gebhart/patrepeval huggingface dataset:
A class-based approach to parallelization of legacy codes (1997)

Computation-intensive legacy codes for numerical models stand to benefit from application of parallel computing. However, parallelization of legacy codes poses special challenges. These codes are very large and complex. Manual parallelization has proven to be extremely time-consuming and error-prone. Furthermore, while a large number of parallelization tools exist, they cannot handle these complex legacy codes. Development of automatic parallelization tools for legacy codes remains a research area of considerable interest.
This thesis describes a new approach to automatic parallelization of legacy codes. Our approach focuses on special classes of codes as opposed to parallelization of arbitrary codes. The advantage is that we are able to use high-level knowledge of the special class to manage the complexity of the parallelization problem. This approach provides a pragmatic solution for parallelization: it requires the user to specify the high-level knowledge, but automates tasks which are time-consuming, tedious, and error-prone for the user.
Using this new approach, we have developed parAgent--a parallelizing tool which facilitates quick development of efficient parallel codes for legacy Fortran-77 codes based on the explicit time-marching finite difference model. parAgent has been used on several well-known and widely-used Mesoscale Meteorological codes. It took only a few weeks to parallelize each of these legacy codes. Qualitatively, the performance of parallelization have been found to be on par with manual parallelization.
This new approach can be applied to a variety of problem domains. The key benefits are: substantial reuse of existing software and considerable saving of time and effort for developing efficient parallel code. Although the new approach and parAgent have been developed with parallelization as the main objective, the information provided by the tool can be used for various purposes. For example, the information about the underlying numerical method and the exchange of data is valuable to the application scientist.
Determination of amide hydrogen exchange by mass spectrometry: A new tool for protein structure elucidation (1993)

A new method based on protein fragmentation and directly coupled microbore high-performance liquid chromatography-fast atom bombardment mass spectrometry (HPLC-FABMS) is described for determining the rates at which peptide amide hydrogens in proteins undergo isotopic exchange. Horse heart cytochrome c was incubated in D2O as a function of time and temperature to effect isotopic exchange, transferred into slow exchange conditions (pH 2-3, 0 degrees C), and fragmented with pepsin. The number of peptide amide deuterons present in the proteolytic peptides was deduced from their molecular weights, which were determined following analysis of the digest by HPLC-FABMS. The present results demonstrate that the exchange rates of amide hydrogens in cytochrome c range from very rapid (k > 140 h-1) to very slow (k < 0.002 h-1). The deuterium content of specific segments of the protein was determined as a function of incubation temperature and used to indicate participation of these segments in conformational changes associated with heating of cytochrome c. For the present HPLC-FABMS system, approximately 5 nmol of protein were used for each determination. Results of this investigation indicate that the combination of protein fragmentation and HPLC-FABMS is relatively free of constraints associated with other analytical methods used for this purpose and may be a general method for determining hydrogen exchange rates in specific segments of proteins.
Riboswitches: Structures and Mechanisms (2010)

A critical feature of the hypothesized RNA world would have been the ability to control chemical processes in response to environmental cues. Riboswitches present themselves as viable candidates for a sophisticated mechanism of regulatory control in RNA-based life. These regulatory elements in the modern world are most commonly found in the 5'-untranslated regions of bacterial mRNAs, directly interacting with metabolites as a means of regulating expression of the coding region via a secondary structural switch. In this review, we focus on recent insights into how these RNAs fold into complex architectures capable of both recognizing a specific small molecule compound and exerting regulatory control over downstream sequences, with an emphasis on transcriptional regulation.
Hematopoietic and Endothelial Development of Mouse Embryonic Stem Cells in Culture (2004)

Embryonic stem (ES) cells differentiate efficiently in vitro and give rise to many different somatic cell types. Hematopoietic progenitors present within differentiated ES cells (embryoid bodies, EBs) can be identified by replating EB cells into semisolid media with hematopoietic growth factors. The developmental kinetics of various hematopoietic lineage precursors within EBs and molecular and cellular studies of these cells have suggested that the sequence of events leading to the onset of hematopoiesis within EBs is similar to that found within the mouse embryo. Thus, the in vitro differentiation model of ES cells provides a unique opportunity to study onset mechanisms involved in hematopoietic development.
The cys-loop ligand-gated ion channel gene superfamily of the nematode, Caenorhabditis elegans (2008)

