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Metabotropic glutamate receptors are class C G-protein-coupled receptors which respond to the neurotransmitter glutamate. Structural studies have been restricted to the amino-terminal extracellular domain, providing little understanding of the membrane-spanning signal transduction domain. Metabotropic glutamate receptor 5 is of considerable interest as a drug target in the treatment of fragile X syndrome, autism, depression, anxiety, addiction and movement disorders. Here we report the crystal structure of the transmembrane domain of the human receptor in complex with the negative allosteric modulator, mavoglurant. The structure provides detailed insight into the architecture of the transmembrane domain of class C receptors including the precise location of the allosteric binding site within the transmembrane domain and key micro-switches which regulate receptor signalling. This structure also provides a model for all class C G-protein-coupled receptors and may aid in the design of new small-molecule drugs for the treatment of brain disorders. An X-ray structure is presented for metabotropic glutamate receptor 5, a class C G-protein-coupled glutamate receptor linked to fragile X syndrome and neurological disorders; this study provides insights into the protein’s mechanism of action. Structure of a class C GPCR This manuscript presents the X-ray crystal structure of the transmembrane portion of the metabotropic glutamate receptor 5 (mGlu5), a class C G-protein-coupled receptor (GPCR), in the presence of mavoglurant, a negative allosteric modulator. Negative allosteric modulators of mGlu5 are in clinical trials for the treatment of fragile X syndrome, depression, anxiety, migraine and dyskinesias; positive allosteric modulators of mGlu5 might be useful for the treatment of schizophrenia and cognitive disorders. In this structure, mavoglurant is found in a pocket that is about 8 Å from the extracellular receptor surface.

Energy-efficient equipment appliances (EEEAs) offer great potential for domestic energy saving. This study aims to explore the direct influence of TPB constructs (i.e., attitude, subjective norm, and perceived behavioral control), eco labels, and green trust on the intention to buy EEEAs with green environmental concern as moderator. We employed quantitative methodology to test the relationship in the proposed model with an Indian sample of 321 respondents. Both Confirmatory Factor Analysis and Structural Equation Modeling were used for data analysis with AMOS 22.0. The findings reveal that eco-labels and green trust fully mediate the relationship between attitude and PBC to intention to buy EEEAs. The results also suggest that eco-labels and green trust play a positive and vital role in leading to purchase sustainable appliances. Through this study, we contribute to literature encompassing energy-efficient product consumption, achieved through heightened eco-labels perceptions and green trust. The EEEAs purchases can be stimulated among the consumers with higher green environmental concern.

Aims: This study aims to compare clinical outcomes in patients of recurrent implantation failure (RIF), who had embryo transfer (ET) following a receptive (R) endometrial receptivity array (ERA) and a personalized embryo transfer (pET) after a nonreceptive (NR) ERA. Settings and Design: This was a retrospective observational study. Study Period: July 2013-September 2017. Subjects and Methods: Two hundred and forty-eight patients having unexplained RIF who underwent ERA test were included in the study. Clinical outcomes were compared between patients having a receptive (R) ERA and those having a NR ERA who underwent a pET-based on ERA. Statistical Analysis Used: Chi-square and t-test. Results: ERA predicted receptive (R) endometrium at P + 5 in 82.3% (204/248) patients and NR in 17.7% (44/248) patients. Average failed previous in vitro fertilization cycles were 3.67 ± 1.67 among receptive ERA patients and 4.09 ± 1.68 among NR ERA patients. Pregnancy rate (PR), clinical PR, implantation rate (IR), abortion rate (AR), ongoing pregnancy rate (OPR), and cumulative PR were comparable between patients having receptive ERA who had a routine Embryo Transfer (ET) and those with an NR ERA who underwent a pET. Conclusions: ERA is helpful in identifying the window of implantation (WOI) through genetic expressions of the endometrium to pinpoint embryo transfer timing. pET guided by ERA in patients of RIF with displaced WOI improves IRs and OPRs.

Purpose This study aims to explore the underdog brand biography dimensions that emerging-country consumers identify with (Study 1) and attempts to uncover the effects of these dimensions on brand affinity and purchase intention moderated by self-identity and brand trust (Study 2). Design/methodology/approach Study 1, using data from 359 young Indians, reveals three underlying dimensions integral to underdog brand biography in emerging markets. Study 2 uses an experimental setup with a single-factorial design among 332 young Mexican consumers to investigate the direct effects of three identified underdog brand biography dimensions on purchase intention, mediated by brand affinity and moderated by consumer self-identity and brand trust. Findings Study 1 reveals three dimensions underlying underdog brand biographies: unfavorable circumstances, striving in adversities and passion, and persistent will to succeed. Study 2 reveals that consumers with higher self-identity demonstrate greater purchase intentions for an underdog brand than a top dog one. Practical implications The results indicate that marketers can successfully use underdog narratives to influence consumer decision-making, thereby increasing brand affinity and purchase intention. Originality/value This study delineates the link between different dimensions of underdog brand biographies with brand affinity and purchase intention in emerging countries and builds on the understanding of the moderating role played by self-identity and brand trust.

The impact of high shear melt conditioning on the morphology and distribution of Fe intermetallic compounds was investigated in the processing of recycled AA6111 alloy by the twin roll casting process. The optical and scanning electron microscope (SEM) micrograph studies were carried out on twin roll casting (TRC) and melt conditioning twin roll casting (MC-TRC) samples. The microstructural analysis showed fine and uniformly distributed Fe-rich intermetallic phases for MC-TRC strips compared with the TRC strips. There was a significant improvement in the mechanical properties of MC-TRC strips after applying melt conditioning. The as-cast MC-TRC samples showed 18.7%, 19.2% and 9.8% increases in elongation, yield strength and ultimate tensile strength, respectively, in the longitudinal direction, while in the transverse section, the MC-TRC samples showed 32.3%, 2.2% and 3.8% increases in elongation, yield strength and ultimate tensile strength, respectively.

