing signals, and the critical roles it plays in pivotal biological functions in the protection and maturation of neurons and stems cells, immune and inflammatory responses, sensory gating, mnemonic and attentional processes. In addition research and development of novel drugs has also promoted an intense debate on the role of activation, desensitization, β -amyloid oligomers, glutamate, and alpha7 nAChR, in cognition, neuronal survival, and neurodegeneration. The initial alpha7 nAChRs transducing enzyme, aptly named after Janus the two-faced roman deity for crossroads and gateways, reflects the dichotomy of reports on alpha7 nAChRs in promoting neuronal survival and cognitive processes, or as the target of β- amyloid oligomers to destabilize neuronal homeostasis leading to an irreversible neurochemical demise and dementia. It is therefore important to understand the functional neural bases of alpha7 nAChRs-mediated improvement of biological functions. The promise of alpha7 nAChR-directed drugs has already recently translated into proof-of-concept in controlled clinical trials but the full promise of this target(s) will be fully unraveled when its impact on neuronal health and survival is tested in controlled long-term clinical trials of disease progression.
Calcium dobesilate potentiates endothelium‐derived hyperpolarizing factor‐mediated relaxation of human penile resistance arteries (2003)

1 We have evaluated the participation of endothelium-derived hyperpolarizing factor (EDHF) in the endothelium-dependent relaxation of isolated human penile resistance arteries (HPRA) and human corpus cavernosum (HCC) strips. In addition, the effect of the angioprotective agent, calcium dobesilate (DOBE), on the endothelium-dependent relaxation of these tissues was investigated. 2 Combined inhibition of nitric oxide synthase (NOS) and cyclooxygenase (COX) nearly abolished the endothelium-dependent relaxation to acetylcholine (ACh) in HCC, while 60% relaxation of HPRA was observed under these conditions. Endothelium-dependent relaxation of HPRA resistant to NOS and COX inhibition was prevented by raising the extracellular concentration of K(+) (35 mM) or by blocking Ca(2)(+)-activated K(+) channels, with apamin (APA; 100 nM) and charybdotoxin (CTX; 100 nM), suggesting the involvement of EDHF in these responses. 3 Endothelium-dependent relaxation to ACh was markedly enhanced by DOBE (10 micro M) in HPRA but not in HCC. The potentiating effects of DOBE on ACh-induced responses in HPRA, remained after NOS and COX inhibition, were reduced by inhibition of cytochrome P450 oxygenase with miconazole (0.3 mM) and were abolished by high K(+) or a combination of APA and CTX. 4 In vivo, DOBE (10 mg kg(-1) i.v.) significantly potentiated the erectile responses to cavernosal nerve stimulation in male rats. 5 EDHF plays an important role in the endothelium-dependent relaxation of HPRA but not in HCC. DOBE significantly improves endothelium-dependent relaxation of HPRA mediated by EDHF and potentiates erectile responses in vivo. Thus, EDHF becomes a new therapeutic target for the treatment of erectile dysfunction (ED) and DOBE could be considered a candidate for oral therapy for ED.
Computational and Clinical Approaches to Pattern Recognition and Concept Formation (2013)

The ninth volume in this highly acclaimed series discusses the computational and clinical approaches to pattern recognition and concept formation regarding: visual and spatial processing models; computational models, templates and hierarchical models. An ideal reference for students and professionals in experimental psychology and behavioral analysis.
Prediction of spontaneous autoimmune diabetes in NOD mice by quantification of autoreactive T cells in peripheral blood (2003)

Autoimmune (type 1) diabetes mellitus results from the destruction of insulin-producing pancreatic cells by T lymphocytes. Prediction of cell-mediated autoimmune diseases by direct detection of autoreactive T cells in peripheral blood has proved elusive, in part because of their low frequency and reduced avidity for peptide MHC ligands. We demonstrate here that MHC class I tetramers complexed to a high-avidity analogue of an immunodominant cell epitope detect diabetogenic CD8 + T cells in the peripheral blood of NOD mice ex vivo and that the quantification of this autoreactive T cell population in peripheral blood is a powerful predictor of autoimmune diabetes.
Introducción (1989)

