gebhart/patrepeval huggingface dataset:
Rev-erbα, a Heme Sensor That Coordinates Metabolic and Circadian Pathways (2007)

The circadian clock temporally coordinates metabolic homeostasis in mammals. Central to this is heme, an iron-containing porphyrin that serves as prosthetic group for enzymes involved in oxidative metabolism as well as transcription factors that regulate circadian rhythmicity. The circadian factor that integrates this dual function of heme is not known. We show that heme binds reversibly to the orphan nuclear receptor Rev-erbalpha, a critical negative component of the circadian core clock, and regulates its interaction with a nuclear receptor corepressor complex. Furthermore, heme suppresses hepatic gluconeogenic gene expression and glucose output through Rev-erbalpha-mediated gene repression. Thus, Rev-erbalpha serves as a heme sensor that coordinates the cellular clock, glucose homeostasis, and energy metabolism.
Singularity Probability Analysis for Sparse Random Linear Network Coding (2011)

Motivated by the sparse random linear network coding approach, we consider the problem of characterizing the probability of having a full rank (or nonsingular) square transfer matrix over a finite field, for which the probability of choosing the zero element is different from that of choosing a nonzero element. We found that for a sufficiently large field size, whether the transfer matrix is singular or not is determined with probability one by the zero pattern of the matrix, i.e., where the zeroes are located in the matrix. This result provides insight for optimizing sparse random linear network coding schemes and allows the problem of determining the probability of having a nonsingular transfer matrix over a large field size to be transformed into a combinatorial problem. By using some combinatorial arguments, useful upper and lower bounds on the singularity probability of the random transfer matrix are derived.
Concurrent Isolation of Lymphocytes and Granulocytes Using Prefocused Free Flow Acoustophoresis (2015)

Microchip-based free flow acoustophoresis (FFA) in combination with two-dimensional cell prefocusing enables concurrent multiple target outlet fractionation of leukocytes into subpopulations (lymphocytes, monocytes, and granulocytes); we report on this method here. We also observed significantly increased accuracy in size-based fractionation of microbeads as compared to previously presented FFA multiple outlet systems. Fluorescence microscopy illustrates the importance of two-dimensional prefocusing where a sample mixture of 3, 7, and 10 μm beads are separated into well-confined particle streams and collected in their respective target outlets. Flow cytometry data for lymphocytes and granulocytes, respectively, in their corresponding outlets verify concurrent isolation of leukocyte subpopulations with high purity (95.2 ± 0.6% and 98.5 ± 0.7%) and high recovery (86.5 ± 10.9% and 68.4 ± 10.6%). A relatively low purity and high recovery of monocytes (25.2% ± 5.4% and 83.1 ± 4.3%) was obtained in the third target outlet. No subpopulation bias was observed. These data demonstrate an unprecedented separation of leukocyte subpopulations at flow rates of ∼100 μL/min and ∼1 M cells/mL sample concentrations, not previously reported in acoustofluidic systems. Two-dimensional prefocusing FFA with multiple target outlets is a viable alternative to current methods for particle fractionation and cell isolation, requiring a minimum of sample preparation and lowering analysis time and cost.
5'-Triphosphate RNA Is the Ligand for RIG-I (2006)

The structural basis for the distinction of viral RNA from abundant self RNA in the cytoplasm of virally infected cells is largely unknown. We demonstrated that the 5'-triphosphate end of RNA generated by viral polymerases is responsible for retinoic acid-inducible protein I (RIG-I)-mediated detection of RNA molecules. Detection of 5'-triphosphate RNA is abrogated by capping of the 5'-triphosphate end or by nucleoside modification of RNA, both occurring during posttranscriptional RNA processing in eukaryotes. Genomic RNA prepared from a negative-strand RNA virus and RNA prepared from virus-infected cells (but not from noninfected cells) triggered a potent interferon-alpha response in a phosphatase-sensitive manner. 5'-triphosphate RNA directly binds to RIG-I. Thus, uncapped 5'-triphosphate RNA (now termed 3pRNA) present in viruses known to be recognized by RIG-I, but absent in viruses known to be detected by MDA-5 such as the picornaviruses, serves as the molecular signature for the detection of viral infection by RIG-I.
Nucleotide sequence analysis of genes essential for capsular polysaccharide biosynthesis in Streptococcus pneumoniae type 19F (1994)

