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Abstract Directed evolution (DE) is a powerful tool to optimize protein fitness for a specific application. However, DE can be inefficient when mutations exhibit non-additive, or epistatic, behavior. Here, we present Active Learning-assisted Directed Evolution (ALDE), an iterative machine learning-assisted DE workflow that leverages uncertainty quantification to explore the search space of proteins more efficiently than current DE methods. We apply ALDE to an engineering landscape that is challenging for DE: optimization of five epistatic residues in the active site of an enzyme. In three rounds of wet-lab experimentation, we improve the yield of a desired product of a non-native cyclopropanation reaction from 12% to 93%. We also perform computational simulations on existing protein sequence-fitness datasets to support our argument that ALDE can be more effective than DE. Overall, ALDE is a practical and broadly applicable strategy to unlock improved protein engineering outcomes.

The current study deals with the evaluation of vibrations and noise generated by a diesel engine powered by Calophyllum inophyllum biodiesel blend (B20) and molybdenum trioxide (MoO3) nanoparticles, predicted using machine learning algorithms. The nanoparticles were spread out in B20 at a level of 75 ppm, along with a surfactant and a dispersant to make sure they mixed evenly with the fuel samples. The stability of the nanoparticles was then tested using the principle of photo spectroscopy and it was found that the stability of nanoparticles to which surfactants and dispersants had been added was increased. The experiment with the diesel engine was carried out to evaluate the vibrations and noise by varying different loads (3, 6, 9, and 12 kgf) and injection pressures (200, 220, and 240 bar). The vibrations and noise intensity were reduced with B20 compared to normal diesel and a further reduction was observed by adding nanoparticles together with the dispersant. With increasing load, the RMS velocity and the RMS noise also increased, but these decreased with increasing injection pressure. The most favourable result for RMS velocity and RMS noise was B20+MoO3 75 ppm+ Dispersant 75ppm. At an injection pressure of 240 bar and a full load of 12 kgf, the RMS velocity was 0.568 m s-1 and 55.265 dB, which corresponds to an improvement of 28.76 % and 9.78 % respectively compared to conventional diesel for B20+MoO375ppm+ Dispersant 75ppm. Finally, the entire experimental data of 60 were predicted using various machine learning (ML) algorithms, such as Random Forest (RF), Decision Trees (DT), Artificial Neural Networks (ANNs), Support Vector Machines (SVM) and XG Boost and the predicted results correlated well with the experimental values. All algorithms have shown a good association, but XGBoost has shown a better correlation coefficient (R2). The R2 of each algorithm is in the range of 0.94–0.99, the MRE and RSME are also in the significant range for both RMS velocity and RMS noise.

Abstract Introduction To achieve epidemic control of infectious diseases, engaging higher‐burden populations with accessible diagnostic services is critical. HIV self‐testing (HIVST) is a promising option. Methods We implemented an online HIVST programme for key populations across India. Eligible clients were 18 years or older, self‐reported a negative or unknown HIV status and reported not taking antiretroviral therapy. Clients who reported a prior HIV diagnosis were not eligible to receive an HIVST kit. HIVST clients received kits via courier or in person at pre‐determined pick‐up points supported by trained counselling staff. Virtual counsellors engaged clients online and by phone and offered support to register, access, and complete HIVST free of cost. Virtual counsellors supported clients to report results and engage with follow‐up services. Follow‐up included linking clients with a positive result to confirmatory testing and HIV care services. We assessed programmatic data across HIV continuum outcomes and conducted a qualitative evaluation through interviews with purposively sampled clients. Results Between 30 June 2021 and 30 September 2022, 5324 clients ordered an HIVST kit (76% men, 13% women, 7% transgender people, 4% unknown gender). Of the 4282 clients reporting results (94% of those who received a kit), 6% screened positive, among whom 72% (n = 184) completed confirmatory testing. Themes from 41 client interviews included satisfaction about the convenience and privacy of services and the discreet nature of kit delivery. Respondents were drawn to the convenience of HIVST and appreciated gaining courage and comfort throughout the process from virtual counsellor support. For respondents who screened positive, challenges to care linkage included fearing judgemental questions from public providers and wanting more time before starting treatment. Clients shared concerns about kit accuracy and suggested that instructional materials be provided with more diverse language options. Conclusions Web‐based HIVST services with tailored support appeared to facilitate HIV service access and engagement of harder‐to‐reach populations across India. Assistance from a community‐oriented counsellor proved important to overcome literacy barriers and mistrust in order to support the HIVST process and service linkage. Learnings can inform global efforts to improve the critical step of diagnosis in achieving epidemic control for HIV and other infectious diseases.

