gebhart/patrepeval huggingface dataset:
Exposure to acute hypoxia induces a transient DNA damage response which includes Chk1 and TLK1 (2010)

Severe hypoxia has been demonstrated to induce a replication arrest which is associated with decreased levels of nucleotides. Chk1 is rapidly phosphorylated in response to severe hypoxia and in turn deactivates TLK1 through phosphorylation. Loss of Chk1 has been shown to sensitize cells to hypoxia/reoxygenation. After short (acute) exposure to hypoxia this is due to an increased rate of reoxygenation-induced replication restart and subsequent p53-dependent apoptosis. After longer (chronic) exposure to hypoxia S phase cells do not undergo reoxygenation-induced replication restart. Cells exposed to these levels of hypoxia however are sensitive to loss of Chk1. This suggests a new role for Chk1 in the cell cycle response to reoxygenation.
IgM-Enriched Intravenous Immunoglobulin Therapy in Neonatal Sepsis (1988)

Despite the development of newer generation of antibiotics, mortality from neonatal sepsis remains high. In a prospective, randomized study, we investigated the use of IgM-enriched immunoglobulin therapy in neonatal sepsis. Two groups of 30 infants each (matched for gestational age, sex, weight, and other variables) were randomly allocated to receive either antibiotics alone (control group) or antibiotics plus 5 mL/kg/d for four days of IgM-enriched immunoglobulin intravenously (immunotherapy group). Mortality from sepsis in the control group was 20% (6/30), while in the immunotherapy group it was 3.3% (1/30). We conclude that IgM-enriched immunoglobulin therapy in conjunction with antibiotic therapy significantly reduces mortality from neonatal sepsis.
Carbon Nanomaterials in Biosensors: Should You Use Nanotubes or Graphene? (2010)

Abstract From diagnosis of life‐threatening diseases to detection of biological agents in warfare or terrorist attacks, biosensors are becoming a critical part of modern life. Many recent biosensors have incorporated carbon nanotubes as sensing elements, while a growing body of work has begun to do the same with the emergent nanomaterial graphene, which is effectively an unrolled nanotube. With this widespread use of carbon nanomaterials in biosensors, it is timely to assess how this trend is contributing to the science and applications of biosensors. This Review explores these issues by presenting the latest advances in electrochemical, electrical, and optical biosensors that use carbon nanotubes and graphene, and critically compares the performance of the two carbon allotropes in this application. Ultimately, carbon nanomaterials, although still to meet key challenges in fabrication and handling, have a bright future as biosensors.
Measuring the pH environment of DNA delivered using nonviral vectors: Implications for lysosomal trafficking (2002)

The degradation of DNA in lysosomes represents a major obstacle to efficient nonviral gene delivery. The rational design of vectors that overcome this obstacle requires a better understanding of the lysosomal barrier to gene delivery, which in turn requires a means to investigate this intermediate step. To this end, we developed a technique to measure the pH environment of delivered DNA, from which the degree to which vectors avoided trafficking to acidic Iysosomes could be determined. The measured average pH of DNA delivered using poly-L-lysine (PLL) polyplexes was 4.5, suggesting that PLL polyplexes were trafficked to acidic lysosomes. Other vectors could avoid or buffer the pH of Iysosomes as DNA delivered using Lipofectamine Plus, polyethylenimine (PEI), linear polyethylenimine (LPEI), and two degradable poly(β-amino ester)s (poly-1 and poly-2) had average pH values of 7.1, 5.9, 5.0, 6.7, and 6.4, respectively. © 2002 Wiley Periodicals, Inc. Biotechnol Bioeng 78: 503–508, 2002.
Efficient bulk deletes in relational databases (2002)

Many applications require that large amounts of data are deleted from a database - typically, such bulk deletes are carried out periodically and involve old or out-of-date data. If the data is not partitioned in such a way that bulk deletes can be carried out by simply deleting whole partitions, then most current database products execute such bulk delete operations very poorly. The reason is that every record is deleted from each index individually. This paper proposes and evaluates a new class of techniques to support bulk delete operations more efficiently. These techniques outperform the "record-at-a-time" approach implemented in many database products by about an order of magnitude.
The genetic basis of early T-cell precursor acute lymphoblastic leukaemia (2012)

