Miracle-dz/UniFAR-FTUs huggingface dataset:
Cyclocoagulation of the ciliary bodies by high-intensity focused ultrasound: a 12-month multicenter study.

PURPOSE To evaluate the safety and efficacy of high-intensity focused ultrasound (HIFU) cyclocoagulation in reducing intraocular pressure (IOP) in patients with refractory glaucoma by using a novel miniaturized delivery device (EyeOP1). METHODS We conducted a 12-month open-label multicenter prospective study (EyeMUST1 Study). Patients with primary (primary open-angle glaucoma [POAG]) or secondary refractory glaucoma were treated in two groups depending on the duration of each ultrasound shot (group 1: 4 seconds; group 2: 6 seconds). The primary efficacy outcome was based on IOP reduction at 6 and 12 months. RESULTS Fifty-two patients were enrolled: 36 (69%) had POAG and 16 (31%) had secondary glaucoma. Group 1 (n = 24) and group 2 (n = 28) had similar demographics and baseline characteristics. In group 1, IOP was reduced from a mean preoperative value of 29.7 ± 7.7 mm Hg (n = 3.5 glaucoma medications) to a mean postoperative value of 21.3 ± 6.7 mm Hg (n = 3.5 glaucoma medications) and 20.1 ± 6.7 mm Hg (n = 3.2 glaucoma medications) at 6 and 12 months, respectively. In group 2, IOP was reduced from a mean preoperative value of 29.0 ± 7.4 mm Hg (n = 3.3 glaucoma medications) to a mean postoperative value of 20.2 ± 7.4 mm Hg (n = 3.4 glaucoma medications) and 18.5 ± 6.6 mm Hg (n = 3.5 glaucoma medications) at 6 and 12 months, respectively. At 12 months, the IOP reduction was sustained in both groups (32% IOP reduction in group 1 and 36% IOP reduction in group 2). The overall tolerance of the technique was good, with no serious adverse events. CONCLUSIONS The new miniaturized HIFU EyeOP1 delivery device seems to be effective in decreasing IOP in patients with refractory glaucoma. The technology offers a good safety profile. (ClinicalTrials.gov number, NCT01338467.).
Unified Method to Quantify Aggregate Shape Angularity and Texture Using Fourier Analysis

Aggregates are an important constituent of asphalt concrete, hydraulic cement concrete, and granular base. The shape, angularity, and surface texture of aggregates are basically variations of asperities at different dimensional scales and affect mixture properties in different ways. This paper presents a unified Fourier morphological analysis method to quantify the shape, angularity, and surface texture of aggregates. Evaluation of these characteristics of 10 aggregates of known quality indicates that Fourier morphological analysis quantitatively ranks these aggregates in consistence with qualitative evaluations.
Globalisation , Productivity and Technology Research Paper 2010 / 04 Globalisation , Multinationals and Productivity in Japan ’ s Lost Decade

Myriad hypotheses have been advanced to explain the dismal performance of the post-1990 Japanese economy. In this paper we use plant and firm data to investigate the issue. The low rate of productivity growth in Japan is also often seen as a product of Japanese MNEs offshoring production and shutting plants that are relative to others in their industry, high productivity. We find that this is true, plants shut by MNEs are relatively more productive than the industry average, but they are generally weaker elements of the MNE more generally. This behaviour is also not distinct to MNEs. Our analysis suggests that the rate of productivity growth within firms is also partly a consequence of low entry and exit rates. Generally we find that the determinants of productivity change are similar to those found for other countries, but that productivity improvement is lower in industries in which globalisation is higher. The low rate of entry and exit in Japan therefore means that this affects more firms than would otherwise have been the case. JEL classification: D21, E0, F14, F23,
Computational Redox Potential Predictions: Applications to Inorganic and Organic Aqueous Complexes, and Complexes Adsorbed to Mineral Surfaces

