High throughput, automated prediction of focusing patterns for inertial microfluidics

Visual inspections for identifying focusing points in inertial microfluidic flows are prone to misinterpreting stable locations and focusing shifts in the case of non-trivial focusing patterns. We develop and deploy an approach for automating the calculation of focusing patterns for a general channel geometry, and thereby reduce the dependence on empirical/visual procedures to confirm the presence of stable locations. We utilize concepts from interpolation theory (to represent continuous force-fields using discrete points), and stability theory to identify basins of attraction and quantitatively identify stable equilibrium points. Our computational experiments reveal that predicting equilibrium points accurately requires upto ×10-20 times more refined force-maps that conventionally used, which highlights the spatial resolution required for an accurate representation of cross-sectional forces. These focusing patterns are validated using experimental results for a rectangular channel, and triangular channel with an apex angle of 90∘. We then apply the approach to predict and explain focusing patterns and shifts for a 90∘-isosceles triangular channel across a range of Reynolds numbers for aH=0.4(particle-to-channel size ratio). We observe that the predicted focusing patterns match experiments well. The force-maps also reveal certain clouds of localized stable points, which aid in explaining the onset of bifurcation observed in experiments. The current algorithm is agnostic to channel cross-sections and straight/curved channels, which could pave way to generating a library of focusing patterns as a function of channel geometry, and Re, to assist in design of novel devices for tailored particle-streams

Adventures in Crypto Dark Matter: Attacks, Fixes for Weak Pseudorandom Functions

A weak pseudorandom function (weak PRF) is one of the most important cryptographic primitives for its efficiency although it has lower security than a standard PRF. Recently, Boneh et al. (TCC\u2718) introduced two types of new weak PRF candidates, which are called a basic Mod-2/Mod-3 and alternative Mod-2/Mod-3 weak PRF. Both use the mixture of linear computations defined on different small moduli to satisfy conceptual simplicity, low complexity (depth-2 ${\sf ACC^0}$) and MPC friendliness. In fact, the new candidates are conjectured to be exponentially secure against any adversary that allows exponentially many samples, and a basic Mod-2/Mod-3 weak PRF is the only candidate that satisfies all features above. However, none of the direct attacks which focus on basic and alternative Mod-2/Mod-3 weak PRFs use their own structures. In this paper, we investigate weak PRFs from two perspectives; attacks, fixes. We first propose direct attacks for an alternative Mod-2/Mod-3 weak PRF and a basic Mod-2/Mod-3 weak PRF when a circulant matrix is used as a secret key. For an alternative Mod-2/Mod-3 weak PRF, we prove that the adversary\u27s advantage is at least $2^{-0.105n}$, where $n$ is the size of the input space of the weak PRF. Similarly, we show that the advantage of our heuristic attack to the weak PRF with a circulant matrix key is larger than $2^{-0.21n}$, which is contrary to the previous expectation that `structured secret key\u27 does not affect the security of a weak PRF. Thus, for an optimistic parameter choice $n = 2\lambda$ for the security parameter $\lambda$, parameters should be increased to preserve $\lambda$-bit security when an adversary obtains exponentially many samples. Next, we suggest a simple method for repairing two weak PRFs affected by our attack while preserving the parameters

Early Growth Response Factor-1 Is Associated With Intraluminal Thrombus Formation in Human Abdominal Aortic Aneurysm

