Abstract We report measurements of the transverse diffusion of electrons in P-10 gas (90% Ar, 10% CH 4 ) in a laboratory-scale time projection chamber (TPC) utilizing a novel pixelated signal capture ...and digitization technique known as Q-Pix. The Q-Pix method incorporates a precision switched integrating transimpedance amplifier whose output is compared to a threshold voltage. Upon reaching the threshold, a comparator sends a 'reset' signal, initiating a discharge of the integrating capacitor. The time difference between successive resets is inversely proportional to the average current at the pixel in that time interval, and the number of resets is directly proportional to the total collected charge. We developed a 16-channel Q-Pix prototype fabricated from commercial off-the-shelf components and coupled them to 16 concentric annular anode electrodes to measure the spatial extent of the electron swarm that reaches the anode after drifting through the uniform field of the TPC. The swarm is produced at a gold photocathode using pulsed UV light. The measured transverse diffusion agrees with simulations in PyBoltz across a range of operating pressures (200–1500 Torr). These results demonstrate that a Q-Pix readout can successfully reconstruct the ionization topology in a TPC.
The scientific publication landscape is changing quickly, with an enormous increase in options and models. Articles can be published in a complex variety of journals that differ in their presentation ...format (online-only or in-print), editorial organizations that maintain them (commercial and/or society-based), editorial handling (academic or professional editors), editorial board composition (academic or professional), payment options to cover editorial costs (open access or pay-to-read), indexation, visibility, branding, and other aspects. Additionally, online submissions of non-revised versions of manuscripts prior to seeking publication in a peer-reviewed journal (a practice known as pre-printing) are a growing trend in biological sciences. In this changing landscape, researchers in biochemistry and molecular biology must re-think their priorities in terms of scientific output dissemination. The evaluation processes and institutional funding for scientific publications should also be revised accordingly. This article presents the results of discussions within the Department of Biochemistry, University of São Paulo, on this subject.
Virtually all eukaryotic cell functions and signaling pathways are regulated by protein phosphorylation. The Rad53 kinase plays crucial roles in the DNA damage response in Saccharomyces cerevisiae ...and is widely used as a surrogate marker for DNA damage checkpoint activation by diverse genotoxic agents. Most currently available assays for Rad53 activation are based on either electrophoretic mobility shifts or semiquantitative in situ autophosphorylation activity on protein blots. Here, we describe direct quantitative measures to assess Rad53 activity using immunoprecipitation kinase assays and quantitative mass spectrometric analysis of Rad53 activation loop autophosphorylation states. Both assays employ a highly specific Rad53 antibody, and thus enable the analysis of the untagged endogenous protein under physiological conditions. The principles of these assays are readily transferable to other protein kinases for which immunoprecipitation-grade antibodies are available, and thus potentially applicable to a wide range of eukaryotic signaling pathways beyond yeast.
Consider a fully connected network where up to $t$ processes may crash and all processes start in an arbitrary memory state. The self-stabilizing firing squad problem consists of eventually ...guaranteeing simultaneous response to an external input. This is modeled by requiring that the noncrashed processes "fire" simultaneously if some correct process received an external "go" input, and that they only fire as a response to some process receiving such an input. This paper presents FireSquad, the first self-stabilizing firing squad algorithm. A firing squad algorithm facilitates the use of algorithms that need to start in the same round. It allows a smooth transition between algorithms whose executions need to be disjoint. The FireSquad algorithm combines two forms of fault-tolerance properties: self-stabilization to allow recovery from arbitrary transient errors and resilience to crash failures to handle permanent ones. The FireSquad algorithm is optimal in two respects: (a) once the algorithm is in a safe state, it fires in response to a go input as fast as any other algorithm does, and (b) starting from an arbitrary state, it converges to a safe state as fast as any other algorithm does.
Consider a distributed network of n nodes that is connected to a global source of “beats”. All nodes receive the “beats” simultaneously, and operate in lock-step. A scheme that produces a “pulse” ...every Cycle beats is shown. That is, the nodes agree on “special beats”, which are spaced Cycle beats apart. Given such a scheme, a clock synchronization algorithm is built. The “pulsing” scheme is self-stabilized despite any transient faults and the continuous presence of up to \documentclass12pt{minimal}
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\begin{document}$f < \frac{n}{3}$\end{document}Byzantin nodes. Therefore, the clock synchronization built on top of the “pulse” is highly fault tolerant. In addition, a highly fault tolerant general stabilizer algorithm is constructed on top of the “pulse” mechanism.
