gebhart/patrepeval huggingface dataset:
Easy Access to (E,Z)-β-Nitro-α,β-olefinated Hydrazones, 6-Oxo-1,6-dihydropyridazines, and 4-Chloro-1-aminopyrroles by Domino Reactions of 1,2-Diaza-1,3-butadienes with Halogen-Coactivated Methylene or Methine Compounds (1999)

In the presence of a catalytic amount of sodium methoxide, 1-aminocarbonyl-1,2-diaza-1,3-butadienes react with bromonitromethane to give stereoselectively β-nitro-α,β-olefinated hydrazones as E,Z stereoisomers. In the presence of a stoichiometric amount of sodium hydride, the same substrates with dialkyl halomalonates furnish the expected α,β-olefinated hydrazones, and in the presence of a stoichiometric amount of sodium hydroxide, the unexpected dialkyl 3-methyl-6-oxo-1,6-dihydropyridazine-4,5-dicarboxylates are obtained in one pot by a domino process concluding in a [4 + 2] cyclization. α,β-Olefinated hydrazones have been shown to be the possible intermediates in the formation of 1,6-dihydropyridazine derivatives. The domino reaction of 1-aminocarbonyl-1,2-diaza-1,3-butadienes with α,α-dichloroacetophenone produces directly alkyl 4-chloro-2(chloromethyl)-5-phenyl- or alkyl 4-chloro-2(methoxymethyl)-5-phenyl-1H-aminopyrrole-3-carboxylates as a consequence of [3 + 2] cyclization and chlorine transfer.
NRG-1-induced cardiomyocyte hypertrophy. Role of PI-3-kinase, p70S6K, and MEK-MAPK-RSK (1999)

Neuregulins are a family of growth-promoting peptides known to be important in neural and mesenchymal tissue development. Targeted disruption of neuregulin (NRG)-1 or one of two of its cognate receptors, ErbB2 or ErbB4, results in embryonic lethality because of failure of the heart to develop. Although expression of NRGs and their receptors declines after midembryogenesis, both ErbB2 and ErbB4 are present in cardiac myocytes, and NRG-1 expression remains inducible in primary cultures of coronary microvascular endothelial cells from adult rat ventricular muscle. In neonatal rat ventricular myocytes, a soluble NRG-1, recombinant human glial growth factor-2, increased [(3)H]phenylalanine uptake and induced expression of atrial natriuretic factor (ANF) and sarcomeric F-actin polymerization. The effect of NRG-1 on [(3)H]phenylalanine uptake and sarcomeric F-actin polymerization was maximal at 20 ng/ml but declined at higher concentrations. NRG-1 activated p42/p44 mitogen-activated protein kinase (MAPK) [extracellular signal-regulated kinase (ERK)-2/ERK1] and ribosomal S6 kinase (RSK)-2 (90-kDa ribosomal S6 kinase), both of which could be inhibited by the MAPK/ERK kinase-1 antagonist PD-098059. NRG-1 also activated 70-kDa ribosomal S6 kinase, which was inhibited by either rapamycin or wortmannin. Activation of these pathways exhibited the same "biphasic" response to increasing NRG-1 concentrations. Wortmannin and LY-294002 blocked sarcomeric F-actin polymerization but not [(3)H]phenylalanine uptake or ANF expression, whereas PD-098059 consistently blocked both [(3)H]phenylalanine uptake and ANF expression but not actin polymerization. In contrast, rapamycin inhibited [(3)H]phenylalanine uptake and F-actin polymerization but not ANF expression. Thus NRG-ErbB signaling triggers multiple nonredundant pathways in postnatal ventricular myocytes.
POOLING VERSUS MODEL SELECTION FOR NOWCASTING GDP WITH MANY PREDICTORS: EMPIRICAL EVIDENCE FOR SIX INDUSTRIALIZED COUNTRIES (2012)

