Modulus Computational Entropy

The so-called {\em leakage-chain rule} is a very important tool used in many security proofs. It gives an upper bound on the entropy loss of a random variable $X$ in case the adversary who having already learned some random variables $Z_{1},\ldots,Z_{\ell}$ correlated with $X$, obtains some further information $Z_{\ell+1}$ about $X$. Analogously to the information-theoretic case, one might expect that also for the \emph{computational} variants of entropy the loss depends only on the actual leakage, i.e. on $Z_{\ell+1}$. Surprisingly, Krenn et al.\ have shown recently that for the most commonly used definitions of computational entropy this holds only if the computational quality of the entropy deteriorates exponentially in $|(Z_{1},\ldots,Z_{\ell})|$. This means that the current standard definitions of computational entropy do not allow to fully capture leakage that occurred "in the past", which severely limits the applicability of this notion. As a remedy for this problem we propose a slightly stronger definition of the computational entropy, which we call the \emph{modulus computational entropy}, and use it as a technical tool that allows us to prove a desired chain rule that depends only on the actual leakage and not on its history. Moreover, we show that the modulus computational entropy unifies other,sometimes seemingly unrelated, notions already studied in the literature in the context of information leakage and chain rules. Our results indicate that the modulus entropy is, up to now, the weakest restriction that guarantees that the chain rule for the computational entropy works. As an example of application we demonstrate a few interesting cases where our restricted definition is fulfilled and the chain rule holds.Comment: Accepted at ICTS 201

Block of NMDA receptor channels by endogenous neurosteroids: implications for the agonist induced conformational states of the channel vestibule

N-methyl-D-aspartate receptors (NMDARs) mediate synaptic plasticity, and their dysfunction is implicated in multiple brain disorders. NMDARs can be allosterically modulated by numerous compounds, including endogenous neurosteroid pregnanolone sulfate. Here, we identify the molecular basis of the use-dependent and voltage-independent inhibitory effect of neurosteroids on NMDAR responses. The site of action is located at the extracellular vestibule of the receptor's ion channel pore and is accessible after receptor activation. Mutations in the extracellular vestibule in the SYTANLAAF motif disrupt the inhibitory effect of negatively charged steroids. In contrast, positively charged steroids inhibit mutated NMDAR responses in a voltage-dependent manner. These results, in combination with molecular modeling, characterize structure details of the open configuration of the NMDAR channel. Our results provide a unique opportunity for the development of new therapeutic neurosteroid-based ligands to treat diseases associated with dysfunction of the glutamate system

Lead Exposure Is Associated with Decreased Serum Paraoxonase 1 (PON1) Activity and Genotypes

Lead exposure causes cardiac and vascular damage in experimental animals. However, there is considerable debate regarding the causal relationship between lead exposure and cardiovascular dysfunction in humans. Paraoxonase 1 (PON1), a high-density lipoprotein-associated antioxidant enzyme, is capable of hydrolyzing oxidized lipids and thus protects against atherosclerosis. Previous studies have shown that lead and several other metal ions are able to inhibit PON1 activity in vitro. To investigate whether lead exposure has influence on serum PON1 activity, we conducted a cross-sectional study of workers from a lead battery manufactory and lead recycling plant. Blood samples were analyzed for whole-blood lead levels, serum PON1 activity, and three common PON1 polymorphisms (Q192R, L55M, −108C/T). The mean blood lead level (± SD) of this cohort was 27.1 ± 15 μg/dL. Multiple linear regression analysis showed that blood lead levels were significantly associated with decreased serum PON1 activity (p < 0.001) in lead workers. This negative correlation was more evident for workers who carry the R192 allele, which has been suggested to be a risk factor for coronary heart disease. Taken together, our results suggest that the decrease in serum PON1 activity due to lead exposure may render individuals more susceptible to atherosclerosis, particularly subjects who are homozygous for the R192 allele

MM-VID: Advancing Video Understanding with GPT-4V(ision)

We present MM-VID, an integrated system that harnesses the capabilities of GPT-4V, combined with specialized tools in vision, audio, and speech, to facilitate advanced video understanding. MM-VID is designed to address the challenges posed by long-form videos and intricate tasks such as reasoning within hour-long content and grasping storylines spanning multiple episodes. MM-VID uses a video-to-script generation with GPT-4V to transcribe multimodal elements into a long textual script. The generated script details character movements, actions, expressions, and dialogues, paving the way for large language models (LLMs) to achieve video understanding. This enables advanced capabilities, including audio description, character identification, and multimodal high-level comprehension. Experimental results demonstrate the effectiveness of MM-VID in handling distinct video genres with various video lengths. Additionally, we showcase its potential when applied to interactive environments, such as video games and graphic user interfaces.Comment: Project page at https://multimodal-vid.github.io

Crosstalk between histone modifications and DNA methylation in patients with intellectual disability due to JARID1C mutations

CCMG Oral Abstract Presentations – Commonwealth A: A01The X-linked gene, JARID1C, encodes a H3K4 demethylase. Mutations in this gene cause intellectual disability (ID). We hypothesized that JARID1C mutations would dysregulate DNA methylation at specific genomic targets ...postprintThe 34th Annual Scientific Meeting of the Canadian College of Medical Geneticists (CCMG 2010), Halifax, NS., 21-23 October 2010. In Abstract Book of the 34th CCMG, 2010, p.

