gebhart/patrepeval huggingface dataset:
Real-time tracking of highly articulated structures in the presence of noisy measurements (2002)

This paper presents a novel approach for model-based real-time tracking of highly articulated structures such as humans. This approach is based on an algorithm which efficiently propagates statistics of probability distributions through a kinematic chain to obtain maximum a posteriori estimates of the motion of the entire structure. This algorithm yields the least squares solution in linear time (in the number of components of the model) and can also be applied to non-Gaussian statistics using a simple but powerful trick. The resulting implementation runs in real-time on standard hardware without any pre-processing of the video data and can thus operate on live video. Results from experiments performed using this system are presented and discussed.
Do we have enough biomarkers? (2004)

ADVERTISEMENT RETURN TO ISSUEEDITORIALNEXTDo we have enough biomarkers?William S. HancockCite this: J. Proteome Res. 2004, 3, 4, 685Publication Date (Web):August 9, 2004Publication History Published online9 August 2004Published inissue 1 August 2004https://pubs.acs.org/doi/10.1021/pr040025nhttps://doi.org/10.1021/pr040025nnewsACS Publications. This publication is available under these Terms of Use. Request reuse permissions This publication is free to access through this site. Learn MoreArticle Views277Altmetric-Citations3LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail PDF (38 KB) Get e-Alertsclose SUBJECTS:Biomarkers Get e-Alerts
Phase 1 Clinical Testing of HQK-1001, a Novel Oral Fetal Globin Gene Inducer (2008)

Abstract Development of non-cytotoxic, orally-active therapeutics, which induce fetal globin production, would be beneficial for treatment of beta-thalassemias and hemoglobinopathies. The short-chain fatty acids (SCFA) butyrate and phenylbutyrate are active fetal globin inducers, but their clinical application has been limited by inhibition of erythropoiesis and unfavorable PK profiles. HQK-1001 is a SCFA which stimulates fetal globin gene expression in reporter gene assays, erythroid progenitors, transgenic mice, and anemic baboons. HQK-1001 also stimulates human erythroid progenitor (BFU-E) proliferation by a mean of 30% above controls, and increased red blood cell counts in phlebotomized baboons. HQK-1001 has demonstrated a wide safety margin in pre-clinical toxicology testing, with no significant adverse effects in sub-chronic (6-month) studies and negative mutagenicity testing. Based on these pre-clinical data, a placebo-controlled, randomized, blinded, single-dose escalating Phase 1 trial was conducted to evaluate HQK-1001 at 4 dose levels ranging from 2 to 20 mg/kg in 32 normal volunteers. The drug was welltolerated, with no significant adverse events. Pharmacokinetic analyses showed low intersubject variability, a linear increase in Cmax and AUC with increasing dose, and T½ of 11 hours, indicating suitability for once-daily dosing. Administration under fed conditions demonstrated equivalent AUC to fasting conditions. In a subsequent 14-day Phase 1 dosing study in 41 normal subjects, the drug was also well-tolerated, with no significant adverse effects at the studied dose levels (5, 10 and 15 mg/kg). F-reticulocytes increased in subjects treated with 5 to 10 mg/kg doses. Absolute reticulocytes increased significantly above baseline (p &amp;lt;0.02 – 0.002) following 14-day dosing at all dose levels, while no significant change occurred in placebo controls. These first-in-human clinical studies demonstrating safety of HQK-1001 in 73 normal volunteer subjects and an improved pharmacologic profile over prior SCFAs indicate that HQK-1001 merits further clinical investigation in anemic patients with beta-globin gene disorders.
Ruffling-Induced Chirality:  Synthesis, Metalation, and Optical Resolution of Highly Nonplanar, Cyclic, Benzimidazole-Based Ligands (2003)

