gebhart/patrepeval huggingface dataset:
Managing drug-resistant epilepsy: challenges and solutions (2016)

Despite the development of new antiepileptic drugs (AEDs), ~20%-30% of people with epilepsy remain refractory to treatment and are said to have drug-resistant epilepsy (DRE). This multifaceted condition comprises intractable seizures, neurobiochemical changes, cognitive decline, and psychosocial dysfunction. An ongoing challenge to both researchers and clinicians alike, DRE management is complicated by the heterogeneity among this patient group. The underlying mechanism of DRE is not completely understood. Many hypotheses exist, and relate to both the intrinsic characteristics of the particular epilepsy (associated syndrome/lesion, initial response to AED, and the number and type of seizures prior to diagnosis) and other pharmacological mechanisms of resistance. The four current hypotheses behind pharmacological resistance are the "transporter", "target", "network", and "intrinsic severity" hypotheses, and these are reviewed in this paper. Of equal challenge is managing patients with DRE, and this requires a multidisciplinary approach, involving physicians, surgeons, psychiatrists, neuropsychologists, pharmacists, dietitians, and specialist nurses. Attention to comorbid psychiatric and other diseases is paramount, given the higher prevalence in this cohort and associated poorer health outcomes. Treatment options need to consider the economic burden to the patient and the likelihood of AED compliance and tolerability. Most importantly, higher mortality rates, due to comorbidities, suicide, and sudden death, emphasize the importance of seizure control in reducing this risk. Overall, resective surgery offers the best rates of seizure control. It is not an option for all patients, and there is often a significant delay in referring to epilepsy surgery centers. Optimization of AEDs, identification and treatment of comorbidities, patient education to promote adherence to treatment, and avoidance of triggers should be periodically performed until further insights regarding causative pathology can guide better therapies.
HaploRec: efficient and accurate large-scale reconstruction of haplotypes (2006)

Our experimental results with simulated and real data show that HaploRec is a powerful method for the large scale haplotyping needed in association studies. With sample sizes large enough for gene mapping it appeared to be the best compared to all other tested methods (Phase, fastPhase, PL-EM, Snphap, Gerbil; simulated data), with small samples it was competitive with the best available methods (real data). HaploRec is several orders of magnitude faster than Phase and comparable to the other methods; the running times are roughly linear in the number of subjects and the number of markers. HaploRec is publicly available at http://www.cs.helsinki.fi/group/genetics/haplotyping.html.
Genomic imbalances in human lung adenocarcinomas and squamous cell carcinomas (2001)

Comparative genomic hybridization analysis was performed on 67 non-small-cell lung cancers (NSCLCs), including 32 squamous cell carcinomas (SCCs) and 35 adenocarcinomas (ACs), to identify differences in the patterns of genomic imbalance between these two histologic subtypes. Among the entire tumor set, the chromosome arms most often overrepresented were 1q, 3q, 5p, and 8q, each detected in 50-55% of cases. The most frequently underrepresented arms were 9q, 3p, 8p, and 17p. The number of imbalances was similar in SCCs and ACs (median number/case: 12 and 11, respectively). Moreover, many imbalances, such as gains of 1q, 5p, and 8q, occurred at a high frequency in both histologic subgroups. Several statistically significant differences, however, were found. The most prominent difference was gain of 3q24-qter, seen in 81% of SCCs compared with 31% of ACs (P < 0.0001), with amplification at 3q25-26 being detected in eight of 32 (25%) SCCs but in only two of 35 (6%) ACs. Gain of 20p13 and loss of 4q also were seen at a significantly higher rate in SCCs than in ACs, whereas overrepresentation of 6p was more common in ACs. Gains of 7q and 8q each were associated with higher-stage tumors and either positive nodal involvement or higher tumor grade. These data suggest that genes located in several chromosomal regions, particularly 3q25-26, may be associated with phenotypic properties that differentiate lung SCCs from ACs. Furthermore, certain imbalances, prominent among them gains of 7q and 8q, may be indicative of tumor aggressiveness in NSCLCs.
Synthesis of Bifunctional Au/Pt/Au Core/Shell Nanoraspberries for in Situ SERS Monitoring of Platinum-Catalyzed Reactions (2011)

