gebhart/patrepeval huggingface dataset:
α-Synuclein Immunotherapy Blocks Uptake and Templated Propagation of Misfolded α-Synuclein and Neurodegeneration (2014)

Accumulation of misfolded alpha-synuclein (α-syn) into Lewy bodies (LBs) and Lewy neurites (LNs) is a major hallmark of Parkinson's disease (PD) and dementia with LBs (DLB). Recent studies showed that synthetic preformed fibrils (pffs) recruit endogenous α-syn and induce LB/LN pathology in vitro and in vivo, thereby implicating propagation and cell-to-cell transmission of pathological α-syn as mechanisms for the progressive spread of LBs/LNs. Here, we demonstrate that α-syn monoclonal antibodies (mAbs) reduce α-syn pff-induced LB/LN formation and rescue synapse/neuron loss in primary neuronal cultures by preventing both pff uptake and subsequent cell-to-cell transmission of pathology. Moreover, intraperitoneal (i.p.) administration of mAb specific for misfolded α-syn into nontransgenic mice injected intrastriatally with α-syn pffs reduces LB/LN pathology, ameliorates substantia nigra dopaminergic neuron loss, and improves motor impairments. We conclude that α-syn antibodies could exert therapeutic effects in PD/DLB by blocking entry of pathological α-syn and/or its propagation in neurons.
Polyelectrolyte Multilayers with a Tunable Young's Modulus:  Influence of Film Stiffness on Cell Adhesion (2005)

Mechanical properties of model and natural gels have recently been demonstrated to play an important role in various cellular processes such as adhesion, proliferation, and differentiation, besides events triggered by chemical ligands. Understanding the biomaterial/cell interface is particularly important in many tissue engineering applications and in implant surgery. One of the final goals would be to control cellular processes precisely at the biomaterial surface and to guide tissue regeneration. In this work, we investigate the substrate mechanical effect on cell adhesion for thin polyelectrolyte multilayer (PEM) films, which can be easily deposited on any type of material. The films were cross linked by means of a water-soluble carbodiimide (EDC), and the film elastic modulus was determined using the AFM nanoindentation technique with a colloidal probe. The Young's modulus could be varied over 2 orders of magnitude (from 3 to 400 kPa) for wet poly(L-lysine)/hyaluronan (PLL/HA) films by changing the EDC concentration. The chemical changes upon cross linking were characterized by means of Fourier transform infrared spectroscopy (FTIR). We demonstrated that the adhesion and spreading of human chondrosarcoma cells directly depend on the Young's modulus. These data indicate that, besides the chemical properties of the polyelectrolytes, the substrate mechanics of PEM films is an important parameter influencing cell adhesion and that PEM offer a new way to prepare thin films of tunable mechanical properties with large potential biomedical applications including drug release.
Nanoporous gold plasmonic structures for sensing applications (2011)

The fabrication, characterization and functionalization of periodically patterned nanoporous gold layers is presented. The material shows plasmonic properties in the near infrared range, with excitation and propagation of surface plasmon polaritons. Functionalization shows a marked enhancement in the optical response in comparison with evaporated gold gratings, due to a great increase of the active surface. Due to its superior response, nanoporous gold patterns appear promising for the realization of compact plasmonic platforms for sensing purposes.
Gate leakage current mechanisms in AlGaN/GaN heterostructure field-effect transistors (2000)

Gate leakage currents in AlGaN/GaN heterostructure field-effect transistor (HFET) structures with conventional and polarization-enhanced barriers have been studied. Comparisons of extensive gate leakage current measurements with two-dimensional simulations show that vertical tunneling is the dominant mechanism for gate leakage current in the standard-barrier HFET and that the enhanced-barrier structure suppresses this mechanism in order to achieve a reduced leakage current. An analytical model of vertical tunneling in a reverse-biased HFET gate-drain diode is developed to evaluate the plausibility of this conclusion. The model can be fit to the measured data, but suggests that additional leakage mechanisms such as lateral tunneling from the edge of the gate to the drain or defect-assisted tunneling also contribute to the total leakage current. The vertical tunneling current mechanism is shown to be more significant to the gate leakage current in III–V nitride HFETs than in HFETs fabricated in other III–V material systems, in which the lateral tunneling current component generally dominates the gate leakage current.
Sialyl-Tn Polysaccharide A1 as an Entirely Carbohydrate Immunogen: Synthesis and Immunological Evaluation (2016)

