gebhart/patrepeval huggingface dataset:
Perforin-Dependent Neurologic Injury in a Viral Model of Multiple Sclerosis (1998)

In this study we demonstrate perforin-mediated cytotoxic effector function is necessary for viral clearance and may directly contribute to the development of neurologic deficits after demyelination in the Theiler's murine encephalomyelitis virus (TMEV) model of multiple sclerosis. We previously demonstrated major histocompatability complex (MHC) class I-deficient (beta2m-deficient) mice with an otherwise resistant genotype develop severe demyelination with minimal neurologic disease when chronically infected with TMEV. These studies implicate CD8(+) T cells as the pathogenic cell in the induction of neurologic disease after demyelination. To determine which effector mechanisms of CD8(+) T cells, granule exocytosis or Fas ligand expression, play a role in the development of demyelination and clinical disease, we infected perforin-deficient, lpr (Fas mutation), and gld (Fas ligand mutation) mice with TMEV. Perforin-deficient mice showed viral persistence in the CNS, chronic brain pathology, and demyelination in the spinal cord white matter. Perforin-deficient mice demonstrated severely impaired MHC class I-restricted cytotoxicity against viral epitopes, but normal MHC class II-restricted delayed-type hypersensitivity responses to virus antigen. Despite demyelination, virus-infected perforin-deficient mice showed only minimal neurologic deficits as indicated by clinical disease score, activity monitoring, and footprint analysis. Perforin- and MHC class II-deficient mice (with functional CD8(+) T cells and perforin molecules and an H-2(b) haplotype) had comparable demyelination and genotype, however, only the latter showed severe clinical disease. Gld and lpr mice demonstrated normal TMEV-specific cytotoxicity and maintained resistance to TMEV-induced demyelinating disease. These studies implicate perforin release by CD8(+) T cells as a potential mechanism by which neurologic deficits are induced after demyelination.
Pharmacokinetics of controlled-release polymers in the subarachnoid space after subarachnoid hemorrhage in rabbits (2004)

In this study the authors define the rate and extent of diffusion of EBD from controlled-release polymers placed in the subarachnoid space under conditions of SAH. Evans blue dye diffused through the entire rabbit CNS, covering a distance greater than that of the longest dimension of the hemicircumference of the subarachnoid space around the human brain. The pharmacokinetic properties of EBD-EVAc polymers are comparable to those of antivasospasm agents that are successfully used in animal models of SAH.
LANDMARC: indoor location sensing using active RFID (2004)

Growing convergence among mobile computing devices and embedded technology sparks the development and deployment of "context-aware" applications, where location is the most essential context. We present LANDMARC, a location sensing prototype system that uses Radio Frequency Identification (RFID) technology for locating objects inside buildings. The major advantage of LANDMARC is that it improves the overall accuracy of locating objects by utilizing the concept of reference tags. Based on experimental analysis, we demonstrate that active RFID is a viable and cost-effective candidate for indoor location sensing. Although RFID is not designed for indoor location sensing, we point out three major features that should be added to make RFID technologies competitive in this new and growing market.
α-Glycosylceramides Enhance the Antitumor Cytotoxicity of Hepatic Lymphocytes Obtained from Cancer Patients by Activating CD3−CD56+ NK Cells In Vitro (2000)