Background: There is no consensus regarding optimal endometrial thickness and duration of estrogen supplementation in embryo transfer cycles, at present. Aims: To observe the effect of endometrial thickness and/or duration of estrogen supplementation on in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) outcomes in fresh ovum/embryo donation cycles. Settings and Design: This was a retrospective observational study. The study was conducted from January 2015 to November 2017. Subjects and Methods: Nine hundred and fifty seven fresh blastocyst transfer cycles in the recipients of oocyte/embryo donation regardless of reproductive history and diagnosis conducted at Nova IVF Fertility, Ahmedabad, Gujarat, India. Of these, 315 women had single embryo transfer (SET), while 642 had double embryo transfer (DET). Only fresh blastocysts derived from oocytes of young donors (≤30 years) and transferred in a uniform hormone replacement therapy (HRT) cycle were included. The effect of endometrial thickness and duration of estrogen on live birth rate (LBR) and other IVF/ICSI outcomes were analyzed. Statistical Analysis: Univariate logistic regression. Results: A significant improvement in LBR was noted in the recipients with each millimeter increase in endometrial thickness starting from 6 mm after transfer of either single (odds ratio [OR] = 1.3, P = 0.003) or double (OR = 1.14, P = 0.0218) blastocysts. Lower LBR was observed in recipients having SET and who received estrogen supplementation of <10 days (OR = 0.72; P = 0.02). Implantation rate and clinical pregnancy rate also improved significantly with endometrial thickness, but there was no change in clinical abortion rate and ectopic pregnancy rate. Conclusions: After minimizing the possible oocyte factor by including only donor oocytes and that of COH using a uniform HRT protocol, LBR improved with each millimeter increase in endometrial thickness starting from 6 mm. Shorter duration of estrogen supplementation (<10 days) reduced the chances of live birth in recipients after transfer of a single blastocyst.

Casting is the first step toward the production of majority of metal products whether the final processing step is casting or other thermomechanical processes such as extrusion or forging. The high shear melt conditioning provides an easily adopted pathway to producing castings with a more uniform fine-grained microstructure along with a more uniform distribution of the chemical composition leading to fewer defects as a result of reduced shrinkage porosities and the presence of large oxide films through the microstructure. The effectiveness of high shear melt conditioning in improving the microstructure of processes used in industry illustrates the versatility of the high shear melt conditioning technology. The application of high shear process to direct chill and twin roll casting process is demonstrated with examples from magnesium melts.

High shear melt conditioning technology refines the as-cast structure of light alloy melts, thereby improving the mechanical properties of the casting and reducing the occurrence of defects, without requiring chemical grain refiners. To upscale the technology and apply it to processes involving larger melt volumes, a computational fluid dynamics study is conducted with three rotor–stator mixers operating in both batch and continuous modes. Analysis of the results show that rotor–stator mixers with smaller stator holes outperform those with larger ones because of larger shear rates—increasing the deagglomeration rate—and larger volume flow rates—increasing the dispersion of the intensively sheared melt in the bulk liquid. Compared with batch mode, continuous operation results in lower mass flow rate through the mixer and reduced mixing, although the mixer design has a larger impact on both measures.

In addition to impurities in recycled aluminum alloys, non-metallic inclusions are a significant factor that deteriorates the material’s castability and final mechanical properties. This, therefore, restricts the ability to transition from a primary to secondary aluminum alloy. In this study, the cleanliness of the recycled A357 alloy was evaluated through non-metallic inclusions’ characterization, hydrogen content measurement, fluidity test, and casting defects identification. The non-metallic inclusions generated during the recycling process of A357 alloy were collected by the pressurized melt filtration technique. All of the inclusion types collected during filtration were examined and identified by analytical scanning electron microscopy (SEM). Extra additions of up to 2 wt.% swarf in these secondary A357 alloys were designed to simulate highly contaminated alloys. Different to the conventional melt cleaning technologies that mainly focus on complete removal of inclusions, this study developed a novel approach that combines the removal of easily removeable inclusions while preserving well-dispersed inclusions that do not adversely affect the mechanical properties. This study demonstrates that high shear melt conditioning (HSMC) technology can achieve well-dispersed small non-metallic inclusions, low hydrogen content, improved fluidity, and fewer casting defects. As a result, the melt quality of the recycled A357 alloys has achieved a quality comparable to that of primary A357 alloy.

A continuous high-shear melt conditioning twin-roll casting process has been developed for production of recycled aluminum alloy strip with minimum casting defects. High-shear melt conditioning is applied to increase the impurities tolerance of recycled aluminum. The results of this study showed that solidification during twin-roll casting can be controlled by using intensive melt conditioning prior to casting, which can promote equiaxed growth with minimal defects and result in improved sheet quality. Melt-conditioned twin-roll cast (MC-TRC) AA5754 alloy exhibited fine equiaxed grains and homogenized matrix structure while centerline segregation was eliminated. As-cast melt-conditioned twin-roll cast AA5754 strips showed clear grain recrystallization after thermomechanical treatment at 430°C for 30 min, representing an improvement over conventional twin-roll casting. The MC-TRC strip showed 57.2% higher elongation and 4.1% higher ultimate tensile strength compared with the TRC strip after applying melt conditioning with thermomechanical treatment.