Topological nonsymmorphic insulator versus Dirac semimetal in KZnBi

KZnBi was discovered recently as a new three-dimensional (3D) Dirac semimetal with a pair of bulk Dirac fermions in contrast to the $\mathbb{Z}_2$ trivial insulator reported earlier. In order to address this discrepancy, we have performed electronic structure and topological state analysis of KZnBi using the local, semilocal, and hybrid exchange-correlation (XC) functionals within the density functional theory framework. We find that various XC functionals, including the SCAN meta-GGA and hybrid functionals with 25$\%$ Hartree-Fock (HF) exchange, resolve a topological nonsymmorphic insulator state with the glide-mirror protected hourglass surface Dirac fermions. By carefully tuning the modified Becke-Jhonson (mBJ) potential parameters, we recover the correct orbital ordering and Dirac semimetal state of KZnBi. We further show that increasing the default HF exchange in hybrid functionals ($> 40\%$) can also capture the desired Dirac semimetal state with the correct orbital ordering of KZnBi. The calculated energy dispersion and carrier velocities of Dirac states are found to be in excellent agreement with the available experimental results. Our results demonstrate that KZnBi is a unique topological material where large electron correlations are crucial to realize the Dirac semimetal state

Hybrid nodal line semimetal states in anisotropic lattice materials

Understanding the role of lattice geometry in shaping topological states and their properties is of fundamental importance to condensed matter and device physics. Here we demonstrate how an anisotropic crystal lattice drives a topological hybrid nodal line in transition metal tetraphosphides $Tm$P$_4$ ($Tm$ = Transition metal). $Tm$P$_4$ constitutes a unique class of black phosphorus materials formed by intercalating transition metal ions between the phosphorus layers without destroying the characteristic anisotropic band structure of the black phosphorous. Based on the first-principles calculations and $k \cdot p$ theory, we show that $Tm$P$_4$ harbor a single hybrid nodal line formed between oppositely-oriented anisotropic $Tm~d$ and P states unhinged from the high-symmetry planes. The nodal line consists of both type-I and type-II nodal band crossings whose nature and location are determined by the effective-mass anisotropies of the intersecting bands. We further discuss a possible topological phase transition to exemplify the formation of the hybrid nodal line state in $Tm$P$_4$. Our results offer a comprehensive study for understanding the interplay between structural motifs-driven mass anisotropies and topology in anisotropic lattice materials to realize hybrid semimetal states

Study protocol for THINK : a multinational open-label phase I study to assess the safety and clinical activity of multiple administrations of NKR-2 in patients with different metastatic tumour types

Introduction: NKR-2 are autologous T cells genetically modified to express a chimeric antigen receptor (CAR) comprising a fusion of the natural killer group 2D (NKG2D) receptor with the CD3 zeta signalling domain, which associates with the adaptor molecule DNAX-activating protein of 10 kDa (DAP10) to provide co-stimulatory signal upon ligand binding. NKG2D binds eight different ligands expressed on the cell surface of many tumour cells and which are normally absent on non-neoplastic cells. In preclinical studies, NKR-2 demonstrated long-term antitumour activity towards a breadth of tumour indications, with maximum efficacy observed after multiple NKR-2 administrations. Importantly, NKR-2 targeted tumour cells and tumour neovasculature and the local tumour immunosuppressive microenvironment and this mechanism of action of NKR-2 was established in the absence of preconditioning. Methods and analysis: This open-label phase I study will assess the safety and clinical activity of NKR-2 treatment administered three times, with a 2-week interval between each administration in different tumour types. The study will contain two consecutive segments: a dose escalation phase followed by an expansion phase. The dose escalation study involves two arms, one in solid tumours (five specific indications) and one in haematological tumours (two specific indications) and will include three dose levels in each arm: 3x10(8), 1x10(9) and 3x10(9) NKR-2 per injection. On the identification of the recommended dose in the first segment, based on dose-limiting toxicity occurrences, the study will expand to seven different cohorts examining the seven different tumour types separately. Clinical responses will be determined according to standard Response Evaluation Criteria In Solid Tumors (RECIST) criteria for solid tumours or international working group response criteria in haematological tumours. Ethics approval and dissemination: Ethical approval has been obtained at all sites. Written informed consent will be taken from all participants. The results of this study will be disseminated through presentation at international scientific conferences and reported in peer-reviewed scientific journals

Design and implementation of an affordable, public sector electronic medical record in rural Nepal

