gebhart/patrepeval huggingface dataset:
Cathepsin C Inhibitors: Property Optimization and Identification of a Clinical Candidate (2014)

A lead generation and optimization program delivered the highly selective and potent CatC inhibitor 10 as an in vivo tool compound and potential development candidate. Structural studies were undertaken to generate SAR understanding.
Jamming-Aware Traffic Allocation for Multiple-Path Routing Using Portfolio Selection (2010)

Multiple-path source routing protocols allow a data source node to distribute the total traffic among available paths. In this paper, we consider the problem of jamming-aware source routing in which the source node performs traffic allocation based on empirical jamming statistics at individual network nodes. We formulate this traffic allocation as a lossy network flow optimization problem using portfolio selection theory from financial statistics. We show that in multisource networks, this centralized optimization problem can be solved using a distributed algorithm based on decomposition in network utility maximization (NUM). We demonstrate the network's ability to estimate the impact of jamming and incorporate these estimates into the traffic allocation problem. Finally, we simulate the achievable throughput using our proposed traffic allocation method in several scenarios.
Infrared Fluorescent Detection of D1S80 Alleles from Blood and Body Fluid Collected on IsoCode™ Devices (1997)

A genetic locus D1S80 (pMCT 118) containing variable number of tandem repeats (VNTR) has been used extensively in forensic analysis and paternity testing. In the current research, DNA was isolated from blood saliva and nasal secretions collected on two types of IsoCode paper-based devices. The D1S80 locus was amplified using PCR technology, and the alleles were separated by gel electrophoresis and then detected using an infrared (IR) fluorescence automated DNA sequencer. IR-labeled amplification products were generated from human genomic DNA using oligonucleotide primers, which were covalently linked to an infrared fluorescent dye (IRD41) at the 5' end. This system combines IR fluorescence chemistry and laser technology, thus eliminating the need for post-electrophoretic gel handling for the detection of the alleles. Real-time detection after separation of the alleles is valuable for visualization of the data. The VNTR alleles are displayed as familiar autoradiogram-like images, which can also be analyzed by computer. Since DNA is eluted from the IsoCode devices only with sterile distilled water and without time-consuming methods of extraction, amplification can be performed from numerous samples within a short period of time.
The identification of an enzyme that regulates ether lipid signaling pathways in cancer (2007)

AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA

4500 

Many metabolic enzymes, including lipases, oxidoreductases, and glutathione S-transferases, are believed to make key contributions to primary tumor progression, invasion, and metastasis. As such, there is an urgent need for elucidating the precise roles that metabolic enzymes play in cancer biology, so as to uncover new potential therapeutic targets and biomarkers. Using activity-based protein profiling (ABPP), an advanced proteomic technology that assesses the activity of many enzymes in parallel within native proteomes, we have identified the serine hydrolase KIAA1363 as being highly elevated in numerous pathogenic human cancer cell lines. These included cell lines from several tumorigenic origins including the breast, ovary, and skin. Moreover, this enzyme was found at elevated levels in a number of primary human tumors compared to their corresponding normal tissues. Together, these data suggest an important role for KIAA1363 in human tumorigenesis. Using retroviral gene transfer in combination with either RNAi or overexpression technology we have demonstrated that KIAA1363 is not only necessary but also sufficient to support several of the in vitro and in vivo pathogenic properties of both breast and ovarian human cancer cell lines. The overexpression of KIAA1363 leads to an augmentation of the in vitro proliferation and migration potential and the in vivo tumor growth of cancer cells. Moreover, a reduction of KIAA1363 levels decreased both the migration potential and the in vivo tumor growth of cancer cells. Importantly, KIAA1363’s ability to regulate these properties was entirely dependent upon its catalytic activity. The molecular mechanism by which KIAA1363 regulates the pathogenic properties of human cancer cell lines was addressed using a global metabolite profiling strategy in combination with metabolic labeling studies to determine that KIAA1363 serves as a central node in an ether lipid signaling pathway that bridges platelet-activating factor (PAF) and lysophosphatidic acid (LPA). Biochemical studies revealed that KIAA1363 regulates this network by hydrolyzing the metabolic intermediate 2-acetyl monoalkylglycerol to monoalkylglycerol (MAGE), which then leads onto the production of LPA and PAF. Perturbation of KIAA1363 levels or catalytic activity in human cancer cell lines directly correlates with changes in the concentration of these metabolites. This is significant because LPA is not only an established biomarker of ovarian cancer but it also influences many of the pathogenic properties of cancer cell lines. We have found that at least one of these properties, increased migration aptitude, which is regulated by KIAA1363, is more than likely though regulation of LPA levels as the migratory defect found in KIAA1363-knockdown cells is rescued by the addition of as little as 10 nM alkyl-LPA. These findings indicate that KIAA1363 is an important molecule in human cancer biology.
The African Swine Fever Virus Protein j4R Binds to the Alpha Chain of Nascent Polypeptide-Associated Complex (2002)

