gebhart/patrepeval huggingface dataset:
Constitutive Expression of the B7h Ligand for Inducible Costimulator on Naive B Cells Is Extinguished after Activation by Distinct B Cell Receptor and Interleukin 4 Receptor–mediated Pathways and Can Be Rescued by CD40 Signaling (2002)

The recently described ligand-receptor pair, B7h-inducible costimulator (ICOS), is critical for germinal center formation and antibody responses. In contrast to the induced expression of the related costimulatory ligands B7.1 and B7.2, B7h is constitutively expressed on naive B cells and is surprisingly extinguished after antigen engagement and interleukin (IL)-4 cytokine signaling. Although signaling through both B cell receptor (BCR) and IL-4 receptor (R) converge on the extinction of B7h mRNA levels, BCR down-regulation occurs through Ca2+ mobilization, whereas IL-4R down-regulation occurs through a distinct Stat6-dependent pathway. During antigen-specific B cell activation, costimulation through CD40 signaling can reverse both BCR- and IL-4R-mediated B7h down-regulation. These data suggest that the CD40-CD40 ligand signaling pathway regulates B7h expression on activated B cells and may control whether antigen-activated B cells can express B7h and costimulate cognate antigen-activated T cells through ICOS.
Adenovirus–Adeno-Associated Virus Hybrid for Large-Scale Recombinant Adeno-Associated Virus Production (2009)

Recombinant adeno-associated virus (rAAV) holds promise for applications in gene therapy. Advances in clinical studies of rAAV-based gene therapeutics have generated an encouraging momentum in the field of gene therapy; however, one of the major obstacles to the eventual clinical success of rAAV-mediated gene therapy is the need for large-scale production of clinical-grade vectors. The transfection-based rAAV production method is well suited for preclinical studies in small animal models, but it is difficult to support large-scale clinical studies with this method. In the past decade, several scalable rAAV production methods have emerged from extensive efforts to develop large-scale manufacturing processes. Among those, the recombinant adenovirus-AAV infection method has some unique features in vector quality and yield. This minireview provides an overview of this scaleable rAAV production platform, describing its basic components and biological mechanisms and process.
DUSP4 deficiency caused by promoter hypermethylation drives JNK signaling and tumor cell survival in diffuse large B cell lymphoma (2015)

The epigenetic dysregulation of tumor suppressor genes is an important driver of human carcinogenesis. We have combined genome-wide DNA methylation analyses and gene expression profiling after pharmacological DNA demethylation with functional screening to identify novel tumor suppressors in diffuse large B cell lymphoma (DLBCL). We find that a CpG island in the promoter of the dual-specificity phosphatase DUSP4 is aberrantly methylated in nodal and extranodal DLBCL, irrespective of ABC or GCB subtype, resulting in loss of DUSP4 expression in 75% of >200 examined cases. The DUSP4 genomic locus is further deleted in up to 13% of aggressive B cell lymphomas, and the lack of DUSP4 is a negative prognostic factor in three independent cohorts of DLBCL patients. Ectopic expression of wild-type DUSP4, but not of a phosphatase-deficient mutant, dephosphorylates c-JUN N-terminal kinase (JNK) and induces apoptosis in DLBCL cells. Pharmacological or dominant-negative JNK inhibition restricts DLBCL survival in vitro and in vivo and synergizes strongly with the Bruton's tyrosine kinase inhibitor ibrutinib. Our results indicate that DLBCL cells depend on JNK signaling for survival. This finding provides a mechanistic basis for the clinical development of JNK inhibitors in DLBCL, ideally in synthetic lethal combinations with inhibitors of chronic active B cell receptor signaling.
Contribution of Salmonella typhimurium type III secretion components to needle complex formation (2000)

The prgHIJK operon encodes components of the Salmonella typhimurium pathogenicity island 1 type III secretion system (TTSS). Previously, prgH and prgK were shown to be required for formation of the supramolecular type III secretion needle complex (NC) [Kubori, T., et al. (1998) Science 280, 602-605]. This work indicates that all prg operon genes are required for NC formation. PrgH multimerizes into a distinct tetrameric-shaped structure that may be an early intermediate of NC assembly and may provide the structural foundation required for PrgK oligomerization. PrgH and PrgK, in the absence of other TTSS components, oligomerize into ring-shaped structures identical in appearance and size to the base of the NC, indicating that they are likely the major inner membrane structural components required for secretion. PrgI and PrgJ cofractionate with the NC and are secreted into the culture supernatant. NC from prgI and prgJ mutants have an identical morphology to the envelope-spanning (basal body) NC components, but are missing the external needle, indicating that PrgI and PrgJ are required for full NC assembly and are likely components of the external needle. Therefore, PrgI and PrgJ are secreted through the NC basal body, composed in part of PrgH/K and InvG/H rings, to participate in assembly of the more distal components of the NC.
Nano-artifact metrics based on random collapse of resist (2014)

