gebhart/patrepeval huggingface dataset:
Oncolysis of Multifocal Hepatocellular Carcinoma in the Rat Liver by Hepatic Artery Infusion of Vesicular Stomatitis Virus (2004)

Hepatocellular carcinoma (HCC) is a lethal malignancy with poor prognosis and few effective treatments, as well as ever-increasing frequencies in the Western world. Viruses that replicate selectively in cancer cells hold considerable promise as novel therapeutic agents for the treatment of malignancy. Vesicular stomatitis virus (VSV) is a negative-strand RNA virus with intrinsic oncolytic specificity due to significantly attenuated antiviral responses in many tumor cells. The aim of this study was to evaluate the potential of VSV, administered via the hepatic artery, as an effective and safe therapeutic agent for treating "multifocal" HCC in the rat liver. Recombinant VSV vector expressing beta-galactosidase (rVSV-beta-gal) was generated by reverse genetics and infused into the hepatic artery of Buffalo rats bearing orthotopically implanted multifocal HCC. Access by the virus to multifocal HCC lesions in the liver, as well as the kinetic profiles of intratumoral viral replication and spread, was established by X-gal staining of liver and tumor sections. Plaque assays were also performed to determine the infectious viral yields in tumor and normal liver tissues. Pharmacotoxicology studies, including serum chemistries and proinflammatory cytokine production, as well as organ histopathology, were performed. Buffer- or vector-treated tumor-bearing rats were followed for survival and the results were analyzed by the Kaplan-Meier method and the log-rank test. Hepatic arterial infusion of rVSV-beta-gal at the maximum tolerated dose in tumor-bearing rats resulted in efficient viral transduction of multifocal HCC lesions in their livers, tumor-selective viral replication, and extensive oncolysis. Importantly, no significant vector-associated toxicities were noted and, in particular, no damage to the hepatic parenchyma was seen. Finally, survival of vector-treated rats was substantially prolonged over that of animals in the control treatment group (p < 0.028). Thus, hepatic arterial administration of VSV is both effective and safe in an orthotopic animal model of multifocal HCC. The results suggest that oncolytic VSV can be developed into an effective and safe therapeutic modality for patients with multifocal HCC in the future.
A New Stoicism (1997)

What would stoic ethics be like today if stoicism had survived as a systematic approach to ethical theory, if it had coped successfully with the challenges of modern philosophy and experimental science? This book proposes an answer to that question, offered from within the stoic tradition but without the metaphysical and psychological assumptions that modern philosophy and science have abandoned. The book argues that a secular version of the stoic ethical project, based on contemporary cosmology and developmental psychology, provides the basis for a sophisticated form of ethical naturalism, in which virtually all the hard doctrines of the ancient Stoics can be clearly restated and defended.
Use of glnQ as a Counterselectable Marker for Creation of Allelic Exchange Mutations in Group B Streptococci (2005)

Efficient allelic exchange mutagenesis in group B streptococci (GBS) has been hampered by the lack of a counterselectable marker system. Growth inhibition of GBS by the glutamine analog gamma-glutamyl hydrazide requires glnQ. We have used this phenomenon to create a counterselectable marker system for efficient selection of allelic exchange mutants in GBS.
Helminth Infection Can Reduce Insulitis and Type 1 Diabetes through CD25- and IL-10-Independent Mechanisms (2009)

Parasitic helminth infection has been shown to modulate pathological inflammatory responses in allergy and autoimmune disease. The aim of this study was to examine the effects of infection with a helminth parasite, Heligmosomoides polygyrus, on type 1 diabetes (T1D) in nonobese diabetic (NOD) mice and to elucidate the mechanisms involved in this protection. H. polygyrus inoculation at 5 weeks of age protected NOD mice from T1D until 40 weeks of age and also inhibited the more aggressive cyclophosphamide-induced T1D. Moreover, H. polygyrus inoculation as late as 12 weeks of age reduced the onset of T1D in NOD mice. Following H. polygyrus inoculation of NOD mice, pancreatic insulitis was markedly inhibited. Interleukin-4 (IL-4), IL-10, and IL-13 expression and the frequency of CD4(+) CD25(+) FoxP3(+) regulatory T cells were elevated in mesenteric and pancreatic lymph nodes. Depletion of CD4(+) CD25(+) T cells in vivo did not abrogate H. polygyrus-induced T1D protection, nor did anti-IL-10 receptor blocking antibody. These findings suggest that infection with H. polygyrus significantly inhibits T1D in NOD mice through CD25- and IL-10-independent mechanisms and also reduces the severity of T1D when administered late after the onset of insulitis.
Characterization of the human zona pellucida from fertilized and unfertilized eggs (1988)