Early T-cell precursor acute lymphoblastic leukaemia (ETP ALL) is an aggressive malignancy of unknown genetic basis. We performed whole-genome sequencing of 12 ETP ALL cases and assessed the frequency of the identified somatic mutations in 94 T-cell acute lymphoblastic leukaemia cases. ETP ALL was characterized by activating mutations in genes regulating cytokine receptor and RAS signalling (67% of cases; NRAS, KRAS, FLT3, IL7R, JAK3, JAK1, SH2B3 and BRAF), inactivating lesions disrupting haematopoietic development (58%; GATA3, ETV6, RUNX1, IKZF1 and EP300) and histone-modifying genes (48%; EZH2, EED, SUZ12, SETD2 and EP300). We also identified new targets of recurrent mutation including DNM2, ECT2L and RELN. The mutational spectrum is similar to myeloid tumours, and moreover, the global transcriptional profile of ETP ALL was similar to that of normal and myeloid leukaemia haematopoietic stem cells. These findings suggest that addition of myeloid-directed therapies might improve the poor outcome of ETP ALL.
Molecular Signatures of Self-Renewal, Differentiation, and Lineage Choice in Multipotential Hemopoietic Progenitor Cells In Vitro (2003)

The molecular mechanisms governing self-renewal, differentiation, and lineage specification remain unknown. Transcriptional profiling is likely to provide insight into these processes but, as yet, has been confined to "static" molecular profiles of stem and progenitors cells. We now provide a comprehensive, statistically robust, and "dynamic" analysis of multipotent hemopoietic progenitor cells undergoing self-renewal in response to interleukin-3 (IL-3) and multilineage differentiation in response to lineage-affiliated cytokines. Cells undergoing IL-3-dependent proliferative self-renewal displayed striking complexity, including expression of genes associated with different lineage programs, suggesting a highly responsive compartment poised to rapidly execute intrinsically or extrinsically initiated cell fate decisions. A remarkable general feature of early differentiation was a resolution of complexity through the downregulation of gene expression. Although effector genes characteristic of mature cells were upregulated late, coincident with morphological changes, lineage-specific changes in gene expression were observed prior to this, identifying genes which may provide early harbingers of unilineage commitment. Of particular interest were genes that displayed differential behavior irrespective of the lineage elaborated, many of which were rapidly downregulated within 4 to 8 h after exposure to a differentiation cue. These are likely to include genes important in self-renewal, the maintenance of multipotentiality, or the negative regulation of differentiation per se.
Reduction of threading dislocation densities in AlN∕sapphire epilayers driven by growth mode modification (2006)

A strategy to reduce the density of threading dislocations (TDs) in AlN epilayers grown on sapphire substrates is reported. The TDs experience a redirection of their line orientation which is found to coincide with imposed increases in both of V/III ratio and overall flux rate leading to the formation of an internal subinterface delineated by the changes in dislocation orientation. Threading dislocations either experience large kinks and then redirect into threading orientation or form dipole half loops via annihilation of redirected threading segments of opposite sign with the latter leading to a significant dislocation density reduction. These phenomena can be accounted for by a transition of growth mode from atomic step flow to two-dimensional layer-by-layer growth which accompanies the imposed changes in V/III ratio and flux. As this occurs, macrosteps (several atomic layers thick) laterally overgrow pre-existing dislocation outcrops. Image forces initiate the redirection processes and create trailing segments parallel to the interface between the advancing macrostep and the surface outcrop. This horizontal segment can be forced to redirect into threading orientation should another macrostep traveling in the opposite direction be encountered. Image forces again nucleate the redirected segment which is then replicated as the crystal grows. A dipole half loop will form if two dislocations with opposite sign are redirected so as to meet each other.
Fully convolutional networks for multi-modality isointense infant brain image segmentation (2016)