The African swine fever virus (ASFV) j4R protein is expressed late during the virus replication cycle and is present in both the nucleus and the cytoplasm of infected cells. By using the yeast two-hybrid system, direct binding, and coprecipitation from cells, we showed that the j4R protein binds to the alpha chain of nascent polypeptide-associated complex (alpha NAC). Confocal microscopy indicated that a proportion of j4R and alpha NAC interact in areas close to the plasma membrane, as well as through the cytoplasm in cells. In vitro binding studies suggested that binding of j4R to alpha NAC did not interfere with the binding of alpha- and beta NAC subunits (the BTF3 transcription factor).
Enrichment and detection of live antigen-specific CD4+ and CD8+ T cells based on cytokine secretion (1999)

Following appropriate antigen-specific stimulation, CD4+ and CD8+ T lymphocytes rapidly express cytokines. Based on this stimulation-induced cytokine secretion and using cell suface affinity matrix technology we have developed a new method that permits specific, rapid and efficient detection, isolation and characterization of live antigen-specific CD4+ and CD8+ T lymphocytes. The power of this technique is demonstrated here for HLA-A0201-restricted influenza matrix protein peptide 58-66-specific CD8+ cytotoxic T lymphocytes, influenza A virus- and recombinant tetanus toxin C fragment-specific Th1 cells and tetanus toxoid-specific Th2 cells.
Analysis of the cell cycle in sugarbeet seed during development, maturation and germination. (2009)

Cell cycle activity in sugarbeet seed was studied by flow cytometry. During embryo development the G2/G1 ratio decreases up to 24-28 days after pollination and then cell cycle activity is arrested (the G2/G1 ratio becomes constant). This is an indication that the embryo is already physiologically fully developed at this early stage. Under optimal conditions of maturation, drying and storage of the seeds, the G2/G1 ratio usually remains constant, decreasing slightly only after drying. It increases again at 24-48 h of imbibition, after completing DNA repair processes. It was found that environmental conditions during maturation of the seed, especially heavy rainfalls, could also increase the G2/G1 ratio of embryonic cells. When the seeds were collected at commercial harvest time (mature seeds) and 2 weeks before this (immature seeds), higher G2/G1 ratios were observed in the embryos of mature seeds, as compared with those from immature seeds. This phenomenon was most probably due to rainfalls and lower than optimal temperatures during the last 2 weeks of maturation, which induced germination while the seeds were still attached to the mother plant. A correlation was found between the G2/G1 ratio, vigour and laboratory and field test parameters, which suggests that this ratio can be used as an indicator of the physiological status of a seed. It is concluded that flow cytometry can be helpful in understanding and predicting sugarbeet seed quality.
Demonstrating the benefits of source-mask optimization and enabling technologies through experiment and simulations (2010)

