gebhart/patrepeval huggingface dataset:
The 13C-Xylose Breath Test for the Diagnosis of Small Bowel Bacterial Overgrowth in Children (1997)

Our preliminary results suggest that with a dose of 50 mg 13C-xylose, breath test results reliably predict small-bowel bacterial overgrowth in susceptible children.
Divergent synthetic nucleotide motif recognition pattern: design and development of potent immunomodulatory oligodeoxyribonucleotide agents with distinct cytokine induction profiles (2003)

Unmethylated CpG dinucleotides present within certain specific sequence contexts in bacterial and synthetic DNA stimulate innate immune responses and induce cytokine secretion. Recently, we showed that CpG DNAs containing two 5'-ends, immunomers, are more potent in both regards. In this study, we show that an immunomer containing a synthetic CpR motif (R = 2'-deoxy-7-deazaguanosine) is a potent immunostimulatory agent. However, the profile of cytokine induction is different from that with immunomers containing a natural CpG motif. In general, a CpR immunomer induced higher interleukin (IL)-12 and lower IL-6 secretion. Compared with conventional CpG DNAs, both types of immunomers showed a rapid and enhanced activation of the transcription factor NF-kappaB in J774 cells. NF-kappaB activation by CpG DNA corresponded to degradation of IkappaBalpha in J774 cells. All three immunostimulatory oligonucleotides activated the p38 mitogen-activated protein kinase pathway as expected. Immunomers containing CpG and CpR motifs showed potent reversal of the antigen-induced Th2 immune response towards a Th1 type in antigen-sensitized mouse spleen cell cultures. Immunomers containing a CpR motif showed significant antitumor activity in nude mice bearing MCF-7 human breast cancer and U87MG glioblastoma xenografts. These studies suggest the ability for a divergent synthetic nucleotide motif recognition pattern of the receptor involved in the immunostimulatory pathway and the possibility of using synthetic nucleotides to elicit different cytokine response patterns.
Monolithic Tetracycline‐containing Fibers for Controlled Delivery to Periodontal Pockets (1983)

For the purpose of developing controlled delivery devices for periodontal therapy which would release over several days, six fiber types made of tetracycline-loaded biocompatible polymers were manufactured and tested. Polyethylene, polypropylene, polycaprolactone, polyurethane and cellulose acetate propionate all released their drug load within 1 day. Ethylene vinyl acetate fibers, however, provided in vitro sustained release for periods up to 9 days. A bioassay was designed to measure levels of tetracycline achieved by local delivery which used growth inhibition of Bacillus cereus as a measure of the amount of tetracycline in measured volumes of gingival sulcus fluid on filter paper strips. By this assay, fibers made from 25% loaded ethylene vinyl acetate established initial concentrations of approximately 500 micrograms/ml. The measurement of tetracycline concentration resulting from the placement of these fibers into deep periodontal pockets as a packing material provided indication that concentrations of greater than 50 micrograms/ml could be maintained for months by weekly to monthly replacement. These studies indicate that monolithic fibers made of tetracycline-loaded ethylene vinyl acetate have characteristics which could prove useful as the basis of a tetracycline delivery system for the treatment of periodontal disease.
Single-carbon discrimination by selected peptides for individual detection of volatile organic compounds (2015)

Although volatile organic compounds (VOCs) are becoming increasingly recognized as harmful agents and potential biomarkers, selective detection of the organic targets remains a tremendous challenge. Among the materials being investigated for target recognition, peptides are attractive candidates because of their chemical robustness, divergence, and their homology to natural olfactory receptors. Using a combinatorial peptide library and either a graphitic surface or phenyl-terminated self-assembled monolayer as relevant target surfaces, we successfully selected three interesting peptides that differentiate a single carbon deviation among benzene and its analogues. The heterogeneity of the designed target surfaces provided peptides with varying affinity toward targeted molecules and generated a set of selective peptides that complemented each other. Microcantilever sensors conjugated with each peptide quantitated benzene, toluene and xylene to sub-ppm levels in real time. The selection of specific receptors for a group of volatile molecules will provide a strong foundation for general approach to individually monitoring VOCs.
Computer display of curved surfaces (1971)

