Search

PURPOSE Small-cell lung cancer (SCLC) is an aggressive malignancy with limited treatments. Delta-like ligand 3 (DLL3) is aberrantly expressed in most SCLC. Tarlatamab (AMG 757), a bispecific T-cell engager molecule, binds both DLL3 and CD3 leading to T-cellb–mediated tumor lysis. Herein, we report phase I results of tarlatamab in patients with SCLC. PATIENTS AND METHODS This study evaluated tarlatamab in patients with relapsed/refractory SCLC. The primary end point was safety. Secondary end points included antitumor activity by modified RECIST 1.1, overall survival, and pharmacokinetics. RESULTS By July 19, 2022, 107 patients received tarlatamab in dose exploration (0.003 to 100 mg; n = 73) and expansion (100 mg; n = 34) cohorts. Median prior lines of anticancer therapy were 2 (range, 1-6); 49.5% received antiprogrammed death-1/programmed death ligand-1 therapy. Any-grade treatment-related adverse events occurred in 97 patients (90.7%) and grade b % 3 in 33 patients (30.8%). One patient (1%) had grade 5 pneumonitis. Cytokine release syndrome was the most common treatment-related adverse event, occurring in 56 patients (52%) including grade 3 in one patient (1%). Maximum tolerated dose was not reached. Objective response rate was 23.4% (95% CI, 15.7 to 32.5) including two complete and 23 partial responses. The median duration of response was 12.3 months (95% CI, 6.6 to 14.9). The disease control rate was 51.4% (95% CI, 41.5 to 61.2). The median progression-free survival and overall survival were 3.7 months (95% CI, 2.1 to 5.4) and 13.2 months (95% CI, 10.5 to not reached), respectively. Exploratory analysis suggests that selecting for increased DLL3 expression can result in increased clinical benefit. CONCLUSION In patients with heavily pretreated SCLC, tarlatamab demonstrated manageable safety with encouraging response durability. Further evaluation of this promising molecule is ongoing.

Aparna Rao,* Sardar Mohd Khan,* Sujoy Mukherjee Glaucoma Service, LV Prasad Eye Institute, Bhubaneswar, Odisha, 751024, India*These authors contributed equally to this workCorrespondence: Aparna Rao, Glaucoma Service, LV Prasad Eye Institute, MTC Campus, Bhubaneswar, Odisha, 751024, India, Tel +91 674 2653001, Fax +91 674 2653130, Email aparna@lvpei.org; vinodini10375@yahoo.comPurpose: To report the early postoperative causes of intraocular pressure (IOP) spikes after complete circumferential gonioscopy-assisted transluminal trabeculotomy (GATT) using anterior segment optical coherence tomography (ASOCT).Methods: This was retrospective interventional case series of patients who underwent circumferential GATT by a single surgeon (APR) from 2021 to 2022 at a tertiary eye care in East India and who developed IOP spikes at 1 day-2 weeks (immediate) or early (> 2 weeks– 2 months) after GATT. The intraocular pressure (IOP), glaucoma medications, and angle evaluation by ASOCT at 1 week, and 1 month were compared between the two groups.Results: Thirty-two eyes of 32 consecutive patients, aged 40± 20.1 years (20 exfoliation glaucoma, 9 juvenile open-angle, and 3 developmental glaucoma), that developed IOP spikes between immediate (n=20) or early (n=12) IOP spikes after GATT, were included. Immediate postoperative spikes were seen in 20 eyes due to retained viscoelastic (n=8), hyphema (n=8) in uncontrolled hypertension, and peripheral anterior synechiae (PAS) (n=6) of which only one eye required medication at 2 months. Causes of immediate IOP spikes on ASOCT included an inverted/reattached trabecular shelf, iris strands in eyes with abnormal iris in developmental glaucoma, and PAS in 1– 2 quadrants. Causes of early IOP spikes included PAS > 3 quadrants (n=8), and hyperreflective fibrotic tissue over TM (n=4) with 50% requiring medications at 2 months. The ASOCT features predicting the need for medications were PAS > 3 quadrants (OR=8.4[2.2– 14.3], p=0.03) and fibrotic TM closure (OR=5.4, [3.6– 10.2], p=0.003). One eye with macrohyphema 3 days after surgery owing to uncontrolled hypertension (owing to the stoppage of medicines), required additional incisional trabeculectomy within 1 month of surgery.Conclusion: Immediate IOP spikes are mostly self-resolving as opposed to early IOP spikes > 2 weeks that require medications after GATT. Gonioscopic PAS > 3 quadrants, and fibrotic TM closure were the main identifiable ASOCT causes predicting the need for medications after GATT.Keywords: GATT, MIGS, angle surgery, intraocular pressure, anterior segment OCT, glaucoma surgery

