Heterochromatin-Encoded Satellite RNAs Induce Breast Cancer.

Heterochromatic repetitive satellite RNAs are extensively transcribed in a variety of human cancers, including BRCA1 mutant breast cancer. Aberrant expression of satellite RNAs in cultured cells induces the DNA damage response, activates cell cycle checkpoints, and causes defects in chromosome segregation. However, the mechanism by which satellite RNA expression leads to genomic instability is not well understood. Here we provide evidence that increased levels of satellite RNAs in mammary glands induce tumor formation in mice. Using mass spectrometry, we further show that genomic instability induced by satellite RNAs occurs through interactions with BRCA1-associated protein networks required for the stabilization of DNA replication forks. Additionally, de-stabilized replication forks likely promote the formation of RNA-DNA hybrids in cells expressing satellite RNAs. These studies lay the foundation for developing novel therapeutic strategies that block the effects of non-coding satellite RNAs in cancer cells.

Transcriptome-wide association mapping provides insights into the genetic basis and candidate genes governing flowering, maturity and seed weight in rice bean (Vigna umbellata).

BACKGROUND: Rice bean (Vigna umbellata), an underrated legume, adapts to diverse climatic conditions with the potential to support food and nutritional security worldwide. It is used as a vegetable, minor food crop and a fodder crop, being a rich source of proteins, minerals, and essential fatty acids. However, little effort has been made to decipher the genetic and molecular basis of various useful traits in this crop. Therefore, we considered three economically important traits i.e., flowering, maturity and seed weight of rice bean and identified the associated candidate genes employing an associative transcriptomics approach on 100 diverse genotypes out of 1800 evaluated rice bean accessions from the Indian National Genebank. RESULTS: The transcriptomics-based genotyping of one-hundred diverse rice bean cultivars followed by pre-processing of genotypic data resulted in 49,271 filtered markers. The STRUCTURE, PCA and Neighbor-Joining clustering of 100 genotypes revealed three putative sub-populations. The marker-trait association analysis involving various genome-wide association study (GWAS) models revealed significant association of 82 markers on 48 transcripts for flowering, 26 markers on 22 transcripts for maturity and 22 markers on 21 transcripts for seed weight. The transcript annotation provided information on the putative candidate genes for the considered traits. The candidate genes identified for flowering include HSC80, P-II PsbX, phospholipid-transporting-ATPase-9, pectin-acetylesterase-8 and E3-ubiquitin-protein-ligase-RHG1A. Further, the WRKY1 and DEAD-box-RH27 were found to be associated with seed weight. Furthermore, the associations of PIF3 and pentatricopeptide-repeat-containing-gene with maturity and seed weight, and aldo-keto-reductase with flowering and maturity were revealed. CONCLUSION: This study offers insights into the genetic basis of key agronomic traits in rice bean, including flowering, maturity, and seed weight. The identified markers and associated candidate genes provide valuable resources for future exploration and targeted breeding, aiming to enhance the agronomic performance of rice bean cultivars. Notably, this research represents the first transcriptome-wide association study in pulse crop, uncovering the candidate genes for agronomically useful traits.

Modulation of terpenoid indole alkaloid pathway via elicitation with phytosynthesized silver nanoparticles for the enhancement of ajmalicine, a pharmaceutically important alkaloid.