Abstract : The report describes a method for producing shaded pictures of curved surfaces. It uses a small polygon approximation of the surface to solve efficiently the hidden parts detection, and then computes the shading on each polygon in such a way that visual discontinuities between adjacent polygons disappear, thus restoring the apparent smoothness of the surface and increasing greatly the realism of the pictures produced. The smooth shading technique described here has been used to produce a large variety of pictures of which several airplanes, a car, a human face and some mathematical surfaces are included to illustrate the effect of the method. (Author)
Steryl glycosides: a characteristic feature of the Helicobacter spp.? (1995)

The lipids of different species of Helicobacter (H.felis, H. muridarum, H. mustelae, H. fennelliae, and H. cinaedi) were studied. Different types of cholesteryl glucosides were found in all of the species studied except H. cinaedi. The total amount of cholesteryl glucosides varied from 14.8% of total lipids in H. mustelae to 33.1% of total lipids in H. felis. The different types of cholesteryl glucosides and their species distribution are cholesteryl-6-O-acyl-alpha-D-glucopyranoside (cholesteryl-6-O-tetradecanoyl-alpha-D-glucopyranoside in H. felis and cholesteryl-6-O-dodecanoyl-alpha-D-glucopyranoside in H. muridarum), cholesteryl-alpha-D-glucopyranoside (H. felis, H. muridarum, H. mustelae, and H. fennelliae), and cholesteryl-6-O-phosphatidyl-alpha-D-glucopyranoside (H. fennelliae). The neutral lipid fractions showed a high percentage of cholesterol, with selective accumulation of free cholesterol. The study thus shows that the characteristic presence of steryl glycosides in Helicobacter spp. may be an important chemotaxonomic marker for many of the species, and the helicobacters show a selective accumulation of free cholesterol from the media.
Expression of growth factor receptors in unilineage differentiation culture of purified hematopoietic progenitors (1996)

We have evaluated the expression of growth factor receptors (GFRs) on early hematopoietic progenitor cells (HPCs) purified from human adult peripheral blood and induced in liquid suspension culture to unilineage differentiation/maturation through the erythroid (E), granulocytic (G), megakaryocytic (Mk), or monocytic (Mo) lineage. The receptors for basic fibroblast GF (bFGF), erythropoietin (Epo), thrombopoietin (Tpo), and macrophage colony-stimulating factor (MCSF) have been only assayed at mRNA level; the majority of GFRs have been evaluated by both mRNA and protein analyses: the expression patterns were consistent at both levels. In quiescent HPCs the receptors for early-acting [flt3 ligand (FL), c-kit ligand (KL), bFGF, interleukin-6 (IL-6)] and multilineage [IL-3, granulocyte-macrophage CSF (GM-CSF)] HGFs are expressed at significant levels but with different patterns, eg, kit and flt3 are detected on a majority and minority of HPCs, respectively, whereas IL-3Rs and GM-CSFRs are present on almost all HPCs. In the four differentiation pathways, expression of early-acting receptors shows a progressive decrease, more rapidly for bFGFR-1 and flt3 than for c-kit; furthermore, c-kit is more slowly downmodulated in the E and Mk than the G and Mo lineages. As a partial exception, IL-6Rs are still detected through the early or late stages of maturation in the Mk and Mo lineages, respectively. IL-3R expression is progressively and rapidly downmodulated in both E and Mk pathways, whereas it moderately decreases in the Mo lineage and is sustained in the G series. The expression of GM-CSFR is gradually downmodulated in all differentiation pathways, ie, the receptor density markedly decreases but late erythroblasts are still partially GM-CSFR+ and terminal G, Mk and Mo cells are essentially GM-CSFR+. Expression of receptors for late-acting cytokines is lineage-specific. Thus, EpoR, G-CSFR, TpoR, and M-CSFR exhibit a gradual induction followed by a sustained expression in the E, G, MK, and Mo lineages, respectively. In the other differentiation pathways the expression of these receptors is either absent or initially low and there-after suppressed. These observations are compatible with the following multi-step model. (1) The early-acting GFRs are expressed on quiescent HPCs with different patterns, whereas the multilineage GFRs are present on > or = 90% to 95% HPCs. (2) Multilineage GFs, potentiated by early-acting HGFs, trigger HPCs into cycling. HPC proliferation/differentiation is followed by declining expression of the early-acting GFRs and in part of multilineage GFRs (see above). (3) Multilineage GFs trigger the expression of the unilineage GFRs (see Testa U, et al: Blood 81:1442, 1993). Interaction of each unilineage GF with its receptor leads to sustained expression of the receptor (possibly via transcription factors activating the receptor promoter) and thus mediates differentiation/maturation through the pertinent lineage.
Bioassay Analysis usingR (2005)

