Miracle-dz/UniFAR-FTUs huggingface dataset:
Mice Deﬁcient in the Fused Homolog Do Not Exhibit Phenotypes Indicative of Perturbed Hedgehog Signaling during Embryonic Development

Hedgehog (Hh) signaling plays a major role in multiple aspects of embryonic development. To understand how a single Hh signal is capable of generating distinct readouts in Hh-responsive cells requires elucidation of the signal transduction cascade at the molecular level. Key components that mediate Hh signal transduction downstream of the receptor include Fused (Fu), Suppressor of fused (Sufu), and Costal-2 (Cos2) or the vertebrate homologs Kif27/Kif7. Studies with both invertebrates and vertebrates have led to a model in which a protein complex composed of Fu, Sufu, and Cos2 controls the processing, activity, and subcellular distribution of the Ci/Gli transcription factors responsible for Hh target gene activation. These converging results obtained with different species reafﬁrm the prevailing view of pathway conservation during evolution. Genetic studies of Fu, Sufu, and Kif27/Kif7 in mice are required to provide further veriﬁcation of Hh pathway conservation. To this end, we generated a gene-targeted allele of Fu in mice. Surprisingly, our analysis indicates that Fu -deﬁcient mice do not exhibit any embryonic phenotypes indicative of perturbed Hh signaling. This could be due to either functional redundancy or Hh pathway divergence and clearly indicates greater com- plexity of Hh signaling in vertebrates. Hedgehog blotting of tail tip DNA and were mated with C57BL/6, 129/Sv, 129/Ola, or Swiss-Webster females to maintain the Fu mutant allele in different genetic backgrounds. The majority of the analyses were performed in the Swiss- Webster mixed background. Homozygous mice were produced by crossing heterozygotes and identiﬁed by Southern blotting. Histology and in situ hybridization. Embryo collection, histological analysis, whole-mount in situ hybridization using digoxigenin-labeled probes, and section in situ hybridization using 33 P-labeled riboprobes were performed as previously described (59, 99).
13 C-Carrier DNA Shortens the Incubation Time Needed To Detect Benzoate-Utilizing Denitrifying Bacteria by Stable-Isotope Probing

The active bacterial community able to utilize benzoate under denitrifying conditions was elucidated in two coastal sediments using stable-isotope probing (SIP) and nosZ gene ampliﬁcation. The SIP method employed samples from Norfolk Harbor, Virginia, and a Long-Term Ecosystem Observatory (no. 15) off the coast of Tuckerton, New Jersey. The SIP method was modiﬁed by use of archaeal carrier DNA in the density gradient separation. The carrier DNA signiﬁcantly reduced the incubation time necessary to detect the 13 C-labeled bacterial DNA from weeks to hours in the coastal enrichments. No denitriﬁer DNA was found to contaminate the archaeal 13 C-carrier when [ 12 C]benzoate was used as a substrate in the sediment enrichments. Shifts in the activity of the benzoate-utilizing denitrifying population could be detected throughout a 21-day incubation. These results suggest that temporal analysis using SIP can be used to illustrate the initial biodegrader(s) in a bacterial population and to document the cross-feeding microbial community.
A NSGA-II application with different gene expression technologies integration

— Thanks to genetic expression, biomarkers related to much kind of diseases could be obtained. However, depending on the previous experimental constraints, these biomarkers can become too many, especially if they are intended to be used in a classification process. Multi-Objective Genetic Algorithm (MOGA) has been thought of as a suitable solution to get a trade-off among candidate biomarkers and classification accuracy. In this sense, genetic expression and Non Sorting Genetic Algorithm (NSGA) are combined in order to obtain the minimum number of possible genes that achieve the maximum classification accuracy. Only with a few genes, the classifier is expected to be more computationally efficient and faster than with all the genes, besides not endangering the final accuracy.
Characterisation of chronic hepatitis B virus infection in the UK and risk factors for hepatocellular carcinoma: a large electronic health record-based retrospective cohort study in the QResearch primary care database.

