gebhart/patrepeval huggingface dataset:
Combining Mass Spectrometry and Peptide Arrays to Profile the Specificities of Histone Deacetylases (2009)

In profile: We describe the use of peptide arrays to probe the substrate specificities of several histone deacetylase (HDAC) enzymes. The combination with SAMDI-MS avoids the need for labels, which we demonstrate can perturb enzyme activity and lead to altered enzyme specificity. Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Revisiting the mechanism of coagulation factor XIII activation and regulation from a structure/functional perspective (2016)

The activation and regulation of coagulation Factor XIII (FXIII) protein has been the subject of active research for the past three decades. Although discrete evidence exists on various aspects of FXIII activation and regulation a combinatorial structure/functional view in this regard is lacking. In this study, we present results of a structure/function study of the functional chain of events for FXIII. Our study shows how subtle chronological submolecular changes within calcium binding sites can bring about the detailed transformation of the zymogenic FXIII to its activated form especially in the context of FXIIIA and FXIIIB subunit interactions. We demonstrate what aspects of FXIII are important for the stabilization (first calcium binding site) of its zymogenic form and the possible modes of deactivation (thrombin mediated secondary cleavage) of the activated form. Our study for the first time provides a structural outlook of the FXIIIA2B2 heterotetramer assembly, its association and dissociation. The FXIIIB subunits regulatory role in the overall process has also been elaborated upon. In summary, this study provides detailed structural insight into the mechanisms of FXIII activation and regulation that can be used as a template for the development of future highly specific therapeutic inhibitors targeting FXIII in pathological conditions like thrombosis.
Expression of vascular endothelial growth factor does not promote transformation but confers a growth advantage in vivo to Chinese hamster ovary cells. (1993)

Vascular endothelial growth factor (VEGF) is a mitogen with a specificity for endothelial cells in vitro and an angiogenic inducer in vivo. We tested the hypothesis that VEGF may confer on expressing cells a growth advantage in vivo. Dihydrofolatereductase--Chinese hamster ovary cells were transfected with expression vectors which direct the constitutive synthesis of VEGF. Neither the expression nor the exogenous administration of VEGF stimulated anchorage-dependent or anchorage-independent growth of Chinese hamster ovary cells in vitro. However, VEGF-expressing clones, unlike control cells, demonstrated an ability to proliferate in nude mice. Histologic examination revealed that the proliferative lesions were compact, well vascularized, and nonedematous. Ultrastructural analysis revealed that capillaries within the lesions were of the continuous type. These findings indicate that the expression of VEGF may confer on cells the ability to grow in vivo in the absence of transformation by purely paracrine mechanisms. Since VEGF is a widely distributed protein, this property may have relevance for a variety of physiological and pathological proliferative processes.
Delayed Gastric Emptying after Billroth I Pylorus-Preserving Pancreatoduodenectomy (1999)

After Billroth I PPPD, gastric emptying is delayed but recovers by 6 months after surgery. Tachygastria may play a part in the pathogenesis of delayed gastric emptying, but it can be treated with cisapride.
Reactivation of mutant p53 by a one-hybrid adaptor protein. (2003)

The most frequent genetic alteration in cancer is a mutation of p53. In most cases, this leads to a sharp increase of the p53 protein levels but abolishes p53's function as an activator of transcription. To correct this defect, wild-type p53 is being reintroduced into tumor cells through gene therapy vectors, thereby inducing cell death. However, this effect is not necessarily specific for tumor cells. Furthermore, mutant p53 in tumor cells trans-dominantly impairs the function of wild-type p53. As an approach to overcome these obstacles, we have developed an adaptor protein that reactivates mutant p53 rather than stimulating transcription on its own. The DNA binding and tetramerizing portions of the p53-homologue p73 were fused to the oligomerization domain of p53. This chimera binds to the DNA of p53-responsive promoters through the p73-derived portions, and it binds to mutant p53 by the p53-derived oligomerization domain. Through this one-hybrid system, mutant p53 is re-enabled to activate transcription. When the adaptor was expressed in tumor cells that contain mutant p53, expression of p53-responsive genes was activated, and growth was inhibited. No such effects were observed in cells that contain wild-type p53 or no p53 at all. When the adaptor was expressed through an adenovirus vector, tumor cells containing mutant p53 were specifically induced to undergo apoptosis. This strategy can turn mutant p53 into an inhibitor of tumor cell growth and might enable gene therapy to eliminate cancer cells with specificity.
A hybrid ensemble model of kriging and neural network for ore grade estimation (2006)