IntroductionGlobally, electronic medical records are central to the infrastructure of modern healthcare systems. Yet the vast majority of electronic medical records have been designed for resource-rich environments and are not feasible in settings of poverty. Here we describe the design and implementation of an electronic medical record at a public sector district hospital in rural Nepal, and its subsequent expansion to an additional public sector facility.DevelopmentThe electronic medical record was designed to solve for the following elements of public sector healthcare delivery: 1) integration of the systems across inpatient, surgical, outpatient, emergency, laboratory, radiology, and pharmacy sites of care; 2) effective data extraction for impact evaluation and government regulation; 3) optimization for longitudinal care provision and patient tracking; and 4) effectiveness for quality improvement initiatives.ApplicationFor these purposes, we adapted Bahmni, a product built with open-source components for patient tracking, clinical protocols, pharmacy, laboratory, imaging, financial management, and supply logistics. In close partnership with government officials, we deployed the system in February of 2015, added on additional functionality, and iteratively improved the system over the following year. This experience enabled us then to deploy the system at an additional district-level hospital in a different part of the country in under four weeks. We discuss the implementation challenges and the strategies we pursued to build an electronic medical record for the public sector in rural Nepal.DiscussionOver the course of 18 months, we were able to develop, deploy and iterate upon the electronic medical record, and then deploy the refined product at an additional facility within only four weeks. Our experience suggests the feasibility of an integrated electronic medical record for public sector care delivery even in settings of rural poverty

The International Natural Product Sciences Taskforce (INPST) and the power of Twitter networking exemplified through #INPST hashtag analysis

Background: The development of digital technologies and the evolution of open innovation approaches have enabled the creation of diverse virtual organizations and enterprises coordinating their activities primarily online. The open innovation platform titled "International Natural Product Sciences Taskforce" (INPST) was established in 2018, to bring together in collaborative environment individuals and organizations interested in natural product scientific research, and to empower their interactions by using digital communication tools. Methods: In this work, we present a general overview of INPST activities and showcase the specific use of Twitter as a powerful networking tool that was used to host a one-week "2021 INPST Twitter Networking Event" (spanning from 31st May 2021 to 6th June 2021) based on the application of the Twitter hashtag #INPST. Results and Conclusion: The use of this hashtag during the networking event period was analyzed with Symplur Signals (https://www.symplur.com/), revealing a total of 6,036 tweets, shared by 686 users, which generated a total of 65,004,773 impressions (views of the respective tweets). This networking event's achieved high visibility and participation rate showcases a convincing example of how this social media platform can be used as a highly effective tool to host virtual Twitter-based international biomedical research events

Life cycle assessment: Blazing a trail for bioresources management

The life cycle assessment (LCA) is a well-established tool that has been used to provide data-driven analysis of environmental performances. LCA offers insights via selecting appropriate feedstocks, suitable technology, energy and environmental trade-off to be considered during the policy designing phase. In the present review, LCA analysis of each biomass based biorefinery and its impact assessment has been elaborated. The LCA literature clearly shows that transportation and manufacturing contributes majorly (up to 92.19%) to energy consumption. Further, the major global warming potential (GWP) was contributed by the electricity (86%) consumed in biorefinery industry. Thus, utilizing greener energy sources such as hydroelectricity or bioelectricity for energy and transportation needs can help in minimizing the environmental impacts. Further, development of integrated biorefineries can significantly decrease greenhouse gas (GHG) emissions by 83% as compared to petroleum fuels and can fulfill the requirements for renewable fuel standards (RFS). The generation of multiple products at a single unit can help in adjusting the potential trade-offs and promoting environmentally beneficial processes during the designing phase for future refinery and energy systems. LCA is also a rational tool towards designing process blueprint for bioresources management through multi-products integrated biorefineries. It can be expanded further to cover the techno-economic, social, and health impacts in addition to environmental impacts (integrated sustainability assessment) for future integrated biorefineries and policy decisions

Spatially Encoded Transfer of 1H Polarization to 13C for Uniform 1 JCH-Response in HSQC

Two dimensional (2D) NMR display better resolution than one-dimensional (1D) 1H NMR. However, 2D NMR does not display a straightforward quantitative aspect due to J-dependent polarization/coherence transfer. 1D 1H NMR is versatile for quantification; however, it displays significant spectral overlap in biological or organic complex mixtures, which forbids quantification of a large number of signals in 1D 1H NMR. The significant variations in 1H13C scalar couplings, T1, T2, and pulse imperfections are the main problems. Although T1, T2 can be suitably chosen to minimize their adverse effect on quantification, the large variations in 1H - 13C couplings lead to variations in cross peak intensity, which is more influenced by the amount of polarization transfer rather than the quantity of metabolites or amount of analytes in a complex mixture. In the present work, we show that spatial encoding of the polarization transfer periods can be executed in 1H13C HSQC using sweep frequency pulses in the presence of a magnetic field gradient. As a result, uniform transfer of polarization from 1H to 13C over a range of 1H - 13C couplings can be performed, subsequently improving the quantitative aspect of HSQC or improve the intensity of cross-peaks, which are mistuned in regular HSQ

Selective inhibition of antigen-specific T lymphocyte proliferation by acute ethanol exposure: the role of impaired monocyte antigen presentation capacity and mediator production

