Miracle-dz/UniFAR-FTUs huggingface dataset:
Retinal Changes Precede Visual Dysfunction in the Complement Factor H Knockout Mouse

We previously reported that aged mice lacking complement factor H (CFH) exhibit visual defects and structural changes in the retina. However, it is not known whether this phenotype is age-related or is the consequence of disturbed development. To address this question we investigated the effect of Cfh gene deletion on the retinal phenotype of young and mid-age mice. Cfh −/− mouse eyes exhibited thickening of the retina and reduced nuclear density, but relatively normal scotopic and photopic electroretinograms. At 12 months there was evidence of subtle astroglial activation in the Cfh −/− eyes, and significant elevation of the complement regulator, decay-accelerating factor (DAF) in Müller cells. In the retinal pigment epithelium (RPE) of young control and Cfh −/− animals mitochondria and melanosomes were oriented basally and apically respectively, whereas the apical positioning of melanosomes was significantly perturbed in the mid-age Cfh −/− RPE. We conclude that deletion of Cfh in the mouse leads to defects in the retina that precede any marked loss of visual function, but which become progressively more marked as the animals age. These observations are consistent with a lifelong role for CFH in retinal homeostasis.
Broadcast Authentication Protocol with Time Synchronization and Quadratic Residues Chain

Assuring information authenticity is an important issue in the field of information security. A new broadcast authentication protocol is proposed. The protocol is based on time synchronization and uses chains constructed with the squaring function. The proposed solution is efficient for transmissions over long periods of time since the chains have an unbounded length. The protocol assures information authenticity at the reduced cost of almost one modular multiplication for each broadcasted packet. Time synchronization issues are discussed and the security of the protocol is equivalent to factoring since the squaring function is used. A failure mode analysis of the protocol is done; this is also an aspect of novelty and applies to other protocols based on time synchronization as well
On the Influence of Heart Rate and Coupling Interval Prematurity on Heart Rate Turbulence

<italic>Objective:</italic> Heart rate turbulence (HRT) has been successfully explored for cardiac risk stratification. While HRT is known to be influenced by the heart rate (HR) and the coupling interval (CI), nonconcordant results have been reported on how the CI influences HRT. The purpose of this study is to investigate HRT changes in terms of CI and HR by means of an especially designed protocol. <italic>Methods:</italic> A dataset was acquired from 11 patients with structurally normal hearts for which CI was altered by different pacing trains and HR by isoproterenol during electrophysiological study (EPS). The protocol was designed so that, first, the effect of HR changes on HRT and, second, the combined effect of HR and CI could be explored. As a complement to the EPS dataset, a database of 24-h Holters from 61 acute myocardial infarction (AMI) patients was studied for the purpose of assessing risk. Data analysis was performed by using different nonlinear ridge regression models, and the relevance of model variables was assessed using resampling methods. The EPS subjects, with and without isoproterenol, were analyzed separately. <italic>Results:</italic> The proposed nonlinear regression models were found to account for the influence of HR and CI on HRT, both in patients undergoing EPS without isoproterenol and in low-risk AMI patients, whereas this influence was absent in high-risk AMI patients. Moreover, model coefficients related to CI were not statistically significant, <inline-formula><tex-math notation="LaTeX">$p > 0.05$</tex-math></inline-formula>, on EPS subjects with isoproterenol. <italic>Conclusion:</italic> The observed relationship between CI and HRT, being in agreement with the baroreflex hypothesis, was statistically significant (<inline-formula><tex-math notation="LaTeX">$p < 0.05$ </tex-math></inline-formula>), when decoupling the effect of HR and normalizing the CI by the HR. <italic>Significance: </italic> The results of this study can help to provide new risk indicators that take into account physiological influence on HRT, as well as to model how this influence changes in different cardiac conditions.
Sexual conflict and female immune suppression in the cricket, Allonemobious socius

