Miracle-dz/UniFAR-FTUs huggingface dataset:
Single Molecule Localization Microscopy of DNA Damage Response Pathways in Cancer.

The collective DNA Damage Response (DDR) network of cellular pathways serves to prevent, recognize, and repair DNA damage resulting from both endogenous and exogenous sources. Unchecked or misrepaired, DNA damage causes genomic instability and mutagenesis, cell death, and various types of cancer [1]. DNA replication during S phase is a process particularly prone to endogenous damage because of the requirement for the entire genomic DNA to be unwound and duplicated over a relatively short time period (minutes in yeast, hours in mammals). To achieve this, any impediments or corruptions to the DNA template such as bound transcription complexes, small molecules, or unusual secondary structures, must be removed. If these impediments are not easily removed they can cause replication fork (RF) slowing, stalling, and eventual regression or collapse. In the latter case, the single sided double strand break (DSB) that occurs must be repaired with high fidelity to ensure the viability of the cell. To do this, the homologous recombination (HR) DSB repair machinery completes a number of sequential operations: first to resect the DSB to generate a ssDNA overhang, then to generate a Rad51/ssDNA nucleofilament which conducts a homology search of the genomic DNA, and then synthesis of new DNA using the homologous sequence [2].
Dysregulated balance of Th 17 and Th 1 cells in systemic lupus erythematosus

Introduction: Interleukin (IL)-17 is a proinflammatory cytokine that is produced largely by a unique CD4 T-helper (Th) subset called Th17 cells. The development of Th17 cells is suppressed by interferon (IFN)-g produced by Th1 cells, suggesting cross-regulation between Th17 and Th1 cells. Thus, this study analyzed the balance of CD4 Th17 and Th1 cell responses in peripheral blood from patients with systemic lupus erythematosus (SLE) and healthy subjects. Methods: Twenty-five adult patients with SLE and 26 healthy subjects matched for gender and age (± 2 years) were recruited. Peripheral blood mononuclear cells (PBMCs) from patients and healthy subjects were stimulated for 4 h ex vivo with phorbol myristate acetate (PMA) and ionomycin. The frequency of CD4 T cells producing IL-17 and/or IFN-g was measured by using flow cytometry. Expression of Th17-associated chemokine receptors CCR4 and CCR6 on CD4 T cells as well as plasma levels of Th17-polarizing cytokines were assessed. Disease activity was evaluated by the SLE disease activity index score (SLEDAI). Unpaired t test and Pearson correlation were used for statistical analyses. Results: Patients with SLE had an increased frequency of CD4IL-17 T cells compared with healthy subjects. However, the frequency of CD4IFN-g T cells was similar between the two groups, indicating an altered balance of Th17 and Th1 cell responses in SLE. Patients with SLE also had an increased frequency of CD4CCR4CCR6 T cells that are known to produce IL-17. The frequency of CD4IL-17 T cells and CD4CCR4CCR6 T cells correlated with disease activity. In measuring plasma levels of the Th17-polarizing cytokines, levels of IL-6 were higher in patients with SLE than in healthy subjects, although levels of IL-1b, IL-21, IL-23, and transforming growth factor (TGF)-b were not different between the two groups. Conclusions: We demonstrate an enhanced Th17 cell response that correlates with disease activity in patients with SLE, suggesting a role for IL-17 in the pathogenesis of lupus. Our data indicate that the mechanisms involved in balancing Th1 and Th17 regulation, as well as in producing IL-6, are aberrant in SLE, leading to an increased Th17 response. We suggest that CCR4 and CCR6 expression on CD4 T cells should be considered as markers of disease activity, and that IL-17 blocking may offer a therapeutic target in SLE.
The features of circulating and tumor-infiltrating γδ T cells in melanoma patients display critical perturbations with prognostic impact on clinical outcome

