Near-Field Analysis of Terahertz Pulse Generation From Photo-Excited Charge Density Gradients

Excitation of photo-current transients at semiconductor surfaces by subpicosecond optical pulses gives rise to emission of electromagnetic pulses of terahertz (THz) frequency radiation. To correlate the THz emission with the photo-excited charge density distribution and the photo-current direction, we mapped near-field and far-field distributions of the generated THz waves from GaAs and Fe-doped InGaAs surfaces. The experimental results show that the charge dynamics in the plane of the surface can radiate substantially stronger THz pulses than the charge dynamics in the direction normal to the surface, which is generally regarded as the dominant origin of the emission

The effect of exposure to biomass smoke on respiratory symptoms in adult rural and urban Nepalese populations

Peer reviewedPublisher PD

MicroRNA-146 and cell trauma down-regulate expression of the psoriasis-associated atypical chemokine receptor ACKR2

Chemokines are the principal regulators of leukocyte migration and are essential for initiation and maintenance of inflammation. Atypical chemokine receptor 2 (ACKR2) binds and scavenges proinflammatory CC-chemokines, regulates cutaneous T-cell positioning, and limits the spread of inflammation in vivo. Altered ACKR2 function has been implicated in several inflammatory disorders, including psoriasis, a common and debilitating T-cell–driven disorder characterized by thick erythematous skin plaques. ACKR2 expression is abnormal in psoriatic skin, with decreased expression correlating with recruitment of T-cells into the epidermis and increased inflammation. However, the molecular mechanisms that govern ACKR2 expression are not known. Here, we identified specific psoriasis-associated microRNAs (miRs) that bind ACKR2, inhibit its expression, and are active in primary cultures of human cutaneous cells. Using both in silico and in vitro approaches, we show that miR-146b and miR-10b directly bind the ACKR2 3′-UTR and reduce expression of ACKR2 transcripts and protein in keratinocytes and lymphatic endothelial cells, respectively. Moreover, we demonstrate that ACKR2 expression is further down-regulated upon cell trauma, an important trigger for the development of new plaques in many psoriasis patients (the Koebner phenomenon). We found that tensile cell stress leads to rapid ACKR2 down-regulation and concurrent miR-146b up-regulation. Together, we provide, for the first time, evidence for epigenetic regulation of an atypical chemokine receptor. We propose a mechanism by which cell trauma and miRs coordinately exacerbate inflammation via down-regulation of ACKR2 expression and provide a putative mechanistic explanation for the Koebner phenomenon in psoriasis

Host Inflammatory Response to Mosquito Bites Enhances the Severity of Arbovirus Infection

Aedes aegypti mosquitoes are responsible for trans- mitting many medically important viruses such as those that cause Zika and dengue. The inoculation of viruses into mosquito bite sites is an important and common stage of all mosquito-borne virus infec- tions. We show, using Semliki Forest virus and Bunyamwera virus, that these viruses use this inflam- matory niche to aid their replication and dissemina- tion in vivo. Mosquito bites were characterized by an edema that retained virus at the inoculation site and an inflammatory influx of neutrophils that coordi- nated a localized innate immune program that inad- vertently facilitated virus infection by encouraging the entry and infection of virus-permissive myeloid cells. Neutrophil depletion and therapeutic blockade of inflammasome activity suppressed inflammation and abrogated the ability of the bite to promote infec- tion. This study identifies facets of mosquito bite inflammation that are important determinants of the subsequent systemic course and clinical outcome of virus infection

Reduction of circulating cholesterol and apolipoprotein levels during sepsis

Sepsis with multiple organ failure is frequently associated with a substantial decrease of cholesterol levels. This decrease of cholesterol is strongly associated with mortality suggesting a direct relation between inflammatory conditions and altered cholesterol homeostasis. The host response during sepsis is mediated by cytokines and growth factors, which are capable of influencing lipid metabolism. Conversely lipoproteins are also capable of modulating cytokine production during the inflammatory response. Therefore the decrease in circulating cholesterol levels seems to play a crucial role in the pathophysiology of sepsis. In this review the interaction between cytokines and lipid metabolism and its clinical consequences will be discussed

Mapping the distribution of photo-currents responsible for generation of terahertz pulses at semiconductor surfaces

Photo-excited charge carriers at semiconductor surfaces generate pulses of terahertz (THz) radiation. By mapping the spatial distribution of the THz radiation in the near-field and the angular emission pattern in the far-field, we link the THz generation process to the photo-current direction. We find that inplane carrier dynamics play an important role and can even be the dominant source of THz radiation

Bridging the data gaps in the epidemiology of hepatitis C virus infection in Malaysia using multi-parameter evidence synthesis