Expedient five-step syntheses of a cyclic bis(benzimidazole)-based amide 5 and two sterically more hindered analogues 23-24 have been developed. These amides are chiral due to the inherent ruffling of the macrocyclic plane. Racemization of the optical antipodes of these compounds has been studied using dynamic chiral stationary phase HPLC. These studies reveal that, while the parent amide 5 racemizes rapidly, for the sterically more hindered amides 23-24, the rate of racemization is significantly reduced. Bis(benzimidazole)-based amides 5 and 23-24 form stable Ni(II) complexes 25-27, respectively. Like their parent ligands, complexes 25-27 are chiral due to their highly ruffled geometry. Studies of these complexes by chiral stationary phase HPLC reveal that metalation leads to a much lower rate of racemization. Incorporation of a strap can slow racemization even further. A series of strapped cyclic amides 54-57, along with their corresponding dimers 58-61, have been prepared. The rate of racemization for amides 54-57 is strongly dependent on the length of the strap. X-ray single-crystal structure analysis of the Ni(II) complex of strapped amide 54 reveals that the bis(benzimidazole) core retains its highly ruffled shape, with the two phenyl rings of the macrocycle located anti to the strap. Chiral separation of strapped ligands 54-57 and their corresponding Ni(II) complexes is shown to be facile by chiral stationary phase HPLC.
Ontology-based approach for information fusion (2003)

Ontologies have received increasing interest in the computer science community and their benefits have been recognized in many areas. In this paper, we discuss the role of ontologies to facilitate information fusion fiom heterogeneous data and knowledge sources in support of high-level information fusion processes. We review several approaches where ontologies help provide semantic integration of information. We present preliminary work about ontological engineering for level 2 and 3 information fusion that should help semantic integration. Ontology development methods and tools should support the ontological engineering process. To this end, we propose a methodological approach and a flexible environment for ontology management that enables the building of extensible ontologies, and the mappingfiom ontologies to information sources.
Envelope Glycoprotein gB of Kaposi's Sarcoma-Associated Herpesvirus Is Essential for Egress from Infected Cells (2005)

Kaposi's sarcoma-associated herpesvirus (KSHV) envelope glycoprotein gB interacts with cell surface heparan sulfate (HS) and alpha3beta1 integrin and plays roles in the initial binding and entry into the target cells and in the induction of preexisting host cell signal pathways. To define gB function further, using a bacterial artificial chromosome (BAC) system carrying the KSHV genome (BAC36wt-KSHV), we constructed a recombinant virus genome with the gB open reading frame (ORF) deleted by replacing a 2-kb gB ORF with a 1.3-kb Kan(r) gene. Stable 293T cells carrying BAC36wt-KSHV and DeltagBBAC36-KSHV genomes were generated. Transcript analyses and immunoprecipitation reactions confirmed the absence of gB in the 293T-DeltagBBAC36 cells. When monolayers of 293T-BAC36wt and 293T-DeltagBBAC36 cells were induced with tetradecanoylphorbol-13-acetate, infectious virus was detected only from the 293T-BAC36wt cell supernatants. No significant amount of DNase I-resistant viral DNA was detected in the supernatants of 293T-DeltagBBAC36 cells. BAC36wt-KSHV infected the target cells, and in contrast, no viral DNA and transcripts could be detected in cells infected with DeltagBBAC36-KSHV. Electron microscopy of 293T-DeltagBBAC36 cells revealed capsids in the nuclei, cytoplasmic vesicles with core-containing capsids, and occasional enveloped virions in the cytoplasm. However, enveloped virus particles were observed in the extracellular compartments of 293T-BAC36wt cells only and not in 293T-DeltagBBAC36 cells. Transfection of 293T-DeltagBBAC36 cells with plasmid expressing full-length gB restored the recovery of infectious KSHV in the supernatant. These results suggest that, besides its role in virus binding and entry into the target cells, KSHV gB also plays a role in the maturation and egress of virus from the infected cells.
Monoclonal antibody recognizing a species-specific protein from Streptococcus pneumoniae (1990)

Monoclonal antibodies (MAbs) against a nonencapsulated strain (R36A) of Streptococcus pneumoniae were produced to aid in a search for antigens common to this species. By Western immunoblot analysis, a species-specific 37-kilodalton (kDa) protein was found in lysates of 24 different encapsulated strains of S. pneumoniae. Monoclonal antibodies against the 37-kDa antigen did not react with 55 heterologous strains representing 19 genera and 36 species of bacteria that can also cause acute lower respiratory tract disease. Immunogold staining suggests that the antigen is synthesized inside the pneumococcal cell. However, MAbs to the 37-kDa antigen bound whole cells in the enzyme-linked immunosorbent assay and the indirect immunofluorescence assay. Antibody-binding epitopes of the antigen are probably exposed on the outer surface of the pneumococcus cell wall. The effectiveness of the 37-kDa antigen as a useful diagnostic marker is under study.
Identification of the NKG2D Haplotypes Associated with Natural Cytotoxic Activity of Peripheral Blood Lymphocytes and Cancer Immunosurveillance (2006)

