gebhart/patrepeval huggingface dataset:
Predicting survival in patients with metastatic kidney cancer by gene-expression profiling in the primary tumor (2003)

To identify potential molecular determinants of tumor biology and possible clinical outcomes, global gene-expression patterns were analyzed in the primary tumors of patients with metastatic renal cell cancer by using cDNA microarrays. We used grossly dissected tumor masses that included tumor, blood vessels, connective tissue, and infiltrating immune cells to obtain a gene-expression "profile" from each primary tumor. Two patterns of gene expression were found within this uniformly staged patient population, which correlated with a significant difference in overall survival between the two patient groups. Subsets of genes most significantly associated with survival were defined, and vascular cell adhesion molecule-1 (VCAM-1) was the gene most predictive for survival. Therefore, despite the complex biological nature of metastatic cancer, basic clinical behavior as defined by survival may be determined by the gene-expression patterns expressed within the compilation of primary gross tumor cells. We conclude that survival in patients with metastatic renal cell cancer can be correlated with the expression of various genes based solely on the expression profile in the primary kidney tumor.
Highly specific and accurate selection of siRNAs for high-throughput functional assays (2004)

jdopazo@cnio.es.
An activated set point of T-cell and monocyte inflammatory networks in recent-onset schizophrenia patients involves both pro- and anti-inflammatory forces (2011)

We recently described a pro-inflammatory gene expression signature in the monocytes of 60% of patients with recent-onset schizophrenia (SCZ). Here we investigated whether the T-cell system is also in a pro-inflammatory state. A detailed fluorescence-activated cell sorting (FACS) analysis, e.g. of CD3+CD25+ T cells, IFN-γ+, IL-4+, IL-17A+ (CD4+) lymphocytes and CD4+CD25highFoxP3+ regulatory T cells, was performed on peripheral blood of 26 patients with recent-onset SCZ (in 19 of whom the inflammatory gene expression signature of the monocyte had been determined) and in age-/gender-matched healthy controls. Various relevant T-cell cytokines, e.g. sCD25, IFN-γ, IL-17A and IL-4, were measured in serum by a multiplex assay. We detected: (a) not only higher percentages of pro-inflammatory-prone monocytes, activated CD3+CD25+ T cells and pro-inflammatory Th17 cells in patients, but also higher percentages of anti-inflammatory CD4+CD25highFoxP3+ regulatory T cells and IL-4+ lymphocytes; (b) that this activated T-cell set point was reflected in significantly raised serum levels of sCD25; (c) that the up-regulation of IL-4+-containing lymphocytes was predominantly found in patients characterized by a monocyte pro-inflammatory set point; and (d) that regulatory T-cell and Th17-cell numbers were higher in patients irrespective of the pro-inflammatory state of the monocytes. Our data do not support the concept that the T-cell system is in a simple pro-inflammatory state in recent-onset SCZ, but do show that the monocyte and T-cell networks are activated and involve both pro- and anti-inflammatory forces. This suggests control within an activated inflammatory system.
Contemporary Management and Research Directions in Advanced Heart Failure: Where Are We Going? (2011)

Advanced heart failure (AHF) is not a uniform disorder, but is rather a heterogeneous group of patients with varying clinical presentations and definitions. It is growing in magnitude and represents a major public health problem. Herein we describe contemporary care of the patient with AHF, novel medical therapies, and mechanical circulatory assist devices. We speculate where progress has been made and where the major gaps in knowledge remain. Clearly, there is ample opportunity for research and discovery to further advance the care of these very sick patients.
Long-Term Memory Is Facilitated by cAMP Response Element-Binding Protein Overexpression in the Amygdala (2001)

