A Robust Self-calibrating Transmission Scheme for On-Chip Networks

Systems-on-Chip (SoC) design involves several challenges, stemming from the extreme miniaturization of the physical features and from the large number of devices and wires on a chip. Since most SoCs are used within embedded systems, specific concerns are increasingly related to correct, reliable, and robust operation. We believe that in the future most SoCs will be assembled by using large-scale macro-cells and interconnected by means of on-chip networks. We examine some physical properties of on-chip interconnect busses, with the goal of achieving fast, reliable, and low-energy communication. These objectives are reached by dynamically scaling down the voltage swing, while ensuring data integrity-in spite of the decreased signal to noise ratio-by means of encoding and retransmission schemes. In particular, we describe a closed-loop voltage swing controller that samples the error retransmission rate to determine the operational voltage swing. We present a control policy which achieves our goals with minimal complexity; such simplicity is demonstrated by implementing the policy in a synthesizable controller. Such a controller is an embodiment of a self-calibrating circuit that compensates for significant manufacturing parameter deviations and environmental variations. Experimental results show that energy savings amount up to 42%, while at the same time meeting performance requirements

Total Ionizing Dose Effects on CMOS Image Sensor for the ULTRASAT Space Mission

ULTRASAT (ULtraviolet TRansient Astronomy SATellite) is a wide-angle space telescope that will perform deep time-resolved surveys in the near-ultraviolet spectrum. ULTRASAT is a space mission led by the Weizmann Institute of Science and the Israel Space Agency and is planned for launch in 2025. The camera implements backside-illuminated, stitched pixel sensors. The pixel has a dual-conversion-gain 4T architecture, with a pitch of $9.5$ $\mu m$ and is produced in a $180$ $nm$ process by Tower Semiconductor. Before the final sensor was available for testing, test sensors provided by Tower were used to gain first insights into the pixel's radiation tolerance. One of the main contributions to sensor degradation due to radiation for the ULTRASAT mission is Total Ionizing Dose (TID). TID measurements on the test sensors have been performed with a Co-60 gamma source at Helmholz Zentrum Berlin and CC-60 facility at CERN and preliminary results are presented.Comment: Part of the conference: Frontier Detectors for Frontier Physics: 15th Pisa Meeting on Advanced Detectors, La Biodola - Isola d'Elba Published in: Nuclear Instruments and Methods in Physics Research Section A: Accelerators, Spectrometers, Detectors and Associated Equipment Available online 15 June 2023, 168463. In Press, Journal Pre-proo

Characterisation of the key determinants of Phd antitoxin mediated Doc toxin inactivation in Salmonella

In the search for novel antimicrobial therapeutics, toxin-antitoxin (TA) modules are promising yet underexplored targets for overcoming antibiotic failure. The bacterial toxin Doc has been associated with the persistence of Salmonella in macrophages, enabling its survival upon antibiotic exposure. After developing a novel method to produce the recombinant toxin, we have used antitoxin-mimicking peptides to thoroughly investigate the mechanism by which its cognate antitoxin Phd neutralizes the activity of Doc. We reveal insights into the molecular detail of the Phd–Doc relationship and discriminate antitoxin residues that stabilize the TA complex from those essential for inhibiting the activity of the toxin. Coexpression of Doc and antitoxin peptides in Salmonella was able to counteract the activity of the toxin, confirming our in vitro results with equivalent sequences. Our findings provide key principles for the development of chemical tools to study and therapeutically interrogate this important class of protein–protein interactions

DNA Methylation of the ABO Promoter Underlies Loss of ABO Allelic Expression in a Significant Proportion of Leukemic Patients