ABSTRACT γδT cells hold a pivotal role in tumor immunosurveillance through their prompt activation and cytokine secretion, their ability to kill tumor cells in an Human Leukocyte Antigen (HLA)-unrestricted manner, and their combination of features of both innate and adaptive immunity. These unique properties and functional plasticity render them very attractive both as targets and vectors for cancer immunotherapy. Yet, these potent and fascinating antitumor effectors have not been extensively explored in melanoma. We provided here a detailed investigation of the phenotypic and functional properties of circulating and tumor-infiltrating γδT cells in melanoma patients, and their impact on clinical evolution. High proportions of circulating- and tumor-infiltrating γδT and δ2+ subset were associated with better clinical outcome. We reported however that circulating and tumor-infiltrating γδT cells from melanoma patients displayed an altered expression of NCR, KIR, and immune checkpoints, and identified NKp44, PD1, 41BB/41BBL, TIM3, and LAG3 as crucial checkpoints allowing immune escape and tumor progression. Notably, melanoma drastically impaired the ability of γδT cells to exhibit activation molecules, secrete cytokines, and display cytotoxicity toward melanoma in response to stimulation with phosphoantigens. It drove them toward regulatory and Th17 profiles associated with poor clinical outcomes. Our study highlights that melanoma hijacked γδT cells to escape from immune control, and revealed that circulating and tumor-infiltrating γδT cell features are promising potential biomarkers of clinical evolution. Such understanding of the physiopathology of γδT cells may help designing new therapeutic approaches exploiting the antitumor potential of γδT cells while counteracting their skewing by tumors to improve patient outcomes.
Characterization and quantification of mRNA transcripts in ejaculated spermatozoa of fertile men by serial analysis of gene expression.

BACKGROUND Accumulated evidence proves that mature spermatozoa contain a complex yet specific array of mRNA, which could provide information on the past events of spermatogenesis. OBJECTIVE To quantitatively microdissect these mRNA transcripts by a digital approach. METHODS Serial analysis of gene expression (SAGE) was used to study the mRNA transcripts from ejaculate of a fertile individual and of a pool of 10 fertile men. Online DAVID software suite was also utilized to cluster the UniGene data. RESULTS A SAGE library from the individual produced 20,237 raw tags representing 2459 unique tags and that from pooled 10 men generated 21,052 raw tags representing 2712 unique tags. When the unique tags occurring > or = 4 times were analysed, 564 overlapping tags were produced by 638 unique tags from the individual and 682 from the pooled library. Fifty-four of these overlapped tags were considered to be novel genes. Online analysis of the overlapping tags revealed 25 functional gene groups, with the dominant one comprising 96 nuclear protein genes involving transcription and transcription regulation and also a group with 84 ribosomal subunit genes involving protein synthesis. CONCLUSION A SAGE analysis of ejaculate from fertile men has revealed a large number of transcripts, which occur in steady frequencies and probably have important roles in spermatogenesis and fertilization.
Pregnancy outcomes and outdoor air pollution: an ecological study in districts of the Czech Republic 1986-8.

OBJECTIVES: Outdoor air pollution has consistently been shown to predict mortality. The finding that this association is stronger in infants than in children or adults raises the question whether air pollution could also be related to pregnancy outcomes--such as birthweight and stillbirth. The association between outdoor air pollution and stillbirths and low birthweight in the Czech Republic, where air pollution was high, was examined. METHODS: An ecological study was conducted, with routinely collected data on stillbirths and low birthweight (< 2500 g), air pollution (total suspended particulates, sulphur dioxide (SO2), and nitrogen oxides (NOx)), and socioeconomic factors (mean income, car ownership, divorce rate, etc). The analyses were restricted to 45 districts on which data on air pollution were available for the period 1986-8. The effects of exposure variables on frequency of pregnancy outcomes were estimated by logistic regression with district-years as the units of analysis. RESULTS: Stillbirth rate (4.2/1000 births in monitored districts) was not significantly associated with any indicator of air pollution, and was weakly related to mean income and proportion of births outside marriage. Crude prevalence of low birthweight (prevalence 5.5%) showed highly significant associations with several socioeconomic factors; after controlling for these, odds ratios (ORs)/50 micrograms/m3 increase in pollutant were: 1.04 (95% confidence interval (95% CI) 0.96 to 1.12) for total suspended particles, 1.10 (1.02 to 1.17) for SO2, and 1.07 (0.98 to 1.16) for NOx. When all pollutants were included in one model, SO2 remained related to low birthweight (OR 1.10 (1.01 to 1.20), p = 0.033). CONCLUSION: These results are consistent with a recent study in China where birthweight was also associated with total suspended particles and SO2 but ecological studies must be interpreted cautiously. Residual confounding by socioeconomic factors cannot be ruled out. The association between air pollution and birthweight requires further investigation.
Wait Times in Diagnostic Evaluation and Treatment for Patients With Stage III Non-Small Cell Lung Cancer in British Columbia

