Miracle-dz/UniFAR-FTUs huggingface dataset:
Allosteric Activation of the Follicle-stimulating Hormone (FSH) Receptor by Selective, Nonpeptide Agonists*

The pituitary glycoprotein hormones, luteinizing hormone and follicle-stimulating hormone (FSH), act through their cognate receptors to initiate a series of coordinated physiological events that results in germ cell maturation. Given the importance of FSH in regulating folliculogenesis and fertility, the development of FSH mimetics has been sought to treat infertility. Currently, purified and recombinant human FSH are the only FSH receptor (FSH-R) agonists available for infertility treatment. By screening unbiased combinatorial chemistry libraries, using a cAMP-responsive luciferase reporter assay, we discovered thiazolidinone agonists (EC50's = 20 μm) of the human FSH-R. Subsequent analog library screening and parallel synthesis optimization resulted in the identification of a potent agonist (EC50 = 2 nm) with full efficacy compared with FSH that was FSH-R-selective and -dependent. The compound mediated progesterone production in Y1 cells transfected with the human FSH-R (EC50 = 980 nm) and estradiol production from primary rat ovarian granulosa cells (EC50 = 10.5 nm). This and related compounds did not compete with FSH for binding to the FSH-R. Use of human FSH/thyroid-stimulating hormone (TSH) receptor chimeras suggested a novel mechanism for receptor activation through a binding site independent of the natural hormone binding site. This study is the first report of a high affinity small molecule agonist that activates a glycoprotein hormone receptor through an allosteric mechanism. The small molecule FSH receptor agonists described here could lead to an oral alternative to the current parenteral FSH treatments used clinically to induce ovarian stimulation for both in vivo and in vitro fertilization therapy.
Efficacy and safety of alogliptin in Japanese patients with type 2 diabetes mellitus: a randomized, double-blind, dose-ranging comparison with placebo, followed by a long-term extension study

Abstract Objective: To compare the efficacy and safety of different dosages of alogliptin with that of placebo and voglibose in drug-naïve Japanese patients with type 2 diabetes inadequately controlled by diet and exercise. Research design and methods: In the double-blind, placebo-controlled phase of this two-part study, 480 patients aged ≥20 years with type 2 diabetes mellitus (HbA1c ≥6.9% to <10.4%) were randomized to monotherapy with alogliptin 6.25, 12.5, 25 or 50 mg once daily, placebo, or voglibose 0.2 mg three times daily for a period of 12 weeks. In a subsequent open-label, long-term extension phase, patients continued on the same treatment for an additional 40 weeks (patients in the placebo group were reassigned equally to one of the four alogliptin dosages). Main outcome measures: The primary efficacy endpoint was the change in HbA1c from the baseline value at week 12 of treatment. Safety endpoints were the occurrence of adverse events, vital sign measurements, physical examination and ECG findings, and laboratory test results recorded over the entire 52-week period. Results: HbA1c was dose-dependently reduced by alogliptin, and the changes versus baseline were statistically significant with all four dosages in comparison with both placebo and voglibose. In addition, changes in fasting plasma glucose and postprandial plasma glucose AUC0–2h values were significantly greater with all four dosages of alogliptin in comparison with placebo. The incidence of adverse events with alogliptin over 52 weeks was not dose-dependent and was lower than with voglibose. Hypoglycemia occurred infrequently and was generally rated as mild. Changes in body weight with alogliptin were minimal (<0.5 kg) and not clinically meaningful. Conclusions: Alogliptin was well tolerated and dose-dependently improved glycemic parameters in patients with type 2 diabetes inadequately controlled on diet and exercise.
BER of OFDM with directional antennas in time-variant environments

This paper derives the theoretical average bit error rate (BER) expressions of Orthogonal Frequency Division Multiplexing (OFDM) systems employing binary phase shift keying (BPSK), differential BPSK (DBPSK) and M-ary phase shift keying (MPSK) in a multi-path fading channel using the angle-of-arrival probability density function (pdf) at the mobile where a directional antenna is mounted. The channel introduces Doppler shift with the maximum Doppler spread fd. Two special cases are considered (i) fd is Gaussian distributed and (ii) fd is Rayleigh distributed. Two major diversity techniques are considered: (i) selective combining (SC), and (ii) maximal ratio combining. Detailed discussions and comparisons on performance of OFDM systems employing SC, MRC with directional antennas are given.
Cold exposure and low back pain in store workers in Israel.

