gebhart/patrepeval huggingface dataset:
Computational Technology for Effective Health Care (2009)

Despite a strong commitment to delivering quality health care, persistent problems involving medical errors and ineffective treatment continue to plague the industry. Many of these problems are the consequence of poor information and technology (IT) capabilities, and most importantly, the lack cognitive IT support. Clinicians spend a great deal of time sifting through large amounts of raw data, when, ideally, IT systems would place raw data into context with current medical knowledge to provide clinicians with computer models that depict the health status of the patient. Computational Technology for Effective Health Care advocates re-balancing the portfolio of investments in health care IT to place a greater emphasis on providing cognitive support for health care providers, patients, and family caregivers; observing proven principles for success in designing and implementing IT; and accelerating research related to health care in the computer and social sciences and in health/biomedical informatics. Health care professionals, patient safety advocates, as well as IT specialists and engineers, will find this book a useful tool in preparation for crossing the health care IT chasm.
GATA Factors Lie Upstream of Nkx 2.5 in the Transcriptional Regulatory Cascade That Effects Cardiogenesis (2005)

Members of the GATA-4, -5, and -6 subfamily of transcription factors are co-expressed with the homeoprotein Nkx 2.5 in the precardiac mesoderm during the earliest stages of its specification and are known to be important determinants of cardiac gene expression. Ample evidence suggests that GATA factors and Nkx 2.5 cross-regulate each other's expression; however, the temporal order of the expression of these transcription factors in vivo remains unresolved, and thus precise definition of the role of the products of the genes they transcribe in early development has been difficult to assess. We employed P19 CL6 mouse embryonic carcinoma cells as a model to investigate this problem, because these cells, like embryonic stem cells, can be induced to differentiate along multiple lineages. Here we demonstrate that when P19 CL6 cells are induced to differentiate to a cardiogenic lineage, the expression of GATA-4 and GATA-6 is up-regulated prior to the transcriptional activation of Nkx 2.5. Moreover, over-expression of GATA-4 or -6 at the time of Nkx 2.5 induction results in a significant up-regulation of endogenous Nkx 2.5 transcription. Finally, it is known that a Nkx-dependent enhancer is necessary for GATA-6 expression within cardiomyocytes of the developing mouse embryo. We demonstrate that within undifferentiated P19 CL6 cells, GATA-6 expression is subject to active repression by a novel upstream element that possesses binding sites for factors involved in transcriptional repression that are conserved between mammalian species.
Hypoxia Inducible Double Plasmid System for Myocardial Ischemia Gene Therapy (2002)

Coronary artery disease frequently involves repeated bouts of myocardial ischemia. To automatically up-regulate the cardioprotective transgenes under hypoxic ischemia, a “vigilant vector” gene therapy system was developed and tested in a rat embryonic myocardial cell line (H9c2). In the vigilant vector, a hypoxia response element-incorporated promoter was used as a switch to turn on the gene expression in response to hypoxic signal. Furthermore, a novel double plasmid system was designed to elevate the potency of the vigilant vector. Instead of putting the promoter and the reporter gene in the same plasmid (single plasmid system), we separated them into two plasmids: the transactivator plasmid and reporter plasmid (double plasmid system). The hypoxia response element (HRE)-incorporated promoter increased the expression of a chimeric transcription factor consisting of the yeast GAL4 DNA binding domain and the human nuclear (transcription) factor-κB (NF-κB) p65 activation domain. The powerful chimeric regulator binds specifically to the upstream activating sequence for GAL4 in the reporter plasmid and activates the transcription of the transgene. Our experiments showed that the HRE-mediated expression could quickly increase 2.08±0.75-fold within 6 hours of hypoxia and further augmented 7.12±1.52-fold when the hypoxia condition was prolonged to 24 hours. The hypoxia-inducible double plasmid system dramatically amplified the transgene expression under both hypoxia and normoxia by 412.79±185.27-fold and 205.35±65.44-fold, respectively, relative to the single plasmid system. From these results, we concluded that this hypoxia inducible double plasmid system could be used therapeutically to switch on genes that have proven beneficial effects in myocardial ischemia.
10.3 Gbit/s burst-mode PIN-TIA module with high sensitivity, wide dynamic range and quick response (2008)

