gebhart/patrepeval huggingface dataset:
Biochemical and Structural Characterization of HDAC8 Mutants Associated with Cornelia de Lange Syndrome Spectrum Disorders (2015)

Cornelia de Lange Syndrome (CdLS) spectrum disorders are characterized by multiple organ system congenital anomalies that result from mutations in genes encoding core cohesin proteins SMC1A, SMC3, and RAD21, or proteins that regulate cohesin function such as NIPBL and HDAC8. HDAC8 is the Zn(2+)-dependent SMC3 deacetylase required for cohesin recycling during the cell cycle, and 17 different HDAC8 mutants have been identified to date in children diagnosed with CdLS. As part of our continuing studies focusing on aberrant HDAC8 function in CdLS, we now report the preparation and biophysical evaluation of five human HDAC8 mutants: P91L, G117E, H180R, D233G, and G304R. Additionally, the double mutants D233G-Y306F and P91L-Y306F were prepared to enable cocrystallization of intact enzyme-substrate complexes. X-ray crystal structures of G117E, P91L-Y306F, and D233G-Y306F HDAC8 mutants reveal that each CdLS mutation causes structural changes that compromise catalysis and/or thermostability. For example, the D233G mutation disrupts the D233-K202-S276 hydrogen bond network, which stabilizes key tertiary structure interactions, thereby significantly compromising thermostability. Molecular dynamics simulations of H180R and G304R HDAC8 mutants suggest that the bulky arginine side chain of each mutant protrudes into the substrate binding site and also causes active site residue Y306 to fluctuate away from the position required for substrate activation and catalysis. Significantly, the catalytic activities of most mutants can be partially or fully rescued by the activator N-(phenylcarbamothioyl)-benzamide, suggesting that HDAC8 activators may serve as possible leads in the therapeutic management of CdLS.
Neuronal Death in Amyotrophic Lateral Sclerosis Is Apoptosis (1999)

The mechanisms for neurodegeneration in amyotrophic lateral sclerosis (ALS) are not understood. We found that motor neuron degeneration in ALS structurally resembles apoptosis. The progression of neuronal death is divisible into 3 sequential stages: chromatolysis, somatodendritic attrition, and apoptosis. In ALS spinal cord anterior horn and motor cortex, DNA fragmentation is detectable in situ and in gels and is internucleosomal, occurring in the presence of DNA fragmentation factor-45/40 activation and increased caspase-3 activity. By immunoblotting, changes occur in the subcellular distribution of cell death proteins that would promote apoptosis. In selectively vulnerable CNS regions in ALS compared with controls, the proapoptotic proteins Bax and Bak are elevated in the mitochondrial-enriched membrane compartment, but are reduced or unchanged in the cytosol. In contrast, the antiapoptotic protein Bcl-2 is decreased in the mitochondrial-enriched membrane compartment of vulnerable regions in ALS, but is increased in the cytosol, whereas Bcl-xL levels are unchanged in both subcellular compartments. Coimmunoprecipitation experiments showed that Bax-Bax interactions are greater in the mitochondrial-enriched membrane compartment of ALS motor cortex compared with controls, whereas Bax-Bcl-2 interactions are lower in the membrane compartment of ALS motor cortex compared with controls. We conclude that a PCD mechanism, involving cytosol-to-membrane and membrane-to-cytosol redistribution of cell death proteins and caspase-3 activation, participates in the pathogenesis of ALS.
The role of Co in sulphidised Co–Mo hydrodesulphurisation catalysts supported on carbon and alumina (1987)