SUMMARY This paper discusses pooling versus model selection for nowcasting with large datasets in the presence of model uncertainty. In practice, nowcasting a low‐frequency variable with a large number of high‐frequency indicators should account for at least two data irregularities: (i) unbalanced data with missing observations at the end of the sample due to publication delays; and (ii) different sampling frequencies of the data. Two model classes suited in this context are factor models based on large datasets and mixed‐data sampling (MIDAS) regressions with few predictors. The specification of these models requires several choices related to, amongst other things, the factor estimation method and the number of factors, lag length and indicator selection. Thus there are many sources of misspecification when selecting a particular model, and an alternative would be pooling over a large set of different model specifications. We evaluate the relative performance of pooling and model selection for nowcasting quarterly GDP for six large industrialized countries. We find that the nowcast performance of single models varies considerably over time, in line with the forecasting literature. Model selection based on sequential application of information criteria can outperform benchmarks. However, the results highly depend on the selection method chosen. In contrast, pooling of nowcast models provides an overall very stable nowcast performance over time. Copyright © 2012 John Wiley &amp; Sons, Ltd.
Impaired organization and function of myofilaments in single muscle fibers from a mouse model of Pompe disease (2010)

Pompe disease, a deficiency of lysosomal acid alpha-glucosidase, is a disorder of glycogen metabolism that can affect infants, children, or adults. In all forms of the disease, there is progressive muscle pathology leading to premature death. The pathology is characterized by accumulation of glycogen in lysosomes, autophagic buildup, and muscle atrophy. The purpose of the present investigation was to determine if myofibrillar dysfunction in Pompe disease contributes to muscle weakness beyond that attributed to atrophy. The study was performed on isolated myofibers dissected from severely affected fast glycolytic muscle in the alpha-glucosidase knockout mouse model. Psoas muscle fibers were first permeabilized, so that the contractile proteins could be directly relaxed or activated by control of the composition of the bathing solution. When normalized by cross-sectional area, single fibers from knockout mice produced 6.3 N/cm2 of maximum Ca2+-activated tension compared with 12.0 N/cm2 produced by wild-type fibers. The total protein concentration was slightly higher in the knockout mice, but concentrations of the contractile proteins myosin and actin remained unchanged. Structurally, X-ray diffraction showed that the actin and myosin filaments, normally arranged in hexagonal arrays, were disordered in the knockout muscle, and a lower fraction of myosin cross bridges was near the actin filaments in the relaxed muscle. The results are consistent with a disruption of actin and myosin interactions in the knockout muscles, demonstrating that impaired myofibrillar function contributes to weakness in the diseased muscle fibers.
Babinda growers team up with Landcare and Reef Rescue to repair eroded river (2013)

Unmistakable in the crystal-clear brook, a school of black bream (sooty grunter) darts upstream as Steve Destro carefully steers his utility along a headland at the family cane farm on the banks of beautiful Babinda Creek.
Transgenesis for pig models (2016)

Animal models, particularly pigs, have come to play an important role in translational biomedical research. There have been many pig models with genetically modifications via somatic cell nuclear transfer (SCNT). However, because most transgenic pigs have been produced by random integration to date, the necessity for more exact gene-mutated models using recombinase based conditional gene expression like mice has been raised. Currently, advanced genome-editing technologies enable us to generate specific gene-deleted and -inserted pig models. In the future, the development of pig models with gene editing technologies could be a valuable resource for biomedical research.
Type III TGF-β receptor downregulation generates an immunotolerant tumor microenvironment (2013)

Cancers subvert the host immune system to facilitate disease progression. These evolved immunosuppressive mechanisms are also implicated in circumventing immunotherapeutic strategies. Emerging data indicate that local tumor-associated DC populations exhibit tolerogenic features by promoting Treg development; however, the mechanisms by which tumors manipulate DC and Treg function in the tumor microenvironment remain unclear. Type III TGF-β receptor (TGFBR3) and its shed extracellular domain (sTGFBR3) regulate TGF-β signaling and maintain epithelial homeostasis, with loss of TGFBR3 expression promoting progression early in breast cancer development. Using murine models of breast cancer and melanoma, we elucidated a tumor immunoevasion mechanism whereby loss of tumor-expressed TGFBR3/sTGFBR3 enhanced TGF-β signaling within locoregional DC populations and upregulated both the immunoregulatory enzyme indoleamine 2,3-dioxygenase (IDO) in plasmacytoid DCs and the CCL22 chemokine in myeloid DCs. Alterations in these DC populations mediated Treg infiltration and the suppression of antitumor immunity. Our findings provide mechanistic support for using TGF-β inhibitors to enhance the efficacy of tumor immunotherapy, indicate that sTGFBR3 levels could serve as a predictive immunotherapy biomarker, and expand the mechanisms by which TGFBR3 suppresses cancer progression to include effects on the tumor immune microenvironment.
Cytokine release from innate immune cells: association with diverse membrane trafficking pathways (2011)

