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The phase Ib KEYNOTE-173 study was conducted to assess the safety and preliminary antitumor activity of neoadjuvant chemotherapy plus pembrolizumab in high-risk, early-stage, non-metastatic triple-negative breast cancer (TNBC). Six pembrolizumab plus chemotherapy regimens were evaluated (cohorts A–F). All cohorts received a pembrolizumab 200-mg run-in dose (cycle 1), then eight cycles of pembrolizumab in combination with a taxane with or without carboplatin for 12 weeks, and then doxorubicin and cyclophosphamide for an additional 12 weeks before surgery. Primary end points were safety and recommended phase II dose (RP2D); secondary end points were pathological complete response (pCR) rate, objective response rate, and event-free and overall survival. Exploratory end points were the relationship between outcome and potential biomarkers, such as tumor programmed death ligand 1 (PD-L1) expression (combined positive score) and stromal tumor-infiltrating lymphocyte levels (sTILs). Sixty patients were enrolled between 18 February 2016, and 28 February 2017. Dose-limiting toxicities occurred in 22 patients, most commonly febrile neutropenia (n = 10 across cohorts). Four cohorts (B, C, D, F) did not meet the RP2D threshold; two cohorts did (A, E). The most common grade ≥3 treatment-related adverse event was neutropenia (73%). Immune-mediated adverse events and infusion reactions occurred in 18 patients (30%) and were grade ≥3 in six patients (10%). The pCR rate (ypT0/Tis ypN0) across all cohorts was 60% (range 49%–71%). Twelve-month event-free and overall survival rates ranged from 80% to 100% across cohorts (100% for four cohorts). Higher pre-treatment PD-L1 combined positive score, and pre- and on-treatment sTILs were significantly associated with higher pCR rates (P = 0.0127, 0.0059, and 0.0085, respectively). Combination neoadjuvant chemotherapy and pembrolizumab for high-risk, early-stage TNBC showed manageable toxicity and promising antitumor activity. In an exploratory analysis, the pCR rate showed a positive correlation with tumor PD-L1 expression and sTIL levels. ClinicalTrials.gov identifier: NCT02622074. • Neoadjuvant pembrolizumab + chemotherapy showed no unexpected safety findings in patients with high-risk, early-stage TNBC. • Two chemotherapy regimens met the RP2D threshold: nab-paclitaxel 125 mg/m2 qw; paclitaxel 80 mg/m2 qw + carboplatin AUC5 q3w. • pCR rate (ypT0/Tis ypN0) across all cohorts was 60% and 12-month EFS and OS rates ranged from 80% to 100% across cohorts. • pCR rate showed positive correlation with tumor PD-L1 expression and stromal tumor-infiltrating lymphocyte levels. [ABSTRACT FROM AUTHOR]

Some basic parameters for equine in vitro embryo production have not yet been established, including the optimum temperature for maturation and embryo culture, and the optimum CO2 concentration and pH during early embryo development. To explore this, we first performed cultures in incubators set at 37.2°C, 37.7°C or 38.2°C. At these temperatures, the corresponding maturation rates were 33%, 38% and 42%; cleavage rates were 84%, 86% and 88%; and blastocyst rates were 35%, 44% and 44% per injected oocyte. These rates did not differ significantly (P > 0.2). We then evaluated three different CO2 concentrations (6%, 6.5% or 7% CO2) in 5% O2 for culture over Days 0–5 after intracytoplasmic sperm injection, using a commercial human embryo medium with added serum, at 38.2°C. The pH values of these media were 7.36, 7.33 and 7.29 respectively. In the presence of 6%, 6.5% or 7% CO2, cleavage rates were 68%, 80% and 70% respectively, and blastocyst rates per injected oocyte were 42%, 54% and 27% respectively. The blastocyst rate for the 7% CO2 treatment was significantly lower than that for the 6.5% CO2 treatment (P < 0.05). We conclude that equine in vitro embryo production is equally effective within the range of 37.2–38.2°C, but that equine early cleavage stage development is sensitive to small changes in CO2 atmosphere and/or medium pH. Some basic parameters for equine embryo culture are not yet established. We found that blastocyst development after intracytoplasmic sperm injection was not affected by incubator temperature between 37.2°C and 38.2°C, but was reduced under high CO2 tension (7%), associated with lower medium pH (7.29), during cleavage stage culture. These findings will help optimise the culture environment for in vitro equine embryo production. [ABSTRACT FROM AUTHOR]

This report describes a case of idiopathic permanent atrial standstill (PAS) with histopathological evidence of right atrial replacement fibrosis in a mixed-breed female dog that underwent echocardiographic and electrocardiographic follow-up examinations during 4 consecutive years, until its death from chronic renal and pre-renal azotemia. To the best of the authors' knowledge, this is the longest survival time reported in the veterinary literature of a dog with PAS that never received pacemaker therapy. [ABSTRACT FROM AUTHOR]

