Differential Interleukin-2 Transcription Kinetics Render Mouse but Not Human T Cells Vulnerable to Splicing Inhibition Early after Activation

T cells are nodal players in the adaptive immune response against pathogens and malignant cells. Alternative splicing plays a crucial role in T cell activation, which is analyzed mainly at later time points upon stimulation. Here we have discovered a 2-h time window early after stimulation where optimal splicing efficiency or, more generally, gene expression efficiency is crucial for successful T cell activation. Reducing the splicing efficiency at 4 to 6 h poststimulation significantly impaired murine T cell activation, which was dependent on the expression dynamics of the Egr1-Nab2-interleukin-2 (IL-2) pathway. This time window overlaps the time of peak IL-2 de novo transcription, which, we suggest, represents a permissive time window in which decreased splicing (or transcription) efficiency reduces mature IL-2 production, thereby hampering murine T cell activation. Notably, the distinct expression kinetics of the Egr1-Nab2-IL-2 pathway between mouse and human render human T cells refractory to this vulnerability. We propose that the rational temporal modulation of splicing or transcription during peak de novo expression of key effectors can be used to fine-tune stimulation-dependent biological outcomes. Our data also show that critical consideration is required when extrapolating mouse data to the human system in basic and translational research

Bandgap Change of Carbon Nanotubes: Effect of Small Tensile and Torsional Strain

We use a simple picture based on the $\pi$ electron approximation to study the bandgap variation of carbon nanotubes with uniaxial and torsional strain. We find (i) that the magnitude of slope of bandgap versus strain has an almost universal behaviour that depends on the chiral angle, (ii) that the sign of slope depends on the value of $(n-m) \bmod 3$ and (iii) a novel change in sign of the slope of bandgap versus uniaxial strain arising from a change in the value of the quantum number corresponding to the minimum bandgap. Four orbital calculations are also presented to show that the $\pi$ orbital results are valid.Comment: Revised. Method explained in detai

"Narrow" Graphene Nanoribbons Made Easier by Partial Hydrogenation

It is a challenge to synthesize graphene nanoribbons (GNRs) with narrow widths and smooth edges in large scale. Our first principles study on the hydrogenation of GNRs shows that the hydrogenation starts from the edges of GNRs and proceeds gradually toward the middle of the GNRs so as to maximize the number of carbon-carbon $\pi$-$\pi$ bonds. Furthermore, the partially hydrogenated wide GNRs have similar electronic and magnetic properties as those of narrow GNRs. Therefore, it is not necessary to directly produce narrow GNRs for realistic applications because partial hydrogenation could make wide GNRs "narrower"

In silico analysis of alternative splicing events implicated in intracellular trafficking during B-lymphocyte differentiation

There are multiple regulatory layers that control intracellular trafficking and protein secretion, ranging from transcriptional to posttranslational mechanisms. Finely regulated trafficking and secretion is especially important for lymphocytes during activation and differentiation, as the quantity of secretory cargo increases once the activated cells start to produce and secrete large amounts of cytokines, cytotoxins, or antibodies. However, how the secretory machinery dynamically adapts its efficiency and specificity in general and specifically in lymphocytes remains incompletely understood. Here we present a systematic bioinformatics analysis to address RNA-based mechanisms that control intracellular trafficking and protein secretion during B-lymphocyte activation, and differentiation, with a focus on alternative splicing. Our in silico analyses suggest that alternative splicing has a substantial impact on the dynamic adaptation of intracellular traffic and protein secretion in different B cell subtypes, pointing to another regulatory layer to the control of lymphocyte function during activation and differentiation. Furthermore, we suggest that NERF/ELF2 controls the expression of some COPII-related genes in a cell type-specific manner. In addition, T cells and B cells appear to use different adaptive strategies to adjust their secretory machineries during the generation of effector and memory cells, with antibody secreting B cell specifically increasing the expression of components of the early secretory pathway. Together, our data provide hypotheses how cell type-specific regulation of the trafficking machinery during immune cell activation and differentiation is controlled that can now be tested in wet lab experiments

Screening of suitable cationic dopants for solar absorber material CZTS/Se: A first principles study

The earth abundant and non-toxic solar absorber material kesterite Cu2ZnSn(S/Se)(4) has been studied to achieve high power conversion efficiency beyond various limitations, such as secondary phases, antisite defects, band gap adjustment and microstructure. To alleviate these hurdles, we employed screening based approach to find suitable cationic dopant that can promote the current density and the theoretical maximum upper limit of the energy conversion efficiency (P(%)) of CZTS/Se solar devices. For this task, the hybrid functional (Heyd, Scuseria and Ernzerhof, HSE06) were used to study the electronic and optical properties of cation (Al, Sb, Ga, Ba) doped CZTS/Se. Our in-depth investigation reveals that the Sb atom is suitable dopant of CZTS/CZTSe and also it has comparable bulk modulus as of pure material. The optical absorption coefficient of Sb doped CZTS/Se is considerably larger than the pure materials because of easy formation of visible range exciton due to the presence of defect state below the Fermi level, which leads to an increase in the current density and P(%). Our results demonstrate that the lower formation energy, preferable energy gap and excellent optical absorption of the Sb doped CZTS/Se make it potential component for relatively high efficient solar cells

