Miracle-dz/UniFAR-FTUs huggingface dataset:
Evidence for postsynaptic mediation of the hypothermic effect of 5‐HT1A receptor activation

1 The 5‐HT1A ligand BMY 7378 (8‐[2[4‐(2‐methoxyphenyl)‐1‐piperazinyl]ethyl]8‐azaspirol [4,5]‐decane‐7,9‐dione dihydrochloride, 0.032–2 mg kg−1, s.c. ) caused hyperphagia, a response to the activation of presynaptic 5‐HT1A receptors. 2 BMY 7378 (8 mg kg−1, s.c.) and the 5‐HT1A agonist (8‐hydroxy‐2‐(di‐n‐propylamino) tetralin (8‐OH‐DPAT), 0.10 and 0.25 mg kg−1 s.c. ) also caused hypothermia. This was inhibited by (−)‐pindolol (1 mg kg−1, i.p.) and not prevented by pretreatments with p‐chlorophenylalanine which grossly depleted 5‐hydroxytryptamine (5‐HT) from terminal regions. The hypothermic effects are explicable by activation of postsynaptic 5‐HT1A receptors. Infusion of BMY 7378 (8–64 μg) into the dorsal raphe was without convincing hypothermic effect. 3 BMY 7378 (8 mg kg−1, s.c.) inhibited another effect of activation of postsynaptic 5‐HT1A receptors, i.e., the induction of components of the 5‐HT syndrome by 8‐OH‐DPAT (0.5, 1.0 mg kg−1, s.c.) which suggests that BMY 7378 has antagonistic as well as agonistic effects at these sites. 4 Partial agonist properties of BMY 7378 at postsynaptic sites were also indicated by doses for hypothermia being much greater than those for hyperphagia i.e., ED50 (hypothermia) > 2 mg kg−1, ED50 (hyperphagia) = 0.010 mg kg−1. This contrasts with the similar ED50 values for both the hypothermic (ED50 = 0.08–0.10 mg kg−1) and hyperphagic (ED50 = 0.06–0.10 mg kg−1) effects of 8‐OH‐DPAT. 5 The evidence obtained for mediation of the hypothermic response to 5‐HT1A agonists by postsynaptic sites is relevant to the interpretation of the effects on it of antidepressant treatments and depressive illness.
Gene silencing of the BDNF/TrkB axis in multiple myeloma blocks bone destruction and tumor burden in vitro and in vivo

Osteolytic bone diseases are a prominent feature of multiple myeloma (MM), resulting from aberrant osteoclastic bone resorption that is uncoupled from osteoblastic bone formation. Myeloma stimulates osteoclastogenesis, which is largely dependent on an increase in receptor activator of NF‐κB ligand (RANKL) and a decrease in osteoprotegerin (OPG) within the bone marrow milieu. Recently, brain‐derived neurotrophic factor (BDNF) was identified as a MM‐derived factor that correlates with increased RANKL levels and contributes to osteolytic bone destruction in myeloma patients. Because tyrosine receptor kinase B (TrkB), the receptor of BDNF, is abundantly expressed in osteoblasts, we sought to evaluate the role of BDNF/TrkB in myeloma–osteoblast interactions and the effect of this pathway on the RANKL/OPG ratio and osteoclastogenesis. Coculture systems constructed with noncontact transwells revealed that, in vitro, MM‐derived BDNF increased RANKL and decreased OPG production in osteoblasts in a time‐ and dose‐dependent manner. These effects were completely abolished by a specific small interfering RNA for TrkB. BDNF regulates RANKL/OPG expression in osteoblasts through the TrkB/ERK pathway. To investigate the biological effects of BDNF on myeloma in vivo, a SCID‐RPMI8226 mice model was constructed using lentiviral short hairpin RNA‐transfected RPMI8226 cells. In this system, stable knockdown of BDNF in MM cells significantly restored the RANKL/OPG homostasis, inhibited osteolytic bone destruction and reduced angiogenesis and tumor burden. Our studies provide further support for the potential osteoclastogenic effects of BDNF, which mediates stroma–myeloma interactions to disrupt the balance of RANKL/OPG expression, ultimately increasing osteoclastogenesis in MM.
Membrane Recycling in the Neuronal Growth Cone Revealed by FM1–43 Labeling

