Miracle-dz/UniFAR-FTUs huggingface dataset:
Alpha-2 adrenergic receptor agonists are neuroprotective in experimental models of glaucoma.

PURPOSE The glaucomas are characterized by chronic progressive ganglion cell loss over many years. A drug with neuroprotective activity should increase the resistance of retinal ganglion cells (RGC) to chronic stress or injury and therefore enhance survival. Brimonidine is a highly selective and potent alpha-2 adrenergic receptor agonist, which lowers intra-ocu-lar pressure (IOP) and is neuroprotective. Immunohistochemistry data have shown that the specific receptor targets, the alpha-2 receptors, are located in the inner retina. METHODS Brimonidine 0.1 mg/kg given intraperitoneally promoted RGC survival compared with vehicle using the optic nerve crush model even when administered up to 24 hours before injury. Using the chronic ocular hypertensive rat model, brimonidine 1 mg/kg/day (with osmotic pump) significantly prevented the loss of RGCs when compared with vehicle or timolol. This ability was due to the neuroprotective action of brimonidine, since it did not affect IOP. In addition, brimonidine 0.1 mg/day reached concentrations in the retina of Sprague-Dawley rats within 30 minutes of injection, which was sufficient to activate the alpha-2 receptor (Y 2 nM) and maintained these concentrations for 6 hours. CONCLUSIONS Having demonstrated that: a. the specific receptor target of brimonidine is located in the retina, which is important for optic neuroprotection, b. the agent shows neuroprotective ability in animal models, c. pharmacological concentrations of the drug can be reached in the retina, clinical trial has been initiated to determine whether brimonidine is neuroprotective in patients with nonarteritic ischaemic optic neuropathy. Eur J Ophthalmol 2001; 11 (Suppl 2): S30-S35.
Pentoxifylline downregulates profibrogenic cytokines and procollagen I expression in rat secondary biliary fibrosis

Background: The trisubstituted methylxanthine derivative pentoxifylline inhibits hepatic stellate cell proliferation and collagen synthesis in vitro. The antifibrotic effect of pentoxifylline in a suitable in vivo model of chronic liver fibrogenesis remains to be tested. Methods: Groups of adult rats (n=20–23) received oral pentoxifylline at a dose of 8 mg/kg/day from week 1 to week 6, and 16 mg/kg/day from week 1 to week 6 or week 4 to week 6 after complete bile duct occlusion. Animals who underwent sham operation that received 16 mg/kg/day pentoxifylline and untreated rats with bile duct occlusion alone served as controls. After six weeks, animals were sacrificed and parameters of fibrogenesis determined. Results: Bile duct occlusion caused portal cirrhosis with a 10-fold increased hepatic collagen content in the absence of inflammation or necrosis. This was accompanied by an 11-fold elevated serum aminoterminal procollagen III peptide (PIIINP). The drug induced a dramatic eightfold downregulation of procollagen I mRNA, and suppression of the fibrogenic factors transforming growth factor β1 and connective tissue growth factor by 60–70%. However, profibrogenic tissue inhibitor of metalloproteinase 1 (TIMP-1) mRNA was increased twofold, resulting in only a moderate decrease in liver collagen, fibrosis score, and PIIINP. Conclusions: We conclude that targeting pentoxifylline to the fibrogenic cells, thereby avoiding upregulation of TIMP-1, could become a potent antifibrogenic tool in chronic liver disease.
Role of mitogen‐activated protein kinases, nuclear factor‐κB, and interferon regulatory factor 3 in Toll‐like receptor 4‐mediated activation of HIV long terminal repeat

