gebhart/patrepeval huggingface dataset:
Multiple Ca2+-Binding Sites in the Extracellular Domain of the Ca2+-Sensing Receptor Corresponding to Cooperative Ca2+ Response (2008)

A small change in the extracellular Ca(2+) concentration ([Ca(2+)](o)) integrates cell signaling responses in multiple cellular and tissue networks and functions via activation of Ca(2+)-sensing receptors (CaSR). Mainly through binding of Ca(2+) to the large extracellular domain (ECD) of the dimeric CaSR, intracellular Ca(2+) responses are highly cooperative with an apparent Hill coefficient ranging from 2 to 4. We have previously reported the identification of two continuous putative Ca(2+)-binding sites by grafting CaSR-derived, Ca(2+)-binding peptides to a scaffold protein, CD2, that does not bind Ca(2+). In this paper, we predict more potential noncontinuous Ca(2+)-binding sites in the ECD. We dissect the intact CaSR into three globular subdomains, each of which contains two to three predicted Ca(2+)-binding sites. This approach enables us to further understand the mechanisms underlying the binding of multiple metal ions to extended polypeptides derived from a location within the ECD of the CaSR, which would be anticipated to more closely mimic the structure of the native CaSR ECD. Tb(3+) luminescence energy transfer, ANS fluorescence, and NMR studies show biphasic metal-binding components and Ca(2+)-dependent conformational changes in these subdomains. Removing the predicted Ca(2+)-binding ligands in site 1 and site 3 abolishes the first binding step and second binding step, respectively. Studies on these subdomains suggest the existence of multiple metal-binding sites and metal-induced conformational changes that might be responsible for the switching on and off the CaSR by the transition between its open inactive form and closed active form.
Exploring the Potential of Next-Generation Sequencing in Detection of Respiratory Viruses (2014)

Efficient detection of human respiratory viral pathogens is crucial in the management of patients with acute respiratory tract infection. Sequence-independent amplification of nucleic acids combined with next-generation sequencing technology and bioinformatics analyses is a promising strategy for identifying pathogens in clinical and public health settings. It allows the characterization of hundreds of different known pathogens simultaneously and of novel pathogens that elude conventional testing. However, major hurdles for its routine use exist, including cost, turnaround time, and especially sensitivity of the assay, as the detection limit is dependent on viral load, host genetic material, and sequencing depth. To obtain insights into these aspects, we analyzed nasopharyngeal aspirates from a cohort of 81 Thai children with respiratory disease for the presence of respiratory viruses using a sequence-independent next-generation sequencing approach and routinely used diagnostic real-time reverse transcriptase PCR (real-time RT-PCR) assays. With respect to the detection of rhinovirus and human metapneumovirus, the next-generation sequencing approach was at least as sensitive as diagnostic real-time RT-PCR in this small cohort, whereas for bocavirus and enterovirus, next-generation sequencing was less sensitive than real-time RT-PCR. The advantage of the sequencing approach over real-time RT-PCR was the immediate availability of virus-typing information. Considering the development of platforms capable of generating more output data at declining costs, next-generation sequencing remains of interest for future virus diagnosis in clinical and public health settings and certainly as an additional tool when screening results from real-time RT-PCR are negative.
Intestinal Commitment and Maturation of Human Pluripotent Stem Cells Is Independent of Exogenous FGF4 and R-spondin1 (2015)

Wnt/beta-catenin signaling plays a central role in guiding the differentiation of the posterior parts of the primitive gut tube into intestinal structures in vivo and some studies suggest that FGF4 is another crucial factor for intestinal development. The aim of this study was to define the effects of Wnt and FGF4 on intestinal commitment in vitro by establishing conditions for differentiation of human pluripotent stem cells (hPSC) into posterior endoderm (hindgut) and further to self-renewing intestinal-like organoids. The most prominent induction of the well-established intestinal marker gene CDX2 was achieved when hPSC-derived definitive endoderm cells were treated with Wnt agonist molecule CHIR99021 during differentiation to hindgut. FGF4 was found to be dispensable during intestinal commitment, but it had an early role in repressing development towards the hepatic lineage. When hindgut stage cells were further cultured in 3D, they formed self-renewing organoid structures containing all major intestinal cell types even without exogenous R-spondin1 (RSPO1), a crucial factor for the culture of epithelial organoids derived from adult intestine. This may be explained by the presence of a mesenchymal compartment in the hPSC-derived organoids. Addition of WNT3A increased the expression of the Paneth cell marker Lysozyme in hPSC-derived organoid cultures, whereas FGF4 inhibited both the formation and maturation of intestinal-like organoids. Similar hindgut and organoid cultures were established from human induced pluripotent stem cells, implying that this approach can be used to create patient-specific intestinal tissue models for disease modeling in vitro.
Current Saturation and Electrical Breakdown in Multiwalled Carbon Nanotubes (2001)

