gebhart/patrepeval huggingface dataset:
Molecular Architecture of the 40S⋅eIF1⋅eIF3 Translation Initiation Complex (2014)

Eukaryotic translation initiation requires the recruitment of the large, multiprotein eIF3 complex to the 40S ribosomal subunit. We present X-ray structures of all major components of the minimal, six-subunit Saccharomyces cerevisiae eIF3 core. These structures, together with electron microscopy reconstructions, cross-linking coupled to mass spectrometry, and integrative structure modeling, allowed us to position and orient all eIF3 components on the 40S⋅eIF1 complex, revealing an extended, modular arrangement of eIF3 subunits. Yeast eIF3 engages 40S in a clamp-like manner, fully encircling 40S to position key initiation factors on opposite ends of the mRNA channel, providing a platform for the recruitment, assembly, and regulation of the translation initiation machinery. The structures of eIF3 components reported here also have implications for understanding the architecture of the mammalian 43S preinitiation complex and the complex of eIF3, 40S, and the hepatitis C internal ribosomal entry site RNA.
An Inexpensive, All Solid-state Video and Data Recorder for Accident Reconstruction (1999)

&lt;div class="section abstract"&gt;&lt;div class="htmlview paragraph"&gt;An accurate record of the events preceding a traffic accident is useful to trucking companies, car rental agencies, commercial carriers, and insurance providers, as well as to passenger car drivers. A video and data recording is very helpful for accurate accident reconstruction. We have made a prototype of a “personal eye witness”: a small video camera with solid state memory and a short recording time. The camera records continuously until it senses an accident, then it saves a video record of the events surrounding the accident in time. Since video is available from both before and after the collision, accident reconstruction becomes easier. The camera uses only solid state memory with no moving parts, can be manufactured inexpensively, and can be packaged in a crash-resistant and tamper-resistant module. Automobile data can be added as sideband data or overlaid text to the video data storage path.&lt;/div&gt;&lt;/div&gt;
Pre-Clinical Development Of a Novel Chimerical Antigen Receptor Targeting High-Risk Pediatric ALL Over-Expressing Tslpr (2013)

Abstract Background While current upfront therapy will cure over 80% of patients, B-cell precursor acute lymphoblastic leukemia ALL (BCP-ALL) remains a leading cause of cancer-related death in children, and outcomes for those patients who relapse have not been changed substantially over recent decades. Immunotherapy with a chimeric antigen receptor (CAR) targeting CD19 has resulted in impressive clinical responses, but alternative CAR targets are needed as not all patients respond and CD19 negative relapses have been observed. Thymic stromal lymphoprotein receptor (TSLPR) is coded by the CRLF2 gene. CRLF2 genetic alterations occur in 5-16% of pediatric and adult BCP-ALL and result in TSLPR over-expression that is associated with poor prognosis. Furthermore, emerging data suggests that TSLPR overexpression is functionally important for leukemic blasts. Thus, TSLPR is an ideal immunotherapeutic target. We constructed TSLPR-specific CARs and tested their therapeutic efficacy in vitro and in vivo. Methods Hybridomas producing TSLPR-specific antibodies were used to clone variable regions of the heavy and light chains for constructing TSLPR-specific scFv. The scFv was linked with the CD8α hinge and transmembrane domain, 4-1BB intracellular domain and CD3ζ chain, and then cloned into a 3rd generation lentiviral vector. For optimization of the CAR configuration, an IgG heavy chain constant domain (CH2CH3) spacer was fused to scFv to generate a “long” TSLPR CAR. Human T cells were transduced with CAR vectors and the transduced cells were evaluated in vitro and in vivo against TSLPR-overexpressing ALL, including a TSLPR-transduced REH cell line (REH-TSLPR) and patient-derived xenografts naturally overexpressing TSLPR. Results Both long and short TSLPR CARs could be efficiently transduced (approximately 60-80%) into human T cells using a lentiviral system. T cells expressing both long and short TSLPR CARs produced high levels of cytolytic cytokines upon co-culture with of TSLPR-overexpressing ALL. However, only the short TSLPR CAR demonstrated effective killing against TSLPR-expression ALL cells in vitro. Short TSLPR-expressing T cells completely eradicated leukemia in NSG xenografts mice bearing REH-TSLPR (figure 1) as well as TSLPR-expressing patient xenografts. The long TSLPR CAR did not show any activity in vivo. Conclusion TSLPR-targeted CAR T cells is promising therapeutic approach in high risk BCP-ALL and represents the first example of an oncogene-specific cellular therapy in BCP-ALL. Disclosures: Grupp: Novatis: Research Funding.
Interleukin 13 Is Secreted by and Stimulates the Growth of Hodgkin and Reed-Sternberg Cells (1999)

