gebhart/patrepeval huggingface dataset:
Whole-genome and multisector exome sequencing of primary and post-treatment glioblastoma reveals patterns of tumor evolution (2015)

Glioblastoma (GBM) is a prototypical heterogeneous brain tumor refractory to conventional therapy. A small residual population of cells escapes surgery and chemoradiation, resulting in a typically fatal tumor recurrence ∼ 7 mo after diagnosis. Understanding the molecular architecture of this residual population is critical for the development of successful therapies. We used whole-genome sequencing and whole-exome sequencing of multiple sectors from primary and paired recurrent GBM tumors to reconstruct the genomic profile of residual, therapy resistant tumor initiating cells. We found that genetic alteration of the p53 pathway is a primary molecular event predictive of a high number of subclonal mutations in glioblastoma. The genomic road leading to recurrence is highly idiosyncratic but can be broadly classified into linear recurrences that share extensive genetic similarity with the primary tumor and can be directly traced to one of its specific sectors, and divergent recurrences that share few genetic alterations with the primary tumor and originate from cells that branched off early during tumorigenesis. Our study provides mechanistic insights into how genetic alterations in primary tumors impact the ensuing evolution of tumor cells and the emergence of subclonal heterogeneity.
White Spot Syndrome Virus in cultured shrimp: A review (2007)

Shrimp is one of the main aquaculture species in the world. Different viruses affect them, which causes serious mortality to economically important species, such as Penaeus monodon, Litopenaeus vannamei and L. stylirostris, among others. White spot syndrome virus or WSSV is a highly lethal, stress-dependent virus, which belongs to the family Nimaviridae, genus Whispovirus. Three WSSV virus isolates were first detected in 1992 in Thailand, Taiwan and China. Later, a fourth isolate of the virus was detected in the Americas in 1999. This virus has a large circular double-stranded DNA genome with different sizes (292.9–307.2 kb), where the diverse isolates show differences in virulence. This virus infects a wide range of aquatic crustaceans by vertical and horizontal transmission, with different mortality results. The spread of infection between regions may be due to infected shrimp and carriers such as other crustaceans, seabirds, aquatic arthropods or other vectors. The aim of this work is to describe the current knowledge on the status, transmission, pathology, isolation, control and genomic characteristics of WSSV.
Staphylococcal protein A induces biased production of Ig by VH3-expressing B lymphocytes. (1994)

Staphylococcal protein A (SPA) is known to bind preferentially to the VH3 family of Ig heavy chain variable gene products. The current studies were conducted to examine the functional capacity of SPA to induce Ig production by VH3-expressing human B cells preferentially. Human peripheral blood B cells stimulated with anti-CD3-activated T cells or the Wood 46 strain of Staphylococcus aureus, which lacks SPA, expressed IgM containing all VH families, as detected by reverse transcription-PCR. In contrast, stimulation with SPA containing S. aureus or SPA-Sepharose resulted in biased expression of VH3 containing IgM. Similarly, cord blood B cells that require costimulation for Ig production induced by anti-CD3-activated T cells produced only VH3 containing IgM on costimulation with SPA containing S. aureus. The sequences of 21 VH3 IgM gene products derived from different B cell sources were determined and found to include at least nine members of the VH3 family, which were both in germ-line configuration and somatically mutated. Use of DH and JH was diverse. Analysis of these VH3 gene products revealed conserved residues in FR1 and 3'CDR2/FR3, which are candidates to play a role in SPA-mediated activation of VH3-expressing B cells. Like T cell superantigens, SPA probably interacts with residues in the partially solvent exposed regions of the heavy chain molecule outside the classical Ag binding site and provides a signal that can lead to Ig production by human B cells expressing VH3.
Natural Biocombinatorics in the Polyketide Synthase Genes of the Actinobacterium Streptomyces avermitilis (2006)

