Miracle-dz/UniFAR-FTUs huggingface dataset:
Phosphorylation at S87 Is Enhanced in Synucleinopathies, Inhibits α-Synuclein Oligomerization, and Influences Synuclein-Membrane Interactions

Increasing evidence suggests that phosphorylation may play an important role in the oligomerization, fibrillogenesis, Lewy body (LB) formation, and neurotoxicity of α-synuclein (α-syn) in Parkinson disease. Herein we demonstrate that α-syn is phosphorylated at S87 in vivo and within LBs. The levels of S87-P are increased in brains of transgenic (TG) models of synucleinopathies and human brains from Alzheimer disease (AD), LB disease (LBD), and multiple system atrophy (MSA) patients. Using antibodies against phosphorylated α-syn (S129-P and S87-P), a significant amount of immunoreactivity was detected in the membrane in the LBD, MSA, and AD cases but not in normal controls. In brain homogenates from diseased human brains and TG animals, the majority of S87-P α-syn was detected in the membrane fractions. A battery of biophysical methods were used to dissect the effect of S87 phosphorylation on the structure, aggregation, and membrane-binding properties of monomeric α-syn. These studies demonstrated that phosphorylation at S87 expands the structure of α-syn, increases its conformational flexibility, and blocks its fibrillization in vitro. Furthermore, phosphorylation at S87, but not S129, results in significant reduction of α-syn binding to membranes. Together, our findings provide novel mechanistic insight into the role of phosphorylation at S87 and S129 in the pathogenesis of synucleinopathies and potential roles of phosphorylation in α-syn normal biology.
On Distributed Storage Allocations for Memory-Limited Systems

In this paper we consider distributed allocation problems with memory constraint limits. Firstly, we propose a tractable relaxation to the problem of optimal symmetric allocations. The approximated problem is based on the Q-error function, and its solution approaches the solution of the initial problem, as the number of storage nodes in the network grows. Secondly, exploiting this relaxation, we are able to formulate and to solve the problem for storage allocations for memory-limited DSS storing and arbitrary memory profiles. Finally, we discuss the extension to the case of multiple data objects, stored in the DSS.
Immunophenotypic characterization of mixed type gingival vascular Immunophenotypic characterization of mixed type gingival vascular hamartoma in a calf - a case report hamartoma in a calf - a case report

A one month-old heifer calf affected by gingival vascular hamartoma, of measured mass 3×2.5×2 cm is presented. This gingival vascular hamartoma was a mixture of redundant vessels ranging from capillaries or capillary buds and large arteries separated by edematous and loose fi brostroma. The results of Immunohistochemistry showed strong expression of the alpha smooth muscle Actin, weak reaction of the Von Willebrand factor and negative reaction of Vimentin, CD31, Ki67 and PCNA in endothelial cells, suggesting vascular hamartoma.
European airline reform; An empirical welfare analysis

This study empirically explores welfare effects associated with bilateral airline liberalisation on European interstate routes. To this end, a sample of 34 routes with varying liberalisation status has been investigated econometrically for the period 1988 to 1992. The estimated fare and frequency equations show that standard economy fares are lower and departure frequencies are higher on fully liberalised routes than on routes without such liberalisation. Welfare calculations based on the estimated demand equation indicate that full bilateral liberalisation has resulted in consumer welfare gains. © The London School of Economics and the University of Bath 2002
Encoding of Whisker Vibration by Rat Barrel Cortex Neurons: Implications for Texture Discrimination