BACKGROUND In recent years the demand for frozen food in the Western world has been growing, and the number of cold storeroom has increased proportionately. There are very few studies documenting cold exposure as a risk factor for musculoskeletal symptoms (MSS). This study describes the prevalence of MSS, in particular low back pain (LBP) among cold storeroom workers in Israel and explores the connection between exposure to cold at work and MSS. METHODS A cross-section survey included 122 males between the ages of 20-45 who had been employed for at least 1 year in three food stores in Israel. The subjects were classified as an exposed group working at temperatures of -20 degrees C and a control group working at room temperatures (20 degrees C to 25 degrees C). The prevalence rate of MSS, in particular LBP, was assessed using the Standardized Nordic Questionnaire. RESULTS Cold storeroom workers had increased odds of reporting back symptoms in the previous 12 months (odds ratio (OR) = 2.9, 95% CI = 1.3-6.7) and during work (OR = 4.8, 95% CI = 1.8-13.0) compared with their colleagues working in storerooms at regular temperatures. Among workers who described themselves as satisfied at work, the cold storeroom workers had increased odds of reporting back symptoms in the last 12 months and during work (OR = 3.9, 95% CI = 1.5-10.6, OR = 9.4, 95% CI = 2.0-44.6, respectively) while there was no association between store type and LBP among dissatisfied workers. CONCLUSIONS The results of this study strengthen the hypothesis that workers in cold environments are at a greater risk of LBP.
Theranostics With Multifunctional Magnetic Gold Nanoshells: Photothermal Therapy and T2* Magnetic Resonance Imaging

Objectives:To investigate the multifunctional imaging and therapeutic capabilities of core-shell nanoparticles composed of a superparamagnetic iron oxide (SPIO) core and a gold shell (SPIO@AuNS). Materials and Methods:The magnetic/optical properties of SPIO@AuNS were examined both in an agar gel phantom and in vivo by evaluating contrast-enhanced magnetic resonance imaging (MRI) and by measuring near-infrared (NIR) light-induced temperature changes mediated by SPIO@AuNS. In addition, the biodistribution and pharmacokinetics of 111In-labeled SPIO@AuNS after intravenous injection in mice bearing A431 tumors were evaluated in the presence and absence of an external magnet. Results:In agar phantoms containing SPIO@AuNS, a significant contrast enhancement in T2-weighted MRI was observed and a linear increase in temperature was observed with increasing concentration and laser output power when irradiated with NIR light centered at an 808 nm. In vivo, T2*-MRI delineated SPIO@AuNS and magnetic resonance temperature imaging of the same tumors revealed significant temperature elevations when intratumorally injected with SPIO@AuNS (1 × 1011 particles/mouse) and irradiated with NIR light (65.70°C ± 0.69°C vs. 44.23°C ± 0.24°C for saline + laser). Biodistribution studies in mice intravenously injected with 111In-labeled-SPIO@AuNS(1 × 1013 particles/mouse) had an approximately 2-fold increase in SPIO@AuNS delivered into tumors in the presence of an external magnet compared with tumors without the magnet. Conclusions:Owing to its ability to mediate efficient photothermal ablation of cancer cells under MRI guidance, as well as the ability to be directed to solid tumors with an external magnetic field gradient, multifunctional SPIO@AuNS is a promising theranostic nanoplatform.
Androgen receptor expression and its relationship with clinicopathological parameters in an Iranian population with invasive breast carcinoma

