Miracle-dz/UniFAR-FTUs huggingface dataset:
Systems Biology Perspectives on Cerebellar Long-Term Depression

Long-term depression (LTD) at parallel fiber-Purkinje cell (PF-PC) synapses is thought to be the cellular correlate of cerebellar associative learning. The molecular processes are, in brief, phosphorylation of AMPA-type glutamate receptors (AMPARs) and their subsequent removal from the surface of the PF-PC synapse. In order to elucidate the fundamental mechanisms for cerebellar LTD and further the understanding of its computational role, we have investigated its systems biology and proposed the following hypotheses, some of which have already been experimentally verified: (1) due to the mitogen-activated protein kinase (MAPK)-protein kinase C (PKC) positive feedback loop, phosphorylation of AMPARs is an all-or-none event; (2) the inositol 1,4,5-triphosphate receptor detects concurrent PF and climbing fiber inputs, forming the cellular basis for associative learning, and (3) the local concentration of nitric oxide in the PC dendrite reflects the relevance of a given context, enabling context-dependent selection of learning modules within the cerebellum. In this review, we first introduce theoretical studies on cerebellar LTD, mainly focusing on our own published work, followed by a discussion of the effects of stochasticity, localization, diffusion, and scaffolding. Neurons embody two features that are apparently contradictory, yet necessary for synaptic memory: stability and plasticity. We will also present models for explaining how neurons solve this dilemma. In the final section, we propose a conceptual model in which a cascade of excitable dynamics with different time scales, i.e., Ca2+-induced Ca2+ release, the MAPK-PKC positive feedback loop, and protein kinase Mζ (PKMζ)-induced PKMζ synthesis, provides a mechanism for stable memory that is still amenable to modifications.
Is the Structure of Happiness Equations the Same in Poor and Rich Countries? The Case of South Africa

Are happiness patterns structurally the same when comparing poor and rich countries? Using cross-sectional data from the SALDRU93 survey, we show that the relationships between subjective well-being and socioeconomic variables have a similar structure and is U-shaped in age in South Africa as in developed countries. Well-being rises with income. Unemployment is detrimental to reported well-being, both at the individual- and household-level. Living standard indicators such as durable assets ownership seem to determine happiness levels as well as income. Relative income also matters to well-being, after controlling for community wealth.
Pattern Recognition Receptors in HIV Transmission

Dendritic cells (DCs), Langerhans cells (LCs), and macrophages are innate immune cells that reside in genital and intestinal mucosal tissues susceptible to HIV-1 infection. These innate cells play distinct roles in initiation of HIV-1 infection and induction of anti-viral immunity. DCs are potent migratory cells that capture HIV-1 and transfer virus to CD4+ T cells in the lymph nodes, whereas LCs have a protective anti-viral function, and macrophages function as viral reservoirs since they produce viruses over prolonged times. These differences are due to the different immune functions of these cells partly dependent on the expression of specific pattern recognition receptors. Expression of Toll-like receptors, C-type lectin receptors, and cell-specific machinery for antigen uptake and processing strongly influence the outcome of virus interactions.
Study of the Electronic Properties of Three- and Two-Dimensional Transition Metal Dichalcogenides

Transition metal dichalcogenides (TMDCs) are a class of materials that have been studied for decades due to the rich nature of their d-orbitals, which have granted researchers the power to design new materials with unique and novel properties. Metallic TMDCs such as 1T-TaS2 develop series of charge density waves (CDW) and superconductivity below some onset temperatures. Such materials are interesting for device applications, especially if a way could be found for electrically controlling the transition between each CDW phase. Although these TMDC materials have been studied for a long time, recent advances studies of these materials have offered various attractive features for use in the next generation electronic and optoelectronic devices. Thus, this opens up new opportunities for carefully investigating different TMDCs from bulk to their corresponding single layer (SL). Interest in the SL derives from new properties resulting from the reduction of symmetry in the SL as well as the strict electronic confinement in the SL; for example, MoS2 is characterized by a bandgap that changes from indirect in the bulk to direct in single layer. Thus, SL TMDCs provide an ideal platform to pursue new fundamental research and achieve technological innovations. However, it is still very challenging to grow high quality SL TMDCs with very big domain size. The epitaxial growth procedures developed in our group to make high-quality and large area SL TMDCs are presented in this thesis. We describe the synthesis of single to few layers of TaS2 on Au(111). The electronic structures of these samples are studied with angle resolved photoemission spectroscopy (ARPES). The experimental results of SL TaS2/Au(111) from ARPES are then compared with density-functional theory (DFT) calculations, for both a free-standing layer and when the metallic substrate is taken into account. The morphology and crystal structure of SL TaS2/Au(111) are characterized by scanning tunneling microscopy (STM) and low-energy electron diffraction (LEED). The suppression of the CDW in SL TaS2/Au(111) is revealed by the low-temperature STM/STS studies. The absence
Individual Monitoring of Immune Response in Atlantic Salmon Salmo salar following Experimental Infection with Infectious Salmon Anaemia Virus (ISAV)

