Miracle-dz/UniFAR-FTUs huggingface dataset:
Occurrence of birefringent retinal inclusions in cynomolgus monkeys after high doses of canthaxanthin.

PURPOSE To reproduce and investigate in a primate animal model the phenomenon of the red carotenoid canthaxanthin (beta, beta-carotene-4'4'-dione) to induce crystal-like retinal deposits as they have been observed in the ocular fundus of humans after high canthaxanthin intake (i.e., more than 30 mg/day). METHODS Groups of four cynomolgus monkeys (Macaca fascicularis) per gender and dose were administered 5.4, 16.2, or 48.6 mg canthaxanthin/kg body weight daily by oral gavage for 2.5 years. Eight control animals received placebo. In vivo ophthalmoscopy was performed at intervals of 3 months along with electroretinography after 12 and 24 months and retinal biomicroscopy just before the monkeys were killed. Retinal wholemounts or frozen sections were investigated postmortem by polarization, bright field, and differential interference contrast microscopy. Retinal and preterminal plasma canthaxanthin concentrations were determined by high-performance liquid chromatography (HPLC). RESULTS By ophthalmoscopy and retinal biomicroscopy in vivo, no crystals or other light-reflecting particles were observed in the central paramacular retina. However, postmortem polarization microscopy of all 24 canthaxanthin-treated animals showed a circular zone in the peripheral retina containing birefringent, polymorphous red, orange, or white inclusions. The density of these inclusions was diminished within 1 to 8 mm posterior to the ora serrata. These inclusions were located mainly in the inner retinal layers, that is the nerve fiber layer and ganglion cell layer, inner plexiform layer, and inner nuclear layer. Twelve of the 24 canthaxanthin-treated animals showed yellow, golden birefringent inclusions in the macula. Retinas of placebo-treated monkeys were free of birefringent, crystal-like inclusions. The HPLC confirmed the presence of all-trans canthaxanthin, and 4-OH-echinenone and isozeaxanthin as well, in the retinas of all canthaxanthin-treated animals. Neither electroretinography nor histopathology indicated any adverse effects of the canthaxanthin-induced retinal inclusions seen in this study. CONCLUSIONS A high intake of canthaxanthin for 2.5 years led to the deposition of crystal-like birefringent inclusions in the inner layers of the peripheral retina and, to some extent, the central retina of cynomolgus monkeys. The presence of these deposits did not interfere with morphology nor with retinal function.
Reinventing the IT function: the Role of IT Agility and IT Ambidexterity in Supporting Digital Business Transformation

The immanent opportunities and threats from digital business transformation significantly affect the role of the IT function. Line functions increasingly expect that the internal IT function provides support for digital value creation in addition to traditional IT services. This dual focus bears the potential for tensions as competing in digital business environments means to act fast and to explore, while managing traditional enterprise IT requires stability, reliability, and exploitation of existing resources. Therefore, our study empirically examines the role of two key capabilities—IT agility and IT ambidexterity—on the IT function’s digitization support. Based on a survey including 258 IT executives, we find that IT agility is a main driver of the IT function’s ability to support digitization. Furthermore, our results show that an ambidextrous focus of IT functions is best suited to find a balance between opposing demands.
How to look like a mallow: evidence of floral mimicry between Turneraceae and Malvaceae

Abundant, many-flowered plants represent reliable and rich food sources for animal pollinators, and may even sustain guilds of specialized pollinators. Contrastingly, rare plants need alternative strategies to ensure pollinators' visitation and faithfulness. Flower mimicry, i.e. the sharing of a similar flower colour and display pattern by different plant species, is a means by which a rare species can exploit a successful model and increase its pollination services. The relationship between two or more rewarding flower mimic species, or Müllerian mimicry, has been proposed as mutualistic, in contrast to the unilaterally beneficial Batesian floral mimicry. In this work, we show that two different geographical colour phenotypes of Turnera sidoides ssp. pinnatifida resemble co-flowering Malvaceae in colour as seen by bees' eyes, and that these pollinators do not distinguish between them when approaching flowers in choice tests. Main pollinators of T. sidoides are bees specialized for collecting pollen in Malvaceae. We demonstrate that the similarity between at least one of the geographical colour phenotypes of T. sidoides and co-flowering Malvaceae is adaptive, since the former obtains more pollination services when growing together with its model than when growing alone. Instead of the convergent evolution pattern attributed to Müllerian mimicry, our data rather suggest an advergent evolution pattern, because only T. sidoides seems to have evolved to be more similar to its malvaceous models.
A folding inhibitor of the HIV‐1 protease

