Miracle-dz/UniFAR-FTUs huggingface dataset:
Diagnostic strategies in CADASIL

Diagnostic strategies in CADASIL To the Editor: The low sensitivity of skin biopsy for diagnosis of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) reported by Markus et al.1 is a helpful contribution that is in agreement with our own experience. However, methodologic issues suggest that skin biopsy may in fact perform even more poorly than the authors suggest. Markus et al. used nondetection of a mutation on the notch3 gene as the criterion to exclude the presence of CADASIL. The genetic tool used to screen exon 2 and exons 5 to 23 was single strand conformation polymorphism (SSCP) analysis. The sensitivity of this technique in detecting mutations varies, but is typically 80 to 85%. Recent work has shown that tools such as high performance density liquid chromatography may detect mutations missed on screening with SSCP2 and even complete gene sequencing will fail to detect certain types of molecular pathology. This would imply that the genetic tools employed by the authors are not the sole basis on which the diagnosis of CADASIL can be refuted. Indeed, genetic tests alone should not be used as the basis for exclusion of inherited disorders. The report documents 3 of 35 mutation-negative patients who
A Formal Theory of Relevancy in Problem Solving A Formal Theory of Relevancy in Problem Solving

When computer scientists discuss the computational complexity of, e.g., finding the shortest path from building A to building B in some town or city, their starting point typically is a formal description of the problem at hand, e.g., a graph with weights on every edge where buildings correspond to vertices, routes between buildings to edges, and route-distances to edge-weights. Given such a formal description, either tractability or intractability of the problem is established, by proving that the problem enjoys a polynomial time algorithm, respectively is NP-hard. However, this problem description is in fact an abstraction of the actual problem of being in A and desiring to go to B: it focuses on the relevant aspects of the problem (e.g., distances between landmarks and crossings) and leaves out a lot of irrelevant details. This abstraction step is often overlooked, but may well contribute to the overall complexity of solving the problem at hand. For example, it appears that "going from A to B" is rather easy to abstract: it is fairly clear that the distance between A and the next crossing is relevant, and that the color of the roof of B is typically not. However, when the problem to be solved is "make X love me", where the current state is (assumed to be) "X doesn't love me", it is hard to agree on all the relevant aspects of this problem. In this paper a framework is presented in order to capture the notion of relevance in finding a suitable problem representation. It is shown that it is in itself intractable in general to find a minimal relevant subset of all features that might or might not be relevant to the problem. The paper aims to contribute a formal notion of ‘relevancy’ in problem solving, in order to be able to separate ‘easy to abstract’ from ‘hard to abstract’ problems and discuss individual differences in the abstraction task, e.g., when experts in a particular domain are compared with novice problem solvers.
Development of mitral cells and olfactory bulb layers in neonatally undernourished rats

Abstract Cell alterations in the central nervous system are consistent consequences of early undernourishment. Because little is known about the effects of neonatal udernourishment upon the main olfactory bulb (OB) in Golgi–Cox stained material, we evaluated the total OB cross-sectional area, the area of individual OB layers, and the area of type II mitral cells perikarya and their dendritic processes in undernourished Wistar rats of 7, 14, and 21 days of age. Data showed that neonatal undernourishment reduced both the OB and the individual layers areas; minimal perikarya effects and significant reductions in the number and extension of MC dendrites. Although macroneurons are formed prenatally, neonatal undernourishment at critical periods may have long-lasting effects that interfere with the functional maturity of the OB. These findings may have relevant consequences for early odor discrimination of the offspring, since olfaction is a fundamental sensorial avenue for newborn adaptive responses and maternal care.
Measurement of Human Cytochrome P450 Enzyme Induction Based on Mesalazine and Mosapride Citrate Treatments Using a Luminescent Assay

