Miracle-dz/UniFAR-FTUs huggingface dataset:
Mathematical models for cell migration with real-time cell cycle dynamics

Fluorescent ubiquitination-based cell cycle indicator, also known as FUCCI, allows the visualisation of the G1 and S/G2/M cell cycle phases of individual cells. FUCCI consists of two fluorescent probes, so that cells in the G1 phase fluoresce red and cells in the S/G2/M phase fluoresce green. FUCCI reveals real-time information about cell cycle dynamics of individual cells, and can be used to explore how the cell cycle relates to the location of individual cells, local cell density, and different cellular microenvironments. In particular, FUCCI is used in experimental studies examining cell migration, such as malignant invasion and wound healing. Here we present new mathematical models which can describe cell migration and cell cycle dynamics as indicated by FUCCI. The fundamental model describes the two cell cycle phases, G1 and S/G2/M, which FUCCI directly labels. The extended model includes a third phase, early S, which FUCCI indirectly labels. We present experimental data from scratch assays using FUCCI-transduced melanoma cells, and show that the predictions of spatial and temporal patterns of cell density in the experiments can be described by the fundamental model. We obtain numerical solutions of both the fundamental and extended models, which can take the form of travelling waves. These solutions are mathematically interesting because they are a combination of moving wavefronts and moving pulses. We derive and confirm a simple analytical expression for the minimum wave speed, as well as exploring how the wave speed depends on the spatial decay rate of the initial condition.
Growth behavior of IMC at SnAgCu(SnPb)/Ni and SnAgCu(SnPb)/Cu interface during thermal shock

IMC growth behavior at SnAgCu(SnPb)/Ni and SnAgCu(SnPb)/Cu interface was studied in order to obtain more information about the compatibility of SnAgCu with Cu and Ni during metallization.The results show that Cu and Sn dissolved in the solder affect the evolution of IMC at interface during thermal shock.NiAu surface coating has better long term reliability than HASL surface coating because its IMC growth rate is slower and no Kirkendall voids are found at interface.When the SnAg Cu solder is used,Kirkendall voids are less than that of SnPb solder and IMC growth rate is slower than that of SnPb solder.
Towards a cohesive, holistic view of top predation: a definition, synthesis and perspective

Research on the ecology of top predators – upper trophic level consumers that are relatively free from predation once they reach adult size – has provided regular contributions to general ecology and is a rapidly expanding and increasingly experimental, multidisciplinary and technological endeavour. Yet, an exponentially expanding literature coupled with rapid disintegration into specialized, disconnected subfields for study (e.g. vertebrate predators versus invertebrate predators, community ecology versus biological control etc.) increasingly means that we are losing a coherent, integrated understating of the role and importance of these species in ecosystems. This process of canalization is likely to hinder sharing of scientific discovery and continued progress, especially as there is a growing need to understand the generality of the top–down forcing, as demonstrated for some members of this group. Here, we propose ways to facilitate synthesis by promoting changes in mentality and awareness among specialists through increased debate and collaboration, conceptual reviews and a series of exemplary case studies. The strategy will rely on the collective contribution by all scientists in the field and will strive to consolidate and formalise top-order predation as a holistic, cohesive, cross-taxonomical field of research studying the ecology, evolution and behaviour of apex predators and their capability to exert top–down forcing on lower trophic levels.
Surface ozone at Nam Co in the inland Tibetan Plateau: variation, synthesis comparison and regional representativeness