Background: Androgen receptor (AR) status and its association with prognosis in Iranian breast cancer population are uncertain. We examined AR expression and its relationship with clinicopathological parameters among Iranian patients with invasive breast carcinoma. Materials and Methods: This study was performed on formalin fixed and paraffin embedded tissue specimens with a diagnosis of invasive breast carcinoma archived at two University Hospitals in Isfahan city, Iran. Antibodies were used for evaluation of AR, human epidermal growth factor receptor 2 (HER2), estrogen receptor (ER), and progesterone receptor (PR). Other data were gathered from patients′ documents. Results: A total of 70 cases were evaluated including 55 (78.6%) ductal, 9 (12.9%) lobular, 2 (2.9%) medullary, and 4 (5.7%) mucinous carcinomas. Overall, 48.6%, 42.9%, 64.3%, and 57.1% of the samples were positive for ER, PR, AR, and HER2, respectively. Thirty three (47.1%) cases were ER− PR− and 17.1% were triple negative. AR + cases were younger and more frequently positive for ER and showed less frequently tumor size of > 2 cm. Although tumor grade and stage were relatively higher among AR− cases compared to AR + ones, the difference between the two groups was not statistically significant. Conclusions: AR expression was found to be frequently present in breast carcinoma in the studied population. Since half of the ER negative and half of the triple negative tumors were found to be AR positive, AR positive cases may benefit from alternative endocrine therapeutic strategies other than the conventional endocrine-targeted medications.
Multiple Pudendal Sensory Pathways Reflexly Modulate Bladder and Urethral Activity in Persons with Spinal Cord Injury

Purpose— Electrical stimulation of pudendal afferents can evoke reflex bladder contractions with relaxation of the external urethral sphincter in cats. This voiding reflex is mediated by pudendal sensory fibers innervating the penile and prostatic urethra that engage either a spinal or spinobulbospinal micturition pathway, respectively. However, the clinical translation of this potential therapy in persons with spinal cord injury (SCI) is limited by the lack of evidence demonstrating analogous reflex mechanisms in humans. Materials and Methods— We investigated the presence of excitatory pudendal-to-bladder reflexes in seven individuals with chronic SCI. The isovolumetric bladder pressure and perineal electromyogram (EMG) were recorded in response to intraurethral (IU) electrical stimulation at varying amplitudes and frequencies. Results— Selective electrical stimulation of the proximal and distal segments of the urethra evoked sustained reflex bladder contractions in different subsets of participants: 24.9 ± 13.9 cmH 2 O (n = 3) and 23.3 ± 16.1 cmH 2 O (n = 3), respectively. In contrast, the corresponding reflex perineal EMG exhibited a differential activation pattern between proximal and distal IU stimulation (normalized EMG, p < 0.05): 1.3 ± 0.2 and 0.3 ± 0.1, respectively. Conclusions— This study presents the first clinical evidence of two independent excitatory pudendal-to-bladder reflex pathways that can, in turn, differentially modulate efferent pudendal output. Both reflex mechanisms involve a complex interaction of multiple sensory inputs and may provide a neural substrate for restoring the bladder and muscle to selective intraurethral (IU)
A high efficient driver design for LED lighting system

As a result of changing in illumination systems, Light Emitting Diode (LED) lighting system has been widely used instead of traditional illumination system. The importance of LED lighting has been increasing day by day because of its less energy consumption, low production cost, long life and multiplicity of control algorithm. In recently, several methods have been used for increasing efficiency of LED lighting system. In this study, a LED lighting system has designed for a park illumination. The ratio of daylight has been detected with a central sensor. This value has been converted into numerical data and sent illumination pillars that placed into the park with Radio Frequency (RF). Pulse Width Modulation (PWM) signal required for buck converter put on the pillars as LED driver is generated with regard to the numerical data converted from the ratio of daylight. Thus, brightness of LED has been calibrated and during the pass of day-night, soft light pass has been provided.
HIV gp120 and morphine alter mu opiate receptor expression in human vascular endothelium.

We find that chronic exposure of human saphenous vein, atria and internal thoracic artery endothelium to the human immunodeficiency virus surface glycoprotein gp120, results in an increase in endothelial mu opioid receptor expression (52%). gp120 acts, in this regard, as a proinflammatory cytokine (e.g. interleukin-1-alpha) by increasing endothelial mu opioid receptor expression. In contrast, morphine decreases mu opioid receptor expression by 90% in a dose dependent fashion. Pretreatment of these tissues with the respective antagonists e.g., naloxone and anti-gp120 blocks the opiate decrease and increase gp120 induced increase in mu expression, respectively. Further, pretreatment of these endothelia with morphine inhibits gp120-stimulated mu transcript expression. Therefore, the immune down-regulating action of morphine may prevent viral replication because this process requires immune activation that can, in part, be provided for by gp120 proinflammatory actions.
Structural breaks and unit root in macroeconomic time series: evidence from Nigeria

