Miracle-dz/UniFAR-FTUs huggingface dataset:
GHSR-D2R heteromerization modulates dopamine signaling through an effect on G protein conformation

Significance G protein-coupled receptors (GPCRs) are one of the largest cell surface receptor family that transmit their signal through coupling to intracellular partners, such as G proteins. Receptor oligomerization has been shown to be pivotal in this signaling process. To address how oligomerization can impact on signaling in a major physiological process, dopamine signaling, we used a purified GPCR heteromer composed of the ghrelin and dopamine receptors to which we applied a variety of state-of-the-art biochemical and biophysical approaches. By doing so, we provide a direct experimental evidence for a mechanism where receptor heteromerization affects the conformation of the associated G protein. This sheds light on the way a GPCR oligomer can affect G protein activation to modulate signaling. The growth hormone secretagogue receptor (GHSR) and dopamine receptor (D2R) have been shown to oligomerize in hypothalamic neurons with a significant effect on dopamine signaling, but the molecular processes underlying this effect are still obscure. We used here the purified GHSR and D2R to establish that these two receptors assemble in a lipid environment as a tetrameric complex composed of two each of the receptors. This complex further recruits G proteins to give rise to an assembly with only two G protein trimers bound to a receptor tetramer. We further demonstrate that receptor heteromerization directly impacts on dopamine-mediated Gi protein activation by modulating the conformation of its α-subunit. Indeed, association to the purified GHSR:D2R heteromer triggers a different active conformation of Gαi that is linked to a higher rate of GTP binding and a faster dissociation from the heteromeric receptor. This is an additional mechanism to expand the repertoire of GPCR signaling modulation that could have implications for the control of dopamine signaling in normal and physiopathological conditions.
Speech Commands: A Dataset for Limited-Vocabulary Speech Recognition

Describes an audio dataset of spoken words designed to help train and evaluate keyword spotting systems. Discusses why this task is an interesting challenge, and why it requires a specialized dataset that is different from conventional datasets used for automatic speech recognition of full sentences. Suggests a methodology for reproducible and comparable accuracy metrics for this task. Describes how the data was collected and verified, what it contains, previous versions and properties. Concludes by reporting baseline results of models trained on this dataset.
Light-trapping in solar modules using extra-white textured glass

The objective of this work is the development of a front cover glass for all types of PV modules allowing a significant reduction of optical losses at the glass-air and the polymer-cell interface. The annual relative gain in transmission between a plane surface and a inverse pyramidal-textured (half-angle=45/spl deg/) surface has been calculated to be 8.1% for direct radiation and 6.1% for diffuse radiation for a standard year in Cologne (Germany). This glass has been manufactured on an industrial cast glass furnace during an extra-white campaign. It allows an annual efficiency improvement of 3.1% (2.9% at normal incidence and 9.4% at 70/spl deg/) compared to flat glass with the same composition and measured with polycrystalline Si solar cells. After 9 months outdoor testing (on a dusty test site, 60/spl deg/ tilted to a horizontal surface), a significant advantage of the pyramidal glass (compared to flat glass) is still present.
CAKE PRODUCTION FROM WHEAT (TRITICUM AESTIVUM) AND COWPEA (VIGNA UNGUICULATA) FLOURS USING DATE FRUIT AS A SWEETENER

