A multicentre, double-blind, placebo-controlled randomized trial of Mycobacterium w in critically ill patients with COVID-19 (ARMY-2).

BACKGROUND: Mycobacterium w (Mw), an immunomodulator, resulted in better clinical status in severe coronavirus infectious disease 19 (COVID-19) but no survival benefit in a previous study. Herein, we investigate whether Mw could improve clinical outcomes and survival in COVID-19. MATERIALS AND METHODS: In a multicentric, randomized, double-blind, parallel-group, placebo-controlled trial, we randomized hospitalized subjects with severe COVID-19 to receive either 0.3 mL/day of Mw intradermally or a matching placebo for three consecutive days. The primary outcome was 28-day mortality. The co-primary outcome was the distribution of clinical status assessed on a seven-point ordinal scale ranging from discharged (category 1) to death (category 7) on study days 14, 21, and 28. The key secondary outcomes were the change in sequential organ failure assessment (SOFA) score on days 7 and 14 compared to the baseline, treatment-emergent adverse events, and others. RESULTS: We included 273 subjects (136 Mw, 137 placebo). The use of Mw did not improve 28-day survival (Mw vs. placebo, 18 [13.2%] vs. 12 [8.8%], P = 0.259) or the clinical status on days 14 (odds ratio [OR], 1.33; 95% confidence intervals [CI], 0.79-2.3), 21 (OR, 1.49; 95% CI, 0.83-2.7) or 28 (OR, 1.49; 95% CI, 0.79-2.8) between the two study arms. There was no difference in the delta SOFA score or other secondary outcomes between the two groups. We observed higher injection site reactions with Mw. CONCLUSION: Mw did not reduce 28-day mortality or improve clinical status on days 14, 21 and 28 compared to placebo in patients with severe COVID-19. [Trial identifier: CTRI/2020/04/024846].

Programming tunable active dynamics in a self-propelled robot.

We present a scheme for producing tunable active dynamics in a self-propelled robotic device. The robot moves using the differential drive mechanism where two wheels can vary their instantaneous velocities independently. These velocities are calculated by equating robot's equations of motion in two dimensions with well-established active particle models and encoded into the robot's microcontroller. We demonstrate that the robot can depict active Brownian, run and tumble, and Brownian dynamics with a wide range of parameters. The resulting motion analyzed using particle tracking shows excellent agreement with the theoretically predicted trajectories. Later, we show that its motion can be switched between different dynamics using light intensity as an external parameter. Intriguingly, we demonstrate that the robot can efficiently navigate through many obstacles by performing stochastic reorientations driven by the gradient in light intensity towards a desired location, namely the target. This work opens an avenue for designing tunable active systems with the potential of revealing the physics of active matter and its application for bio- and nature-inspired robotics.

Innate and adaptive immune responses in subjects with CPA secondary to post-pulmonary tuberculosis lung abnormalities.

BACKGROUND: Post-tuberculosis lung abnormality (PTLA) is the most common risk factor for chronic pulmonary aspergillosis (CPA), and 14%-25% of the subjects with PTLA develop CPA. The pathogenesis and the host immune response in subjects with PTLA who develop CPA need to be better understood. METHODS: We prospectively compared the innate and adaptive immune responses mounted by patients of PTLA with or without CPA (controls). We studied the neutrophil oxidative burst (by dihydrorhodamine 123 test), classic (serum C3 and C4 levels) and alternative (mannose-binding lectin [MBL] protein levels) complement pathway, serum immunoglobulins (IgG, IgM and IgA), B and T lymphocytes and their subsets in subjects with PTLA with or without CPA. RESULTS: We included 111 subjects (58 CPA and 53 controls) in the current study. The mean ± SD age of the study population was 42.6 ± 15.7 years. The cases and controls were matched for age, gender distribution and body weight. Subjects with CPA had impaired neutrophil oxidative burst, lower memory T lymphocytes and impaired Th-1 immune response (lower Th-1 lymphocytes) than controls. We found no significant difference between the two groups in the serum complement levels, MBL levels, B-cell subsets and other T lymphocyte subsets. CONCLUSION: Subjects with CPA secondary to PTLA have impaired neutrophil oxidative burst and a lower Th-1 response than controls.