At least two temporally and mechanistically distinct forms of memory are conserved across many species: short-term memory that persists minutes to hours after training and long-term memory (LTM) that persists days or longer. In general, repeated training trials presented with intervening rest intervals (spaced training) is more effective than massed training (the same number of training trials presented with no or short intervening rest intervals) in producing LTM. LTM requires de novo protein synthesis, and cAMP response element-binding protein (CREB) may be one of the transcription factors regulating the synthesis of new proteins necessary for the formation of LTM. Here we show that rats given massed fear conditioning training show no or weak LTM, as measured by fear-potentiated startle, compared with rats given the same amount of training but presented in a spaced manner. Increasing CREB levels specifically in the basolateral amygdala via viral vector-mediated gene transfer significantly increases LTM after massed fear training. The enhancing effect of CREB overexpression on LTM formation is shown to be specific in terms of biochemistry, anatomy, time course, and the training procedure used. These results suggest that CREB activity in the amygdala serves as a molecular switch for the formation of LTM in fear conditioning.
Melanocortin-4 Receptor Signaling Is Required for Weight Loss after Gastric Bypass Surgery (2012)

MC4R is the first gene identified that is required for the sustained effects of bariatric surgery. The need for MC4R signaling for the weight loss effects of RYGB in mice underscores the physiological mechanisms of action of this procedure and demonstrates that RYGB both influences and is dependent on the normal pathways that regulate energy balance.
Requirement for RORγ in Thymocyte Survival and Lymphoid Organ Development (2000)

Most developing thymocytes undergo apoptosis because they cannot interact productively with molecules encoded by the major histocompatibility complex. Here, we show that mice lacking the orphan nuclear hormone receptor RORgamma lose thymic expression of the anti-apoptotic factor Bcl-xL. RORgamma thus regulates the survival of CD4+8+ thymocytes and may control the temporal window during which thymocytes can undergo positive selection. RORgamma was also required for development of lymph nodes and Peyer's patches, but not splenic follicles. In its absence, there was loss of a population of CD3-CD4+CD45+ cells that normally express RORgamma and that are likely early progenitors of lymphoid organs. Hence, RORgamma has critical functions in T cell repertoire selection and lymphoid organogenesis.
Targeting mitochondrial responses to intra-articular fracture to prevent posttraumatic osteoarthritis (2018)

We tested whether inhibiting mechanically responsive articular chondrocyte mitochondria after severe traumatic injury and preventing oxidative damage represent a viable paradigm for posttraumatic osteoarthritis (PTOA) prevention. We used a porcine hock intra-articular fracture (IAF) model well suited to human-like surgical techniques and with excellent anatomic similarities to human ankles. After IAF, amobarbital or <i>N</i>-acetylcysteine (NAC) was injected to inhibit chondrocyte electron transport or downstream oxidative stress, respectively. Effects were confirmed via spectrophotometric enzyme assays or glutathione/glutathione disulfide assays and immunohistochemical measures of oxidative stress. Amobarbital or NAC delivered after IAF provided substantial protection against PTOA at 6 months, including maintenance of proteoglycan content, decreased histological disease scores, and normalized chondrocyte metabolic function. These data support the therapeutic potential of targeting chondrocyte metabolism after injury and suggest a strong role for mitochondria in mediating PTOA.
Amantadine and levodopa in the treatment of Parkinson's disease (1972)

Twenty‐eight ambulatory patients with Parkinson's disease participated in successive double‐blind crossover trials of amantadine and levodopa. A comprehensive battery of tests was used to evaluate patient preference, neurologic symptoms and signs, quantitative neurologic performance, practical skills used in daily living, and neuropsychological performance. These permitted differential assessment of specific areas of function affected. Levodopa ameliorated functional disabilities, tremor, and loss of associated movements. It also improved grip strength, foot speed, foot coordination, gait, and several skilled activities more than did amantadine. The combination of levodopa and amantadine was more effective than levodopa alone in the management of total functional disability, tremor, and gait and in tests of grip strength, finger coordination, tracking, and tandem gait, as well as in the practiced skills of zipping, cutting, and opening a door. One neuropsychologic test‐picture completion‐was also better on the combination. The safety of the combination was affirmed and the relative efficacy quantitated.
Transformation guided image completion (2013)

In this paper, we describe a new interactive image completion system that allows users to easily specify various forms of mid-level structures in the image. Our system supports the specification of four basic symmetric types: reflection, translation, rotation, and glide. The user inputs are automatically converted into guidance maps that encode possible candidate shifts and, indirectly, local transformations of rotation and scale. These guidance maps are used in conjunction with a color matching cost for image completion. We show that our system is capable of handling a variety of challenging examples.
Exercise testing for non-invasive assessment of atrial electrophysiology in patients with persistent atrial fibrillation (2006)