Modular polyketide synthases (PKSs) of bacteria provide an enormous reservoir of natural chemical diversity. Studying natural biocombinatorics may aid in the development of concepts for experimental design of genes for the biosynthesis of new bioactive compounds. Here we address the question of how the modularity of biosynthetic enzymes and the prevalence of multiple gene clusters in Streptomyces drive the evolution of metabolic diversity. The phylogeny of ketosynthase (KS) domains of Streptomyces PKSs revealed that the majority of modules involved in the biosynthesis of a single compound evolved by duplication of a single ancestor module. Using Streptomyces avermitilis as a model organism, we have reconstructed the evolutionary relationships of different domain types. This analysis suggests that 65% of the modules were altered by recombinational replacements that occurred within and between biosynthetic gene clusters. The natural reprogramming of the biosynthetic pathways was unambiguously confined to domains that account for the structural diversity of the polyketide products and never observed for the KS domains. We provide examples for natural acyltransferase (AT), ketoreductase (KR), and dehydratase (DH)-KR domain replacements. Potential sites of homologous recombination could be identified in interdomain regions and within domains. Our results indicate that homologous recombination facilitated by the modularity of PKS architecture is the most important mechanism underlying polyketide diversity in bacteria.
The unique transcriptome through day 3 of human preimplantation development (2004)

Successful human development is dependent upon a cascade of events following fertilization. Unfortunately, knowledge of these critical events in humans is remarkably incomplete. Although hundreds of thousands of human embryos are cultured yearly at infertility centers worldwide, the vast majority fail to develop in culture or following transfer to the uterus. In this study, we sought to characterize global patterns of gene expression in individual, normal embryos during the first three days of embryonic life using microarrays; we then compared gene expression between normally growing and growth-arrested embryos using quantitative PCR. Our results documented several novel findings. First, we found that a complex pattern of gene expression exists; most genes that are transcriptionally modulated during the first three days following fertilization are not upregulated, as was previously thought, but are downregulated. Second, we observed that the majority of genes exhibiting differential expression during preimplantation development are of unknown identity and/or function. Third, we show that embryonic transcriptional programs are clearly established by day 3 following fertilization, even in embryos that arrested prematurely with 2-, 3- or 4-cells. This indicates that failure to activate transcription is not associated with the majority of human preimplantation embryo loss. Finally, taken together, these results provide the first global analysis of the human preimplantation embryo transcriptome, and demonstrate that RNA can be amplified from single oocytes and embryos for analysis by cDNA microarray technology, thus lending credence to additional studies of genetic regulation in these cell types, as well as in other small biological samples.
Maintaining perioperative normothermia (2003)

Perioperative hypothermia can have a wide range of underappreciated, detrimental effects. These include increased rates of wound infection, morbid cardiac events, blood loss, and length of stay in both recovery and hospital. Maintaining core temperature at or above 36°C can be beneficial for the patient and cost effective.

Frank et al studied high risk cardiac patients undergoing thoracic, abdominal, and vascular surgery.1 Patients randomised to routine thermal care were, on average, 1.3°C cooler than patients warmed more aggressively. Despite this small difference the incidence of perioperative morbid cardiac events, assessed in a double blind fashion, was 300% higher in the cooler group. Frank et al thought that this may be the a consequence of the dramatic increase in noradrenaline release seen in even mild hypothermia.

It has also been said that the increase in noradrenaline may contribute to the higher number of wound infections seen in hypothermic patients. A randomised study of patients undergoing colorectal surgery showed that 1.9°C hypothermia resulted in an infection rate of 19% compared with 6% in the normothermic …
Simple and Efficient Methods for Enrichment and Isolation of Endonuclease Modified Cells (2014)