Applications of redox processes range over a number of scientific fields. This review article summarizes the theory behind the calculation of redox potentials in solution for species such as organic compounds, inorganic complexes, actinides, battery materials, and mineral surface-bound-species. Different computational approaches to predict and determine redox potentials of electron transitions are discussed along with their respective pros and cons for the prediction of redox potentials. Subsequently, recommendations are made for certain necessary computational settings required for accurate calculation of redox potentials. This article reviews the importance of computational parameters, such as basis sets, density functional theory (DFT) functionals, and relativistic approaches and the role that physicochemical processes play on the shift of redox potentials, such as hydration or spin orbit coupling, and will aid in finding suitable combinations of approaches for different chemical and geochemical applications. Identifying cost-effective and credible computational approaches is essential to benchmark redox potential calculations against experiments. Once a good theoretical approach is found to model the chemistry and thermodynamics of the redox and electron transfer process, this knowledge can be incorporated into models of more complex reaction mechanisms that include diffusion in the solute, surface diffusion, and dehydration, to name a few. This knowledge is important to fully understand the nature of redox processes be it a geochemical process that dictates natural redox reactions or one that is being used for the optimization of a chemical process in industry. In addition, it will help identify materials that will be useful to design catalytic redox agents, to come up with materials to be used for batteries and photovoltaic processes, and to identify new and improved remediation strategies in environmental engineering, for example the reduction of actinides and their subsequent immobilization. Highly under-investigated is the role of redox-active semiconducting mineral surfaces as catalysts for promoting natural redox processes. Such knowledge is crucial to derive process-oriented mechanisms, kinetics, and rate laws for inorganic and organic redox processes in nature. In addition, molecular-level details still need to be explored and understood to plan for safer disposal of hazardous materials. In light of this, we include new research on the effect of iron-sulfide mineral surfaces, such as pyrite and mackinawite, on the redox chemistry of actinyl aqua complexes in aqueous solution.
Sorafenib inhibits the shedding of major histocompatibility complex class I–related chain A on hepatocellular carcinoma cells by down‐regulating a disintegrin and metalloproteinase 9

The ectodomain of major histocompatibility complex class I–related chain A (MICA) is shed from tumor cells, and may be an important means of evading antitumor immunity. This study investigated the roles of a disintegrin and metalloproteinase 9 (ADAM9) in the shedding of MICA in human hepatocellular carcinoma (HCC). Small interfering RNA–mediated knockdown (KD) of ADAM9 resulted in up‐regulation of membrane‐bound MICA expression on the HepG2 and PLC/PRF/5 cellular surfaces and down‐regulation of soluble MICA levels in their culture supernatant. ADAM9 was cleaved at a site between Gln347 and Val348 of MICA in vitro. We constructed a plasmid of the MICA gene with mutation or deletion of the ADAM9 cleavage site to examine the detailed mechanism of MICA shedding by ADAM9 protease. The results suggested that MICA might be cleaved at the intracellular ADAM9‐recognized cleavage site and was further cleaved at the extracellular ADAM9‐independent cleavage site in HCC cells, resulting in the production of soluble MICA. Immunohistochemical analysis revealed that ADAM9 was overexpressed in human HCC compared to normal liver tissues. The cytolytic activity of natural killer (NK) cells against ADAM9KD‐HCC cells was higher than that against control cells, and the enhancement of this cytotoxicity depended on the MICA/B and NK group 2, member D pathway. Sorafenib treatment resulted in decreased expression of ADAM9, increased expression of membrane‐bound MICA expression, and decreased levels of soluble MICA in HCC cells. Adding sorafenib enhanced the NK sensitivity of HCC cells via increased expression of membrane‐bound MICA. Conclusion: ADAM9 is involved in MICA ectodomain shedding in HCC cells, and sorafenib can modulate ADAM9 expression. Sorafenib therapy may have a previously unrecognized effect on antitumor immunity in patients with HCC. (HEPATOLOGY 2010.)
WCET Analysis with MRU Caches: Challenging LRU for Predictability