Sialyl Thomsen-nouveau (STn) is a tumor-associated carbohydrate antigen (TACA) that is overexpressed in a variety of carcinomas such as breast, ovarian, and colon cancer. In normal tissue, STn is not detectable, which is critical for opportunities in developing cancer immunotherapies. A novel, entirely carbohydrate, semisynthetic STn-polysaccharide (PS) A1 conjugate was prepared and evaluated in C57BL/6 mice. STn-PS A1 was combined with commercially available monophosphoryl lipid A-based adjuvant, and after immunization, ELISA indicated a strong immune response for inducing anti-STn IgM/IgG antibodies. The specificity of these antibodies was concomitantly investigated using FACS analysis, and the results indicated excellent cell surface binding events to STn-expressing cancer cell lines MCF-7 and OVCAR-5. An INF-γ ELISpot assay was conducted to further confirm a robust cellular immunity invoked by STn-PS A1. Most importantly, the raised antibodies conferred complement-dependent cellular cytotoxicity against MCF-7 and OVCAR-5 cells.
Assignment of the Four Disulfides in the N-terminal Somatomedin B Domain of Native Vitronectin Isolated from Human Plasma (2004)

The primary sequence of the N-terminal somatomedin B (SMB) domain of native vitronectin contains 44 amino acids, including a framework of four disulfide bonds formed by 8 closely spaced cysteines in sequence patterns similar to those found in the cystine knot family of proteins. The SMB domain of vitronectin was isolated by digesting the protein with endoproteinase Glu-C and purifying the N-terminal 1-55 peptide by reverse-phase high performance liquid chromatography. Through a combination of techniques, including stepwise reduction and alkylation at acidic pH, peptide mapping with matrix-assisted laser desorption ionization mass spectrometry and NMR, the disulfide bonds contained in the SMB domain have been determined to be Cys(5):Cys(9), Cys(19):Cys(31), Cys(21):Cys(32), and Cys(25):Cys(39). This pattern of disulfides differs from two other connectivities that have been reported previously for recombinant forms of the SMB domain expressed in Escherichia coli. This arrangement of disulfide bonds in the SMB domain from native vitronectin forms a rigid core around the Cys(19): Cys(31) and Cys(21):Cys(32) disulfides. A small positively charged loop is created at the N terminus by the Cys(5): Cys(9) cystine. The most prominent feature of this disulfide-bonding pattern is a loop between Cys(25) and Cys(39) similar to cystine-stabilized alpha-helical structures commonly observed in cystine knots. This alpha-helix has been confirmed in the solution structure determined for this domain using NMR (Mayasundari, A., Whittemore, N. A., Serpersu, E. H., and Peterson, C. B. (2004) J. Biol. Chem. 279, 29359-29366). It confers function on the SMB domain, comprising the site for binding to plasminogen activator inhibitor type-1 and the urokinase receptor.
PROTEASES AND THEIR TARGETS IN ESCHERICHIA COLI (1996)

Proteolysis in Escherichia coli serves to rid the cell of abnormal and misfolded proteins and to limit the time and amounts of availability of critical regulatory proteins. Most intracellular proteolysis is initiated by energy-dependent proteases, including Lon, ClpXP, and HflB; HflB is the only essential E. coli protease. The ATPase domains of these proteases mediate substrate recognition. Recognition elements in target are not well defined, but are probably not specific amino acid sequences. Naturally unstable protein substrates include the regulatory sigma factors for heat shock and stationary phase gene expression, sigma 32 and RpoS. Other cellular proteins serve as environmental sensors that modulate the availability of the unstable proteins to the proteases, resulting in rapid changes in sigma factor levels and therefore in gene transcription. Many of the specific proteases found in E. coli are well-conserved in both prokaryotes and eukaryotes, and serve critical functions in developmental systems.
Load Balancing Optimization in LTE/LTE-A Cellular Networks: A Review (2014)

