The Effect of HMGB1 and HMGB2 on Transcriptional Regulation Differs in Neuroendocrine and Adenocarcinoma Models of Prostate Cancer.

Human high-mobility group-B (HMGB) proteins regulate gene expression in prostate cancer (PCa), a leading cause of oncological death in men. Their role in aggressive PCa cancers, which do not respond to hormonal treatment, was analyzed. The effects of HMGB1 and HMGB2 silencing upon the expression of genes previously related to PCa were studied in the PCa cell line PC-3 (selected as a small cell neuroendocrine carcinoma, SCNC, PCa model not responding to hormonal treatment). A total of 72% of genes analyzed, using pre-designed primer panels, were affected. HMGB1 behaved mostly as a repressor, but HMGB2 as an activator. Changes in SERPINE1, CDK1, ZWINT, and FN1 expression were validated using qRT-PCR after HMGB1 silencing or overexpression in PC-3 and LNCaP (selected as an adenocarcinoma model of PCa responding to hormonal treatment) cell lines. Similarly, the regulatory role of HMGB2 upon SERPINE1, ZWINT, FN1, IGFPB3, and TYMS expression was validated, finding differences between cell lines. The correlation between the expression of HMGB1, HMGB2, and their targets was analyzed in PCa patient samples and also in PCa subgroups, classified as neuroendocrine positive or negative, in public databases. These results allow a better understanding of the role of HMGB proteins in PCa and contribute to find specific biomarkers for aggressive PCa.

Genetic parameters for milk yield and reproductive traits in Honduran Holstein cattle.

The aim of this study was to estimate the (co)variance components and genetic parameters for milk yield adjusted to 305d (MY305), calving-to-conception interval (CCI), number of services per conception (NSC) and calving interval (CI) of Honduran Holstein cows, by fitting a bivariate animal model using Maximum Restricted Likelihood procedures. Model included the fixed effects of calving number, the contemporary calving group (farm-season-year of calving and the cow age as covariate). The estimated means and standard deviations for MY, CCI, NSC and CI were, 5098.60 ± 1564.32 kg, 168.27 ± 104.71 days, 2.46 ± 1.69 services, and 448.73 ± 109.16 days, respectively; and their estimated heritabilities were 0.21 ± 0.05, 0.03 ± 0.028, 0.02 ± 0.024 and 0.06 ± 0.04, respectively. The genetic correlations between MY305 and CCI, NSC and CI were positive and antagonist, with values of 0.64 ± 0.52, 0.99 ± 0.56, and 0.32 ± 0.24 respectively. Even though moderate to low heritability was estimated for MY305, systematic selection for milk yield, with a reduction in reproductive efficiency, if considered as the only selection criterion is important to be considered. By including reproductive traits and considering permanent environment effects into the breeding program, might yield a slow, but constant and permanent improvement over time.

A noninvasive method for whole-genome skin methylome profiling.

BACKGROUND: Ageing, disease and malignant transformation of the skin are associated with changes in DNA methylation. So far, mostly invasive methodologies such as biopsies have been applied in collecting DNA methylation signatures. Tape stripping offers a noninvasive option for skin diagnostics. It enables the easy but robust capture of biologic material in large numbers of participants without the need for specialized medical personnel. OBJECTIVES: To design and validate a methodology for noninvasive skin sample collection using tape stripping for subsequent DNA -methylation analysis. METHODS: A total of 175 participants were recruited and provided tape-stripping samples from a sun-exposed area; 92 provided matched tape-stripping samples from a sun-protected area, and an additional 5 provided matched skin-shave biopsies from the same area. Using -enzymatic conversion and whole-genome Illumina sequencing, we generated genome-wide DNA methylation profiles that were used to evaluate the feasibility of noninvasive data acquisition, to compare with established sampling approaches and to investigate biomarker identification for age and ultraviolet (UV) exposure. RESULTS: We found that tape-stripping samples showed strong concordance in their global DNA methylation landscapes to those of conventional invasive biopsies. Moreover, we showed sample reproducibility and consistent global methylation profiles in skin tape-stripping samples collected from different areas of the body. Using matched samples from sun-protected and sun-exposed areas of the body we were able to validate the capacity of our method to capture the effects of environmental changes and ageing in a cohort covering various ages, ethnicities and skin types. We found DNA methylation changes on the skin resulting from UV exposure and identified significant age-related hypermethylation of CpG islands, with a pronounced peak effect at 50-55 years of age, including methylation changes in well-described markers of ageing. CONCLUSIONS: These data demonstrate the feasibility of using tape stripping combined with whole-genome sequencing as a noninvasive approach to measuring DNA methylation changes in the skin. In addition, they outline a viable experimental framework for the use of skin tape stripping, particularly when it is performed in large cohorts of patients to identify biomarkers of skin ageing, UV damage and, possibly, to track treatment response to therapeutic interventions.