We investigate the limits of high energy transport in multiwalled carbon nanotubes (MWNTs). In contrast to metal wires, MWNTs do not fail in the continuous, accelerating manner typical of electromigration. Instead, they fail via a series of sharp, equally sized current steps. We assign these steps to the sequential destruction of individual nanotube shells, consistent with the MWNT's concentric-shell geometry. Furthermore, the initiation of this failure is very sensitive to air exposure. In air failure is initiated by oxidation at a particular power, whereas in vacuum MWNTs can withstand much higher power densities and reach their full current carrying capacities.
Long‐term effect ofbifidobacteriaand Neosugar on precursor lesions of colonic cancer in cf1 mice (1991)

This investigation was undertaken to study the role of Bifidobacteria and bifidogenic factor Neosugar in the process of 1,2-dimethylhydrazine-induced colonic carcinogenesis in CF1 mice. Intestinal colonization and selective proliferation of Bifidobacteria were achieved by oral administration of indigenous Bifidobacteria and the incorporation of 5% Neosugar in the diet of animals. The Bifidobacteria were isolated from the feces of CF1 mice and were identified to be Bifidobacterium pseudolongum biovar b. This incidence of aberrant crypts and foci were significantly lower 38 weeks after the last injection of the carcinogen in animals fed Bifidobacteria than in animals treated with the carcinogen alone. The aberrance also appeared to be confined to the more distal end of the colon in animals fed bifidogenic diet. Such changes in the precursor lesions of colonic carcinogenesis are presumably due to the increase in the number of Bifidobacteria and their acidifying action in the lower intestinal tract of the animals.
Mean shift: a robust approach toward feature space analysis (2002)

A general non-parametric technique is proposed for the analysis of a complex multimodal feature space and to delineate arbitrarily shaped clusters in it. The basic computational module of the technique is an old pattern recognition procedure: the mean shift. For discrete data, we prove the convergence of a recursive mean shift procedure to the nearest stationary point of the underlying density function and, thus, its utility in detecting the modes of the density. The relation of the mean shift procedure to the Nadaraya-Watson estimator from kernel regression and the robust M-estimators; of location is also established. Algorithms for two low-level vision tasks discontinuity-preserving smoothing and image segmentation - are described as applications. In these algorithms, the only user-set parameter is the resolution of the analysis, and either gray-level or color images are accepted as input. Extensive experimental results illustrate their excellent performance.
Associatively Segmenting Instances and Semantics in Point Clouds (2019)

A 3D point cloud describes the real scene precisely and intuitively.To date how to segment diversified elements in such an informative 3D scene is rarely discussed. In this paper, we first introduce a simple and flexible framework to segment instances and semantics in point clouds simultaneously. Then, we propose two approaches which make the two tasks take advantage of each other, leading to a win-win situation. Specifically, we make instance segmentation benefit from semantic segmentation through learning semantic-aware point-level instance embedding. Meanwhile, semantic features of the points belonging to the same instance are fused together to make more accurate per-point semantic predictions. Our method largely outperforms the state-of-the-art method in 3D instance segmentation along with a significant improvement in 3D semantic segmentation. Code has been made available at: https://github.com/WXinlong/ASIS.
MicroRNAs and small interfering RNAs can inhibit mRNA expression by similar mechanisms (2003)