Rats, using their whiskers, have excellent capabilities in texture discrimination. What is the representation of texture in rat somatosensory cortex? We hypothesize that as rats “whisk” over a surface, the spatial frequency of a grooved or pebbled texture is converted to a temporal frequency of whisker vibration. Surface features such as groove depth or grain size modulate the amplitude of this vibration. Validation of the hypothesis depends on showing that vibration parameters have distinct neuronal representations in cortex. To test this, we delivered sinusoidal vibrations to the whisker shaft and analyzed cortical neuronal activity. Seven amplitudes and seven frequencies were combined to construct 49 stimuli while recording activity through a 10 × 10 microelectrode array inserted into the middle layers of barrel cortex. We find that cortical neurons do not explicitly encode vibration frequency (f) or amplitude (A) by any coding measure (average spike counts over different time windows, spike timing patterns in the peristimulus time histograms or in autocorrelograms). Instead, neurons explicitly encode the product of frequency and amplitude, which is proportional to the mean speed of the vibration. The quantity Af is an invariant because neuronal response encodes this feature independently of the values of the individual terms A and f. This was true across a wide time scale of firing rate measurements, from 5 to 500 msec. We conclude that vibration kinetics are rapidly and reliably encoded in the firing rate of cortical ensembles. Therefore, the cortical representation of vibration speed could underlie texture discrimination.
Characterization of a murine model of metastatic human non-small cell lung cancer and effect of CXCR4 inhibition on the growth of metastases

Despite successful preclinical testing carried out through the use of subcutaneous xenografted tumors, many anti-cancer agents have gone on to fail in human trials. One potential factor accounting for this discrepancy may relate to the inadequacy of the commonly employed preclinical models to recapitulate the human disease, particularly when it comes to discovery of agents that are effective against advanced disease. Herein, we report the characterization of a NSCLC model and an exploration of the impact that a CXCR4 inhibitor, AMD3100, had on NCI-H1299-derived metastasis. These cells express a variety of metastasis-promoting factors, hence we selected them for a study of their metastatic colonization potential. To accomplish this, luciferase-expressing H1299 (H1299-luc2) cells were inoculated into athymic mice via the intracardiac route. This strategy produced adrenal, bone, ovarian, and pancreatic metastases, sites commonly involved in human metastatic NSCLC. Notably, micro-computed tomography and histological evaluation of the skeletal lesions revealed the presence of extensive osteolysis. To investigate the potential role of CXCR4 in mediating metastatic colonization of tissues, AMD3100 was administered to mice inoculated with H1299-luc2 cells. While this treatment did not appreciably alter the frequency of metastatic colonization, it was able to slow the growth of macrometastases. This model, recapitulating some of the events seen in late-stage human NSCLC, may prove useful in the evaluation of new therapies targeting metastatic disease.
Role of Estrogen in Thyroid Function and Growth Regulation

Thyroid diseases are more prevalent in women, particularly between puberty and menopause. It is wellknown that estrogen (E) has indirect effects on the thyroid economy. Direct effects of this steroid hormone on thyroid cells have been described more recently; so, the aim of the present paper was to review the evidences of these effects on thyroid function and growth regulation, and its mechanisms. The expression and ratios of the two E receptors, α and β, that mediate the genomic effects of E on normal and abnormal thyroid tissue were also reviewed, as well as nongenomic, distinct molecular pathways. Several evidences support the hypothesis that E has a direct role in thyroid follicular cells; understanding its influence on the growth and function of the thyroid in normal and abnormal conditions can potentially provide new targets for the treatment of thyroid diseases.
Optical and Magnetic Properties of Dust Grains

The optical and magnetic properties of dust grains are reviewed , as they relate to the problem of interstellar grain alignment. Grain geometry plays an important role in determining the optical properties , and scattering and absorption of starlight will produce radiative torques which may drive grains to suprathermal rates of rotation in in-terstellar clouds; these radiative torques appear likely to play an active role in the alignment process. The likely magnetic properties of grains are discussed, with particular attention to the imaginary part of the magnetic susceptibility.
Epithelial-to-Mesenchymal Transition of RPE Cells In Vitro Confers Increased β1,6-N-Glycosylation and Increased Susceptibility to Galectin-3 Binding