Molecular Basis of Cerebral Vasospasm: What Can We Learn from Transcriptome and Temporal Gene Expression Profiling in Intracranial Aneurysm?

Cerebral vasospasm (CV) is a significant complication following aneurysmal subarachnoid hemorrhage (aSAH), and lacks a comprehensive molecular understanding. Given the temporal trajectory of intracranial aneurysm (IA) formation, its rupture, and development of CV, altered gene expression might be a molecular substrate that runs through these clinical events, influencing both disease inception and progression. Utilizing RNA-Seq, we analyzed tissue samples from ruptured IAs with and without vasospasm to identify the dysregulated genes. In addition, temporal gene expression analysis was conducted. We identified seven dysregulated genes in patients with ruptured IA with vasospasm when compared with those without vasospasm. We found 192 common genes when the samples of each clinical subset of patients with IA, that is, unruptured aneurysm, ruptured aneurysm without vasospasm, and ruptured aneurysm with vasospasm, were compared with control samples. Among these common genes, TNFSF13B, PLAUR, OSM, and LAMB3 displayed temporal expression (progressive increase) with the pathological progression of disease that is formation of aneurysm, its rupture, and consequently the development of vasospasm. We validated the temporal gene expression pattern of OSM at both the transcript and protein levels and OSM emerges as a crucial gene implicated in the pathological progression of disease. In addition, RSAD2 and ATP1A2 appear to be pivotal genes for CV development. To the best of our knowledge, this is the first study to compare the transcriptome of aneurysmal tissue samples of aSAH patients with and without CV. The findings collectively provide new insights on the molecular basis of IA and CV and new leads for translational research.

An ultra energy-efficient hardware platform for neuromorphic computing enabled by 2D-TMD tunnel-FETs.

Brain-like energy-efficient computing has remained elusive for neuromorphic (NM) circuits and hardware platform implementations despite decades of research. In this work we reveal the opportunity to significantly improve the energy efficiency of digital neuromorphic hardware by introducing NM circuits employing two-dimensional (2D) transition metal dichalcogenide (TMD) layered channel material-based tunnel-field-effect transistors (TFETs). Our novel leaky-integrate-fire (LIF) based digital NM circuit along with its Hebbian learning circuitry operates at a wide range of supply voltages, frequencies, and activity factors, enabling two orders of magnitude higher energy-efficient computing that is difficult to achieve with conventional material and/or device platforms, specifically the silicon-based 7 nm low-standby-power FinFET technology. Our innovative 2D-TFET based NM circuit paves the way toward brain-like energy-efficient computing that can unleash major transformations in future AI and data analytics platforms.

Arrhenius law for interacting diffusive systems.

Finding the mean time it takes for a particle to escape from a metastable state due to thermal fluctuations is a fundamental problem in physics, chemistry, and biology. Here, we consider the escape rate of interacting diffusive particles, from a deep potential trap within the framework of the macroscopic fluctuation theory-a nonequilibrium hydrodynamic theory. For systems without excluded volume, our investigation reveals adherence to the well-established Arrhenius law. However, in the presence of excluded volume, a universality class emerges, fundamentally altering the escape rate. Remarkably, the modified escape rate within this universality class is independent of the interactions at play. The universality class, demonstrating the importance of excluded volume effects, may bring insights to the interpretation of escape processes in the realm of chemical physics.

Emerging universality classes in thermally assisted activation of interacting diffusive systems: A perturbative hydrodynamic approach.

Thermal activation of a particle from a deep potential trap follows the Arrhenius law. Recently, this result has been generalized for interacting diffusive particles in the trap, revealing two universality classes-the Arrhenius class and the excluded volume class. The result was demonstrated with the aid of numerical analysis. Here, we present a perturbative hydrodynamic approach to analytically validate the existence and range of validity for the two universality classes.

Estimation of dietary intake of sodium, potassium, phosphorus and protein in healthy Indian population and patients with chronic kidney disease.