Background: Chronic hepatitis B infection (CHB) is the leading global cause of hepatocellular carcinoma (HCC), however the CHB population in the UK is not well characterised, and few investigations of risk factors for progression to HCC in multiethnic populations have been undertaken. Methods: We identified CHB individuals from the English primary care database QResearch, containing >35 million patient records. Individuals [≥]18 years with a record of CHB between 1999-2019 were included. Risk factors for HCC were investigated using Cox proportional hazards modelling. Results: We identified 8039 individuals with CHB in whom median follow-up was 3.87 years (interquartile range (IQR) 6.30 years). Most individuals (60.4%) were males of non-White ethnicities (>70%), and 44% were in the fifth (most deprived) Townsend deprivation quintile. In multivariable Cox proportional hazards models (undertaken in a subset of 7029 individuals with longitudinal data), 161 HCC cases occurred. Increased hazards of HCC associated with male sex (adjusted hazards ratio (aHR) 3.44, 95% Confidence Interval (95CI) 2.07-5.73), older age (for age groups 56-55 and [≥]66 years of age, compared to 26-35 years, aHRs 7.52 (95CI 4.14-13.67) and 11.89 (95CI 6.26-22.60) respectively), socioeconomic deprivation (aHR for fifth Townsend deprivation quintile 1.69, 95CI 1.01-2.84, compared to third), Caribbean ethnicity (aHR 3.32, 95CI 1.43-7.71, compared to White ethnicity), ascites (aHR 1.85, 95CI 1.02-3.36), cirrhosis (aHR 6.52, 95CI 4.54-9.37) and peptic ulcer disease (aHR 2.20, 95CI 1.39-3.49). Reduced HCC hazards associated with statin use (aHR 0.47, 95CI 0.22-0.99). Conclusions: We identified novel risk factors for HCC in an ethnically diverse and socioeconomically deprived population of adults living with CHB.
Costs related to serious road injuries

Costs related to serious injuries constitute an important input variable to assess the cost-efficiency of road safety measures, which is one of the objectives of the H2020 EU project SafetyCube. A survey collecting crash costs in European countries showed considerable variation in the costs related to serious injuries. The applied methodology to estimate human costs appeared to have a large influence. Other potential explanations are the applied definition, the registration procedure of crashes with serious injuries and the cost components that are included. Detailed analyses of medical costs and production loss showed the importance of assessing medical costs on the long term and taking into account the variation of these costs for different subgroups of traffic victims. To estimate monetary values for human costs, most countries use the Willingness To Pay method. While having a sound theoretical background, this method is rather limited in the specification of injuries. The use of Quality Adjusted Life Years (QALYs) gives the possibility to provide values for a larger diversity of injury types. of after
Guaranteed cost control of linear uncertain singular time-delay systems

The guaranteed cost control problem via memoryless state feedback is studied in this paper for a class of linear singular time-delay systems with norm-bounded time-varying parametric uncertainty and a given quadratic cost function. First, one sufficient condition for the stability of singular time-delay system is got. Then the sufficient conditions for the existence of guaranteed cost controller are given in terms of linear matrix inequalities (LMIs). Furthermore, one simple example is shown to illustrate the application of the proposed method.
The precision of PiCCO (cid:2) measurements in hypothermic post-cardiac arrest patients

Summary The aim of the present study was to determine the precision of the PiCCO (cid:2) system for post-cardiac arrest patients who underwent therapeutic hypothermia. The precision of the measurements for cardiac output, global end-diastolic volume, extravascular lung water and the pulmonary vascular permeability index was assessed using the least signiﬁcant change; this was regarded as precise when less than 15%. A total of 462 measurement sets were prospectively performed on 88 patients following successful resuscitation after cardiac arrest. Using the mean value of three injections for a measurement, the least signiﬁcant change for the cardiac output, global end-diastolic volume, extravascular lung water and pulmonary vascular permeability index measurements were found to be 7.8%, 8.5%, 7.8% and 12.1%, respectively. No signiﬁcant differences between hypothermia (n = 150) and non-hypothermia (n = 312) were found. The PiCCO-derived variables were found to be precise for post-cardiac arrest patients even under conditions of varying body temperature.
Hermes: Accelerating Long-Latency Load Requests via Perceptron-Based Off-Chip Load Prediction

