Miracle-dz/UniFAR-FTUs huggingface dataset:
The somatostatin analogue octreotide inhibits angiogenesis in the earliest, but not in advanced, stages of portal hypertension in rats

Background: Angiogenesis is an important determinant of the pathophysiology of portal hypertension contributing to the formation of portosystemic collateral vessels and the hyperdynamic splanchnic circulation associated to this syndrome. Somatostatin and its analogues, like octreotide, have been shown to be powerful inhibitors of experimental angiogenesis. Aim: To determine whether octreotide has angioinhibitory effects in portal hypertensive rats. Methods: Partial portal vein‐ligated (PPVL) rats were treated with octreotide or vehicle during 4 or 7 days. Splanchnic neovascularization and VEGF expression were determined by histological analysis and western blotting. Expression of the somatostatin receptor subtype 2 (SSTR2), which mediates the anti‐angiogenic effects of octreotide, was also analyzed. Formation of portosystemic collaterals (radioactive microspheres) and hemodynamic parameters were also measured. Results: Octreotide treatment during 4 days markedly and significantly decreased splanchnic neovascularization, VEGF expression by 63% and portal pressure by 15%, whereas portosystemic collateralization and splanchnic blood flow were not modified. After 1 week of octreotide injection, portal pressure was reduced by 20%, but inhibition of angiogenesis escaped from octreotide therapy, a phenomenon that could be related to the finding that expression of SSTR2 receptor decreased progressively (up to 78% reduction) during the evolution of portal hypertension. Conclusion: This study provides the first experimental evidence showing that octreotide may be an effective anti‐angiogenic therapy early after induction of portal hypertension, but not in advanced stages most likely due to SSTR2 down‐regulation during the progression of portal hypertension in rats. These findings shed light on new mechanisms of action of octreotide in portal hypertension.
Cortical Feedback Controls the Frequency and Synchrony of Oscillations in the Visual Thalamus

Thalamic circuits have an intrinsic capacity to generate state-dependent oscillations of different frequency and degrees of synchrony, but little is known of how synchronized oscillation is controlled in the intact brain or what function it may serve. The influence of cortical feedback was examined using slice preparations of the visual thalamus and computational models. Cortical feedback was mimicked by stimulating corticothalamic axons, triggered by the activity of relay neurons. This artificially coupled network had the capacity to self-organize and to generate qualitatively different rhythmical activities according to the strength of corticothalamic feedback stimuli. Weak feedback (one to three shocks at 100–150 Hz) phase-locked the spontaneous spindle oscillations (6–10 Hz) in geniculate and perigeniculate nuclei. However, strong feedback (four to eight shocks at 100–150 Hz) led to a more synchronized oscillation, slower in frequency (2–4 Hz) and dependent on GABABreceptors. This increase in synchrony was essentially attributable to a redistribution of the timing of action potential generation in lateral geniculate nucleus cells, resulting in an increased output of relay cells toward the cortex. Corticothalamic feedback is thus capable of inducing highly synchronous slow oscillations in physiologically intact thalamic circuits. This modulation may have implications for a better understanding of the descending control of thalamic nuclei by the cortex, and the genesis of pathological rhythmical activity, such as absence seizures.
Law of large numbers for the SIR epidemic on a random graph with given degrees

We study the susceptible‐infective‐recovered (SIR) epidemic on a random graph chosen uniformly subject to having given vertex degrees. In this model infective vertices infect each of their susceptible neighbours, and recover, at a constant rate. Suppose that initially there are only a few infective vertices. We prove there is a threshold for a parameter involving the rates and vertex degrees below which only a small number of infections occur. Above the threshold a large outbreak occurs with probability bounded away from zero. Our main result is that, conditional on a large outbreak, the evolutions of certain quantities of interest, such as the fraction of infective vertices, converge to deterministic functions of time. We also consider more general initial conditions for the epidemic, and derive criteria for a simple vaccination strategy to be successful. In contrast to earlier results for this model, our approach only requires basic regularity conditions and a uniformly bounded second moment of the degree of a random vertex. En route, we prove analogous results for the epidemic on the configuration model multigraph under much weaker conditions. Essentially, our main result requires only that the initial values for our processes converge, i.e. it is the best possible. © 2014 Wiley Periodicals, Inc. Random Struct. Alg. , 45, 726–763, 2014
Eect of the Imf B Y Component on the Ionospheric ¯ow Overhead at Eiscat: Observations and Theory

