Post-transplant proteinuria associated with everolimus: Definition of main features with proteomics

Little is known on both the composition and mechanism(s) of proteinuria associated with the use of mTOR inhibitors, in particular of Everolimus (E). We characterized urinary proteins utilizing an integrated proteomics approach (quantitative essays, 2‐DE, MALDI‐TOF, Western blot) in 48 renal transplant recipients who were alternatively treated with E (n = 31) or with enteric coated mycophenolic acid (EC‐MPA) (n = 17). Twelve E patients (39%) developed high (>3 g/day) or intermediate proteinuria (1–3 g) compared to four (23%) of the EC‐MPA group. Urinary proteins (p<0.001), β2 microglobulin (p<0.001) and α1microglobulin (p<0.025) were higher in E than in EC‐MPA, appeared more rapidly and were inversely correlated with the day of treatment. Proteomics showed a marked increase of all urinary components in E and EC‐MPA patients, major changes involving typical components of glomerular damage (albumin, α1‐Zn glycoprotein, α2HS glycoprotein, leucin‐richα2‐glycoprotein) and specific bio‐markers for E (clusters of α1‐antitrypsin fragments and monoclonal λ chains). Finally, inter‐α‐trypsin‐inhibitor heavy chain H4 precursor was decreased in E and EC‐MPA urine compared to normal urine. In conclusion, E induced massive and generalized proteinuria of mixed glomerular and tubular origin that was correlated with the start of treatment and reached a nephrotic range in few cases. Specific urinary markers reflect renal alterations related to the transplant or specific alterations associated with the drug.     

Regional sub-hourly extreme rainfall estimates in Sicily under a scale invariance framework

Design of urban drainage systems or flood risk assessment in small catchments often requires knowledge of very short-duration rainfall events (less than 1 h). Unfortunately, data for these events are often unavailable or too scarce for a reliable statistical inference. However, regularities in the temporal pattern exhibited by storm records, known as scaling properties of rainfall, could help in characterizing extreme storms at partially gauged sites better than the application of traditional statistical techniques. In this work, a scaling approach for estimating the distribution of sub-hourly extreme rainfall in Sicily (Italy) is presented based on data from high-resolution rain gauges with a short functioning period and from low-resolution rain gauges with longer samples. First, simple scaling assumption was tested for annual maxima rainfall (AMR) data from 10 min to 24 h duration, revealing that the simple scaling regime holds from 20 to 60 min for most of the stations. Then, scaling homogeneous regions were classified based on the values of the scaling exponent. In each region, this parameter was regionalized through power-law relationships with the median of 1 h AMR data. After that, regional Depth Duration Frequency (DDF) curves were developed by combining the scale-invariant framework with the generalized extreme value (GEV) probability distribution and used to estimate T-year sub-hourly extreme rainfalls at sites where only rainfall data for longer durations (≥ 1 h) were available. The regional GEV simple scaling model was validated against sub-hourly historical observations at ten rain gauges, generally yielding, in relation to the scaling exponent value, to similar or better sub-hourly estimates than empirical approach.

     

中等传输距离下的无线功率传输链路第1部分:实现工作状态最优化

中程无线功率传输(WPT)可以采用几种不同的方式实现,如通过电感或电容耦合、谐振或非谐振网络实现.本文主要研究了通过感应耦合谐振器实现的WPT链路,而且只着重研究了利用2个谐振器的链路(直接链路)并工作在主谐振频率下的情况.研究结果表明,当工作在主谐振频率下,可以根据网络参数来对传输效率或负载功率进行优化.     

A2A Receptor Dysregulation in Dystonia DYT1 Knock-Out Mice

We aimed to investigate A2A receptors in the basal ganglia of a DYT1 mouse model of dystonia. A2A was studied in control Tor1a+/+ and Tor1a+/− knock-out mice. A2A expression was assessed by anti-A2A antibody immunofluorescence and Western blotting. The co-localization of A2A was studied in striatal cholinergic interneurons identified by anti-choline-acetyltransferase (ChAT) antibody. A2A mRNA and cyclic adenosine monophosphate (cAMP) contents were also assessed. In Tor1a+/+, Western blotting detected an A2A 45 kDa band, which was stronger in the striatum and the globus pallidus than in the entopeduncular nucleus. Moreover, in Tor1a+/+, immunofluorescence showed A2A roundish aggregates, 0.3–0.4 μm in diameter, denser in the neuropil of the striatum and the globus pallidus than in the entopeduncular nucleus. In Tor1a+/−, A2A Western blotting expression and immunofluorescence aggregates appeared either increased in the striatum and the globus pallidus, or reduced in the entopeduncular nucleus. Moreover, in Tor1a+/−, A2A aggregates appeared increased in number on ChAT positive interneurons compared to Tor1a+/+. Finally, in Tor1a+/−, an increased content of cAMP signal was detected in the striatum, while significant levels of A2A mRNA were neo-expressed in the globus pallidus. In Tor1a+/−, opposite changes of A2A receptors’ expression in the striatal-pallidal complex and the entopeduncular nucleus suggest that the pathophysiology of dystonia is critically dependent on a composite functional imbalance of the indirect over the direct pathway in basal ganglia.     

Formalizing and Analyzing the Needham-Schroeder Symmetric-Key Protocol by Rewriting

This paper reports on work in progress on using rewriting techniques for the specification and the verification of communication protocols. As in Genet and Klay's approach to formalizing protocols, a rewrite system describes the steps of the protocol and an intruder's ability of decomposing and decrypting messages, and a tree automaton encodes the initial set of communication requests and an intruder's initial knowledge. In a previous work we have defined a rewriting strategy that, given a term t that represents a property of the protocol to be proved, suitably expands and reduces t using the rules in and the transitions in to derive whether or not t is recognized by an intruder. In this paper we present a formalization of the Needham-Schroeder symmetric-key protocol and use the rewriting strategy for deriving two well-known authentication attacks.     

Salt reduction in film‐ripened,semihard Edam cheese

As a potential measure to improve public health, this study aimed to reduce the sodium (Na) content of film‐ripened, semihard Edam cheese to ≤0.4 g Na/100 g (≤1 g NaCl/100 g), while retaining typical quality and safety characteristics. For this, mineral salt substitutions containing potassium (K) were compared with simple NaCl reduction in brine, alongside an adjustment of starter cultures in an effort to enhance taste. Desired Na and K values were achieved, and microbial quality was not compromised in Na‐reduced Edam after six weeks of ripening. However, all Na‐reduced cheeses tasted bitter and were therefore organoleptically unsatisfactory.