Gene expression patterns can provide vital clues to the pathogenesis of neoplastic diseases. We investigated the expression of 950 genes in Hodgkin's disease (HD) by analyzing differential mRNA expression using microarrays. In two independent microarray experiments, the HD-derived cell lines L428 and KMH2 were compared with an Epstein-Barr virus (EBV)-immortalized lymphoblastoid B cell line, LCL-GK. Interleukin (IL)-13 and IL-5 were found to be highly expressed in the HD-derived cell lines. Examination of IL-13 and IL-5 expression by Northern blot analysis and enzyme-linked immunosorbent assay confirmed these results and revealed the expression of IL-13 in a third HD-derived cell line, HDLM2. Control LCL and EBV-negative non-Hodgkin lymphoma-derived cell lines did not express IL-13. In situ hybridization of lymph node tissue from HD patients showed that elevated levels of IL-13 were specifically expressed by Hodgkin/Reed-Sternberg (H/RS) tumor cells. Treatment of a HD-derived cell line with a neutralizing antibody to IL-13 resulted in a dose-dependent inhibition of H/RS cell proliferation. These data suggest that H/RS cells produce IL-13 and that IL-13 plays an important role in the stimulation of H/RS cell growth, possibly by an autocrine mechanism. Modulation of the IL-13 signaling pathway may be a logical objective for future therapeutic strategies.
A 54-kDa normal cellular protein may be the precursor of the scrapie agent protease-resistant protein. (1986)

Scrapie is the best understood of the transmissible spongiform encephalopathies. These neurologic disorders include the human diseases kuru and Creutzfeldt-Jakob disease and are caused by pathogens with unique biological and molecular properties. One major protein, protease-resistant protein (PrP)-27-30, is present in fractions isolated from scrapie-infected hamster brain that contain highly purified scrapie agent. PrP-27-30 appears to be the major protein component of the hamster scrapie agent. An antiserum generated to electrophoretically purified hamster scrapie PrP-27-30 identified higher molecular weight proteins in immunoblots of homogenates of uninfected hamster and mouse brains. Antibodies to hamster and mouse scrapie agent proteins were obtained by immunoaffinity purification of this antiserum. These antibodies to hamster and mouse PrPs recognized a 54-kDa protein present in uninfected brain homogenates. Antibodies immunoaffinity purified from this antiserum using whole immunoblots of normal brain antigens also identified the 54-kDa protein and PrPs. Our findings demonstrate that scrapie agent proteins share epitopes with normal proteins and suggest that the 54-kDa protein is the normal protein precursor of the scrapie agent PrPs.
A transcription-activating polymorphism in the ACHE promoter associated with acute sensitivity to anti-acetylcholinesterases (2000)

Hypersensitivity to acetylcholinesterase inhibitors (anti-AChEs) causes severe nervous system symptoms under low dose exposure. In search of direct genetic origin(s) for this sensitivity, we studied six regions in the extended 22 kb promoter of the ACHE gene in individuals who presented adverse responses to anti-AChEs and in randomly chosen controls. Two contiguous mutations, a T-->A substitution, disrupting a putative glucocorticoid response element, and a 4-bp deletion, abolishing one of two adjacent HNF3 binding sites, were identified 17 kb upstream of the transcription start site. Allele frequencies for these mutations were 0.006 and 0.012, respectively, in 333 individuals of various ethnic origins, with a strong linkage between the deletion and the biochemically neutral H322N mutation in the coding region of ACHE. Heterozygous carriers of the deletion included a proband who presented with acute hypersensitivity to the anti-AChE pyridostigmine and another with unexplained excessive vomiting during a fourth pregnancy following three spontaneous abortions. Electromobility shift assays, transfection studies and measurements of AChE levels in immortalized lymphocytes as well as in peripheral blood from both carriers and non-carriers, revealed functional relevance for this mutation both in vitro and in vivo and showed it to increase AChE expression, probably by alleviating competition between the two hepatocyte nuclear factor 3 binding sites. Moreover, AChE-overexpressing transgenic mice, unlike normal FVB/N mice, displayed anti-AChE hypersensitivity and failed to transcriptionally induce AChE production following exposure to anti-AChEs. Our findings point to promoter polymorphism(s) in the ACHE gene as the dominant susceptibility factor(s) for adverse responses to exposure or to treatment with anti-AChEs.
Systemic therapy with tumor suppressor FUS1-nanoparticles for stage IV lung cancer (2007)