Monitoring the immune response in fish over the progression of a disease is traditionally carried out by experimental infection whereby animals are killed at regular intervals and samples taken. We describe here a novel approach to infectiology for salmonid fish where blood samples are collected repeatedly in a small group of PIT-tagged animals. This approach contributes to the reduction of animals used in research and to improved data quality. Two groups of 12 PIT-tagged Atlantic salmon (Salmo salar) were i.p infected with Infectious Salmon Anaemia Virus (ISAV) or culture medium and placed in 1 m3 tanks. Blood samples were collected at 0, 4, 8, 12, 16, 21 and 25 days post infection. The viral load, immune and stress response were determined in individual fish by real-time quantitative PCR (QPCR) on the blood cells, as well as the haematocrit used as an indicator of haemolysis, a clinical consequence of ISAV infection. “In-tank” anaesthesia was used in order to reduce the stress related to chase and netting prior to sampling. The data were analysed using a statistical approach which is novel with respect to its use in fish immunology. The repeated blood collection procedure did not induce stress response as measured by HSP70 and HSP90 gene expression in the un-infected animals. A strong increase in viraemia as well as a significant induction of Mx and γIP gene expression were observed in the infected group. Interleukin 10 was found induced at the later stage of the infection whereas no induction of CD8 or γ IFN could be detected. These results and the advantages of this approach are discussed.
Papnet-assisted, primary screening of cervico-vaginal smears.

PURPOSE The Papnet system was initially designed for rescreening negative Pap tests but may also be an effective primary screener. METHODS A set of 2,200 archival slides diagnosed by conventional, manual screening as 2,000 (90%) WNL, 47 (2.1%) carcinomas, 50 (2.3%), HSIL, 50 (2.3%) LSIL, and 53 (2.4%) ASCUS/AGUS were compared to the results of Papnet-assisted, primary screening. Following Papnet scanning, the digitized images were triaged and classified as abnormal or negative. All abnormals had a full manual screening, whereas negatives had a limited screening. Results by each screening method were compared and discordant cases were peer reviewed for a consensus result. Screening efficacy by each method was measured against a standard result composed of the concordant and consensus results. RESULTS There were 101 concordant and 181 discordant abnormal results. The standard result for the slide set was 1,953 (88.9%) WNL, 87 (3.9%) ASCUS/AGUS, 52 (2.4%) LSIL, 62 (2.8%) HSIL, 39 (1.8%) carcinomas, and 5 (0.2%) unsatisfactory. Papnet versus manual sensitivity rates were 87.6% vs 72.3% at the ASCUS/AGUS threshold, 85.6% vs 82.4% at the LSIL threshold, and 89.1% vs 90.1% at the HSIL threshold. CONCLUSIONS Papnet-assisted, primary screening equals conventional, manual screening in the detection of a wide range of cell abnormalities and is more effective in the detection of abnormalities at the lower end of the abnormal spectrum.
Hepatitis-C-virus genotypes and hepatitis-G-virus infection in Lebanese thalassaemics

