gebhart/patrepeval huggingface dataset:
Two pathways for serum regulation of the c-fos serum response element require specific sequence elements and a minimal domain of serum response factor. (1994)

The c-fos serum response element (SRE) is necessary and sufficient for induction of the c-fos gene in response to serum and growth factors. This activation is dependent upon serum response factor (SRF), a transcriptional activator which binds the SRE. A factor, p62TCF, which binds in conjunction with SRF to the SRE and which is activated by mitogen-activated protein kinase, has also been implicated in c-fos regulation. By using a reporter gene system with weak SRE mutations that is dependent upon overexpression of SRF for serum induction, we have found that there are at least two pathways for serum induction that converge on the SRE. Loss of TCF binding by mutations in SRF and the SRE did not reduce serum induction of the reporter genes. We have found a pathway for serum induction that is sensitive to mutations in the A/T-containing central sequence of the SRE and which is independent of TCF. When this pathway was mutated, activation was dependent upon TCF binding, demonstrating that TCF can also function in serum induction. Both of the signalling pathways required a minimal domain of SRF. This domain, spanning SRF's DNA binding domain, was sufficient for serum induction when fused to a heterologous transcriptional activation domain.
Novel therapeutic strategies for the treatment of Type 2 diabetes (1998)

Diabetes mellitus is the most common endocrine disease, accounting for over 200 million people affected worldwide. It is characterized by a lack of insulin secretion and/or increased cellular resistance to insulin, resulting in hyperglycemia and other metabolic disturbances. People with diabetes suffer from increased morbidity and premature mortality related to cardiovascular, microvascular and neuropathic complications. The Diabetes Control and Complication Trial (DCCT) has convincingly demonstrated the relationship of hyperglycemia to the development and progression of complications and showed that improved glycemic control reduced these complications. Although the DCCT exclusively studied patients with Type 1 diabetes, there is ample evidence to support the belief that the same relationship between metabolic control and clinical outcome exists in patients with Type 2 diabetes. Therefore, a major effort should be made to develop and implement more effective treatment regimes. This article reviews those novel drugs that have been recently introduced for the management of Type 2 diabetes, or that have reached an advanced level of study and will soon be proposed for preliminary clinical trials. They include: (i) compounds that promote the synthesis/secretion of insulin by the beta-cell; (ii) inhibitors of the alpha-glucosidase activity of the small intestine; (iii) substances that enhance the action of insulin at the level of the target tissues; and (iv) inhibitors of free fatty acid oxidation.
TRAF molecules in cell signaling and in human diseases (2013)

The tumor necrosis factor receptor (TNF-R)-associated factor (TRAF) family of intracellular proteins were originally identified as signaling adaptors that bind directly to the cytoplasmic regions of receptors of the TNF-R superfamily. The past decade has witnessed rapid expansion of receptor families identified to employ TRAFs for signaling. These include Toll-like receptors (TLRs), NOD-like receptors (NLRs), RIG-I-like receptors (RLRs), T cell receptor, IL-1 receptor family, IL-17 receptors, IFN receptors and TGFβ receptors. In addition to their role as adaptor proteins, most TRAFs also act as E3 ubiquitin ligases to activate downstream signaling events. TRAF-dependent signaling pathways typically lead to the activation of nuclear factor-κBs (NF-κBs), mitogen-activated protein kinases (MAPKs), or interferon-regulatory factors (IRFs). Compelling evidence obtained from germ-line and cell-specific TRAF-deficient mice demonstrates that each TRAF plays indispensable and non-redundant physiological roles, regulating innate and adaptive immunity, embryonic development, tissue homeostasis, stress response, and bone metabolism. Notably, mounting evidence implicates TRAFs in the pathogenesis of human diseases such as cancers and autoimmune diseases, which has sparked new appreciation and interest in TRAF research. This review presents an overview of the current knowledge of TRAFs, with an emphasis on recent findings concerning TRAF molecules in signaling and in human diseases.
A chronic inflammatory response dominates the skeletal muscle molecular signature in dystrophin-deficient mdx mice (2002)