The nematode, Caenorhabditis elegans, possesses the most extensive known superfamily of cys-loop ligand-gated ion channels (cys-loop LGICs) consisting of 102 subunit-encoding genes. Less than half of these genes have been functionally characterised which include cation-permeable channels gated by acetylcholine (ACh) and gamma-aminobutyric acid (GABA) as well as anion-selective channels gated by ACh, GABA, glutamate and serotonin. Following the guidelines set for genetic nomenclature for C. elegans, we have designated unnamed subunits as lgc genes (ligand-gated ion channels of the cys-loop superfamily). Phylogenetic analysis shows that several of these lgc subunits form distinct groups which may represent novel cys-loop LGIC subtypes.
利益群体、制度和区域特点—中国地方经济政策的解释 (2003)

如何解释中国各省区在投资环境上表现出来的差异?有三个主要原因是值得重视的:当地经济利益群体的规模和特点的差异、中央政府政策中的地位以及改革前的区域特征和传统.前两个原因,可以从统计资料得到支持,而中央政策变动的影响却缺乏相应的证据.因此,为了更好地理解利益群体压力和地区特征的综合影响作用,要做进一步的统计检验和案例研究.
Quantitative analysis of aberrant p16 methylation using real-time quantitative methylation-specific polymerase chain reaction. (1999)

We have developed a quantitative method for methylation analysis of the p16 gene based on real-time methylation-specific PCR (MSP). Real-time MSP is sensitive enough to detect down to 10 genome equivalents of the methylated p16 sequence. Application of real-time MSP to DNA from tumor-derived cell lines revealed complete concordance with conventional MSP analysis. Quantitative data generated by real-time MSP were expressed as the methylation index, which was defined as the percentage of bisulfite-converted DNA that consisted of methylated target sequences. The methylation index was shown to be inversely correlated with p16 gene transcription during demethylation treatment of cell lines with 5-aza-2'-deoxycytidine. The application of real-time MSP to bone marrow aspirates from patients with multiple myeloma revealed complete concordance with conventional MSP analysis. Real-time quantitative MSP may have applications in elucidating diverse biological processes involving DNA methylation and may become a valuable diagnostic tool for detecting tumor-associated epigenetic changes in cancer patients.
Comparison of Legionella pneumophila isolates by arbitrarily primed PCR and pulsed-field gel electrophoresis: analysis from seven epidemic investigations (1995)

Arbitrarily primed PCR (AP-PCR) and pulsed-field gel electrophoresis (PFGE) subtyping were applied to clinical and environmental isolates from seven unrelated outbreaks of Legionnaires' disease. The patterns observed with each method matched patient isolates and the epidemiologically linked source of disease for each of the seven outbreaks. PFGE allowed more discrimination among various isolates, although AP-PCR usually gave comparable results. With both methods, certain patterns appeared to predominate in the comparison of the seven outbreaks. Of five clinical isolates not associated with the outbreaks, three gave profiles distinct from those observed in the outbreaks by both methods. This suggests that there are at least two predominant subtypes of Legionella pneumophila serogroup 1 associated with outbreaks. Investigations of outbreaks of legionellosis should employ either PFGE or AP-PCR in addition to monoclonal antibody analysis.
Induction of therapeutic levels of HbF in genome‐edited primary β039‐thalassaemia haematopoietic stem and progenitor cells (2020)

Hereditary persistence of fetal haemoglobin (HPFH) is the major modifier of the clinical severity of β-thalassaemia. The homozygous mutation c.-196 C>T in the Aγ-globin (HBG1) promoter, which causes Sardinian δβ<sup>0</sup> -thalassaemia, is able to completely rescue the β-major thalassaemia phenotype caused by the β<sup>0</sup> 39-thalassaemia mutation, ensuring high levels of fetal haemoglobin synthesis during adulthood. Here, we describe a CRISPR/Cas9 genome-editing approach, combined with the non-homologous end joining (NHEJ) pathway repair, aimed at reproducing the effects of this naturally occurring HPFH mutation in both HBG promoters. After selecting the most efficient guide RNA in K562 cells, we edited the HBG promoters in human umbilical cord blood-derived erythroid progenitor 2 cells (HUDEP-2) and in haematopoietic stem and progenitor cells (HSPCs) from β<sup>0</sup> -thalassaemia patients to assess the therapeutic potential of HbF induction. Our results indicate that small deletions targeting the -196-promoter region restore high levels of fetal haemoglobin (HbF) synthesis in all cell types tested. In pools of HSPCs derived from homozygous β<sup>0</sup> 39-thalassaemia patients, a 20% editing determined a parallel 20% increase of HbF compared to unedited pools. These results suggest that editing the region of HBG promoters around the -196 position has the potential to induce therapeutic levels of HbF in patients with most types of β-thalassaemia irrespective of the β-globin gene (HBB) mutations.
Human hepatoblast phenotype maintained by hyaluronan hydrogels (2006)

