Miracle-dz/UniFAR-FTUs huggingface dataset:
Information Security Risks Assessment: A Case Study

Owing to recorded incidents of Information technology inclined organisations failing to respond effectively to threat incidents, this project outlines the benefits of conducting a comprehensive risk assessment which would aid proficiency in responding to potential threats. The ultimate goal is primarily to identify, quantify and control the key threats that are detrimental to achieving business objectives. This project carries out a detailed risk assessment for a case study organisation. It includes a comprehensive literature review analysing several professional views on pressing issues in Information security. In the risk register, five prominent assets were identified in respect to their owners. The work is followed by a qualitative analysis methodology to determine the magnitude of the potential threats and vulnerabilities. Collating these parameters enabled the valuation of individual risk per asset, per threat and vulnerability. Evaluating a risk appetite aided in prioritising and determining acceptable risks. From the analysis, it was deduced that human being posed the greatest Information security risk through intentional/ unintentional human error. In conclusion, effective control techniques based on defence in-depth were devised to mitigate the impact of the identified risks from risk register.
cAMP-dependent activation of the Rac guanine exchange factor P-REX1 by type I protein kinase A (PKA) regulatory subunits

Regulatory subunits of protein kinase A (PKA) inhibit its kinase subunits. Intriguingly, their potential as cAMP-dependent signal transducers remains uncharacterized. We recently reported that type I PKA regulatory subunits (RIα) interact with phosphatidylinositol 3,4,5-trisphosphate–dependent Rac exchange factor 1 (P-REX1), a chemotactic Rac guanine exchange factor (RacGEF). Because P-REX1 is known to be phosphorylated and inhibited by PKA, its interaction with RIα suggests that PKA regulatory and catalytic subunits may fine-tune P-REX1 activity or those of its target pools. Here, we tested whether RIα acts as a cAMP-dependent factor promoting P-REX1–mediated Rac activation and cell migration. We observed that Gs-coupled EP2 receptors indeed promote endothelial cell migration via RIα-activated P-REX1. Expression of the P-REX1–PDZ1 domain prevented RIα/P–REX1 interaction, P-REX1 activation, and EP2-dependent cell migration, and P-REX1 silencing abrogated RIα-dependent Rac activation. RIα-specific cAMP analogs activated P-REX1, but lost this activity in RIα-knockdown cells, and cAMP pulldown assays revealed that P-REX1 preferentially interacts with free RIα. Moreover, purified RIα directly activated P-REX1 in vitro. We also found that the RIα CNB-B domain is critical for the interaction with P-REX1, which was increased in RIα mutants, such as the acrodysostosis-associated mutant, that activate P-REX1 at basal cAMP levels. RIα and Cα PKA subunits targeted distinct P-REX1 molecules, indicated by an absence of phosphorylation in the active fraction of P-REX1. This was in contrast to the inactive fraction in which phosphorylated P-REX1 was present, suggesting co-existence of dual stimulatory and inhibitory effects. We conclude that PKA's regulatory subunits are cAMP-dependent signal transducers.
Maintenance and reappearance of extremely divergent intra-host HIV-1 variants

Abstract Understanding genetic variation in human immunodeficiency virus (HIV) is clinically and immunologically important for patient treatment and vaccine development. We investigated the longitudinal intra-host genetic variation of HIV in over 3,000 individuals in the US National HIV Surveillance System with at least four reported HIV-1 polymerase (pol) sequences. In this population, we identified 149 putative instances of superinfection (i.e. an individual sequentially infected with genetically divergent, polyphyletic viruses). Unexpectedly, we discovered a group of 240 individuals with consecutively sampled viral strains that were >0.015 substitutions/site divergent, despite remaining monophyletic in the phylogeny. Viruses in some of these individuals had a maximum genetic divergence approaching that found between two random, unrelated HIV-1 subtype-B pol sequences within the US population. Individuals with these highly divergent viruses tended to be diagnosed nearly a decade earlier in the epidemic than people with superinfection or virus with less intra-host genetic variation, and they had distinct transmission risk factor profiles. To better understand this genetic variation in cases with extremely divergent, monophyletic viruses, we performed molecular clock phylogenetic analysis. Our findings suggest that, like Hepatitis C virus, extremely divergent HIV lineages can be maintained within an individual and reemerge over a period of years.
Molecular phylogenetics supports a clade of red algal parasites retaining native plastids: taxonomy and terminology revised