MicroRNAs (miRNAs) are endogenously encoded small noncoding RNAs, derived by processing of short RNA hairpins, that can inhibit the translation of mRNAs bearing partially complementary target sequences. In contrast, small interfering RNAs (siRNAs), which are derived by processing of long double-stranded RNAs and are often of exogenous origin, degrade mRNAs bearing fully complementary sequences. Here, we demonstrate that an endogenously encoded human miRNA is able to cleave an mRNA bearing fully complementary target sites, whereas an exogenously supplied siRNA can inhibit the expression of an mRNA bearing partially complementary sequences without inducing detectable RNA cleavage. These data suggest that miRNAs and siRNAs can use similar mechanisms to repress mRNA expression and that the choice of mechanism may be largely or entirely determined by the degree of complementary of the RNA target.
Uveitis induction in the rabbit by muramyl dipeptides (1986)

Intraocular inflammation (uveitis) was produced in rabbits by intravenous or subcutaneous treatment with N-acetylmuramyl-L-alanyl-D-isoglutamine and several of its synthetic analogs at doses of greater than or equal to 0.2 mg/kg in saline. A dose-dependent increase in permeability of the ocular blood-aqueous barrier as measured by leakage of protein or fluoresceinated dextran from the serum into the eye was observed from 2 to 14 h after glycopeptide treatment. Peak response occurred at approximately 3 h postdose. The lowest dose found to produce maximal vascular leakage for the most active glycopeptide analogs was 1 mg/kg. The adjuvant-inactive L-L stereoisomer of N-acetylmuramyl-L-alanyl-D-isoglutamine was inactive, even at doses as high as 10 mg/kg. Analogs of N-acetylmuramyl-L-alanyl-D-isoglutamine which were homologous in the lactyl side chain were found to cause less uveitis. Chronic biweekly intravenous treatment of rabbits for 1 month with either N-acetyl-L-alpha-aminobutyryl-D-isoglutamine or its lipophilic 6-O-stearoyl derivative at 1 mg/kg, but not with murabutide, resulted in leukocytic inflammatory lesions unique to the uveal tract of the eye. The uveitis was potentially reversible and occurred with decreased severity as long as 2 months after cessation of chronic treatment. Vascular leakage but not cellular infiltrate in the choroid could be modulated by pharmacologic means. Pyrogenicity but not adjuvanticity correlated with ability of glycopeptides to induce vascular leakage. Several adjuvant-active muramyl dipeptide analogs with minimal ability to cause acute vascular leakage or chronic inflammation in the rabbit eye have been identified.
Transvaginal Hysterectomy: Rationale and Surgical Approach (2004)

Abdominal hysterectomy is performed in the United States at a 3:1 ratio over vaginal hysterectomy, despite evidence that vaginal hysterectomy offers advantages over abdominal hysterectomy with regard to operative time, complication rates, recovery, return to daily activities, and overall costs of treatment. In fact, the predominance of the abdominal approach may be based on factors other than clinical considerations, including resident training, use of limited or obsolete guidelines, greater third-party compensation for abdominal procedures, a presumption rather than a confirmation that pathology exists that contraindicates a vaginal approach, and misconceptions about the safety and cost of vaginal hysterectomy. A number of studies spanning several years demonstrate that the use of more systematic guidelines for selecting the route of hysterectomy results in a major shift toward the vaginal approach. Evidence also shows that transvaginal hysterectomy is both feasible and optimum for types of patients who have long been considered inappropriate candidates for the vaginal route. New instrumentation facilitates the vaginal approach and contributes to improved hemostasis and decreased operative time. Included here is a step-by-step approach to determining appropriate candidates for the vaginal approach via assessment of access, uterus size, and extent of pathology.
Inherited thrombocytopenias: toward a molecular understanding of disorders of platelet production (2004)

Although inherited syndromes of thrombocytopenia are rare, characterization of mutations in these disorders has contributed greatly to our understanding of megakaryocyte and platelet development. A systematic registry of congenitally thrombocytopenic individuals would almost certainly lead to new genetic discoveries.
No-carrier-added iodine-131-FIBG: evaluation of an MIBG analog. (1997)

Iodine-131-FIBG is an analog of MIBG with prolonged binding to neuroblastoma cells in vitro and retention in the myocardium in vivo.
Structure of HIV-1 TAR RNA in the absence of ligands reveals a novel conformation of the trinucleotide bulge (1996)

