Improved bounds for testing Dyck languages

In this paper we consider the problem of deciding membership in Dyck languages, a fundamental family of context-free languages, comprised of well-balanced strings of parentheses. In this problem we are given a string of length $n$ in the alphabet of parentheses of $m$ types and must decide if it is well-balanced. We consider this problem in the property testing setting, where one would like to make the decision while querying as few characters of the input as possible. Property testing of strings for Dyck language membership for $m=1$, with a number of queries independent of the input size $n$, was provided in [Alon, Krivelevich, Newman and Szegedy, SICOMP 2001]. Property testing of strings for Dyck language membership for $m \ge 2$ was first investigated in [Parnas, Ron and Rubinfeld, RSA 2003]. They showed an upper bound and a lower bound for distinguishing strings belonging to the language from strings that are far (in terms of the Hamming distance) from the language, which are respectively (up to polylogarithmic factors) the $2/3$ power and the $1/11$ power of the input size $n$. Here we improve the power of $n$ in both bounds. For the upper bound, we introduce a recursion technique, that together with a refinement of the methods in the original work provides a test for any power of $n$ larger than $2/5$. For the lower bound, we introduce a new problem called Truestring Equivalence, which is easily reducible to the $2$-type Dyck language property testing problem. For this new problem, we show a lower bound of $n$ to the power of $1/5$

A Simple PLL-Based True Random Number Generator for Embedded Digital Systems

The paper presents a simple True Random Number Generator (TRNG) which can be embedded in digital Application Specific Integrated Circuits (ASICs) and Field Programmable Logic Devices (FPLDs). As a source of randomness, it uses on-chip noise generated in the internal analog Phase-Locked Loop (PLL) circuitry. In contrast to traditionally used free-running oscillators, it uses a novel method of randomness extraction based on two rationally related synthesized clock signals. The generator has been developed for embedded cryptographic applications, where it significantly increases the system security, but it can be used in a wide range of other applications. The functionality of the proposed solution is demonstrated for the Altera Apex FPLD family, but the same principle can be used for all recent ASICs or FPLDs that include an on-chip reconfigurable analog PLL. The quality of the TRNG output is confirmed by applying special DIEHARD and NIST statistical tests, which pass even for high output bit-rates of several hundreds of Kbits/s

Multiparametric ultrasound findings in acute kidney failure due to rare renal cortical necrosis

Renal cortical necrosis (RCN) is a rare cause of acute kidney failure and is usually diagnosed on the basis of characteristic enhancement patterns on cross-sectional imaging. Contrast-enhanced ultrasound (CEUS) offers benefits in patients with kidney failure in the clinical setting including the use of a nonnephrotoxic intravascular contrast agent and the fact that it can be performed at the bedside in critical cases. Therefore, the aim of this study is to investigate whether CEUS can reliably identify typical imaging features of RCN. We retrospectively analyzed 12 patients with RCN examined in our department and confirmation of the diagnosis by either histopathology, other contrast-enhanced cross-sectional imaging tests, and/or CEUS follow-up. Assessed parameters in conventional US were reduced echogenicity, loss of corticomedullary differentiation, length and width of kidney, hypoechoic rim, resistance index and in CEUS delayed wash-in of contrast agent (>20 s), reverse rim sign, maximum nonenhancing rim and additional renal infarction. Furthermore, imaging features in RCN were compared with the findings in renal vein thrombosis (RVT), among them echogenicity, corticomedullar differentiation, hypoechoic rim, RI value, delayed cortical enhancement, total loss of cortical perfusion and enhancement of renal medulla. All 12 patients showed the reverse rim sign, while a hypoechogenic subcapsular rim was only visible in four patients on B-mode ultrasound. A resistance index (RI) was available in 10 cases and was always less than 1. RI was a strong differentiator in separating RVT from RCN (RI>1 or not measurable due to hypoperfusion as differentiator, p=0.001). CEUS showed total loss of medullary enhancement in all cases of RVT. With its higher temporal resolution, CEUS allows dynamic assessment of renal macro- and microcirculation and identification of the typical imaging findings of RCN with use of a nonnephrotoxic contrast agent