Background: Loss of A, B and H antigens from the red blood cells of patients with myeloid malignancies is a frequent occurrence. Previously, we have reported alterations in ABH antigens on the red blood cells of 55% of patients with myeloid malignancies. Methodology/Principal Findings: To determine the underlying molecular mechanisms of this loss, we assessed ABO allelic expression in 21 patients with ABH antigen loss previously identified by flow cytometric analysis as well as an additional 7 patients detected with ABH antigen changes by serology. When assessing ABO mRNA allelic expression, 6/12 (50%) patients with ABH antigen loss detected by flow cytometry and 5/7 (71%) of the patients with ABH antigen loss detected by serology had a corresponding ABO mRNA allelic loss of expression. We examined the ABO locus for copy number and DNA methylation alterations in 21 patients, 11 with loss of expression of one or both ABO alleles, and 10 patients with no detectable allelic loss of ABO mRNA expression. No loss of heterozygosity (LOH) at the ABO locus was observed in these patients. However in 8/11 (73%) patients with loss of ABO allelic expression, the ABO promoter was methylated compared with 2/10 (20%) of patients with no ABO allelic expression loss (P = 0.03). Conclusions/Significance: We have found that loss of ABH antigens in patients with hematological malignancies is associated with a corresponding loss of ABO allelic expression in a significant proportion of patients. Loss of ABO allelic expression was strongly associated with DNA methylation of the ABO promoter.Tina Bianco-Miotto, Damian J. Hussey, Tanya K. Day, Denise S. O'Keefe and Alexander Dobrovi

Search for the Weak Decay of an H Dibaryon

We have searched for a neutral $H$ dibaryon decaying via $H\to\Lambda n$ and $H\to\Sigma^0 n$. Our search has yielded two candidate events from which we set an upper limit on the $H$ production cross section. Normalizing to the inclusive $\Lambda$ production cross section, we find $(d\sigma_H/d\Omega) / (d\sigma_\Lambda/d\Omega) < 6.3\times 10^{-6}$ at 90% C.L., for an $H$ of mass $\approx$ 2.15 GeV/$c^2$.Comment: 11 pages, 6 postscript figures, epsfig, aps, preprint, revte

Global Diversity Hotspots and Conservation Priorities for Sharks

Sharks are one of the most threatened groups of marine animals, as high exploitation rates coupled with low resilience to fishing pressure have resulted in population declines worldwide. Designing conservation strategies for this group depends on basic knowledge of the geographic distribution and diversity of known species. So far, this information has been fragmented and incomplete. Here, we have synthesized the first global shark diversity pattern from a new database of published sources, including all 507 species described at present, and have identified hotspots of shark species richness, functional diversity and endemicity from these data. We have evaluated the congruence of these diversity measures and demonstrate their potential use in setting priority areas for shark conservation. Our results show that shark diversity across all species peaks on the continental shelves and at mid-latitudes (30–40 degrees N and S). Global hotspots of species richness, functional diversity and endemicity were found off Japan, Taiwan, the East and West coasts of Australia, Southeast Africa, Southeast Brazil and Southeast USA. Moreover, some areas with low to moderate species richness such as Southern Australia, Angola, North Chile and Western Continental Europe stood out as places of high functional diversity. Finally, species affected by shark finning showed different patterns of diversity, with peaks closer to the Equator and a more oceanic distribution overall. Our results show that the global pattern of shark diversity is uniquely different from land, and other well-studied marine taxa, and may provide guidance for spatial approaches to shark conservation. However, similar to terrestrial ecosystems, protected areas based on hotspots of diversity and endemism alone would provide insufficient means for safeguarding the diverse functional roles that sharks play in marine ecosystems

International consensus on (ICON) anaphylaxis

ICON: Anaphylaxis provides a unique perspective on the principal evidence-based anaphylaxis guidelines developed and published independently from 2010 through 2014 by four allergy/immunology organizations. These guidelines concur with regard to the clinical features that indicate a likely diagnosis of anaphylaxis -- a life-threatening generalized or systemic allergic or hypersensitivity reaction. They also concur about prompt initial treatment with intramuscular injection of epinephrine (adrenaline) in the mid-outer thigh, positioning the patient supine (semi-reclining if dyspneic or vomiting), calling for help, and when indicated, providing supplemental oxygen, intravenous fluid resuscitation and cardiopulmonary resuscitation, along with concomitant monitoring of vital signs and oxygenation. Additionally, they concur that H1-antihistamines, H2-antihistamines, and glucocorticoids are not initial medications of choice. For self-management of patients at risk of anaphylaxis in community settings, they recommend carrying epinephrine auto-injectors and personalized emergency action plans, as well as follow-up with a physician (ideally an allergy/immunology specialist) to help prevent anaphylaxis recurrences. ICON: Anaphylaxis describes unmet needs in anaphylaxis, noting that although epinephrine in 1 mg/mL ampules is available worldwide, other essentials, including supplemental oxygen, intravenous fluid resuscitation, and epinephrine auto-injectors are not universally available. ICON: Anaphylaxis proposes a comprehensive international research agenda that calls for additional prospective studies of anaphylaxis epidemiology, patient risk factors and co-factors, triggers, clinical criteria for diagnosis, randomized controlled trials of therapeutic interventions, and measures to prevent anaphylaxis recurrences. It also calls for facilitation of global collaborations in anaphylaxis research. In addition to confirming the alignment of major anaphylaxis guidelines, ICON: Anaphylaxis adds value by including summary tables and citing 130 key references. It is published as an information resource about anaphylaxis for worldwide use by healthcare professionals, academics, policy-makers, patients, caregivers, and the public