MAIN CONCLUSION: The use of silver nanoparticles as elicitors in cell cultures of Rauwolfia serpentina resulted in increased levels of ajmalicine, upregulated structural and regulatory genes, elevated MDA content, and reduced activity of antioxidant enzymes. These findings hold potential for developing a cost-effective method for commercial ajmalicine production. Plants possess an intrinsic ability to detect various stress signals, prompting the activation of defense mechanisms through the reprogramming of metabolites to counter adverse conditions. The current study aims to propose an optimized bioprocess for enhancing the content of ajmalicine in Rauwolfia serpentina callus through elicitation with phytosynthesized silver nanoparticles. Initially, callus lines exhibiting elevated ajmalicine content were established. Following this, a protocol for the phytosynthesis of silver nanoparticles using seed extract from Rauwolfia serpentina was successfully standardized. The physicochemical attributes of the silver nanoparticles were identified, including their spherical shape, size ranging from 6.7 to 28.8 nm in diameter, and the presence of reducing-capping groups such as amino, carbonyl, and amide. Further, the findings indicated that the presence of 2.5 mg L-1 phytosynthesized silver nanoparticles in the culture medium increased the ajmalicine content. Concurrently, structural genes (TDC, SLS, STR, SGD, G10H) and regulatory gene (ORCA3) associated with the ajmalicine biosynthetic pathway were observed to be upregulated. A notable increase in MDA content and a decrease in the activities of antioxidant enzymes were observed. A notable increase in MDA content and a decrease in the activities of antioxidant enzymes were also observed. Our results strongly recommend the augmentation of ajmalicine content in the callus culture of R. serpentina through supplementation with silver nanoparticles, a potential avenue for developing a cost-effective process for the commercial production of ajmalicine.

MAPK signaling regulates c-MYC for melanoma cell adaptation to asparagine restriction.

Amino acid restriction is among promising potential cancer treatment strategies. However, cancer cells employ a multitude of mechanisms to mount resistance to amino acid restriction, which impede the latter's clinical development. Here we show that MAPK signaling activation in asparagine-restricted melanoma cells impairs GSK3-ß-mediated c-MYC degradation. In turn, elevated c-MYC supports ATF4 translational induction by enhancing the expression of the amino acid transporter SLC7A5, increasing the uptake of essential amino acids, and the subsequent maintenance of mTORC1 activity in asparagine-restricted melanoma cells. Blocking the MAPK-c-MYC-SLC7A5 signaling axis cooperates with asparagine restriction to effectively suppress melanoma cell proliferation. This work reveals a previously unknown axis of cancer cell adaptation to asparagine restriction and informs mechanisms that may be targeted for enhanced therapeutic efficacy of asparagine limiting strategies.

BRCA1/BARD1-dependent ubiquitination of NF2 regulates Hippo-YAP1 signaling.

Coordination of growth and genomic stability is critical for normal cell physiology. Although the E3 ubiquitin ligase BRCA1 is a key player in maintenance of genomic stability, its role in growth signaling remains elusive. Here, we show that BRCA1 facilitates stabilization of YAP1 protein and turning "off" the Hippo pathway through ubiquitination of NF2. In BRCA1-deficient cells Hippo pathway is "turned On." Phosphorylation of YAP1 is crucial for this signaling process because a YAP1 mutant harboring alanine substitutions (Mt-YAP5SA) in LATS1 kinase recognition sites not only resists degradation but also rescues YAP1 transcriptional activity in BRCA1-deficient cells. Furthermore, an ectopic expression of the active Mt-YAP5SA, but not inactive Mt-YAP6SA, promotes EGF-independent proliferation and tumorigenesis in BRCA1-/- mammary epithelial cells. These findings establish an important role of BRCA1 in regulating stability of YAP1 protein that correlates positively with cell proliferation.

Nonequilibrium Carrier Transport in Quantum Dot Heterostructures.

Understanding carrier dynamics and transport in quantum dot based heterostructures is crucial for unlocking their full potential for optoelectronic applications. Here we report the direct visualization of carrier propagation in PbS CQD solids and quantum-dot-in-perovskite heterostructures using femtosecond transient absorption microscopy. We reveal three distinct transport regimes: an initial superdiffusive transport persisting over hundreds of femtoseconds, an Auger-assisted subdiffusive transport before thermal equilibrium is achieved, and a final hopping regime. We demonstrate that the superdiffusive transport lengths correlate strongly with the degree of energetic disorder and carrier delocalization. By tailoring the perovskite content in heterostructures, we obtained a superdiffusive transport length exceeding 90 nm at room temperature and an equivalent diffusivity of up to 106 cm2 s-1, which is 4 orders of magnitude higher than the steady-state values. These findings introduce promising strategies to harness nonequilibrium transport phenomena for more efficient optoelectronic devices.