Membrane dynamics within the chick ciliary neuronal growth cone were investigated by using the membrane-impermeant dye FM1–43. A depolarization-evoked endocytosis was observed that shared many properties with the synaptic vesicle recycling previously described at the presynaptic terminal. In addition, in the absence of depolarization a basal level of constitutive endocytotic activity was observed at ∼30% of the rate of evoked endocytosis. This constitutive endocytosis accounted for large amounts of membrane retrieval: the equivalent of the entire growth cone surface area could be internalized within a 30 min period. Endosomes generated via constitutive and evoked processes were highly mobile and could move considerable distances both within the growth cone and out to the neurite. In addition to their different requirements for formation, evoked and constitutive endosomes displayed a significant difference in release properties. After a subsequent depolarization of labeled growth cones, evoked endosomes were released although constitutive endosomes were not released. Furthermore, treatment with latrotoxin released evoked endosomes, but not constitutive endosomes. Although the properties of evoked endosomes are highly reminiscent of synaptic vesicles, constitutive endosomes appear to be a separate pool resulting from a distinct and highly active process within the neuronal growth cone.
Prognostic Implications of Extracapsular Extension of Pelvic Lymph Node Metastases in Urothelial Carcinoma of the Bladder

To determine whether extracapsular extension of pelvic lymph node metastases from urothelial carcinoma of the bladder is of prognostic significance. From a consecutive series of 507 patients with urothelial carcinoma of the bladder preoperatively staged N0M0, 101 of 124 patients with lymph node metastases detected on histologic examination fulfilled the inclusion criteria for this study and were evaluated. All underwent radical cystectomy between 1985 and 2000 with standardized extended bilateral pelvic lymphadenectomy in curative intent and were prospectively followed for recurrence-free (RFS) and overall (OS) survival. Staging was done according to UICC 2002. A total of 2375 lymph nodes were examined. The median number of nodes examined per patient was 22 (range, 10-43). The median number of positive nodes was 2 (range, 1-24). Median RFS and OS were 17 and 21 months (range for both, 1-191), respectively. The 5-year RFS and OS rates were 32% and 30%, respectively. There were 59 patients (58%) with extracapsular extension of lymph node metastases. They had a significantly decreased RFS (median, 12 vs. 60 months, P = 0.0003) and OS (median, 16 vs. 60 months, P < 0.0001) compared with those with intranodal metastases. There were no significant differences in survival between pN1 and pN2 categories with extracapsular extension of the lymph node metastases (RFS, P = 0.70; OS, P = 0.65) or those without extension (RFS, P = 0.47; OS, P = 0.34). On a multivariate analysis, extracapsular extension of lymph node metastases was the strongest negative predictor for RFS. Meticulous lymph node resection and subsequent thorough histologic examination in patients undergoing radical cystectomy for bladder cancer reveals a high incidence of lymph node-positive disease (24%) despite negative preoperative staging. Lymph node metastases with extracapsular extension in pN1 and pN2 stages carry a very poor prognosis. Therefore, this feature should be used to designate a separate pN category in the staging system. The discrimination of pN1/pN2 in the UICC 2002 classification seems to be arbitrary and of no significant prognostic relevance.
A Multiple Inlet Swirler for Gas Turbine Combustors

The central recirculation zone (CRZ) in a swirl stabilized gas turbine combustor has a dominant effect on the fuel air mixing process and flame stability. Most of state of the art swirlers share one disadvantage; the fixed swirl number for the same swirler configuration. Thus, in a mathematical sense, Reynolds number becomes the sole parameter for controlling the flow characteristics inside the combustor. As a result, at low load operation, the generated swirl is more likely to become feeble affecting the flame stabilization and mixing process. This paper introduces a new swirler concept which overcomes the mentioned weakness of the modern configurations. The new swirler introduces air tangentially and axially to the combustor through tangential vanes and an axial vanes respectively. Therefore, it provides different swirl numbers for the same configuration by regulating the ratio between the axial and tangential flow momenta. The swirler aerodynamic performance was investigated using four CFD simulations in order to demonstrate the impact of tangential to axial flow rate ratio on the CRZ. It was found that the length of the CRZ is directly proportional to the tangential to axial air flow rate ratio.
A Correlation of Cervical Magnetic Resonance Imaging and Discography/Computed Tomographic Discograms