LB-348 The tumor suppressor gene FUS1 is frequently inactivated early in the development of lung cancer. FUS1 mediates apoptosis in cancer cells but not normal cells through its interaction with Apaf1. We developed a DOTAP:cholesterol nanoparticle encapsulating a FUS1 expression plasmid that showed selective uptake by cancer cells compared to normal cells. In this clinical trial a DOTAP:cholesterol FUS1 nanoparticle was injected intravenously in stage IV lung cancer patients who had progressive disease after cisplatin combination chemotherapy based on preclinical data showing successful treatment of metastatic lung cancer in mouse xenograft models. Nanoparticle-DNA complexes were manufactured in GMP facilities to meet specifications of OD400, size, appearance, and transfection efficiency. Patients received doses ranging from 0.01-0.03mg/kg at 3 week intervals for a maximum of 6 doses. Dexamethasone and diphenhydramine premedications were added and eliminated the only clinically significant toxicity of fever. To date 13 patients have been entered on the study at three different doses (0.1, 0.02, 0.03mg/kg). All patients could be evaluated for the primary endpoint of toxicity, and with pretreatment, there was no significant drug related toxicity. Four patients received only one dose because of rapidly progressing disease at a site requiring local treatment. Eight patients received two or more doses and can be evaluated for response with 3 patients achieving stable disease (3 - 7 months) and 5 patients progressing. Median survival time for all patients is 14.6 months which compares favorably to the published 7 months median survival for second line chemotherapy and 4 months for best supportive care for non-small cell lung cancer. Actuarial survival at 12 months was 55%. A maximum tolerated dose (MTD) has not been reached. Pre and 24 hour posttreatment tumor biopsies were obtained from 3 patients. A quantitative real time reverse transcriptase PCR (RT-PCR) analysis using a plasmid FUS1 sequence-specific probe was performed on samples blinded to time of biopsy. A high level of plasmid FUS1 expression was detected in all 3 posttreatment samples but not in three pretreatment samples and negative controls by RT-PCR. DOTAP:cholesterol FUS1 nanoparticles can be safely administered intravenously in patients with stage IV lung cancer. Gene expression is detected in tumors, and there is an indication of anti-tumor activity.
Electromorphic characterization and description of conserved epitopes of the lipooligosaccharides of group A Neisseria meningitidis (1988)

We studied the lipooligosaccharides (LOS) of 28 group A Neisseria meningitidis of epidemiologically diverse origins to investigate whether each of the LOS serotypes found in serogroup A could be identified physically as well as antigenically. Using a dot blot assay with LOS-specific monoclonal antibodies (MAbs), we identified four epitopes that were serotype specific. The LOS from strains of each serotype were electromorphically and antigenically distinct when analyzed by silver-stained sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblotting. The LOS of L8 strains contained a 3,600-Mr component that bound the L8 MAb. The LOS of L9 strains contained two major components of 4,500 and 4,200 Mr. They bound the L9 MAb to the larger component. The LOS of L10 strains had a single major component of 4,000 Mr that bound the L10 MAb. The LOS of L11 strains contained a major 3,600-Mr component that could not be distinguished from the 3,600-Mr LOS of L8 strains by SDS-PAGE but that bound the L11 MAb. LOS of group A strains contained a highly conserved epitope in addition to a serotype-specific epitope. This was identified by a MAb that bound to all the strains on dot-blots and to multiple LOS components of various Mrs on immunoblots. We conclude that the LOS which bear the L9, L10, and L11 determinants are physically distinct and can be identified by SDS-PAGE or MAb binding or both. L8 and L11 are both borne on a 3.6-kilodalton LOS and can only be distinguished serologically.
IVEE: an Information Visualization and Exploration Environment (2002)