Assessment of preferable site for temperature measurement using non contact infra-red temperature among pediatric patients.

BACKGROUND: Accurate temperature measurement with little or no discomfort that is safe, without risk of hospital-acquired infections or perforations, is the preferred choice of medical professionals in pediatric settings. The objective was to discover the preferable site for body temperature measurement using non-contact infra-red thermometer (NCIT) among pediatric patients. METHODS: NCIT measurement at mid forehead (F), right temporal region (T), right side of neck- over-carotid artery area (N), jugular notch (J), sternum (S), umbilical region and sublingual region (U) were compared with digital axillary temperature (DAT) in a single attempt in 500 patients, aged between 2 to 5 years with fever. Data was analyzed using Pearson's correlation, paired T-test and Bland-Altman plot to assess the correlation and agreement between the DAT and NCIT sites. RESULTS: The mean temperature of NCIT-T (38.42 ± 0.64 °C) was more agreeable with DAT (38.42 ± 0.63 °C) compared to other body sites. The minimum mean bias of -0.00480 °C was noted for NCIT-F with 95% CI of -0.164-0.15; however, NCIT-F revealed many outliers as compared to NCIT-J. A strong positive correlation existed between DAT and NCIT sites (r value: 0.99-0.98). However, significant difference was found between DAT and NCIT-N, NCIT-F and NCIT-U (p value < 0.0001). CONCLUSIONS: NCIT-J is the most preferable choice for measuring body temperature and can be interchanged with DAT. It will help to deliver fast results with enhanced patient comfort due to its non-invasive nature.

Tuning the oscillatory dynamics of the Belousov-Zhabotinsky reaction using ruthenium nanoparticle decorated graphene.

The classic Belousov-Zhabotinsky (BZ) reaction, which involves transition metal catalysed redox reactions, represents a family of nonlinear chemical oscillators. Here, we show that it is possible to tune the oscillatory dynamics of the BZ reaction by using a hybrid 2D material, i.e., graphene-based nanosheets decorated with Ru nanoparticles. Specifically, we demonstrate that the frequency of chemical oscillations in a BZ reaction increases, by up to four-fold, when catalyzed by the Ru-graphene nanocomposite. We show that this observed behaviour is attributed to enhanced access to active catalytic sites on Ru nanoparticles, as well as the rapid shuttling of electrons facilitated by the highly conductive graphene platform. We further demonstrate that this enhancement of oscillations facilitated by the graphene platform can be simulated using the Oregonator model. Our numerical simulations reveal a strong correlation between the rate of charge transfer and the frequency of chemical oscillations. This ability of a 2D material, like graphene, to influence the dynamics of an oscillatory chemical reaction, as showcased in this work, is studied for the first time and opens up new avenues to tune the dynamics of chemical oscillators. We anticipate that these findings would enable us to design a variety of intrinsically powered biomimetic systems with controllable dynamic behavior.

HIV-1 Vpr redirects host ubiquitination pathway.

UNLABELLED: HIV-1 modulates key host cellular pathways for successful replication and pathogenesis through viral proteins. By evaluating the hijacking of the host ubiquitination pathway by HIV-1 at the whole-cell level, we now show major perturbations in the ubiquitinated pool of the host proteins post-HIV-1 infection. Our overexpression- and infection-based studies of T cells with wild-type and mutant HIV-1 proviral constructs showed that Vpr is necessary and sufficient for reducing whole-cell ubiquitination. Mutagenic analysis revealed that the three leucine-rich helical regions of Vpr are critical for this novel function of Vpr, which was independent of its other known cellular functions. We also validated that this effect of Vpr was conserved among different subtypes (subtypes B and C) and circulating recombinants from Northern India. Finally, we establish that this phenomenon is involved in HIV-1-mediated diversion of host ubiquitination machinery specifically toward the degradation of various restriction factors during viral pathogenesis. IMPORTANCE: HIV-1 is known to rely heavily on modulation of the host ubiquitin pathway, particularly for counteraction of antiretroviral restriction factors, i.e., APOBEC3G, UNG2, and BST-2, etc.; viral assembly; and release. Reports to date have focused on the molecular hijacking of the ubiquitin machinery by HIV-1 at the level of E3 ligases. Interaction of a viral protein with an E3 ligase alters its specificity to bring about selective protein ubiquitination. However, in the case of infection, multiple viral proteins can interact with this multienzyme pathway at various levels, making it much more complicated. Here, we have addressed the manipulation of ubiquitination at the whole-cell level post-HIV-1 infection. Our results show that HIV-1 Vpr is necessary and sufficient to bring about the redirection of the host ubiquitin pathway toward HIV-1-specific outcomes. We also show that the three leucine-rich helical regions of Vpr are critical for this effect and that this ability of Vpr is conserved across circulating recombinants. Our work, the first of its kind, provides novel insight into the regulation of the ubiquitin system at the whole-cell level by HIV-1.