The advent of Transcription Activator-Like Effector Nucleases (TALENs), and similar technologies such as CRISPR, provide a straightforward and cost effective option for targeted gene knockout (KO). Yet, there is still a need for methods that allow for enrichment and isolation of modified cells for genetic studies and therapeutics based on gene modified human cells. We have developed and validated two methods for simple enrichment and isolation of single or multiplex gene KO's in transformed, immortalized, and human progenitor cells. These methods rely on selection of a phenotypic change such as resistance to a particular drug or ability to grow in a selective environment. The first method, termed co-transposition, utilizes integration of a piggyBac transposon vector encoding a drug resistance gene. The second method, termed co-targeting, utilizes TALENs to KO any gene that when lost induces a selectable phenotype. Using these methods we also show removal of entire genes and demonstrate that TALENs function in human CD34+ progenitor cells. Further, co-transposition can be used to generate conditional KO cell lines utilizing an inducible cDNA rescue transposon vector. These methods allow for robust enrichment and isolation of KO cells in a rapid and efficient manner.
The role of proteases during apoptosis (1996)

The importance of proteases during apoptosis is becoming increasingly apparent. Because apoptosis contributes to a diverse variety of disease processes, understanding the roles played by proteases and their inhibitors might provide insight into the pathogenesis of these conditions and suggest novel therapeutic strategies. In this review, we discuss the involvement and role of specific proteases, substrates, and protease inhibitors that appear to participate in the apoptotic process.
Water‐fat imaging with direct phase encoding (1997)

A new method is introduced for water-fat imaging. With three acquisitions, a general direct phase encoding (DPE) of the chemical shift information is achieved. Pixels containing both water and fat are solved directly. Pixels with only a single component are resolved with local and global orientation filters, which use phase information from neighboring pixels. The fact that a single component is more likely to be water than fat in living tissues is also useful. A second pass solution yields water and fat images with superior signal-to-noise ratio. Unlike other methods, DPE does not rely on the error-prone phase unwrapping; also, it easily handles disconnected tissues. Because the magnetization vectors of water and fat are sampled not only at parallel or antiparallel, they can be not only separated but also identified respectively, which is desirable for routine clinical work. DPE has been implemented on several imagers at various field strengths and has been demonstrated in a large number of clinical cases to be useful and robust in various parts of the body.
RALF, a 5-kDa ubiquitous polypeptide in plants, arrests root growth and development (2001)

A 5-kDa polypeptide was isolated from tobacco leaves that induced a rapid alkalinization of the culture medium of tobacco suspension-cultured cells and a concomitant activation of an intracellular mitogen-activated protein kinase. An N-terminal sequence was obtained, and a cDNA coding for the 49-aa polypeptide was isolated from a tobacco cDNA library. The cDNA encoded a preproprotein of 115 amino acids that contained the polypeptide at its C terminus. A search among known expressed sequence tags revealed that genes encoding Rapid ALkalinization Factor (RALF) preproproteins were present in various tissues and organs from 16 species of plants representing 9 families. A tomato homolog of the polypeptide was synthesized and, when supplied to germinating tomato and Arabidopsis seeds, it caused an arrest of root growth and development. Although its specific role in growth has not been established, the polypeptide joins the ranks of the increasing number of polypeptide hormones that are known to regulate plant stress, growth, and development.
Central and autonomic nervous system interaction is altered by short-term meditation (2009)

Five days of integrative body-mind training (IBMT) improves attention and self-regulation in comparison with the same amount of relaxation training. This paper explores the underlying mechanisms of this finding. We measured the physiological and brain changes at rest before, during, and after 5 days of IBMT and relaxation training. During and after training, the IBMT group showed significantly better physiological reactions in heart rate, respiratory amplitude and rate, and skin conductance response (SCR) than the relaxation control. Differences in heart rate variability (HRV) and EEG power suggested greater involvement of the autonomic nervous system (ANS) in the IBMT group during and after training. Imaging data demonstrated stronger subgenual and adjacent ventral anterior cingulate cortex (ACC) activity in the IBMT group. Frontal midline ACC theta was correlated with high-frequency HRV, suggesting control by the ACC over parasympathetic activity. These results indicate that after 5 days of training, the IBMT group shows better regulation of the ANS by a ventral midfrontal brain system than does the relaxation group. This changed state probably reflects training in the coordination of body and mind given in the IBMT but not in the control group. These results could be useful in the design of further specific interventions.
Time-space-conversion optical signal processingusing arrayed-waveguide grating (1997)

