gebhart/patrepeval huggingface dataset:
Vaccination of Alzheimer's model mice with Aβ derivative in alum adjuvant reduces Aβ burden without microhemorrhages (2006)

Immunotherapy holds great promise for Alzheimer's disease (AD) and other conformational disorders but certain adverse reactions need to be overcome. The meningoencephalitis observed in the first AD vaccination trial was likely related to excessive cell-mediated immunity caused by the immunogen, amyloid-beta (Abeta) 1-42, and the adjuvant, QS-21. To avoid this toxicity, we have been using Abeta derivatives in alum adjuvant that promotes humoral immunity. Other potential side effects of immunotherapy are increased vascular amyloid and associated microhemorrhages that may be related to rapid clearance of parenchymal amyloid. Here, we determined if our immunization strategy was associated with this form of toxicity, and if the therapeutic effect was age-dependent. Tg2576 mice and wild-type littermates were immunized from 11 or 19 months and their behaviour evaluated prior to killing at 24 months. Subsequently, plaque- and vascular-Abeta burden, Abeta levels and associated pathology was assessed. The therapy started at the cusp of amyloidosis reduced cortical Abeta deposit burden by 31% and Abeta levels by 30-37%, which was associated with cognitive improvements. In contrast, treatment from 19 months, when pathology is well established, was not immunogenic and therefore did not reduce Abeta burden or improve cognition. Significantly, the immunotherapy in the 11-24 months treatment group, that reduced Abeta burden, did not increase cerebral bleeding or vascular Abeta deposits in contrast to several Abeta antibody studies. These findings indicate that our approach age-dependently improves cognition and reduces Abeta burden when used with an adjuvant suitable for humans, without increasing vascular Abeta deposits or microhemorrhages.
Free energies of protein–protein association determined by electrospray ionization mass spectrometry correlate accurately with values obtained by solution methods (2006)

The advantages of electrospray ionization mass spectrometry (ESIMS) to measure relative solution-phase affinities of tightly bound protein-protein complexes are demonstrated with selected variants of the Bacillus amyloliquefaciens protein barstar (b*) and the RNAase barnase (bn), which form protein-protein complexes with a range of picomolar to nanomolar dissociation constants. A novel chemical annealing procedure rapidly establishes equilibrium in solutions containing competing b* variants with limiting bn. The relative ion abundances of the complexes and those of the competing unbound monomers are shown to reflect the relative solution-phase concentrations of those respective species. No measurable dissociation of the complexes occurs either during ESI or mass detection, nor is there any evidence for nonspecific binding at protein concentrations < 25 microM. Differences in DeltaDeltaG of dissociation between variants were determined with precisions < 0.1 kcal/mol. The DeltaDeltaG values obtained deviate on average by 0.26 kcal/mol from those measured with a solution-phase enzyme assay. It is demonstrated that information about the protein conformation and covalent modifications can be obtained from differences in mass and charge state distributions. This method serves as a rapid and precise means to interrogate protein-protein-binding surfaces for complexes that have affinities in the picomolar to nanomolar range.
Immune system and endometriosis. (1992)

Many experimental and clinical findings indicate a disimmune pathogenesis of infertility associated with endometriosis. The most important modifications of cell-mediated immunity in endometriosis concern macrophage activity, increased both quantitatively and qualitatively. Peritoneal macrophages (PM) acquire the ability of producing lytic enzymes, that would be able to enhancing and stimulating implantation and proliferation of endometrial cells in peritoneal cavity. In these last years many experimental and clinical demonstrations have showed an immunosuppressive action of Danazol similar to corticosteroids. The Authors report their study on a comparison among Danazol 600 mg/daily for 3 months plus a local immunosuppressive treatment combined with superovulation and IPI, Danazol for 3 months plus superovulation and IPI and, as a control group, superovulation and IPI.
Image and depth from a conventional camera with a coded aperture (2007)

A conventional camera captures blurred versions of scene information away from the plane of focus. Camera systems have been proposed that allow for recording all-focus images, or for extracting depth, but to record both simultaneously has required more extensive hardware and reduced spatial resolution. We propose a simple modification to a conventional camera that allows for the simultaneous recovery of both (a) high resolution image information and (b) depth information adequate for semi-automatic extraction of a layered depth representation of the image.
Micropatterned mammalian cells exhibit phenotype-specific left-right asymmetry (2011)

