gebhart/patrepeval huggingface dataset:
Co-expression of fatty acid synthase and caveolin-1 in pancreatic ductal adenocarcinoma: Implications for tumor progression and clinical outcome (2008)

Pancreatic cancer is a devastating disease that afflicts over 35,000 Americans every year. Since therapeutic options are limited, understanding the molecular aspects of this disease is critical for moving towards targeted treatment of this aggressive form of cancer. Caveolin-1 (Cav-1) and fatty acid synthase (FASN) are two proteins that have been shown to be dysregulated in a number of cancers. Functionally these proteins have been shown to be involved in the process of tumorigenesis. We thus surveyed the expression of both these critical proteins in a series of pancreatic precancerous lesions (pancreatic intraepithelial neoplasia, PanIN) and pancreatic cancers. Cav-1 and FASN expression correlated predominantly with clinical characteristics, such as histologic grade and advanced tumor stage (e.g., high Cav-1 and FASN expression correlated with poor differentiation status) and a significant survival advantage was found in patients with low co-expressing FASN and Cav-1 tumors. Cav-1 and FASN expression was absent in PanIN lesions and the normal ducts and acini. Of note, Cav-1 expression was detected in the fibroblasts of the desmoplastic pancreatic cancer stroma, but not in stromal cells of the normal pancreas. Mechanistically, these data support the notion that these proteins are co-regulated either directly or indirectly by another factor. Importantly, the co-expression of these proteins significantly correlates with clinical features and survival status of pancreatic cancer patients. Thus, Cav-1 and FASN may functionally cooperate in the process of pancreatic tumorigenesis, and as such, may be good candidate prognostic markers and targets for therapeutic intervention.
Efficacy and Safety of Aprotinin in Cardiac Surgery (2004)

Cardiac surgery and cardiopulmonary bypass produces bleeding and the need for allogenic blood product transfusions in many patients. Blood conservation is important in the perioperative management of patients. Aprotinin, a serine protease inhibitor isolated from bovine lung, is a complex protease inhibitor that is an antifibrinolytic, inhibits contact activation, and decreases the inflammatory response to cardiopulmonary bypass. Aprotinin reduces blood loss and transfusion requirements in adult and pediatric patients undergoing cardiac surgery with cardiopulmonary bypass. Full-dose aprotinin significantly reduces postoperative blood loss and has been demonstrated in multiple prospective blinded studies to be safe and effective. One of the major adverse effects is anaphylaxis that occurs on re-exposure to aprotinin.
Characterization and chemistry of imidazolidinyl urea and diazolidinyl urea (2006)

For several decades, the cosmetic preservatives imidazolidinyl urea (IU) and diazolidinyl urea (DU) have not only been poorly characterized but have also had misleading chemical structures assigned to them. The most common trade names of IU and DU are Germall 115 and Germall II, respectively. This publication gives an insight into what these 2 well-known contact allergens consist of and their degradation patterns. Approximately, 30-40% of both products can be characterized by mixtures of allantoin (synthetic starting material), (4-hydroxymethyl-2,5-dioxo-imidazolidin-4-yl)-urea (compound HU) and presumably 1-(3,4-bis-hydroxymethyl-2,5-dioxo-imidazolidin-4-yl)-1,3-bis-hydroxymethyl-urea (compound BHU). A full chemical characterization of compound HU is shown. The remaining part of both IU and DU are believed to be polymers of allantoin-formaldehyde condensation products. The analytical methods used to characterize IU and DU are capillary electrophoresis and nuclear magnetic resonance and mass spectroscopy studies.
Spermidine-condensed DNA and cone-shaped lipids improve delivery and expression of exogenous DNA transfer by liposomes (1996)