Abstract Exposure to hepatitis C virus (HCV), hepatitis G virus (HGV) and the carrier 'rate' for hepatitis B virus (HBsAg) were investigated in thalassaemia patients in Lebanon, a group that has not been studied in the past. The HCV genotypes and their distribution in the 395 thalassaemics, all of whom had been registered at the Chronic Care Center (CCC) in Hazmieh since 1996, were also studied. Of the 55 samples (14%) found positive for anti-HCV, 19 were also positive for HCV RNA. The 19 samples of HCV RNA were mostly of genotype 4 (37%), followed by 1a and 3a (21% each), 1b (16%) and 2b (5%). Most (14; 74%) of the 19 HCV-RNA-positive samples, but only 13 (36%) of the 36 samples that were negative for HCV RNA although anti-HCV-positive, were positive for anti-HGV. Among 100 anti-HCV-negative samples, eight (8%) were anti-HGV positive. Only one (0.28%) of all 395 patients investigated was found to be HBsAg-positive. All of the HBV- and HCV-positive patients had initially been found positive in 1996, when they were first registered at the CCC, and none of the remaining patients had seroconverted since. As none of the patients had been checked for anti-HGV until the present study, the history of their exposure to HGV was unknown. These results emphasise the importance of screening all blood donations collected in Lebanon for HBsAg and anti-HCV. This and stringent infection-control measures are necessary steps to limit the spread of HBV, HCV and perhaps HGV to thalassaemics.
Effects of Collagen Tripeptide Supplement on Photoaging and Epidermal Skin Barrier in UVB-exposed Hairless Mice

Collagen tripeptide (CTP) is a functional food material with several biological effects such as improving dry skin and wound and bone fracture healing. This study focused on the anti-photoaging effects of CTP on a hairless mouse model. To evaluate the effects of CTP on UVB-induced skin wrinkle formation in vivo, the hairless mice were exposed to UVB radiation with oral administration of CTP for 14 weeks. Compared with the untreated UVB control group, mice treated with CTP showed significantly reduced wrinkle formation, skin thickening, and transepidermal water loss (TEWL). Skin hydration and hydroxyproline were increased in the CTP-treated group. Moreover, oral administration of CTP prevented UVB-induced MMP-3 and -13 activities as well as MMP-2 and -9 expressions. Oral administration of CTP increased skin elasticity and decreased abnormal elastic fiber formation. Erythema was also decreased in the CTP-treated group. Taken together, these results strongly suggest that CTP has potential as an anti-photoaging agent.
REGAL: A Regularization based Algorithm for Reinforcement Learning in Weakly Communicating MDPs

We provide an algorithm that achieves the optimal regret rate in an unknown weakly communicating Markov Decision Process (MDP). The algorithm proceeds in episodes where, in each episode, it picks a policy using regularization based on the span of the optimal bias vector. For an MDP with S states and A actions whose optimal bias vector has span bounded by H, we show a regret bound of O(HS√AT). We also relate the span to various diameter-like quantities associated with the MDP, demonstrating how our results improve on previous regret bounds.
Telepsychology: Public Speaking Fear Treatment on the Internet

UNTIL VERY RECENTLY , the possibility of starting real telemedicine or telepsychology systems was restricted by the cost of the equipment and by the lack of adequate infrastructures. Nonetheless, the technological advances we are witnessing at present have allowed the publication of a series of pioneering works with good and promising results. The analysis of what is happening in the field of telepsychology points to an important development to come in the following years. This work presents a telepsychology system to the treatment of public speaking fear. The system is composed of: (a) an assessment protocol that gives the patient a diagnosis of his/her problem, including the interference it is causing him/her, its severity, and the degree of fear and avoidance it is producing; (b) a structured treatment protocol, organized in separate blocks reflecting the patient’s progress; in this way, it is possible to ensure that the patient does not skip any step in the treatment (something quite common in the traditional self-help manuals), gaining more control over the process; and (c) an outcome protocol that assesses treatment effectiveness, not only at its end, but also at every intermediate step. It is the first work in a promising research line that examines the possibility of using the Internet for the treatment of psychological disorders. If the program proposed here achieves the necessary effectiveness and soundness, the range of psychological problems to which the program could be applied will broaden in the near future.
Foliar Symptoms Triggered by Ozone Stress in Irrigated Holm Oaks from the City of Madrid, Spain

