Critical behavior of thermopower and conductivity at the metal-insulator transition in high-mobility Si-MOSFET's

This letter reports thermopower and conductivity measurements through the metal-insulator transition for 2-dimensional electron gases in high mobility Si-MOSFET's. At low temperatures both thermopower and conductivity show critical behavior as a function of electron density which is very similar to that expected for an Anderson transition. In particular, when approaching the critical density from the metallic side the diffusion thermopower appears to diverge and the conductivity vanishes. On the insulating side the thermopower shows an upturn with decreasing temperature.Comment: 4 pages with 3 figure

Lineages, Sub-Lineages and Variants of Enterovirus 68 in Recent Outbreaks

Enterovirus 68 (EV68) was first isolated in 1962. Very few cases of EV68 infection were described over the ensuing 40 years. However, in the past few years, an increase in severe respiratory tract infections associated with EV68 has been reported. We identified two clusters of EV68 infection in South London, UK, one each in the autumn/winters of 2009 and 2010. Sequence comparison showed significant homology of the UK strains with those from other countries including the Netherlands, Japan and the Philippines, which reported EV68 outbreaks between 2008 and 2010. Phylogenetic analysis of all available VP1 sequences indicated the presence of two modern EV68 lineages. The 2010 UK strains belonged to lineage 2. Lineage 1 could be further divided into two sub-lineages: some Japanese and Dutch strains collected between 2004 and 2010 form a distinct sub-lineages (sub-lineage 1.1), whereas other strains from the UK, Japan, Netherlands and Philippines collected between 2008 and 2010 represent sub-lineage 1.2. The UK 2009 strains together with several Dutch and Japanese strains from 2009/2010 represents one variant (1.2.1), whereas those from the Philippines a second variant (1.2.2). Based on specific deletions and substitutions, we suggest rules for the assignment of lineages and sub-lineages. Molecular epidemiological analysis indicates rapid recent evolution of EV68 and this may explain the recent findings of a global resurgence of EV68. Continuous global monitoring of the clinical and molecular epidemiology of EV68 is recommended

Assessing the Privacy Benefits of Domain Name Encryption

As Internet users have become more savvy about the potential for their Internet communication to be observed, the use of network traffic encryption technologies (e.g., HTTPS/TLS) is on the rise. However, even when encryption is enabled, users leak information about the domains they visit via DNS queries and via the Server Name Indication (SNI) extension of TLS. Two recent proposals to ameliorate this issue are DNS over HTTPS/TLS (DoH/DoT) and Encrypted SNI (ESNI). In this paper we aim to assess the privacy benefits of these proposals by considering the relationship between hostnames and IP addresses, the latter of which are still exposed. We perform DNS queries from nine vantage points around the globe to characterize this relationship. We quantify the privacy gain offered by ESNI for different hosting and CDN providers using two different metrics, the k-anonymity degree due to co-hosting and the dynamics of IP address changes. We find that 20% of the domains studied will not gain any privacy benefit since they have a one-to-one mapping between their hostname and IP address. On the other hand, 30% will gain a significant privacy benefit with a k value greater than 100, since these domains are co-hosted with more than 100 other domains. Domains whose visitors' privacy will meaningfully improve are far less popular, while for popular domains the benefit is not significant. Analyzing the dynamics of IP addresses of long-lived domains, we find that only 7.7% of them change their hosting IP addresses on a daily basis. We conclude by discussing potential approaches for website owners and hosting/CDN providers for maximizing the privacy benefits of ESNI.Comment: In Proceedings of the 15th ACM Asia Conference on Computer and Communications Security (ASIA CCS '20), October 5-9, 2020, Taipei, Taiwa

Thiolutin is a zinc chelator that inhibits the Rpn11 and other JAMM metalloproteases

Thiolutin is a disulfide-containing antibiotic and anti-angiogenic compound produced by Streptomyces. Its biological targets are not known. We show that reduced thiolutin is a zinc chelator that inhibits the JAB1/MPN/Mov34 (JAMM) domain–containing metalloprotease Rpn11, a deubiquitinating enzyme of the 19S proteasome. Thiolutin also inhibits the JAMM metalloproteases Csn5, the deneddylase of the COP9 signalosome; AMSH, which regulates ubiquitin-dependent sorting of cell-surface receptors; and BRCC36, a K63-specific deubiquitinase of the BRCC36-containing isopeptidase complex and the BRCA1–BRCA2-containing complex. We provide evidence that other dithiolopyrrolones also function as inhibitors of JAMM metalloproteases

Exploring natural products for treatment and prophylaxis of Malaria.