Most previous work in cache analysis for WCET estimation assumes a particular replacement policy called LRU. In contrast, much less work has been done for non-LRU policies, since they are generally considered to be very "unpredictable". However, most commercial processors are actually equipped with these non-LRU policies, since they are more efficient in terms of hardware cost, power consumption and thermal output, but still maintaining almost as good average-case performance as LRU. In this work, we study the analysis of MRU, a non-LRU replacement policy employed in mainstream processor architectures like Intel Nehalem. Our work shows that the predictability of MRU has been significantly underestimated before, mainly because the existing cache analysis techniques and metrics, originally designed for LRU, do not match MRU well. As our main technical contribution, we propose a new cache hit/miss classification, k-Miss, to better capture the MRU behavior, and develop formal conditions and efficient techniques to decide the k-Miss memory accesses. A remarkable feature of our analysis is that the k-Miss classifications under MRU are derived by the analysis result of the same program under LRU. Therefore, our approach inherits all the advantages in efficiency, precision and composability of the state-of-the-art LRU analysis techniques based on abstract interpretation. Experiments with benchmarks show that the estimated WCET by our proposed MRU analysis is rather close to (5% # 20% more than) that obtained by the state-of-the-art LRU analysis, which indicates that MRU is also a good candidate for the cache replacement policy in real-time systems.
On the convergence of moment problems

We study the problem of estimating a nonnegative density, given a finite number of moments. Such problems arise in numerous practical applications. As the number of moments increases, the estimates will always converge weak * as measures, but need not converge weakly in L₁. This is related to the existence of functions on a compact metric space which are not essentially Riemann integrable (in some suitable sense). We characterize the type of weak convergence we can expect in terms of Riemann integrability, and in some cases give error bounds. When the estimates are chosen to minimize an objective function with weakly compact level sets (such as the Bolzmann-Shannon entropy) they will converge weakly in L₁. When an Lp norm (1 < p < ∞) is used as the objective, the estimates actually converge in norm. These results provide theoretical support to the growing popularity of such methods in practice.
Tubulopathy Consecutive to Tenofovir-containing Antiretroviral Therapy in Two Patients Infected with Human Immunodeficiency Virus-1

Tenofovir disopril fumarate, a new nucleotide analogue against human immunodeficiency virus-1 (HIV-1), can induce hypophosphataemia, the mechanism of which is unclear. Moreover, a renal tubulopathy can occur in long-term treated patients, as observed in 2 HIV-1-infected patients after 12 months of tenofovir therapy, with polyuria–polydipsia, proteinuria, glycosuria and amino-aciduria, which resolved after discontinuation of tenofovir. The risk of renal tubulopathy symptoms in patients on long-term tenofovir therapy should be noted.
Exclusion of CD45 inhibits activity of p56lck associated with glycolipid-enriched membrane domains

p56lck (Lck) is a lymphoid-specific Src family tyrosine kinase that is critical for T-cell development and activation. Lck is also a membrane protein, and approximately half of the membrane-associated Lck is associated with a glycolipid-enriched membrane (GEM) fraction that is resistant to solubilization by Triton X-100 (TX-100). To compare the membrane-associated Lck present in the GEM and TX-100-soluble fractions of Jurkat cells, Lck from each fraction was immunoblotted with antibody to phosphotyrosine. Lck in the GEM fraction was found to be hyperphosphorylated on tyrosine, and this correlated with a lower kinase specific activity relative to the TX-100-soluble Lck. Peptide mapping and phosphatase diagests showed that the hyperphosphorylation and lower kinase activity of GEM-associated Lck was due to phosphorylation of the regulatory COOH-terminal Tyr505. In addition, we determined that the membrane-bound tyrosine phosphatase CD45 was absent from the GEM fraction. Cells lacking CD45 showed identical phosphorylation of Lck in GEM and TX-100-soluble membranes. We propose that the GEM fraction represents a specific membrane domain present in T-cells, and that the hyperphosphorylation of tyrosine and lower kinase activity of GEM-associated Lck is due to exclusion of CD45 from these domains. Lck associated with the GEM domains may therefore consitute a reservoir of enzyme that can be readily activated.
Nonlinear Methods of Cardiovascular Physics and their Clinical Applicability

