Nonequilibrium molecular dynamics simulation of dendrimers and hyperbranched polymer melts undergoing planar elongational flow

The planar elongational melt rheology and structural properties of dendrimers and hyperbranched polymers of different molecular weights (generations 1-4) and their linear counterparts have been studied using nonequilibrium molecular dynamics simulation techniques in the isothermal-isobaric ensemble. The extensional viscosity showed three distinctive regions against strain-rate, including an initial Newtonian region at low strain-rates, followed by a thickening behavior at medium strain-rates and terminated with a thinning region at very high strain-rates, in agreement with the Sarkar and Gupta model [J. Rein. Plast. Comp. 20, 1473-1484 (2001)]. In addition, a structural analysis was performed to study the size, shape, and spatial distributions within globular dendrimers and hyperbranched polymer molecules under planar elongational flow (PEF). Ratios of the eigenvalues of the gyration tensor showed that contrary to shear flow, under PEF even at low strain rates, dendrimers and hyperbranched molecules have ellipsoidal conformations and change to a much more flattened prolate shape at higher strain rates. In combination with the eigenvalue ratios, the distribution of monomers from the central core of the molecules showed that the thickening region occurs due to branches being stretched, and terminal thinning behavior stems primarily from flow-induced alignment and finite extensibility effects

Two Decades of Global Progress in Authorized Advanced Therapy Medicinal Products: An Emerging Revolution in Therapeutic Strategies

The introduction of advanced therapy medicinal products (ATMPs) to the global pharma market has been revolutionizing the pharmaceutical industry and has opened new routes for treating various types of cancers and incurable diseases. In the past two decades, a noticeable part of clinical practices has been devoting progressively to these products. The first step to develop such an ATMP product is to be familiar with other approved products to obtain a general view about this industry trend. The present paper depicts an overall perspective of approved ATMPs in different countries, while reflecting the degree of their success in a clinical point of view and highlighting their main safety issues and also related market size as a whole. In this regard, published articles regarding safety, efficacy, and market size of approved ATMPs were reviewed using the search engines PubMed, Scopus, and Google Scholar. For some products which the related papers were not available, data on the relevant company website were referenced. In this descriptive study, we have introduced and classified approved cell, gene, and tissue engineering-based products by different regulatory agencies, along with their characteristics, manufacturer, indication, approval date, related regulatory agency, dosage, product description, price and published data about their safety and efficacy. In addition, to gain insights about the commercial situation of each product, we have gathered accessible sale reports and market size information that pertain to some of these products

Expression profiling of candidate genes in sugar beet leaves treated with leonardite-based biostimulant

Leonardite-based biostimulants are a large class of compounds, including humic acid substances. Foliar application of biostimulants at field level improves plant growth, yield and quality through metabolic changes and stimulation of plant proton pumps. The present study aimed at identifying optimum dosage of BLACKJAK, a humic acid-based substance, which is able to modify genes involved in sugar beet growth. Thirty-three genes belonging to various biochemical pathway categories were tested in leaves of treated sugar beet (Beta vulgaris L.) samples to assess gene expression profiling in response to BLACKJAK. Seedlings of a diploid and multigerm variety were grown in plastic pots and sprayed with two dilutions of BLACKJAK (dilution 1:500-1.0 mg C L-1 and dilution 1:1000-0.5 mg C L-1). Leaf samples were collected after 24, 48, and 72 h treatment with BLACKJAK for each dilution. RNA was extracted and the quantification of gene expression was performed while using an OpenArray platform. Results of analysis of variance demonstrated that, 15 genes out of a total of 33 genes tested with OpenArray qPCR were significantly affected by treatment and exposure time. Analysis for annotation of gene products and pathways revealed that genes belonging to the mitochondrial respiratory pathways, nitrogen and hormone metabolisms, and nutrient uptake were up-regulated in the BLACKJAK treated samples. Among the up-regulated genes, Bv_PHT2;1 and Bv_GLN1 expression exerted a 2-fold change in 1:1000 and 1:500 BLACKJAK concentrations. Overall, the gene expression data in the BLACKJAK treated leaves demonstrated the induction of plant growth-related genes that were contributed almost to amino acid and nitrogen metabolism, plant defense system, and plant growth

Comparative Survival Analysis of Immunomodulatory Therapy for Coronavirus Disease 2019 Cytokine Storm.

