REinforcement learning based Adaptive samPling: REAPing Rewards by Exploring Protein Conformational Landscapes

One of the key limitations of Molecular Dynamics simulations is the computational intractability of sampling protein conformational landscapes associated with either large system size or long timescales. To overcome this bottleneck, we present the REinforcement learning based Adaptive samPling (REAP) algorithm that aims to efficiently sample conformational space by learning the relative importance of each reaction coordinate as it samples the landscape. To achieve this, the algorithm uses concepts from the field of reinforcement learning, a subset of machine learning, which rewards sampling along important degrees of freedom and disregards others that do not facilitate exploration or exploitation. We demonstrate the effectiveness of REAP by comparing the sampling to long continuous MD simulations and least-counts adaptive sampling on two model landscapes (L-shaped and circular), and realistic systems such as alanine dipeptide and Src kinase. In all four systems, the REAP algorithm consistently demonstrates its ability to explore conformational space faster than the other two methods when comparing the expected values of the landscape discovered for a given amount of time. The key advantage of REAP is on-the-fly estimation of the importance of collective variables, which makes it particularly useful for systems with limited structural information

The phytosociological analysis of saline area of Tehsil Ferozewala, District Sheikhupura (Punjab), Pakistan

This study is a broad ecological survey, and classification of the vegetation of Agro Farm plantations of a Tehsil Ferozewala (District Sheikhupura) Punjab, Pakistan. The vegetation survey description and classification was according to Zurich-Montpellier School of thought is based on over 300 Relevé Method. In all twelve associations i.e. Suaedetum fruticosae, Kochietum indicum Diplachnetum fuscae, Desmostochyetum bipinnatae, maurorae, Polypogaetum monspeliensae, Erythraeo-Polypogaetum monspeliensae, Veteviarietum cylindrieae, Scirpetum maritimae and Typhetum angustitae are recognized and each association is further sub-divided into sub-associations and classified into its respective class, order and alliances according to central European Phyto-sociological methods. Several relationships of the plant community types have been worked out during this study. The soil characteristics of each vegetation type are discussed in relation to soil texture; pH, Conductivity, Carbonates, Bicarbonates, Chlorides and Sulphate as well as ecological affinities of each association are also described. By reintegrating these trees and shrubs back into agriculture landscape to reverse salinity such as Atriplex amnicla, Tamarix aphylla, Phoenix dactilifera, Prosopis spp. Susbenia bispinasa, Sesbenia sesbena, Casorina, Grewia asiatie, Psidium guava etc. The incorporation of these plants (grasses, shrubs and trees) into agriculture land system of the Punjab has potential to increase crop, fiber, wood and animal production and degradation of land will also be halted.Key words: Phyto-sociological, agroforestry, relev’es, plant associations, characteristic species, differential species, companion species

Simulation and Optimization of Coal Gasification in a Moving-bed Reactor to Produce Synthesis Gas Suitable for Methanol Production Unit

This paper presents process simulation and optimization of coal gasification process in a moving-bed reactor using Pittsburgh No. 8 coal as feed. The system of differential equations for the mass and energy balances was solved using 4th-order Runge-Kutta method and optimized by non-dominated sorting genetic algorithm-II (NSGA-II) method. The simulation was used to predict solid and gas temperature profile and gas composition along the reactor. The simulation results were compared successfully with experimental data relevant to Westfield plant in Scotland. In addition, the effect of operating parameters such as coal-to-oxygen molar ratio, steam-to-oxygen molar ratio, inlet gas temperature, reactor pressure, and oxygen mole fraction in inlet air on amount of synthesis gas (syngas) production, hydrogen to carbon monoxide molar ratio (HCMR) in produced syngas, and coal conversion was investigated. Finally, the reactor performance was optimized to produce the highest syngas production with a HCMR of two using NSGA-II method. This work is licensed under a Creative Commons Attribution 4.0 International License

Evaluation of the middle ear in water buffaloes (Bubalus bubalis) by gross anatomy and cone-beam computed tomography