Introduction: Poor nutritious diet is a major risk element for non-communicable diseases (NCD), which are of considerable public health concern. Given the diverse dietary patterns in India, precise determination of nutrient consumption is crucial for disease management. The present study assessed the dietary intake of sodium, potassium, protein, and phosphorus among North Indians. Methods: This cross-sectional study included healthy adults and adults with stage 2 to 4 chronic kidney disease (CKD). We analysed sodium, protein, potassium and phosphorus intakes using one-time 24-h urinary excretion. Dietary intake was also analysed in subgroups based on sex, body mass index, blood pressure and abdominal obesity. We evaluated the performance of various equations available to estimate sodium intake using a spot urine sample with respect to the sodium excretion measured in a 24-h urine sample. Descriptive statistics was used along with t-test for statistical significance. Results: A total of 404 subjects (182 adult healthy subjects and 222 adults with CKD) with a mean age of 47.01 ± 11.46 years were studied. Mean dietary intakes of sodium, salt, potassium, protein and phosphorus were 2.94 ± 1.68 g/day, 7.42 ± 4.24 g/day, 1.43 ± 0.59 g/day, 47.67 ± 14.73 g/day and 0.86 ± 0.39 g/day, respectively. There were no differences in nutrient consumption between adults who were healthy and those with CKD. Consumption of sodium, salt, protein, potassium, and phosphorus among healthy population vs. those with CKD were 2.81 ± 1.60 vs. 3.05 ± 1.73 g/day (p = 0.152), 7.08 ± 4.04 vs. 7.70 ± 4.37 g/day (p = 0.143), 47.16 ± 14.59 vs. 48.08 ± 14.86 g/day (p = 0.532), 1.38 ± 0.59 vs. 1.48 ± 0.58 g/day (p = 0.087) and 0.86 ± 0.41 vs. 0.87 ± 0.37 g/day (p = 0.738), respectively. Men had higher consumption of these nutrients than women. Compared to non-hypertensives, hypertensive subjects had higher consumption of salt (8.23 ± 4.89 vs. 6.84 ± 3.59 g/day, p = 0.002) and potassium (1.51 ± 0.63 vs. 1.38 ± 0.55 g/day, p = 0.024), however, no difference were found in protein and phosphorus intakes. In terms of performance of equations used to estimate 24-h sodium intake from spot urinary sodium concentration against the measured 24-h urinary sodium excretion, INTERSALT 2 equation exhibited the least bias [1.08 (95% CI, -5.50 to 7.66)]. Conclusion: The study shows higher-than-recommended salt and lower-than-recommended potassium intake in the north Indian population compared to those recommended by guidelines. The dietary protein intake is below the recommended dietary allowance. These findings help the development of targeted policies for dietary modification to reduce the risk of the development and progression of CKD.

A FACS-based novel isolation technique identifies heterogeneous CTCs in oral squamous cell carcinoma.

