A Comparative Performance Analysis of Explainable Machine Learning Models With And Without RFECV Feature Selection Technique Towards Ransomware Classification

Ransomware has emerged as one of the major global threats in recent days. The alarming increasing rate of ransomware attacks and new ransomware variants intrigue the researchers in this domain to constantly examine the distinguishing traits of ransomware and refine their detection or classification strategies. Among the broad range of different behavioral characteristics, the trait of Application Programming Interface (API) calls and network behaviors have been widely utilized as differentiating factors for ransomware detection, or classification. Although many of the prior approaches have shown promising results in detecting and classifying ransomware families utilizing these features without applying any feature selection techniques, feature selection, however, is one of the potential steps toward an efficient detection or classification Machine Learning model because it reduces the probability of overfitting by removing redundant data, improves the model's accuracy by eliminating irrelevant features, and therefore reduces training time. There have been a good number of feature selection techniques to date that are being used in different security scenarios to optimize the performance of the Machine Learning models. Hence, the aim of this study is to present the comparative performance analysis of widely utilized Supervised Machine Learning models with and without RFECV feature selection technique towards ransomware classification utilizing the API call and network traffic features. Thereby, this study provides insight into the efficiency of the RFECV feature selection technique in the case of ransomware classification which can be used by peers as a reference for future work in choosing the feature selection technique in this domain.Comment: arXiv admin note: text overlap with arXiv:2210.1123

Novel Neuroprotective Function of Apical-Basal Polarity GeneCrumbs in Amyloid Beta 42 (Aβ42) Mediated Neurodegeneration

Alzheimer\u27s disease (AD, OMIM: 104300), a progressive neurodegenerative disorder with no cure to date, is caused by the generation of amyloid-beta-42 (Aβ42) aggregates that trigger neuronal cell death by unknown mechanism(s). We have developed a transgenic Drosophilaeye model where misexpression of human Aβ42 results in AD-like neuropathology in the neural retina. We have identified an apical-basal polarity gene crumbs (crb) as a genetic modifier of Aβ42-mediated-neuropathology. Misexpression of Aβ42 caused upregulation of Crb expression, whereas downregulation of Crb either by RNAi or null allele approach rescued the Aβ42-mediated-neurodegeneration. Co-expression of full length Crb with Aβ42 increased severity of Aβ42-mediated-neurodegeneration, due to three fold induction of cell death in comparison to the wild type. Higher Crb levels affect axonal targeting from the retina to the brain. The structure function analysis identified intracellular domain of Crb to be required for Aβ42-mediated-neurodegeneration. We demonstrate a novel neuroprotective role of Crb in Aβ42-mediated-neurodegeneration

A Positive Feedback Loop of Hippo- and c-Jun-Amino-Terminal Kinase Signaling Pathways Regulates Amyloid-Beta-Mediated Neurodegeneration

Alzheimer\u27s disease (AD, OMIM: 104300) is an age-related disorder that affects millions of people. One of the underlying causes of AD is generation of hydrophobic amyloid-beta 42 (Aβ42) peptides that accumulate to form amyloid plaques. These plaques induce oxidative stress and aberrant signaling, which result in the death of neurons and other pathologies linked to neurodegeneration. We have developed a Drosophila eye model of AD by targeted misexpression of human Aβ42 in the differentiating retinal neurons, where an accumulation of Aβ42 triggers a characteristic neurodegenerative phenotype. In a forward deficiency screen to look for genetic modifiers, we identified a molecularly defined deficiency, which suppresses Aβ42-mediated neurodegeneration. This deficiency uncovers hippo (hpo) gene, a member of evolutionarily conserved Hippo signaling pathway that regulates growth. Activation of Hippo signaling causes cell death, whereas downregulation of Hippo signaling triggers cell proliferation. We found that Hippo signaling is activated in Aβ42-mediated neurodegeneration. Downregulation of Hippo signaling rescues the Aβ42-mediated neurodegeneration, whereas upregulation of Hippo signaling enhances the Aβ42-mediated neurodegeneration phenotypes. It is known that c-Jun-amino-terminal kinase (JNK) signaling pathway is upregulated in AD. We found that activation of JNK signaling enhances the Aβ42-mediated neurodegeneration, whereas downregulation of JNK signaling rescues the Aβ42-mediated neurodegeneration. We tested the nature of interactions between Hippo signaling and JNK signaling in Aβ42-mediated neurodegeneration using genetic epistasis approach. Our data suggest that Hippo signaling and JNK signaling, two independent signaling pathways, act synergistically upon accumulation of Aβ42 plaques to trigger cell death. Our studies demonstrate a novel role of Hippo signaling pathway in Aβ42-mediated neurodegeneration