Because the human immunodeficiency virus type 1 protease (HIV‐1‐PR) is an essential enzyme in the viral life cycle, its inhibition can control AIDS. The folding of single‐domain proteins, like each of the monomers forming the HIV‐1‐PR homodimer, is controlled by local elementary structures (LES, folding units stabilized by strongly interacting, highly conserved, as a rule hydrophobic, amino acids). These LES have evolved over myriad generations to recognize and strongly attract each other, so as to make the protein fold fast and be stable in its native conformation. Consequently, peptides displaying a sequence identical to those segments of the monomers associated with LES are expected to act as competitive inhibitors and thus destabilize the native structure of the enzyme. These inhibitors are unlikely to lead to escape mutants as they bind to the protease monomers through highly conserved amino acids, which play an essential role in the folding process. The properties of one of the most promising inhibitors of the folding of the HIV‐1‐PR monomers found among these peptides are demonstrated with the help of spectrophotometric assays and circular dichroism spectroscopy. Proteins 2006. © 2005 Wiley‐Liss, Inc.
The analysis of interleukin-6 in patients with systemic IgG4-related plasmacytic syndrome--expansion of SIPS to the territory of Castleman's disease.

vasculitis [8] and autoimmune thyroid disease [5]. High levels of lymph node mRNA expression and serum levels of TNFand IL-6 have been reported [9, 10], suggesting a hypercytokinaemia commonly seen in CTDs. Frequently, considerable effort must be spent in order to differentiate this entity from adult onset Still’s disease, RA and SLE [3, 5, 6]. The clinical outcome of AILT remains poor (median survival <3 years, 5-year survival 30–35%) [5]. Combination chemotherapy may lead to complete remission (50%) but relapse rates remain high. Overall combination chemotherapy appears to be superior to glucocorticosteroids alone [5] but studies are limited. Furthermore, some patients develop secondary diffuse large B-cell lymphoma (DLBCL) [3]. Recognition of AILT is therefore important as the management of the differential diagnoses may lead to inappropriate treatment. In summary, we present a rare case of AILT with clinical features of autoimmune disease. Rapid escalation and deescalation of the lymphadenopathy, combined with more prominent symptoms from the joints, gave the strong impression of an underlying disorder like RA. AILT should be considered in the differential diagnosis of late-onset RA or Still’s disease in older patients presenting with a recent history of lymphadenopathy and fever. In such patients, sites of lymph-node involvement nonapparent by physical examination should be investigated.
Variational Learning for Recurrent Spiking Networks

We derive a plausible learning rule for feedforward, feedback and lateral connections in a recurrent network of spiking neurons. Operating in the context of a generative model for distributions of spike sequences, the learning mechanism is derived from variational inference principles. The synaptic plasticity rules found are interesting in that they are strongly reminiscent of experimental Spike Time Dependent Plasticity, and in that they differ for excitatory and inhibitory neurons. A simulation confirms the method's applicability to learning both stationary and temporal spike patterns.
PROGNOSTIC SIGNIFICANCE OF CYCLOOXYGENASE-2 IN BREAST AND ESOPHAGEAL CARCINOMA

