CARIOCA: a fast binary front-end implemented in 0.25μ0.25\mu CMOS using a Novel current-mode technique for the LHCb muon detector

The CARIOCA front-end is an amplifier discriminator chip, using 0.25mm CMOS technology, developed with a very fast and low noise preamplifier. This prototype was designed to have input impedance below 10W. Measurements showed a peaking time of 14ns and noise of 450e- at zero input capacitance, with a noise slope of 37.4 e-/pF. The sensitivity of 8mV/fC remains almost unchanged up to a detector capacitance of 120pF

Design methodology for ultra low-power analog circuits using next generation BSIM6 MOSFET compact model

The recently proposed BSIM6 bulk MOSFET compact model is set to replace the hitherto widely used BSIM3 and BSIM4 models as the de-facto industrial standard. Unlike its predecessors which were threshold voltage based, the BSIM6 core is charge based and thus physically continuous at all levels of inversion from linear operation to saturation. Hence, it lends itself conveniently for the use of a design methodology suited for low-power analog circuit design based on the inversion coefficient (IC) that has been extensively used in conjugation with the EIN model and allows to make simple calculations of, for example, transconductance efficiency, gain bandwidth product, etc. This methodology helps to make a near-optimal selection of transistor dimensions and operating points even in moderate and weak inversion regions. This paper will discuss the IC based design methodology and its application to the next generation BSIM6 compact MOSFET model. (C) 2013 Elsevier Ltd. All rights reserved

Direct measurement of the pion valence quark momentum distribution, the pion light-cone wave function squared

We present the first direct measurements of the pion valence quark momentum distribution which is related to the square of the pion light-cone wave function. The measurements were carried out using data on diffractive dissociation of 500 GeV/c $\pi^-$ into di-jets from a platinum target at Fermilab experiment E791. The results show that the $|q\bar {q}>$ light-cone asymptotic wave function, which was developed using perturbative QCD methods, describes the data well for $Q^2 \sim 10 ~{\rm (GeV/c)^2}$ or more. We also measured the transverse momentum distribution of the diffractive di-jets.Comment: 13 pages, 4 figure

2022 report from the Auger-TA working group on UHECR arrival directions

After over 60 years, the powerful engines that accelerate ultra-high-energy cosmic rays (UHECRs) to the formidable energies at which we observe them from Earth remain mysterious. Assuming standard physics, we expect UHECR sources to lie within the local Universe (up to a few hundred~Mpc). The distribution of matter in the local Universe is anisotropic, and we expect this anisotropy to be imprinted on the distribution of UHECR arrival directions. Even though intervening intergalactic and Galactic magnetic fields deflect charged UHECRs and can distort these anisotropies, some amount of information on the distribution of the sources is preserved. In this proceedings contribution, we present the results of the joint Pierre Auger Observatory and Telescope Array searches for (a) the largest-scale anisotropies (the harmonic dipole and quadrupole) and (b) correlations with a sample of nearby starburst galaxies and the 2MRS catalogue tracing stellar mass within~250~Mpc. This analysis updates our previous results with the most recent available data, notably with the addition of 3~years of new Telescope Array data. The main finding is a correlation between the arrival directions of $12.1\%_{-3.1\%}^{+4.5\%}$~of UHECRs detected with $E \geq 38$~EeV by~Auger or with~$E \gtrsim 49$~EeV by~TA and the positions of nearby starburst galaxies on a ${15.1\text{deg}}_{-3.0\text{deg}}^{+4.6\text{deg}}$~angular scale, with a $4.7\sigma$~post-trial significance, up from $4.2\sigma$ obtained in our previous study.Comment: proceedings of the 6th International Symposium on Ultra High Energy Cosmic Rays (UHECR2022), 3-7 October 2022, L'Aquila, Ital

Tau and mTOR: The Hotspots for Multifarious Diseases in Alzheimer's Development

The hyperphosphorylation of tau protein and the overexpression of mTOR are considered to be the driving force behind Aβ plaques and Neurofibrillay Tangles (NFT's), hallmarks of Alzheimer's disease (AD). It is now evident that miscellaneous diseases such as Diabetes, Autoimmune diseases, Cancer, etc. are correlated with AD. Therefore, we reviewed the literature on the causes of AD and investigated the association of tau and mTOR with other diseases. We have discussed the role of insulin deficiency in diabetes, activated microglial cells, and dysfunction of blood-brain barrier (BBB) in Autoimmune diseases, Presenilin 1 in skin cancer, increased reactive species in mitochondrial dysfunction and deregulated Cyclins/CDKs in promoting AD pathogenesis. We have also discussed the possible therapeutics for AD such as GSK3 inactivation therapy, Rechaperoning therapy, Immunotherapy, Hormonal therapy, Metal chelators, Cell cycle therapy, γ-secretase modulators, and Cholinesterase and BACE 1-inhibitors which are thought to serve a major role in combating pathological changes coupled with AD. Recent research about the relationship between mTOR and aging and hepatic Aβ degradation offers possible targets to effectively target AD. Future prospects of AD aims at developing novel drugs and modulators that can potentially improve cell to cell signaling, prevent Aβ plaques formation, promote better release of neurotransmitters and prevent hyperphosphorylation of tau