The abstract with its heading should not be more than 75 mm long. This is equivalent to 18 lines of text. Leave 1 line space at the bottom of the abstract before continuing with the next heading. The autonomic nervous system modulates atrial electrophysiology in atrial fibrillation (AF). The purpose of this study was (1) to non-invasively characterize the effects of exercise on atrial fibrillatory rate as marker of atrial refractoriness in patients with persistent AF and (2) to identify clinical and electrocardiographic predictors for rate response. In 15 patients with persistent AF, mean fibrillatory rate assessed by spatiotemporal QRST cancellation and time-frequency analysis remained unchanged with exercise. There were, however, 6 responders (rate change&amp;gt; 2.5%), with either a rate increase (N=5, 25±9 fpm) or decrease (N=1,-13 fpm). Absolute fibrillatory rate change (%) correlated inversely with baseline fibrillatory rate (r =-0.543, p=.045). In conclusion, sympathetic activation by exercise modulates atrial electrophysiology in some patients which can be monitored using time-frequency analysis. Higher baseline fibrillatory rates are associated with less autonomic modulation indicating advanced electrical remodeling. 1.
Inhibition of activator protein 1 activity and cell growth by purified green tea and black tea polyphenols in H-ras-transformed cells: structure-activity relationship and mechanisms involved. (1999)

ras gene mutation, which perpetually turns on the growth signal transduction pathway, occurs frequently in many cancer types. The mouse epidermal JB6 cell line has been transfected with a mutant H-ras gene to mimic carcinogenesis in vitro. These transformed cells (30.7b Ras 12) are able to grow in soft agar, exhibiting anchorage independence and high endogenous activator protein 1 (AP-1) activity, which can be detected by a stable AP-1 luciferase reporter. The present study investigated the ability of different pure green and black tea polyphenols to inhibit this ras signaling pathway. The major green tea polyphenols (catechins), (-)-epigallocatechin-3-gallate (EGCG), (-)-epigallocatechin, (-)-epicatechin-3-gallate, (-)-epicatechin, and their epimers, and black tea polyphenols, theaflavin, theaflavin-3-gallate, theaflavin-3'-gallate, and theaflavin-3,3'-digallate (TFdiG), were compared with respect to their ability to inhibit the growth of 30.7b Ras 12 cells and AP-1 activity. All of the tea polyphenols except (-)-epicatechin showed strong inhibition of cell growth and AP-1 activity. Among the catechins, both the galloyl structure on the B ring and the gallate moiety contributed to the growth inhibition and AP-1 activity; the galloyl structure appeared to have a stronger effect on the inhibitory action than the gallate moiety. The epimers of the catechins showed similar inhibitory effects on AP-1 activity. The addition of catalase to the incubation of the cells with EGCG or TFdiG did not prevent the inhibitory effect on AP-1 activity, suggesting that H2O2 does not play a significant role in the inhibition by tea polyphenols. Both EGCG and TFdiG inhibited the phosphorylation of p44/42 (extracellular signal-regulated kinase 1 and 2) and c-jun without affecting the levels of phosphorylated-c-jun-NH2-terminal kinase. TFdiG inhibited the phosphorylation of p38, but EGCG did not. EGCG lowered the level of c-jun, whereas TFdiG decreased the level of fra-1. These results suggest that tea polyphenols inhibited AP-1 activity and the mitogen-activated protein kinase pathway, which contributed to the growth inhibition; however, different mechanisms may be involved in the inhibition by catechins and theaflavins.
Microfluidic Patterning of Cellular Biopolymer Matrices (2003)

Due to the complex structures of living systems, the use of microtechnology to recreate in vivo architecture has exciting potential applications. Living tissues maintain a well-organized three-dimensional (3-D) architecture, with “micro” and “nano” scale features. Microtechnologies offer the new possibility of designing and building sensors and devices in dimensional scales close to that of living tissues.1–2 However, most available microscale systems are two-dimensional, and few 3-D systems are being explored. Therefore, we have developed a versatile technique to create a 3-D microscale hierarchical system for cells and biopolymers. By taking advantage of the contraction of hydrogel matrix biopolymers, one can achieve multiple layers of cells within biopolymers using microchannels, and eventually form a hierarchical layered microstructure of cells and biopolymer. Pressure-driven microfluidics using a syringe pump (Harvard Apparatus, Model 11‘) was applied to transport cells within matrix biopolymers thro...
Controlling the Particle Size of ZrO2 Nanoparticles in Hydrothermally Stable ZrO2/MWCNT Composites (2012)