Alpha-glycosylceramides, such as alpha-galactosylceramide and alpha-glucosylceramide, induce antitumor immunity in various murine cancer models. In the murine hepatic metastasis model, V alpha 14 TCR+NK1.1+ T cells, which accumulate preferentially in the liver, are considered to play a key role in the induction of antitumor immunity by alpha-glycosylceramides. We recently reported that V alpha 24 TCR+ NKT cells, the human homologues of murine V alpha 14 TCR+NK1.1+ cells, are rarely seen among freshly isolated human hepatic lymphocytes. Therefore, it is important to examine whether alpha-glycosylceramides also enhance the antitumor cytotoxicity of human hepatic lymphocytes, as they have been shown to do in murine systems, to determine the usefulness of alpha-glycosylceramides in cancer immunotherapy in humans. Here, we show that alpha-glycosylceramides greatly enhance the cytotoxicity of human hepatic lymphocytes obtained from cancer patients against the tumor cell lines, K562 and Colo201, in vitro. The direct effector cells of the elicited cytotoxicity were CD3-CD56+ NK cells. Even though V alpha 24 TCR+NKT cells proliferated remarkably in response to alpha-glycosylceramides, they did not contribute directly to the cytotoxicity. Our observations strongly suggest the potential usefulness of alpha-glycosylceramides for immunotherapy of liver cancer in humans based on their ability to activate CD3-CD56+ NK cells in the liver.
The Catalytic Properties of Tyrosyl Ribonucleic Acid Synthetases from Escherichia coli and Bacillus subtilis* (1966)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTThe Catalytic Properties of Tyrosyl Ribonucleic Acid Synthetases from Escherichia coli and Bacillus subtilis*Richard Calendar and Paul BergCite this: Biochemistry 1966, 5, 5, 1690–1695Publication Date (Print):May 1, 1966Publication History Published online1 May 2002Published inissue 1 May 1966https://pubs.acs.org/doi/10.1021/bi00869a034https://doi.org/10.1021/bi00869a034research-articleACS PublicationsRequest reuse permissionsArticle Views368Altmetric-Citations141LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Chirality Controls Reaction‐Diffusion of Nanoparticles for Inhibiting Cancer Cells (2016)

Reaction-diffusion (RD) is the most important inherent feature of living organism, but it has yet to be used for developing biofunctional nanoparticles (NPs). Here we show the use of chirality to control the RD of NPs for selectively inhibiting cancer cells. We observe that L-phosphotyrosine (L-pY) decorated NPs (NP@L-pYs) are innocuous to cells, but D-pY decorated ones (NP@D-pYs) selectively inhibit cancer cells. Our study shows that alkaline phosphatases (ALP), presented in the culture and overexpressed on the cancer cells, dephosphorylates NP@L-pYs much faster than NP@D-pYs. Such a rate difference allows the NP@D-pYs to be mainly dephosphorylated on cell surface, thus adhering selectively on the cancer cells to result in poly(ADP-ribose)polymerase (PARP) hyperactivation mediated cell death. Without phosphate groups or being prematurely dephosphorylated before reaching cancer cells (as the case of NP@L-pYs), the NPs are innocuous to cells. Moreover, NP@D-pYs even exhibit more potent activity than cisplatin for inhibiting platinum-resistant ovarian cancer cells (e.g., A2780-cis). As the first example of chirality controlling RD process of NPs for inhibiting cancer cells, this work illustrates a fundamentally new way for developing nanomedicine based on RD processes and nanoparticles.
Defective Lymphoid Development in Mice Lacking Jak3 (1995)

The Janus tyrosine kinases (Jaks) play a central role in signaling through cytokine receptors. Although Jak1, Jak2, and Tyk2 are widely expressed, Jak3 is predominantly expressed in hematopoietic cells and is known to associate only with the common gamma (gamma c) chain of the interleukin (IL)-2, IL-4, IL-7, IL-9, and IL-15 receptors. Homozygous mutant mice in which the Jak3 gene had been disrupted were generated by gene targeting. Jak3-deficient mice had profound reductions in thymocytes and severe B cell and T cell lymphopenia similar to severe combined immunodeficiency disease (SCID), and the residual T cells and B cells were functionally deficient. Thus, Jak3 plays a critical role in gamma c signaling and lymphoid development.
Epigenetics: The Role of Methylation in the Mechanism of Action of Tumor Suppressor Genes (2003)

Epigenetics is the study of mitotically heritable changes in gene expression without any changes in the primary DNA sequence. The major step in epigenetic gene regulation is gene inactivation by hypermethylation of CpG islands located in the promoter region. Specific enzymes and methylated DNA binding proteins play a major role in causing reduced expression of tumor suppressor genes, resulting in tumor formation and its progression. Prevention approaches are needed to avoid tumor formation. One approach to inhibiting inactivation of tumor suppressor genes is to use chemical agents such as 5-azacytidine to prevent hypermethylation of DNA. Increased understanding of the mechanism of epigenetic silencing and the identification of additional molecular mechanisms (e.g., histone methylases) that may be targeted by pharmaceutical interventions may lead to more preventive strategies. The current status of the epigenetic regulation of tumor suppressor genes is discussed in this review article.
Ectopic induction of cartilage and bone by water‐soluble proteins from bovine bone using a polyanhydride delivery vehicle (1990)

