Identification and expression analysis of type II and type III Pi transporters in the opossum kidney cell line.

New Findings: What is the central question of this study? The opossum kidney (OK) cell line is the main in vitro model of proximal tubular Pi transport, but it is incomplete because only the NaPiIIa Pi transporter has been identified. What is the main finding and its importance? We have cloned and characterized the Pi transporters NaPiIIc, PiT1 and PiT2 from OK cells and have analysed the relevance of the four transporters to Pi transport. All four transporters are involved in the upregulated Pi transport of cells incubated using a low-Pi medium, and only PiT1 is not involved in basal transport. Abstract: The apical membrane of renal proximal tubular epithelial cells is the main controller of phosphate homeostasis, because it determines the rate of urinary Pi excretion. The opossum kidney (OK) cell line is a good model for studying this function, but only NaPiIIa (NaPi4) has been identified to date as a Pi transporter in this cell line. In this work, we have identified three additional Pi transporters that are present in OK cells: NaPiIIc, PiT1 and PiT2. All three sequences are similar to the corresponding orthologues, but PiT1 is missing the first transmembrane domain. Confluent cells exhibit characteristics of type II Pi transport, which increases with alkalinity and is inhibited by phosphonoformic acid (PFA), and they mainly express NaPiIIa and NaPiIIc, with a low abundance of PiT1 and PiT2. Proliferating cells show a higher expression of PiT1 and PiT2 and a low expression of NaPiIIa and NaPiIIc. Adaptation to a low Pi concentration for 24 h induces the expression of RNA from NaPiIIa and NaPiIIc, which is not prevented by actinomycin D. Small interfering RNA transfections revealed that PiT1 is not necessary for Pi transport, but it is necessary for adaptation to a low Pi, similar to NaPiIIa and PiT2. Our study reveals the complexity of the coordination between the four Pi transporters, the variability of RNA expression according to confluence and the heterogeneous correlation between Pi transport and RNA levels

SCMA: Plaintext Classification Assisted Side Channel Spectral Modulation Attacks. Towards Noise-insensitive SCA Attacks...

Side-channel analysis (SCA) attacks manifest a significant challenge to the security of cryptographic devices. In turn, it is generally quite expensive to protect from SCAs (energy, area, performance etc.). In this work we exhibit a significant change in paradigm for SCA attacks: our proposed attack is quite different from conventional SCA attacks and is able to filter out physical measurement noise, algorithmic noise, as well as thwart various countermeasures, and extract information from the entire leakage waveform as a whole and not only points-of-interest. We demonstrate on measured devices break of masking schemes of orders 2 and 3, supported by a model and also shuffling and dual-rail based countermeasures model; all performed efficiently with the same methodology, and with orders of magnitude less measurements and smaller computation time; underpinning the importance of this form of attack. In essence, in our attack we assume nothing different than a standard side-channel attack, i.e., a known plaintext scenario. However, we further group and classify leakages associated with specific subsets of plaintexts bits. The fact that we group specific (sub-)plaintexts associated leakages, and than in the next stage group or concatenate the associated leakages of these large groups in a predefined ordered sequence (modulation), enables far stronger attacks against SCA protected and unprotected designs. The evaluation-domain or the modulation-domain is the frequency domain in which per frequency it is possible to build a two feature constellation diagrams (amplitude and phase) and construct distinguishers over these diagrams. On top of the methodological contribution of this new SCA, the main observation we push forward is that practically such an attack is devastating for many countermeasures we were used to consider as secure to some level, such as masking or shuffling with large permutation size. As an example, leakage from a third order masked design can be detected with merely 100 leakage traces from the first statistical moment of the leakage as compared to $15\cdot10^6$ traces with conventional SCA leakage detection test from the third statistical order

Revealing the Secrets of Radio-Enabled Embedded Systems: on extraction of raw information from any on-board signal through RF