The composite of multiwalled carbon nanotubes (MWCNTs) decorated with ZrO(2) nanoparticles, synthesized by a grafting method followed by high-temperature annealing, was studied. The oxygen functionalized MWCNT surface uniformly disperses and stabilizes the oxide nanoparticles to an extent that is controlled by the metal oxide loading and thermal annealing temperature. This ZrO(2)/MWCNT also withstands decomposition in a hydrothermal environment providing potential applications in the catalysis of biomass conversion (e.g., aqueous phase reforming). The ZrO(2)/MWCNT have been characterized by (scanning) transmission electron microscopy ((S)TEM), X-ray diffraction (XRD), in situ small-angle X-ray scattering (SAXS), in situ wide-angle X-ray scattering (WAXS), and near edge X-ray fine structure (NEXAFS) for the purpose of a comprehensive analysis of the ZrO(2) particle size and particle size stability.
The role of CD40 in the regulation of humoral and cell-mediated immunity (1994)

The dynamic and reciprocal communication between T helper (Th) cells and B cells appears to rely on the provision of multiple signals. The first is antigen specific and is mediated by the interaction between the T-cell receptor (TCR) and antigen bound to the major histocompatibility complex (MHC). The subsequent signals are provided by the binding of accessory molecules such as CD28 and CD40 to their respective ligands. Here, Fiona Durie and colleagues discuss the co-stimulatory role of the interaction between CD40 on B cells and CD40 ligand (CD40L, gp39) on T cells, and review evidence that suggests blocking this interaction may induce T-cell tolerance.
Superconducting transmission lines (1997)

In 1947 Pippard pointed out that a wave would be slowed when it propagated along a superconducting transmission line. This effect is due to the increase in inductance of the transmission line because of the penetration of the external magnetic field into the superconductor. The effect increases as the proportion of the magnetic field inside the superconductor increases relative to the proportion of the external magnetic field. This is not the only effect of using superconductors in transmission lines. Provided the transmission line propagates in a TEM mode, a superconducting transmission line is dispersionless, due to the penetration depth not varying with frequency. This is in contrast with a normal conductor where the skin depth is a function of frequency, and increasing the frequency has the effect of reducing the skin depth and hence increasing the velocity due to the decrease of internal inductance. However, for application purposes the most important effect of using superconductors is the very low loss of the transmission line.
Engineering Globular Protein Vesicles through Tunable Self‐Assembly of Recombinant Fusion Proteins (2017)

Vesicles assembled from folded, globular proteins have potential for functions different from traditional lipid or polymeric vesicles. However, they also present challenges in understanding the assembly process and controlling vesicle properties. From detailed investigation of the assembly behavior of recombinant fusion proteins, this work reports a simple strategy to engineer protein vesicles containing functional, globular domains. This is achieved through tunable self-assembly of recombinant globular fusion proteins containing leucine zippers and elastin-like polypeptides. The fusion proteins form complexes in solution via high affinity binding of the zippers, and transition through dynamic coacervates to stable hollow vesicles upon warming. The thermal driving force, which can be tuned by protein concentration or temperature, controls both vesicle size and whether vesicles are single or bi-layered. These results provide critical information to engineer globular protein vesicles via self-assembly with desired size and membrane structure.
Mouse Models in Arrhythmogenic Right Ventricular Cardiomyopathy (2012)

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a heart muscle disorder characterized by fibro-fatty replacement of cardiomyocytes. The cardinal manifestations are arrhythmias, sudden cardiac death, and seldom heart failure. Mutations in genes encoding desmosomal proteins and their interaction partners have been implicated in the pathogenesis of ARVC and it is now widely accepted that ARVC is a disease caused by abnormal cell-cell adhesion. The mechanism(s) by which mutations in desmosomal proteins lead to fibro-fatty replacement remains to be fully elucidated. To this aim over the last 10 years different transgenic and targeted mouse models have been developed, these models and what they have taught us will be discussed in this review.
First Human Trial of FTY720, a Novel Immunomodulator, in Stable Renal Transplant Patients (2002)