During the past few decades wireless technology has seen a tremendous growth. The recent introduction of high-end mobile devices has further increased subscriber's demand for high bandwidth. Current cellular systems require manual configuration and management of networks, which is now costly, time consuming and error prone due to exponentially increasing rate of mobile users and nodes. This leads to introduction of self organizing capabilities for network management with minimum human involvement. It is expected to permit higher end user Quality of Service (QoS) along with less operational and maintenance cost for telecom service providers. Self organized cellular networks incorporate a collection of functions for automatic configuration, optimization and maintenance of cellular networks. As mobile end users continue to use network resources while moving from a cell boundary to other, traffic load within a cell does not remain constant. Thus Load balancing as a part of self organized network solution, has become one of the most active and emerging fields of research in Cellular Network. It involves transfer of load from overloaded cells to the neighbouring cells with free resources for more balanced load distribution in order to maintain appropriate end-user experience and network performance. In this paper, review of various load balancing techniques currently used in mobile networks is presented, with special emphasis on techniques that are suitable for self optimization feature in future cellular networks.
Mechanism of MDSC induced T cell tolerance in cancer (88.26) (2009)

Abstract Tumor antigen-specific T-cell tolerance is a critical element of tumor escape. It is known that MDSC can induce antigen-specific CD8+ T cell tolerance in an experimental system with adoptive transfer of transgenic T cells. In this study we addressed the critical question whether a similar phenomenon can be observed in a "natural" non-transgenic experimental model. Balb/C mice were subcutaneously inoculated with two different tumor cell lines, a derivative A2L2 cell line, which expresses high levels of HER2/neu and the parental cell line 66.3. HER2/neu specific CD8+T cells were generated by immunization of mice with peptide. MDSC were able to tolerize antigen-specific T cells in vivo if they were collected from A2L2 but not from 66.3 tumor-bearing mice indicating the tumor-specific nature of T cell tolerance induced by MDSC. Next we investigated the type of signaling caused by MDSC in CD8+T cells that could lead to tolerance. MDSC dramatically reduced the ability of CD8+ T cells to respond to the specific peptide. However, study of various signaling molecules using different experimental systems and tests found that MDSC did not induce negative signaling in T cells. This conclusion was confirmed in adoptive transfer experiments with CD8+T cells expressing dual TCR: LCMV glycoprotein peptide gp33-41 and OVA-derived H-2Kb-restricted peptide ova257-264. We found that MDSC loaded with peptide specific for one TCR induced tolerance only against that specific epitope but CD8+ T cells retained the ability to respond to the peptide specific for the other TCR expressed on the same cell.
Genetics and genomics of Candida albicans biofilm formation (2006)

Biofilm formation by the opportunistic fungal pathogen Candida albicans is a complex process with significant consequences for human health: it contributes to implanted medical device-associated infections. Recent advances in gene expression profiling and genetic analysis have begun to clarify the mechanisms that govern C. albicans biofilm development and acquisition of unique biofilm phenotypes. Such studies have identified candidate adhesin genes, and have revealed that biofilm drug resistance is multifactorial. Newly defined cell-cell communication pathways also have profound effects on biofilm formation. Future challenges include the elucidation of the structure and function of the extracellular exopolymeric substance that surrounds biofilm cells, and the extension of in vitro biofilm observations to newly developed in vivo biofilm models.
TGFbeta1 activates c-Jun and Erk1 via alphaVbeta6 integrin. (2003)

