Crowdsourcing Cybersecurity: Cyber Attack Detection using Social Media

Social media is often viewed as a sensor into various societal events such as disease outbreaks, protests, and elections. We describe the use of social media as a crowdsourced sensor to gain insight into ongoing cyber-attacks. Our approach detects a broad range of cyber-attacks (e.g., distributed denial of service (DDOS) attacks, data breaches, and account hijacking) in an unsupervised manner using just a limited fixed set of seed event triggers. A new query expansion strategy based on convolutional kernels and dependency parses helps model reporting structure and aids in identifying key event characteristics. Through a large-scale analysis over Twitter, we demonstrate that our approach consistently identifies and encodes events, outperforming existing methods.Comment: 13 single column pages, 5 figures, submitted to KDD 201

Migalastat HCl reduces globotriaosylsphingosine (lyso-Gb3) in Fabry transgenic mice and in the plasma of Fabry patients

Fabry disease (FD) results from mutations in the gene ( GLA ) that encodes the lysosomal enzyme α-galactosidase A (α-Gal A), and involves pathological accumulation of globotriaosylceramide (GL-3) and globotriaosylsphingosine (lyso-Gb 3 ). Migalastat hydrochloride (GR181413A) is a pharmacological chaperone that selectively binds, stabilizes, and increases cellular levels of α-Gal A. Oral administration of migalastat HCl reduces tissue GL-3 in Fabry transgenic mice, and in urine and kidneys of some FD patients. A liquid chromatography-tandem mass spectrometry method was developed to measure lyso-Gb 3 in mouse tissues and human plasma. Oral administration of migalastat HCl to transgenic mice reduced elevated lyso-Gb 3 levels up to 64%, 59%, and 81% in kidney, heart, and skin, respectively, generally equal to or greater than observed for GL-3. Furthermore, baseline plasma lyso-Gb 3 levels were markedly elevated in six male FD patients enrolled in Phase 2 studies. Oral administration of migalastat HCl (150 mg QOD) reduced urine GL-3 and plasma lyso-Gb 3 in three subjects (range: 15% to 46% within 48 weeks of treatment). In contrast, three showed no reductions in either substrate. These results suggest that measurement of tissue and/or plasma lyso-Gb 3 is feasible and may be warranted in future studies of migalastat HCl or other new potential therapies for FD

Nurturing lifelong learning in communities through the National University of Lesotho: prospects and challenges

This paper analyses one aspect of a pan-African action research project called ITMUA (Implementing the Third Mission of Universities in Africa). This particular paper draws on the data from that project to explore the National University of Lesotho’s contribution to lifelong learning in its communities. It provides background information on the ITMUA initiative and analyses interview and focus group responses to two case studies in terms of their contribution to lifelong learning. It uses, as its analytical framework, a modified version of Mbigi’s African perspective on the four De Lors’ ‘pillars’, by adding a fifth pillar, courtesy of Torres. The paper argues that community engagement is a two-way process between universities and their wider constituencies with opportunities for mutual lifelong learning. But there are also challenges of understanding and process which must be addressed if the full range of these lifelong learning pillars is to be accommodated within African contexts. The paper provides an introduction to the history of community engagement in Africa as a university mission, followed by a brief discussion of lifelong learning within African perspectives. After describing the particular context of Lesotho, the concept of community service and community engagement in contemporary African contexts introduces the action research project and the case studies. The final part of the paper presents and discusses the research findings

Migalastat HCl reduces globotriaosylsphingosine (Lyso- Gb3) in Fabry transgenic mice and in the plasma of Fabry patients

Fabry disease (FD) results from mutations in the gene (GLA) that encodes the lysosomal enzyme a-galactosidase A (a-Gal A), and involves pathological accumulation of globotriaosylceramide (GL-3) and globotriaosylsphingosine (lyso-Gb3). Migalastat hydrochloride (GR181413A) is a pharmacological chaperone that selectively binds, stabilizes, and increases cellular levels of a-Gal A. Oral administration of migalastat HCl reduces tissue GL-3 in Fabry transgenic mice, and in urine and kidneys of some FD patients. A liquid chromatography-tandem mass spectrometry method was developed to measure lyso-Gb3 in mouse tissues and human plasma. Oral administration of migalastat HCl to transgenic mice reduced elevated lyso-Gb3 levels up to 64%, 59%, and 81% in kidney, heart, and skin, respectively, generally equal to or greater than observed for GL-3. Furthermore, baseline plasma lyso-Gb3 levels were markedly elevated in six male FD patients enrolled in Phase 2 studies. Oral administration of migalastat HCl (150 mg QOD) reduced urine GL-3 and plasma lyso-Gb3 in three subjects (range: 15% to 46% within 48 weeks of treatment). In contrast, three showed no reductions in either substrate. These results suggest that measurement of tissue and/or plasma lyso-Gb3 is feasible and may be warranted in future studies of migalastat HCl or other new potential therapies for FD