Left-right (LR) asymmetry (handedness, chirality) is a well-conserved biological property of critical importance to normal development. Changes in orientation of the LR axis due to genetic or environmental factors can lead to malformations and disease. While the LR asymmetry of organs and whole organisms has been extensively studied, little is known about the LR asymmetry at cellular and multicellular levels. Here we show that the cultivation of cell populations on micropatterns with defined boundaries reveals intrinsic cell chirality that can be readily determined by image analysis of cell alignment and directional motion. By patterning 11 different types of cells on ring-shaped micropatterns of various sizes, we found that each cell type exhibited definite LR asymmetry (p value down to 10(-185)) that was different between normal and cancer cells of the same type, and not dependent on surface chemistry, protein coating, or the orientation of the gravitational field. Interestingly, drugs interfering with actin but not microtubule function reversed the LR asymmetry in some cell types. Our results show that micropatterned cell populations exhibit phenotype-specific LR asymmetry that is dependent on the functionality of the actin cytoskeleton. We propose that micropatterning could potentially be used as an effective in vitro tool to study the initiation of LR asymmetry in cell populations, to diagnose disease, and to study factors involved with birth defects in laterality.
Building Clinical Classifiers Using Incomplete Observations – A Neural Network Ensemble for Hepatoma Detection in Patients with Cirrhosis (1995)

One objective of liver transplant evaluation is to identify patients that harbor a hepatoma, but standard screening techniques are not sensitive enough. We trained neural network ensembles to predict the presence of hepatoma in patients with cirrhosis, based on information collected at the time of transplant evaluation. Network architecture and training were modified to handle missing observations. Three ensembles were trained: ensemble A using the subset with no missing observations (528 patients); ensemble B using the complete set, which included missing observations (853 patients); and ensemble C using the smaller subset, originally with complete data, but after a fixed number of observations were deleted (i.e., made "missing"). Ensemble performance on testing sets was very good. The areas under the ROC curves were 0.91, 0.89, and 0.90, for ensembles A, B, and C, respectively. Neural networks can successfully perform this classification task, and strategies can be developed that allow use of incomplete observations.
Guided Upsampling Network for Real-Time Semantic Segmentation (2018)

Semantic segmentation architectures are mainly built upon an encoder-decoder structure. These models perform subsequent downsampling operations in the encoder. Since operations on high-resolution activation maps are computationally expensive, usually the decoder produces output segmentation maps by upsampling with parameters-free operators like bilinear or nearest-neighbor. We propose a Neural Network named Guided Upsampling Network which consists of a multiresolution architecture that jointly exploits high-resolution and large context information. Then we introduce a new module named Guided Upsampling Module (GUM) that enriches upsampling operators by introducing a learnable transformation for semantic maps. It can be plugged into any existing encoder-decoder architecture with little modifications and low additional computation cost. We show with quantitative and qualitative experiments how our network benefits from the use of GUM module. A comprehensive set of experiments on the publicly available Cityscapes dataset demonstrates that Guided Upsampling Network can efficiently process high-resolution images in real-time while attaining state-of-the art performances.
Increased surveillance of cells in mitosis by human NK cells suggests a novel strategy for limiting tumor growth and viral replication (2006)

The threat from cancer cells is inherently linked to cell-cycle progression, and viral genomes commonly replicate, for example, within episomes or proviruses, during mitosis. We report here that human natural killer (NK) cells bound cells in mitosis and attacked pathogenic cells in mitosis more effectively than the same cells in other stages of the cell cycle. Thus, cells in mitosis warrant and undergo heightened surveillance, a novel strategy for immunologic assessment of danger. Recognition of cells in mitosis involved ligation of activating NK-cell receptors and binding to target-cell hyaluronan, a component of the pericellular matrix known to be increased during mitosis. Direct interaction between activating NK-cell receptors and hyaluronan is possible, but other mechanisms consistent with our data are also discussed.
Protein-tyrosine Phosphatases PTP1B and Syp Are Modulators of Insulin-stimulated Translocation of GLUT4 in Transfected Rat Adipose Cells (1997)