In this tutorial we present recently developed nonlinear methods of cardiovascular physics and show their potentials to clinically relevant problems in cardiology. The first part describes methods of cardiovascular physics, especially data analysis and modeling of noninvasively measured biosignals, with the aim to improve clinical diagnostics and to improve the understanding of cardiovascular regulation. Applications of nonlinear data analysis and modeling tools are various and outlined in the second part of this tutorial: monitoring-, diagnosis-, course and mortality prognoses as well as early detection of heart diseases. We show, that these data analyses and modeling methods lead to significant improvements in different medical fields.
The hinge region of the human estrogen receptor determines functional synergy between AF-1 and AF-2 in the quantitative response to estradiol and tamoxifen

Human estrogen receptors α and β (ERα and ERβ) greatly differ in their target genes, transcriptional potency and cofactor-binding capacity, and are differentially expressed in various tissues. In classical estrogen response element (ERE)-mediated transactivation, ERβ has a markedly reduced activation potential compared with ERα; the mechanism underlying this difference is unclear. Here, we report that the binding of steroid receptor coactivator-1 (SRC-1) to the AF-1 domain of ERα is essential but not sufficient to facilitate synergy between the AF-1 and AF-2 domains, which is required for a full agonistic response to estradiol (E2). Complete synergy is achieved through the distinct hinge domain of ERα, which enables combined action of the AF-1 and AF-2 domains. AF-1 of ERβ lacks the capacity to interact with SRC-1, which prevents hinge-mediated synergy between AF-1 and AF-2, thereby explaining the reduced E2-mediated transactivation of ERβ. Transactivation of ERβ by E2 requires only the AF-2 domain. A weak agonistic response to tamoxifen occurs for ERα, but not for ERβ, and depends on AF-1 and the hinge-region domain of ERα.
Frequency of virulence genes in Escherichia coli strains isolated from piglets with diarrhea in the North Parana State, Brazil

Identification of Escherichia coli causing porcine postweaning diarrhea requires knowledge regarding the prevalent pathotypes within a given region. A total of 100 Escherichia coli isolates from piglets with diarrhea in Londrina city, Parana State, South Brazil, were screened for the presence of genes for F4, F5, F6, F18, F41 fimbrial antigens by specific probes and for enterotoxins (STa, STb, LT and STx2e) by polymerase chain reaction (PCR). The results showed that 60% of the isolates were positive for one or more of the fimbrial antigens and 92% were positive at least for one of the virulence factors examined. Virulence factor genes detected were F4 (44%), F18 (38%), F5 (30%), F41 (32%), F6 (25%), LTp-I (71%), STa (40%), STb (47%) and STx2e (3%). Twenty four patterns of virulence factor according to the different virulence genes form were found and the most frequent virulence gene pattern was F4, F18, F41, STa, STb and LT. Most of the isolates that carried genes for adhesins also harboured genes for toxins.
MLESAC: A New Robust Estimator with Application to Estimating Image Geometry

Abstract A new method is presented for robustly estimating multiple view relations from point correspondences. The method comprises two parts. The first is a new robust estimator MLESAC which is a generalization of the RANSAC estimator. It adopts the same sampling strategy as RANSAC to generate putative solutions, but chooses the solution that maximizes the likelihood rather than just the number of inliers. The second part of the algorithm is a general purpose method for automatically parameterizing these relations, using the output of MLESAC. A difficulty with multiview image relations is that there are often nonlinear constraints between the parameters, making optimization a difficult task. The parameterization method overcomes the difficulty of nonlinear constraints and conducts a constrained optimization. The method is general and its use is illustrated for the estimation of fundamental matrices, image–image homographies, and quadratic transformations. Results are given for both synthetic and real images. It is demonstrated that the method gives results equal or superior to those of previous approaches.
Differentially Private Mixture of Generative Neural Networks