Background For primary triple-negative breast cancer (TNBC) treated with neoadjuvant chemotherapy (NAC), higher pretreatment tumor-infiltrating lymphocytes (TILs) correlates with increased pathologic complete response (pCR) rates, and improved survival. We evaluated the added prognostic value of residual disease (RD) TILs to residual cancer burden (RCB) in predicting survival post-NAC. Patients and methods We combined four TNBC NAC patient cohorts who did not achieve pCR. RD TILs were investigated for associations with recurrence-free survival (RFS), and overall survival (OS) using Cox models with stromal TILs as a continuous variable (per 10% increment). The likelihood ratio test was used to evaluate added prognostic value of RD TILs. Results A total of 375 RD TNBC samples were evaluable for TILs and RCB. The median age was 50 years, with 62% receiving anthracycline/taxane chemotherapy. The RCB class after NAC was 11%, 50%, and 39% for I, II, and III, respectively. The median RD TIL level was 20% (IQR 10–40). There was a positive correlation between RD TIL levels and CD8+ T-cell density (ρ  = 0.41). TIL levels were significantly lower with increasing post-NAC tumor (P  =   0.005), nodal stage (P  =   0.032), but did not differ by RCB class (P  =   0.84). Higher RD TILs were significantly associated with improved RFS (HR: 0.86; 95% CI 0.79–0.92; P  <   0.001), and improved OS (HR: 0.87; 95% CI 0.80–0.94; P  <   0.001), and remained significant predictors in multivariate analysis (RFS P  =   0.032; OS P  =   0.038 for OS). RD TILs added significant prognostic value to multivariate models including RCB class (P  <   0.001 for RFS; P  =   0.021 for OS). The positive prognostic effect of RD TILs significantly differed by RCB class for RFS (P Int=0.003) and OS (P Int=0.008) with a greater magnitude of positive effect observed for RCB class II than class III. Conclusions TIL levels in TNBC RD are significantly associated with improved RFS and OS and add further prognostic information to RCB class, particularly in RCB class II. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to evaluate the differential effects of conventional and Piezo-driven ICSI on blastocyst development, and on sperm component remodeling and oocyte activation, in an equine model.Methods: In vitro-matured equine oocytes underwent conventional (Conv) or Piezo ICSI, the latter utilizing fluorocarbon ballast. Blastocyst development was compared between treatments to validate the model. Then, oocytes were fixed at 0, 6, or 18 h after injection, and stained for the sperm tail, acrosome, oocyte cortical granules, and chromatin. These parameters were compared between injection techniques and between sham-injected and sperm-injected oocytes among time periods.Results: Blastocyst rates were 39 and 40%. The nucleus number was lower, and the nuclear fragmentation rate was higher, in blastocysts produced by Conv. Cortical granule loss started at 0H after both sperm and sham injection. The acrosome was present at 0H in both ICSI treatments, and persisted to 18H in significantly more Conv than Piezo oocytes (72 vs. 21%). Sperm head area was unchanged at 6H in Conv but significantly increased at this time in Piezo; correspondingly, at 6H significantly more Conv than Piezo oocytes remained at MII (80 vs. 9.5%). Sham injection did not induce significant meiotic resumption.Conclusions: These data show that Piezo ICSI is associated with more rapid sperm component remodeling and oocyte meiotic resumption after sperm injection than is conventional ICSI, and with higher embryo quality at the blastocyst stage. This suggests that there is value in exploring the Piezo technique, utilized with a non-toxic fluorocarbon ballast, for use in clinical human ICSI. [ABSTRACT FROM AUTHOR]

Male fertility can be evaluated through complete semen analysis. Plants belonging to the Tribulus genus are known for their role in enhancing sex hormone levels and semen quality. The aim of this study was to evaluate the effects of T. terrestris on semen quality and physiological parameters. Sixty-five men with abnormal semen evaluation were included in this study, in which they were prescribed with oral administration of Androsten® (250 mg of Tribulus terrestris dried extract per capsule). Body fat percentage, lean muscle mass gain, fluctuation in steroid hormone levels and all semen parameters were analysed during the period of treatment. The results demonstrated that decrease in the percentage of body fat and increase in lean mass were significant, as well as increase in dihydrotestosterone levels. Complete semen analysis evaluated at the end of treatment showed significant enhancement in sperm concentration, motility and liquefaction time. Protodioscin, the main phytochemical agent of the Tribulus genus, acts on sertoli cells, germ cell proliferation and growth of seminiferous tubules. This component is known to convert testosterone into dihydrotestosterone, which plays important roles in male attributes. Our results indicate the therapeutic use of Tribulus terrestris by men presenting altered semen parameters, and/or undergoing infertility treatment. [ABSTRACT FROM AUTHOR]

A high percentage of the heat that is supplied to thermoelectric power plants is discarded to ambient and must be handled by an external cooling system. This cooling system typically consists of wet cooling towers because of the excellent thermo-physical properties of water. However, the amount of water consumed for power production has reached alarming levels in developed countries. Air-cooled heat exchangers (ACHXs) appear to be the most adequate technology to substitute for wet cooling towers, but the use of this technology has some limitations. The most important limitation is the higher condenser pressures in the cycle, which produce backpressures at the condensing turbine's exit, increases in heat rejection and losses in the net plant efficiency. This paper presents a concept for the use of ACHXs in the cooling systems of power plants using an absorption refrigeration system (ARS) as an intermediary. Heat from the steam condenser is handled by the evaporator of the ARS and “lifted” to a higher temperature level, where the ACHXs are fitted to work. The generator of the ARS is fed by the power plant itself, extracting (bleeding off) some of the steam that flows through the steam turbine at the correct pressure and temperature. [ABSTRACT FROM AUTHOR]

The study of lake-atmosphere interactions was the main purpose of a 2014 summer experiment at Alqueva reservoir in Portugal. Near-surface fluxes of momentum, heat and mass [water vapour (H2O) and carbon dioxide (CO2)] were obtained with the new Campbell Scientific's IRGASON Integrated Open-Path CO2/H2O Gas Analyser and 3D Sonic Anemometer between 2 June and 2 October. On average, the reservoir was releasing energy in the form of sensible and latent heat flux during the study period. At the end of the 75 d, the total evaporation was estimated as 490.26 mm. A high correlation was found between the latent heat flux and the wind speed (R = 0.97). The temperature gradient between air and water was positive between 12 and 21 UTC, causing a negative sensible heat flux, and negative during the rest of the day, triggering a positive sensible heat flux. The reservoir acted as a sink of atmospheric CO2 with an average rate of -0.026 mg m-2 s-1. However, at a daily scale we found an unexpected uptake between 0 and 9 UTC and almost null flux between 13 and 19 UTC. Potential reasons for this result are further discussed. The net radiation was recorded for the same period and water column heat storage was estimated using water temperature profiles. The energy balance closure for the analysed period was 81%. In-water solar spectral downwelling irradiance profiles were measured with a new device allowing measurements independent of the solar zenith angle, which enabled the computation of the attenuation coefficient of light in the water column. The average attenuation coefficient for the photosynthetically active radiation spectral region varied from 0.849 ± 0.025 m-1 on 30 July to 1.459 ± 0.007 m-1 on 25 September. [ABSTRACT FROM AUTHOR]

