gebhart/patrepeval huggingface dataset:
Two abundant proteasome subtypes that uniquely process some antigens presented by HLA class I molecules (2010)

Most antigenic peptides presented by MHC class I molecules result from the degradation of intracellular proteins by the proteasome. In lymphoid tissues and cells exposed to IFNγ, the standard proteasome is replaced by the immunoproteasome, in which all of the standard catalytic subunits β1, β2, and β5 are replaced by their inducible counterparts β1i, β2i, and β5i, which have different cleavage specificities. The immunoproteasome thereby shapes the repertoire of antigenic peptides. The existence of additional forms of proteasomes bearing a mixed assortment of standard and inducible catalytic subunits has been suggested. Using a new set of unique subunit-specific antibodies, we have now isolated, quantified, and characterized human proteasomes that are intermediate between the standard proteasome and the immunoproteasome. They contain only one (β5i) or two (β1i and β5i) of the three inducible catalytic subunits of the immunoproteasome. These intermediate proteasomes represent between one-third and one-half of the proteasome content of human liver, colon, small intestine, and kidney. They are also present in human tumor cells and dendritic cells. We identified two tumor antigens of clinical interest that are processed exclusively either by intermediate proteasomes β5i (MAGE-A3(271-279)) or by intermediate proteasomes β1i-β5i (MAGE-A10(254-262)). The existence of these intermediate proteasomes broadens the repertoire of antigens presented to CD8 T cells and implies that the antigens presented by a given cell depend on their proteasome content.
Akt Inhibits Apoptosis Downstream of BID Cleavage via a Glucose-Dependent Mechanism Involving Mitochondrial Hexokinases (2003)

The serine/threonine kinase Akt/protein kinase B inhibits apoptosis induced by a variety of stimuli, including overexpression or activation of proapoptotic Bcl-2 family members. The precise mechanisms by which Akt prevents apoptosis are not completely understood, but Akt may function to maintain mitochondrial integrity, thereby preventing cytochrome c release following an apoptotic insult. This effect may be mediated, in part, via promotion of physical and functional interactions between mitochondria and hexokinases. Here we show that growth factor deprivation induced proteolytic cleavage of the proapoptotic Bcl-2 family member BID to yield its active truncated form, tBID. Activated Akt inhibited mitochondrial cytochrome c release and apoptosis following BID cleavage. Akt also antagonized tBID-mediated BAX activation and mitochondrial BAK oligomerization, two downstream events thought to be critical for tBID-induced apoptosis. Glucose deprivation, which impaired the ability of Akt to maintain mitochondrion-hexokinase association, prevented Akt from inhibiting BID-mediated apoptosis. Interestingly, tBID independently elicited dissociation of hexokinases from mitochondria, an effect that was antagonized by activated Akt. Ectopic expression of the amino-terminal half of hexokinase II, which is catalytically active and contains the mitochondrion-binding domain, consistently antagonized tBID-induced apoptosis. These results suggest that Akt inhibits BID-mediated apoptosis downstream of BID cleavage via promotion of mitochondrial hexokinase association and antagonism of tBID-mediated BAX and BAK activation at the mitochondria.
CD38 signaling by agonistic monoclonal antibody prevents apoptosis of human germinal center B cells (1994)

The present study demonstrates that an agonistic anti-CD38 monoclonal antibody (mAb) (IB4) is capable of preventing apoptosis of human tonsillar germinal center (GC) B cells as measured by either morphological methods on Giemsa-stained cytospin preparations or flow cytometry on propidium iodide-stained cells. Two other anti-CD38 mAb (Leu-17 and OKT10) consistently failed to prevent apoptosis in the same cells, even when tested over a wide range of concentrations. Furthermore, exposure of GC B cells to IB4 mAb up-regulates the bcl-2 proto-oncogene product in a manner similar to that observed with CD40 ligand (CD40L). The ability of IB4 mAb to prevent apoptosis of GC B cells was inferior to that of both anti-CD40 mAb and CD40L. No synergistic or additive effects were observed when IB4 mAb was used together with CD40L. Unlike anti-CD40 mAb or CD40L, IB4 mAb neither induced a proliferation of GC B cells nor increased their proliferative response to anti-CD40, CD40L or recombinant interleukin-4, used alone or in combination. The present results are consistent with the recent findings on either the feature of the CD38 molecules to deliver activation signals and on the mechanisms of selection of B cells that operates in the GC.
Schistosome-Infected IL-4 Receptor Knockout (KO) Mice, in Contrast to IL-4 KO Mice, Fail to Develop Granulomatous Pathology While Maintaining the Same Lymphokine Expression Profile (1999)

