gebhart/patrepeval huggingface dataset:
Targeting Tumor Specific Translocations in Sarcomas in Pediatric Patients for Immunotherapy (2000)

In an effort to develop more effective therapies for various sarcomas in pediatric patients, the authors have focused on using recurrent tumor-specific translocations as potential novel tumor antigens. In general, these translocations generate fusion transcription factors. Because cytotoxic T cell lymphocyte receptors recognize peptide fragments bound to major histocompatibility complex Class 1 molecules, it is possible that unique peptides spanning the translocation breakpoint region may be processed, bound to major histocompatibility complex Class I molecules and displayed on the tumor cell surface where they could be susceptible to cytotoxic T cell lymphocyte killing. The authors have investigated the PAX-3-FKHR fusion product seen in alveolar rhabdomyosarcoma, and the EWS-FLI-1 fusion product seen in Ewing's sarcoma. Peptides spanning these fusion regions contain potential major histocompatibility complex Class 1 and Class II binding motifs suggesting they may serve as novel T cell antigens. Preliminary mouse experiments suggest that cytotoxic T cell lymphocytes specific for the PAX-3-FKHR fusion peptide can be generated and can recognize and kill tumor cells bearing the PAX-3-FKHR fusion protein. Clinical trials are ongoing to determine whether this approach will be useful.
The pebble gene is required for cytokinesis in Drosophila (1992)

Cytokinesis is developmentally controlled during Drosophila embryogenesis. It is omitted during the initial nuclear division cycles. The nuclei of the resulting syncytium are then cellularized at a defined stage, and cytokinesis starts in somatic cells with mitosis 14. However, cytokinesis never occurs in somatic cells of embryos homozygous or transheterozygous for mutations in the pebble gene. Interestingly, the process of cellularization, which involves steps mechanistically similar to cytokinesis, is not affected. Moreover, all the nuclear aspects of mitosis (nuclear envelope breakdown, chromosome condensation, spindle assembly and function) proceed normally in pebble mutant embryos, indicating that pebble is specifically required for the coordination of mitotic spindle and contractile ring functions. The pebble phenotype is also observed, but only with very low penetrance, during the early divisions of the germ line progenitors (the pole cells). alpha-Amanitin injection experiments indicate that these early pole cell divisions, the first cell divisions during embryogenesis, do not require zygotic gene expression. These divisions might therefore rely on maternally contributed pebble function. The maternal contribution from heterozygous mothers might be insufficient in rare cases for all the pole cell divisions.
Changing Computing Paradigms Towards Power Efficiency (2016)

Power awareness is fast becoming immensely important in computing, ranging from the traditional high-performance computing applications to the new generation of data centric workloads. In this work, we describe our efforts towards a power-efficient computing paradigm that combines low- and high-precision arithmetic. We showcase our ideas for the widely used kernel of solving systems of linear equations that finds numerous applications in scientific and engineering disciplines as well as in large-scale data analytics, statistics and machine learning. Towards this goal, we developed tools for the seamless power profiling of applications at a fine-grain level. In addition, we verify here previous work on post-FLOPS/W metrics and show that these can shed much more light in the power/energy profile of important applications.
Glutamate receptor ligands attenuate allodynia and hyperalgesia and potentiate morphine effects in a mouse model of neuropathic pain (2008)

Recent studies have indicated that metabotropic glutamate receptors mGluR5, mGluR2/3 and mGluR7 are present in the regions of central nervous system important for nociceptive transmission, but their involvement in neuropathic pain has not been well established. We demonstrated that acute and chronic administration of MPEP (mGluR5 antagonist), LY379268 (mGluR2/3 agonist), and AMN082 (mGluR7 agonist) attenuated allodynia (von Frey test) and hyperalgesia (cold plate test) as measured in Swiss albino mice on day seven after chronic constriction injury (CCI) to the sciatic nerve. Moreover, single administration of MPEP (30 mg/kg; i.p.) or LY379268 (10mg/kg; i.p.) injected 30 min before morphine potentiated morphine's effects (20mg/kg; i.p.) in the mouse CCI model, as measured by both the tests mentioned above. However, a single administration of AMN082 (3mg/kg; i.p.) potentiated the effects of a single morphine injection (20mg/kg; i.p.) in the von Frey test only. Chronic administration (7 days) of low doses of MPEP, LY379268 or AMN082 (all drugs at 3mg/kg; i.p.) potentiated the effects of single doses of morphine (3, 10, and 20mg/kg; i.p.) administered on day seven; however, AMN082 only potentiated the effect in the cold plate test. Additionally, the same doses of MPEP and LY379268 (but not AMN082) chronically co-administered with morphine (40 mg/kg; i.p.) attenuated the development of morphine tolerance in CCI-exposed mice. Our data suggest that mGluR5, mGluR2/3, and mGluR7 are involved in injury-induced plastic changes in nociceptive pathways and that the mGluR5 and mGluR2/3 ligands enhanced morphine's effectiveness in neuropathy, which could have therapeutic implications.
Discovery of GSK837149A, an inhibitor of human fatty acid synthase targeting the β‐ketoacyl reductase reaction (2008)