The segmentation of infant brain tissue images into white matter (WM), gray matter (GM), and cerebrospinal fluid (CSF) plays an important role in studying early brain development. In the isointense phase (approximately 6-8 months of age), WM and GM exhibit similar levels of intensity in both T1 and T2 MR images, resulting in extremely low tissue contrast and thus making the tissue segmentation very challenging. The existing methods for tissue segmentation in this isointense phase usually employ patch-based sparse labeling on single T1, T2 or fractional anisotropy (FA) modality or their simply-stacked combinations without fully exploring the multi-modality information. To address the challenge, in this paper, we propose to use fully convolutional networks (FCNs) for the segmentation of isointense phase brain MR images. Instead of simply stacking the three modalities, we train one network for each modality image, and then fuse their high-layer features together for final segmentation. Specifically, we conduct a convolution-pooling stream for multimodality information from T1, T2, and FA images separately, and then combine them in high-layer for finally generating the segmentation maps as the outputs. We compared the performance of our approach with that of the commonly used segmentation methods on a set of manually segmented isointense phase brain images. Results showed that our proposed model significantly outperformed previous methods in terms of accuracy. In addition, our results also indicated a better way of integrating multi-modality images, which leads to performance improvement.
Comparative Genomics of the Vitamin B12 Metabolism and Regulation in Prokaryotes (2003)

Using comparative analysis of genes, operons, and regulatory elements, we describe the cobalamin (vitamin B12) biosynthetic pathway in available prokaryotic genomes. Here we found a highly conserved RNA secondary structure, the regulatory B12 element, which is widely distributed in the upstream regions of cobalamin biosynthetic/transport genes in eubacteria. In addition, the binding signal (CBL-box) for a hypothetical B12 regulator was identified in some archaea. A search for B12 elements and CBL-boxes and positional analysis identified a large number of new candidate B12-regulated genes in various prokaryotes. Among newly assigned functions associated with the cobalamin biosynthesis, there are several new types of cobalt transporters, ChlI and ChlD subunits of the CobN-dependent cobaltochelatase complex, cobalt reductase BluB, adenosyltransferase PduO, several new proteins linked to the lower ligand assembly pathway, l-threonine kinase PduX, and a large number of other hypothetical proteins. Most missing genes detected within the cobalamin biosynthetic pathways of various bacteria were identified as nonorthologous substitutes. The variable parts of the cobalamin metabolism appear to be the cobalt transport and insertion, the CobG/CbiG- and CobF/CbiD-catalyzed reactions, and the lower ligand synthesis pathway. The most interesting result of analysis of B12 elements is that B12-independent isozymes of the methionine synthase and ribonucleotide reductase are regulated by B12 elements in bacteria that have both B12-dependent and B12-independent isozymes. Moreover, B12 regulons of various bacteria are thought to include enzymes from known B12-dependent or alternative pathways.
Laboratory animal models in periodontology (1999)

Animal models are needed to objectively evaluate the pathogenesis of human periodontal diseases and its various treatment modalities. Selection of the appropriate animal model depends on the similarity of the periodontium and the nature of the disease to that of humans. The more commonly used animal models for studying the pathogenesis of periodontal disease, use of implants and guided tissue regeneration have been dogs and nonhuman primates. Periodontal disease in rodents has not been found to be as closely related to the human varieties. Rats and hamsters are best suited for caries and calculus research. Ferrets may be a promising new model for studying periodontal disease and calculus formation. Variables unique to each animal species are manifested by a wide range of clinical and histopathological features. Different species have distinct diets, habits, life spans, tissue structures, host defense mechanisms and genetic traits. This article describes the diversity seen in animal models used to study microbiological, immunological, and clinical features of periodontal disease and its prevention and treatment.
The wavelength dilation concept in lightwave networks-implementation and system considerations (1993)

The dilation concept in switching networks is generalized and extended to the wavelength dimension, resulting in a new class of dynamic wavelength-routing cross-connects. These wavelength-dilated switches (WDSs) are reconfigurable and fault-tolerant, and they feature suppressed crosstalk and denser wavelength-spacings. They are scalable, with switch-complexity of alpha N log/sub 2/ N, where alpha is the dilation constant, typically 4.6, and N is the number of ports. It is shown, that by careful wavelength grouping, the crosstalk is reduced significantly. A switch architecture is suggested to fully exploit the advantages of this method. An example is given showing how such a fabric can be used to reduce the coherent crosstalk in wavelength-routing switches based on acoustooptic tunable filters (AOTF), making them practical for networks with subnanometer wavelength spacings. The WDS can be used in a broad range of applications from interconnection networks to wide-area networks (WANs) on a national scale. Large cross connects can support tens of thousands of channels using only few tens of wavelengths.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Direct Conversion of Alcohols to Acetals and H2 Catalyzed by an Acridine-Based Ruthenium Pincer Complex (2009)