We have analysed a database of $300 h of tristatic ionospheric velocity measurements obtained overhead at Tromsù (66.3° magnetic latitude) by the EISCAT UHF radar system, for the presence of ¯ow eects associated with the y-component of the IMF. Since it is already known that the ¯ow depends upon IMF B z , a least-squares multivariate analysis has been used to determine the ¯ow dependence on both IMF B y and B z simultaneously. It is found that signi®cant ¯ow variations with IMF B y occur, predominantly in the midnight sector ($2100±0300 MLT), but also pre-dusk ($1600±1700 MLT), which are directed eastward for IMF B y positive and westward for IMF B y negative. The ¯ows are of magnitude 20±30 m s)1 nT)1 in the midnight sector, and smaller, 10±20 m s)1 nT)1 , pre-dusk, and are thus associated with signi®cant changes of ¯ow of order a few hundred m s)1 over the usual range of IMF B y of about 5 nT. At other local times the IMF B y-related perturbation ¯ows are much smaller, less than $5 m s)1 nT)1 , and consistent with zero within the uncertainty estimates. We have investigated whether these IMF B y-dependent ¯ows can be accounted for quantitatively by a theoretical model in which the equatorial ¯ow in the inner magnetosphere is independent of IMF B y , but where distortions of the magneto-spheric magnetic ®eld associated with a ``penetrating'' component of the IMF B y ®eld changes the mapping of the ®eld to the ionosphere, and hence the ionospheric ¯ow. We ®nd that the principal ¯ow perturbation produced by this eect is an east±west ¯ow whose sense is determined by the north±south component of the unperturbed ¯ow. Perturbations in the north±south ¯ow are typically smaller by more than an order of magnitude , and generally negligible in terms of observations. Using equatorial ¯ows which are determined from EISCAT data for zero IMF B y , to which the corotation ¯ow has been added, the theory predicts the presence of zonal perturbation ¯ows which are generally directed eastward in the Northern Hemisphere for IMF B y positive and westward for IMF B y negative at all local times. However, although the day and night eects are therefore similar in principle, the model perturbation ¯ows are much larger on the nightside than on the dayside, as observed, due to the day-night asymmetry in the …
Thrombosis in Systemic Lupus Erythematosus

Systemic lupus erythematosus (SLE) is a potentially fatal multiorgan inflammatory disease that primarily affects females. Due to the heterogeneity of clinical manifestations and lack of laboratory tests that are both specific and sensitive for the disease, diagnosis of SLE can often be difficult. Although the precise etiology remains to be fully elucidated, it is probable that various environmental, genetic, and hormonal factors contribute to the development of the disease. Patients with SLE have an increased risk for premature thrombosis and/or atherosclerosis, with up to half experiencing a thrombotic event. Furthermore, antiphospholipid antibodies probably play a key role in the development of thrombosis by affecting various hemostatic protein interactions with phospholipids and cell surfaces as well as platelet function. Despite recent advances in knowledge related to the factors that contribute to the pathophysiology of SLE, numerous challenges related to earlier diagnosis as well as the prediction and prevention of thrombotic events remain to be fully addressed.
Circadian abnormalities in mouse models of smith–magenis syndrome: Evidence for involvement of RAI1

Smith–Magenis syndrome (SMS; OMIM 182290) is a genomic disorder characterized by multiple congenital anomalies, intellectual disability, behavioral abnormalities, and disordered sleep resulting from an ∼3.7 Mb deletion copy number variant (CNV) on chromosome 17p11.2 or from point mutations in the gene RAI1. The reciprocal duplication of this region results in another genomic disorder, Potocki–Lupski syndrome (PTLS; OMIM 610883), characterized by autism, intellectual disability, and congenital anomalies. We previously used chromosome‐engineering and gene targeting to generate mouse models for PTLS (Dp(11)17/+), and SMS due to either deletion CNV or gene knock‐out (Df(11)17‐2/+ and Rai1+/−, respectively) and we observed phenotypes in these mouse models consistent with their associated human syndromes. To investigate the contribution of individual genes to the circadian phenotypes observed in SMS, we now report the analysis of free‐running period lengths in Rai1+/− and Df(11)17‐2/+ mice, as well as in mice deficient for another known circadian gene mapping within the commonly deleted/duplicated region, Dexras1, and we compare these results to those previously observed in Dp(11)17/+ mice. Reduced free‐running period lengths were seen in Df(11)17‐2/+, Rai1+/−, and Dexras1−/−, but not Dexras1+/− mice, suggesting that Rai1 may be the primary gene underlying the circadian defects in SMS. However, we cannot rule out the possibility that cis effects between multiple haploinsufficient genes in the SMS critical interval (e.g., RAI1 and DEXRAS1) either exacerbate the circadian phenotypes observed in SMS patients with deletions or increase their penetrance in certain environments. This study also confirms a previous report of abnormal circadian function in Dexras1−/− mice. © 2013 Wiley Periodicals, Inc.
Flooding for Reliable Multicast in Multi-Hop Ad Hoc Networks

