gebhart/patrepeval huggingface dataset:
Concise Review: Neural Stem Cell-Mediated Targeted Cancer Therapies (2018)

Cancer is one of the leading causes of morbidity and mortality worldwide, with 1,688,780 new cancer cases and 600,920 cancer deaths projected to occur in 2017 in the U.S. alone. Conventional cancer treatments including surgical, chemo-, and radiation therapies can be effective, but are often limited by tumor invasion, off-target toxicities, and acquired resistance. To improve clinical outcomes and decrease toxic side effects, more targeted, tumor-specific therapies are being developed. Delivering anticancer payloads using tumor-tropic cells can greatly increase therapeutic distribution to tumor sites, while sparing non-tumor tissues therefore minimizing toxic side effects. Neural stem cells (NSCs) are tumor-tropic cells that can pass through normal organs quickly, localize to invasive and metastatic tumor foci throughout the body, and cross the blood-brain barrier to reach tumors in the brain. This review focuses on the potential use of NSCs as vehicles to deliver various anticancer payloads selectively to tumor sites. The use of NSCs in cancer treatment has been studied most extensively in the brain, but the findings are applicable to other metastatic solid tumors, which will be described in this review. Strategies include NSC-mediated enzyme/prodrug gene therapy, oncolytic virotherapy, and delivery of antibodies, nanoparticles, and extracellular vesicles containing oligonucleotides. Preclinical discovery and translational studies, as well as early clinical trials, will be discussed. Stem Cells Translational Medicine 2018;7:740-747.
Prospective phase II trial of alternating intravesical Bacillus Calmette-Gu�rin (BCG) and Interferon alpha IIB in the treatment and prevention of superficial transitional cell carcinoma of the urinary bladder: Preliminary results (2000)

Alternating intravesical BCG and IFN is effective and well tolerated therapy for superficial TCC of urinary bladder.
Temporal Profile of Amyloid-β (Aβ) Oligomerization in an in Vivo Model of Alzheimer Disease (2005)

Accumulation of amyloid-beta (Abeta) is one of the earliest molecular events in Alzheimer disease (AD), whereas tau pathology is thought to be a later downstream event. It is now well established that Abeta exists as monomers, oligomers, and fibrils. To study the temporal profile of Abeta oligomer formation in vivo and to determine their interaction with tau pathology, we used the 3xTg-AD mice, which develop a progressive accumulation of plaques and tangles and cognitive impairments. We show that SDS-resistant Abeta oligomers accumulate in an age-dependent fashion, and we present evidence to show that oligomerization of Abeta appears to first occur intraneuronally. Finally, we show that a single intrahippocampal injection of a specific oligomeric antibody is sufficient to clear Abeta pathology, and more importantly, tau pathology. Therefore, Abeta oligomers may play a role in the induction of tau pathology, making the interference of Abeta oligomerization a valid therapeutic target.
CGRP receptor antagonists and antibodies against CGRP and its receptor in migraine treatment (2015)

Recently developed calcitonin gene-related peptide (CGRP) receptor antagonistic molecules have shown promising results in clinical trials for acute treatment of migraine attacks. Drugs from the gepant class of CGRP receptor antagonists are effective and do not cause vasoconstriction, one of the major limitations in the use of triptans. However their use had to be discontinued because of risk of liver toxicity after continuous exposure. As an alternative approach to block CGRP transmission, fully humanized monoclonal antibodies towards CGRP and the CGRP receptor have been developed for treatment of chronic migraine (attacks >15 days/month). Initial results from phase I and II clinical trials have revealed promising results with minimal side effects and significant relief from chronic migraine as compared with placebo. The effectiveness of these various molecules raises the question of where is the target site(s) for antimigraine action. The gepants are small molecules that can partially pass the blood-brain barrier (BBB) and therefore, might have effects in the CNS. However, antibodies are large molecules and have limited possibility to pass the BBB, thus effectively excluding them from having a major site of action within the CNS. It is suggested that the antimigraine site should reside in areas not limited by the BBB such as intra- and extracranial vessels, dural mast cells and the trigeminal system. In order to clarify this topic and surrounding questions, it is important to understand the localization of CGRP and the CGRP receptor components in these possible sites of migraine-related regions and their relation to the BBB.
mxiA of Shigella flexneri 2a, which facilitates export of invasion plasmid antigens, encodes a homolog of the low-calcium-response protein, LcrD, of Yersinia pestis (1992)

