Miracle-dz/UniFAR-FTUs huggingface dataset:
High susceptibility to experimental myopia in a mouse model with a retinal on pathway defect.

PURPOSE Nob mice share the same mutation in the Nyx gene that is found in humans with complete congenital stationary night blindness (CSNB1). Nob mutant mice were studied to determine whether this defect resulted in myopia, as it does in humans. METHODS Refractive development was measured in unmanipulated wild-type C57BL/6J (WT) and nob mice from 4 to 12 weeks of age by using an infrared photorefractor. The right eye was form deprived by means of a skull-mounted goggling apparatus at 4 weeks of age. Refractive errors were recorded every 2 weeks after goggling. The content of dopamine and the dopamine metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) were measured by HPLC with electrochemical detection (HPLC-ECD) in retinas of nob and WT mice under light- and dark-adapted conditions. RESULTS The nob mice had greater hyperopic refractive errors than did the WT mice under normal visual conditions, until 12 weeks of age when both strains had similar refractions. At 6 weeks of age, refractions became less hyperopic in the nob mice but continued to become more hyperopic in the WT mice. After 2 weeks of form deprivation (6 weeks of age), the nob mice displayed a significant myopic shift (~4 D) in refractive error relative to the opposite and control eyes, whereas WT mice required 6 weeks of goggling to elicit a similar response. As expected with loss of ON pathway transmission, light exposure did not alter DOPAC levels in the nob mice. However, dopamine and DOPAC levels were significantly lower in the nob mice compared with WT. CONCLUSIONS Under normal laboratory visual conditions, only minor differences in refractive development were observed between the nob and WT mice. The largest myopic shift in the nob mice resulted after form deprivation, suggesting that visual pathways dependent on nyctalopin and/or abnormally low dopaminergic activity play a role in regulating refractive development. These findings demonstrate an interaction of genetics and environment in refractive development.
Default Option and the Cross-Section of Stock Returns

We argue that default option is important for equity valuation and construct a model that explicitly prices the option to default or abandon the firm. An investment strategy that buys stocks that are classified as undervalued by our model and shorts overvalued stocks generates an annual 4-factor alpha of about 11% for U.S. stocks. The model’s performance is stronger for stocks with higher value of default option, such as distressed or highly volatile stocks. We construct a similar strategy in a sample of nine most highly capitalized developed markets and find consistent results. Our findings suggest that investors do not properly incorporate the value of default options in stock prices.
A 42-kD tyrosine kinase substrate linked to chromaffin cell secretion exhibits an associated MAP kinase activity and is highly related to a 42-kD mitogen-stimulated protein in fibroblasts

The localization of the protein tyrosine kinase pp60c-src to the plasma membrane and to the membrane of secretory vesicles in neurally derived bovine chromaffin cells has suggested that tyrosine phosphorylations may be associated with the process of secretion. In the present study we have identified two cytosolic proteins of approximately 42 and 45 kD that become phosphorylated on tyrosine in response to secretagogue treatment. Phosphorylation of these proteins reached a maximum (3 min after stimulation) before maximum catecholamine release was observed (5- 10 min after stimulation). Both secretion and tyrosine phosphorylation of p42 and p45 required extracellular Ca2+. Tyrosine-phosphorylated proteins of similar Mr have previously been identified in 3T3-L1 adipocytes stimulated with insulin (MAP kinase; Ray, L. B., and T. W. Sturgill. 1987. Proc. Natl. Acad. Sci. USA. 84:1502-1506) and in avian and rodent fibroblasts stimulated with a variety of mitogenic agents (Cooper, J. A., D. F. Bowen-Pope, E. Raines, R. Ross, and T. Hunter. 1982. Cell. 31:263-273; Nakamura, K. D., R. Martinez, and M. J. Weber. 1983. Mol. Cell. Biol. 3:380-390). Comparisons of the secretion- associated 42-kD protein of chromaffin cells with the 42-kD protein of Swiss 3T3 fibroblasts and 3T3-L1 adipocytes provide evidence that these three proteins are highly related. This evidence includes comigration during one-dimensional SDS-PAGE, cochromatography using ion exchange and hydrophobic matrices, similar isoelectric points, identical cyanogen-bromide peptide maps, and cochromatography of MAP kinase activity with the tyrosine-phosphorylated form of pp42. This protein(s), which appears to be activated in a variety of cell types, may serve a common function, perhaps in signal transduction involving a cascade of kinases.
Integrating specific knowledge: insights from the Kennedy Space Center