A controlled-release delivery vehicle for water-soluble osteogenic proteins from demineralized bone matrix was constructed using purified type I collagen. The water-soluble proteins were isolated from a 4 M GdnHCl extract of bone matrix. Although the water-soluble proteins were capable of inducing cartilage formation in vitro, they were incapable of inducing cartilage or bone in vivo when implanted intramuscularly into mice in the absence of an appropriate delivery vehicle. The collagen-based delivery vehicle alone was also incapable of inducing osteogenesis in vivo. However, when the water-soluble proteins were incorporated into the delivery vehicle, the combination was capable of inducing cartilage and bone 76% of the time. These results demonstrate that it is possible to formulate a controlled-release delivery vehicles for soluble bioactive factors which upon release interact with local responsive cells.
Histological and compositional evaluations of three types of calcium phosphate cements when implanted in subcutaneous tissue immediately after mixing (1999)

To evaluate the soft tissue response of calcium phosphate cement (CPC), consisting of an equimolar mixture of tetracalcium phosphate (TTCP) and dicalcium phosphate anhydrous (DCPA) under conditions close to those encountered in actual surgical procedures, we implanted three types of CPC [conventional CPC (c-CPC), fast-setting CPC (FSCPC), and antiwashout type FSCPC (aw-FSCPC; formerly called nondecay type FSCPC or nd-FSCPC)] subcutaneously in the abdomens of rats immediately (1 min) after mixing. At 1 week after surgery, histological examination and compositional analysis were performed using light microscopy and powder X-ray diffraction (XRD), respectively. The implanted c-CPC was crumbled completely, whereas FSCPC and aw-FSCPC retained their shape. Large vesicles containing copious inflammatory effusion were subcutaneously formed around the c-CPC. Histologically, many foreign-body giant cells were collected around the c-CPC, and moderate inflammatory cell infiltration was observed at 1 week after surgery. In contrast, the FSCPC and aw-FSCPC were covered with a thin layer of granulation tissue that included few giant cells and presented slight inflammatory cell infiltration, and no effusion was observed. The XRD analysis of the c-CPC revealed the presence of some unreacted DCPA even 1 week after implantation, whereas almost no DCPA was found in the FSCPC or aw-FSCPC. In conclusion, it was found that CPC does not always show excellent tissue response. When c-CPC is implanted subcutaneously in rats immediately after mixing, it fails to set and causes a severe inflammatory response. Therefore, the type of CPC should be chosen according to the clinical particulars. CPC should be used in a manner that assures its setting reaction. We recommend the use of FSCPC and aw-FSCPC for surgical applications, such as orthopedics, plastic and reconstructive surgery, and oral and maxillofacial surgery, where the cement might otherwise crumble due to the pressure before setting.
Nd:Glass Laser Design for Laser ICF Fission Energy (LIFE) (2009)

We have developed preliminary conceptual laser system designs for the Laser ICF (Inertial Confinement Fusion) Fission Energy (LIFE) application. Our approach leverages experience in high-energy Nd:glass laser technology developed for the National Ignition Facility (NIF), along with high-energy-class diode-pumped solid-state laser (HEC-DPSSL) technology developed for the DOE's High Average Power Laser (HAPL) Program and embodied in LLNL's Mercury laser system. We present laser system designs suitable for both indirect-drive, hot spot ignition and indirect-drive, fast ignition targets. Main amplifiers for both systems use laser-diode-pumped Nd:glass slabs oriented at Brewster's angle, as in NIF, but the slabs are much thinner to allow for cooling by high-velocity helium gas as in the Mercury laser system. We also describe a plan to mass-produce pump-diode lasers to bring diode costs down to the order of $0.01 per Watt of peak output power, as needed to make the LIFE application economically attractive.
Expression of the Ca 2+ -Activated Chloride Channel Genes CLCA1 and CLCA2 Is Downregulated in Human Colorectal Cancer (2001)