In this work we are interested in evaluating the possibility of extracting information from radio-enabled embedded-systems from a long distance. That is, our focus is capturing information from sources in the micrometer to tens of centimeters scale, such as intra- or inter- device busses, board-level routing traces etc. Moreover, we focus on distances in the range of millimeters to tens of centimeters from the (on-chip or on-board) embedded-system Tx Antenna to the signal source. Side-channels denotes presence of information in illegitimate channels. Side-channel analysis (SCA) attacks typically require statistical analysis and many leakage traces, focusing on micrometer level signals (sources) which emanate direct Near-Field information up to centimeters-level distances. In the same context (Near-Field and micrometer-level) simple power analysis (SPA) like attacks typically extract either direct raw information from one or few leakages or utilize statistical analysis on various samples from the same trace, similarly to horizontal attacks. Lately, radio-enabled systems were shown to emanate to a large distance (Far-Field), information from micrometer level sources, such as CPU processing, through the RF Tx Antenna: so far, SCA-like statistical analysis were shown. On the other hand, various reports exist on direct information eavesdropping/ sniffing or data exfiltration, emanated from centimeter to tens of centimeters scale sources, e.g., SATA, USB, Power-lines, Serial interface, Air-Gap systems, Screens and even optical fibers. All these elements are typically being used as a source and a direct Tx Antenna (huge, several to tens of centimeters) of the sensitive information. These antennas typically transmit information to short distances and the decay is very steep (proportional to $r^{-2}$-$r^{-3}$ depending on various factors and models). To the best of our knowledge, we report here for the first time an alarming security challenge: any signal in the embedded system, from serial ports, DMA-controlled memory-access, JTAG and SPI interfaces, on-board signals with galvanic connection to the Tx Antenna-chip and \emph{on-board signals without galvanic connection to the Tx Antenna-chip itself, all leak direct information up to tens of centimeters from source to the Tx Antenna}. This alarming situation induce signal-integrity implications within the embedded system, and significant implications relating to device-isolation and user-isolation, it may also affect standards and specifications for e.g., electromagnetic compatibility (EMC), on-board signal shielding, electromagnetic and RF interference (EMI, RFI), cross-talk, and generally design-for-manufacturing (DFM) guidelines for both intra-IC and PCB board. We demonstrate such direct readout of signals with commercial and low-cost equipment indicating how problematic the situation is. The existence of such leakage is demonstrated both over an ultra-low-cost platform such as the nRF52832(nRF) embedded-system and on a more advanced ESP32-c3-devkitc-02 board which is far more widespread in ISM radio applications and meets certification like FCC and CE (as compared to the nRF device). We have constructed an experiment to demonstrate leakage scenarios from (1) on- and (2) off-chip, on-board or (3) signals without galvanic connection to the RF front-end chip, showing the severity of the leakage, repetitively and systematic nature of the phenomena over various devices. We further demonstrate how sophisticated adversaries can build a code-injection Gadget which can carry sensitive-data and modulate it to be best extracted by the RF-channel. The main observation we push forward is that unless concrete interference and isolation standards appear with security metrics in mind, which are significantly different than ones needed for communication, it would be hard to prevent such leakages

Effect of ischemia reperfusion on sodium-dependent phosphate transport in renal brush border membranes

AbstractThe effect of ischemia induced acute renal failure (ARF) on the transport of phosphate (Pi) after early (15–30 min) and prolonged (60 min) ischemia in the brush border membrane vesicles (BBMV) from rat renal cortex was studied. Sodium-dependent transport of Pi declined significantly and progressively due to ischemia. Western blot analysis of BBM from ischemic rats showed decreased expression of NaPi-2. A compensatory increase was observed in Pi uptake in BBMV from contralateral kidneys. There was no significant difference in NaPi-2 expression between BBMV from sham and contralateral kidneys. Early blood reperfusion for 15 min after 30 min ischemia caused further decline in Pi uptake. Prolonged reperfusion for 120 min caused partial reversal of transport activities in 30-min ischemic rats. However, no improvement in the transport of Pi was observed in 60-min ischemic rats after 120 min of blood reperfusion. Kinetic studies showed that the effect of ischemia and blood reperfusion was dependent on the Vmax of the Na-Pi transporter. Western blot analysis showed increased expression of NaPi-2 in the BBMs from ischemia–reperfusion animals. Further, a shift in the association of Na ions to transport one molecule of Pi was observed under different extracellular Na concentrations [Na]o. Feeding rats with low Pi diet and/or treatment with thyroid hormone (T3) prior to ischemia resulted in increased basal Pi transport. Ischemia caused similar decline in Pi transport in BBM from LPD and/or T3 animals. However, recovery in these animals was faster than the normal Pi diet fed (NPD) animals. The study suggests a change in the intrinsic properties of the Na-Pi transporter in rat kidneys due to ischemia. The study also indicates that treatment with T3 and feeding LPD prior to ischemia caused faster recovery of phosphate uptake due to ischemia–reperfusion injury