Abstract. Ozone is an important pollutant and greenhouse gas, and tropospheric ozone variations are generally associated with both natural and anthropogenic processes. As one of the most pristine and inaccessible regions in the world, the Tibetan Plateau has been considered as an ideal region for studying processes of the background atmosphere. Due to the vast area of the Tibetan Plateau, sites in the southern, northern and central regions exhibit different patterns of variation in surface ozone. Here, we present continuous measurements of surface ozone mixing ratios at Nam Co Station over a period of ∼ 5 years (January 2011 to October 2015), which is a background site in the inland Tibetan Plateau. An average surface ozone mixing ratio of 47.6 ± 11.6 ppb (mean ± standard deviation) was recorded, and a large annual cycle was observed with maximum ozone mixing ratios in the spring and minimum ratios during the winter. The diurnal cycle is characterized by a minimum in the early morning and a maximum in the late afternoon. Nam Co Station represents a background region where surface ozone receives negligible local anthropogenic emissions inputs, and the anthropogenic contribution from South Asia in spring and China in summer may affect Nam Co Station occasionally. Surface ozone at Nam Co Station is mainly dominated by natural processes involving photochemical reactions, vertical mixing and downward transport of stratospheric air mass. Model results indicate that the study site is affected differently by the surrounding areas in different seasons: air masses from the southern Tibetan Plateau contribute to the high ozone levels in the spring, and enhanced ozone levels in the summer are associated with air masses from the northern Tibetan Plateau. By comparing measurements at Nam Co Station with those from other sites on the Tibetan Plateau, we aim to expand the understanding of ozone cycles and transport processes over the Tibetan Plateau. This work may provide a reference for future model simulations.
Drug Induced Steatohepatitis: An Uncommon Culprit of a Common Disease

Nonalcoholic fatty liver disease (NAFLD) is a leading cause of liver disease in developed countries. Its frequency is increasing in the general population mostly due to the widespread occurrence of obesity and the metabolic syndrome. Although drugs and dietary supplements are viewed as a major cause of acute liver injury, drug induced steatosis and steatohepatitis are considered a rare form of drug induced liver injury (DILI). The complex mechanism leading to hepatic steatosis caused by commonly used drugs such as amiodarone, methotrexate, tamoxifen, valproic acid, glucocorticoids, and others is not fully understood. It relates not only to induction of the metabolic syndrome by some drugs but also to their impact on important molecular pathways including increased hepatocytes lipogenesis, decreased secretion of fatty acids, and interruption of mitochondrial β-oxidation as well as altered expression of genes responsible for drug metabolism. Better familiarity with this type of liver injury is important for early recognition of drug hepatotoxicity and crucial for preventing severe forms of liver injury and cirrhosis. Moreover, understanding the mechanisms leading to drug induced hepatic steatosis may provide much needed clues to the mechanism and potential prevention of the more common form of metabolic steatohepatitis.
Dysbiosis of Inferior Turbinate Microbiota Is Associated with High Total IgE Levels in Patients with Allergic Rhinitis

ABSTRACT Abnormalities in the human microbiota are associated with the etiology of allergic diseases. Although disease site-specific microbiota may be associated with disease pathophysiology, the role of the nasal microbiota is unclear. We sought to characterize the microbiota of the site of allergic rhinitis, the inferior turbinate, in subjects with allergic rhinitis (n = 20) and healthy controls (n = 12) and to examine the relationship of mucosal microbiota with disease occurrence, sensitized allergen number, and allergen-specific and total IgE levels. Microbial dysbiosis correlated significantly with total IgE levels representing combined allergic responses but not with disease occurrence, the number of sensitized allergens, or house dust mite allergen-specific IgE levels. Compared to the populations in individuals with low total IgE levels (group IgElow), low microbial biodiversity with a high relative abundance of Firmicutes phylum (Staphylococcus aureus) and a low relative abundance of Actinobacteria phylum (Propionibacterium acnes) was observed in individuals with high total serum IgE levels (group IgEhigh). Phylogeny-based microbial functional potential predicted by the 16S rRNA gene indicated an increase in signal transduction-related genes and a decrease in energy metabolism-related genes in group IgEhigh as shown in the microbial features with atopic and/or inflammatory diseases. Thus, dysbiosis of the inferior turbinate mucosa microbiota, particularly an increase in S. aureus and a decrease in P. acnes, is linked to high total IgE levels in allergic rhinitis, suggesting that inferior turbinate microbiota may be affected by accumulated allergic responses against sensitized allergens and that site-specific microbial alterations play a potential role in disease pathophysiology.
Importance of Extracellular Environment for Regenerative Medicine and Tissue Engineering of Cartilagious Tissue

