Uncertainty in the evolution of climate feedback traced to the strength of the Atlantic Meridional Overturning Circulation

In most coupled climate models, effective climate sensitivity increases for a few decades following an abrupt CO2 increase. The change in the climate feedback parameter between the first 20 years and the subsequent 130 years is highly model dependent. In this study, we suggest that the intermodel spread of changes in climate feedback can be partially traced to the evolution of the Atlantic Meridional Overturning Circulation. Models with stronger Atlantic Meridional Overturning Circulation recovery tend to project more amplified warming in the Northern Hemisphere a few decades after a quadrupling of CO2. Tropospheric stability then decreases as the Northern Hemisphere gets warmer, which leads to an increase in both the lapse‐rate and shortwave cloud feedbacks. Our results suggest that constraining future ocean circulation changes will be necessary for accurate climate sensitivity projections

Where is the chromospheric response to conductive energy input from a hot pre-flare coronal loop?

Before the onset of a flare is observed in hard X-rays there is often a pro- longed pre-flare or pre-heating phase with no detectable hard X-ray emission but pronounced soft X-ray emission suggesting that energy is being released and deposited into the corona and chromosphere already at this stage. This work analyses the temporal evolution of coronal source heating and the chromospheric response during this pre-heating phase to investigate the origin and nature of early energy release and transport during a solar flare. Simultaneous X-ray, EUV, and microwave observations of a well observed flare with a prolonged pre-heating phase are analysed to study the time evolution of the thermal emission and to determine the onset of particle acceleration. During the 20 minutes duration of the pre-heating phase we find no hint of accelerated electrons, neither in hard X-rays nor in microwave emission. However, the total energy budget during the pre-heating phase suggests that energy must be supplied to the flaring loop to sustain the observed temperature and emission measure. Under the assumption of this energy being transported toward the chromosphere via thermal conduc- tion, significant energy deposition at the chromosphere is expected. However, no detectable increase of the emission in the AIA wavelength channels sensitive to chromospheric temperatures is observed. The observations suggest energy release and deposition in the flaring loop before the onset of particle acceleration, yet a model in which energy is conducted to the chromosphere and subsequent heating of the chromosphere is not supported by the observations

Does CSR Influence firm performance indicators? evidence from Chinese pharmaceutical enterprises

This research is carried out in the backdrop of increasing product quality and environmental degradation scandals associated with Chinese Pharmaceuticals in recent years. We examine the data of 125 Chinese Pharmaceuticals between 2010-2016 to investigate the impact of overall CSR (Corporate Social Responsibility) performance as well as five unique aspects of CSR performance such as shareholders, employees, customers and suppliers, environmental practices, and the society to gauge the impact of these individual dimensions on firm’s financial performance. A mixed method approach is adopted where twenty experts from the Pharmaceutical industry firstly rate the importance of different stakeholder dimensions based on a five-point Lickert scale. Subsequently, the CSR scoring system is developed by incorporating the weighted average of experts’ scores and the performance of CSR indicators obtained from the Hexun CSR rating. The firm performance is measured by Tobin’s Q, ROA, ROE, and EPS ratios. The outcome of panel based regression models reveal that CSR has a positive and significant influence on firm’s financial performance. Moreover, although all the CSR dimensions relate positively to firm performance nonetheless environmental aspect of CSR has the most profound impact on firm performance followed by customer & suppliers, and employees. However, shareholders and society dimensions have relatively lesser influence on firm performance. These results imply that Chinese Pharmaceuticals shall further optimize their CSR performance as it can not only create a favorable brand image for various stakeholders but also results in superior financial performance.info:eu-repo/semantics/publishedVersio

Glioblastoma: is there any blood biomarker with true clinical relevance?

Glioblastoma (GBM) is the most frequent malignant primary brain tumor in adults, characterized by a highly aggressive, inflammatory and angiogenic phenotype. It is a remarkably heterogeneous tumor at several levels, including histopathologically, radiographically and genetically. The 2016 update of the WHO Classification of Tumours of the Central Nervous System highlighted molecular parameters as paramount features for the diagnosis, namely IDH1/2 mutations that distinguish primary and secondary GBM. An ideal biomarker is a molecule that can be detected/quantified through simple non- or minimally invasive methods with the potential to assess cancer risk; promote early diagnosis; increase grading accuracy; and monitor disease evolution and treatment response, as well as fundamentally being restricted to one aspect. Blood-based biomarkers are particularly attractive due to their easy access and have been widely used for various cancer types. A number of serum biomarkers with multiple utilities for glioma have been reported that could classify glioma grades more precisely and provide prognostic value among these patients. At present, screening for gliomas has no clinical relevance. This is because of the low incidence, the lack of sensitive biomarkers in plasma, and the observation that gliomas may develop apparently de novo within few weeks or months. To the best of our knowledge, there is no routine use of a serum biomarker for clinical follow-up. The purpose of this paper is to review the serum biomarkers described in the literature related to glioblastoma and their possible relationship with clinical features