Th2 lymphocytes have been postulated to play a major role in the immunopathology induced by Schistosoma mansoni infection. Nevertheless, infected IL-4 knockout (KO) and wild-type (wt) mice develop egg granulomas comparable in size. To further investigate the function of the Th2 response in egg pathology we studied IL-4Ralpha-deficient mice, which are nonresponsive to both IL-4 and IL-13. In striking contrast to IL-4 KO animals, infected IL-4Ralpha KO mice developed only minimal hepatic granulomas and fibrosis despite the presence of CD3+ T cells in the residual egg lesions. Moreover, liver lymphokine mRNA levels in these animals and IL-4 KO mice were equivalent. In addition, infected IL-4Ralpha-deficient, IL-4-deficient, and wt animals developed similar egg Ag-specific IgG Ab titers, arguing that CD4-dependent Th activity is intact in KO mice. As expected, IFN-gamma secretion was strongly up-regulated in mesenteric lymph node cultures from both groups of deficient animals, a change reflected in increased serum IgG2a and IgG2b Ab levels. Surprisingly, Th2 cytokine production in infected IL-4Ralpha KO mice was not abolished but was only reduced and resembled that previously documented in IL-4 KO animals. This residual Th2 response is likely to explain the ability of IL-4 KO mice to generate egg granulomas, which cannot be formed in IL-4Ralpha-deficient animals because of their lack of responsiveness to the same cytokine ligands. Taken together, these findings argue that tissue pathology in schistosomiasis requires, in addition to egg-specific CD4+ lymphocytes, a previously unrecognized IL-4Ralpha+ non-T cell effector population.
The MHC class I peptide repertoire is molded by the transcriptome (2008)

Under steady-state conditions, major histocompatibility complex (MHC) I molecules are associated with self-peptides that are collectively referred to as the MHC class I peptide (MIP) repertoire. Very little is known about the genesis and molecular composition of the MIP repertoire. We developed a novel high-throughput mass spectrometry approach that yields an accurate definition of the nature and relative abundance of unlabeled peptides presented by MHC I molecules. We identified 189 and 196 MHC I-associated peptides from normal and neoplastic mouse thymocytes, respectively. By integrating our peptidomic data with global profiling of the transcriptome, we reached two conclusions. The MIP repertoire of primary mouse thymocytes is biased toward peptides derived from highly abundant transcripts and is enriched in peptides derived from cyclins/cyclin-dependent kinases and helicases. Furthermore, we found that approximately 25% of MHC I-associated peptides were differentially expressed on normal versus neoplastic thymocytes. Approximately half of those peptides are derived from molecules directly implicated in neoplastic transformation (e.g., components of the PI3K-AKT-mTOR pathway). In most cases, overexpression of MHC I peptides on cancer cells entailed posttranscriptional mechanisms. Our results show that high-throughput analysis and sequencing of MHC I-associated peptides yields unique insights into the genesis of the MIP repertoire in normal and neoplastic cells.
Robust Reconstruction of MRSI Data Using a Sparse Spectral Model and High Resolution MRI Priors (2010)

We introduce a novel algorithm to address the challenges in magnetic resonance (MR) spectroscopic imaging. In contrast to classical sequential data processing schemes, the proposed method combines the reconstruction and postprocessing steps into a unified algorithm. This integrated approach enables us to inject a range of prior information into the data processing scheme, thus constraining the reconstructions. We use high resolution, 3-D estimate of the magnetic field inhomogeneity map to generate an accurate forward model, while a high resolution estimate of the fat/water boundary is used to minimize spectral leakage artifacts. We parameterize the spectrum at each voxel as a sparse linear combination of spikes and polynomials to capture the metabolite and baseline components, respectively. The constrained model makes the problem better conditioned in regions with significant field inhomogeneity, thus enabling the recovery even in regions with high field map variations. To exploit the high resolution MR information, we formulate the problem as an anatomically constrained total variation optimization scheme on a grid with the same spacing as the magnetic resonance imaging data. We analyze the performance of the proposed scheme using phantom and human subjects. Quantitative and qualitative comparisons indicate a significant improvement in spectral quality and lower leakage artifacts.
Selectin-mediated rolling of neutrophils on immobilized platelets (1993)