The thiophene hydrodesulphurisation activities of cobalt sulphide catalysts supported on activated carbon have been measured in a flow microreactor operating at atmospheric pressure. The cobalt content was varied between 1.3 and 13.3 wt% Co, and the oxidic precursor catalysts were dried by three different procedures. Structural characteristics and the degree of Co dispersion in the oxidic precursor and in the sulphidised state of the catalysts were obtained by X-ray photoelectron spectroscopy. The oxidic cobalt phase present in the precursor catalysts was found to be inhomogeneously dispersed over the carbon carrier surface. Dispersion decreased significantly during catalyst sulphidation. XPS results showed that the cobalt was fully sulphidised, although sulphur was found to be present in excess of the amount corresponding to stoichiometric Co9S8.The catalysts demonstrated very high hydrodesulphurisation activities, which were by far superior to those of corresponding carbon- or alumina-supported molybdenum catalysts. By extrapolation of the inverse activities to zero loading the activities of the optimally dispersed cobalt and molybdenum sulphide were determined. Comparison of the activity of carbon-supported Co–Mo with the activities of the optimally dispersed catalyst supported on carbon demonstrated that the so-called promoter effect in sulphidised Co–Mo catalysts can be explained completely by the exceptionally high catalytic activity of cobalt sites and showed that the role of MoS2 in these catalysts is mainly to function as a support for optimally dispersed cobalt ions.
Structure and Function of VEGF/VEGF-receptor System Involved in Angiogenesis. (2001)

Angiogenesis is an essential biological process not only in embryogenesis but also in the progression of a variety of major diseases such as cancer, diabetes and inflammation. Vascular endothelial growth factor (VEGF) family and its receptor system has been shown to be the fundamental regulator in the cell signaling of angiogenesis. Other systems, Angiopoietin-Tie and EphrinB2-Eph4B etc. are also involved in and cooperate with VEGF system to establish the dynamic blood vessel structures. VEGF receptor belongs to PDGF receptor super-gene family, and carries seven Ig-domains in the extracellular region and a tyrosine kinase domain in the intracellular region. Three members of VEGF receptor family, Flt-1, KDR/Flk-1 and Flt-4, have unique characteristics in terms of the signal transduction, and regulate angiogenesis, lymphangiongenesis and vascular permeability. Further studies on VEGF-VEGF receptor system may significantly facilitate our understanding on the physiological as well as pathological vascular systems in the body and the development of new strategies to control and suppress the major diseases in humans.
DNA lesions, inducible DNA repair, and cell division: three key factors in mutagenesis and carcinogenesis. (1993)

DNA lesions that escape repair have a certain probability of giving rise to mutations when the cell divides. Endogenous DNA damage is high: 10(6) oxidative lesions are present per rat cell. An exogenous mutagen produces an increment in lesions over the background rate of endogenous lesions. The effectiveness of a particular lesion depends on whether it is excised by a DNA repair system and the probability that it gives rise to a mutation when the cell divides. When the cell divides, an unrepaired DNA lesion has a certain probability of giving rise to a mutation. Thus, an important factor in the mutagenic effect of an exogenous agent whether it is genotoxic or non-genotoxic, is the increment it causes over the background cell division rate (mitogenesis) in cells that appear to matter most in cancer, the stem cells, which are not on their way to being discarded. Increasing their cell division rate increases mutation and therefore cancer. There is little cancer from nondividing cells. Endogenous cell division rates can be influenced by hormone levels, decreased by calorie restriction, or increased by high doses of chemicals. If both the rate of DNA lesions and cell division are increased, then there will be a multiplicative effect on mutagenesis (and carcinogenesis), for example, by high doses of a mutagen that also increases mitogenesis through cell killing. The defense system against reactive electrophilic mutagens, such as the glutathione transferases, are also almost all inducible and buffer cells against increments in active forms of chemicals that can cause DNA lesions. A variety of DNA repair defense systems, almost all inducible, buffer the cell against any increment in DNA lesions. Therefore, the effect of a particular chemical insult depends on the level of each defense, which in turn depends on the past history of exposure. Exogenous agents can influence the induction and effectiveness of these defenses. Defenses can be partially disabled by lack of particular micronutrients in the diet (e.g., antioxidants).
Soft lithographic methods for nano-fabrication (1997)

Soft lithography is a low-cost, non-photolithographic strategy for carrying out micro- and nano-fabrication. This unconventional approach consists of techniques based on self-assembly and replica molding of organic molecules and polymeric materials. Four such techniques, microcontact printing (µCP), replica molding, micromolding in capillaries (MIMIC), and microtransfer molding (µTM), have been demonstrated for the fabrication of patterns and structures of a variety of materials with dimension ≥30 nm. This review describes these techniques and their applications in fabrication and manufacturing at the sub-100 nm scale.
Embolization of arteriovenous malformations with peripheral aneurysms using ethylene vinyl alcohol copolymer (1991)