In this work we proposed to evaluate the corrosion resistance of four different alloys by electrochemical techniques, a binary alloy Cu10Al, and three ternary alloys Cu10Al-xAg (x = 5, 10, and 15 wt.%) to be used like biomaterials in dental application. Biomaterials proposed were tested in artificial saliva at 37°C for 48 h. In addition, pure metals Cu, Al, Ag, and Ti as reference materials were evaluated. In general the short time tests indicated that the Ag addition increases the corrosion resistance and reduces the extent of localized attack of the binary alloy. Moreover, tests for 48 hours showed that the Ag addition increases the stability of the passive layer, thereby reducing the corrosion rate of the binary alloy. SEM analysis showed that Cu10Al alloy was preferably corroded by grain boundaries, and the Ag addition modified the form of attack of the binary alloy. Cu-rich phases reacted with SCN− anions forming a film of CuSCN, and the Ag-rich phase is prone to react with SCN− anions forming AgSCN. Thus, binary and ternary alloys are susceptible to tarnish in the presence of thiocyanate ions. [ABSTRACT FROM AUTHOR]

This study was undertaken to evaluate the possible role of several reproductive hormone receptors on the disruption of the hypothalamic-pituitary-testis (HPT) axis activity induced by perfluorooctane sulfonate (PFOS). The studied receptors are the gonadotropin-releasing hormone receptor (GnRHr), luteinizing hormone receptor (LHr), follicle-stimulating hormone receptor (FSHr), and the androgen receptor (Ar). Adult male rats were orally treated with 1.0; 3.0 and 6.0 mg of PFOS kg −1 d −1 for 28 days. In general terms, PFOS can modify the relative gene and protein expressions of these receptors in several tissues of the reproductive axis. At the testicular level, apart from the expected inhibition of both gene and protein expressions of FSHr and Ar, PFOS also stimulates the GnRHr protein and the LHr gene expression. The receptors of the main hormones involved in the HPT axis may have an important role in the disruption exerted by PFOS on this axis. [ABSTRACT FROM AUTHOR]

Perfluorooctane sulfonate (PFOS) is the most representative of a rising class of persistent organic pollutants perfluorochemicals. In the present study, its neurotoxicity was examined using adult male rats orally treated with 0.5; 1.0; 3.0 and 6.0 mg of PFOS/kg/day for 28 days. At the end of the treatment, the dopamine concentration and its metabolism expressed like the ratio 3,4-dihydroxyphenylacetic acid (DOPAC)/dopamine and homovanillic acid (HVA)/dopamine were measured in the amygdala, prefrontal cortex and hippocampus. Gene and protein expression of the dopamine receptors D1 and D2 were also determined in these limbic areas. The obtained results suggest that: (1) PFOS can alter the dopamine system by modifying its neuronal activity and/or its D1 and D2 receptors in the studied brain regions; (2) the dopamine concentration and metabolism seem to be more sensitive against PFOS toxicity in the hippocampus than in the other analyzed brain areas; (3) the inhibited gene and protein expression of the D1 receptors induced by PFOS in the amygdala could be related to several changes in the HPA axis activity, and lastly; (4) the observed alterations on the dopamine system induced by PFOS could be a possible neurotoxicity mechanism of PFOS, leading to many neurological diseases. [ABSTRACT FROM AUTHOR]

Perfluorooctane sulfonate (PFOS) is a fluorinated organic compound. This chemical is neurotoxic and can alter the pituitary secretion. This is an initial study aimed at knowing the toxic effects of high doses of PFOS on prolactin secretion and the possible mechanisms involved in these alterations. For that, adult male rats were orally treated with 3.0 and 6.0 mg of PFOS/kg body weight (b.w.)/day for 28 days. At the end of the treatment, the serum levels of prolactin and estradiol as well as the concentration of dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and gamma-aminobutyric acid (GABA) were quantified in the anterior and in the mediobasal hypothalamus. PFOS, at the administered doses, reduced prolactin and estradiol secretion, increased the concentration of dopamine and GABA in the anterior hypothalamus, and decreased the ratios DOPAC/dopamine and HVA/dopamine in this same hypothalamic area. The outcomes reported in this study suggest that (1) high doses of PFOS inhibit prolactin secretion in adult male rats; (2) only the periventricular-hypophysial dopaminergic (PHDA) neurons seem to be involved in this inhibitory effect but not the tuberoinfundibular dopaminergic (TIDA) and the tuberohypophysial dopaminergic (THDA) systems; (3) GABAergic cells from the paraventricular and supraoptic nuclei could be partially responsible for the PFOS action on prolactin secretion; and finally (4) estradiol might take part in the inhibition exerted by elevated concentration of PFOS on prolactin release. [ABSTRACT FROM AUTHOR]

Irradiation by a medium-pressure mercury (Hg) lamp was used to study the photodegradation of chlorpyrifos ( O , O -diethyl- O -3,5,6-trichloropyridin-2-yl phosphorothioate) in salt, deionized water (unbuffered), and a natural saline water. The UV irradiation produces 3,5,6-trichloro-2-pyridinol (TCP) with accelerated photodegradation kinetics of the parent compound. The results show that chlorpyrifos photolysis followed pseudo-first-order kinetics in the presence and absence of salt with no significant difference between the photodegradation rates in saline waters and unbuffered deionized water. Addition of Suwannee River natural organic matter (SRNOM) to mimic the mixing of freshwaters with seawaters significantly changed the photodegradation rate constant of chlorpyrifos in saline waters. The influence of hydrolysis and volatilization was also evaluated. While photolysis was found to be the main transformation process in unbuffered deionized water, both volatilization and photolysis can be important pathways of chlorpyrifos loss in natural saline waters and under aerated conditions. [ABSTRACT FROM AUTHOR]

This work presents a method for static contingency analysis. The complex bus voltages after the outage of a transmission line (or a transformer) are estimated from one base case power flow solution and sensitivity relationships. As the steady-state power network equations are expressed in rectangular coordinates, the linearity of the Jacobian and the invariance of the Hessian allow the computation of sensitivity relationships with extra second-order information. This increases considerably the accuracy of the estimates of the power system variables and makes easier to handle the reactive power generation constraints, thus resulting in higher accuracy in the voltage estimation with limited additional computational effort. Numerical results with both test systems of different sizes and a real system illustrate the characteristics of the proposed methodology. [ABSTRACT FROM AUTHOR]