Drug metabolism mostly occurs in the liver. Cytochrome P450 (CYP) is a drug-metabolizing enzyme that is responsible for many important drug metabolism reactions. Recently, the US FDA and EU EMA have suggested that CYP enzyme induction can be measured by both enzymatic activity and mRNA expression. However, these experiments are time-consuming and their inter-assay variability can lead to misinterpretations of the results. To resolve these problems and establish a more powerful method to measure CYP induction, we determined CYP induction by using luminescent assay. Luminescent CYP assays link CYP enzyme activity to firefly luciferase luminescence technology. In this study, we measured the induction of CYP isozymes (1A2, 2B6, 2C9, and 3A4) in cryopreserved human hepatocytes (HMC424, 478, and 493) using a luminometer. We then examined the potential induction abilities (unknown so far) of mesalazine, a drug for colitis, and mosapride citrate, which is used as an antispasmodic drug. The results showed that mesalazine promotes CYP2B6 and 3A4 activities, while mosapride citrate promotes CYP1A2, 2B6, and 3A4 activities. Luminescent CYP assays offer rapid and safe advantages over LC-MS/MS and qRT-PCR methods. Furthermore, luminescent CYP assays decrease the interference between the optical properties of the test compound and the CYP substrates. Therefore, luminescent CYP assays are less labor intensive, rapid, and can be used as robust tools for high-throughput CYP screening during early drug discovery.
Truncated initiation factor eIF4G lacking an eIF4E binding site can support capped mRNA translation

Picornavirus proteases cleave translation initiation factor eIF4G into a C‐terminal two‐thirds fragment (hereafter named p100) and an N‐terminal one‐third fragment, which interacts with the cap‐binding factor eIF4E. As the timing of this cleavage correlates broadly with the shut‐off of host cell protein synthesis in infected cells, a very widespread presumption has been that p100 cannot support capped mRNA translation. Through the use of an eIF4G‐depleted reticulocyte lysate system, we show that this presumption is incorrect. Moreover, recombinant p100 can also reverse the inhibition of capped mRNA translation caused either by m7GpppG cap analogue, by 4E‐BP1, which sequesters eIF4E and thus blocks its association with eIF4G, or by cleavage of endogenous eIF4G by picornavirus proteases. The concentration of p100 required for maximum translation of capped mRNAs is ∼4‐fold higher than the endogenous eIF4G concentration in reticulocyte lysates. Our results imply that picornavirus‐induced shut‐off is not due to an intrinsic inability of p100 to support capped mRNA translation, but to the viral RNA outcompeting host cell mRNA for the limiting concentration of p100.
Helioseismic Probing of Solar Variability: The Formalism and Simple Assessments

We derive formulae connecting the frequency variations in the spectrum of solar oscillations to the dynamical quantities that are expected to change over the solar activity cycle. This is done for both centroids and the asymmetric part of the fine structure (so-called even-a coefficients). We consider the near-surface, small-scale magnetic and turbulent velocity fields, as well as horizontal magnetic fields buried near the base of the convective zone. For the centroids we also discuss the effect of temperature variation. We demonstrate that there is a full, one-to-one correspondence between the expansion coefficients of the fine structure and those of both the averaged small-scale velocity and magnetic fields. Measured changes in the centroid frequencies and the even-a coefficients over the rising phase solar cycle may be accounted for by a decrease in the turbulent velocity of order 1%. We show that the mean temperature decrease associated with the net decrease in the efficiency of convective transport may also significantly contribute to the increase of the centroid frequencies. Alternatively, the increase may be accounted for by an increase of the small-scale magnetic field of order 100 G, if the growing field is predominantly radial. We also show that global seismology can be used to detect a field at the level of a few times 105 G, if such a field were present and confined to a thin layer near the base of the convective envelope.
Anodic oxidation of oxytetracycline: Influence of the experimental conditions on the degradation rate and mechanism

The anodic oxidation of oxytetracycline was performed with success using as anode a boron-doped diamond electrode. The experiments were conducted in batch mode, using two different electrochemical cells: an up-flow cell, with recirculation, that was used to evaluate the influence of recirculation flow rate; and a stirred cell, used to determine the influence of the applied current density. Besides oxytetracyclin electrodegradation rate and mineralization extent, oxidation by-products were also assessed. Both the flow rate and the applied current density have shown positive influence on the oxytetracycline oxidation rate. On the other hand, the mineralization degree presented the highest values at the lowest flow rate and the lowest current density tested. The main oxidation by-products detected were oxalic, oxamic and maleic acids.
Oxidation of Hepatic Carnitine Palmitoyl Transferase-I (CPT-I) Impairs Fatty Acid Beta-Oxidation in Rats Fed a Methionine-Choline Deficient Diet