The Information Visualization and Exploration Environment (NEE) is a system for automatic creation of dynamic queries applications. IVEE imports database relations and automatically creates environments holding visualizations and query devices. IVEE offers multiple visualizations such as maps and starfields, and multiple query devices, such as sliders, alphasliders, and toggles. Arbitrary graphical objects can be attached to database objects in visualizations. Multiple visualizations may be active simultaneously. Users can interactively lay out and change between types of query devices. Users may retrieve details-on-demand by clicking on visualization objects. An HTML file may be provided along with the database, specifying how details-on-demand information should be presented, allowing for presentation of multimedia information in database objects. Finally, multiple IVEE clients running on separate workstations on a network can communicate by letting one user's actions affect the visualization in an another IVEE client.
SRM inverter topologies: a comparative evaluation (1991)

Several inverter power circuits suitable for switched reluctance motor (SRM) drives are analyzed and compared. Five inverter circuits are considered with the objective of establishing the most appropriate topology for an SRM drive. The comparison is based on the peak voltage and peak current ratings of the DC link components. Because the power converter choice depends on the motor design, the converter analysis and selection are done for a high-speed, 6/2 SRM suitable for a spindle drive and a high-torque 8/6 motor. Experimental results obtained for a high-torque drive are included.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Expression and role of the cell surface protease seprase/fibroblast activation protein-α (FAP-α) in astroglial tumors (2010)

Seprase or fibroblast activation protein-α (FAP-α) is a cell-surface serine protease that was previously described nearly exclusively on reactive and tumor stromal fibroblasts and thought to be involved in tissue remodeling. We investigated the expression and significance of FAP-α in astrocytomas/glioblastomas. As shown by quantitative reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemistry, FAP-α was elevated in whole glioblastoma tissues and in particular in most glioma cells in situ and in vitro. In glioma stem-like cells (gliospheres), FAP-α was detected at low levels; however, FAP-α was considerably induced upon differentiation with 10% fetal calf serum. To explore its functional role, FAP-α was silenced by siRNA transfection. In Boyden chamber assays, FAP-α silenced cells migrated similar as control cells through non-coated or Matrigel (basal lamina)-coated porous membranes, but significantly slower through membranes coated with gelatin or brevican, a major component of brain extracellular matrix. Furthermore, FAP-α-silenced glioma cells migrated through murine brain slices much slower under the conditions tested than differentially fluorescent-labeled control cells. Thus, FAP-α is highly expressed on the surface of glioma cells and contributes to diffuse glioma invasion through extracellular matrix components.
Large-Scale Analysis of Yeast Filamentous Growth by Systematic Gene Disruption and Overexpression (2007)

Under certain conditions of nutrient stress, the budding yeast Saccharomyces cerevisiae initiates a striking developmental transition to a filamentous form of growth, resembling developmental transitions required for virulence in closely related pathogenic fungi. In yeast, filamentous growth involves known mitogen-activated protein kinase and protein kinase A signaling modules, but the full scope of this extensive filamentous response has not been delineated. Accordingly, we have undertaken the first systematic gene disruption and overexpression analysis of yeast filamentous growth. Standard laboratory strains of yeast are nonfilamentous; thus, we constructed a unique set of reagents in the filamentous Sigma1278b strain, encompassing 3627 integrated transposon insertion alleles and 2043 overexpression constructs. Collectively, we analyzed 4528 yeast genes with these reagents and identified 487 genes conferring mutant filamentous phenotypes upon transposon insertion and/or gene overexpression. Using a fluorescent protein reporter integrated at the MUC1 locus, we further assayed each filamentous growth mutant for aberrant protein levels of the key flocculence factor Muc1p. Our results indicate a variety of genes and pathways affecting filamentous growth. In total, this filamentous growth gene set represents a wealth of yeast biology, highlighting 84 genes of uncharacterized function and an underappreciated role for the mitochondrial retrograde signaling pathway as an inhibitor of filamentous growth.
Phospholamban Inhibitory Function Is Activated by Depolymerization (1997)