Ethanol consumption is associated with impaired immunity. Our data demonstrate that even a single dose of a biologically relevant concentration (25-150 mM) of ethanol can down-regulate antigen-specific T lymphocyte proliferation. In contrast, ethanol augmented mitogen-induced T cell proliferation, suggesting that its inhibitory effect on antigen-specific T cell proliferation was due to its effects on monocytes (m phi s) rather than on T cells. The immunodepressive effects of ethanol on m phi antigen-presenting cell (APC) capacity were manifested whether alcohol treatment was limited to the antigen uptake-processing period only or was present during the entire period of antigen presentation. These inhibitory effects of ethanol were also evident on both the high-antigen-presenting, Fc gamma RI-negative (-31 +/- 17%), and low-antigen-presenting, Fc gamma RI-positive (-42 +/- 15%) m phi subpopulations. Further analysis demonstrated that ethanol inhibits the production of interleukin-1 beta (IL-1 beta) and induces transforming growth factor beta (TGF-beta) and prostaglandin E2 (PGE2), monocyte-derived mediators that can affect T cell proliferation. Ethanol resulted in a dose-dependent down-regulation of secreted and cell-associated IL-1 beta protein as well as IL-1 beta mRNA levels induced by adherence or bacterial stimulation. The causal relationship between decreased m phi IL-1 beta production, elevated TGF-beta levels, and the decreased m phi APC capacity was further substantiated when exogenous IL-1 beta protein or anti-TGF-beta neutralizing antibody prevented the down-regulatory effect of ethanol on antigen-specific T cell proliferation. Utilizing a cyclooxygenase inhibitor, we also demonstrated that the ethanol-induced decrease in m phi APCs is not mediated by enhanced PGE2 production

Down-regulation of tumor necrosis factor alpha activity by acute ethanol treatment in human peripheral blood monocytes

As the most commonly used drug that can modulate both metabolic and immune pathways, ethanol is evaluated in this report as a regulator of tumor necrosis factor alpha (TNF alpha) production in human peripheral blood monocytes (M phi) in combination with a variety of stimuli. While acute ethanol treatment did not induce TNF alpha in M phi, it was a potent down-regulator of M phi TNF alpha production whether induced by the combination of interferon-gamma plus muramyl dipeptide (MDP) (P \u3c 0.001), lipopolysaccharide (LPS) alone (P \u3c 0.01), or interferon-gamma plus LPS. Down-regulation of M phi TNF alpha by ethanol was dose dependent and statistically significant in the biologically relevant, 25-150 mM, ethanol concentration range. We also demonstrate that these ethanol concentrations did not affect M phi viability. TNF alpha down-regulation by ethanol was most effective when ethanol was administered 4 hr prior to MDP stimulation; however, it was also effective--though to a lesser extent--if it was added at the time of MDP stimulation. Furthermore, ethanol also down-regulated TNF alpha production of the in vivo preactivated M phi of trauma patients, which produce hyperelevated levels of TNF alpha. We have previously shown that the majority of posttrauma elevated M phi TNF alpha is produced by the M phi subpopulation expressing high-affinity type I Fc gamma receptors (Fc gamma RI). When the Fc gamma RI cross-linking-stimulated M phi subpopulation was treated with acute ethanol, TNF alpha production was suppressed again both in in vivo preactivated M phi of trauma patients and in M phi of normal controls.(ABSTRACT TRUNCATED AT 250 WORDS

Regulatory potential of ethanol and retinoic acid on human monocyte functions

Retinoic acid (RA), a metabolic product of vitamin A, has been shown to affect a variety of immune functions, including monocytes. Monocyte functions and mediator production are also modulated by ethanol exposure. This study demonstrates that therapeutic doses of RA (0.1-10 microM) significantly increase transforming growth factor-beta (TGF beta) production both in THP-1, human myelomonocytic cells, and in human peripheral blood monocytes. We have previously reported TGF beta induction by ethanol in human M theta. Combination of RA stimulation with acute in vitro ethanol treatment, however, resulted in significantly lower M theta TGF beta production than TGF beta levels induced by RA alone (p \u3c 0.003). Down-regulation of M theta TGF beta production by ethanol was tested at the concentration range of 25-150 mM and occurred both at high and low RA concentrations (10-0.1 microM). In contrast to its inhibitory effect on RA-induced M theta TGF beta production, ethanol augmented TGF beta production induced by muramyl dipeptide (20 micrograms/ml), suggesting that ethanol can either up- or down-regulate M theta TGF beta production, depending on the costimulatory factors. RA also induced a moderate increase in M theta tumor necrosis factor-alpha (TNF alpha) production, which was down-regulated by ethanol both at the level of secreted and cell-associated TNF alpha. In addition to regulation of cytokine production, both RA and ethanol decreased expression of CD4 on THP-1 cells. The degree of inhibition of CD4 expression by RA was more significant than by ethanol, but RA-induced decrease in CD4 expression was not significantly affected by the combined stimulation with ethanol.(ABSTRACT TRUNCATED AT 250 WORDS