Interaction between neutrophils and platelets at the site of vascular damage or in ischaemic tissue may promote thrombosis and/or vascular occlusion. To study this interaction, we have developed a novel technique that allows visualization of adhesion of flowing neutrophils to immobilized, activated platelets. The total number of adherent neutrophils decreased with increasing wall shear stress in the range 0.05 to 0.4 Pa. Although a proportion of the adherent neutrophils were stationary, most were rolling with a velocity greater than 0.4 micron/s. The percentage of rolling cells increased with increasing wall shear stress, but the mean rolling cell velocity was nearly independent of shear stress. Adhesion of neutrophils was nearly abolished by treatment of the platelets with antibody to P-selectin, or by treatment of neutrophils with either neuraminidase, dextran sulfate, or EDTA. Studies with a series of antibodies to L-selectin (TQ-1, Dreg- 56, LAM1–3, and LAM1–10) suggested that this molecule was one neutrophil ligand for rolling adhesion. Thus, sialylated carbohydrate on neutrophils appears essential for P-selectin-mediated adhesion, and a proportion of this ligand may be presented by L-selectin. Treatment of the neutrophils with N-formyl-methionyl-leucyl-phenylalanine decreased the number of rolling cells, and increased the rolling velocity, possibly due to shedding of neutrophil ligand(s) and/or cell shape change. In vivo, immobilized platelets could play an important role in promoting attachment of neutrophils to vessel walls, eg, by slowing neutrophils so that integrin-mediated immobilization could occur.
CD62 and endothelial cell-leukocyte adhesion molecule 1 (ELAM-1) recognize the same carbohydrate ligand, sialyl-Lewis x. (1991)

The leukocyte receptor CD62, which is expressed on activated platelets and endothelial cells, is shown to mediate cell adhesion by binding a sialylated carbohydrate structure, sialyl-Lewis x, found on neutrophils, monocytes, and tumor cells. This structure has previously been identified as the ligand for another member of the LEC-CAM family of cell adhesion molecules, endothelial cell-leukocyte adhesion molecule 1, which also binds neutrophils and monocytes. The results demonstrate that although the two LEC-CAMs differ in their biological activities by their distribution and mode of expression, they are capable of mediating cell adhesion by recognition of the same carbohydrate ligand.
Phasing of RecA monomers on quasi‐random DNA sequences (2003)

We show that some arbitrarily chosen DNA sequences have the ability to influence the positioning of RecA monomers in RecA-DNA complexes. The preferential phase of binding of RecA monomers is shown to depend on the DNA sequence and its nucleotide composition. A simple rearrangement of bases in a limited DNA stretch influences the phasing of RecA monomers. On the other hand, that some features of DNA sequences interfere with the phasing on specific DNA sites demonstrates the existence of mechanisms for both positive and negative regulation of phasing on natural DNAs. The possible role of phasing of RecA monomers on DNA is discussed.
Functional Assessment of Temperature-Gated Ion-Channel Activity Using a Real-Time PCR Machine (2009)

The functional activity of a number of ion channels is highly sensitive to large changes in temperature. Foremost among these are the thermosensing TRP channels which include cold- (TRPM8, TRPA1), warmth- (TRPV3, TRPV4), and heat-sensing (TRPV1, TRPV2) members. TRPV1, also known as the vanilloid receptor (VR1), is activated by ligands such as capsaicin, acidic pH, and heat (an increase in temperature to approximately 42 degrees C will lead to channel opening). Screening against the thermal gating of TRPV1 is generally performed using perfusion systems or water baths for temperature control, in conjunction with electrophysiology or Ca2 + influx readouts for direct functional assessment. These approaches are very useful, but have limited throughput or minimal thermo-temporal control. A standard real-time PCR machine with standard microplates allowed us to combine fluorescent Ca2 + detection with precise temperature manipulation to develop a homogeneous (Z' = 0.53), cell-based assay that uses temperature as the agonist. A temperature response curve of TRPV1 was obtained, which provided a T50 of 46.1 degrees C, and IC50 values against heat agonism were determined for known TRPV1 antagonists. Furthermore, we expanded this approach to a cold-activated ion channel, TRPM8. We developed and validated an analytical technique with broad applications for the study and screening of temperature-gated ion channels.
Integrated Maneuvering Control Design And Experiments: Report For Phase III (1997)

