Extra-renal locations of the a4 subunit of H+ATPase

Abstract Background Vacuolar-type proton pumps help maintain acid–base homeostasis either within intracellular compartments or at specialised plasma membranes. In mammals they are made up of 13 subunits, which form two functional domains. A number of the subunits have variants that display tissue restricted expression patterns such that in specialised cell types they replace the generic subunits at some sub-cellular locations. The tissue restricted a4 subunit has previously been reported at the plasma membrane in the kidney, inner ear, olfactory epithelium and male reproductive tract. Results In this study novel locations of the a4 subunit were investigated using an Atp6v0a4 knockout mouse line in which a LacZ reporter cassette replaced part of the gene. The presence of a4 in the olfactory epithelium was further investigated and the additional presence of C2 and d2 subunits identified. The a4 subunit was found in the uterus of pregnant animals and a4 was identified along with d2 and C2 in the embryonic visceral yolk sac. In the male reproductive tract a4 was seen in the novel locations of the prostatic alveoli and the ampullary glands as well as the previously reported epididymis and vas deferens. Conclusions The identification of novel locations for the a4 subunit and other tissue-restricted subunits increases the range of unique subunit combinations making up the proton pump. These studies suggest additional roles of the proton pump, indicating a further range of homologue-specific functions for tissue-restricted subunits

DC Microgrid Modeling and Energy Storage Placement to Enhance System Stability

The work of this thesis represents a joint venture between the University of Wisconsin-Milwaukee and the University of Wisconsin-Madison. A DC microgrid is selected for the efficiency benefits, lack of reactive power in the system, and ease of connecting to an AC grid. The system modeling relies on physical parameters and industry standard methods for the estimation of loads and lines. An example model is created for the University of Wisconsin - Milwaukee\u27s Campus. Due to the high penetration of renewable energy sources in the example model, system stability is a concern. To help mitigate stability issues, analysis is performed to have the ideal placement of energy storage. The analysis relies heavily on the deep properties of the system such as Eigenvalues and system controllability. Energy storage placement is verified and evaluated with model simulations

Synchronizing Automata on Quasi Eulerian Digraph

In 1964 \v{C}ern\'{y} conjectured that each $n$-state synchronizing automaton posesses a reset word of length at most $(n-1)^2$. From the other side the best known upper bound on the reset length (minimum length of reset words) is cubic in $n$. Thus the main problem here is to prove quadratic (in $n$) upper bounds. Since 1964, this problem has been solved for few special classes of \sa. One of this result is due to Kari \cite{Ka03} for automata with Eulerian digraphs. In this paper we introduce a new approach to prove quadratic upper bounds and explain it in terms of Markov chains and Perron-Frobenius theories. Using this approach we obtain a quadratic upper bound for a generalization of Eulerian automata.Comment: 8 pages, 1 figur

Renal peroxiredoxin 6 interacts with anion exchanger 1 and plays a novel role in pH homeostasis.

Peroxiredoxin 6 (PRDX6) is one of the six members of the PRDX family, which have peroxidase and antioxidant activity. PRDX6 is unique, containing only one conserved cysteine residue (C47) rather than the two found in other PRDXs. A yeast two-hybrid screen found PRDX6 to be a potential binding partner of the C-terminal tail of anion exchanger 1 (AE1), a Cl(-)/HCO(3)(-) exchanger basolaterally expressed in renal α-intercalated cells. PRDX6 immunostaining in human kidney was both cytoplasmic and peripheral and colocalized with AE1. Analysis of native protein showed that it was largely monomeric, whereas expressed tagged protein was more dimeric. Two methionine oxidation sites were identified. In vitro and ex vivo pull-downs and immunoprecipitation assays confirmed interaction with AE1, but mutation of the conserved cysteine resulted in loss of interaction. Prdx6 knockout mice had a baseline acidosis with a major respiratory component and greater AE1 expression than wild-type animals. After an oral acid challenge, PRDX6 expression increased in wild-type mice, with preservation of AE1. However, AE1 expression was significantly decreased in knockout animals. Kidneys from acidified mice showed widespread proximal tubular vacuolation in wild-type but not knockout animals. Knockdown of PRDX6 by siRNA in mammalian cells reduced both total and cell membrane AE1 levels. Thus, PRDX6-AE1 interaction contributes to the maintenance of AE1 during cellular stress such as during metabolic acidosis.Human kidney sections were prepared by Suzy Haward, Addenbrooke's Human Research Tissue Bank, which is supported by the Cambridge Biomedical Research Centre. We thank Dr. Aron Fisher (Institute for Environmental Science, University of Pennsylvania) for the kind gift of Prdx6−/− mice and reagents, Carsten Wagner (Zurich) for antisera, Jane Clarke (University of Cambridge) for modified pRSET-A vector, and Kamburapola Jayawardena for mass spectrometry (CIMR). This work was funded by the Wellcome Trust (award 088489/Z/09/Z to FEKF and Strategic award 100140/Z/12/Z to the Cambridge Institute for Medical Research), and the Jack Kent Cooke Foundation (scholarship to SLS).This is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/ki.2015.27

Accuracy of urine pH testing in a regional metabolic renal clinic: is the dipstick accurate enough?