Parasitism is a life strategy that has repeatedly evolved within the Florideophyceae. Historically, the terms adelphoparasite and alloparasite have been used to distinguish parasites based on the relative phylogenetic relationship of host and parasite. However, analyses using molecular phylogenetics indicate that nearly all red algal parasites infect within their taxonomic family, and a range of relationships exist between host and parasite. To date, all investigated adelphoparasites have lost their plastid, and instead, incorporate a host derived plastid when packaging spores. In contrast, a highly reduced plastid lacking photosynthesis genes was sequenced from the alloparasite Choreocolax polysiphoniae. Here we present the complete Harveyella mirabilis plastid genome, which has also lost genes involved in photosynthesis, and a partial plastid genome from Leachiella pacifica. The H. mirabilis plastid shares more synteny with free-living red algal plastids than that of C. polysiphoniae. Phylogenetic analysis demonstrates that C. polysiphoniae, H. mirabilis, and L. pacifica form a robustly supported clade of parasites, which retain their own plastid genomes, within the Rhodomelaceae. We therefore transfer all three genera from the exclusively parasitic family, Choreocolacaceae, to the Rhodomelaceae. Additionally, we recommend applying the terms archaeplastic parasites (formerly alloparasites), and neoplastic parasites (formerly adelphoparasites) to distinguish red algal parasites using a biological framework rather than taxonomic affiliation with their hosts.
Embedding Training Within Warnings Improves Skills of Identifying Phishing Webpages

Objective: Evaluate the effectiveness of training embedded within security warnings to identify phishing webpages. Background: More than 20 million malware and phishing warnings are shown to users of Google Safe Browsing every week. Substantial click-through rate is still evident, and a common issue reported is that users lack understanding of the warnings. Nevertheless, each warning provides an opportunity to train users about phishing and how to avoid phishing attacks. Method: To test use of phishing-warning instances as opportunities to train users’ phishing webpage detection skills, we conducted an online experiment contrasting the effectiveness of the current Chrome phishing warning with two training-embedded warning interfaces. The experiment consisted of three phases. In Phase 1, participants made login decisions on 10 webpages with the aid of warning. After a distracting task, participants made legitimacy judgments for 10 different login webpages without warnings in Phase 2. To test the long-term effect of the training, participants were invited back a week later to participate in Phase 3, which was conducted similarly as Phase 2. Results: Participants differentiated legitimate and fraudulent webpages better than chance. Performance was similar for all interfaces in Phase 1 for which the warning aid was present. However, training-embedded interfaces provided better protection than the Chrome phishing warning on both subsequent phases. Conclusion: Embedded training is a complementary strategy to compensate for lack of phishing webpage detection skill when phishing warning is absent. Application: Potential applications include development of training-embedded warnings to enable security training at scale.
hnRNP L‐dependent protection of normal mRNAs from NMD subverts quality control in B cell lymphoma

The human nonsense‐mediated mRNA decay pathway (NMD) performs quality control and regulatory functions within complex post‐transcriptional regulatory networks. In addition to degradation‐promoting factors, efficient and accurate detection of NMD substrates involves proteins that safeguard normal mRNAs. Here, we identify hnRNP L as a factor that protects mRNAs with NMD‐inducing features including long 3′UTRs. Using biochemical and transcriptome‐wide approaches, we provide evidence that the susceptibility of a given transcript to NMD can be modulated by its 3′UTR length and ability to recruit hnRNP L. Integrating these findings with the previously defined role of polypyrimidine tract binding protein 1 in NMD evasion enables enhanced prediction of transcript susceptibility to NMD. Unexpectedly, this system is subverted in B cell lymphomas harboring translocations that produce BCL2:IGH fusion mRNAs. CRISPR/Cas9 deletion of hnRNP L binding sites near the BCL2 stop codon reduces expression of the fusion mRNAs and induces apoptosis. Together, our data indicate that protection by hnRNP L overrides the presence of multiple 3′UTR introns, allowing these aberrant mRNAs to evade NMD and promoting BCL2 overexpression and neoplasia.
Metformin or Acarbose Treatment Significantly Reduced Albuminuria in Patients with Newly Diagnosed Type 2 Diabetes Mellitus and Low-Grade Albuminuria