The role of ion channels in carcinogenesis and tumor progression remains unclear. We have used suppression subtractive hybridization of mRNA from paired normal colon epithelium and tumor, followed by quantitative kinetic RT-PCR, to demonstrate that the transcription of two members of a novel Ca(2+)-dependent chloride channel family, CLCA1 and CLCA2, was significantly downregulated in approximately 80% of colorectal carcinomas. This figure rose to >90% when expression was adjusted for tumor cell proliferation. In normal colon epithelium, CLCA1 mRNA levels were significantly associated with c-myc transcription but became decoupled in the tumor samples. There was no association between CLCA2 and either CLCA1 or c-myc mRNA levels. Transcription of both genes in three colorectal cancer cell lines, T84, HT29, and Caco2, was barely detectable. Illegitimate transcription of CLCA1 was detected in 12 of 15 blood samples taken from healthy volunteers, making its use as a marker for the detection of tumor spread unreliable. Our results suggest that CLCA1 could specify a new tumor suppressor and that, as in breast cancer, CLCA2 may function as a tumor suppressor in colorectal cancer.
Monitoring of adalimumab and antibodies-to-adalimumab levels in patient serum by the homogeneous mobility shift assay (2013)

This report describes the analytical validation and application of the homogeneous mobility shift assay (HMSA) method for the measurement of adalimumab and human antibodies-to-adalimumab (ATA) in serum samples from patients who have lost response to adalimumab treatment. Validation of the ATA- and the adalimumab-HMSA revealed a lower limit of detection to be 0.026 U/mL for ATA and 0.018 μg/mL for adalimumab in serum samples. Intra-assay and inter-assay precision determination yielded a coefficient of variation of less than 15%, and the accuracy of both assays was within 20%. Adalimumab drug tolerance in the ATA-HMSA was up to 20 μg/mL in the test serum. Serum samples from 100 drug-naïve healthy subjects were tested to set-up the cut point of 0.55 U/mL for ATA and 0.68 μg/mL for adalimumab. Analysis of 100 serum samples from patients who were losing response to adalimumab showed that 26% had an adalimumab level below the cut point, of these 68% were ATA positive. Overall, 44% of the patients (44/100) were positive for ATA. This study presents evidence that drug and anti-drug antibody levels are important determinants of patient response to therapy.
Geometric, electronic, and magnetic structure ofCo2FeSi: Curie temperature and magnetic moment measurements and calculations (2005)

In this work a simple concept was used for a systematic search for materials with high spin polarization. It is based on two semiempirical models. First, the Slater-Pauling rule was used for estimation of the magnetic moment. This model is well supported by electronic structure calculations. The second model was found particularly for ${\mathrm{Co}}_{2}$ based Heusler compounds when comparing their magnetic properties. It turned out that these compounds exhibit seemingly a linear dependence of the Curie temperature as function of the magnetic moment. Stimulated by these models, ${\mathrm{Co}}_{2}\mathrm{FeSi}$ was revisited. The compound was investigated in detail concerning its geometrical and magnetic structure by means of x-ray diffraction, x-ray absorption, and M\"ossbauer spectroscopies as well as high and low temperature magnetometry. The measurements revealed that it is, currently, the material with the highest magnetic moment $(6{\ensuremath{\mu}}_{B})$ and Curie temperature (1100 K) in the classes of Heusler compounds as well as half-metallic ferromagnets. The experimental findings are supported by detailed electronic structure calculations.
Nuclear translocation of an exogenous fusion protein containing HIV Tat requires unfolding (1995)

HIV-1 Tat can act as a vector to drive polypeptides into the nucleoplasm of living cells. The inhibitor effects of MTX on the nuclear localization of Tat-DHFR suggest that an unfolding step is required for the internalization of exogenous Tat.
Endotoxemia and human liver transplantation. (1989)