Ad hoc networks are gaining popularity as a result of advances in smaller, more versatile and powerful mobile computing devices. The distinguishing feature of these networks is the universal mobility of all hosts. This requires re-engineering of basic network services including reliable multicast communication. This paper considers the special case of highly mobile fast-moving ad hoc networks and argues that, for such networks, traditional multicast approaches are not appropriate. Flooding is suggested as a possible alternative for reliable multicast and simulation results are used to illustrate its effects. The experimental results also demonstrate a rather interesting outcome that even flooding is insufficient for reliable multicast in ad hoc networks when mobility is very high. Some alternative, more persistent variations of flooding are sketched out.
Molecular characterization of conditionally immortalized cell lines derived from mouse early embryonic inner ear

Inner ear sensory hair cells (HCs), supporting cells (SCs), and sensory neurons (SNs) are hypothesized to develop from common progenitors in the early embryonic otocyst. Because little is known about the molecular signals that control this lineage specification, we derived a model system of early otic development: conditionally immortalized otocyst (IMO) cell lines from the embryonic day 9.5 Immortomouse. This age is the earliest stage at which the otocyst can easily be separated from surrounding mesenchymal, nervous system, and epithelial cells. At 9.5 days post coitum, there are still pluripotent cells in the otocyst, allowing for the eventual identification of both SN and HC precursors—and possibly an elusive inner ear stem cell. Cell lines derived from primitive precursor cells can also be used as blank canvases for transfections of genes that can affect lineage decisions as the cells differentiate. It is important, therefore, to characterize the “baseline state” of these cell lines in as much detail as possible. We characterized seven representative “precursor‐like” IMO cell populations and the uncloned IMO cells, before cell sorting, at the molecular level by polymerase chain reaction (PCR) and immunocytochemistry (IHC), and one line (IMO‐2B1) in detail by real‐time quantitative PCR and IHC. Many of the phenotypic markers characteristic of differentiated HCs or SCs were detected in IMO‐2B1 proliferating cells, as well as during differentiation for up to 30 days in culture. These IMO cell lines represent a unique model system for studying early stages of inner ear development and determining the consequences of affecting key molecular events in their differentiation. Developmental Dynamics 231:815–827, 2004. © 2004 Wiley‐Liss, Inc.
Characterization and Leach Testing for PUREX Cladding Waste Sludge (Group 3) and REDOX Cladding Waste Sludge (Group 4) Actual Waste Sample Composites

A testing program evaluating actual tank waste was developed in response to Task 4 from the M-12 External Flowsheet Review Team (EFRT) issue response plan. (a) The testing program was subdivided into logical increments. The bulk water-insoluble solid wastes that are anticipated to be delivered to the Waste Treatment and Immobilization Plant (WTP) were identified according to type such that the actual waste testing could be targeted to the relevant categories. Eight broad waste groupings were defined. Samples available from the 222S archive were identified and obtained for testing. The actual wastetesting program included homogenizing the samples by group, characterizing the solids and aqueous phases, and performing parametric leaching tests. Two of the eight defined groups—plutonium-uranium extraction (PUREX) cladding waste sludge (Group 3, or CWP) and reduction-oxidation (REDOX) cladding waste sludge (Group 4, or CWR)—are the subjects of this report. Both the Group 3 and 4 waste composites were anticipated to be high in gibbsite, requiring caustic leaching. Characterization of the composite Group 3 and Group 4 waste samples confirmed them to be high in gibbsite. The focus of the Group 3 and 4 testing was on determining the behavior of gibbsite during caustic leaching. The waste-type definition, archived sample conditions, homogenization activities, characterization (physical, chemical, radioisotope, and crystal habit), and caustic leaching behavior as functions of time, temperature, and hydroxide concentration are discussed in this report. Testing was conducted according to TP-RPP-WTP-467.
Obsolescence of Durable Goods and Optimal Consumption

