Detecting Poisoning Attacks on Hierarchical Malware Classification Systems

Anti-virus software based on unsupervised hierarchical clustering (HC) of malware samples has been shown to be vulnerable to poisoning attacks. In this kind of attack, a malicious player degrades anti-virus performance by submitting to the database samples specifically designed to collapse the classification hierarchy utilized by the anti-virus (and constructed through HC) or otherwise deform it in a way that would render it useless. Though each poisoning attack needs to be tailored to the particular HC scheme deployed, existing research seems to indicate that no particular HC method by itself is immune. We present results on applying a new notion of entropy for combinatorial dendrograms to the problem of controlling the influx of samples into the data base and deflecting poisoning attacks. In a nutshell, effective and tractable measures of change in hierarchy complexity are derived from the above, enabling on-the-fly flagging and rejection of potentially damaging samples. The information-theoretic underpinnings of these measures ensure their indifference to which particular poisoning algorithm is being used by the attacker, rendering them particularly attractive in this setting

Nanomolar CFTR Inhibition by Pore-Occluding Divalent Polyethylene Glycol-Malonic Acid Hydrazides

SummaryInhibitors of the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel have potential application as antisecretory therapy in cholera. We synthesized mono- and divalent CFTR inhibitors consisting of a malonic acid hydrazide (MalH) coupled via a disulfonic stilbene linker to polyethylene glycols (PEGs; 0.2–100 kDa). IC50 values for CFTR inhibition were 10–15 μM for the monovalent MalH-PEGs, but substantially lower for divalent MalH-PEG-MalH compounds, decreasing from 1.5 to 0.3 μM with increasing PEG size and showing positive cooperativity. Whole-cell patch-clamp showed voltage-dependent CFTR block with inward rectification. Outside-out patch-clamp showed shortened single-channel openings, indicating CFTR pore block from the extracellular side. Luminally added MalH-PEG-MalH blocked by >90% cholera toxin-induced fluid secretion in mouse intestinal loops (IC50 ∼10 pmol/loop), and greatly reduced mortality in a suckling mouse cholera model. These conjugates may provide safe, inexpensive antisecretory therapy

Radio and Millimeter Monitoring of Sgr A*: Spectrum, Variability, and Constraints on the G2 Encounter

We report new observations with the Very Large Array, Atacama Large Millimeter Array, and Submillimeter Array at frequencies from 1.0 to 355 GHz of the Galactic Center black hole, Sagittarius A*. These observations were conducted between October 2012 and November 2014. While we see variability over the whole spectrum with an amplitude as large as a factor of 2 at millimeter wavelengths, we find no evidence for a change in the mean flux density or spectrum of Sgr A* that can be attributed to interaction with the G2 source. The absence of a bow shock at low frequencies is consistent with a cross-sectional area for G2 that is less than $2 \times 10^{29}$ cm$^2$. This result fits with several model predictions including a magnetically arrested cloud, a pressure-confined stellar wind, and a stellar photosphere of a binary merger. There is no evidence for enhanced accretion onto the black hole driving greater jet and/or accretion flow emission. Finally, we measure the millimeter wavelength spectral index of Sgr A* to be flat; combined with previous measurements, this suggests that there is no spectral break between 230 and 690 GHz. The emission region is thus likely in a transition between optically thick and thin at these frequencies and requires a mix of lepton distributions with varying temperatures consistent with stratification.Comment: Accepted for publication in Ap

Factors Influencing Return to Play and Second Anterior Cruciate Ligament Injury Rates in Level 1 Athletes After Primary Anterior Cruciate Ligament Reconstruction:2-Year Follow-up on 1432 Reconstructions at a Single Center

BACKGROUND: Despite the importance of return-to-play (RTP) rates, second anterior cruciate ligament (ACL) injury rates, and patient-reported outcomes of athletes returning to sports after ACL reconstruction (ACLR), these outcomes have not been evaluated together across a single cohort nor the pre- and intraoperative factors influencing outcomes explored. PURPOSE: To prospectively report outcomes after ACLR relating to RTP, second ACL injury, and International Knee Document Committee (IKDC) scores in a large cohort of athletes at a single center to examine the influence of pre- and intraoperative variables on these outcomes. DESIGN: Cohort study; Level of evidence, 3. METHODS: A consecutive cohort of 1432 athletes undergoing primary ACLR by 2 orthopaedic surgeons was followed up prospectively more than 2 years after surgery. Pre- and intraoperative findings were reported with outcomes at follow-up relating to RTP, second ACL injury, and IKDC. Between-group differences for each outcome were reported and the predictive ability of pre- and intraoperative variables relating to each outcome assessed with logistic regression. RESULTS: There was >95% follow-up 2 years after surgery. The RTP rate was 81%, and of those who returned, 1.3% of those with patellar tendon grafts and 8.3% of those with hamstring grafts experienced ipsilateral rerupture (hazard ratio, 0.17). The contralateral ACL injury rate was 6.6%, and the IKDC score at follow-up was 86.8, with a greater proportion of patients with patellar tendon grafts scoring <80 on the IKDC (odds ratio, 1.56; 95% CI, 1.15–3.12). There was no relationship between time to RTP and second ACL injury, and there was a moderate correlation between ACL–Return to Sport After Injury score and RTP at follow-up (P < .001, rho = 0.46). There were a number of differences in pre- and intraoperative variables between groups for each outcome, but they demonstrated a poor ability to predict outcomes in level 1 athletes at 2-year follow-up. CONCLUSION: Findings demonstrated high overall RTP rates, lower reinjury rates with patellar tendon graft after 2-year follow-up in level 1 athletes, and no influence of time to RTP on second ACL injury. Despite differences between groups, there was poor predictive ability of pre- and intraoperative variables. Results suggest pre- and intraoperative variables for consideration to optimize outcomes in level 1 athletes after ACLR, but future research exploring other factors, such as physical and psychological recovery, may be needed to improve outcome prediction after ACLR

FOXO1 Modulates Osteoblast Differentiation

Forkhead box O1 (FOXO1) is upregulated during bone formation and in response to stimulation by bone morphogenetic proteins. Studies presented here examined the functional role of FOXO1 in a well defined culture system in which pre-osteoblastic cells undergo terminal differentiation in vitro. Mineralizing cultures of MC3T3-E1 cells were examined with or without FOXO1 knockdown by RNAi. Normal cells show the upregulation of FOXO1 and RUNX2 DNA binding activity, alkaline phosphatase activity, and mRNA levels of FOXO1, RUNX2, type 1 collagen, osteocalcin and MMP13 during formation of mineralizing nodules. In FOXO1 depleted cells each of these measurements was significantly reduced compared to values in control cells transfected with scrambled siRNA (P \u3c 0.05). Depletion of FOXO1 also reduced the number of mineralized nodules formed. Moreover, chromatin immunoprecipitation assays revealed a direct interaction of FOXO1 with the RUNX2 promoter. Overexpression of FOXO1 reduced the MC3T3-E1 cell number and the number of PCNA positive cells with little effect on apoptosis. These findings indicate that FOXO1 plays an important role in promoting osteoblast differentiation and suppressing proliferation in differentiating cells