gebhart/patrepeval huggingface dataset:
Changes in sperm plasma membrane lipid diffusibility after hyperactivation during in vitro capacitation in the mouse. (1986)

We have used the technique of fluorescence recovery after photobleaching to measure the diffusibility of the fluorescent lipid analogue, 1,1'-dihexadecyl 3,3,3',3'-tetramethylindocarbocyanine perchlorate on the morphologically distinct regions of the plasma membranes of mouse spermatozoa, and the changes in lipid diffusibility that result from in vitro hyperactivation and capacitation with bovine serum albumin. We found that, as previously observed on ram spermatozoa, lipid analogue diffusibility is regionalized on mouse spermatozoa, being fastest on the flagellum. The bovine serum albumin induced changes in diffusibility that occur with hyperactivation are also regionalized. Specifically, if we compare serum incubated in control medium, which maintains normal motility, with those hyperactivated in capacitating medium, we observe with hyperactivation an increase in lipid analogue diffusion rate in the anterior region of the head, the midpiece, and tail, and a decrease in diffusing fraction in the anterior region of the head.
Synthese von 2‐Oxo‐5H‐furanen unter Wittig‐Horner Bedingungen (1984)

Abstract Es wird die Synthese der 2‐Oxo‐ 5H ‐furane 3a‐e und 7a‐e aus den α‐Hydroxy‐oxo‐verbindungen 1a, b bzw. den α‐Halogen‐oxo‐verbindungen 5a‐e und den α‐Phosphonocarbonsäureestern 2a‐c , α‐Phosphonocarbonsäuren 4a, b bzw. den Kaliumsalzen der α‐Phosphonocarbonsäuren 6a, b unter Wittig‐Horner ‐Bedingungen beschrieben.
Killed but Metabolically Active Recombinant Listeria monocytogenes as an Antigen Delivery and Activation Platform for Human Dendritic Cell-Based Cancer Immunotherapy. (2004)

Abstract Dendritic cells (DCs) are bone marrow-derived professional antigen presenting cells which play a pivotal role in initiating immune responses. To achieve optimal potency for priming of naive T cells, DCs must not only present high levels of MHC peptide complexes, but must also undergo maturation. An ideal DC-targeting vaccine formulation, therefore, should simultaneously deliver multiple antigens and activate DCs to increase expression of surface MHC-peptide complexes, costimulatory molecules, and production of immuno-stimulatory cytokines. Despite the development of a variety of ex vivo methods, no standard efficient and cost effective methods combining antigen loading and activation/maturation of DCs for clinical use currently exist. Here we report the development of a novel DC antigen-loading platform based on killed, but metabolically active (KBMA) recombinant Listeria monocytogenes (Lm). While recombinant Lm has a relatively long history as a cancer vaccine platform, its utility as a DC activation and loading platform has not been fully explored. KBMA Lm were 8-logs more sensitive to photochemical inactivation by the combined treatment of S-59 psoralen (amotosalen HCl) and long-wave ultraviolet light (S-59/UVA), by virtue of abrogation of nucleotide excision repair (NER) capacity, through engineered deletion of the bacterial UvrAB genes. Due to random distribution of infrequent psoralen adducts, KBMA Lm cannot propagate, but are metabolically active and can express their genetic repertoire, and program presentation of expressed heterologous antigens via the MHC class I and class II pathways. Infection of human monocyte-derived or blood myeloid DCs with KBMA Listeria induced their maturation and production of pro-inflammatory and pro- Th1 cytokines. The DCs achieved a fully mature phenotype, comparable to that induced by the standard maturation stimulus MCM-mimic. To determine whether KBMA Lm could program presentation of encoded antigens by the MHC class I pathway, we constructed a recombinant Lm vaccine expressing CD8+ T cell epitopes of influenza matrix protein (MP58–66) and MelanA/Mart-1 protein (Mart126–35). DCs infected with the recombinant KBMA Lm vaccine presented the recombinant class I epitopes and induced IFN-γ production by MP58–66- or Mart126–35-specific human CD8+ T cell clones. These studies demonstrate that KBMA Listeria is a novel and powerful ex vivo DC antigen loading platform combining a potent DC-maturation stimulus with the cytosolic delivery of recombinant antigen for presentation.
Biosynthesis of the modified nucleoside Q in transfer RNA (1976)