We study a model with a durable good subject to abrupt, periodic obsolescence, and characterize the optimal purchasing policy. Consumers optimally synchronize new purchases with the arrival of new durable models. Hence, some agents use a "flexible" optimal replacement rule that switches between two adjacent replacement frequencies at irregular intervals. These agents react to wealth shocks by changing the timing of future purchases. The model has distinct comparative statics on obsolescence and durability and can explain how durables with high depreciation rates may have more volatile expenditure. The model also predicts how demand fluctuations respond to a change in product variety. These predictions match the observed changes in volatility of the US auto sales after the introduction of smaller foreign cars in the 1970s
Visual Attention Measures Predict Pedestrian Detection in Central Field Loss: A Pilot Study

Purpose The ability of visually impaired people to deploy attention effectively to maximize use of their residual vision in dynamic situations is fundamental to safe mobility. We conducted a pilot study to evaluate whether tests of dynamic attention (multiple object tracking; MOT) and static attention (Useful Field of View; UFOV) were predictive of the ability of people with central field loss (CFL) to detect pedestrian hazards in simulated driving. Methods 11 people with bilateral CFL (visual acuity 20/30-20/200) and 11 age-similar normally-sighted drivers participated. Dynamic and static attention were evaluated with brief, computer-based MOT and UFOV tasks, respectively. Dependent variables were the log speed threshold for 60% correct identification of targets (MOT) and the increase in the presentation duration for 75% correct identification of a central target when a concurrent peripheral task was added (UFOV divided and selective attention subtests). Participants drove in a simulator and pressed the horn whenever they detected pedestrians that walked or ran toward the road. The dependent variable was the proportion of timely reactions (could have stopped in time to avoid a collision). Results UFOV and MOT performance of CFL participants was poorer than that of controls, and the proportion of timely reactions was also lower (worse) (84% and 97%, respectively; p = 0.001). For CFL participants, higher proportions of timely reactions correlated significantly with higher (better) MOT speed thresholds (r = 0.73, p = 0.01), with better performance on the UFOV divided and selective attention subtests (r = −0.66 and −0.62, respectively, p<0.04), with better contrast sensitivity scores (r = 0.54, p = 0.08) and smaller scotomas (r = −0.60, p = 0.05). Conclusions Our results suggest that brief laboratory-based tests of visual attention may provide useful measures of functional visual ability of individuals with CFL relevant to more complex mobility tasks.
The usefulness of cystatin C and related formulae in pediatrics

Abstract Serum creatinine does not share the properties of an ideal marker of glomerular filtration rate (GFR) like inulin, but continues to be the most widely used endogenous marker of GFR. In the search of a better biomarker of GFR, the small molecular weight protein cystatin C has been introduced with features more similar to that of inulin, such as constant production and no non-renal elimination. However, it has not enjoyed widespread use despite its significantly improved diagnostic performance in the detection of impaired GFR and its independence of body composition. A variety of formulae based on either cystatin C or creatinine or both have been developed to estimate GFR. We summarize the currently used methods of GFR measurement, their limitations and analytical errors. The review also summarizes the history, features and the feasibility of cystatin C measurements as well as the most widely used formulae for the estimation of GFR in children. The diagnostic performance of the cystatin C derived eGFR formulae at various levels of GFR is also discussed. An eGFR formula derived from pooled studies analyzing both creatinine and cystatin C, and using a biology-based mathematical approach may be advantageous.
High-dose Weekly Liposomal Amphotericin B Antifungal Prophylaxis in Patients Undergoing Liver Transplantation: A Prospective Phase II Trial

