gebhart/patrepeval huggingface dataset:
A Multivalent Marine Lectin from <i>Crenomytilus grayanus</i> Possesses Anti-cancer Activity through Recognizing Globotriose Gb3 (2016)

In this study, we report the structure and function of a lectin from the sea mollusk Crenomytilus grayanus collected from the sublittoral zone of Peter the Great Bay of the Sea of Japan. The crystal structure of C. grayanus lectin (CGL) was solved to a resolution of 1.08 Å, revealing a β-trefoil fold that dimerizes into a dumbbell-shaped quaternary structure. Analysis of the crystal CGL structures bound to galactose, galactosamine, and globotriose Gb3 indicated that each CGL can bind three ligands through a carbohydrate-binding motif involving an extensive histidine- and water-mediated hydrogen bond network. CGL binding to Gb3 is further enhanced by additional side-chain-mediated hydrogen bonds in each of the three ligand-binding sites. NMR titrations revealed that the three binding sites have distinct microscopic affinities toward galactose and galactosamine. Cell viability assays showed that CGL recognizes Gb3 on the surface of breast cancer cells, leading to cell death. Our findings suggest the use of this lectin in cancer diagnosis and treatment.
Stability of Large Segmental Duplications in the Yeast Genome (2006)

The high level of gene redundancy that characterizes eukaryotic genomes results in part from segmental duplications. Spontaneous duplications of large chromosomal segments have been experimentally demonstrated in yeast. However, the dynamics of inheritance of such structures and their eventual fixation in populations remain largely unsolved. We analyzed the stability of a vast panel of large segmental duplications in Saccharomyces cerevisiae (from 41 kb for the smallest to 268 kb for the largest). We monitored the stability of three different types of interchromosomal duplications as well as that of three intrachromosomal direct tandem duplications. In the absence of any selective advantage associated with the presence of the duplication, we show that a duplicated segment internally translocated within a natural chromosome is stably inherited both mitotically and meiotically. By contrast, large duplications carried by a supernumerary chromosome are highly unstable. Duplications translocated into subtelomeric regions are lost at variable rates depending on the location of the insertion sites. Direct tandem duplications are lost by unequal crossing over, both mitotically and meiotically, at a frequency proportional to their sizes. These results show that most of the duplicated structures present an intrinsic level of instability. However, translocation within another chromosome significantly stabilizes a duplicated segment, increasing its chance to get fixed in a population even in the absence of any immediate selective advantage conferred by the duplicated genes.
Fast Three Dimensional Pharmacophore Virtual Screening of New Potent Non-Steroid Aromatase Inhibitors (2008)

Suppression of estrogen biosynthesis by aromatase inhibition is an effective approach for the treatment of hormone sensitive breast cancer. Third generation non-steroid aromatase inhibitors have shown important benefits in recent clinical trials with postmenopausal women. In this study we have developed a new ligand-based strategy combining important pharmacophoric and structural features according to the postulated aromatase binding mode, useful for the virtual screening of new potent non-steroid inhibitors. A small subset of promising drug candidates was identified from the large NCI database, and their antiaromatase activity was assessed on an in vitro biochemical assay with aromatase extracted from human term placenta. New potent aromatase inhibitors were discovered to be active in the low nanomolar range, and a common binding mode was proposed. These results confirm the potential of our methodology for a fast in silico high-throughput screening of potent non-steroid aromatase inhibitors.
The Effect of Structural Modifications on Charge Migration in Mesomorphic Phthalocyanines (1994)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTThe Effect of Structural Modifications on Charge Migration in Mesomorphic PhthalocyaninesPieter G. Schouten, John M. Warman, Matthijs P. de Haas, Cornelus F. van Nostrum, Gerwin H. Gelinck, Roeland J. M. Nolte, Marc J. Copyn, Jan W. Zwikker, Michael K. Engel, and Cite this: J. Am. Chem. Soc. 1994, 116, 15, 6880–6894Publication Date (Print):July 1, 1994Publication History Published online1 May 2002Published inissue 1 July 1994https://doi.org/10.1021/ja00094a048RIGHTS & PERMISSIONSArticle Views572Altmetric-Citations147LEARN 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 InReddit PDF (2 MB) Get e-Alertsclose Get e-Alerts
Carpooling Service for Large-Scale Taxicab Networks (2016)