This paper presents a new hybrid methodology involving kriging and artificial neural network for ore grade estimation of two variables namely, Al2O3% and SiO2%, in a bauxite deposit. The dataset was divided into three statistically similar subsets: training, calibration and validation sets using a genetic algorithm. The proposed hybrid ensemble model was formed using a kriging model and several neural network models. The outputs of these component models were combined using two methods to produce a unified prediction. The results indicated that the hybrid model was not a better estimator than the kriging model for the variable Al2O3%. However, it provides slightly better performance in comparison to any of the other component models in the ensemble for the variable SiO2%.
Human Leukocyte Antigen-A, B, C, DRB1, and DQB1 Allele and Haplotype Frequencies in a Subset of 237 Donors in the South African Bone Marrow Registry (2018)

Human leukocyte antigen- (HLA-) A, HLA-B, HLA-C, HLA-DRB1, and HLA-DQB1 allele and haplotype frequencies were studied in a subset of 237 volunteer bone marrow donors registered at the South African Bone Marrow Registry (SABMR). Hapl-o-Mat software was used to compute allele and haplotype frequencies from individuals typed at various resolutions, with some alleles in multiple allele code (MAC) format. Four hundred and thirty-eight HLA-A, 235 HLA-B, 234 HLA-DRB1, 41 HLA-DQB1, and 29 HLA-C alleles are reported. The most frequent alleles were A∗02:02g (0.096), B∗07:02g (0.082), C∗07:02g (0.180), DQB1∗06:02 (0.157), and DRB1∗15:01 (0.072). The most common haplotype was A∗03:01g~B∗07:02g~C∗07:02g~DQB1∗06:02~DRB1∗15:01 (0.067), which has also been reported in other populations. Deviations from Hardy-Weinberg equilibrium were observed in A, B, and DRB1 loci, with C~DQB1 being the only locus pair in linkage disequilibrium. This study describes allele and haplotype frequencies from a subset of donors registered at SABMR, the only active bone marrow donor registry in Africa. Although the sample size was small, our results form a key resource for future population studies, disease association studies, and donor recruitment strategies.
In Vitro Osteogenic Differentiation of Human Mesenchymal Stem Cells and In Vivo Bone Formation in Composite Nanofiber Meshes (2008)

Tissue engineering has become an alternative method to traditional surgical treatments for the repair of bone defects, and an appropriate scaffold supporting bone formation is a key element in this approach. In the present study, nanofibrous organic and inorganic composite scaffolds containing nano-sized demineralized bone powders (DBPs) with biodegradable poly(L-lactide) (PLA) were developed using an electrospinning process for engineering bone. To assess their biocompatibility, in vitro osteogenic differentiation of human mandible-derived mesenchymal stem cells (hMSCs) cultured on PLA or PLA/DBP composite nanofiber scaffolds were examined. The mineralization of hMSCs cultured with osteogenic supplements on the PLA/DBP nanofiber scaffolds was remarkably greater than on the PLA nanofiber scaffold during the first 14 days of culture but reached the same level after 21 days. The in vivo osteoconductive effect of PLA/DBP nanofibrous scaffolds was further investigated using rats with critical-sized skull defects. Micro-computerized tomography revealed that a greater amount of newly formed bone extended across the defect area in PLA/DBP scaffolds than in the nonimplant and PLA scaffolds 12 weeks after implantation and that the defect size was almost 90% smaller. Therefore, PLA/DBP composite nanofiber scaffolds may serve as a favorable matrix for the regeneration of bone tissue.
Functional management of an antiviral cytotoxic T-cell response (1997)

Lymphocytic choriomeningitis virus (LCMV) is known to induce strong, polyclonal cytotoxic T-lymphocyte (CTL) responses. Using a set of variant peptides derived from the major CTL epitope of LCMV, we analyzed the functional fine specificity of the LCMV-specific CTL response. During the primary response, almost all the tested peptides were recognized. In contrast, the secondary response was purged of all minor cross-reactivities and very few peptides were significantly recognized. This study is the first demonstration of the functional maturation of a T-cell response and has important clinical and biological implications.
Behavioral Interaction Between Nicotine and Ethanol: Possible Modulation by Mouse Cerebellar Glutamate (2006)