Monocytes/macrophages are known to represent a potential reservoir of human immunodeficiency virus type 1 (HIV‐1), which ensures continuous replication of the virus in patients on highly active antiretroviral therapy (HAART). Infected macrophages are a highly productive source of HIV‐1 during infections with common opportunistic pathogens. Previous studies report that toll like receptors (TLR)s play a role in HIV‐1 replication in macrophages. Here, we investigate the three main pathways activated through TLR4 and the interactions with the HIV‐1 long terminal repeat (LTR), using human embryonic kidney (HEK) 293 cells expressing TLR4 and transfected with a luciferase reporter under the control of the HIV‐1 LTR. Here, we demonstrate, that TLR4‐mediated activation of HIV‐LTR is largely governed by the nuclear factor‐κB pathway. Neither of the mitogen‐activated protein kinases ERK1/2, JNK, or p38 nor the transcription factor interferon regulatory factor 3 were involved in the direct transactivation of HIV‐LTR through stimulation of TLR4.
Immediate and delayed effect of governance in entrepreneurship: an analysis by country income level

Entrepreneurship and business creation is a priority area for many governments worldwide. Public administration can help to promote entrepreneurship through its decisions and the definition and implementation of public policies. This study analyzes the effect of six dimensions of quality of governance in business creation. We used panel data for a sample of 206 countries over the period of 2004 to 2014, divided into four subsamples generated from the income level of the countries. Furthermore, the study adopted a dual perspective, considering both immediate effects and delayed effects, resulting in two research hypotheses. The results show that for high-income countries, the political stability and absence of violence variable is significant. Adopting two-year lags in the statistical model resulted in a greater number of statistically significant explanatory variables. No homogeneous pattern is observed in the variables for statistical significance regarding the four income levels. This finding implies that the focus on good governance should primarily be regarded as a long-term perspective, rather than in terms of short cycles or simply electoral cycles.
“Just take your medicine and everything will be fine”: Responsibilisation narratives in accounts of transitioning young people with HIV into adult care services in Australia

ABSTRACT Young people who have grown up with perinatally acquired HIV in wealthy nations are increasingly transitioning into adult care settings which expect more independence and self-regulation than paediatric care. Drawing on the first qualitative study on growing up with HIV in Australia, this paper examines “responsibilisation” narratives in semi-structured interviews conducted with young people with HIV and their paediatric and adult care providers. Three dominant narratives were identified: responsibilisation as imperative, practice and contest. This suggests that while young people growing up with HIV in an advanced liberal setting such as Australia may value the independence of adult care, and appreciate the need to take responsibility for their health, the practices involved in becoming a responsible health citizen are shaped by individual histories and circumstances, and in some cases, can lead to serious contestation and conflict with care providers. Placing a stronger emphasis on what young people can gain from taking an active role in managing their health may more successfully foster responsibilisation, rather than focusing on what they will lose. Clinicians could benefit from greater support regarding how to engage young people with the elements of responsibilisation likely to resonate more meaningfully at different points in their lives.
Language and the Development of Cognitive Control

We review the relationships between language, inner speech, and cognitive control in children and young adults, focusing on the domain of cognitive flexibility. We address the role that inner speech plays in flexibly shifting between tasks, addressing whether it is used to represent task rules, provide a reminder of task order, or aid in task retrieval. We also consider whether the development of inner speech in childhood serves to drive the development of cognitive flexibility. We conclude that there is a close association between inner speech and cognitive flexibility in both adults and children. Experimental work has begun to specify in detail the role that inner speech might play in adult performance, suggesting that language plays a facilitative but not essential role in representing and activating the relevant task set, processes that occur on both switch and nonswitch trials. While developmental studies suggest an increase in the spontaneous use of verbal strategies with age, implying an increase in top-down control during shifting, experimental work is needed to specify more precisely the nature and precise role that inner speech plays in the development of cognitive control through childhood.
In vitro susceptibility of Ehrlichia sennetsu to antibiotics

Antibiotic efficacies were evaluated by Diff-Quik (Dade, Düdingen, Federal Republic of Germany) staining of Ehrlichia sennetsu in P388D1 murine macrophages grown in 96-well microtiter plates. Sennetsu disease is generally cured with tetracyclines. In vivo, E. sennetsu is susceptible to doxycycline and is resistant to erythromycin, penicillin, and chloramphenicol. Our study confirmed, in vitro, the efficacy of doxycycline, which had an MIC of 0.125 micrograms/ml. E. sennetsu was found to be resistant to erythromycin, chloramphenicol, penicillin, gentamicin, and co-trimoxazole, while it was very susceptible to ciprofloxacin (MIC, 0.125 micrograms/ml) and rifampin (MIC, 0.5 micrograms/ml).
Influence of temperature gradient on electromigration failures in 3D packaging