There is growing evidence that mitochondrial dysfunction, and more specifically fatty acid β-oxidation impairment, is involved in the pathophysiology of non-alcoholic steatohepatitis (NASH). The goal of the present study was to achieve more understanding on the modification/s of carnitinepalmitoyltransferase-I (CPT-I), the rate-limiting enzyme of the mitochondrial fatty acid β-oxidation, during steatohepatitis. A high fat/methionine-choline deficient (MCD) diet, administered for 4 weeks, was used to induce NASH in rats. We demonstrated that CPT-Iactivity decreased, to the same extent, both in isolated liver mitochondria and in digitonin-permeabilized hepatocytes from MCD-diet fed rats. At the same time, the rate of total fatty acid oxidation to CO2 and ketone bodies, measured in isolated hepatocytes, was significantly lowered in treated animals when compared to controls. Finally, an increase in CPT-I mRNA abundance and protein content, together with a high level of CPT-I protein oxidation was observed in treated rats. A posttranslational modification of rat CPT-I during steatohepatitis has been here discussed.
An Empirical Study on Web Mining of Parallel Data

This paper presents an empirical approach to mining parallel corpora. Conventional approaches use a readily available collection of comparable, non-parallel corpora to extract parallel sentences. This paper attempts the much more challenging task of directly searching for high-quality sentence pairs from the Web. We tackle the problem by formulating good search query using 'Learning to Rank' and by filtering noisy document pairs using IBM Model 1 alignment. End-to-end evaluation shows that the proposed approach significantly improves the performance of statistical machine translation.
Analysis and validation of a real-time AC drive simulator

This paper presents the analysis and validation of a real-time AC drive simulator. Real-time simulation has been used for over a decade in power systems engineering to test controllers thoroughly, efficiently, and safely. The development and testing of large DC drives could benefit from this type of simulation, but real-time power system simulators have modeling restrictions preventing stable and accurate simulation of isolated drives switching at high frequencies. These restrictions can be overcome by combining in a single model both the power converter and motor models. After discussing the salient issues related to the real-time simulation of DC drives, a prototype real-time simulator for drives is described. Its ability to accurately emulate the behavior of large drives is demonstrated through two case studies. A first case study demonstrates the feasibility of simulating a drive of typical complexity in real-time. The second case study demonstrates how the controller for a PWM VSI fed induction motor, switching at 4 kHz, is designed, implemented in a microcontroller and tested in real-time using a simulated inverter, motor and load. Comparisons against results obtained with another simulation tool, which uses extremely accurate variable-step integration algorithms, demonstrates the validity of our approach.
Quartic polynomial approximation for fluctuations of separation of trajectories in chaos and correlation dimension

We consider the cumulant generating function of the logarithm of the distance between two infinitesimally close trajectories of a chaotic system. Its long-time behavior is given by the generalized Lyapunov exponent providing the logarithmic growth rate of the kth moment of the distance. The Legendre transform of is a large deviations function that gives the probability of rare fluctuations where the logarithmic rate of change of the distance is much larger or much smaller than the mean rate defining the first Lyapunov exponent. The only non-trivial zero of is at minus the correlation dimension of the attractor which for incompressible flows reduces to the space dimension. We describe here general properties constraining the form of and the Gallavotti–Cohen type relations that hold when there is symmetry under time-reversal. This demands studying joint growth rates of infinitesimal distances and volumes. We demonstrate that quartic polynomial approximation for does not violate the Marcinkiewicz theorem on invalidity of polynomial form for the generating function. We propose that this quartic approximation will fit many experimental situations, not having the effective time-reversibility and the short correlation time properties of the quadratic Grassberger–Procaccia estimates. We take the existing for turbulent channel flow and demonstrate that the quartic fit is nearly perfect. The violation of time-reversibility for the Lagrangian trajectories of the incompressible Navier–Stokes (NS) turbulence below the viscous scale is considered. We demonstrate how the fit can be used for finding the correlation dimensions of strange attractors via easily measurable quantities. We provide a simple formula via the Lyapunov exponents, holding in quadratic approximation, and describe the construction of the quartic approximation. A different approximation scheme for finding the correlation dimension from expansion in the flow compressibility is also provided.
On Shape Recovery from Two Shading Patterns

