A new stereoselective route to the carbocyclic nucleoside cyclobut-A

A new synthesis of cyclobut-A, a carbocyclic nucleoside analogue of oxetanocin is described. The key step involves a stereoselective intramolecular [2+2] photocycloaddition to provide a trisubstituted cyclobutane derivative with the desired stereochemistry. The nucleoside linkage was established through nucleophilic displacement of an acetate group by adenine

From Gut to Gray Matter: The Surprising Links Between The Microbiome and Brain

The gut microbiome has been implicated in the pathogenesis of a wide array of immune-related neurological disorders, including psychiatric and neurological disorders. This fascinating journey from the gut to the gray matter reveals an astonishing dimension of scientific exploration. The intricate interconnectedness of the gut-brain axis and the microbiota's impact on brain function carries substantial implications for mental well-being. This burgeoning field not only holds great promise for insights into the prevention and treatment of neurological conditions but also underscores the significance of maintaining a well-balanced and nurtured microbiomes for overall cognitive health

Work-Related Musculoskeletal Disorder an Increasing Concern in Garment Industry

  Background:  Musculoskeletal Disorders (MSDs)-related occupational health concerns are becoming a growing problem for the clothing industry, which is influenced by the repetitive tasks, prolonged static postures and poor ergonomic conditions that characterise the nature of work in this industry. This study aims to provide a thorough assessment of the numerous musculoskeletal problems that are prevalent in the garment industry and to recommend useful intervention strategies to mitigate their consequences. Methods:  One hundred thirty textile workers aged between 25 to 45 years were taken randomly from five different textile manufacturing sites of Baranagar, West Bengal. A modified Nordic musculoskeletal questionnaire was applied to evaluate the postural stress of the garment’s workers. The discomfort/pain intensity in different body parts were evaluated by Body Part Discomfort (BPD) scale . Appropriate statistical tests were applied. Results: Discomfort or pain in hip and lower back were found to be maximum among workers. Conclusion: Pain, discomfort and postural stress among various body parts like upper back, lower back and hip are verry much common for the workers. Despite efforts to deal with these problems, more thorough research and efficient intervention strategies are required to reduce musculoskeletal ailments in the garment industry.

Prevalence Of Work-Related Musculoskeletal Disorders Among Construction Workers

Construction workers frequently have work-related musculoskeletal disorders (WRMSDs) with significant adverse health and financial effects. The aim of this study is to look at the reasons, effects, and prevention measures for WRMSDs among construction workers.Methods: In the study, one hundred thirty-six male construction workers between the ages of 30 and 56 participated. The postural stress experienced by the construction workers was assessed using a modified Nordic musculoskeletal questionnaire. The Body Part Discomfort (BPD) scale was used to assess the severity of the discomfort/pain in various body areas.Results: Discomfort or pain in neck portion was found to be maximum percentage of workers. BPD scaling revealed that neck, lower back and shoulder are among three most susceptible body parts in relation to pain sensation.Conclusion: Manual construction workers in the construction industry are particularly vulnerable to developing work-related musculoskeletal disorders (WRMSDs), working hours and MSD symptoms, particularly in the lower limb, are significantly correlated

Scaling of Fock space propagator in quasiperiodic many-body localizing systems

Recently many body localized systems have been treated as a hopping problem on a Fock space lattice with correlated disorder, where the many-body eigenstates exhibit multi-fractal character. The many-body propagator in Fock space has been shown to be useful for capturing this multifractality and extracting a Fock-space localization length for systems with random disorder in real space. Here we study a one-dimensional interacting system of spinless Fermions in the presence of a deterministic quasiperiodic potential using the Fock-space propagator. From the system-size scaling of the self-energy associated with the diagonal elements and the scaling of the off-diagonal elements of the propagator, we extract fractal characteristics and FS localization lengths, respectively, which behave similarly to that in the random system. We compute the sample-to-sample fluctuations of the typical self-energy and the off-diagonal propagator over different realizations of the potential and show that the fluctuations in the self-energy distinguish quasiperiodic and random systems, whereas the fluctuations of the off-diagonal elements cannot demarcate the two types of potential.Comment: 13 pages, 13 figure

Indolicidin Targets Duplex DNA: Structural and Mechanistic Insight through a Combination of Spectroscopy and Microscopy