Booting the booters: Evaluating the effects of police interventions in the market for Denial-of-Service attacks

Illegal booter services offer denial of service (DoS) attacks for a fee of a few tens of dollars a month. Internationally, police have implemented a range of different types of intervention aimed at those using and offering booter services, including arrests and website takedown. In order to measure the impact of these interventions we look at the usage reports that booters themselves provide and at measurements of reflected UDP DoS attacks, leveraging a five year measurement dataset that has been statistically demonstrated to have very high coverage. We analysed time series data (using a negative binomial regression model) to show that several interventions have had a statistically significant impact on the number of attacks. We show that, while there is no consistent effect of highly-publicised court cases, takedowns of individual booters precede significant, but short-lived, reductions in recorded attack numbers. However, more wide-ranging disruptions have much longer effects. The closure of HackForums' booter market reduced attacks for 13 weeks globally (and for longer in particular countries) and the FBI's coordinated operation in December 2018, which involved both takedowns and arrests, reduced attacks by a third for at least 10 weeks and resulted in lasting change to the structure of the booter market.This work was supported by the Engineering and Physical Sciences Research Council (EPSRC) [grant number EP/M020320/1]

Towards the reconstruction of the genome-scale metabolic model of Lactobacillus acidophilus La-14

Lactobacillus acidophilus is a probiotic lactic acid bacterium used in food and dietary supplements for many years. However, despite its importance for industrial development and recognized health-promoting effects, no genome-scale metabolic model has been reported. A GSM model for L. acidophilus La-14 was developed, accounting 494 genes and 783 reactions. A genome annotation was performed to identify the metabolic potential of the bacterium. The biomass composition was determined based on information available in literature and previously published models. The model was validated by comparing in silico simulations with experimental data, regarding the aerobic and anaerobic growth. The reconstruction of the metabolic model has confirmed the fastidious requirements of L. acidophilus for amino acids, fatty acids, and vitamins. This model can be used for a better understanding of the metabolism of this bacterium and identification of industrially desirable compounds.This study was performed under the scope of the project “BIODATA.PT – Portuguese Biological Data Network” (ref. LISBOA-01-0145-FEDER-022231), funded by FCT/MCTES, through national funds of PIDDAC, Fundo Europeu de Desenvolvimento Regional (FEDER), Programa Operacional de Competitividade e Internacionalização (POCI) and Programa Operacional Regional de Lisboa (Lisboa 2020).info:eu-repo/semantics/publishedVersio

Migalastat HCl Reduces Globotriaosylsphingosine (Lyso-Gb(3)) in Fabry Transgenic Mice and in the Plasma of Fabry Patients

Fabry disease (FD) results from mutations in the gene (GLA) that encodes the lysosomal enzyme α-galactosidase A (α-Gal A), and involves pathological accumulation of globotriaosylceramide (GL-3) and globotriaosylsphingosine (lyso-Gb3). Migalastat hydrochloride (GR181413A) is a pharmacological chaperone that selectively binds, stabilizes, and increases cellular levels of α-Gal A. Oral administration of migalastat HCl reduces tissue GL-3 in Fabry transgenic mice, and in urine and kidneys of some FD patients. A liquid chromatography-tandem mass spectrometry method was developed to measure lyso-Gb3 in mouse tissues and human plasma. Oral administration of migalastat HCl to transgenic mice reduced elevated lyso-Gb3 levels up to 64%, 59%, and 81% in kidney, heart, and skin, respectively, generally equal to or greater than observed for GL-3. Furthermore, baseline plasma lyso-Gb3 levels were markedly elevated in six male FD patients enrolled in Phase 2 studies. Oral administration of migalastat HCl (150 mg QOD) reduced urine GL-3 and plasma lyso-Gb3 in three subjects (range: 15% to 46% within 48 weeks of treatment). In contrast, three showed no reductions in either substrate. These results suggest that measurement of tissue and/or plasma lyso-Gb3 is feasible and may be warranted in future studies of migalastat HCl or other new potential therapies for FD

Association between loop diuretic dose changes and outcomes in chronic heart failure: observations from the ESC-EORP Heart Failure Long-Term Registry

