Highly Mutable Linker Regions Regulate HIV-1 Rev Function and Stability.

HIV-1 Rev is an essential viral regulatory protein that facilitates the nuclear export of intron-containing viral mRNAs. It is organized into structured, functionally well-characterized motifs joined by less understood linker regions. Our recent competitive deep mutational scanning study confirmed many known constraints in Rev's established motifs, but also identified positions of mutational plasticity, most notably in surrounding linker regions. Here, we probe the mutational limits of these linkers by testing the activities of multiple truncation and mass substitution mutations. We find that these regions possess previously unknown structural, functional or regulatory roles, not apparent from systematic point mutational approaches. Specifically, the N- and C-termini of Rev contribute to protein stability; mutations in a turn that connects the two main helices of Rev have different effects in different contexts; and a linker region which connects the second helix of Rev to its nuclear export sequence has structural requirements for function. Thus, Rev function extends beyond its characterized motifs, and is tuned by determinants within seemingly plastic portions of its sequence. Additionally, Rev's ability to tolerate many of these massive truncations and substitutions illustrates the overall mutational and functional robustness inherent in this viral protein

Acute Exacerbation of Heart Failure in a 35-Year-Old Hispanic Female With Premature Coronary Artery Disease Status Post CABG X 4 and Multiple Comorbidities: A Case Report

Background: Coronary artery disease (CAD) is the leading cause of death in adults worldwide.1 Although CHD prevalence is highest in adults of middle age and above, it is important to be aware of risk factors in young adults that predispose them to premature CAD and its complications. We present a case of a young Hispanic female with acute exacerbation of heart failure (HF), CAD, and multiple comorbidities. Case: A 35-year-old Hispanic female with past medical history of CAD status post coronary artery bypass graft (CABG) X 4, HF with reduced ejection fraction (EF) of 40-45%, chronic kidney disease stage 4, type 2 diabetes mellitus, and hypertension presented with shortness of breath for one day. No other associated symptoms. Vitals revealed she was tachycardic (110s) and hypertensive (160s/90s). Physical exam revealed decreased breath sounds. Echocardiogram revealed an EF of 20-25%. The patient was successfully managed with furosemide, isosorbide dinitrate, hydralazine, and fluid restriction. Conclusions: This is a rare case of premature CAD with multiple complications (CABG X4) in a young female. Approximately 3% of all CAD cases occur in patients less than 40 years old.2 This prevalence is likely underreported due to young patients exhibiting less symptoms. Risk factors for CAD in young adults, such as smoking, diabetes, hypercholesterolemia, and obesity,2 should be considered when assessing for CAD in populations with a high prevalence of comorbidities such as the Rio Grande Valley, Tx. Careful observation for these factors can lead to prevention of CAD and its complications

Estimation of properties of low-lying excited states of Hubbard models : a multi-configurational symmetrized projector quantum Monte Carlo approach

We present in detail the recently developed multi-configurational symmetrized projector quantum Monte Carlo (MSPQMC) method for excited states of the Hubbard model. We describe the implementation of the Monte Carlo method for a multi-configurational trial wavefunction. We give a detailed discussion of issues related to the symmetry of the projection procedure which validates our Monte Carlo procedure for excited states and leads naturally to the idea of symmetrized sampling for correlation functions, developed earlier in the context of ground state simulations. It also leads to three possible averaging schemes. We have analyzed the errors incurred in these various averaging procedures and discuss and detail the preferred averaging procedure for correlations that do not have the full symmetry of the Hamiltonian. We study the energies and correlation functions of the low-lying excited states of the half-filled Hubbard model in 1-D. We have used this technique to study the pair-binding energies of two holes in $4n$ and $4n+2$ systems, which compare well the Bethe ansatz data of Fye, Martins and Scalettar. We have also studied small clusters amenable to exact diagonalization studies in 2-D and have reproduced their energies and correlation functions by the MSPQMC method. We identify two ways in which a multiconfigurational trial wavefunction can lead to a negative sign problem. We observe that this effect is not severe in 1-D and tends to vanish with increasing system size. We also note that this does not enhance the severity of the sign problem in two dimensions.Comment: 29 pages, 2 figures available on request, submitted to Phys. Rev.

An Initial Value Technique using Exponentially Fitted Non Standard Finite Difference Method for Singularly Perturbed Differential-Difference Equations

In this paper, an exponentially fitted non standard finite difference method is proposed to solve singularly perturbed differential-difference equations with boundary layer on left and right sides of the interval. In this method, the original second order differential difference equation is replaced by an asymptotically equivalent singularly perturbed problem and in turn the problem is replaced by an asymptotically equivalent first order problem. This initial value problem is solve by using exponential fitting with non standard finite differences. To validate the applicability of the method, several model examples have been solved by taking different values for the delay parameter δ , advanced parameter η and the perturbation parameter ε . Comparison of the results is shown to justify the method. The effect of the small shifts on the boundary layer solutions has been investigated and presented in figures. The convergence of the scheme has also been investigated

Role of Panchashirisha Agada in Dermatological Toxicity w.s.r. to Visha - A Review

Ayurveda consists of many branches of which Agada Tantra is one of them, which deals with toxicology. Any substance which comes in contact with skin gets easily absorbed. So, in case, if any Visha (Toxin) comes in contact then for sure there will be consequences. My aim is to study these Dermatological manifestations occurring due to various Visha. For its management, various formulations are mentioned in Samhita. Among which Panchashirisha Agada is considered to be best in treating any Vishajanya condition. It has both Vishaghna and dermatological properties like Kushthghna, Kandughna, Twachya, Varnya, Shothaghna. It can be used both internally and externally. This review is an attempt to explore the role of Panchashirisha Agada in dermatological toxicity