Background To assess the safety and tolerability of high-dose weekly (10 mg/kg) liposomal amphotericin B (LamB) for antifungal prophylaxis in liver transplantation (LT) recipients with predefined risk factors for invasive fungal infection (IFI), a prospective phase II noncomparative trial was performed at our center over a 4-year period. Methods In the selected LT recipients, LamB was administered weekly until hospital discharge after LT for minimum 2 weeks. Criteria for early discontinuing prophylaxis were: (i) any adverse event (AE); (ii) suspicion of IFI. Safety and tolerability were assessed according to the incidence of grades 3 to 4 AEs based on Common Toxicity Criteria (CTC) classification. Post-LT follow-up was of 180 days. Results Overall, 76 patients were included. Liposomal amphotericin B was started within a median of 1 (interquartile range, 1–4) day after LT. Overall, 66 of 76 (86.8%) patients completed the prophylaxis, 10 discontinued the study protocol: 6 for infusion-related AE, 4 for suspected IFI. Adverse events consisted of five cases of lumbar pain and one case of thoracic pain which occurred after a median of 1.5 (interquartile range, 1–2) LamB infusions. None of the patients reported CTC grades 3 to 4 hypokalemia, three reported CTC grade 3 acute renal injury, none of which were deemed directly attributable to LamB. No drug-drug interactions with immunosuppressive drugs were reported, and no episode of rejection occurred during the prophylaxis. In only two of the four patients with suspected IFI was the diagnosis of invasive candidiasis confirmed. Conclusion Our results suggest high-dose weekly LamB may be a safe prophylactic strategy for high-risk LT recipients.
Time delay effects on oscillation profiles in cyclic gene regulatory networks: Harmonic balance approach

Oscillatory gene expression is closely connected to periodic physiological functions. In this paper, we provide a systematic method to study the oscillation profiles of gene expression in large-scale cyclic genetic regulatory networks based on multivariable harmonic balance. In particular, we here turn our attention to time delay in transcription and translation process, and analytically derive the relation between biological parameters and the frequency, phase and amplitude of the oscillations. Then, the roles of the time delay are revealed.
The Local Lyα Forest. II. Distribution of H I Absorbers,Doppler Widths, and Baryon Content

In Paper I of this series we described observations of 15 extragalactic targets taken with the Hubble Space Telescope+GHRS+G160M grating for studies of the low-z Lyα forest. We reported the detection of 111 Lyα absorbers at significance level (SL) ≥3 σ, 81 with SL ≥ 4 σ, in the redshift range 0.002 < z < 0.069, over a total path length cΔz = 116,000 km s-1 (Δz = 0.387). In this second paper, we evaluate the physical properties of these Lyα absorbers and compare them to their high-z counterparts. The SL ≥ 4 σ distribution of Doppler parameters is similar to that at high redshift, with ⟨b⟩ = 38.0 ± 15.7 km s-1. The true Doppler parameter may be somewhat lower, owing to component blends and nonthermal velocities. The distribution of equivalent widths exhibits a significant break at 𝒲 ≤ 133 mÅ, with an increasing number of weak absorbers (10 mÅ < 𝒲 < 100 mÅ). Adopting a curve of growth with b = 25 ± 5 km s-1 and applying a sensitivity correction as a function of equivalent width and wavelength, we derive the distribution in column density, N for 12.5 ≤ log ≤ 14.0. We find no redshift evolution within the current sample at z < 0.07, but we do see a significant decline in d𝒩/dz compared to values at z > 1.6. Similar to the high equivalent width (𝒲 > 240 mÅ) absorbers, the number density of low-𝒲 absorbers at z = 0 is well above the extrapolation of d𝒩/dz from z > 2, but we observe no difference in the mean evolution of d𝒩/dz between absorbers of high (𝒲 > 240 mÅ) and low (𝒲 ≤ 100 mÅ) equivalent width. While previous work has suggested slower evolution in number density of lower 𝒲 absorbers, our new data do not support this conclusion. A consistent evolutionary pattern is that the slowing in the evolution of the low column density clouds occurs at lower redshift than for the higher column density clouds. A 4-5 σ signal in the two-point correlation function of Lyα absorbers for velocity separations Δv ≤ 150 km s-1 is consistent with results at high z, but with somewhat greater amplitude. Applying a photoionization correction, we find that the low-z Lyα forest may contain ~20% of the total number of baryons, with closure parameter ΩLyα = (0.008 ± 0.001)h, for a standard absorber size and ionizing radiation field. Some of these clouds appear to be primordial matter, owing to the lack of detected metals (Si III) in a composite spectrum, although current limits on composite metallicity are not strong.