During biosynthesis of the modified nucleoside Q, 7-(4,5-DIHYDROXYL-1-1-CYCLOPENTEN-3-YL-AMINOMETHYL)-7-DEAZAGUANOSINE, IN TRNA, the carbon atom at position 8 in precursor molecule guanine was expelled together with the nitrogen atom N-7 in a fashion similar to that in the biosynthesis of the nucleoside antibiotic toyocamycin.
Controlled Structure and Properties of Thermoresponsive Nanoparticle–Hydrogel Composites (2004)

Nanocomposite hydrogels consisting of colloidal gold nanoparticles and thermoresponsive N-isopropylacrylamide copolymers (see Figure) are synthesized. The size, morphology, and stability of the nanoparticles are controlled by the amount of thiol group in the polymer side chains. Compared with non-Au-containing hydrogels, remarkably different bulk properties of equilibrium swelling and thermoresponsive phase transition are displayed. Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2089/2004/c6516_s.pdf or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
The Lambda variant of SARS-CoV-2 has a better chance than the Delta variant to escape vaccines (2021)

The newly emerging variants of SARS-CoV-2 from India (Delta variant) and South America (Lambda variant) have led to a higher infection rate of either vaccinated or unvaccinated people. We found that sera from Pfizer-BioNTech vaccine remain high reactivity toward the receptor binding domain (RBD) of Delta variant while it drops dramatically toward that of Lambda variant. Interestingly, the overall titer of antibodies of Pfizer-BioNTech vaccinated individuals drops 3-fold after 6 months, which could be one of major reasons for breakthrough infections, emphasizing the importance of potential third boost shot. While a therapeutic antibody, Bamlanivimab, decreases binding affinity to Delta variant by ~20 fold, it fully lost binding to Lambda variant. Structural modeling of complexes of RBD with human receptor, Angiotensin Converting Enzyme 2 (ACE2), and Bamlanivimab suggest the potential basis of the change of binding. The data suggest possible danger and a potential surge of Lambda variant in near future.
Emergence of Tetracycline Resistance in Helicobacter pylori : Multiple Mutational Changes in 16S Ribosomal DNA and Other Genetic Loci (2002)

Tetracycline is useful in combination therapies against the gastric pathogen Helicobacter pylori. We found 6 tetracycline-resistant (Tet(r)) strains among 159 clinical isolates (from El Salvador, Lithuania, and India) and obtained the following four results: (i) 5 of 6 Tet(r) isolates contained one or two nucleotide substitutions in one part of the primary tetracycline binding site in 16S rRNA (AGA(965-967) [Escherichia coli coordinates] changed to gGA, AGc, guA, or gGc [lowercase letters are used to represent the base changes]), whereas the sixth (isolate Ind75) retained AGA(965-967); (ii) PCR products containing mutant 16S ribosomal DNA (rDNA) alleles transformed recipient strains to Tet(r) phenotypes, but transformants containing alleles with single substitutions (gGA and AGc) were less resistant than their Tet(r) parents; (iii) each of 10 Tet(r) mutants of reference strain 26695 (in which mutations were induced with metronidazole, a mutagenic anti-H. pylori agent) contained the normal AGA(965-967) sequence; and (iv) transformant derivatives of Ind75 and of one of the Tet(r) 26695 mutants that had acquired mutant rDNA alleles were resistant to tetracycline at levels higher than those to which either parent strain was resistant. Thus, tetracycline resistance in H. pylori results from an accumulation of changes that may affect tetracycline-ribosome affinity and/or other functions (perhaps porins or efflux pumps). We suggest that the rarity of tetracycline resistance among clinical isolates reflects this need for multiple mutations and perhaps also the deleterious effects of such mutations on fitness. Formally equivalent mutations with small but additive effects are postulated to contribute importantly to traits such as host specificity and virulence and to H. pylori's great genetic diversity.
Comparison of recombinant xylose-fermenting saccharomyces and natural xylose-fermenting yeasts in fermenting mixed sugars containing both glucose and xylose (1995)

Cellulosic biomass is an ideal renewable feedstock for the production of ethanol fuels. A Saccharomyces yeast has been genetically engineered to ferment xylose, a constituent of biomass. Results are described and compared with other natural xylose-fermenting yeasts.
Overexpression of DWARF4 in the brassinosteroid biosynthetic pathway results in increased vegetative growth and seed yield in Arabidopsis (2001)