Efficient transcription from the human immunodeficiency virus (HIV) promoter depends on binding of the viral regulatory protein Tat to a cis-acting RNA regulatory element, TAR. Tat binds at a trinucleotide bulge located near the apex of the TAR stem-loop structure. An essential feature of Tat-TAR interaction is that the protein induces a conformational change in TAR that repositions the functional groups on the bases and the phosphate backbone that are critical for specific intermolecular recognition of TAR RNA. We have previously determined a high resolution structure for the bound form of TAR RNA using heteronuclear NMR. Here, we describe a high resolution structure of the free TAR RNA based on 871 experimentally determined restraints. In the free TAR RNA, bulged residues U23 and C24 are stacked within the helix, while U25 is looped out. This creates a major distortion of the phosphate backbone between C24 and G26. In contrast, in the bound TAR RNA, each of the three residues from the bulge are looped out of the helix and U23 is drawn into proximity with G26 through contacts with an arginine residue that is inserted between the two bases. Thus, TAR RNA undergoes a transition from a structure with an open and accessible major groove to a much more tightly packed structure that is folded around basic side chains emanating from the Tat protein.
Thermosensitive polymers for drug delivery (1996)

Thermosensitive polymers (TSP) demonstrating temperature-dependent temperature-dependent swelling in water have been extensively studied in recent years. Their molecular and physical properties have been tailored for a variety of biomedical and engineering uses. This presentation will discuss TSP based on poly(N-isopropylacrylamide) and its crosslinked networks modified with hydrophobic or hydrophilic components by copolymerization blending and formation of interpenetrating polymer networks (IPNs). TSP designed for three different areas of drug delivery will be presented. First, heparin releasing temperature-sensitive polymers for the prevention of surface induced thrombosis will be presented as an example of a local macromolecular delivery from a surface of a medical device. Second, a new oral delivery device based on a novel mechanical squeezing concept, utilizing specific swelling-deswelling characteristics of temperature- and temperature/pH-sensitive hydrogels will be described. These hydrogels were synthesized to exhibit a controlled swelling-deswelling kinetics, hence a variety of release profiles may be generated: a delayed, a zero-order or an {open_quotes}on-off{close_quotes} release profile. Finally, thermally reversible polymeric gels as an extracellular matrix for the entrapment of pancreatic islet cells in biohybrid artificial pancreas for insulin delivery will be discussed.
Wide-field coherent anti-Stokes Raman scattering microscopy (2004)

We suggest a variant of coherent anti-Stokes Raman scattering (CARS) microscopy, which is a nonlinear microscopy method that has recently proven very successful in functional imaging of living cells with vibrational contrast. Whereas existing CARS microscopy techniques involve confocal scanning, in our setup excitation and detection are performed in a wide-field (nonconfocal) geometry, similar to a combination of dark-field and epifluorescence microscopy. The use of a nanosecond laser system rather than the typically used pico- or femtosecond systems furthermore implies a high spectroscopic resolution for various Raman-active substances. We demonstrate the feasibility of the wide-field approach on test samples and discuss its prospects to become a complemental method to confocal scanning CARS microscopy.
Bamboo-like Composites of V2O5/Polyindole and Activated Carbon Cloth as Electrodes for All-Solid-State Flexible Asymmetric Supercapacitors (2016)

A bamboo-like nanomaterial composed of V2O5/polyindole (V2O5/PIn) decorated onto the activated carbon cloth was fabricated for supercapacitors. The PIn could effectively enhance the electronic conductivity and prevent the dissolution of vanadium. And the activation of carbon cloth with functional groups is conducive to anchoring the V2O5 and improving surface area, which results in an enhancement of electrochemical performance and leads to a high specific capacitance of 535.5 F/g. Moreover, an asymmetric flexible supercapacitor based on V2O5/PIn@activate carbon cloth and reduced graphene oxide (rGO)@activate carbon cloth exhibits a high energy density (38.7 W h/kg) at a power density of 900 W/kg and good cyclic stability (capacitance retention of 91.1% after 5000 cycles). And the prepared device is shown to power the light-emitting diode bulbs efficiently.
SIRT1 and caloric restriction: an insight into possible trade-offs between robustness and frailty (2009)

