gebhart/patrepeval huggingface dataset:
Relationship between degree of P2Y12 receptor blockade and inhibition of P2Y12-mediated platelet function (2010)

The thienopyridine P2Y12 receptor antagonists clopidogrel and prasugrel prevent arterial thrombosis and are routinely used following percutaneous coronary intervention. However, the optimal level of P2Y12 blockade to effectively inhibit platelet function is unknown. These studies utilised the active metabolite of prasugrel (R-138727) to achieve a range of P2Y12 blockade in vitro and assessed several aspects of platelet function. Blood from healthy volunteers was incubated with R-138727 (0-10 microM). P2Y12 receptor number was assessed using a 33P-2MeSADP binding assay. Platelet aggregation (PA) was measured by optical aggregometry with ADP 2-20 microM. VASP phosphorylation, annexin V binding, microparticle formation and P-selectin expression were assessed by flow cytometry. Increasing numbers of unblocked receptors were required for a sustained aggregation response with decreasing concentrations of ADP. A P2Y12 receptor blockade of 60-80% resulted in strong inhibition of final PA response, P-selectin expression, microparticle formation and vasodilator-stimulated phosphoprotein (VASP). PA induced by ADP 2 microM and P-selectin expression were particularly sensitive to low levels of receptor blockade whereas the VASP phosphorylation assay was relatively insensitive, requiring 60% receptor blockade to achieve substantial inhibition. Different assays varied in their ability to discriminate particular ranges of P2Y12 blockade and 80% or greater P2Y12 receptor blockade is required for consistently strong inhibition of several aspects of platelet function. These data guide the interpretation of results from different assays used to monitor the effects of P2Y12 receptor antagonists.
Quantitative Molecular Pharmacology and Informatics in Drug Discovery (1999)

Drug Discovery. Measurement of Drug Affinity. Efficacy. Pharmacological Assays Used in Screening for Therapeutic Ligands. Finding the Optimal Assay Format for the Chemical Target. Mathematical and Statistical Framework for Problems in Drug Discovery. Statistical Methods for Target Identification and Validation. Experimental Design. Analysis and Interpretation of Data. Index.
Interleukin-21-Producing HIV-1-Specific CD8 T Cells Are Preferentially Seen in Elite Controllers (2010)

A hallmark of human immunodeficiency virus type 1 (HIV-1) pathogenesis is the rapid loss of CD4 T cells leading to generalized immune dysfunction, including an exhausted CD8 T cell phenotype. Understanding the necessary factors that govern the functional quality and protective potential of antiviral T cell responses would facilitate rational vaccine design and improve therapeutic strategies to combat persistent infections. Mouse models of chronic viral infection demonstrate that interleukin-21 (IL-21), produced primarily by CD4 T cells, is required for the generation and maintenance of functionally competent CD8 T cells and viral containment. We reasoned that preserved IL-21 production during HIV-1 infection would be associated with enhanced CD8 T cell function, allowing improved viral control. Here we analyzed the ability of CD4 and CD8 T cells to produce several cytokines in addition to IL-21 ex vivo following stimulation with overlapping HIV-1 peptides. Both CD4 and CD8 T cells were able to produce IL-21 in response to HIV-1 infection, with the latter cell type more closely associated with viral control. Furthermore, IL-21-producing HIV-1-specific CD4 T cells (compared to those producing other cytokines) were the best indicator of functional CD8 T cells. Our results demonstrate that HIV-1-specific IL-21-producing CD8 T cells are induced following primary infection and enriched in elite controllers, suggesting a critical role for these cells in the maintenance of viremia control.
Correlations between RNA and protein expression profiles in 23 human cell lines (2009)