Perfluorooctane sulfonate (PFOS) is an endocrine disruptor, whose exposure can induce several alterations on the reproductive axis activity in males during adulthood. This study was undertaken to evaluate the possible role of serotonin and neuropeptide Y (NPY) on the disruption of the hypothalamic–pituitary–testicular (HPT) axis induced by PFOS in adult male rats. For that, adult male rats were orally treated with 0.5; 1.0; 3.0 and 6.0 mg of PFOS/kg/day for 28 days. After PFOS exposure, serotonin concentration increased in the anterior and mediobasal hypothalamus as well as in the median eminence. The metabolism of this amine (expressed as the ratio 5-hydroxyindolacetic acid (5-HIAA)/serotonin) was diminished except in the anterior hypothalamus, with the doses of 3.0 and 6.0 mg/kg/day, being this dose 0.5 mg/kg/day in the median eminence. In general terms, PFOS-treated rats presented a decrease of the hypothalamic concentration of the gonadotropin releasing hormone (GnRH) and NPY. A diminution of the serum levels of the luteinizing hormone (LH), testosterone and estradiol were also shown. These results suggest that both serotonin and NPY could be involved in the inhibition induced by PFOS on the reproductive axis activity in adult male rats. [ABSTRACT FROM AUTHOR]

The occurrence of pharmaceutical compounds in wastewater treatment plants and surface waters has been detected worldwide, constituting a potential risk for aquatic ecosystems. Adult zebrafish, of both sexes, were exposed to three common pharmaceutical compounds (atenolol, ketoprofen and diclofenac) and their UV photolysis by-products over seven days. The results show that diclofenac was removed to concentrations < LOD after 5 min of UV irradiation. The oxidative stress response of zebrafish to pharmaceuticals and their photolysis by-products was evaluated through oxidative stress enzymes (glutathione-S-transferase, catalase, superoxide dismutase) and lipid peroxidation. Results suggest that the photolysis by-products of diclofenac were more toxic than those from the other compounds tested, showing an increase in GST and CAT levels, which are also supported by higher MDA levels. Overall, the toxicity of waters containing atenolol and ketoprofen was reduced after the parent compounds were transformed by photolysis, whereas the toxicity increased significantly from the by-products generated through diclofenac photolysis. Therefore, diclofenac photolysis would possibly necessitate higher irradiation time to ensure that the associated by-products are completely degraded to harmless form(s). [ABSTRACT FROM AUTHOR]

Background: The morphological evaluation of tumor-infiltrating lymphocytes (TILs) in breast cancer (BC) is gaining momentum as evidence strengthens for the clinical relevance of this immunological biomarker. Accumulating evidence suggests that the extent of lymphocytic infiltration in tumor tissue can be assessed as a major parameter by evaluation of hematoxylin and eosin (H&E)-stained tumor sections. TILs have been shown to provide prognostic and potentially predictive value, particularly in triple-negative and human epidermal growth factor receptor 2-overexpressing BC. Design: A standardized methodology for evaluating TILs is now needed as a prerequisite for integrating this parameter in standard histopathological practice, in a research setting as well as in clinical trials. This article reviews current data on the clinical validity and utility of TILs in BC in an effort to foster better knowledge and insight in this rapidly evolving field, and to develop a standardized methodology for visual assessment on H&E sections, acknowledging the future potential of molecular/multiplexed approaches. Conclusions: The methodology provided is sufficiently detailed to offer a uniformly applied, pragmatic starting point and improve consistency and reproducibility in the measurement of TILs for future studies. [ABSTRACT FROM AUTHOR]

This paper presents a framework to analyse critical levels of the power system loadability from the point of view of reactive power generation. Three main aspects are addressed: (1) the preliminary identification of the critical points of reactive power generation in terms of the power system loadability through a predictor scheme, (2) the solution of an optimisation problem to precisely determine these points in the corrector step, and (3) the classification of these critical points in terms of bifurcation type by using by-products of the optimisation process. The conventional power flow equations are expressed in rectangular coordinates, since this type of formulation allows both an accurate estimation of the power network variables in the predictor step and the computation of fast and robust solutions in the correction step. Numerical results obtained with two power networks are shown to illustrate the performance of the proposed methodology. [ABSTRACT FROM AUTHOR]

New approaches to inducing altitude acclimation in a relatively short timeframe are needed, as it is not practical for many soldiers and athletes to gain access to specialized training facilities. Acclimation to one environmental stressor could enhance adaptation to various other stressors in animals and humans. This phenomenon has been described as cross-tolerance and involves the activation of common protective pathways. The purpose of this review is to discuss possible mechanisms involved in the cross-tolerance between heat and hypoxia. Future data could potentially support the use of a cross-tolerance model as a means for military personnel to prepare for deployment to high-altitude environments, as well as for athletes competing at high altitude [ABSTRACT FROM AUTHOR]

Poly(3,4-ethylenedioxythiophene) nanowires (nw-PEDOT), between 6.7-13.8 nm diameter, were obtained by electrochemical methods utilizing modified electrodes with silicon oxide as a template to afford a Pt/nw-PEDOT electrode. Dopamine electro-polymerization was next accomplished upon this electrode (Pt/nw-PEDOT/PDA). The Pt/nw-PEDOT/PDA assembly is capable of hindering interfering signals such as those from ascorbic and uric acid, enabling thus the selective detection of dopamine. Amperometric determination studies allowed limit of detection and limit of quantification limits of 0.47 and 1.59 µM, respectively, to be established. These limits were lower than those obtained with the same conducting polymer but without a nanowire structure. [ABSTRACT FROM AUTHOR]