BACKGROUND:Cytokine storm is a marker of coronavirus disease 2019 (COVID-19) illness severity and increased mortality. Immunomodulatory treatments have been repurposed to improve mortality outcomes. RESEARCH QUESTION:Do immunomodulatory therapies improve survival in patients with COVID-19 cytokine storm (CCS)? STUDY DESIGN AND METHODS:We conducted a retrospective analysis of electronic health records across the Northwell Health system. COVID-19 patients hospitalized between March 1, 2020, and April 24, 2020, were included. CCS was defined by inflammatory markers: ferritin, \u3e 700 ng/mL; C-reactive protein (CRP), \u3e 30 mg/dL; or lactate dehydrogenase (LDH), \u3e 300 U/L. Patients were subdivided into six groups: no immunomodulatory treatment (standard of care) and five groups that received either corticosteroids, anti-IL-6 antibody (tocilizumab), or anti-IL-1 therapy (anakinra) alone or in combination with corticosteroids. The primary outcome was hospital mortality. RESULTS:Five thousand seven hundred seventy-six patients met the inclusion criteria. The most common comorbidities were hypertension (44%-59%), diabetes (32%-46%), and cardiovascular disease (5%-14%). Patients most frequently met criteria with high LDH (76.2%) alone or in combination, followed by ferritin (63.2%) and CRP (8.4%). More than 80% of patients showed an elevated D-dimer. Patients treated with corticosteroids and tocilizumab combination showed lower mortality compared with patients receiving standard-of-care (SoC) treatment (hazard ratio [HR], 0.44; 95% CI, 0.35-0.55; P \u3c .0001) and with patients treated with corticosteroids alone (HR, 0.66; 95% CI, 0.53-0.83; P = .004) or in combination with anakinra (HR, 0.64; 95% CI, 0.50-0.81; P = .003). Corticosteroids when administered alone (HR, 0.66; 95% CI, 0.57-0.76; P \u3c .0001) or in combination with tocilizumab (HR, 0.43; 95% CI, 0.35-0.55; P \u3c .0001) or anakinra (HR, 0.68; 95% CI, 0.57-0.81; P \u3c .0001) improved hospital survival compared with SoC treatment. INTERPRETATION:The combination of corticosteroids with tocilizumab showed superior survival outcome when compared with SoC treatment and treatment with corticosteroids alone or in combination with anakinra. Furthermore, corticosteroid use either alone or in combination with tocilizumab or anakinra was associated with reduced hospital mortality for patients with CCS compared with patients receiving SoC treatment

Wave-guided optical waveguides

This work primarily aims to fabricate and use two photon polymerization (2PP) microstructures capable of being optically manipulated into any arbitrary orientation. We have integrated optical waveguides into the structures and therefore have freestanding waveguides, which can be positioned anywhere in the sample at any orientation using optical traps. One of the key aspects to the work is the change in direction of the incident plane wave, and the marked increase in the numerical aperture demonstrated. Hence, the optically steered waveguide can tap from a relatively broader beam and then generate a more tightly confined light at its tip. The paper contains both simulation, related to the propagation of light through the waveguide, and experimental demonstrations using our BioPhotonics Workstation. In a broader context, this work shows that optically trapped microfabricated structures can potentially help bridge the diffraction barrier. This structure-mediated paradigm may be carried forward to open new possibilities for exploiting beams from far-field optics down to the subwavelength domain. (C)2012 Optical Society of Americ

Breastfeeding and infant care as ‘sexed’ care work: reconsideration of the three Rs to enable women’s rights, economic empowerment, nutrition and health

Women’s1 lifelong health and nutrition status is intricately related to their reproductive history, including the number and spacing of their pregnancies and births, and for how long and how intensively they breastfeed their children. In turn, women’s reproductive biology is closely linked to their social roles and situation, including regarding economic disadvantage and disproportionate unpaid work. Recognizing, as well as reducing and redistributing women’s care and domestic work (known as the ‘Three Rs’), is an established framework for addressing women’s inequitable unpaid care work. However, the care work of breastfeeding presents a dilemma, and is even a divisive issue, for advocates of women’s empowerment, because reducing breastfeeding and replacing it with commercial milk formula risks harming women’s and children’s health. It is therefore necessary for the interaction between women’s reproductive biology and infant care role to be recognized in order to support women’s human rights and enable governments to implement economic, employment and other policies to empower women. In this paper, we argue that breastfeeding–like childbirth–is reproductive work that should not be reduced and cannot sensibly be directly redistributed to fathers or others. Rather, we contend that the Three Rs agenda should be reconceptualized to isolate breastfeeding as ‘sexed’ care work that should be supported rather than reduced with action taken to avoid undermining breastfeeding. This means that initiatives toward gender equality should be assessed against their impact on women’s ability to breastfeed. With this reconceptualization, adjustments are also needed to key global economic institutions and national statistical systems to appropriately recognize the value of this work. Additional structural supports such as maternity protection and childcare are needed to ensure that childbearing and breastfeeding do not disadvantage women amidst efforts to reduce gender pay gaps and gender economic inequality. Distinct policy interventions are also required to facilitate fathers’ engagement in enabling and supporting breastfeeding through sharing the other unpaid care work associated with parents’ time-consuming care responsibilities, for both infants and young children and related household work