In recent years the potential of Source-Mask Optimization (SMO) as an enabling technology for 22nm-and-beyond lithography has been explored and documented in the literature.<sup>1-5</sup> It has been shown that intensive optimization of the fundamental degrees of freedom in the optical system allows for the creation of non-intuitive solutions in both the mask and the source, which leads to improved lithographic performance. These efforts have driven the need for improved controllability in illumination<sup>5-7</sup> and have pushed the required optimization performance of mask design.<sup>8, 9 </sup>This paper will present recent experimental evidence of the performance advantage gained by intensive optimization, and enabling technologies like pixelated illumination. Controllable pixelated illumination opens up new regimes in control of proximity effects,<sup>1, 6, 7</sup> and we will show corresponding examples of improved through-pitch performance in 22nm Resolution Enhancement Technique (RET). Simulation results will back-up the experimental results and detail the ability of SMO to drive exposure-count reduction, as well as a reduction in process variation due to critical factors such as Line Edge Roughness (LER), Mask Error Enhancement Factor (MEEF), and the Electromagnetic Field (EMF) effect. The benefits of running intensive optimization with both source and mask variables jointly has been previously discussed.<sup>1-3</sup> This paper will build on these results by demonstrating large-scale jointly-optimized source/mask solutions and their impact on design-rule enumerated designs.
Dissecting the response to dehydration and salt (NaCl) in the resurrection plant Craterostigma plantagineum (2003)

ABSTRACT Although desiccation tolerant, the resurrection plant Craterostigma plantagineum is sensitive to relatively low levels of sodium chloride. Exposure to sodium chloride, but not dehydration, led to accumulation of sodium ions in leaves and roots and caused irreversible wilting. The effects of salt and dehydration on transcript accumulation patterns were studied by using selected cDNA clones that were related to water stress. Most of the clones represented genes that were up‐regulated in response to both treatments. Among the transcripts specifically up‐regulated by dehydration were RNAs encoding transcripts with homology to aquaporins. Expression analysis revealed dehydration‐specific profiles of l ate e mbryogenesis a bundant ( LEA ) genes, which differed from the patterns observed for the same genes under sodium chloride stress. The interconversion of octulose and sucrose, which is characteristic for the desiccation/rehydration cycle in C. plantagineum leaves, was not activated by sodium chloride. The present results suggest that dehydration‐specific responses involve the synchronized expression of specific genes and the presence of a determined concentration of sucrose. These dehydration responses were not detected in response to sodium chloride treatment.
Schlafen 3, a novel gene, regulates colonic mucosal growth during aging (2009)

Although aging is associated with increased proliferation and decreased apoptosis in the colonic mucosa of Fischer 344 rats, the regulatory mechanisms are poorly understood. Gene expression profiling (Illumina platform) was carried out in freshly isolated colonic mucosal cells from young (4-6 mo old) and aged (22-24 mo old) Fischer 344 rats. Sixty-six genes were differentially expressed in the colonic mucosa between young and old animals (P<0.05). In particular, the expression of schlafen 3, a negative regulator of proliferation, was decreased by 8- to 10-fold in the colonic mucosa of aged rats. Administration of wortmannin, which inhibited colonic mucosal proliferation in the colonic mucosa of aged rats, stimulated the expression of schlafen 3, indicating a growth regulatory role of this gene. To further determine the growth regulatory properties of schlafen 3 gene, schlafen 3 cDNA was transfected in colon cancer HCT-116 cells. This resulted in a 30-40% inhibition of cellular growth, accompanied by decreased expression of PCNA and cyclin D1 and reduced phosphorylation of retinoblastoma protein. In conclusion, our present study demonstrates that several genes involved in proliferation and apoptosis are differentially expressed in the colonic mucosa of young and aged rats. Schlafen 3, a novel negative regulator of growth, which is markedly downregulated in the colonic mucosa of the aged, may play a role in regulating colonic mucosal growth during aging.
Expressed Protein Ligation to Study Protein Interactions: Semi-Synthesis of the G-Protein Alpha Subunit (2005)

Interactions between G proteins and GPCRs are fundamental for transmitting signals for a multitude of physiologic responses. Little is known regarding the protein-protein interface between the G protein and the receptor, much less the mechanisms for receptor activation of G proteins. Here, we will describe how expressed protein ligation will aid in the study of protein-protein interactions between semi-synthetic G alpha subunits and GPCRs.
High-definition mapping of retroviral integration sites identifies active regulatory elements in human multipotent hematopoietic progenitors (2010)

