Correlated Electrical and Chemical Nanoscale Properties in Potassium-Passivated, Triple-Cation Perovskite Solar Cells

Perovskite semiconductors are an exciting class of materials due to their promising performance outputs in photovoltaic devices. To boost their efficiency further, researchers introduce additives during sample synthesis, such as KI. However, it is not well understood how KI changes the material and, often, leaves precipitants. To fully resolve the role of KI, multiple microscopy techniques are applied and the electrical and chemical behavior of a Reference (untreated) and a KI‐treated perovskite are compared. Upon correlation between electrical and chemical nanoimaging techniques, it is discovered that these local properties are linked to the macroscopic voltage enhancement of the KI‐treated perovskite. The heterogeneity revealed in both the local electrical and chemical responses indicates that the additive partially migrates to the surface, yet surprisingly does not deteriorate the performance locally, rather, the voltage response homogeneously increases. The research presented within provides a diagnostic methodology, which connects the nanoscale electrical and chemical properties of materials, relevant to other perovskites, including multication and Pb‐free alternatives

Correlated Electrical and Chemical Nanoscale Properties in Potassium-Passivated, Triple-Cation Perovskite Solar Cells

Perovskite semiconductors are an exciting class of materials due to their promising performance outputs in optoelectronic devices. To boost their efficiency further, researchers introduce additives during sample synthesis, such as KI. However, it is not well understood how KI changes the material and, often, leaves precipitants. To fully resolve the role of KI, a multiple microscopy techniques is applied and the electrical and chemical behavior of a Reference (untreated) and a KI-treated perovskite are compared. Upon correlation between electrical and chemical nanoimaging techniques, it is discovered that these local properties are linked to the macroscopic voltage enhancement of the KI-treated perovskite. The heterogeneity revealed in both the local electrical and chemical responses indicates that the additive partially migrates to the surface, yet surprisingly; does not deteriorate the performance locally, rather, the voltage response homogeneously increases. The research presented within provides a diagnostic methodology, which connects the nanoscale electrical and chemical properties of materials, relevant to other perovskites, including multication and Pb-free alternatives.University of Maryland All-S.T.A.R. Fellowship Hulka Energy Research Fellowship National Science Foundation US Department of Energy The Royal Society Office of Naval Researc

Quantum biology on the edge of quantum chaos

We give a new explanation for why some biological systems can stay quantum coherent for long times at room temperatures, one of the fundamental puzzles of quantum biology. We show that systems with the right level of complexity between chaos and regularity can increase their coherence time by orders of magnitude. Systems near Critical Quantum Chaos or Metal-Insulator Transition (MIT) can have long coherence times and coherent transport at the same time. The new theory tested in a realistic light harvesting system model can reproduce the scaling of critical fluctuations reported in recent experiments. Scaling of return probability in the FMO light harvesting complex shows the signs of universal return probability decay observed at critical MIT. The results may open up new possibilities to design low loss energy and information transport systems in this Poised Realm hovering reversibly between quantum coherence and classicality

Inflation and dark matter in two Higgs doublet models

We consider the Higgs inflation in the extension of the Standard Model with two Higgs doublets coupled to gravity non-minimally. In the presence of an approximate global U(1) symmetry in the Higgs sector, both radial and angular modes of neutral Higgs bosons drive inflation where large non-Gaussianity is possible from appropriate initial conditions on the angular mode. We also discuss the case with single-field inflation for which the U(1) symmetry is broken to a Z_2 subgroup. We show that inflationary constraints, perturbativity and stability conditions restrict the parameter space of the Higgs quartic couplings at low energy in both multi- and single-field cases. Focusing on the inert doublet models where Z_2 symmetry remains unbroken at low energy, we show that the extra neutral Higgs boson can be a dark matter candidate consistent with the inflationary constraints. The doublet dark matter is always heavy in multi-field inflation while it can be light due to the suppression of the co-annihilation in single-field inflation. The implication of the extra quartic couplings on the vacuum stability bound is also discussed in the light of the recent LHC limits on the Higgs mass.Comment: (v1) 28 pages, 8 figures; (v2) 29 pages, a new subsection 3.3 added, references added and typos corrected, to appear in Journal of High Energy Physic

Defining the temporal evolution of gut dysbiosis and inflammatory responses leading to hepatocellular carcinoma in Mdr2 -/- mouse model.