In this paper, we analyze the problem of recovering the shape of a smooth Lambertian surface from two images obtained by consecutive illumination of the surface by distant point light-sources from two different directions. We discuss the issues of existence and uniqueness of solutions to the corresponding system of two first-order non-linear partial differential equations. We show that generically this system has, up to a constant, a unique solution. We also examine exceptional cases for which there is no such uniqueness.
Postoperative pain management following scoliosis surgery

Purpose of review The control of pain after scoliosis surgery is a real challenge for the anesthesiologist. The first reason is that major spine surgery for correction of scoliosis deformation causes severe postoperative pain, and second that patients undergoing these operations are most often children or adolescents who are known to suffer from increased pain sensation compared with adults. Recent findings A multimodal postoperative pain therapy is a well established procedure to control the pain after scoliosis surgery. Recently, prospective, well controlled studies have emphasized the key role of regional techniques in this context. Epidural analgesia has shown significant benefits regarding pain score, bowel recovery and patients' satisfaction. However, different modes of epidural analgesia application have been performed. Several issues including local anaesthetic concentration and infusion rate, duration of application and number of catheters placed will be discussed. The safety concerns associated with this type of analgesia will also be emphasized. Summary Significant improvements have been made in the control of postoperative pain after correction of scoliosis deformation in recent years. The introduction of epidural analgesia has cleared the way for better analgesic techniques in this surgical context. Properly performed and assessed, the addition of epidural analgesia after scoliosis surgery is a safe and effective form of analgesia and the benefits far outweigh the risks.
An on-demand QoE resource allocation algorithm for multi-flow LTE eMBMS

Recent multimedia studies show that the Quality-of-Experience(QoE) more accurately represents the user's level of satisfaction than the Quality-of-Service (QoS) does. Long Term Evolution (LTE) Multimedia Broadcast Multicast Operation (MBMS), via MBMS Operation On-Demand (MooD), enables dynamic resource configuration of multicast flows. In order to maximize the QoE of all users in a LTE MooD system we propose a resource allocation method which efficiently allocates resources based on both the demand of each live video stream and the channel conditions of the users. We compare our method against other methods; our method achieves the highest QoE and demonstrates efficient resource allocation regardless of whenever resources are sufficient or not.
A Short Proof of the Random Ramsey Theorem

In this paper we give a short proof of the Random Ramsey Theorem of Rödl and Ruciński: for any graph F which contains a cycle and r ≥ 2, there exist constants c, C > 0 such that $$ \begin{equation*} \Pr[G_{n,p} \rightarrow (F)_r^e] = \begin{cases} 1-o(1) &p\ge Cn^{-1/m_2(F)},\\ o(1) &p\le cn^{-1/m_2(F)}, \end{cases} \end{equation*} $$ where $$ \begin{equation*} m_2(F) = \max_{J\subseteq F, v_J\ge 2} \frac{e_J-1}{v_J-2}. \end{equation*} $$ The proof of the 1-statement is based on the recent beautiful hypergraph container theorems by Saxton and Thomason, and Balogh, Morris and Samotij. The proof of the 0-statement is elementary.
InP nanowire array solar cell with cleaned sidewalls

We have fabricated InP nanowire array solar cells with an axial p-n junction. Catalyst gold nanoparticles were first patterned into an array by nanoimprint lithography. The nanowire array was grown in 19 minutes by vapor-liquid-solid growth. The sidewalls were in-situ etched by HCl and ex-situ cleaned with a piranha etch. With this cleaning procedure, we could remove the sidewall extrusions and carbon contamination on the nanowire sidewall. We obtained a Voc of 0.68V, a fill factor of 71%, a diode rectification ratio of 107, an ideality factor of 2.12, a solar cell efficiency of 10.2% and a >90% device yield.
Role of the alveolar macrophage in lung injury: studies with ultrafine particles.