When is a single molecule heterogeneous? A multidimensional answer and its application to dynamics near the glass transition.

Even for apparently simple condensed-phase processes, bulk measurements of relaxation often yield nonexponential decays; the rate appears to be dispersed over a range of values. Taking averages over individual molecules is an intuitive way to determine whether heterogeneity is responsible for such rate dispersion. However, this method is in fundamental conflict with ergodic behavior and often yields ambiguous results. This paper proposes a new definition of rate heterogeneity for ergodic systems based on multidimensional time correlation functions. Averages are taken over both time and molecules. Because the data set is not subdivided, the signal-to-noise ratio is improved. Moment-based quantities are introduced to quantify the concept of rate dispersion. As a result, quantitative statements about the fraction of the dispersion due to heterogeneity are possible, and the experimental noise is further averaged. The practicality of this approach is demonstrated on single-molecule, linear-dichroism trajectories for R6G in poly(cyclohexyl acrylate) near its glass transition. Single-molecule averaging of these data does not provide useful conclusions [C. Y. Lu and D. A. Vanden Bout, J. Chem. Phys. 125, 124701 (2006)]. However, full-ensemble, two- and three-dimensional averages of the same data give clear and quantitative results: the rate dispersion is 95% ± 5% due to heterogeneity, and the rate exchange is at least 11 times longer than the mean rotation time and possibly much longer. Based on these results, we suggest that the study of heterogeneous materials should not focus on "ensemble" versus "single-molecule" experiments, but on one-dimensional versus multidimensional measurements.

Rationally designed transmembrane peptide mimics of the multidrug transporter protein Cdr1 act as antagonists to selectively block drug efflux and chemosensitize azole-resistant clinical isolates of Candida albicans.

Drug-resistant pathogenic fungi use several families of membrane-embedded transporters to efflux antifungal drugs from the cells. The efflux pump Cdr1 (Candida drug resistance 1) belongs to the ATP-binding cassette (ABC) superfamily of transporters. Cdr1 is one of the most predominant mechanisms of multidrug resistance in azole-resistant (AR) clinical isolates of Candida albicans. Blocking drug efflux represents an attractive approach to combat the multidrug resistance of this opportunistic human pathogen. In this study, we rationally designed and synthesized transmembrane peptide mimics (TMPMs) of Cdr1 protein (Cdr1p) that correspond to each of the 12 transmembrane helices (TMHs) of the two transmembrane domains of the protein to target the primary structure of the Cdr1p. Several FITC-tagged TMPMs specifically bound to Cdr1p and blocked the efflux of entrapped fluorescent dyes from the AR (Gu5) isolate. These TMPMs did not affect the efflux of entrapped fluorescent dye from cells expressing the Cdr1p homologue Cdr2p or from cells expressing a non-ABC transporter Mdr1p. Notably, the time correlation of single photon counting fluorescence measurements confirmed the specific interaction of FITC-tagged TMPMs with their respective TMH. By using mutant variants of Cdr1p, we show that these TMPM antagonists contain the structural information necessary to target their respective TMHs of Cdr1p and specific binding sites that mediate the interactions between the mimics and its respective helix. Additionally, TMPMs that were devoid of any demonstrable hemolytic, cytotoxic, and antifungal activities chemosensitize AR clinical isolates and demonstrate synergy with drugs that further improved the therapeutic potential of fluconazole in vivo.