In this paper, influence of temperature gradient in interconnects due to Joule heating in 3D packaging on electromigration failure is presented. Black's Mean Time to Failure (MTF) model relates exponentially to the temperature of interconnects which is assumed to be constant hence does not take into account temperature gradient. The developed electromigration model incorporates the driving force due to temperature gradient in addition to the effects of current density, vacancy concentration gradients and stress gradients in the interconnects and due to coefficient of thermal expansion mismatch with surrounding materials. Effectiveness of the developed finite element model is illustrated complex C4 solder bumps of flip-chip packages using COMSOL Mutliphysics software. It is shown that for same current density in the complex C4 solder bumps of flip-chip packages it is possible that failure times could be lower for lower solder average temperature with higher temperature gradient than for higher solder temperature with low temperature gradient.
Preventive Dental Care and Long-Term Dental Outcomes among ALL Kids Enrollees.

OBJECTIVE To investigate whether early or regular preventive dental visit (PDV) reduces restorative or emergency dental care and costs for low-income children. STUDY SETTING Enrollees during 1998-2012 in the Alabama CHIP program, ALL Kids. STUDY DESIGN Retrospective cohort study using claims data for children continuously enrolled in ALL Kids for at least 4 years. Analyses are conducted separately for children 0-4 years, 4-9 years, and >9 years. For 0-4 years, the intervention of interest is whether they have at least one PDV before age 3. For the other two age groups, interventions of interest are if they have regular PDVs during each of the first 3 years, and if they have claims for a sealant in the first 3 years. Outcomes-namely restorative and emergency dental service and costs-are measured in the fourth year. To account for selection into PDV, a high-dimensional propensity scores approach is utilized. DATA EXTRACTION Claims data were obtained from ALL Kids. PRINCIPAL FINDINGS Only sealants are associated with a reduced likelihood of using restorative and emergency services and costs. CONCLUSIONS Whether PDVs without sealants actually reduce restorative/emergency pediatric dental services is questionable. Further research into benefits of PDV is needed.
Antibody Recognition of Cell Surface-Associated NS1 Triggers Fc-γ Receptor-Mediated Phagocytosis and Clearance of West Nile Virus-Infected Cells

ABSTRACT Previous studies have suggested that monoclonal antibodies (MAbs) to flavivirus nonstructural protein-1 (NS-1) protect against infection in mice through an Fc-γ receptor-dependent pathway. To identify a specific mechanism, we evaluated the protective activity of anti-NS1 MAbs to WNV using mice and cells with deficiencies of specific Fc-γ receptors. Our results suggest that only MAbs that recognize cell surface-associated NS1 trigger Fc-γ receptor I- and/or IV-mediated phagocytosis and clearance of WNV-infected cells. These findings may be relevant for generating novel therapeutic MAbs or vaccines against flaviviruses that target the NS1 protein.
High-Order Dual-Band Superconducting Bandpass Filter With Controllable Bandwidths and Multitransmission Zeros

In this paper, a compact dual-mode hairpin ring resonator (HRR) with two controllable resonances is proposed to design high-order dual-band high-temperature superconducting (HTS) bandpass filters. Its noncoupled dual-mode resonant characteristics and the mechanism for inherent transmission zero (TZ) production are studied. Moreover, a general dual-path coupling scheme is introduced for high-order coupling realization and applied to the third-order and eighth-order dual-band filter design. Also, two coupling structures for the adjacent HRRs with different orientations are proposed to excite TZs between the passbands for high selectivity. Besides, dual-parallel input–output feeding structure is adopted to tune the external quality factors of the dual-mode HRR individually so that the two passband are realized easily using high-order structure. For demonstration, an eighth-order dual-band HTS filter both operating at 1.9 and 2.6 GHz for mobile communications application are designed and analyzed. Compared with the third-order one, the selectivity of the eighth-order filter has at least 4.2 times improvement and five TZs are produced for high band-edge selectivity. Finally, the eighth-order dual-band filter is fabricated on MgO substrate with YBCO thin films. Measured results agree well with the simulations and show the excellent performance with 0.12-dB minimum insertion loss and better than −75-dB rejection level up to 5 GHz. In addition, the nonlinear characteristics of the fabricated HTS filter is observed by experiment, which shows the temperature dependence of filter center frequency performance and microwave insertion loss.
Increased diffusion in the brain of professional boxers: a preclinical sign of traumatic brain injury?