In this report, a Cooperative Intelligent Cruise Control (CICC) System is proposed to increase highway capacity and provide safety and comfort to drivers. The method requires an automatic throttle and brake control and simple infrastructure-vehicle communication. The system is designed to let a vehicle operate under a conventional cruise control system as well as a distancing control system. The performance of the CICC is evaluated through simulations with a non-linear vehicle model.
Interferon Induction and Action (1971)

INTRODUCTION . . . . . . .. . . . . . .... . . . . . . . . . . . .. : . . . . . . . . . . . . . . . . . . . .. 333 MECHANISMS OF SYNTHESIS AND RELEASE OF INTERFERON. . .. 334 INDUCERS OF INTERFERON . . . • . • • . . . . • '. . . . . . . • . • . . . . . . . . . . . . . . . . . . . . .. 334 Inducers active only in vivo. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 335 Inducers active in vivo and in vitro.... . .. . . . . . . . . .. . . . . . . . . . . . . . . . . . .. 337 THE SPECIFICITY OF INTERFERON INDUCTION IN CELL CULTURE. . . . . . . . .. 338 RECEPTOR SITE PROTEIN. . . . . . . . . . . . . . . . . . • . • . . . . . . . . . . . . . . . . . . . . . . .. 345 PROPERTIES OF INTERFERON • • . • . • . • . • . . . • . . . • ' . . . . . . . . • . . . . . . . . . . . . .. 347 ANTIVIRAL ACTIVITY OF INTERFERON 348 REGULATION OF INTERFERON SYNTHESIS AND ACTIVITy . . . . . . 353
Aging changes in Bruch's membrane. A histochemical and morphologic study. (1990)

Using histochemical staining techniques and electron microscopy, the authors have examined the histochemical properties and ultrastructure of Bruch's membrane in 30 human eyes with an age range of 1 to 95 years. The results analyzed in three age groups (0-30 years, 31-60 years, and older than 60 years) show that there is a progressive accumulation of lipids in Bruch's membrane with relation to age. Differences were found in the specific types of lipids in individual eyes. Five eyes stained for neutral lipids alone, four stained predominantly for phospholipids, and nine stained intensely for both neutral lipids and phospholipids. The deposits were associated with the progressive destruction of the native architecture of Bruch's membrane but no correlation was identified between specific inclusions in Bruch's membrane with a particular lipid. These results are significant to age-related macular disease (ARMD), and the lipid rich barrier in Bruch's membrane is implicated as a cause of photoreceptor dysfunction and pigment epithelial detachment.
Post‐transcriptional silencing of pectin methylesterase gene in transgenic tomato fruits results from impaired pre‐mRNA processing (1998)

Summary Transgenic tomato fruit expressing a truncated fruit pectin methylesterase (PME) sense transgene under the control of CaMV 35S promoter show developmentally regulated co‐silencing of the endogenous fruit PME and sense transgene. This co‐silencing is associated with the onset of fruit PME gene expression. Detectable levels of PME protein and mRNA were not present in ripening transgenic fruits. However, several smaller transgene RNA species hybridizing to the 3′ end of the transgene are present in transgenic fruits, indicating degradation of sense transgene transcript. RT–PCR analyses of nuclear RNA from wild‐type and transgenic fruits, primed with oligo(dT), show the presence of spliced and unspliced transcripts for the fruit PME and the transgene, indicating a post‐transcriptional regulation of gene silencing. However, an accumulation of unspliced fruit PME transcript was obtained in the nuclei of transgenic fruit, using the randomly primed cDNAs in PCR amplification. Taken together, these results suggest that the ectopic expression of the fruit PME sense transgene interferes with processing of the endogenous PME pre‐mRNA.
Final results of phase Ib of tarextumab (TRXT, OMP-59R5, anti-Notch2/3) in combination with etoposide and platinum (EP) in patients (pts) with untreated extensive-stage small-cell lung cancer (ED-SCLC). (2015)