Purpose: Isolating circulating tumour cells (CTCs) from the blood is challenging due to their low abundance and heterogeneity. Limitations of conventional CTC detection methods highlight the need for improved strategies to detect and isolate CTCs. Currently, the Food and Drug Administration (FDA)-approved CellSearch™ and other RUO techniques are not available in India. Therefore, we wanted to develop a flexible CTC detection/isolation technique that addresses the limitation(s) of currently available techniques and is suitable for various downstream applications. Methods: We developed a novel, efficient, user-friendly CTC isolation strategy combining density gradient centrifugation and immuno-magnetic hematogenous cell depletion with fluorescence-activated cell sorting (FACS)-based positive selection using multiple CTC-specific cell-surface markers. For FACS, a stringent gating strategy was optimised to exclude debris and doublets by side scatter/forward scatter (SSC/FSC) discriminator, remove dead cells by 4',6-diamidino-2-phenylindole (DAPI) staining, and eliminate non-specific fluorescence using a "dump" channel. APC-labelled anti-CD45mAB was used to gate remaining hematogenous cells, while multiple epithelial markers (EpCAM, EGFR, and Pan-Cytokeratin) and an epithelial-mesenchymal transition (EMT) marker (Vimentin) labelled with fluorescein isothiocyanate (FITC) were used to sort cancer cells. The technique was initially developed by spiking Cal 27 cancer cells into the blood of healthy donors and then validated in 95 biopsy-proven oral squamous cell carcinoma (OSCC) patients. CTCs isolated from patients were reconfirmed by Giemsa staining, immuno-staining, and whole transcriptome amplification (WTA), followed by qRT-PCR. In vitro culture and RNA sequencing (RNA-Seq) were also performed to confirm their suitability for various downstream applications. Results: The mean detection efficiency for the Cal 27 tongue cancer cells spiked in the whole blood of healthy donors was 32.82% ± 12.71%. While ~75% of our patients (71/95) had detectable CTCs, the CTC positivity was independent of the TNM staging. The isolated potential cancer cells from OSCC patients were heterogeneous in size. They expressed different CTC-specific markers in various combinations as identified by qRT-PCR after WTA in different patients. Isolated CTCs were also found to be suitable for downstream applications like short-term CTC culture and RNA-Seq. Conclusion: We developed a sensitive, specific, flexible, and affordable CTC detection/isolation technique, which is scalable to larger patient cohorts, provides a snapshot of CTC heterogeneity, isolates live CTCs ready for downstream molecular analysis, and, most importantly, is suitable for developing countries.

Operational priorities for engaging with India's private healthcare sector for the control of tuberculosis: a modelling study.

OBJECTIVES: To estimate the potential impact of expanding services offered by the Joint Effort for Elimination of Tuberculosis (JEET), the largest private sector engagement initiative for tuberculosis (TB) in India. DESIGN: We developed a mathematical model of TB transmission dynamics, coupled with a cost model. SETTING: Ahmedabad and New Delhi, two cities with contrasting levels of JEET coverage. PARTICIPANTS: Estimated patients with TB in Ahmedabad and New Delhi. INTERVENTIONS: We investigated the epidemiological impact of expanding three different public-private support agency (PPSA) services: provider recruitment, uptake of cartridge-based nucleic acid amplification tests and uptake of adherence support mechanisms (specifically government supplied fixed-dose combination drugs), all compared with a continuation of current TB services. RESULTS: Our results suggest that in Delhi, increasing the use of adherence support mechanisms among private providers should be prioritised, having the lowest incremental cost-per-case-averted between 2020 and 2035 of US$170 000 (US$110 000-US$310 000). Likewise in Ahmedabad, increasing provider recruitment should be prioritised, having the lowest incremental cost-per-case averted of US$18 000 (US$12 000-US$29 000). CONCLUSION: Results illustrate how intervention priorities may vary in different settings across India, depending on local conditions, and the existing degree of uptake of PPSA services. Modelling can be a useful tool for identifying these priorities for any given setting.

Role of FoxO1 in Acne and Effect of Isotretinoin on FoxO1 Expression.

Background: Nodulocystic acne is a severe type of acne that is known to improve after treatment with isotretinoin. Melnik has hypothesized a unifying concept on the mechanism of acne pathogenesis involving altered expression of Forkhead box O transcription factor (FoxO1) and role of isotretinoin in improving acne via modulating this pathway. Aim: To evaluate the pathway proposed by Melnik in acne pathogenesis by analysing the difference in the expression of FoxO1, peroxisome proliferator-activated receptor (PPARγ), and androgen receptor (AR) between acne patients and non-acne controls and the effect of treatment with isotretinoin on change in expression of these genes in acne patients. Results: The gene expression of FoxO1 was non significantly higher in acne patients as compared to controls. After treatment with isotretinoin, a significant decrease in FoxO1 expression in acne patients at mRNA (P = 0.05) level was observed. There was a significant decrease in grade 3 positivity of FoxO1 at protein level (P = 0.0009). A decrease in androgen receptor positivity (P = 0.055) at protein level was also observed. Conclusion: Reduction in FoxO1 expression appears to be an important mechanism of action of isotretinoin in acne.

Directional synchrony among self-propelled particles under spatial influence.