Cuando mis investigaciones sobre La Cristiada me llevaron a viajar por el occidente de la República en busca de eventuales raíces de inconformidad o de protesta populares, me encontre casualmente con el personaje de Manuel Lozada. Digo casualmente porque mi ignorancia era grande. Y fue entonces cuando leí, a fines de 1967, si mal no recuerdo, que: Hay allá, muy en el intenor de la Republica Mexicana, al extremo occidental del estado de Jalisco, una extensa comarca, sobre cuya faz y cuya histo...
Synergistic interaction between exercise and insulin on peripheral glucose uptake. (1981)

The interaction of exercise and insulin on glucose metabolism was examined in 10 healthy volunteers. Four study protocols were used: study 1: plasma insulin was raised by approximately 100 microunits/ml while plasma glucose was maintained at basal levels for 2 h (insulin clamp). Study 2: subjects performed 30 min of bicycle exercise at 40% of VO2 max. Study 3: an insulin clamp was performed as per study 1. Following 60 min of sustained hyperinsulinemia, however, subjects exercised for 30 min as per study 2. Study 4: subjects were studied as per study 3 except that catheters were inserted into the femoral artery and vein to quantitate leg glucose uptake. During the 60-90 min period of hyperinsulinemia (study 1), glucose uptake averaged 8.73 +/- 0.10 mg/kg per min. With exercise alone (study 2), the increment in peripheral glucose uptake was 1.43 +/- 0.30 mg/kg per min. When hyperinsulinemia and exercise were combined (study 3), glucose uptake averaged 15.06 +/- 0.98 mg/kg per min (P less than 0.01) and this was significantly (P less than 0.001) greater than the sum of glucose uptake when exercise and the insulin clamp were performed separately. The magnitude of rise in glucose uptake correlated closely with the increase in leg blood flow (r = 0.935, P less than 0.001), suggesting that the synergism is the result of increased blood flow and increased capillary surface area to exercising muscle. More than 85% of total body glucose metabolism during studies 1 and 3 was accounted for by skeletal muscle uptake. These results demonstrate that (a) insulin and exercise act synergistically to enhance glucose disposal in man, and (b) muscle is the primary tissue responsible for the increase in glucose metabolism following hyperinsulinemia and exercise.
Role for Interferon-γ in the Immunomodulatory Activity of Human Bone Marrow Mesenchymal Stem Cells (2005)

Mesenchymal stem cells (MSCs) inhibit the proliferation of HLA-unrelated T lymphocytes to allogeneic stimulation, but the mechanisms responsible for this activity are not fully understood. We show here that MSCs suppress the proliferation of both CD4+ and CD8+ T lymphocytes, as well as of natural killer (NK) cells, whereas they do not have an effect on the proliferation of B lymphocytes. The antiproliferative effect of MSCs was not associated with any effect on the expression of cell-activation markers, induction of cell apoptosis, or mimicry/enhancement of T regulatory cell activity. The suppressive activity of MSCs was not contact-dependent and required the presence of interferon (IFN)-gamma produced by activated T cells and NK cells. Accordingly, even activated B cells became susceptible to the suppressive activity of MSCs in the presence of exogenously added IFN-gamma. The suppressive effect of IFN-gamma was related to its ability to stimulate the production by MSCs of indoleamine 2,3-dioxygenase activity, which in turn inhibited the proliferation of activated T or NK cells. These findings suggest that the beneficial effect on graft-versus-host disease induced by in vivo coinfusion with the graft of MSCs may be due to the activation of the immunomodulatory properties of MSCs by T cell- derived IFN-gamma.
Visible 405 nm SLD light photo‐destroys methicillin‐resistant Staphylococcus aureus (MRSA) in vitro (2008)

At low doses, blue light photo-destroys HA-MRSA and CA-MRSA in vitro; raising the prospect that phototherapy may be an effective clinical tool in the on-going effort to stem MRSA infections.
Cell Migration into a Wounded Area In Vitro (2003)