Malaria is the number one parasitic disease worldwide with half of the world's population at risk and nearly one million death annually. Natural products have had an enormous impact in malaria chemotherapy as the majority of current antimalarial agents are natural products or derive from a natural product scaffold isolated from plants traditionally used against malaria. The development of resistance by the deadliest parasite species Plasmodium falciparum against many antimalarial agents, including the artemisinin combinations, has become a great concern for global public health. Hence, new antimalarial drugs for chemotherapy and prophylaxis are urgently needed. Type II fatty acid biosynthesis pathway (FAS-II) has been recently shown to be indispensable for the liver stage parasites. Fatty acid biosynthesis is a crucial pathway for all living organisms as fatty acids are essential for membrane formation and energy production. Plasmodium employs type II FAS with fundamental structural and organisational differences versus the type I human FAS. This renders plasmodial FAS-II to be an excellent target for liver stage parasites and causal malaria prophylaxis. Thus, the essential FAS-II enzymes FabI, FabG and FabZ were included in the screening for new malaria prophylactic agents. One approach in the search for natural antimalarial drugs was the screening of pure natural products. Selected secondary lichen metabolites (evernic acid, vulpic acid, psoromic acid and (+)-usnic acid) were assessed for their potency against P. falciparum blood stage parasites and P.yoelii liver stage parasites, plasmodial FAS-II enzymes and their cytotoxicity. Evernic acid was identified as first natural product with potential against liver stage parasites (IC50 19.5 μM) and the FAS-II enzyme FabZ as potential target, for which it is a competitive inhibitor. Another set of natural products tested in this study were 22 selected natural chalcones, a chemical group that acts as precursors for the well-known family of flavonoids. The assessment against P. falciparum blood stage parasites identified 2',6'-dihydroy-4,4'- dimethoxydihydrochalcone as chalcone with the best antiplasmodial activity (IC50 3.7 μM), next to the known inhibitor licochalcone A (IC50 1.0 μM). In addition butein, homobutein, eriodictyolchalcone and licochalcone A were identified as promising inhibitors of the FAS- II enzyme FabZ. Structure-activity relationship studies were performed. Another approach was the screening of selected Turkish plants Anthemis cretica subsp. anatolica, Anthemis pestalozzae (Asteraceae), Salvia virgata (Lamiaceae), Scrophularia lucida and Scrophularia pinardii (Scrophulariaceae). Previous studies have shown that members of the genera Anthemis, Salvia and Scrophularia displayed significant antiplasmodial potential. Hence aerial parts and roots were extracted separately with methanol (crude extracts), which was followed by liquid-liquid partitioning and yielded the hexane, chloroform and aqueous methanol subextracts. The crude extracts and subextracts were screened for their potential against P. falciparum blood stage parasites, FAS-II enzymes and for cytotoxicity. All species showed good to moderate antiplasmodial activity and inhibition against at least one FAS-II enzyme. The aerial parts of the completely unstudied endemic Turkish plant Anthemis pestalozzae (Asteraceae) showed the most interesting profile and were selected for bioactivity-guided fractionation using a variety of chromatographic methods. Four compounds could be isolated and were identified as the cyanogenic glycoside lucumin, the benzoic acid derivative 2,6-dihydroxybenzoic acid, the indole glycoside 3-carboxymethyl-indole-l-N-β-D-glucopyranoside and a sesquiterpene lactone. The first three compounds were identified for the first time in the genus Anthemis. The sesquiterpene lactone was identified to possess the structure which was postulated for sivasinolide, however comparison of NMR data revealed significant differences. Our data suggest that the compound originally declared to be sivasinolide is very likely a different compound. In addition, the presence of the flavonoid rutin in the aqueous methanol subextract could be shown by HPLC analysis. An extensive analysis of the fatty acid composition of several fractions from the aerial parts of Antbhemis pestalozzae showed the presence of 37 different fatty acids

Computing Transverse T-Designs

In this paper, we develop a computational method for constructing transverse t-designs. An algorithm is presented that computes the G-orbits of k-element subsets transverse to a partition given that an automorphism group G is provided. We then use this method to investigate transverse Steiner quadruple systems. We also develop recursive constructions for transverse Steiner quadruple systems, and we provide a table of existence results for these designs when the number of points v 24. Finally, some results on transverse t-designs with t > 3 are also presented.

The RNA helicase FRH is an ATP-dependent regulator of CK1a in the circadian clock of Neurospora crassa

The Neurospora clock protein FRQ forms a complex with casein kinase 1a (CK1a) and FRH, a DEAD box-containing RNA helicase with a clock-independent essential function in RNA metabolism. In the course of a circadian period, FRQ is progressively hyperphosphorylated and eventually degraded. Timed hyperphosphorylation of FRQ is crucial for timekeeping of the clock. Here we show that the ATPase activity of FRH attenuates the kinetics of CK1a-mediated hyperphosphorylation of FRQ. Hyperphosphorylation of FRQ is strictly dependent on site-specific recruitment of a CK1a molecule that is activated upon binding. The FRH ATPase cycle regulates the access of CK1a to phosphorylation sites in FRQ in cis, suggesting that FRH is an ATP-dependent remodelling factor acting on the protein complex. We show that the affinity of CK1a for FRQ decreases with increasing FRQ phosphorylation, suggesting functional inactivation of FRQ in the negative feedback loop of the circadian clock before and independent of its degradation