In this study, a dynamic model is used for the position control of an ionic polymer-metal composite (IPMC) actuated underwater propulsor. A time trace of actuation parameters versus voltage input is observed. The transfer function between the applied voltage and tip displacement is almost linear and flat before the cut-off frequency because of the mechanical damping. Also, a transfer function between the applied voltage and tip velocity is taken and this particular transfer function shows a sudden rise while approaching resonant frequency. This observation is clear to suggest that at this stage, highest vibration velocity is achieved by the fin tip. It can be seen from bode plots that the optimal range of actuation frequency can be identified and it will be helpful in getting maximum thrust production. Since Reynolds number depends on the length and width of IPMC, consideration of the length of IPMC propulsor is an important factor. The length of the IPMC propulsor is considered to be small as one of the objectives of the present study is to design miniaturized propulsor. Power consumption by the propulsor is an important factor, and it has also been considered in this study. Further, swimming speed is calculated for various input sinusoidal voltages. Power spent during actuation is calculated for various conditions. A parametric study is done by taking different fluid viscosities, IPMC strip lengths, widths of IPMC strip, and different voltage inputs to compare the results for different conditions. It can be seen that the average thrust and Reynolds number values depend on the length and width of IPMC strip as well as on input voltage. In order to give controlled input and obtain controlled system response, a proportional integral derivative (PID) control is implemented on the transfer functions. In this study, the displacement of 2 mm is considered as the desired value of deflection for the particular input and it is achieved via controlled input voltage. It was found that the system can be controlled for displacement by controlling the input voltage using a PID closed-loop position control. Also, a comparison is done with a fuzzy controller with improved controlled parameters like overshoot, settling time, and steady-state error.

In this paper, electro-mechanical dynamic modeling of a biomimetic propulsor based on undulating ribbon fin is proposed. Kinematics of the system is considered as the sinusoidal undulating motion of the ribbon fin which is guided by the actuating ionic polymer metal composite material. This is a smart material that actuates when an input voltage is applied and composed of a simple RC circuit. Elongated body theory is used to produce system dynamics considering the kinematics and also the hydrodynamic parameters like drag is undertaken as the application aspect is underwater environment. The proposed model has been used to evaluate the speed and thrust of the biomimetic system. Also, the thrust efficiency can be obtained for the different input frequencies. The proposed model may contribute to the understanding of an undulating ribbon fin inspired by IPMC for the underwater locomotion.

Replacing expensive Pd-catalysts by a low cost and sustainable catalytic system is one of the major challenging areas of research in synthetic organic chemistry. Herein, we report a new Cu(II)-anchored mesoporous catalyst (SBA-NH2-L-Cu) by immobilizing Cu(II) over organic ligand (L) anchored amino functionalized mesoporous SBA-15 (SBA-NH2-L) material. SBA-NH2-L-Cu has been characterized by different physicochemical techniques like powder X-ray diffraction (PXRD), Fourier-transform infrared (FTIR), high resolution transmission electron microscopy (HRTEM), N2 sorption, X-ray photoelectron spectroscopy (XPS), electron paramagnetic resonance (EPR) and thermo-gravimetric analysis (TGA). SBA-NH2-L-Cu has been employed as an efficient heterogeneous catalyst in the Sonogashira C–C cross-coupling reaction for the synthesis of aromatic alkynes in the 1: 1 solvent mixture of 1,4-dioxan and water in the presence of K2CO3 base and very minor amount of Pd/C (5% on active charcoal, 0.25 mol%) as co-catalyst at 80 °C in 4 h reaction time. The catalyst is easy to handle and recycled for several times without any significant loss in catalytic activity.