Human hepatoblasts and hepatic stem cells, pluripotent hepatic progenitors that give rise to hepatocytes and biliary cells, were isolated from fetal livers and found to express hyaluronan receptors (CD44) in both the freshly isolated cells and after culture. This implicates an in vivo connection to hyaluronan (HA), an embryonic matrix component, as a candidate 3-dimensional (3-D) scaffold for hepatic progenitor cell expansion and/or differentiation. To assess HAs as scaffolds, hepatoblasts and hepatic stem cells were seeded into HA hydrogels with a serum-free, hormonally defined medium tailored for expansion of hepatic progenitors. Cell aggregates formed within the HA hydrogels and remained viable, proliferative, and demonstrated a stable phenotype intermediate between that of hepatic stem cells and hepatoblasts throughout more than 4 weeks of culturing, with little evidence of lineage restriction towards either hepatocytic or biliary pathways. The phenotype consisted of stable co-expression of both hepatocytic and biliary markers such as biliary-specific cytokeratin, CK19, low levels of expression of albumin, and urea synthesis. HA hydrogels are ideal as 3-D scaffolds for pluripotent hepatic progenitors and should be useful for generating cells to be used in bioartificial livers or tissue engineered liver grafts.
DC-SIGN (CD209) Mediates Dengue Virus Infection of Human Dendritic Cells (2003)

Dengue virus is a single-stranded, enveloped RNA virus that productively infects human dendritic cells (DCs) primarily at the immature stage of their differentiation. We now find that all four serotypes of dengue use DC-SIGN (CD209), a C-type lectin, to infect dendritic cells. THP-1 cells become susceptible to dengue infection after transfection of DC-specific ICAM-3 grabbing nonintegrin (DC-SIGN), or its homologue L-SIGN, whereas the infection of dendritic cells is blocked by anti-DC-SIGN antibodies and not by antibodies to other molecules on these cells. Viruses produced by dendritic cells are infectious for DC-SIGN- and L-SIGN-bearing THP-1 cells and other permissive cell lines. Therefore, DC-SIGN may be considered as a new target for designing therapies that block dengue infection.
Immunocytochemical Diagnosis of Acute Promyelocytic Leukemia (M3) With the Monoclonal Antibody PG-M3 (Anti-PML) (1997)

Acute promyelocytic leukemia (APL) is characterized by a reciprocal 15; 17 chromosomal translocation, which fuses the promyelocytic leukemia (PML) and retinoic acid receptor alpha (RARalpha) genes, leading to the expression of the PML/RARalpha fusion oncoprotein. Immunocytochemical labeling of the wild-type PML protein with the PG-M3 monoclonal antibody (MoAb) directed against the amino terminal portion of the human PML gene product, produces a characteristic nuclear speckled pattern that is due to localization of the protein into discrete dots (5 to 20 per nucleus), named PML nuclear bodies. The architecture of PML nuclear bodies appears to be disrupted in APL cells that bear the t(15; 17), thus resulting in a change of the nuclear staining pattern from speckled (wild-type PML protein) to microgranular (PML-RARalpha fusion protein). To assess whether the PG-M3 MoAb could assist in the diagnosis of APL (M3), bone marrow and/or peripheral blood samples from 100 cases of acute nonlymphoid leukemias of different subtypes were blindly immunostained with the PG-M3 MoAb, using the immunoalkaline phosphatase (APAAP) or immunofluorescence technique as detection system. Notably, the abnormal (micropunctate) pattern of the PML/RARalpha fusion protein (usually >/=50 small granules/per nucleus) was observed in APL (M3) samples, but not in other types of acute nonlymphoid leukemias. Immunocytochemical labeling with PG-M3 was particularly useful in the diagnosis of microgranular variant of APL (M3V) (three cases misdiagnosed as M4 and M5), and also to exclude a morphologic misdiagnosis of APL (six of 78 cases). In all cases investigated, immunocytochemical results were in agreement with those of reverse transcription-polymerase chain reaction (RT-PCR) for PML/RARalpha. Because the epitope identified by PG-M3 is located in the aminoterminal portion of PML (AA 37 to 51), the antibody was suitable for recognizing APL cases characterized by breakpoint occurring at different sites of PML (bcr 1, bcr 2 and bcr 3). In conclusion, immunocytochemical labeling with PG-M3 represents a rapid, sensitive, and highly-specific test for the diagnosis of APL that bears the t(15; 17). This should allow an easy and correct diagnosis of this subtype of acute leukemia to any laboratory provided with a minimal equipment for immunocytochemistry work.
NKG2D recognition mediates Toll-like receptor 3 signaling-induced breakdown of epithelial homeostasis in the small intestines of mice (2007)

