gebhart/patrepeval huggingface dataset:
Epilepsy (generalised). (2010)

In this systematic review we present information relating to the effectiveness and safety of the following interventions: monotherapy using carbamazepine, gabapentin, lamotrigine, levetiracetam, phenobarbital, phenytoin, sodium valproate, or topiramate; addition of second-line drugs (lamotrigine or levetiracetam) for drug-resistant epilepsy; and hemispherectomy for drug-resistant epilepsy.
A Single Amino Acid Substitution in Nonstructural Protein 3A Can Mediate Adaptation of Foot-and-Mouth Disease Virus to the Guinea Pig (2001)

The genetic changes selected during the adaptation of a clonal population of foot-and-mouth disease virus (FMDV) to the guinea pig have been analyzed. FMDV clone C-S8c1 was adapted to the guinea pig by serial passage in the animals until secondary lesions were observed. Analysis of the virus directly recovered from the lesions developed by the animals revealed the selection of variants with two amino acid substitutions in nonstructural proteins, I(248)-->T in 2C and Q(44)-->R in 3A. On further passages, an additional mutation, L(147)-->P, was selected in an important antigenic site located in the G-H loop of capsid protein VP1. The amino acid substitution Q(44)-->R in 3A, either alone or in combination with the replacement I(248)-->T in 2C, was sufficient to give FMDV the ability to produce lesions. This was shown by using infectious transcripts which generated chimeric viruses with the relevant amino acid substitutions. Clinical symptoms produced by the artificial chimeras were similar to those produced by the naturally adapted virus. These results obtained with FMDV imply that one or very few replacements in nonstructural viral proteins, which should be within reach of the mutant spectra of replicating viral quasispecies, may result in adaptation of a virus to a new animal host.
22q11.2 deletion syndrome as a natural model for COMT haploinsufficiency-related dopaminergic dysfunction in ADHD (2006)

In the current issue of IJNP Gothelf and co-workers report an important study which sheds light on the association between chromosome 22q11.2 deletion syndrome (22q11.2 DS; velocardiofacial syndrome, VCFS), dopaminergic transmission, and psychiatric disorders. 22q11.2 DS occurs in at least 1/5000 live births and thus is the most common chromosomal deletion syndrome in humans (Botto et al., 2003). The deletion in the long arm of chromosome 22, usually comprises up to 3 Mb, and is transmitted dominantly, although most patients suffer from de-novo mutations. The clinical phenotype ranges from immune deficiency with thymal aplasia, congenital heart abnormalities, velopharyngeal insufficiency with hypernasal speech, slight dysmorphy with characteristic facies, to severe syndromal developmental abnormalities with mental retardation (Shprintzen, 2000). Most interestingly for the field of neuropsychiatry, 22q11.2 DS is associated with an increased rate of variety of psychiatric disorders. In childhood and adolescence, 22q11.2 DS is associated with attention deficit hyperactivity disorder (ADHD; Antshel et al., 2005; Niklasson et al., 2002), affecting up to 55% of the patients (Gothelf et al., 2004). Another, less frequent comorbidity in adolescence seems to be obsessive–compulsive disorder (OCD; Gothelf et al., 2006). Finally, there is an increased prevalence for comorbidity with schizophrenic and bipolar affective psychoses in adulthood (Murphy, 2005).
Antigen Spreading Contributes to MAGE Vaccination-Induced Regression of Melanoma Metastases (2011)