Background A urine albumin to creatinine ratio (UACR) >30 mg/g is considered to represent albuminuria, but in type 2 diabetes mellitus, even low-grade albuminuria is associated with increased risk of cardiovascular disease. This study aimed to investigate the effects of metformin and acarbose treatment on urine albumin excretion in Chinese patients with newly diagnosed diabetes and low-grade albuminuria. Material/Methods Patients with newly diagnosed diabetes (n=589) were divided into Group I (with a baseline UACR <10 mg/g) (n=331), and Group II (with a baseline UACR of 10–30 mg/g) (n=258). Following 48 weeks of treatment with metformin or acarbose, the UACR, blood pressure, body mass index (BMI), blood glucose, lipid profiles, and homeostasis model assessment of insulin resistance (HOMA-IR) were compared. Results Baseline diastolic blood pressure, levels of blood glucose and low-density lipoprotein cholesterol (LDL-C), and HOMA-IR were significantly increased in Group II compared with Group I (all P<0.05). In Group II, both metformin and acarbose treatment significantly reduced the UACR (P<0.001); the effect was significantly greater following acarbose treatment compared with metformin treatment (P<0.05). In Group I, neither metformin nor acarbose treatment significantly changed the UACR, but both Group I and Group II showed a significant and comparable reduction in BMI, blood glucose, blood pressure, and HOMA-IR. Conclusions In a group of Chinese patients with newly diagnosed type 2 diabetes mellitus, low-grade albuminuria (baseline UACR of 10–30 mg/g) was associated with metabolic factors before treatment. Treatment with either metformin or acarbose significantly reduced albumin excretion.
Long noncoding RNA SMRG regulates Drosophila macrochaetes by antagonizing scute through E(spl)mβ

ABSTRACT It is obvious that the majority of cellular transcripts are long noncoding RNAs (lncRNAs). Although studies suggested that lncRNAs participate in many biological processes through diverse mechanisms, however, little is known about their effects on epidermal mechanoreceptors. Here, we identified one novel Drosophila lncRNA, Scutellar Macrochaetes Regulatory Gene (SMRG), which regulates scutellar macrochaetes that act as mechanoreceptors by antagonizing the proneural gene scute (sc), through the repressor Enhancer-of-split mβ (E(spl)mβ). SMRG deficiency induced supernumerary scutellar macrochaetes and simultaneously a high sc RNA level in the adult thorax. Genetically, sc overexpression enhanced this supernumerary phenotype, while heterozygous sc mutant rescued this phenotype, both of which were mediated by E(spl)mβ. At the molecular level, SMRG recruited E(spl)mβ to the sc promoter region, which in turn suppressed sc expression. Our work presents a novel function of lncRNA and offers insights into the molecular mechanism underlying mechanoreceptor development.
NGF-Dependent Changes in Ubiquitin Homeostasis Trigger Early Cholinergic Degeneration in Cellular and Animal AD-Model