The synthesis of bifunctional Au/Pt/Au nanoraspberries for use in quantitative in situ monitoring of platinum-catalyzed reactions by surface-enhanced Raman scattering (SERS) is presented. Highly convolved SERS spectra of reaction mixtures can be decomposed into the contributions of distinct molecular species by multivariate data analysis.
Isolation and identification of hepatitis E virus in Xinjiang, China (1992)

This paper describes isolation and identification of a virus (termed strain 87A) which has the cytopathic effect and haemagglutination properties of hepatitis E virus (HEV). This virus was isolated by tissue culture from the faeces of a patient with acute non-A, non-B enteric hepatitis in Xinjiang, China. The isolated virus was neutralized by acute phase sera obtained from other patients with acute non-A, non-B enteric hepatitis. The virus particles also could be specifically aggregated with acute phase sera from patients with known HEV hepatitis in China, Burma, India and the U.S.S.R., and with acute and convalescent sera from an HEV-infected chimpanzee. Crystalline arrangements of virus particles in the cytoplasm were observed by electron microscopy in ultrathin sections of infected cells. The sedimentation coefficient of the strain 87A virus particles in sucrose gradients was 176S. Purified virus particles revealed a protein band of about 76K on SDS-PAGE and Western blotting. The evidence indicates that the strain 87A virus is an HEV. Our ability to propagate HEV in cell culture should facilitate research on this hepatotropic virus.
The COPS (Common Open Policy Service) Protocol (2000)

This document describes a simple client/server model for supporting policy control over QoS signaling protocols. The model does not make any assumptions about the methods of the policy server, but is based on the server returning decisions to policy requests. The model is designed to be extensible so that other kinds of policy clients may be supported in the future. However, this document makes no claims that it is the only or the preferred approach for enforcing future types of policies.
Highly Conductive PEDOT:PSS Treated with Formic Acid for ITO-Free Polymer Solar Cells (2014)

We proposed a facile film treatment with formic acid to enhance the conductivity of poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS) by 4 orders of magnitude. The effect of formic acid concentration on conductivity was investigated; conductivity increased fast with increasing concentration up to 10 M and then increased slightly, the highest conductivity being 2050 S cm(-1) using 26 M concentration. Formic acid treated PEDOT:PSS films also exhibited very high transmittances. The mechanism of conductivity enhancement was explored through SEM, AFM, and XPS. Formic acid with its high dielectric constant screens the charge between PEDOT and PSS bringing about phase separation between them. Increased carrier concentration, removal of PSS from the film, morphology, and conformation change with elongated and better connected PEDOT chains are the main mechanisms of conductivity enhancement. ITO-free polymer solar cells were also fabricated using PEDOT:PSS electrodes treated with different concentrations of formic acid and showed equal performance to that of ITO electrodes. The concentrated acid treatment did not impair the desirable film properties as well as stability and performance of the solar cells.
Dasatinib, an orally active small molecule inhibitor of both the src and abl kinases, selectively inhibits growth of basal-type/“triple-negative” breast cancer cell lines growing in vitro (2007)

Dasatinib is an orally active small molecule kinase inhibitor of both the src and abl proteins. To evaluate the potential role of dasatinib in breast cancer we used 39 human breast cancer cell lines that have been molecular profiled using Agilent Microarrays. They represent both luminal and basal breast cancer subtypes based on the relative gene expression of cytokeratin (CK) 8/CK18 and CK5/CK17, respectively, and those that have undergone an epithelial-to-mesenchymal transition (post-EMT) based on their expression of vimentin and the loss of CKs. When treated with 1 mICROM dasatinib in vitro 8 of them were highly sensitive (>60% growth inhibition), 10 of them were moderately sensitive (40-59% growth inhibition), and 21 were resistant to dasatinib. A highly significant relationship between breast cancer subtype and sensitivity to dasatinib was observed (chi2 = 9.66 and P = 0.008). Specifically, basal-type and post-EMT breast cancer cell lines were most sensitive to growth inhibition by dasatinib. In an attempt to identify potential predictive markers of dasatinib response other than breast cancer subtype we analyzed the baseline gene expression profiles for differentially expressed genes. We identified a set of three biologically relevant genes whose elevated expression is associated with dasatinib inhibition including moesin, caveolin-1, and yes-associated protein-1 with a sensitivity and specificity of 88 and 86%, respectively. Importantly, these data provide scientific rationale for the clinical development of dasatinib in the treatment of women with "triple-negative" breast cancer, a subtype that is categorized as being aggressive and lacking effective treatments (i.e. hormonal manipulation or trastuzumab).
Neuroprotective agents in traumatic brain injury (2001)