Segmentation process is very popular in Speech recognition, word count, speaker indexing and speaker diarization process. This paper describes the speaker segmentation system which detects the speaker change point in an audio recording of multi speakers with the help of feature extraction and proposed distance metric algorithms. In this new approach, pre-processing of audio stream includes noise reduction, speech compression by using discrete wavelet transform (Daubechies wavelet 'db40' at level 2) and framing. It is followed by two feature extraction algorithms pyknogram and nonlinear energy operator (NEO). Finally, the extracted features of each frame are used to detect speaker change point which is accomplished by applying dissimilarity measures to find the distance between two frames. To realize it, a sliding window is moved across the whole data stream to find the highest peak which corresponds to the speaker change point. The distance metrics incorporated are standard "Bayesian Information Criteria (BIC)", "Kullback Leibler Divergence (KLD)", "T-test" and proposed algorithm to detect the speaker boundaries. At the end, threshold value is applied and their results are evaluated with Recall, Precision and F-measure. Best result of 99.34% is shown by proposed distance metric with pyknogram as compare to BIC, KLD and T-test algorithms.

Summary: Coupled resonant cavities can enable strong photon energy confinement to facilitate the miniaturization of functional photonic devices for applications in designs of sensors, modulators, couplers, waveguides, color filters etc. Typically, the resonances in subwavelength plasmonic cavities rely on the excitation of surface plasmons at specific phase-matching conditions, usually determined by the lattice parameters and constituent material properties. Contrary to this notion, we experimentally demonstrate the control and manipulation of cavity resonances via suitably modifying the split ring resonator geometry in hybrid plasmonic-metasurface (dipole cavity-SRR) configuration without altering the lattice parameters. This results to the excitation of dual resonance peaks. Such dual channel characteristics demonstrate high quality (Q) factor, multi-band resonances, not permissible with typical (unhybridized) plasmonic dipole cavities. We envisage such hybrid meta-cavity designs can become important ingredients for futuristic terahertz devices that can hold the key for sixth generation (6G) communications, designer filters, dual channel sensors etc.

Abstract Single nucleotide polymorphisms (SNPs) may act as biological markers, as they can relate to the genes that are associated with various complex diseases such as heart diseases, diabetes, cancer, schizophrenia, blood pressure, migraine, and Alzheimer. These SNPs mostly locate within a gene or in a regulatory region near a gene and can affect the gene’s function to play a more direct role in disease. Hence, SNPs allow scientists to develop candidate drug therapy by evaluating an individual’s genetic makeup to develop a particular disease. Gene-gene interactions generally complicate migraine and its genetics and further gene-environmental interactions that often misguide the true defying causes of this disease. Due to its complex nature, it is difficult for scientists to reveal a complete list of SNPs or even all the genes that are related with the pathogenesis of this disease. Nowadays, much work has been done in this direction and new variants of migraine are being constantly identified. In this review article, the role of various SNPs reported to be disease-associated in published migraine GWAS has been discussed. To understand the molecular mechanisms of migraine attack by identifying new genetic variants of migraine can be a key to develop new therapeutic strategies in the future.

Abstract The objective of the present investigation is to explore the influence of ternary (diesel‐biodiesel‐alcohol) fuel blends on the combustion and vibration parameters of a variable compression ratio compression ignition engine. Kusum seed oil biodiesel and isobutyl alcohol were blended with conventional diesel to make a ternary fuel. The blend of biodiesel‐diesel (B20) was made in proportion of 20% and 80% by volume, respectively. Furthermore, isobutyl alcohol was added at diverse proportions (ie, 0.25%, 0.5%, 0.75%, and 1%). The investigation was carried at different compression ratios (CRs), namely, 16.5, 17.5, and 18.5. The study shows that, upon the addition of isobutyl alcohol, the combustion characteristics (ie, cylinder pressure [CP] and net heat release rate [NHRR]) are significantly enhanced, whereas the mechanical vibration level maintains stable. The CP and NHRR of B20+ 1% isobutyl alcohol are greatly improved for corresponding values of 4.55% and 8.39%, respectively, except for the conventional diesel at CR 18.5. Furthermore, the root mean square velocity (vibration) decreases when increasing the quantity of isobutyl alcohol and attained a minimum with B20+ 1% isobutyl alcohol. The experimental results show that the isobutyl alcohol up to 1% with diesel‐biodiesel blends can be used in the CI engine with no further adjustments.

Objective: To determine pattern of health care utilization and extent of out-of-pocket healthcare expenditure in rural areas of Punjab in India. Methods: Using multi stage sampling procedure, 660 participants were selected from 110 villages, out of all 22 districts; 440 participants had utilized outpatient care in past 15 days, and 220 had been hospitalized in past one year. Pretested semistructured questionnaires were used to enquire about household and healthcare expenditures. Out-of-pocket (OoP) expenditure included only direct costs of healthcare. Sevety seven 77 (12%) participants could not provide expenditures, hence were excluded from analysis. More than 10% of total household expenditure on healthcare was considered catastrophic. Results: Majority of the participants had used public sector health facilities for outpatient (57%) and inpatient (51.5%) care. Public sector facilities were utilized more often for communicable diseases and gynaecological problems whereas private sector services were used more commonly for accidents and non-communicable diseases. Mean healthcare expenditure on outpatient and inpatient healthcare services was Indian Rupees (INR) 8501 and INR 53889 respectively. Expenditure in private sector was significantly higher compared to the public sector facilities. Catastrophic expenditure was incurred by 7% of the households while seeking outpatient care and by 53% while seeking inpatient care. To pay for outpatient and inpatient care, 23.3% and 61.5% of the participants respectively had to borrow money or sell their assets. Conclusions: Healthcare expenditure places households under considerable financial strain in rural areas of Punjab in India. Improvements of public hospitals may increase their utilization and decrease financial burden.