Plants unable to synthesize or perceive brassinosteroids (BRs) are dwarfs. Arabidopsis dwf4 was shown to be defective in a steroid 22alpha hydroxylase (CYP90B1) step that is the putative rate-limiting step in the BR biosynthetic pathway. To better understand the role of DWF4 in BR biosynthesis, transgenic Arabidopsis plants ectopically overexpressing DWF4 (AOD4) were generated, using the cauliflower mosaic virus 35S promoter, and their phenotypes were characterized. The hypocotyl length of both light- and dark-grown AOD4 seedlings was increased dramatically as compared to wild type. At maturity, inflorescence height increased >35% in AOD4 lines and >14% in tobacco DWF4 overexpressing lines (TOD4), relative to controls. The total number of branches and siliques increased more than twofold in AOD4 plants, leading to a 59% increase in the number of seeds produced. Analysis of endogenous BR levels in dwf4, Ws-2 and AOD4 revealed that dwf4 accumulated the precursors of the 22alpha-hydroxylation steps, whereas overexpression of DWF4 resulted in increased levels of downstream compounds relative to Ws-2, indicative of facilitated metabolic flow through the step. Both the levels of DWF4 transcripts and BR phenotypic effects were progressively increased in dwf4, wild-type and AOD4 plants, respectively. This suggests that it will be possible to control plant growth by engineering DWF4 transcription in plants.
Occurrence of high-level aminoglycoside resistance in environmental isolates of enterococci (1995)

High-level resistance to aminoglycosides was observed in environmental isolates of enterococci. Various aquatic habitats, including agricultural runoff, creeks, rivers, wastewater, and wells, were analyzed. Strains of Enterococcus faecalis, E. faecium, E. gallinarum, and other Enterococcus spp. demonstrated multiple antibiotic resistance patterns to aminoglycosides.
Crowdsourcing research opportunities (2012)

Although the field has led to promising early results, the use of crowdsourcing as an integral part of science projects is still regarded with skepticism by some, largely due to a lack of awareness of the opportunities and implications of utilizing these new techniques. We address this lack of awareness, firstly by highlighting the positive impacts that crowdsourcing has had on Natural Language Processing research. Secondly, we discuss the challenges of more complex methodologies, quality control, and the necessity to deal with ethical issues. We conclude with future trends and opportunities of crowdsourcing for science, including its potential for disseminating results, making science more accessible, and enriching educational programs.
Curtobacterium plantarum sp. nov. Is Ubiquitous in Plant Leaves and Is Seed Transmitted in Soybean and Corn (1989)

A total of 22 strains of a yellow-pigmented bacterium which I designated YB, which were isolated from leaves of various plants, were compared with the type strains of Curtobacterium citreum, Curtobacterium albidum, Curtobacterium luteum, and Curtobacterium pusillum and six strains of Curtobacterium flaccumfaciens, a pathogen of soybeans and garden beans. These species comprise the genus Curtobacterium. YB was nonpathogenic when it was inoculated onto leaves of soybeans and garden beans and produced β-carotene, as did both C. citreum and C. luteum. These species and YB were all originally isolated from plants. YB could be distinguished from all previously described species of the genus Curtobacterium on the basis of more rapid production of acid from maltose and xylose, more rapid hydrolysis of gelatin, susceptibility to bacteriophage PYB-3 infection, inability to hydrolyze hippurate, growth in the presence of 10% sodium chloride, and higher deoxyribonucleic acid guanine-plus-cytosine content. Because the YB strains represent a new center of variation in the genus Curtobacterium, a new species, Curtobacterium plantarum, is proposed. This bacterium was isolated from leaves of three soybean cultivars at weekly intervals. Mean populations, expressed in colony-forming units (CFU) per gram of leaf tissue, increased gradually over the season from 28 CFU/g at 5 weeks after planting to 158 CFU/g at plant maturity. The bacterium was also isolated from leaves of 10 soybean cultivars and 10 corn inbred lines in each of 3 years, from leaves in one soybean field and one corn field in each of 25 Iowa counties, and from leaves of each of 100 soybean plants from one field and 100 corn plants from one field. Over a 2-year period, it was isolated from all 200 plant species sampled. The samples represented 62 plant families and included trees (both broad leaved, and conifers), shrubs, annuals, and perennials. The bacterium was isolated from field-grown immature and mature soybean seeds and from leaves of soybean and corn seedlings grown in a microbe-free environment from seeds treated to eliminate external microorganisms. I concluded that C. plantarum sp. nov. is seed transmitted in soybeans and corn and is ubiquitous in the leaves of plants.
In vivo efficacy of STI571 in xenografted human small cell lung cancer alone or combined with chemotherapy (2004)

