Direct surface cyclotron resonance terahertz emission from a quantum cascade structure

A strong magnetic field applied along the growth direction of a semiconductor quantum well gives rise to a spectrum of discrete energy states, the Landau levels. By combining quantum engineering of a quantum cascade structure with a static magnetic field, we can selectively inject electrons into the excited Landau level of a quantum well and realize a tunable surface emitting device based on cyclotron emission. By applying the appropriate magnetic field between 0 and 12 T, we demonstrate emission from a single device over a wide range of frequencies (1-2 THz and 3-5 THz)

Differential Regulation of the Period Genes in Striatal Regions following Cocaine Exposure

Several studies have suggested that disruptions in circadian rhythms contribute to the pathophysiology of multiple psychiatric diseases, including drug addiction. In fact, a number of the genes involved in the regulation of circadian rhythms are also involved in modulating the reward value for drugs of abuse, like cocaine. Thus, we wanted to determine the effects of chronic cocaine on the expression of several circadian genes in the Nucleus Accumbens (NAc) and Caudate Putamen (CP), regions of the brain known to be involved in the behavioral responses to drugs of abuse. Moreover, we wanted to explore the mechanism by which these genes are regulated following cocaine exposure. Here we find that after repeated cocaine exposure, expression of the Period (Per) genes and Neuronal PAS Domain Protein 2 (Npas2) are elevated, in a somewhat regionally selective fashion. Moreover, NPAS2 (but not CLOCK (Circadian Locomotor Output Cycles Kaput)) protein binding at Per gene promoters was enhanced following cocaine treatment. Mice lacking a functional Npas2 gene failed to exhibit any induction of Per gene expression after cocaine, suggesting that NPAS2 is necessary for this cocaine-induced regulation. Examination of Per gene and Npas2 expression over twenty-four hours identified changes in diurnal rhythmicity of these genes following chronic cocaine, which were regionally specific. Taken together, these studies point to selective disruptions in Per gene rhythmicity in striatial regions following chronic cocaine treatment, which are mediated primarily by NPAS2. © 2013 Falcon et al

Combinations of β-lactam or aminoglycoside antibiotics with plectasin are synergistic against methicillin-sensitive and methicillin-resistant Staphylococcus aureus.

Bacterial infections remain the leading killer worldwide which is worsened by the continuous emergence of antibiotic resistance. In particular, methicillin-sensitive (MSSA) and methicillin-resistant Staphylococcus aureus (MRSA) are prevalent and the latter can be difficult to treat. The traditional strategy of novel therapeutic drug development inevitably leads to emergence of resistant strains, rendering the new drugs ineffective. Therefore, rejuvenating the therapeutic potentials of existing antibiotics offers an attractive novel strategy. Plectasin, a defensin antimicrobial peptide, potentiates the activities of other antibiotics such as β-lactams, aminoglycosides and glycopeptides against MSSA and MRSA. We performed in vitro and in vivo investigations to test against genetically diverse clinical isolates of MSSA (n = 101) and MRSA (n = 115). Minimum inhibitory concentrations (MIC) were determined by the broth microdilution method. The effects of combining plectasin with β-lactams, aminoglycosides and glycopeptides were examined using the chequerboard method and time kill curves. A murine neutropenic thigh model and a murine peritoneal infection model were used to test the effect of combination in vivo. Determined by factional inhibitory concentration index (FICI), plectasin in combination with aminoglycosides (gentamicin, neomycin or amikacin) displayed synergistic effects in 76-78% of MSSA and MRSA. A similar synergistic response was observed when plectasin was combined with β-lactams (penicillin, amoxicillin or flucloxacillin) in 87-89% of MSSA and MRSA. Interestingly, no such interaction was observed when plectasin was paired with vancomycin. Time kill analysis also demonstrated significant synergistic activities when plectasin was combined with amoxicillin, gentamicin or neomycin. In the murine models, plectasin at doses as low as 8 mg/kg augmented the activities of amoxicillin and gentamicin in successful treatment of MSSA and MRSA infections. We demonstrated that plectasin strongly rejuvenates the therapeutic potencies of existing antibiotics in vitro and in vivo. This is a novel strategy that can have major clinical implications in our fight against bacterial infections

Room temperature ferromagnetism in intercalated Fe3-xGeTe2 van der Waals magnet

Among several well-known transition metal-based compounds, the van der Waals (vdW) Fe3-xGeTe2 (FGT) magnet is a strong candidate for use in two-dimensional (2D) magnetic devices due to its strong perpendicular magnetic anisotropy, sizeable Curie temperature (TC ~ 154 K), and versatile magnetic character that is retained in the low-dimensional limit. While the TC remains far too low for practical applications, there has been a successful push toward improving it via external driving forces such as pressure, irradiation, and doping. Here we present experimental evidence of a novel room-temperature (RT) ferromagnetic phase induced by the electrochemical intercalation of common tetrabutylammonium cations (TBA+) into FGT bulk crystals. We obtained Curie temperatures as high as 350 K with chemical and physical stability of the intercalated compound. The temperature-dependent Raman measurements in combination with vdW-corrected ab initio calculations suggest that charge transfer (electron doping) upon intercalation could lead to the observation of RT ferromagnetism. This work demonstrates that molecular intercalation is a viable route in realizing high-temperature vdW magnets in an inexpensive and reliable manner