The discourse on the properties of macroeconomic time series has received a considerable interest in recent literature. This is because the presence of unit in a realization of a stochastic process implies that shocks to the time series have a persistent effect with policy implications. Hence, this paper investigates the unit root properties of ten Nigerian macroeconomic time series using quarterly data from 1981-2015. For comparison, first we apply the conventional augmented Dickey-Fuller unit root test to examine the null of a unit root in the ten macroeconomic series, and we proceed to examine the unit root properties using the Lagrange Multiplier (LM) endogenous unit root tests that account for the presence of one-break and two-break as proposed by Lee and Strazicich (2003, 2013). On employing the augmented Dickey-Fuller test that does not account for structural breaks, our empirical results indicate that the unit root null hypothesis cannot be rejected for nine of the ten series considered in the study. However, on utilizing the Lagrange Multiplier (LM) endogenous one and two structural breaks test, we reject the unit root null in favour of the one and two-break stationary alternative for six of the ten series (60% rejection) considered in our study. These results imply that unit root tests that do not account sufficiently for the presence of structural breaks lead to misleading inference. These findings have important implications for the macroeconomic policy-making, modeling and forecasting of the Nigerian economy. We therefore, recommend that structural breaks should be taken into account in the econometric analysis of Nigerian macroeconomic variables.
Global Optimization for Satisfiability (SAT) Problem

The satisfiability (SAT) problem is a fundamental problem in mathematical logic, inference, automated reasoning, VLSI engineering, and computing theory. Following CNF and DNF local search methods, we introduce the Universal SAT problem model, UniSAT, which transforms the discrete SAT problem on Boolean space {0, 1}/sup m/ into an unconstrained global optimization problem on real space E/sup m/. A direct correspondence between the solution of the SAT problem and the global minimum point of the UniSAT objective function is established. Many existing global optimization algorithms can be used to solve the UniSAT problems. Combined with backtracking/resolution procedures, a global optimization algorithm is able to verify satisfiability as well as unsatisfiability. This approach achieves significant performance improvements for certain classes of conjunctive normal form (CNF) formulas. It offers a complementary approach to the existing SAT algorithms. >
Forward‐looking intravascular orthogonal‐solenoid coil for imaging and guidance in occlusive arterial disease

Recent intravascular imaging coil configurations have focused on side‐viewing catheters capable of imaging the vessel wall of a patent vessel. These designs suffer from the presence of signal nulls and the inability to image in front of a device when it is oriented along the main static field. This is of particular importance when a device is being navigated through an occlusive lesion. To address these limitations we propose a new intravascular coil design consisting of two independent orthogonal solenoids located at the catheter tip. The two coils are oriented in such a way that signal nulls are eliminated and imaging is possible in planes located directly in front of the catheter. Complete characterization of the spatial signal‐to‐noise ratio (SNR) distribution of the design is presented. The coil configuration was fabricated on a 6F guide catheter, and its use is demonstrated in phantoms and in vivo. Magn Reson Med 60:489–495, 2008. © 2008 Wiley‐Liss, Inc.
SUPPRESSIVE EFFECTS OF DIESEL EXHAUST PARTICLES ON CYTOKINE RELEASE FROM HUMAN AND MURINE ALVEOLAR MACROPHAGES

Epidemiological studies have shown an increase in the number of hospital admissions for respiratory diseases in association with high concentrations of particulate matter smaller than 10 μ m (PM 10) . Diesel exhaust particles (DEP) are important components of PM 10. This study was designed to test the effect of DEP on the release of cytokines from alveolar macrophages (AMs). Human and murine AMs were exposed to DEP for 24 hours, and the concentrations of tumor necrosis factor (TNF)- α, interleukin (IL)-6, and IL-8 were measured in the supernatants by enzyme-linked immunosorbent assay (ELISA). DEP (10 μ g/mL) suppressed the spontaneous release of TNF- α and IL-6 from murine AMs (P<.05). This suppression was not seen with exposure to carbon particles. Soluble components of DEP had a similar suppressive effect, suggesting that the chemical composition of DEP is responsible for the suppression. Lipopolysaccharide (LPS)- or IFN- γ -induced TNF- α and IL-6 production by murine AMs were suppressed by DEP in a dose-dependent manner (P<.05). DEP also inhibited LPS-stimulated production of TNF- α, IL-6, and IL-8 from human AMs (P<.05). Pretreatment of AMs with superoxide dismutase (SOD) (300 IU/mL) prevented the suppressive effect of DEP on AM cytokine production (P<.05). The authors conclude that DEP exposure suppressed the release of cytokines from AMs, and speculate that this suppression could impair normal host defenses. alveolar macrophage diesel exhaust particles IL-6 TNF- α
Influence of Tourist Geographical Context on Customer-Based Destination Brand Equity: An Empirical Analysis