A, Turpeenniemi-Hujanen T: Association of cyclooxygenase-2 and matrix metalloproteinase-2 expression in human breast cancer. elevated cyclooxygenase-2 expression in patients with adenocarcinoma of Lanschot JJB, Ristimäki A: Prognostic role of cyclooxygenase-2 expression in patients with squamous cell carcinoma of the esophagus. Int J Cancer, in press. The original publications are reprinted with the permission of the copyright holders. 6 ABBREVIATIONS AA arachidonic acid ACF aberrant crypt foci Apc adenomatous polyposis gene cDNA complementary deoxyribonucleic acid COX cyclooxygenase DDFS distant disease-free survival DCIS ductal carcinoma in situ DMBA 7,12-dimethylbenz(a)anthracene ER estrogen receptor FAP familial adenomatous polyposis IL interleukin Min multiple intestinal neoplasia mRNA messenger ribonucleic acid MMP matrix metalloproteinase NSAID nonsteroidal anti-inflammatory drug
Trabeculae carneae as models of the ventricular walls: implications for the delivery of oxygen

Trabeculae carneae are the smallest naturally arising collections of linearly arranged myocytes in the heart. They are the preparation of choice for studies of function of intact myocardium in vitro. In vivo, trabeculae are unique in receiving oxygen from two independent sources: the coronary circulation and the surrounding ventricular blood. Because oxygen partial pressure (PO2) in the coronary arterioles is identical in specimens from both ventricles, whereas that of ventricular blood is 2.5-fold higher in the left ventricle than in the right ventricle, trabeculae represent a “natural laboratory” in which to examine the influence of “extravascular” PO2 on the extent of capillarization of myocardial tissue. We exploit this advantage to test four hypotheses. (1) In trabeculae from either ventricle, a peripheral annulus of cells is devoid of capillaries. (2) Hence, sufficiently small trabeculae from either ventricle are totally devoid of capillaries. (3) The capillary-to-myocyte ratios in specimens from either ventricle are identical to those of their respective walls. (4) Capillary-to-myocyte ratios are comparable in specimens from either ventricle, reflecting equivalent energy demands in vivo, driven by identical contractile frequencies and comparable wall stresses. We applied confocal fluorescent imaging to trabeculae in cross section, subsequently using semi-automated segmentation techniques to distinguish capillaries from myocytes. We quantified the capillary-to-myocyte ratios of trabeculae from both ventricles and compared them to those determined for the ventricular free walls and septum. Quantitative interpretation was furthered by mathematical modeling, using both the classical solution to the diffusion equation for elliptical cross sections, and a novel approach applicable to cross sections of arbitrary shape containing arbitrary disposition of capillaries and non-respiring collagen cords.
Reduced Mitochondrial Oxidative Capacity and Increased Mitochondrial Uncoupling Impair Myocardial Energetics in Obesity

Background— Obesity is a risk factor for cardiovascular disease and is strongly associated with insulin resistance and type 2 diabetes. Recent studies in obese humans and animals demonstrated increased myocardial oxygen consumption (M&OV0312;o2) and reduced cardiac efficiency (CE); however, the underlying mechanisms remain unclear. The present study was performed to determine whether mitochondrial dysfunction and uncoupling are responsible for reduced cardiac performance and efficiency in ob/ob mice. Methods and Results— Cardiac function, M&OV0312;o2, mitochondrial respiration, and ATP synthesis were measured in 9-week-old ob/ob and control mouse hearts. Contractile function and M&OV0312;o2 in glucose-perfused ob/ob hearts were similar to controls under basal conditions but were reduced under high workload. Perfusion of ob/ob hearts with glucose and palmitate increased M&OV0312;o2 and reduced CE by 23% under basal conditions, and CE remained impaired at high workload. In glucose-perfused ob/ob hearts, mitochondrial state 3 respirations were reduced but ATP/O ratios were unchanged. In contrast, state 3 respiration rates were similar in ob/ob and control mitochondria from hearts perfused with palmitate and glucose, but ATP synthesis rates and ATP/O ratios were significantly reduced in ob/ob, which suggests increased mitochondrial uncoupling. Pyruvate dehydrogenase activity and protein levels of complexes I, III, and V were reduced in obese mice. Conclusions— These data indicate that reduced mitochondrial oxidative capacity may contribute to cardiac dysfunction in ob/ob mice. Moreover, fatty acid but not glucose-induced mitochondrial uncoupling reduces CE in obese mice by limiting ATP production and increasing M&OV0312;o2.
Compensation of particle accelerator load using converter-controlled pulse compensator