ObjectiveNon-small cell lung cancer (NSCLC) is associated with poor prognosis. Although this is mostly due to the aggressive natural history of the disease, the effect of treatment delays on patient outcomes is unclear. This study examines various time intervals in the diagnostic evaluation, staging, and treatment of patients with unresectable stage III NSCLC. MethodsA case-control study of patients with stage III NSCLC in British Columbia was carried out. One hundred nineteen patients treated radically with chemoradiotherapy were matched with 238 patients treated palliatively. Multivariate analysis was used to compare treatment delays and prognostic factors in the 2 groups. ResultsCompared with radically treated cases, patients treated palliatively had shorter median times from first symptom to first abnormal test (32 vs. 58 d) and from first symptom to pathologically confirmed diagnosis (67 vs. 90 d). More radically treated patients (61% vs. 50%) were first assessed by a thoracic surgeon, whereas more palliatively treated patients (73% vs. 50%) were initially assessed by a respirologist. The median time from diagnosis to referral to a cancer center was similar between the 2 groups, but palliative cases were 5 times more likely to have a delay of >55 days between diagnosis and referral. This delay was observed in 24% of palliatively treated and 7% of radically treated cases. ConclusionsThe wait time from first symptom to referral to a regional cancer center in British Columbia for stage III NSCLC was approximately 3 to 4 months. Efforts to reduce wait times are warranted to reduce patient distress and possibly disease progression.
Design of Novel Teaching Episodes in Medical Education Using Emerging Experiential Digital Assets: Technology Enabled Medical Education Beyond the Gimmicky

Medical education has always been about experiential hands on training to prepare future doctors to create the necessary skillset to deal with the sensitive and immediate nature of their work. Contemporary experiential technologies such as Virtual and Augmented reality offer a realistic but consequence free test-bed in which to interact safely and cope with emotional challenges pertaining to the realistic tasks simulated through these media. This work describes the design guidelines and workflow for incorporating these novel virtual assets in medical education through serious role play learning episodes. This approach consists of the case selection, the identification of roles, information flow and narrative requirements, implementation of technological narrative tools and implementation of the learning episode. Using a specific example of case transfer through this model we describe the process, outline implementation, assessment and technological considerations. Finally rationale for this work as a counterweight to technological hype fluctuations and integration of these media into the mainstream curricula is discussed.
Causality of 3D extended gravity theories

Causality is one of the most important properties to understand gravity theories. It gives us not only a method to confirm that the gravity theories are really consistent, but also gives implications about the properties which unknown fundamental physics should obey. We investigate the causality of three-dimensional (3D) gravity theories, which are considered to be important, by using the Shapiro time delay effect in the Shock wave geometry. One of such gravity theories is the Zwei-Dreibein Gravity (ZDG) theory, which is a consistent 3D gravity theory. In ZDG theory, the serious problems can be removed that have appeared in another important gravity theory called New Massive Gravity (NMG). We study whether the ZDG theory could preserve the causality without losing the above good properties and how the causality structure is related to the structure of the NMG theory.
Relative Speech Emotion Recognition Based Artificial Neural Network