Zonae pellucidae were isolated from a variety of human eggs collected from follicular aspirates for in-vitro fertilization. Zonae were removed from pools of eggs classified as fertilized but unsuitable for embryo transfer, inseminated but not fertilized, and immature and not inseminated. Isolated zonae were heat solubilized, iodinated and separated by two-dimensional electrophoresis. Under reducing conditions, zonae from unfertilized eggs separated into three acidic proteins with molecular weight ranges of 90,000-110,000 (ZP1), 64,000-78,000 (ZP2) and 57,000-73,000 (ZP3). Under non-reducing conditions, ZP1 and ZP2 co-migrated at Mr 92,000-120,000. An identical pattern was seen from zonae isolated from eggs that were not inseminated. Therefore, if chemical modification of the zona is effected by spermatozoa, these changes were not apparent in the electrophoretic patterns. The electrophoretic pattern of zonae isolated from eggs classified as fertilized revealed fertilization-associated modification of the zona pellucida. This was expressed as a modification of the ZP1 molecule, and was only evident after reduction of the sample. We suggest that this modification may be effected by egg cortical granule dehiscence after fertilization and that the chemical modification of the zona may be involved in a zona block to polyspermy.
Interaction of the guidance molecule Slit with cellular receptors (2006)

Slits are large secreted glycoproteins characterized by an unusual tandem of four LRR (leucine-rich repeat) domains in their N-terminal half. Slit proteins were initially described as repulsive guidance cues in neural development, but it has become clear that they have additional important functions, for instance in the vasculature and immune system. Genetic studies have identified two types of cellular receptors for Slits: Robos (Roundabout) and the HS (heparan sulphate) proteoglycan syndecan. The intracellular signalling cascade downstream of Robo activation is slowly being elucidated, but the mechanism of transmembrane signalling by Robo has remained obscure. No active signalling role for syndecan has yet been demonstrated. Slit-HS interactions may be important for shaping the presumed Slit gradient or presenting Slit at its target cell surface. Recent studies have mapped the binding sites for Robos and HS/heparin to discrete Slit domains. Robos bind to the second LRR domain of Slit, whereas HS/heparin binds with very high affinity to the C-terminal portion of Slit. Slit activity is likely to be modulated by physiological proteolytic cleavage in the region separating the Robo and HS/heparin-binding sites.
The Cytosolic DNA Sensor cGAS Forms an Oligomeric Complex with DNA and Undergoes Switch-like Conformational Changes in the Activation Loop (2014)

The presence of DNA in the cytoplasm is a danger signal that triggers immune and inflammatory responses. Cytosolic DNA binds to and activates cyclic GMP-AMP (cGAMP) synthase (cGAS), which produces the second messenger cGAMP. cGAMP binds to the adaptor protein STING and activates a signaling cascade that leads to the production of type I interferons and other cytokines. Here, we report the crystal structures of human cGAS in its apo form, representing its autoinhibited conformation as well as in its cGAMP- and sulfate-bound forms. These structures reveal switch-like conformational changes of an activation loop that result in the rearrangement of the catalytic site. The structure of DNA-bound cGAS reveals a complex composed of dimeric cGAS bound to two molecules of DNA. Functional analyses of cGAS mutants demonstrate that both the protein-protein interface and the two DNA binding surfaces are critical for cGAS activation. These results provide insights into the mechanism of DNA sensing by cGAS.
Electrical Detection of Metal Ions Using Field-Effect Transistors Based on Micropatterned Reduced Graphene Oxide Films (2011)

The electrical property of graphene is highly sensitive to its local environment, which makes graphene an ideal channel material in electronic sensors. Reduced graphene oxide (rGO) has been used as the desirable alternative to the pristine graphene due to its low-cost, solution-processable, and scalable production. In this paper, we present a field-effect transistor sensor using micropatterned, protein-functionalized rGO film as the conducting or sensing channel. Such a nanoelectronic sensor is able to detect various metal ions in real-time with high sensitivity.
Visibility Computations in Densely Occluded Polyhedral Environments (1992)