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\begin{document}$f < \frac{n}{3}$\end{document} and have exponential convergence time that also depends on the value of max-clock (the clock wrap around value). The proposed scheme combines the best of both worlds: it converges in linear time that is independent of max-clock and is tolerant to up to \documentclass12pt{minimal}
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\begin{document}$f < \frac {n}{3}$\end{document}Byzantin nodes. Moreover, considering problems in a self-stabilizing, Byzantin tolerant environment that require nodes to know the global state (clock synchronization, token circulation, agreement, etc.), the work presented here is the first protocol to operate in a network that is not fully connected.
ADP‐ribosylation, a modification of proteins, nucleic acids, and metabolites, confers broad functions, including roles in stress responses elicited, for example, by DNA damage and viral infection and ...is involved in intra‐ and extracellular signaling, chromatin and transcriptional regulation, protein biosynthesis, and cell death. ADP‐ribosylation is catalyzed by ADP‐ribosyltransferases (ARTs), which transfer ADP‐ribose from NAD+ onto substrates. The modification, which occurs as mono‐ or poly‐ADP‐ribosylation, is reversible due to the action of different ADP‐ribosylhydrolases. Importantly, inhibitors of ARTs are approved or are being developed for clinical use. Moreover, ADP‐ribosylhydrolases are being assessed as therapeutic targets, foremost as antiviral drugs and for oncological indications. Due to the development of novel reagents and major technological advances that allow the study of ADP‐ribosylation in unprecedented detail, an increasing number of cellular processes and pathways are being identified that are regulated by ADP‐ribosylation. In addition, characterization of biochemical and structural aspects of the ARTs and their catalytic activities have expanded our understanding of this protein family. This increased knowledge requires that a common nomenclature be used to describe the relevant enzymes. Therefore, in this viewpoint, we propose an updated and broadly supported nomenclature for mammalian ARTs that will facilitate future discussions when addressing the biochemistry and biology of ADP‐ribosylation. This is combined with a brief description of the main functions of mammalian ARTs to illustrate the increasing diversity of mono‐ and poly‐ADP‐ribose mediated cellular processes.
ADP‐ribosylation, the transfer of ADP‐ribose from NAD+ onto substrates, is catalyzed by proteins with an ADP‐ribosyltransferase (ART) domain. This fully reversible modification can occur as mono‐ or poly‐ADP‐ribosylation. Here, we propose an updated nomenclature for mammalian ARTs and provide a brief description of the main functions of these proteins to illustrate the increasing diversity of the cellular processes that are regulated by mono‐ and poly‐ADP‐ribosylation.
Hypertension promotes atherosclerosis and is a major source of morbidity and mortality. We show that mice lacking T and B cells (RAG-1-/- mice) have blunted hypertension and do not develop ...abnormalities of vascular function during angiotensin II infusion or desoxycorticosterone acetate (DOCA)-salt. Adoptive transfer of T, but not B, cells restored these abnormalities. Angiotensin II is known to stimulate reactive oxygen species production via the nicotinamide adenosine dinucleotide phosphate (NADPH) oxidase in several cells, including some immune cells. Accordingly, adoptive transfer of T cells lacking the angiotensin type I receptor or a functional NADPH oxidase resulted in blunted angiotensin II-dependent hypertension and decreased aortic superoxide production. Angiotensin II increased T cell markers of activation and tissue homing in wild-type, but not NADPH oxidase-deficient, mice. Angiotensin II markedly increased T cells in the perivascular adipose tissue (periadventitial fat) and, to a lesser extent the adventitia. These cells expressed high levels of CC chemokine receptor 5 and were commonly double negative (CD3+CD4-CD8-). This infiltration was associated with an increase in intercellular adhesion molecule-1 and RANTES in the aorta. Hypertension also increased T lymphocyte production of tumor necrosis factor (TNF) alpha, and treatment with the TNFalpha antagonist etanercept prevented the hypertension and increase in vascular superoxide caused by angiotensin II. These studies identify a previously undefined role for T cells in the genesis of hypertension and support a role of inflammation in the basis of this prevalent disease. T cells might represent a novel therapeutic target for the treatment of high blood pressure.