The role of neuroprotection in traumatic brain injury (TBI) is reviewed. Basic research and experimental investigations have identified many different compounds with potential neuroprotective effect. However, none of the Phase III trials performed in TBI have been successful in convincingly demonstrating efficacy in the overall population. A common misconception is that consequently these agents are ineffective. The negative results as reported in the overall population may in part be caused by specific aspects of the head injury population as well as by aspects of clinical trial design and analysis. The heterogeneity of the TBI population causes specific problems, such as a risk of imbalances between placebo and treated groups but also causes problems when a possible treatment effect is evaluated in relation to the prognostic effect present. Trials of neuroprotective agents should be targeted first of all to a population in which the mechanism at which the agent is directed is likely to be present and secondly to a population in which the chances of demonstrating efficacy are realistic, e.g., to patients with an intermediate prognosis. The possibilities for concomitant or sequential administration of different neuroprotective agents at different times deserve consideration. The potential for neuroprotection in TBI remains high and we should not be discouraged by recent failures obtained up until now. Rather, prior to initiating new trials, careful consideration of experimental evidence is required in order to optimise chances for mechanistic targeting and lessons learned from previous experience need to be taken to heart in the design of future studies.
A programmable network interface for a message-based multicomputer (1994)

As fiber-optic gigabit networks are being deployed, supercomputer network interfaces are becoming the communication bottleneck. The Network Interface Unit (NIU) is a high-performance network interface for Pixel Planes 5, a custom, message-based multicomputer. The design offers both performance and programmability through a balance of data-handling in hardware an embedded processor. In this paper, we describe the NIU hardware and firmware architecture. We present results of performance measurements and assess the applicability of this design for the targeted environment. We also comment on its suitability for other environments and outline plans for the future work.
Sustained Loss of a Neoplastic Phenotype by Brief Inactivation of MYC (2002)

Pharmacological inactivation of oncogenes is being investigated as a possible therapeutic strategy for cancer. One potential drawback is that cessation of such therapy may allow reactivation of the oncogene and tumor regrowth. We used a conditional transgenic mouse model for MYC-induced tumorigenesis to demonstrate that brief inactivation of MYC results in the sustained regression of tumors and the differentiation of osteogenic sarcoma cells into mature osteocytes. Subsequent reactivation of MYC did not restore the cells' malignant properties but instead induced apoptosis. Thus, brief MYC inactivation appears to cause epigenetic changes in tumor cells that render them insensitive to MYC-induced tumorigenesis. These results raise the possibility that transient inactivation of MYC may be an effective therapy for certain cancers.
New Twist on Neuronal Insulin Receptor Signaling in Health, Disease, and Therapeutics (2005)