Synchronization is one of the emerging collective phenomena in interacting particle systems. Its ubiquitous presence in nature, science, and technology has fascinated the scientific community over the decades. Moreover, a great deal of research has been, and is still being, devoted to understand various physical aspects of the subject. In particular, the study of interacting active particles has led to exotic phase transitions in such systems which have opened up a new research front-line. Motivated by this line of work, in this paper, we study the directional synchrony among self-propelled particles. These particles move inside a bounded region, and crucially their directions are also coupled with spatial degrees of freedom. We assume that the directional coupling between two particles is influenced by the relative spatial distance which changes over time. Furthermore, the nature of the influence is considered to be both short and long-ranged. We explore the phase transition scenario in both the cases and propose an approximation technique which enables us to analytically find the critical transition point. The results are further supported with numerical simulations. Our results have potential importance in the study of active systems like bird flocks, fish schools, and swarming robots where spatial influence plays a pertinent role.

Prognosticating acute traumatic spinal cord injury using Neurofilament (NF), Neuron Specific Enolase (NSE), Matrix Metalloproteinases (MMPs), and S-100B as biomarkers.

BACKGROUND: Spinal cord injury (SCI) can result in lifelong disability. Currently, the literature suggests that biomarkers are helpful in prognosticating SCI, but there is no specific biomarker to date. This is the first study that predicted the prognosis dynamically using biomarkers. AIM: To elucidate the role of biomarkers in prognosticating acute traumatic SCI. METHODS: Blood samples were obtained from 35 patients of acute traumatic SCI at presentation, immediate post-op, and at 6 weeks. At 6 months follow-up, patients were divided into two groups, i.e, improved and non-improved based on the improvement in the ASIA grade compared to presentation. A non-parametric test was used for comparing mean NSE, MMP-2, S100-B, and NF serum levels at presentation, immediate post-op, and 6 weeks post-op follow-up between the two groups. RESULTS: There was a significant difference (p = 0.03) in the NF values at presentation between the two groups. The difference of NSE values at 6 weeks was also significant (p = 0.016) between the two groups. S-100B levels were also significantly different between both groups at presentation (p=0.016), and at the immediate post-op stage (p=0.007). MMP-2 levels neither displayed any specific trend nor any significant difference between the two groups. CONCLUSION: Higher NF values at presentation, and higher S-100B levels at presentation and immediate post-operative period correlated with poor outcome. Also, increased NSE values after surgery are indicative of no improvement. These levels can be used at various stages to predict the prognosis. However, further studies are required on this topic extensively to know the exact cut-off values of these markers to predict the prognosis accurately. CLINICAL TRIALS REGISTRY NUMBER: REF/2020/01/030616.

Construction of Triboelectric Series and Chirality Detection of Amino Acids Using Triboelectric Nanogenerator.

Triboelectrification necessitates a frictional interaction between two materials, and their contact electrification is characteristically based on the polarity variance in the triboelectric series. Utilizing this fundamental advantage of the triboelectric phenomenon, different materials can be identified according to their contact electrification capability. Herein, an in-depth analysis of the amino acids present in the stratum corneum of human skin is performed and these are quantified regarding triboelectric polarization. The principal focus of this study lies in analyzing and identifying the amino acids present in copious amounts in the stratum corneum to explain their positive behavior during the contact electrification process. Thus, an augmented triboelectric series of amino acids with quantified triboelectric charging polarity by scrutinizing the transfer charge, work function, and atomic percentage is presented. Furthermore, the chirality of aspartic acid as it is most susceptible to racemization with clear consequences on the human skin is detected. The study is expected to accelerate research exploiting triboelectrification and provide valuable information on the surface properties and biological activities of these important biomolecules.

Guanidinium-Functionalized Polymer Dielectrics for Triboelectric Bacterial Detection.