Cytokines released from innate immune cells play key roles in the regulation of the immune response. These intercellular messengers are the source of soluble regulatory signals that initiate and constrain inflammatory responses to pathogens and injury. Although numerous studies describe detailed signaling pathways induced by cytokines and their specific receptors, there is little information on the mechanisms that control the release of cytokines from different cell types. Indeed, the pathways, molecules, and mechanisms of cytokine release remain a "black box" in immunology. Here, we review research findings and new approaches that have begun to generate information on cytokine trafficking and release by innate immune cells in response to inflammatory or infectious stimuli. Surprisingly complex machinery, multiple organelles, and specialized membrane domains exist in these cells to ensure the selective, temporal, and often polarized release of cytokines in innate immunity.
Prospects of glutamate antagonists in the therapy of Parkinson's disease (1998)

It has been suggested that the excitatory amino acid glutamate, acting as both a neurotoxin and a neurotransmitter, might play a central role in the pathophysiology of Parkinson's disease (PD). Intrinsic energetic defects of the neurons of the substantia nigra pars compacta, the brain area where the degenerative process of PD takes place, may render nigral neurons highly vulnerable to the effects of glutamate, which acts as a neurotoxin in the presence of impaired cellular energy metabolism. Degeneration of dopamine nigral neurons and striatal dopaminergic denervation cause a cascade of functional modifications in the activity of basal ganglia nuclei. Due to the close relationship that links dopaminergic and glutamatergic neurotransmission, glutamate is directly involved in the functional alterations of basal ganglia circuitry that lead to the development of parkinsonian motor symptoms. Drugs counteracting the effects of glutamate might therefore provide new protective and symptomatic strategies for therapy of PD.
Long-term protection of hematopoiesis against the cytotoxic effects of multiple doses of nitrosourea by retrovirus-mediated expression of human O6-alkylguanine-DNA-alkyltransferase (1996)

A human O6-alkylguanine-DNA-alkyltransferase (ATase) cDNA-containing retrovirus was used to infect murine long-term primary bone marrow cultures. High levels of ATase expression were obtained, and colony- forming cells of the granulocyte-macrophage lineage from the cultures transduced with the human ATase retrovirus were three times more resistant to the alkylating agent, N-methyl-N-nitrosourea (MNU), than control cultures. Furthermore, expression of the human ATase protected long-term hematopoiesis, measured as the output of progenitor cells to the nonadherent fraction of the culture, against the cytotoxic effects of repeated exposures to MNU. These results clearly show that a human ATase cDNA-containing retrovirus can be used to infect long-term primary bone marrow cultures and that this attenuates their sensitivity to nitrosoureas.
HLA-B7–Restricted EBV-Specific CD8+ T Cells Are Dysregulated in Multiple Sclerosis (2012)

It was hypothesized that the EBV-specific CD8(+) T cell response may be dysregulated in multiple sclerosis (MS) patients, possibly leading to a suboptimal control of this virus. To examine the CD8(+) T cell response in greater detail, we analyzed the HLA-A2-, HLA-B7-, and HLA-B8-restricted EBV- and CMV-specific CD8(+) T cell responses in a high number of MS patients and control subjects using tetramers. Content in cytolytic granules, as well as cytotoxic activity, of EBV- and CMV-specific CD8(+) T cells was assessed. We found that MS patients had a lower or a higher prevalence of HLA-A2 and HLA-B7, respectively. Using HLA class I tetramers in HLA-B7(+) MS patients, there was a higher prevalence of MS patients with HLA-B*0702/EBV(RPP)-specific CD8(+) T cells ex vivo. However, the magnitude of the HLA-B*0702/EBV(RPP)-specific and HLA-B*0702/CMV(TPR)-specific CD8(+) T cell response (i.e., the percentage of tetramer(+) CD8(+) T cells in a study subject harboring CD8(+) T cells specific for the given epitope) was lower in MS patients. No differences were found using other tetramers. After stimulation with the HLA-B*0702/EBV(RPP) peptide, the production of IL-2, perforin, and granzyme B and the cytotoxicity of HLA-B*0702/EBV(RPP)-specific CD8(+) T cells were decreased. Altogether, our findings suggest that the HLA-B*0702-restricted viral (in particular the EBV one)-specific CD8(+) T cell response is dysregulated in MS patients. This observation is particularly interesting knowing that the HLA-B7 allele is more frequently expressed in MS patients and considering that EBV is associated with MS.
A 20Gb/s NRZ/PAM-4 1V transmitter in 40nm CMOS driving a Si-photonic modulator in 0.13µm CMOS (2013)