The plasmid-encoded invasion plasmid antigen (Ipa) export accessory locus of Shigella flexneri 2a, mxiA, was cloned, and the complete DNA sequence of the gene was determined. The mixA open reading frame was found to encode a polypeptide of 74.03 kDa with a pI of 5.02. A hydropathy analysis of the predicted protein revealed a hydrophilic C terminus and an extremely hydrophobic N terminus without a cleavable signal sequence but with several potential membrane-spanning regions. While a homology search did not reveal any significant relatedness of the mxiA DNA sequence to any known bacterial gene sequences, the derived amino acid sequence of MxiA was found to be highly homologous (68%) to the sequence of the protein encoded by the low-calcium-response locus, lcrD, of Yersinia pestis. The lcrD encodes an inner membrane regulatory protein that has an N-terminal membrane anchor and that is implicated in facilitating the export of Y. pestis outer membrane proteins (G. V. Plano, S. S. Barve, and S. C. Straley, J. Bacteriol. 173:7293-7303, 1991). Congo red binding, HeLa cell invasion, and Ipa excretion were restored in two avirulent mxiA fusion mutants when they were transformed with a cloned copy of the mxiA gene. Furthermore, the expression of the cloned mxiA gene was independent of any vector-specified promoter, suggesting that the transcription of mxiA is driven by its own promoter in this clone. In contrast, the overexpression of mxiA that resulted when it was placed under the control of the lac promoter was found to be deleterious in Escherichia coli. We conclude that mxiA is a homolog of the Y. pestis lcrD locus and may function similarly in S. flexneri, either by directly affecting the excretion of virulence factors or by regulating the expression of export accessory genes.
Functional characterization of novel human ARFGAP3 (2001)

ADP ribosylation factors (ARFs) are critical in the vesicular trafficking pathway. ARF activity is controlled by GTPase-activating proteins (GAPs). We have identified recently a novel tentative ARF GAP derived from human fetal liver, ARFGAP3 (originally named as ARFGAP1). In the present study, we demonstrated that ARFGAP3 had GAP activity in vitro and remarked that the GAP activity of ARFGAP3 was regulated by phospholipids, i.e. phosphatidylinositol 4,5-diphosphate as agonist and phosphatidylcholine as antagonist. ARFGAP3 is a predominantly cytosolic protein, and concentrated in the perinuclear region. Its transient ectopic overexpression in cultured mammalian cells reduced the constitutive secretion of secreted alkaline phosphatase, indicating that ectopic overexpression of ARFGAP3 inhibits the early secretory pathway of proteins in vivo. These results demonstrated that ARFGAP3 is a novel GAP for ARF1 and might be involved in intracellular traffic of proteins and vesicular transport as predicted.
Battery Test Manual For Electric Vehicles, Revision 3 (2015)

This battery test procedure manual was prepared for the United States Department of Energy (DOE), Office of Energy Efficiency and Renewable Energy (EERE), Vehicle Technologies Office. It is based on technical targets for commercial viability established for energy storage development projects aimed at meeting system level DOE goals for Electric Vehicles (EV). The specific procedures defined in this manual support the performance and life characterization of advanced battery devices under development for EVs. However, it does share some methods described in the previously published battery test manual for plug-in hybrid electric vehicles. Due to the complexity of some of the procedures and supporting analysis, future revisions including some modifications and clarifications of these procedures are expected. As in previous battery and capacitor test manuals, this version of the manual defines testing methods for full-size battery systems, along with provisions for scaling these tests for modules, cells or other subscale level devices. The DOE-United States Advanced Battery Consortium (USABC), Technical Advisory Committee (TAC) supported the development of the manual. Technical Team points of contact responsible for its development and revision are Chul Bae of Ford Motor Company and Jon P. Christophersen of the Idaho National Laboratory. The development of this manual was funded by the Unites States Department of Energy, Office of Energy Efficiency and Renewable Energy, Vehicle Technologies Office. Technical direction from DOE was provided by David Howell, Energy Storage R&D Manager and Hybrid Electric Systems Team Leader. Comments and questions regarding the manual should be directed to Jon P. Christophersen at the Idaho National Laboratory (jon.christophersen@inl.gov).
Comprehensive comparative-genomic analysis of Type 2 toxin-antitoxin systems and related mobile stress response systems in prokaryotes (2009)