A burst-mode PIN-TIA module has been developed using SiGe BiCMOS technology and successfully operated at 10.3 Gbit/s with an instantaneous response of 10 ns, a high sensitivity of −19.5 dBm and a wide dynamic range of 20.5 dB.
CXCR3 Axis: Role in Inflammatory Bowel Disease and its Therapeutic Implication (2007)

There is a great need for new intervention and prevention strategies against Crohn's disease (CD), a chronic, relapsing tissue-destructive inflammatory bowel disease (IBD). Estimates indicate more than 1 million cases of IBD in the United States occur annually, with 50% involving CD. The clinical features of CD correlate with certain mouse models of colitis, including the spontaneous colitis observed in interleukin-10 deficient (IL-10(-/-)), senescence accelerated mice (SAMP1/Yit) and trinitrobenzene sulfonic acid (TNBS)-treated mice. Chemokines undoubtedly play a pivotal role in the regulation (i.e., initiation, maintenance, and suppression) of mucosal inflammation and tissue destruction. A number of key advances have led to greater understanding of the steps responsible for colitis and the roles played by chemokines. In fact, CXCR3 and the ligands for this chemokine receptor, monokine-induced by interferon-gamma (IFN-gamma) (MIG/CXCL9), IFN-gamma-inducible 10 kDa protein (IP-10/CXCL10), and IFN-gamma-inducible T cell alpha-chemoattractant (I-TAC/CXCL11) are differentially expressed at sites of colitis in IL-10(-/-) mice and in clinical cases of CD. While we have demonstrated that antibodies directed against CXCL10 could both prevent the onset and cure of pre-existing colitis in IL-10(-/-) mice, studies by other investigators have shown the efficacy of CXCR3 blockade to mitigate colitis and other inflammatory diseases. This review describes the hallmarks of IBD, CXCL9-11, and CXCR3 expression during murine colitis and IBD, gives an overview of the antagonist therapies targeting the CXCR3 axis, details current and pending bio-therapies for IBD, and discusses what is known about the cellular and CXCR3-mediated mechanisms of colitis.
Biologic TNFα-inhibitors that cross the human blood-brain barrier (2010)

Tumor necrosis factor (TNF)α inhibitors (TNFI) are a major class of biologic therapeutics, and include decoy receptor and monoclonal antibody (MAb) therapeutics that block TNFα action. TNFα is a pro-inflammatory cytokine in brain disease, such as stroke, brain or spinal cord injury, or Alzheimer disease. However, the biologic TNFIs cannot be developed for the brain, because these large molecules do not cross the blood-brain barrier (BBB). Brain penetrating forms of TNFα decoy receptors or anti-TNFα antibody therapeutics can be re-engineered as IgG fusion proteins with a BBB molecular Trojan horse, such as the mAb against the human insulin receptor (HIR). The HIRMAb undergoes receptor-mediated transport across the BBB via the endogenous insulin receptor, and carries into brain the fused biologic TNFI. A fusion protein of the HIRMAb and the type II TNF receptor (TNFR) extracellular domain, designated the HIRMAb-TNFR fusion protein, has been engineered and expressed in stably transfected Chinese hamster ovary (CHO) cells. The HIRMAb-TNFR fusion protein binds both the HIR and TNFα with low nM affinity. The HIRMAb cross reacts with the Rhesus monkey insulin receptor, and the HIRMAb-TNFR is rapidly, and selectively, taken up by primate brain at concentrations that inhibit TNFα. In addition, a fusion protein of the HIRMAb and a therapeutic single chain Fv (ScFv) antibody has been engineered and also expressed in stably transfected CHO cells. The BBB molecular Trojan horse platform technology allows for the engineering of brain-penetrating recombinant proteins as new biologic therapeutics for the human brain.
Scheme for ranking potential HLA-A2 binding peptides based on independent binding of individual peptide side-chains. (1994)