Identification of lncRNAs Deregulated in Epithelial Ovarian Cancer Based on a Gene Expression Profiling Meta-Analysis.

Epithelial ovarian cancer (EOC) is one of the deadliest gynecological cancers worldwide, mainly because of its initially asymptomatic nature and consequently late diagnosis. Long non-coding RNAs (lncRNA) are non-coding transcripts of more than 200 nucleotides, whose deregulation is involved in pathologies such as EOC, and are therefore envisaged as future biomarkers. We present a meta-analysis of available gene expression profiling (microarray and RNA sequencing) studies from EOC patients to identify lncRNA genes with diagnostic and prognostic value. In this meta-analysis, we include 46 independent cohorts, along with available expression profiling data from EOC cell lines. Differential expression analyses were conducted to identify those lncRNAs that are deregulated in (i) EOC versus healthy ovary tissue, (ii) unfavorable versus more favorable prognosis, (iii) metastatic versus primary tumors, (iv) chemoresistant versus chemosensitive EOC, and (v) correlation to specific histological subtypes of EOC. From the results of this meta-analysis, we established a panel of lncRNAs that are highly correlated with EOC. The panel includes several lncRNAs that are already known and even functionally characterized in EOC, but also lncRNAs that have not been previously correlated with this cancer, and which are discussed in relation to their putative role in EOC and their potential use as clinically relevant tools.

Association between offensive and defensive playing style variables and ranking position in a national football league.

The aim of this study was to determine the association of playing style and efficacy variables with football success in a professional football league. Match statistics were obtained from 23 football teams competing in the 2017-2018 and 2018-2019 seasons of the Spanish national league(LaLiga). Offensive and defensive playing style and efficacy variables were calculated. Pearson's correlation coefficient tests and principal component analysis (PCA) were applied to establish the influence of these variables on the number of points obtained at the end of the season and on the ranking position. In isolation, the efficacy of completion showed the highest association with ranking points and position. A two-dimension PCA explained 77.8% of the variance in the ranking position. In dimension-1 (58.5%), game initiative and attack building, and in dimension-2 (19.3%), efficacy of defensive containment and a lower rate of long passes were within the variables that explained more variance in the ranking position. Success in football, measured by ranking position at the end of the Spanish national league, was associated with several playing style and efficacy variables. Overall, a dominant game style with high efficacy to finish attacking plays, and an offensive game initiative, are most associated with successful football.

A Fully Integrated, Power-Efficient, 0.07-2.08 mA, High-Voltage Neural Stimulator in a Standard CMOS Process.

This paper presents a fully integrated high-voltage (HV) neural stimulator with on-chip HV generation. It consists of a neural stimulator front-end that delivers stimulation currents up to 2.08 mA with 5 bits resolution and a switched-capacitor DC-DC converter that generates a programmable voltage supply from 4.2 V to 13.2 V with 4 bits resolution. The solution was designed and fabricated in a standard 180 nm 1.8 V/3.3 V CMOS process and occupied an active area of 2.34 mm2. Circuit-level and block-level techniques, such as a proposed high-compliance voltage cell, have been used for implementing HV circuits in a low-voltage CMOS process. Experimental validation with an electrical model of the electrode−tissue interface showed that (1) the neural stimulator can handle voltage supplies up to 4 times higher than the technology's nominal supply, (2) residual charge­without passive discharging phase­was below 0.12% for the whole range of stimulation currents, (3) a stimulation current of 2 mA can be delivered with a voltage drop of 0.9 V, and (4) an overall power efficiency of 48% was obtained at maximum stimulation current.