A core challenge in cancer immunotherapy is to understand the basis for efficacious vaccine responses in human patients. In previous work we identified a melanoma patient who displayed a low-level antivaccine cytolytic T-cell (CTL) response in blood with tumor regression after vaccination with melanoma antigens (MAGE). Using a genetic approach including T-cell receptor β (TCRβ) cDNA libraries, we found very few antivaccine CTLs in regressing metastases. However, a far greater number of TCRβ sequences were found with several of these corresponding to CTL clones specific for nonvaccine tumor antigens, suggesting that antigen spreading was occurring in regressing metastases. In this study, we found another TCR belonging to tumor-specific CTL enriched in regressing metastases and detectable in blood only after vaccination. We used the TCRβ sequence to detect and clone the desired T cells from tumor-infiltrating lymphocytes isolated from the patient. This CD8 clone specifically lysed autologous melanoma cells and displayed HLA-A2 restriction. Its target antigen was identified as the mitochondrial enzyme caseinolytic protease. The target antigen gene was mutated in the tumor, resulting in production of a neoantigen. Melanoma cell lysis by the CTL was increased by IFN-γ treatment due to preferential processing of the antigenic peptide by the immunoproteasome. These results argue that tumor rejection effectors in the patient were indeed CTL responding to nonvaccine tumor-specific antigens, further supporting our hypothesis. Among such antigens, the mutated antigen we found is the only antigen against which no T cells could be detected before vaccination. We propose that antigen spreading of an antitumor T-cell response to truly tumor-specific antigens contributes decisively to tumor regression.
The investment and marketing of transload facilities: a statistical evaluation (1997)

This paper examines the basic relationships which shippers, carriers, and facility operators have developed in the design and operation of bulk intermodal facilities, or transload terminals. The analysis is based on 349 truck-served transload facilities throughout the United States. The facilities are examined for commodity types being handled and the types of handling equipment being used. The results demonstrate a strong relationship between certain handling procedures and commodity types. Additionally, the size and volume of the facilities are related by commodity types and the number of rail spots. Finally, the specialization or dedication of a large number of facilities to individual commodities is addressed, as well as the basic thoughts on their investment needs to attract suitable customers. The information provided demonstrates that the market is very segmented on the basis of materials being handled, and that many facilities are commodity, and initially customer driven. These findings are important to transload providers in increasing their asset utilization, and also to users that seek efficient and effective transportation alternatives to meet their logistical needs.
A complete remote-control system for reliable preparation of [18F]altanserin (1999)

A complete remote control system was constructed for production of the PET 5-HT2A ligand [18F]altanserin by nitro-for-fluoro exchange. Comparing with published methods, the key features include (1) conducting azeotropic distillation and nucleophilic displacement in an open vessel heated by a commercial microwave oven; (2) purifying the product by a single HPLC procedure and (3) removing HPLC solvent by solid phase extraction. The preparation took 114 min with 23% yield and high quality.
Maleic Anhydride, Maleic Acid, and Fumaric Acid (2001)

Abstract Scientific and technological developments in the manufacture and use of maleic anhydride, maleic acid, and fumaric acid are reviewed over the past 20 years. Physical and chemical properties for these three chemicals are updated with literature citations when available. Key derivatives are summarized, including acid chlorides and reaction products of these chemicals formed from acylation, alkylation, amidation, concerted nonpolar reactions of various kinds, decomposition and decarboxylation, electrophilic addition, esterification, free‐radical reactions, Grignard‐type reactions, halogenation, hydration and dehydration, hydroformylation, isomerization, ligation‐to‐metal atoms, nucleophilic addition, oxidation, polymerization, reduction, and sulfonation. Manufacturing processes for maleic anhydride are described, including those using fixed‐ fluidized‐ and transport‐bed technologies for selective oxidation of butane. A survey is given of catalyst developments through the end of 2000. Regardless of the reactor type used, all catalysts producing maleic anhydride from butane consist of a vanadyl pyrophosphate phase, (VO) 2 P 2 O 7 . Details are presented on maleic anhydride and its two diacid isomers with respect to shipment, economic aspects, specifications, analytical and test methods, toxicology, and principal uses.
Effect of NaCl on a Nonionic Surfactant Microemulsion System (1995)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTEffect of NaCl on a Nonionic Surfactant Microemulsion SystemS. Ajith and Animesh Kumar RakshitCite this: Langmuir 1995, 11, 4, 1122–1126Publication Date (Print):April 1, 1995Publication History Published online1 May 2002Published inissue 1 April 1995https://doi.org/10.1021/la00004a015Request reuse permissionsArticle Views402Altmetric-Citations21LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (513 KB) Get e-Alertsclose Get e-Alerts
RNAi therapy targeting KRAS in combination with chemotherapy for locally advanced pancreatic cancer patients (2015)