Changes in consumer demand for new pastries due to the high rate of diabetes, obesity and celiac disease are causing an unprecedented spur in the processing and ingredient system developments within the pastry production sector. Consumers demand healthier pastries that are low in sugar, fat, cholesterol, and calories in general and contain in addition health-promoting components such as protein, unsaturated fatty acids, and fibres. This project reports the proximate, mineral, functional and sensory characteristics of cakes produced from blends of wheat and cowpea flour using date as a sweetener. Six cake samples were produced with different formulations which include wheat flour and sugar (WHS), wheat flour and date fruit extracts (WHD), composite flour of wheat and cowpea in the ratio 50:50 with sugar (COS) and dates respectively (COD) and cowpea flour with sugar (CWS) and date fruit extracts (CWD) respectively. The protein content of the wheat, cowpea and composite flours ranged from 14.20-15.37%, moisture; 4.76-5.58%, ash; 0.52-0.53, crude fat; 0.99-1.53%, crude fibre; 0.20-0.23% and carbohydrate; 77.42-78.45%. The loose bulk density, packed bulk density, water absorption capacity and oil absorption capacity had a range of 0.450. 50g/mL, 0.68-0.73g/mL, 0.76-2.06g water/g flour and 0.70-1.20g oil/ g flour respectively. The proximate composition of the cakes varied significantly with cake produced from cowpea sweetened with sugar having the highest protein content and cake from wheat flour sweetened with date having the lowest. Generally, cakes produced from composite flour sweetened with sugar had higher contents of calcium than cakes sweetened with dates while the iron and potassium contents were higher in cakes sweetened with date extract. Cakes produced with sugar as the sweetener had better ratings than those with date fruit, however, all the cakes compared favourably well with the control (cake produced from 100% wheat flour sweetened with sugar) in all the parameters measured.
Isolation of Maedi/Visna Virus from a Sheep in Japan

ABSTRACT Maedi/visna (MV) is a lentiviral disease of sheep caused by the maedi/visna virus (MVV). Although MV is prevalent in many countries, it had not been reported in Japan. In 2011, however, three sheep in northern Japan were reported to be seropositive against the MVV antigen, indicating a persistent MVV infection. In the present study, we isolated MVV from one sheep to confirm MVV infection and conducted genomic classification of the virus. The co-culture of leukocytes from a seropositive sheep with fetal goat lung cells resulted in the formation of syncytial cells and the amplification of a long terminal repeat sequence of MVV by polymerase chain reaction. The isolate was confirmed as being MVV, rather than the caprine arthritis-encephalitis virus based on phylogenetic analysis of the gag gene sequence. Although the sheep was asymptomatic, nonpurulent meningitis and demyelination were found in the spinal cord. These were considered to be early lesions associated with pathogenic MVV infection. Therefore, the present study demonstrated that MVV is distributed in Japan.
The computational form of craving is a selective multiplication of economic value

Significance Craving is a specific desire state that biases choice toward the desired object. Although extremely common, and in its pathological form a major contributor to negative health outcomes as in addiction and obesity, craving is not well understood. In a laboratory model of craving, we find “craving” is reflected in people’s momentary willingness to pay for the things they desire, and for subjectively similar things, consistent with a transient, good-selective change in subjective valuation. We further find the value of the desired goods increases multiplicatively, which might explain several escalation behaviors associated with craving in real-world environments. This opens more lines of research regarding the computational form of craving in health and disease, with implications for marketing actions and consumer choice. Craving is thought to be a specific desire state that biases choice toward the desired object, be it chocolate or drugs. A vast majority of people report having experienced craving of some kind. In its pathological form craving contributes to health outcomes in addiction and obesity. Yet despite its ubiquity and clinical relevance we still lack a basic neurocomputational understanding of craving. Here, using an instantaneous measure of subjective valuation and selective cue exposure, we identify a behavioral signature of a food craving-like state and advance a computational framework for understanding how this state might transform valuation to bias choice. We find desire induced by exposure to a specific high-calorie, high-fat/sugar snack good is expressed in subjects’ momentary willingness to pay for this good. This effect is selective but not exclusive to the exposed good; rather, we find it generalizes to nonexposed goods in proportion to their subjective attribute similarity to the exposed ones. A second manipulation of reward size (number of snack units available for purchase) further suggested that a multiplicative gain mechanism supports the transformation of valuation during laboratory craving. These findings help explain how real-world food craving can result in behaviors inconsistent with preferences expressed in the absence of craving and open a path for the computational modeling of craving-like phenomena using a simple and repeatable experimental tool for assessing subjective states in economic terms.
Tacrolimus enhances the potency of posaconazole against Rhizopus oryzae in vitro and in an experimental model of mucormycosis.