A method to predict the relative binding strengths of all possible nonapeptides to the MHC class I molecule HLA-A2 has been developed based on experimental peptide binding data. These data indicate that, for most peptides, each side-chain of the peptide contributes a certain amount to the stability of the HLA-A2 complex that is independent of the sequence of the peptide. To quantify these contributions, the binding data from a set of 154 peptides were combined together to generate a table containing 180 coefficients (20 amino acids x 9 positions), each of which represents the contribution of one particular amino acid residue at a specified position within the peptide to binding to HLA-A2. Eighty peptides formed stable HLA-A2 complexes, as assessed by measuring the rate of dissociation of beta 2m. The remaining 74 peptides formed complexes that had a half-life of beta 2m dissociation of less than 5 min at 37 degrees C, or did not bind to HLA-A2, and were included because they could be used to constrain the values of some of the coefficients. The "theoretical" binding stability (calculated by multiplying together the corresponding coefficients) matched the experimental binding stability to within a factor of 5. The coefficients were then used to calculate the theoretical binding stability for all the previously identified self or antigenic nonamer peptides known to bind to HLA-A2. The binding stability for all other nonamer peptides that could be generated from the proteins from which these peptides were derived was also predicted. In every case, the previously described HLA-A2 binding peptides were ranked in the top 2% of all possible nonamers for each source protein. Therefore, most biologically relevant nonamer peptides should be identifiable using the table of coefficients. We conclude that the side-chains of most nonamer peptides to the first approximation bind independently of one another to the HLA-A2 molecule.
Tyrosine kinase activation provides an early and requisite signal for Fas-induced apoptosis. (1994)

Selective cell death plays a critical role in the development of the immune repertoire and in the elimination of target cells expressing foreign Ags. The apoptosis induced by ligation of the Fas Ag, a member of the TNFR/nerve growth factor receptor superfamily, contributes to both of these modes of cell loss. However, in spite of the molecular cloning of the Fas Ag and the identification of a specific cytoplasmic domain required for its function, it remains unclear as to which Fas-induced second messengers mediate the development of programmed cell death. We, therefore, evaluated Fas-initiated signal transduction in susceptible cell types. We determined that Fas ligation induces the rapid tyrosine phosphorylation of multiple cellular proteins. These phosphorylation events occur within 1 min and decline toward baseline by 30 min. In addition, Fas ligation increases the in vitro protein kinase activity of the tyrosine phosphorylated proteins. Pharmacologic inhibitors of protein tyrosine kinases block, in a concentration-dependent manner, Fas-induced DNA fragmentation and prolong cell survival. These results suggest that protein tyrosine kinase activation is an early and obligatory signal in Fas-induced apoptosis.
A microfluidic droplet generator based on a piezoelectric actuator (2008)

Droplet based microfluidic systems have been shown to be most valuable in biology and chemistry research. However droplet modulation and manipulation requires still further improvement in order to make this technology feasible particularly for biological applications. On demand generation of droplets and droplet synchronization, which is crucial for coalescence, remain largely unanswered. The present study describes a simple and robust droplet generator based on a piezoelectric actuator which is integrated into a microfluidic device. The droplet generator is able to independently control the droplet size, rate of formation and distance between droplets. Moreover, the droplet uniformity is especially high, deviating from the mean value by less than 0.3%. The cross flow and T-junction configurations are tested and show no significant differences, yet the inlet to main channel ratio is found to be important. As this ratio increases, droplets tend to be generated in bursts instead of individually. The physical mechanisms involved are discussed, providing insight into optimized design of such systems.
Pictorial deduction in spatial information systems (2002)

Though visual access to spatial database systems has attracted much attention in recent years, only few deductive visual languages for spatial information systems have been proposed. One reason for this may be that most of the spatial visual languages stick to the classical metaphor of map manipulation. We argue that more powerful metaphors are needed to facilitate the development of pictorial languages for spatial deduction that are readily comprehensible and formally manageable at the same time. This paper introduces a fully deductive pictorial language for spatial information based on sketching.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Serum microRNA profiling and breast cancer risk: the use of miR-484/191 as endogenous controls (2012)