The need for more bandwidth driven by streaming video and other data intensive applications has been steadily pushing the optical link speed to the 40G/100G domain. Compared to VCSEL and ring resonator, Mach-Zehnder Interferometer (MZI) is the best solution for long distance (>500m), high data rate (>28Gb/s) optical communications [1–3]. However, high power consumption, low link density and high cost seriously prevent traditional MZI from being the next generation of optical link technology. To fundamentally reduce the cost of MZI, it is highly desirable to make the process CMOS compatible with high efficiency, thus the modulation voltage, size, and power can be reduced to a level where advanced sub-1V CMOS circuits can be used as the driver. This paper presents two CMOS-MZI-based optical transmitters, NRZ or configurable PAM-N (N = 4,16), featuring 20Gb/s data rate and sub-pJ/bit modulation energy (PAM-4) using a 1V supply. The fully CMOS compatible photonic device is highly cost-effective in terms of integration, manufacturability and scalability.
Changes in secondary metabolism and deposition of an unusual lignin in the ref8 mutant of Arabidopsis (2002)

The end products of the phenylpropanoid pathway play important roles in plant structure and development, as well as in plant defense mechanisms against biotic and abiotic stresses. From a human perspective, phenylpropanoid pathway-derived metabolites influence both human health and the potential utility of plants in agricultural contexts. The last known enzyme of the phenylpropanoid pathway that has not been characterized is p-coumarate 3-hydroxylase (C3H). By screening for plants that fail to accumulate soluble fluorescent phenylpropanoid secondary metabolites, we have identified a number of Arabidopsis mutants that display a reduced epidermal fluorescence (ref) phenotype. We have now shown that the ref8 mutant is defective in the gene encoding C3H. Phenotypic characterization of the ref8 mutant has revealed that the lack of C3H activity in the mutant leads to diverse changes in phenylpropanoid metabolism. The ref8 mutant accumulates p-coumarate esters in place of the sinapoylmalate found in wild-type plants. The mutant also deposits a lignin formed primarily from p-coumaryl alcohol, a monomer that is at best a minor component in the lignin of other plants. Finally, the mutant displays developmental defects and is subject to fungal attack, suggesting that phenylpropanoid pathway products downstream of REF8 may be required for normal plant development and disease resistance.
The phosphate recognition site of Escherichia coli maltodextrin phosphorylase (1991)

The role of two positively charged amino acid residues located at the active site of Escherichia coli maltodextrin phosphorylase was investigated by site-directed mutagenesis. Substitution of Lys539 by an arginine caused a 600-fold reduction, substitution of Arg534 by a glutamine caused an even larger 7000-fold reduction of the catalytic rate while substrate binding remained essentially unaffected. Since the Arg534----Gln exchange reduces the catalytic rate near to inactivity and even the conservative Lys534----Arg exchange caused a marked decrease of activity, the central functional role of both positively charged residues in phosphorylase catalysis anticipated by the crystallographic analysis of the corresponding amino acid residues Arg569 and Lys574 in the catalytic site of phosphorylase b was confirmed.
Basic Relationship between Channel Coherence Time and Beamwidth in Vehicular Channels (2015)

The availability of large bandwidth at millimeter wave (mmWave) frequencies makes mmWave an ideal candidate to realize multi-Gbps data rates. MmWave has been applied to indoor applications (e.g. IEEE 802.11ad), and it is also being considered for cellular. There is not much work, however, in applying mmWave to vehicular channels. This is likely due to the misconception that the Doppler spread will be too high at small mmWave wavelengths, which is true only for omnidirectional communication. In this work, closed form approximate expressions relating the coherence time and beamwidth are derived taking directional communication into account. The result shows that the coherence time increases at least proportional to the inverse of the beamwidth. The derivation also takes the beam misalignment due to receiver movement into account and it can be shown that the optimal beamwidth is non-zero in contrast to models that assume perfect beam pointing.
Liposome contrast agent for CT‐based detection and localization of neoplastic and inflammatory lesions in rabbits: validation with FDG‐PET and histology (2010)

