gebhart/patrepeval huggingface dataset:
Identification of Genes Associated with Morphology in Aspergillus niger by Using Suppression Subtractive Hybridization (2004)

The morphology of citric acid production strains of Aspergillus niger is sensitive to a variety of factors, including the concentration of manganese (Mn(2+)). Upon increasing the Mn(2+) concentration in A. niger (ATCC 11414) cultures to 14 ppb or higher, the morphology switches from pelleted to filamentous, accompanied by a rapid decline in citric acid production. The molecular mechanisms through which Mn(2+) exerts effects on morphology and citric acid production in A. niger cultures have not been well defined, but our use of suppression subtractive hybridization has identified 22 genes responsive to Mn(2+). Fifteen genes were differentially expressed when A. niger was grown in media containing 1,000 ppb of Mn(2+) (filamentous form), and seven genes were expressed in 10 ppb of Mn(2+) (pelleted form). Of the 15 filament-associated genes, seven are novel and eight share 47 to 100% identity with genes from other organisms. Five of the pellet-associated genes are novel, and the other two genes encode a pepsin-type protease and polyubiquitin. All 10 genes with deduced functions are either involved in amino acid metabolism-protein catabolism or cell regulatory processes. Northern blot analysis showed that the transcripts of all 22 genes were rapidly enhanced or suppressed by Mn(2+). Steady-state mRNA levels of six selected filament-associated genes remained high during 5 days of culture in a filamentous state and remained low under pelleted growth conditions. The opposite behavior was observed for four selected pellet-associated genes. The full-length cDNA of the filament-associated clone, Brsa-25, was isolated. Antisense expression of Brsa-25 permitted pelleted growth and increased citrate production at concentrations of Mn(2+) that were higher than the parent strain could tolerate. These results suggest the involvement of the newly isolated genes in the regulation of A. niger morphology.
A Synthetic Lethal Screen Reveals Enhanced Sensitivity to ATR Inhibitor Treatment in Mantle Cell Lymphoma with ATM Loss-of-Function (2014)

These data suggest that single-agent ATR inhibitors have therapeutic utility and that ATR uses a complex and coordinated set of proteins to maintain genomic stability that could be further exploited.
Exploring the applications of user-expertise assessment for intelligent interfaces (1993)

An adaptive user interface relies, to a large extent, upon an adequate user model (e.g., a representation of user-expertise). However, building a user model may be a tedious and time consuming task that will render such an interface unattractive to developers. We thus need an effective means of inferring the user model at low cost. In this paper, we describe a technique for automatically inferring a fine-grain model of a user's knowledge state based on a small number of observations. With this approach, the domain of knowledge to be evaluated is represented as a network of nodes (knowledge units—KU) and links (implications) induced from empirical user profiles. The user knowledge state is specified as a set of weights attached to the knowledge units that indicate the likelihood of mastery. These weights are updated every time a knowledge unit is reassigned a new weight (e.g., by a question-and-answer process). The updating scheme is based on the Dempster-Shafer algorithm. A User Knowledge Assessment Tool (UKAT) that employs this technique has been implemented. By way of simulations we explore an entropy-based method of choosing questions, and compare the results with a random sampling method. The experimental results show that the proposed knowledge assessment and questioning methods are useful and efficient in inferring detailed models of user-expertise, but the entropy-based method can induce a bias in some circumstances.
Inorganic Sulfites: Efficient Reducing Agents and Supplemental Activators for Atom Transfer Radical Polymerization (2012)

Inorganic sulfites such as sodium dithionite (Na<sub>2</sub>S<sub>2</sub>O<sub>4</sub>), sodium metabisulfite (Na<sub>2</sub>S<sub>2</sub>O<sub>5</sub>), and sodium bisulfite (NaHSO<sub>3</sub>) have been studied as reducing agents for atom transfer radical polymerization (ATRP). They act not only as very efficient reducing agents but also as supplemental activators for SARA (supplemental activator and reducing agent) ATRP of methyl acrylate in DMSO at ambient temperature. In combination with Cu(II)Br<sub>2</sub>/Me<sub>6</sub>TREN, they produced poly(methyl acrylate) with controlled molecular weight, low dispersity (<i>M</i><sub>w</sub>/<i>M</i><sub>n</sub> = 1.05), and well-defined chain-end functionality. Sulfites are eco-friendly, approved by FDA as food and beverage additives, and used commercially in many industrial processes.
Femtosecond real-time probing of reactions. V. The reaction of IHgI (1989)