Perfluorooctane sulfonate (PFOS) is a neurotoxic agent and it can disrupt the endocrine system activity. This work was undertaken to evaluate the possible effects of PFOS exposure on the hypothalamic–pituitary–testicular axis (HPT) in adult male rats, and to evaluate the possible morphological alterations induced by PFOS in the endocrine tissues of this axis. Adult male rats were orally treated with 0.5; 1.0; 3.0 and 6.0 mg of PFOS/kg/day for 28 days. After PFOS exposure, hypothalamic noradrenaline concentration increased in the anterior hypothalamus and in the median eminence, not changing in the mediobasal hypothalamus. PFOS treated rats presented a decrease of the gonadotropin releasing hormone (GnRH) gene expression, increasing the mRNA levels of the luteinizing hormone (LH) in rats treated with all doses administered except with the dose of 6 mg/kg/day. PFOS also induced a raise of the follicle stimulating hormone (FSH) gene expression in the animals exposed to 0.5 and 1.0 mg of PFOS/kg/day. After PFOS exposure, hypothalamic GnRH concentration was modified, LH and testosterone release was inhibited and FSH secretion was stimulated. Moreover, PFOS induced several histopathological alterations in the hypothalamus, pituitary gland and testis. The results obtained in the present study suggest in general terms that PFOS can inhibit the physiological activity of the reproductive axis in adult male rats, which could be explained, at least in part, by the structural alterations showed in the animals exposed to this chemical: very dense chromatin, condensed ribosomes and a loss of the morphology in the hypothalamus; a degeneration of the gonadotrophic cells, as well as a loss and degeneration of the spermatozoids and a very marked edema in the testis. [ABSTRACT FROM AUTHOR]

Highlights: [•] We report obtaining a new electrode modified with a hybrid film PEDOT/PDA. [•] PEDOT/PDA is a selective electrode for dopamine in the presence of interferents. [•] The hybrid film PEDOT/PDA displays good stability and reproducibility. [•] PEDOT/PDA presents detection limits of 0.6μM and limit of quantification of 1.7μM. [ABSTRACT FROM AUTHOR]

Abstract: Pharmaceutical compounds such as ketoprofen, diclofenac and atenolol are frequently detected at relatively high concentrations in secondary effluents from wastewater treatment plants. Therefore, it is important to assess their transformation kinetics and intermediates in subsequent disinfection processes, such as direct ultraviolet (UV) irradiation. The photodegradation kinetics of these compounds using a medium pressure (MP) lamp was assessed in pure water, as well as in filtered and unfiltered treated wastewater. Ketoprofen had the highest time- and fluence-based rate constants in all experiments, whereas atenolol had the lowest values, which is consistent with the corresponding decadic molar absorption coefficient and quantum yield. The fluence-based rate constants of all compounds were evaluated in filtered and unfiltered wastewater matrices as well as in pure water. Furthermore, transformation products of ketoprofen, diclofenac and atenolol were identified and monitored throughout the irradiation experiments, and photodegradation pathways were proposed for each compound. This enabled the identification of persistent transformation products, which are potentially discharged from WWTP disinfection works employing UV photolysis. [Copyright &y& Elsevier]

Abstract: Clofibric acid (CLF) is the pharmaceutically active metabolite of lipid regulators clofibrate, etofibrate and etofyllinclofibrate, and it is considered both environmentally persistent and refractory. This work studied the biotransformation of CLF in aerobic sequencing batch reactors (SBRs) with mixed microbial cultures, monitoring the efficiency of biotransformation of CLF and the production of metabolites. The maximum removal achieved was 51% biodegradation (initial CLF concentration=2mgL−1), where adsorption and abiotic removal mechanisms were shown to be negligible, showing that CLF is indeed biodegradable. Tests showed that the observed CLF biodegradation was mainly carried out by heterotrophic bacteria. Three main metabolites were identified, including α-hydroxyisobutyric acid, lactic acid and 4-chlorophenol. The latter is known to exhibit higher toxicity than the parent compound, but it did not accumulate in the SBRs. α-Hydroxyisobutyric acid and lactic acid accumulated for a period, where nitrite accumulation may have been responsible for inhibiting their degradation. A metabolic pathway for the biodegradation of CLF is proposed in this study. [Copyright &y& Elsevier]

We present the experimental realization and characterization of an acoustic metamaterial with negative bulk modulus. The metamaterial consists of a two-dimensional array of cylindrical cavities, and the bulk modulus is controlled by their radius size and length. Experiments are performed in a two-dimensional waveguide where a slab of seven layers is used to extract the parameters of the metamaterial. A complete characterization of the constructed structure is reported, including the dispersion relation of the acoustic bands and the skin depth effect, which both have been measured, and the data are well supported by semianalytical models and by finite-element simulations. [ABSTRACT FROM AUTHOR]

The use of load and resistance factor design (LRFD) to design geotechnical components of transportation infrastructure in the United States is now mandated by the Federal Highway Administration (FHWA). The advantages of LRFD over working stress design (WSD) may lead to its gradual adoption in geotechnical design even in the absence of any mandates. If load and resistance factors are based on reliability analysis, a mechanically stabilized earth (MSE) wall may be designed to a target reliability index (or a target probability of failure). Load and resistance factor design of MSE walls must consider multiple ultimate limit states, associated with both external and internal stabilities. This paper develops factors for use for the two ultimate limit states, sliding and overturning, used in design that are related to the external stability of MSE walls. Equations that closely reproduce the ultimate limit states with as little uncertainty as possible are proposed. The uncertainties of the parameters and the transformations for ultimate limit state equations are assessed using data from an extensive literature review. The first-order reliability method (FORM) is then used to produce resistance factor values for each limit state for different levels of target reliability index. [ABSTRACT FROM AUTHOR]

The impact of lakes in numerical weather prediction is investigated in a set of global simulations performed with the ECMWF Integrated Forecasting System (IFS). A Fresh shallow-water Lake model (FLake) is introduced allowing the coupling of both resolved and subgrid lakes (those that occupy less than 50% of a grid-box) to the IFS atmospheric model. Global fields for the lake ancillary conditions (namely lake cover and lake depth), as well as initial conditions for the lake physical state, have been derived to initialise the forecast experiments. The procedure for initialising the lake variables is described and verified with particular emphasis on the importance of surface water temperature and freezing conditions. The response of short-range near surface temperature to the representation of lakes is examined in a set of forecast experiments covering one full year. It is shown that the impact of subgrid lakes is beneficial, reducing forecast error over the Northern territories of Canada and over Scandinavia particularly in spring and summer seasons. This is mainly attributed to the lake thermal effect, which delays the temperature response to seasonal radiation forcing. [ABSTRACT FROM AUTHOR]