Indolicidin (IR13), a 13‐residue antimicrobial peptide from the cathelicidin family, is known to exhibit a broad spectrum of antimicrobial activity against various microorganisms. This peptide inhibits bacterial DNA synthesis resulting in cell filamentation. However, the precise mechanism remains unclear and requires further investigation. The central PWWP motif of IR13 provides a unique structural element that can wrap around, and thus stabilize, duplex B‐type DNA structures. Replacements of the central Trp‐Trp pair with Ala‐Ala, His‐His, or Phe‐Phe residues in the PxxP motif significantly affects the ability of the peptide to stabilize duplex DNA. Results of microscopy studies in conjunction with spectroscopic data confirm that the DNA duplex is stabilized by IR13, thereby inhibiting DNA replication and transcription. In this study we provide high‐resolution structural information on the interaction between indolicidin and DNA, which will be beneficial for the design of novel therapeutic antibiotics based on peptide scaffolds. That′s a wrap! The PWWP short peptide derived from indolicidin provides a unique structural element that stabilizes the DNA duplex. Substitution of Trp residues in PWWP with Ala, His, or Phe significantly destabilizes the DNA duplex structure, thereby establishing a strong correlation between the surface area of the residues (decreasing order: Ala<His≤Phe<Trp) present between the PxxP domain and DNA stabilization.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/108345/1/cmdc_201402215_sm_miscellaneous_information.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/108345/2/2052_ftp.pd

Morphology and Physico-Mechanical Threshold of α-Cellulose as Filler in an E-SBR Composite

In the current context of green mobility and sustainability, the use of new generation natural fillers, namely, α-cellulose, has gained significant recognition. The presence of hydroxyl groups on α-cellulose has generated immense eagerness to map its potency as filler in an elastomeric composite. In the present work, α-cellulose-emulsion-grade styrene butadiene rubber (E-SBR) composite is prepared by conventional rubber processing method by using variable proportions of α-cellulose (1 to 40 phr) to assess its reinforce ability. Rheological, physical, visco-elastic and dynamic-mechanical behavior have clearly established that 10 phr loading of α-cellulose can be considered as an optimized dosage in terms of performance parameters. Morphological characterization with the aid of scanning electron microscope (SEM) and transmission electron microscopy (TEM) also substantiated that composite with 10 phr loading of α-cellulose has achieved the morphological threshold. With this background, synthetic filler (silica) is substituted by green filler (α-cellulose) in an E-SBR-based composite. Characterization of the compound has clearly established the reinforcement ability of α-cellulose

Safety and efficacy of ruxolitinib in an open-label, multicenter, single-arm phase 3b expanded-access study in patients with myelofibrosis: A snapshot of 1144 patients in the JUMP trial

JUMP is a phase 3b expanded-access trial for patients without access to ruxolitinib outside of a clinical study; it is the largest clinical trial to date in patients with myelofibrosis who have been treated with ruxolitinib. Here, we present safety and efficacy findings from an analysis of 1144 patients with intermediate- or high-risk myelofibrosis, as well as a separate analysis of 163 patients with intermediate-1-risk myelofibrosis – a population of patients not included in the phase 3 COMFORT studies. Consistent with ruxolitinib’s mechanism of action, the most common hematologic adverse events were anemia and thrombocytopenia, but these led to treatment discontinuation in only a few cases. The most common non-hematologic adverse events were primarily grade 1/2 and included diarrhea, pyrexia, fatigue, and asthenia. The rates of infections were low and primarily grade 1/2, and no new or unexpected infections were observed. The majority of patients achieved a ≥50% reduction from baseline in palpable spleen length. Improvements in symptoms were rapid, with approximately half of all patients experiencing clinically significant improvements, as assessed by various quality-of-life questionnaires. The safety and efficacy profile in intermediate-1-risk patients was consistent with that in the overall JUMP population and with that previously reported in intermediate-2- and high-risk patients. Overall, ruxolitinib provided clinically meaningful reductions in spleen length and symptoms in patients with myelofibrosis, including those with intermediate-1-risk disease, with a safety and efficacy profile consistent with that observed in the phase 3 COMFORT studies. This trial was registered as NCT01493414 at ClinicalTrials.gov