Miracle-dz/UniFAR-FTUs huggingface dataset:
Hippo pathway regulation by cell morphology and stress fibers

The Hippo signaling pathway plays an important role in regulation of cell proliferation. Cell density regulates the Hippo pathway in cultured cells; however, the mechanism by which cells detect density remains unclear. In this study, we demonstrated that changes in cell morphology are a key factor. Morphological manipulation of single cells without cell-cell contact resulted in flat spread or round compact cells with nuclear or cytoplasmic Yap, respectively. Stress fibers increased in response to expanded cell areas, and F-actin regulated Yap downstream of cell morphology. Cell morphology- and F-actin-regulated phosphorylation of Yap, and the effects of F-actin were suppressed by modulation of Lats. Our results suggest that cell morphology is an important factor in the regulation of the Hippo pathway, which is mediated by stress fibers consisting of F-actin acting upstream of, or on Lats, and that cells can detect density through their resulting morphology. This cell morphology (stress-fiber)-mediated mechanism probably cooperates with a cell-cell contact (adhesion)-mediated mechanism involving the Hippo pathway to achieve density-dependent control of cell proliferation.
Smoking and thyroid-associated ophthalmopathy: A novel explanation of the biological link.

INTRODUCTION Cigarette smoking is the strongest modifiable risk factor for developing thyroid-associated ophthalmopathy (TAO), and the severity of TAO is related to the current number of cigarettes smoked per day. We aimed to establish the effects of cigarette smoke extract (CSE) on an in vitro model of TAO. METHODS Orbital tissue was taken during surgery from 10 patients with TAO and nine control subjects. Orbital fibroblasts were cultured and exposed to CSE, and intercellular adhesion molecule 1 (ICAM1) expression was measured by flow cytometry. Glycosaminoglycan production was measured by hyaluronic acid ELISA. Orbital fibroblasts were grown in adipogenic media with or without CSE and/or IL-1, and the degree of adipogenesis was quantified. RESULTS Fibroblasts from patients with TAO and controls showed similar responses. ICAM1 expression was not affected by CSE. Hyaluronic acid production was stimulated by CSE in a dose-dependent manner (correlation coefficient, 0.978; P = 0.022), with 5% CSE causing an increase of 44% (P = 0.001). CSE increased adipogenesis in a dose-related manner, as did IL-1. The effects of CSE and IL-1 on adipogenesis were synergistic, with the degree of adipogenesis in the well containing both 5% CSE and 0.1 ng/ml IL-1 being double the magnitude of the sum of the values obtained from either stimulus alone (P < 0.001). Addition of an anti-IL-1 antibody to the well containing both 5% CSE and 0.1 ng/ml IL-1 reduced the degree of adipogenesis by 82% (P < 0.001). CONCLUSION These findings may help explain how cigarette smoking has a detrimental effect in TAO and suggests that IL-1 may be an attractive therapeutic target in TAO.
Cardiac-directed adenylyl cyclase expression improves heart function in murine cardiomyopathy.

BACKGROUND We tested the hypothesis that increased cardiac myocyte adenylyl cyclase (AC) content increases cardiac function and response to catecholamines in cardiomyopathy. METHODS AND RESULTS Transgenic mice with cardiac-directed expression of AC type VI (ACVI) were crossbred with mice with cardiomyopathy induced by cardiac-directed Gq expression. Gq mice had dilated left ventricles, reduced heart function, decreased cardiac responsiveness to catecholamine stimulation, and impaired beta-adrenergic receptor (betaAR)-dependent and AC-dependent cAMP production. Gq/AC mice showed improved basal cardiac function in vivo (P=0.01) and ex vivo (P<0.0005). When stimulated through the betaAR, cardiac responsiveness was increased (P=0.02), and cardiac myocytes showed increased cAMP production in response to isoproterenol (P=0.03) and forskolin (P<0.0001). CONCLUSIONS Increasing myocardial ACVI content in cardiomyopathy restores cAMP-generating capacity and improves cardiac function and responsiveness to betaAR stimulation.
Breast skin-line detection using dynamic programming