Background: The purpose of this study was to provide a description of gross middle ear morphology in water buffaloes, augmented with additional data on the osseous structures of middle ear derived from cone-beam computed tomography (CBCT). Materials and methods: Skulls of 10 young adult male water buffaloes were used to examine their middle ears. Results: Anatomical features noted included the presence of tympanic cells in the tympanic bulla, the location of malleus head and neck, and all of incus in the dorsal epitympanic recess, the oval tympanic membrane, absence of a prominent notch on the articular surface of malleus, positional variations of the lateral process of malleus relative to the muscular process and muscular process relative to the rostral process of malleus, absence of complete coverage of the articular facet of malleus head by incus body, and presence of the lenticular process of incus. In CBCT images, the osseous part of external acoustic meatus, the petrous part of temporal bone and the details of the ossicles were seen, except for stapes. Conclusions: Although tympanic membrane, malleus and stapes of water buffaloes are similar to those of ox, the incus of water buffaloes is more similar to that of goats. The heaviest ossicles among the ruminants studied belonged to water buffaloes; the mean length of malleus head and neck, total length and width of incus body as well as length of stapes head were greatest in water buffaloes too. The auditory ossicles of water buffaloes show ‘transitional type’ morphological characteristics. These features suggest a relatively wide frequency range of hearing, but not one biased towards especially low or especially high frequencies

Cold Flow Verification Test Facility

The cold flow verification test facility consists of a 15-foot high, 3-foot diameter, domed vessel made of clear acrylic in two flanged sections. The unit can operate up to pressures of 14 psig. The internals include a 10-foot high jetting fluidized bed, a cylindrical baffle that hangs from the dome, and a rotating grate for control of continuous solids removal. The fluid bed is continuously fed solids (20 to 150 lb/hr) through a central nozzle made up of concentric pipes. It can either be configured as a half or full cylinder of various dimensions. The fluid bed has flow loops for separate air flow control for conveying solids (inner jet, 500 to 100000 scfh) , make-up into the jet (outer jet, 500 to 8000 scfh), spargers in the solids removal annulus (100 to 2000 scfh), and 6 air jets (20 to 200 scfh) on the sloping conical grid. Additional air (500 to 10000 scfh) can be added to the top of the dome and under the rotating grate. The outer vessel, the hanging cylindrical baffles or skirt, and the rotating grate can be used to study issues concerning moving bed reactors. There is ample allowance for access and instrumentation in the outer shell. Furthermore, this facility is available for future Cooperative Research and Development Program Manager Agreements (CRADA) to study issues and problems associated with fluid- and fixed-bed reactors. The design allows testing of different dimensions and geometries

Male obesity associated gonadal dysfunction and the role of bariatric surgery

Obesity is an ever growing pandemic and a prevalent problem among men of reproductive age that can both cause and exacerbate male-factor infertility by means of endocrine abnormalities, associated comorbidities, and direct effects on the precision and throughput of spermatogenesis. Robust epidemiologic, clinical, genetic, epigenetic, and preclinical data support these findings. Clinical studies on the impact of medically induced weight loss on serum testosterone concentrations and spermatogenesis is promising but may show differential and unsustainable results. In contrast, literature has demonstrated that weight loss after bariatric surgery is correlated with an increase in serum testosterone concentrations that is superior than that obtained with only lifestyle modifications, supporting a further metabolic benefit from surgery that may be specific to the male reproductive system. The data on sperm and semen parameters is controversial to date. Emerging evidence in the burgeoning field of genetics and epigenetics has demonstrated that paternal obesity can affect offspring metabolic and reproductive phenotypes by means of epigenetic reprogramming of spermatogonial stem cells. Understanding the impact of this reprogramming is critical to a comprehensive view of the impact of obesity on subsequent generations. Furthermore, conveying the potential impact of these lifestyle changes on future progeny can serve as a powerful tool for obese men to modify their behavior. Healthcare professionals treating male infertility and obesity need to adapt their practice to assimilate these new findings to better counsel men about the importance of paternal preconception health and the impact of novel non-medical therapeutic interventions. Herein, we summarize the pathophysiology of obesity on the male reproductive system and emerging evidence regarding the potential role of bariatric surgery as treatment of male obesity-associated gonadal dysfunction