The results suggested that glutamate modulates the functional interaction between nicotine and ethanol because NMDA and AMPA enhanced the nicotine-induced attenuation of ethanol ataxia, whereas (+)-MK-801 and NBQX reduced the attenuation.
Free-Space Tunable and Drop Optical Filters Using Vertical Bragg Mirrors on Silicon (2006)

Vertical Bragg grating mirrors are realized by the anisotropic etching of Si using deep reactive ion etching (DRIE), thus producing multiple vertical interfaces between Si and air. The Bragg mirrors are used to realize two optical filter configurations. The first is a tunable Fabry-Peacuterot cavity composed of two mirrors, where tuning is achieved by moving one of the mirrors using silicon-on-insulator (SOI) electrostatic microelectromechanical system (MEMS) actuation. The second is a drop filter, where a tilted Bragg mirror acts as a wavelength selective reflector. The enhanced etching process involving a mix of cryogenic and Bosch DRIE processes is presented. The realized structures, fabrication process, as well as measured performance are also presented
Overall survival (OS) and safety of dasatinib/docetaxel versus docetaxel in patients with metastatic castration-resistant prostate cancer (mCRPC): Results from the randomized phase III READY trial. (2013)

LBA8 Background: SRC kinases may contribute to androgen independence of mCRPC.Dasatinib (DAS) inhibits tyrosine kinases including SRC kinases with preclinical evidence for antimetastatic activity, inhibition of osteoclast function in tumor microenvironment, and synergistic activity with docetaxel (D). In phase I/II trials of mCRPC patients (pts), DAS in combination with D had an acceptable safety profile with objective response rates (ORR) improved over historical data and decreased levels of bone turnover markers. Methods: READY was a multinational, randomized, double-blinded, placebo-controlled, phase III study. Pts with mCRPC (n = 1,522) were randomized (1:1) to receive either D 75 mg/m 2 q3wk + prednisone with double-blinded DAS 100 mg qd (DAS/D, n = 762) or placebo (PBO/D, n = 760). Primary endpoint was overall survival (OS). Secondary endpoints were ORR, time to first skeletal-related event (TFSRE), time to prostate-specific antigen progression (TPSAP), urinary N-telopeptide (uNTX) reduction, pain reduction, progression-free survival (PFS), and safety. Results: No OS difference between DAS/D and PBO/D (median, 21.5 vs. 21.2 mos; hazard ratio [HR], 0.99; log-rank P = 0.90) was observed. Results of secondary endpoints for DAS/D vs. PBO/D were: ORR (30.5 vs. 31.9%); TFSRE (median, not reached vs. 31.1 mos; HR, 0.81 [95% CI, 0.64-1.02]); uNTX reduction (66.0 vs. 60.6%); PFS (median, 11.8 vs. 11.1 mos; HR, 0.92); TPSAP (median, 8.0 vs. 7.6 mos; HR, 0.91), and pain reduction (66.6 vs. 71.5%). Twenty-three percent of DAS/D and 14% of PBO/D pts received therapy for &lt;3 mos. Most common AEs in DAS/D arm included diarrhea, fatigue, alopecia, and nausea. Grade 3-4 AEs of interest for DAS/D vs. PBO/D included anemia (8.0 vs.5.9%), neutropenia (6.2 vs. 5.5%), hypocalcemia (3.5 vs.3.1%), GI bleeding (2.6 vs.1.3%), and pleural effusion (1.3 vs. 0.4%). Conclusions: The addition of DAS to standard-of-care chemotherapy in mCRPC pts did not improve OS. There was a modest reduction in the risk of TFSRE with DAS/D vs. PBO/D. With a median follow-up of 19 mos of 761 DAS/D-treated pts, no unexpected toxicities for DAS were observed. Clinical trial information: NCT00744497.
Inflammation and the pathogenesis of age-related macular degeneration (2009)

It is now well-known that AMD is a multi-factorial disease, with environmental causes and genetics all playing a role.
A Sol–Gel-Based Microfluidics System Enhances the Efficiency of RNA Aptamer Selection (2011)

RNA and DNA aptamers that bind to target molecules with high specificity and affinity have been a focus of diagnostics and therapeutic research. These aptamers are obtained by SELEX often requiring many rounds of selection and amplification. Recently, we have shown the efficient binding and elution of RNA aptamers against target proteins using a microfluidic chip that incorporates 5 sol-gel binding droplets within which specific target proteins are imbedded. Here, we demonstrate that our microfluidic chip in a SELEX experiment greatly improved selection efficiency of RNA aptamers to TATA-binding protein, reducing the number of selection cycles needed to produce high affinity aptamers by about 80%. Many aptamers were identical or homologous to those isolated previously by conventional filter-binding SELEX. The microfluidic chip SELEX is readily scalable using a sol-gel microarray-based target multiplexing. Additionally, we show that sol-gel embedded protein arrays can be used as a high-throughput assay for quantifying binding affinities of aptamers.
The overshoot effect in transient electroluminescence from organic bilayer light emitting diodes: Experiment and theory (1997)