Urine pH is a useful marker for assessing treatment need and efficacy in patients with nephrolithiasis. Though the gold standard of measurement is with a pH electrode, dipsticks offer the convenience of cost, ease of use, and the possibility of patients measuring their own values outside the clinic. The aim of this study was to determine whether dipsticks offer the same accuracy as the electrode. Paired measurements of freshly voided urine pH with both electrode and dipstick were analysed in a multidisciplinary renal clinic. We found that although there was a high Pearson correlation between the samples (0.89, p = 0.001), urine dipstick measurements carried an approximately 1 in 4 risk of producing clinically significant differences (pH differences  > 0.5 pH unit) from meter values. We also found that at high and low urine pH, the dipstick tended to over- and underestimate true pH readings, respectively. Examining the values in the 98 patients where a need for pharmacological urinary pH manipulation was indicated by the true pH, we found 14 who would not have been appropriately treated, and 5 who would have been unnecessarily medicated, if the stick pH value had been used. We conclude that dipstick pH measurement is insufficiently reliable for guiding clinical decision-making

Size-Exclusion Chromatography Separation Reveals That Vesicular and Non-Vesicular Small RNA Profiles Differ in Cell Free Urine.

Urinary extracellular vesicles (EVs) and their RNA cargo are a novel source of biomarkers for various diseases. We aimed to identify the optimal method for isolating small (<200 nm) EVs from human urine prior to small RNA analysis. EVs from filtered healthy volunteer urine were concentrated using three methods: ultracentrifugation (UC); a precipitation-based kit (PR); and ultrafiltration (UF). EVs were further purified by size-exclusion chromatography (SEC). EV preparations were analysed with transmission electron microscopy (TEM), Western blotting, nanoparticle tracking analysis (NTA) and an Agilent Bioanalyzer Small RNA kit. UF yielded the highest number of particles both before and after SEC. Small RNA analysis from UF-concentrated urine identified two major peaks at 10-40 nucleotides (nt) and 40-80 nt. In contrast, EV preparations obtained after UC, PR or SEC combined with any concentrating method, contained predominantly 40-80 nt sized small RNA. Protein fractions from UF+SEC contained small RNA of 10-40 nt in size (consistent with miRNAs). These data indicate that most of the microRNA-sized RNAs in filtered urine are not associated with small-sized EVs, and highlights the importance of removing non-vesicular proteins and RNA from urine EV preparations prior to small RNA analysis

Quantum Weakly Nondeterministic Communication Complexity

We study the weakest model of quantum nondeterminism in which a classical proof has to be checked with probability one by a quantum protocol. We show the first separation between classical nondeterministic communication complexity and this model of quantum nondeterministic communication complexity for a total function. This separation is quadratic.Comment: 12 pages. v3: minor correction

Synchronizing automata with a letter of deficiency 2

AbstractWe present two infinite series of synchronizing automata with a letter of deficiency 2 whose shortest reset words are longer than those for synchronizing automata obtained by a straightforward modification of Černý’s construction

The development of the Meaning in Life Index (MILI) and its relationship with personality and religious behaviours and beliefs among UK undergraduate students

The scales available for assessing meaning in life appear to be confounded with several related constructs, including purpose in life, satisfaction with life, and goal-directed behaviour. The Meaning in Life Index (MILI), a new instrument devised as a specific measure of meaning in life, was developed from responses to a pool of 22 items rated by a sample of 501 undergraduate students in Wales. The nine-item scale demonstrated sufficient face validity, internal consistency, and scale reliability to commend the instrument for future use. With respect to personality, the MILI scores were most strongly predicted by neuroticism (negatively), and less strongly by extraversion (positively) and psychoticism (negatively). With respect to several religious behavioural variables, those who attended church at least weekly returned significantly higher MILI scores than those who attended church less frequently. Intrinsic religiosity was the only orientation to be significantly associated with the MILI scale scores, although the magnitude of the association was smaller than anticipated. These results suggest that meaning in life is associated more strongly with individual differences in personality than with specific religious behaviours and attitudes. The implications of these results are discussed in terms of individual's personal values and attitudes that might underlie their experience of a meaning in life

Quantum fingerprinting

Classical fingerprinting associates with each string a shorter string (its fingerprint), such that, with high probability, any two distinct strings can be distinguished by comparing their fingerprints alone. The fingerprints can be exponentially smaller than the original strings if the parties preparing the fingerprints share a random key, but not if they only have access to uncorrelated random sources. In this paper we show that fingerprints consisting of quantum information can be made exponentially smaller than the original strings without any correlations or entanglement between the parties: we give a scheme where the quantum fingerprints are exponentially shorter than the original strings and we give a test that distinguishes any two unknown quantum fingerprints with high probability. Our scheme implies an exponential quantum/classical gap for the equality problem in the simultaneous message passing model of communication complexity. We optimize several aspects of our scheme.Comment: 8 pages, LaTeX, one figur