Single-cell deconvolution of head and neck squamous cell carcinoma

Complexities in cell-type composition have rightfully led to skepticism and caution in the interpretation of bulk transcriptomic analyses. Recent studies have shown that deconvolution algorithms can be utilized to computationally estimate cell-type proportions from the gene expression data of bulk blood samples, but their performance when applied to tumor tissues, including those from head and neck, remains poorly characterized. Here, we use single-cell data (~6000 single cells) collected from 21 head and neck squamous cell carcinoma (HNSCC) samples to generate cell-type-specific gene expression signatures. We leverage bulk RNA-seq data from \u3e500 HNSCC samples profiled by The Cancer Genome Atlas (TCGA), and using single-cell data as a reference, apply two newly developed deconvolution algorithms (CIBERSORTx and MuSiC) to the bulk transcriptome data to quantitatively estimate cell-type proportions for each tumor in TCGA. We show that these two algorithms produce similar estimates of constituent/major cell-type proportions and that a high T-cell fraction correlates with improved survival. By further characterizing T-cell subpopulations, we identify that regulatory T-cells (

Genome-wide Linkage and Regional Association Study of Obesity-related Phenotypes: The GenSalt study

ObjectiveTo identify chromosomal regions harboring quantitative trait loci (QTL) for waist circumference (WC) and body mass index (BMI).Design and MethodsWe conducted a genome-wide linkage scan and regional association study WC and BMI among 633 Chinese families.ResultsA significant linkage signal for WC was observed at 22q13.31–22q13.33 in the overall analysis (LOD=3.13). Follow-up association study of 22q13.31–13.33 revealed an association between the TBC1D22A gene marker rs16996195 and WC (false discovery rate (FDR)-Q<0.05). In gender-stratified analysis, suggestive linkage signals were attained for WC at 2p24.3–2q12.2 and 22q13.33 among females (LOD=2.54 and 2.15, respectively). Among males, 6q12–6q13 was suggestively linked to BMI (LOD= 2.03). Single marker association analyses at these regions identified male-specific relationships of 6 single nucleotide polymorphisms (SNPs) at 2p24.3–2q12.2 (rs100955, rs13020676, rs13014034, rs12990515, rs17024325 and rs2192712) and 5 SNPs at 6q12–6q13 (rs7747318, rs7767301, rs12197115, rs12203049, and rs9454847) with the obesity-related phenotypes (all FDR-Q<0.05). At chromosome 6q12–6q13, markers rs7755450 and rs11758293 predicted BMI in females (both FDR-Q<0.05).ConclusionsWe described genomic regions on chromosomes 2, 6, and 22 which may harbor important obesity-susceptibility loci. Follow-up study of these regions revealed several novel variants associated with obesity related traits. Future work to confirm these promising findings is warranted

Electrically pumped continuous-wave III–V quantum dot lasers on silicon

Reliable, efficient electrically pumped silicon-based lasers would enable full integration of photonic and electronic circuits, but have previously only been realized by wafer bonding. Here, we demonstrate continuous-wave InAs/GaAs quantum dot lasers directly grown on silicon substrates with a low threshold current density of 62.5 A cm–2, a room-temperature output power exceeding 105 mW and operation up to 120 °C. Over 3,100 h of continuous-wave operating data have been collected, giving an extrapolated mean time to failure of over 100,158 h. The realization of high-performance quantum dot lasers on silicon is due to the achievement of a low density of threading dislocations on the order of 105 cm−2 in the III–V epilayers by combining a nucleation layer and dislocation filter layers with in situ thermal annealing. These results are a major advance towards reliable and cost-effective silicon-based photonic–electronic integration

Hematopoietic Cell Transplantation in Patients With Primary Immune Regulatory Disorders (PIRD): A Primary Immune Deficiency Treatment Consortium (PIDTC) Survey.

Primary Immune Regulatory Disorders (PIRD) are an expanding group of diseases caused by gene defects in several different immune pathways, such as regulatory T cell function. Patients with PIRD develop clinical manifestations associated with diminished and exaggerated immune responses. Management of these patients is complicated; oftentimes immunosuppressive therapies are insufficient, and patients may require hematopoietic cell transplant (HCT) for treatment. Analysis of HCT data in PIRD patients have previously focused on a single gene defect. This study surveyed transplanted patients with a phenotypic clinical picture consistent with PIRD treated in 33 Primary Immune Deficiency Treatment Consortium centers and European centers. Our data showed that PIRD patients often had immunodeficient and autoimmune features affecting multiple organ systems. Transplantation resulted in resolution of disease manifestations in more than half of the patients with an overall 5-years survival of 67%. This study, the first to encompass disorders across the PIRD spectrum, highlights the need for further research in PIRD management