The active earth pressure used in the design of gravity walls is calculated based on the internal friction angle of the retained soil or backfill. However, the friction angle of a soil changes during the deformation process. For drained loading, the mobilized friction angle varies between the peak and critical-state friction angles, depending on the level of shear strain in the retained soil. Consequently, there is not a single value of friction angle for the retained soil mass, and the active earth pressure coefficient changes as the wall moves away from the backfill and plastic shear strains in the backfill increase. In this paper, the finite element method is used to study the evolution of the active earth pressure behind a gravity retaining wall, as well as the shear patterns developing in the backfill and foundation soil. The analyses relied on use of a two-surface plasticity constitutive model for sands, which is based on critical-state soil mechanics. [ABSTRACT FROM AUTHOR]

Pharmaceuticals and personal care products (PPCPs) are becoming increasingly recognised as important micropollutants to be monitored in wastewater treatment plants (WWTPs), since WWTP effluents represent an important point source to natural aquatic systems. In this study, the abundance of 65 PPCPs was analysed in 5 Portuguese WWTPs during the spring and autumn. Due to the fact that analytical approaches normally used to quantify the abundance of these compounds are labour intensive and require various specific procedures, this study proposes a set of simplified analytical methods for the quantification of pharmaceutically active compounds (PhACs) and polycyclic musks in liquid and sludge samples. The analytical methods were validated using influent wastewater matrices, showing comparable limits of detection and quantification as literature values for most PPCP s, with the exception of the estrogenic compounds. The PhAC concentrations detected in the WWTP survey were in the range of 0.050-100mg L21 in the influent and up to 50mgL21 in the effluent, where the non-steroidal anti-inflammatory drugs (NSAIDs) were the most abundant and frequently detected group. Some musks were detected up to 11.5mg L21 in the influent and 0.9mg L21 in the effluent, and adsorbed in the sludge up to 22.6mgg21. [ABSTRACT FROM AUTHOR]

Oncogenesis in the oral cavity is believed to result from genetic alterations that cause a stepwise transformation of the mucosa to invasive carcinoma. In oral squamous cell carcinoma (OSCC) multiple cytogenetic abnormalities have been reported, but their practical significance remains uncertain. To evaluate the usefulness of the assessment of CCND1, MYC, EGFR, ERBB2 and TP53 in OSCC and lymph node metastases. Fifty-one consecutive samples of OSCC, nine lymph node biopsies showing metastatic spread from OSCC, 16 biopsies diagnosed as oral leucoplakia (OLK), 13 samples corresponding to oral lichen planus (OLP) and 14 samples from normal oral mucosa were included in the study. Clinical and histopathological characteristics were reviewed. The genetic and protein status of the CCND1, MYC, EGFR, ERBB2 oncogenes and the TP53 tumour suppressor gene were assessed by fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC). The obtained results were compared with the clinical characteristics and the outcome of the OSCCs. TP53 gene losses and MYC, ERBB2, CCND1 and EGFR copy number gains and amplifications were detected in a higher proportion in OSCC and lymph node samples than in OLK and OLP samples ( P < 0·005). Overexpression of p53, Myc, Cyclin D1, c-erbB-2 and epidermal growth factor receptor (EGFR) was more prevalent in malignant samples than benign samples ( P < 0·05). Correlation between FISH and IHC results was demonstrated in MYC, EGFR and CCND1 studies. The presence of two or more genetic abnormalities in the studied loci was exclusively detected in primary and metastatic OSCC. In our series, genetic abnormalities in TP53, MYC, CCND1, ERBB2 and EGFR detected by FISH were absent in inflammatory lesions, infrequent in precursor lesions and common in tumoral lesions. Evaluation of the genetic status of TP53, MYC, CCND1, ERBB2 and EGFR may be an additional diagnostic tool in distinguishing benign from malignant oral lesions in histopathologically challenging cases. [ABSTRACT FROM AUTHOR]

Sand dilates with shearing at a rate that increases with increasing relative density (DR) and decreases with increasing effective confining stress (σc′). The peak friction angle of a sand depends on its critical-state friction angle and on dilatancy. In this paper, we develop a simple correlation between peak friction angle, critical-state friction angle, and dilatancy based on triaxial compression and plane-strain compression test data for sand for a range of confining pressures from very low levels to approximately 196 kPa. [ABSTRACT FROM AUTHOR]

Rowe's stress-dilatancy relation for frictional (cohesionless) materials has been a cornerstone of soil mechanics. The original derivation of this relationship was based on incorrect energy minimisation considerations, but the relationship was proven later by De Josselin de Jong using friction laws, and has been confirmed by a large body of experimental results. In contrast, the validity of Rowe's stress-dilatancy relation for cohesive-frictional materials, which has also been used, although not as extensively, was never verified. This paper shows that Rowe's stress-dilatancy relation for Mohr-Coulomb soils (cohesive-frictional materials) is in fact incorrect. The paper also provides a correct stress-dilatancy relationship for non-associated Mohr-Coulomb soils that have both cohesive and frictional strength components. The derivation of the relationship for cohesive-frictional soils presented in this paper relies on use of the sawtooth model together with the application of the laws of friction. [ABSTRACT FROM AUTHOR]