Development of rapid detection strategies that target potentially pathogenic bacteria has gained increasing attention due to the increasing awareness for better health and safety. In this study, we evaluate an intrinsically antimicrobial polymer, 2Gdm, which is a poly(norbornene)-based functional polymer featuring guanidinium groups as side chains, for bacterial detection by the means of triboelectric nanogenerators (TENGs) and triboelectric nanosensors (TENSs). Attachment of bacteria to the sensing layer is anticipated to alter the overall triboelectric properties of the underlying polymer layer. The positively charged guanidinium functional groups can interact with the negatively charged phospholipid bilayer of bacteria and lead to bacterial death, which can then be detected by optical microscopy, X-ray photoelectron microscopy, and more advanced self-powered sensing techniques such as TENGs and TENSs. The double bonds present along the poly(norbornene) backbone allow for thermally induced cross-linking to obtain X-2Gdm and thus rendering materials remain stable in water. By monitoring the change in voltage output after immersion in various concentrations of Gram-negative Escherichia coli (E. coli) and Gram-positive Streptococcus pneumoniae (S. pneumoniae), we have demonstrated the utility of X-2Gdm as a new polymer dielectric for autonomous bacterial detection. As the bacterial concentration increases, the amount of adsorbed bacteria also increases, resulting in a decrease in the surface potential of the X-2Gdm thin film; this reduction in surface potential can cause a decrease in the triboelectric output for both TENGs and TENSs, which serves as a key working mechanism for facile bacterial detection. TENG and TENS systems are capable of detecting E. coli and S. pneumoniae within a range of 4 × 105 to 4 × 108 CFU/mL with a limit of detection of 106 CFU/mL. This report highlights the promising prospects of employing TENGs and TENSs as innovative sensing technologies for rapid bacterial detection by leveraging the electrostatic interactions between bacterial cell membranes and cationic groups present on polymer surfaces.

Thermodynamic trade-off relation for first passage time in resetting processes.

Resetting is a strategy for boosting the speed of a target-searching process. Since its introduction over a decade ago, most studies have been carried out under the assumption that resetting takes place instantaneously. However, due to its irreversible nature, resetting processes incur a thermodynamic cost, which becomes infinite in the case of instantaneous resetting. Here, we take into consideration both the cost and the first passage time (FPT) required for a resetting process, in which the reset or return to the initial location is implemented using a trapping potential over a finite but random time period. An iterative generating function and a counting functional method à la Feynman and Kac are employed to calculate the FPT and the average work for this process. From these results, we obtain an explicit form of the time-cost trade-off relation, which provides the lower bound of the mean FPT for a given work input when the trapping potential is linear. This trade-off relation clearly shows that instantaneous resetting is achievable only when an infinite amount of work is provided. More surprisingly, the trade-off relation derived from the linear potential seems to be valid for a wide range of trapping potentials. In addition, we have also shown that the fixed-time or sharp resetting can further enhance the trade-off relation compared to that of the stochastic resetting.

Rate enhancement of gated drift-diffusion process by optimal resetting.

"Gating" is a widely observed phenomenon in biochemistry that describes the transition between the activated (or open) and deactivated (or closed) states of an ion-channel, which makes transport through that channel highly selective. In general, gating is a mechanism that imposes an additional restriction on a transport, as the process ends only when the "gate" is open and continues otherwise. When diffusion occurs in the presence of a constant bias to a gated target, i.e., to a target that switches between an open and a closed state, the dynamics essentially slow down compared to ungated drift-diffusion, resulting in an increase in the mean completion time, ⟨TG⟩ > ⟨T⟩, where T denotes the random time of transport and G indicates gating. In this work, we utilize stochastic resetting as an external protocol to counterbalance the delay due to gating. We consider a particle in the positive semi-infinite space that undergoes drift-diffusion in the presence of a stochastically gated target at the origin and is moreover subjected to rate-limiting resetting dynamics. Calculating the minimal mean completion time ⟨Tr⋆G⟩ rendered by an optimal resetting rate r⋆ for this exactly solvable system, we construct a phase diagram that owns three distinct phases: (i) where resetting can make gated drift-diffusion faster even compared to the original ungated process, ⟨Tr⋆G⟩<⟨T⟩<⟨TG⟩, (ii) where resetting still expedites gated drift-diffusion but not beyond the original ungated process, ⟨T⟩≤⟨Tr⋆G⟩<⟨TG⟩, and (iii) where resetting fails to expedite gated drift-diffusion, ⟨T⟩<⟨TG⟩≤⟨Tr⋆G⟩. We also highlight various non-trivial behaviors of the completion time as the resetting rate, gating parameters, and geometry of the set-up are carefully ramified. Gated drift-diffusion aptly models various stochastic processes such as chemical reactions that exclusively take place in certain activated states of the reactants. Our work predicts the conditions under which stochastic resetting can act as a useful strategy to enhance the rate of such processes without compromising their selectivity.