The dissociation reaction of HgI2 is examined experimentally using femtosecond transition-state spectroscopy (FTS). The reaction involves symmetric and antisymmetric coordinates and the transition-state is well-defined: IHgI*→[IHgI]‡*QS′Qa′q→HgI+I. FTS is developed for this class of ABA-type reactions and recurrences are observed for the vibrating fragments (symmetric coordinate) along the reaction coordinate (antisymmetric coordinate). The translational motion is also observed as a ‘‘delay time’’ of the free fragments. Analysis of our FTS results indicates that the reaction wave packet proceeds through two pathways, yielding either I(2P3/2) or I*(2P1/2) as one of the final products. Dissociation into these two pathways leads to HgI fragments with different vibrational energy, resulting in distinct trajectories. Hence, oscillatory behaviors of different periods in the FTS transients are observed depending on the channel probed (∼300 fs to ∼1 ps). These results are analyzed using the standard FTS description, and by classical trajectory calculations performed on model potentials which include the two degrees of freedom of the reaction. Quantum calculations of the expected fluorescence of the fragment are also performed and are in excellent agreement with experiments.
Retinoic acid-mediated growth inhibition of small cell lung cancer cells is associated with reduced myc and increased p27Kip1 Expression (1999)

Human lung cancer cells, including small cell lung carcinoma (SCLC), frequently lose expression of retinoic acid receptor beta (RAR-beta) and are resistant to the growth inhibitory activity of all-trans retinoic acid (RA). To elucidate the role of RAR-beta in the growth regulation of SCLC by retinoids, we restored RAR-beta expression in RAR-beta-negative H209 SCLC cells by retroviral transduction (H209-RAR-beta). We found that H209-RAR-beta, but not parental H209 cells, underwent growth inhibition upon RA treatment. RA-treated H209-RAR-beta cells arrested in G1 and displayed reduced L-myc expression and cyclin-dependent kinase 2 (cdk2) activity compared with untreated cells. RA treatment of H209-RAR-beta cells was also accompanied by increased expression of the cdk inhibitor p27Kip1, whereas no differences in the expression of L-myc or p27Kip1 were detected upon RA treatment of parental H209 cells. The RA-induced growth arrest of H82 SCLC cells, which express endogenous RAR-beta, was also associated with reduced c-myc and increased p27Kip1 expression. We found that ectopic expression of p27Kip1 induced growth inhibition in both H209 and H82 cells, and that sustained myc expression in H209-RAR-beta cells promoted the induction of apoptosis upon RA addition. Our observations indicate that RAR-beta gene transfer can restore RA sensitivity in SCLC cells and suggest that myc and p27Kip1 may represent critical mediators of the RA-induced cell cycle arrest in SCLC cells expressing RAR-beta.
Cloning, Golgi Localization, and Enzyme Activity of the Full-length Heparin/Heparan Sulfate-Glucuronic Acid C5-epimerase (2001)

While studying the cellular localization and activity of enzymes involved in heparan sulfate biosynthesis, we discovered that the published sequence for the glucuronic acid C5-epimerase responsible for the interconversion of d-glucuronic acid and l-iduronic acid residues encodes a truncated protein. Genome analysis and 5'-rapid amplification of cDNA ends was used to clone the full-length cDNA from a mouse mastocytoma cell line. The extended cDNA encodes for an additional 174 amino acids at the amino terminus of the protein. The murine sequence is 95% identical to the human epimerase identified from genomic sequences and fits with the general size and structure of the gene from Drosophila melanogaster and Caenorhabditis elegans. Full-length epimerase is predicted to have a type II transmembrane topology with a 17-amino acid transmembrane domain and an 11-amino acid cytoplasmic tail. An assay with increased sensitivity was devised that detects enzyme activity in extracts prepared from cultured cells and in recombinant proteins. Unlike other enzymes involved in glycosaminoglycan biosynthesis, the addition of a c-myc tag or green fluorescent protein to the highly conserved COOH-terminal portion of the protein inhibits its activity. The amino-terminally truncated epimerase does not localize to any cellular compartment, whereas the full-length enzyme is in the Golgi, where heparan sulfate synthesis is thought to occur.
Purification of Peroxisomes Using a Density Barrier in a Swinging-Bucket Rotor (2002)