A new liposome system containing spermidine-condensed DNA and negative cone-forming lipids designed to improve gene delivery and expression is described. The compacted nature of condensed DNA forms permitted a higher extent of encapsulation of DNA in liposomes. These vesicles contained fusogenic cone-shaped lipids to increase fusion between liposomes and membranes to enhance the amount of DNA delivery into the cells. In addition, the insensitivity of condensed DNA forms to endonucleases and restriction enzymes, as well as their higher activity in both replication and transcription, improve foreign DNA expression. These improvements in condensed DNA encapsulation in liposomes, transfer into the cells, and DNA expression increase the number of transfected cells and produce a higher level of gene expression in most transfected cells. This is reflected in the 60-fold cell culture transfection increase compared with traditional liposome transfection systems. This liposome system does not cause any apparent damage to the transfected cells; furthermore, the liposomes are small, 400-500 nm, and have negative surface charges that can prolong their circulation half-lives in vivo, permitting their use for in vivo gene therapy applications.
Computer Organization and Design, Fourth Edition, Fourth Edition: The Hardware/Software Interface (The Morgan Kaufmann Series in Computer Architecture and Design) (2008)

The classic textbook for computer systems analysis and design, Computer Organization and Design, has been thoroughly updated to provide a new focus on the revolutionary change taking place in industry today: the switch from uniprocessor to multicore microprocessors. This new emphasis on parallelism is supported by updates reflecting the newest technologies with examples highlighting the latest processor designs, benchmarking standards, languages and tools. As with previous editions, a MIPS processor is the core used to present the fundamentals of hardware technologies, assembly language, computer arithmetic, pipelining, memory hierarchies and I/O. Along with its increased coverage of parallelism, this new edition offers new content on Flash memory and virtual machines as well as a new and important appendix written by industry experts covering the emergence and importance of the modern GPU (graphics processing unit), the highly parallel, highly multithreaded multiprocessor optimized for visual computing.A new exercise paradigm allows instructors to reconfigure the 600 exercises included in the book to easily generate new exercises and solutions of their own. A CD provides a toolkit of simulators and compilers along with tutorials for using them as well as additional problems and solutions, and references.
An Introduction to Fluid Dynamics (2000)

First published in 1967, Professor Batchelor's classic text on fluid dynamics is still one of the foremost texts in the subject. The careful presentation of the underlying theories of fluids is still timely and applicable, even in these days of almost limitless computer power. This re-issue should ensure that a new generation of graduate students see the elegance of Professor Batchelor's presentation.
Characterization of FaRB7, a near root-specific gene from strawberry (Fragariaxananassa Duch.) and promoter activity analysis in homologous and heterologous hosts (2006)

Many insect and fungal pathogens posing agronomically important threats specifically target the roots in strawberry. The use of a root-specific promoter to confer expression of resistance genes in a targeted manner has the potential appreciably to benefit the genetic improvement of commercial strawberry varieties. A novel gene, FaRB7, was isolated from strawberry (Fragariaxananassa Duch.) and found to contain motifs characteristic of tonoplast intrinsic proteins (TIPs). Phylogenetic analysis revealed that FaRB7 represents an RB7-type TIP. In strawberry, this gene is expressed predominantly in roots, with very low expression in petioles. A 2.843 kb region representing the FaRB7 gene upstream regulatory sequence was isolated and found to share a number of sequence motifs with the promoter of the Nicotiana tabacum TobRB7 root-specific RB7-type TIP. When cloned upstream of the gusA reporter gene and introduced into strawberry plants, the FaRB7 promoter was shown to direct strong, near root-specific expression with expression patterns very similar to that of the endogenous gene. Furthermore, the FaRB7 promoter was found to confer constitutive expression, comparable to that produced by the cauliflower mosaic virus (CaMV) 35S RNA promoter, in tobacco. Thus, the FaRB7 promoter may be used to achieve near-root-specific transgene expression in strawberry and also represents an alternative to the CaMV 35S promoter for producing constitutive foreign gene expression in heterologous hosts. The FaRB7 full-length genomic sequence and 5' upstream regulatory region have been submitted to the EMBL/GenBank database under accession number DQ178022.
On the capacity of MIMO broadcast channels with partial side information (2005)