This paper presents a theoretical model of knowledge integration, by developing a classification of types of specific knowledge (context-specific, technology-specific, and context-and-technology-specific) and examining the effects of four knowledge integration mechanisms (exchange, direction, socialization, and internalization) on the integration of these knowledge types. Based on prior literature, we argue that: 1) different types of specific knowledge are characterized by different levels of common knowledge; 2) different knowledge integration mechanisms require different levels of common knowledge; and 3) integration mechanisms can be matched with knowledge types based on efficiency/effectiveness considerations. Empirical research at the John F. Kennedy Space Center, which involved two rounds of interviews and a questionnaires survey of 159 individuals, explores the relationships among the four knowledge integration mechanisms, the three types of specific knowledge, and satisfaction with knowledge integration. Results indicate that exchange, socialization, and internalization support the integration of context-specific, technology-specific, and context-and-technology-specific types of knowledge, respectively. Direction and internalization, but not exchange and socialization, influence satisfaction with knowledge integration. Implications for practice and future research are examined.
SLE: Another Autoimmune Disorder Influenced by Microbes and Diet?

Systemic lupus erythematosus (SLE) is a multi-system autoimmune disease. Despite years of study, the etiology of SLE is still unclear. Both genetic and environmental factors have been implicated in the disease mechanisms. In the past decade, a growing body of evidence has indicated an important role of gut microbes in the development of autoimmune diseases, including type 1 diabetes, rheumatoid arthritis, and multiple sclerosis. However, such knowledge on SLE is little, though we have already known that environmental factors can trigger the development of lupus. Several recent studies have suggested that alterations of the gut microbial composition may be correlated with SLE disease manifestations, while the exact roles of either symbiotic or pathogenic microbes in this disease remain to be explored. Elucidation of the roles of gut microbes – as well as the roles of diet that can modulate the composition of gut microbes – in SLE will shed light on how this autoimmune disorder develops, and provide opportunities for improved biomarkers of the disease and the potential to probe new therapies. In this review, we aim to compile the available evidence on the contributions of diet and gut microbes to SLE occurrence and pathogenesis.
Decomposing Neural Synchrony: Toward an Explanation for Near-Zero Phase-Lag in Cortical Oscillatory Networks

Background Synchronized oscillation in cortical networks has been suggested as a mechanism for diverse functions ranging from perceptual binding to memory formation to sensorimotor integration. Concomitant with synchronization is the occurrence of near-zero phase-lag often observed between network components. Recent theories have considered the importance of this phenomenon in establishing an effective communication framework among neuronal ensembles. Methodology/Principal Findings Two factors, among possibly others, can be hypothesized to contribute to the near-zero phase-lag relationship: (1) positively correlated common input with no significant relative time delay and (2) bidirectional interaction. Thus far, no empirical test of these hypotheses has been possible for lack of means to tease apart the specific causes underlying the observed synchrony. In this work simulation examples were first used to illustrate the ideas. A quantitative method that decomposes the statistical interdependence between two cortical areas into a feed-forward, a feed-back and a common-input component was then introduced and applied to test the hypotheses on multichannel local field potential recordings from two behaving monkeys. Conclusion/Significance The near-zero phase-lag phenomenon is important in the study of large-scale oscillatory networks. A rigorous mathematical theorem is used for the first time to empirically examine the factors that contribute to this phenomenon. Given the critical role that oscillatory activity is likely to play in the regulation of biological processes at all levels, the significance of the proposed method may extend beyond systems neuroscience, the level at which the present analysis is conceived and performed.
Enhancement of robust foreground detection through masked greyworld and color co-occurrence approach