[Abstract] Aims. Guidelines recommend down-titration of loop diuretics (LD) once euvolaemia is achieved. In outpatients with heart failure (HF), we investigated LD dose changes in daily cardiology practice, agreement with guideline recommendations, predictors of successful LD down-titration and association between dose changes and outcomes. Methods and results. We included 8130 HF patients from the ESC-EORP Heart Failure Long-Term Registry. Among patients who had dose decreased, successful decrease was defined as the decrease not followed by death, HF hospitalization, New York Heart Association class deterioration, or subsequent increase in LD dose. Mean age was 66±13 years, 71% men, 62% HF with reduced ejection fraction, 19% HF with mid-range ejection fraction, 19% HF with preserved ejection fraction. Median [interquartile range (IQR)] LD dose was 40 (25–80) mg. LD dose was increased in 16%, decreased in 8.3% and unchanged in 76%. Median (IQR) follow-up was 372 (363–419) days. Diuretic dose increase (vs. no change) was associated with HF death [hazard ratio (HR) 1.53, 95% confidence interval (CI) 1.12–2.08; P = 0.008] and nominally with cardiovascular death (HR 1.25, 95% CI 0.96–1.63; P = 0.103). Decrease of diuretic dose (vs. no change) was associated with nominally lower HF (HR 0.59, 95% CI 0.33–1.07; P = 0.083) and cardiovascular mortality (HR 0.62 95% CI 0.38–1.00; P = 0.052). Among patients who had LD dose decreased, systolic blood pressure [odds ratio (OR) 1.11 per 10 mmHg increase, 95% CI 1.01–1.22; P = 0.032], and absence of (i) sleep apnoea (OR 0.24, 95% CI 0.09–0.69; P = 0.008), (ii) peripheral congestion (OR 0.48, 95% CI 0.29–0.80; P = 0.005), and (iii) moderate/severe mitral regurgitation (OR 0.57, 95% CI 0.37–0.87; P = 0.008) were independently associated with successful decrease. Conclusion. Diuretic dose was unchanged in 76% and decreased in 8.3% of outpatients with chronic HF. LD dose increase was associated with worse outcomes, while the LD dose decrease group showed a trend for better outcomes compared with the no-change group. Higher systolic blood pressure, and absence of (i) sleep apnoea, (ii) peripheral congestion, and (iii) moderate/severe mitral regurgitation were independently associated with successful dose decrease

Sex- and age-related differences in the management and outcomes of chronic heart failure: an analysis of patients from the ESC HFA EORP Heart Failure Long-Term Registry

Aims: This study aimed to assess age- and sex-related differences in management and 1-year risk for all-cause mortality and hospitalization in chronic heart failure (HF) patients. Methods and results: Of 16 354 patients included in the European Society of Cardiology Heart Failure Long-Term Registry, 9428 chronic HF patients were analysed [median age: 66 years; 28.5% women; mean left ventricular ejection fraction (LVEF) 37%]. Rates of use of guideline-directed medical therapy (GDMT) were high (angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, beta-blockers and mineralocorticoid receptor antagonists: 85.7%, 88.7% and 58.8%, respectively). Crude GDMT utilization rates were lower in women than in men (all differences: P\ua0 64 0.001), and GDMT use became lower with ageing in both sexes, at baseline and at 1-year follow-up. Sex was not an independent predictor of GDMT prescription; however, age >75 years was a significant predictor of GDMT underutilization. Rates of all-cause mortality were lower in women than in men (7.1% vs. 8.7%; P\ua0=\ua00.015), as were rates of all-cause hospitalization (21.9% vs. 27.3%; P\ua075 years. Conclusions: There was a decline in GDMT use with advanced age in both sexes. Sex was not an independent predictor of GDMT or adverse outcomes. However, age >75 years independently predicted lower GDMT use and higher all-cause mortality in patients with LVEF 6445%

4-(4-nitrobenzyl)pyridine tests for alkylating agents following chemical oxidative activation

A chemical activation system (CAS) designed to mimic the mammalian mixed-function oxidase enzymes was found to activate target compounds to reactive electrophiles. Activated compounds were assayed by reaction with 4-(4-nitrobenzyl)pyridine (NBP). A model nucleophile of 7-alkylguanine of nucleic acids, NBP produces a violet color following alkylation. Twenty compounds from several chemical classes were tested. The test generally gave positive and negative responses where expected. Two compounds, trichloroethylene and diethylnitrosamine, exhibited a linear Beer's law relationship in the concentration range tested. A high degree of linear correlation (r>0.97) was obtained for these compounds. Other compounds showed varying degrees of linear correlation from high correlation (r=0.94) to weak correlation (r=0.44). The CAS-NBP assay results were compared to bacterial mutagenicity and animal carcinogenicity test results when information was available. A good correlation (r=0.80) existed between direct alkylating activity and direct mutagenicity. Similar correlations existed between NBP alkylation following activation and mutagenicity following microsomal activation (r=0.73). Also, different correlations were observed between carcinogenicity and NBP alkylation following activation (r=0.69) and without activation (r=0.38).Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/48076/1/244_2004_Article_BF00213289.pd