Transient electroluminescence (EL) from organic bilayer light emitting diodes addressed by a rectangular voltage pulse often features an overshoot when the voltage is switched off. Experimental results are presented for a variety of hole transporting layers in contact with an oxadiazole layer simultaneously acting both as a blockade for holes and as an electron transport layer. The overshoot occurs in spin coated yet not in vapor deposited samples. A model is developed to rationalize charge recombination under the premise (i) of an interfacial layer of finite thickness between hole and electron transport layers in which both transport molecules coexist and (ii) of interfacial energy barriers impeding both hole and electron passage. It predicts the occurrence of an EL overshoot due to the recombination of stored electrons and holes under the action of their mutual space charge field when the external voltage is switched off. The temporal pattern of the predicted transient EL signal is in good agreement with experiment.
Internal eight‐band WWAN/LTE handset antenna using loop shorting strip and chip‐capacitor‐loaded feeding strip for bandwidth enhancement (2011)

Abstract A planar inverted‐F antenna (PIFA) with a loop shorting strip and a chip‐capacitor‐loaded feeding strip to achieve a small size yet wideband operation for eight‐band WWAN/LTE operation (698˜960/1710˜2690 MHz) in the mobile handset is presented.The antenna occupies a small no‐ground footprint of 15 × 35 mm 2 on the main circuit board of the handset and is closely integrated with the surrounding system ground plane to achieve compact integration inside the handset. By applying the proposed shorting strip and feeding strip, a dual‐resonance excitation at about 800 MHz which forms the antenna's wide lower band to cover the LTE700/GSM850/900 operation is obtained. Further, the proposed shorting strip and feeding strip lead to the generation of additional higher‐order resonant modes to assist in forming a wide upper band for the antenna to cover the GSM1800/1900/UMTS/LTE2300/2500 operation. The proposed antenna also shows good radiation characteristics over the eight operating bands. The obtained SAR values of the antenna are well less than the limit of 1.6 W/kg for 1‐g head tissue for practical handset applications. © 2011 Wiley Periodicals, Inc. Microwave Opt Technol Lett 53:1217–1222, 2011; View this article online at wileyonlinelibrary.com. DOI 10.1002/mop.25983
Structural and Biophysical Insights into the Role of CD4 and CD8 in T Cell Activation (2013)

T cell receptors (TCRs) recognize peptides presented by MHC molecules (pMHC) on an antigen-presenting cell (APC) to discriminate foreign from self-antigens and initiate adaptive immune responses. In addition, T cell activation generally requires binding of this same pMHC to a CD4 or CD8 co-receptor, resulting in assembly of a TCR-pMHC-CD4 or TCR-pMHC-CD8 complex and recruitment of Lck via its association with the co-receptor. Here we review structural and biophysical studies of CD4 and CD8 interactions with MHC molecules and TCR-pMHC complexes. Crystal structures have been determined of CD8αα and CD8αβ in complex with MHC class I, of CD4 bound to MHC class II, and of a complete TCR-pMHC-CD4 ternary complex. Additionally, the binding of these co-receptors to pMHC and TCR-pMHC ligands has been investigated both in solution and in situ at the T cell-APC interface. Together, these studies have provided key insights into the role of CD4 and CD8 in T cell activation, and into how these co-receptors focus TCR on MHC to guide TCR docking on pMHC during thymic T cell selection.
Enhanced production of interleukin‐6 in mice with type II collagen–induced arthritis (1989)