In many animal systems, females exhibit a localized immune response to insemination that helps defend against sexually transmitted disease. However, this response may also kill sperm, reducing a male's reproductive potential. If males could suppress this response, they may be able to increase their sperm's representation in the female's reproductive tract, thereby increasing their fitness. Here we address the hypothesis that, under conditions of sperm competition, males interfere with female immunity. To test our hypothesis, we manipulated levels of female mating frequency (single vs. multiply mated) and seminal diversity (monandrous vs. polyandrous) in the cricket, Allonemobius socius and measured female immune response. As mating frequency increased, female hemocyte load decreased, indicating a general reproductive cost. As seminal diversity increased, phenoloxidase (PO) activity (in vitro measure of ‘potential’ macroparasitic defense) increased and encapsulation ability (in vivo measure of ‘realized’ macroparasitic defense) decreased in polyandrous females. These results suggest that males may manipulate female immunity by interrupting the pro‐PO cascade, which begins with the activation of PO and ends in the encapsulation of invading foreign bodies. In other words, female immune function may serve as a battleground over which a sexual conflict is fought.
Association between overweight/obesity and increased risk of periodontitis.

OBJECTIVE To investigate periodontitis as a co-morbidity of overweight/obesity in an age-matched sample of periodontitis cases or periodontally healthy controls. METHODS Participants were periodontally assessed using whole mouth clinical periodontal measures. Multivariable conditional logistic regression was used to calculate the odds ratio for diagnosis of periodontitis when body mass index (kg/m2 ), overweight (BMI 25-29.99 kg/m2 , or obese BMI ≥ 30 kg/m2 ) were the explanatory variables. A receiver operating characteristic (ROC) curve was generated of all possible BMI (kg/m2 ) cut-off points discriminating individuals for diagnosis of periodontitis. RESULTS The study comprised 286 participants. BMI showed a dose-response association with increased odds (1.12 per increase of 1 kg/m2 , 95% CI 1.05-1.20, p = 0.001) of being a case compared to a control independent of gender, ethnicity, smoking status and dental plaque level. Similarly overweight/obese were independently associated with increased odds of diagnosis of periodontitis for overweight (OR = 2.56, 95% CI 1.210-5.400, p = 0.014) and for obese (OR = 3.11, 95% CI 1.052-6.481, p = 0.015) compared to normal weight individuals. The ROC curve analysis confirmed diagnosis of periodontitis was 1.6 times more likely in an individual with the BMI ≥ 24.32 kg/m2 . CONCLUSIONS Overweight/obese individuals are more likely to suffer from periodontitis compared to normal weight individuals in this case-control sample.
Continuous Energy Minimization for Multitarget Tracking

Many recent advances in multiple target tracking aim at finding a (nearly) optimal set of trajectories within a temporal window. To handle the large space of possible trajectory hypotheses, it is typically reduced to a finite set by some form of data-driven or regular discretization. In this work, we propose an alternative formulation of multitarget tracking as minimization of a continuous energy. Contrary to recent approaches, we focus on designing an energy that corresponds to a more complete representation of the problem, rather than one that is amenable to global optimization. Besides the image evidence, the energy function takes into account physical constraints, such as target dynamics, mutual exclusion, and track persistence. In addition, partial image evidence is handled with explicit occlusion reasoning, and different targets are disambiguated with an appearance model. To nevertheless find strong local minima of the proposed nonconvex energy, we construct a suitable optimization scheme that alternates between continuous conjugate gradient descent and discrete transdimensional jump moves. These moves, which are executed such that they always reduce the energy, allow the search to escape weak minima and explore a much larger portion of the search space of varying dimensionality. We demonstrate the validity of our approach with an extensive quantitative evaluation on several public data sets.
Shp-2 Tyrosine Phosphatase Functions as a Negative Regulator of the Interferon-Stimulated Jak/STAT Pathway