Long-latency load requests continue to limit the performance of modern high-performance processors. To increase the latency tolerance of a processor, architects have primarily relied on two key techniques: sophisticated data prefetchers and large on-chip caches. In this work, we show that: (1) even a sophisticated state-of-the-art prefetcher can only predict half of the off-chip load requests on average across a wide range of workloads, and (2) due to the increasing size and complexity of on-chip caches, a large fraction of the latency of an off-chip load request is spent accessing the on-chip cache hierarchy to solely determine that it needs to go off-chip. The goal of this work is to accelerate off-chip load requests by removing the on-chip cache access latency from their critical path. To this end, we propose a new technique called Hermes, whose key idea is to: (1) accurately predict which load requests might go off-chip, and (2) speculatively fetch the data required by the predicted off-chip loads directly from the main memory, while also concurrently accessing the cache hierarchy for such loads. To enable Hermes, we develop a new lightweight, perceptron-based off-chip load prediction technique that learns to identify off-chip load requests using multiple program features (e.g., sequence of program counters, byte offset of a load request). For every load request generated by the processor, the predictor observes a set of program features to predict whether or not the load would go off-chip. If the load is predicted to go off-chip, Hermes issues a speculative load request directly to the main memory controller once the load’s physical address is generated. If the prediction is correct, the load eventually misses the cache hierarchy and waits for the ongoing speculative load request to finish, and thus Hermes completely hides the on-chip cache hierarchy access latency from the critical path of the correctly-predicted off-chip load. Our extensive evaluation using a wide range of workloads shows that Hermes provides consistent performance improvement on top of a state-of-the-art baseline system across a wide range of configurations with varying core count, main memory bandwidth, high-performance data prefetchers, and on-chip cache hierarchy access latencies, while incurring only modest storage overhead. The source code of Hermes is freely available at: https://github.com/CMU-SAFARI/Hermes.
Epac2 Mediates Cardiac (cid:533) 1 -Adrenergic Dependent SR Ca 2+ Leak and Arrhythmia

: Background — (cid:533) -adrenergic receptor ( (cid:533) -AR) activation can provoke cardiac arrhythmias mediated by cAMP-dependent alterations of Ca 2+ signaling. However cAMP can activate both PKA and an Exchange protein directly activated by cAMP ( Epac ) but their functional interaction is unclear. In heart selective Epac activation can induce potentially arrhythmogenic sarcoplasmic reticulum (SR) Ca 2+ release that involves CaMKII effects on the ryanodine receptor (RyR). Methods and Results — We tested whether physiological (cid:533) -AR activation causes Epac-mediated SR Ca 2+ leak and arrhythmias, whether it requires Epac1 vs. Epac2, (cid:533) 1 -AR vs. (cid:533) 2 -AR and CaMKII (cid:303) -dependent phosphorylation of RyR2-S2814. We used knockout mice for Epac1, Epac2 or both (DKO). All knockouts exhibited unaltered basal cardiac function, Ca 2+ handling and hypertrophy in response to pressure overload. However, SR Ca 2+ leak induced by the specific Epac activator 8-CPT in wild-type was abolished in Epac2-KO and DKO, but unaltered in Epac1-KO. (cid:533) -AR-induced arrhythmias were also less inducible in Epac2-KO vs. wild-type. (cid:533) AR activation with PKA inhibition, mimicked 8-CPT effects on SR Ca 2+ leak, and was prevented by blockade of (cid:533) 1 -AR but not (cid:533) 2 -AR. CaMKII inhibition (KN93) and genetic ablation of either CaMKII (cid:303) or CaMKII phosphorylation on RyR2-S2814 prevented 8-CPT-induced SR Ca 2+ leak. phosphorylation of RyR2-S2814. This pathway contributes to (cid:533) -AR-induced arrhythmias and reduced cardiac function. phosphomimetic RyR2-S2814D mice. In conclusion, our work indicates that (cid:533) (cid:1187) -AR activates Epac2-dependent SR Ca 2+ leak and arrhythmia via CaMKII (cid:303) -dependent phosphorylation of RyR2-S2814. These findings give new insights into Epac physiology and pathology. Indeed, Epac seems non-essential for baseline cardiac function, and does not significantly attenuate the acute inotropic response to potent (cid:533) -AR activation or the early hypertrophic response to pressure overload. However, we demonstrate a specific role for the Epac2 isoform in mediating PKA-independent SR Ca 2+ leak via (cid:533) (cid:1187) -AR causing RyR-S2814 phosphorylation by CaMKII (cid:303) and SR Ca 2+ leak. Further investigations understand why both Epac and PKA are activated by (cid:533) 1 -AR stimulation and the role of Epac1 (nuclear signaling vs. RyR function or transition to HF). isissolololatatatededed rrratatat
The safety and efficacy of SDLT-2 (Sodium-glucose co-transporter 2) inhibitor versus placebo in the treatment of heart failure in patients with or without T2DM (Type 2 diabetes mellitus): A Systemic Review and Meta-analysis. CURRENT STATUS: POSTED