Carpooling has long held the promise of reducing gas consumption by decreasing mileage to deliver coriders. Although ad hoc carpools already exist in the real world through private arrangements, little research on the topic has been done. In this article, we present the first systematic work to design, implement, and evaluate a carpool service, called coRide , in a large-scale taxicab network intended to reduce total mileage for less gas consumption. Our coRide system consists of three components, a dispatching cloud server, passenger clients, and an onboard customized device, called TaxiBox . In the coRide design, in response to the delivery requests of passengers, dispatching cloud servers calculate cost-efficient carpool routes for taxicab drivers and thus lower fares for the individual passengers. To improve coRide ’s efficiency in mileage reduction, we formulate an NP-hard route calculation problem under different practical constraints. We then provide (1) an optimal algorithm using Linear Programming, (2) a 2-approximation algorithm with a polynomial complexity, and (3) its corresponding online version with a linear complexity. To encourage coRide ’s adoption, we present a win-win fare model as the incentive mechanism for passengers and drivers to participate. We test the performance of coRide by a comprehensive evaluation with a real-world trial implementation and a data-driven simulation with 14,000 taxi data from the Chinese city Shenzhen. The results show that compared with the ground truth, our service can reduce 33% of total mileage; with our win-win fare model, we can lower passenger fares by 49% and simultaneously increase driver profit by 76%.
Survival of hypoxic human mesenchymal stem cells is enhanced by a positive feedback loop involving miR-210 and hypoxia-inducible factor 1 (2013)

The use of mesenchymal stem cells (MSCs) has emerged as a potential new treatment for myocardial infarction. However, the poor viability of MSCs after transplantation critically limits the efficacy of this new strategy. The expression of microRNA-210 (miR-210) is induced by hypoxia and is important for cell survival under hypoxic conditions. Hypoxia increases the levels of hypoxia inducible factor-1 (HIF-1) protein and miR-210 in human MSCs (hMSCs). miR-210 positively regulates HIF-1α activity. Furthermore, miR-210 expression is also induced by hypoxia through the regulation of HIF-1α. To investigate the effect of miR-210 on hMSC survival under hypoxic conditions, survival rates along with signaling related to cell survival were evaluated in hMSCs over-expressing miR-210 or ones that lacked HIF-1α expression. Elevated miR-210 expression increased survival rates along with Akt and ERK activity in hMSCs with hypoxia. These data demonstrated that a positive feedback loop involving miR-210 and HIF-1α was important for MSC survival under hypoxic conditions.
Structure and Site-directed Mutagenesis of a Flavoprotein fromEscherichia coli That Reduces Nitrocompounds (2001)

The crystal structure of a major oxygen-insensitive nitroreductase (NfsA) from Escherichia coli has been solved by the molecular replacement method at 1.7-A resolution. This enzyme is a homodimeric flavoprotein with one FMN cofactor per monomer and catalyzes reduction of nitrocompounds using NADPH. The structure exhibits an alpha + beta-fold, and is comprised of a central domain and an excursion domain. The overall structure of NfsA is similar to the NADPH-dependent flavin reductase of Vibrio harveyi, despite definite difference in the spatial arrangement of residues around the putative substrate-binding site. On the basis of the crystal structure of NfsA and its alignment with the V. harveyi flavin reductase and the NADPH-dependent nitro/flavin reductase of Bacillus subtilis, residues Arg(203) and Arg(208) of the loop region between helices I and J in the vicinity of the catalytic center FMN is predicted as a determinant for NADPH binding. The R203A mutant results in a 33-fold increase in the K(m) value for NADPH indicating that the side chain of Arg(203) plays a key role in binding NADPH possibly to interact with the 2'-phosphate group.
Androgenic up-regulation of androgen receptor cDNA expression in androgen-independent prostate cancer cells (1996)