The authors propose time-space-conversion optical signal processing using an arrayed-waveguide grating. It provides a wide time window, compatibility with fibre optics, compactness, and integration capabilities. Pulse train generation is demonstrated to confirm its performance at the wavelength of 1.55 µm.
Bi‐stable and Dynamic Current Modulation in Electrochemical Organic Transistors (2002)

Novel electrochemical transistors, based on the conductive polymer PEDOT, operating at driving voltages of only a few volts in bulk material, and with little demand on substrate planarity, are described by the authors. The underlying polymer ion pair PEDOT:PSS is conductive in both oxidized and reduced state. Two transistor architectures, a bi-stable and a dynamic transistor (the first electrochemical specimen of its kind) with an on/off ratio of 105 and 200 Hz modulation speed, were realized.
Photoreactivities and thermal properties of psoralen cross-links (1988)

We have studied the photoreaction of 8-methoxypsoralen (8-MOP), 4,5',8-trimethylpsoralen (TMP), and 4'-(hydroxymethyl)-4,5',8-trimethylpsoralen (HMT) with a pair of 18-base-long oligonucleotides in which a 14-base region is complementary. Only one 5'TpA site, favored for both monoadduct and cross-link formation with psoralen, is present in this oligonucleotide pair. We have used this model system to demonstrate, for the first time, strand specificity in the photoreaction of psoralen with DNA. We found that the two types of cross-links which form at this site have large differences in thermal stabilities. In addition, the denaturation of each cross-link isomer duplex occurred in at least three stages, which can be visualized as three bands in thermal equilibrium under the conditions of a denaturing polyacrylamide gel. This novel observation suggests that there are several domains differing in thermal stability in a psoralen cross-link.
Fibrinogen-binding protein/clumping factor from Staphylococcus aureus (1989)

The binding of staphylococcal components to fibrinogen was studied. Fibrinogen-binding material from lysed staphylococcal cells or culture supernatants was affinity purified on fibrinogen-Sepharose and analyzed on Western (immuno-) blots by the use of fibrinogen and antifibrinogen antibodies. Two main bands of 87 and 19 kilodaltons (kDa) and a weaker band of 35 kDa bound specifically to fibrinogen. A monoclonal antibody bound to all three bands, indicating that these were of the same origin. The yield of these components was much higher in the culture supernatant than on washed cells, suggesting that these molecules are essentially extracellular products. In a plasma coagulase test, the 87-kDa band, but not the 19-kDa band, clotted rabbit plasma, demonstrating that the 87-kDa molecule is coagulase. This was further confirmed by the fact that the 87-kDa band binds specifically to prothrombin. It was shown that the 87- and the 19-kDa molecules were present on the cell surface by surface labeling the cells with 125I. In addition, the fact that killed and washed cells could induce plasma clotting demonstrates that staphylococci have coagulase exposed on the surface. It was concluded that cell-bound coagulase has affinity for fibrinogen also in the absence of prothrombin and thus is responsible for the clumping of staphylococci in fibrinogen.
A Microprocessor-Based PSK Modem for Packet Transmission Over Satellite Channels (1978)

This paper describes a microprocessor-based modem developed for use in a packet switching network over satellite channels. This digital modem can process both BPSK and QPSK packets with near optimum error rate performance over channels with marginal signal energy-to-noise density ratio. Of principal concern is the development of the discrete time algorithms which form the basis of the microinstruction program. The processing of a packet can be decomposed into two basic stages: (1) the detection of the packet preamble and the rapid estimation of signal parameters (symbol timing and carrier frequency offset) for the specific packet, and (2) the demodulation of the data portion of the packet including the tracking of both symbol timing and carrier offset phase, phase ambiguity resolution and data symbol estimation. The paper concludes with details on the performance of the modem under operational conditions and a brief discussion of implementation of the processor.
Tissue-specific post-transcriptional regulation of c-myc expression in normal and H-2K/human c-myc transgenic mice. (1989)