Serotonin (5-hydroxytryptamine, 5-HT) is an intrinsically fluorescent neurotransmitter found in organisms spanning a wide evolutionary range. Serotonin exerts its diverse actions by binding to distinct cell membrane receptors which are classified into many groups. Serotonin receptors are involved in regulating a diverse array of physiological signaling pathways and belong to the family of either G protein-coupled receptors (GPCRs) or ligand-gated ion channels. Serotonergic signaling appears to play a key role in the generation and modulation of various cognitive and behavioral functions such as sleep, mood, pain, anxiety, depression, aggression, and learning. Serotonin receptors act as drug targets for a number of diseases, particularly neuropsychiatric disorders. The signaling mechanism and efficiency of serotonin receptors depend on their amazing ability to rapidly access multiple conformational states. This conformational plasticity, necessary for the wide variety of functions displayed by serotonin receptors, is regulated by binding to various ligands. In this review, we provide a succinct overview of recent developments in generating and analyzing high-resolution structures of serotonin receptors obtained using crystallography and cryo-electron microscopy. Capturing structures of distinct conformational states is crucial for understanding the mechanism of action of these receptors, which could provide important insight for rational drug design targeting serotonin receptors. We further provide emerging information and insight from studies on interactions of membrane lipids (such as cholesterol) with serotonin receptors. We envision that a judicious combination of analysis of high-resolution structures and receptor-lipid interaction would allow a comprehensive understanding of GPCR structure, function and dynamics, thereby leading to efficient drug discovery.

Advances in the field of new smart materials suggested investigating their capabilities as energy harvesters. Ionic polymer-metal composite (IPMC) is a relatively new type of smart materials and it belongs to the class of electroactive polymers (EAP). IPMC has already been considered as a potential candidate for energy harvester by several researchers. In this paper, a tapered (in thickness) IPMC energy harvester is considered to investigate the effects of modification of geometric configurations on energy harvesting capabilities. A mathematical model for the tapered IPMC harvester is developed. The energy harvester is analyzed using the proposed mathematical model. Numerical results show that the present harvester configuration can generate a significant amount of power. Moreover, the tapered IPMC energy harvester improves the fatigue life of the harvester as the tapered geometry reduces stress concentration at the fixed point. Therefore, the tapered IPMC energy harvester can be considered for several engineering applications such as wearable sensors, micro-electro-mechanical devices, etc.

We define a map from second quandle homology to the Schur multiplier and examine its properties. Furthermore, we express the second homology of Alexander quandles in terms of exterior algebras. Additionally, we present a self-contained proof of its structure and provide some computational examples., 16 pages

Purpose: To identify the correlation between the broken foveal avascular zone (FAZ) on fundus fluorescein angiography (FFA) with the outer retinal changes on the optical coherence tomography (OCT) and its relationship with visual acuity. Methods: The study included the patients with diabetic retinopathy, non-proliferative and proliferative, with broken FAZ on FFA, and were compared with the controls selected from the eyes without retinopathy and intact FAZ. The OCT scanning with enhanced depth imaging (EDI) through the area of broken FAZ was reviewed. Results: Thirty eyes (mean age 51+12.92 years) with broken FAZ were included-18 eyes showed broken inner segment- outer segment (IS-OS) on OCT (p=0.21). Mean diabetic age was 8.3+4.01 years. Eight eyes in the study group had >20/30 best-corrected visual acuity (p=0.26). Macular thickness and visual acuity did not have a linear correlation. The duration of diabetes had a significant correlation with broken IS-OS junction (p=0.004). The odds of poor vision with broken FAZ were 2.5 (95% CI 0.5-12.4). The positive predictive value (PPV) of disrupted IS-OS junction in broken FAZ was 47.37% (95% CI (range 30.98% to 64.18%) and the negative predictive value (NPV) of intact IS-OS junction in broken FAZ was 50% (95% CI range 29.12% to 70.88%). The combined PPV of poor vision (9 years) was 88.89% (range 51.75% to 99.72%) and the NPV was 100% (range 71.51% to 100%). Conclusion: Disrupted IS-OS junction could indicate an ischemic macula, but correlation with visual acuity is important.