The combination of siG12D-LODER™ and chemotherapy is well tolerated, safe and demonstrated a potential efficacy in patients with LAPC. NCT01188785.
Lymphoma Immunotherapy: Vaccines, Adoptive Cell Transfer and Immunotransplant (2009)

Therapy for non-Hodgkin lymphoma has benefited greatly from basic science and clinical research such that chemotherapy and monoclonal antibody therapy have changed some lymphoma subtypes from uniformly lethal to curable, but the majority of lymphoma patients remain incurable. Novel therapies with less toxicity and more specific targeting of tumor cells are needed and immunotherapy is among the most promising of these. Recently completed randomized trials of idiotype vaccines and earlier-phase trials of other vaccine types have shown the ability to induce antitumor T cells and some clinical responses. More recently, trials of adoptive transfer of antitumor T cells have demonstrated techniques to increase the persistence and antitumor effect of these cells. Herein, we discuss lymphoma immunotherapy clinical trial results and what lessons can be taken to improve their effect, including the combination of vaccination and adoptive transfer in an approach we have dubbed 'immunotransplant'.
OVARIAN STEROID HORMONES (1985)

Estradiol and progesterone both accumulate in the brain. Specific cytosol receptors are present in certain CNS regions. Estradiol increases but progesterone decreases the brain's excitability. The effects can be mediated via monoamine systems or a change in monoamine metabolizing enzymes, but other mechanisms are possible. The combination of estradiol and progesterone seem to provoke a negative mood change in certain sensitive women. Estradiol and progesterone singly seem not to have these negative effects on mood, but perhaps positive effects instead.
KEAP1 Is a Redox Sensitive Target That Arbitrates the Opposing Radiosensitive Effects of Parthenolide in Normal and Cancer Cells (2013)

Elevated oxidative stress is observed more frequently in cancer cells than in normal cells. It is therefore expected that additional exposure to a low level of reactive oxygen species (ROS) will push cancer cells toward death, whereas normal cells might maintain redox homeostasis through adaptive antioxidant responses. We previously showed that parthenolide enhances ROS production in prostate cancer cells through activation of NADPH oxidase. The present study identifies KEAP1 as the downstream redox target that contributes to parthenolide's radiosensitization effect in prostate cancer cells. In vivo, parthenolide increases radiosensitivity of mouse xenograft tumors but protects normal prostate and bladder tissues against radiation-induced injury. Mechanistically, parthenolide increases the level of cellular ROS and causes oxidation of thioredoxin (TrX) in prostate cancer cells, leading to a TrX-dependent increase in a reduced state of KEAP1, which in turn leads to KEAP1-mediated PGAM5 and Bcl-xL (BCL2L1) degradation. In contrast, parthenolide increases oxidation of KEAP1 in normal prostate epithelial cells, leading to increased Nrf2 (NFE2L2) levels and subsequent Nrf2-dependent expression of antioxidant enzymes. These results reveal a novel redox-mediated modification of KEAP1 in controlling the differential effect of parthenolide on tumor and normal cell radiosensitivity. Furthermore, they show it is possible to develop a tumor-specific radiosensitizing agent with radioprotective properties in normal cells.
The essence of three-phase AC/AC converter systems (2008)