Abstract Background The Central Dogma of biology holds, in famously simplified terms, that DNA makes RNA makes proteins, but there is considerable uncertainty regarding the general, genome-wide correlation between levels of RNA and corresponding proteins. Therefore, to assess degrees of this correlation we compared the RNA profiles (determined using both cDNA- and oligo-based microarrays) and protein profiles (determined immunohistochemically in tissue microarrays) of 1066 gene products in 23 human cell lines. Results A high mean correlation coefficient (0.52) was obtained from the pairwise comparison of RNA levels determined by the two platforms. Significant correlations, with correlation coefficients exceeding 0.445, between protein and RNA levels were also obtained for a third of the specific gene products. However, the correlation coefficients between levels of RNA and protein products of specific genes varied widely, and the mean correlations between the protein and corresponding RNA levels determined using the cDNA- and oligo-based microarrays were 0.25 and 0.20, respectively. Conclusion Significant correlations were found in one third of the examined RNA species and corresponding proteins. These results suggest that RNA profiling might provide indirect support to antibodies' specificity, since whenever a evident correlation between the RNA and protein profiles exists, this can sustain that the antibodies used in the immunoassay recognized their cognate antigens.
TP53 alterations in relation to the cell cycle-associated proteins p21, cyclin D1, CDK4, RB, MDM2, and EGFR in cancers of the uterine corpus (1999)

In the present study, TP53 alterations have been analysed and compared with the expression of the proteins p21, cyclin D1, cdk4, RB, EGFR, and MDM2 in 53 cancers of the uterine corpus. TP53 gene mutations analysed by CDGE/DGGE and direct sequencing showed a TP53 gene mutation in 18 per cent of the cases. TP53 gene mutations were not significantly related to overexpression or down-regulation of any of the proteins. Immunohistochemically, there was an increased protein level of TP53 in 77 per cent, p21 in 36 per cent, cyclin D1 in 45 per cent, cdk4 in 77 per cent, EGFR in 8 per cent, and MDM2 in 32 per cent of the cases. Expression of RB protein was normal in all cancers. Significant association of protein expression was seen between TP53 and MDM2 (p=0.005) and p21 and MDM2 (p=0.001). Furthermore, there may be an association between TP53 and p21 (p=0. 038) and cyclin D1 and cdk4 (p=0.045). The results revealed increased levels of TP53 protein in all MDM2-positive cases that did not show TP53 mutations, indicating TP53 protein stabilization and inactivation by complex formation with MDM2. In summary, the high number of cases showing an increased level of TP53 and cdk4 proteins suggests that these proteins play an important role in the neoplastic process in cancers of the uterine corpus.
Noise Analysis and Characterization of a Sigma-Delta Capacitive Microaccelerometer (2006)

This paper reports a high-sensitivity low-noise capacitive accelerometer system with one micro-g//spl radic/Hz resolution. The accelerometer and interface electronics together operate as a second-order electromechanical sigma-delta modulator. A detailed noise analysis of electromechanical sigma-delta capacitive accelerometers with a final goal of achieving sub-/spl mu/g resolution is also presented. The analysis and test results have shown that amplifier thermal and sensor charging reference voltage noises are dominant in open-loop mode of operation. For closed-loop mode of operation, mass-residual motion is the dominant noise source at low sampling frequencies. By increasing the sampling frequency, both open-loop and closed-loop overall noise can be reduced significantly. The interface circuit has more than 120 dB dynamic range and can resolve better than 10 aF. The complete module operates from a single 5-V supply and has a measured sensitivity of 960 mV/g with a noise floor of 1.08 /spl mu/g//spl radic/Hz in open-loop. This system can resolve better than 10 /spl mu/g//spl radic/Hz in closed-loop.
COLLAGEN SUBSTRATA FOR STUDIES ON CELL BEHAVIOR (1972)

A simple technique is described for the preparation of collagen substrata containing 0 1% of collagen by weight, in the form of native bundles with a 640 A period, the substrata are similar in these respects to soft-tissue matrices These substrate are hydrated collagen lattices (HCLs) in which the watery milieu is held within a fibrous collagen net mainly by capillary forces. HCLs have been characterized in terms of the course of collagen precipitation and aggregation, ultrastructure, and their stability under various conditions. The ways in which HCLs can be employed as both two- and three-dimensional substrata in cell behavioral studies are illustrated with some preliminary observations on the form, motility, adhesion, and growth of human diploid cells and two lines of malignant cells.
Challenges of studying and processing dialects in social media (2015)

Dialect features typically do not make it into formal writing, but flourish in social media. This enables largescale variational studies.
Experimental investigation of quantum key distribution through transparent optical switch elements (2003)