OBJECTIVES: To describe the changes in ventilator management over time in patients with neurologic disease at ICU admission and to estimate factors associated with 28-day hospital mortality. DESIGN: Secondary analysis of three prospective, observational, multicenter studies. SETTING: Cohort studies conducted in 2004, 2010, and 2016. PATIENTS: Adult patients who received mechanical ventilation for more than 12 hours. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among the 20,929 patients enrolled, we included 4,152 (20%) mechanically ventilated patients due to different neurologic diseases. Hemorrhagic stroke and brain trauma were the most common pathologies associated with the need for mechanical ventilation. Although volume-cycled ventilation remained the preferred ventilation mode, there was a significant (p < 0.001) increment in the use of pressure support ventilation. The proportion of patients receiving a protective lung ventilation strategy was increased over time: 47% in 2004, 63% in 2010, and 65% in 2016 (p < 0.001), as well as the duration of protective ventilation strategies: 406 days per 1,000 mechanical ventilation days in 2004, 523 days per 1,000 mechanical ventilation days in 2010, and 585 days per 1,000 mechanical ventilation days in 2016 (p < 0.001). There were no differences in the length of stay in the ICU, mortality in the ICU, and mortality in hospital from 2004 to 2016. Independent risk factors for 28-day mortality were age greater than 75 years, Simplified Acute Physiology Score II greater than 50, the occurrence of organ dysfunction within first 48 hours after brain injury, and specific neurologic diseases such as hemorrhagic stroke, ischemic stroke, and brain trauma. CONCLUSIONS: More lung-protective ventilatory strategies have been implemented over years in neurologic patients with no effect on pulmonary complications or on survival. We found several prognostic factors on mortality such as advanced age, the severity of the disease, organ dysfunctions, and the etiology of neurologic disease.

Based on the presentation of the Kauffman bracket skein module of the torus given by the third author in previous work, Charles D. Frohman and R\u{a}zvan Gelca established a complete description of the multiplicative operation leading to a famous product-to-sum formula. In this paper, we study the multiplicative structure of the Kauffman bracket skein algebra of the thickened four-holed sphere. We present an algorithm to compute the product of any two elements of the algebra, and give an explicit formula for some families of curves. We surmise that the algorithm has quasi-polynomial growth with respect to the number of crossings of a pair of curves. Further, we conjecture the existence of a positive basis for the algebra., Comment: 19 pages, 10 figures

The offshore Lakshmi Field, located in the southern part of Cambay Basin in the CB/OS-2 block in western India, is a success story of transitioning from a plateauing gas field to an oil-producing asset. Hydrocarbons sourced from Hazira Shale at Lakshmi Field are trapped in inversion-related four-way dip closures. The reservoirs are within the Miocene-age Tarkeshwar and overlying Babaguru formations; both have excellent reservoir quality with porosity ranging from 25% to 30% and Darcy-scale permeability. During the initial exploration stage, presence of oil was established in the deeper lower Tarkeshwar sands. However, the full oil potential of the field was not realized in the early stage of development due to difficulty in characterizing laterally and vertically discontinuous thin sands. These sands are often not detected in conventional 3D seismic data due to severe attenuation-related masking by overlying thick gas sands. Given the uncertainty of the oil potential of the field, a revised look using advanced seismic technologies was undertaken to drive a new infill drilling campaign. Seismic reprocessing using Q-tomographic inversion was performed to address the gas-attenuation problem, resulting in an improved seismic image. The new seismic data enabled characterization of thin reservoir sands using analytical techniques such as spectral decomposition and amplitude-variation-with-offset (AVO) attribute analysis. An integrated reservoir-characterization approach using field analogs, interpretation within a sequence stratigraphic framework, concepts of seismic geomorphology, and quantitative seismic analysis helped identify optimal areas of the sand fairway for infill well placement. Several infill wells have since been drilled that encountered good pay zones, validating the integrated approach. This successful campaign doubled oil production at Lakshmi and extended the field life by increasing reserves.