BACKGROUND: Emerging evidence implicates the gut microbiome in liver inflammation and hepatocellular carcinoma (HCC) development. We aimed to characterize the temporal evolution of gut dysbiosis, in relation to the phenotype of systemic and hepatic inflammatory responses leading to HCC development. In the present study, Mdr2 -/- mice were used as a model of inflammation-based HCC. Gut microbiome composition and function, in addition to serum LPS, serum cytokines/chemokines and intrahepatic inflammatory genes were measured throughout the course of liver injury until HCC development. RESULTS: Early stages of liver injury, inflammation and cirrhosis, were characterized by dysbiosis. Microbiome functional pathways pertaining to gut barrier dysfunction were enriched during the initial phase of liver inflammation and cirrhosis, whilst those supporting lipopolysaccharide (LPS) biosynthesis increased as cirrhosis and HCC ensued. In parallel, serum LPS progressively increased during the course of liver injury, corresponding to a shift towards a systemic Th1/Th17 proinflammatory phenotype. Alongside, the intrahepatic inflammatory gene profile transitioned from a proinflammatory phenotype in the initial phases of liver injury to an immunosuppressed one in HCC. In established HCC, a switch in microbiome function from carbohydrate to amino acid metabolism occurred. CONCLUSION: In Mdr2 -/- mice, dysbiosis precedes HCC development, with temporal evolution of microbiome function to support gut barrier dysfunction, LPS biosynthesis, and redirection of energy source utilization. A corresponding shift in systemic and intrahepatic inflammatory responses occurred supporting HCC development. These findings support the notion that gut based therapeutic interventions could be beneficial early in the course of liver disease to halt HCC development

Genetic Labeling of Neuronal Subsets through Enhancer Trapping in Mice

The ability to label, visualize, and manipulate subsets of neurons is critical for elucidating the structure and function of individual cell types in the brain. Enhancer trapping has proved extremely useful for the genetic manipulation of selective cell types in Drosophila. We have developed an enhancer trap strategy in mammals by generating transgenic mice with lentiviral vectors carrying single-copy enhancer-detector probes encoding either the marker gene lacZ or Cre recombinase. This transgenic strategy allowed us to genetically identify a wide variety of neuronal subpopulations in distinct brain regions. Enhancer detection by lentiviral transgenesis could thus provide a complementary method for generating transgenic mouse libraries for the genetic labeling and manipulation of neuronal subsets

Genetic dissection of an amygdala microcircuit that gates conditioned fear

The role of different amygdala nuclei (neuroanatomical subdivisions) in processing Pavlovian conditioned fear has been studied extensively, but the function of the heterogeneous neuronal subtypes within these nuclei remains poorly understood. Here we use molecular genetic approaches to map the functional connectivity of a subpopulation of GABA-containing neurons, located in the lateral subdivision of the central amygdala (CEl), which express protein kinase C-δ (PKC-δ). Channelrhodopsin-2-assisted circuit mapping in amygdala slices and cell-specific viral tracing indicate that PKC-δ^+ neurons inhibit output neurons in the medial central amygdala (CEm), and also make reciprocal inhibitory synapses with PKC-δ^− neurons in CEl. Electrical silencing of PKC-δ^+ neurons in vivo suggests that they correspond to physiologically identified units that are inhibited by the conditioned stimulus, called Cel_(off) units. This correspondence, together with behavioural data, defines an inhibitory microcircuit in CEl that gates CEm output to control the level of conditioned freezing

Molecular cloning and preliminary function study of iron responsive element binding protein 1 gene from cypermethrin-resistant Culex pipiens pallens

<p>Abstract</p> <p>Background</p> <p>Insecticide resistance jeopardizes the control of mosquito populations and mosquito-borne disease control, which creates a major public health concern. Two-dimensional electrophoresis identified one protein segment with high sequence homology to part of <it>Aedes aegypti </it>iron-responsive element binding protein (IRE-BP).</p> <p>Method</p> <p>RT-PCR and RACE (rapid amplification of cDNA end) were used to clone a cDNA encoding full length IRE-BP 1. Real-time quantitative RT-PCR was used to evaluate the transcriptional level changes in the Cr-IRE strain <it>Aedes aegypti </it>compared to the susceptible strain of <it>Cx. pipiens pallens</it>. The expression profile of the gene was established in the mosquito life cycle. Methyl tritiated thymidine (³H-TdR) was used to observe the cypermethrin resistance changes in C6/36 cells containing the stably transfected IRE-BP 1 gene of <it>Cx. pipiens pallens</it>.</p> <p>Results</p> <p>The complete sequence of iron responsive element binding protein 1 (IRE-BP 1) has been cloned from the cypermethrin-resistant strain of <it>Culex pipiens pallens </it>(Cr-IRE strain). Quantitative RT-PCR analysis indicated that the IRE-BP 1 transcription level was 6.7 times higher in the Cr-IRE strain than in the susceptible strain of 4th instar larvae. The IRE-BP 1 expression was also found to be consistently higher throughout the life cycle of the Cr-IRE strain. A protein of predicted size 109.4 kDa has been detected by Western blotting in IRE-BP 1-transfected mosquito C6/36 cells. These IRE-BP 1-transfected cells also showed enhanced cypermethrin resistance compared to null-transfected or plasmid vector-transfected cells as determined by ³H-TdR incorporation.</p> <p>Conclusion</p> <p>IRE-BP 1 is expressed at higher levels in the Cr-IRE strain, and may confer some insecticide resistance in <it>Cx. pipiens pallens</it>.</p

