gebhart/patrepeval huggingface dataset:
Valproate‐induced hyperammonemia (1982)

A patient with carbamyl phosphate synthetase deficiency had four episodes of hyperammonemia, up to 226 microM, associated with valproate (VPA) treatment. These were accompanied by vomiting, lethargy, and coma. A group of epileptic patients receiving VPA remained asymptomatic but had significantly higher mean plasma ammonium levels when compared to epileptic patients receiving other anticonvulsants: 33.6 +/- 1.9 (SEM) versus 23.6 +/- 1.5 microM. Thus, VPA caused symptomatic hyperammonemia in a patient with an impairment in urea synthesis and resulted in mildly elevated ammonium levels in epileptic patients. These data suggest that ammonium levels should be monitored in patients receiving VPA who exhibit signs of vomiting or lethargy.
Designing Scaffolds to Enhance Transplanted Myoblast Survival and Migration (2006)

Myoblast transplantation is currently limited by poor survival and integration of these cells into host musculature. Transplantation systems that enhance the viability of the cells and induce their outward migration to populate injured muscle may enhance the success of this approach to muscle regeneration. In this study, enriched populations of primary myoblasts were seeded onto delivery vehicles formed from alginate, and the role of vehicle design and local growth factor delivery in cell survival and migration were examined. Only 5 +/- 2.5% of cells seeded into nanoporous alginate gels survived for 24 h and only 4 +/- 0.5% migrated out of the gels. Coupling cell adhesion peptides (G4RGDSP) to the alginate prior to gelling slightly increased the viability of cells within the scaffold to 16 +/- 1.4% and outward migration to 6 +/- 1%. However, processing peptide-modified alginate gels to yield macroporous scaffolds, in combination with sustained delivery of HGF and FGF2 from the material, dramatically increased the viability of seeded cells over a 5-day time course and increased outward migration to 110 +/- 12%. This data indicate long-term survival and migration of myoblasts placed within polymeric delivery vehicles can be greatly increased by appropriate scaffold composition, architecture, and growth factor delivery. This system may be particularly useful in the regeneration of muscle tissue and be broadly useful in the regeneration of other tissues as well.
Reduction of stacking fault density in m-plane GaN grown on SiC (2008)

We report the reduction in basal-plane stacking faults (BSFs) in m-plane GaN grown on m-plane SiC. The origin of BSFs is linked to heteronucleation of m-plane GaN and the presence of N-face basal-plane sidewalls of three-dimensional islands. Graded AlGaN layers help to alleviate mismatched nucleation and the generation of BSFs. Transmission electron microscopy shows that the density of BSFs is decreased to the low 105cm−1. Anisotropy in on-axis x-ray rocking curves, a salient feature in m-plane GaN heteroepitaxial layers, is greatly reduced. A possible mechanism of BSF generation, and the demonstration of improved InGaN∕GaN quantum well emission are presented.
Digital gene expression profiling of primary acute lymphoblastic leukemia cells (2011)

We determined the genome-wide digital gene expression (DGE) profiles of primary acute lymphoblastic leukemia (ALL) cells from 21 patients taking advantage of 'second-generation' sequencing technology. Patients included in this study represent four cytogenetically distinct subtypes of B-cell precursor (BCP) ALL and T-cell lineage ALL (T-ALL). The robustness of DGE combined with supervised classification by nearest shrunken centroids (NSC) was validated experimentally and by comparison with published expression data for large sets of ALL samples. Genes that were differentially expressed between BCP ALL subtypes were enriched to distinct signaling pathways with dic(9;20) enriched to TP53 signaling, t(9;22) to interferon signaling, as well as high hyperdiploidy and t(12;21) to apoptosis signaling. We also observed antisense tags expressed from the non-coding strand of ~50% of annotated genes, many of which were expressed in a subtype-specific pattern. Antisense tags from 17 gene regions unambiguously discriminated between the BCP ALL and T-ALL subtypes, and antisense tags from 76 gene regions discriminated between the 4 BCP subtypes. We observed a significant overlap of gene regions with alternative polyadenylation and antisense transcription (P<1 × 10(-15)). Our study using DGE profiling provided new insights into the RNA expression patterns in ALL cells.
Cell type-specific response to growth on soft materials (2005)