In this paper, an effort is made to measure and verify analytical and experimental aspects of a cantilevered smart material of various dimensions which is electrically actuated for various applications. The smart material is taken as ionic polymer-metal composite (IPMC). The supported cantilevered beam model is analyzed, the relations for block force are provided, and the same is used to derive displacement at the free end. In order to make a proper agreement between the analytical results and measured results from an experimental setup, a comparison is made using a bending beam equation for the cantilevered condition with determined physical properties. The effect of water content in the parameters like deflection under the voltage actuation of IPMC is observed during the experimental process for underwater conditions.

Mechanical energy harvesting from human motion is new technology for generating clean and reasonable electrical energy for powering wearable devices used in health monitoring, gait analysis and so on. In this document, design and analysis of ionic polymer metal composite-based shoe energy harvester is proposed. Ionic polymer metal composite (IPMC) is a smart material of electroactive polymer categories and functionally similar to piezoelectric material and can be used as actuator, sensors or energy harvester. The harvester is based on specially designed two initially curved plates of spring steel attached together back to back and is placed under the heel of the shoe. It is found that IPMC in series produced the voltage of 6.4 V and power of 0.699 W across the load resistance of 2 Ω at walking speed of 2 steps per seconds. From these results, it is concluded that IPMC can be used for energy harvesting application. This work demonstrates the feasibility of IPMC for shoe-based energy harvesting to power wearable sensors.

Protein-protein interaction networks are critical components of cellular regulation. Hub proteins, defined by their ability to interact with numerous protein partners, are the pivots of these networks. A hypothesis that an ensemble of rapidly interconverting conformational states contributes significantly to the ability of hub proteins to interact with diverse partners has been proposed. The master gene regulator p53 is a prototype multidomain hub protein. Its DNA-binding domain alone is involved in interactions with many of its partner proteins. We investigated the dynamics of the p53 DNA-binding domain by 15N-NMR Carr-Purcell-Meiboom-Gill relaxation methods. In the DNA-bound state, we detected conformational exchanges in the domain in the microsecond to millisecond timescale, while dynamics at this timescale was not detectable in the free state. This suggests that the binding of p53 to specific DNA sequences promotes exchange between two or more conformational states, creating a broad conformational repertoire necessary for interacting with many partner proteins.

One of the Key Technology used for Autonomous Driving is "Trajectory Tracking and Planning". the prior safety actions should be taken for Roll-Over Stability Control and Yaw Stability Control where the Majority of car crashes and accidents takes place. In this paper we developed a mathematical driver model for trajectory tracking in autonomous driving. We designed control algorithms in order to track a given trajectory using different control techniques like a classical PID (Proportional Integral Derivative) controller and some advanced control techniques like LQR (Linear Quadratic Regulator) and MPC (Model Predictive Control) which are dynamic controllers. Efforts have been made to perform closed loop simulation in MATLAB, this paper gives a crisp comparison about performance of each controller. This simulation results indicate that the mathematical driver model successfully replicate’s human driving performance and can be used for dynamics analysis of vehicle. This research compares different controllers’ performances for trajectory tracking in autonomous driving.

This paper has partially a novel and partially a survey character. We start with a short review of rack (two term) homology of self distributive algebraic structures (shelves) and their connections to knot theory. We concentrate on a sub-family of quandles satisfying the graphic axiom. For a large family of graphic quandles (including infinite ones), we compute the second rack homology groups. Finally, we propose conjectures based on our computational data., 12 pages, 2 figures

Mutations in the core domain of tumor suppressor protein p53 have been associated with ∼50% of the occurrences of human cancers. A majority of these mutations inactivate p53 function by destabilizing its native structure. Although studies have shown p53's function can be restored by stabilizing the mutants to their wild-type conformation with immense therapeutic potential, its applicability has been restricted because of our limited understanding of the precise nature of destabilization arising from changes in the mutant p53's structure and dynamics. Here, using nuclear magnetic resonance (NMR) spectroscopy and molecular dynamics simulations, we have probed the conformational flexibility in three of the most widespread and clinically important "hot spot" mutants of the p53 core domain. Our results show that NMR order parameter-derived conformational entropy is linearly correlated with the change in free energy of urea-mediated denaturation, the latter being a well-established reporter of stability in p53 core domain mutants. Using a linear regression function, we show that the three parameters of equilibrium denaturation experiments, i.e., the free energy of denaturation (Δ GD-NH2O), the slope of the transition ( m), and the urea concentration at 50% denaturation ([urea]50%), can be used to predict the conformational entropy in p53 core domain mutants, thereby demonstrating a method for using these parameters as predictors of a protein's conformational entropy, which has been known to shape the functional properties of proteins.