We show that the steady-state levels of c-myc mRNAs vary considerably in different organs of normal adult mice, maximal expression being observed in lymphoid organs and minimal expression in liver and brain. Nuclear run-on analysis of c-myc gene transcription in adult liver and spleen reveals that the difference in c-myc gene expression in these two organs is due to differential post-transcriptional control. Moreover, these nuclear run-on assays indicate that no premature termination of c-myc gene transcription takes place in the nuclei of the three adult tissues analysed. In fetal liver development, we observe a decrease in c-myc mRNA, but this is not due to changes in transcriptional activity implicating post-transcriptional regulatory mechanisms. Our studies of c-myc gene expression in organs of H-2K/myc transgenic mice, harboring an H-2K promoter driven human c-myc gene, confirm that the in vivo c-myc regulation is mainly post-transcriptional and shows that sequences shared by the murine and human c-myc proto-oncogenes are involved in this control.
Calreticulin: one protein, one gene, many functions (1999)

The endoplasmic reticulum (ER) plays a critical role in the synthesis and chaperoning of membrane-associated and secreted proteins. The membrane is also an important site of Ca2+ storage and release. Calreticulin is a unique ER luminal resident protein. The protein affects many cellular functions, both in the ER lumen and outside of the ER environment. In the ER lumen, calreticulin performs two major functions: chaperoning and regulation of Ca2+ homoeostasis. Calreticulin is a highly versatile lectin-like chaperone, and it participates during the synthesis of a variety of molecules, including ion channels, surface receptors, integrins and transporters. The protein also affects intracellular Ca2+ homoeostasis by modulation of ER Ca2+ storage and transport. Studies on the cell biology of calreticulin revealed that the ER membrane is a very dynamic intracellular compartment affecting many aspects of cell physiology.
Using active NVRAM for I/O staging (2011)

With HPC machines moving to the exascale, scaling the I/O performance of applications is a well known problem. Also, a closely related problem is, how to efficiently analyze and extract useful information from I/O data, viz. data post processing. With advent of nonvolatile memory technologies (NVMs) like SSD, PCM and Memristor, research has been focusing on how to improve the file systems performance and optimizations to overcome disk latencies. In the other end, there has been extensive focus on 'DataStaging' or 'in situ' I/O processing where I/O data are moved from computational cores to memory buffers of dedicated data processing or staging nodes using high performance I/O channels. The I/O data gets processed in these nodes before writing them to persistent storage like disks. However, issues with such approaches include (1) the limitation that they cannot easily analyze temporal data relationships or characteristics embedded in multiple simulation output steps, due to the limited aggregate memory capacity of staging nodes, and (2) the need to 'right size' such staging memory, sometimes even for single output/checkpoint steps when data volumes are large. Failing to properly allocate staging memory buffers (2) can cause applications to block and severely degrade the performance improvements sought by the extensive parallelization efforts undertaken by application developers. The limitation posed by (1) can degrade the utility of the Staging approach seen by end users.
alpha-Amino-N-butyric acid stimulates fetal hemoglobin in the adult (1988)

The effect of alpha-amino-N-butyric acid (alpha ABA) on fetal hemoglobin production in the adult was examined in vivo after being administered to normal and anemic baboons and in erythroid progenitor cell cultures. Infusion of alpha ABA for five days resulted in four- to fivefold increases in the level of F reticulocytes of normal or chronically anemic baboons. The induction of HbF by alpha ABA was strikingly enhanced by the administration of 5-azacytidine. The addition of alpha ABA in culture produced a concentration-related increase of HbF in baboon CFUe and e-cluster colonies. In addition to the induction of HbF, alpha ABA stimulated the growth of all classes of erythroid progenitors in vivo or in culture. The activation of gamma-globin gene expression by alpha ABA is attributed to an interaction between regulatory sites of globin chromatin modified by alpha ABA and the immature intracellular environment of the expanding erythropoiesis. The combination of chromatin modification, DNA methylation, and the immature intracellular environment of rapid erythroid regeneration may explain the synergistic induction of HbF by alpha ABA and 5-azacytidine.