TCRs with segment TRAV9-2 or a CDR3 histidine are overrepresented among nickel-specific CD4+ T cells

Background: Nickel is the most frequent cause of T cell-mediated allergic contact dermatitis worldwide. In vitro, CD4+ T cells from all donors respond to nickel but the involved αβ T cell receptor (TCR) repertoire has not been comprehensively analyzed. Methods: We introduce CD154 (CD40L) upregulation as a fast, unbiased, and quantitative method to detect nickel-specific CD4+ T cells ex vivo in blood of clinically characterized allergic and non allergic donors. Naïve (CCR7+ CD45RA+) and memory (not naïve) CD154+ CD4+ T cells were analyzed by flow cytometry after 5 hours of stimulation with 200 µmol/L NiSO4 ., TCR α- and β-chains of sorted nickel-specific and control cells were studied by high-throughput sequencing. Results: Stimulation of PBMCs with NiSO4 induced CD154 expression on ~0.1% (mean) of naïve and memory CD4+ T cells. In allergic donors with recent positive patch test, memory frequencies further increased ~13-fold and were associated with markers of in vivo activation. CD154 expression was TCR-mediated since single clones could be specifically restimulated. Among nickel-specific CD4+ T cells of allergic and non allergic donors, TCRs expressing the α-chain segment TRAV9-2 or a histidine in their α- or β-chain complementarity determining region 3 (CDR3) were highly overrepresented. Conclusions: Induced CD154 expression represents a reliable method to study nickel-specific CD4+ T cells. TCRs with particular features respond in all donors, while strongly increased blood frequencies indicate nickel allergy for some donors. Our approach may be extended to other contact allergens for the further development of diagnostic and predictive in vitro tests

Expansion of oxygen minimum zones may reduce available habitat for tropical pelagic fishes

Climate model predictions1, 2 and observations3, 4 reveal regional declines in oceanic dissolved oxygen, which are probably influenced by global warming5. Studies indicate ongoing dissolved oxygen depletion and vertical expansion of the oxygen minimum zone (OMZ) in the tropical northeast Atlantic Ocean6, 7. OMZ shoaling may restrict the usable habitat of billfishes and tunas to a narrow surface layer8, 9. We report a decrease in the upper ocean layer exceeding 3.5 ml l−1 dissolved oxygen at a rate of ≤1 m yr−1 in the tropical northeast Atlantic (0–25° N, 12–30° W), amounting to an annual habitat loss of ~5.95×1013 m3, or 15% for the period 1960–2010. Habitat compression and associated potential habitat loss was validated using electronic tagging data from 47 blue marlin. This phenomenon increases vulnerability to surface fishing gear for billfishes and tunas8, 9, and may be associated with a 10–50% worldwide decline of pelagic predator diversity10. Further expansion of the Atlantic OMZ along with overfishing may threaten the sustainability of these valuable pelagic fisheries and marine ecosystems

Evaluation of HIV Protease Inhibitor Use and the Risk of Sudden Death or Nonhemorrhagic Stroke

Concerns have arisen about possible effects of protease inhibitors (PIs) on cardiac conductivity. We found no significant association between current or recent PI exposure and sudden death or nonhemorrhagic stroke (adjusted rate ratio, 1.22; 95% confidence interval, .95-1.57), whereas cumulative exposure to PIs was associated with an increased risk (adjusted rate ratio, 1.06 per year of exposure; 95% confidence interval, 1.01-1.11