Generative models are used in an increasing number of applications that rely on large amounts of contextually rich information about individuals. Owing to possible privacy violations, however, publishing or sharing generative models is not always viable. In this paper, we introduce a novel solution for privately releasing generative models and entire high-dimensional datasets produced by these models. We model the generator distribution of the training data by a mixture of k generative neural networks. These are trained together and collectively learn the generator distribution of a dataset. Data is divided into k clusters, using a novel differentially private kernel k-means, then each cluster is given to separate generative neural networks, such as Restricted Boltzmann Machines or Variational Autoencoders, which are trained only on their own cluster using differentially private gradient descent. We evaluate our approach using the MNIST dataset and a large Call Detail Records dataset, showing that it produces realistic synthetic samples, which can also be used to accurately compute arbitrary number of counting queries.
Kinesin-1 and mitochondrial motility control by discrimination of structurally equivalent but distinct subdomains in Ran-GTP-binding domains of Ran-binding protein 2

The pleckstrin homology (PH) domain is a versatile fold that mediates a variety of protein–protein and protein–phosphatidylinositol lipid interactions. The Ran-binding protein 2 (RanBP2) contains four interspersed Ran GTPase-binding domains (RBDn = 1–4) with close structural homology to the PH domain of Bruton's tyrosine kinase. The RBD2, kinesin-binding domain (KBD) and RBD3 comprise a tripartite domain (R2KR3) of RanBP2 that causes the unfolding, microtubule binding and biphasic activation of kinesin-1, a crucial anterograde motor of mitochondrial motility. However, the interplay between Ran GTPase and R2KR3 of RanBP2 in kinesin-1 activation and mitochondrial motility is elusive. We use structure–function, biochemical, kinetic and cell-based assays with time-lapse live-cell microscopy of over 260 000 mitochondrial-motility-related events to find mutually exclusive subdomains in RBD2 and RBD3 towards Ran GTPase binding, kinesin-1 activation and mitochondrial motility regulation. The RBD2 and RBD3 exhibit Ran-GTP-independent, subdomain and stereochemical-dependent discrimination on the biphasic kinetics of kinesin-1 activation or regulation of mitochondrial motility. Further, KBD alone and R2KR3 stimulate and suppress, respectively, multiple biophysical parameters of mitochondrial motility. The regulation of the bidirectional transport of mitochondria by either KBD or R2KR3 is highly coordinated, because their kinetic effects are accompanied always by changes in mitochondrial motile events of either transport polarity. These studies uncover novel roles in Ran GTPase-independent subdomains of RBD2 and RBD3, and KBD of RanBP2, that confer antagonizing and multi-modal mechanisms of kinesin-1 activation and regulation of mitochondrial motility. These findings open new venues towards the pharmacological harnessing of cooperative and competitive mechanisms regulating kinesins, RanBP2 or mitochondrial motility in disparate human disorders.
Human RIF1 and protein phosphatase 1 stimulate DNA replication origin licensing but suppress origin activation

The human RIF1 protein controls DNA replication, but the molecular mechanism is largely unknown. Here, we demonstrate that human RIF1 negatively regulates DNA replication by forming a complex with protein phosphatase 1 (PP1) that limits phosphorylation‐mediated activation of the MCM replicative helicase. We identify specific residues on four MCM helicase subunits that show hyperphosphorylation upon RIF1 depletion, with the regulatory N‐terminal domain of MCM4 being particularly strongly affected. In addition to this role in limiting origin activation, we discover an unexpected new role for human RIF1‐PP1 in mediating efficient origin licensing. Specifically, during the G1 phase of the cell cycle, RIF1‐PP1 protects the origin‐binding ORC1 protein from untimely phosphorylation and consequent degradation by the proteasome. Depletion of RIF1 or inhibition of PP1 destabilizes ORC1, thereby reducing origin licensing. Consistent with reduced origin licensing, RIF1‐depleted cells exhibit increased spacing between active origins. Human RIF1 therefore acts as a PP1‐targeting subunit that regulates DNA replication positively by stimulating the origin licensing step, and then negatively by counteracting replication origin activation.