Two-Dimensional Fluctuation Correlation Spectroscopy (2D-FlucCS): A Method to Determine the Origin of Relaxation Rate Dispersion.

Relaxation rate dispersion, i.e., nonexponential or multicomponent kinetics, is observed in complex systems when measuring relaxation kinetics. Often, the origin of rate dispersion is associated with the heterogeneity in the system. However, both homogeneous (where all molecules experience the same rate but inherently nonexponential) and heterogeneous (where all molecules experience different rates) systems can exhibit rate dispersion. A multidimensional correlation analysis method has been demonstrated to detect and quantify rate dispersion observed in molecular rotation, diffusion, solvation, and reaction kinetics. One-dimensional (1D) autocorrelation function detects rate dispersion and measures its extent. Two-dimensional (2D) autocorrelation function measures the origin of rate dispersion and distinguishes homogeneous from heterogeneous. In a heterogeneous system, implicitly there exist subensembles of molecules experiencing different rates. A three-dimensional (3D) autocorrelation function measures subensemble exchange if present and reveals if the system possesses static or dynamic heterogeneity. This perspective discusses the principles, applications, and potential and also presents a future outlook of two-dimensional fluctuation correlation spectroscopy (2D-FlucCS). The method is applicable to any experiment or simulation where a time series of fluctuation in an observable (emission, scattering, current, etc.) around a mean value can be obtained in steady state (equilibrium or nonequilibrium), provided the system is ergodic.

Practical Aspects of Acne Scar Management: ASAP 2024.

Acne scars are one of the most common complications of acne. They can significantly affect the patient's quality of life. Often, several types of atrophic acne scars are observed simultaneously; therefore, consideration must be given to the type of scar while choosing the treatment modality. Effective treatment is not only important to prevent and improve acne scars but also crucial in preventing psychosocial effects. Treatment of acne scars requires an algorithmic approach that targets each component of the scars, and combination therapy on a patient-specific basis may offer the best chance for significant improvement. The goal of the current article is to discuss the practical aspects of management of atrophic acne scars using the vast modalities of treatment available. The panel of dermatologists and plastic surgeons, each one with at least 20 years of experience in acne scar treatment, participated in a series of 'Practical Aspects of Acne Scar Management' (ASAP) meetings: ASAP 2024. ASAP meetings were organized by "Scar Forum India" from March 2023 to July 2023 in four Indian cities (Mumbai, Delhi, Bengaluru, and Kolkata), each one for a duration of at least three hours. During these meetings and discussions, panelists reviewed and discussed the acne scar-related literature, their clinical experience in its management, available treatment options, along with recent advances. Consequently, a summary of the discussion and practical approach for the management of acne scars is developed. It was concluded that, though there is no specific guideline available to optimize acne scar management despite the multitude of treatment options, the best results can be achieved through the synergy of multiple treatment modalities and using the algorithmic approach.

Inhibition of ß-TrcP-dependent ubiquitination of p53 by HIV-1 Vpu promotes p53-mediated apoptosis in human T cells.

HIV-1 viral protein U (Vpu) is involved in ubiquitination and degradation of BM stromal cell Ag 2 and surface receptor CD4 through their recruitment to SCF(ß-TrcP) (Skp1/Cul1/F-box) ubiquitin ligase (SCF) complex. Here, we show that specific interaction of wild-type Vpu protein with SCF complex leads to inhibition of ubiquitination and proteasomal degradation of p53 protein in a ß-TrcP-dependent manner. Successful interaction of SCF(ß-TrcP) complex with ß-TrcP binding motif (DS(52)GNES(56)) present in Vpu is essential because mutant Vpu possessing specific alanine substitutions (DA(52)GNEA(56)) in the ß-TrcP binding motif not only failed to stabilize p53 protein but was also unable to inhibit ubiquitination of p53 protein. Furthermore, Vpu competes efficiently with the interaction of p53 protein with the ß-TrcP subunit of the SCF complex and inhibits subsequent ubiquitination of p53 proteins in a dose-dependent manner. We also observed potent apoptotic activity in a p53 null cell line (H-1299) that was cotransfected with p53 and Vpu-expressing plasmids. Furthermore, MOLT-3 (human T-lymphoblast) cells when infected with vesicular stomatitis virus glycoprotein-pseudotypic HIV-1 possessing wild-type vpu gene exhibited maximum activation of p53/Bax proteins and p53-mediated cell death. These findings establish a novel function of Vpu in modulating the stability of p53 protein that correlates positively with apoptosis during late stages of HIV-1 infection.