ABSTRACT Shp-2 is an SH2 domain-containing protein tyrosine phosphatase. Although the mechanism remains to be defined, substantial experimental data suggest that Shp-2 is primarily a positive regulator in cell growth and development. We present evidence here that Shp-2, while acting to promote mitogenic signals, also functions as a negative effector in interferon (IFN)-induced growth-inhibitory and apoptotic pathways. Treatment of mouse fibroblast cells lacking a functional Shp-2 with IFN-α or IFN-γ resulted in an augmented suppression of cell viability compared to that of wild-type cells. To dissect the molecular mechanism, we examined IFN-induced activation of signal transducers and activators of transcription (STATs) by electrophoretic mobility shift assay, using a specific DNA probe (hSIE). The amounts of STAT proteins bound to hSIE upon IFN-α or IFN-γ stimulation were significantly increased in Shp-2−/− cells. Consistently, tyrosine phosphorylation levels of Stat1 upon IFN-γ treatment and, to a lesser extent, upon IFN-α stimulation were markedly elevated in mutant cells. Furthermore, IFN-γ induced a higher level of caspase 1 expression in Shp-2−/− cells than in wild-type cells. Reintroduction of wild-type Shp-2 protein reversed the hypersensitivity of Shp-2−/− fibroblasts to the cytotoxic effect of IFN-α and IFN-γ. Excessive activation of STATs by IFNs was also diminished in mutant cells in which Shp-2 had been reintroduced. Together, these results establish that Shp-2 functions as a negative regulator of the Jak/STAT pathway. We propose that Shp-2 acts to promote cell growth and survival through two mechanisms, i.e., the stimulation of growth factor-initiated mitogenic pathways and the suppression of cytotoxic effect elicited by cytokines, such as IFNs.
Development of an Oncolytic Adenovirus with Enhanced Spread Ability through Repeated UV Irradiation and Cancer Selection

Oncolytic adenoviruses (Ads) have been shown to be safe and have great potential for the treatment of solid tumors. However, the therapeutic efficacy of Ads is antagonized by limited spread within solid tumors. To develop Ads with enhanced spread, viral particles of an E1-wildtype Ad5 dl309 was repeatedly treated with UV type C irradiation and selected for the efficient replication and release from cancer cells. After 72 cycles of treatment and cancer selection, AdUV was isolated. This vector has displayed many favorable characteristics for oncolytic therapy. AdUV was shown to lyse cancer cells more effectively than both E1-deleted and E1-wildtype Ads. This enhanced cancer cell lysis appeared to be related to increased AdUV replication in and release from infected cancer cells. AdUV-treated A549 cells displayed greater expression of the autophagy marker LC3-II during oncolysis and formed larger viral plaques upon cancer cell monolayers, indicating increased virus spread among cancer cells. This study indicates the potential of this approach of irradiation of entire viral particles for the development of oncolytic viruses with designated therapeutic properties.
Deep Learning for Genomics: A Concise Overview

Advancements in genomic research such as high-throughput sequencing techniques have driven modern genomic studies into "big data" disciplines. This data explosion is constantly challenging conventional methods used in genomics. In parallel with the urgent demand for robust algorithms, deep learning has succeeded in a variety of fields such as vision, speech, and text processing. Yet genomics entails unique challenges to deep learning since we are expecting from deep learning a superhuman intelligence that explores beyond our knowledge to interpret the genome. A powerful deep learning model should rely on insightful utilization of task-specific knowledge. In this paper, we briefly discuss the strengths of different deep learning models from a genomic perspective so as to fit each particular task with a proper deep architecture, and remark on practical considerations of developing modern deep learning architectures for genomics. We also provide a concise review of deep learning applications in various aspects of genomic research, as well as pointing out potential opportunities and obstacles for future genomics applications.
Dynamic regulation of CFTR bicarbonate permeability by [Cl-]i and its role in pancreatic bicarbonate secretion.