This paper was reviewed by Kenn Gerdes (nominated by Arcady Mushegian), Daniel Haft, Arcady Mushegian, and Andrei Osterman. For full reviews, go to the Reviewers' Reports section.
Thread-spawning schemes for speculative multithreading (2004)

Speculative multithreading has been recently proposed to boost performance by means of exploiting thread-level parallelism in applications difficult to parallelize. The performance of these processors heavily depends on the partitioning policy used to split the program into threads. Previous work uses heuristics to spawn speculative threads based on easily-detectable program constructs such as loops or subroutines. In this work we propose a profile-based mechanism to divide programs into threads by searching for those parts of the code that have certain features that could benefit from potential thread-level parallelism. Our profile-based spawning scheme is evaluated on a Clustered Speculative Multithreaded Processor and results show large performance benefits. When the proposed spawning scheme is compared with traditional heuristics, we outperform them by almost 20%. When a realistic value predictor and a 8-cycle thread initialization penalty is considered, the performance difference between them is maintained. The speed-up over a single thread execution is higher than 5x for a 16-thread-unit processor and close to 2x for a 4-thread-unit processor.
Abstract 18593: Use of a CRISPR/Cas System for Cardiovascular Disease Modeling and Therapeutic Applications (2013)

Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas) systems have recently emerged as a new technology with which to perform genome editing in mammalian cells. We have tested the targeting efficiency of a CRISPR/Cas system in human pluripotent stem cells (hPSCs) by designing CRISPRs targeting eight loci in seven genes--AKT2, CELSR2, CIITA, GLUT4, LDLR, LINC00116, and SORT1. We found that different CRISPRs yield mutant clones at efficiencies of 51%-79%, with homozygous mutant clones generated at efficiencies of 7%-25%--far superior to any other genome-editing tool evaluated to date. Using this CRISPR/Cas system, we have generated isogenic cell lines with and without disease mutations, followed by differentiation into different cell types relevant to cardiovascular and metabolic diseases, including hepatocytes, adipocytes, and cardiomyocytes, which allows for rigorous human disease modeling and elucidation of new disease mechanisms. For example, using this system we have discovered that the novel gene LINC00116 has a role in lipid metabolism in adipocytes. We are building on these initial results by testing the CRISPR/Cas system for in vivo genome editing in mice, with a view towards establishing a novel therapeutic modality. We have delivered in vitro transcribed RNAs encoding Cas9 nuclease and CRISPRs targeting genes of therapeutic interest--e.g., the PCSK9 gene--formulated in lipid nanoparticles specific to mouse liver, with the intent of knocking out the gene in liver. These experiments provide a proof-of-principle that a CRISPR/Cas system could be used for human therapeutic applications in the future.
Involvement of an AFP1-binding site in cell-specific transcription of the pre-S1 region of the human hepatitis B virus surface antigen gene (1989)

Human hepatitis B virus infection is characterized by a high degree of hepatotropism which may be due to the dependency of viral genes on specific host factors for their expression. To learn more about such a requirement and the molecular basis of the viral tissue tropism we analyzed the promoter function in the pre-S1 region of the surface antigen gene. DNase I footprinting and competition gel retardation assays showed that a sequence with an AT-rich core (AT motif) in the pre-S1 promoter region interacts with AFP1, a hepatoma nuclear factor that binds to the α-fetoprotein enhancer and promoter. Functional analysis of the pre-S1 AT motif by transient transfection assays showed that this element is important in cell-specific transcriptional initiation. These results suggest that AFP1 may be one of the factors determining the liver specificity of human hepatitis B virus.
Effect of methionine sulfoximine in man (1961)

Flour bleached with nitrogen trichloride (agene) has been known to cause canine hysteria or “running fits” in dogs and other animals but not in man. Methionine sulfoximine, the active toxic material in flour so treated, was shown in this study to produce toxic psychosis in man, associated in one instance with reoersible electroencephalographic changes. The toxicity of methionine sulfoximine was prevented in 1 subject hy the simultaneous administration of large doses of methionine.
Effects of pH and salinity on the antimicrobial properties of clavanins (1997)