The expression of the androgen receptor (AR) gene is regulated by androgens. Although androgens down-regulate AR mRNA in most cell lines and tissues, including the prostate, up-regulation occurs in some tissues. Androgen-mediated reduction in AR mRNA is reproduced in COSI cells and in the androgen-sensitive human prostate cancer cell line LNCaP when each expresses the AR cDNA. We have previously established that the AR cDNA contains the requisite sequences for this down-regulation. Here we shown that androgen promoted up-regulation of AR mRNA in two androgen-independent human prostate cancer cell lines, PC3 and DU145, when each was transfected with a human AR cDNA. This effect was due to the AR cDNA and not to the heterologous promoter driving AR expression. In addition to up-regulation of AR mRNA, androgen induced comparable increases in AR protein levels in PC3 cells stably expressing an AR cDNA (PC3/AR). Up-regulation of AR in PC3/AR cells was accompanied by failure of these cells to undergo desensitization or inactivation of AR following prolonged (96 h) androgen administration, whereas the same conditions resulted in desensitization of AR transactivation in LNCaP cells and in CVI cells that stably express the AR cDNA. Androgen treatment of PC3/AR cells resulted in induction of an androgen-regulated reporter gene (MMTV-CAT) as well as the native prostate-specific antigen gene, which is silent in untransfected PC3 but is androgen up-regulated in LNCaP and in the prostate. These results suggest that ectopic expression of AR in androgen-independent prostate cancer cell lines establishes both typical and atypical androgenic responses in a target gene-specific manner. Androgenic up-regulation of AR cDNA expression may be due to distinct signaling mechanisms that influence androgen action in androgen-independent prostate cancer cells.
Mutations of basic amino acids of NCp7 of human immunodeficiency virus type 1 affect RNA binding in vitro (1996)

The nucleocapsid (NC) protein of human immunodeficiency virus type 1 is required for packaging of viral RNA and for virion assembly. It contains two clusters of basic amino acids, consisting of five and four amino acid residues, flanking the first of its two zinc fingers. These amino acid residues have been mutagenized to neutral ones individually, as well as in various combinations, by site-directed mutagenesis. Wild-type NCp7 and the mutant proteins were expressed as recombinant proteins in Escherichia coli, with six histidines as tags at their amino termini in order to allow efficient purification. The purified proteins were analyzed for RNA binding in vitro with human immunodeficiency virus type 1 5' leader RNA transcribed in vitro. Assays comprised Northwestern blots at various salt concentrations and filter binding tests which allowed determination of the dissociation constants of the various mutants. The results indicated that mutations of the amino acid R-7 and of R-32 and K-33 were more critical for RNA binding than other mutations. Mutation of the other amino acid residues reduced the binding affinity in proportion to the number of mutations. Mutation of seven of the nine basic amino acid residues reduced the binding of RNA by 50- to 90-fold.
Variable analysis for freeway work zone capacity prediction (2010)