GSK837149A has been identified as a selective inhibitor of human fatty acid synthase (FAS). The compound was first isolated as a minor impurity in a sample found to be active against the enzyme in a high‐throughput screening campaign. The structure of this compound was confirmed by NMR and MS studies, and evaluation of the newly synthesized molecule confirmed its activity against FAS. The compound and other analogs synthesized, all being symmetrical structures containing a bisulfonamide urea, act by inhibiting the β‐ketoacyl reductase activity of the enzyme. GSK837149A inhibits FAS in a reversible mode, with a K i value of ∼ 30 n m , and it possibly binds to the enzyme–ketoacyl‐ACP complex. Although initial results suggest that cell penetration for these compounds is impaired, they still can be regarded as useful tools with which to probe and explore the β‐ketoacyl reductase active site in FAS, helping in the design of new inhibitors.
ChemInform Abstract: Carotenoids—Free Radical Interactions (2001)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
DNS Resolver MIB Extensions (1994)

This document specifies an Internet standards track protocol for the Internet community, and requests discussion and suggestions for improvements.
Regulation of platelet membrane levels of glycoprotein VI by a platelet-derived metalloproteinase (2004)

Thrombosis can be initiated when activated platelets adhere to injured blood vessels via the interaction of subendothelial collagen with its platelet receptor, glycoprotein (GP) VI. Here we observed that incubation of platelets with convulxin, collagen, or collagen-related peptide (CRP) resulted in GPVI signaling-dependent loss of surface GPVI and the appearance of an approximately 55-kDa soluble fragment of GPVI as revealed by immunoblotting. Ethylenediaminetetraacetic acid (EDTA) or GM6001 (a metalloproteinase inhibitor with broad specificity) prevented this loss. In other receptor systems, calmodulin binding to membrane-proximal cytoplasmic sequences regulates metalloproteinase-mediated ectodomain shedding. In this regard, we have previously shown that calmodulin binds to a positively charged, membrane-proximal sequence within the cytoplasmic tail of GPVI. Incubation of platelets with calmodulin inhibitor W7 (150 microM) resulted in a time-dependent loss of GPVI from the platelet surface. Both EDTA and GM6001 prevented this loss. Surface plasmon resonance demonstrated that W7 specifically blocked the association of calmodulin with an immobilized synthetic peptide corresponding to the calmodulin-binding sequence of GPVI. These findings suggest that disruption of calmodulin binding to receptor cytoplasmic tails by agonist binding to the receptor triggers metalloproteinase-mediated loss of GPVI from the platelet surface. This process may represent a potential mechanism to regulate GPVI-dependent platelet adhesion.
Detection of circulating cytokeratin-positive cells in the blood of breast cancer patients using immunomagnetic enrichment and digital microscopy. (2002)

Breast carcinoma cells can be detected in the blood from a significant fraction of metastatic breast cancer patients using immunomagnetic cell enrichment and digital microscopy. The incidence of CK+ cells was low in those with resected N+ disease (at most 26%) and those with resected N- breast cancer (at most 14%). This technique could be used in large prospective studies of patients with breast cancer to learn whether the detection of rare carcinoma cells is a useful predictive or prognostic factor.
<title>Design of a high-speed high-resolution teleradiology system</title> (1992)