These results demonstrate that liposome-CT can be considered for effective screening of neoplastic and inflammatory diseases, as well as subsequent image-guided biopsy. Moreover, the differential accumulation of the liposomal agent at tumor and inflammatory sites highlights its potential role in increasing the specificity of image-based diagnosis.
Sputum Eosinophilia Predicts Benefit from Prednisone in Smokers with Chronic Obstructive Bronchitis (1998)

A reliable predictor of benefit from corticosteroid treatment in patients with chronic airflow limitation is needed. In a single-blind, sequential crossover trial of placebo and prednisone (30 mg/day) treatment, with each given for 2 wk, we investigated whether an increased proportion of sputum eosinophils (>= 3%) predicts a beneficial effect of prednisone in smokers with severe obstructive bronchitis. Patients were seen before and after each treatment. Clinical measurements were made blind to the laboratory findings and vice-versa. Eighteen of 20 patients completed the study. Eight had sputum eosinophilia and similar clinical and physiologic characteristics to those of 10 patients without a finding of sputum eosinophilia. Only in patients with sputum eosinophilia did prednisone, as compared with placebo, produce a statistically significant and clinically important mean effect on effort dyspnea of 0.8 (95% confidence interval [CI]: 0.3 to 1.2), p = 0.008, and in quality of life of 1.96 (95% CI: 0.5 to 3.3), p = 0.01, associated with a small improvement in FEV1 of 0.11 L (95% CI: - 0.04 to 0.23 L), p = 0.05. In these patients, prednisone also produced a significant decline in the median sputum eosinophil percentage, from 9.7% to 0.5% (p = 0.002), eosinophil cationic protein (ECP), from 6, 000 microgram/L to 1,140 microgram/L (p < 0.001), and fibrinogen, from 25. 3 mg/L to 5.4 mg/L (p < 0.001). These findings indicate that in smokers with severe airflow limitation, sputum eosinophilia predicts a beneficial effect of prednisone treatment. Improvement in FEV1, after prednisone treatment in this population, is small, and may not be appreciated in clinical practice.
Opposite phenotypes of hypomorphic and Y766 phosphorylation site mutations reveal a function for Fgfr1 in anteroposterior patterning of mouse embryos (1998)

Intercellular communication is needed for both the generation of the mesodermal germ layer and its division into distinct subpopulations. To dissect the functions of fibroblast growth factor receptor-1 (FGFR1) during mouse gastrulation as well as to gain insights into its possible roles during later embryonic development, we have introduced specific mutations into the Fgfr1 locus by gene targeting. Our results show functional dominance of one of the receptor isoforms and suggest a function for the autophosphorylation of site Y766 in the negative regulation of FGFR1 activity. Y766F and hypomorphic mutations in Fgfr1 generate opposite phenotypes in terms of homeotic vertebral transformations, suggesting a role for FGFR1 in patterning the embryonic anteriorposterior axis by way of regulation of Hox gene activity.
The cell cycle inhibitor p27 is an independent prognostic marker in small (T1a,b) invasive breast carcinomas. (1997)

Breast carcinomas < or = 1 cm in size (T1a,b) are being detected more frequently as a result of screening. Because traditional prognostic parameters are either lacking (tumor size) or rare (nodal metastases), a marker(s) is needed to identify the subset of patients who could benefit from adjuvant therapy. A retrospective series of 202 patients with stage T1a,b invasive breast carcinomas was evaluated. The clinicopathological features (age, histological grade, extensive in situ carcinoma, hormone receptor status, and nodal metastasis) as well as microvessel density and the expression of c-erb-B2, p53, MIB-1/Ki-67, and cdc25B were assessed. In addition, expression of the cell cycle inhibitor p27 was evaluated. Nineteen patients (18% of patients who had axillary dissection) had locoregional lymph node metastases. Forty-two % of them died of disease (median survival, 112 months), whereas mortality was 11% in node-negative patients (median survival, 168 months; P = 0.0055). Patients with low p27 expression had a median survival of 139 months (17% mortality) versus 174 months (9% mortality) in the group with high p27 expression (P = 0.0233). Lack of p27 was associated with poor prognosis when node-positive patients were excluded (P = 0.0252). Nodal status and low p27 were found to be the only independent prognostic parameters by both univariate and multivariate analysis, with relative risks of dying of disease of 4.9 (P = 0.001) and 3.4 (P = 0.0306), respectively. Assessment of p27, which yields prognostic information in node-negative patients, could be useful to identify patients with small, invasive breast carcinomas who might benefit from adjuvant therapy.