In vitro wound healing is a complex phenomenon in which cells mechanically released from tight confluence migrate in an oriented fashion to an area made free of cells (1). Moreover, beyond migrating, cells at the advancing border often re-enter the cell cycle (2–4). In the perspective of adhesion molecules, the process involves remodeling of the cellular adhesive interactions both with the adjoning cells and with the extracellular matrix. Therefore, aspects of cell physiology related to the molecules controlling adhesion to neighboring cells (5–7) and to substrate (8), to components of the cytoskeleton (9–12), as well as to extracellular matrix remodeling (13–15) can be studied during the transition from the resting to the migratory/proliferative phenotype.
The effect of arteriovenous sheathotomy on cystoid macular oedema secondary to branch retinal vein occlusion (2003)

Complete resolution of CMO after AV sheathotomy occurred in one third of patients, and postoperative vision improved significantly in this group. However, in the majority of cases, despite an improvement in CMO, there was no improvement in vision after AV sheathotomy.
Dynamics of the dissipative two-state system (1987)

This paper presents the results of a functional-integral approach to the dynamics of a two-state system coupled to a dissipative environment. It is primarily an extended account of results obtained over the last four years by the authors; while they try to provide some background for orientation, it is emphatically not intended as a comprehensive review of the literature on the subject. Its contents include (1) an exact and general prescription for the reduction, under appropriate circumstances, of the problem of a system tunneling between two wells in the presence of a dissipative environment to the "spin-boson" problem; (2) the derivation of an exact formula for the dynamics of the latter problem; (3) the demonstration that there exists a simple approximation to this exact formula which is controlled, in the sense that we can put explicit bounds on the errors incurred in it, and that for almost all regions of the parameter space these errors are either very small in the limit of interest to us (the "slow-tunneling" limit) or can themselves be evaluated with satisfactory accuracy; (4) use of these results to obtain quantitative expressions for the dynamics of the system as a function of the spectral density $J(\ensuremath{\omega})$ of its coupling to the environment. If $J(\ensuremath{\omega})$ behaves as ${\ensuremath{\omega}}^{s}$ for frequencies of the order of the tunneling frequency or smaller, the authors find for the "unbiased" case the following results: For $s&lt;1$ the system is localized at zero temperature, and at finite $T$ relaxes incoherently at a rate proportional to $\mathrm{exp}\ensuremath{-}{(\frac{{T}_{0}}{T})}^{1\ensuremath{-}s}$. For $s&gt;2$ it undergoes underdamped coherent oscillations for all relevant temperatures, while for $1&lt;s&lt;2$ there is a crossover from coherent oscillation to overdamped relaxation as $T$ increases. Exact expressions for the oscillation and/or relaxation rates are presented in all these cases. For the "ohmic" case, $s=1$, the qualitative nature of the behavior depends critically on the dimensionless coupling strength $\ensuremath{\alpha}$ as well as the temperature $T$: over most of the ($\ensuremath{\alpha}$,$T$) plane (including the whole region $\ensuremath{\alpha}&gt;1$) the behavior is an incoherent relaxation at a rate proportional to ${T}^{2\ensuremath{\alpha}\ensuremath{-}1}$, but for low $T$ and $0&lt;\ensuremath{\alpha}&lt;\frac{1}{2}$ the authors predict a combination of damped coherent oscillation and incoherent background which appears to disagree with the results of all previous approximations. The case of finite bias is also discussed.
Rigorous coupled-wave analysis of planar-grating diffraction (1981)

A rigorous coupled-wave approach is used to analyze diffraction by general planar gratings bounded by two different media. The grating fringes may have any orientation (slanted or unslanted) with respect to the grating surfaces. The analysis is based on a state-variables representation and results in a unifying, easily computer-implementable matrix formulation of the general planar-grating diffraction problem. Accurate diffraction characteristics are presented for the first time to the authors’ knowledge for general slanted gratings. This present rigorous formulation is compared with rigorous modal theory, approximate two-wave modal theory, approximate multiwave coupled-wave theory, and approximate two-wave coupled-wave theory. Typical errors in the diffraction characteristics introduced by these various approximate theories are evaluated for transmission, slanted, and reflection gratings. Inclusion of higher-order waves in a theory is important for obtaining accurate predictions when forward-diffracted orders are dominant (transmission-grating behavior). Conversely, when backward-diffracted orders dominate (reflection-grating behavior), second derivatives of the field amplitudes and boundary diffraction need to be included to produce accurate results.
Transient Accumulation of Glycine Betaine and Dynamics of Endogenous Osmolytes in Salt-Stressed Cultures of Sinorhizobium meliloti (1997)