Mutations in dystrophin cause Duchenne muscular dystrophy (DMD), but absent dystrophin does not invariably cause necrosis in all muscles, life stages and species. Using DNA microarray, we established a molecular signature of dystrophinopathy in the mdx mouse, with evidence that secondary mechanisms are key contributors to pathogenesis. We used variability controls, adequate replicates and stringent analytic tools, including significance analysis of microarrays to estimate and manage false positive rates. In leg muscle, we identified 242 differentially expressed genes, >75% of which have not been previously reported as altered in human or animal dystrophies. Data provide evidence for coordinated activity of numerous components of a chronic inflammatory response, including cytokine and chemokine signaling, leukocyte adhesion and diapedesis, invasive cell type-specific markers, and complement system activation. Selective chemokine upregulation was confirmed by RT-PCR and immunoblot, and may be a key determinant of the nature of the inflammatory response in dystrophic muscle. Up-regulation of secreted phosphoprotein 1 (minopontin, osteopontin) mRNA and protein in dystrophic muscle identified a novel linkage between inflammatory cells and repair processes. Extracellular matrix genes were up-regulated in mdx to levels similar to those in DMD. Since, unlike DMD, mdx exhibits little fibrosis, data suggest that collagen regulation at post-transcriptional stages mediates extensive fibrosis in DMD. Taken together, these data identify a relatively neglected aspect of DMD, suggest new treatment avenues, and highlight the value of genome-wide profiling in study of complex disease processes.
Phosphoinositide 3-Kinase Gamma (PI3K&#947;) Inhibitors for the Treatment of Inflammation and Autoimmune Disease (2009)

Phosphoinositide 3-kinase gamma (PI3Kgamma) is a lipid kinase in leukocytes that generates phosphatidylinositol 3,4,5-trisphosphate to recruit and activate downstream signaling molecules. Distinct from other members in the PI3K family, PI3Kgamma is activated by G-protein coupled-receptors responding to chemotactic ligands. PI3Kgamma plays an important role in migration of both myeloid and lymphoid cells. It is also required for other leukocyte functions such as neutrophil oxidative burst, T cell proliferation and mast degranulation. Mice with PI3Kgamma inactivated by genetic or pharmacological approaches are protected from disease development in a number of inflammation and autoimmune disease models. The function of PI3Kgamma depends on its kinase activity and therefore it has been suggested by many reports that small molecules inhibiting its kinase activity could be promising for the treatment of inflammation and autoimmune diseases. Over the last five years, a number of pharmaceutical companies have reported a wide variety of PI3Kgamma inhibitors, of which several x-ray crystal structures with PI3Kgamma have been elucidated. The structural characteristics and selectivity profiles of these inhibitors, in particular thiazolidinones and 2-aminoheterocycles, and those disclosed in related patent applications are summarized in this review.
Relaxed Negative Selection in Germinal Centers and Impaired Affinity Maturation in bcl-xL Transgenic Mice (1999)

The role of apoptosis in affinity maturation was investigated by determining the affinity of (4-hydroxy-3-nitrophenyl)acetyl (NP)-specific antibody-forming cells (AFCs) and serum antibody in transgenic mice that overexpress a suppressor of apoptosis, Bcl-xL, in the B cell compartment. Although transgenic animals briefly expressed higher numbers of splenic AFCs after immunization, the bcl-xL transgene did not increase the number or size of germinal centers (GCs), alter the levels of serum antibody, or change the frequency of NP-specific, long-lived AFCs. Nonetheless, the bcl-xL transgene product, in addition to endogenous Bcl-xL, reduced apoptosis in GC B cells and resulted in the expansion of B lymphocytes bearing VDJ rearrangements that are usually rare in primary anti-NP responses. Long-lived AFCs bearing these noncanonical rearrangements were frequent in the bone marrow and secreted immunoglobulin G(1) antibodies with low affinity for NP. The abundance of noncanonical cells lowered the average affinity of long-lived AFCs and serum antibody, demonstrating that Bcl-xL and apoptosis influence clonal selection/maintenance for affinity maturation.
Personalized Music Emotion Recognition Using Electroencephalography (EEG) (2014)