Phospholamban (PLN), a homopentameric, integral membrane protein, reversibly inhibits cardiac sarcoplasmic reticulum Ca2+-ATPase (SERCA2a) activity through intramembrane interactions. Here, alanine-scanning mutagenesis of the PLN transmembrane sequence was used to identify two functional domains on opposite faces of the transmembrane helix. Mutations in one face diminish inhibitory interactions with transmembrane sequences of SERCA2a, but have relatively little effect on the pentameric state, while mutations in the other face activate inhibitory interactions and enhance monomer formation. Double mutants are monomeric, but loss of inhibitory function is dominant over activation of inhibitory function. These observations support the proposal that the SERCA2a interaction site lies on the helical face which is not involved in pentamer formation. Four highly inhibitory mutants are effectively devoid of pentamer, suggesting that pentameric PLN represents a less active or inactive reservoir that dissociates to provide inhibitory monomeric PLN subunits. A model is presented in which the degree of PLN inhibition of SERCA2a activity is ultimately determined by the concentration of the inhibited PLN monomer.SERCA2a heterodimeric complex. The concentration of this inhibited complex is determined by the dissociation constant for the PLN pentamer (which is mutation-sensitive) and by the dissociation constant for the PLN/SERCA2a heterodimer (which is likely to be mutation-sensitive).
Clinical edge: Ultrasound in the acute abdomen (2015)

The term 'acute abdomen' denotes the rapid onset of abdominal symptoms which may indicate potentially life-threatening pathology and the need for urgent surgical intervention, and generally excludes trauma as an underlying cause.
Haematoma scavenging in intracerebral haemorrhage: from mechanisms to the clinic (2017)

The products of erythrocyte lyses, haemoglobin (Hb) and haem, are recognized as neurotoxins and the main contributors to delayed cerebral oedema and tissue damage after intracerebral haemorrhage (ICH). Finding a means to efficiently promote absorption of the haemolytic products (Hb and haem) around the bleeding area in the brain through stimulating the function of the body's own garbage cleaning system is a novel clinical challenge and critical for functional recovery after ICH. In this review, available information of the brain injury mechanisms underlying ICH and endogenous haematoma scavenging system is provided. Meanwhile, potential intervention strategies are discussed. Intracerebral blood itself has 'toxic' effects beyond its volume effect after ICH. Haptoglobin-Hb-CD163 as well as haemopexin-haem-LRP1 is believed to be the most important endogenous scavenging pathway which participates in blood components resolution following ICH. PPARγ-Nrf2 activates the aforementioned clearance pathway and then accelerates haematoma clearance. Meanwhile, the scavenger receptors as novel targets for therapeutic interventions to treat ICH are also highlighted.
Forming of Ceramic Laminates Comprising Thin Layers of a Few Particles (2008)

In this paper, a water‐based colloidal processing method for manufacturing multilayers with very thin zirconia layers between thick alumina‐based layers is presented. The procedure involves the dip coating of green tapes in binder‐containing slurries and further lamination and sintering. Dipping studies show that thickness increases with soaking time until a higher limit is achieved, indicating the existence of interaction between slurry and substrate. After sintering, homogeneous, dense, and continuous zirconia layers with thicknesses between 3 and 0.8 μm alternated with 350 μm layers of alumina are obtained, thus meaning that the cross section of these thin layers range from four or five to only one or two grains. Although the residual stresses are estimated to be around 2 GPa, indentation cracks do not shown any interaction when passing through the compressive layers, indicating the existence of a lower thickness limit to achieve a threshold stress.
α‐Thymidin (1960)

Abstract Die Kondensation von Monoquecksilberthymin mit Di‐ p ‐toluyl‐desoxy‐ D ‐ribofuranosylchlorid führt vorwiegend zum α‐Thymidinderivat, wenn man sie in stark polaren Verdünnungsmitteln wie Dimethylformamid ausführt. Daß es sich nicht um eine Kondensation am N‐3 des Thymins handelt, kann durch Methylierung des Produktes am N‐3 gezeigt werden.