Pertuzumab, trastuzumab, and chemotherapy in HER2-positive gastric/gastroesophageal junction cancer: end-of-study analysis of the JACOB phase III randomized clinical trial

Cáncer gástrico; Metastásico; PertuzumabCàncer gàstric; Metastàtic; PertuzumabGastric cancers; Metastatic; PertuzumabBackground Dual-targeted anti-HER2 therapy significantly improves outcomes in HER2-positive breast cancer and could be beneficial in other HER2-positive cancers. JACOB’s end-of study analyses aimed to evaluate the long-term efficacy and safety of pertuzumab plus trastuzumab and chemotherapy for previously untreated HER2-positive metastatic gastric or gastroesophageal junction cancer. Methods Eligible patients were randomized 1:1 to pertuzumab/placebo plus trastuzumab and chemotherapy every 3 weeks. Primary endpoint: overall survival (OS). Secondary endpoints included progression-free survival (PFS), objective response rate (ORR), duration of response (DoR), and safety. Results The intention-to-treat population comprised 388 patients in the pertuzumab arm and 392 in the placebo arm. The safety population comprised 385 and 388 patients, respectively. Median follow-up was ≥ 44.4 months. Median OS was increased by 3.9 months (hazard ratio 0.85 [95% confidence intervals, 0.72–0.99]) and median PFS by 1.3 months (hazard ratio 0.73 [95% confidence intervals, 0.62–0.85]) in the pertuzumab vs. the placebo arm. ORR was numerically higher (57.0% vs. 48.6%) and median DoR 1.8 months longer with pertuzumab treatment. There was a trend for more favorable hazard ratios in certain subgroups related to HER2 amplification/overexpression. Safety was comparable between arms, except for serious and grade 3–5 adverse events, and any-grade diarrhea, which were more frequent with pertuzumab. Conclusions JACOB did not meet its primary endpoint. Nonetheless, the study continues to demonstrate some, albeit limited, evidence of treatment activity and an acceptable safety profile for pertuzumab plus trastuzumab and chemotherapy in previously untreated HER2-positive metastatic gastric or gastroesophageal junction cancer after long-term follow-up.This study was sponsored by F. Hoffmann-La Roche Ltd. The sponsor, F. Hoffmann-La Roche Ltd, contributed to the design of this study. Data collected by the investigators were analyzed by statisticians at F. Hoffmann-La Roche Ltd. Authors employed by the study sponsor contributed to the conduct of the study, collection, management, analysis, and interpretation of the data, and preparation, review, and approval of the manuscript, as well as the decision to submit the manuscript for publication

Preliminary studies of the tardigrada communities from a polymetallic nodule area of the deep South China Sea

Knowledge about marine tardigrades from the South China Sea is very scarce, with only four species from shallow waters recorded to date. The present study investigated the structure and diversity of tardigrade communities from the deep sea (1517-1725 m) at 8 stations in a polymetallic nodule area of the northern South China Sea. A total of 151 arthrotardigrades were collected belonging to 11 genera (Angursa, Batillipes, Coronarctus, Euclavarctus, Exoclavarctus, Halechiniscus, Moebjergarctus, Raiarctus, Rhomboarctus, Tanarctus and Tholoarctus), representing 17 species. Two Angursa species (Angursa sp. 4 and Angursa sp. 3) were the most abundant (25.2% and 14.6%, respectively), followed by Moebjergarctus sp. (13.9%). Specimens were mostly (90.7%) distributed in the upper layer of the sandy-mud sediment (0-1 cm). The SIMPROF test showed that the composition of tardigrade communities at all stations was not significantly different. At different stations, the number of species, Shannon-Wiener diversity index and Pielou’s evenness index ranged from 4 to 10, 1.94 to 2.87, and 0.75 to 1.00, respectively. The average taxonomic distinctness (D+) ranged from 72.50 to 90.00, and the variation in taxonomic distinctness (L+) ranged from 316.67 to 1181.25. This study provides some basic information about the biodiversity of the marine tardigrade community in the South China Sea.info:eu-repo/semantics/publishedVersio

Towards Accurate Run-Time Hardware-Assisted Stealthy Malware Detection: A Lightweight, yet Effective Time Series CNN-Based Approach