BACKGROUND We hypothesized that tacrolimus, an inhibitor of the calcineurin pathway, would enhance the in vivo activity of posaconazole against Rhizopus oryzae, the Mucorales species most commonly associated with mucormycosis. METHODS We examined patterns of growth inhibition and fungicidal activity of posaconazole and tacrolimus, alone and in combination, against R. oryzae in vitro, using multiple methods (ie, hyphal metabolic and fluorescent vital dye reduction assays and measurement of chitin concentrations), and in vivo, using 2 mucormycosis models: an invertebrate model (Drosophila) and a nonlethal murine model of cutaneous mucormycosis. RESULTS Combinations of posaconazole and tacrolimus were synergistic in checkerboard assays for 4 clinical isolates of R. oryzae (48-hour fractional inhibitory concentration index, 0.187-0.281). Pharmacodynamic analysis of the combination revealed that the 90% effective concentration threshold of posaconazole activity against R. oryzae could be achieved with 2-fold lower drug concentrations (0.5-1 mg/L) when administered with tacrolimus (0.007-2 mg/L). In vivo, combination therapy was associated with improved survival in the fly model of mucormycosis (65% vs 57% posaconazole alone) and with significant reductions in cutaneous lesions and R. oryzae fungal burden, compared with animals that received posaconazole monotherapy, in the cutaneous model of mucormycosis. CONCLUSIONS Combination posaconazole-tacrolimus therapy displays synergism in vitro and improved antifungal efficacy in vivo in 2 phylogenetically distinct models of mucormycosis.
Patient's Decision to Disclose the Use of Traditional and Complementary Medicine to Medical Doctor: A Descriptive Phenomenology Study

Nondisclosure of traditional and complementary medicine (T&CM) use may cause individual to be at risk of undue harm. This study aimed to explore patient's experience and views on their decision to disclose the use of T&CM to the doctor. An exploratory qualitative study using in-depth interview involving 10 primary care clinics attendees in Kuching was conducted. The results indicated that disclosure of T&CM use will motivate them to get information, increase doctor's awareness, and get support from family and friends for disclosure. Fear of negative relationship and negative response from doctors was a barrier for disclosure. Doctor's interpersonal and communication skills of being involved, treating patients respectfully, listening attentively, respecting privacy, and taking time for the patient were a critical component for disclosure. Intrapersonal trust regarding doctor influences their satisfaction on healthcare. Women are more open and receptive to a health concern and expressing negative emotions and tend to share problems, whereas men always described themselves as healthy, tended to keep their own personal feeling to themselves, and tended to not share. The doctor should consider gender differences in disclosure, their attitude towards T&CM use, and gained patient's trust in the delivery of healthcare services. Good interpersonal and communication skills must be maintained between doctor and patients.
CYP2C9 polymorphisms in epilepsy: influence on phenytoin treatment

Phenytoin (PHT) is an antiepileptic drug widely used in the treatment of focal epilepsy and status epilepticus, and effective in controlling focal seizures with and without tonic–clonic generalization and status epilepticus. The metabolization of PHT is carried out by two oxidative cytochrome P450 enzymes CYP2C9 and CYP2C19; 90% of this metabolization is done by CYP2C9 and the remaining 10% by CYP2C19. Genetic polymorphism of CYP2C9 may reduce the metabolism of PHT by 25–50% in patients with variants *2 and *3 compared to those with wild-type variant *1. The frequency distribution of CYP2C9 polymorphism alleles in patients with epilepsy around the world ranges from 4.5 to 13.6%, being less frequent in African-Americans and Asians. PHT has a narrow therapeutic range and a nonlinear pharmacokinetic profile; hence, its poor metabolization has significant clinical implications as it causes more frequent and more serious adverse effects requiring discontinuation of treatment, even if it had been effective. There is evidence that polymorphisms of CYP2C9 and the use of PHT are associated with an increase in the frequency of some side effects, such as cerebellar atrophy, gingival hypertrophy or acute cutaneous reactions. The presence of HLA-B*15:02 and CYP2C9 *2 or *3 in the same patient increases the risk of Stevens–Johnson syndrome and toxic epidermal necrolysis; hence, PHT should not be prescribed in these patients. In patients with CYP2C9 *1/*2 or *1/*3 alleles (intermediate metabolizers), the usual PHT maintenance dose (5–10 mg/kg/day) must be reduced by 25%, and in those with CYP2C9 *2/*2, *2/*3 or *3/*3 alleles (poor metabolizers), the dose must be reduced by 50%. It is controversial whether CYP2C9 genotyping should be done before starting PHT treatment. In this paper, we aim to review the influence of CYP2C9 polymorphism on the metabolization of PHT and the clinical implications of poor metabolization in the treatment of epilepsies.
Interfacial effect on the electromechanical behaviors of piezoelectric/elastic composite smart beams