In multiple-antenna broadcast channels, unlike point-to-point multiple-antenna channels, the multiuser capacity depends heavily on whether the transmitter knows the channel coefficients to each user. For instance, in a Gaussian broadcast channel with M transmit antennas and n single-antenna users, the sum rate capacity scales like Mloglogn for large n if perfect channel state information (CSI) is available at the transmitter, yet only logarithmically with M if it is not. In systems with large n, obtaining full CSI from all users may not be feasible. Since lack of CSI does not lead to multiuser gains, it is therefore of interest to investigate transmission schemes that employ only partial CSI. We propose a scheme that constructs M random beams and that transmits information to the users with the highest signal-to-noise-plus-interference ratios (SINRs), which can be made available to the transmitter with very little feedback. For fixed M and n increasing, the throughput of our scheme scales as MloglognN, where N is the number of receive antennas of each user. This is precisely the same scaling obtained with perfect CSI using dirty paper coding. We furthermore show that a linear increase in throughput with M can be obtained provided that M does not not grow faster than logn. We also study the fairness of our scheduling in a heterogeneous network and show that, when M is large enough, the system becomes interference dominated and the probability of transmitting to any user converges to 1/n, irrespective of its path loss. In fact, using M=/spl alpha/logn transmit antennas emerges as a desirable operating point, both in terms of providing linear scaling of the throughput with M as well as in guaranteeing fairness.
Trehalose and Trehalase in Arabidopsis (2001)

Trehalase is ubiquitous in higher plants. So far, indications concerning its function are scarce, although it has been implicated in the detoxification of exogenous trehalose. A putative trehalase gene, T19F6.15, has been identified in the genome sequencing effort in Arabidopsis. Here we show that this gene encodes a functional trehalase when its cDNA is expressed in yeast, and that it is expressed in various plant organs. Furthermore, we present results on the distribution and activity of trehalase in Arabidopsis and we describe how inhibition of trehalase by validamycin A affects the plants response to exogenous trehalose (alpha-D-glucopyranosyl-[1, 1]-alpha-D-glucopyranoside). Trehalase activity was highest in floral organs, particularly in the anthers (approximately 700 nkat g(-1) protein) and maturing siliques (approximately 250 nkat g(-1) protein) and much lower in leaves, stems, and roots (less than 50 nkat g(-1) protein). Inhibition of trehalase in vivo by validamycin A led to the accumulation of an endogenous substance that had all the properties of trehalose, and to a strong reduction in sucrose and starch contents in flowers, leaves, and stems. Thus, trehalose appears to be an endogenous substance in Arabidopsis, and trehalose and trehalase may play a role in regulating the carbohydrate allocation in plants.
Annotation Error in Public Databases: Misannotation of Molecular Function in Enzyme Superfamilies (2009)

Due to the rapid release of new data from genome sequencing projects, the majority of protein sequences in public databases have not been experimentally characterized; rather, sequences are annotated using computational analysis. The level of misannotation and the types of misannotation in large public databases are currently unknown and have not been analyzed in depth. We have investigated the misannotation levels for molecular function in four public protein sequence databases (UniProtKB/Swiss-Prot, GenBank NR, UniProtKB/TrEMBL, and KEGG) for a model set of 37 enzyme families for which extensive experimental information is available. The manually curated database Swiss-Prot shows the lowest annotation error levels (close to 0% for most families); the two other protein sequence databases (GenBank NR and TrEMBL) and the protein sequences in the KEGG pathways database exhibit similar and surprisingly high levels of misannotation that average 5%-63% across the six superfamilies studied. For 10 of the 37 families examined, the level of misannotation in one or more of these databases is >80%. Examination of the NR database over time shows that misannotation has increased from 1993 to 2005. The types of misannotation that were found fall into several categories, most associated with "overprediction" of molecular function. These results suggest that misannotation in enzyme superfamilies containing multiple families that catalyze different reactions is a larger problem than has been recognized. Strategies are suggested for addressing some of the systematic problems contributing to these high levels of misannotation.
Risk for New Onset of Depression During the Menopausal Transition (2006)