Identification of hip fracture patients from radiographs using Fourier analysis of the trabecular structure: a cross-sectional study

Peer reviewedPublisher PD

Observationally constrained aerosol–cloud semi-direct effects

Absorbing aerosols, like black carbon (BC), give rise to rapid adjustments, and the associated perturbation to the atmospheric temperature structure alters the cloud distribution. The level of scientific understanding of these rapid cloud adjustments—otherwise known as semi-direct effects (SDEs)—is considered low, with models indicating a likely negative (−0.44 to +0.1 Wm−2) forcing. Recent studies suggest this negative SDE is primarily driven by decreases in high-level clouds and enhanced longwave cooling. Here, we investigate the SDE using multiple models driven by observationally constrained fine-mode aerosol forcing without dust and sea salt. Unlike aerosol simulations, which yield a relatively vertically uniform aerosol atmospheric heating profile with significant upper-tropospheric heating, observation-based heating peaks in the lower-troposphere and then decays to zero in the mid-troposphere. We find a significant global annual mean decrease in low- and mid-level clouds, and weaker decreases in high-level clouds, which leads to a positive SDE dominated by shortwave radiation. Thus, in contrast to most studies, we find a robust positive SDE, implying cloud adjustments act to warm the climate system. Sensitivity tests with identical average, but vertically uniform observationally constrained aerosol atmospheric heating result in a negative SDE, due to enhanced longwave cooling as a result of large reductions in high-level clouds. Our results therefore suggest that model simulations lead to a negatively biased SDE, due to an aerosol atmospheric heating profile that is too vertically uniform

Transactivation of EGFR by LPS induces COX-2 expression in enterocytes

Necrotizing enterocolitis (NEC) is the leading cause of gastrointestinal morbidity and mortality in preterm infants. NEC is characterized by an exaggerated inflammatory response to bacterial flora leading to bowel necrosis. Bacterial lipopolysaccharide (LPS) mediates inflammation through TLR4 activation and is a key molecule in the pathogenesis of NEC. However, LPS also induces cyclooxygenase-2 (COX-2), which promotes intestinal barrier restitution through stimulation of intestinal cell survival, proliferation, and migration. Epidermal growth factor receptor (EGFR) activation prevents experimental NEC and may play a critical role in LPS-stimulated COX-2 production. We hypothesized that EGFR is required for LPS induction of COX-2 expression. Our data show that inhibiting EGFR kinase activity blocks LPS-induced COX-2 expression in small intestinal epithelial cells. LPS induction of COX-2 requires Src-family kinase signaling while LPS transactivation of EGFR requires matrix metalloprotease (MMP) activity. EGFR tyrosine kinase inhibitors block LPS stimulation of mitogen-activated protein kinase ERK, suggesting an important role of the MAPK/ERK pathway in EGFR-mediated COX-2 expression. LPS stimulates proliferation of IEC-6 cells, but this stimulation is inhibited with either the EGFR kinase inhibitor AG1478, or the selective COX-2 inhibitor Celecoxib. Taken together, these data show that EGFR plays an important role in LPS-induction of COX-2 expression in enterocytes, which may be one mechanism for EGF in inhibition of NEC

Ezrin interacts with the SARS coronavirus spike protein and restrains infection at the entry stage

© 2012 Millet et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Background: Entry of Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) and its envelope fusion with host cell membrane are controlled by a series of complex molecular mechanisms, largely dependent on the viral envelope glycoprotein Spike (S). There are still many unknowns on the implication of cellular factors that regulate the entry process. Methodology/Principal Findings: We performed a yeast two-hybrid screen using as bait the carboxy-terminal endodomain of S, which faces the cytosol during and after opening of the fusion pore at early stages of the virus life cycle. Here we show that the ezrin membrane-actin linker interacts with S endodomain through the F1 lobe of its FERM domain and that both the eight carboxy-terminal amino-acids and a membrane-proximal cysteine cluster of S endodomain are important for this interaction in vitro. Interestingly, we found that ezrin is present at the site of entry of S-pseudotyped lentiviral particles in Vero E6 cells. Targeting ezrin function by small interfering RNA increased S-mediated entry of pseudotyped particles in epithelial cells. Furthermore, deletion of the eight carboxy-terminal amino acids of S enhanced S-pseudotyped particles infection. Expression of the ezrin dominant negative FERM domain enhanced cell susceptibility to infection by SARS-CoV and S pseudotyped particles and potentiated S-dependent membrane fusion. Conclusions/Significance: Ezrin interacts with SARS-CoV S endodomain and limits virus entry and fusion. Our data present a novel mechanism involving a cellular factor in the regulation of S-dependent early events of infection.This work was supported by the Research Grant Council of Hong Kong (RGC#760208)and the RESPARI project of the International Network of Pasteur Institutes