Artifact metrics is an information security technology that uses the intrinsic characteristics of a physicalobject for authentication and clone resistance. Here, we demonstrate nano-artifact metrics based on siliconnanostructures formed via an array of resist pillars that randomly collapse when exposed to electron-beamlithography. The proposed technique uses conventional and scalable lithography processes, and because ofthe random collapse of resist, the resultant structure has extremely fine-scale morphology with a minimumdimension below 10 nm, which is less than the resolution of current lithography capabilities. By evaluatingfalse match, false non-match and clone-resistance rates, we clarify that the nanostructured patterns based onresist collapse satisfy the requirements for high-performance security applications.
Doxorubicin-Induced Id2A Gene Transcription Is Targeted at an Activating Transcription Factor/Cyclic AMP Response Element Motif through Novel Mechanisms Involving Protein Kinases Distinct from Protein Kinase C and Protein Kinase A (1995)

We have recently shown that doxorubicin (Dox), an antineoplastic drug and an inhibitor of terminal differentiation of myogenic and adipogenic cells, induces expression of Id, a gene encoding a helix-loop-helix transcriptional inhibitor. In this study we have investigated the molecular mechanisms underlying Dox-induced Id2A expression. We have also attempted to determine whether the genetic responses to Dox are related to the UV response, a well-characterized set of reactions to UV and DNA-damaging compounds that is partly mediated by AP-1. Transient transfection of a series of deletions and point mutation derivatives of the human Id2A promoter sequence shows that two closely spaced and inverted short elements similar to an activating transcription factor (ATF) binding site or a cyclic AMP response element (CRE) are necessary and sufficient for a full response to Dox. We refer to this element as the IdATF site. Sequences containing an IdATF site conferred Dox inducibility on a minimal heterologous promoter. An electrophoretic mobility shift assay showed nuclear proteins specifically interacting with the IdATF sequence. While oligonucleotides containing either legitimate ATF/CRE or AP-1 binding sequences competed for binding, antibody supershift experiments suggested that neither CREB/ATF-1 nor AP-1 are major factors binding to IdATF. Several independent criteria suggest that Dox inducibility was independent of Ca2+/phospholipid-dependent protein kinase (protein kinase C), cyclic AMP-dependent protein kinase (protein kinase A), and tyrosine kinase. Moreover, we found that Dox also induces transcription from promoters of immediate-early genes through an AP-1-independent pathway. Taken together, our results suggest that Dox elicits a novel genetic response distinct from the classical UV response.
Nitrogen Transfer from a Nitridomanganese(V) Complex:  Amination of Silyl Enol Ethers (1996)

ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTNitrogen Transfer from a Nitridomanganese(V) Complex: Amination of Silyl Enol EthersJ. Du Bois, Jason Hong, Erick M. Carreira, and Michael W. DayView Author Information Contribution No. 9155, Arnold and Mabel Beckman Laboratory for Chemical Synthesis and Beckman Institute, X-Ray Crystallography Laboratory California Institute of Technology Pasadena, California 91125Cite this: J. Am. Chem. Soc. 1996, 118, 4, 915–916Publication Date (Web):January 31, 1996Publication History Received31 October 1995Published online31 January 1996Published inissue 1 January 1996https://pubs.acs.org/doi/10.1021/ja953659rhttps://doi.org/10.1021/ja953659rrapid-communicationACS PublicationsCopyright © 1996 American Chemical SocietyRequest reuse permissionsArticle Views3902Altmetric-Citations149LEARN 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-AlertscloseSupporting Info (2)»Supporting Information Supporting Information SUBJECTS:Ethers,Ligands,Nitrides,Nitrogen,Reagents Get e-Alerts
Radiation Dosimetry for177Lu-PSMA I&T in Metastatic Castration-Resistant Prostate Cancer: Absorbed Dose in Normal Organs and Tumor Lesions (2016)