The protein-tyrosine phosphatases PTP1B and Syp have both been implicated as modulators of the mitogenic actions of insulin. However, the roles of these protein-tyrosine phosphatases in the metabolic actions of insulin are not well characterized. In this study, we directly assessed the ability of PTP1B and Syp to modulate insulin-stimulated translocation of the insulin-responsive glucose transporter GLUT4 in a physiologically relevant insulin target cell. Primary cultures of rat adipose cells were transiently transfected with either wild-type PTP1B (PTP1B-WT), wild-type Syp (Syp-WT), or the catalytically inactive mutants PTP1B-C/S or Syp-C/S. The effects of overexpression of these constructs on insulin-stimulated translocation of a co-transfected epitope-tagged GLUT4 were studied. Cells overexpressing either PTP1B-C/S or Syp-WT had insulin dose-response curves similar to those obtained with control cells expressing only epitope-tagged GLUT4. In contrast, for cells overexpressing PTP1B-WT the level of GLUT4 on the cell surface at each insulin dose (ranging from 0 to 60 nM) was significantly lower than that observed in the control cells. Interestingly, cells overexpressing the dominant inhibitory mutant Syp-C/S also had a small but statistically significant impairment in insulin responsiveness. At a maximally stimulating concentration of insulin (60 nM), cell surface epitope-tagged GLUT4 was approximately 20% less than that of the control cells. It is possible that effects from high level overexpression of Syp and PTP1B constructs may not reflect what occurs under physiological conditions. Nevertheless, our data raise the possibility that PTP1B may be a negative regulator of insulin-stimulated glucose transport, while Syp may have a small role as a positive mediator of the metabolic actions of insulin.
INTRAVITREAL BEVACIZUMAB (AVASTIN) TREATMENT OF PROLIFERATIVE DIABETIC RETINOPATHY COMPLICATED BY VITREOUS HEMORRHAGE (2006)

Initial treatment results of patients with vitreous hemorrhage and proliferative diabetic retinopathy did not reveal any short-term safety concerns. Intravitreal bevacizumab resulted in marked regression of neovascularization and rapid resolution of vitreous hemorrhage. The favorable short-term results suggest further study is needed in a larger group of patients.
Abnormal microRNA-16 locus with synteny to human 13q14 linked to CLL in NZB mice (2007)

Abstract New Zealand black (NZB) mice with autoimmune and B lymphoproliferative disease (B-LPD) are a model for human chronic lymphocytic leukemia (CLL). A genomewide linkage scan of the NZB loci associated with lymphoma was conducted in F1 backcrosses of NZB and a control strain, DBA/2. Of 202 mice phenotyped for the presence or absence of LPD, surface maker expression, DNA content, and microsatellite polymorphisms, 74 had disease. The CD5+, IgM+, B220dim, hyperdiploid LPD was linked to 3 loci on chromosomes 14, 18, and 19 that are distinct from previously identified autoimmunity-associated loci. The region of synteny with mouse D14mit160 is the human 13q14 region, associated with human CLL, containing microRNAs mir-15a16-1. DNA sequencing of multiple NZB tissues identified a point mutation in the 3′ flanking sequence of the identical microRNA, mir-16-1, and this mutation was not present in other strains, including the nearest neighbor, NZW. Levels of miR-16 were decreased in NZB lymphoid tissue. Exogenous miR-16 delivered to an NZB malignant B-1 cell line resulted in cell-cycle alterations and increased apoptosis. Linkage of the mir-15a/16-1 complex and the development of B-LPD in this spontaneous mouse model suggest that the altered expression of the mir-15a/16-1 is the molecular lesion in CLL.
Cell‐mediated cytotoxicity to trinitrophenyl‐modified syngeneic lymphocytes (1974)