BACKGROUND & AIMS Pancreatic bicarbonate (HCO3-) secretion is important for a healthy pancreas as well as digestive physiology. However, how human pancreatic duct cells secrete copious amounts of HCO3- has long been a puzzle. Here, we report that a dynamic increase in the cystic fibrosis transmembrane conductance regulator (CFTR) HCO3- permeability by intracellular Cl- concentration ([Cl-]i)-sensitive mechanisms plays a pivotal role in pancreatic HCO3- secretion. METHODS The role of [Cl-]i-sensitive kinases in CFTR-mediated HCO3- transport was examined in heterologous expression systems, PANC1 human pancreatic duct cells, and human and guinea pig pancreatic tissues using an integrated molecular and physiologic approach. RESULTS In human pancreatic tissues, CFTR-positive duct cells abundantly expressed with-no-lysine (WNK1) kinase, oxidative stress-responsive kinase 1 (OSR1), and sterile 20/SPS1-related proline/alanine-rich kinase (SPAK), which are known to be activated by low [Cl-]i. Interestingly, CFTR activation rapidly decreased [Cl-]i in response to luminal Cl- depletion in polarized PANC1 human pancreatic duct cells. Notably, the WNK1-mediated OSR1 and SPAK activation by low [Cl-]i strongly increased CFTR HCO3- permeability in CFTR-transfected HEK 293T, PANC1, and guinea pig pancreatic duct cells, making CFTR primarily an HCO3- channel, which is essential for the secretion of pancreatic juice containing HCO3- at a concentration greater than 140 mmol/L. In contrast, OSR1 and SPAK activation inhibited CFTR-dependent Cl-/HCO3- exchange activity that may reabsorb HCO3- from the high HCO3--containing pancreatic juice. CONCLUSIONS These results indicate that the [Cl-]i-sensitive activation of the WNK1-OSR1/SPAK pathway is the molecular switch to generate HCO3--rich fluid in the human pancreatic duct.
Basic FGF Increases Communication between Cells of the Developing Neocortex

We have found that basic fibroblast growth factor (bFGF), applied to cortical progenitor cells in vitro, produces an increase in the expression of the gap junction protein connexin (Cx) 43 and in the mRNA encoding Cx 43. This effect was evident in both proliferating and nonproliferating cells. The elevated levels of mRNA suggest that bFGF is likely to exert its effect by upregulating the rate of transcription of the Cx 43 gene. We have further shown that the increase in Cx 43 expression is mediated through the receptor tyrosine kinase pathway and is associated with enhanced intercellular dye-coupling mediated by gap junctions. These results suggest that gap junction channels provide a direct conduit for mitogens released in response to bFGF to effectively regulate proliferation during corticogenesis.
Adhesion molecules and C-reactive protein are associated to adverse events in angina pectoris

Abstract Objectives. To examine the prognostic value of soluble Cellular Adhesion Molecules (CAMs) and highly sensitive C reactive protein (hsCRP) on long-term outcome for patients with stable angina pectoris (SAP). Design. In a prospective study, 291 patients referred for coronary angiography due to clinically suspected SAP had serum level of soluble intercellular adhesion molecule-1 (sICAM-1), vascular adhesion molecule-1 (sVCAM-1), sP-selectin and hsCRP determined at baseline. The primary outcome was predefined as death from any cause, myocardial infarction or stroke during a mean follow-up of 7.1 years. Results. Thirty four patients experienced the primary outcome. Hazard ratios and 95% confidence intervals for the primary outcome were: sVCAM-1: 2.4 [1.1–4.9], sICAM-1: 3.3 [1.5–7.2], sP-selectin: 1.2 [0.6–2.6] and hs-CRP: 3.1 [1.5–6.3], when comparing patients in the 4th quartile with those in lower quartiles in a multivariable model. Higher risk of adverse outcome was observed in patients having levels of both hsCRP and sICAM-1 (HR 4.7 [1.7–9.9]) or hsCRP and sVCAM-1 (HR 4.2 [1.7–9.9]) in the 4th quartile. Conclusions. sVCAM-1, sICAM-1 and hsCRP were significantly associated with long term outcomes of patients with SAP beyond the risk associated with traditional risk factors. Risk predictions were improved when combining information about sCAMs and hsCRP.
Effects of iodine supplementation during pregnancy on child growth and development at school age

Growth and development of 207 children (49% males; mean age 5.4 years [SD 0.2], range 4 to 7.3 years whose mothers received iodine during pregnancy, and children who received iodine first in their 2nd year, were examined in 1996; 192 children(49% males; mean age 6.5 years[SD 0.2], range 5.8 to 6.9 years) whose mothers received iodine while pregnant were seen in 1998. Children were from the southern part of China's Xinjiang Province which has the lowest levels of iodine in water and soil ever recorded. Head circumference but not height was improved for those who received iodine during pregnancy (compared with those receiving iodine at age 2) and for those supplemented before the end of the 2nd trimester (relative to those supplemented during the 3rd trimester). Iodine before the 3rd trimester predicted higher psychomotor test scores for children relative to those provided iodine later in pregnancy or at 2 years. Results from the test for cognitive development resulted in trend only differences between those children supplemented during pregnancy versus later. The results address the question of when maternal iodine supplements should begin in public health programs world wide. Findings may be relevant to the treatment of maternal and newborn thyroid deficiency in industrialized countries, particularly for those infants delivered before the end of the second trimester.
Nitroso–Redox Interactions in the Cardiovascular System