In this paper, we present a novel method to extract the breast skin-line based on dynamic programming. Skin-line extraction is an important preprocessing step in CAD systems; however, it is a challenging problem due to the presence of noise, underexposed regions, which results in a low contrast area near the skin-air interface, and artifacts such as labels. Our proposal utilizes the stroma edge to constrain searching for the border. In order to cope with noise, we consider several candidate points for the border interface which are obtained by the Laplace operator applied in pre-defined directions in the mammogram. The breast contour is obtained from the candidate points using a dynamic programming algorithm. This utilizes a criterion of optimality to obtain the optimum contour by minimization of a cost function. The method was evaluated using 82 mammograms whose contour were manually extracted by a radiologist from the mini-MIAS database. The Polyline Distance Measure was evaluated for each contour selected with the proposed method, obtaining a mean error of 2.05 pixels and a standard deviation of 0.80.
Hybrid CPU-GPU Framework for Network Motifs

Massively parallel architectures such as the GPU are becoming increasingly important due to the recent proliferation of data. In this paper, we propose a key class of hybrid parallel graphlet algorithms that leverages multiple CPUs and GPUs simultaneously for computing k-vertex induced subgraph statistics (called graphlets). In addition to the hybrid multi-core CPU-GPU framework, we also investigate single GPU methods (using multiple cores) and multi-GPU methods that leverage all available GPUs simultaneously for computing induced subgraph statistics. Both methods leverage GPU devices only, whereas the hybrid multi-core CPU-GPU framework leverages all available multi-core CPUs and multiple GPUs for computing graphlets in large networks. Compared to recent approaches, our methods are orders of magnitude faster, while also more cost effective enjoying superior performance per capita and per watt. In particular, the methods are up to 300 times faster than the recent state-of-the-art method. To the best of our knowledge, this is the first work to leverage multiple CPUs and GPUs simultaneously for computing induced subgraph statistics.
Structural Stability of Supersonic Contact Discontinuities in Three-Dimensional Compressible Steady Flows

In this paper, we study the structurally nonlinear stability of supersonic contact discontinuities in three-dimensional compressible isentropic steady flows. Based on the weakly linear stability result and the $L^2$-estimates obtained in [Y. -G. Wang and F. Yu, J. Differential Equations, 255 (2013), pp. 1278--1356] for the linearized problems of three-dimensional compressible isentropic steady equations at a supersonic contact discontinuity satisfying certain stability conditions, we first derive tame estimates of solutions to the linearized problem in higher order norms by exploring the behavior of vorticities. Since the supersonic contact discontinuities are only weakly linearly stable, so the tame estimates of solutions to the linearized problems have loss of regularity with respect to both background states and initial data. Thus, to use the tame estimates to study the nonlinear problem we adapt the Nash--Moser--Hormander iteration scheme to conclude that supersonic contact discontinuities in three-dim.
Femtosecond extreme ultraviolet ion imaging of ultrafast dynamics in electronically excited helium nanodroplets

A novel femtosecond extreme ultraviolet (EUV) ion-imaging technique is applied to study ultrafast dynamics in electronically excited helium nanodroplets. Ion mass spectra recorded by single-photon EUV ionization and by transient EUV-pump/IR-probe two-photon ionization differ significantly for EUV photon energies below and above ~24 eV, in agreement with recently performed synchrotron measurements. Pump-probe time-delay-dependent ion kinetic energy (KE) spectra exhibit two major contributions: a decaying high KE component and a rising low KE component, which are attributed to the different excitation regimes. A model is presented that describes the excitation energy dependence of the relaxation and ionization dynamics within the framework of bulk and surface states. The model is supported by recent ab initio calculations on electronically excited states of 25-atom clusters. An intraband relaxation mechanism is proposed that proceeds on a ~10-20-ps time scale and that corresponds to the transfer of electronic excitation in the Rydberg n = 2 manifold from bulk to surface states.
Sparsely faceted arrays: a mechanism supporting parallel allocation, communication, and garbage collection