The present work seeks to address significant research gaps relating to brand equity and Service-Dominant Logic, specifically examining the influence of tourist geographical context on Consumer-based Destination Brand Equity (CBDBE). The purpose of the study is to identify an explanatory model for CBDBE, considering the indirect effects that tourists from a nearby geographical location may exert on CBDBE, because of their proximity and shared context. Self-congruity, tourist motivations, and value-creation are found to be antecedent variables of CBDBE. A spatial econometric model was used that took into account the spatial spillover-effect of geographical proximity on the variable CBDBE, and the direct and indirect effects of the antecedent variables. The results of the study make a contribution to the specialized literature on brand destination and Service-Dominant Logic, and offer interesting implications for the professional domain, with clear implications for the identification of market development patterns and trends.
The immunodetected yeast purine—cytosine permease is not N‐linked glycosylated, nor are glycosylation sequences required to have a functional permease

The purine‐cytosine permease (PCP) of the yeast Saccharomyces cerevisiae was detected by immunological methods. Using antibodies directed against synthetic peptides, whose sequences were derived from the primary structure of the PCP, immunoprecipitation of [35S]methionine‐labelled PCP was achieved either from cellular extracts or from in vitro translation mixtures. Non‐labelled PCP was also detected on Western blots of membrane proteins. Similar migration rates were observed for PCP originating both from immunoprecipitated cellular extracts and from in vitro translation mixtures. Hence, post‐translational processing, if any, only slightly affects the size of the protein. Also no evidence was found for N‐linked core‐glycosylation: identical migration rates were observed when immunoprecipitated PCP molecules were extracted from cells labelled for 10 min with [35S]methionine, pretreated or not with tunicamycin.
Process and Energy Analysis of Pelleting Agricultural and Woody Biomass Blends

Unprocessed biomass has low energy density and high transportation cost. The energy generated through biomass can be enhanced by the pelletizing technique. In order to evaluate the energy requirement for the pelletizing of agricultural biomass, three different particle sizes (150–300, 300–425, and 425–600 µm) of reed canary grass (RCG), timothy hay (TH), and switchgrass (SW) were selected in the present work. Furthermore, two woody biomasses (spruce and pine) were also considered under similar experimental conditions for comparison purposes. An Instron machine attached to an in-house built pelletizer unit was employed to produce a single pellet. The energy demand for compacting ground biomass (spruce) with a particle size of 150 µm was lower (2.07 kJ) than those required for particle sizes of 300 µm (2.24 kJ) and 425 µm (2.43 kJ). The energy required for compacting ground reed canary grass, timothy hay, and switchgrass was lower (1.61, 1.97, and 1.68 kJ, respectively) than that required for spruce (2.36 kJ) and pine (2.35 kJ), evaluated at a 159-MPa load and at temperature of about 80 °C. The energy demand for blended biomass was around 2 kJ with the pellet quality approaching that of the pellets made from woody biomass. Overall, blending helped to improve the quality of pellets and lower the compaction energy requirements.
Horizontal semicircular canal variant of benign positional vertigo

We report the clinical features and results of quantitative eye-movement testing in 13 patients with episodic positional vertigo and nonfatiguing direction-changing horizontal positional nystagmus (beating to the right with the head turned to the right and beating to the left with the head turned to the left). The benign history and lack of associated neurologic findings support a peripheral localization of the lesion. This syndrome probably represents a horizontal semicircular canal variant of benign positional vertigo. Free-floating debris in one horizontal canal may explain many of the clinical and oculographic findings.