Epithelial-to-mesenchymal transition (EMT) of retinal pigment epithelial cells is a crucial event in the onset of proliferative vitreoretinopathy (PVR), the most common reason for treatment failure in retinal detachment surgery. We studied alterations in the cell surface glycan expression profile upon EMT of RPE cells and focused on its relevance for the interaction with galectin-3 (Gal-3), a carbohydrate binding protein, which can inhibit attachment and spreading of human RPE cells in a dose- and carbohydrate-dependent manner, and thus bares the potential to counteract PVR-associated cellular events. Lectin blot analysis revealed that EMT of RPE cells in vitro confers a glycomic shift towards an abundance of Thomsen-Friedenreich antigen, poly-N-acetyllactosamine chains, and complex-type branched N-glycans. Using inhibitors of glycosylation we found that both, binding of Gal-3 to the RPE cell surface and Gal-3-mediated inhibition of RPE attachment and spreading, strongly depend on the interaction of Gal-3 with tri- or tetra-antennary complex type N-glycans and sialylation of glycans but not on complex-type O-glycans. Importantly, we found that β1,6 N-acetylglucosaminyltransferase V (Mgat5), the key enzyme catalyzing the synthesis of tetra- or tri-antennary complex type N-glycans, is increased upon EMT of RPE cells. Silencing of Mgat5 by siRNA and CRISPR-Cas9 genome editing resulted in reduced Gal-3 binding. We conclude from these data that binding of recombinant Gal-3 to the RPE cell surface and inhibitory effects on RPE attachment and spreading largely dependent on interaction with Mgat5 modified N-glycans, which are more abundant on dedifferentiated than on the healthy, native RPE cells. Based on these findings we hypothesize that EMT of RPE cells in vitro confers glycomic changes, which account for high affinity binding of recombinant Gal-3, particularly to the cell surface of myofibroblastic RPE. From a future perspective recombinant Gal-3 may disclose a therapeutic option allowing for selectively targeting RPE cells with pathogenic relevance for development of PVR.
The Size Evolution of High-Redshift Galaxies

Hubble Space Telescope images of high-redshift galaxies selected via color and photometric redshifts are used to examine the size and axial ratio distribution of galaxies as a function of redshift at look-back times t > 8 Gyr. These parameters are measured at rest-frame UV wavelengths (1200 Å < λ < 2000 Å) on images with a rest-frame resolution of less than 0.8 kpc. Galaxy radii are found to scale with redshift approximately as the Hubble parameter H-1(z). This is in accord with the theoretical expectation that the typical sizes of the luminous parts of galaxies should track the expected evolution in the virial radius of dark matter halos. The mean ratio of the semimajor axis to the semiminor axis for a bright well-resolved sample of galaxies at z ~ 4 is b/a = 0.65, suggesting that these Lyman break galaxies are not drawn from a spheroidal population. However, the median concentration index of this sample is C = 3.5, which is closer to the typical concentration indices of nearby elliptical galaxies (C ~ 4) than to the values for local disk galaxies of type Sb and later (C < 2).
Comprehensive Characterization of Mesenchymal Stem Cells from Human Placenta and Fetal Membrane and Their Response to Osteoactivin Stimulation

Mesenchymal stem cells (MSCs) are the most promising seed cells for cell therapy and can be isolated from various sources of human adult tissues such as bone marrow (BM-MSC) and adipose tissue. However, cells from these tissues must be obtained through invasive procedures. We, therefore, characterized MSCs isolated from fresh placenta (Pl-MSC) and fetal membrane (Mb-MSC) through morphological and fluorescent-activated cell sorting (FACS). MSC frequency is higher in membrane than placenta (2.14% ± 0.65 versus 15.67% ± 0.29%). Pl/Mb-MSCs in vitro expansion potential was significantly higher than BM-MSCs. We demonstrated that one of the MSC-specific marker is sufficient for MSC isolation and that culture in specific media is the optimal way for selecting very homogenous MSC population. These MSCs could be differentiated into mesodermal cells expressing cell markers and cytologic staining consistent with mature osteoblasts and adipocytes. Transcriptomic analysis and cytokine arrays demonstrated broad similarity between placenta- and membrane-derived MSCs and only discrete differences with BM-MSCs with enrichment of networks involved in bone differentiation. Pl/Mb-MSCs displayed higher osteogenic differentiation potential than BM-MSC when their response to osteoactivin was evaluated. Fetal-tissue-derived mesenchymal cells may, therefore, be considered as a major source of MSCs to reach clinical scale banking in particular for bone regeneration.
Genotype by environment interaction and breeding for robustness in livestock