A Low-Resources TDC for Multi-Channel Direct ToF Readout Based on a 28-nm FPGA.

In this paper, we present a proposed field programmable gate array (FPGA)-based time-to-digital converter (TDC) architecture to achieve high performance with low usage of resources. This TDC can be employed for multi-channel direct Time-of-Flight (ToF) applications. The proposed architecture consists of a synchronizing input stage, a tuned tapped delay line (TDL), a combinatory encoder of ones and zeros counters, and an online calibration stage. The experimental results of the TDC in an Artix-7 FPGA show a differential non-linearity (DNL) in the range of [-0.953, 1.185] LSB, and an integral non-linearity (INL) within [-2.750, 1.238] LSB. The measured LSB size and precision are 22.2 ps and 26.04 ps, respectively. Moreover, the proposed architecture requires low FPGA resources.

Architecture-Level Optimization on Digital Silicon Photomultipliers for Medical Imaging.

Silicon photomultipliers (SiPMs) are arrays of single-photon avalanche diodes (SPADs) connected in parallel. Analog silicon photomultipliers are built in custom technologies optimized for detection efficiency. Digital silicon photomultipliers are built in CMOS technology. Although CMOS SPADs are less sensitive, they can incorporate additional functionality at the sensor plane, which is required in some applications for an accurate detection in terms of energy, timestamp, and spatial location. This additional circuitry comprises active quenching and recharge circuits, pulse combining and counting logic, and a time-to-digital converter. This, together with the disconnection of defective SPADs, results in a reduction of the light-sensitive area. In addition, the pile-up of pulses, in space and in time, translates into additional efficiency losses that are inherent to digital SiPMs. The design of digital SiPMs must include some sort of optimization of the pixel architecture in order to maximize sensitivity. In this paper, we identify the most relevant variables that determine the influence of SPAD yield, fill factor loss, and spatial and temporal pile-up in the photon detection efficiency. An optimum of 8% is found for different pixel sizes. The potential benefits of molecular imaging of these optimized and small-sized pixels with independent timestamping capabilities are also analyzed.

Effects of seed priming on germination and seedling growth of desiccation-sensitive seeds from Mexican tropical rainforest.

Seed priming increases the vigor of seeds and seedlings through metabolic and biochemical processes occurring during controlled hydration, followed by dehydration. In the field, seeds are exposed to hydration-dehydration events in and on the soil after dispersal, as in seed priming. Nevertheless, seed priming has been sparsely tested on desiccation-sensitive seeds, which are vulnerable to climate change effects. We evaluated the effect of two priming methods on seeds from two tropical rainforest species: Cupania glabra and Cymbopetalum baillonii. For hydropriming, the seeds were fully hydrated and then dehydrated to three dehydration levels. For natural priming, the seeds were buried for 12 days in either closed forest or forest gap. Primed seeds were sown in 1% agar medium and placed in an environmental chamber. The growth of the seedlings from the highest germination priming treatments was evaluated for 1 year in the field. Our results showed that for C. glabra and C. baillonii, hydroprimed seeds varied in their germination response, depending on the degree of their dehydration. However, for C. baillonii, hydropriming seems to invigorate seeds, compared to non-imbibed seeds of the same dehydration level. Natural priming increased germination speed in both species without any difference between closed forest and forest gap. Moreover, seeds with natural priming had a higher final germination percentage than seeds with hydropriming. Seedlings from seeds with natural priming showed a higher growth rate than the controls in both species, whereas hydropriming produced a similar effect in C. glabra. Both priming methods could be used for restoration practices with the studied species, natural priming being a novel method. The ecological implications of priming in desiccation sensitive seeds are discussed in this study.

Estimation of body weight in hair ewes using an indirect measurement method.