Toll-like receptors (TLRs) and NK receptors are the two most important receptor families in innate immunity. Although it has been observed that TLR signaling can induce or up-regulate the expression of the ligands for stimulatory NK receptors on monocytes or muscle cells, there is not yet a report indicating whether TLR signaling can break down self-tolerance through NK receptors. The present work reports that TLR3 signaling by polyinosinic-polycytidylic acid stimulation induces intestinal epithelial cells (IECs) to express retinoic acid early inducible-1 (a ligand for NKG2D) and to induce NKG2D expression on CD8alphaalpha intestinal intraepithelial lymphocytes by IL-15 derived from TLR3-activated IECs. The blockade of interaction between NKG2D and Rae1 inhibits the cytotoxicity of intraepithelial lymphocytes against IECs in a cell-cell contact-dependent manner and therefore alleviates polyinosinic-polycytidylic acid-induced epithelial destruction and acute mucosal injury of small intestine. These results demonstrate that TLR signaling induces tissue injury through the NKG2D pathway, suggesting that TLR signaling may break down self-tolerance through induction of abnormal expression of ligands for stimulatory NK receptors.
Physical Layer Design for a Spread Spectrum Wireless LAN (1996)

A wireless local area network (LAN) system is proposed to provide mobility for exist-ing data communication services. This thesis presents a physical layer design for a direct sequence spread spectrum ISM band radio LAN system. This radio system employs spread spectrum communication technology and a differential binary phase shift keying/quadrature phase shift keying (BPSK/QPSK) non-coherent receiver to overcome the adverse indoor wireless environment. Moreover, a variable data rate transmission technique is used to dy-namically configure the spread spectrum system according to channel performance. This physical layer incorporates the Zilog Z2000 Evaluation Board performing direct sequence spread spectrum processing, a Grayson 900 MHz radio receiver and a transmitter module which was designed and built at Virginia Tech. The transmitted spectrum occupies a 4 MHz bandwidth in the 900 MHz ISM band and this system supports a data rate of up to 363 Kbits/sec. The spread spectrum system design along with detailed descriptions of hardware and control software development are presented. ACKNOWLEDGEMENTS I would like to express my deep appreciation to my advisor, Professor Dennis G. Sweeney
Improved Time Delay Analysis/Synthesis for Parametric Stereo Audio Coding (2006)

For parametric stereo and multi-channel audio coding, it has been proposed to use level difference, time difference, and coherence cues between audio channels to represent the perceptual spatial features of stereo and multi-channel audio signals. In practice, it has turned out that by merely considering level difference and coherence cues a high audio quality can already be achieved. Time difference cue analysis/synthesis did not contribute much to a higher audio quality, or, even decreases audio quality when not done properly. However, for binaural audio signals, e.g. binaural recordings or signals mixed with HRTFs, time differences play an important role. We investigate problems of time difference analysis/synthesis with such critical signals and propose algorithms for improving it. A subjective evalution indicates significant improvements over previous time difference analysis/synthesis.
Differential Rates of Somatic Hypermutation in VH Genes Among Subsets of Chronic Lymphocytic Leukemia Defined by Chromosomal Abnormalities (1997)