Background Sodium-glucose co-transporter 2 (SGLT2) inhibitor which is a type of drug used for the treatment of diabetes mellitus, has been reported by many trials that it could be beneficial for patients with established heart failure. A meta-analysis on this subject could obtain more reliable estimates of the efficacy and safety outcomes. A systematic review and meta-analysis of randomized, placebo-controlled trials of SGLT2 inhibitor in patients with heart failure was conducted. We searched PubMed, Cochrane Library, and Web of Science for trials published from inception to March, 2018. PRISMA guidelines (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) was used to conduct the review. For quality assessment of included studies. The methodological quality of the included trials was assessed using the Cochrane tool for assessing randomized clinical trials (RCT). Efficacy outcomes included hospitalization for heart failure and all-cause death. Safety outcomes consisted of serious adverse event (SAE) and volume depletion. (aged female
The All Seeing Eye and Apate: Bridging the Gap between IDS and Honeypots

—Timing attacks are a challenge for current intrusion detection solutions. Timing attacks are dangerous for web applications because they may leak information about side channel vulnerabilities. This paper presents a methodology that is especially good at detecting timing attacks. Unlike current solutions, the proposed Intrusion Detection System uses a huge number of sensors for vulnerability detection. Honeypots are used in IT Security to detect and gather information about ongoing intrusions by presenting an interactive system as attractive target to an attacker. The longer an attacker interacts with a honeypot, the more valuable information about the attack can be collected. Honeypots should appear like a valuable target to motivate an attacker. This paper presents, in addition to the possibilities of timing attack vulnerabilities, a novel way to inject honeypot and analysis capabilities in any software based on x64 or i386 architecture. It fulﬁlls two basic requirements: it can be injected into machine code without the need of recompilation and it can be conﬁgured during runtime. This means the honeypot is able to change the behavior of any function during runtime. The concept uses sophisticated stealth technologies to provide stealthiness. In conclusion, the research presents a novel way to detect side channel vulnerabilities and an inbuilt hypervisor to provide conﬁgurable honeypot capabilities to explore these vulnerabilities to an attacker. The proposed solution in this paper offers a highly conﬁgurable injection technology, which can change the behavior of any function without the need of recompilation or even reinstallation. It is able to provide these capabilities in the kernel or userland of actual *Nix systems.
Microwave subsurface remote sensing in the Negev Desert: monitoring of soil water-content

We report the use of the microwave remote sensing as a technique with great potential for the mapping of subsurface properties including the monitoring of soil water conditions. Remote sensing experiments with microwave instrumentation were conducted in the Negev desert in Israel. The remote sensors used were a P-band (68 cm, 441 MHz) scatterometer and an ERS-2 C-band (5.3 cm, 5.7 GHz) SAR (synthetic aperture radar) along with the collection of ground truth data such as volumetric and gravimetric soil water-content, surface roughness and dielectric measurements. Corner reflectors in the field were used for calibration and geo-rectification of the SAR data. The results of the microwave experiments are in a good agreement with the developed theoretical models that take into account the effects of the random surface roughness. The optical modelling of microwave processes is presented as a tool for developing the physical basis for empirical studies. This practice simplifies testing theoretical predictions and reduces the immense cost of running field and laboratory measurements in the microwave range.
Pea and seeds as protein sources in growing-finishing heavy pig diets: effect on growth performance, carcass characteristics and on fresh and seasoned Parma ham quality