We have previously shown that natural cytotoxic activity of peripheral blood lymphocytes was inversely related to cancer development based on a prospective cohort study. The genetic fraction of cytotoxic activity needs to be clarified, identifying individuals immunogenetically susceptible to cancer. A case-control study within the cohort members was designed: 102 cancer cases with peripheral lymphocyte DNA available and three control groups, each of which consisted of 204 subjects with each tertile level of cytotoxic activity. We first compared two control groups with high and low cytotoxic activity in terms of the single nucleotide polymorphisms in the natural killer complex gene region on chromosome 12p, identifying the haplotype alleles that were associated with the activity. Next, cancer risks were assessed for these haplotypes. We found two haplotype blocks, each of which generated two major haplotype alleles: low-activity-related LNK1 (frequency 0.478 and 0.615 in groups with high and low activity, respectively; P < 0.00008) and high-activity-related HNK1 (0.480 and 0.348; P < 0.0001), LNK2 (0.711 and 0.821; P < 0.0002), and HNK2 (0.272 and 0.174; P < 0.0008). These NKG2D haplotype alleles showed a significant difference between cases (0.632 for LNK1 and 0.333 for HNK1) and controls (0.554 for LNK1 and 0.406 for HNK1). The haplotype HNK1/HNK1 revealed a decreased risk of cancer (odds ratio, 0.471; 95% confidence interval, 0.233-0.952) compared with LNK1/LNK1. Individuals who are genetically predisposed to have low or high natural cytotoxic activity can in part be determined by NKG2D haplotyping, which in turn reveals an increased or decreased risk of cancer development.
Chinook winds and migraine headache (2000)

Both prechinook and high-wind chinook days increase the probability of migraine onset in a subset of migraineurs. Because few subjects were found to be sensitive to both weather types, the mechanisms for these weather effects may be independent. This is supported by the presence of an age interaction for high-wind chinook days but not for prechinooks day.
Vectors based on reducible polycations facilitate intracellular release of nucleic acids (2003)

These results demonstrate that lipid-mediated activation of RPC-based polyplexes is a useful strategy to enhance intracellular delivery of nucleic acids and potentiate therapeutic activity.
Evaluation of a Sphere-Templated Polymeric Scaffold as a Subcutaneous Implant (2013)

Sphere-templated poly(HEMA) implanted as a subcutaneous tissue scaffold stimulates a minimal inflammatory response and supports cellular infiltration, collagen formation, and neovascularization. Because of its tightly controlled porous structure, poly-(HEMA) appears to induce less scar-type ingrowth compared with HDPPE.
Memory efficient folding algorithms for circular RNA secondary structures (2006)

The circular folding algorithm is implemented in the current version of the of RNAfold program of the Vienna RNA Package, which can be downloaded from http://www.tbi.univie.ac.at/RNA/
Methionine Redox Controlled Crystallization of Biosynthetic Silk Spidroin (1999)

The formation of intractable β-sheet crystallites is a major cause of insolubility in proteins that can form β-sheets. To study this phenomenon, recombinant DNA techniques were used to prepare a protein modeling the consensus sequence of Nephila clavipes spider dragline silk, incorporating redox “triggering” residues. X-ray diffraction, electron diffraction, transmission electron microscopy (TEM), and Fourier transform infrared spectroscopy (FTIR) were used to characterize the ability of the recombinant protein to form β-sheet crystals dependent on the redox trigger oxidation state. Changes in the crystallinity were observed when triggered (oxidized/soluble) and untriggered (reduced/insoluble) protein samples were compared. The β-sheet content was undetectable in the triggered state, while clear evidence of β-sheet crystallinity was observed in the untriggered state. TEM and electron diffraction data of thin films of the untriggered protein indicated that spontaneous local orientation of needlelike crystalline aggregates occurs over small regions, suggestive of morphologies analogous to native dragline silk. There was also evidence of a liquid crystalline or oriented amorphous phase in the untriggered protein, but the d-spacings observed for the liquid crystal did not match any structure reported for the natural spider silk. To elucidate the behavior of the amorphous phase, we synthesized a water-soluble 27-residue peptide model of the dragline silk consensus amorphous sequence. The interchain packing distance observed for crystals of this peptide matched the d-spacing observed for the amorphous phase in the untriggered recombinant dragline silk protein. The results suggest that methionine-modified silks assemble into a silk-like structure in the reduced state (untriggered), structure which is lost upon oxidation or activation of the triggers.
On some applications of finite-state automata theory to natural language processing (1996)