Prostate-specific membrane antigen (PSMA)-targeted radioligand therapy is increasingly used in metastatic castration-resistant prostate cancer. We aimed to estimate the absorbed doses for normal organs and tumor lesions using <sup>177</sup>Lu-PSMA I&T (I&T is imaging and therapy) in patients undergoing up to 4 cycles of radioligand therapy. Results were compared with pretherapeutic Glu-NH-CO-NH-Lys-(Ahx)-[<sup>68</sup>Ga(HBEDCC)] (<sup>68</sup>Ga-PSMA-HBED-CC) PET. <b>Methods:</b> A total of 34 cycles in 18 patients were analyzed retrospectively. In 15 patients the first, in 9 the second, in 5 the third, and in 5 the fourth cycle was analyzed, respectively. Whole-body scintigraphy was performed at least between 30-120 min, 24 h, and 6-8 d after administration. Regions of interest covering the whole body, organs, and up to 4 tumor lesions were drawn. Organ and tumor masses were derived from pretherapeutic <sup>68</sup>Ga-PSMA-HBED-CC PET/CT. Absorbed doses for individual cycles were calculated using OLINDA/EXM. SUVs from pretherapeutic PET were compared with absorbed doses and with change of SUV. <b>Results:</b> The mean whole-body effective dose for all cycles was 0.06 ± 0.03 Sv/GBq. The mean absorbed organ doses were 0.72 ± 0.21 Gy/GBq for the kidneys; 0.12 ± 0.06 Gy/GBq for the liver; and 0.55 ± 0.14 Gy/GBq for the parotid, 0.64 ± 0.40 Gy/GBq for the submandibular, and 3.8 ± 1.4 Gy/GBq for the lacrimal glands. Absorbed organ doses were relatively constant among the 4 different cycles. Tumor lesions received a mean absorbed dose per cycle of 3.2 ± 2.6 Gy/GBq (range, 0.22-12 Gy/GBq). Doses to tumor lesions gradually decreased, with 3.5 ± 2.9 Gy/GBq for the first, 3.3 ± 2.5 Gy/GBq for the second, 2.7 ± 2.3 Gy/GBq for the third, and 2.4 ± 2.2 Gy/GBq for the fourth cycle. SUVs of pretherapeutic PET moderately correlated with absorbed dose (<i>r</i> = 0.44, <i>P</i> < 0.001 for SUV<sub>max</sub>; <i>r</i> = 0.43, <i>P</i> < 0.001 for SUV<sub>mean</sub>) and moderately correlated with the change of SUV (<i>r</i> = 0.478, <i>P</i> < 0.001 for SUV<sub>max</sub>, and <i>r</i> = 0.50, <i>P</i> < 0.001 for SUV<sub>mean</sub>). <b>Conclusion:</b> Organ- and tumor-absorbed doses for <sup>177</sup>Lu-PSMA I&T are comparable to recent reports and complement these with information on an excellent correlation between the 4 therapy cycles. With the kidneys representing the critical organ, a cumulative activity of 40 GBq of <sup>177</sup>Lu-PSMA I&T appears to be safe and justifiable. The correlation between pretherapeutic SUV and absorbed tumor dose emphasizes the need for PSMA-ligand PET imaging for patient selection.
Necrotic Arachnidism (1958)

SummaryNecrotic arachnidism in Missouri is strikingly similar to "gangrenous spot" or cutaneous arachnidism of South America caused by Loxosceles laeta. A typical case report presents a distinctive clinical picture quite unlike that due to a black widow bite. Severe pain develops at the site of the bite and within the next 24 to 36 hours a systemic response is likely to occur, characterized by restlessness, fever, and at times the development of a generalized scarlatiniform eruption. Locally an ischemic area develops, surrounded by redness and extravasated blood, and becoming rapidly neerotic, with a central sloughing area which forms a deep ulcer exposing at times the underlying muscles. Slow gradual evolution with scarring follows. Experiments with Loxosceles reclusus, the probable agent of necrotic arachnidism in Missouri, and laboratory animals showed that the spider produces a powerful necrotoxin which it can readily inject into the skin of mammals, producing in the guinea pig tissue damage characterized by local hemorrhage, acute inflammatory cell reaction and, within three or four days, liquefaction with the formation of an abscess resulting in granulation and scarring. There is some species variation, rabbits being more susceptible than guinea pigs. The venom of both sexes of L. reclusus was found to be toxic. Rabbits were immunized after four bites or injections of venom. L. reclusus has been collected readily from the homes of patients with "brown spider bite" and appears to be a common house spider in Missouri.
Association of C-Reactive Protein With Carotid Atherosclerosis in Men and Women: The Framingham Heart Study (2002)