Abstract Spleen cells from B10 congenic mouse strains were cultured in vitro by a modification of the Mishell‐Dutton technique with trinitrophenyl (TNP)‐modified syngeneic spleen cells. Five days later, the effector cells generated were incubated with 51 Cr‐labeled unmodified or TNP‐modified spleen or tumor target cells, and the percentage of specific lysis determined. The results obtained using modified syngeneic as well as congenic target cells indicated that although TNP‐modification of the target cells was necessary to obtain lysis, the cytotoxicity was not specific for TNP exclusively, but was primarily directed against modified syngeneic cell surface components which may or may not have included the TNP moiety as an integral part of the recognition unit. A number of criteria were used to demonstrate that the phenomenon was attributed to T cell‐mediated cytotoxicity, and was not due to lymphocyte‐dependent antibody (LDA). These included: (a) failure of TNP‐lysine to block the effector phase; (b) lack of detectable LDA in the culture media; (c) failure of spleen cells from athymic nude donors to generate effector cells; (d) sensitivity of effector cells to rabbit anti‐mouse brain serum; and (e) the generation of effector cells by cortisone‐resistant thymocytes. The specificity observed between the syngeneic TNP‐modified sensitizing and target cells is compatible with the hypothesis that the TNP is altering cell surface proteins which are controlled by genes within distinct regions of the H‐2 major histocompatibility complex, and that these proteins are conformationally changed so as to be immunogenic to syngeneic thymus‐derived lymphocytes.
Transcriptional and posttranscriptional regulation of endothelial nitric oxide synthase expression (2006)

The ability of the endothelium to produce nitric oxide is essential to maintenance of vascular homeostasis; disturbance of this ability is a major contributor to the pathogenesis of vascular disease. In vivo studies have demonstrated that expression of endothelial nitric oxide synthase (eNOS) is vital to endothelial function and have led to the understanding that eNOS expression is subject to modest but significant degrees of regulation. Subsequently, numerous physiological and pathophysiological stimuli have been identified that modulate eNOS expression via mechanisms that alter steady-state eNOS mRNA levels. These mechanisms involve changes in the rate of eNOS gene transcription (transcriptional regulation) and alteration of eNOS mRNA processing and stability (posttranscriptional regulation). In cultured endothelial cells, shear stress, transforming growth factor-beta1, lysophosphatidylcholine, cell growth, oxidized linoleic acid, 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, and hydrogen peroxide have been shown to increase eNOS expression. In contrast, tumor necrosis factor-alpha, hypoxia, lipopolysaccaride, thrombin, and oxidized LDL can decrease eNOS mRNA levels. For many of these stimuli, both transcriptional and posttranscriptional mechanisms contribute to regulation of eNOS expression. Recent studies have begun to further define signaling pathways responsible for changes in eNOS expression and have characterized cis- and trans-acting regulatory elements. In addition, a role has been identified for epigenetic control of eNOS mRNA levels. This review will discuss transcriptional and posttranscriptional regulation of eNOS with emphasis on the molecular mechanisms that have been identified for these processes.
Palladium-Catalyzed Cross-Coupling Reactions of Triorganoindium Compounds with Vinyl and Aryl Triflates or Iodides (1999)

A novel palladium-catalyzed cross-coupling reaction of organoindium compounds with vinyl and aryl triflates or iodides is described. The reaction proceeds for alkyl-, vinyl-, alkynyl-, and arylindium compounds in excellent yields and high chemoselectivity without any excess of the organometallic. Remarkably, indium organometallics transfer efficiently the three organic groups attached to the metal.
Increased β1 Integrin Is Associated with Decreased Survival in Invasive Breast Cancer (2007)

Aberrant microenvironments and loss of balance in cell-extracellular matrix signaling are associated with breast cancer invasion, metastasis, and resistance to therapy. We have recently shown that increased beta1 integrin signaling is involved in malignant progression and that inhibitory antibody to beta1 integrin leads to selective apoptosis and decreased proliferation in three-dimensional cultures and in xenograft models of breast cancer in vivo. To investigate the clinical importance of these findings, in the present study we examined the expression of beta1 integrin and extracellular beta1 integrin ligands fibronectin and laminin-1 in a cohort of 249 breast cancer patients who had a median follow-up of 8.4 years. Among the 149 scorable cases, the highest beta1 integrin intensity score (3+ versus 0-2+) was associated with significantly decreased 10-year overall survival of 48% versus 71% (P<0.03) and decreased disease-free survival of 50% versus 80% (P<0.05). Importantly, high fibronectin expression was associated with decreased overall and disease-free survival on univariate analysis (P<0.04) and beta1 integrin intensity score was significantly correlated with fibronectin expression (Kendall's tau-b=0.19; P=0.03). In a multivariate Cox proportional hazards model, beta1 integrin intensity score remained a significant independent predictor of overall survival [hazard ratio (HR), 1.69; 95% confidence interval (95% CI), 1.19-2.38; P<0.003] and disease-free survival (HR, 1.87; 95% CI, 1.21-2.88; P<0.005). These findings show that beta1 integrin expression has potential prognostic value in invasive breast cancer and that coexpression of fibronectin may help identify patients with more aggressive tumors who may benefit from targeted therapy.
A Conceptual Model for DNAPL Transport in Karst Ground Water Basins (2001)