We describe new applications of the theory of automata to natural language processing: the representation of very large scale dictionaries and the indexation of natural language texts. They are based on new algorithms that we introduce and describe in detail. In particular, we give pseudocodes for the determinisation of string to string transducers, the deterministic union of p -subsequential string to string transducers, and the indexation by automata. We report on several experiments illustrating the applications.
Expression and clinical significance of genes frequently mutated in small cell lung cancers defined by whole exome/RNA sequencing (2015)

Small cell lung cancer (SCLC) is the most aggressive type of lung cancer. Only 15% of SCLC patients survive beyond 2 years after diagnosis. Therefore, for the improvement of patients' outcome in this disease, it is necessary to identify genetic alterations applicable as therapeutic targets in SCLC cells. The purpose of this study is the identification of genes frequently mutated and expressed in SCLCs that will be targetable for therapy of SCLC patients. Exome sequencing was performed in 28 primary tumors and 16 metastatic tumors from 38 patients with SCLCs. Expression of mutant alleles was verified in 19 cases by RNA sequencing. TP53, RB1 and PTEN were identified as being significantly mutated genes. Additional 36 genes were identified as being frequently (≥10%) mutated in SCLCs by combining the results of this study and two recent studies. Mutated alleles were expressed in 8 of the 36 genes, TMEM132D, SPTA1, VPS13B, CSMD2, ANK2, ASTN1, ASPM and FBN3. In particular, the TMEM132D, SPTA1 and VPS13B genes were commonly mutated in both early and late stage tumors, primary tumors and metastases, and tumors before and after chemotherapy, as in the case of the TP53 and RB1 genes. Therefore, in addition to TP53, RB1 and PTEN, TMEM132D, SPTA1 and VPS13B could be also involved in SCLC development, with the products from their mutated alleles being potential therapeutic targets in SCLC patients.
The intracellular pharmacology of antiretroviral protease inhibitors (2004)

Therapeutic drug monitoring (TDM) of antiretroviral protease inhibitors (PIs) has been suggested to have the potential to both reduce toxicity and optimize individual therapy. However, the major target of PIs is within cells infected with HIV. Therefore clinical outcome ultimately must be related to intracellular drug concentrations since antiviral activity of PIs is highly correlated with intracellular concentrations in vitro. Intracellular pharmacokinetics provides information regarding drug disposition in a compartment where HIV replication occurs and combined with plasma data may be useful in understanding therapeutic failure in relation to cellular resistance. In order to improve therapeutic efficacy, it is therefore important that the intracellular pharmacokinetics of drugs, such as PIs, is studied in addition to plasma pharmacokinetics. Multidrug resistance transporters may result in a lower cellular concentration of drug via an efflux mechanism, thus contributing to sanctuary site formation. However, conclusive proof that transporters contribute to clinical drug resistance is still lacking, although recent studies have attempted to address this issue. In relation to host and cellular factors, this review considers several issues involved in influencing intracellular drug concentrations and discusses the intracellular levels of PIs recently published from cellular studies.
Binding Strength Between Cell Adhesion Proteoglycans Measured by Atomic Force Microscopy (1995)

Measurement of binding forces intrinsic to adhesion molecules is necessary to assess their contribution to the maintenance of the anatomical integrity of multicellular organisms. Atomic force microscopy was used to measure the binding strength between cell adhesion proteoglycans from a marine sponge. Under physiological conditions, the adhesive force between two cell adhesion molecules was found to be up to 400 piconewtons. Thus a single pair of molecules could hold the weight of 1600 cells. High intermolecular binding forces are likely to form the basis for the integrity of the multicellular sponge organism.
Reduction Potentials of One-Electron Couples Involving Free Radicals in Aqueous Solution (1989)