The current study suggests that within a similarly aged population of women with no lifetime history of depression, those who enter the menopausal transition earlier have a significant risk for first onset of depression. Further studies are needed to determine more definitively whether other factors, such as the presence of vasomotor symptoms, use of hormone therapy, and the occurrence of adverse life events, independently modify this risk. Physical symptoms associated with the menopausal transition and mood changes seen during this period may affect many women as they age and may lead to a significant burden of illness.
Genetic influences on the neural basis of social cognition (2006)

The neural basis of social cognition has been the subject of intensive research in both human and non-human primates. Exciting, provocative and yet consistent findings are emerging. A major focus of interest is the role of efferent and afferent connectivity between the amygdala and the neocortical brain regions, now believed to be critical for the processing of social and emotional perceptions. One possible component is a subcortical neural pathway, which permits rapid and preconscious processing of potentially threatening stimuli, and it leads from the retina to the superior colliculus, to the pulvinar nucleus of the thalamus and then to the amygdala. This pathway is activated by direct eye contact, one of many classes of potential threat, and may be particularly responsive to the 'whites of the eyes'. In humans, autonomic arousal evoked by this stimulus is associated with the activity in specific cortical regions concerned with processing visual information from faces. The integrated functioning of these pathways is modulated by one or more X-linked genes, yet to be identified. The emotional responsiveness of the amygdala, and its associated circuits, to social threat is also influenced by functional polymorphisms in the promoter of the serotonin transporter gene. We still do not have a clear account of how specific allelic variation, in candidate genes, increases susceptibility to developmental disorders, such as autism, or psychiatric conditions, such as anxiety or depressive illness. However, the regulation of emotional responsiveness to social cues lies at the heart of the problem, and recent research indicates that we may be nearing a deeper and more comprehensive understanding.
Coded cooperation under slow fading, fast fading, and power control (2003)

User cooperation provides uplink transmit diversity even when mobile units cannot accommodate multiple antennas due to size constraints. Recently, a versatile user cooperation method called coded cooperation diversity was introduced, in which standard channel coding methods are used to implement cooperation. This method achieves remarkable gains compared to a conventional (non-cooperative) system while maintaining the same information rate and transmit power. In this work, we investigate the performance of coded cooperation under a variety of conditions. We investigate slow Rayleigh fading scenarios where the users have either similar or significantly different quality channels to the base station. We compare coded cooperation with the amplify-and-forward protocol proposed by Laneman, Wornell, and Tse. Furthermore, we consider the effects of conventional power control on cooperating users for the slow fading case. Finally, we present some results for the case of fast Rayleigh fading.
Natural History of Paroxysmal Nocturnal Hemoglobinuria (1995)

PNH is a chronic disorder that curtails life. A spontaneous long-term remission can occur, which must be taken into account when considering potentially dangerous treatments, such as bone marrow transplantation. Platelet transfusions should be given, as appropriate, and long-term anticoagulation therapy should be considered for all patients.
The road to providing human embryo stem cells for therapeutic use: the UK experience (2006)

Harnessing the unparalleled properties of human embryo stem cells (hESCs) for the therapeutic treatment of disease and injury will require a convergence of scientific developments with regulatory standards. In the case of the latter, it is especially critical that standards for clinically assisted reproduction be harmonized with those governing human cell and tissue transplantation, most notably with respect to procurement, donation, testing, processing, preservation, storage and distribution of cells. In the UK, existing infrastructure to address these considerations is undergoing extensive reorganization to keep pace with evolving European Union standards. The present best paradigm for defining standards for the therapeutic use of embryo-derived stem cells is experience with adult haematopoietic stem cells (HSC). However, compared with adult-derived stem cell, the origin of embryo-derived stem cells from limiting quantities of tissue and their absolute dependence on in vitro culture to realise their therapeutic potential, makes optimization of their isolation and cultivation of even greater importance. Most notable is the requirement to create animal cell product-free culture environments to reduce the risk of cross-specific disease transmission. In the present paper, we review present and emerging standards in the isolation and banking of human embryo-derived stem cells for therapeutic use in the UK and international progress in the development of defined culture systems for this purpose.
Dasatinib (BMS-354825), a Dual SRC/ABL Kinase Inhibitor, Inhibits the Kinase Activity of Wild-Type, Juxtamembrane, and Activation Loop Mutant KIT Isoforms Associated with Human Malignancies (2006)