It has been demonstrated that there are abundant stable microRNAs (miRNAs) in plasma/serum, which can be detected and are potentially disease specific. However, the lack of suitable endogenous controls for serum miRNA detection is the restriction for the widely usage of this kind of biomarkers and for the between-laboratory comparison of the findings. We first systematically screened for endogenous control miRNAs (ECMs) by testing 10 pooling samples (using both Solexa sequencing and TaqMan low density array) and 50 individual samples (using quantitative reverse transcription-PCR) of different cancer traits and healthy controls. Then we assessed serum miRNAs used as potential biomarkers for breast cancer risk prediction based on a two-stage case-control analysis, including 48 breast cancer patients and 48 controls for the discovery stage and 76 breast cancer patients and 76 controls for validation. We identified two candidate ECMs (miRNA-191 and miRNA-484). Normalized by the two ECMs, we found four miRNAs (miR-16, miR-25, miR-222 and miR-324-3p) that were consistently differentially expressed between breast cancer cases and controls. The area under the receiver operating characteristic curve is 0.954 for the four-miRNA signature in the discovery stage (sensitivity = 0.917 and specificity = 0.896) and 0.928 in the validation stage (sensitivity = 0.921 and specificity = 0.934). In conclusion, the four-miRNA signature from serum may serve as a non-invasive prediction biomarker for breast cancer. Furthermore, we proposed the combination of miRNA-484 and miRNA-191 as endogenous control for serum miRNA detection, at least for most common cancers.
Comparison between an image reconstruction method of filtering backprojection and the filtered backprojection method (1988)

An image reconstruction method of filtering backprojection is compared with the filtered backprojection method for cases with and without Poisson (signal-dependent) noise in the projection data. The case with noise is especially interesting since the result reveals the noise sensitivity of the two methods. The former method filters in the spatial frequency domain, whereas the latter method works in the space domain. The computer experiment shows that the two methods produce nearly the same qualitative results for both cases and are approximately equal in noise sensitivity.
“On‐off” phenomenon with levodopa therapy in parkinsonism (1974)

Five parkinsonian patients with severe “on-off” effects from levodopa therapy also were given combination carbidopa/levodopa. Serial half-hourly measurements of plasma levels of dopa, 3-O-methyldopa, and homovanillic acid showed partial concordance between clinical fluctuation and plasma dopa levels in patients receiving levodopa alone or in combination with carbidopa. The combination therapy does not lessen “on-off” effects except when administered in greater and more-frequent doses, which are permitted by the improved gastrointestinal tolerance with carbidopa/levodopa. A single intramuscular injection of pyridoxine has no clinical effect and slightly lowers subsequent plasma dopa only in the absence of carbidopa. Possible biochemical mechanisms are discussed.
The Development of Social Behavior Following Neonatal Amygdala Lesions in Rhesus Monkeys (2004)

We examined the role of the amygdala in the development of nonhuman primate social behavior. Twenty-four rhesus monkeys received bilateral ibotenic acid lesions of either the amygdala or the hippocampus or received a sham surgical procedure at 2 weeks of age. Subjects were reared with their mothers and were provided daily access to social rearing cohorts. The subjects were weaned at 6 months of age and then observed while paired with familiar conspecifics at 6 and 9 months of age and with unfamiliar conspecifics at 1 year of age. The subjects were also observed during daily cohort socialization periods. Neither amygdala nor hippocampus lesions altered fundamental aspects of social behavior development. All subjects, regardless of lesion condition, developed a species-typical repertoire of social behavior and displayed interest in conspecifics during social encounters. The amygdala lesions, however, clearly affected behaviors related to fear processing. The amygdala-lesioned subjects produced more fear behaviors during social encounters than did control or hippocampus-lesioned subjects. Although the heightened fear response of the amygdala-lesioned subjects was consistent across different testing paradigms and was observed with both familiar and novel partners, it did not preclude social interactions. In fact, the amygdala-lesioned subjects displayed particular social behaviors, such as following, cooing, grunting, presenting to be groomed, and presenting to be mounted more frequently than either control or hippocampus-lesioned subjects. These findings are consistent with the view that the amygdala is not needed to develop fundamental aspects of social behavior and may be more related to the detection and avoidance of environmental dangers.
Tunable Optical Frequency Comb with a Crystalline Whispering Gallery Mode Resonator (2008)

We report on the experimental demonstration of a tunable monolithic optical frequency comb generator. The device is based on four-wave mixing in a crystalline calcium fluoride whispering gallery mode resonator. The frequency spacing of the comb is given by an integer number of the free spectral range of the resonator. We select the desired number by tuning the frequency of the pumping laser with respect to the corresponding resonator mode. We also observe a rich variety of optical combs and high-frequency hyperparametric oscillation, depending on the experimental conditions. A potential application of the comb for generating tunable narrow band frequency microwave signals is demonstrated.
Ordered Mesoporous Silica to Study the Preparation of Ni/SiO2 ex Nitrate Catalysts: Impregnation, Drying, and Thermal Treatments (2008)