A computational study of Si–H bonds as precursors for neutral E' centres in amorphous silica and at the Si/SiO2 interface

Using computational modelling we investigate whether Si–H Bonds can serve as precursors for neutral E′E′ centre formation in amorphous silica and at the Si/SiO2 interface. Classical inter-atomic potentials are used to construct models of a-SiO2 containing Si–H bonds. We then investigate the mechanism of dissociation of a Si–H bond to create a neutral E′E′ defect, that is a 3-coordinated silicon with an unpaired electron localised on it. We show that the Si–H bond is extremely stable, but as a result of hole injection it is significantly weakened and may dissociate, creating a neutral E′E′ centre and a proton attached to one of the nearby oxygen atoms. The proton can diffuse around the E′E′ centre and has a profound effect on the defect levels. We show that at a Si/SiO2 interface, the position of the proton can facilitate electron transfer from the Si substrate onto the defect, making it negatively charged

Advances in ab-initio theory of Multiferroics. Materials and mechanisms: modelling and understanding

Within the broad class of multiferroics (compounds showing a coexistence of magnetism and ferroelectricity), we focus on the subclass of "improper electronic ferroelectrics", i.e. correlated materials where electronic degrees of freedom (such as spin, charge or orbital) drive ferroelectricity. In particular, in spin-induced ferroelectrics, there is not only a {\em coexistence} of the two intriguing magnetic and dipolar orders; rather, there is such an intimate link that one drives the other, suggesting a giant magnetoelectric coupling. Via first-principles approaches based on density functional theory, we review the microscopic mechanisms at the basis of multiferroicity in several compounds, ranging from transition metal oxides to organic multiferroics (MFs) to organic-inorganic hybrids (i.e. metal-organic frameworks, MOFs)Comment: 22 pages, 9 figure

Precision farming and archaeology

With a significant growth in the agricultural technology industry a vast amount of agricultural data is now being collected on farms throughout the world. Farmers aim to utilise these technologies to regularly record and manage the variation of crops and soils within their fields, to reduce inputs, increase yields and enhance environmental sustainability. In this paper we aim to highlight the variety of different data types and methodological processes involved in modern precision farming and explore how potentially interconnected these systems are with the archaeological communit

Observation of the nonlinear Hall effect under time reversal symmetric conditions

The electrical Hall effect is the production of a transverse voltage under an out-of-plane magnetic field. Historically, studies of the Hall effect have led to major breakthroughs including the discoveries of Berry curvature and the topological Chern invariants. In magnets, the internal magnetization allows Hall conductivity in the absence of external magnetic field. This anomalous Hall effect (AHE) has become an important tool to study quantum magnets. In nonmagnetic materials without external magnetic fields, the electrical Hall effect is rarely explored because of the constraint by time-reversal symmetry. However, strictly speaking, only the Hall effect in the linear response regime, i.e., the Hall voltage linearly proportional to the external electric field, identically vanishes due to time-reversal symmetry. The Hall effect in the nonlinear response regime, on the other hand, may not be subject to such symmetry constraints. Here, we report the observation of the nonlinear Hall effect (NLHE) in the electrical transport of the nonmagnetic 2D quantum material, bilayer WTe2. Specifically, flowing an electrical current in bilayer WTe2 leads to a nonlinear Hall voltage in the absence of magnetic field. The NLHE exhibits unusual properties sharply distinct from the AHE in metals: The NLHE shows a quadratic I-V characteristic; It strongly dominates the nonlinear longitudinal response, leading to a Hall angle of about 90 degree. We further show that the NLHE directly measures the "dipole moment" of the Berry curvature, which arises from layer-polarized Dirac fermions in bilayer WTe2. Our results demonstrate a new Hall effect and provide a powerful methodology to detect Berry curvature in a wide range of nonmagnetic quantum materials in an energy-resolved way

Negotiating different disciplinary discourses: biology students’ ritualized and exploratory participation in mathematical modeling activities

Non-mathematics specialists’ competence and confidence in mathematics in their disciplines have been highlighted as in need of improvement. We report from a collaborative, developmental research project which explores the conjecture that greater integration of mathematics and biology in biology study programs, for example through engaging students with Mathematical Modeling (MM) activities, is one way to achieve this improvement. We examine the evolution of 12 first-semester biology students’ mathematical discourse as they engage with such activities in four sessions which ran concurrently with their mandatory mathematics course and were taught by a mathematician with extensive experience with MM. The sessions involved brief introductions to different aspects of MM, followed by small-group work on tasks set in biological contexts. Our analyses use the theory of commognition to investigate the tensions between ritualized and exploratory participation in the students’ MM activity. We focus particularly on a quintessential routine in MM, assumption building: we trace attempts which start from ritualized engagement in the shape of “guesswork” and evolve into more productively exploratory formulations. We also identify signs of persistent commognitive conflict in the students’ activity, both intra-mathematical (concerning what is meant by a “math task”) and extra-mathematical (concerning what constitutes a plausible solution to the tasks in a biological sense). Our analyses show evidence of the fluid interplay between ritualized and exploratory engagement in the students’ discursive activity and contribute towards what we see as a much needed distancing from operationalization of the commognitive constructs of ritual and exploration as an unhelpfully dichotomous binary