This thesis investigates the extent to which precomputation and storage of visibility information can be utilized to accelerate on-line culling and rendering during an interactive visual simulation of a densely occluded geometric model. &lt;p&gt;Architectural walkthroughs and other visual simulation applications demand enormously powerful graphics hardware to achieve interactive frame rates. Standard computer graphics rendering schemes waste much computational effort processing objects that are not visible to the simulated observer. An alternative is to precompute superset visibility information about the model, by determining what portions of the model will definitely be invisible for an observer in certain locations. This information can then be used during the simulation phase to dramatically reduce the number of model entities that must be processed during each time frame. &lt;p&gt;The visibility precomputation phase first subdivides the model into cells by partitioning the space embedding the model along the planes of large opaque polygonal occluders, such as walls, floors, and ceilings. The remainder of the geometric data, for example furniture and wall trim, are considered to be non-occluding detail objects. For each cell, a coarse visibility determination is first made as to what other cells might be visible from it. The detail objects are then inserted into the subdivision, and a finer-grain visibility determination is made for these objects and stored with each cell. &lt;p&gt;The online culling phase dynamically tracks the position and field of view of the simulated observer through the cells of the spatial subdivision. The precomputed visibility information is subjected to further on-line culling operations that use the observer's exact position and field of view. The resulting reduced set of objects is issued to graphics hardware, where a discrete depth-buffer solves the hidden-surface problem in screen space. &lt;p&gt;The visibility framework is defined generally in terms of conforming spatial subdivisions that support a small number of abstract operations. All visibility determinations are proven to produce a superset of the objects actually visible to the observer. This is crucial, since omitting any visible object would cause an erroneous display. The generally small set of invisible objects produced by the on-line culling operation is then removed by the graphics rendering hardware. &lt;p&gt;We implemented these abstract notions for several interesting and realistic input classes, i.e., axial and non-axial scenes in two and three dimensions. We evaluated the usefulness of the precomputation and culling scheme using objective metrics of culling effectiveness, pixel depth complexity, and on-line culling and rendering time. The test data was a complex, three-dimensional architectural model comprising ten thousand detail objects and almost three-quarters of a million polygons. On-line frame times decreased from about ten seconds for the unprocessed model, to a tenth of a second, thus accelerating frame rates by a factor of about one hundred
STAT3 Regulates Cytokine-mediated Generation of Inflammatory Helper T Cells (2007)

Interleukin-17 (IL-17)-producing helper T (TH) cells, named as TH(IL-17), TH17, or inflammatory TH (THi), have been recently identified as a novel effector lineage. However, how cytokine signals mediate THi differentiation is unclear. We found that IL-6 functioned to up-regulate IL-23R and that IL-23 synergized with IL-6 in promoting THi generation. STAT3, activated by both IL-6 and IL-23, plays a critical role in THi development. A hyperactive form of STAT3 promoted THi development, whereas this differentiation process was greatly impaired in STAT3-deficient T cells. Moreover, STAT3 regulated the expression of retinoic acid receptor-related orphan receptor gamma-T (RORgamma t), a THi-specific transcriptional regulator; STAT3 deficiency impaired RORgamma t expression and led to elevated expression of T-box expressed in T cells (T-bet) and Forkhead box P3 (Foxp3). Our data thus demonstrate a pathway whereby cytokines regulate THi differentiation through a selective STAT transcription factor that functions to regulate lineage-specific gene expression.
Refinement of theBCL2/immunoglobulin heavy chain fusion gene in t(14;18)(q32;q21) by polymerase chain reaction amplification for long targets (1998)