The crystallographically characterized ruthenium complex RuHCl(A-(i)Pr-PNP)(CO) (1) [A-(i)Pr-PNP = 4,5-bis-(diisopropylphosphinomethyl)acridine], which bears a nonplanar acridine moiety, catalyzes in a neutral medium the transformation of primary alcohols to the corresponding acetals with the liberation of H(2). In the presence of base, complex 1 catalyzes the dehydrogenative coupling of alcohols to form esters. Acetal formation may involve hemiacetal dehydration to form an enol ether followed by alcohol addition to the double bond.
Effects of the Tumor Microenvironment on the Efficacy of Tumor Immunotherapy (2006)

Cancer immunotherapy utilizes vaccines targeting tumor antigens or tumor endothelium to prevent or regress tumors. Many cancer vaccines are designed to induce antigen-specific effector T cells that migrate to the tumor site. In an optimal situation, the effector T cells penetrate the tumor, release their effector molecules, induce tumor cell death and tumor regression. However, the tumor microenvironment is frequently immunosuppressive and contributes to a state of immune ignorance, impacting on the vaccine's ability to break tolerance to tumor antigen/s. This review discusses the factors in the tumor microenvironment that can affect the efficacy of cancer vaccines. In particular, the review focuses on pathways leading to effector T cell penetration of tumors or the inhibition of this process.
HLA Class II nucleotide sequences, 1992 (1992)

The HLA Class II sequences included in this compilation are taken from publications listed in the papers: Nomenclature for factors of the HLA system, 1991 (1), Nomenclature for factors of the HLA system, 1990 (2), and Nomenclature for factors of the HLA system, 1989 (3). Where discrepancies have arisen between reported sequences, the original authors have been contacted, where possible, and necessary amendments to published sequences have been incorporated into this alignment. Future sequencing may identify errors in this list and we would welcome any evidence that helps to maintain the accuracy of this compilation. In the sequence alignments, identity between residues is indicated by a hyphen (-). An unavailable sequence is indicated by an asterisk (*), gaps in the sequence are inserted to maintain the alignment between different alleles showing variation in amino acid number.
Breast cancer in young women (≤35 years): Genomic aberrations detected by comparative genomic hybridization (2003)

Sporadic breast cancer in young women is different from the one in older patients regarding pathological features and aggressiveness of the tumors, but the spectrum of genetic alterations are largely unknown. We used comparative genomic hybridization (CGH) to analyze DNA copy number changes in 88 tumor samples from women </=35 years of age. Findings were compared to histopathological data including tumor type, grading, lymph nodes and metastasis. Genomic gains clustered to chromosome arms 1q (64.8%), 8q (61.4%), 17q (50.0%), 20q (33.0%), 3q (20.5%), 1p (17.0%), 5p (17.0%) and 15q (17%). Losses were commonly located on 8p (19.3 %), 11q (11.4%), 16q (11.4%), 17p (11.4%) and 18q (10.2%). A comparison with published CGH data from breast carcinomas of similar type and grade showed the following differences: (1) gains were much more frequent than losses, and (2) losses on 8p22-p23 were more prevalent in patients with positive lymph node metastasis (p = 0.02), and Grade III tumors were associated with gains on the long arm of chromosome 8 (p = 0.01). Therefore, alterations in these genomic regions may be responsible for the reduced survival of patients with early onset breast cancer.
CD8+ T Cell Epitope-Flanking Mutations Disrupt Proteasomal Processing of HIV-1 Nef (2005)