The aim of the present study was to develop and evaluate an equation to predict body weight (BW) using hip width (HW) in Pelibuey ewe lambs and ewes. Five hundred seventy-seven 2-month-old to 3-year-old, non-pregnant, non-lactating, clinically healthy ewe lambs and adult ewes with a mean BW of 34.7 ± 12.4 kg and HW of 15.6 ± 3.4 cm were considered. Three equations were evaluated: BW (kg): - 19.17 + 3.46 × HW (Eq. 1), BW (kg): - 17.79 + 3.25 × HW + 0.007 × HW2 (Eq. 2) and BW (kg): 0.39 × HW1.63 (Eq. 3). Independent data from 80 animals with similar characteristics (BW of 23.4 ± 10.9 kg and HW of 12 ± 3.1 cm) were also considered to evaluate the developed equations. The evaluation was based on the relationship between the observed and predicted values of BW analysed using a linear regression, the mean squared error of prediction (MSEP), the root MSEP (RMSEP) and the concordance correlation coefficients (CCCs). Additionally, cross-validation analyses were performed using the k-folds validation (k = 10) procedure. The correlation coefficient (r) between BW and HW was 0.94 (P < 0.001). The parameters for precision and accuracy showed that the proposed equations had high precision (R2 > 0.95%), accuracy (Cb > 0.98) and reproducibility (CCC > 0.96) in predicting the BW of ewe lambs and adult ewes. Equation (1) accurately predicted observed BW, with a bias (observed - predicted) of 4.3 kg and RMSEP of 9.68% with respect to the observed BW (random error of 84.23%); it also generated the best prediction according to the residual mean squared prediction error, coefficient of determination and mean absolute error. In conclusion, the highly correlated relationship between BW and HW in Pelibuey ewe lambs and adult ewes under humid tropic conditions enabled the development of mathematical models herein to estimate BW with an adequate goodness of fit. The linear model showed the best performance according to the goodness-of-fit evaluation and internal and external validation; hence, this model is proposed for use in both the experimental and commercial farms.

[Effects of changing the appearance of medications in safety and adherence in chronic patients over 65 years of age in primary care. CAMBIMED Study]. / Efectos del cambio de apariencia de medicamentos en seguridad y adherencia en pacientes crónicos mayores de 65 años en atención primaria. Estudio CAMBIMED.

OBJECTIVE: To study whether the changes in bioequivalent drugs with different appearances are associated with an increase in lack of adherence and medication use errors, in patients >65years old treated with antihypertensive and lipid-lowering medications. DESIGN: Observational longitudinal prospective cohort study with a one-year follow-up period between 1 January 2013 and 31 December 2014. LOCATION: Primary Healthcare Centres in the Community of Madrid. PARTICIPANTS: Patients ≥65years-old with a diagnosis of hypertension and/or dyslipidaemia receiving treatment with Enalapril and/or Amlodipine and/or Simvastatin. MAIN MEASUREMENTS: Variables collected during a Primary Care consultation by means of a personal interview were: sociodemographic (age, gender, level of education), clinical variables, adherence (Morisky-Green test and direct counting), medication errors (number and type), medication changes and number, analytical (total cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides) and combined variable (error and/or adherence). There were 1 baseline and 4 quarterly visits. RESULTS: The study included 274 patients with a mean age 72 (6.6) years, of whom 47.8% were female. Some medication changes were observed in 134 patients (48.9%), with a median of 3 (IQR 1-5) and a maximum of 11 changes. The risk of presenting with a medication use error or decreased adherence was increased in patients exposed to changes in all visits with RR 1.14 (1.16-1.69) at one year of follow-up. The most frequent error was the loss of dose. For each change in medication, the probability of a combined event increases by 41%. CONCLUSIONS: The changes made in bioequivalent drugs with different appearance could increase the number of medication use errors and decrease the adherence. More studies should be carried out to assess how much this affects the control of the disease. The intervention section is not considered because it is an observational study.

The HMGB protein Ixr1 interacts with Ssn8 and Tdh3 involved in transcriptional regulation.