Study Design The morphology of sagittal T2-weighted magnetic resonance imaging (MRI) of the cervical spine was correlated with provocative discography and subsequent computed tomography (CT) discograms in 52 patients with discogenic pain. Objectives The authors determined if the morphology of cervical spine discs, as seen on MRI, correlates with discography/CT discograms in patients with discogenic pathology. Summary of Background Data Several studies have demonstrated a correlation between MRI and discography in the lumbar spine. No studies have attempted to show if this relationship exists in the cervical spine region. Methods The morphology of cervical T2-weighted MRI was characterized with regard to the disc nuclear signal and posterior anulus status. Provocative discography was evaluated with regard to positive or negative responses. Computed tomography was performed after discography on each patient. Results There was no correlation between pain response or morphology as seen on either discography or CT discography. A significant correlation was found between abnormality as seen on MRI and pain response on discography but the false-positive and false-negative rates were high. Conclusion Our results suggest that several MRI patterns correlate well with positive or negative cervical discography responses while several other patterns are equivocal. Magnetic resonance imaging is a useful adjunct to cervical discography but there are some MRI patterns that cannot be considered pathologic, and discography is required to diagnose discogenic pain syndrome.
Bragg gratings based on long-range surface plasmon-polariton waveguides: comparison of theory and experiment

Measured optical spectra are presented for a family of third-order uniform step-in-width Bragg gratings operating in the long-range surface plasmon-polariton mode supported by thin finite-width Au films in a homogeneous dielectric background. The spectra are compared quantitatively with theoretical predictions generated by a model proposed for the gratings. Physical measurements of critical features achieved on-wafer have been made and the results used in the theoretical model. The measured and modeled results are generally in good agreement. The largest reflectance measured among the set of gratings characterized is 47.4%, the bandwidths (full width at half maximum) measured range from 0.2 to 0.4 nm, and the measured Bragg wavelengths coincide to 1544.2 nm for all of the gratings.
An Experimental Study of Scale-up, Oxidant, and Response Characteristics in PEM Fuel Cells

It is important for fuel cell to become flexible in order to accommodate the situations of application areas for reducing costs and expanding coverage. Scale ups in series and parallel to 1-kW class proton exchange membrane (PEM) fuel cell stack are characterized experimentally with oxidant as air and oxygen. Through a serial scaled-up 4-cell stack with an active area of 25 cm<sup>2</sup> and a parallel scaled-up single cell with an active area of 100 cm<sup>2</sup>, respectively, the 1-kW class 20-cell stack with an active area of 150 cm<sup>2</sup> per cell is scaled up from the basic unit cell with maintaining their performances. The polarization and power curves of the 1-kW class PEM fuel cell stack with the reactants H<sub>2</sub>/air and H<sub>2</sub>/O<sub>2</sub> are evaluated. Sufficient power of the PEM fuel cell can operate at flexible nominal current of 40-80 A and nominal voltage of 12-15 V for providing durability and balance between cells. The 1-kW class PEM fuel cell stack is characterized through the comparison of cell voltage differences utilizing H<sub>2</sub>/air and H<sub>2</sub>/O<sub>2</sub>. Both cell voltages with H<sub>2</sub>/air and H<sub>2</sub>/O<sub>2</sub> follow well the one-twentieth of the responding stack voltages with the small difference.
Stimulation of Vascular Glycosaminoglycan Synthesis by Subpressor Angiotensin II in Rats

The vascular trophic effects of angiotensin II (Ang II) in small doses may precede its hypertension-producing effect, and de novo synthesis of components of extracellular matrix may be a requirement for Ang II-stimulated growth. In the present study, therefore, the incorporation of 35SC4 into glycosaminoglycans (synthesis) of aorta and bladder wall of young adult, male Sprague-Dawley rats was measured ex vivo after 48 hours of Ang II administration at two dose levels, 100 and 200 ng · kg−1 · min−1 IP. Vehicle-infused rats served as controls. Compared with controls, systolic blood pressure was unchanged in rats receiving 100 ng · kg−1 · min−1 Ang II and rose by 13 mm Hg (P<.05) in rats receiving the 200- ng · kg−1 · rain−1 dose. In Ang II-treated rats, glycosaminoglycan synthesis of the aorta was increased by 20% (P<.05) and 52% (p<.005) at the two dose levels, respectively. Glycosaminoglycan synthesis of bladder smooth muscle was also increased in Ang II-treated rats (P<.01), but the response was not dose dependent. By 7 to 10 days of Ang II administration (200 ng · kg−1 · min−1), glycosaminoglycan synthesis of aorta returned toward baseline (P<.10, >.05). The rate of synthesis of subtypes of glycosaminogrycans in the aorta was proportionately increased by Ang II. The early occurrence, magnitude, and arterial pressure independence of Ang H-induced glycosaminoglycan synthesis suggest that restructuring of extracellular matrix may play an important role in both the trophic and hypertension-producing action of Ang II.
System Design for a Long-Line Quantum Repeater