BACKGROUND AND PURPOSE Professional boxing is associated with chronic, repetitive head blows that may cause brain injuries. Diffusion-weighted imaging is sensitive to microscopic changes and may be a useful tool to quantify the microstructural integrity of the brain. In this study, we sought to quantify microscopic alterations associated with chronic traumatic brain injury in professional boxers. METHODS MR and diffusion-weighted imaging were performed in 24 boxers and in 14 age- and sex-matched control subjects with no history of head trauma. Using distribution analysis, the average diffusion constant of the entire brain (BD(av)) and diffusion distribution width (sigma) were calculated for each subject; findings in professional boxers were compared with those of control subjects. In the boxer group, correlations between diffusion changes and boxing history and diffusion changes and MR imaging findings were assessed. RESULTS The measured diffusion values in the boxer group were significantly higher than those measured in the control group (BD(av), P <. 0001; sigma, P <. 01). In the boxer group, a robust correlation was found between increased BD(av) and frequency of hospitalization for boxing injuries (r = 0.654, P <.05). The most common MR finding in the boxer group was volume loss inappropriate to age followed by cavum septum pellucidum, subcortical white matter disease, and periventricular white matter disease. CONCLUSION Boxers had higher diffusion constants than those in control subjects. Our data suggest that microstructural damage of the brain associated with chronic traumatic brain injury may elevate whole-brain diffusion. This global elevation can exist even when routine MR findings are normal.
Lawrence Berkeley National Laboratory Recent Work Title Investigations into the impact of locally modified sensor architectures on the detection efficiency of silicon microstrip sensors

The High Luminosity Upgrade of the LHC will require the replacement of the Inner Detector of ATLAS with the Inner Tracker (ITk) in order to cope with higher radiation levels and higher track densities. Prototype silicon strip detector modules are currently developed and their performance is studied in both particle test beams and X-ray beams. In previous test beam studies of prototype modules, the response of silicon sensors has been studied in detailed scans across individual sensor strips. These studies found instances of sensor strips collecting charge across areas on the sensor deviating from the geometrical width of a sensor strip. The variations have been linked to local features of the sensor architecture. This paper presents results of detailed sensor measurements in both X-ray and particle beams investigating the impact of sensor features (metal pads and p-stops) on the sensor strip response.
Nevirapine‐associated hepatotoxicity was not predicted by CD4 count ≥250 cells/μL among women in Zambia, Thailand and Kenya

Objective The aim of the study was to determine risk factors for developing severe hepatotoxicity (grade 3 or 4 hepatotoxicity) and rash‐associated hepatotoxicity (rash with ≥grade 2 hepatotoxicity) among women initiating nevirapine‐based antiretroviral therapy (ART).
China Tourism Research: A Review of Publications from Four Top International Journals

ABSTRACT Two-hundred and fifty-seven research articles on China tourism published between 1979 and 2015 in four leading international tourism journals (i.e. Annals of Tourism Research, Journal of Sustainable Tourism, Journal of Travel Research and Tourism Management) were reviewed to delineate the status of China tourism research and indicate areas for future academic inquiry. The most common research themes within the body of literature reviewed were identified as tourist behavior, tourism governance and policy issues as well as tourism economics. Methodologically, a balanced distribution of research methods was identified. This review examines the relationship between authorship and fieldwork, and its impact on research interpretations. This review paper calls for more rigorous fieldwork reflecting genuine observations of tourism development and the relevant sociocultural and political developments in transitional China.
Epoxide opening versus silica condensation during sol-gel hybrid biomaterial synthesis.