Ixr1 is a Saccharomyces cerevisiae transcriptional factor that extensively regulates the response to hypoxia and controls other important cellular functions and DNA repair. During aerobic growth, the Ixr1 repressor function is predominant on regulated promoters of hypoxic genes, although activator effects are also observed on other genes. During hypoxia, Ixr1 expression increases and the number of genes activated by Ixr1 also increase. In this work we demonstrate that the NH2-terminal region of Ixr1 is involved in transcriptional activation. We also present the first analysis about Ixr1 interactions with three factors that have been previously identified as important players in the yeast hypoxic response, Cyc8, Tup1 and Ssn8; results demonstrate that only Ssn8 binds to Ixr1. We have also looked for other Ixr1-binding proteins associated with transcriptional regulation, by co-purification and mass spectrometry identification. Tdh3, a protein involved in transcriptional silencing, is among the new identified Ixr1-binding proteins. Differential phosphorylation of Ixr1 is found when comparing aerobic and hypoxic yeast growth. Implication of these results in transcriptional regulation mediated by Ixr1 is discussed.

Effect of condensed tannins from Leucaena leucocephala on rumen fermentation, methane production and population of rumen protozoa in heifers fed low-quality forage.

OBJECTIVE: The aim of the experiment was to assess the effect of increasing amounts of Leucaena leucocephala forage on dry matter intake (DMI), organic matter intake (OMI), enteric methane production, rumen fermentation pattern and protozoa population in cattle fed Pennisetum purpureum and housed in respiration chambers. METHODS: Five crossbred heifers (Bos taurus×Bos indicus) (BW: 295±6 kg) were fed chopped P. purpureum grass and increasing levels of L. leucocephala (0%, 20%, 40%, 60%, and 80% of dry matter [DM]) in a 5×5 Latin square design. RESULTS: The voluntary intake and methane production were measured for 23 h per day in respiration chambers; molar proportions of volatile fatty acids (VFAs) were determined at 6 h postprandial period. Molar concentration of VFAs in rumen liquor were similar (p>0.05) between treatments. However, methane production decreased linearly (p<0.005), recording a maximum reduction of up to ~61% with 80% of DM incorporation of L. leucocephala in the ration and no changes (p>0.05) in rumen protozoa population were found. CONCLUSION: Inclusion of 80% of L. leucocephala in the diet of heifers fed low-quality tropical forages has the capacity to reduce up to 61.3% enteric methane emission without affecting DMI, OMI, and protozoa population in rumen liquor.

Compensation of PVT Variations in ToF Imagers with In-Pixel TDC.

The design of a direct time-of-flight complementary metal-oxide-semiconductor (CMOS) image sensor (dToF-CIS) based on a single-photon avalanche-diode (SPAD) array with an in-pixel time-to-digital converter (TDC) must contemplate system-level aspects that affect its overall performance. This paper provides a detailed analysis of the impact of process parameters, voltage supply, and temperature (PVT) variations on the time bin of the TDC array. Moreover, the design and characterization of a global compensation loop is presented. It is based on a phase locked loop (PLL) that is integrated on-chip. The main building block of the PLL is a voltage-controlled ring-oscillator (VCRO) that is identical to the ones employed for the in-pixel TDCs. The reference voltage that drives the master VCRO is distributed to the voltage control inputs of the slave VCROs such that their multiphase outputs become invariant to PVT changes. These outputs act as time interpolators for the TDCs. Therefore the compensation scheme prevents the time bin of the TDCs from drifting over time due to the aforementioned factors. Moreover, the same scheme is used to program different time resolutions of the direct time-of-flight (ToF) imager aimed at 3D ranging or depth map imaging. Experimental results that validate the analysis are provided as well. The compensation loop proves to be remarkably effective. The spreading of the TDCs time bin is lowered from: (i) 20% down to 2.4% while the temperature ranges from 0 °C to 100 °C; (ii) 27% down to 0.27%, when the voltage supply changes within ±10% of the nominal value; (iii) 5.2 ps to 2 ps standard deviation over 30 sample chips, due to process parameters' variation.

Characterization of mussel H2A.Z.2: a new H2A.Z variant preferentially expressed in germinal tissues from Mytilus.