ObjectivesThe goal of this study was to investigate the expression of early growth response-1 (Egr-1), a vascular pathogenic transcription factor, and its potential relationship with tissue factor (TF), a key player during the thrombus formation in the abdominal aortic aneurysm (AAA) wall.BackgroundAlthough intraluminal thrombus is a common finding in human AAA, the molecular mechanism of the thrombus formation has not been studied.MethodsDuring the elective AAA repair, specimens were taken from the thrombus-covered and thrombus-free portions of the aneurysmal wall in each of 16 patients with AAA and analyzed to assess the differential expression of Egr-1 and TF. The proinflammatory and prothrombogenic activities of Egr-1 in vasculature were evaluated in vitro and in vivo by overexpressing it using adenovirus.ResultsThe expression of both Egr-1 and TF was significantly increased in the thrombus-covered wall compared with the thrombus-free wall, in which their up-regulation in the thrombus-covered wall was strongly correlated with each other (p < 0.005, r = 0.717). Adenoviral overexpression of Egr-1 in human vascular smooth muscle and endothelial cells was found to up-regulate the expression of TF and inflammation-related genes. Moreover, Egr-1 overexpression in endothelial cells increased their adhesiveness to monocytes and also substantially promoted the intravascular thrombus formation in vivo, as shown in the inferior vena cava ligation experiment of the rat.ConclusionsThe present study demonstrates the differential up-regulation of Egr-1 in the thrombus-covered wall of human AAA and also suggests its possible contribution to the thrombogenic and inflammatory pathogenesis in human AAA

Inertial focusing in triangular microchannels with various apex angles

We consider inertial focusing of particles in channels with triangular cross sections. The number and the location of inertial focusing positions in isosceles triangular channels can change with varying blockage ratios (a/H) and Reynolds numbers (Re). In triangular channels, asymmetric velocity gradient induced by the sloped sidewalls leads to changes in the direction and the strength of the inertial lift forces. Therefore, varying the configuration (specifically, angle) of the triangular cross section is expected to lead to a better understanding of the nature of the inertial lift forces. We fabricated triangular microchannels with various apex angles using channel molds that were shaped by a planing process, which provides precise apex angles and sharp corners. The focusing position shift was found to be affected by the channel cross section, as expected. It was determined that the direction of the focusing position shift can be reversed depending on whether the vertex is acute or obtuse. More interestingly, corner focusing modes and splitting of the corner focusing were observed with increasing Re, which could explain the origin of the inertial focusing position changes in triangular channels. We conducted fluid dynamic simulations to create force maps under various conditions. These force maps were analyzed to identify the basins of attraction of various attractors and pinpoint focusing locations using linear stability analysis. Calculating the relative sizes of the basins of attractions and exhaustively identifying the focusing positions, which are very difficult to investigate experimentally, provided us a better understanding of trends in the focusing mechanism

Aldosterone Upregulates Connective Tissue Growth Factor Gene Expression via p38 MAPK Pathway and Mineralocorticoid Receptor in Ventricular Myocytes

The effect of aldosterone on connective tissue growth factor (CTGF) was examined in rat embryonic ventricular myocytes. Upon aldosterone treatment, CTGF expression was significantly increased in a dose and time-dependent manner. To explore the molecular mechanism for this upregulation, we examined the role of mineralocorticoid receptor. Pre-treatment of an antagonist (spironolactone) at 5-fold excess of aldosterone blocked the CTGF induction by aldosterone, suggesting that the upregulation was mediated by mineralocorticoid receptor. Aldosterone treatment resulted in activation of ERK1/2, p38 MAPK, and JNK pathways with a more transient pattern in p38 MAPK. Blocking studies using pre-treatment of the inhibitor of each pathway revealed that p38 MAPK cascade may be important for aldosterone-mediated CTGF upregulation as evidenced by the blocking of CTGF induction by SB203580 (p38 MAPK inhibitor), but not by PD098059 (ERK1/2 inhibitor) and JNK inhibitor I. Interestingly, JNK inhibitor I and PD098059 decreased the basal level of CTGF expression. On the other hand, pre-treatment of spironolactone abrogated the p38 MAPK activation, indicating that mineralocorticoid receptor mechanism is linked to p38 MAPK pathway. Taken together, our findings suggest that aldosterone induces CTGF expression via both p38 MAPK cascade and mineralocorticoid receptor and that cross-talk exists between the two pathways