A teleradiology system acquires radiographic images from one location and transmits them to one or more distant sites where they are displayed and/or converted to hardcopy film recordings. The long term goal of this research is to demonstrate that teleradiology systems can provide diagnostically equivalent results when compared to conventional radiographic film interpretation. If this hypothesis is proven, the following radiology tasks will be improved: (1) providing for primary interpretation of radiological images for patients in under served areas as well as other medical facilities; (2) integration of radiological services for multi- hospital/clinic health care provides consortiums (HMOs); (3) improving emergency service and intensive care unit coverage; (4) offering consulting-at-a-distance with sub-speciality radiologists; and (5) providing radiologists in the community or in rural areas immediate access to large academic centers for help in the interpretation of difficult and problematic cases. We are designing a high-speed, high-resolution teleradiology system between our level I medical center and several outlying medical centers within the metropolitan area. CT, MR and screen-film examinations will be digitized to 2 K or 4 K at the remote sites, transmitted to the central referral facility and sent to a laser film printer, reproducing the original film. The film can then be used for primary diagnosis, overreading/consultative purposes or for emergency room preparation. Inherently digital modality data (e.g. MR and CT) can be sent without digitization of the multi-format film is desired. A teleradiology system using a Wide Area Network (WAN) is to be connected to the following sites: (1) Olive View Medical Center; (2) Harbor General Medical Center; (3) UCLA Department of Radiological Sciences; and (4) two radiologist''s private residences. The wide area network (WAN) consists of a local carrier (GTE California Incorporated) and an inter-exchange carrier (US Sprint). Each affiliated hospital site is equipped with: (1) a radiographic film digitizer; (2) an interactive grayscale display workstation; (3) a computer system with teleradiology application software; (4) a local area network (LAN); (5) a LAN-WAN router; and (6) and dial-up (multiple switched N X 56 kbps lines) DS-1 WAN interfaces. The UCLA site is equipped with a local area image management network (PACS) for archiving, displaying, laser printed film hardcopy recordings, and WAN interfaces. The radiologists private residence is equipped with a grayscale station and a DS-0 56 kbps modem. We estimate the hardware costs at each remote site to be $DLR160,000, $DLR200,000 for the central referring facility, and under $DLR20,000 for the radiologist private residence.
Production and characterization of monoclonal antibodies to the glycosyl phosphatidylinositol‐anchored lymphocyte differentiation antigen ecto‐5′‐nucleotidase (CD73). (1990)

A panel of monoclonal antibodies to the 69 kDa glycosyl phosphatidylinositol anchored lymphocyte differentiation antigen ecto-5'-nucleotidase (ecto-5'-NT, CD73) was produced using highly purified human placental 5'-NT as immunogen. Antibodies 1E9.28.1 and 7G2.2.11 inhibit soluble placental 5'-NT activity and recognize lymphocyte CD73 in indirect immunofluorescence and immunoprecipitation assays. In addition, 1E9.28.1 induces vigorous T cell proliferation in the presence of submitogenic doses of phorbol myristate and F(ab')2 goat anti-mouse Ig. Both antibodies can be used to purify the three major forms of placental 5'-NT by affinity chromatography. By two-color immunofluorescence, CD73 was found to be expressed on 19 +/- 5% of CD3+, 11 +/- 4% of CD4+, 51 +/- 14% of CD8+, 25 +/- 8% of CD28+, 15 +/- 5% of CD29+, 27 +/- 7% of CD45RA+, and 70 +/- 6% of CD19+ lymphocytes. Within T cells, CD73 expression is restricted to the CD28+ subset. Thus, CD73 is found on subsets of both T and B lymphocytes, with the highest expression on B cells and CD8+ T cells. In sections of hyperplastic tonsil, CD73 expression is restricted to the small lymphocytes of the follicular mantle zone, a small subset of extrafollicular lymphocytes situated within the epithelium of the tonsillar crypt, and to follicular dendritic cells within the lower part of the "light-zone." CD73 is also detected on subsets of endothelial cells of capillaries and venules and the basal layer of non-keratinizing squamous epithelium and transitional cell type mucosa of many tissues. Given the tissue distribution of CD73, along with its glycosyl phosphatidylinositol membrane anchoring and the observation that some CD73 antibodies are mitogenic, we propose that this interesting antigen may play a role in cell activation, lymphocyte homing, and/or cell adhesion.
Erythropoietin protects primary hippocampal neurons increasing the expression of brain‐derived neurotrophic factor (2005)