Long after the pioneering studies documenting the existence of insulin (year 1967) and insulin receptor (year 1978) in brain, the last decade has witnessed extraordinary progress in the understanding of brain region-specific multiple roles of insulin receptor signalings in health and disease. In the hypothalamus, insulin regulates food intake, body weight, peripheral fat deposition, hepatic gluconeogenesis, reproductive endocrine axis, and compensatory secretion of counter-regulatory hormones to hypoglycemia. In the hippocampus, insulin promotes learning and memory, independent of the glucoregulatory effect of insulin. Defective insulin receptor signalings are associated with the dementia in normal aging and patients with age-related neurodegenerative diseases (e.g., Alzheimer's disease); the cognitive impairment can be reversed with systemic administration of insulin in the euglycemic condition. Intranasal administration of insulin enhances memory and mood and decreases body weight in healthy humans, without causing hypoglycemia. In the hypothalamus, insulin-induced activation of the phosphoinositide 3-kinase pathway followed by opening of ATP-sensitive K+ channel has been shown to be related to multiple effects of insulin. However, the precise molecular mechanisms of insulin's pleiotropic effects still remain obscure. More importantly, much remains unknown about the quality control mechanisms ensuring correct conformational maturation of the insulin receptor, and the cellular mechanisms regulating density of cell surface functional insulin receptors.
Enrichment of Sialylated IgG by Lectin Fractionation Does Not Enhance the Efficacy of Immunoglobulin G in a Murine Model of Immune Thrombocytopenia (2011)

Intravenous immunoglobulin G (IVIg) is widely used against a range of clinical symptoms. For its use in immune modulating therapies such as treatment of immune thrombocytopenic purpura high doses of IVIg are required. It has been suggested that only a fraction of IVIg causes this anti immune modulating effect. Recent studies indicated that this fraction is the Fc-sialylated IgG fraction. The aim of our study was to determine the efficacy of IVIg enriched for sialylated IgG (IVIg-SA⁺) in a murine model of passive immune thrombocytopenia (PIT). We enriched IVIg for sialylated IgG by Sambucus nigra agglutinin (SNA) lectin fractionation and determined the degree of sialylation. Analysis of IVIg-SA⁺ using a lectin-based ELISA revealed that we enriched predominantly for Fab-sialylated IgG, whereas we did not find an increase in Fc-sialylated IgG. Mass spectrometric analysis confirmed that Fc sialylation did not change after SNA lectin fractionation. The efficacy of sialylated IgG was measured by administering IVIg or IVIg-SA⁺ 24 hours prior to an injection of a rat anti-mouse platelet mAb. We found an 85% decrease in platelet count after injection of an anti-platelet mAb, which was reduced to a 70% decrease by injecting IVIg (p<0.01). In contrast, IVIg-SA⁺ had no effect on the platelet count. Serum levels of IVIg and IVIg-SA⁺ were similar, ruling out enhanced IgG clearance as a possible explanation. Our results indicate that SNA lectin fractionation is not a suitable method to enrich IVIg for Fc-sialylated IgG. The use of IVIg enriched for Fab-sialylated IgG abolishes the efficacy of IVIg in the murine PIT model.
Quick prototyping of flip chip assembly with MEMS (2002)

This paper describes a process to transfer microelectromechanical systems (MEMS) devices to a secondary substrate using flip-chip thermosonic bonding. A standard wire-bonding machine was used to place /spl sim/100-/spl mu/m bumps on unreleased MEMS chiplets. The bumped chiplet was then flip-chip bonded to a secondary substrate containing a microwave coplanar waveguide (CPW). After bonding, the entire assembly was run through the MEMS release process, after which the MEMS host substrate was removed. The thermosonic bonding was a very reliable prototyping tool with a 100% bonding yield. The transfer process can be used with any MEMS that can be wire bonded. The process can also be applied to a variety of applications.
Ripple Current Reduction of a Fuel Cell for a Single-Phase Isolated Converter using a DC Active Filter with a Center Tap (2009)

This paper proposes a ripple reduction method in current without using any additional switching devices. The current ripple that has double frequency component of the power supply is generated in the DC part when a single-phase PWM inverter is used for a grid connection. The current ripple causes short lifetime for electrolytic capacitors, batteries and fuel cells. The proposed circuit realizes a DC active filter function without increasing the number of the switching device because the energy buffer capacitor is connected to the center tap of the isolation transformer. In addition, the buffer capacitor voltage is controlled by the common mode voltage of the inverter. This paper describes the features of the proposed circuit, control strategy and experimental results. As a result, about 1/5 times of the ripple can be reduced.
MHC genes modify systemic autoimmune disease. The role of the I-E locus (1996)