Optical Photometry of the GRB 010222 Afterglow

The optical afterglow of GRB 010222 was observed using the recently installed 2-m telescope at the Indian Astronomical Observatory, Hanle, and the telescopes at the Vainu Bappu Observatory, Kavalur, beginning ~ 0.6 day after the detection of the event. The results based on these photometric observations combined with others reported in the literature are presented in this paper. The R band light curve shows an initial decline of intensities proportional to t^{-0.542} which steepens, after 10.3 hours, to t^{-1.263}. Following the model of collimated outflow, the early break in the light curve implies a very narrow beam angle (~ 2-3 deg). The two decay rates are consistent with the standard jet model in a uniform density ambient medium, but require a hard spectrum of electron power density with p ~ 1.5. The R band light between 14 and 17 hours since outburst departs from the power law fit by 0.1 mag and shows some evidence for fluctuations over timescales of an hour in the observer's frame. Such deviations are expected due to density inhomogeneities if the ambient medium is similar to the local interstellar medium. GRB 010222 is thus an example of a highly collimated outflow with a hard spectrum of electron energy distribution in normal interstellar environment.Comment: 15 pages, Latex, including 2 postscript figures, to appear in the Bull. astro. Soc. India, September 2001 issu

AUTOMATIC HELMET WIPER

An improvised helmet design which is integrated with a circuitry for automatic rain sensing mini wiper located on the eye shield. The presence of a automatic helmet wiper will make two wheeler riding easier and safer in rainy season, since the driver won't be bothered by the continuous rain drops disturbing his/her vision. The wiper will automatically start as soon as it detects the presence of rain drops on the rain sensor mounted on the top of the helmet. This makes the rider to drive safety in the rain

A cross sectional study of various types of acute poisoning; pharmacological management and their outcome in a tertiary care hospital

Background: Acute poisoning is a common and life-threatening crisis, leading to serious complications and death of patients. Poisoning may be due to self-consumption, accidental exposure of chemical compounds, medications and poisonous animal bites/stings. Aim of current study was to investigate the pattern of drug utilization, poisoning agents and outcome in patients with acute poisoning treated at a tertiary care teaching hospital, Vadodara, Gujarat. Methods: This prospective cross-sectional study was done on patients of acute poisoning admitted in emergency department, SSG Hospital during August 2021-March 2022. Results: 400 patients were enrolled during the study, from which 262 (65.50%) were male and 138 (34.50%) were female. Mean age of patients was 30.30 ± 13.79 years. The commonest mode of poisoning observed was Suicidal (66.25%). The most common cause of poisoning was due to Pesticides (33.25%), followed by venomous animal exposures (30.75%). Death was recorded in 53 (13.25%) patients with highest number seen in suicidal poisoning (14.34%) compared to accidental poisonings (11.19%). Mainly, multivitamins (19.03%), Antimicrobials (16.65%), Proton Pump Inhibitors (15.85%) and Antiemetics (11.10%) were prescribed. Antidotes used were Atropine (4.81%), Pralidoxime (4.46%) and Anti-snake venom (2.80%). Median number of drugs per patient was 8; range: 2-25. Conclusions: Pattern and magnitude of poisoning are multidimensional and demand multi-sectoral approach for facing this problem. Due to high incidence of snakebites, hospital stockpiles should be regularly checked for availability of antivenom. There is a need for stringent pesticide regulation laws, counselling and training programs to reduce incidence of poisonings and deaths due to it

Artificial intelligence-driven patient monitoring for adverse event detection in clinical trials

Artificial intelligence (AI) keeps an eye on people in clinical studies to find out when bad things happen. This is a big way that AI is changing healthcare. It goes into a lot of detail about how AI has changed this field and stresses how important it is to use complicated formulas, always keep an eye on things, and follow the rules. These days, we have tools like deep learning frameworks, controlled and unsupervised learning models, and others that help us find bad things faster and more accurately. Tracking in real time is possible with early warning systems and constant data analysis. It helps make sure the experiment is done right and puts the safety of the people being tested first. AI-driven tracking systems can only work in an honest and reliable way if they follow the rules set by regulatory bodies such as the FDA and the EMA. The fact that AI has the ability to change the way medical research is done today, with benefits like making it faster and more accurate, makes its problems even more important. The report comes to the conclusion that more research, better teamwork, and a wider use of AI technologies are needed to make it more reliable to find bad events in clinical studies over time

Structural Instability in Polyacene : A Projector Quantum Monte Carlo Study

We have studied polyacene within the Hubbard model to explore the effect of electron correlations on the Peierls' instability in a system marginally away from one-dimension. We employ the projector quantum Monte Carlo method to obtain ground state estimates of the energy and various correlation functions. We find strong similarities between polyacene and polyacetylene which can be rationalized from the real-space valence-bond arguments of Mazumdar and Dixit. Electron correlations tend to enhance the Peierls' instability in polyacene. This enhancement appears to attain a maximum at $U/t \sim 3.0$ and the maximum shifts to larger values when the alternation parameter is increased. The system shows no tendency to destroy the imposed bond-alternation pattern, as evidenced by the bond-bond correlations. The cis- distortion is seen to be favoured over the trans- distortion. The spin-spin correlations show that undistorted polyacene is susceptible to a SDW distortion for large interaction strength. The charge-charge correlations indicate the absence of a CDW distortion for the parameters studied.Comment: 13 pages, 10 figures available on reques