Conventional parallel computer architectures do not provide support for non-uniformly distributed objects. In this thesis, I introduce sparsely faceted arrays (SFAs), a new lowlevel mechanism for naming regions of memory, or facets, on different processors in a distributed, shared memory parallel processing system. Sparsely faceted arrays address the disconnect between the global distributed arrays provided by conventional architectures (e.g. the Cray T3 series), and the requirements of high-level parallel programming methods that wish to use objects that are distributed over only a subset of processing elements. A sparsely faceted array names a virtual globally-distributed array, but actual facets are lazily allocated. By providing simple semantics and making efficient use of memory, SFAs enable efficient implementation of a variety of non-uniformly distributed data structures and related algorithms. I present example applications which use SFAs, and describe and evaluate simple hardware mechanisms for implementing SFAs. Keeping track of which nodes have allocated facets for a particular SFA is an important task that suggests the need for automatic memory management, including garbage collection. To address this need, I first argue that conventional tracing techniques such as mark/sweep and copying GC are inherently unscalable in parallel systems. I then present a parallel memory-management strategy, based on reference-counting, that is capable of garbage collecting sparsely faceted arrays. I also discuss opportunities for hardware support of this garbage collection strategy. I have implemented a high-level hardware/OS simulator featuring hardware support for sparsely faceted arrays and automatic garbage collection. I describe the simulator and outline a few of the numerous details associated with a “real” implementation of SFAs and SFA-aware garbage collection. Simulation results are used throughout this thesis in the evaluation of hardware support mechanisms. Thesis Supervisor: Thomas F. Knight, Jr. Title: Senior Research Scientist
Single molecule measurement of the “speed limit” of DNA polymerase

Although DNA replication is often imagined as a regular and continuous process, the DNA polymerase enzyme is a complicated machine and can pause upon encountering physical and chemical barriers. We used single molecule measurements to make a detailed characterization of this behavior as a function of the template's secondary structure and the sequence context. Strand displacement replication through a DNA hairpin by single DNA polymerase molecules was measured in real time with near single base resolution and physiological concentrations of nucleotides. These data enabled the measurement of the intrinsic “speed limit” of DNA polymerase by separating the burst synthesis rate from pausing events. The strand displacement burst synthesis rate for Escherichia coli DNA Polymerase I (KF) was found to be an order of magnitude faster than the reported bulk strand displacement rate, a discrepancy that can be accounted for by to sequence specific pausing. The ability to follow trajectories of single molecules revealed that the burst synthesis rate is also highly stochastic and varies up to 50-fold from molecule to molecule. Surprisingly, our results allow a unified explanation of strand displacement and single strand primer extension synthesis rates.
The quality of record keeping in primary care: a comparison of computerised, paper and hybrid systems.

BACKGROUND Computerised record keeping in primary care is increasing. However, no study has systematically examined the completeness of computer records in practices using different forms of record keeping. AIM To compare computer-only record keeping to paper-only and hybrid systems, by measuring the number of consultations and symptoms recorded within individual consultations. DESIGN OF STUDY Retrospective cohort study. SETTING Eighteen general practices in the Exeter Primary Care Trust. METHOD This study was part of a retrospective case control study of cancer patients aged over 40 years. All recorded consultations for a 2-year period were identified and coded for 1396 patients. Records were classified as paper, computer, or hybrid, depending on which medium stored the clinical information from consultations. RESULTS More consultations were recorded in hybrid systems (median in 2 years = 11, interquartile range [IQR] = 6-18) than computer systems (median in 2 years = 9, IQR = 4-16.5) or paper systems (median in 2 years = 8, IQR = 5-14,): P <0.001. In a Poisson regression analysis, which included age, sex, and future cancer diagnosis, the rates of consultations recorded in paper and computer systems were 16% and 11% lower, respectively, than in hybrid systems. Fewer telephone consultations were recorded in paper systems, and fewer home visits in computer systems. Fewer symptoms were recorded in individual consultations on computer systems. Recording of absent symptoms and severity of symptoms was highest in paper systems. CONCLUSION Hybrid systems of primary care record keeping document higher numbers of consultations than computer-only or paper-only systems. The quality of individual consultation recording is highest in paper-only systems. This has medicolegal implications and may impact upon continuity of care.
Thermal Conductivity Design and Evaluation of Zirconium Phosphate Bonded Silicon Nitride Porous Ceramics