Integration of retroviral vectors in the human genome follows nonrandom patterns that favor insertional deregulation of gene expression and increase the risk of their use in clinical gene therapy. The molecular basis of retroviral target site selection is still poorly understood. We used deep sequencing technology to build genomewide, high-definition maps of > 60 000 integration sites of Moloney murine leukemia virus (MLV)- and HIV-based retroviral vectors in the genome of human CD34(+) multipotent hematopoietic progenitor cells (HPCs) and used gene expression profiling, chromatin immunoprecipitation, and bioinformatics to associate integration to genetic and epigenetic features of the HPC genome. Clusters of recurrent MLV integrations identify regulatory elements (alternative promoters, enhancers, evolutionarily conserved noncoding regions) within or around protein-coding genes and microRNAs with crucial functions in HPC growth and differentiation, bearing epigenetic marks of active or poised transcription (H3K4me1, H3K4me2, H3K4me3, H3K9Ac, Pol II) and specialized chromatin configurations (H2A.Z). Overall, we mapped 3500 high-frequency integration clusters, which represent a new resource for the identification of transcriptionally active regulatory elements. High-definition MLV integration maps provide a rational basis for predicting genotoxic risks in gene therapy and a new tool for genomewide identification of promoters and regulatory elements controlling hematopoietic stem and progenitor cell functions.
AlN Barriers for Capacitance Reduction in Phase-Change RF Switches (2016)

We demonstrate four-terminal GeTe-based RF switches with independent thermal actuation (switching). These devices incorporate an AlN-based dielectric separating high-conductivity W micro-heaters from the RF signal path. With dc, pulsed, and RF testing, we show that an AlN barrier decreases the switch parasitic capacitance with minimal increases in the switching power. Decoupling these design variables, with the high thermal conductivity of the AlN, makes it possible to increase the electrical separation with a thicker AlN film for lower parasitic capacitance with minimal decrease in desirable thermal coupling. Increasing the AlN thickness from 105 to 170 nm results in switches with an improvement in cutoff frequency, f <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">CO</sub> from 5.3 to 8 THz, a C <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">OFF</sub> improvement from 15 to 10 fF, while maintaining the R <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">ON</sub> at 2 Ω. This improvement was accompanied by normalized minimum power to amorphize increases of only 14% (from 1.5 to 1.7 W) for a 100-ns heater pulse.
Fabrication of novel high surface area mushroom gilled fibers and their effects on human adipose derived stem cells under pulsatile fluid flow for tissue engineering applications (2019)

Abstract The fabrication and characterization of novel high surface area hollow gilled fiber tissue engineering scaffolds via industrially relevant, scalable, repeatable, high speed, and economical nonwoven carding technology is described. Scaffolds were validated as tissue engineering scaffolds using human adipose derived stem cells (hASC) exposed to pulsatile fluid flow (PFF). The effects of fiber morphology on the proliferation and viability of hASC, as well as effects of varied magnitudes of shear stress applied via PFF on the expression of the early osteogenic gene marker runt related transcription factor 2 (RUNX2) were evaluated. Gilled fiber scaffolds led to a significant increase in proliferation of hASC after seven days in static culture, and exhibited fewer dead cells compared to pure PLA round fiber controls. Further, hASC-seeded scaffolds exposed to 3 and 6 dyn/cm resulted in significantly increased mRNA expression of RUNX2 after one hour of PFF in the absence of soluble osteogenic induction factors. This is the first study to describe a method for the fabrication of high surface area gilled fibers and scaffolds. The scalable manufacturing process and potential fabrication across multiple nonwoven and woven platforms makes them promising candidates for a variety of applications that require high surface area fibrous materials. Statement of Significance We report here for the first time the successful fabrication of novel high surface area gilled fiber scaffolds for tissue engineering applications. Gilled fibers led to a significant increase in proliferation of human adipose derived stem cells after one week in culture, and a greater number of viable cells compared to round fiber controls. Further, in the absence of osteogenic induction factors, gilled fibers led to significantly increased mRNA expression of an early marker for osteogenesis after exposure to pulsatile fluid flow. This is the first study to describe gilled fiber fabrication and their potential for tissue engineering applications. The repeatable, industrially scalable, and versatile fabrication process makes them promising candidates for a variety of scaffold-based tissue engineering applications. Graphical abstract
Silk-based microneedle transdermal immunization with EV71 vaccines elicits potent immune responses in mice (2016)