Liana communities exhibit different species composition, diversity and community structure across forest types in the Congo Basin

Lianas are poorly characterized for central African forests. We quantify variation in liana composition, diversity and community structure in different forest types in the Yangambi Man and Biosphere Reserve, Democratic Republic of Congo. These attributes of liana assemblages were examined in 12 1-ha plots, randomly demarcated within regrowth forest, old growth monodominant forest, old growth mixed forest and old growth edge forest. Using a combination of multivariate and univariate community analyses, we visualize the patterns of these liana assemblage attributes and/or test for their significant differences across forest types. The combined 12 1-ha area contains 2,638 lianas (>= 2 cm diameter) representing 105 species, 49 genera and 22 families. Liana species composition differed significantly across forest types. Taxonomic diversity was higher in old growth mixed forests compared to old growth monodominant and regrowth forests. Trait diversity was higher than expected in the regrowth forest as opposed to the rest of forest types. Similarly, the regrowth forest differed from the rest of forest types in the pattern of liana species ecological traits and diameter frequency distribution. The regrowth forest was also less densely populated in lianas and had lower liana total basal area than the rest of forest types. We speculate that the mechanism of liana competitive exclusion by dominant tree species is mainly responsible for the lower liana species diversity in monodominant compared to mixed forests. We attribute variation in liana community structure between regrowth and old growth forests mostly to short development time of size hierarchies

The Substitutions L50F, E166A, and L167F in SARS-CoV-2 3CLpro Are Selected by a Protease Inhibitor In Vitro and Confer Resistance To Nirmatrelvir.

The SARS-CoV-2 main protease (3CLpro) has an indispensable role in the viral life cycle and is a therapeutic target for the treatment of COVID-19. The potential of 3CLpro-inhibitors to select for drug-resistant variants needs to be established. Therefore, SARS-CoV-2 was passaged in vitro in the presence of increasing concentrations of ALG-097161, a probe compound designed in the context of a 3CLpro drug discovery program. We identified a combination of amino acid substitutions in 3CLpro (L50F E166A L167F) that is associated with a >20× increase in 50% effective concentration (EC50) values for ALG-097161, nirmatrelvir (PF-07321332), PF-00835231, and ensitrelvir. While two of the single substitutions (E166A and L167F) provide low-level resistance to the inhibitors in a biochemical assay, the triple mutant results in the highest levels of resistance (6× to 72×). All substitutions are associated with a significant loss of enzymatic 3CLpro activity, suggesting a reduction in viral fitness. Structural biology analysis indicates that the different substitutions reduce the number of inhibitor/enzyme interactions while the binding of the substrate is maintained. These observations will be important for the interpretation of resistance development to 3CLpro inhibitors in the clinical setting. IMPORTANCE Paxlovid is the first oral antiviral approved for treatment of SARS-CoV-2 infection. Antiviral treatments are often associated with the development of drug-resistant viruses. In order to guide the use of novel antivirals, it is essential to understand the risk of resistance development and to characterize the associated changes in the viral genes and proteins. In this work, we describe for the first time a pathway that allows SARS-CoV-2 to develop resistance against Paxlovid in vitro. The characteristics of in vitro antiviral resistance development may be predictive for the clinical situation. Therefore, our work will be important for the management of COVID-19 with Paxlovid and next-generation SARS-CoV-2 3CLpro inhibitors

Sn-Beta zeolites with borate salts catalyse the epimerization of carbohydrates via an intramolecular carbon shift

Carbohydrate epimerization is an essential technology for the widespread production of rare sugars. In contrast to other enzymes, most epimerases are only active on sugars substituted with phosphate or nucleotide groups, thus drastically restricting their use. Here we show that Sn-Beta zeolite in the presence of sodium tetraborate catalyses the selective epimerization of aldoses in aqueous media. Specifically, a 5 wt% aldose (for example, glucose, xylose or arabinose) solution with a 4:1 aldose:sodium tetraborate molar ratio reacted with catalytic amounts of Sn-Beta yields near-equilibrium epimerization product distributions. The reaction proceeds by way of a 1,2 carbon shift wherein the bond between C-2 and C-3 is cleaved and a new bond between C-1 and C-3 is formed, with C-1 moving to the C-2 position with an inverted configuration. This work provides a general method of performing carbohydrate epimerizations that surmounts the main disadvantages of current enzymatic and inorganic processes.National Science Foundation (U.S.). Materials Research Science and Engineering Centers (Program) (Award DMR-0819762)DuPont MIT Alliance (Graduate Research Fellowship)National Institutes of Health (U.S.) (Grant EB-001960)National Institutes of Health (U.S.) (Grant EB-002026)National Science Foundation (U.S.). Graduate Research Fellowship Program (Grant 1122374