Reduction of an electron acceptor (oxidant), A, or oxidation of an electron donor (reductant), A2−, is often achieved stepwise via one-electron processes involving the couples A/A⋅− or A⋅−/A2− (or corresponding prototropic conjugates such as A/AH⋅ or AH⋅/AH2). The intermediate A⋅−(AH⋅) is a free radical. The reduction potentials of such one-electron couples are of value in predicting the direction or feasibility, and in some instances the rate constants, of many free-radical reactions. Electrochemical methods have limited applicability in measuring these properties of frequently unstable species, but fast, kinetic spectrophotometry (especially pulse radiolysis) has widespread application in this area. Tables of ca. 1200 values of reduction potentials of ca. 700 one-electron couples in aqueous solution are presented. The majority of organic oxidants listed are quinones, nitroaryl and bipyridinium compounds. Reductants include phenols, aromatic amines, indoles and pyrimidines, thiols and phenothiazines. Inorganic couples largely involve compounds of oxygen, sulfur, nitrogen and the halogens. Proteins, enzymes and metals and their complexes are excluded.
In Vivo Expansion of Activated Naive CD8+ T Cells and NK Cells Driven by Complexes of IL-2 and Anti-IL-2 Monoclonal Antibody As Novel Approach of Cancer Immunotherapy (2009)

IL-2 is potent imunostimulatory molecule that plays a key role in T and NK cell activation and expansion. IL-2 is approved by the FDA to treat metastatic renal cancer and melanoma, but its extremely short half-life and serious toxicities are significant limitations of its use. It was reported that in vivo biological activity of IL-2 can be increased by association of IL-2 with anti-IL-2 mAb (S4B6). IL-2/S4B6 mAb immunocomplexes were described to be highly stimulatory for NK and memory CD8(+) T cells and intermediately also for regulatory T cells. IL-2/JES6-1 mAb immunocomplexes are stimulatory solely for regulatory T cells. In this study we show that although both mentioned IL-2 immunocomplexes are less potent than free IL-2 in vitro, they possess extremely high stimulatory activity to expand activated naive CD8(+) T cells in vivo. IL-2 immunocomplexes expand activated naive CD8(+) T cells several hundred-fold times after four doses and more than 1000-fold times after six doses (1.5 microg/dose of IL-2), whereas free IL-2 given at the same dosage shows negligible activity. IL-2/S4B6 mAb immunocomplexes also induce massive expansion of NK cells (40% of DX5(+)NK1.1(+) cells in spleen). Importantly, activated naive CD8(+) T cells expanded by IL-2 immunocomplexes form robust population of functional memory cells. We also demonstrate in two distinct tumor models that IL-2/S4B6 mAb immunocomplexes possess considerable antitumor activity. Finally, by using radioactively labeled IL-2, we provide for first time direct evidence that IL-2 immunocomplexes have much longer half-life in circulation than free IL-2, being approximately 3 h vs <15 min, respectively.
Farnesyl Diphosphate Synthase. Altering the Catalytic Site To Select for Geranyl Diphosphate Activity (2000)

Farnesyl diphosphate synthase (FPPase) catalyzes chain elongation of the C(5) substrate dimethylallyl diphosphate (DMAPP) to the C(15) product farnesyl diphosphate (FPP) by addition of two molecules of isopentenyl diphosphate (IPP). The synthesis of FPP proceeds in two steps, where the C(10) product of the first addition, geranyl diphosphate (GPP), is the substrate for the second addition. The product selectivity of avian FPPase was altered to favor synthesis of GPP by site-directed mutagenesis of residues that form the binding pocket for the hydrocarbon residue of the allylic substrate. Amino acid substitutions that reduced the size of the binding pocket were identified by molecular modeling. FPPase mutants containing seven promising modifications were constructed. Initial screens using DMAPP and GPP as substrates indicated that two of the substitutions, A116W and N144'W, strongly discriminated against binding of GPP to the allylic site. These observations were confirmed by an analysis of the products from reactions with DMAPP in the presence of excess IPP and by comparing the steady-state kinetic constants for the wild-type enzyme and the A116W and N114W mutants.