Clavanins are histidine-rich, amidated alpha-helical antimicrobial peptides that were originally isolated from the leukocytes (hemocytes) of a tunicate, Styela clava. The activities of clavanin A amide and clavanin A acid against Escherichia coli, Listeria monocytogenes, and Candida albicans were substantially greater at pH 5.5 than at pH 7.4. In contrast, clavanin AK, a synthetic variant of clavanin A acid containing 4 histidine-->lysine substitutions exerted substantial activity at both pH 7.4 and pH 5.5. Each of these three clavanins permeabilized the outer and inner membranes of E. coli very effectively at pH 5.5, but only clavanin AK did so at pH 7.4. Unlike magainin 1 and cecropin P1, alpha-helical antimicrobial peptides from frog skin and porcine intestine, respectively, clavanins were broadly effective against gram-positive bacteria, including methicillin-resistant Staphylococcus aureus, as well as gram-negative organisms. Because clavanins exert substantial antimicrobial activity in 0.1 to 0.3 M NaCl, they provide templates for designing broad-spectrum peptide antibiotics intended to function in extracellular environments containing normal or elevated NaCl concentrations. The pH-dependent properties of histidine-rich antimicrobial peptides may allow the design of agents that would function selectively in acidic compartments, such as the gastric lumen, or within phagolysosomes.
New and existing combinations in Palaeotropical Phlegmariurus (Lycopodiaceae) and lectotypification of the type species Phlegmariurus phlegmaria (L.) T.Sen & U.Sen (2013)

The genus Phlegmariurus Holubis recognised more widely than originally proposed and is circumscribed to include both Neotropic and Palaeotropic epiphytic and terrestrial species of Huperzioid Lycopodiaceae that have isotomous shoots, lack bulbils in their sporophyllous shoots and have spores with convex lateral margins and foveolate-fossulate sculpture restricted to their distal surfaces. New combinations with Phlegmariurus are proposed for 81 species and existing combinations identified for 33 species originating from the Palaeotropics. This installs a generic circumscription that is consistent between the Neotropics and Palaeotropics. A lectotype is designated for the type species of the genus, Phlegmariurus phlegmaria (L.) T.Sen & U.Sen.
Schedule-dependent synergism of combinations of hydroxyurea with adriamycin and 1-beta-D-arabinofuranosylcytosine with adriamycin. (1981)

The lethal effects of combinations of adriamycin (ADR) and either hydroxyurea (HU) or 1-beta-d-arabinofuranosylcytosine (ara-C) were studied in relation to drug-scheduling interval in Sarcoma 180 cells grown in vitro. Drug lethality was determined by cell cloning in soft agar. Serial kinetic changes induced by a priming dose of HU or ara-C were monitored by flow cytometry and related to schedule-dependent cell killing by ADR. All drug exposures were for 1 hr. When ADR was given together with either HU or ara-C, cell log kill was additive. However, when ADR was given after exposure to either HU or ara-C, cell killing was increased up to 200- to 500-fold, respectively. Maximum schedule-dependent synergism was observed at a drug-scheduling interval of 2 hr; schedule-dependent synergism decreased as the interval between drugs was increased beyond 2 hr. Schedule-dependent synergism was not observed when the same drug combinations were given in reversed order. Drug-induced changes in the DNA histogram were not seen until 5 hr after HU exposure and 8 hr after ara-C exposure. Thus, the schedule-dependent synergism between ADR and either HU or ara-C cannot be explained by cell cycle blockade with synchronization of cells in S phase.
A body-worn gait analysis system for evaluating hemiplegic gait (1995)

This paper describes a system for measuring the temporal parameters of hemiplegic gait. This system uses shoe insoles with sensors, acting as switches, placed under the heel, head of the first metatarsal, head of the fifth metatarsal and the big toe. This system is able to monitor gait for up to 10 min and can be used by the patient over any surface. Parameters for evaluating hemiplegic gait are defined, including scuffing during swing and the degree of inversion during stance.
Molecular organization of the cell wall ofCandida albicansand its relation to pathogenicity (2005)