Many cell types respond to forces as acutely as they do to chemical stimuli, but the mechanisms by which cells sense mechanical stimuli and how these factors alter cellular structure and function in vivo are far less explored than those triggered by chemical ligands. Forces arise both from effects outside the cell and from mechanochemical reactions within the cell that generate stresses on the surface to which the cells adhere. Several recent reviews have summarized how externally applied forces may trigger a cellular response (Silver FH and Siperko LM. Crit Rev Biomed Eng 31: 255-331, 2003; Estes BT, Gimble JM, and Guilak F. Curr Top Dev Biol 60: 91-126, 2004; Janmey PA and Weitz DA. Trends Biochem Sci 29: 364-370, 2004). The purpose of this review is to examine the information available in the current literature describing the relationship between a cell and the rigidity of the matrix on which it resides. We will review recent studies and techniques that focus on substrate compliance as a major variable in cell culture studies. We will discuss the specificity of cell response to stiffness and discuss how this may be important in particular tissue systems. We will attempt to link the mechanoresponse to real pathological states and speculate on the possible biological significance of mechanosensing.
Deubiquitinating function of ataxin-3: Insights from the solution structure of the Josephin domain (2005)

Spinocerebellar ataxia type 3 is a human neurodegenerative disease resulting from polyglutamine tract expansion. The affected protein, ataxin-3, which contains an N-terminal Josephin domain followed by tandem ubiquitin (Ub)-interacting motifs (UIMs) and a polyglutamine stretch, has been implicated in the function of the Ub proteasome system. NMR-based structural analysis has now revealed that the Josephin domain binds Ub and has a papain-like fold that is reminiscent of that of other deubiquitinases, despite primary sequence divergence but consistent with its deubiqutinating activity. Mutation of the catalytic Cys enhances the stability of a complex between ataxin-3 and polyubiquitinated proteins. This effect depends on the integrity of the UIM region, suggesting that the UIMs are bound to the substrate polyubiquitin during catalysis. We propose that ataxin-3 functions as a polyubiquitin chain-editing enzyme.
Second-order contributions to relativistic time delay in the parametrized post-Newtonian formalism (1983)

Using a parametrized expansion of the solar metric to second order in the Newtonian potential, we calculate the relativistic delay in the round-trip travel time of a radar signal reflected from a nearby planet. We find that one second-order contribution to the delay is on the order of ten nanoseconds, which is comparable to the uncertainties in present-day experiments involving the Viking spacecraft.
Opening and Closing Motions in the Periplasmic Vitamin B12 Binding Protein BtuF (2006)

BtuF is the periplasmic binding protein (PBP) in the vitamin B(12) uptake system in Escherichia coli where it is associated with the ABC transporter BtuCD. When the ligand binds, PBPs generally display large conformational changes, commonly termed the Venus flytrap mechanism. BtuF belongs to a group of PBPs that, on the basis of crystal structures, does not appear to display such behavior. Using 480 ns multicopy molecular dynamics simulations of apo and holo forms of the protein, we investigate the dynamics of BtuF. We find BtuF to be more flexible than previously assumed, displaying clear opening and closing motions which are more pronounced in the apo form. The protein behavior is compatible with a PBP functional model that postulates a closed conformation for the ligand-bound state, whereas the empty form fluctuates between open and closed conformations. Elastic network normal-mode analysis suggests that all BtuF-like PBPs are capable of similar opening and closing motions. It also makes the typical Venus flytrap domain motions a likely common means of how PBP-ABC transporter interaction could occur.
Key agreement in dynamic peer groups (2000)

As a result of the increased popularity of group-oriented applications and protocols, group communication occurs in many different settings: from network multicasting to application layer tele- and videoconferencing. Regardless of the application environment, security services are necessary to provide communication privacy and integrity. This paper considers the problem of key agreement in dynamic peer groups. (Key agreement, especially in a group setting, is the stepping stone for all other security services.) Dynamic peer groups require not only initial key agreement (IKA) but also auxiliary key agreement (AKA) operations, such as member addition, member deletion, and group fusion. We discuss all group key agreement operations and present a concrete protocol suite, CLIQUES, which offers complete key agreement services. CLIQUES is based on multiparty extensions of the well-known Diffie-Hellman key exchange method. The protocols are efficient and provably secure against passive adversaries.
Antigen binding and biological activities of engineered mutant chimeric antibodies with human tumor specificities (1990)