The effect of pea and faba bean inclusion in growing-finishing heavy pig diets was evaluated. The following iso-lysinic and iso-energetic diets offered to the pigs in three phases (40-80; 80-120; 120-160 kg) were compared: CTR, control diet with soybean meal (SBM) as protein source; RP, CTR diet where pea replaced SBM; RF, CTR diet where faba bean replaced SBM. 126 animals were randomly distributed in 3 homogeneous groups with 42 animals each (7 pens with 6 animals each per treatment). The RP and RF diets did not negatively affect the carcass characteristics both of the pigs slaughtered at the conventional weight (127.5 kg) and heavy pigs (158.5 kg). The pigs fed the RP and RF diets ate similarly to the pigs fed the CTR overall the trial but RF pigs grew better than CTR animals. The subcutaneous fat of the fresh hams destined for Parma ham production and obtained from pigs fed RP diet had a higher omega 3 fatty acid percentage. Moreover, the RP and RF diets resulted in fat with better omega 3/omega 6 ratio compared with CTR. All the fat samples had iodine numbers within the limit value (70) reported by the Production Disciplinary of Parma ham. No treatment effect was found on the analytical and sensorial characteristics of the Parma hams, except for the aged taste which was more intense in the hams obtained from pigs fed the RF diet. These results indicate that pea and faba bean may be used as an alternative to imported SBM.
Capital Goods for the Common Good

This thesis utilises the second fundamental law of capitalism in order to study the development of income inequality in Sweden, from the start of the 19 th century to the beginning of the 21 st century. The law is studied from a historical perspective (examination of national accounts as time series), and empirically analysed (regression analysis). The results retrieved indicate that the income diverging force of savings exceed the income converging force of growth (via income, innovation, and education). This means that income inequality is predicted to increase. The main conclusion drawn is that choosing whether to save or not on behalf of every individual affects the capital stock of the aggregate economy. When individual savings pile up the aggregate capital stock increases, and if this increase surpasses the growth in national income the capital-to-income ratio increases. This ratio is in a sense a measure of how capitalistic the country is. More income inequality is expected to be found the higher this ratio gets.
Hepatocyte Nuclear Factor 3 b Is Involved in Pancreatic b -Cell-Speciﬁc Transcription of the pdx-1 Gene

The mammalian homeobox gene pdx-1 is expressed in pluripotent precursor cells in the dorsal and ventral pancreatic bud and duodenal endoderm, which will produce the pancreas and the rostral duodenum. In the adult, pdx-1 is expressed principally within insulin-secreting pancreatic islet b cells and cells of the duodenal epithelium. Our objective in this study was to localize sequences within the mouse pdx-1 gene mediating selective expression within the islet. Studies of transgenic mice in which a genomic fragment of the mouse pdx-1 gene from kb 2 4.5 to 1 8.2 was used to drive a b -galactosidase reporter showed that the control sequences sufﬁcient for appropriate developmental and adult speciﬁc expression were contained within this region. Three nuclease-hypersensitive sites, located between bp 2 2560 and 2 1880 (site 1), bp 2 1330 and 2 800 (site 2), and bp 2 260 and 1 180 (site 3), were identiﬁed within the 5 * -ﬂanking region of the endogenous pdx-1 gene. Pancreatic b -cell-speciﬁc expression was shown to be controlled by sequences within site 1 from an analysis of the expression pattern of various pdx-1 –herpes simplex virus thymidine kinase promoter expression constructs in transfected b -cell and non- b -cell lines. Furthermore, we also established that this region was important in vivo by demonstrating that expression from a site 1-driven b -galactosidase reporter construct was directed to islet b -cells in transgenic mice. The activity of the site 1-driven constructs was reduced substantially in b -cell lines by mutating a hepatocyte nuclear factor 3 (HNF3)-like site located between nucleotides 2 2007 and 2 1996. Gel shift analysis indicated that HNF3 b present in islet b cells binds to this element. Immunohistochemical studies revealed that HNF3 b was present within the nuclei of almost all islet b cells and subsets of pancreatic acinar cells. Together, these results suggest that HNF3 b , a key regulator of endodermal cell lineage development, plays an essential role in the cell-type-speciﬁc transcription of the pdx-1 gene in the pancreas.