STI571, or imatinib, selectively inhibits BCR/ABL, PDGFR and c-kit kinase activity. It has been reported that a large proportion of small cell lung cancer (SCLC) cell lines and tumors express c-kit and that STI571 inhibits tumor cell growth. We therefore investigated the therapeutic efficacy of STI571, alone or combined with chemotherapy, in human SCLC cells or tumors xenografted into nude mice. The level of c-kit mRNA expression was variable in SCLC tumors (positive for 2 of 4 xenografts), and c-kit protein was not detected by immunohistochemistry. On the 4 xenografted tumors, PDGFRalpha and PDGFRbeta were not detected by immunohistochemistry. STI571 induced inhibition of proliferation of the SCLC6 cell line without inducing apoptosis; in contrast, in combination with etoposide or topotecan, the growth inhibition of SCLC6 cells induced by STI571 was increased, with apoptotic DNA fragmentation. Four human SCLC xenografts (SCLC6, SCLC61, SCLC74 and SCLC108) were transplanted into mice. After intraperitoneal injection of STI571, we observed 80%, 40% and 78% growth inhibition of SCLC6, SCLC61 and SCLC108 tumors, respectively, without any significant inhibition of SCLC74 tumor growth. In mice bearing responsive SCLC tumors, we observed an increase of growth inhibition induced by chemotherapy (etoposide + ifosfamide or topotecan) by concomitant and continuous administration of STI571, associated with an increase of toxic deaths. In SCLC6-bearing mice receiving sequential treatments, we observed a reduction of toxic deaths but a decrease of synergistic antitumor efficacy. In conclusion, the efficacy of STI571 alone in SCLC xenografted tumors was variable and did not depend on c-kit expression. Moreover, a significant increase of chemotherapy-induced growth inhibition was obtained by concomitant administration of STI571 that should be carefully investigated in SCLC patients.
Introduction to Pharmacokinetics (2006)

One of the most interesting and challenging aspects of early phase clinical trials is studying the pharmacokinetics of a new drug, in order to determine how a body processes it. For those readers with limited knowledge of the subject, this article is intended to provide an overview of pharmacokinetics, and the pharmacokinetic terms that are commonly used in medical journals. The article will also introduce the concepts of bioavailability, therapeutic range, accumulation and steady state, and dose proportionality.
Charge injection and transport in single-layer organic light-emitting diodes (1998)

We present experimental and device model results for the current–voltage characteristics of a series of organic diodes. We consider three general types of structures: electron only, hole only, and bipolar devices. Electron and hole mobility parameters are extracted from the corresponding single carrier structures and then used to describe the bipolar devices. The device model successfully describes the experimental results for: electron only devices as thickness is varied, hole only devices as the contact metals are varied, and bipolar devices are both the thickness and the contact metals are varied.
TerpreT: A Probabilistic Programming Language for Program Induction (2016)

We study machine learning formulations of inductive program synthesis; given input-output examples, we try to synthesize source code that maps inputs to corresponding outputs. Our aims are to develop new machine learning approaches based on neural networks and graphical models, and to understand the capabilities of machine learning techniques relative to traditional alternatives, such as those based on constraint solving from the programming languages community. Our key contribution is the proposal of TerpreT, a domain-specific language for expressing program synthesis problems. TerpreT is similar to a probabilistic programming language: a model is composed of a specification of a program representation (declarations of random variables) and an interpreter describing how programs map inputs to outputs (a model connecting unknowns to observations). The inference task is to observe a set of input-output examples and infer the underlying program. TerpreT has two main benefits. First, it enables rapid exploration of a range of domains, program representations, and interpreter models. Second, it separates the model specification from the inference algorithm, allowing like-to-like comparisons between different approaches to inference. From a single TerpreT specification we automatically perform inference using four different back-ends. These are based on gradient descent, linear program (LP) relaxations for graphical models, discrete satisfiability solving, and the Sketch program synthesis system. We illustrate the value of TerpreT by developing several interpreter models and performing an empirical comparison between alternative inference algorithms. Our key empirical finding is that constraint solvers dominate the gradient descent and LP-based formulations. We conclude with suggestions for the machine learning community to make progress on program synthesis.
Nonmyeloablative Immunosuppressive Regimen Prolongs In Vivo Persistence of Gene-Modified Autologous T Cells in a Nonhuman Primate Model (2001)