BACKGROUND: Collecting adequate information on key epidemiological indicators is a prerequisite to informing a public health response to reduce the impact of hepatitis C virus (HCV) infection in Malaysia. Our goal was to overcome the acute data shortage typical of low/middle income countries using statistical modelling to estimate the national HCV prevalence and the distribution over transmission pathways as of the end of 2009. METHODS: Multi-parameter evidence synthesis methods were applied to combine all available relevant data sources - both direct and indirect - that inform the epidemiological parameters of interest. RESULTS: An estimated 454,000 (95% credible interval [CrI]: 392,000 to 535,000) HCV antibody-positive individuals were living in Malaysia in 2009; this represents 2.5% (95% CrI: 2.2-3.0%) of the population aged 15-64 years. Among males of Malay ethnicity, for 77% (95% CrI: 69-85%) the route of probable transmission was active or a previous history of injecting drugs. The corresponding proportions were smaller for male Chinese and Indian/other ethnic groups (40% and 71%, respectively). The estimated prevalence in females of all ethnicities was 1% (95% CrI: 0.6 to 1.4%); 92% (95% CrI: 88 to 95%) of infections were attributable to non-drug injecting routes of transmission. CONCLUSIONS: The prevalent number of persons living with HCV infection in Malaysia is estimated to be very high. Low/middle income countries often lack a comprehensive evidence base; however, evidence synthesis methods can assist in filling the data gaps required for the development of effective policy to address the future public health and economic burden due to HCV. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12879-014-0564-6) contains supplementary material, which is available to authorized users

Optical Phase Lock Loop as High-Quality Tuneable Filter for Optical Frequency Comb Line Selection

This paper describes an optical phase lock loop (OPLL) implemented as an ultraselective optical frequency comb line filter. The OPLL is based on a photonic integrated circuit (PIC) fabricated for the first time through a generic foundry approach. The PIC contains a distributed Bragg reflector (DBR) laser whose frequency and phase are stabilized by reference to an optical frequency comb generator. The OPLL output is a single-mode DBR laser line; other comb lines and noise at the output of the OPLL filter are attenuated by >58 dB below the peak power of the OPLLfilter output line. The OPLL bandwidth is up to 200 MHz, giving a filter quality factor greater than 1,000,000. The DBR laser can be tuned over 1 THz (8 nm), enabling different comb lines to be selected. Locking to a comb line with a frequency offset precisely selectable between 4 and 12 GHz is also possible. The coherence between the DBR laser and the comb lines is demonstrated by measurements of the heterodyne signal residual phase noise level, which is below −100 dBc/Hz at 5 kHz offset from the carrier. The OPLL-filter output can be up to 6 dB higher than the peak power of the comb line to be isolated by the filter. This optical gain is a unique characteristic which can significantly improve the SNR of communication or spectroscopy systems. This OPLL is envisaged to be used for high purity, tuneable microwave, millimetre-wave, and THz generation

The GATA1s isoform is normally down-regulated during terminal haematopoietic differentiation and over-expression leads to failure to repress MYB, CCND2 and SKI during erythroid differentiation of K562 cells

Background: Although GATA1 is one of the most extensively studied haematopoietic transcription factors little is currently known about the physiological functions of its naturally occurring isoforms GATA1s and GATA1FL in humans—particularly whether the isoforms have distinct roles in different lineages and whether they have non-redundant roles in haematopoietic differentiation. As well as being of general interest to understanding of haematopoiesis, GATA1 isoform biology is important for children with Down syndrome associated acute megakaryoblastic leukaemia (DS-AMKL) where GATA1FL mutations are an essential driver for disease pathogenesis. <p/>Methods: Human primary cells and cell lines were analyzed using GATA1 isoform specific PCR. K562 cells expressing GATA1s or GATA1FL transgenes were used to model the effects of the two isoforms on in vitro haematopoietic differentiation. <p/>Results: We found no evidence for lineage specific use of GATA1 isoforms; however GATA1s transcripts, but not GATA1FL transcripts, are down-regulated during in vitro induction of terminal megakaryocytic and erythroid differentiation in the cell line K562. In addition, transgenic K562-GATA1s and K562-GATA1FL cells have distinct gene expression profiles both in steady state and during terminal erythroid differentiation, with GATA1s expression characterised by lack of repression of MYB, CCND2 and SKI. <p/>Conclusions: These findings support the theory that the GATA1s isoform plays a role in the maintenance of proliferative multipotent megakaryocyte-erythroid precursor cells and must be down-regulated prior to terminal differentiation. In addition our data suggest that SKI may be a potential therapeutic target for the treatment of children with DS-AMKL