Bipolar magnetic switching and large exchange-bias in Fe-substituted SmCrO3.

Rare-earth orthochromite is an interesting system in the view of its complex magnetic ordering due to competing interaction between different magnetic ions. Here, Fe-substituted SmCrO3samples were prepared by solid-state route to investigate their intriguing magnetic properties towards exploring its application potential. The magnetic studies revealed antiferromagnetic (AFM) ordering at Nèel temperature (TN) ∼ 181 K, magnetic compensation temperatures (TCOMP) at ∼137 K and 50 K, and spin-reorientation temperature (TSR) at 64 K in SmCr0.8Fe0.2O3sample. Additionally, the system exhibited negative magnetization under field-cooled conditions which allowed the field as well as temperature controllable magnetization switching behavior. Notably, the Fe-substituted SmCrO3sample displayed a remarkable exchange bias (HEB) value of ∼1.39 T at 10 K due to the coexistence of ferromagnetic and AFM ordering at different cationic sites. TheM-Hloops recorded under positive and negative field-cooled conditions ruled out the minor-loop effect. Theoretical models applied on the training effect studies confirmed the observed exchange-bias effect.

Dysregulated Genes and Signaling Pathways in the Formation and Rupture of Intracranial Aneurysm.

Intracranial aneurysm (IA) has the potential to rupture. Despite scientific advances, we are still not in a position to screen patients for IA and identify those at risk of rupture. It is critical to comprehend the molecular basis of disease to facilitate the development of novel diagnostic strategies. We used transcriptomics to identify the dysregulated genes and understand their role in the disease biology. In particular, RNA-Seq was performed in tissue samples of controls, unruptured IA, and ruptured IA. Dysregulated genes (DGs) were identified and analyzed to understand the functional aspects of molecules. Subsequently, candidate genes were validated at both transcript and protein level. There were 314 DGs in patients with unruptured IA when compared to control samples. Out of these, SPARC and OSM were validated as candidate molecules in unruptured IA. PI3K-AKT signaling pathway was found to be an important pathway for the formation of IA. Similarly, 301 DGs were identified in the samples of ruptured IA when compared with unruptured IAs. CTSL was found to be a key candidate molecule which along with Hippo signaling pathway may be involved in the rupture of IA. We conclude that activation of PI3K-AKT signaling pathway by OSM along with up-regulation of SPARC is important for the formation of IA. Further, regulation of Hippo pathway through PI3K-AKT signaling results in the down-regulation of YAP1 gene. This along with up-regulation of CTSL leads to further weakening of aneurysm wall and its subsequent rupture.

Mpemba effect in a Langevin system: Population statistics, metastability, and other exact results.

The Mpemba effect is a fingerprint of the anomalous relaxation phenomenon wherein an initially hotter system equilibrates faster than an initially colder system when both are quenched to the same low temperature. Experiments on a single colloidal particle trapped in a carefully shaped double well potential have demonstrated this effect recently [A. Kumar and J. Bechhoefer, Nature 584, 64 (2020)]. In a similar vein, here, we consider a piece-wise linear double well potential that allows us to demonstrate the Mpemba effect using an exact analysis based on the spectral decomposition of the corresponding Fokker-Planck equation. We elucidate the role of the metastable states in the energy landscape as well as the initial population statistics of the particles in showcasing the Mpemba effect. Crucially, our findings indicate that neither the metastability nor the asymmetry in the potential is a necessary or a sufficient condition for the Mpemba effect to be observed.