In iodixanol, peroxisomes are the densest organelle in the light mitochondrial fraction and are therefore easily separated from the other components (lysosomes, mitochondria, etc.) in a preformed isosmotic continuous gradient. Because of the large difference in density between peroxisomes and the next densest organelle (mitochondria), a density barrier is effective. The resolution of the peroxisomes is far superior than that in sucrose and, unlike in Percoll, there is no contamination from endoplasmic reticulum.
A Chatbot-based Interactive Question Answering System (2007)

Interactive question answering (QA) systems, where a dialogue interface enables followup and clarification questions, are a recent field of research. We report our experience on the design, implementation and evaluation of a chatbot-based dialogue interface for our open-domain QA system, showing that chatbots can be effective in supporting interactive QA. 1
Measures of Placental Growth in Relation to Birth Weight and Gestational Age (2005)

Fetal growth depends in part on placental growth. The authors tested placental measures derived from digital images for reliability and to evaluate their association with birth weight and gestational age. A total of 628 women recruited into the Pregnancy, Infection, and Nutrition Study, a prospective cohort study of preterm birth in central North Carolina between 2002 and 2004, delivered singleton liveborn infants after 24 completed weeks' gestation. Novel chorionic plate morphometric parameters captured off digital images of the gross placenta were analyzed as estimators of gestational age and birth weight. Without acknowledgment to placental weight, digitally obtained lateral chorionic plate growth measures accounted for 17 percent of gestational age variance and 35 percent of birth weight variance, overall. Chorionic plate measures accounted for 10 percent of birth weight variance beyond that accounted for by placental weight alone. Among preterm births, 34 percent of gestational age variance and 63 percent of birth weight variance were accounted for by lateral chorionic plate growth measures. Intraclass correlation coefficients for the novel digital measures ranged from 0.96 to 0.98. Reliable digital measures of lateral chorionic plate growth estimate birth weight variance more strongly than gestational age, project variance that is not accounted for by placental weight, and project these outcomes to a greater degree in preterm births than at term.
Estimation of projected circle centers from array circles and its application in camera calibration (2009)

A method of detecting projected circle centers (PCC) based on array circles is proposed. The perspective distortion of projected circle centers could be eliminated from coplanar circles. By utilizing the property of projected coplanar circles, lines connecting PCCs are computed from projective invariant points defined by the projected circles (PCs), and then the PCCs are determined from the intersection of the computed lines. Once PCCs are recovered, the camera could be calibrated from classic method such as Zhang's. Both synthetic and real data have been used to testify the proposed algorithm and good results have been obtained. The calibration results show that the estmation of projected circle centre bears high stability and accuracy, even when the image noise is massive.
Erasure of kinase phosphorylation in astrocytes during oxygen–glucose deprivation is controlled by ATP levels and activation of phosphatases (2003)

We have examined the relationship between adenosine triphosphate (ATP) concentration and loss of maintenance of kinase-signalling cascades in primary cortical astrocytes during oxygen-glucose deprivation (OGD) as this may constitute an irreversible step that commits astrocytes to cell death. We report that the phosphorylation of Akt, ERK, JNK and p38 kinases, whose activities depend on serine, threonine and tyrosine phosphorylation, were all increased during OGD. All these phosphorylations were reduced to below detection limits when ATP levels were less than 10% of normal levels. Using ERK and Akt as representative examples, we show that this erasure is not irreversible as both ERK and Akt phosphorylations can be partially restored by addition of glucose under anoxic conditions. We further investigated whether OGD caused any change in phosphatase activity. The PP1/PP2A phosphatase inhibitors okadaic acid and caliculyn A, but not cyclosporine A, delayed the removal of ERK and Akt phosphorylation under OGD. By comparing the extent of phosphorylation increase under OGD and normoxic conditions, we calculate that phosphatase activity was increased by approximately 3.6-fold during OGD. These data show that ATP levels control an important checkpoint in kinase function, and that ATP levels may need to be considered when studies of kinase function in relation to OGD are conducted.
Exciting New Advances in Neuro-Oncology: The Avenue to a Cure for Malignant Glioma (2010)