Highly Variable Rates of Genome Rearrangements between Hemiascomycetous Yeast Lineages

Hemiascomycete yeasts cover an evolutionary span comparable to that of the entire phylum of chordates. Since this group currently contains the largest number of complete genome sequences it presents unique opportunities to understand the evolution of genome organization in eukaryotes. We inferred rates of genome instability on all branches of a phylogenetic tree for 11 species and calculated species-specific rates of genome rearrangements. We characterized all inversion events that occurred within synteny blocks between six representatives of the different lineages. We show that the rates of macro- and microrearrangements of gene order are correlated within individual lineages but are highly variable across different lineages. The most unstable genomes correspond to the pathogenic yeasts Candida albicans and Candida glabrata. Chromosomal maps have been intensively shuffled by numerous interchromosomal rearrangements, even between species that have retained a very high physical fraction of their genomes within small synteny blocks. Despite this intensive reshuffling of gene positions, essential genes, which cluster in low recombination regions in the genome of Saccharomyces cerevisiae, tend to remain syntenic during evolution. This work reveals that the high plasticity of eukaryotic genomes results from rearrangement rates that vary between lineages but also at different evolutionary times of a given lineage

Assessment of Renal Transplant Perfusion by Contrast-Enhanced Ultrasound after Switch from Calcineurin Inhibitor to Belatacept: A Pilot Study

Calcineurin inhibitors (CNIs) have improved short-term kidney allograft survival but are nephrotoxic and vasoconstrictive. Vasoconstriction is potentially reversible after switching from CNIs to belatacept. The kidney allograft shows optimal requirements for dynamic perfusion imaging using contrast-enhanced ultrasound (CEUS). We performed standardized CEUS in patients after switching from CNIs to belatacept for clinical indication to study the suitability of CEUS, in order to assess the effects of CNI cessation on kidney allograft perfusion. Eleven kidney transplant patients were enrolled from February 2020 until November 2020. Demographic, clinical, and laboratory parameters, as well as perfusion imaging, were assessed at baseline and 6 months after switching immunosuppression. Quantification of perfusion imaging on CEUS was performed using a post-processing software tool on uncompressed DICOM cine loops. After CNI cessation, estimated glomerular filtration rate increased by 4.8 mL/min/1.73 m(2) (16%). Despite good quality of fit and comparable regions of interest in baseline and follow-up CEUS examinations, quantification of perfusion imaging showed a slightly improved cortical perfusion without reaching statistical significance after CNI cessation. This is the first study that systematically investigates the suitability of CEUS to detect changes of microvascular perfusion in kidney transplant recipients in vivo. No significant differences could be detected in perfusion measurements before and after CNI cessation

Crystal structure of Saccharomyces cerevisiae mitochondrial GatFAB reveals a novel subunit assembly in tRNA-dependent amidotransferases

Yeast mitochondrial Gln-mtRNAGln is synthesized by the transamidation of mischarged Glu-mtRNAGln by a non-canonical heterotrimeric tRNA-dependent amidotransferase (AdT). The GatA and GatB subunits of the yeast AdT (GatFAB) are well conserved among bacteria and eukaryota, but the GatF subunit is a fungi-specific ortholog of the GatC subunit found in all other known heterotrimeric AdTs (GatCAB). Here we report the crystal structure of yeast mitochondrial GatFAB at 2.0 Å resolution. The C-terminal region of GatF encircles the GatA-GatB interface in the same manner as GatC, but the N-terminal extension domain (NTD) of GatF forms several additional hydrophobic and hydrophilic interactions with GatA. NTD-deletion mutants displayed growth defects, but retained the ability to respire. Truncation of the NTD in purified mutants reduced glutaminase and transamidase activities when glutamine was used as the ammonia donor, but increased transamidase activity relative to the full-length enzyme when the donor was ammonium chloride. Our structure-based functional analyses suggest the NTD is a trans-acting scaffolding peptide for the GatA glutaminase active site. The positive surface charge and novel fold of the GatF-GatA interface, shown in this first crystal structure of an organellar AdT, stand in contrast with the more conventional, negatively charged bacterial AdTs described previousl

How warm was Greenland during the last interglacial period?