Total robustness to illumination change is difficult to solve just using a single approach. Our approach to improvement in accuracy and robustness to illumination change is by fusing two different methods, namely, color constancy and color co-occurrence. A “grey world” assumption is used to handle sudden illumination change while color cooccurrence modelling is used to handle gradual illumination change. The novelty of our approach is the introduction of a mask and a probabilistic approach for adjustment of the grey constant values. In addition, because of our novel color cooccurrence approach, our algorithm can distinguish between “moving” background and moving foreground. The results prove that our method perform the best among the compared methods and manage to reduce the error rate by half compared to the Renno et al. [1] method. In conclusion, the fusion of the approach manages to improve robustness to illumination change and moving background.
The Ca2+-calmodulin dependent protein kinase II system of skeletal muscle sarcoplasmic reticulum

It is well known that skeletal muscle sarcoplasmic reticulum (SR) contains a Ca 2+-calmodulin (CaM) dependent protein kinase (CaMKII) system. In the last twenty years, much experimental work has clarified the biochemical-functional properties of this kinase system. SR-bound CaMKII is formed by the holoenzyme and by anchoring proteins, called αKAP. The holoenzyme is composed by a muscle specific form of β subunit (β Μ), and by γ and δ subunits. In rabbit skeletal muscle, β Μ seems to be expressed in greater amounts in slow-twitch muscle. Two isoforms of αKAP of 23-21 kDa are present in isolated SR fragments of rabbit fast-twitch muscle, whereas only the 23 kDa αKAP splice variant is expressed in slow-twitch muscle. Based on biochemical work on isolated SR vesicles, the kinetic properties of SR-bound CaMKII do not significantly differ from those of CaMKII in other tissues. CaMKII is localized on the cytoplasmic side of SR membranes, and is ubiquitously distributed between longitudinal SR and junctional SR. In slow-twitch muscle, CaMKII is mainly involved in regulation of SR Ca 2+-transport, as indicated by phosphory-lation of SERCA2a isoform of Ca 2+-ATPase and of SERCA2a-regulatory protein phos-pholamban. In fast-twitch muscle, the main role of CaMKII seems to be the control of Ca 2+-release. Much experimental evidence seems to negate that ryanodine receptor/SR Ca 2+-release channel of skeletal muscle (RyR1) is a substrate of phosphorylation of endogenous CaMKII. The main undisputed, junctional SR-specific protein substrate of CaMKII is tri-adin, which interacts structurally and functionally with RyR1. The functional effect on RyR1 of CaMKII-dependent phosphorylation of junctional SR membranes remains somewhat controversial, even though the bulk of experimental evidence suggests a negative regulation of the calcium channel by the kinase. Additional protein substrates of SR-bound CaMKII are histidine-rich Ca 2+-binding protein, glycogen synthase and 21 kDa αKAP. Therefore, SR-bound CaMKII is involved in regulation of Ca 2+-homeostasis and, likely, of glucose metabolism. A putative role in regulation of gene expression remains to be established. Ca 2+-calmodulin (CaM) dependent protein kinase II [CaMKII] is a ubiquitous, pleiotropic serine/threonine protein kinase. Upon elevation of intracellular Ca 2+ concentration , apo-CaM binds Ca 2+. In turn, Ca 2+-CaM binds to CaMKII, which becomes activated and able to act on a broad spectrum of substrates in vitro and in vivo. For this reason, CaMKII is called multifunctional. This wide substrate specificity allows CaMKII to play a role in the regulation of a multiplicity of …
Serum levels of IGF‐I and IGFBP‐III and their relation with carcinoembryonic antigen and carbohydrate antigen 19‐9 in cases of esophageal cancer