The t(14;18)(q32;q21) translocation, involving the BCL2 gene and junctional segments (JH) of the immunoglobulin heavy chain gene (IGH), constitutes the most common chromosomal translocation in non-Hodgkin's lymphoma of B-cell type. Although the breakpoints in BCL2 are largely clustered within the major breakpoint region (MBR) and minor cluster region (mcr), it is known that some breakpoints map away from these regions, resulting in negative amplification of the junctional sequence by polymerase chain reaction (PCR) for < 1 kb targets. To circumvent this problem, we applied a novel PCR technology for long DNA targets, long-distance (LD-) PCR, to the detection of t(14;18) in clinical materials. Oligonucleotide primers were designed to be quite distant from the two known cluster regions in BCL2, and those for the corresponding IGH were complementary to the enhancer and constant regions. In all 52 cases identified as carrying BCL2/JH fusion by conventional Southern blot analysis, LD-PCR successfully amplified fragments encompassing the junctions, which were readily identifiable on ethidium bromide-stained gel. The size of the LD-PCR products ranged from 3.9 kb to 10.7 kb in MBR/IGH fusion and 1.9 kb to 16 kb in mcr/IGH fusion. Furthermore, we established an LD-PCR protocol for > 20 kb targets, which covered the intervening region between the MBR and mcr. Restriction analysis of the LD-PCR products revealed that breakpoints in 33 cases fell within the 150 bp-MBR region, and in 3 cases were within the mcr determined previously by others. In contrast, the breakpoints of the remaining 16 cases were distributed over a large region from the MBR through mcr. Nucleotide sequence analysis of a potential cluster region revealed the presence of an Alu repeat sequence. Restriction analysis of LD-PCR products with BstEII demonstrated a predominant usage of the JH6 segment (71%) at the BCL2/JH junctions. LD-PCR using primers for the constant region genes showed that class switch recombination occurred in more than 80% of the IGH genes on the der(14) chromosome. Our study showed that LD-PCR was capable of detecting virtually any t(14;18) that occurred within the approximately 30 kb region downstream of the MBR, and thus is suitable for initial diagnosis of lymphoma tissues. Furthermore, as amplified fragments obtained by the LD-PCR contained distinctive regions of BCL2 and IGH, restriction analysis and nucleotide sequencing of the products refined the characteristics of t(14;18).
Analyzing Parallel Programs with Pin (2010)

Software instrumentation provides the means to collect information on and efficiently analyze parallel programs. Using Pin, developers can build tools to detect and examine dynamic behavior including data races, memory system behavior, and parallelizable loops. Pin is a software system that performs runtime binary instrumentation of Linux and Microsoft Windows applications. Pin's aim is to provide an instrumentation platform for building a wide variety of program analysis tools, called pintools. By performing the instrumentation on the binary at runtime, Pin eliminates the need to modify or recompile the application's source and supports the instrumentation of programs that dynamically generate code.
Synthesis of phosphatidylinositol 4,5-bisphosphate in the endoplasmic reticulum of Chinese hamster ovary cells. (1991)

We have investigated the intracellular localization and synthesis of phosphatidylinositol 4,5-bisphosphate (PtdInsP2) in Chinese hamster ovary (CHO) cells by analyzing membrane fractions that were obtained by sucrose density gradient centrifugation. After labeling the cells for 24 h with [3H]inositol, the bulk of [3H] PtdInsP2 was found in the plasma membrane fraction, yet this lipid was also distinctly present in the microsomal fraction (20% of total cellular [3H]PtdInsP2). To determine the origin of this microsomal PtdInsP2, gradient fractions from unlabeled CHO cells were incubated with [3H]inositol in the presence of an ATP-generating system. Under these conditions of labeling, [3H]PtdIns was exclusively present in the microsomal fractions and found to be partially converted to [3H] phosphatidylinositol 4-phosphate ([3H]PtdInsP) and phosphatidylinositol 4-phosphate ([3H]PtdInsP) and [3H]PtdInsP2. The ability of microsomes to synthesize PtdInsP and PtdInsP2 was confirmed by assaying the gradient fractions for PtdIns and PtdInsP kinase activity using endogenous substrate and [gamma-32P]ATP. In the presence of exogenous substrate and Triton X-100, PtdInsP kinase activity was particularly high in the plasma membrane fractions. When phosphoinositide synthesis was studied in permeabilized CHO cells under conditions of sustained membrane vesicle flow (Helms, J. B., Karrenbauer, A., Wirtz, K. W. A., Rothman, J. E., and Wieland, F. T. (1990) J. Biol. Chem. 265, 20027-20032), no lag-time could be detected between the synthesis of [3H]PtdIns and the formation of [3H]PtdInsP2. Moreover, when lipid transport pathways were blocked in these permeabilized cells either by omission of membrane-free cytosol, addition of GTP gamma S and brefeldin A, or temperature block, PtdInsP2 formation still occurred at normal levels. These results strongly suggest that PtdInsP2 can be formed at the site of PtdIns synthesis, i.e. the endoplasmic reticulum (ER). The relationship between PtdInsP2, generated in the ER, and PtdInsP2 present in the plasma membrane, remains to be established.
A circuit for measuring the gap voltage of a scanning tunneling microscope on a nanosecond time scale (1999)