In this Paper, Five Fundamental Effective Thermal Conductivity Structural Models (Series, Parallel, Two Forms of Maxwell-Eucken and Effective Medium Theory) Were Used to Analyze and Design Silicon Nitride Porous Ceramics. Then α-Si3N4 Matrix Porous Ceramics Were Prepared with ZrP2O7 as a Binder and Thermal Conductivity of ZrP2O7 Bonded Si3N4 Porous Ceramic Was Evaluated. ZrP2O7 Bonded Si3N4 Porous Ceramic Had Open and Interconnected Pore Structure which is either in EMT or in Maxwell-Euken 2. The Thermal Conductivity of ZrP2O7 Bonded Si3N4 Porous Ceramics Changes from 2.0 to 0.5 W/m•K with Increasing the Porosity from 20% to 51%. The Obtained Results Showed that the External Porosity Material with Maxwell-Euken 2 Structure Had the Lowest Thermal Conductivity in All Porous Materials. The Open and Interconnected Pore Structure of ZrP2O7 Bonded Si3N4 Porous Ceramics Provided much Lower Thermal Conductivity.
Geometric frustration in small colloidal clusters

We study the structure of clusters in a model colloidal system with competing interactions using Brownian dynamics simulations. A short-ranged attraction drives clustering, while a weak, long-ranged repulsion is used to model electrostatic charging in experimental systems. The former is treated with a short-ranged Morse attractive interaction, the latter with a repulsive Yukawa interaction. We consider the yield of clusters of specific structure as a function of the strength of the interactions, for clusters with m = 3,4,5,6,7,10 and 13 colloids. At sufficient strengths of the attractive interaction (around 10kBT), the average bond lifetime approaches the simulation timescale and the system becomes nonergodic. For small clusters, m≤5, where geometric frustration is not relevant, despite nonergodicity, for sufficient strengths of the attractive interaction the yield of clusters which maximize the number of bonds approaches 100%. However for m = 7 and higher, in the nonergodic regime we find a lower yield of these structures where we argue geometric frustration plays a significant role. m = 6 is a special case, where two structures, of octahedral and C2v symmetry, compete, with the latter being favoured by entropic contributions in the ergodic regime and by kinetic trapping in the nonergodic regime. We believe that our results should be valid as long as the one-component description of the interaction potential is valid. A system with competing electrostatic repulsions and van der Waals attractions may be such an example. However, in some cases, the one-component description of the interaction potential may not be appropriate.
Surface roughness parameters measurements by digital holographic microscopy (DHM)

Digital Holographic Microscopes (DHM) allows the capture of all the information necessary to provide 3D phase measurements with a nanometer vertical resolution in a single image acquisition. DHM images provide measurements of the surface topography which can be used for surface analysis, roughness measurements for example. In this paper we present roughness measurements on micro-balls of different sizes for which numerical procedures are applied for form factor and waviness removal. DHM thus permits quantitative measurements of the roughness on a 2 dimensional area allowing enlarged information compared to common profilometers. Mean roughness of 5 to 30 nm are measured and compared to values obtained by a profilometer.
Inducible Ablation of Melanopsin-Expressing Retinal Ganglion Cells Reveals Their Central Role in Non-Image Forming Visual Responses