FTY720 is a novel immunomodulator to be developed for use in organ transplantation. The primary objective of this study was to measure safety, single-dose pharmacokinetics, and pharmacodynamics in stable renal transplant patients-the first human use of FTY720. This study used a randomized, double-blind, placebo-controlled design that explored single oral doses of FTY720 from 0.25 to 3.5 mg in 20 stable renal transplant patients on a cyclosporine-based regimen. Safety assessments and blood samples were taken predose and at multiple time points during a 96-h period postdose. Standard pharmacokinetic parameters were derived from the FTY720 whole blood concentrations, measured by HPLC/MS/MS. FTY720 was well tolerated, with no serious adverse events. Transient, asymptomatic bradycardia occurred after administration in 10 of 24 doses of FTY720. Pharmacokinetics are characterized by a prolonged absorption phase; the terminal elimination phase started 36 h after the administration, with elimination half-life (t(1/2)) ranging from 89 to 157 h independent of dose. Maximum plasma concentration and AUC were proportional to dose with low intersubject variability, the apparent volume of distribution (V(d)/F) ranged from 1116 to 1737 L. FTY pharmacodynamics were characterized by a reversible transient lymphopenia within 6 h, the nadir being 42% of baseline. The lymphocyte count returned to baseline within 72 h in all dosing cohorts except the highest. Single oral doses of FTY720 ranging from 0.25 to 3.5 mg were well tolerated and caused a reversible selective lymphopenia. Transient, but asymptomatic bradycardia was the most common adverse event. The long t(1/2) suggests less frequent dosing intervals. The size of V(d)/F is in excess of blood volume, consistent with widespread tissue distribution
In vitro and in vivo effects of polyethylene glycol (PEG)-modified lipid in DOTAP/cholesterol-mediated gene transfection (2010)

The eminent in vivo transfection potency of DOTAP/cholesterol-based lipoplexes is well established for expression in lung tumors, but it is unsuitable for expression in non first pass organs such as xenograft flank tumors in mice even after addition of a PEG-lipid in the formulation.
An online credential repository for the Grid: MyProxy (2002)

Grid portals, based on standard Web technologies, are increasingly used to provide user interfaces for computational and data grids. However, such Grid portals do not integrate cleanly with existing Grid security systems such as the Grid Security Infrastructure (GSI), due to lack of delegation capabilities in Web security mechanisms. We solve this problem using an online credentials repository system, called MyProxy. MyProxy allows Grid portals to use the GSI to interact with Grid resources in a standard, secure manner. We examine the requirements of Grid portals, give an overview of the GSI, and demonstrate how MyProxy enables them to function together. The architecture and security of the MyProxy system are described in detail.
N‐linked glycosylation of the liver cancer biomarker GP73 (2007)

The association between elevated circulating levels of GP73 (and fucosylated GP73 in particular) and hepatocellular carcinoma suggests that a thorough analysis of the extent of GP73 glycosylation is warranted. Detailed analysis of the glycosylation patterns of such low abundance proteins are hampered by technical difficulties. Using conventional lectin affinity chromatography, we have established that three quarters of the GP73 secreted from a cell line derived from HCC is fucosylated. Using mass spectrometry, we have established that at least two of three potential sites of N-linked glycosylation are occupied on most molecules of GP73 secreted from cultured hepatoma cells. Furthermore, the oligosaccharides added to recombinant GP73 resemble those present in the bulk of secreted protein, mostly bi-antennary with core fucose, with a smaller fraction of tri- and tetra-antennary structures. The frequency of fucosylation observed on the recombinant protein agrees well with the pattern of lectin binding of the endogenous secreted protein. Finally, we have developed a method to interrogate the glycans added to either the near full length protein or at a particular sequon, providing proof of concept that a small peptide embedded in a heterologous context can preserve both fucosylation and a high level of branching of oligosaccharides added.