Tumour markers are used for diagnosis, staging, evaluation of response to treatment, prognosis and detection of recurrences in clinical oncology. In this study, we aim to investigate the levels of insulin‐like growth factor (IGF)‐I and IGF‐binding protein (IGFBP)‐III in cases with oesophageal carcinoma. We investigated their possible use as tumour markers and their relation to other tumour markers.
Trade Wars and Trade Talks with Data

How large are optimal tariffs? What tariffs would prevail in a worldwide trade war? How costly would be a breakdown of international trade policy cooperation? And what is the scope for future multilateral trade negotiations? I address these and other questions using a unified framework which nests traditional, new trade, and political economy motives for protection. I find that optimal tariffs average 62 percent, world trade war tariffs average 63 percent, the government welfare losses from a breakdown of international trade policy cooperation average 2.9 percent, and the possible government welfare gains from future multilateral trade negotiations average 0.5 percent. Optimal tariffs are tariffs which maximize a political economy augmented measure of real income.
The Role of Osteoimmunology in Periodontal Disease

Periodontal disease is a pathological condition that involves inflammation of the tooth supporting structures. It occurs in response to the presence of bacterial plaque on the tooth structure. The host defense system, including innate and adaptive immunity, is responsible for combating the pathologic bacteria invading the periodontal tissue. Failure to eradicate the invading pathogens will result in a continuous state of inflammation where inflammatory cells such as lymphocytes, PMNs, and macrophages will continue to produce inflammatory mediators in an effort to destroy the invaders. Unfortunately, these inflammatory mediators have a deleterious effect on the host tissue as well as foreign microbes. One of the effects of these mediators on the host is the induction of matrix degradation and bone resorption through activation of proteases and other inflammatory mediators that activate osteoclasts.
Induction of Phenolic Compounds in Wheat (Triticum aestivum L.) Tissue Cultures by Streptomycin

The tissue cultures of wheat (Triticum aestivum L.) were induced from the mature embryos (explants) of the dry grains and grown on MS medium containing kinetin (0.1 mg/l) and 2,4 D (1.0 mg/l). The cultures were incubated for two weeks at (25 ± 2) °C under a light/dark regime (16 h light daily). The formed calli were subcultured at the beginning of the stationary growth phase (15 days) with fresh MS medium containing 0, 5, 10, 25, 50, 100, 150 mg/l streptomycin elicitor and maintained for two weeks for three subcultures. A significant increase in phenylalanine ammonia lyase (PAL) activity coincided with the increase of the total phenolic compounds after elicitation with streptomycin. Maximum induction was recorded during the first two weeks, then gradually declined during the rest of the experimental period, but the values attained were still markedly higher than that of the control. The endogenous cinnamic acid content was also increased significantly with the increase in PAL activity making about 2-18% of the total phenolic acids. The growth and accumulation of phenolic compounds were inversely related. However, accumulation of phenolic compounds became limited for growth of wheat tissue culture especially during the long term cultivation.
First report of the nematode Leidynema appendiculata from Periplaneta fuliginosa

The smokybrown cockroach Periplaneta fuliginosa has spread all over the world, and is now one of the most undesired invasive alien pests in Japan. Because cockroaches are generally infected by thelastomatid nematodes, they are being distributed around the world with their parasitic nematodes. Nothing is known about parasitic nematode species in P. fuliginosa differences, or similarity of the parasite’s population structures between the different countries of the host cockroaches. Here we investigated the P. fuliginosa invasive to Japan and found that 100% of individuals were infected with one nematode species. According to the morphology and the sequence of the D2/D3 expansion segment of the 28S ribosomal RNA gene, we identified the parasite as Leidynema appendiculata. This nematode reproduced by haplodiploidy and its developmental timing under various conditions is quite divergent. Their population in the hindgut of P. fuliginosa was controlled with a few adult females and a male. This is the first report of the thelastomatid nematode isolated from the smokybrown cockroach, and is the basis for our future research examining the origin, distribution route and immigration history of the cockroach and the impact of L. appendiculata on native Japanese cockroach species.
Recognition of mutant and cryptic 5' splice sites by the U1 small nuclear ribonucleoprotein in vitro