Histones are the fundamental constituents of the eukaryotic chromatin, facilitating the physical organization of DNA in chromosomes and participating in the regulation of its metabolism. The H2A family displays the largest number of variants among core histones, including the renowned H2A.X, macroH2A, H2A.B (Bbd), and H2A.Z. This latter variant is especially interesting because of its regulatory role and its differentiation into 2 functionally divergent variants (H2A.Z.1 and H2A.Z.2), further specializing the structure and function of vertebrate chromatin. In the present work we describe, for the first time, the presence of a second H2A.Z variant (H2A.Z.2) in the genome of a non-vertebrate animal, the mussel Mytilus. The molecular and evolutionary characterization of mussel H2A.Z.1 and H2A.Z.2 histones is consistent with their functional specialization, supported on sequence divergence at promoter and coding regions as well as on varying gene expression patterns. More precisely, the expression of H2A.Z.2 transcripts in gonadal tissue and its potential upregulation in response to genotoxic stress might be mirroring the specialization of this variant in DNA repair. Overall, the findings presented in this work complement recent reports describing the widespread presence of other histone variants across eukaryotes, supporting an ancestral origin and conserved role for histone variants in chromatin.

Prediction of rectal temperature using non-invasive physiologic variable measurements in hair pregnant ewes subjected to natural conditions of heat stress.

Rectal temperature (RT) is the foremost physiological variable indicating if an animal is suffering hyperthermia. However, this variable is traditionally measured by invasive methods, which may compromise animal welfare. Models to predict RT have been developed for growing pigs and lactating dairy cows, but not for pregnant heat-stressed ewes. Our aim was to develop a prediction equation for RT using non-invasive physiological variables in pregnant ewes under heat stress. A total of 192 records of respiratory frequency (RF) and hair coat temperature in various body regions (i.e., head, rump, flank, shoulder, and belly) obtained from 24 Katahdin × Pelibuey pregnant multiparous ewes were collected during the last third of gestation (i.e., d 100 to lambing) with a 15 d sampling interval. Hair coat temperatures were taken using infrared thermal imaging technology. Initially, a Pearson correlation analysis examined the relationship among variables, and then multiple linear regression analysis was used to develop the prediction equations. All predictor variables were positively correlated (P<0.01; r=0.59-0.67) with RT. The adjusted equation which best predicted RT (P<0.01; Radj(2)=56.15%; CV=0.65%) included as predictors RF and head and belly temperatures. Comparison of predicted and observed values for RT indicates a suitable agreement (P<0.01) between them with moderate accuracy (Radj(2)=56.15%) when RT was calculated with the adjusted equation. In general, the final equation does not violate any assumption of multiple regression analysis. The RT in heat-stressed pregnant ewes can be predicted with an adequate accuracy using non-invasive physiologic variables, and the final equation was: RT=35.57+0.004 (RF)+0.067 (heat temperature)+0.028 (belly temperature).

Study CAMBIMED: Effects of changes in medication appearance on safety of antihypertensive and hypolipidemic treatments in chronic patients older than 65 years in primary health care.

BACKGROUND: Different studies have investigated the effects that changes in drug appearance have on the control of chronic diseases and drug safety. The main objective of the proposed study is to evaluate if changes in the appearance of the packaging and presentation of drugs having the same active ingredient are related to a decrease in adherence and an increase in usage errors for chronic treatment using antihypertensive (enalapril and amlodipine) and hypolipidemic agents (simvastatin) in patients ≥65 years old, over a one-year follow-up period. METHODS/DESIGN: We propose a multicentric observational longitudinal cohort study with a one-year follow-up period in 8 primary health care centers (PHCC) in the Community of Madrid. 259 patients who are ≥65 years old, hypertensive and/or dyslipidemic, undergoing treatment with enalapril and/or amlodipine and/or simvastatin, and under formal follow-up of chronic patients in primary health care will be selected by simple random sampling. The main outcome variable will be a final combined variable (adherence and medication usage errors). Other included variables will be: sociodemographic and clinical variables of the patient, degree of disease control, drug taken, number of changes in the appearance of each drug by the pharmacy, and the type and frequency of both avoidable and non-avoidable adverse effects during the follow-up period. A descriptive and a multivariate analysis of the variables will be carried out by means of a logistic regression model, using the final combined variable as the dependent variable (error and/or inadequate usage of the drug), and variables shown to be related to it during the bivariate analysis as the independent variables. DISCUSSION: For drugs of the same active ingredient, the effect that different package appearances and presentation may have on the safety of patients undergoing chronic treatments is unknown under the new legislative framework. There are various initiatives that promote the iso-appearance of drugs: "If they are the same, make them look the same". It is to be expected that older, multi-medicated patients with chronic pathologies will be the ones under a greater risk of suffering from this problem.