Transforming growth factor beta (TGFbeta) plays an important role in animal development and many cellular processes. A variety of cellular functions that are required for tumor metastasis are controlled by integrins, a family of cell adhesion receptors. Overexpression of alphaVbeta6 integrin is associated with lymph node metastasis of gastric carcinomas. It has been demonstrated that a full TGFbeta1 signal requires both alphaVbeta6 integrin and SMAD pathway. TGFbeta1 binds to alphaVbeta6 via the DLXXL motif, a freely accessible amino acid sequence in the mature form of TGFbeta1. Binding of mature TGFbeta1 to alphaVbeta6 leads to immobilization and tyrosine phosphorylation of proteins, which are associated with focal adhesions, a hallmark of integrin-mediated signal transduction. Here, we show that binding of mature TGFbeta1 recruits the mitogen-activated protein kinase kinase kinase 1 (MEKK1), a mediator of c-Jun activation, and the extracellular signaling-regulated kinase-1 (Erk1) to focal adhesions. In addition, the p21-activated kinase 1 (PAK1) is associated with focal adhesions and differentially phosphorylated upon TGFbeta1 stimulation. We conclude that TGFbeta1 activates c-Jun via the MEKK1/p38 MAP kinase pathway and influences cytoskeletal organization. These finding may provide a link between TGFbeta1 and the metastatic behavior of cancers.
Heart failure in older people: causes, diagnosis and treatment (2002)

Congestive heart failure affects >5% of those aged 65-75 and 10-20% of those aged >80 in the UK, and levels are likely to rise in the wake of improved therapies for hypertension and myocardial infarction. It is often multifactorial in this group. The most common causes are hypertension and coronary heart disease, with valvular heart disease playing an increasing role. The most common precipitant of pre-existing heart failure is non-compliance with medication or diet; non-steroidal anti-inflammatory drugs are particularly likely to exacerbate the condition. Diagnosis may be difficult since typical signs are often absent or masked in older people, but plasma levels of brain natriuretic peptide appear to be a reliable indicator and may provide diagnostic test in the future. Systolic heart failure is managed by conventional therapy (diuretics, angiotensin-converting enzyme inhibitors and beta-blockers). The management of diastolic heart failure is less well defined, but symptoms should be managed, ischaemia prevented and the underlying causes identified and treated. Nurse-directed, multidisciplinary intervention (including education of patient and family, social support, review of medication, dietary modification and weight monitoring) have resulted in improvements in event-free survival and quality of life.
Optimal and near-optimal test sequencing algorithms with realistic test models (1999)

In this paper, we first present the formulation and solution of the basic test sequencing problem. We then consider generalized test sequencing problems that incorporate various practical features such as precedence constraints and setup operations for tests, multi-outcome tests, modular diagnosis, and rectification. We develop various AO/sup */ and information heuristic-based algorithms to solve these practical test sequencing problems. We also discuss the issues involved in implementation of the test sequencing algorithms for solving large problems efficiently, and show that our preprocessing techniques result in considerable speed-ups.
Sequential deformation and physiological considerations in unipolar right or left ventricular pacing (2006)

Ventricular pacing disrupts the natural sequence of shortening along the myocardial band, and the resultant dyssynchrony impairs LV function.
Antitumor effects of HSV-TK–engineered donor lymphocytes after allogeneic stem-cell transplantation (2007)

The extensive exploitation of the antitumor effect of donor lymphocytes infused after allogeneic hematopoietic stem-cell transplantation (allo-HSCT) is limited by the risk of graft-versus-host disease (GvHD). To overcome this limitation, we investigated the therapeutic potential of donor lymphocytes engineered with the suicide gene thymidine kinase of herpes simplex virus (TK) in 23 patients experiencing recurrence of hematologic malignancies after allo-HSCT. Long-term follow-up of infused patients included analysis of engraftment of genetically engineered lymphocytes, in vivo assessment of antitumor effect, and control of GvHD by ganciclovir. All 17 patients evaluable for engraftment and graft-versus-leukemia (GvL) had circulating TK(+) cells detectable beginning at a median time of 18 days. Eleven patients (65%) experienced a substantial clinical benefit resulting in 6 (35%) complete remissions and 5 (29%) partial responses. The antitumor effect tightly correlated with the in vivo expansion of TK(+) cells. Seven patients received ganciclovir, resulting in elimination of TK(+) cells and effective and selective treatment of GvHD. Immunization against HSV-TK was observed in 7 patients but did not preclude an effective GvL. These data validate the feasibility, safety, and efficacy of TK(+) cells in the context of allografting and represent the basis for a broader application of this technology.
Improved deep metric learning with multi-class N-pair loss objective (2016)