7508 Background: Notch signaling is implicated in cancer stem cell self-renewal and proliferation; thus being an appealing target in the treatment of SCLC. Tarextumab (TRXT), a fully human IgG2 antibody targeting Notch2 and 3 receptors, has shown preclinical efficacy in SCLC models with cisplatin. This Phase Ib study explores the MTD, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary efficacy of TRXT with EP in chemo-naive ED-SCLC. Methods: Notch signaling is implicated in cancer stem cell self-renewal and proliferation; thus being an appealing target in the treatment of SCLC. Tarextumab (TRXT), a fully human IgG2 antibody targeting Notch2 and 3 receptors, has shown preclinical efficacy in SCLC models with cisplatin. This Phase Ib study explores the MTD, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary efficacy of TRXT with EP in chemo-naive ED-SCLC. Results: By November 18, 2014, 27 pts were treated with TRXT at dose range from 5 mg/kg to 15 mg/kg. The MTD was not reached and TRXT 15 mg/kg was determined to be the Phase 2 dose. One DLT of Grade 3 nausea and vomiting was reported in the 10 mg/kg dose cohort. Frequently reported ( ≥ 15%) TRXT-related adverse events were: diarrhea (59.3%), fatigue (44.4%), nausea (40.7%), anemia (25.9%), decreased appetite (25.9%) and vomiting (25.9%); most were Grade 1 or 2 and managed with supportive care. The overall response rate was 84%. The median duration of treatment was 128 days (6 cycles) with mPFS and mOS of 124 and 228 days, respectively. The median follow-up for PFS and OS was of 86 and 107 days respectively. Conclusions: TRXT with EP is well tolerated. Encouraging anti-tumor activity has been observed. Final safety, efficacy, PK, immunogenicity and predictive biomarker results will be presented. TRXT at a dose of 15 mg/kg has been selected for the phase 2 randomized, placebo-controlled portion of the study, which is ongoing. Clinical trial information: NCT01859741.
Contrasting one- and two-cation binding behavior in syn- and anti-anthraquinone bibracchial podand (BiP) mono- and dianions assessed by cyclic voltammetry and electron paramagnetic resonance spectroscopy (1988)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTContrasting one- and two-cation binding behavior in syn- and anti-anthraquinone bibracchial podand (BiP) mono- and dianions assessed by cyclic voltammetry and electron paramagnetic resonance spectroscopyMilagros. Delgado, Deborah A. Gustowski, Hyunsook K. Yoo, Vincent J. Gatto, George W. Gokel, and Luis. EchegoyenCite this: J. Am. Chem. Soc. 1988, 110, 1, 119–124Publication Date (Print):January 1, 1988Publication History Published online1 May 2002Published inissue 1 January 1988https://pubs.acs.org/doi/10.1021/ja00209a019https://doi.org/10.1021/ja00209a019research-articleACS PublicationsRequest reuse permissionsArticle Views524Altmetric-Citations82LEARN 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
Production of unusual bacterial polyesters by Pseudomonas oleovorans through cometabolism (1992)

Pseudomonas oleovorans is an adaptable, aerobic bacterium that can produce a wide range of storage polyesters (poly-β-hydroxyalkanoates, PHAs). With few exceptions, the PHAs obtained when this bacterium is grown with single organic substrates capable of polymer production are generally copolymers. With two different polymer-producing substrates the copolymers formed contain units derived from each substrate often in direct proportion to the amounts in the medium. With such substrates or with non-producing substrates, or with non-growth substrates, the ability of P. oleovorans to utilize different types of individual organic compounds can be classified into three different categories, as follows: group A—the organic compound can support both growth and polymer production; or group B—the organic compound can support growth but not polymer production; or group C—the organic compounds cannot support growth. For organic compounds in groups B and C, new and unusual copolymers containing units derived from these substrates can often be obtained if that compound is cofed with a good polymer-producing substrate for P. oleovorans, such as either octanoic acid or nonanoic acid. The PHAs obtained by this type of cometabolism from a variety of such substrates are described.
Production of axenic cultures of algae by an osmotic method (1982)

No abstract available.