There is a graded association between CRP and carotid atherosclerosis in women but not in men. The significance of this difference between sexes merits further investigation.
Promoter Hypermethylation of FANCF (2004)

Patients with advanced stage invasive cervical cancer (CC) exhibit highly complex genomic alterations and respond poorly to conventional treatment protocols. In our efforts to understand the molecular genetic basis of CC, we examined the role of Fanconi Anemia (FA)-BRCA pathway. Here, we show that FANCF gene is disrupted by either promoter hypermethylation and/or deregulated gene expression in a majority of CC. Inhibition of DNA methylation and histone deacetylases induces FANCF gene re-expression in CC cell lines. FANCF-deregulated CC cell lines also exhibit a chromosomal hypersensitivity phenotype after exposure to an alkylating agent, a characteristic of FA patients. We also show the involvement of BRCA1 gene by promoter hypermethylation or down-regulated expression in a small subset of CC patients. Thus, we have found inactivation of genes in the FA-BRCA pathway by epigenetic alterations in a high proportion of CC patients, suggesting a major role for this pathway in the development of cervical cancer. Thus, these results have important implications in understanding the molecular basis of CC tumorigenesis and clinical management in designing targeted experimental therapeutic protocols.
Drive-By Localization of Roadside WiFi Networks (2008)

We use a steerable beam directional antenna mounted on a moving vehicle to localize roadside WiFi access points (APs), located outdoors or inside buildings. Localizing APs is an important step towards understanding the topologies and network characteristics of large scale WiFi networks that are deployed in a chaotic fashion in urban areas. The idea is to estimate the angle of arrival of frames transmitted from the AP using signal strength information on different directional beams of the antenna - as the beam continuously rotates while the vehicle is moving. This information together with the GPS locations of the vehicle are used in a triangulation approach to localize the APs. We show how this method must be extended using a clustering approach to account for multi-path reflections in cluttered environments. Our technique is completely passive requiring minimum effort beyond driving the vehicle around in the neighborhood where the APs need to be localized, and is able to improve the localization accuracy by an order of magnitude compared with trilateration approaches using omnidirectional antennas, and by a factor of two relative to other known techniques using directional antennas.
Whisky Lactone Precursors from the Wood of Platycarya strobilacea (1996)

The first whisky lactone precursors, (3S,4S)-3-methyl-4-hydroxyoctanoic acid 3-O-β-d-glucopyranoside and its 6‘-O-gallate, were isolated from the wood of Platycarya strobilacea, together with 10 known tannins and related compounds. Their structures were determined on the basis of spectroscopic and chemical evidence.
Activation of Immune System Effector Function by T-cell or Fc Receptor Intracellular Domains (1992)

It has recently become apparent that a number of the most prominent receptors in the immune system share common structural features and mediate similar activation pathways. These receptors include the T-cell and B-cell antigen receptors and several myeloid, natural killer cell, and mast cell Fc receptors. This paper focuses on the common attributes of some T-cell and Fc receptor chains and an Fc receptor subtype originally thought to function by a different mechanism.
Identification of Peptide Vaccine Candidates for Prostate Cancer Patients with HLA-A3 Supertype Alleles (2005)

We identified prostate-related antigen-derived new peptide candidates for HLA-A11-, HLA-A31-, and HLA-A33-positive prostate cancer patients. This information could facilitate the development of a peptide-based anticancer vaccine for patients with alleles other than HLA-A2 and HLA-A24.
Analysis of Gag-specific Cytotoxic T Lymphocytes in Simian Immunodeficiency Virus–infected Rhesus Monkeys by Cell Staining with a Tetrameric Major Histocompatibility Complex Class I–Peptide Complex (1998)