Basal forebrain cholinergic neurons (BFCNs) depend on nerve growth factor (NGF) for their survival/differentiation and innervate cortical and hippocampal regions involved in memory/learning processes. Cholinergic hypofunction and/or degeneration early occurs at prodromal stages of Alzheimer’s disease (AD) neuropathology in correlation with synaptic damages, cognitive decline and behavioral disability. Alteration(s) in ubiquitin-proteasome system (UPS) is also a pivotal AD hallmark but whether it plays a causative, or only a secondary role, in early synaptic failure associated with disease onset remains unclear. We previously reported that impairment of NGF/TrkA signaling pathway in cholinergic-enriched septo-hippocampal primary neurons triggers “dying-back” degenerative processes which occur prior to cell death in concomitance with loss of specific vesicle trafficking proteins, including synapsin I, SNAP-25 and α-synuclein, and with deficit in presynaptic excitatory neurotransmission. Here, we show that in this in vitro neuronal model: (i) UPS stimulation early occurs following neurotrophin starvation (-1 h up to -6 h); (ii) NGF controls the steady-state levels of these three presynaptic proteins by acting on coordinate mechanism(s) of dynamic ubiquitin-C-terminal hydrolase 1 (UCHL-1)-dependent (mono)ubiquitin turnover and UPS-mediated protein degradation. Importantly, changes in miniature excitatory post-synaptic currents (mEPSCs) frequency detected in -6 h NGF-deprived primary neurons are strongly reverted by acute inhibition of UPS and UCHL-1, indicating that NGF tightly controls in vitro the presynaptic efficacy via ubiquitination-mediated pathway(s). Finally, changes in synaptic ubiquitin and selective reduction of presynaptic markers are also found in vivo in cholinergic nerve terminals from hippocampi of transgenic Tg2576 AD mice, even from presymptomatic stages of neuropathology (1-month-old). By demonstrating a crucial role of UPS in the dysregulation of NGF/TrkA signaling on properties of cholinergic synapses, these findings from two well-established cellular and animal AD models provide novel therapeutic targets to contrast early cognitive and synaptic dysfunction associated to selective degeneration of BFCNs occurring in incipient early/middle-stage of disease.
Changes in potential mammal diversity in national parks and their implications for conservation

Abstract Observed species richness (OSR) is a widely used and well-studied biodiversity metric. However, non-observed species in favorable ecosystems are also relevant. Two metrics that include observed and potential species were recently defined: potential biodiversity (hereafter potential species richness—PSR) and geometric mean of favorabilities (GMF). We used these metrics to evaluate the national park network of mainland Spain at two time periods (2002 and 2015), using terrestrial mammals on a UTM 100-km2 grid. PSR and GMF are based on the favorability function, a species distribution model that assesses how favorable an area is for the presence of a species, over and above its prevalence in the study area. For each park and for the whole network, we calculated the mean and sum of OSR, PSR, and GMF in each time period, as well as changes between periods. OSR and PSR were higher inside than outside the park network in both time periods. Thus, although the network covers a very small proportion of the country, it performs well for the representation of mammal species and their favorable areas. However, mean PSR was lower in 2015 than in 2002 inside the national park network, whereas the opposite was the case outside the network. Mountainous Parks generally not only concentrated highly favorable areas for mammals, but they also showed less favorable areas in 2015 compared to 2002, although the reduction was moderate to low. This is a result to consider for future analyses because if the tendency increases, it may have consequences for the conservation of mammals and for the adequacy of the national park network.
Combining Ensemble Learning with a Fragment-Based Topological Approach To Generate New Molecular Diversity in Drug Discovery: In Silico Design of Hsp90 Inhibitors

Machine learning methods have revolutionized modern science, providing fast and accurate solutions to multiple problems. However, they are commonly treated as “black boxes”. Therefore, in important scientific fields such as medicinal chemistry and drug discovery, machine learning methods are restricted almost exclusively to the task of performing predictions of large and heterogeneous data sets of chemicals. The lack of interpretability prevents the full exploitation of the machine learning models as generators of new chemical knowledge. This work focuses on the development of an ensemble learning model for the prediction and design of potent dual heat shock protein 90 (Hsp90) inhibitors. The model displays accuracy higher than 80% in both training and test sets. To use the ensemble model as a generator of new chemical knowledge, three steps were followed. First, a physicochemical and/or structural interpretation was provided for each molecular descriptor present in the ensemble learning model. Second, the term “pseudolinear equation” was introduced within the context of machine learning to calculate the relative quantitative contributions of different molecular fragments to the inhibitory activity against the two Hsp90 isoforms studied here. Finally, by assembling the fragments with positive contributions, new molecules were designed, being predicted as potent Hsp90 inhibitors. According to Lipinski’s rule of five, the designed molecules were found to exhibit potentially good oral bioavailability, a primordial property that chemicals must have to pass early stages in drug discovery. The present approach based on the combination of ensemble learning and fragment-based topological design holds great promise in drug discovery, and it can be adapted and applied to many different scientific disciplines.
Health beliefs and chronic illnesses of refugees: a systematic review