Erythropoietin, the principal regulator of erythroids progenitor cells, also promotes neuronal survival. Using primary cultures of rat hippocampal neurons, we investigated whether erythropoietin could mediate neuroprotection favouring the transcription of brain-derived neurotrophic factor (BDNF). Erythropoietin 2.7 nm reduced by approximately 50% the neuronal death triggered by the prototypic neurotoxicant trimethyltin (TMT) and time-dependently induced BDNF mRNA. This effect resulted in an increased production of biologically active BDNF, which led to a sustained activation of the specific BDNF receptor tyrosine kinase B (TrkB). Reduction of TMT-induced neuronal death by erythropoietin was specifically prevented by a neutralizing anti-BDNF antibody (15 microg/mL), indicating the involvement of this neurotrophin in erythropoietin neuroprotective effect. Intracerebroventricular administration of erythropoietin in mice significantly increases BDNF mRNA expression in brain, supporting the idea of the involvement of this neurotrophin in erythropoietin action within the CNS. BDNF expression in neuronal cells is induced by activation of voltage Ca(2+)-channels and recruitment of Ca(2+)-sensitive transcription factors. Consistently, 2.7 nm erythropoietin increased intracellular Ca(2+) in 5 min and cAMP response element binding protein (CREB) phosphorylation at Ser 133 in 30 min. Both effects were abolished by 1 microm nitrendipine, a selective blocker of L-type voltage Ca(2+)-channels. These data demonstrate that erythropoietin activates the CREB transcription pathway and increases BDNF expression and production, which contributes to erythropoietin mediated neuroprotection.
Genes for epidermal growth factor receptor, transforming growth factor alpha, and epidermal growth factor and their expression in human gliomas in vivo. (1991)

Anomalies of the epidermal growth factor receptor (EGFR) gene, including amplification, rearrangement, and overexpression, have been reported in malignant human gliomas in vivo. In vitro glioma cell lines coexpress EGFR and at least one of its ligands, transforming growth factor alpha, suggesting the existence of an autocrine growth stimulatory loop. We have studied the tumor tissue from 62 human glioma patients and examined the structure and quantity of the EGFR gene and its transcripts, as well as the quantity of the receptor protein. In addition we have examined the genes and transcripts coding for the pre-pro forms of epidermal growth factor and transforming growth factor alpha, the two endogenous EGFR ligands. EGFR gene amplification was detected in 16 of the 32 malignancy grade IV gliomas (glioblastoma) studied (50%), but only in 1 of 30 gliomas of lesser malignancy grade (I-III). All tumors with an amplified gene overexpressed EGFR mRNA. More than one-half (62.5%) of the glioblastomas with amplified EGFR genes also showed coamplification of rearranged EGFR genes and concomitant expression of aberrant mRNA species. Overexpression, without gene amplification, was observed in some of the low grade gliomas, and aberrant EGFR transcripts were also seen in some cases without gene amplification or detected gene rearrangements. mRNA expression for one or both of the pre-pro forms of the ligands was detected in every tumor studied. Thus, several mechanisms for the activation of the EGFR-mediated growth stimulating pathway are possible in human gliomas in vivo: expression of a structurally altered receptor that may have escaped normal control mechanisms; and/or auto-, juxta-, or paracrine stimulating mechanisms involving coexpression of receptor and ligands, with or without overexpression of the receptor.
Expression of serum Dickkopf-1 in gastric cancer patients (2015)

The expression of serum DKK-1 protein in gastric cancer patients is increased. Level of serum DKK-1 is related to TNM staging, microvascular invasion, differentiation degree and infiltration depth. DKK-1 detection can be used as a reference index in monitoring gastric cancer progress and biological behavior.
Identification of putative tumor suppressor gene activities in nasopharyngeal carcinoma (2002)

Identification of putative tumor suppressor gene activities in nasopharyngeal carcinoma by Yue Cheng thesis 2002 xviii, 192 leaves : ill. (some col.) ; 30 cm Nasopharyngeal carcinoma (NPC) is a cancer that is rare in most areas of the world,…Read more ›
Switchable cylindrical dielectric resonator antenna (1996)

A switchable cylindrical dielectric resonator antenna, operating in four different radiation modes, is reported. Two linear polarised, one circular polarised, and a nonradiating mode are implemented. The experimental results of the resonant frequency, boresight axial ratio, gain, unloaded Q-factor, impedance bandwidth and radiation efficiency are presented for the operating modes and compared with the theoretical values.
Akt is altered in an animal model of Huntington's disease and in patients (2005)