Activating mutations of the activation loop of KIT are associated with certain human neoplasms, including the majority of patients with systemic mast cell disorders, as well as cases of seminoma, acute myelogenous leukemia (AML), and gastrointestinal stromal tumors (GISTs). The small-molecule tyrosine kinase inhibitor imatinib mesylate is a potent inhibitor of wild-type (WT) KIT and certain mutant KIT isoforms and has become the standard of care for treating patients with metastatic GIST. However, KIT activation loop mutations involving codon D816 that are typically found in AML, systemic mastocytosis, and seminoma are insensitive to imatinib mesylate (IC50 > 5-10 micromol/L), and acquired KIT activation loop mutations can be associated with imatinib mesylate resistance in GIST. Dasatinib (formerly BMS-354825) is a small-molecule, ATP-competitive inhibitor of SRC and ABL tyrosine kinases with potency in the low nanomolar range. Some small-molecule SRC/ABL inhibitors also have potency against WT KIT kinase. Therefore, we hypothesized that dasatinib might inhibit the kinase activity of both WT and mutant KIT isoforms. We report herein that dasatinib potently inhibits WT KIT and juxtamembrane domain mutant KIT autophosphorylation and KIT-dependent activation of downstream pathways important for cell viability and cell survival, such as Ras/mitogen-activated protein kinase, phosphoinositide 3-kinase/Akt, and Janus-activated kinase/signal transducers and activators of transcription. Furthermore, dasatinib is a potent inhibitor of imatinib-resistant KIT activation loop mutants and induces apoptosis in mast cell and leukemic cell lines expressing these mutations (potency against KIT D816Y >> D816F > D816V). Our studies suggest that dasatinib may have clinical efficacy against human neoplasms that are associated with gain-of-function KIT mutations.
Changes in affect and future exercise intentions as a result of exposure to a regular exercise programme using the Wii Fit (2010)

This research study had two aims, firstly, to track changes in affect and secondly to explore intentions to exercise as a result of regular exposure to programmed exercise. Seven sedentary women used a Wii Fit for eight 30-minute sessions across three to five weeks. On-going measurements of affect were plotted on the circumplex model. On average everyone moved towards a positive valence pre- to post-exercise but fluctuations in valence were evident during exercise sessions. Thematic analysis of future exercise intentions found that five participants intended to change their exercise behaviour but at a four-week follow-up only two had changed. In conclusion, exercise using the Wii Fit appears to have a differential impact upon affect and an eight-session programmed use of the Wii Fit was not enough to increase the likelihood of exercise uptake in this sample of sedentary women.
Dopamine D1 and D2 receptor gene expression in the striatum in Huntington's disease (1997)

The cellular expression of dopamine D1 and D2 receptor mRNAs was investigated in the postmortem human caudate nucleus of control cases and genetically and pathologically confirmed cases of Huntington's disease (HD) by using quantitative in situ hybridization. The HD cases were categorized (0-4) by severity of striatal neuropathology according to the Vonsattel scale. For the HD grade 0 case, a pronounced reduction in the number of D1 and D2 mRNA-positive cells was observed compared with controls; however, the abundance of both receptor mRNAs per remaining cell was within the control range. For D2 receptor mRNA, the number of detectable D2-positive medium-sized cells decreased with increasing pathology; this decrease was accompanied by a gradual reduction in the intensity of D2 signal per cell. By contrast, for D1 receptor mRNA, despite a decrease in the number of D1 mRNA-positive cells detected, the average cellular expression of D1 mRNA was markedly reduced in the HD grade 1 case and then increased (relative to the grade 1 case) with increasing pathology, presumably reflecting the relative survival of D1-expressing striatal interneurons. The implications of these findings for providing further information on the neurodegenerative process in HD are discussed.