Hybrid organic-inorganic solids represent an important class of engineering materials, usually prepared by sol-gel processes by cross-reaction between organic and inorganic precursors. The choice of the two components and control of the reaction conditions (especially pH value) allow the synthesis of hybrid materials with novel properties and functionalities. 3-Glycidoxypropyltrimethoxysilane (GPTMS) is one of the most commonly used organic silanes for hybrid-material fabrication. Herein, the reactivity of GPTMS in water at different pH values (pH 2-11) was deeply investigated for the first time by solution-state multinuclear NMR spectroscopic and mass spectrometric analysis. The extent of the different and competing reactions that take place as a function of the pH value was elucidated. The NMR spectroscopic and mass spectrometric data clearly indicate that the pH value determines the kinetics of epoxide hydrolysis versus silicon condensation. Under slighly acidic conditions, the epoxy-ring hydrolysis is kinetically more favourable than the formation of the silica network. In contrast, under basic conditions, silicon condensation is the main reaction that takes place. Full characterisation of the formed intermediates was carried out by using NMR spectroscopic and mass spectrometric analysis. These results indicate that strict control of the pH values allows tuning of the reactivity of the organic and inorganic moities, thus laying the foundations for the design and synthesis of sol-gel hybrid biomaterials with tuneable properties.
Subspace-based interference removal methods for a multichannel biomagnetic sensor array

Objective. In biomagnetic signal processing, the theory of the signal subspace has been applied to removing interfering magnetic fields, and a representative algorithm is the signal space projection algorithm, in which the signal/interference subspace is defined in the spatial domain as the span of signal/interference-source lead field vectors. This paper extends the notion of this conventional (spatial domain) signal subspace by introducing a new definition of signal subspace in the time domain. Approach. It defines the time-domain signal subspace as the span of row vectors that contain the source time course values. This definition leads to symmetric relationships between the time-domain and the conventional (spatial-domain) signal subspaces. As a review, this article shows that the notion of the time-domain signal subspace provides useful insights over existing interference removal methods from a unified perspective. Main results and significance. Using the time-domain signal subspace, it is possible to interpret a number of interference removal methods as the time domain signal space projection. Such methods include adaptive noise canceling, sensor noise suppression, the common temporal subspace projection, the spatio-temporal signal space separation, and the recently-proposed dual signal subspace projection. Our analysis using the notion of the time domain signal space projection reveals implicit assumptions these methods rely on, and shows that the difference between these methods results only from the manner of deriving the interference subspace. Numerical examples that illustrate the results of our arguments are provided.
Image-Based Single Cell Profiling: High-Throughput Processing of Mother Machine Experiments

Background Microfluidic lab-on-chip technology combined with live-cell imaging has enabled the observation of single cells in their spatio-temporal context. The mother machine (MM) cultivation system is particularly attractive for the long-term investigation of rod-shaped bacteria since it facilitates continuous cultivation and observation of individual cells over many generations in a highly parallelized manner. To date, the lack of fully automated image analysis software limits the practical applicability of the MM as a phenotypic screening tool. Results We present an image analysis pipeline for the automated processing of MM time lapse image stacks. The pipeline supports all analysis steps, i.e., image registration, orientation correction, channel/cell detection, cell tracking, and result visualization. Tailored algorithms account for the specialized MM layout to enable a robust automated analysis. Image data generated in a two-day growth study (≈ 90 GB) is analyzed in ≈ 30 min with negligible differences in growth rate between automated and manual evaluation quality. The proposed methods are implemented in the software molyso (MOther machine AnaLYsis SOftware) that provides a new profiling tool to analyze unbiasedly hitherto inaccessible large-scale MM image stacks. Conclusion Presented is the software molyso, a ready-to-use open source software (BSD-licensed) for the unsupervised analysis of MM time-lapse image stacks. molyso source code and user manual are available at https://github.com/modsim/molyso.