In this contribution, we investigated the preparation of Ni/SiO2 catalysts with aqueous [Ni(OH2)6](NO3)2 solutions via the impregnation and drying method using ordered mesoporous silica SBA-15 (mesopore diameter of 9 nm) as model support to study each step in the preparation: impregnation, drying, calcination, and reduction. After impregnation, not all the mesopores of SBA-15 appeared filled with precursor solution. Consecutive drying led to formation of 9 nm Ni3(NO3)2(OH)4 crystallites exclusively within the mesopores. During air calcination, severe sintering and redistribution took place, resulting in a low NiO dispersion, including large NiO crystals outside of the mesopores and rodlike NiO particles inside the mesopores. The degree of sintering depended on the concentration of Ni3(NO3)2(OH)4 decomposition products (NO2, N2O, O2 and H2O), and in particular NO2 and O2 were found to promote sintering and redistribution. Therefore, maintaining low concentrations of the latter components during the thermal nitrate decomposition is advocated, which was achieved by carrying out the treatment in the presence of H2. The latter treatment prevented formation of NO2/O2 as decomposition products, moderated the decomposition rate of Ni3(NO3)2(OH)4 into NiO as observed from in situ XRD experiments, and led to NiO particles of 3 nm on average at a loading of 20 wt % Ni/SiO2.
Beyond the Gene (2007)

This paper is a response to the increasing difficulty biologists find in agreeing upon a definition of the gene, and indeed, the increasing disarray in which that concept finds itself. After briefly reviewing these problems, we propose an alternative to both the concept and the word gene-an alternative that, like the gene, is intended to capture the essence of inheritance, but which is both richer and more expressive. It is also clearer in its separation of what the organism statically is (what it tangibly inherits) and what it dynamically does (its functionality and behavior). Our proposal of a genetic functor, or genitor, is a sweeping extension of the classical genotype/phenotype paradigm, yet it appears to be faithful to the findings of contemporary biology, encompassing many of the recently emerging-and surprisingly complex-links between structure and functionality.
Clinical, Cognitive, and Neurophysiologic Correlates of Short-Term Treatment with Carbamazepine, Oxcarbazepine, and Levetiracetam in Healthy Volunteers (2004)

After short-term treatment in healthy volunteers, carbamazepine induced major clinical and neurophysiologic changes. Oxcarbazepine was better tolerated than carbamazepine. Levetiracetam interfered least with clinical and neurophysiologic test results.
Mutations in the spliceosome machinery, a novel and ubiquitous pathway in leukemogenesis (2012)

Myelodysplastic syndromes (MDSs) are chronic and often progressive myeloid neoplasms associated with remarkable heterogeneity in the histomorphology and clinical course. Various somatic mutations are involved in the pathogenesis of MDS. Recently, mutations in a gene encoding a spliceosomal protein, SF3B1, were discovered in a distinct form of MDS with ring sideroblasts. Whole exome sequencing of 15 patients with myeloid neoplasms was performed, and somatic mutations in spliceosomal genes were identified. Sanger sequencing of 310 patients was performed to assess phenotype/genotype associations. To determine the functional effect of spliceosomal mutations, we evaluated pre-mRNA splicing profiles by RNA deep sequencing. We identified additional somatic mutations in spliceosomal genes, including SF3B1, U2AF1, and SRSF2. These mutations alter pre-mRNA splicing patterns. SF3B1 mutations are prevalent in low-risk MDS with ring sideroblasts, whereas U2AF1 and SRSF2 mutations are frequent in chronic myelomonocytic leukemia and advanced forms of MDS. SF3B1 mutations are associated with a favorable prognosis, whereas U2AF1 and SRSF2 mutations are predictive for shorter survival. Mutations affecting spliceosomal genes that result in defective splicing are a new leukemogenic pathway. Spliceosomal genes are probably tumor suppressors, and their mutations may constitute diagnostic biomarkers that could potentially serve as therapeutic targets.