The authors report three cases of arteriovenous malformations (AVM's) with aneurysms arising from the feeding artery; all were successfully treated with a new nonadhesive liquid embolic material, ethylene vinyl alcohol copolymer (EVAL). In two patients the AVM's were totally removed without difficulty, and in one the AVM was managed conservatively after embolization. No new neurological deficits appeared during or after embolization. After road-mapping techniques, EVAL was injected slowly until the feeding artery and aneurysm were completely obliterated. This embolic agent is easy to handle and is considered safe compared with other adhesive liquid embolic agents, such as isobutyl-2-cyanoacrylate or n-butyl cyanoacrylate. It is concluded that EVAL is an excellent agent for embolizing an AVM with a peripheral aneurysm on the feeding artery.
Toward defining the autoimmune microbiome for type 1 diabetes (2010)

Several studies have shown that gut bacteria have a role in diabetes in murine models. Specific bacteria have been correlated with the onset of diabetes in a rat model. However, it is unknown whether human intestinal microbes have a role in the development of autoimmunity that often leads to type 1 diabetes (T1D), an autoimmune disorder in which insulin-secreting pancreatic islet cells are destroyed. High-throughput, culture-independent approaches identified bacteria that correlate with the development of T1D-associated autoimmunity in young children who are at high genetic risk for this disorder. The level of bacterial diversity diminishes overtime in these autoimmune subjects relative to that of age-matched, genotype-matched, nonautoimmune individuals. A single species, Bacteroides ovatus, comprised nearly 24% of the total increase in the phylum Bacteroidetes in cases compared with controls. Conversely, another species in controls, represented by the human firmicute strain CO19, represented nearly 20% of the increase in Firmicutes compared with cases overtime. Three lines of evidence are presented that support the notion that, as healthy infants approach the toddler stage, their microbiomes become healthier and more stable, whereas, children who are destined for autoimmunity develop a microbiome that is less diverse and stable. Hence, the autoimmune microbiome for T1D may be distinctly different from that found in healthy children. These data also suggest bacterial markers for the early diagnosis of T1D. In addition, bacteria that negatively correlated with the autoimmune state may prove to be useful in the prevention of autoimmunity development in high-risk children.
Central Nervous System-directed AAV2/5-Mediated Gene Therapy Synergizes with Bone Marrow Transplantation in the Murine Model of Globoid-cell Leukodystrophy (2006)

Globoid-cell leukodystrophy (GLD) is a rapidly progressing inherited neurodegenerative disorder caused by a deficiency in galactosylceramidase activity. Previous studies in the murine model of GLD (Twitcher mouse) have shown that both bone marrow transplantation (BMT) and central nervous system (CNS)-directed gene therapy can be moderately effective at ameliorating certain aspects of GLD. As BMT and CNS-directed gene therapy target fundamentally different tissues, we tested the hypothesis that combining these disparate therapies would be more efficacious than either therapy alone. Mice receiving myeloreductive conditioning at birth followed by syngeneic BMT had approximately 25-35% donor chimerism. Untreated Twitcher mice, Twitcher mice treated with BMT alone, AAV2/5 alone, or a combination of BMT and AAV2/5 had mean lifespans of 39, 44, 49, and 104 days, respectively. Twitcher mice treated with a combination of BMT and AAV2/5 also had significantly improved performance in several behavioral tests and greater reduction in demyelination, astrocytosis, and macrophage infiltration compared to untreated Twitcher mice or mice that received either therapy alone. These data suggest that CNS-directed gene therapy synergizes with BMT. The combination of these disparate therapeutic approaches may form the basis for more effective treatment of this inherited neurodegenerative disorder.
Methyl‐CpG‐binding proteins (2001)