Malignant gliomas are the most common and deadly brain tumors. Nevertheless, survival for patients with glioblastoma, the most aggressive glioma, although individually variable, has improved from an average of 10 months to 14 months after diagnosis in the last 5 years due to improvements in the standard of care. Radiotherapy has been of key importance to the treatment of these lesions for decades, and the ability to focus the beam and tailor it to the irregular contours of brain tumors and minimize the dose to nearby critical structures with intensity-modulated or image-guided techniques has improved greatly. Temozolomide, an alkylating agent with simple oral administration and a favorable toxicity profile, is used in conjunction with and after radiotherapy. Newer surgical techniques, such as fluorescence-guided resection and neuroendoscopic approaches, have become important in the management of malignant gliomas. Furthermore, new discoveries are being made in basic and translational research, which are likely to improve this situation further in the next 10 years. These include agents that block 1 or more of the disordered tumor proliferation signaling pathways, and that overcome resistance to already existing treatments. Targeted therapies such as antiangiogenic therapy with antivascular endothelial growth factor antibodies (bevacizumab) are finding their way into clinical practice. Large-scale research efforts are ongoing to provide a comprehensive understanding of all the genetic alterations and gene expression changes underlying glioma formation. These have already refined the classification of glioblastoma into 4 distinct molecular entities that may lead to different treatment regimens. The role of cancer stem-like cells is another area of active investigation. There is definite hope that by 2020, new cocktails of drugs will be available to target the key molecular pathways involved in gliomas and reduce their mortality and morbidity, a positive development for patients, their families, and medical professionals alike.
Simplified CRISPR tools for efficient genome editing and streamlined protocols for their delivery into mammalian cells and mouse zygotes (2017)

Genome editing using the CRISPR/Cas9 system requires the presence of guide RNAs bound to the Cas9 endonuclease as a ribonucleoprotein (RNP) complex in cells, which cleaves the host cell genome at sites specified by the guide RNAs. New genetic material may be introduced during repair of the double-stranded break via homology dependent repair (HDR) if suitable DNA templates are delivered with the CRISPR components. Early methods used plasmid or viral vectors to make these components in the host cell, however newer approaches using recombinant Cas9 protein with synthetic guide RNAs introduced directly as an RNP complex into cells shows faster onset of action with fewer off-target effects. This approach also enables use of chemically modified synthetic guide RNAs that have improved nuclease stability and reduces the risk of triggering an innate immune response in the host cell. This article provides detailed methods for genome editing using the RNP approach with synthetic guide RNAs using lipofection or electroporation in mammalian cells or using microinjection in murine zygotes, with or without addition of a single-stranded HDR template DNA.
Mathematical models: A key tool for outbreak response (2014)

Proceedings of the National Academy of Sciences (PNAS), a peer reviewed journal of the National Academy of Sciences (NAS) - an authoritative source of high-impact, original research that broadly spans the biological, physical, and social sciences.
Sustained decrease in brain regional blood flow after microsphere embolism in rats. (1993)

Microsphere embolism resulted in a sustained decrease in regional blood flow and production of cerebral infarction in the brain regions of the microsphere-injected hemisphere.
Fibronectin Enhances Healing of Excised Wounds in Rats (1988)