Emotion recognition of music objects is one of the promising research issues in the field of music information retrieval. Usually, music emotion recognition could be considered as a training/classification problem. However, even if we have a benchmark (a training data with ground truth) and employ effective classification algorithms, music emotion recognition remains a challenging problem. Based on our literature review, most of previous work only focuses on music acoustic content without considering the individual difference (i.e., Personalization issue). In addition, the assessment of emotions are usually self-reported. Such kind of self-reported assessment (e.g., Emotion tags) might be inaccurate, and even inconsistent. The electroencephalography (EEG) is a non-invasive brain-machine interface, which utilizes neurophysiological signals from the brain to external machines without surgery. The less-intrusive EEG signals, captured from the central nervous system, have been utilized for exploring emotions. In this paper, we would like to propose an evidence-based and personalized model for music emotion recognition. In the model construction and training phase, we construct two predictive and generic models (both models are trained by artificial neural network). With having the generic model and the corresponding individual difference, we construct the personalized model H by the projective transformation accordingly. In the testing phase, given a music object, we extract features from music audio content, calculate the vector in the arousal-valence emotion space, and apply the transformation matrix H to determine the personalized emotion vector. To show the effectiveness of our approach, we also perform experiments and obtain promising results.
ON THE MECHANISM OF RIBONUCLEASE ACTION (1969)

All the suggestions that have been made for the mechanism of action of ribonuclease can be classified into one or another of two classes, depending on the geometry of the displacement in the first step. Studies of related model compounds indicate that one of these two classes should include as a part of the mechanism a pentacoordinate intermediate, which undergoes pseudorotation before product can be formed. It is unlikely that the pseudorotation would be rate-limiting in the reaction of the normal substrate.
High Expression of Fas Ligand by Synovial Fluid-Derived γδ T Cells in Lyme Arthritis (2003)

Gamma delta T cells accumulate at epithelial barriers and at sites of inflammation in various infectious and autoimmune diseases, yet little is understood about the function of tissue-infiltrating gamma delta T cells. We observe that gamma delta T cells of the V delta 1 subset accumulate in synovial fluid of human Lyme arthritis and are intensely cytolytic toward a wide array of target cells. Particularly striking is that the cytolytic activity is highly prolonged, lasting for at least 3 wk after stimulation of the gamma delta T cells with Borrelia burgdorferi. Cytolysis is largely Fas dependent and results from very high and prolonged expression of surface Fas ligand, which is transcriptionally regulated. This also manifests in a substantial level of self-induced apoptosis of the gamma delta T cells. In this capacity, certain gamma delta T cell subsets may serve as cytolytic sentinels at sites of inflammation, and perhaps at epithelial barriers.
By train or by car? Detecting the user's motion type through smartphone sensors data (2012)

Nowadays, the increasing popularity of smartphone devices equipped with multiple sensors (e.g. accelerometer, gyroscope, etc) have opened several possibilities to the deployment of novel and exciting context-aware mobile applications. In this paper, we exploit one of this possibility, by investigating how to detect the user motion type through sensors data collected by a smartphone. Our study combines experimental and analytical contributions, and it is structured in three parts. First, we collected experimental data that demonstrate the existence of specific sensors data patterns associated to each motion type, and we propose methods for data analysis and features extraction. Second, we compare the performance of different supervised algorithms for motion type classification, and we demonstrate that jointly utilizing the multiple sensor inputs of a smartphone (i.e. the accelerometer and the gyroscope) can significantly improve the accuracy of the classifiers. At the same time, we analyze the impact of sampling parameters (e.g. the sampling rate) on the system performance, and the corresponding trade-off between classification accuracy and energy consumption of the device. Third, we integrate the motion type recognition algorithm into an Android application, that allows to associate a specific smartphone configuration to each detected motion type, and to provide this information at system-level to other context-aware Android applications. Experimental results demonstrate the ability of our application in detecting the user's motion type with high accuracy, and in mitigating the classification errors caused by random data fluctuations.
Phosphoenolypyruvate (PEP) Effects on Fresh and Stored Red Blood Cells (1982)