Cultures of the obligate psychrophilic diatom Fragilariopsis cylindrus (Grunow) were grown for 4 months under steady-state conditions at -1 degrees C and +7 degrees C (50 micromol photons m(-2) ...s(-1)) prior to measurements in order to investigate long-term acclimation of photosynthesis to both temperatures. No differences in maximum intrinsic quantum yield of PS II (F(V)/F(M)) and relative electron transport rates could be detected at either temperature after 4 months of acclimation. Measurements of photosynthesis (relative electron transport rates) vs. irradiance (P vs. E curves) revealed similar values for relative light utilization efficiency (alpha = 0.57 at -1 degrees C, alpha = 0.60 at +7 degrees C) but higher values for irradiance levels at which photosynthesis saturates (E(K)) at -1 degrees C and, therefore, higher maximum photosynthesis (P(MAX) = 54 (relative units) at -1 degrees C, P(MAX) = 49 at +7 degrees C). Nonphotochemical quenching (NPQ) measurements at 385 mumol photons m(-2) s(-1) indicated higher (37%) NPQ for diatoms grown at -1 degrees C compared to +7 degrees C, which was possibly related to a 2-fold increase in the concentration of the pigment diatoxanthin and a 9-fold up-regulation of a gene encoding a fucoxanthin chlorophyll a,c-binding protein. Expression of the D1 protein encoding gene psbA was ca. 1.5-fold up-regulated at -1 degrees C, whereas expression levels of other genes from Photosystem II (psbC, psbU, psbO), as well as rbcL, the gene encoding the Rubisco large subunit were similar at both temperatures. However, a 2-fold up-regulation of a plastid glyceraldehyde-P dehydrogenase at -1 degrees C indicated enhanced Calvin cycle activity. This study revealed for the first time that a polar diatom could efficiently acclimate photosynthesis over a wide range of polar temperatures given enough time. Acclimation of photosynthesis at -1 degrees C was probably regulated similarly to high light acclimation.
Atrial fibrillation (AF) is associated with an increased risk of stroke due almost exclusively to emboli from left atrial appendage (LAA) thrombi. Recently, we reported that AF was associated with ...endocardial dysfunction, limited to the left atrium (LA) and LAA and manifest as reduced nitric oxide (NO*) production and increased expression of plasminogen activator inhibitor-1. We hypothesized that reduced LAA NO* levels observed in AF may be associated with increased superoxide (O2*-) production.
After a week of AF induced by rapid atrial pacing in pigs, O2*- production from acutely isolated heart tissue was measured by 2 independent techniques, electron spin resonance and superoxide dismutase-inhibitable cytochrome C reduction assays. Compared with control animals with equivalent ventricular heart rates, basal O2*- production was increased 2.7-fold (P<0.01) and 3.0-fold (P<0.02) in the LA and LAA, respectively. A similar 3.0-fold (P<0.01) increase in LAA O2*- production was observed using a cytochrome C reduction assay. The increases could not be explained by changes in atrial total superoxide dismutase activity. Addition of either apocyanin or oxypurinol reduced LAA O2*-, implying that NADPH and xanthine oxidases both contributed to increased O2*- production in AF. Enzyme assays of atrial tissue homogenates confirmed increases in LAA NAD(P)H oxidase (P=0.04) and xanthine oxidase (P=0.01) activities. Although there were no changes in expression of the NADPH oxidase subunits, the increase in superoxide production was accompanied by an increase in GTP-loaded Rac1, an activator of the NADPH oxidase.
AF increased O2*- production in both the LA and LAA. Increased NAD(P)H oxidase and xanthine oxidase activities contributed to the observed increase in LAA O2*- production. This increase in O2*- and its reactive metabolites may contribute to the pathological consequences of AF such as thrombosis, inflammation, and tissue remodeling.
This book takes an extensive look at the many different types of users and cultures that comprise the popular social media platform Tumblr. Though it does not receive nearly as much attention as ...other social media such as Twitter or Facebook, Tumblr and its users have been hugely influential in creating and shifting popular culture, especially progressive youth culture, with the New York Times referring to 2014 as the dawning of the “age of Tumblr activism.” Perfect for those unfamiliar with the platform as well as those who grew up on it, this volume contains essays and artwork that span many different topics: fandom; platform structure and design; race, gender and sexuality, including queer and trans identities; aesthetics; disability and mental health; and social media privacy and ethics. An entire generation of young people that is now beginning to influence mass culture and politics came of age on Tumblr, and this volume is an indispensable guide to the many ways this platform works.
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