A tetrameric recombinant major histocompatibility complex (MHC) class I-peptide complex was used as a staining reagent in flow cytometric analyses to quantitate and define the phenotype of Gag-specific cytotoxic T lymphocytes (CTLs) in the peripheral blood of simian immunodeficiency virus macaque (SIVmac)-infected rhesus monkeys. The heavy chain of the rhesus monkey MHC class I molecule Mamu-A*01 and beta2-microglobulin were refolded in the presence of an SIVmac Gag synthetic peptide (p11C, C-M) representing the optimal nine-amino acid peptide of Mamu-A*01-restricted predominant CTL epitope to create a tetrameric Mamu-A*01/p11C, C-M complex. Tetrameric Mamu-A*01/p11C, C-M complex bound to T cells of SIVmac-infected, Mamu-A*01(+), but not uninfected, Mamu-A*01(+), or infected, Mamu-A*01(-) rhesus monkeys. Specific staining of peripheral blood mononuclear cells (PBMC) from SIVmac-infected, Mamu-A*01(+) rhesus monkeys was only found in the cluster of differentiation (CD)8alpha/beta+ T lymphocyte subset and the percentage of CD8alpha/beta+ T cells in the peripheral blood of four SIVmac-infected, Mamu-A*01+ rhesus monkeys staining with this complex ranged from 0.7 to 10.3%. Importantly, functional SIVmac Gag p11C-specific CTL activity was seen in sorted and expanded tetrameric Mamu-A*01/p11C, C-M complex-binding, but not nonbinding, CD8alpha/beta+ T cells. Furthermore, the percentage of CD8alpha/beta+ T cells binding this tetrameric Mamu-A*01/p11C, C-M complex correlated well with p11C-specific cytotoxic activity as measured in both bulk and limiting dilution effector frequency assays. Finally, phenotypic characterization of the cells binding this tetrameric complex indicated that this lymphocyte population is heterogeneous. These studies indicate the power of this approach for examining virus-specific CTLs in in vivo settings.
RANK ligand inhibition with denosumab for the management of osteoporosis (2006)

Receptor activator of nuclear factor-kappaB ligand (RANKL) is a cytokine member of the tumour necrosis factor family that is the principal final mediator of osteoclastic bone resorption. It plays a major role in the pathogenesis of postmenopausal osteoporosis, as well bone loss associated with rheumatoid arthritis, metastatic cancer, multiple myeloma, aromatase inhibitor therapy and androgen deprivation therapy. Denosumab (AMG 162) is an investigational fully human monoclonal antibody with a high affinity and specificity for RANKL. By inhibiting the action of RANKL, denosumab reduces the differentiation, activity and survival of osteoclasts, thereby slowing the rate of bone resorption. Denosumab has been shown to increase bone mineral density (BMD) and reduce bone turnover in postmenopausal women with low BMD. Denosumab is a potential treatment for osteoporosis and other skeletal disorders.
Steel Factor Induces Tyrosine Phosphorylation of CRKL and Binding of CRKL to a Complex Containing c-Kit, Phosphatidylinositol 3-Kinase, and p120CBL (1997)

Steel factor (SF) is a growth and survival factor for hematopoietic cells. The receptor for SF, c-Kit, contains intrinsic tyrosine kinase activity, and binding of SF induces rapid tyrosine phosphorylation of several cellular proteins, including c-Kit itself. Activation of c-Kit is shown here to induce tyrosine phosphorylation of CRKL, and CRKL coprecipitated with c-Kit through an interaction that required the CRKL SH3 domains and not the SH2 domain. CRKL associated with c-Kit indirectly as part of a larger complex of proteins. Two proteins in this complex were identified as the p85 regulatory subunit of phosphatidylinositol 3-kinase (p85(PI3K)) and the proto-oncoprotein p120(CBL). Because p85(PI3K) is known to bind to the activated c-Kit receptor, the possibility that CRKL interacted with c-Kit indirectly through p85(PI3K) was investigated. Far Western blotting with a CRKL-SH3 glutathione S-transferase fusion protein showed that CRKL binds directly to p85(PI3K )in vitro. However, although a small amount of CRKL was preassociated with p85(PI3K), the interaction was increased after SF stimulation, suggesting that the interactions of these three proteins are complex. We conclude that SF induces the formation of a signaling complex potentially containing CRKL and p120(CBL), both of which bind to c-Kit through p85(PI3K). These data suggest that one function of CRKL in normal cells might be to recruit signaling molecules such as CBL into a complex with PI3K. Such complexes could be important in propagating signals involving PI3K such as gene expression and adhesion.