A phase IIb, open-label, randomized controlled dose ranging multi-centre trial to evaluate the safety, tolerability, pharmacokinetics and exposure-response relationship of different doses of delpazolid in combination with bedaquiline delamanid moxifloxacin in adult subjects with newly diagnosed, uncomplicated, smear-positive, drug-sensitive pulmonary tuberculosis

BACKGROUND: Linezolid is an effective, but toxic anti-tuberculosis drug that is currently recommended for the treatment of drug-resistant tuberculosis. Improved oxazolidinones should have a better safety profile, while preserving efficacy. Delpazolid is a novel oxazolidinone developed by LegoChem Biosciences Inc. that has been evaluated up to phase 2a clinical trials. Since oxazolidinone toxicity can occur late in treatment, LegoChem Biosciences Inc. and the PanACEA Consortium designed DECODE to be an innovative dose-ranging study with long-term follow-up for determining the exposure-response and exposure-toxicity relationship of delpazolid to support dose selection for later studies. Delpazolid is administered in combination with bedaquiline, delamanid and moxifloxacin. METHODS: Seventy-five participants with drug-sensitive, pulmonary tuberculosis will receive bedaquiline, delamanid and moxifloxacin, and will be randomized to delpazolid dosages of 0 mg, 400 mg, 800 mg, 1200 mg once daily, or 800 mg twice daily, for 16 weeks. The primary efficacy endpoint will be the rate of decline of bacterial load on treatment, measured by MGIT liquid culture time to detection from weekly sputum cultures. The primary safety endpoint will be the proportion of oxazolidinone class toxicities; neuropathy, myelosuppression, or tyramine pressor response. Participants who convert to negative liquid media culture by week 8 will stop treatment after the end of their 16-week course and will be observed for relapse until week 52. Participants who do not convert to negative culture will receive continuation phase treatment with rifampicin and isoniazid to complete a six-month treatment course. DISCUSSION: DECODE is an innovative dose-finding trial, designed to support exposure-response modelling for safe and effective dose selection. The trial design allows assessment of occurrence of late toxicities as observed with linezolid, which is necessary in clinical evaluation of novel oxazolidinones. The primary efficacy endpoint is the change in bacterial load, an endpoint conventionally used in shorter dose-finding trials. Long-term follow-up after shortened treatment is possible through a safety rule excluding slow-and non-responders from potentially poorly performing dosages. TRIAL REGISTRATION: DECODE was registered in ClinicalTrials.gov before recruitment start on 22 October 2021 (NCT04550832)

Analysis and verification of the HMGB1 signaling pathway

Background\ud Recent studies have found that overexpression of the High-mobility group box-1 (HMGB1) protein, in conjunction with its receptors for advanced glycation end products (RAGEs) and toll-like receptors (TLRs), is associated with proliferation of various cancer types, including that of the breast and pancreatic.\ud \ud Results\ud We have developed a rule-based model of crosstalk between the HMGB1 signaling pathway and other key cancer signaling pathways. The model has been simulated using both ordinary differential equations (ODEs) and discrete stochastic simulation. We have applied an automated verification technique, Statistical Model Checking, to validate interesting temporal properties of our model.\ud \ud Conclusions\ud Our simulations show that, if HMGB1 is overexpressed, then the oncoproteins CyclinD/E, which regulate cell proliferation, are overexpressed, while tumor suppressor proteins that regulate cell apoptosis (programmed cell death), such as p53, are repressed. Discrete, stochastic simulations show that p53 and MDM2 oscillations continue even after 10 hours, as observed by experiments. This property is not exhibited by the deterministic ODE simulation, for the chosen parameters. Moreover, the models also predict that mutations of RAS, ARF and P21 in the context of HMGB1 signaling can influence the cancer cell's fate - apoptosis or survival - through the crosstalk of different pathways