This paper studies the use of a voltage-source converter (VSC) with dc capacitors as an energy storage medium for the compensation of pulsating active and reactive power of the European Organization for Nuclear Research's (CERN's) proton synchrotron (PS) particle accelerator. The PS accelerator load demands periodic, active, and reactive power pulses of about 2-s duration and a magnitude of up to 45 MW and 65 Mvar. The proposed compensator is able to control both reactive and active power exchange with the network in order to eliminate network disturbances. The controllability study reveals that the best control strategy is to use a q-axis converter input for active power and a d-axis input for reactive power regulation. An analytical system model is created to study the system dynamics and to aid the controller design. The eigenvalue study with the MATLAB model reveals that with large energy storage units and small converter losses, there is only a small interaction between the control channels. The final testing is done with a detailed nonlinear model in PSCAD/EMTDC. The simulation results show that it is possible to fully compensate the active power exchange with the network during typical accelerator cycles and, at the same time, to achieve excellent ac voltage control.
RNA-sequencing of a mouse-model of spinal muscular atrophy reveals tissue-wide changes in splicing of U12-dependent introns

Spinal Muscular Atrophy (SMA) is a neuromuscular disorder caused by insufficient levels of the Survival of Motor Neuron (SMN) protein. SMN is expressed ubiquitously and functions in RNA processing pathways that include trafficking of mRNA and assembly of snRNP complexes. Importantly, SMA severity is correlated with decreased snRNP assembly activity. In particular, the minor spliceosomal snRNPs are affected, and some U12-dependent introns have been reported to be aberrantly spliced in patient cells and animal models. SMA is characterized by loss of motor neurons, but the underlying mechanism is largely unknown. It is likely that aberrant splicing of genes expressed in motor neurons is involved in SMA pathogenesis, but increasing evidence indicates that pathologies also exist in other tissues. We present here a comprehensive RNA-seq study that covers multiple tissues in an SMA mouse model. We show elevated U12-intron retention in all examined tissues from SMA mice, and that U12-dependent intron retention is induced upon siRNA knock-down of SMN in HeLa cells. Furthermore, we show that retention of U12-dependent introns is mitigated by ASO treatment of SMA mice and that many transcriptional changes are reversed. Finally, we report on missplicing of several Ca2+ channel genes that may explain disrupted Ca2+ homeostasis in SMA and activation of Cdk5.
Solution structure of the matrix attachment region-binding domain of chicken MeCP2.

Methyl-CpG-binding protein 2 (MeCP2) is a multifunctional protein involved in chromatin organization and silencing of methylated DNA. MAR-BD, a 125-amino-acid residue domain of chicken MeCP2 (cMeCP2, originally named ARBP), is the minimal protein fragment required to recognize MAR elements and mouse satellite DNA. Here we report the solution structure of MAR-BD as determined by multidimensional heteronuclear NMR spectroscopy. The global fold of this domain is very similar to that of rat MeCP2 MBD and MBD1 MBD (the methyl-CpG-binding domains of rat MeCP2 and methyl-CpG-binding domain protein 1, respectively), exhibiting a three-stranded antiparallel beta-sheet and an alpha-helix alpha1. We show that the C-terminal portion of MAR-BD also contains an amphipathic helical coil, alpha2/alpha3. The hydrophilic residues of this coil form a surface opposite the DNA interface, available for interactions with other domains of MeCP2 or other proteins. Spectroscopic studies of the complex formed by MAR-BD and a 15-bp fragment of a high-affinity binding site from mouse satellite DNA indicates that the coil is also involved in protein.DNA interactions. These studies provide a basis for discussion of the consequences of six missense mutations within the helical coil found in Rett syndrome cases.
Document Instantiation for Relevance Feedback in the Bayesian Network Retrieval Model