The constant region of the human gamma 1 chain was mutated either by deleting the second domain (CH2) or by mutating the two hinge region cysteine residues, normally involved in the inter-heavy chain disulfide bond formation, to serines. The effects of these mutations on chain assembly, antigen binding, complement-dependent cytotoxicity (CDC), and antibody-dependent cellular cytotoxicity (ADCC) were measured after expressing the human constant regions together with mouse variable regions encoding anti-tumor cell specificities. The CH2-deleted chimeric antibody was found to have increased antigen binding activity and little (ADCC) or no (CDC) biological activity. The cysteine to serine hinge region mutant antibody had normal or slightly reduced antigen binding activity, greatly reduced ADCC activity, and a reduced, but still significant, ability to mediate CDC. These results reflect the complexity of the interactions between the immunoglobulin domains and their role in balancing the antigen binding and effector functions of antibodies. They suggest further that such antibodies may be useful in applications, such as the in vivo imaging of tumors, where the loss of effector function (e.g., Fc receptor binding) is desired.
Hybrid Video Coding Based on High-Resolution Displacement Vectors (2001)

Common motion compensated hybrid video coding standards such as H.263, MPEG-1, MPEG-2, MPEG-4 are based on a fractional-pel displacement vector resolution of 1/2-pel. Recent approaches like MPEG-4 ACE and H.26L (TML5) use a 1/4-pel displacement vector resolution. In order to estimate and compensate fractional-pel displacements, the image signal has to be interpolated. Therefore different interpolation filters are used in the standards. In this paper an enhanced motion compensated hybrid video codec is presented, which is based on high-resolution displacement vectors. For this purpose, displacement vector resolutions of 1/8- and 1/16-pel are used in order to improve the motion compensated prediction and the coding efficiency. The coding results for different resolutions are presented and the dependence on different interpolation filters is analysed. It turned out that the higher the displacement vector resolution is, the higher the influence of the filter on the coding gain is. A gain up to 3.0 dB PSNR is obtained compared to a hybrid video codec, which is based on 1/2-pel resolution and bilinear interpolation like H.263, MPEG-1,2,4. Compared to 1/4-pel displacement vector resolution and a wiener interpolation filter as it is used in MPEG-4 ACE and H.26L (TML5), a gain up to 1.0 dB PSNR is obtained.
The Immune Modulator FTY720 Targets Sphingosine 1-Phosphate Receptors (2002)

Immunosuppressant drugs such as cyclosporin have allowed widespread organ transplantation, but their utility remains limited by toxicities, and they are ineffective in chronic management of autoimmune diseases such as multiple sclerosis. In contrast, the immune modulating drug FTY720 is efficacious in a variety of transplant and autoimmune models without inducing a generalized immunosuppressed state and is effective in human kidney transplantation. FTY720 elicits a lymphopenia resulting from a reversible redistribution of lymphocytes from circulation to secondary lymphoid tissues by unknown mechanisms. Using FTY720 and several analogs, we show now that FTY720 is phosphorylated by sphingosine kinase; the phosphorylated compound is a potent agonist at four sphingosine 1-phosphate receptors and represents the therapeutic principle in a rodent model of multiple sclerosis. Our results suggest that FTY720, after phosphorylation, acts through sphingosine 1-phosphate signaling pathways to modulate chemotactic responses and lymphocyte trafficking.
A 60 GHz Power Amplifier With 14.5 dBm Saturation Power and 25% Peak PAE in CMOS 65 nm SOI (2010)

A 60 GHz wideband power amplifier (PA) is fabricated in a standard CMOS SOI 65 nm process. The PA is based on two cascode stages. Input, output and inter-stage matching use coplanar wave guide (CPW) transmission lines that have low losses thanks to the high-resistivity SOI substrate (3 kΩ · cm). The PA measurements are carried out for supply voltages V <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">DD</sub> going from 1.2 V to 2.6 V and achieve a saturation power of 10 dBm to 16.5 dBm respectively. The peak power-added efficiency (PAE) is higher than 20% for all applied V <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">DD</sub> values.
The Penn Discourse TreeBank 2.0. (2008)

We present the second version of the Penn Discourse Treebank, PDTB-2.0, describing its lexically-grounded annotations of discourse relations and their two abstract object arguments over the 1 million word Wall Street Journal corpus. We describe all aspects of the annotation, including (a) the argument structure of discourse relations, (b) the sense annotation of the relations, and (c) the attribution of discourse relations and each of their arguments. We list the differences between PDTB-1.0 and PDTB-2.0. We present representative statistics for several aspects of the annotation in the corpus. 1.
Fertility of superovulated ewes after intrauterine or oviducal insemination with low numbers of fresh or frozen-thawed spermatozoa (1993)