Previous studies have shown that the capsular polysaccharide synthesis (cps) locus of the type 19F Streptococcus pneumoniae strain SSZ was closely linked to a copy of the insertion sequence IS1202 (J.K. Morona, A. Guidolin, R. Morona, D. Hansman, and J.C. Paton, J. Bacteriol. 176:4437-4443, 1994). In the present study, we used plasmid insertion and rescue and inverse PCR to clone 6,322 bp of flanking DNA upstream of IS1202. Sequence analysis indicated that this region contains six complete open reading frames (ORFs) and one partial ORF that are arranged as a single transcriptional unit. Chromosomal disruption of any of these ORFs in a smooth-type 19F strain leads to a rough (unencapsulated) phenotype, indicating that this operon is essential for capsule production. The ORFs have therefore been designated cps19fA to cps19fG, where cps19fA is the first gene of the type 19F cps locus. Furthermore, many of the gene products from this incomplete operon exhibit strong similarities to proteins known to be involved in the production of capsular polysaccharide, exopolysaccharide, teichoic acid, enterobacterial common antigen, and lipopolysaccharide from numerous other bacterial species. This has allowed us to propose functions for many of the type 19F cps gene products. Southern hybridization studies reveal that cps19fA and cps19fB are conserved among all 12 pneumococcal serotypes tested, whereas genes downstream of cps19fB are conserved among some, but not all, of the serotypes tested.
Purified Group X Secretory Phospholipase A2 Induced Prominent Release of Arachidonic Acid from Human Myeloid Leukemia Cells (1999)

Group X secretory phospholipase A(2) (sPLA(2)-X) possesses several structural features characteristic of both group IB and IIA sPLA(2)s (sPLA(2)-IB and -IIA) and is postulated to be involved in inflammatory responses owing to its restricted expression in the spleen and thymus. Here, we report the purification of human recombinant COOH-terminal His-tagged sPLA(2)-X, the preparation of its antibody, and the purification of native sPLA(2)-X. The affinity-purified sPLA(2)-X protein migrated as various molecular species of 13-18 kDa on SDS-polyacrylamide gels, and N-glycosidase F treatment caused shifts to the 13- and 14-kDa bands. NH(2)-terminal amino acid sequencing analysis revealed that the 13-kDa form is a putative mature sPLA(2)-X and the 14-kDa protein possesses a propeptide of 11 amino acid residues attached at the NH(2) termini of the mature protein. Separation with reverse-phase high performance liquid chromatography revealed that N-linked carbohydrates are not required for the enzymatic activity and pro-sPLA(2)-X has a relatively weak potency compared with the mature protein. The mature sPLA(2)-X induced the release of arachidonic acid from phosphatidylcholine more efficiently than other human sPLA(2) groups (IB, IIA, IID, and V) and elicited a prompt and marked release of arachidonic acid from human monocytic THP-1 cells compared with sPLA(2)-IB and -IIA with concomitant production of prostaglandin E(2). A prominent release of arachidonic acid was also observed in sPLA(2)-X-treated human U937 and HL60 cells. Immunohistochemical analysis of human lung preparations revealed its expression in alveolar epithelial cells. These results indicate that human sPLA(2)-X is a unique N-glycosylated sPLA(2) that releases arachidonic acid from human myeloid leukemia cells more efficiently than sPLA(2)-IB and -IIA.
CMOS Technology (2011)

Recent developments in Schottky source/drain high-k/metal gate CMOS transistors (SSDT) will be presented. Bulk SSDTs with 1.5-2 nm HfO 2 (or HfAlO) gate dielectric and HfN/TaN metal gate have been fabricated using a novel low temperature process. The Si N-SSDT using YbSi 2-x silicide, due to the lower Schottky electron barrier of YbSi 2-x /Si, has demonstrated a record high I on /I off ratio of ∼10 7 and a steep subthreshold slope of 75 mV/dec. For P-SSDT, the Si SSDT using PtSi silicide S/D shows excellent I on /I off of ∼ 10 7 - 10 8 and subthreshold slope of ∼ 66 mV/dec, while the Ge SSDT using NiGe S/D shows Ion - 5 times larger than that of the Si counterpart with PtSi S/D, due to the lower hole Schottky barrier and the higher hole mobility of Ge channel. The implant-free low temperature process relaxes the thermal budget of high-k dielectric and metal gate Fermi pinning. More improved performances are expected by using ultra-thin-body (UTB) SOI or GOI structures, showing great potential of this low temperature process SSDTs for future sub-tenth micron CMOS technology.
Sampling and Electrophoretic Analysis of Segmented Flow Streams Using Virtual Walls in a Microfluidic Device (2008)