対流圏に見られる鉛直微細構造

We report the design, synthesis, detailed characterization, and analysis of a new multifunctional pi-conjugated bola-amphiphilic chromophore: oligo-(p-phenyleneethynylene)-dicarboxylic acid with dialkoxyoctadecyl side chains (OPE-C-18-1). OPE-C-18-1 shows two polymorphs at 123 K (OPE-C-18-1') and 373 K (OPE-C-18-1 `'), whose crystal structures were characterized via single crystal X-ray diffraction. OPE-C-18-1 also exhibits thermotropic liquid crystalline property revealing a columnar phase. The inherent pi-conjugation of OPE-C-18-1 imparts luminescence to the system. Photoluminescence measurements on the mesophase also reveal similar luminescence as in the crystalline state. Additionally, OPE-C-18-1 shows mechano-hypsochromic luminescence behavior. Density functional theory (DFT)-based calculations unravel the origins behind the simultaneous existence of all these properties. Nanoindentation experiments on the single crystal reveal its mechanical strength and accurately correlate the molecular arrangement with the liquid crystalline and mechanochromic luminescence behavior

Induced chromosome deletions cause hypersociability and other features of Williams-Beuren syndrome in mice

The neurodevelopmental disorder Williams-Beuren syndrome is caused by spontaneous similar to 1.5 Mb deletions comprising 25 genes on human chromosome 7q11.23. To functionally dissect the deletion and identify dosage-sensitive genes, we created two half-deletions of the conserved syntenic region on mouse chromosome 5G2. Proximal deletion (PD) mice lack Gtf2i to Limk1, distal deletion (DD) mice lack Limk1 to Fkbp6, and the double heterozygotes (D/P) model the complete human deletion. Gene transcript levels in brain are generally consistent with gene dosage. Increased sociability and acoustic startle response are associated with PD, and cognitive defects with DD. Both PD and D/P males are growth-retarded, while skulls are shortened and brains are smaller in DD and D/P. Lateral ventricle (LV) volumes are reduced, and neuronal cell density in the somatosensory cortex is increased, in PD and D/P. Motor skills are most impaired in D/P. Together, these partial deletion mice replicate crucial aspects of the human disorder and serve to identify genes and gene networks contributing to the neural substrates of complex behaviours and behavioural disorders

The Potential Involvement of E-cadherin and β-catenins in Meningioma

To investigate the potential involvements of E-cadherin and β-catenin in meningioma.Immunohistochemistry staining was performed on samples from patients with meningioma. The results were graded according to the positive ratio and intensity of tissue immunoreactivity. The expression of E-cadherin and β-catenin in meningioma was analyzed by its relationship with WHO2007 grading, invasion, peritumoral edema and postoperative recurrence.The positive rates of E-cadherin in meningioma WHO I, II, III were 92.69%, 33.33% and 0, respectively, (P<0.05); while the positive rates of β-catenin in meningioma WHO I, II, III were 82.93%, 33.33% and 20.00%, respectively, (P<0.05). The positive rate of E-cadherin in meningioma without invasion (94.12%) was higher than that with invasion (46.67%) (P<0.05). The difference in the positive rate of β-catenin between meningioma without invasion (88.24%) and meningioma with invasion (33.33%, P<0.05) was also statically significant. The positive rates of E-cadherin in meningioma with peritumoral edema 0, 1, 2, 3 were 93.75%, 85.71%, 60.00% and 0 respectively, (P<0.05); the positive rates of β-catenin in meningioma with peritumoral edema 0, 1, 2, 3 were 87.50%, 85.71%, 30.00% and 0 respectively, (P<0.01). The positive rates of E- cadherin in meningioma with postoperative recurrence were 33.33%, and the positive rate with postoperative non-recurrence was 90.00% (P<0.01). The positive rates of β-catenin in meningioma with postoperative recurrence and non-recurrence were 11.11%, 85.00%, respectively (P<0.01).The expression levels of E- cadherin and β-catenin correlated closely to the WHO 2007 grading criteria for meningioma. In atypical or malignant meningioma, the expression levels of E-cadherin and β-catenin were significantly lower. The expression levels of E- cadherin and β-catenin were also closely correlated with the invasion status of meningioma, the size of the peritumoral edema and the recurrent probabilities of the meningioma, all in an inverse correlationship. Taken together, the present study provided novel molecular targets in clinical treatments to meningioma