Convalescent plasma (hyperimmune immunoglobulin) for COVID-19 management: An update.

The pandemic COVID-19 has spread widely throughout the globe and has been responsible for millions of deaths worldwide. Recently, it has been identified that there is no specific and 100% effective treatment available to manage the infection especially for the severe cases. A significant amount of research efforts and clinical trials have been undertaken globally and many more are underway to find the potential treatment option. Earlier, convalescent plasma or hyperimmune immunoglobulin was effectively used in the treatment of many endemic or epidemic viral infections as a part of passive immunization. In this article, we have touched upon the immunopathology of COVID-19 infection, a basic understanding of convalescent plasma, it's manufacturing as well as evaluation, and have reviewed the scientific developments focussing on the potential of convalescent plasma vis-à-vis other modalities for the management of COVID-19. The article also covers various research approaches, clinical trials conducted globally, and the clinical trials which are at various stages for exploring the efficacy and safety of the convalescent plasma therapy (CPT) to predict its future perspective to manage COVID-19.

Brief intervention to enhance cessation of smokeless tobacco use in newly diagnosed patients with head and neck cancers: A randomized controlled trial in patient-relative dyads.

Introduction: Tobacco use is a major causative factor for head and neck cancers (HNC). Continued use of tobacco even after cancer diagnosis is common and is associated with all-cause and cancer-specific mortality, cancer recurrence and poor treatment response. Evidence suggests that behavioral interventions, help achieve greater smoking cessation rates in HNC patients. However, intervention studies focussed on HNC patients using smokeless tobacco, which is more common than smoking in India, are sparse. Materials and Methods: We conducted a parallel arm randomized controlled trial (RCT) on dyads of patients with recently diagnosed HNC and a close relative. The experimental arm received a brief tobacco cessation intervention (BTCI) and the control arm received treatment as usual (TAU); 27 and 25 dyads in each arm completed the trial. Results: Overall for the dyads using SLT, the relative risk of continuing to use SLT was 3.23 times higher (odds ratio = 7.01) if BTCI was not undertaken at one-month follow-up and 4.43 times higher (odds ratio = 8.65) at 3-months follow-up. For patients only, the relative risk of continuing to use SLT at one-month and 3-months follow-ups was 4.99 and 12.04 times higher, respectively, if BTCI was not undertaken. For relatives only, the corresponding relative risk values were 2.14 and 2.2. Conclusion: We conclude that BTCI delivered to patient-relative dyads, compared to TAU, is effective in enhancing the discontinuation rates of the use of SLT in newly diagnosed patients with HNC. This form of intervention is significantly effective for discontinuing SLT use in the relatives too.

Understanding ligand interaction with different structures of G-quadruplex DNA: evidence of kinetically controlled ligand binding and binding-mode assisted quadruplex structure alteration.