We present a new control algorithm and system design for a network of quantum repeaters, and outline the end-to-end protocol architecture. Such a network will create long-distance quantum states, supporting quantum key distribution as well as distributed quantum computation. Quantum repeaters improve the reduction of quantum-communication throughput with distance from exponential to polynomial. Because a quantum state cannot be copied, a quantum repeater is not a signal amplifier. Rather, it executes algorithms for quantum teleportation in conjunction with a specialized type of quantum error correction called purification to raise the fidelity of the quantum states. We introduce our banded purification scheme, which is especially effective when the fidelity of coupled qubits is low, improving the prospects for experimental realization of such systems. The resulting throughput is calculated via detailed simulations of a long line composed of shorter hops. Our algorithmic improvements increase throughput by a factor of up to 50 compared to earlier approaches, for a broad range of physical characteristics.
A simple characterization of Du Bois singularities

We prove the following theorem characterizing Du Bois singularities. Suppose that $Y$ is smooth and that $X$ is a reduced closed subscheme. Let $\pi : \tilde{Y} \rightarrow Y$ be a log resolution of $X$ in $Y$ that is an isomorphism outside of $X$. If $E$ is the reduced pre-image of $X$ in $\tilde{Y}$, then $X$ has Du Bois singularities if and only if the natural map $\mathcal{O}_X \rightarrow R \pi_* \mathcal{O}_E$ is a quasi-isomorphism. We also deduce Kollár's conjecture that log canonical singularities are Du Bois in the special case of a local complete intersection and prove other results related to adjunction.
Improving Hypernymy Detection with an Integrated Path-based and Distributional Method

Detecting hypernymy relations is a key task in NLP, which is addressed in the literature using two complementary approaches. Distributional methods, whose supervised variants are the current best performers, and path-based methods, which received less research attention. We suggest an improved path-based algorithm, in which the dependency paths are encoded using a recurrent neural network, that achieves results comparable to distributional methods. We then extend the approach to integrate both path-based and distributional signals, significantly improving upon the state-of-the-art on this task.
Antihyperlipidemic activities of Pleurotus ferulae on biochemical and histological function in hypercholesterolemic rats

BACKGROUND: Pleurotus ferulae is an edible mushroom has been widely used for nutritional and medicinal purposes. Irrespective of the medicinal importance or therapeutic potentials of P. ferulae, there have not been studies on anti-hyperlipidemic properties. Therefore, the present study investigates the effects of dietary P. ferulae fruiting bodies on plasma and feces biochemical and on the liver histological status in hypercholesterolemic rats. METHODS: Six weeks old female Sprague-Dawley albino rats were divided into three groups of 10 rats each. Then biochemical and histological examinations were performed. RESULTS: Feeding of a diet containing 5% P. ferulae fruiting bodies to hypercholesterolemic rat reduced plasma total cholesterol, triglyceride, low-density lipoprotein (LDL), total lipid, phospholipids, and LDL/high-density lipoprotein ratio by 30.02, 49.31, 71.15, 30.23, 21.93, and 65.31%, respectively. Mushroom also significantly reduced body weight in hypercholesterolemic rats. However, it had no adverse effects on plasma albumin, total bilirubin, direct bilirubin, creatinin, blood urea nitrogen, uric acid, glucose, total protein, calcium, sodium, potassium, chloride, inorganic phosphate, magnesium, and enzyme profiles. Feeding mushroom increased total lipid and cholesterol excretion in feces. The plasma lipoprotein fraction, separated by agarose gel electrophoresis, indicated that P. ferulae significantly reduced plasma β and pre-β-lipoprotein, while increased the α-lipoprotein. A histological study of hepatic cells by conventional hematoxylin-eosin and oil red O staining showed normal findings for mushroom-fed hypercholesterolemic rats. CONCLUSIONS: The present study suggests that 5% P. ferulae diet supplement provides health benefits, at least partially, by acting on the atherogenic lipid profile in hypercholesterolemic rats.
Ebola hemorrhagic Fever: novel biomarker correlates of clinical outcome.