Development of a transdiagnostic, low-intensity, psychological intervention for common adolescent mental health problems in Indian secondary schools

Background: The PRIDE programme aims to establish a suite of transdiagnostic psychological interventions organised around a stepped care system in Indian secondary schools. This paper describes the development of a low-intensity, first-line component of the PRIDE model. Method: Contextual and global evidence informed an intervention ‘blueprint’ with problem solving as the primary practice element. Successive iterations were tested and modified across two pilot cohort studies (N=45; N=39). Participants were aged 13–20 years and presenting with elevated mental health symptoms in New Delhi schools. Results: The first iteration of the intervention, based on a guided self-help modality, showed promising outcomes and user satisfaction when delivered by psychologists. However, delivery was not feasible within the intended 6-week schedule, and participants struggled to use materials outside ‘guidance’ sessions. In Pilot 2, a modified counsellor-led problem-solving intervention was implemented by less experienced counsellors over a 3–4 week schedule. Outcomes were maintained, with indications of enhanced feasibility and acceptability. High demand was observed across both pilots, leading to more stringent eligibility criteria and a modified sensitisation plan. Discussion: Findings have shaped a first-line intervention for common adolescent mental health problems in low-resource settings. A forthcoming randomised controlled trial will test its effectiveness

Notch Signaling Activates Yorkie Non-Cell Autonomously in Drosophila

In Drosophila imaginal epithelia, cells mutant for the endocytic neoplastic tumor suppressor gene vps25 stimulate nearby untransformed cells to express Drosophila Inhibitor-of-Apoptosis-Protein-1 (DIAP-1), conferring resistance to apoptosis non-cell autonomously. Here, we show that the non-cell autonomous induction of DIAP-1 is mediated by Yorkie, the conserved downstream effector of Hippo signaling. The non-cell autonomous induction of Yorkie is due to Notch signaling from vps25 mutant cells. Moreover, activated Notch in normal cells is sufficient to induce non-cell autonomous Yorkie activity in wing imaginal discs. Our data identify a novel mechanism by which Notch promotes cell survival non-cell autonomously and by which neoplastic tumor cells generate a supportive microenvironment for tumor growth

The effectiveness of a low-intensity problem-solving intervention for common adolescent mental health problems in New Delhi, India: protocol for a school-based, individually randomized controlled trial with an embedded stepped-wedge cluster randomized controlled recruitment trial

Background Conduct, anxiety and depressive disorders account for over 75% of the adolescent mental health burden globally. The current protocol will test a low-intensity problem-solving intervention for school-going adolescents with common mental health problems in India. The protocol also tests the effects of a classroom-based sensitization intervention on the demand for counselling services in an embedded recruitment trial. Methods We will conduct a two-arm individually randomized controlled trial in six Government-run secondary schools in New Delhi. The targeted sample is 240 adolescents in grades 9-12 with persistent, elevated mental health symptoms and associated impact. Participants will receive either a brief problem-solving intervention delivered over 3 weeks by lay counsellors (intervention), or enhanced usual care comprised of problem-solving booklets (control). Self-reported adolescent mental health symptoms and idiographic problems will be assessed at 6 weeks (co-primary outcomes) and again at 12 weeks post-randomization. In addition, adolescent-reported impact of mental health difficulties, perceived stress, mental wellbeing and clinical remission, as well as parent-reported adolescent mental health symptoms and impact scores, will be assessed at 6 and 12 weeks post-randomization. We will also complete a parallel process evaluation, including estimations of the costs of delivering the interventions. An embedded recruitment trial will apply a stepped-wedge, cluster (class)-randomized controlled design in 70 classes across the six schools. This will evaluate the added impact of a classroom-based sensitization intervention over school-level recruitment sensitization activities on the primary outcome of referral rate into the host trial (i.e. the proportion of adolescents referred as a function of the total sampling frame in each condition of the embedded recruitment trial). Other outcomes will be the proportion of referrals eligible to participate in the host trial, proportion of self-generated referrals, and severity and pattern of symptoms among referred adolescents in each condition. Power calculations were undertaken separately for each trial. A detailed statistical analysis plan will be developed separately for each trial prior to unblinding. Discussion Both trials were initiated on 20 August 2018. A single research protocol for both trials offers a resource-efficient methodology for testing the effectiveness of linked procedures to enhance uptake and outcomes of a school-based psychological intervention for common adolescent mental health problems