Cartilage degeneration caused by osteoarthritis (OA) and trauma is of great clinical conse‐ quence, given the limited intrinsic healing potential of the cartilaginous tissue. OA is the most common joint disease in world populations. Pain during activities of daily living is a common presenting complaint of individuals with OA and is also associated with a decrease in quality of life for people with OA. Its incidence increases with age, and thus this degenerative disease is a major problem in ageing populations. OA is a multifactorial disease of the joints charac‐ terized by gradual loss of articular cartilage. In the recent years, the mechanism of chondrocyte differentiation has come to be well understood owing to the advancement of molecular biology, and researches have rapidly progressed for bioengineering or tissue engineering technique, where it is aimed to regenerate/reconstruct tissues by simulating the process of cell or tissue differentiation during development. Articular cartilage is composed mainly of collagen/proteoglycan (PG) and water. PG accounts for about 7 10% of cartilage tissues, and aggrecan, which is a member of PG representing macromolecules, plays a key role for mitigation of mechanical stress imposed on the cartilage tissues (Maroudas, 1979). A fall in PG concentration is one of the first changes in OA with consequent deleterious effects on the mechanical behaviour of cartilaginous tissues (McDevitt & Muir, 1976, Venn & Maroudas 1977). Among the components of aggrecan, negatively-charged Glycosaminoglycan (GAG) produces a high osmotic pressure in the cartilage tissue, and water is therefore absorbed in the cartilage tissues. As a result, the collagen networks are inflated, and the cartilage tissues acquire elastic resistance characteristic to cartilage tissues to protect from compression force. Thus, the
Early colon cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up.

R. Labianca1, B. Nordlinger2, G. D. Beretta3, S. Mosconi1, M. Mandalà1, A. Cervantes4 & D. Arnold5 on behalf of the ESMO Guidelines Working Group* Ospedale Papa Giovanni XXIII, Bergamo, Italy; Hospital Ambroise Parè, Paris, France; Humanitas Gavazzeni Clinic, Bergamo, Italy; Department of Hematology and Medical Oncology, INCLIVA, University of Valencia, Valencia, Spain; Department of Medical Oncology, Tumor Biology Center, Freiburg, Germany
Synaptic plasticity in the medial superior olive of hearing, deaf, and cochlear‐implanted cats

The medial superior olive (MSO) is a key auditory brainstem structure that receives binaural inputs and is implicated in processing interaural time disparities used for sound localization. The deaf white cat, a proven model of congenital deafness, was used to examine how deafness and cochlear implantation affected the synaptic organization at this binaural center in the ascending auditory pathway. The patterns of axosomatic and axodendritic organization were determined for principal neurons from the MSO of hearing, deaf, and deaf cats with cochlear implants. The nature of the synapses was evaluated through electron microscopy, ultrastructure analysis of the synaptic vesicles, and immunohistochemistry. The results show that the proportion of inhibitory axosomatic terminals was significantly smaller in deaf animals when compared with hearing animals. However, after a period of electrical stimulation via cochlear implants the proportion of inhibitory inputs resembled that of hearing animals. Additionally, the excitatory axodendritic boutons of hearing cats were found to be significantly larger than those of deaf cats. Boutons of stimulated cats were significantly larger than the boutons in deaf cats, although not as large as in the hearing cats, indicating a partial recovery of excitatory inputs to MSO dendrites after stimulation. These results exemplify dynamic plasticity in the auditory brainstem and reveal that electrical stimulation through cochlear implants has a restorative effect on synaptic organization in the MSO. J. Comp. Neurol. 520:2202–2217, 2012. © 2012 Wiley Periodicals, Inc.
Subsampling for graph power spectrum estimation

In this paper we focus on subsampling stationary random signals that reside on the vertices of undirected graphs. Second-order stationary graph signals are obtained by filtering white noise and they admit a well-defined power spectrum. Estimating the graph power spectrum forms a central component of stationary graph signal processing and related inference tasks. We show that by sampling a significantly smaller subset of vertices and using simple least squares, we can reconstruct the power spectrum of the graph signal from the subsampled observations, without any spectral priors. In addition, a near-optimal greedy algorithm is developed to design the subsampling scheme.
Clonal Analysis of Meningococci during a 26 Year Period Prior to the Introduction of Meningococcal Serogroup C Vaccines