Two experiments investigated the effects of number of spermatozoa inseminated and time and site of insemination of fresh and frozen-thawed semen on fertility in Merino ewes treated with intravaginal progestagen pessaries and a combination of pregnant mare serum gonadotrophin and follicle stimulating hormone. In Experiment 1, ewes were inseminated in the uterus or oviducts with totals of 10(4), 10(5), 10(6) or 10(7) fresh spermatozoa 44 or 68 h after pessary removal. Ova recovered 48 h later were classified as fertilized if they had cleaved. Proportion of fertile ewes (ewes with fertilized ova per ewes inseminated) and fertilization rate of ova (ova fertilized per ova recovered) were higher for inseminations 44 h (63% and 45%) than 68 h (38% and 19%) after pessary removal (P < 0.001). More ewes were fertile after oviducal (61%) than after intrauterine insemination (39%; P < 0.05), and with high (10(6) and 10(7)) than with low (10(4) and 10(5)) doses of spermatozoa for intrauterine (54% v. 24%; P < 0.05) but not for oviducal inseminations (63% v. 59%). Fertilization of ova was better after oviducal than after intrauterine inseminations (44% v. 22%; P < 0.001), and with high than with low doses of spermatozoa (45% v. 21%; P < 0.001). In Experiment 2, ewes were inseminated with 10(5), 5 x 10(5) or 10(6) total fresh or frozen-thawed spermatozoa in the uterus or oviducts, 44 h after pessary removal.(ABSTRACT TRUNCATED AT 250 WORDS)
Revisiting the dystrophin-ATP connection: How half a century of research still implicates mitochondrial dysfunction in Duchenne Muscular Dystrophy aetiology (2015)

Duchenne Muscular Dystrophy (DMD) is a fatal neuromuscular disease that is characterised by dystrophin-deficiency and chronic Ca(2+)-induced skeletal muscle wasting, which currently has no cure. DMD was once considered predominantly as a metabolic disease due to the myriad of metabolic insufficiencies evident in the musculature, however this aspect of the disease has been extensively ignored since the discovery of dystrophin. The collective historical and contemporary literature documenting these metabolic nuances has culminated in a series of studies that importantly demonstrate that metabolic dysfunction exists independent of dystrophin expression and a mild disease phenotype can be expressed even in the complete absence of dystrophin expression. Targeting and supporting metabolic pathways with anaplerotic and other energy-enhancing supplements has also shown therapeutic value. We explore the hypothesis that DMD is characterised by a systemic mitochondrial impairment that is central to disease aetiology rather than a secondary pathophysiological consequence of dystrophin-deficiency.
Synthesis and Characterization of Proteoglycan-Mimetic Graft Copolymers with Tunable Glycosaminoglycan Density (2014)

Proteoglycans (PGs) are important glycosylated proteins found on the cell surface and in the extracellular matrix. They are made up of a core protein with glycosaminoglycan (GAG) side chains. Variations in composition and number of GAG side chains lead to a vast array of PG sizes and functions. Here we present a method for the synthesis of proteoglycan-mimetic graft copolymers (or neoproteoglycans) with tunable GAG side-chain composition. This is done using three different GAGs: hyaluronan, chondroitin sulfate, and heparin. Hyaluronan is functionalized with a hydrazide-presenting linker. Either chondroitin sulfate or heparin is grafted by the reducing end on to the hyaluronan backbone through reductive amination. PG mimics with heparin or chondroitin sulfate side chains and four different ratios of GAG side chain result in graft copolymers with a wide range of sizes. The chemistry is confirmed through attentuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) and (1)H NMR. Effective hydrodynamic diameter and zeta potential are determined using dynamic light scattering and electrophoretic mobility measurements. Graft copolymers were tested for their ability to bind and deliver basic fibroblast growth factor (FGF-2) to mesenchymal stem cells (MSCs). The chondroitin sulfate-containing graft copolymers successfully deliver FGF-2 to cells from surfaces. The lowest graft density of heparin-containing PG mimic also performs well with respect to growth factor delivery from a surface. This new method for preparation of GAG-based graft copolymers enables a wide range of graft density, and can be used to explore applications of PG mimics as new biomaterials with tunable biochemical and biomechanical functions.
Efecto de enjuagues de fluoruro de sodio al 2 por ciento en la incidencia de caries dental en una población escolarizada (1998)