According to recent security analysis reports, malicious software (a.k.a. malware) is rising at an alarming rate in numbers, complexity, and harmful purposes to compromise the security of modern computer systems. Recently, malware detection based on low-level hardware features (e.g., Hardware Performance Counters (HPCs) information) has emerged as an effective alternative solution to address the complexity and performance overheads of traditional software-based detection methods. Hardware-assisted Malware Detection (HMD) techniques depend on standard Machine Learning (ML) classifiers to detect signatures of malicious applications by monitoring built-in HPC registers during execution at run-time. Prior HMD methods though effective have limited their study on detecting malicious applications that are spawned as a separate thread during application execution, hence detecting stealthy malware patterns at run-time remains a critical challenge. Stealthy malware refers to harmful cyber attacks in which malicious code is hidden within benign applications and remains undetected by traditional malware detection approaches. In this paper, we first present a comprehensive review of recent advances in hardware-assisted malware detection studies that have used standard ML techniques to detect the malware signatures. Next, to address the challenge of stealthy malware detection at the processor’s hardware level, we propose StealthMiner, a novel specialized time series machine learning-based approach to accurately detect stealthy malware trace at run-time using branch instructions, the most prominent HPC feature. StealthMiner is based on a lightweight time series Fully Convolutional Neural Network (FCN) model that automatically identifies potentially contaminated samples in HPC-based time series data and utilizes them to accurately recognize the trace of stealthy malware. Our analysis demonstrates that using state-of-the-art ML-based malware detection methods is not effective in detecting stealthy malware samples since the captured HPC data not only represents malware but also carries benign applications’ microarchitectural data. The experimental results demonstrate that with the aid of our novel intelligent approach, stealthy malware can be detected at run-time with 94% detection performance on average with only one HPC feature, outperforming the detection performance of state-of-the-art HMD and general time series classification methods by up to 42% and 36%, respectively

Glucose metabolism and gene expression in juvenile zebrafish (Danio rerio) challenged with a high carbohydrate diet: effects of an acute glucose stimulus during late embryonic life

Knowledge on the role of early nutritional stimuli as triggers of metabolic pathways in fish is extremely scarce. The objective of the present study was to assess the long-term effects of glucose injection in the yolk (early stimulus) on carbohydrate metabolism and gene regulation in zebrafish juveniles challenged with a high-carbohydrate low-protein (HC) diet. Eggs were microinjected at 1 d post-fertilisation (dpf) with either glucose (2 M) or saline solutions. Up to 25 dpf, fish were fed a low-carbohydrate high-protein (LC) control diet, which was followed by a challenge with the HC diet. Survival and growth of 35 dpf juveniles were not affected by injection or the HC diet. Glucose stimulus induced some long-term metabolic changes in the juveniles, as shown by the altered expression of genes involved in glucose metabolism. On glycolysis, the expression levels of hexokinase 1 (HK1) and phosphofructokinase-6 (6PFK) were up-regulated in the visceral and muscle tissues, respectively, of juveniles exposed to the glucose stimulus, indicating a possible improvement in glucose oxidation. On gluconeogenesis, the inhibition of the expression levels of PEPCK in fish injected with glucose suggested lower production of hepatic glucose. Unexpectedly, fructose-1,6-bisphosphatase (FBP) expression was induced and 6PFK expression reduced by glucose stimulus, leaving the possibility of a specific regulation of the FBP-6PFK metabolic cycle. Glucose metabolism in juveniles was estimated using a [C-14]glucose tracer; fish previously exposed to the stimulus showed lower retention of [C-14]glucose in visceral tissue (but not in muscle tissue) and, accordingly, higher glucose catabolism, in comparison with the saline group. Globally, our data suggest that glucose stimulus at embryo stage has the potential to alter particular steps of glucose metabolism in zebrafish juveniles.Fundacao para a Ciencia e Tecnologia (FCT, Portugal) [PTDC/CVT/102481/2008]; FCT (Portugal) [SFRH/BD/74921/2010, SFRH/BPD/49051/2008]info:eu-repo/semantics/publishedVersio

Interrogating the Venom of the Viperid Snake Sistrurus catenatus edwardsii by a Combined Approach of Electrospray and MALDI Mass Spectrometry

The complete sequence characterization of snake venom proteins by mass spectrometry is rather challenging due to the presence of multiple isoforms from different protein families. In the present study, we investigated the tryptic digest of the venom of the viperid snake Sistrurus catenatus edwardsii by a combined approach of liquid chromatography coupled to either electrospray (online) or MALDI (offline) mass spectrometry. These different ionization techniques proved to be complementary allowing the identification a great variety of isoforms of diverse snake venom protein families, as evidenced by the detection of the corresponding unique peptides. For example, ten out of eleven predicted isoforms of serine proteinases of the venom of S. c. edwardsii were distinguished using this approach. Moreover, snake venom protein families not encountered in a previous transcriptome study of the venom gland of this snake were identified. In essence, our results support the notion that complementary ionization techniques of mass spectrometry allow for the detection of even subtle sequence differences of snake venom proteins, which is fundamental for future structure-function relationship and possible drug design studies