We describe an add-on package for the language and environment R which allows simultaneous fitting of several non-linear regression models. The focus is on analysis of dose response curves, but the functionality is applicable to arbitrary non-linear regression models. Features of the package is illustrated in examples.
Effect of molten carbonate composition on the generation of carbon material (2017)

Ambient CO<sub>2</sub> is readily split into zerovalent carbon at diverse electrolytes.
Investigations of Pd-Catalyzed ArX Coupling Reactions Informed by Reaction Progress Kinetic Analysis (2006)

This Perspective highlights how the methodology of reaction progress kinetic analysis can provide a rapid and comprehensive kinetic profile of complex catalytic reaction networks under synthetically relevant conditions in a fraction of the number of experiments required by classical kinetic analysis. This approach relies on graphical manipulation of the extensive data sets available from accurate in situ monitoring of reaction progress under conditions where two concentration variables are changing simultaneously. A series of examples from Pd-catalyzed coupling reactions of aryl halides demonstrates how a wealth of kinetic information may be extracted from just three experiments in each case. Even before proposing a reaction mechanism, we can determine reaction orders in substrates, propose a resting state for the catalyst, and probe catalyst stability. Carrying out this kinetic analysis at the outset of a mechanistic investigation provides a framework for further work aimed at seeking a molecular-level understanding of the nature of the species within the catalytic cycle. To be considered plausible, any independent mechanistic proposal must be shown to be consistent with this global kinetic analysis.
Measurement of the Sintering Pressure in Ceramic Films (1988)

An experimental technique is described to estimate the intrinsic sintering pressure in ceramic films. It involves measuring the time‐dependent axial strain of the film during isothermal sintering under a varying tensile load. The applied stress when the axial strain rate goes to zero gives the measurement of the sintering pressure. Such experiments with titania tapes fabricated by tape casting showed the intrinsic sintering pressure to lie in the range of 200 to 130 kPa for densities in the range of 85% to 95% of the theoretical density. The sintering pressure decreased with increasing density. These results are in agreement with measurements of sintering pressure in alumina and titania obtained from sinter‐forging experiments.
Predicting consumer behavior with Web search (2010)

Recent work has demonstrated that Web search volume can "predict the present," meaning that it can be used to accurately track outcomes such as unemployment levels, auto and home sales, and disease prevalence in near real time. Here we show that what consumers are searching for online can also predict their collective future behavior days or even weeks in advance. Specifically we use search query volume to forecast the opening weekend box-office revenue for feature films, first-month sales of video games, and the rank of songs on the Billboard Hot 100 chart, finding in all cases that search counts are highly predictive of future outcomes. We also find that search counts generally boost the performance of baseline models fit on other publicly available data, where the boost varies from modest to dramatic, depending on the application in question. Finally, we reexamine previous work on tracking flu trends and show that, perhaps surprisingly, the utility of search data relative to a simple autoregressive model is modest. We conclude that in the absence of other data sources, or where small improvements in predictive performance are material, search queries provide a useful guide to the near future.
Stochastic computing with biomolecular automata (2004)

Stochastic computing has a broad range of applications, yet electronic computers realize its basic step, stochastic choice between alternative computation paths, in a cumbersome way. Biomolecular computers use a different computational paradigm and hence afford novel designs. We constructed a stochastic molecular automaton in which stochastic choice is realized by means of competition between alternative biochemical pathways, and choice probabilities are programmed by the relative molar concentrations of the software molecules coding for the alternatives. Programmable and autonomous stochastic molecular automata have been shown to perform direct analysis of disease-related molecular indicators in vitro and may have the potential to provide in situ medical diagnosis and cure.
Transaldolase deficiency influences the pentose phosphate pathway, mitochondrial homoeostasis and apoptosis signal processing (2008)