Meningococcal disease remains a public health burden in the UK and elsewhere. Invasive Neisseria meningitidis, isolated in Scotland between 1972 and 1998, were characterised retrospectively to examine the serogroup and clonal structure of the circulating population. 2607 isolates causing invasive disease were available for serogroup and MLST analysis whilst 2517 were available for multilocus sequence typing (MLST) analysis only. Serogroup distribution changed from year to year but serogroups B and C were dominant throughout. Serogroup B was dominant throughout the 1970s and early 1980s until serogroup C became dominant during the mid-1980s. The increase in serogroup C was not associated with one particular sequence type (ST) but was associated with a number of STs, including ST-8, ST-11, ST-206 and ST-334. This is in contrast to the increase in serogroup C disease seen in the 1990s that was due to expansion of the ST-11 clonal complex. While there was considerable diversity among the isolates (309 different STs among the 2607 isolates), a large proportion of isolates (59.9%) were associated with only 10 STs. These data highlight meningococcal diversity over time and the need for ongoing surveillance during the introduction of new meningococcal vaccines.
Differential protein stability of EGFR mutants determines responsiveness to tyrosine kinase inhibitors

Non-small cell lung cancer (NSCLC) patients carrying specific EGFR kinase activating mutations (L858R, delE746-A750) respond well to tyrosine kinase inhibitors (TKIs). However, drug resistance develops within a year. In about 50% of such patients, acquired drug resistance is attributed to the enrichment of a constitutively active point mutation within the EGFR kinase domain (T790M). To date, differential drug-binding and altered ATP affinities by EGFR mutants have been shown to be responsible for differential TKI response. As it has been reported that EGFR stability plays a role in the survival of EGFR driven cancers, we hypothesized that differential TKI-induced receptor degradation between the sensitive L858R and delE746-A750 and the resistant T790M may also play a role in drug responsiveness. To explore this, we have utilized an EGFR-null CHO overexpression system as well as NSCLC cell lines expressing various EGFR mutants and determined the effects of erlotinib treatment. We found that erlotinib inhibits EGFR phosphorylation in both TKI sensitive and resistant cells, but the protein half-lives of L858R and delE746-A750 were significantly shorter than L858R/T790M. Third generation EGFR kinase inhibitor (AZD9291) inhibits the growth of L858R/T790M-EGFR driven cells and also induces EGFR degradation. Erlotinib treatment induced polyubiquitination and proteasomal degradation, primarily in a c-CBL-independent manner, in TKI sensitive L858R and delE746-A750 mutants when compared to the L858R/T790M mutant, which correlated with drug sensitivity. These data suggest an additional mechanism of TKI resistance, and we postulate that agents that degrade L858R/T790M-EGFR protein may overcome TKI resistance.
Vaccine-Linked Chemotherapy Improves Benznidazole Efficacy for Acute Chagas Disease

ABSTRACT Chagas disease affects 6 to 7 million people worldwide, resulting in significant disease burdens and health care costs in countries of endemicity. Chemotherapeutic treatment is restricted to two parasiticidal drugs, benznidazole and nifurtimox. Both drugs are highly effective during acute disease but are only minimally effective during chronic disease and fraught with significant adverse clinical effects. In experimental models, vaccines can be used to induce parasite-specific balanced TH1/TH2 immune responses that effectively reduce parasite burdens and associated inflammation while minimizing adverse effects. The objective of this study was to determine the feasibility of vaccine-linked chemotherapy for reducing the amount of benznidazole required to significantly reduce blood and tissue parasite burdens. In this study, we were able to achieve a 4-fold reduction in the amount of benznidazole required to significantly reduce blood and tissue parasite burdens by combining the low-dose benznidazole with a recombinant vaccine candidate, Tc24 C4, formulated with a synthetic Toll-like 4 receptor agonist, E6020, in a squalene oil-in-water emulsion. Additionally, vaccination induced a robust parasite-specific balanced TH1/TH2 immune response. We concluded that vaccine-linked chemotherapy is a feasible option for advancement to clinical use for improving the tolerability and efficacy of benznidazole.
Calyx Juice of Hibiscus sabdariffa Linn (Malvaceae): A Possible Therapeutic Supplement to Antiretroviral Drugs

More than three decades after its outbreak, the Acquired Immune Deficiency Syndrome (AIDS) remains a great mystery because there is neither an existing vaccine against its causative agent (the human immune deficiency virus) nor a cure against it. Worst of all is the popular attention that is tuned to the AIDS virus, ignoring oxidative stress which is the major cause of mortality in HIV/AIDS as in many other chronic diseases. Antiretroviral drugs introduced in 1996 have been shown to increase oxidative stress among other drug-related complications. With these backdrops, an antioxidant therapy is necessary to accompany antiretroviral treatment without which its beneficial effects are null. The present review aims to discuss the role of Calyx juice of Hibiscus sabdariffa Linn (Malvaceae) as a possible therapeutic supplement to antiretroviral drugs.
Should we individualize lipid profiling in women with polycystic ovary syndrome?