We established an interleukin-6 (IL-6)-dependent cell line from murine plasmacytoma MOPC-104E cells. This cell line (designated PIL-6) was found to respond to murine and to human IL-6, but not to any other cytokines. We used this cell line to investigate the involvement of IL-6 production in type II collagen-induced arthritis in DBA/1 mice. Only marginal IL-6 activity was detected in sera from DBA/1 mice inoculated with Freund's complete adjuvant (FCA) alone, with an unrelated protein (bovine serum albumin) plus FCA, or with type II collagen plus Freund's incomplete adjuvant. However, enhanced IL-6 activity was observed in DBA/1 mice that had been injected with type II collagen plus FCA to induce arthritis. The elevated level of serum IL-6 activity was associated with high levels of IL-6 produced when lymph node cells from arthritic mice were stimulated in vitro with type II collagen. We also found that the L3T4+ T cell subset is responsible for the enhanced production of IL-6 in arthritic mice. The results are discussed in the context of potential roles of IL-6 in the induction and/or expression of chronic, progressive arthritis.
The SU.FOL.OM3 Study: a secondary prevention trial testing the impact of supplementation with folate and B-vitamins and/or Omega-3 PUFA on fatal and non fatal cardiovascular events, design, methods and participants characteristics (2008)

Current Controlled Trials ISRCTN41926726.
Addition of an endoplasmic reticulum retrieval sequence to ricin A chain significantly increases its cytotoxicity to mammalian cells. (1993)

An Escherichia coli expression system was used to produce recombinant ricin A chain (RTA) and RTA modified either by the addition of a carboxyl-terminal endoplasmic reticulum retrieval sequence Lys-Asp-Glu-Leu (RTAKDEL) or a nonfunctional analogue Lys-Asp-Glu-Ala (RTAKDEA). These RTA molecules can enter mammalian cells by fluid phase endocytosis. RTAKDEL was significantly more cytotoxic than either RTA or RTAKDEA to both Vero cells and HeLa cells (250- and 10-fold, respectively), despite the fact that all these RTA molecules had comparable enzymatic activities. This difference did not result from KDEL-mediated binding of RTAKDEL to the cell surface. Enhanced cytotoxicity could be correlated with an increased level of ribosome inactivation, measured as the RTA-catalyzed depurination of 28 S ribosomal RNA. These results indicate that the added KDEL sequence facilitated RTA entry into the cytosol. We propose that interaction with the intracellular KDEL receptor promotes retrograde transport of the toxin to the endoplasmic reticulum, where translocation of RTA into the cytosol occurs.
Sequence-Specific Histone Methylation Is Detectable on Circulating Nucleosomes in Plasma (2008)

if validated in further studies, our findings may be a basis for investigations of cancer-specific alterations in histone modifications in the circulation.
Induction of Radiosensitization by Indolocarbazole Derivatives: The Role of DNA Topoisomerase I (2004)

DNA topoisomerase I (TOP1) mediates the induction of radiosensitization (RS) by camptothecin derivatives in mammalian cells. Many indolocarbazole (INDO) derivatives have been shown to induce TOP1-mediated DNA damage (T1DD). In the current study, we characterized the cytotoxic and radiosensitizing activities of six INDO derivatives in relation to their efficiencies to induce T1DD. Evaluated by clonogenic survival assay, the INDO derivatives F1, F5, and F7, but not F43, F44, or F71, were shown to induce significant levels of RS in the human breast cancer MCF-7 cells at noncytotoxic concentrations. Analyzed by the single-hit multitarget (SHMT) model, F1, F5, and F7, like camptothecin, induce RS by obliterating the "shoulder" of radiation survival curve. In contrast to the Chinese hamster DC3F cells, the TOP1 mutant DC3F/C10 cells demonstrated cross-resistance to the cytotoxicity of F7 and the induction of RS by F7 and F1. The efficiencies to induce T1DD were determined by 1) drug-stimulated TOP1 cleavage assay in vitro and 2) K+-SDS coprecipitation assay in vivo. These compounds exhibited varying efficiencies in inducing T1DD with the following order: F71, F7 > F44, F1 > F5 > F43. It is surprising that the individual efficiency of these compounds to induce T1DD correlates well with their individual cytotoxicity but not RS activity. Taken together, our data demonstrate that certain, but not all, INDO derivatives capable of inducing T1DD can induce RS in mammalian cells. The INDO derivatives F1, F5, and F7 have the potential to be developed as a new class of radiation sensitizers
Clinical and Immune Responses in Resected Colon Cancer Patients Treated With Anti-Idiotype Monoclonal Antibody Vaccine That Mimics the Carcinoembryonic Antigen (1999)

CeaVac consistently generated a potent anti-CEA humoral and cellular immune response in all 32 patients entered onto this trial. A number of very high-risk patients continue on study. 5-FU regimens, which are the standard of care for patients with Dukes' C disease, did not affect the immune response. These data warrant a phase III trial for patients with resected colon cancer.