We demonstrate a new circuit design for fast measurements of the voltage drop across the gap of a scanning tunneling microscope (STM) based on the simultaneous operation of two different amplifiers. The first is a fast instrumentation amplifier, sensing directly the voltage drop across the tunneling barrier, the second is a medium speed current amplifier with an overall gain of 108 V/A, suitable for normal STM operation. We obtained a time resolution of 10 ns measuring the plasma ignition under a STM tip during illumination with an intense 10 ns laser pulse. Possible applications include the study of STM point contacts.
Development of ultra-compact plastic-packaged high-isolation GaAs SPDT switch (1996)

A high-isolation switch IC with 31 dB isolation and 0.88 dB insertion loss at 1.65 GHz, sealed in a six-pin ultra-compact plastic package with approximately 1/4 of the conventional area, was developed for the first time. Analysis using electromagnetic-field simulation of the isolation characteristics between lead pins of the ultra-compact package and a new design method (which takes into account deterioration of the isolation characteristics due to the plastic molding) were used for this IC. Layout design using electromagnetic-field simulation also attempted to minimize chip size.
Genomic Characterization of Large Heterochromatic Gaps in the Human Genome Assembly (2014)

The largest gaps in the human genome assembly correspond to multi-megabase heterochromatic regions composed primarily of two related families of tandem repeats, Human Satellites 2 and 3 (HSat2,3). The abundance of repetitive DNA in these regions challenges standard mapping and assembly algorithms, and as a result, the sequence composition and potential biological functions of these regions remain largely unexplored. Furthermore, existing genomic tools designed to predict consensus-based descriptions of repeat families cannot be readily applied to complex satellite repeats such as HSat2,3, which lack a consistent repeat unit reference sequence. Here we present an alignment-free method to characterize complex satellites using whole-genome shotgun read datasets. Utilizing this approach, we classify HSat2,3 sequences into fourteen subfamilies and predict their chromosomal distributions, resulting in a comprehensive satellite reference database to further enable genomic studies of heterochromatic regions. We also identify 1.3 Mb of non-repetitive sequence interspersed with HSat2,3 across 17 unmapped assembly scaffolds, including eight annotated gene predictions. Finally, we apply our satellite reference database to high-throughput sequence data from 396 males to estimate array size variation of the predominant HSat3 array on the Y chromosome, confirming that satellite array sizes can vary between individuals over an order of magnitude (7 to 98 Mb) and further demonstrating that array sizes are distributed differently within distinct Y haplogroups. In summary, we present a novel framework for generating initial reference databases for unassembled genomic regions enriched with complex satellite DNA, and we further demonstrate the utility of these reference databases for studying patterns of sequence variation within human populations.
Handbook of Pharmaceutical Manufacturing Formulations (2004)

The fourth volume in the six-volume Handbook of Pharmaceutical Manufacturing Formulations, this book covers semi-solid drugs. It includes ointments, lotions, gels, and suppositories, from publicly available but widely dispersed information from FDA New Drug Applications (NDA), patent applications, and the BASF book of generic formulations. Each ent
High-mobility AlGaN/GaN heterostructures grown by molecular-beam epitaxy on GaN templates prepared by hydride vapor phase epitaxy (2000)

We report on the growth and transport properties of high-mobility two-dimensional electron gases (2DEGs) confined at the AlGaN/GaN interface grown by plasma-assisted molecular-beam epitaxy on GaN templates prepared by hydride vapor phase epitaxy. We have grown samples over a broad range of electron densities ranging from ns=6.9×1011 to 1.1×1013 cm−2, and at T=4.2 K, observe a peak mobility of 53 300 cm2/V s at a density of 2.8×1012 cm−2. Magnetotransport studies on these samples display exceptionally clean signatures of the quantum Hall effect. Our investigation of the dependence of 2DEG mobility on carrier concentration suggests that the low-temperature mobility in our AlGaN/GaN heterostructures is currently limited by the interplay between charged dislocation scattering and interface roughness.