STUDY QUESTION Is it necessary to monitor lipid profiles in all young women with polycystic ovary syndrome (PCOS)? SUMMARY ANSWER Lipid profiling is required when women with PCOS develop type 2 diabetes (T2D) or hypertension, but rarely changes clinical care before the age of 35 years. WHAT IS KNOWN ALREADY PCOS consensus statements and guidelines recommend that women with PCOS should be screened for dyslipidaemia every second year or annually. STUDY DESIGN, SIZE, DURATION Women from Denmark, Norway, Finland and Sweden, who had participated in research projects or clinical trials or in whom lipid profiles had been determined routinely as part of clinical care since 2000 were included. PARTICIPANTS/MATERIALS, SETTING, METHODS One thousand three hundred and twenty-seven women with PCOS (Rotterdam criteria) were included. Based on individual cardiovascular risk score and lipid levels, treatment level was guided by the European Society of Cardiology and the European Atherosclerosis Society Task Force for the management of dyslipidaemias. Change in clinical care was defined as need to (i) immediately start statin treatment or (ii) consider statin treatment if life-style intervention fails. MAIN RESULTS AND THE ROLE OF CHANCE All in all, 74 (5.6%) women with PCOS should immediately start statin treatment, and statin treatment should be considered in 33 women (2.5%). Among women with T2D, 27/28 (96.4%) should initiate statin treatment and the corresponding number for women with hypertension was 42/57 (73.7%). In PCOS women who had not yet developed T2D or hypertension, lipid profiling only changed clinical care in 28 (2.3%). This number was further reduced to 12 (1.2%) in women below the age of 35 years, and to zero in normal-weight women below the age of 35 years. LIMITATIONS, REASONS FOR CAUTION Findings can only be generalized to countries with low cardiovascular mortality rates. WIDER IMPLICATIONS OF THE FINDINGS Lipid profiling is required when women with PCOS develop T2D or hypertension. However, lipid profiling rarely changes the clinical care of low risk PCOS patients before the age of 35, especially in the normal-weight women. STUDY FUNDING/COMPETING INTERESTS The Academy of Finland, Sigrid Juselius Foundation and the Nordic Federation of Obstetrics and Gynecology. There are no conflicts of interest to be declared.
Schistosomiasis in the People's Republic of China: the Era of the Three Gorges Dam

SUMMARY The potential impact of the Three Gorges Dam (TGD) on schistosomiasis transmission in China has invoked considerable global concern. The TGD will result in changes in the water level and silt deposition downstream, favoring the reproduction of Oncomelania snails. Combined with blockages of the Yangtze River's tributaries, these changes will increase the schistosomiasis transmission season within the marshlands along the middle and lower reaches of the Yangtze River. The changing schistosome transmission dynamics necessitate a comprehensive strategy to control schistosomiasis. This review discusses aspects of the epidemiology and transmission of Schistosoma japonicum in China and considers the pathology, clinical outcomes, diagnosis, treatment, immunobiology, and genetics of schistosomiasis japonica together with an overview of current progress in vaccine development, all of which will have an impact on future control efforts. The use of synchronous praziquantel (PZQ) chemotherapy for humans and domestic animals is only temporarily effective, as schistosome reinfection occurs rapidly. Drug delivery requires a substantial infrastructure to regularly cover all parts of an area of endemicity. This makes chemotherapy expensive and, as compliance is often low, a less than satisfactory control option. There is increasing disquiet about the possibility that PZQ-resistant schistosomes will develop. Consequently, as mathematical modeling predicts, vaccine strategies represent an essential component in the future control of schistosomiasis in China. With the inclusion of focal mollusciciding, improvements in sanitation, and health education into the control scenario, China's target of reducing the level of schistosome infection to less than 1% by 2015 may be achievable.