Quantum key distribution (QKD) enables unconditional physical layer security for the distribution of cryptographic key material. However, most experimental demonstrations have relied on simple point-to-point optical links. In this paper we investigate the compatibility of QKD with reconfigurable optical networks. By performing the first tests of QKD transmission through optical switches, we study if there are impairment mechanisms other than switch insertion loss that impact the sifted and error corrected secret bit yield. Three types of transparent optical switch elements are investigated including lithium niobate (LiNbO/sub 3/), microelectromechanical systems (MEMS), and optomechanical. We show that QKD can be extended beyond point-to-point links to switched multinode architectures including protected ring networks to enhance quantum channel availability.
Broad Tuning of the Human Bitter Taste Receptor hTAS2R46 to Various Sesquiterpene Lactones, Clerodane and Labdane Diterpenoids, Strychnine, and Denatonium (2007)

Sesquiterpene lactones are a major class of natural bitter compounds occurring in vegetables and culinary herbs as well as in aromatic and medicinal plants, where they often represent the main gustatory and pharmacologically active component. Investigations on sesquiterpene lactones have mainly focused on their bioactive potential rather than on their sensory properties. In the present study, we report about the stimulation of heterologously expressed human bitter taste receptors, hTAS2Rs, by the bitter sesquiterpene lactone herbolide D. A specific response to herbolide D was observed i.a. for hTAS2R46, a so far orphan bitter taste receptor without any known ligand. By further investigation of its agonist pattern, we characterized hTAS2R46 as a bitter receptor broadly tuned to sesquiterpene lactones and to clerodane and labdane diterpenoids as well as to the unrelated bitter substances strychnine and denatonium.
Mel Frequency Cepstral Coefficients For Music Modeling. (2000)

[TODO] Add abstract here.
Irish Potato, Control of Potato-Infesting Aphids, 1991 (1992)

Abstract Aphid foliar and systemic experiments were arranged in a randomized complete block design replicated six times. Experiments were conducted at Preseque Isle, ME on land that was in clover in 1990. The planting dates were I 21 and 20 May respectively. The 3.0 m space between blocks and the 1.8 m space between the four-row plots were sown to oats on 28 Jun in the foliar 1 experiment. These areas were left fallow in the other experiment. All rows were planted with an assisted-feed planter 0.9 m apart and 15.0 m long and the whole 'Katahdin' seed pieces (ca. 75 g) were planted 30 cm apart. Fertilizer and hilling practices were normal for the area. Early and late blight were controlled by three foliar applications of Dithane M-45 (80 WP) (1.12 kg/ha on 18, 26 Jul, and 2 Aug) and Bravo 720 (840 g/ha on 9 and 23 Aug). Furrow j applications of insecticides were made by hand with a plastic tube applying previously weighed amounts of insecticide. Foliar insecticide applications were i made with a Century boom sprayer, three nozzles per row at 6.3 kg/cm2 pressure and 940 liters/ha. Numbers of aphids (by species) were counted on top, middle, and bottom leaves of 25 plants in the middle row of each plot. When dates of count and application were the same, aphid counts were made prior I to applications of the insecticide. Analyses of variance were calculated following transformation of the data using logi0(x + 1) for Aphid-B. Transformed means of the total number of wingless aphids were compared using DMRT and then applied to the actual means. The soil was classified as Caribou Loam, pH 5.2, Total monthly rainfall for Jun, Jul, and Aug was 3.1, 1.9, and 21.7 cm, respectively. The average temperature for each of the same 3 months was 17.1, 19.0, and 19.3 deg. C.
[Fecal Biomarker for Colorectal Cancer Diagnosis]. (2015)

The fecal occult blood test (FOBT) is widely used for colorectal cancer (CRC) screening to reduce the mortality rate associated with this cancer. However, several problems exist, as FOBT results can contain some false-negative CRC patients and some-false positive healthy subjects. Thus, to resolve these problems, several fecal biomarkers based on fecal protein, fecal DNA, and fecal RNA have been reported. Fecal calprotectin, which indicates intestinal bleeding or inflammation of the colon mucosa, and fecal tumor M2-PK, which is produced by cancer cells, have been extensively investigated as fecal protein biomarkers. To detect small amounts of CRC-specific proteins, the chemiluminescent enzyme immunoassay (CLEIA), which is a highly sensitive protein detection method using immunomagnetic beads, will be used. DNA mutation of APC, KRAS, and TP53 genes and DNA methylation of VIM, TFPI2, BMP3, NDRG4, and SFRP2 genes were reported as fecal DNA biomarkers. Consequently, a fecal DNA test named Cologuard from Exact Sciences was approved by the FDA in August 2014. Fecal COX2, MMP7, miR-106a, miR-92a, and miR-223 were also reported as fecal RNA biomarkers. This review article summarizes fecal biomarkers using fecal samples for CRC diagnosis.
Curvature-Tuned Preparation of Nanoliposomes (2009)