Ninety liver transplantations were performed in 81 patients. Plasma endotoxin was measured preoperatively, at the end of the anhepatic phase, and on postoperative days 1, 3, and 7. The presence of high endotoxin levels preoperatively and at the end of the anhepatic period was associated with graft failure and a high mortality. Patients with primary nonfunction of their transplants typically had severe endotoxemia. Endotoxemia could be a cause rather than an effect of perioperative complications and graft loss.
WEIGHTED STACKING FOR ROCK PROPERTY ESTIMATION AND DETECTION OF GAS* (1987)

ABSTRACT Amplitude versus offset concepts can be used to generate weighted stacking schemes (here called geo‐stack) which can be used in an otherwise standard seismic data processing sequence to display information about rock properties. The Zoeppritz equations can be simplified and several different approximations appear in the literature. They describe the variation of P‐wave reflection coefficients with the angle of incidence of a P‐wave as a function of the P‐wave velocities, the S‐wave velocities and the densities above and below an interface. Using a smooth, representative interval velocity model (from boreholes or velocity analyses) and assuming no dip, the angle of incidence can be found as a function of time and offset by iterative ray tracing. In particular, the angle of incidence can be computed for each sample in a normal moveout corrected CMP gather. The approximated Zoeppritz equation can then be fitted to the amplitudes of all the traces at each time sample of the gather, and certain rock properties can be estimated. The estimation of the rock properties is achieved by the application of time‐ and offset‐variant weights to the data samples before stacking. The properties which can be displayed by geo‐stack are: P‐wave reflectivity (or true zero‐offset reflectivity), S‐wave reflectivity, and the reflectivity of P‐wave velocity divided by S‐wave velocity (or ‘pseudo‐Poisson's ratio reflectivity’). If assumptions are made about the relation between P‐wave velocity and S‐wave velocity for water‐bearing clastic silicate rocks, then it is possible to create a display which highlights the presence of gas.
Profiling of differentially expressed genes in human primary cervical cancer by complementary DNA expression array. (1998)

The profiling of differentially expressed genes from primary tumor samples using cDNA expression array can reveal new tumor markers as well as target genes for therapeutic intervention. Using cDNA expression array technology, we produced an expression profile of genes that are associated with human cervical cancer. Hybridization of the cDNA blotting membrane (588 genes on a single membrane) was performed with 32P-labeled cDNA probes synthesized from RNA isolated from either normal cervix or cervical cancer. Parallel analyses of the hybridized signals enabled us to profile genes that were differentially expressed in cervical cancer. In each experiment, the extent of hybridization of each gene was evaluated by comparison with the most abundant mRNAs in the human cervix. These include myc proto-oncogene, 40S ribosomal protein S19, heat shock proteins, leukosialin S (CD43), integrin alphaL (CD11A), calgranulin (A), and CDK4 inhibitor (p16ink4). No detectable changes were observed in the expression levels of these genes. Several mRNAs, such as those encoding guanine nucleotide-binding protein Gs (alpha subunit), leukocyte adhesion protein (LFA1-beta), nuclear factor NF45, homeobox protein Hox-A1, and beta-catenin were detected in increased levels in cervical cancer. Genes that showed decreased expression in cervical cancer tissue were a group of apoptosis-related proteins, cell adhesion molecules, nuclear transcription factors, and a homeobox protein (Hox7). For example, the expression levels of Smad1 and Hox7 were consistently decreased in all tumor tissues tested. Northern analysis of Smad1 and Hox7 RNA in primary cervical tumor tissues and cervical carcinoma cell lines indicated that, in general, the mRNA levels of these genes were decreased in human cervical cancer. The precise relationship between the altered expression of these genes and cervical tumorigenesis is a matter of further investigation.
Inhaled nitric oxide (1998)

The great expectancies generated by inhaled NO action have led researchers to design personal inhaled NO delivery systems, but only with mitigated results. At present, medical companies are finding a financial interest in designing a delivery system which will suit the needs of clinicians and this, along with official governmental approval, will only then permit the use of inhaled NO safely and on a larger scale.