The in vivo persistence of gene-modified cells can be limited by host immune responses to transgene-encoded proteins. In this study we evaluated in a nonhuman primate model whether the administration of a nonmyeloablative regimen consisting of low-dose total-body irradiation with 200 cGy followed by immunosuppression with mycophenolate mofetil and cyclosporin A for 28 and 35 days, respectively, could be used to facilitate persistence of autologous gene-modified T cells when a transgene-specific immune response had already been established or to induce long-lasting tolerance in unprimed recipients. Two macaques (Macaca nemestrina) received infusions of T cells transduced to express either the enhanced green fluorescent protein and neomycin phosphotransferase genes or the hygromycin phosphotransferase and herpes simplex virus thymidine kinase genes. In the absence of immunosuppression, both macaques developed potent class I major histocompatibility complex-restricted CD8(+) cytotoxic T-lymphocyte (CTL) responses that rapidly eliminated the gene-modified T cells and that persisted long term as memory CTL. Treatment with the nonmyeloablative regimen failed to abrogate preexisting memory CTL responses but interfered with the induction of transgene-specific CTL and facilitated in vivo persistence of gene-modified cells in an unprimed host. However, sustained tolerance to gene-modified T cells was not achieved with this regimen, indicating that further modifications will be required to permit sustained persistence of gene-modified T cells.
Evaluation of combinations of interferons and cytotoxic drugs in murine tumor models in vivo. (1990)

This investigation was conducted to provide preclinical in vivo tumor response data collected under standardized conditions with a range of clinically useful drugs combined with type I (alpha/beta) or type II (gamma) interferon. Murine tumor models used were P388 leukemia, Meth A sarcoma, and B16 melanoma. Eleven cytotoxic drugs were studied. Interferon combinations with cytosine arabinoside provided consistent indications of activity greater than that of the respective single agents. Doxorubicin and cisplatin each prolonged the time to treatment failure, relative to single-agent results, when they were combined with gamma-interferon in the Meth A and B16 models. Interferon combinations with methotrexate, 6-mercaptopurine, 6-thioguanine, ampligen, suramin, 5-fluorouracil, cyclophosphamide, and vinblastine yielded no evidence of any positive therapeutic interactions under the conditions of this study.
Development of Benzophenone‐Alkyne Bifunctional Sigma Receptor Ligands (2012)

Sigma (σ) receptors are unique non-opioid binding sites that are associated with a broad range of disease states. Sigma-2 receptors provide a promising target for diagnostic imaging and pharmacological interventions to curb tumor progression. Most recently, the progesterone receptor (PGRMC1, 25 kDa) has been shown to have σ2 receptor-like binding properties, thus highlighting the need to understand the biological function of an 18 kDa protein that exhibits σ2-like photoaffinity labeling (denoted here as σ2-18k) but the amino acid sequence of which is not known. In order to provide new tools for the study of the σ2-18k protein, we have developed bifunctional σ receptor ligands each bearing a benzophenone photo-crosslinking moiety and an alkyne group to which an azide-containing biotin affinity tag can be covalently attached through click chemistry after photo-crosslinking. Although several compounds showed favorable σ2 binding properties, the highest affinity (2 nM) and the greatest potency in blocking photolabeling of σ2-18k by a radioactive photoaffinity ligand was shown by compound 22. These benzophenone-alkyne σ receptor ligands might therefore be amenable for studying the σ2-18k protein through chemical biology approaches. To the best of our knowledge, these compounds represent the first reported benzophenone-containing clickable σ receptor ligands, which might potentially have broad applications based on the "plugging in" of various tags.
Identification of an antagonist that selectively blocks the activity of prostamides (prostaglandin‐ethanolamides) in the feline iris (2006)

The ability of AGN 204396 to selectively block prostamide responses suggests the existence of prostamide sensitive receptors as entities distinct from receptors recognizing PGF2alpha and PGE2-glyceryl ester.