Deep metric learning has gained much popularity in recent years, following the success of deep learning. However, existing frameworks of deep metric learning based on contrastive loss and triplet loss often suffer from slow convergence, partially because they employ only one negative example while not interacting with the other negative classes in each update. In this paper, we propose to address this problem with a new metric learning objective called multi-class N-pair loss. The proposed objective function firstly generalizes triplet loss by allowing joint comparison among more than one negative examples - more specifically, N-1 negative examples - and secondly reduces the computational burden of evaluating deep embedding vectors via an efficient batch construction strategy using only N pairs of examples, instead of (N+1) x N. We demonstrate the superiority of our proposed loss to the triplet loss as well as other competing loss functions for a variety of tasks on several visual recognition benchmark, including fine-grained object recognition and verification, image clustering and retrieval, and face verification and identification.
Vaccination of chimpanzees against infection by thehepatitis C virus. (1994)

A high incidence of community-acquired hepatitis C virus infection that can lead to the progressive development of chronic active hepatitis, liver cirrhosis, and primary hepatocellular carcinoma occurs throughout the world. A vaccine to control the spread of this agent that represents a major cause of chronic liver disease is therefore needed. Seven chimpanzees (Pan troglodytes) have been immunized with both putative envelope glycoproteins [E1 (gp33) and E2 (gp72)] that were copurified from HeLa cells infected with a recombinant vaccinia virus expression vector. Despite the induction of a weak humoral immune response to these viral glycoproteins in experimentally infected chimpanzees, a strong humoral immune response was obtained in all vaccines. The five highest responders showed complete protection against an i.v. challenge with homologous hepatitis C virus 1. The remaining two vaccines became infected, but both infection and disease may have been ameliorated in comparison with four similarly challenged control chimpanzees, all of which developed acute hepatitis and chronic infections. These results provide considerable encouragement for the eventual control of hepatitis C virus infection by vaccination.
Rematerialization (1992)

This paper examines a problem that arises during global register allocation – rematerialization . If a value cannot be kept in a register, the allocator should recognize when it is cheaper to recompute the value (rematerialize it) than to store and reload it. Chaitin's original graph-coloring allocator handled simple instance of this problem correctly. This paper details a general solution to the problem and presents experimental evidence that shows its importance. Our approach is to tag individual values in the procedure's SSA graph with information specifying how it should be spilled. We use a variant of Wegman and Zadeck's sparse simple constant algorithm to propagate tags throughout the graph. The allocator then splits live ranges into values with different tags. This isolates those values that can be easily rematerialized from values that require general spilling. We modify the base allocator to use this information when estimating spill costs and introducing spill code. Our presentation focuses on rematerialization in the context of Chaitin's allocator; however, the problem arises in any global allocator. We believe that our approach will work in other allocators–while the details of implementation will vary, the key insights should carry over directly.
Use of Glycated Hemoglobin in the Diagnosis of Diabetes Mellitus and Pre-diabetes and Role of Fasting Plasma Glucose, Oral Glucose Tolerance Test. (2013)

As a screening tool for newly diagnosed diabetes and pre-diabetes, the HbA1C level performed better than FPG and 2-h OGTT in this general Saudi population. High diagnostic power of A1C may contribute to the decrease in the number of undiagnosed patients.
Simple but useful tools for interactive WWW development (2002)

An important area for World Wide Web (WWW) development is customized educational web pages incorporating interactive features. Unfortunately, it is usually necessary for an engineering instructor to expend a substantial amount of time to learn the peculiarities of programming and debugging web-based interactive applications. To help eliminate this time hurdle a description is given in this paper of a set of software routines which allow an instructor to prepare a set of quiz questions or drill problems in the form of ordinary text files, then to convert the files automatically into hypertext markup language (HTML) with an interactive "forms" interface for inclusion in a web site. The relatively simple examples considered in this paper are intended to serve as templates for those individuals who are interested in probing more deeply into the intricacies of web software. Examples and computer code are also available.