Background Despite abatement programs of precursors implemented in many industrialized countries, ozone remains the principal air pollutant throughout the northern hemisphere with background concentrations increasing as a consequence of economic development in former or still emerging countries and present climate change. Some of the highest ozone concentrations are measured in regions with a Mediterranean climate but the effect on the natural vegetation is alleviated by low stomatal uptake and frequent leaf xeromorphy in response to summer drought episodes characteristic of this climate. However, there is a lack of understanding of the respective role of the foliage physiology and leaf xeromorphy on the mechanistic effects of ozone in Mediterranean species. Particularly, evidence about morphological and structural changes in evergreens in response to ozone stress is missing. Results Our study was started after observing ozone -like injury in foliage of holm oak during the assessment of air pollution mitigation by urban trees throughout the Madrid conurbation. Our objectives were to confirm the diagnosis, investigate the extent of symptoms and analyze the ecological factors contributing to ozone injury, particularly, the site water supply. Symptoms consisted of adaxial and intercostal stippling increasing with leaf age. Underlying stippling, cells in the upper mesophyll showed HR-like reactions typical of ozone stress. The surrounding cells showed further oxidative stress markers. These morphological and micromorphological markers of ozone stress were similar to those recorded in deciduous broadleaved species. However, stippling became obvious already at an AOT40 of 21 ppm•h and was primarily found at irrigated sites. Subsequent analyses showed that irrigated trees had their stomatal conductance increased and leaf life -span reduced whereas the leaf xeromorphy remained unchanged. These findings suggest a central role of water availability versus leaf xeromorphy for ozone symptom expression by cell injury in holm oak.
Phase III trial comparing radical radiotherapy with and without cisplatin chemotherapy in patients with advanced squamous cell cancer of the cervix.

PURPOSE To test the hypothesis that cisplatin (CDDP) administered concurrently with standard radiotherapy (RT) would improve pelvic control and survival in patients with advanced squamous cell cancer of the cervix. PATIENTS AND METHODS A total of 259 patients with International Federation of Gynecology and Obstetrics stage IB to IVA squamous cell cervical cancer with central disease greater-than-or-equal 5 cm or histologically confirmed pelvic lymph node involvement were randomized to receive RT (external-beam RT plus brachytherapy) plus weekly CDDP chemotherapy (40 mg/m(2)) (arm 1) or the same RT without chemotherapy (arm 2). RESULTS A total of 253 patients were available for analysis. Median follow-up was 82 months. No significant difference was found in progression-free survival (P =.33). No significant difference in 3- and 5-year survival rates was found (69% v 66% and 62% v 58%, respectively; P =.42). The hazard ratio for survival (arm 2 to arm 1) was 1.10 (95% confidence interval, 0.75 to 1.62). CONCLUSION This study did not show a benefit to either pelvic control or survival by adding concurrent weekly CDDP chemotherapy in a dose of 40 mg/m(2) to radical RT as given in this trial. Careful attention to RT details is important for achieving optimum outcome for patients with this disease.
Differential Constitutive and Cytokine-Modulated Expression of Human Toll-like Receptors in Primary Neutrophils, Monocytes, and Macrophages

Human Toll-like receptors (TLRs) comprise a family of proteins that recognizes pathogen-associated molecular patterns (PAMPs) and initiates host innate immune responses. Neutrophils, monocytes, and macrophages are critical cellular components of the human innate immune system. Proinflammatory cytokines, such as granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), macrophage colony-stimulating factor (M-CSF), and interferon-γ (IFN-γ), have been shown to up-regulate microbicidal activity in these effector cells of innate immunity. Currently, the cellular and molecular mechanisms responsible for these effects are not completely understood. We hypothesized that these cytokines may up-regulate TLR expression as a mechanism to facilitate microbial recognition and augment the innate immune response. Using quantitative realtime rt-PCR technology, we examined constitutive expression of TLR2, TLR4, TLR5, and TLR9 mRNA and the effects of G-CSF, GM-CSF, M-CSF, and IFN-γ on TLR mRNA expression in purified populations of normal human neutrophils, monocytes, and monocyte-derived macrophages. Relative constitutive expression of TLR2, TLR4, and TLR9 was similar in neutrophils and monocytes. Constitutive expression of TLR5 was less in neutrophils compared to monocytes. Constitutive expression of TLR4 was greater and that of TLR9 lower in monocyte-derived macrophages compared to monocytes. Of the cytokines examined, IFN-γ and GM-CSF caused the greatest effects on TLR expression. IFN- γ up-regulated TLR2 and TLR4 in neutrophils and monocytes. GM-CSF up-regulated expression of TLR2 and TLR4 in neutrophils and TLR2 in monocytes. TLR5 was down-regulated by inflammatory cytokines in monocytes. These results suggest a potential role for IFN- γ and/or GM-CSF as therapeutic immunomodulators of the host defense to infection.
Evaluation of Maximum and Minimum Signal Intensity and the Linear Relationship between Concentration and Signal Intensity in Saturation Recovery T1-weighted Images by use of a Turbo Fast Low-Angle Shot Sequence