Fibronectin (Fn) is a normal plasma and extracellular matrix glycoprotein that is involved in each phase of wound healing. For example, it is incorporated into both fibrin and collagen fibers; it opsonizes circulating tissue debris for removal by the reticuloendothelial system; it is used by macrophages, fibroblasts, and epithelial cells to move into the wound; and fragments of Fn are chemotactic for fibroblasts. In this study, experiments with rats showed that excised lesions treated with Fn healed more rapidly than paired control lesions treated with the carrier alone. Applications of Fn once a day for two days were as effective in speeding healing as twice-daily applications of Fn for 12 days. A single treatment with Fn soon after the initial injury was nearly as effective as more prolonged treatment regimens.
Fusion of artificial membranes with mammalian spermatozoa (1993)

The fusogenic properties of bovine and human spermatozoa membranes were investigated, using phospholipid bilayers (liposomes) as target membranes. Fusion was monitored by following lipid mixing, as revealed by an assay based on resonance-energy transfer. In addition, fusion was visualized by fluorescence microscopy, using fluorescent lipid vesicles. Cryopreserved bovine sperm fused with liposomes before induction of the acrosome reaction, fluorescence being located in essentially all spermatozoa membrane domains. Fresh bovine and human spermatozoa fused with liposomes only after the induction of the acrosome reaction, as triggered by calcium ionophore A23187 or zonae pellucidae (proteins), while the fluorescence distribution was mainly restricted to the equatorial segment (ES). However, with spermatozoa that had undergone a freeze/thawing cycle, domains other than ES also became labeled. Hence, the redistribution of the lipid probes over the entire membrane occurring during lipid mixing with cryopreserved bovine sperm is probably related to membrane perturbations caused by long-term cryopreservation. Fusion with liposomes was governed by spermatozoa factors and required the presence of acidic phospholipids like cardiolipin and phosphatidylserine in the liposomal bilayer. Incorporation of the zwitterionic lipid phosphatidylcholine in the vesicles inhibited the fusion reaction. Fusion was pH dependent. The results indicate that the ES is the primary domain of spermatozoa membranes that harbours the fusogenic capacity of sperm. Liposomes appear a valuable tool in further characterizing the properties of this domain, which has been claimed [Yanagimachi, R. (1988) in The physiology of reproduction (Knobil, E. & Neill, J., eds) pp. 135-185, Raven Press, New York] to represent the putative, initial fusion site for the oocyte.
How I treat acute myeloid leukemia (2010)

More than one quarter of a million adults throughout the world are diagnosed annually with acute myeloid leukemia (AML). Despite considerable progress during the past 3 decades in the therapy of AML, two-thirds of young adults and 90% of older adults still die of their disease. The reported median age has increased over the past few decades, mostly because of a greater willingness of physicians to diagnose and treat older patients, and now is 72 years. The greatest challenge is in this age group. However, much improvement in therapy is needed for all adults with AML. Recent advances in allogeneic transplantation, a better understanding of prognostic factors, and development of targeted agents have only modestly improved overall outcome when large populations of patients are considered. Although an explosion in knowledge about the molecular pathogenesis of AML has outpaced treatment advances, such insights hold promise for the development of new therapies directed at specific molecular abnormalities that perturb malignant cell survival pathways. The current approach in 2010 to the management of this disease is presented through a discussion of illustrative cases.
Prognostic Value of Psychological Testing in Patients Undergoing Spinal Cord Stimulation: A Prospective Study (1996)

Because our study population was selected on the basis of recognized prognostic factors and long clinical experience, it may not be possible to generalize our findings to the overall pain clinic referral population. In the subpopulation we have chosen for SCS trials, psychological testing is of modest value and explains little of the observed variance in outcome. We find little evidence for selecting patients for SCS on the basis of psychological testing. Because self-reported outcome measures may themselves reflect the patient's psychological state, these findings should be considered carefully, in overall clinical context. A prospective study with additional objective outcome measures is underway, which will address some of these issues.
Association of Telomere Length of Peripheral Blood Leukocytes With Hematopoietic Relapse, Malignant Transformation, and Survival in Severe Aplastic Anemia (2010)

In a cohort of patients with severe aplastic anemia receiving immunosuppressive therapy, telomere length was unrelated to response but was associated with risk of relapse, clonal evolution, and overall survival.