The present studies were performed to evaluate the effects of phosphoenolpyruvate (PEP) on fresh and stored red blood cells as a possible adjunct to citrate phosphate dextrose (CPD) for preservation of blood. Red cell concentrates prepared from fresh blood drawn from human volunteers were incubated with CPD alone or CPD containing PEP. At 37° and an initial pH of less than 6.2, a significant increase in 2,3-DPG and maintenance of ATP were observed. A dose-dependent increase in 2,3-DPG was noted in blood incubated in CPD-PEP from 13 to 52 mM. 2,3-DPG did not change during incubation at either 4° or 25°. A significant increase in ATP was observed at 25°; ATP remained unchanged at 4° and 37°. Storage related depletion of 2,3-DPG and ATP was reversed by PEP incubation (26 mM) even when blood was stored for 42 days in CPD. In fact, 2,3-DPG levels two or three times greater than normal were regularly observed. The persistence, in vivo, of the PEP-induced increase in 2,3-DPG and P50 was demonstrated by 33% exchange transfusions in rats with homologous blood treated for 4 hr with 26 mM PEP. Unlike other preservation additives, incubation with PEP results in a dramatic increase in 2,3-DPG without depletion of ATP, a property which is maintained in vivo. Evidence shows that PEP should be considered as a potential adjunct to conventional blood preservation systems.
Isolation and characterization of a sheep cysteine-rich cuticle keratin pseudogene (1992)

The cysteine-rich keratin proteins of the hair cuticle are derived from a multigene family that has been highly conserved during mammalian evolution. We have recently characterized one cuticle keratin gene isolated from a sheep lambda library, and Southern blot analysis of that clone suggested the presence of a second related gene. In the present paper sequencing of the second gene has now indicated that it is a pseudogene, a finding supported by a lack of expression in vivo. The pseudogene appears to have arisen by gene duplication, possibly from the adjacent functional gene. Key mutations seem to have occurred in the promoter and processing signals of this gene to render it non-functional and two in-frame termination codons are present in the coding region. A possible recombination point between sequences encoding glycine-rich repeats was identified that could have lead to the creation of the in-frame termination codons.
A cluster of dispensable genes within the human cytomegalovirus genome short component: IRS1, US1 through US5, and the US6 family (1992)

By insertional mutagenesis, human cytomegalovirus recombinants deleted of each of the US6 glycoprotein family genes were isolated. A recombinant lacking IRS1, US1 through US5, and most of the US6 family was also isolated. The growth kinetics of these mutants were similar to that of the wild type. A dispensable cluster of genes was identified.
More Than Texts Need Reform in Middle Schools (2003)

Among the many well-taken points in John Hubisz’s article was one less compelling. In box 1 of the article, the answer to the oft-heard lament “Is it too much to ask that middle-school students develop the habit of consulting a dictionary?” should be “yes.” Learning science is sufficiently challenging without continual interruptions, and even more difficult is to know what you don’t know: Many physics words and names have idiosyncrasies of which young students can hardly be expected to be aware.Adding pronunciation keys to the difficult words is a practice that might fruitfully be followed by textbook publishers. A few diacritics don’t take up much space and don’t detract from sentence flow or meaning, but do give the reader a frisson of distinction—that physics words and names are interesting and different! How better to convey the international scope of the physics enterprise than to teach students that “Planck” is pronounced differently from the experimental apparatus for determining mechanical advantage? Pronouncing words and names as if they were English sets students up for embarrassment.I experienced such discomfort the first time I said “heterodyne” out loud in front of people who were experienced enough to know which syllable got the accent, but were insufficiently genteel to correct me privately. If students are embarrassed whenever they talk physics, they may be driven to philosophy and spend their days pondering So-crātes.© 2003 American Institute of Physics.
Effects of EpCAM overexpression on human breast cancer cell lines (2011)

These data show a cell type dependent modification of Wnt signaling components after EpCAM overexpression in breast cancer cell lines, which results in marginal functional changes. Further investigations on the interaction of EpCAM with SFRP1 and TCF7L2 and on additional factors, which may be causal for changes upon EpCAM overexpression, will help to characterize unique molecular properties of EpCAM-positive breast cancer cells.
Myogenic Expression of Mesenchymal Stem Cells within Myotubes of mdx Mice in Vitro and in Vivo (1995)