Sclerostin inhibits Wnt signaling through tandem interaction with two LRP6 ectodomains

Low-density lipoprotein receptor-related protein 6 (LRP6) is a coreceptor of the beta -catenin-dependent Wnt signaling pathway. The LRP6 ectodomain binds Wnt proteins, as well as Wnt inhibitors such as sclerostin (SOST), which negatively regulates Wnt signaling in osteocytes. Although LRP6 ectodomain 1 (E1) is known to interact with SOST, several unresolved questions remain, such as the reason why SOST binds to LRP6 E1E2 with higher affinity than to the E1 domain alone. Here, we present the crystal structure of the LRP6 E1E2-SOST complex with two interaction sites in tandem. The unexpected additional binding site was identified between the C-terminus of SOST and the LRP6 E2 domain. This interaction was confirmed by in vitro binding and cell-based signaling assays. Its functional significance was further demonstrated in vivo using Xenopus laevis embryos. Our results provide insights into the inhibitory mechanism of SOST on Wnt signaling. The low-density lipoprotein receptor-related protein 6 (LRP6) is a co-receptor of the beta -catenin-dependent Wnt signaling pathway and interacts with the Wnt inhibitor sclerostin (SOST). Here the authors present the crystal structure of SOST in complex with the LRP6 E1E2 ectodomain construct, which reveals that the SOST C-terminus binds to the LRP6 E2 domain, and further validate this binding site with in vitro and in vivo experiments.Y

Noninvasive predictors of nonalcoholic steatohepatitis in Korean patients with histologically proven nonalcoholic fatty liver disease

Background/AimsThe aims of this study were (1) to identify the useful clinical parameters of noninvasive approach for distinguishing nonalcoholic steatohepatitis (NASH) from nonalcoholic fatty liver disease (NAFLD), and (2) to determine whether the levels of the identified parameters are correlated with the severity of liver injury in patients with NASH.MethodsOne hundred and eight consecutive patients with biopsy-proven NAFLD (age, 39.8±13.5 years, mean±SD; males, 67.6%) were prospectively enrolled from 10 participating centers across Korea.ResultsAccording to the original criteria for NAFLD subtypes, 67 patients (62.0%) had NASH (defined as steatosis with hepatocellular ballooning and/or Mallory-Denk bodies or fibrosis ≥2). Among those with NAFLD subtype 3 or 4, none had an NAFLD histologic activity score (NAS) below 3 points, 40.3% had a score of 3 or 4 points, and 59.7% had a score >4 points. Fragmented cytokeratin-18 (CK-18) levels were positively correlated with NAS (r=0.401), as well as NAS components such as lobular inflammation (r=0.387) and ballooning (r=0.231). Fragmented CK-18 was also correlated with aspartate aminotransferase (r=0.609), alanine aminotransferase (r=0.588), serum ferritin (r=0.432), and the fibrosis stage (r=0.314). A fragmented CK-18 cutoff level of 235.5 U/L yielded sensitivity, specificity, and positive and negative predictive values of 69.0%, 64.9%, 75.5% (95% CI 62.4-85.1), and 57.1% (95% CI 42.2-70.9), respectively, for the diagnosis of NASH.ConclusionsSerum fragmented CK-18 levels can be used to distinguish between NASH and NAFL. Further evaluation is required to determine whether the combined measurement of serum CK-18 and ferritin levels improves the diagnostic performance of this distinction

Highly clustered complex networks in the configuration model: Random regular small-world network

We propose a method to make a highly clustered complex network within the configuration model. Using this method, we generated highly clustered random regular networks and analyzed their properties. We show that highly clustered random regular networks with appropriate parameters satisfy all the conditions of the small-world network: connectedness, high clustering coefficient, and small-world effect. We also study how clustering affects the percolation threshold in random regular networks. In addition, the prisoner's dilemma game is studied and the effects of clustering and degree heterogeneity on the cooperation level are discussed