AbstractBackground: The relationship between the concentration of contrast agents and signal intensity (SI) are affected by some image parameters, phase-encoding scheme, magnetic field strength, image sequences, and iron oxide nanoparticles used and Gd-DTPA as MRI contrast agents. Objective: In this article, the effect of saturation times (TSs) on the maximum and minimum SI, and also the linear relationship between the concentration of the contrast agent and SI are evaluated. Additionally, we evaluated the concentration of contrast agent that results the minimum SI using a saturation recovery TurboFLASH sequence. Material and Methods: In this experimental study, a phantom was designed to hold vials with different concentrations of Gd-DTPA (0–19.77mmol/L). The mean SI was acquired from the nine central pixels of every vial at various TSs. Results: This study shows that the maximum SI in an image is dependent on short TSs (up to 400ms) and independent of long TSs (400–1000ms). The result also shows that the concentration at which a maximum linear relationship between concentration and SI is maintained that gave an R2 equal to 0.95 and 0.99 dependent on the TS. Moreover, the outcome demonstrates that as TS increases, the concentration of the contrast agent decreases. This causes SI to be minimized. Conclusion: This study demonstrated that the TS is a key parameter for measuring the maximum and minimum SI and also TS plays the role in determining the maximum linear relationship between the MRI contrast agent concentration and SI in an in vivo perfusion study.
The identification and measurement of innovative characteristics of young people: development of the YouthInnovation Skills Measurement Tool

Foreword The challenges of the future-globalisation, climate, technological and demographic change – require a different response from our education system. We need to equip future generations not only with strong basic skills and specialist technical knowledge, but with the attitudes and wider skills to generate radical new solutions and adapt to our rapidly changing world. We need to provide future generation with the skills for innovation to a greater degree than ever before: the confidence and insight to generate a novel idea or new approach; the motivation, commitment and resilience to pursue that idea; the leadership, energy and dynamism to communicate their vision to others and drive it forward from concept to reality. For these skills to have currency in education we need to be able to identify and measure them. We are delighted to have supported this pioneering work from Kingston University, which combines theoretical knowledge on measuring skills with practical understanding about how it can be done. In partnership with Kingston University, we intend to take this work forward with the development of an online tool that will be freely available to young people, so that they can assess their capacity for innovation and appreciate how they can develop it further. Our aim is to transform the UK's capacity for innovation. We invest in early-stage companies, inform innovation policy and encourage a culture that helps innovation to flourish. The Youth Innovation Skills Measurement Tool is an instrument to support the development of the skills and attitudes which young people require if they are to become the innovators of tomorrow. The Tool measures the skills needed for innovation The Tool measures five generic skills that underpin innovative behaviour and form a set of attributes clearly linked to the innovation process: • BLOCKINRisk-propensity (a combination of risk tolerance and the ability to take calculated risks); and • BLOCKINLeadership (vision and the ability to mobilise commitment). The skills were identified through a literature review and through testing the concepts with separate focus groups of young people and teachers from different disciplines in schools and colleges in Greater London and Hampshire. The skills assessed by the Tool are also important for young people's employability and ability to make a wider social contribution. The five skills tested match closely those which employers say they most need in their new recruits, but which they too often find missing. Our current economic climate, where enterprises …