The fate of exogenously supplied glycine betaine and the dynamics of endogenous osmolytes were investigated throughout the growth cycle of salt-stressed cultures of strains of Sinorhizobium meliloti which differ in their ability to use glycine betaine as a growth substrate, but not as an osmoprotectant. We present (sup13)C nuclear magnetic resonance spectral and radiotracer evidence which demonstrates that glycine betaine is only transiently accumulated as a cytoplasmic osmolyte in young cultures of wild-type strains 102F34 and RCR2011. Specifically, these strains accumulate glycine betaine as a preferred osmolyte which virtually prevents the accumulation of endogenous osmolytes during the lag and early exponential phases of growth. Then, betaine levels in stressed cells decrease abruptly during the second half of the exponential phase. At this stage, the levels of glutamate and the dipeptide N-acetylglutaminylglutamine amide increase sharply so that the two endogenous solutes supplant glycine betaine in the ageing culture, in which it becomes a minor osmolyte because it is progressively catabolized. Ultimately, glycine betaine disappears when stressed cells reach the stationary phase. At this stage, wild-type strains of S. meliloti also accumulate the disaccharide trehalose as a third major endogenous osmolyte. By contrast, glycine betaine is always the dominant osmolyte and strongly suppresses the buildup of endogenous osmolytes at all stages of the growth cycle of a mutant strain, S. meliloti GMI766, which does not catabolize this exogenous osmoprotectant under any growth conditions.
Preliminary results from KEYNOTE-055: Pembrolizumab after platinum and cetuximab failure in head and neck squamous cell carcinoma (HNSCC). (2016)

6011 Background: Current treatment options for patients (pts) with recurrent/metastatic (R/M) HNSCC who progress on platinum and cetuximab have very limited efficacy. Pembrolizumab, an anti–PD-1 antibody that blocks the interaction between PD-1 and PD-L1 and PD-L2, showed promising antitumor activity in R/M HNSCC in the KEYNOTE-012 trial. We present preliminary results from the phase 2, nonrandomized KEYNOTE-055 (NCT02255097) study evaluating pembrolizumab after progression on platinum and cetuximab in R/M HNSCC. Methods: Pts receive pembrolizumab 200 mg every 3 weeks. Key eligibility criteria include R/M HNSCC resistant to platinum and cetuximab therapies, measurable disease, and ECOG PS 0-1. Primary outcomes include overall response rate (ORR, RECIST v1.1 by central imaging vendor) performed every 6-9 wk and safety. Adverse events (AEs) were graded using CTCAE, v4.0. Results: In total, 172 pts were enrolled for safety, efficacy, and biomarker analyses. Preliminary analyses for this abstract focus on the first 50 pts enrolled. Median age was 59 y; 80% were male; 84% had ≥ 2 prior lines of therapy for metastatic disease. Median follow-up time was 6.8 mo (range, 0-12.1). Thirty-five (70%) pts experienced a treatment-related AE (TRAE), with 6 (12.0%) pts experiencing a grade 3-5 TRAE. Two (4%) pts discontinued and 1 (2%) pt died because of a TRAE. AEs of special immunologic interest occurred in 11 (22%) pts; hypothyroidism (n = 7; all grade 2) and pneumonitis (n = 2, grade 2; n = 1, grade 5) were the most common. Nine pts had a confirmed PR for an ORR of 18.0% (95% CI 8.6-31.4). Five pts had ongoing responses at the data cutoff. The stable disease rate was 18.0% (n = 9; 95% CI 8.6-31.4). Conclusions: These preliminary results confirm findings from KEYNOTE-012, which demonstrate that pembrolizumab has clinically significant antitumor activity and is well tolerated among pts with heavily pretreated R/M HNSCC. Further analyses in the total study population, including HPV status and response by anatomic site, will be presented. Clinical trial information: NCT02255097.