A method for sampling and electrophoretic analysis of aqueous plugs segmented in a stream of immiscible oil is described. In the method, an aqueous buffer and oil stream flow parallel to each other to form a stable virtual wall in a microfabricated K-shaped fluidic element. As aqueous sample plugs in the oil stream make contact with the virtual wall, coalescence occurs and sample is electrokinetically transferred to the aqueous stream. Using this virtual wall, two methods of injection for channel electrophoresis were developed. In the first, discrete sample zones flow past the inlet of an electrophoresis channel and a portion is injected by electroosmotic flow, termed the "discrete injector". With this approach at least 800 plugs could be injected without interruption from a continuous segmented stream with 5.1% RSD in peak area. This method generated up to 1,050 theoretical plates, although analysis of the injector suggested that improvements may be possible. In a second method, aqueous plugs are sampled in a way that allows them to form a continuous stream that is directed to a microfluidic cross-style injector, termed the "desegmenting injector". This method does not analyze each individual plug but instead allows periodic sampling of a high-frequency stream of plugs. Using this system at least 1000 injections could be performed sequentially with 5.8% RSD in peak area and 53,500 theoretical plates. This method was demonstrated to be useful for monitoring concentration changes from a sampling device with 10 s temporal resolution. Aqueous plugs in segmented flows have been applied to many different chemical manipulations including synthesis, assays, sampling processing and sampling. Nearly all such studies have used optical methods to analyze plug contents. This method offers a new way to analyze such samples and should enable new applications of segmented flow systems.
Identifying the learning needs of nurse managers. application of the critical incident technique. (1996)

Accurate identification of learning needs is the most important component of the staff development process. The critical incident technique is shown to be a valuable tool in identifying the learning needs of nurse managers in a long-term care facility. This technique addresses the real work issues and concerns affecting nurse managers. A step-by-step process is provided to help nurse educators develop a comprehensive inventory of learning needs.
Self-financed wagering mechanisms for forecasting (2008)

We examine a class of wagering mechanisms designed to elicit truthful predictions from a group of people without requiring any outside subsidy. We propose a number of desirable properties for wagering mechanisms, identifying one mechanism - weighted-score wagering - that satisfies all of the properties. Moreover, we show that a single-parameter generalization of weighted-score wagering is the only mechanism that satisfies these properties. We explore some variants of the core mechanism based on practical considerations.
Combination of Farnesyltransferase and Akt Inhibitors Is Synergistic in Breast Cancer Cells and Causes Significant Breast Tumor Regression in ErbB2 Transgenic Mice (2011)

The Akt activation inhibitor triciribine and the farnesyltransferase inhibitor tipifarnib have modest to little activity in clinical trials when used as single agents. In this article, preclinical data show that the combination is more effective than single agents both in cultured cells and in vivo. Combination index data analysis shows that this combination is highly synergistic at inhibiting anchorage-dependent growth of breast cancer cells. This synergistic interaction is also observed with structurally unrelated inhibitors of Akt (MK-2206) and farnesyltransferase (FTI-2153). The triciribine/tipifarnib synergistic effects are seen with several cancer cell lines including those from breast, leukemia, multiple myeloma and lung tumors with different genetic alterations such as K-Ras, B-Raf, PI3K (phosphoinositide 3-kinase), p53 and pRb mutations, PTEN, pRB and Ink4a deletions, and ErbB receptor overexpression. Furthermore, the combination is synergistic at inhibiting anchorage-independent growth and at inducing apoptosis in breast cancer cells. The combination is also more effective at inhibiting the Akt/mTOR/S6 kinase pathway. In an ErbB2-driven breast tumor transgenic mouse model, the combination, but not single agent, treatment with triciribine and tipifarnib induces significant breast tumor regression. Our findings warrant further investigation of the combination of farnesyltransferase and Akt inhibitors.
Stability of a soybean seed‐derived vaccine antigen following long‐term storage, processing and transport in the absence of a cold chain (2009)