TAL (transaldolase) was originally described in the yeast as an enzyme of the PPP (pentose phosphate pathway). However, certain organisms and mammalian tissues lack TAL, and the overall reason for its existence is unclear. Recently, deletion of Ser(171) (TALDeltaS171) was found in five patients causing inactivation, proteasome-mediated degradation and complete deficiency of TAL. In the present study, microarray and follow-up Western-blot, enzyme-activity and metabolic studies of TALDeltaS171 TD (TAL-deficient) lymphoblasts revealed co-ordinated changes in the expression of genes involved in the PPP, mitochondrial biogenesis, oxidative stress, and Ca(2+) fluxing. Sedoheptulose 7-phosphate was accumulated, whereas G6P (glucose 6-phosphate) was depleted, indicating a failure to recycle G6P for the oxidative branch of the PPP. Nucleotide analysis showed depletion of NADPH and NAD(+) and accumulation of ADP-ribose. TD cells have diminished Deltapsi(m) (mitochondrial transmembrane potential) and increased mitochondrial mass associated with increased production of nitric oxide and ATP. TAL deficiency resulted in enhanced spontaneous and H(2)O(2)-induced apoptosis. TD lymphoblasts showed increased expression of CD38, which hydrolyses NAD(+) into ADP-ribose, a trigger of Ca(2+) release from the endoplasmic reticulum that, in turn, facilitated CD20-induced apoptosis. By contrast, TD cells were resistant to CD95/Fas-induced apoptosis, owing to a dependence of caspase activity on redox-sensitive cysteine residues. Normalization of TAL activity by adeno-associated-virus-mediated gene transfer reversed the elevated CD38 expression, ATP and Ca(2+) levels, suppressed H(2)O(2)- and CD20-induced apoptosis and enhanced Fas-induced cell death. The present study identified the TAL deficiency as a modulator of mitochondrial homoeostasis, Ca(2+) fluxing and apoptosis.
Development of TRX518, an aglycosyl humanized monoclonal antibody (Mab) agonist of huGITR. (2010)

e13028 Background: Glucocorticoid-induced tumor necrosis factor receptor (GITR) is expressed on several cell types, including regulatory and effector T cells, B cells, NK cells, and antigen-presenting cells. In murine models, our agonistic anti-mouse (m) GITR antibody was a robust vaccine adjuvant and, in combination with chemotherapy, significantly reduced tumor burden and prolonged survival compared with antibody or chemotherapy alone. The anti-mGITR Mab enhanced effector T cell responses and ablation of T regulatory cell-mediated suppression. A similar effect was observed when a chimeric anti-human (hu) GITR Mab (Ch-6C8-Agly) was used in nonhuman primates (NHP). NHP treated with anti-huGITR had augmented humoral and cellular immune responses compared with controls. Mab treatment was well tolerated with no observed adverse events. Methods: TRX518, a fully humanized IgG1 anti-huGITR Mab, was constructed. In addition to humanization, heavy chain asparagine 297 was substituted with alanine to eliminate N-linked glycosylation. This mutation abrogates Fc region functionality, including antibody-dependent cellular cytotoxicity and complement-mediated lysis. Further in vitro and in vivo characterization of TRX518 was conducted. Results: TRX518 bound to GITR on CD4+ and CD8+ naïve and memory T cells, B cells, NK cells, NKT cells, monocytes, and macrophages, yet was nondepleting. Though TRX518 costimulated suboptimally activated peripheral blood lymphocytes it was not a superagonist, as it did not induce proliferation by itself. Plate-bound TRX518 did not induce appreciable cytokine release (IL-2, IL-6, IL-10, TNFa, IFNg). TRX518 blocked the interaction of GITR with its ligand and enhanced the cytotoxicity of NK cells. However, it did not block an allogeneic mixed lymphocyte reaction (MLR) or enhance an autologous MLR. Cynomolgous macaque and human tissue cross studies and an IND-enabling GMP toxicology study are complete. Conclusions: TRX518 is a promising candidate for evaluation in human cancer indications. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Tolerx Tolerx
Engineering HIV-Resistant Human CD4+ T Cells with CXCR4-Specific Zinc-Finger Nucleases (2011)