Background The genetic alterations that drive the transition from actinic keratoses (AKs) to cutaneous squamous cell carcinomas (SCCs) have not been defined precisely. Amplification and/or overexpression of the MYC proto-oncogene have been demonstrated in several human, malignant tumours including head and neck SCCs. Objectives To evaluate the presence of MYC genomic aberrations in both AKs and SCCs. Methods Skin biopsy specimens corresponding to AKs, SCCs and control samples were included in two paraffin-embedded tissue microarrays. MYC cytogenetic profile was evaluated by fluorescence in situ hybridization (FISH). The results obtained were compared with MYC immunohistochemical expression. Results Twenty-three AKs and 30 SCCs were evaluated. MYC numerical aberrations were observed in eight of 23 (35%) AKs and 19 of 30 (63%) SCCs ( P = 0·05). MYC numerical aberrations were more frequent in moderately to poorly differentiated SCCs (77%) when compared with well-differentiated SCCs (25%; P = 0·027). A significant association between copy number gains of MYC by FISH analysis and MYC protein expression was demonstrated. Conclusions MYC gains and amplifications are frequent cytogenetic abnormalities in SCCs and may play a relevant role in promoting SCC undifferentiation and tumoral progression. [ABSTRACT FROM AUTHOR]

Abstract: Design of shallow foundations relies on bearing capacity values calculated using procedures that are based in part on solutions obtained using the method of characteristics, which assumes a soil following an associated flow rule. In this paper, we use the finite element method to determine the vertical bearing capacity of strip and circular footings resting on a sand layer. Analyses were performed using an elastic–perfectly plastic Mohr–Coulomb constitutive model. To investigate the effect of dilatancy angle on the footing bearing capacity, two series of analyses were performed, one using an associated flow rule and one using a non-associated flow rule. The study focuses on the values of the bearing capacity factors Nq and Nγ and of the shape factors sq and sγ for circular footings. Relationships for these factors that are valid for realistic pairs of friction angle and dilatancy angle values are also proposed. [Copyright &y& Elsevier]

This work deals with the application of tensor methods based on a quadratic model, to solve a set of nonlinear equations. Particular attention is given to the power flow problem, with emphasis on the modelling of the steady state electric network equations in rectangular coordinates. Two formulations of the power flow problem are used for the application of tensor methods. The first is the conventional approach based on active and reactive power mismatches. The second includes the equations of both power injection and the current injection balances. It is shown that the use of tensor models increases the robustness and can speed up the power flow iterative process if the computational effort for calculating the quadratic term is reduced. Numerical results obtained with power systems ranging from 6 to 1916 buses illustrate the application of the proposed methodology. [ABSTRACT FROM AUTHOR]

An analysis is developed to calculate the response of laterally loaded piles in multilayered elastic media. The displacement fields in the analysis are taken to be the products of independent functions that vary in the vertical, radial and circumferential directions. The governing differential equations for the pile deflections in different soil layers are obtained using the principle of minimum potential energy. Solutions for pile deflection are obtained analytically, whereas those for soil displacements are obtained using the one-dimensional finite difference method. The input parameters needed for the analysis are the pile geometry, the soil profile, and the elastic constants of the soil and pile. The method produces results with accuracy comparable with that of a threedimensional finite element analysis but requires much less computation time. The analysis can be extended to account for soil non-linearity. [ABSTRACT FROM AUTHOR]

Abstract: This paper presents a two-surface plasticity constitutive model based on critical-state soil mechanics and describes a practical process for the determination of its parameters. Determination of the constitutive model parameters can be done in a hierarchical manner, starting with the model parameters that have the most bearing on sand behavior and that can be determined using routine experimental procedures. Most parameters can be determined through simple curve fitting through experimental data points. The constitutive model is calibrated against experimental data for Toyoura sand, clean Ottawa sand and mixtures of Ottawa sand with non-plastic silt. The model simulates closely the mechanical response of sands under various loading conditions and predicts both drained and undrained behavior of sands at small and large strains using the actual small-strain shear modulus, as measured in resonant column or bender elements tests, along with realistic values of Poisson’s ratio. Performance of the model in simulating sand response is demonstrated for a variety of initial states and loading conditions. [Copyright &y& Elsevier]

Many of the important developments in the field of foundation engineering have been addressed in Géotechnique papers over the past 60 years. This paper briefly reviews some of these developments and related articles, particularly with respect to shallow and deep foundations. In the early days of Géotechnique, the power to perform sophisticated numerical analyses did not exist. Papers tended to focus on the solution of problems using simple models in which soil was modelled either as linear elastic or as perfectly plastic. Engineers sought simple closed-form analytical solutions for boundary-value problems. With the development of more powerful analytical, computational and experimental capabilities, and of more sophisticated pile installation technology (especially offshore), more recent papers have explored much more sophisticated approaches to a range of foundation problems, striving to achieve more realistic representation of working conditions. Géotechnique papers have attempted to solve the problems faced by the foundation engineering industry, with a strong emphasis on the underlying science; as a result, these papers have played a key role in the advancement of both the science and its applications in our discipline. [ABSTRACT FROM AUTHOR]

The paper examines, using numerical modelling, the problem of the limit shaft resistance of non-displacement piles installed in sands. The modelling makes use of an advanced, two-surface-plasticity constitutive model. The constitutive model predicts the soil response in both the small- and the large-strain range, while taking into account the effects of the intermediate principal effective stress and of the inherent anisotropy of the sand. Finite element analyses of shearing along the pile shaft are performed in order to examine the development of limit unit shaft resistance and the changes in stress state around the shaft upon axial loading of the pile. Special focus is placed on the operative value of the lateral earth pressure coefficient when limit shaft resistance is reached. The analyses offer useful insights regarding the factors controlling the value of unit shaft resistance in sands. The simulations predict a significant build-up of horizontal effective stress for dense sands. Based on these simulations, we propose a relationship between the lateral earth pressure coefficient for use in the calculation of the limit shaft resistance of the pile and the initial density and stress state of the sand. [ABSTRACT FROM AUTHOR]

The method of initial parameters (MIP) was originally developed to solve the problem of a beam on an elastic foundation with applied concentrated forces along the span, which introduce discontinuities in the mathematical formulation of the problem. MIP is modified in this paper so that it can be used for solving the problem of a laterally loaded pile with discontinuities due to soil layering along the length of the pile. In this paper, the basis of MIP is outlined, and its use to find the deflection, slope, bending moment and shear force of laterally loaded piles is illustrated. Example problems of laterally loaded piles embedded in multi-layered soil media are provided. [ABSTRACT FROM AUTHOR]