In this paper the well-known voltage and current DC-link converter systems, used to implement an AC/AC converter, are initially presented. Using this knowledge and their space vector modulation methods we show their connection to the family of indirect matrix converters and then finally the connection to direct matrix converters. A brief discussion of extended matrix converter circuits is given and a new unidirectional three-level matrix converter topology is proposed. This clearly shows the topological connections of the converter circuits that directly lead to an adaptability of the modulation methods. These allow the reader who is familiar with space vector modulation of voltage and current DC-link converters to simply incorporate and identify new modulation methods. A comparison of the converter concepts, with respect to their fundamental, topology-related characteristics, complexity, control and efficiency, then follows. Furthermore, by taking the example of a converter that covers a typical operation region in the torque-speed plane (incl. holding torque at standstill), the necessary silicon area of the power semiconductors is calculated for a maximum junction temperature. This paper concludes with proposals for subjects of further research in the area of matrix converters.
ATP-dependent conjugation of reticulocyte proteins with the polypeptide required for protein degradation. (1980)

The heat-stable polypeptide (APF-1) required for ATP-dependent proteolysis in reticulocytes enters into high molecular weight conjugates upon incubation with the fraction of reticulocytes that is retained by DEAE-cellulose. Conjugate formation requires ATP and Mg2+ and its inhibited by N-ethylmaleimide. UTP and GTP are inactive. These properties are identical to those of ATP-dependent protein breakdown in the same system, suggesting that the conjugates are intermediates in this process. The APF-1 conjugates are stable in sodium dodecyl sulfate/polyacrylamide gel electrophoresis and Sephadex G-75 isolation and are resistant to mild acid, alkali, heat denaturation, and reduction; the conjugates are therefore covalent.
Impact of Schistosoma japonicum Infection on Collagen-Induced Arthritis in DBA/1 Mice: A Murine Model of Human Rheumatoid Arthritis (2011)

Our data provide direct evidence that the Th2 response evoked by prior S. japonicum infection can suppress the Th1 response and pro-inflammatory mediator and that bisexual infection with egg-laying up-regulates the Treg response and down-regulates the Th17 response, resulting in an amelioration of autoimmune arthritis. The beneficial effects might depend on the establishment of a Th2-dominant response rather than the presence of the eggs. Our results suggest that anti-inflammatory molecules from the parasite could treat autoimmune diseases.
Activation of Akt/PKB, increased phosphorylation of Akt substrates and loss and altered distribution of Akt and PTEN are features of Alzheimer's disease pathology (2005)

Studies suggest that activation of phosphoinositide 3-kinase-Akt may protect against neuronal cell death in Alzheimer's disease (AD). Here, however, we provide evidence of increased Akt activation, and hyperphosphorylation of critical Akt substrates in AD brain, which link to AD pathogenesis, suggesting that treatments aiming to activate the pathway in AD need to be considered carefully. A different distribution of Akt and phospho-Akt was detected in AD temporal cortex neurons compared with control neurons, with increased levels of active phosphorylated-Akt in particulate fractions, and significant decreases in Akt levels in AD cytosolic fractions, causing increased activation of Akt (phosphorylated-Akt/total Akt ratio) in AD. In concordance, significant increases in the levels of phosphorylation of total Akt substrates, including: GSK3beta(Ser9), tau(Ser214), mTOR(Ser2448), and decreased levels of the Akt target, p27(kip1), were found in AD temporal cortex compared with controls. A significant loss and altered distribution of the major negative regulator of Akt, PTEN (phosphatase and tensin homologue deleted on chromosome 10), was also detected in AD neurons. Loss of phosphorylated-Akt and PTEN-containing neurons were found in hippocampal CA1 at end stages of AD. Taken together, these results support a potential role for aberrant control of Akt and PTEN signalling in AD.
Observation of valence band electron emission from n-type silicon field emitter arrays (1999)