Circular dichroism enhancement in plasmonic nanorod metamaterials

Optical activity is a fundamental phenomenon originating from the chiral nature of crystals and molecules. While intrinsic chiroptical responses of ordinary chiral materials to circularly polarized light are relatively weak, they can be enhanced by specially tailored nanostructures. Here, nanorod metamaterials, comprising a dense array of vertically aligned gold nanorods, is shown to provide a significant enhancement of the circular dichroism response of an embedded material. A nanorod composite, acting as an artificial uniaxial crystal, is filled with chiral mercury sulfide nanocrystals embedded in a transparent polymer. The metamaterial, being inherently achiral, enables optical activity enhancement or suppression. Unique properties of inherently achiral structures to tailor optical activities pave a way for flexible characterization of optical activity of molecules and nanocrystal-based compounds.EPSRC (UK); ERC iPLASMM (321268); TAU Rector grant; PAZY foundation; German-Israeli Foundation (2399); Israel Sciecnce Foundataion (507/14); Russian Foundation for Basic Research (16-52-00112); Russian Science Foundation (16-12-10287); Ministry of Education and Science of Russian Federation (SP-4248.2016.1, 3.4982.2017/6.7); Royal Society; Wolfson Foundation

The Mechanism of Diabetic Retinopathy Pathogenesis Unifying Key Lipid Regulators, Sirtuin 1 and Liver X Receptor

Diabetic retinopathy (DR) is a complication secondary to diabetes and is the number one cause of blindness among working age individuals worldwide. Despite recent therapeutic breakthroughs using pharmacotherapy, a cure for DR has yet to be realized. Several clinical trials have highlighted the vital role dyslipidemia plays in the progression of DR. Additionally, it has recently been shown that activation of Liver X receptor (LXRα/LXRβ) prevents DR in diabetic animal models. LXRs are nuclear receptors that play key roles in regulating cholesterol metabolism, fatty acid metabolism and inflammation. In this manuscript, we show insight into DR pathogenesis by demonstrating an innovative signaling axis that unifies key metabolic regulators, Sirtuin 1 and LXR, in modulating retinal cholesterol metabolism and inflammation in the diabetic retina. Expression of both regulators, Sirtuin 1 and LXR, are significantly decreased in diabetic human retinal samples and in a type 2 diabetic animal model. Additionally, activation of LXR restores reverse cholesterol transport, prevents inflammation, reduces pro-inflammatory macrophages activity and prevents the formation of diabetes-induced acellular capillaries. Taken together, the work presented in this manuscript highlights the important role lipid dysregulation plays in DR progression and offers a novel potential therapeutic target for the treatment of DR

Circular Dichroism Enhancement in Plasmonic Nanorod Metamaterials

Optical activity is a fundamental phenomenon originating from the chiral nature of crystals and molecules. While intrinsic chiroptical responses of ordinary chiral materials to circularly polarized light are relatively weak, they can be enhanced by specially tailored nanostructures. Here, nanorod metamaterials, comprising a dense array of vertically aligned gold nanorods, is shown to provide significant enhancement of the circular dichroism response of an embedded material. A nanorod composite, acting as an artificial uniaxial crystal, is filled with chiral mercury sulfide nanocrystals embedded in a transparent polymer. The nanorod based metamaterial, being inherently achiral, enables optical activity enhancement or suppression. Unique properties of inherently achiral structures to tailor optical activities pave a way for flexible characterization of optical activity of molecules and nanocrystal-based compounds

On Charged Black Holes in Anti-de Sitter Space

We study the region inside the event horizon of charged black holes in five dimensional asymptotically anti-de Sitter space, using as a probe two-sided correlators which are dominated by spacelike geodesics penetrating the horizon. The spacetimes we investigate include the Reissner-Nordstrom black hole and perturbations thereof. The perturbed spacetimes can be found exactly, enabling us to perform a local scan of the region between the inner and outer horizons. Surprisingly, the two-sided correlators we calculate seem to be geometrically protected from the instability of the inner horizon.Comment: 1+37 pages, 20 ps and eps figures, LaTeX. References added and changes made to section

Closed Timelike Curves and Holography in Compact Plane Waves

We discuss plane wave backgrounds of string theory and their relation to Goedel-like universes. This involves a twisted compactification along the direction of propagation of the wave, which induces closed timelike curves. We show, however, that no such curves are geodesic. The particle geodesics and the preferred holographic screens we find are qualitatively different from those in the Goedel-like universes. Of the two types of preferred screen, only one is suited to dimensional reduction and/or T-duality, and this provides a ``holographic protection'' of chronology. The other type of screen, relevant to an observer localized in all directions, is constructed both for the compact and non-compact plane waves, a result of possible independent interest. We comment on the consistency of field theory in such spaces, in which there are closed timelike (and null) curves but no closed timelike (or null) geodesics.Comment: 21 pages, 3 figures, LaTe