Rod/cone photoreceptors of the outer retina and the melanopsin-expressing retinal ganglion cells (mRGCs) of the inner retina mediate non-image forming visual responses including entrainment of the circadian clock to the ambient light, the pupillary light reflex (PLR), and light modulation of activity. Targeted deletion of the melanopsin gene attenuates these adaptive responses with no apparent change in the development and morphology of the mRGCs. Comprehensive identification of mRGCs and knowledge of their specific roles in image-forming and non-image forming photoresponses are currently lacking. We used a Cre-dependent GFP expression strategy in mice to genetically label the mRGCs. This revealed that only a subset of mRGCs express enough immunocytochemically detectable levels of melanopsin. We also used a Cre-inducible diphtheria toxin receptor (iDTR) expression approach to express the DTR in mRGCs. mRGCs develop normally, but can be acutely ablated upon diphtheria toxin administration. The mRGC-ablated mice exhibited normal outer retinal function. However, they completely lacked non-image forming visual responses such as circadian photoentrainment, light modulation of activity, and PLR. These results point to the mRGCs as the site of functional integration of the rod/cone and melanopsin phototransduction pathways and as the primary anatomical site for the divergence of image-forming and non-image forming photoresponses in mammals.
Optical properties of semiconductor nanocrystals

Preface 1. Electron states in crystals 2. Electron states in an Ideal nanocrystal 3. Growth of nanocrystals 4. General properties of spectrally inhomogeneous media 5. Absorption and emission of light by semiconductor nanocrystals 6. Resonant optical nonlinearities and related many-body effects 7. Interface effects 8. Spatially organized ensembles of nanocrystals.
Mean-risk optimization models for electricity portfolio management

The possibility of controlling risk in stochastic power optimization by incorporating special risk functional, so-called polyhedral risk measures, into the objective is demonstrated. We present an exemplary optimization model for mean-risk optimization of an electricity portfolios of a price-taking retailer. Stochasticity enters the model via uncertain electricity demand, heat demand, spot prices, and future prices. The objective is to maximize the expected overall revenue and, simultaneously, to minimize risk in terms of multiperiod risk measures, i.e., risk measures that take into account intermediate cash values in order to avoid liquidity problems at any time. We compare the effect of different multiperiod polyhedral risk measures that had been suggested in our earlier work
Interaction Between Porcine Circovirus type 2 and the Immune System of the Pig With Special Reference to Immunomodulatory Sequences in the Viral Genome

Porcine circovirus type 2 (PCV2) causes postweaning multisystemic wasting syndrome (PMWS) in growing pigs but generally requires the presence of other infectious or non-infectious factors to produce the full clinical expression of disease. These factors remain to be identified, but management routines, concurrent infections and maternal immunity are thought to influence the risk for PMWS outbreak in swine herds. Pigs presenting with PMWS develop severe immunosuppression and the work of this thesis focuses on the interaction between PCV2 and the immune system of the pig in vivo and in vitro. Development of PMWS was studied in models for experimental infection in young pigs using coinfections with porcine parvovirus (PPV) or Escherichia coli. Three-day-old colostrum-deprived pigs infected with PCV2 and PPV developed severe PMWS, and a possible role for interleukin 10 as well as impaired production of antibodies to PCV2 in the development of disease was observed. Four-week-old colostrum fed pigs infected with PCV2 in combination with E. coli did not develop clinical disease, but alterations of functions of immune cells were observed ex vivo and could be related to the presence of PCV2. DNA from virus and bacteria can act modulatory on immune cells through the interaction between unmethylated CpG motifs and toll-like receptor (TLR) 9. Five sequences with interferon (IFN) alpha-modulatory activity were identified in the genome of PCV2, and the inhibitory characteristics of one of these (ODN PCV2/1) were studied further in vitro. The ODN was an efficient inhibitor of IFN-α production induced in porcine peripheral blood mononuclear cells (PBMCs) by other DNA ODNs as well as bacterial or viral DNA, but could not influence the IFN-α production induced by synthetic or viral RNA. The inhibition was dependent on the ability of ODN PCV2/1 to form secondary structures, but did not require the presence of an unmethylated CpG motif. ODN PCV2/1 also inhibited the expression of mRNA for other porcine cytokines by PBMC stimulated in vitro. The presence of immunomodulatory sequences in the genome of PCV2 may contribute to evasive mechanisms utilized by the virus during persistent infection of immune cells and/or development of clinical disease.