To investigate whether referrals to memory services in London reflect the ethnic diversity of the population.Memory service data including referral rates of BAME was collected from London Clinical Commissioning Groups (CCGs).The expected percentage of BAME referrals using census data was compared against White British population percentages using the chi squared test. We found that within 13,166 referrals to memory services across London, the percentage of people from BAME groups was higher than would be expected (20.3 versus 19.4%; χResults are encouraging and may indicate a significant improvement in awareness of dementia and help seeking behaviour among BAME populations. Prevalence of dementia in some ethnic groups may be higher so these numbers could still indicate under-referral. Due to the data available we were unable to compare disease severity or diagnosis type.

Now a day’s electronics is becoming more and more compact. Electronic circuits and devices need cooling means in order to dissipate heat. Heat sinks are mostly used these days. Piezoelectric fans can also be used for this purpose. Piezoelectric fans are cantilevered uni-morph or bi-morph, containing substrate sandwiched between two layers of piezoelectric material. As sinusoidal voltage is applied to piezoelectric material, cantilever starts to vibrate and generates air flow. The advantage of using piezofans is that they consume less power and are low noise devices. The deflection and frequency play a major role in flow generation. This paper predicts the behavior of displacement and frequency on variation of material properties. Classical Monte Carlo simulation is used for prediction of uncertainty in performance parameter. It is found that uncertainty in material properties causes large deviations in performance parameters, from the predicted ones.

Present paper deals with the fabrication of synthetic fiber, Nylon Reinforced Composites (NRC) material by hand lay-up technique. In this type of composite, nylon act as a reinforcement material while epoxy resin act as the matrix material. Comparison has been made between the NRC and the pure epoxy polymer in terms of tensile strength and the drilling thrust force. The experimental results indicate that tensile strength obtained by NRC is higher than strength of pure epoxy polymer however little variation is found between the obtained values of thrust force.

In recent years, robotics has become an important domain in the field of engineering. It plays a crucial role in various fields, one of them being inspection purpose. In-pipe inspection robots are necessary for the safe and smooth running of industries. Problems arising in the piping network may lead to loss of the transported medium and leakage of which often affect the environment. Hence, it must be continuously inspected which involves large amount of labour. Also, the working environment usually involves possible exposure to hazardous chemicals or gases, humid and low oxygen content air, zones inaccessible to human hands, etc. Robots can act in an inaccessible environment and also reduce human effort. Therefore, inspection robots are strongly demanded. The main objective of the present work is to design a miniature robot which can adapt to narrow surfaces. In-pipe inspection robot using DC Motor (conventional actuators) is developed for this purpose. Modelling of the robot is done in SolidWorks. Simulations were performed for horizontal and vertical configuration of pipe and results were plotted. A prototype is developed and experiments were carried out in horizontal pipe. A comparison of results for different parameters obtained from simulation study and experimental work was done.

s Ionic Polymer Metal Composites (IPMC) are smart materials which are used as sensor and actuators. A cantilever IPMC beam is considered as energy harvester in the fluid environment. An estimation of the power harvested by the cantilever IPMC beam from the base excitation is obtained using a mathematical model. Furthermore, an energy harvester consisting of several IPMC layers is considered for the improvement of the harvesting capabilities. The multilayer IPMC harvester is designed with series and parallel stacking. A significant improvement is found in the power harvested by considering the multilayer IPMC harvester with series stacking. The Power harvested in fluid environment can be used for the application of MEMS devices which requires low power in the range of microwatt to nanowatt.