BACKGROUND Ebola hemorrhagic fever (EHF) outbreaks occur sporadically in Africa and result in high rates of death. The 2000-2001 outbreak of Sudan virus-associated EHF in the Gulu district of Uganda led to 425 cases, of which 216 were laboratory confirmed, making it the largest EHF outbreak on record. Serum specimens from this outbreak had been preserved in liquid nitrogen from the time of collection and were available for analysis. METHODS Available samples were tested using a series of multiplex assays to measure the concentrations of 55 biomarkers. The data were analyzed to identify statistically significant associations between the tested biomarkers and hemorrhagic manifestations, viremia, and/or death. RESULTS Death, hemorrhage, and viremia were independently associated with elevated levels of several chemokines and cytokines. Death and hemorrhage were associated with elevated thrombomodulin and ferritin levels. Hemorrhage was also associated with elevated levels of soluble intracellular adhesion molecule. Viremia was independently associated with elevated levels of tissue factor and tissue plasminogen activator. Finally, samples from nonfatal cases had higher levels of sCD40L. CONCLUSIONS These novel associations provide a better understanding of EHF pathophysiology and a starting point for researching new potential targets for therapeutic interventions.
X-ray Investigations of Liquid Water Transport in Polymer Electrolyte Membrane Fuel Cell Gas Diffusion Layers

Understanding the liquid water transport behaviour in a polymer electrolyte membrane (PEM) fuel cell is key to achieving high performance. The gas diffusion layer (GDL) provides transport pathways for electrons, reactant gases, and product water. However, when liquid water accumulates within the pores of the GDL, the effective porosity of the material is decreased, resulting in a reduced effective diffusivity of reactant gases. This can lead to reactant starvation at the catalyst during high current density operation, causing significant efficiency losses. The aim of this thesis is to investigate the impact of the GDL microstructural properties on water transport in an operating fuel cell. Synchrotron X-ray radiography was used as a probing tool for identifying the water distribution in the GDL in situ. The role of the microporous layer (MPL) on liquid water management was identified through investigating in-plane water distribution in the GDL. Nanopores of the MPL reduced the amount and the size of water clusters in the GDL. Next, the influence of MPL thickness on the water accumulation in the GDL was investigated. The application of a thick MPL on the carbon fibre substrate resulted in less water content at the MPL-substrate interface than that in the GDL with a thin MPL. The effect of substrate thickness was also studied in terms of the fuel cell performance and liquid water distribution. The fuel cell incorporating a thin substrate exhibited
KCNE1 Constrains the Voltage Sensor of Kv7.1 K+ Channels

Kv7 potassium channels whose mutations cause cardiovascular and neurological disorders are members of the superfamily of voltage-gated K+ channels, comprising a central pore enclosed by four voltage-sensing domains (VSDs) and sharing a homologous S4 sensor sequence. The Kv7.1 pore-forming subunit can interact with various KCNE auxiliary subunits to form K+ channels with very different gating behaviors. In an attempt to characterize the nature of the promiscuous gating of Kv7.1 channels, we performed a tryptophan-scanning mutagenesis of the S4 sensor and analyzed the mutation-induced perturbations in gating free energy. Perturbing the gating energetics of Kv7.1 bias most of the mutant channels towards the closed state, while fewer mutations stabilize the open state or the inactivated state. In the absence of auxiliary subunits, mutations of specific S4 residues mimic the gating phenotypes produced by co-assembly of Kv7.1 with either KCNE1 or KCNE3. Many S4 perturbations compromise the ability of KCNE1 to properly regulate Kv7.1 channel gating. The tryptophan-induced packing perturbations and cysteine engineering studies in S4 suggest that KCNE1 lodges at the inter-VSD S4-S1 interface between two adjacent subunits, a strategic location to exert its striking action on Kv7.1 gating functions.