Relevance Feedback consists on formulating automatically a new query, according to the relevance judgements provided by the user after evaluating the set of retrieved documents. In this paper we introduce a new relevance feedback method for the Bayesian Network Retrieval Model. This method is based on the instantiation of the observed documents as relevant or non-relevant in the Bayesian Network. We explain the theoretical bases of the model and propose different schemes for carrying out this task. The quality of the method is tested using a preliminary experimentation with different collections.
STOCK MARKET VOLATILITY: AN EVALUATION

ehaviour of stock market is uncertain, volatile and probabilistic although it is related with the major macroeconomic indicators of the economy. The stability of the stock market needs the strong capital market with high macro fundamentals. In the globalization era, the international trade plays a key role in changing stock market efficiency in the areas of banking and finance. The extreme volatility in the stock market produces instability in the capital market, destabilize the value of currency, as well as hampers international trade and finance. Even, the growth and the stock market volatility are inversely related where causality was found.A developed stock market should be fundamentally more competitive with any other international stock markets in which floating exchange rate mechanism is determined. The monetary and trade policy of a country crucially help in finding factors of stock market volatility to work properly although the patterns of behavior of investors and savers of the stakeholders are unknown where the political super structure and process of the economy are given. But the political factors may change parametrically. This paper evaluated the studies of the major works on stock market volatility on such multidimensional issues.
Smokers With Cervix Cancer Have More Uterine Corpus Invasive Disease and an Increased Risk of Recurrence After Treatment With Chemoradiation

Background Smoking is a risk factor for cervix cancer and causes hypoxemia, which promotes tumor infiltration and potentially impacts on treatment outcome. We performed a retrospective study to determine if smokers had an increased risk of uterine corpus infiltration, which is associated with more advanced disease and/or treatment failure after primary chemoradiation. Methods Results from a prospective database of patients treated with primary chemoradiation for locally advanced cervix cancer with a pretreatment MRI were analyzed. Smoking status was assessed by self-report at presentation. Results Smoking status was recorded for 346 of the 362 patients with 98 current smokers (28%), 56 ex-smokers (16%), and 192 nonsmokers (55%). Median age was 58 years with ever-smokers having a younger age at diagnosis than nonsmokers. Histologic type, International Federation of Gynecology and Obstetrics stage, tumor volume, and nodal involvement were similar across groups, as were toxicities of treatment. Ever-smokers were more likely to have corpus uterine invasion than nonsmokers. Ever-smokers had more recurrences than nonsmokers, with nonsmokers having a longer median overall survival (50.1 vs 38.7 months, P = 0.004) and relapse-free survival (46.8 vs 28.5 months, P = 0.003). In multifactor analysis, ever-smoking status was a significant predictor of developing corpus invasive disease and of inferior relapse-free and overall survival after treatment. Conclusions Smokers have a greater risk for developing corpus invasive cervix cancer. Although nonsmokers have an older age at diagnosis, they live longer and have fewer recurrences after a diagnosis of locally advanced carcinoma of the cervix.
Coronary Pressure Measurement Based Decision Making for Percutaneous Coronary Intervention

The fractional flow reserve (FFR) is a simple, reliable, and reproducible physiologic index of lesion severity. In patients with intermediate stenosis, FFR≥0.75 can be used to safely defer percutaneous coronary intervention (PCI), and patients with FFR≥0.75 have a very low cardiac event rate. Coronary pressure measurement can determine which lesion should be treated with PCI in patients with tandem lesions, and PCI on the basis of FFR has been demonstrated to result in an acceptably low repeat PCI rate. FFR can identify patients with equivocal left main coronary artery disease who benefit from coronary bypass surgery. Coronary pressure measurement distinguishes patients with an abrupt pressure drop pattern from those with a gradual pressure drop pattern, and the former group of patients benefit from PCI. Coronary pressure measurement is clinically useful in evaluating sufficient recruitable coronary collateral blood flow for prevention of ischemia, which affects future cardiac events. FFR is useful for the prediction of restenosis after PCI. As an end-point of PCI, FFR ≥0.95 and ≥0.90 would be appropriate for coronary stenting and coronary angioplasty, respectively. In summary, if you encounter a coronary stenosis in doubt you should measure pressure rather than dilate it.