The insulin-like growth factor I (IGF-1)/Akt pathway plays a crucial role in Huntington's disease by phosphorylating the causative protein, polyQ-huntingtin, and abolishing its toxic properties [Humbert et al. (2002)Dev. Cell, 2, 831-837; Rangone et al. (2004)Eur. J. Neurosci., 19, 273-279]. Therefore, dysregulation of this pathway may be essential for disease progression. In the present report, we thus aimed to analyse the status of Akt in brain or in peripheral tissues in Huntington's disease. Using a genetic model of Huntington's disease in rat that reproduces neuronal dysfunction and death, we show a progressive alteration of Akt during neuronal dysfunction and prior neurodegeneration. By analysing a limited number of lymphoblasts and lymphocytes, we detected modifications of Akt in Huntington's disease patients confirming a dysregulation of Akt in the disease process. Finally, we demonstrate that during late stages of the disease, Akt is cleaved into an inactive form by caspase-3. These observations demonstrate a progressive but marked alteration of this pro-survival pathway in Huntington's disease, and further implicate it as a key transduction pathway regulating the toxicity of huntingtin.
Nondestructive Evaluation of Pavements by Surface Wave Method (1989)

The spectra-analysis of surface waves (SASW) method is a seismic method that can be used to determine elastic modulus profiles of pavement sections nondestructively. This method is based upon the theory of stress wave propagation in layered media. The dispersive characteristics of measured surface waves are used for determining the elastic modulus and thickness of each layer in the profile. This paper contains a description of the in situ testing technique and the in-house data reduction procedure used in conducting SASW tests. Emphasis is placed on demonstrating situations where SASW tests can be utilized more effectively than other nondestructive tests. For example, when bedrock is present at shallow depths or when the pavement layers are thin, use of the SASW method may be preferred. Two case studies illustrating the accuracy, sensitivity, and limitations of the method are also included.
Protein Kinase Cδ Activation Induces Apoptosis in Response to Cardiac Ischemia and Reperfusion Damage (2004)

Heart attacks caused by occlusion of coronary arteries are often treated by mechanical or enzymatic removal of the occlusion and reperfusion of the ischemic heart. It is now recognized that reperfusion per se contributes to myocardial damage, and there is a great interest in identifying the molecular basis of this damage. We recently showed that inhibiting protein kinase Cdelta (PKCdelta) protects the heart from ischemia and reperfusion-induced damage. Here, we demonstrate that PKCdelta activity and mitochondrial translocation at the onset of reperfusion mediates apoptosis by facilitating the accumulation and dephosphorylation of the pro-apoptotic BAD (Bcl-2-associated death promoter), dephosphorylation of Akt, cytochrome c release, PARP (poly(ADP-ribose) polymerase) cleavage, and DNA laddering. Our data suggest that PKCdelta activation has a critical proapoptotic role in cardiac responses following ischemia and reperfusion.
Crosslinked hyaluronic acid dermal fillers: A comparison of rheological properties (2008)

Temporary dermal fillers composed of crosslinked hyaluronic acid (XLHA) are space filling gels that are readily available in the United States and Europe. Several families of dermal fillers based on XLHA are now available and here we compare the physical and rheological properties of these fillers to the clinical effectiveness. The XLHA fillers are prepared with different crosslinkers, using HA isolated from different sources, have different particle sizes, and differ substantially in rheological properties. For these fillers, the magnitude of the complex viscosity, |eta*|, varies by a factor of 20, the magnitude of the complex rigidity modulus, |G*|, and the magnitude of the complex compliance, |J*| vary by a factor of 10, the percent elasticity varies from 58% to 89.9%, and the tan delta varies from 0.11 to 0.70. The available clinical data cannot be correlated with either the oscillatory dynamic or steady flow rotational rheological properties of the various fillers. However, the clinical data appear to correlate strongly with the total concentration of XLHA in the products and to a lesser extent with percent elasticity. Hence, our data suggest the following correlation: dermal filler persistence = [polymer] x [% elasticity] and the clinical persistence of a dermal filler composed of XLHA is dominated by the mass and elasticity of the material implanted. This work predicts that the development of future XLHA dermal filler formulations should focus on increasing the polymer concentration and elasticity to improve the clinical persistence.