CpG methylation, the most common epigenetic modification of vertebrate genomes, is primarily associated with transcriptional repression. MeCP2, MBD1, MBD2, MBD3 and MBD4 constitute a family of vertebrate proteins that share the methyl-CpG-binding domain (MBD). The MBD, consisting of about 70 residues, possesses a unique alpha/beta-sandwich structure with characteristic loops, and is able to bind single methylated CpG pairs as a monomer. All MBDs except MBD4, an endonuclease that forms a complex with the DNA mismatch-repair protein MLH1, form complexes with histone deacetylase. It has been established that MeCP2, MBD1 and MBD2 are involved in histone deacetylase-dependent repression and it is likely that this is also the case for MBD3. The current model proposes that MBD proteins are involved in recruiting histone deacetylases to methyl CpG-enriched regions in the genome to repress transcription. The lack of selectivity for MBD association with particular DNA sequences indicates that other mechanisms account for their recruitment to particular regions in the genome.
High moment CoFe thin films by electrodeposition (1987)

An electrodeposition process was developed for making cobalt-iron thin film. It was found that the electroplated, zero magnetostrictive Co <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">90</inf> Fe <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">10</inf> (wt%) alloy thin film has a very high saturation moment (Bs=19 KG) and fairly good soft magnetic properties, which appears to make it a potential replacement for permalloy as pole material in high density longitudinal and perpendicular recording. The magnetic properties of CoFe thin films were investigated. Thin film heads using CoFe-as the pole-piece material were fabricated and evaluated using 5-1/4 inch sputtered CoNiCr thin film disks with Hc= 1000 Oe, Br= 9,000 Gauss and a 300 A thick overcoat. -45 dB overwrite was achieved with 0.2 micron head-disk spacing.
Identificación biométrica en gemelos (2014)

Análisis de las biometrías más difundidas y sistemas biométricos más utilizados, cuestionando la influencia que posee la genética en la generación de los patrones de identificación, y cómo la formación congénita y posteriores factores ambientales conformarán detalles que permitan una correcta individualización en gemelos.
Current status of mucins in the diagnosis and therapy of cancer (2009)

Mucins are the most abundant high molecular weight glycoproteins in mucus. Their nature and glycosylation content dictates the biochemical and biophysical properties of viscoelastic secretions, pointing out an important role in diverse biological functions, such as differentiation, cell adhesions, immune responses, and cell signaling. Mucins are expressed in tubular organs by specialized epithelial cells in the body. Their aberrant expression is well documented in a variety of inflammatory or malignant diseases. From a prognosis point of view, their expression and alterations in glycosylation are associated with the development and progression of malignant diseases. Therefore, mucins can be used as valuable markers to distinguish between normal and disease conditions. Indeed, this alteration in glycosylation patterns generates several epitopes in the oligosaccharide side chains that can be used as diagnostic and/or prognostic markers. Furthermore, these characteristic tumor-associated epitopes are extensively used as appropriate immunotargets of malignant epithelial cells. Therefore, in an effort to detect and treat cancer at the earliest stage possible, mucins are analyzed as potential markers of disease for diagnosis, progression, and for therapeutic purposes. In this review, we focused on the current status of the distribution of mucins in normal and pathologic conditions and their clinical use both in cancer diagnosis and therapeutics treatments.
Investigating Topic Models' Capabilities in Expression Microarray Data Classification (2012)

In recent years a particular class of probabilistic graphical models-called topic models-has proven to represent an useful and interpretable tool for understanding and mining microarray data. In this context, such models have been almost only applied in the clustering scenario, whereas the classification task has been disregarded by researchers. In this paper, we thoroughly investigate the use of topic models for classification of microarray data, starting from ideas proposed in other fields (e.g., computer vision). A classification scheme is proposed, based on highly interpretable features extracted from topic models, resulting in a hybrid generative-discriminative approach; an extensive experimental evaluation, involving 10 different literature benchmarks, confirms the suitability of the topic models for classifying expression microarray data.
Gabor-Based Region Covariance Matrices for Face Recognition (2008)