espanolPara este estudio se seleccionaron al azar 200 ninos de 6 anos y se dividieron en 2 grupos de 100 ninos cada uno (experimental y control), los cuales fueron examinados previo al inicio del estudio y se determinaron los indices CPOD y ceod. De la poblacion originalmente seleccionada, durante el periodo de estudio, deserto el 19% de los ninos, quedando finalmente la muestra conformada por 81 ninos en cada grupo. Al grupo control se les administro una solucion placebo (NaCl 2%) y una solucion de NaF al 2% al grupo experimental por 4 dias consecutivos y se repitio cada 8 meses a manera de asegurar la efectividad del metodo. Los valores iniciales para el indice CPOD fueron de 0,46±0,72 y 0,29±0,62 para el grupo control y experimental respectivamente y para el ceod de 2,02±1,95 para el grupo control y 2,28±1,78 para el experimental, para ambos indices la comparacion estadistica resulto no significativa estadisticamente (P=NS). Despues de 16 meses de tratamiento se observo una reduccion en indice CPOD de 46,5% la cual fue estadisticamente significativa al compararla con el grupo control (P EnglishFor our study, 200 6 year old children were randomly divided into a control and experimental group. The children were examined and the DMFT and deft index were calculated. Control children were given a placebo solution (NaCl 2%), while experimental children were given a 2% NaF mouthrinse, for 4 consecutive days every 8 months, in order to assess its effectiveness as an aticariogenic method. Initial values of DMFT and deft for both groups before treatment were 0,42±0,72 and 0,29±0,62, and 2,02±1,95 y 2,28±1,78 respectively. After 2 year of treatment, experimental group showed a 46,5% statistically significant reduction in the DMFT index (P
Ubiquitination of p27 is regulated by Cdk-dependent phosphorylation and trimeric complex formation (1999)

The cellular abundance of the cyclin-dependent kinase (Cdk) inhibitor p27 is regulated by the ubiquitin-proteasome system. Activation of p27 degradation is seen in proliferating cells and in many types of aggressive human carcinomas. p27 can be phosphorylated on threonine 187 by Cdks, and cyclin E/Cdk2 overexpression can stimulate the degradation of wild-type p27, but not of a threonine 187-to-alanine p27 mutant [p27(T187A)]. However, whether threonine 187 phosphorylation stimulates p27 degradation through the ubiquitin-proteasome system or an alternative pathway is still not known. Here, we demonstrate that p27 ubiquitination (as assayed in vivo and in an in vitro reconstituted system) is cell-cycle regulated and that Cdk activity is required for the in vitro ubiquitination of p27. Furthermore, ubiquitination of wild-type p27, but not of p27(T187A), can occur in G1-enriched extracts only upon addition of cyclin E/Cdk2 or cyclin A/Cdk2. Using a phosphothreonine 187 site-specific antibody for p27, we show that threonine 187 phosphorylation of p27 is also cell-cycle dependent, being present in proliferating cells but undetectable in G1 cells. Finally, we show that in addition to threonine 187 phosphorylation, efficient p27 ubiquitination requires formation of a trimeric complex with the cyclin and Cdk subunits. In fact, cyclin B/Cdk1 which can phosphorylate p27 efficiently, but cannot form a stable complex with it, is unable to stimulate p27 ubiquitination by G1 extracts. Furthermore, another p27 mutant [p27(CK-)] that can be phosphorylated by cyclin E/Cdk2 but cannot bind this kinase complex, is refractory to ubiquitination. Thus throughout the cell cycle, both phosphorylation and trimeric complex formation act as signals for the ubiquitination of a Cdk inhibitor.
Tumor targeting effects of a novel modified paclitaxel-loaded discoidal mimic high density lipoproteins (2013)

cP-d-rHDL served to restrain remodeling process and drug leakage, at the same time reinforce the targeting effect, and could act as a potential drug delivery system for cancer therapy.
Role of inflammation in neurodegenerative diseases (2005)

Although significant advances have been made in our knowledge of degenerative diseases, there remains controversy regarding whether neuroinflammation and microglial activation are beneficial or detrimental. Strategies aimed at both preventing and boosting microglial activation are presently under investigation, and these studies might reveal new potentially effective treatments for these neurological disorders.