The MHC exerts an important influence on systemic autoimmune disease. In C57BL/6-lpr/lpr (B6/lpr) mice, substitution of the H-2d instead of the H-2b MHC haplotype results in a global reduction in autoantibody levels. Since H-2d expresses both I-A and I-E, while H-2b expresses only I-A, general down-regulation of autoimmunity in the d haplotype might be due to I-E expression. This was tested with I-E alpha d transgenic B6/lpr mice, which expressed a functional surface I-E molecule. Five-month-old transgene-positive B6/lpr mice had much lower total IgG, IgG anti-chromatin, anti-DNA, and IgM rheumatoid factor directed against IgG1 and against IgG2b than transgene-negative littermates (p < or = 0.002), as well as significantly lower spleen and lymph node weights (p < or = 0.002). Decreases in autoantibody levels in the transgenic lpr mice were not due to a nonspecific effect of the I-E alpha d transgene, since transgene-positive B6/lpr.H-2d mice had levels of autoantibodies comparable with transgene-negative B6/lpr.H-2d mice. To determine whether autoantibody was preferentially made by I-E-negative B cells, irradiated (B6/lpr.Igha x B6/lpr.I-E alpha d)F1 mice were reconstituted with equal amounts of B6/lpr.Igha and B6/lpr.I-E alpha d bone marrow. Allotype-specific ELISA showed that most autoantibody was produced by the I-E negative B cells (range 97% to 84%). The results show that a functional I-E molecule in lpr mice leads to generalized reduction in autoantibody levels through a direct effect on the B cell. The molecular mechanism of this effect remains to be determined.
Coronary Vessel Development (2003)

Development of the coronary vascular system is an interesting model in developmental biology with major implications for the clinical setting. Although coronary vessel development is a form of vasculogenesis followed by angiogenesis, this system uses several unique developmental processes not observed in the formation of other blood vessels. This review summarizes the literature that describes the development of the coronary system, highlighting the unique aspects of coronary vessel development. It should be noted that many of the basic mechanisms that govern vasculogenesis in other systems have not been analyzed in coronary vessel development. In addition, we present recent advances in the field that uncover the basic mechanisms regulating the generation of these blood vessels and identify areas in need of additional studies.
Morphology Development of Ultrathin Symmetric Diblock Copolymer Film via Solvent Vapor Treatment (2004)

We have followed the time development of the microdomain structure in symmetric diblock copolymer poly(styrene-b-methyl methacrylate), P(S-b-MMA), ultrathin films via PMMA-selective solvent vapor treatment by atomic force microscopy (AFM). After preparation on a substrate preferentially attracting the PMMA block, PS forms a continuous layer at a film's free surface. With subsequent solvent vapor treatment, the film gradually shows a well-ordered hexagonally packed nanocylinders structure. It is shown that only when the film thickness is less than the 1/2L0 (lamellar repeat spacing), and exposed to PMMA block selective solvent for an appropriate time, can the well-ordered hexagonally packed nanocylinders form. On an extended solvent vapor treatment, a mixed morphology containing nanocylinders and stripes appears, followed by the striped morphologies. When the annealing time is long enough, the film comes back to the flat surface again, however, with PMMA instead of PS dominating the free surface. Thickness confinement and solvent induced reconstruction of the film are shown to be responsible for the P(S-b-MMA) morphology and surface chemistry development.
Biotechnology of Amylodextrin Oligosaccharides (1991)

Two opposing hypotheses attempted to describe the conformation of the α-l,4-linked glucopyranoside polymers in neutral aqueous solutions: the random coil and the segmented helix structure hypotheses. The former one was based mainly on hydrodynamic studies of amylose solutions, the latter on many very different observations, but mainly on the formation and properties of amylose-helix complexes. The formation of cyclodextrins, catalysed by cyclizing enzymes, delivers further proof for the helical structure, and simultaneously is the source of a new technology: the molecular encapsulation of different compounds by cyclodextrin complexation. The significance of the cyclodextrins and their derivatives in commercial applications will be discussed.