Numerous methods have been reported for the preparation of liposomes, many of which, in addition to requiring time-consuming preparative steps and the use of organic solvents, result in heterogeneous liposome populations of incontrollable size. Taking into consideration the phenomenon of spontaneous vesiculation and the theory of curvature, here we present an extremely rapid and simple, solvent-free method for the preparation of monodisperse solutions of highly stable small unilamellar vesicles using both charged and zwitterionic lipids mixed with lyso-palmitoylphosphatidylcholine, exploiting a combination of a rapid pH change followed by a defined period of equilibration. Various experimental parameters and their interactions were evaluated in terms of their effect on resulting liposome size and shape, as well as on liposome stability and size distribution, with transmission electron microscope imaging being used to visualize the formed liposomes, and photon correlation spectroscopy to obtain statistical data on mean diameter and monodispersity of the liposome population. zeta potential measurements also provided information about the interpretation of vesiculation kinetics and liposome stability. The time interval of pH jump, operation temperature, equilibration time, and lipid type were shown to be the determining factors controlling the size, shape, and monodispersity of the liposomes. Buffer type was also found to be important for the long-term storage of the liposomes. Ongoing work is looking at the application of the developed method for encapsulation of bioactive molecules, such as drugs, genetic materials, and enzymes.
QoS provisioning in clusters (2001)

Design of high performance cluster networks (routers) with Quality-of-Service (QoS) guarantees is becoming increasingly important to support a variety of multimedia applications, many of which have real-time constraints. Most commercial routers, which are based on the wormhole-switching paradigm, can deliver high performance, but lack QoS provisioning. In this paper, we present a pipelined wormhole router architecture that can provide high and predictable performance for integrated traffic in clusters. We consider two different implementations—a non-preemptive model and a more aggressive preemptive model. We also present the design of a network interface card (NIC) based on the Virtual Interface Architecture (VIA) design paradigm to support QoS in the NIC. The QoS capable router and NIC designs are evaluated with a mixed workload consisting of best-effort traffic, multimedia streams, and control traffic. Simulation results of an 8-port router and a (2 × 2) mesh network indicate that the preemptive router can provide better performance than the non-preemptive router for dynamically changing workloads. Co-evaluation of the QoS-aware NIC with the proposed router models shows significant performance improvement compared to that with a traditional NIC without any QoS support.
Smart three-dimensional lightweight structure triggered from a thin composite sheet via 3D printing technique (2016)

Complex fabrication process and expensive materials have restricted the development of smart three-dimensional (3D) lightweight structures, which are expected to possess self-shaping, self-folding and self-unfolding performances. Here we present a simple approach to fabricate smart lightweight structures by triggering shape transformation from thin printed composite sheets. The release of the internal strain in printed polymer materials enables the printed composite sheet to keep flat under heating and transform into a designed 3D configuration when cooled down to room temperature. The 3D lightweight structure can be switched between flat and 3D configuration under appropriate thermal stimuli. Our work exploits uniform internal strain in printed materials as a controllable tool to fabricate smart 3D lightweight structures, opening an avenue for possible applications in engineering fields.
First-in-man application of a novel therapeutic cancer vaccine formulation with the capacity to induce multi-functional T cell responses in ovarian, breast and prostate cancer patients (2012)

ClinicalTrials.gov NCT01095848.
Measurement of intestinal permeability using mannitol and lactulose in children with diarrheal diseases (1999)