An efficient electromechanical coupling model is developed to analyze the effect of the interfacial properties on the mechanical behaviors of piezoelectric/elastic composite smart beams. The interface of the composite smart beams is assumed to be imperfectly bonded and is modeled by the shear-lag model. An asymptotic expansion approximation is employed to construct the electric potential distribution in the piezoelectric layer. The governing equation is derived for the piezoelectric/elastic composite smart beams taking into account the electromechanical coupling effect and the interfacial imperfection. In the numerical analysis, both the mechanical and the electrical loadings are considered. The mechanical behaviors of the composite smart beams are illustrated graphically for three types of boundary conditions: (a) clamped supported–freely supported (C-F), (b) clamped supported–hinged supported (C-H), and (c) hinged supported–hinged supported (H-H). The results show that the interfacial properties have significant effect on the mechanical behaviors of the piezoelectric/elastic composite smart beams. For mechanically actuated case, a larger interfacial imperfection causes a larger transverse deflection, while it is contrary for electrically actuated case.
Open-path, closed-path, and reconstructed aerosol extinction at a rural site

ABSTRACT The Handix Scientific open-path cavity ringdown spectrometer (OPCRDS) was deployed during summer 2016 in Great Smoky Mountains National Park (GRSM). Extinction coefficients from the relatively new OPCRDS and from a more well-established extinction instrument agreed to within 7%. Aerosol hygroscopic growth (f(RH)) was calculated from the ratio of ambient extinction measured by the OPCRDS to dry extinction measured by a closed-path extinction monitor (Aerodyne’s cavity-attenuated phase shift particulate matter extinction monitor [CAPS PMex]). Derived hygroscopicity (relative humidity [RH] < 95%) from this campaign agreed with data from 1995 at the same site and time of year, which is noteworthy given the decreasing trend for organics and sulfate in the eastern United States. However, maximum f(RH) values in 1995 were less than half as large as those recorded in 2016—possibly due to nephelometer truncation losses in 1995. Two hygroscopicity parameterizations were investigated using high-time-resolution OPCRDS+CAPS PMex data, and the κext model was more accurate than the gamma model. Data from the two ambient optical instruments, the OPCRDS and the open-path nephelometer, generally agreed; however, significant discrepancies between ambient scattering and extinction were observed, apparently driven by a combination of hygroscopic growth effects, which tend to increase nephelometer truncation losses and decrease sensitivity to the wavelength difference between the two instruments as a function of particle size. There was not a statistically significant difference in the mean reconstructed extinction values obtained from the original and the revised IMPROVE (Interagency Monitoring of Protected Visual Environments) equations. On average, IMPROVE reconstructed extinction was ~25% lower than extinction measured by the OPCRDS, which suggests that the IMPROVE equations and 24-hr aerosol data are moderately successful in estimating current haze levels at GRSM. However, this conclusion is limited by the coarse temporal resolution and the low dynamic range of the IMPROVE reconstructed extinction. Implications: Although light extinction, which is directly related to visibility, is not directly measured in U.S. National Parks, existing IMPROVE protocols can be used to accurately infer visibility for average humidity conditions, but during the large fraction of the year when humidity is above or below average, accuracy is reduced substantially. Furthermore, nephelometers, which are used to assess the accuracy of IMPROVE visibility estimates, may themselves be biased low when humidity is very high. Despite reductions in organic and sulfate particles since the 1990s, hygroscopicity, particles’ affinity for water, appears unchanged, although this conclusion is weakened by the previously mentioned nephelometer limitations.
A meta-analysis of cyclosporine treatment for Stevens–Johnson syndrome/toxic epidermal necrolysis