In order to keep the freeway network in a good state, regular road works such as maintenance and extension are necessary. These road works create physical changes on freeway and result capacity reduction. If the capacity can be predicted, a systematic planning of traffic management can be executed for maintaining certain capacity. However the current work zone capacity prediction models are not sufficiently accurate. The conventional capacity prediction models take limited number of work zone variables into account. Only a few studies mentioned the quantitative impacts of some variables on the capacity while no study is dedicated on. This research evaluates and quantifies the impact of various variables on the capacity. First a comprehensive summary of variables is given. Then all variables are evaluated and selected. A modified neuro-fuzzy model is used to analyze the relation between the capacity and the considered variables for a Dutch case study. The following twelve variables show great influence: percentage of heavy vehicles, lane width, lateral distance, number of lanes, distance to ramp, month factor, sight deprivation, temporary speed limit, work zone length, work zone transition length, work zone layout, work phase. The output of this research can support for a comparably accurate freeway work zone capacity prediction. Furthermore, traffic management measures can be developed based on the findings for each individual variable, e.g. dynamic speed limit measure can be implemented by considering an optimal combination of temporary speed limit and work zone transition length.
Knockdown of wild-type mouse rhodopsin using an AAV vectored ribozyme as part of an RNA replacement approach. (2005)

AAV2-Rz397 led to significant (greater than or equal to 50%) reduction of rhodopsin mRNA and protein in mice. It affected ERG amplitudes only when injected in hemizygous RHO knockout pups. This RNA inhibitor may prove useful in treating animal models of ADRP as part of an RNA replacement approach.
A new mouse model of ADHD for medication development (2016)

ADHD is a major societal problem with increasing incidence and a stagnant track record for treatment advances. A lack of appropriate animal models has partly contributed to the incremental advance of this field. Hence, our goal was to generate a novel mouse model that could be useful for ADHD medication development. We reasoned that hyperactivity is a core feature of ADHD that could easily be bred into a population, but to what extent other hallmark features of ADHD would appear as correlated responses was unknown. Hence, starting from a heterogeneous population, we applied within-family selection over 16 generations to produce a High-Active line, while simultaneously maintaining an unselected line to serve as the Control. We discovered that the High-Active line demonstrated motor impulsivity in two different versions of the Go/No-go test, which was ameliorated with a low dose of amphetamine, and further displayed hypoactivation of the prefrontal cortex and dysregulated cerebellar vermal activation as indexed by c-Fos immunohistochemical staining. We conclude that the High-Active line represents a valid model for the Hyperactive-Impulsive subtype of ADHD and therefore may be used in future studies to advance our understanding of the etiology of ADHD and screen novel compounds for its treatment.
Eye blinking as an indicator of fatigue and mental load—a systematic review (2015)

Preferred Reporting Items For Systematic Reviews And Meta-Analyses (PRISMA) criteria were applied for this review (PLoS_Medicine, 2009). The initial approach comprised an integrated meta-analysis search on the SDI database (Serviço de Documentação e Informação FEUP) for each type of item/resource on the 34 associated scientific magazines and on 28 databases namely Informaworld (Taylor and Francis), Scopus, Web of Science, Springer, IEEE Xplore, PubMed, Science Direct. The reports selection process had two distinct phases.
P3‐307: E2012: A novel gamma‐secretase modulator‐mechanism of action (2010)

Small-molecule γ-secretase modulators (GSM) are a promising therapeutic approach for Alzheimer's disease. We assessed the mechanism of action of E2012, a recently discovered orally-active GSM from a new chemical class. We evaluated the effect of E2012 on the production of various Aβ species by ELISA and MALDI-TOF. We also assessed the specificity of E2012 for different gamma-secretase substrates. E2012 was shown to decrease Aβ(x-40) and Aβ(x-42) and to increase Aβ(1-38) without changing total Aβ(1-x) levels. MALDI-TOF analysis also revealed that E2012 reduced Aβ40 and Aβ42 and increased shorter Aβ peptides, such as Aβ37 and Aβ38. E2012 did not induce the accumulation of APP-CTFs, suggesting that E2012 modulates, but does not inhibit, the cleavage of APP-CTF by gamma-secretase. Production of Notch intracellular domain (NICD) was not inhibited by E2012. We have profiled E2012, a compound from a new chemical class of GSMs, and found that it preferentially reduced gamma-secretase mediated Aβ40 and Aβ42 production over Notch cleavage via a different mechanism from that of classical GSIs. These results provide the basis for the development of E2012 as a new therapeutic agent for Alzheimer's disease.
Improved phase imaging from intensity measurements in multiple planes (2007)