Increasing SIRT1 dosage/activity is effective to provide significant protection from high-fat diet-induced metabolic complications, suggesting that SIRT1 activation likely promotes robustness in the regulation of metabolism. However, caloric restriction itself and caloric restriction mimicry through systemic SIRT1 activation might also generate frailty in response to unexpected environmental stimuli, such as bacterial and viral infections. It will be of great importance to understand the principles of systemic robustness and its spatial and temporal dynamics for the regulation of aging and longevity in mammals in order to achieve an optimal balance between robustness and frailty in our complex physiological system.
The Design and Use of Synchronous Collaborative Software Engineering Tools (2005)

We have developed a framework, CAISE, to support Collaborative Software Engineering (CSE). In this paper, we focus on the development of CSE tools within the CAISE framework. We present examples to illustrate how such tools are constructed and how they support real-time multi-user collaborative software development. We also address issues related to the number of collaborators and discuss performance aspects.
High‐cell‐density fed‐batch cultivation of the docosahexaenoic acid producing marine alga Crypthecodinium cohnii (2003)

The heterotrophic marine alga Crypthecodinium cohnii is known to produce docosahexaenoic acid (DHA), a polyunsaturated fatty acid with food and pharmaceutical applications, during batch cultivation on complex media containing sea salt, yeast extract, and glucose. In the present study, fed-batch cultivation was studied as an alternative fermentation strategy for DHA production. Glucose and acetic acid were compared as carbon sources. For both substrates, the feed rate was adapted to the maximum specific consumption rate of C. cohnii. In glucose-grown cultures, this was done by maintaining a significant glucose concentration (between 5 and 20 g/L) throughout fermentation. In acetic acid-grown cultures, the medium feed was automatically controlled via the culture pH. A feed consisting of acetic acid (50% w/w) resulted in a higher overall volumetric productivity of DHA (r(DHA)) than a feed consisting of 50% (w/v) glucose (38 and 14 mg/L/h, respectively). The r(DHA) was further increased to 48 mg/L/h using a feed consisting of pure acetic acid. The latter fermentation strategy resulted in final concentrations of 109 g/L dry biomass, 61 g/L lipid, and 19 g/L DHA. These are the highest biomass, lipid, and DHA concentrations reported to date for a heterotrophic alga. Vigorous mixing was required to sustain aerobic conditions during high-cell-density cultivation. This was complicated by culture viscosity, which resulted from the production of viscous extracellular polysaccharides. These may present a problem for large-scale industrial production of DHA. Addition of a commercial polysaccharide-hydrolase preparation could decrease the viscosity of the culture and the required stirring.
Phosphine Quenching of Cyanine Dyes as a Versatile Tool for Fluorescence Microscopy (2013)

We report that the cyanine dye Cy5 and several of its structural relatives are reversibly quenched by the phosphine tris(2-carboxyethyl)phosphine (TCEP). Using Cy5 as a model, we show that the quenching reaction occurs by 1,4-addition of the phosphine to the polymethine bridge of Cy5 to form a covalent adduct. Illumination with UV light dissociates the adduct and returns the dye to the fluorescent state. We demonstrate that TCEP quenching can be used for super-resolution imaging as well as for other applications, such as differentiating between molecules inside and outside the cell.
Microtubule changes and cytotoxicity in leukemic cell lines treated with taxol. (1988)

Taxol, a diterpenoid plant product that enhances the polymerization of tubulin, is currently entering clinical trials in the treatment of human leukemia. In order to develop an in vitro assay to predict tumor sensitivity to taxol, human leukemic cell lines were exposed to clinically achievable concentrations of taxol for relevant exposure periods. Changes in microtubules visualized by indirect immunofluorescence were compared to drug sensitivity measured by a clonogenic assay. Taxol produced either multiple mitotic asters in G2/M or microtubule bundling throughout the cell cycle. In cells that were relatively resistant to taxol, microtubule bundling was reversible while microtubule bundling in relatively sensitive cells persisted in the presence or absence of taxol. In contrast, aster formation was unrelated to cytotoxicity in any cell line. In the future, these microtubule effects may be useful in predicting the chemotherapeutic efficacy of taxol.