Mutations in p53’s DNA binding domain (p53DBD) are associated with 50% of all cancers, making it an essential system to investigate and understand the genesis and progression of cancer. In this work, we studied the changes in the structure and dynamics of wild type p53DBD in comparison with two of its “hot-spot” DNA-contact mutants, R248Q and R273H, by analysis of backbone amide chemical shift perturbations and 15N spin relaxation measurements. The results of amide chemical shift changes indicated significantly more perturbations in the R273H mutant than in wild type and R248Q p53DBD. Analysis of 15N spin relaxation rates and the resulting nuclear magnetic resonance order parameters suggests that for most parts, the R248Q mutant exhibits limited conformational flexibility and is similar to the wild type protein. In contrast, R273H showed significant backbone dynamics extending up to its β-sandwich scaffold in addition to motions along the DNA binding interface. Furthermore, comparison of rotational correl...

To describe the clinical characteristics, macular structure and function, and to document sequential changes over 5 years in a 10-year-old boy with bilateral primary foveomacular retinitis. A 10-year-old boy presented with sudden onset scotoma in both eyes, experienced after getting up from bed on a non-eclipse day. He persistently denied direct sun-gazing. He neither had any significant systemic illness, nor was using any medications. In addition to a detailed examination at presentation that included fundus fluorescein angiogram (FFA), electroretinogram (ERG), pattern ERG and electrooculogram (EOG), he was examined periodically for 5 years with Humphrey visual field (HVF), spectral domain optical coherence tomogram (SDOCT), Amsler grid charting and multifocal ERG. The macular structure and functions were analyzed over the years and correlated with the symptoms. All findings were bilaterally symmetrical at each visit. At presentation, his corrected visual acuity was 20/25 with subfoveal yellow dot similar to solar retinopathy, central scotoma with reduced foveal threshold in HVF 24-2, micropsia in Amsler grid, missing of two plates on Ishihara color vision chart, transfoveal full thickness hyper-reflective band on SD OCT, unremarkable FFA and normal foveal peak in mfERG. The flash ERG and EOG were unremarkable. A month later, his VA improved to 20/20, he had relative scotoma in Amsler grid, no scotoma in HVF (10-2), restoration of the inner segment of the photoreceptors with sharp defect involving ellipsoid and photoreceptor interdigitation zone in SDOCT and blunting of foveal peaks in mfERG. Three months later, his corrected VA was 20/20 with relative scotoma in Amsler grid, normal color vision, no scotoma in HVF 10-2 and unchanged SDOCT findings. In subsequent examinations at 6, 9, 14, 29, 39 and 60 months, he was symptomless with VA 20/20, unremarkable fundus, normal Amsler grid and HVF (normal foveal threshold), unchanged SDOCT findings and the reduced foveal peaks on mfERG in both eyes got normalized only at 60 months. Presented here is a case of bilaterally symmetrical idiopathic foveomacular retinitis that had a clinical appearance similar to solar retinopathy. The fundus changes persisted for 4 weeks, the symptoms and changes in Amsler grid lasted for 3 months, and the foveal threshold in visual fields normalized within 3 months. Maximum change in the SDOCT defect occurred within a month, and the extrafoveal defect in the ellipsoid and photoreceptor interdigitation line persisted despite resolution of symptoms and resolution of the visual field defect and normal distance vision. Probably, the foveal lesion detected on SDOCT was too small to cause a reduction in the distance visual acuity or show up in the visual field and mfERG later.

The serotonin 2A receptor (5-HT2A R) is an important member of the G-protein coupled receptor (GPCR) family involved in an array of neuromodulatory functions. Although the high-resolution structures of truncated versions of GPCRs, captured in ligand-bound conformational states, are available, the structures lack several functional regions, which have crucial roles in receptor response. Here, in order to understand the structure and dynamics of the ligand-free form of the receptor, we have performed meticulous modeling of the 5-HT2A R with the third intracellular loop (ICL3). Our analyses revealed that the ligand-free ground state structure of 5-HT2A R has marked distinction with ligand-bound conformations of 5-HT2 subfamily proteins and exhibits extensive backbone flexibility across the loop regions, suggesting the importance of purifying the receptor in its native form for further studies. Hence, we have standardized a strategy that efficiently increases the expression of 5-HT2A R by infecting Sf9 cells with a very low multiplicity of infection of baculovirus in conjunction with production boost additive and subsequently, purify the full-length receptor. Furthermore, we have optimized the selective over-expression of glycosylated and nonglycosylated forms of the receptor merely by switching the postinfection growth time, a method that has not been reported earlier.