We conducted a series of experiments with ultrafine particles (approximately 20 nm) and larger particles (less than 200 nm) of "nuisance" dusts to evaluate the involvement of alveolar macrophages (AM) in particle-induced lung injury and particle translocation in rats. After intratracheal instillation of both ultrafine particles and larger particles of TiO2, we found a highly increased interstitial access of the ultrafine particles combined with a large acute inflammatory reaction as determined by lung lavage parameters. An additional experiment revealed that intratracheal instillation of phagocytized ultrafine TiO2 particles (inside AM) prevented both the pulmonary inflammatory reaction and the interstitial access of the ultrafine particles. Another experiment showed that the influx of polymorphonuclear cells (PMN) into the alveolar space unexpectedly decreased with higher doses of ultrafine particles, whereas alveolar epithelial permeability (protein leakage) increased. The divergence between PMN influx into the alveolar space and changes in alveolar epithelial permeability implies that they are separate events. Pulmonary inflammatory parameters determined by lung lavage analysis correlated best with the surface area of the retained particles rather than with their mass, volume, or numbers. Because higher doses resulted in an increased interstitialized fraction of particles, we suggest that inflammatory events induced by particles in the interstitial space can modify the inflammation in the alveolar space detectable by lung lavage. Our results demonstrate the dual role of AM for modifying particle-induced lung injury, i.e., both preventing such injury and contributing to it. We conclude that the increased pulmonary toxicity of ultrafine particles is related to their larger surface area and to their increased interstitial access. (ABSTRACT TRUNCATED AT 250 WORDS)
Plant-Derived Cannabinoids Modulate the Activity of Transient Receptor Potential Channels of Ankyrin Type-1 and Melastatin Type-8

The plant cannabinoids (phytocannabinoids), cannabidiol (CBD), and Δ9-tetrahydrocannabinol (THC) were previously shown to activate transient receptor potential channels of both vanilloid type 1 (TRPV1) and ankyrin type 1 (TRPA1), respectively. Furthermore, the endocannabinoid anandamide is known to activate TRPV1 and was recently found to antagonize the menthol- and icilin-sensitive transient receptor potential channels of melastatin type 8 (TRPM8). In this study, we investigated the effects of six phytocannabinoids [i.e., CBD, THC, CBD acid, THC acid, cannabichromene (CBC), and cannabigerol (CBG)] on TRPA1- and TRPM8-mediated increase in intracellular Ca2+ in either HEK-293 cells overexpressing the two channels or rat dorsal root ganglia (DRG) sensory neurons. All of the compounds tested induced TRPA1-mediated Ca2+ elevation in HEK-293 cells with efficacy comparable with that of mustard oil isothiocyanates (MO), the most potent being CBC (EC50 = 60 nM) and the least potent being CBG and CBD acid (EC50 = 3.4–12.0 μM). CBC also activated MO-sensitive DRG neurons, although with lower potency (EC50 = 34.3 μM). Furthermore, although none of the compounds tested activated TRPM8-mediated Ca2+ elevation in HEK-293 cells, they all, with the exception of CBC, antagonized this response when it was induced by either menthol or icilin. CBD, CBG, THC, and THC acid were equipotent (IC50 = 70–160 nM), whereas CBD acid was the least potent compound (IC50 = 0.9–1.6 μM). CBG inhibited Ca2+ elevation also in icilin-sensitive DRG neurons with potency (IC50 = 4.5 μM) similar to that of anandamide (IC50 = 10 μM). Our findings suggest that phytocannabinoids and cannabis extracts exert some of their pharmacological actions also by interacting with TRPA1 and TRPM8 channels, with potential implications for the treatment of pain and cancer.