Background Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are dermatologic emergencies with high morbidity and mortality risk. Cyclosporine, an immunomodulatory agent, is sometimes used off-label, and its role continues to be debated. This meta-analysis aimed to provide an update of current evidence and to clarify the role of cyclosporine in SJS/TEN treatment better. Methods Using the keywords [cyclosporine OR cyclosporine OR ciclosporin OR CsA] AND [Steven-Johnson OR SJS OR toxic epidermal OR epidermal necrolysis OR TEN OR hypersensitivity OR dermatologic OR burns], a preliminary search on the PubMed, Ovid, Web of Science, and Google Scholar Database yielded 615 papers published in English between January1, 1960 and July 1, 2017. The inclusion criteria for this review were: 1) published retrospective or prospective study (excluding single case reports); 2) patients with clinical diagnosis of SJS or TEN; 3) trial of cyclosporine treatment; and 4) available survival/mortality data. Results A total of 12 studies, with a total of 358 SJS/TEN patients were reviewed. Two studies were excluded from the meta-analysis as they did not report SCORe of toxic epidermal necrosis/predicted mortality data; one was excluded because of possible data irregularities. Meta-analysis of nine studies revealed a significant reduction in mortality risk with cyclosporine therapy (standardized mortality ratio 0.320; 95% CI: 0.119–0.522; P=0.002). Cyclosporine was also generally well tolerated with little adverse effects or increased infection, albeit the patients tended to be critically ill. Publication bias was observed in the funnel plot and Egger test (P=0.0467). Conclusion Currently available evidence are predominantly open trials and retrospective studies with a significant risk of bias, perhaps owing to the rarity and life-threatening nature of the condition. Given its immunomodulatory actions, cyclosporine could be a potential treatment option for SJS/TEN in addition to best supportive measures. Further confirmation with robust randomized, controlled trials or larger case series is necessary and should be encouraged.
Expression profiles of TRPV1, TRPV4, TLR4 and ERK1/2 in the dorsal root ganglionic neurons of a cancer-induced neuropathy rat model

Background The spread of tumors through neural routes is common in several types of cancer in which patients suffer from a moderate-to-severe neuropathy, neural damage and a distorted quality of life. Here we aim to examine the expression profiles of transient receptor potential vanilloid 1 (TRPV1) and of transient receptor potential vanilloid 4 (TRPV4), toll-like receptor 4 (TLR4) and extracellular signal-regulated kinase (ERK1/2), and to assess the possible therapeutic strategies through blockade of transient receptor potential (TRP) channels. Methods Cancer was induced within the sciatic nerves of male Copenhagen rats, and tissues from dorsal root ganglia (DRG) were collected and used for measurements of immunofluorescence and Western blotting. The TRPV1 antagonist capsazepine, the selective TRPV4 antagonist HC-067047 and the calcium ions inhibitor ruthenium red were used to treat thermal and/or mechanical hyperalgesia. Results Transient receptor potential vanilloid 1 showed a lower expression in DRGs on days 7 and 14. The expression of TRPV4, TLR4 and ERK1/2 showed an increase on day 3 then a decrease on days 7 and 14. TRPV1 and TLR4 as well as TRPV4 and ERK1/2 co-existed on the same neuronal cells. The neuropathic pain was reversed in dose-dependent manners by using the TRP antagonists and the calcium ions inhibitor. Conclusion The decreased expression of TRPV1 and TRPV4 is associated with high activation. The increased expression of TLR4 and ERK1/2 reveals earlier immune response and tumor progression, respectively, and their ultimate decrease is an indicator of nerve damage. We studied the possible role of TRPV1 and TRPV4 in transducing cancer-induced hyperalgesia. The possible treatment strategies of cancer-induced thermal and/or mechanical hyperalgesia using capsazepine, HC-067047 and ruthenium red are examined.