ABSTRACT Objective: To evaluate beliefs, and attitudes about health of refugees with chronic conditions such as diabetes mellitus type 2, hypertension, chronic obstructive pulmonary disease, and posttraumatic stress disorder and the consequent effects on self-care in comparison to resident populations. Design: A systematic review methodology was used. PubMed, Embase, PsycINFO and CINAHL databases were searched for relevant articles. The main terms analysed were health beliefs, chronic conditions and refugee populations. From 844 articles, 45 were retained for further assessment, and finally 5 met the inclusion criteria. Results: Differences in the health beliefs, attitudes and self-care management approaches of refugees compared to resident populations were identified in two studies. The remaining three papers did not make comparisons between the refugees and the resident population, nor did they specifically explore the refugees’ health beliefs. Of the five studies, three were carried out in Sweden and two in the US. Refugees who have poorer mental and physical health as well as higher prevalence of chronic diseases than the populations among which they resettle seem to lack the knowledge about their illness, symptoms and self-management and thus are less able to control their chronic conditions. Conclusion: The findings highlighted the deficiency in the literature of studies which examine health beliefs and attitudes of minority groups such as refugees who have chronic conditions. The findings also gave insight to the need for a distinctive understanding of refugee health and the management of chronic conditions in comparison to other non-refugee migrant groups. Further research is needed to fully understand the differences between refugees and local populations in terms health beliefs, chronic disease and self-management.
Effects of litter floor access and inclusion of experienced hens in aviary housing on floor eggs, litter condition, air quality, and hen welfare

ABSTRACT With different cage‐free (CF) housing styles and management schemes, retailers have developed their own CF criteria. One highly debated aspect is if hens may be kept inside the system for part of the day—during the first few hours after lights‐on. Research is lacking regarding the impacts of such a practice on hen welfare, incidence of eggs laid on the litter floor, litter condition, and air quality. This 14‐mo field study was conducted to help assess such impacts. Hens (Dekalb White) in an aviary house (50,000‐hen nominal capacity) were allowed to have full litter access (FLA) vs. part‐time litter access (PLA) from 10:50 am to 9:00 pm, coupled with the absence or presence of experienced hens (1.5% of the population), hence a 2 × 2 factorial arrangement. The measured variables included a) incidence of floor eggs, b) percentage of birds remaining on litter floor at night, c) mortality, d) body weight (BW) and BW uniformity, e) litter condition (depth, moisture content, texture, amount removed, and bacteria concentration), f) environmental conditions, and g) welfare conditions (10 variables). Compared to FLA, PLA had a significantly lower incidence of floor eggs (1.4 ± 0.1 vs. 12.6 ± 1.1 eggs per hen housed as of 76 weeks of age (WOA), i.e., approximately 89% reduction), less manure deposition on the floor (0.53 ± 0.02 vs. 1.05 ± 0.04 kg/100 hens/d, dry basis, i.e., approximately 50% reduction), and lower ammonia concentrations due to drier litter (averaging 22% lower). Inclusion of 1.5% experienced hens in the young flock did not show benefit of reducing the incidence of floor eggs (P = 0.48). The percentage of hens remaining on the floor at night was low (< 0.01%) in all cases from 24 WOA onward. No differences were detected between FLA and PLA in hen welfare conditions, mortality, BW, BW uniformity, bacteria concentration in the litter, air temperature, or relative humidity.
Cellular senescence: a promising strategy for cancer therapy

Cellular senescence, a permanent state of cell cycle arrest, is believed to have originally evolved to limit the proliferation of old or damaged cells. However, it has been recently shown that cellular senescence is a physiological and pathological program contributing to embryogenesis, immune response, and wound repair, as well as aging and age-related diseases. Unlike replicative senescence associated with telomere attrition, premature senescence rapidly occurs in response to various intrinsic and extrinsic insults. Thus, cellular senescence has also been considered suppressive mechanism of tumorigenesis. Current studies have revealed that therapy-induced senescence (TIS), a type of senescence caused by traditional cancer therapy, could play a critical role in cancer treatment. In this review, we outline the key features and the molecular pathways of cellular senescence. Better understanding of cellular senescence will provide insights into the development of powerful strategies to control cellular senescence for therapeutic benefit. Lastly, we discuss existing strategies for the induction of cancer cell senescence to improve efficacy of anticancer therapy.