The study of ligand interaction with G-quadruplex DNA is an active research area, because many ligands are shown to bind G-quadruplex structures, showing anticancer effects. Here, we show, for the first time, how fluorescence correlation spectroscopy (FCS) can be used to study binding kinetics of ligands with G-quadruplex DNA at the single molecule level. As an example, we study interaction of a benzo-phenoxazine ligand (Cresyl Violet, CV) with antiparallel and (3 + 1) hybrid G-quadruplex structures formed by human telomeric sequence. By using simple modifications in FCS setup, we describe how one can extract the reaction kinetics from diffusion-coupled correlation curves. It is found that the ligand (CV) binds stronger, by an order of magnitude, to a (3 + 1) hybrid structure, compared to an antiparallel one. Ensemble-averaged time-resolved fluorescence experiments are also carried out to obtain the binding equilibrium constants (K) of ligand-quadruplex interactions in bulk solution for the first time, which are found to match very well with FCS results. Global analysis of FCS data provides association (k(+)) and dissociation (k(-)) rates of the ligand in the two structures. Results indicate that stronger ligand binding to the (3 + 1) hybrid structure is controlled by the dissociation rate, rather than the association rate of ligand in the quadruplexes. Circular dichroism (CD) and induced-CD spectra show that the ligand not only binds at different conformations in the quadruplexes, but also induces antiparallel structure to form a mixed-type hybrid structure in Na(+) solution. However, in K(+) solution, the ligand stabilizes the (3 + 1) hybrid structure. Molecular docking studies predict the possible differences in binding sites of the ligand inside two quadruplexes, which strongly support the experimental observations. Results suggest that different binding modes of the ligand to the quadruplex structures actually assist the alteration of structures differently.

Non-equilibrium thermoelectric transport across normal metal-quantum dot-superconductor hybrid system within the Coulomb blockade regime.

A detailed investigation of the non-equilibrium steady-state electric and thermoelectric transport properties of a quantum dot (QD) coupled to the normal metallic and s-wave superconducting reservoirs (N-QD-S) are provided within the Coulomb blockade regime. Using non-equilibrium Keldysh Green's function formalism, initially, various model parameter dependences of thermoelectric transport properties are analysed within the linear response regime. It is observed that the single-particle tunnelling close to the superconducting gap edge can generate a relatively large thermopower and figure of merit. Moreover, the Andreev tunnelling plays a significant role in the suppression of thermopower and figure of merit within the gap region. Further, within the non-linear regime, we discuss two different situations, i.e., the finite voltage biasing between isothermal reservoirs and the finite thermal gradient in the context of thermoelectric heat engine. In the former case, it is shown that the sub-gap Andreev heat current can become finite beyond the linear response regime and play a vital role in asymmetric heat dissipation and thermal rectification effect for low voltage biasing. The rectification of heat current is enhanced for strong on-dot Coulomb interaction and at low background thermal energy. In the latter case, we study the variation of thermovoltage, thermopower, maximum power output, and corresponding efficiency with the applied thermal gradient. These results illustrate that hybrid superconductor-QD nanostructures are promising candidates for the low-temperature thermal applications.

Effectiveness of High Power Laser Therapy on Pain and Isokinetic Peak Torque in Athletes with Proximal Hamstring Tendinopathy: A Randomized Trial.

Athletes such as long-distance runners, sprinters, hockey, and/or football players may have proximal hamstring tendinopathy (PHT). Laser therapy has been shown to be effective in tendinopathies. High power laser therapy (HPLT) is used for the treatment of several musculoskeletal conditions; however, its efficacy on PHT has not been investigated. This study is aimed at examining the effects of HPLT on pain and isokinetic peak torque (IPT) in athletes with PHT. The two-arm comparative pretest-posttest experimental design was used with random allocation of 36 athletes aged 18-35 years into two groups (experimental and conventional group). The experimental group included the application of HPLT for 3 weeks. The conventional group included treatment with a conventional physiotherapy program including ultrasound therapy, moist heat pack, and home exercises for a total of 3 weeks. Pain and IPT of the hamstring muscle were measured before and after the application of the intervention. Pain score decreased, and IPT increased significantly (p < 0.05) after application of HPLT, by 61.26% and 13.18%, respectively. In the conventional group, a significant difference (p < 0.05) was observed in pain scores only, which decreased by 41.14%. No significant difference (p > 0.05) was observed in IPT in the conventional group. When HPLT was compared with conventional physiotherapy, a significant difference was found in pain scores only. HPLT for 3 weeks was found to be effective in improving pain in athletes with PHT. However, no significant difference was found between HPLT and conventional physiotherapy (US, moist heat, and home exercises) in improving the IPT of the hamstring muscle.