HIV-1 entry requires the cell surface expression of CD4 and either the CCR5 or CXCR4 coreceptors on host cells. Individuals homozygous for the ccr5Δ32 polymorphism do not express CCR5 and are protected from infection by CCR5-tropic (R5) virus strains. As an approach to inactivating CCR5, we introduced CCR5-specific zinc-finger nucleases into human CD4+ T cells prior to adoptive transfer, but the need to protect cells from virus strains that use CXCR4 (X4) in place of or in addition to CCR5 (R5X4) remains. Here we describe engineering a pair of zinc finger nucleases that, when introduced into human T cells, efficiently disrupt cxcr4 by cleavage and error-prone non-homologous DNA end-joining. The resulting cells proliferated normally and were resistant to infection by X4-tropic HIV-1 strains. CXCR4 could also be inactivated in ccr5Δ32 CD4+ T cells, and we show that such cells were resistant to all strains of HIV-1 tested. Loss of CXCR4 also provided protection from X4 HIV-1 in a humanized mouse model, though this protection was lost over time due to the emergence of R5-tropic viral mutants. These data suggest that CXCR4-specific ZFNs may prove useful in establishing resistance to CXCR4-tropic HIV for autologous transplant in HIV-infected individuals.
Role of Atomic Scale Roughness in Hot Electron Chemistry (1999)

As already reported, the hydrogen evolution from neutral pH aqueous electrolytes by hot electrons in Al/Al2O3/Ag junctions at the silver/electrolyte interface is observed only when the silver electrode is weakly “activated” (roughened). After a short description of all relevant phenomena we present a simple model which is based on the increase of the average penetration depth of the hot electrons into the electrochemical double layer by scattering at the surface roughness of the silver(111) face. This leads to a more anodic onset of the hydrogen evolution from the dissociation of water, but only at an activated surface. The model also explains why activation does not reduce the overpotential of the normal hydrogen evolution.
Quantitative Imaging in Cancer Clinical Trials (2016)

As anticancer therapies designed to target specific molecular pathways have been developed, it has become critical to develop methods to assess the response induced by such agents. Although traditional, anatomic CT, and MRI examinations are useful in many settings, increasing evidence suggests that these methods cannot answer the fundamental biologic and physiologic questions essential for assessment and, eventually, prediction of treatment response in the clinical trial setting, especially in the critical period soon after treatment is initiated. To optimally apply advances in quantitative imaging methods to trials of targeted cancer therapy, new infrastructure improvements are needed that incorporate these emerging techniques into the settings where they are most likely to have impact. In this review, we first elucidate the needs for therapeutic response assessment in the era of molecularly targeted therapy and describe how quantitative imaging can most effectively provide scientifically and clinically relevant data. We then describe the tools and methods required to apply quantitative imaging and provide concrete examples of work making these advances practically available for routine application in clinical trials. We conclude by proposing strategies to surmount barriers to wider incorporation of these quantitative imaging methods into clinical trials and, eventually, clinical practice. Our goal is to encourage and guide the oncology community to deploy standardized quantitative imaging techniques in clinical trials to further personalize care for cancer patients and to provide a more efficient path for the development of improved targeted therapies.
Temperature-Sensitive Mutants in the Influenza A Virus RNA Polymerase: Alterations in the PA Linker Reduce Nuclear Targeting of the PB1-PA Dimer and Result in Viral Attenuation (2015)

By targeting a discrete domain of the PA polymerase subunit of influenza virus, we were able to identify a series of 9 amino acid positions that are appropriate to engineer temperature-sensitive (ts) mutants. This is the first time that a large number of ts mutations were engineered in such a short domain, demonstrating that rational design of ts mutants can be achieved. We were able to associate this phenotype with a defect of transport of the PA-PB1 complex into the nucleus. Reversion substitutions restored the ability of the complex to move to the nucleus. Two of these ts mutants were shown to be attenuated and able to produce antibodies in mice. These results are of high interest for the design of novel attenuated vaccines and to develop new antiviral drugs.