Sky1 regulates the expression of sulfur metabolism genes in response to cisplatin.

Cisplatin is commonly used in cancer therapy and yeast cells are also sensitive to this compound. We present a transcriptome analysis discriminating between RNA changes induced by cisplatin treatment, which are dependent on or independent of SKY1 function--a gene whose deletion increases resistance to the drug. Gene expression changes produced by addition of cisplatin to W303 and W303-Δsky1 cells were recorded using DNA microarrays. The data, validated by quantitative PCR, revealed 122 differentially expressed genes: 69 upregulated and 53 downregulated. Among the upregulated genes, those related to sulfur metabolism were over-represented and partially dependent on Sky1. Deletions of MET4 or other genes encoding co-regulators of the expression of sulfur-metabolism-related genes, with the exception of MET28, did not modify the cisplatin sensitivity of yeast cells. One of the genes with the highest cisplatin-induced upregulation was SEO1, encoding a putative permease of sulfur compounds. We also measured the platinum, sulfur and glutathione content in W303, W303-Δsky1 and W303-Δseo1 cells after cisplatin treatment, and integration of the data suggested that these transcriptional changes might represent a cellular response that allowed chelation of cisplatin with sulfur-containing amino acids and also helped DNA repair by stimulating purine biosynthesis. The transcription pattern of stimulation of sulfur-containing amino acids and purine synthesis decreased, or even disappeared, in the W303-Δsky1 strain.

One-pot synthesis of 1,3,5-triazine derivatives via controlled cross-cyclotrimerization of nitriles: a mechanism approach.

The reaction of equimolecular amounts of a nitrile and triflic anhydride or triflic acid at low temperature produces an intermediate nitrilium salt that subsequently reacts with 2 equiv of a different nitrile at higher temperature to form 2,4-disusbstituted-6-substituted 1,3,5-triazines in moderate to good yields. This synthetic procedure has also been applied to the preparation of a 1,3,5-triazine having three different substituents. The results are explained in terms of a mechanism based on the relative stability of the intermediate nitrilium salts that are formed through a reversible pathway. The formation of a substituted isoquinoline using benzyl cyanide as the second nitrile supports the postulated mechanism as well as the structure of derivatives of the proposed intermediate when the reaction is carried out in the presence of different nucleophiles other than nitriles. Theoretical calculations and the monitoring of the reaction using (1)H and (13)C NMR spectroscopy are in agreement with the proposed mechanism pathway.

Focal-plane sensing-processing: a power-efficient approach for the implementation of privacy-aware networked visual sensors.

The capture, processing and distribution of visual information is one of the major challenges for the paradigm of the Internet of Things. Privacy emerges as a fundamental barrier to overcome. The idea of networked image sensors pervasively collecting data generates social rejection in the face of sensitive information being tampered by hackers or misused by legitimate users. Power consumption also constitutes a crucial aspect. Images contain a massive amount of data to be processed under strict timing requirements, demanding high-performance vision systems. In this paper, we describe a hardware-based strategy to concurrently address these two key issues. By conveying processing capabilities to the focal plane in addition to sensing, we can implement privacy protection measures just at the point where sensitive data are generated. Furthermore, such measures can be tailored for efficiently reducing the computational load of subsequent processing stages. As a proof of concept, a full-custom QVGA vision sensor chip is presented. It incorporates a mixed-signal focal-plane sensing-processing array providing programmable pixelation of multiple image regions in parallel. In addition to this functionality, the sensor exploits reconfigurability to implement other processing primitives, namely block-wise dynamic range adaptation, integral image computation and multi-resolution filtering. The proposed circuitry is also suitable to build a granular space, becoming the raw material for subsequent feature extraction and recognition of categorized objects.