Hand, foot, and mouth disease (HFMD), caused by EV71 viral infection, has emerged as a serious public health concern in the Asia-Pacific region. The lack of effective treatment has led to a focus on controlling EV71 epidemics through development of vaccines. This study compares the potency of inactivated whole-virus EV71 vaccine with recombinant viral protein (rVP) subunit vaccine, administered by various immunization routes including intraperitoneal (IP), intradermal (ID), or using a microneedle (MN) patch. The MN patches, made of biocompatible silk proteins loaded with antigens and adjuvant, were applied directly to the skin. Both inactivated virus and rVPs vaccines generated substantial EV71 specific serum IgG, but only the former induced neutralizing antibody. Immunization with silk MN patches induced comparable neutralizing antibody titers to the IP and ID. These findings suggest that inactivated EV71 virus was superior to rVP subunit vaccine in stimulating neutralizing antibody and that with some fine-tuning; the silk-based MN patches are an effective and noninvasive delivery platform for EV71 and possibly for other immunogens.
Human Dendritic Cells Very Efficiently Present a Heterologous Antigen Expressed on the Surface of Recombinant Gram-Positive Bacteria to CD4+ T Lymphocytes (1999)

Recombinant Streptococcus gordonii expressing on the surface the C-fragment of tetanus toxin was tested as an Ag delivery system for human monocyte-derived dendritic cells (DCs). DCs incubated with recombinant S. gordonii were much more efficient than DCs pulsed with soluble C-fragment of tetanus toxin at stimulating specific CD4+ T cells as determined by cell proliferation and IFN-gamma release. Compared with DCs treated with soluble Ag, DCs fed with recombinant bacteria required 102- to 103-fold less Ag and were at least 102 times more effective on a per-cell basis for activating specific T cells. S. gordonii was internalized in DCs by conventional phagocytosis, and cytochalasin D inhibited presentation of bacteria-associated Ag, but not of soluble Ag, suggesting that phagocytosis was required for proper delivery of recombinant Ag. Bacteria were also very potent inducers of DC maturation, although they enhanced the capacity of DCs to activate specific CD4+ T cells at concentrations that did not stimulate DC maturation. In particular, S. gordonii dose-dependently up-regulated expression of membrane molecules (MHC I and II, CD80, CD86, CD54, CD40, CD83) and reduced both phagocytic and endocytic activities. Furthermore, bacteria promoted in a dose-dependent manner DC release of cytokines (IL-6, TNF-alpha, IL-1beta, IL-12, TGF-beta, and IL-10) and of the chemokines IL-8, RANTES, IFN-gamma-inducible protein-10, and monokine induced by IFN-gamma. Thus, recombinant Gram-positive bacteria appear a powerful tool for vaccine design due to their extremely high capacity to deliver Ags into DCs, as well as induce DC maturation and secretion of T cell chemoattractans.
Production of Fully Dense Nd-Fe-B Magnets by Hot Pressing Technique Using Semi-Processed HDDR Powders. (2000)

Anisotropic fully dense Nd Fe-B magnets can be produced by compacting the HDDR-processed powder under an orienting magnetic field, and then by hot pressing the green compacts. In this study, we investigated orienting field dependence of the magnetic properties in the hot pressed magnets made from the Nd12.7Dy0.3Fe64.3Co16.0B6.2Zr0.1Ga0.4 powder in the different stages of the HDDR process. It was found that the semi-processed HDDR powder, in which the recombination reaction of the decomposed phases is not completed, can be more highly oriented in the applied magnetic fields less than 1190 kA/m in comparison with the fully HDDR-processed powder. The magnet with Br=1.13 T, HcJ=1280 kA/m, and (BH)mas=230 kJ/m3 can be obtained by dehydrogenating the compact of the semi-processed powder before the hot pressing.
Pooling-Invariant Image Feature Learning (2013)

Unsupervised dictionary learning has been a key component in state-of-the-art computer vision recognition architectures. While highly effective methods exist for patch-based dictionary learning, these methods may learn redundant features after the pooling stage in a given early vision architecture. In this paper, we offer a novel dictionary learning scheme to efficiently take into account the invariance of learned features after the spatial pooling stage. The algorithm is built on simple clustering, and thus enjoys efficiency and scalability. We discuss the underlying mechanism that justifies the use of clustering algorithms, and empirically show that the algorithm finds better dictionaries than patch-based methods with the same dictionary size.