Artificial neural network (ANN) models based on static features vector as well as normalized temporal features vector, were used to recognize emotion state from speech. Moreover, relative features obtained by computing the changes of acoustic features of emotional speech relative to those of neutral speech were adopted to weaken the influence from the individual difference. The methods to relativize static features and temporal features were introduced individually and experiments based Germany database and Mandarin database were implemented. The results show that the performance of relative features excels that of absolute features for emotion recognition as a whole. When speaker is independent, the hybrid of relative static features vector and relative temporal features normalized vector achieves the best results.
A Pilot Study of Rapid Cooling by Cold Saline and Endovascular Cooling Before Reperfusion in Patients With ST-Elevation Myocardial Infarction

Background—Experimental studies have shown that induction of hypothermia before reperfusion of acute coronary occlusion reduces infarct size. Previous clinical studies, however, have not been able to show this effect, which is believed to be mainly because therapeutic temperature was not reached before reperfusion in the majority of the patients. We aimed to evaluate the safety and feasibility of rapidly induced hypothermia by infusion of cold saline and endovascular cooling catheter before reperfusion in patients with acute myocardial infarction. Methods and Results—Twenty patients with acute myocardial infarction scheduled to undergo primary percutaneous coronary intervention were enrolled in this prospective, randomized study. After 4±2 days, myocardium at risk and infarct size were assessed by cardiac magnetic resonance using T2-weighted imaging and late gadolinium enhancement imaging, respectively. A core body temperature of <35°C (34.7±0.3°C) was achieved before reperfusion without significant delay in door-to-balloon time (43±7 minutes versus 40±6 minutes, hypothermia versus control, P=0.12). Despite similar duration of ischemia (174±51 minutes versus 174±62 minutes, hypothermia versus control, P=1.00), infarct size normalized to myocardium at risk was reduced by 38% in the hypothermia group compared with the control group (29.8±12.6% versus 48.0±21.6%, P=0.041). This was supported by a significant decrease in both peak and cumulative release of Troponin T in the hypothermia group (P=0.01 and P=0.03, respectively). Conclusions—The protocol demonstrates the ability to reach a core body temperature of <35°C before reperfusion in all patients without delaying primary percutaneous coronary intervention and that combination hypothermia as an adjunct therapy in acute myocardial infarction may reduce infarct size at 3 days as measured by MRI. Clinical Trial Registration—URL: http://www.clinicaltrials. gov. Unique identifier: NCT00417638.
Optimizing smart energy control strategies for plug-in hybrid electric vehicle charging

The electrification of the vehicle fleet will result in an additional load on the power grid. Adequately dealing with such pluggable (hybrid) electrical vehicles (PHEV) forms part of the challenges and opportunities in the evolution towards Smart Grids. In this paper, we investigate the potential benefits of using control mechanisms, that could be offered by a Home Energy control box, in optimizing energy consumption stemming from PHEV charging in a residential use case. We present smart energy control strategies based on quadratic programming for charging PHEVs, aiming to minimize the peak load and flatten the overall load profile. We compare two strategies, and benchmark them against a business-as-usual scenario assuming full charging starting upon plugging in the PHEV. The first, local strategy only uses information at the home where the PHEV is charged: as a result the charging is optimized for local loads. The local strategy is compared to a global iterative strategy which controls the charging of multiple vehicles based on global load information over a residential area. Both strategies control the duration and rate of charging and result in charging schedules for each vehicle. We present quantitative simulation results over a set of 150 homes, and discuss the strategies in terms of complexity and performance (esp. resulting energy consumption), as well as their requirements concerning infrastructure and communication.
Selective intra-arterial fibrinolysis of acute central retinal artery occlusion.