The excretion ratio of lactulose/mannitol in urine has been used to assess the extension of malabsorption and impairment of intestinal permeability. The recovery of lactulose and mannitol in urine was employed to evaluate intestinal permeability in children with and without diarrhea. Lactulose and mannitol probes were measured using high-performance liquid chromatography with pulsed amperometric detection (HPLC-PAD). Two groups of solutions containing 60 microM sugars were prepared. Group I consisted of glucosamine, mannitol, melibiose and lactulose, and group II of inositol, sorbitol, glucose and lactose. In the study of intra-experiment variation, a sample of 50 microl from each group was submitted to 4 successive determinations. The recovered amounts and retention times of each sugar showed a variation <2 and 1%, respectively. The estimated recovery was >97%. In the study of inter-experiment variation, we prepared 4 independent samples from groups I and II at the following concentrations: 1.0, 0.3, 0.1, 0.03 and 0.01 mM. The amounts of the sugars recovered varied by <10%, whereas the retention times showed an average variation <1%. The linear correlation coefficients were >99%. Retention (k'), selectivity (alpha) and efficiency (N) were used to assess the chromatographic conditions. All three parameters were in the normal range. Children with diarrhea presented a greater lactulose/mannitol ratio compared to children without diarrhea.
Autologous lymphoma vaccines induce human T cell responses against multiple, unique epitopes (2004)

The clonotypic surface Ig receptor expressed by malignant B cells, idiotype, is a tumor-specific antigen and an attractive target for active immunotherapy. While Ab's specific for tumor idiotype have been well described in patients with B cell malignancies, the precise antigenic epitopes in human idiotype recognized by autologous T cells remain largely unknown. We report here that T cell lines generated from lymphoma patients actively immunized with idiotype protein specifically recognized multiple, unique immunodominant epitopes in autologous tumor idiotype. Synthetic peptides corresponding to hypervariable, but not framework, regions of Ig heavy chain specifically stimulated CD4 + and CD8 + T cells to proliferate and secrete proinflammatory cytokines in an MHC-associated manner. Detailed analysis revealed a minimal determinant of an immunodominant epitope, comprising critical residues at the amino terminus that may be a product of somatic hypermutation. Association of idiotype-specific T cell responses with previously documented molecular remissions in idiotype-vaccinated patients suggests that the newly identified T cell epitopes may be clinically relevant. Such antigenic epitopes may serve as candidates for novel peptide-vaccine strategies, and as tools to selectively expand tumor antigen-specific T cells for adoptive immunotherapy and for monitoring T cell immunity in vaccinated patients.
Pneumococcal Diversity: Considerations for New Vaccine Strategies with Emphasis on Pneumococcal Surface Protein A (PspA) (1998)

Streptococcus pneumoniae is a problematic infectious agent, whose seriousness to human health has been underscored by the recent rise in the frequency of isolation of multidrug-resistant strains. Pneumococcal pneumonia in the elderly is common and often fatal. Young children in the developing world are at significant risk for fatal pneumococcal respiratory disease, while in the developed world otitis media in children results in substantial economic costs. Immunocompromised patients are extremely susceptible to pneumococcal infection. With 90 different capsular types thus far described, the diversity of pneumococci contributes to the challenges of preventing and treating S. pneumoniae infections. The current capsular polysaccharide vaccine is not recommended for use in children younger than 2 years and is not fully effective in the elderly. Therefore, innovative vaccine strategies to protect against this agent are needed. Given the immunogenic nature of S. pneumoniae proteins, these molecules are being investigated as potential vaccine candidates. Pneumococcal surface protein A (PspA) has been evaluated for its ability to elicit protection against S. pneumoniae infection in mouse models of systemic and local disease. This review focuses on immune system responsiveness to PspA and the ability of PspA to elicit cross-protection against heterologous strains. These parameters will be critical to the design of broadly protective pneumococcal vaccines.
Systemic fungicides. The synthesis of certain pyrazole analogues of carboxin (1983)

Methods are described for the synthesis of 1,3-dimethyl-N-phenylpyrazole-4-carboxamid (3) and the isomeric 1,5-dimethyl compound (4), structural analogues of the systemic fungicide carboxin. Evidence confirming the structural assignment of the compounds is presented, and a convenient method for the removal of the amino group from some aminopyrazoles is described.
Poly(naphthodithiophene)s: Robust, Conductive Electrochromics via Tandem Cyclization-Polymerizations (2001)

A new and general synthetic strategy for thiophene-based condensed aromatics(see Figure) is described. A tandem cyclization scheme produces aromatized monomers in situ, prior to oxidative polymerization. The poly(naphthodithiophene)s are a family of highly stable and polarizable scaffolds whose polymer backbone energetics are easily altered without sacrificing their environmental stability.