Chronic lymphocytic leukemia (CLL) is a B-cell tumor involving small lymphocytes that generally express the CD5 antigen and low levels of surface Ig. Within this definition, there is heterogeneity among cases in cell morphology, karyotypic abnormalities, and clinical course. Trisomy 12, the most frequent karyotypic abnormality, is commonly found in a subset of CLL with atypical morphology. It has also been associated with advanced disease, and possibly with a less favorable prognosis. A further subset of cases with abnormalities involving chromosome 13q14 have typical lymphocyte morphology. Occasionally, the two abnormalities are found together. To assess the clonal history of the cell of origin in disease subsets defined by these two chromosomal abnormalities, we investigated the usage of V(H) genes and the pattern of somatic mutation in 10 cases of trisomy 12 with atypical morphology and eight cases of 13q14 abnormality with typical morphology. In addition, four cases with both chromosomal abnormalities were analyzed. Results confirm a common usage of the V(H)1 family in all subsets. However, the patterns of somatic mutation were distinct, with cases of trisomy 12 showing a minimal level of mutation (mean +/- SD, 0.34% +/- 0.86%) and cases of 13q14 abnormality showing significant levels (6.5% +/- 1.67%). The four cases with both abnormalities showed a mixed pattern. All mutated cases had intraclonal homogeneity, and three of 10 had a pattern indicative of antigen selection. These results suggest that the clonal history of the two subsets of CLL may differ.
Corrupted DNS Resolution Paths: The Rise of a Malicious Resolution Authority (2008)

We study and document an important development in how attackers are using Internet resources: the creation of malicious DNS resolution paths. In this growing form of attack, victims are forced to use rogue DNS servers for all resolution. To document the rise of this “second secret authority” on the Internet, we studied instances of aberrant DNS resolution on a university campus. We found dozens of viruses that corrupt resolution paths, and noted that hundreds of URLs discovered per week performed drive-by alterations of host DNS settings. We used the rogue servers discovered in this analysis to document numerous live incidents on the university network. To measure this problem on the larger Internet, we generated DNS requests to most of IPv4, using a unique label query for each request. We found 17 million hosts responding, and further tracked the resolution path they used to reach our NS. Unable to find plausible harmless explanations for such a large number of open recursive hosts, we queried 600,000 of these open resolvers for “phishable ” domains, such as banks and anti-virus companies. We found that 2.4 % of this subsample would reply with incorrect answers, which extrapolates to 291,528 hosts on the Internet performing either incorrect or malicious DNS service. With DNS resolution behavior so trivially changed, numerous malware instances in the wild, and so many other hosts providing incorrect and misleading answers, we urge the security community to consider the corruption of the resolution path as an important problem. 1
Oxidation of xenobiotics by recombinant human cytochrome P450 1B1. (1997)

Human cytochrome P450 (P450) 1B1 (CYP1B1) has recently been shown to be an important enzyme in the activation of diverse procarcinogens such as arylarenes, nitroarenes, and arylamines to reactive metabolites that cause DNA damage in the cells. However, it is not known whether this P450 enzyme also plays roles in the oxidation of certain drugs or model substrates commonly used in P450 assays. We examined the substrate oxidation activities of recombinant human CYP1B1 in yeast microsomes and compared these activities with those catalyzed by reconstituted systems containing recombinant CYP1A1 and CYP1A2 which were isolated from membranes of Escherichia coli in which respective cDNAs have been expressed. Catalytic activities towards some of the model substrates of other human P450 enzymes including CYP2A6, 2C9, 2C19, 2D6, 2E1, and 3A4 were also determined and compared. CYP1B1 catalyzed benzo[a]pyrene 3-hydroxylation at rates lower than those of CYP1A1 but higher than those of CYP1A2. The activity towards 7-ethoxyresorufin O-deethylation catalyzed by CYP1B1 was about one-tenth of that of CYP1A1, but the Km values were lower for CYP1B1 than those for CYP1A1 and CYP1A2. CYP1B1 was also able to catalyze the oxidation of theophylline and caffeine, two prototypic substrates for CYP1A2. CYP1B1 did not oxidize other typical P450 substrates such as coumarin, tolbutamide, S-mephenytoin, chlorzoxazone, nifedipine, and testosterone, while low rates of oxidation of bufuralol and 7-ethoxycoumarin were found for CYP1B1. These results indicate that CYP1B1 has catalytic activities overlapping CYP1A1 and CYP1A2 with respect to the oxidation of drugs and model P450 substrates, although the relative catalytic roles in these three P450 enzymes differ depending upon the substrates examined. A distinct marker activity of CYP1B1 has not been identified.