ormal cardiovascular performance requires exquisitebalancing of many complex biochemical processes.Perturbation of this balance may lead to myocardial dysfunc-tion or may be a secondary result of structural heart diseasesuch as myocardial infarction (MI) or cardiomyopathic pro-cesses. Altered signaling systems in turn contribute to theprogression of myocardial dysfunction. The roles of reactiveoxygen species (ROS) and reactive nitrogen species (RNS) innormal and failing myocardium and vasculature have beenthe subject of intense investigation and continue to engenderconsiderabledebate.Adisturbanceintheoxidation–reductionstate of the cell, in which ROS production exceeds antioxi-dant defenses, is called oxidative stress. By analogy, nitrosa-tive stress is an impairment in nitric oxide (NO) signalingcaused by increased amounts of RNS, which may be causedby or associated with a disturbance in the redox state. Thisreview addresses the role of the redox state and nitroso–redoxbalance in determining cardiovascular function in health anddisease.
Ultra-small open access microcavities for enhancement of the light-matter interaction

The design, construction and characterisation of a novel, arrayed, open-access optical microcavity is described. Included in this thesis are the precise fabrication details, making use of the focused ion beam. A technique for analysing and optimising the microcavities constructed, making use of an atomic force microscope is also included. Results from the optical characterisation of the fabricated microcavities are presented, including quality factors of around 104, and fitnesses of around 400. The optical analysis then progressed onto coupling colloidal semiconductor nanocrystals to the microcavity modes. This yielded room temperature Purcell enhancements, single particle sensing, and also allowed for the characterisation of a second iteration of cavities. This improved set was shown to achieve fitnesses in excess of 1800 and quality factors with a lower limit of 15000. The optical identification of single NV centres in nanodiamond is discussed, along with the development of an optical apparatus to couple them to microcavities at cryogenic temperatures. Finally several results from finite difference time domain simulations will be presented, showing ultimate mode volumes of less than 0.5 cubic wavelengths are possible for this approach.
Associations between asymmetry and human attractiveness: Possible direct effects of asymmetry and signatures of publication bias

Background: Fluctuating asymmetry (FA), reflecting developmental instability (DI), may honestly signal individual quality and relate to human attractiveness and measures of sexual behaviour. The evolutionary importance of these associations, however, critically depends on the role of DI in driving these correlations. A direct effect of FA reduces the role of DI. Aim: To explore the direct effects of FA in determining human attractiveness, comparing the strength of associations whether the asymmetries could be observed during the attractiveness ratings or not. Subjects and methods: Literature search and meta-analysis. Results: This study found indications for such a direct role through stronger associations between FA and physical attractiveness when asymmetries are visible. Furthermore, a substantial publication bias emerged and correcting for it resulted in a reduction of 30–50% in effect sizes. When considering the few relatively large with sample size over 100 only, effect sizes were nearly zero. Conclusion: The current literature likely overstates the evolutionary importance of asymmetry in determining human (physical) attractiveness. This study discusses the possible consequences for presumed associations between DI and human sexual behaviour and fitness.
Estimation in Capture‐Recapture Models When Covariates Are Subject to Measurement Errors

Summary. We consider estimation problems in capture‐recapture models when the covariates or the auxiliary variables are measured with errors. The naive approach, which ignores measurement errors, is found to be unacceptable in the estimation of both regression parameters and population size: it yields estimators with biases increasing with the magnitude of errors, and flawed confidence intervals. To account for measurement errors, we derive a regression parameter estimator using a regression calibration method. We develop modified estimators of the population size accordingly. A simulation study shows that the resulting estimators are more satisfactory than those from either the naive approach or the simulation extrapolation (SIMEX) method. Data from a bird species Prinia flaviventris in Hong Kong are analyzed with and without the assumption of measurement errors, to demonstrate the effects of errors on estimations.