Abstract BACKGROUND: Soybean seeds are rich in natural protein and are favorable environments for targeted protein expression. Soybeans represent an ideal platform for the production of novel vaccines that, in theory, do not require a cold chain. This study investigated the stability of a soybean‐derived antigen following long‐term storage, formulation, and shipment overseas in the absence of refrigeration. RESULTS: Transgenic seeds can be stored for more than 4 years at ambient temperature with no detectable loss of FanC antigen stability. Conventional processing methods utilizing heat, mechanical extraction and solvent extraction resulted in practical formulations that could be lyophilized, stored as dried milk powder and rehydrated in water without loss of FanC antigen stability. Overseas shipment of transgenic seed powder and soymilk formulations in the absence of a cold chain had no adverse effects on formulations or the FanC antigen. CONCLUSION: The feasibility of long‐term storage, processing and shipment of transgenic soy products in the absence of a cold chain was demonstrated. Soybeans represent a practical platform for development of novel vaccines to potentially address the worldwide need for vaccines that are cost‐effective, easy to formulate and can be manufactured, stored and transported without refrigeration. Copyright © 2009 Society of Chemical Industry
Influenza A virus M2 protein: monoclonal antibody restriction of virus growth and detection of M2 in virions (1988)

The influenza A virus M2 protein is an integral membrane protein of 97 amino acids that is expressed at the surface of infected cells with an extracellular N-terminal domain of 18 to 23 amino acid residues, an internal hydrophobic domain of approximately 19 residues, and a C-terminal cytoplasmic domain of 54 residues. To gain an understanding of the M2 protein function in the influenza virus replicative pathway, we produced and characterized a monoclonal antibody to M2. The antibody-binding site was located to the extracellular N terminus of M2 as shown by the loss of recognition after proteolysis at the infected-cell surface, which removes 18 N-terminal residues, and by the finding that the antibody recognizes M2 in cell surface fluorescence. The epitope was further defined to involve residues 11 and 14 by comparing the predicted amino acid sequences of M2 from several avian and human strains and the ability of the M2 protein to be recognized by the antibody. The M2-specific monoclonal antibody was used in a sensitive immunoblot assay to show that M2 protein could be detected in virion preparations. Quantitation of the amount of M2 associated with virions by two unrelated methods indicated that in the virion preparations used there are 14 to 68 molecules of M2 per virion. The monoclonal antibody, when included in a plaque assay overlay, considerably showed the growth of some influenza virus strains. This plaque size reduction is a specific effect for the M2 antibody as determined by an analysis of recombinants with defined genome composition and by the observation that competition by an N-terminal peptide prevents the antibody restriction of virus growth.
Kunjin Virus Replicon Vaccine Vectors Induce Protective CD8+T-Cell Immunity (2002)

The ability of self-replicating RNA (replicon) vaccine vectors derived from the Australian flavivirus Kunjin (KUN) to induce protective alphabeta CD8+ T-cell responses was examined. KUN replicons encoding a model immunogen were delivered by three different vaccine modalities: (i) as naked RNA transcribed in vitro, (ii) as plasmid DNA constructed to allow in vivo transcription of replicon RNA by cellular RNA polymerase II (DNA based), and (iii) as replicon RNA encapsidated into virus-like particles. A single immunization with any of these KUN replicon vaccines induced CD8+ T-cell responses at levels comparable to those induced by recombinant vaccinia virus encoding the same immunogen. Immunization with only 0.1 microg of DNA-based KUN replicons elicited CD8+ T-cell responses similar to those seen after immunization with 100 microg of a conventional DNA vaccine. Naked RNA immunization with KUN replicons also protected mice against challenges with recombinant vaccinia virus and B16 tumor cells. These results demonstrate the value of KUN replicon vectors for inducing protective antiviral and anticancer CD8+ T-cell responses.
Novel Synthesis of Desymmetrized Resorcinol Derivatives:  Aryl Fluoride Displacement on Deactivated Substrates (2006)

A short, high-yielding synthesis of differentially substituted resorcinol derivatives has been developed that utilizes 1,3-difluorobenzene as the starting material and employs sequential nucleophilic aromatic substitution (S(N)Ar) reactions to generate desymmetrized products. The scope and limitations of the second S(N)Ar reaction on the deactivated 1-alkoxy-3-fluorobenzene intermediates have been investigated. This methodology has also been employed in the synthesis of desymmetrized catechol derivatives from 1,2-difluorobenzene.
Solution- and Solid-Phase Synthesis of N-Protected Glycopeptide Esters of the Benzyl Type as Substrates for Subtilisin-Catalyzed Glycopeptide Couplings (1998)