BACKGROUND AND PURPOSE Occlusion of the central retinal artery (CRAO) causes a sudden decrease of monocular vision. Because early restoration of blood flow may improve outcome, we attempted to treat CRAO with selective intra-arterial fibrinolysis. METHODS Intra-arterial fibrinolysis was performed within 6 hours after symptom onset in 17 patients with thromboembolic CRAO. Symptoms were painless, acute and severe decrease of vision. Urokinase (100 000 to 900 000 IU) was given through a microcatheter into the ophthalmic artery over 10 to 90 minutes. For comparison, the history and visual outcome of 15 control patients who did not receive fibrinolytics were evaluated. In both groups some of the patients underwent paracentesis and/or received carboanhydrase inhibitors. RESULTS Patients who underwent fibrinolysis fared better than control patients (P=0.01). Three patients (17.6%) recovered completely after fibrinolysis and regained visual acuity of 20/20 (n=2) to 25/20 (n=1). Two additional patients (11.8%) showed a marked improvement to a visual acuity of 20/30. In 6 patients (35. 3%) vision improved slightly. They were able to count fingers, detect hand movements, or perceive light. In 6 patients (35.3%), fibrinolytic treatment was without effect. Among control patients, 1 patient (6.7%) showed partial, 4 patients (26.7%) minimal, and 10 (66.7%) no improvement of vision. CONCLUSIONS A complete or marked improvement of visual acuity was achieved in one third of intra-arterial fibrinolysis patients but in none of the control patients. Intra-arterial fibrinolysis seems to have the potential to "lighten" the spontaneously poor outcome of CRAO.
Reception

Neural Networks can be used to estimate the a posteriori probabilities of the transmitted symbols in digital communication systems. In this paper we apply this prop-erty to the on-line estimation of the bit error rate (BER) in the receiver, without using any reference signal. We discuss two di(cid:11)erent approaches to BER estimation: (1) computing the a posteriori symbol probabilities from estimates of the conditional distributions of the received data, and (2) estimating probabilities by gradient min-imization of a special type of cost functions. We show that Importance Sampling (IS) techniques can be combined with the (cid:12)rst approach to reduce drastically the variance of the probability estimates. Finally, we ana-lyze the e(cid:11)ect of channel variations during transmission.
A self adaptive inertial subgradient extragradient algorithm for variational inequality and common fixed point of multivalued mappings in Hilbert spaces

Abstract We consider a new subgradient extragradient iterative algorithm with inertial extrapolation for approximating a common solution of variational inequality problems and fixed point problems of a multivalued demicontractive mapping in a real Hilbert space. We established a strong convergence theorem for our proposed algorithm under some suitable conditions and without prior knowledge of the Lipschitz constant of the underlying operator. We present numerical examples to show that our proposed algorithm performs better than some recent existing algorithms in the literature.
Plantwide analysis of large-scale stochastic linear discrete-time systems

The distributed operation of critical infrastructures for human society, such as grids or drinking water network, can be modeled as a large-scale stochastic linear discrete-time system. The interaction between subsystems stimulated by random noises would affect the quality of service or even cause stability issues. In this paper, plantwide stability and performance analysis based stochastic quadratic difference form (QdF) is proposed. Both the gain condition from the expectation of external disturbance to the expectation of performance output and the upper bound variance information of the steady state can be obtained in this framework.
Proptosis can be the presenting feature of systemic lupus erythematosus

The patient, a 23 year old student, initially presented to another hospital with swelling of his left eye. Clinical examination showed only isolated proptosis of his left eye. A computed tomographic (CT) scan of his orbits was consistent with orbital pseudotumour, for which he was given a short course of oral steroids, with good clinical response. He was then lost to follow up as he returned home from his studies. A few months later he presented to the physicians in our hospital with a 2 week history of painful swelling of his left eye, accompanied by polyarthralgia, fever with rigors, and lethargy. Further questioning showed he had mild photosensitivity and frequent mouth ulcers of several months’ duration. He had not been receiving any other drug before the onset of symptoms. At the time of admission he was clearly unwell and extremely lethargic, with a temperature of 37.4°C. He had no facial rash, but he did have tender proptosis of his left eye. There was no associated ophthalmoplegia. He …