Abstract Dense nonaqueous phase liquids (DNAPLs) such as perchloroethylene, polychlorinated biphenyls, creosote mixtures, and many solvents and degreasers can be released into karst aquifers through sinkholes and sinking streams in quantities up to tanker car volumes. Although DNAPLs are easily injected into karst aquifers, discharge of the contaminants through springs may be significantly delayed depending on transport mechanism, storm water recharge, and storage sites within the karst aquifer. Storage sites include (1) the epikarst; (2) pools and depressions within underground streams; (3) incorporation of DNAPL within clastic sediments that are present in most conduits; (4) adsorption onto organic materials and onto manganese oxides, iron oxides, and other substrates; and (5) migration to depth within the fracture system. Effective transport of DNAPL contaminants during storm flow pulses requires the exceedance of thresholds best defined in terms of the conduit stream power. Movement of pooled DNAPL requires a boundary shear between the liquid and water flowing over it. DNAPL stored in clastic sediment bleeds out slowly or dissolves into surrounding pore water until storm pulses create a stream flow sufficient to flush the pore water, or possibly move the sediment pile itself. Under extreme flow conditions the entire sediment pile, including the DNAPL, can be entrained and ejected from the conduit system.
C-erbB-2 in Serum of Patients with Breast Cancer (1999)

c-erbB-2 is an oncoprotein which is overexpressed in some breast cancers. Recently it has been established that the extracellular domain of c-erbB-2 is shed into the serum of patients with breast cancer. There appears to be no association between tumor stage and extracellular domain of c-erbB-2 (c-erbB-2/ECD): c-erbB-2/ECD seems to correlate with patient prognosis whatever the stage of disease. The data also suggest that c-erbB-2/ECD may be useful in monitoring for tumor recurrence and in predicting resistance to hormonal therapy, but not as useful in predicting response to chemotherapy. This may relate to the power of this marker to reflect disease burden, which has an overwhelmingly negative impact on outcome.
Non-alcoholic steatohepatitis. (2005)

Non-alcoholic steatohepatitis (NASH) represents only a part of a wide spectrum of non-alcoholic fatty liver disease (NAFLD) and its prevalence is only 2 - 3% in the general population. Obesity, diabetes, hyperlipidemia and female sex are important risk factors for NASH. Two hit theory describes very well the pathogenesis of NASH wherein hepatic steatosis, the first hit is followed up by the second hit, one of which may be reactive oxygen species. Mitochondria is the main source of reactive oxygen species which may trigger steatohepatitis by lipid peroxidation, cytokine induction or induction of fas-ligand. Insulin resistance syndrome is the only metabolic syndrome that has been consistently associated with NASH. The diagnosis rests on the hallmark histological features and rigorous exclusion of significant alcohol consumption. Most patients are asymptomatic, have mild-to-moderate elevations of serum aminotransferase levels, clinical hepatomegaly and features of fatty liver on imaging. Liver biopsy is essential for positive diagnosis and prognostication of NASH. Histologically, fat deposition is typically macrovesicular and inflammation of steatohepatitis is predominantly lobular. Neutrophilic cells in lobular inflammatory infilterate are a distinguishing feature of steatohepatitis and differentiate it from other chronic hepatitis. The pattern of collagen deposition is perivenular & peri-sinusoidal spaces in zone 3. NASH is a progressive disease in more than one in four and has spontaneous regression in less than one in six. Therapy options include weight reduction in obese, good control in diabetics and exercise. Ursodeoxycholic acid has membrane stabilizing, cytoprotective and immunological effect and normalizes raised transaminases. Liver transplantation has been done in NASH but transplanted liver shows re-development in more than two thirds. Many more therapies are in the pipeline and show promise for the future.