ScreenTrack: Using a Visual History of a Computer Screen to Retrieve Documents and Web Pages

Computers are used for various purposes, so frequent context switching is inevitable. In this setting, retrieving the documents, files, and web pages that have been used for a task can be a challenge. While modern applications provide a history of recent documents for users to resume work, this is not sufficient to retrieve all the digital resources relevant to a given primary document. The histories currently available do not take into account the complex dependencies among resources across applications. To address this problem, we tested the idea of using a visual history of a computer screen to retrieve digital resources within a few days of their use through the development of ScreenTrack. ScreenTrack is software that captures screenshots of a computer at regular intervals. It then generates a time-lapse video from the captured screenshots and lets users retrieve a recently opened document or web page from a screenshot after recognizing the resource by its appearance. A controlled user study found that participants were able to retrieve requested information more quickly with ScreenTrack than under the baseline condition with existing tools. A follow-up study showed that the participants used ScreenTrack to retrieve previously used resources and to recover the context for task resumption.Comment: CHI 2020, 10 pages, 7 figure

Bandgap determination from individual orthorhombic thin cesium lead bromide nanosheets by electron energy-loss spectroscopy

Inorganic lead halide perovskites are promising candidates for optoelectronic applications, due to their high photoluminescence quantum yield and narrow emission line widths. Particularly attractive is the possibility to vary the bandgap as a function of the halide composition and the size or shape of the crystals at the nanoscale. Here we present an aberration-corrected scanning transmission electron microscopy (STEM) and monochromated electron energy-loss spectroscopy (EELS) study of extended nanosheets of CsPbBr3. We demonstrate their orthorhombic crystal structure and their lateral termination with Cs–Br planes. The bandgaps are measured from individual nanosheets, avoiding the effect of the size distribution which is present in standard optical spectroscopy techniques. We find an increase of the bandgap starting at thicknesses below 10 nm, confirming the less marked effect of 1D confinement in nanosheets compared to the 3D confinement observed in quantum dots, as predicted by density functional theory calculations and optical spectroscopy data from ensemble measurements

An epoxide intermediate in glycosidase catalysis

Retaining glycoside hydrolases cleave their substrates through stereochemical retention at the anomeric position. Typically, this involves two-step mechanisms using either an enzymatic nucleophile via a covalent glycosyl enzyme intermediate or neighboring-group participation by a substrate-borne 2-acetamido neighboring group via an oxazoline intermediate; no enzymatic mechanism with participation of the sugar 2-hydroxyl has been reported. Here, we detail structural, computational, and kinetic evidence for neighboring-group participation by a mannose 2-hydroxyl in glycoside hydrolase family 99 endo-α-1,2-mannanases. We present a series of crystallographic snapshots of key species along the reaction coordinate: a Michaelis complex with a tetrasaccharide substrate; complexes with intermediate mimics, a sugar-shaped cyclitol β-1,2-aziridine and β-1,2-epoxide; and a product complex. The 1,2-epoxide intermediate mimic displayed hydrolytic and transfer reactivity analogous to that expected for the 1,2-anhydro sugar intermediate supporting its catalytic equivalence. Quantum mechanics/molecular mechanics modeling of the reaction coordinate predicted a reaction pathway through a 1,2-anhydro sugar via a transition state in an unusual flattened, envelope (E 3) conformation. Kinetic isotope effects (k cat/K M) for anomeric-2H and anomeric-13C support an oxocarbenium ion-like transition state, and that for C2-18O (1.052 ± 0.006) directly implicates nucleophilic participation by the C2-hydroxyl. Collectively, these data substantiate this unprecedented and long-imagined enzymatic mechanism