Candida albicans is one of the most important opportunistic pathogenic fungi. Weakening of the defense mechanisms of the host, and the ability of the microorganism to adapt to the environment prevailing in the host tissues, turn the fungus from a rather harmless saprophyte into an aggressive pathogen. The disease, candidiasis, ranges from light superficial infections to deep processes that endanger the life of the patient. In the establishment of the pathogenic process, the cell wall of C. albicans (as in other pathogenic fungi) plays an important role. It is the outer structure that protects the fungus from the host defense mechanisms and initiates the direct contact with the host cells by adhering to their surface. The wall also contains important antigens and other compounds that affect the homeostatic equilibrium of the host in favor of the parasite. In this review, we discuss our present knowledge of the structure of the cell wall of C. albicans, the synthesis of its different components, and the mechanisms involved in their organization to give rise to a coherent composite. Furthermore, special emphasis has been placed on two further aspects: how the composition and structure of C. albicans cell wall compare with those from other fungi, and establishing the role of some specific wall components in pathogenesis. From the data presented here, it becomes clear that the composition, structure and synthesis of the cell wall of C. albicans display both subtle and important differences with the wall of different saprophytic fungi, and that some of these differences are of utmost importance for its pathogenic behavior.
Number of Nodes Examined and Staging Accuracy in Colorectal Carcinoma (1999)

In a sample of patients statistically similar to the sample in the NCDB report, the examination of at least 14 nodes after resection of T2 or T3 carcinoma of the colon and rectum will accurately stage the lymphatic basin.
Polarity of prostate specific membrane antigen, prostate stem cell antigen, and prostate specific antigen in prostate tissue and in a cultured epithelial cell line (2003)

Similar patterns of localization among MDCK and prostatic epithelial cells suggest that the mechanisms of polarized sorting within these cell types are conserved. Thus, MDCK cells offer a useful model system to study mechanisms of targeting of these proteins within the prostate.
Controlled solder self-alignment sequence for an optoelectronic module without mechanical stops (2002)

A new flip-chip solder technology has been developed for the precision self-alignment of an optoelectronic module without using mechanical stops. A main feature of the technology is the controlled self-alignment sequence: the laser is aligned to a polymer waveguide in the lateral and vertical directions, then it slowly makes a contact with the waveguide in the axial direction. The elimination of the use of mechanical stops significantly simplifies the process. The axial distance between the laser and the waveguide is very small; it is determined by the edges and a tilt angle of 12/spl deg/. The lateral accuracy is less than 2 /spl mu/m.
Molecular analysis of Sindbis virus pathogenesis in neonatal mice by using virus recombinants constructed in vitro (1988)

Genetic loci affecting Sindbis virus pathogenesis in neonatal mice have been examined by using a full-length cDNA clone of the virus (Toto1101). The full-length cDNA is linked to a bacteriophage SP6 promoter to facilitate the synthesis of infectious RNA transcripts in vitro. Virus derived from Toto1101 showed reduced virulence (attenuation) in neonatal mice. Replacement of the E1 glycoprotein and 6K genes of Toto1101 with cloned E1 and 6K genes derived from a virulent Sindbis virus strain, AR339 (SB), resulted in a new construct, TR2000, that gave rise to virulent virus. Sequence determinations for the entire substituted regions of TR2000, Toto1101, and related virulent and attenuated strains identified three coding differences in E1 between Toto1101 and TR2000. These differences, individually or in combination, may be responsible for the attenuated phenotype. Previous studies in this laboratory identified another attenuating mutation at amino acid position 114 of the E2 glycoprotein (N.L. Davis, F.J. Fuller, W.G. Dougherty, R.A. Olmsted, and R.E. Johnston, Proc. Natl. Acad. Sci. USA 83:6771-6775, 1986). Substitution of Arg-114 in the mutant SB-RL for Ser-114 of SB appears to confer three distinguishing phenotypes: attenuation in neonatal mice, increased sensitivity to specific E2 monoclonal antibodies, and accelerated penetration of BHK cells. Replacement of TR2000 sequences containing the codon for amino acid 114 of E2 with corresponding fragments from cDNA clones of SB or SB-RL produced two strains of Sindbis virus (TR2100 and TR2200) which were isogenic except for the E2 114 codon (Ser and Arg, respectively). The three diagnostic phenotypes cosegregated according to the origin of the codon for amino acid 114 of E2, confirming the dramatic effect of this single amino acid substitution on these three phenotypes.