The increasing size of the human population is projected to result in an increase in meat consumption. However, at the same time, the dominant position of meat as the center of meals is on the decline. Modern objections to the consumption of meat include public concerns with animal welfare in livestock production systems. Animal breeding practices have become part of the debate since it became recognized that animals in a population that have been selected for high production efficiency are more at risk for behavioral, physiological and immunological problems. As a solution, animal breeding practices need to include selection for robustness traits, which can be implemented through the use of reaction norms analysis, or though the direct inclusion of robustness traits in the breeding objective and in the selection index. This review gives an overview of genotype × environment interactions (the influence of the environment, reaction norms, phenotypic plasticity, canalization, and genetic homeostasis), reaction norms analysis in livestock production, options for selection for increased levels of production and against environmental sensitivity, and direct inclusion of robustness traits in the selection index. Ethical considerations of breeding for improved animal welfare are discussed. The discussion on animal breeding practices has been initiated and is very alive today. This positive trend is part of the sustainable food production movement that aims at feeding 9.15 billion people not just in the near future but also beyond.
A comparative evaluation of impact strength and residual monomer content in denture base resins processed by compression and injection molding technique

Objectives: This In-vitro study was designed to compare the Impact strength and Residual monomer content of conventional and high impact types of denture base resins polymerized by Compression and Injection molding technique with short curing cycle. Materials and Methods: Forty samples were made (twenty from each technique)in the dimension of 60 × 10 × 3 with 2 mm notch on the thickness side. The Impact strength was measured in Izod type of impact tester and Nuclear magnetic resonance method estimated residual monomer content. T-test and Anova were used to statistically analyze the result. Results: High Impact acrylic resin hadsignificantly high impact strength and less residual monomer content than the Conventional acrylic resin in both the techniques. Resins processed by Injection molding technique produced greater Impact strength and reduced Residual monomer content as compared to resins processed by Compression molding technique.
An Optimal Currency Area Perspective of the EU Enlargement to the CEECs

This paper tries to assess whether it would be optimal for the CEECs to form a monetary union with either Germany or the EU. This cannot be done without discussing first the Maastricht criteria, which are the condition « sine qua non » for a country to be eligible. Yet, they are often independent from more structural criteria (Bayoumi and Eichengreen (1996b)). Hence, this paper argues that although the CEECs do not satisfy -yet- the Maastricht criteria, their economic cycle is close enough to that of the EU and Germany for a monetary union to bring them great benefits. Indeed, using a methodology derived by L. Reichlin and M. Forni (1997) and C. Fuss (1997), it can be shown that (i) the percentage of CEECs business cycle fluctuations explained by a German shock is very high,; (ii) furthermore, the impulse responses are positively correlated. These suggest that the CEECs would not suffer from a common monetary policy .
Sarcoplasmic Reticulum Ca 2 and Heart Failure Roles of Diastolic Leak and Ca 2 Transport

Heart failure (HF) is a leading cause of death and enormous effort has focused at understanding the molecular and cellular mechanisms of the decreased cardiac contractility. While changes of other components contribute, it is generally agreed that much of the contractile deficit is due to reduced myocyte Ca transients.1,2 Alterations in Ca current (ICa) and action potential characteristics are also seen in HF, but a central factor limiting Ca transient amplitude is a decrease of sarcoplasmic reticulum (SR) Ca content.3–6 HF is extremely complex, but it is easy to appreciate how reduced SR Ca content would reduce SR Ca release, myofilament activation, and contractility. Despite agreement that SR Ca content is reduced in HF, controversy exists about why SR content is low.
ENTERPRISE ARCHITECTURE STRATEGIC FRAMEWORK