Purpose: The current study focuses on measuring the level of vibration and noise produced by a direct injection diesel engine when running on a mixture of molybdenum trioxide (MoO3) nanoparticles and Calophyllum inophyllum biodiesel (B20). Methods: The nanoparticles were used in an amount of 75 ppm and mixed with a surfactant and dispersant. In addition, the prepared fuel samples were tested on a diesel engine to investigate the vibration and noise characteristics by changing the injection pressures to 200 bar, 220 bar and 240 bar. Results and conclusion: The addition of nanoparticles to B20 has significantly reduced vibration and noise, especially when using nanofuel enriched with dispersants. In addition, the increased pressure during fuel injection resulted in reduced vibration and noise levels. Using B20 + MoO3 75 ppm + Dispersant 75 ppm fuel blend gave the most favourable results regarding RMS velocity and noise levels compared to the base diesel fuel. The progressive reduction in vibration and noise levels was seen as a result of the increased injection pressure. At a pressure of 240 bar, the B20 + MoO3 75 ppm + dispersant 75 ppm has shown a lower vibration and noise intensity than diesel and other fuel samples. The RMS velocity of RMS noise of B20 + MoO3 75 ppm + dispersant 75 ppm are 0.591 m/s, 0.568 m/s, and 0.491 m/s at 200 bar, 220 bar and 240 bar while the RMS noise is 68.266 dB (A), 66.283 dB (A), and 65.857 dB (A) respectively. The most decrease in vibration and noise was 28.76% and 9.78%, respectively compared to regular diesel for B20 + MoO3 75 ppm + dispersant 75 ppm at 240 bar. Finally, the kurtosis and skewness of the vibration data are within the normal range, which indicates that the distribution corresponds to the ideal normal distribution. [ABSTRACT FROM AUTHOR]

The recent trend in research fosters the use of abundant seawater for modifying metal surfaces as electrode materials for energy generation, storage, transport, and water-splitting technologies. Economic and ecofriendly seawater is used as a solvent for modifying the surface of 3D nickel-foam (NiF) to Na2O–NiCl2@NiF as an electrode material in electrochemical supercapacitors and water-splitting electrocatalysis applications. The phase of the as-obtained Na2O–NiCl2 is confirmed from the proposed reaction mechanism, followed various physical measurement tests such as X-ray photoelectron spectroscopy and Fourier transform infrared analysis. The formation of Na2O–NiCl2 is caused by a high operation temperature and pressure of seawater solvent, the presence of lone pair electrons on oxygen, and more reactivity of Na for combining with dissolved oxygen than the lone-pair free Cl (towards Ni). In addition to exceptional HER and OER electrocatalytic activities, i.e., 146.3 mV cm−2 and 217 mV cm−2 at a scan rate of 5 mV s−1 to attain the 10 mA cm−2 current density, the Na2O–NiCl2 has demonstrated moderate energy storage ability with considerable durability, i.e., 2533 F g−1 specific capacitance at 3 A g−1 current density even after 2000 redox cycles. The as-assembled Na2O–NiCl2//Na2O–NiCl2 symmetric electrochemical supercapacitor device has ignited a "CNED" panel consisting of nearly forty LEDs with full brightness, offering applied importance in home appliances. In nutshell, seawater-modified metal surfaces can be used for energy storage and water-splitting applications. [ABSTRACT FROM AUTHOR]

The objective of the present study is to evaluate the performance, combustion, and emission characteristics of a compression‐ignition engine using hydrogen‐compressed natural gas (HCNG)‐enriched Kusum seed biodiesel blend (KSOBD20). The flow rate of HCNG was set at 5, 10, and 15 liters per minute (lpm), and the injection pressure was varied in the range of 180–240 bar. Brake thermal efficiency (BTE) and brake‐specific fuel consumption (BSFC) were improved when HCNG was added to the KSOBD20. Combustion characteristics, namely, cylinder pressure (CP) and net heat release rate (NHRR), were also improved. Emissions of carbon monoxide (CO), hydrocarbons (HC), and smoke were also reduced, with the exception of nitrogen oxides (NOx). The higher injection pressure (240 bar) had a positive effect on operating characteristics. At an injection pressure of 240 bar, for KSOB20 + 15 lpm HCNG, the highest BTE and the lowest BSFC were found to be 32.09% and 0.227 kg/kWh, respectively. Also, the CP and NHRR were 69.34 bar and 66.04 J/deg. CO, HC, and smoke levels were finally reduced to 0.013%, 47 ppm, and 9%, respectively, with increased NOx levels of 1623 ppm. For optimum results in terms of engine characteristics, the fuel combination KSOBD20 + 15 lpm HCNG at fuel injection pressure 240 bar is recommended. Thus, HCNG‐enriched KSOBD20 can be used as an alternative fuel in diesel engines without requiring any modifications to increase performance and reduce emissions. [ABSTRACT FROM AUTHOR]