A new family of yeast genes implicated in ergosterol synthesis is related to the human oxysterol binding protein

We have identified three yeast genes, KES1, HES1 and OSH1, whose products show homology to the human oxysterol binding protein (OSBP). Mutations in these genes resulted in pleiotropic sterol-related phenotypes. These include tryptophan-transport defects and nystatin resistance, shown by double and triple mutants. In addition, mutant combinations showed small but apparently cumulative reductions in membrane ergosterol levels. The three yeast genes are also functionally related as overexpression of HES1 or KES1 alleviated the tryptophan-transport defect in kes1Δ or osh1Δ mutants, respectively. Our study implicates this new yeast gene family in ergosterol synthesis and provides comparative evidence of a role for human OSBP in cholesterol synthesis.     

Role of miRNAs in Human T Cell Leukemia Virus Type 1 Induced T Cell Leukemia: A Literature Review and Bioinformatics Approach

Human T cell leukemia virus type 1 (HTLV-1) was identified as the first pathogenic human retrovirus and is estimated to infect 5 to 10 million individuals worldwide. Unlike other retroviruses, there is no effective therapy to prevent the onset of the most alarming diseases caused by HTLV-1, and the more severe cases manifest as the malignant phenotype of adult T cell leukemia (ATL). MicroRNA (miRNA) dysfunction is a common feature of leukemogenesis, and it is no different in ATL cases. Therefore, we sought to analyze studies that reported deregulated miRNA expression in HTLV-1 infected cells and patients’ samples to understand how this deregulation could induce malignancy. Through in silico analysis, we identified 12 miRNAs that stood out in the prediction of targets, and we performed functional annotation of the genes linked to these 12 miRNAs that appeared to have a major biological interaction. A total of 90 genes were enriched in 14 KEGG pathways with significant values, including TP53, WNT, MAPK, TGF-β, and Ras signaling pathways. These miRNAs and gene interactions are discussed in further detail for elucidation of how they may act as probable drivers for ATL onset, and while our data provide solid starting points for comprehension of miRNAs’ roles in HTLV-1 infection, continuous effort in oncologic research is still needed to improve our understanding of HTLV-1 induced leukemia.     

Warning: statistical benchmarking is addictive. Kicking the habit in machine learning

Algorithm performance evaluation is so entrenched in the machine learning community that one could call it an addiction. Like most addictions, it is harmful and very difficult to give up. It is harmful because it has serious limitations. Yet, we have great faith in practicing it in a ritualistic manner: we follow a fixed set of rules telling us the measure, the data sets and the statistical test to use. When we read a paper, even as reviewers, we are not sufficiently critical of results that follow these rules. Here, we will debate what are the limitations and how to best address them. This article may not cure the addiction but hopefully it will be a good first step along that road.     

Topical Capsaicin in Poly(lactic-co-glycolic)acid (PLGA) Nanoparticles Decreases Acute Itch and Heat Pain

Background: Capsaicin, the hot pepper agent, produces burning followed by desensitization. To treat localized itch or pain with minimal burning, low capsaicin concentrations can be repeatedly applied. We hypothesized that alternatively controlled release of capsaicin from poly(lactic-co-glycolic acid) (PLGA) nanoparticles desensitizes superficially terminating nociceptors, reducing burning. Methods: Capsaicin-loaded PLGA nanoparticles were prepared (single-emulsion solvent evaporation) and characterized (size, morphology, capsaicin loading, encapsulation efficiency, in vitro release profile). Capsaicin-PLGA nanoparticles were applied to murine skin and evaluated in healthy human participants (n = 21) for 4 days under blinded conditions, and itch and nociceptive sensations evoked by mechanical, heat stimuli and pruritogens cowhage, β-alanine, BAM8-22 and histamine were evaluated. Results: Nanoparticles (loading: 58 µg capsaicin/mg) released in vitro 23% capsaicin within the first hour and had complete release at 72 h. In mice, 24 h post-application Capsaicin-PLGA nanoparticles penetrated the dermis and led to decreased nociceptive behavioral responses to heat and mechanical stimulation (desensitization). Application in humans produced a weak to moderate burning, dissipating after 3 h. A loss of heat pain up to 2 weeks was observed. After capsaicin nanoparticles, itch and nociceptive sensations were reduced in response to pruritogens cowhage, β-alanine or BAM8-22, but were normal to histamine. Conclusions: Capsaicin nanoparticles could be useful in reducing pain and itch associated with pruritic diseases that are histamine-independent.     

Error evaluation on experimental stress–strain curve obtained from tube bulging test

To get precise material data for advanced numerical modelling of tube hydroforming process, the tube bulging test is recommended. Stresses and strains in the tube cannot be evaluated easily and several approaches have been proposed. A review is proposed and points out their advantages and drawbacks.     

A linear 60 GHz 65 nm-CMOS power amplifier realization and characterization for OFDM signal

A millimeter-wave Power Amplifier (PA) based on a 65nm CMOS technology from STMicroelectronics has been designed. The targeted feature is the unlicensed band around 60 GHz suitable for wireless personal area network application (WPAN). To optimize the linearity, the PA is designed under class A biasing to have an output compression point (OCP₁) close to its saturated Power (P _sat). S-parameters and large signal measurement results are demonstrated and compared with electromagnetic simulations. The PA offers a P _sat of 8.3 dBm, an OCP₁ of 6 dBm and a gain of 6.7 dB. The die area is 0.29 mm² with pads. Considering those results, one-tone simulations are not sufficient to characterize the linearity performances of the PA in its real conditions of use. Consequently, two-tone simulations are firstly performed. After, linearity figures of merit (FoM) are discussed applying an orthogonal frequency-division multiplexing (OFDM) modulated signal. The PA offers an adjacent channel power ratio (ACPR) of 15 dB and an error vector magnitude (EVM) of 20% at PA compression operating mode.     

A comparison of MOSFETs aging under d.c., a.c. and alternating stress conditions

The effects of static, alternating and dynamic stress conditions on the degradation rate of 0.8μm n- and p-channel LDD MOS transistors have systematically been investigated and compared. The shifts of the threshold voltage, transconductance, linear drain current and charge pumping current were used to monitor the transistor degradation. The results suggest that the aging induced by a dynamic stress cannot be directly explained with static stress models, essentially because it is highly dependent on a larger number of parameters (biases and durations of the top and bottom levels of the pulses, transient times). The correlation of static and dynamic stresses also clarifies the degradation mechanisms, in particular the role of hot holes in the generation of interface states.