The alignment between business and IT is critical for formulating optimal organisational strategies, and obtaining a competitive advantage. Conversely, alignment between the business and IT units is often challenged in many organisations. Some occurrence of deficiencies in the organisation is due to lack of formal approach such as Enterprise Architecture (EA). The deficiencies sometimes threaten activities such as standardisation, implementation and support for ICT infrastructures. Analysis revealed that the deficiencies manifest into complexities and inconsistencies, affecting organisational goals. Also, without EA, some organisations are challenged with a holistic view, to monitor and manage its business processes, information flow, technology selection and deployment. Other factors that pose challenges to the competitive advantage of organisation are adaptive-ness, uniformity and scalability, which EA is intended to address from strategic perspective. Unfortunately, many organisations do not have strategic framework for the implementation of EA. This has significant impact on the organisation’s processes and activities. This study made use of empirical evidences, from qualitative case study to develop a strategic framework, which could be employed in addressing non-technical factors that affect EA.
Susceptibility of western flower thrips Frankliniella occidentalis (Thysanoptera: Thripidae) to some synthetic and botanical insecticides under laboratory conditions

This study was conducted to investigate commercial formulations of insecticides against western flower thrips, Frankliniella occidentalis (Pergande). The insects were collected from commercial greenhouses of cucumber in Varamin, Iran. The tested insecticides were diazinon (EC 60%), cypermethrin (EC 40%), fipronil (EC 2.5%), imidacloprid (SC 35%) and a botanical insecticide oxymatrine (Kingbo, AS 0.6%). Fipronil had the highest efficacy among all tested insecticides (LC50 = 17.97 ppm). However, imidacloprid had the lowest efficacy (LC50 = 2303 ppm). The oxymatrine was effective (LC50 = 69.94 ppm) after fipronil.
Combining Confidence Estimation and Reference-based Metrics for Segment-level MT Evaluation

We describe an effort to improve standard reference-based metrics for Machine Translation (MT) evaluation by enriching them with Confidence Estimation (CE) features and using a learning mechanism trained on human annotations. Reference-based MT evaluation metrics compare the system output against reference translations looking for overlaps at different levels (lexical, syntactic, and semantic). These metrics aim at comparing MT systems or analyzing the progress of a given system and are known to have reasonably good correlation with human judgments at the corpus level, but not at the segment level. CE metrics, on the other hand, target the system in use, providing a quality score to the end-user for each translated segment. They cannot rely on reference translations, and use instead information extracted from the input text, system output and possibly external corpora to train machine learning algorithms. These metrics correlate better with human judgments at the segment level. However, they are usually highly biased by difficulty level of the input segment, and therefore are less appropriate for comparing multiple systems translating the same input segments. We show that these two classes of metrics are complementary and can be combined to provide MT evaluation metrics that achieve higher correlation with human judgments at the segment level.
A Phylometagenomic Exploration of Oceanic Alphaproteobacteria Reveals Mitochondrial Relatives Unrelated to the SAR11 Clade

Background According to the endosymbiont hypothesis, the mitochondrial system for aerobic respiration was derived from an ancestral Alphaproteobacterium. Phylogenetic studies indicate that the mitochondrial ancestor is most closely related to the Rickettsiales. Recently, it was suggested that Candidatus Pelagibacter ubique, a member of the SAR11 clade that is highly abundant in the oceans, is a sister taxon to the mitochondrial-Rickettsiales clade. The availability of ocean metagenome data substantially increases the sampling of Alphaproteobacteria inhabiting the oxygen-containing waters of the oceans that likely resemble the originating environment of mitochondria. Methodology/Principal Findings We present a phylogenetic study of the origin of mitochondria that incorporates metagenome data from the Global Ocean Sampling (GOS) expedition. We identify mitochondrially related sequences in the GOS dataset that represent a rare group of Alphaproteobacteria, designated OMAC (Oceanic Mitochondria Affiliated Clade) as the closest free-living relatives to mitochondria in the oceans. In addition, our analyses reject the hypothesis that the mitochondrial system for aerobic respiration is affiliated with that of the SAR11 clade. Conclusions/Significance Our results allude to the existence of an alphaproteobacterial clade in the oxygen-rich surface waters of the oceans that represents the closest free-living relative to mitochondria identified thus far. In addition, our findings underscore the importance of expanding the taxonomic diversity in phylogenetic analyses beyond that represented by cultivated bacteria to study the origin of mitochondria.