This paper presents a new method for human face recognition by utilizing Gabor-based region covariance matrices as face descriptors. Both pixel locations and Gabor coefficients are employed to form the covariance matrices. Experimental results demonstrate the advantages of this proposed method.
Prospective randomized study of the efficacy of hydrogel, hydrocolloid, and saline solution—moistened dressings on the management of pressure ulcers (1993)

A total of 67 patients with pressure ulcers were randomized into one of three treatment modalities: hydrogel sheet dressing, hydrocolloid, or wet-to-moist gauze. Safety, efficacy, and physical attributes of the three dressings were evaluated. No statistical significance was found in wound healing rate among the three treatments. Hydrogel sheets were advantageous in allowing wound visualization without dressing or wound disruption.
Resonant and non-resonant generation and focusing of surface plasmons with circular gratings (2006)

We report the generation and focusing of surface plasmon polariton (SPP) waves from normally incident light on a planar circular grating milled into a silver film. The focusing mechanism is explained by using a simple coherent interference model of SPP generation on the circular grating by the incident field. Experimental results concur well with theoretical predictions and highlight the requirement for the phase matching of SPP sources in the grating to achieve the maximum enhancement of the SPP wave at the focal point. NSOM measurements show that the plasmonic lens achieves more than a 10-fold intensity enhancement over the intensity of a single ring of the in-plane field components at the focus when the grating design is tuned to the SPP wavelength. We discuss the technique's adaptability for surface enhanced nano-scale spectroscopy.
Control of the size for octahedral FePt nanoparticles and their magnetic properties (2005)

Octahedral FePt nanoparticles were prepared by the alternate deposition of FePt and MgO layers on MgO(001) single crystal substrates. The formation of highly ordered L1/sub 0/ structure with the [001] orientation perpendicular to the plane was confirmed by X-ray diffraction. Cross-sectional transmission electron microscope observation clearly showed that the size of the octahedral FePt nanoparticles can be controlled by the repetition number of FePt and MgO layers.
Xylanase from the extremely thermophilic bacterium "Caldocellum saccharolyticum": overexpression of the gene in Escherichia coli and characterization of the gene product (1990)

A xylanase encoded by the xynA gene of the extreme thermophile "Caldocellum saccharolyticum" was overexpressed in Escherichia coli by cloning the gene downstream from the temperature-inducible lambda pR and pL promoters of the expression vector pJLA602. Induction of up to 55 times was obtained by growing the cells at 42 degrees C, and the xylanase made up to 20% of the whole-cell protein content. The enzyme was located in the cytoplasmic fraction in E. coli. The temperature and pH optima were determined to be 70 degrees C and pH 5.5 to 6, respectively. The xylanase was stable for at least 72 h if incubated at 60 degrees C, with half-lives of 8 to 9 h at 70 degrees C and 2 to 3 min at 80 degrees C. The enzyme had high activity on xylan and ortho-nitrophenyl beta-D-xylopyranoside and some activity on carboxymethyl cellulose and para-nitrophenyl beta-D-cellobioside. The gene was probably expressed from its own promoter in E. coli. Translation of the xylanase overproduced in E. coli seemed to initiate at a GTG codon and not at an ATG codon as previously determined.
Surface Morphologies and Electrical Properties of (Ba, Sr)TiO3 Films Prepared by Two-Step Deposition of Liquid Source Chemical Vapor Deposition (1995)

Protrusions of (Ba, Sr)TiO 3 (BST) crystallites were found to appear on BST film surfaces prepared by liquid source chemical vapor deposition (CVD) at a substrate temperature T s =420° C and a reactor pressure P =1.5 Torr. Such protrusions were successfully suppressed by two-step deposition, where BST films consisted of a buffer layer and a main layer; the buffer layer was a CVD-BST film about 60 Å thick annealed in N 2 ambient. By this two-step deposition on Pt electrodes, the BST film properties of equivalent SiO 2 thickness t eq =0.56 nm, leakage current J L =1.2×10 -8 A/cm 2 at +1.1 V and dielectric loss tan δ=0.011 were achieved at a total film thickness of 230 Å, along with a coverage of 80% at a trench of aspect ratio 0.65 and sufficiently low absorption current.