The myogenic potential of bone marrow- and periosteum-derived mesenchymal stem cells (MSCs) was studied in vitro by coculture of MSCs of snj mice with myoblasts of newborn snj mice or 3-week-old mdx mice. MSCs were labeled with [(3)H]thymidine and cocultured with muscle precursor cells. At 5 different time points, the cocultures were harvested and prepared for autoradiography. Cocultures of MSCs and mdx mouse-derived myoblasts were immunostained for dystrophin before autoradiography. Autoradiographic grains were detected over isolated nuclei in myotubes, which stained positively with antidystrophin antibody. In vivo myogenic potential of MSCs was tested by direct injection into growing muscle of mdx mice. Equal numbers of nonmutant bone marrow-derived MSCs or myoblasts were injected separately into the tibialis anterior muscles of mdx mice. Muscle samples were harvested at 6, 8, and 10 weeks after injection, weighed, and stained with antidystrophin antibody. A small yet significant increase in muscle mass was observed in both the myoblast-injected (11% increase) and MSC-injected muscles (3%), as compared to controls. Muscle injected with myoblasts showed a remarkable conversion from dystrophin-negative to dystrophin-positive fibers (30-40%) in mdx mice injected with normal myoblasts, as previously reported by others. The frequency of dystrophin-positive fibers in mdx mouse muscle injected with marrow-derived MSCs was lower than that of the muscles injected with myoblasts, but was significantly higher than control muscles injected with medium. These results suggest that within the population of MSCs there are cells that are able to differentiate into skeletal muscle.
Procalcitonin for reduced antibiotic exposure in ventilator-associated pneumonia: a randomised study (2009)

In patients with ventilator-associated pneumonia (VAP), guidelines recommend antibiotic therapy adjustment according to microbiology results after 72 h. Circulating procalcitonin levels may provide evidence that facilitates the reduction of antibiotic therapy. In a multicentre, randomised, controlled trial, 101 patients with VAP were assigned to an antibiotic discontinuation strategy according to guidelines (control group) or to serum procalcitonin concentrations (procalcitonin group) with an antibiotic regimen selected by the treating physician. The primary end-point was antibiotic-free days alive assessed 28 days after VAP onset and analysed on an intent-to-treat basis. Procalcitonin determination significantly increased the number of antibiotic free-days alive 28 days after VAP onset (13 (2-21) days versus 9.5 (1.5-17) days). This translated into a reduction in the overall duration of antibiotic therapy of 27% in the procalcitonin group (p = 0.038). After adjustment for age, microbiology and centre effect, the rate of antibiotic discontinuation on day 28 remained higher in the procalcitonin group compared with patients treated according to guidelines (hazard rate 1.6, 95% CI 1.02-2.71). The number of mechanical ventilation-free days alive, intensive care unit-free days alive, length of hospital stay and mortality rate on day 28 for the two groups were similar. Serum procalcitonin reduces antibiotic therapy exposure in patients with ventilator associated pneumonia.
Comparison of time delay estimators in medical ultrasound (2002)

Time delay estimation (TDE) is a common operation in ultrasound signal processing. A variety of TDE algorithms have been developed and applied in medical ultrasound, sonar, radar, and other fields. In this paper we analyze the performances of the widely used normalized and non-normalized correlations, along with normalized covariance, sum absolute differences (SAD), sum squared differences (SSD), hybrid-sign correlation, polarity-coincidence correlation, and Meyr-Spies method. These techniques have been simulated on ultrasound radio frequency data under a variety of conditions. We show how parameters, which include kernel window size, signal decorrelation, and signal to noise ratio (SNR) affect the accuracy of the delay estimate. Simulation results are also compared with the theoretical performance limit set by the Cramer-Rao Lower Bound (CRLB). Results show that for high SNR, high signal correlation, and large kernel size, all of the tested algorithms closely match the theoretical bound, with nearly identical performance. As conditions degrade, the performances begin to differ, with normalized correlation, normalized covariance, and SSD typically outperforming the other algorithms.