Electron emission from the valence band of n-type Si field emitter arrays is reported. High electrostatic field at the surface of Si was achieved by reducing the radius of the emitter tip. Using oxidation sharpening, 1 μm aperture polycrystalline Si gate, n-type Si field emitter arrays with small tip radius (∼10 nm) were fabricated. Three distinct emission regions were observed: conduction band emission at low gate voltages, saturated current emission from the conduction band at intermediate voltages, and valence band plus conduction band emission at high gate voltages. Emission currents at low and high voltages obey the Fowler–Nordheim theory. The ratio of the slopes of the corresponding Fowler–Nordheim fits for these two regions is 1.495 which is in close agreement with the theoretical value of 1.445.
Exendin-4 stimulates both beta-cell replication and neogenesis, resulting in increased beta-cell mass and improved glucose tolerance in diabetic rats. (1999)

Diabetes is a disease of increasing prevalence in the general population and of unknown cause. Diabetes is manifested as hyperglycemia due to a relative deficiency of the production of insulin by the pancreatic beta-cells. One determinant in the development of diabetes is an inadequate mass of beta-cells, either absolute (type 1, juvenile diabetes) or relative (type 2, maturity-onset diabetes). Earlier, we reported that the intestinal hormone glucagon-like peptide I (GLP-I) effectively augments glucose-stimulated insulin secretion. Here we report that exendin-4, a long-acting GLP-I agonist, stimulates both the differentiation of beta-cells from ductal progenitor cells (neogenesis) and proliferation of beta-cells when administered to rats. In a partial pancreatectomy rat model of type 2 diabetes, the daily administration of exendin-4 for 10 days post-pancreatectomy attenuates the development of diabetes. We show that exendin-4 stimulates the regeneration of the pancreas and expansion of beta-cell mass by processes of both neogenesis and proliferation of beta-cells. Thus, GLP-I and analogs thereof hold promise as a novel therapy to stimulate beta-cell growth and differentiation when administered to diabetic individuals with reduced beta-cell mass.
CAP37, a neutrophil-derived multifunctional inflammatory mediator (1995)

Cationic antimicrobial protein of M(r) 37 kDa (CAP37) is a multifunctional protein isolated from the granules of human neutrophils, which has important implications in host defense and inflammation. CAP37 was initially recognized for its strong antibiotic activity against Gram-negative bacteria and was viewed as a component of the oxygen-independent killing mechanism of the neutrophil. However, we now know that CAP37 has more far reaching and important functions. It is a physiological protein released during inflammation with a high potential of regulating monocyte/macrophage functions, such as chemotaxis, increased survival, and differentiation. Recently, it has been demonstrated that CAP37 binds endotoxin. It has the structure of a serine esterase but lacks enzymatic activity. The bactericidal and endotoxin binding domains of the molecule have been delineated. The identification of functional peptides should provide new insight into the mechanisms of endotoxin binding, antimicrobial activity, and chemotaxis and in the long term provide key insights into therapies for treating infections and endotoxic shock.
Long-distance entanglement-based quantum key distribution (2000)

A detailed analysis of quantum key distribution employing entangled states is presented. We tested a system based on photon pairs entangled in energy-time optimized for long-distance transmission. It is based on a Franson-type setup for monitoring quantum correlations, and uses a protocol analogous to the Bennett-Brassard 1984 protocol. Passive-state preparation is implemented by polarization multiplexing in the interferometers. We distributed a sifted key of 0.4 Mbit at a raw rate of 134 Hz and with an error rate of 8.6% over a distance of 8.5 km. We thoroughly discuss the noise sources and practical difficulties associated with entangled-state systems. Finally, the level of security offered by this system is assessed and compared with that of faint-laser-pulse systems.
Morphological Changes in the Overall <b><i>Mycobacterium tuberculosis </i></b>H<sub>37</sub>Ra Cell Shape and Cytoplasm Homogeneity due to <b><i>Mutellina purpurea</i></b> L. Essential Oil and Its Main Constituents (2015)

In this study, the low molecular weight compounds of mono- and sesquiterpenes penetrated/destabilized the complex mycobacterial cell wall and decreased its viability. There is a need for further experiments to explain the mechanism of action of these small particles.