We examined the ability of U1 small nuclear ribonucleoproteins (U1 snRNPs) to recognize mutant and cryptic 5' splice sites on beta-globin pre-mRNA substrates using an RNase T1 protection assay. When U1 snRNPs were prebound to anti-(U1)RNP antibodies, we detected binding to mutant but not to cryptic 5' splice sites on several substrates. By contrast, in a splicing extract at 0 degree C, neither the mutated nor cryptic 5' splice sites of a human beta-globin transcript were selected as protected fragments with the same antibodies. However, after incubation of the transcript in the extract to yield splicing intermediates, fragments that included a cryptic 5' splice site were detected. The results of our analyses suggest that U1 snRNPs are involved in recognizing cryptic 5' splice sites but that interactions with other splicing components are required to stabilize the association.
Zoledronic Acid Sensitizes Renal Cell Carcinoma Cells to Radiation by Downregulating STAT1

Zoledronic acid (ZOL), a third-generation bisphosphonate that strongly inhibits osteoclast activity, is widely used for the treatment of bone metastasis from a variety of malignancies, including renal cell carcinoma (RCC). We previously reported that zoledronic acid (ZOL) clinically potentiates antitumor effects of radiotherapy (RT) on bone metastases from RCC. To date, however, it remains unknown whether ZOL radiosensitizes RCC and if it does, how. Here, we demonstrated that ZOL directly radiosensitizes RCC cells independent of osteoclast activity by potentiating the caspase-3-mediated apoptosis pathway. The radiosensitization by ZOL was observed in 786-O, A-498, and ACHN cells but not in Caki-1 cells. As its underlying molecular mechanism, we found that the signal transducer and activator of transcription 1 (STAT1) plays a key role. The three RCC cell lines, in which ZOL exerted a radiosensitizing effect, expressed STAT1 abundantly but Caki-1 cells did not. ZOL downregulated endogenous STAT1 expression in 786-O, A-498, and ACHN cells by a post-transcriptional modification. We confirmed that knockdown of endogenous STAT1 by siRNA sensitized 786-O cells to RT equivalently to ZOL, and that introduction of exogenous STAT1 rendered Caki-1 cells more RT-resistant. This is the first study to clarify the molecular mechanism by which ZOL directly radiosensitizes tumor cells. Because tumor cells commonly overexpress STAT1 and ZOL reportedly radiosensitizes various types of tumor cells, ZOL warrants further clinical and translational studies as a potent radiosensitizer against RT-resistant tumors overexpressing STAT1.
Scaling and trends of hourly precipitation extremes in two different climate zones – Hong Kong and the Netherlands

Abstract. Hourly precipitation extremes in very long time series from the Hong Kong Observatory and the Netherlands are investigated. Using the 2 m dew point temperature from 4 h before the rainfall event as a measure of near surface absolute humidity, hourly precipitation extremes closely follow a 14% per degree dependency – a scaling twice as large as following from the Clausius-Clapeyron relation. However, for dew point temperatures above 23 °C no significant dependency on humidity was found. Strikingly, in spite of the large difference in climate, results are almost identical in Hong Kong and the Netherlands for the dew point temperature range where both observational sets have sufficient data. Trends in hourly precipitation extremes show substantial increases over the last century for both De Bilt (the Netherlands) and Hong Kong. For De Bilt, not only the long term trend, but also variations in hourly precipitation extremes on an inter-decadal timescale of 30 yr and longer, can be linked very well to the above scaling; there is a very close resemblance between variations in dew point temperature and precipitation intensity with an inferred dependency of hourly precipitation extremes of 10 to 14% per degree. For Hong Kong there is no connection between variations in humidity and those in precipitation intensity in the wet season, May to September. This is consistent with the found zero-dependency of precipitation intensity on humidity for dew points above 23 °C. Yet, outside the wet season humidity changes do appear to explain the positive trend in hourly precipitation extremes, again following a dependency close to twice the Clausius-Clapeyron relation.