Bearing capacity calculations are an important part of the design of foundations. Many of the terms in the bearing capacity equation, as it is used today in practice, are empirical. Shape factors could not be derived in the past because three-dimensional bearing capacity computations could not be performed with any degree of accuracy. Likewise, depth factors could not be determined because rigorous analyses of foundations embedded in the ground were not possible. In this paper, the bearing capacity of strip, square, circular and rectangular foundations in sand are determined for frictional soils following an associated flow rule using finite-element limit analysis. The results of the analyses are used to propose values of the shape and depth factors for calculation of the bearing capacity of foundations in sands using the traditional bearing capacity equation. The traditional bearing capacity equation is based on the assumption that effects of shape and depth can be considered separately for soil self-weight and surcharge (embedment) terms. This assumption is not realistic, so a different form of the bearing capacity equation is also proposed that does not rely on it. [ABSTRACT FROM AUTHOR]

An analysis is developed to determine the response of laterally loaded piles in layered elastic media. The differential equations governing pile deflections in different layers due to a concentrated static force and/or moment acting at the pile head are obtained using the principle of minimum potential energy and calculus of variations. The differential equations are solved analytically using the method of initial parameters. Pile deflection, slope of the deformed axis of the pile, bending moment and shear force can be reliably obtained by this method for the entire pile length. The input parameters needed for the analysis are the pile geometry and the elastic constants of the soil and pile. It is observed that soil layering has a definite impact on pile response and must be taken into account for proper analysis and design. The analysis forms the basis for future formulations that can consider stress-strain nonlinearity. [ABSTRACT FROM AUTHOR]

A cavity expansion-based theory for calculation of cone penetration resistance qc in sand is presented. The theory includes a completely new analysis to obtain cone resistance from cavity limit pressure. In order to more clearly link the proposed theory with the classical cavity expansion theories, which were based on linear elastic, perfectly plastic soil response, linear equivalent values of Young's modulus, Poisson’s ratio and friction and dilatancy angles are given in charts as a function of relative density, stress state, and critical-state friction angle. These linear-equivalent values may be used in the classical theories to obtain very good estimates of cavity pressure. A much simpler way to estimate qc—based on direct reading from charts in terms of relative density, stress state, and critical-state friction angle—is also proposed. Finally, a single equation obtained by regression of qc on relative density and stress state for a range of values of critical-state friction angle is also proposed. Examples illustrate the different ways of calculating cone resistance and interpreting cone penetration test results. [ABSTRACT FROM AUTHOR]

In shallow foundation design, the key improvements offered by LRFD over the traditional working stress design (WSD) are the ability to provide a more consistent level of reliability between different designs and the possibility of accounting for load and resistance uncertainties separately. In the development of LRFD, a framework for the objective, logical assessment of resistance factors is needed. Additionally, in order for LRFD to fulfill its promise for designs with more consistent reliability, the methods used to execute a design must be consistent with the methods assumed in the development of the LRFD factors. In this paper, a methodology for the estimation of soil parameters for use in design equations is proposed that should allow for more statistical consistency in design inputs than is possible in traditional methods. Resistance factors for ultimate bearing capacity are computed using reliability analysis for shallow foundations both in sand and in clay, with input parameters obtained from both the cone penetration test and the standard penetration test, and for both ASCE-7 2000 and AASHTO 1998 load factors. Resistance factor values are dependent upon the values of load factors used. Thus, a method to adjust the resistance factors to account for code-specified load factors is also presented. [ABSTRACT FROM AUTHOR]

LRFD shows promise as a viable alternative to the present working stress design (WSD) approach to shallow foundation design. The key improvements of LRFD over the traditional WSD are the ability to provide a more consistent level of reliability and the possibility of accounting for load and resistance uncertainties separately. For LRFD to gain acceptance in geotechnical engineering, a framework for the objective assessment of resistance factors is needed. Such a framework, based on reliability analysis, is proposed in this paper. Probability density functions (PDFs), representing design variable uncertainties, are required for analysis. A systematic approach to the selection of PDFs is presented. A procedure such as that proposed provides a rational probabilistic basis for the development of LRFD methods in geotechnical engineering. [ABSTRACT FROM AUTHOR]

A methodology to allocate the active power transmission loss among agents of a power pool is proposed. The approach is based on the inclusion of the admittances equivalent to bus power injections in the bus admittance matrix. For a given power-flow solution, the relationship between the branch currents and the load/generator current injections is determined using a modified bus admittance matrix, which allows the power loss of each transmission line to be expressed in terms of bus current injections. The proposed technique is simple to implement and flexible enough to allow the assignment of loss parcels to a preselected set of buses. An example, with a six-bus system illustrates the main steps of the proposed allocation strategy, and numerical results obtained with the IEEE 57-bus system are used to assess the quality of the loss allocation. [ABSTRACT FROM AUTHOR]

Bearing capacity calculations are an important part of the design of foundations. Most of the terms in the bearing capacity equation, as it is used today in practice, are empirical. Shape factors for square and rectangular footings could not be derived in the past because three-dimensional bearing capacity computations could not be performed with any degree of accuracy. Likewise, depth factors could not be determined because rigorous analyses of foundations embedded in the ground were not available. In this paper, the bearing capacities of strip, square, circular and rectangular foundations in clay are determined rigorously based on finite element limit analysis. The results of the analyses are used to propose rigorous, definitive values of the shape and depth factors for foundations in clays. These results are helpful in reducing the uncertainties related to the method of analysis in bearing capacity calculations, paving the way for more cost-effective foundation design. [ABSTRACT FROM AUTHOR]

This paper proposes a framework for the simulation and analysis of the reactive power distribution in electric energy markets of the pool type. Firstly, the analytical formulation of the OPF problem, with three optional performance indexes for the reactive power dispatch, is discussed. These OPF objectives are used to determine the reactive power distribution for a given active power dispatch (obtained through merit-order strategy, for instance). An allocation strategy is used to assess the participation of each power system agent in the loss/reactive power distribution. This strategy uses the premise of co-operative game theory. Numerical results obtained with the Ward--Hale 6-bus test system illustrate the main aspects of the proposed methodology. [ABSTRACT FROM AUTHOR]