Problems stemming from quantitative phase imaging from intensity measurements play a key role in many fields of physics. Techniques based on the transport of intensity equation require an estimate of the axial derivative of the intensity to invert the problem. Derivation formulas in two adjacent planes are commonly used to experimentally compute the derivative of the irradiance. Here we propose a formula that improves the estimate of the derivative by using a higher number of planes and taking the noisy nature of the measurements into account. We also establish an upper and lower limit for the estimate error and provide the distance between planes that optimizes the estimate of the derivative.
Radiotherapy and wound healing (2005)

Radiotherapy is an invaluable weapon when treating cancer. However, the deleterious effects of radiation, both immediate and long-term, may have a significant effect on local tissues. Problematic wound healing in radiation-damaged tissue constitutes a major problem that is frequently overlooked during the management of patients who require radiotherapy, or have had radiotherapy in the past. Poor wound healing may lead to chronic ulceration, pain, secondary infection and psychological distress and compromise the outcome of general or reconstructive surgery. We discuss the pathophysiology of poor wound healing following radiotherapy, specific problems for radiation-damaged tissue and potential treatments to improve wound healing of irradiated tissues.
Cyclophilin D Modulates Mitochondrial F0F1-ATP Synthase by Interacting with the Lateral Stalk of the Complex (2009)

Blue native gel electrophoresis purification and immunoprecipitation of F(0)F(1)-ATP synthase from bovine heart mitochondria revealed that cyclophilin (CyP) D associates to the complex. Treatment of intact mitochondria with the membrane-permeable bifunctional reagent dimethyl 3,3-dithiobis-propionimidate (DTBP) cross-linked CyPD with the lateral stalk of ATP synthase, whereas no interactions with F(1) sector subunits, the ATP synthase natural inhibitor protein IF1, and the ATP/ADP carrier were observed. The ATP synthase-CyPD interactions have functional consequences on enzyme catalysis and are modulated by phosphate (increased CyPD binding and decreased enzyme activity) and cyclosporin (Cs) A (decreased CyPD binding and increased enzyme activity). Treatment of MgATP submitochondrial particles or intact mitochondria with CsA displaced CyPD from membranes and activated both hydrolysis and synthesis of ATP sustained by the enzyme. No effect of CsA was detected in CyPD-null mitochondria, which displayed a higher specific activity of the ATP synthase than wild-type mitochondria. Modulation by CyPD binding appears to be independent of IF1, whose association to ATP synthase was not affected by CsA treatment. These findings demonstrate that CyPD association to the lateral stalk of ATP synthase modulates the activity of the complex.
Enhancement of Fluoresceinyl Cypridina Luciferin Analog Chemiluminescence by Human Serum Albumin for Singlet Oxygen Detection (2006)

Fluoresceinyl cypridina luciferin analog (FCLA) is a chemiluminescence (CL) probe for detecting reactive oxygen species (ROS). Its efficiency for detecting singlet oxygen (1O2) can be significantly enhanced in the presence of human serum albumin (HSA). This phenomenon may apply to important applications for both research and clinical testing, because of the broad presence of HSA in the human system. In the current study the mechanism of the FCLA-HSA CL system is studied by means of direct CL measurement and spectroscopy techniques. Our results show that FCLA can combine with HSA via a single binding site to form a complex. The CL efficiency of the system is largely governed by an intersystem energy transfer between the two components upon interaction with 1O2. The CL production reaches maximum in a synergetic manner when equal amounts of FCLA and HSA are present simultaneously, but production is less at other ratios. The results also show that the combination of FCLA with HSA does not significantly alter the ROS selectivity of FCLA. In conclusion, our study shows that FCLA and HSA can combine and form a complex with higher CL efficiency. This provides us a new approach in designing CL techniques for studying ROS.