The last interglacial period (LIG, ~ 129–116 thousand years ago) provides the most recent case study for multi-millennial polar warming above pre-industrial level and a respective response of the Greenland and Antarctic ice sheets to this warming, as well as a test bed for climate and ice sheet models. Past changes in Greenland ice sheet thickness and surface temperature during this period were recently derived from the NEEM ice core records, North-West Greenland. The NEEM paradox has emerged from an estimated large local warming above pre-industrial level (7.5 ± 1.8 °C at the deposition site 126 ka ago without correction for any overall ice sheet altitude changes between the LIG and pre-industrial) based on water isotopes, together with limited local ice thinning, suggesting more resilience of the real Greenland ice sheet than shown in some ice sheet models. Here, we provide an independent assessment of the average LIG Greenland surface warming using ice core air isotopic composition (δ15N) and relationships between accumulation rate and temperature. The LIG surface temperature at the upstream NEEM deposition site without ice sheet altitude correction is estimated to be warmer by +7 to +11 °C (+8 °C being the most likely estimate according to constraints on past accumulation rate) compared to the pre-industrial period. This temperature estimate is consistent with the 7.5 ± 1.8 °C warming initially determined from NEEM water isotopes. Moreover, we show that under such warm temperatures, melting of snow probably led to a significant firn shrinking by ~ 15 m. Climate simulations performed with present day ice sheet topography lead to much smaller warming but larger amplitudes (up to 5 °C) can be obtained from changes in sea ice extent and ice sheet topography. Still, ice sheet simulations forced by 5 °C surface warming lead to large ice sheet decay that are not compatible with existing data. Our new, independent temperature constrain therefore reinforces the NEEM paradox

Screening for Staphylococcal Superantigen Genes Shows No Correlation with the Presence or the Severity of Chronic Rhinosinusitis and Nasal Polyposis

BACKGROUND: Staphylococcus aureus secretes numerous exotoxins which may exhibit superantigenic properties. Whereas the virulence of several of them is well documented, their exact biological effects are not fully understood. Exotoxins may influence the immune and inflammatory state of various organs, including the sinonasal mucosa: their possible involvement in chronic rhinosinusitis has been suggested and is one of the main trends in current research. The aim of this study was to investigate whether the presence of any of the 22 currently known staphylococcal exotoxin genes could be correlated with chronic rhinosinusitis. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a prospective, multi-centred European study, analysing 93 Staphylococcus aureus positive swabs taken from the middle meatus of patients suffering from chronic rhinosinusitis, with or without nasal polyposis, and controls. Strains were systematically tested for the presence of the 22 currently known exotoxin genes and genotyped according to their agr groups. No direct correlation was observed between chronic rhinosinusitis, with or without nasal polyposis, and either agr groups or the presence of the most studied exotoxins genes (egc, sea, seb, pvl, exfoliatins or tsst-1). However, genes for enterotoxins P and Q were frequently observed in nasal polyposis for the first time, but absent in the control group. The number of exotoxin genes detected was not statistically different among the 3 patient groups. CONCLUSIONS/SIGNIFICANCE: Unlike many previous studies have been suggesting, we did not find any evident correlation between staphylococcal exotoxin genes and the presence or severity of chronic rhinosinusitis with or without nasal polyposis

Tetratricopeptide repeat domain 7A is a nuclear factor that modulates transcription and chromatin structure

A loss-of-function mutation in tetratricopeptide repeat domain 7A (TTC7A) is a recently identified cause of human intestinal and immune disorders. However, clues to related underlying molecular dysfunctions remain elusive. It is now shown based on the study of TTC7A-deficient and wild-type cells that TTC7A is an essential nuclear protein. It binds to chromatin, preferentially at actively transcribed regions. Its depletion results in broad range of epigenomic changes at proximal and distal transcriptional regulatory elements and in altered control of the transcriptional program. Loss of WT_TTC7A induces general decrease in chromatin compaction, unbalanced cellular distribution of histones, higher nucleosome accessibility to nuclease digestion along with genome instability, and reduced cell viability. Our observations characterize for the first time unreported functions for TTC7A in the nucleus that exert a critical role in chromatin organization and gene regulation to safeguard healthy immune and intestinal status.</p