This paper describes the solution- and solid-phase synthesis of glycopeptides containing a GlcNAc moiety at different positions and investigates them as substrates for subtilisin-catalyzed glycopeptide condensation, with an aim to develop enzymatic synthesis of complex glycopeptides and glycoproteins. A systematic study was performed to determine the sites at which the protease subtilisin will accept a glycosylated residue in enzymatic peptide ligations. It was found that Fmoc-glycopeptide esters with unprotected side chains can be prepared by solid-phase methodology using the Rink amide resin. Both removal of the side chain protecting groups as well as release from the resin was accomplished by treatment with acid to provide glycopeptide esters of the benzyl type which were used directly as substrates. One such 12 residue peptide ester was used in a subtilisin-catalyzed glycopeptide condensation in a kinetically controlled mode to demonstrate the utility of this approach.
Loan repayments help pharmacists provide care in medically underserved areas (2003)

Journal Article Loan repayments help pharmacists provide care in medically underserved areas Get access Donna Young Donna Young Search for other works by this author on: Oxford Academic Google Scholar American Journal of Health-System Pharmacy, Volume 60, Issue 21, 1 November 2003, Page 2186, https://doi.org/10.1093/ajhp/60.21.2186 Published: 01 November 2003
Human monoclonal antibody against a tissue polypeptide antigen-related protein from a patient with a signet-ring cell carcinoma of the stomach. (1990)

For a comparative study of the humoral immunity of patients with gastric signet-ring cell carcinoma, lymphocytes from spleen and lymph nodes were fused with the heteromyeloma SPM4-0. Immunoglobulin-producing clones were primarily tested in binding assays on autologous and allogeneic tumor cells and tissues. One of the resulting human monoclonal antibodies, designated 56/16 (IgM, lambda), was found to be suitable for a detailed biochemical characterization. Immunoblotting and comparative two-dimensional gel electrophoresis on cell and tissue extracts as well as on preparations of the cytoskeleton revealed that the main epitope is not an integral membrane molecule but a degradation product of cytokeratin 8, which is a main component of the tumor marker, tissue polypeptide antigen. The Mr 38,000/45,000 antigen could be identified in tumor and normal tissues, with highest expression in secretory cells and organs. Thus, the human monoclonal antibody 56/16 might represent an immune response in the patient against breakdown products of cytokeratin 8, which are released from the tumor cells during cell division, secretion, or cell death. A possible association of the antibody with the secretory activity of signet-ring carcinoma cells is discussed.
Codon Optimization of the Tat Antigen of Human Immunodeficiency Virus Type 1 Generates Strong Immune Responses in Mice following Genetic Immunization (2004)

DNA vaccines have been successful in eliciting potent immune responses in mice. Their efficiency, however, is restricted in larger animals. One reason for the limited performance of the DNA vaccines is the lack of molecular strategies to enhance immune responses. Additionally, genes directly cloned from pathogenic organisms may not be efficiently translated in a heterologous host expression system as a consequence of codon bias. To evaluate the influence of codon optimization on the immune response, we elected to use the Tat antigens of human immunodeficiency virus type 1 (HIV-1) (subtype C) and HIV-2, as these viral antigens are poorly immunogenic in natural infection and in experimental immunization and they are functionally important in viral infectivity and pathogenesis. Substituting codons that are optimally used in the mammalian system, we synthetically assembled Tat genes and compared them with the wild-type counterparts in two different mouse strains. Codon-optimized Tat genes induced qualitatively and quantitatively superior immune responses as measured in a T-cell proliferation assay, enzyme-linked immunospot assay, and chromium release assay. Importantly, while the wild-type genes promoted a mixed Th1-Th2-type cytokine profile, the codon-optimized genes induced a predominantly Th1 profile. Using a pepscan strategy, we mapped an immunodominant T-helper epitope to the core and basic domains of HIV-1 Tat. We also identified cross-clade immune responses between HIV-1 subtype B and C Tat proteins mapped to this T-helper epitope. Developing molecular strategies to optimize the immunogenicity of DNA vaccines is critical for inducing strong immune responses, especially to antigens like Tat. Our identification of a highly conserved T-helper epitope in the first exon of HIV-1 Tat of subtype C and the demonstration of a cross-clade immune response between subtypes B and C are important for a more rational design of an HIV vaccine.