CTL play a critical role in the control of HIV and SIV. However, intrinsic genetic instability enables these immunodeficiency viruses to evade detection by CTL through mutation of targeted antigenic sites. These mutations can impair binding of viral epitopes to the presenting MHC class I molecule or disrupt TCR-mediated recognition. In certain regions of the virus, functional constraints are likely to limit the capacity for variation within epitopes. Mutations elsewhere in the protein, however, might still enable immune escape through effects on Ag processing. In this study, we describe the coincident emergence of three mutations in a highly conserved region of Nef during primary HIV-1 infection. These mutations (R69K, A81G, and H87R) flank the HLA B*35-restricted VY8 epitope and persisted to fixation as the early CTL response to this Ag waned. The variant form of Nef showed a reduced capacity to activate VY8-specific CTL, although protein stability and expression levels were unchanged. This effect was associated with altered processing by the proteasome that caused partial destruction of the VY8 epitope. Our data demonstrate that a variant HIV genotype can significantly impair proteasomal epitope processing and substantiate the concept of immune evasion through diminished Ag generation. These observations also indicate that the scale of viral escape may be significantly underestimated if only intraepitope variation is evaluated.
[Effects of losartan on MT3-MMP and TIMP2 mRNA expressions in diabetic rat kidney]. (2004)

MT3-MMP and the TIMP2 mRNA expressions are significantly increased in diabetic rat kidneys. Losartan can prevent the development of diabetic nephropathy and inhibit MT3-MMP and the TIMP2 mRNA expressions in diabetic rat kidneys.
Enriching Word Embeddings Using Knowledge Graph for Semantic Tagging in Conversational Dialog Systems (2015)

Unsupervised word embeddings provide rich linguistic and conceptual information about words. However, they may provide weak information about domain specific semantic relations for certain tasks such as semantic parsing of natural language queries, where such information about words can be valuable. To encode the prior knowledge about the semantic word relations, we present new method as follows: We extend the neural network based lexical word embedding objective function Mikolov, et.al. 2013 by incorporating the information about relationship between entities that we extract from knowledge bases. Our model can jointly learn lexical word representations from free text enriched by the relational word embeddings from relational data (e.g., Freebase) for each type of entity relations. We empirically show on the task of semantic tagging of natural language queries that our enriched embeddings can provide information about not only short-range syntactic dependencies but also long-range semantic dependencies between words. Using the enriched embeddings, we obtain an average of 2% improvement in F-score compared to the previous baselines.
Experimentelle und theoretische Untersuchung des zwischenmolekularen Übergangs von Elektronenanregungsenergie (1949)

Abstract Im Anschluß an frühere orientierende Messungen wird die wahre Löschwirkung von Rhodamin B auf die Fluoreszenz von Trypaflavin in Methanol untersucht, indem diese von der durch Absorption bedingten Fluoreszenzschwächung experimentell getrennt wird. Es wird eine Theorie der Löschung durch zwischenmolekularen Energieübergang entwickelt und mit den Versuchsergebnissen verglichen.
Purification, Characterization, and Gene Cloning of Purine Nucleosidase from Ochrobactrum anthropi (2001)

A bacterium, Ochrobactrum anthropi, produced a large amount of a nucleosidase when cultivated with purine nucleosides. The nucleosidase was purified to homogeneity. The enzyme has a molecular weight of about 170,000 and consists of four identical subunits. It specifically catalyzes the irreversible N-riboside hydrolysis of purine nucleosides, the K(m) values being 11.8 to 56.3 microM. The optimal activity temperature and pH were 50 degrees C and pH 4.5 to 6.5, respectively. Pyrimidine nucleosides, purine and pyrimidine nucleotides, NAD, NADP, and nicotinamide mononucleotide are not hydrolyzed by the enzyme. The purine nucleoside hydrolyzing activity of the enzyme was inhibited (mixed inhibition) by pyrimidine nucleosides, with K(i) and K(i)' values of 0.455 to 11.2 microM. Metal ion chelators inhibited activity, and the addition of Zn(2+) or Co(2+) restored activity. A 1.5-kb DNA fragment, which contains the open reading frame encoding the nucleosidase, was cloned, sequenced, and expressed in Escherichia coli. The deduced 363-amino-acid sequence including a 22-residue leader peptide is in agreement with the enzyme molecular mass and the amino acid sequences of NH(2)-terminal and internal peptides, and the enzyme is homologous to known nucleosidases from protozoan parasites. The amino acid residues forming the catalytic site and involved in binding with metal ions are well conserved in these nucleosidases.