Miracle-dz/UniFAR-FTUs huggingface dataset:
Revealing mesoscopic structural universality with diffusion

Significance A major challenge in the physical and life sciences is to see the invisible by quantifying the structure of materials and living tissues below nominal imaging resolution. Measurement of molecular diffusion performed at a macroscopic level is a common noninvasive structural probe. Interpreting its results involves identifying which structural features, out of a myriad of parameters, most strongly affect the diffusion coefficient. Here we address this ill-posed problem by classifying media into a relatively small number of universality classes, based on the nature of long-range structural correlations. We show that the time dependence of a macroscopic diffusion coefficient distinguishes between these classes. Using this approach, we identify dominant restrictions to MRI-measured water diffusion in muscles and in cortical gray matter. Measuring molecular diffusion is widely used for characterizing materials and living organisms noninvasively. This characterization relies on relations between macroscopic diffusion metrics and structure at the mesoscopic scale commensurate with the diffusion length. Establishing such relations remains a fundamental challenge, hindering progress in materials science, porous media, and biomedical imaging. Here we show that the dynamical exponent in the time dependence of the diffusion coefficient distinguishes between the universality classes of the mesoscopic structural complexity. Our approach enables the interpretation of diffusion measurements by objectively selecting and modeling the most relevant structural features. As an example, the specific values of the dynamical exponent allow us to identify the relevant mesoscopic structure affecting MRI-measured water diffusion in muscles and in brain, and to elucidate the structural changes behind the decrease of diffusion coefficient in ischemic stroke.
Opioid rotation in chronic non‐malignant pain patients

Background: The clinical advantage of opioid rotation is probably due to incomplete cross‐tolerance favouring analgesia more than adverse effects. The objectives of opioid rotation in chronic non‐malignant patients are 1): rotation between different long‐acting opioids (LAO) to improve analgesia and reduce side‐effects, and 2): rotation from short‐acting opioids (SAO) to LAO to establish stable analgesia in order to minimise withdrawal symptoms, risk of tolerance and addiction.
Pharmacokinetics and Pharmacodynamics of Famotidine in Infants

The pharmacokinetics and pharmacodynamics of intravenous famotidine were evaluated in 10 infants ranging from 5 to 19 days of age who had a therapeutic indication for the prophylactic treatment of stress ulceration. After a 0.5‐mg/kg infusion of famotidine, timed serum (n = 6), urine (24‐hour collection), and repeated measurements of gastric pH were obtained. The mean ± standard deviation maximum plasma concentration (Cmax) was 640.66 ± 250.66 ng/mL, the elimination half‐life (t1/2β) was 10.51 ± 5.43 hours, and the apparent volume of distribution at steady state (Vdss) was 0.82 ± 0.29 L/kg. Plasma clearance (Cl) and renal clearance (ClR) were 0.132 ± 0.061 L/hr/kg and 0.093 ± 0.056 L/hr/kg, respectively. No significant correlations were found between t1/2β, Vdss, Cl, and ClR and age. Six of the nine infants who had intragastric pH monitoring maintained a gastric pH > 4 until the final 24‐hour sampling point. In this study, the t1/2β of famotidine was prolonged and the Vdss, Cl, ClR were reduced compared with corresponding parameters in previously reported studies of children older than one year of age and adults.
Alternative sigma factor interactions in Salmonella: σE and σH promote antioxidant defences by enhancing σS levels

Hierarchical interactions between alternative sigma factors control sequential gene expression in Gram‐positive bacteria, whereas alternative sigma factors in Gram‐negative bacteria are generally regarded to direct expression of discrete gene subsets. In Salmonella enterica serovar Typhimurium (S. Typhimurium), σE responds to extracytoplasmic stress, whereas σH responds to heat shock and σS is induced during nutrient limitation. Deficiency of σE, σH or σS increases S. Typhimurium susceptibility to oxidative stress, but an analysis of double and triple mutants suggested that antioxidant actions of σE and σH might be dependent on σS. Transcriptional profiling of mutant Salmonella lacking σE revealed reduced expression of genes dependent on σH and σS in addition to σE. Further investigation demonstrated that σE augments σS levels during stationary phase via enhanced expression of σH and the RNA‐binding protein Hfq, leading to increased expression of σS‐dependent genes and enhanced resistance to oxidative stress. Maximal expression of the σS‐regulated gene katE required σE in Salmonella‐infected macrophages as well as stationary‐phase cultures. Interactions between alternative sigma factors permit the integration of diverse stress signals to produce coordinated genetic responses.
Circulating filarial antigen detection in brugian filariasis

SUMMARY Human lymphatic filariasis (LF) is a major cause of disability globally. The success of global elimination programmes for LF depends upon effectiveness of tools for diagnosis and treatment. In this study on stage-specific antigen detection in brugian filariasis, L3, adult worm (AW) and microfilarial antigenaemia were detected in around 90–95% of microfilariae carriers (MF group), 50–70% of adenolymphangitis (ADL) patients, 10–25% of chronic pathology (CP) patients and 10–15% of endemic normal (EN) controls. The sensitivity of the circulating filarial antigen (CFA) detection in serum samples from MF group was up to 95%. In sera from ADL patients, unexpectedly, less antigen reactivity was observed. In CP group all the CFA positive individuals were from CP grade I and II only and none from grade III or IV, suggesting that with chronicity the AWs lose fecundity and start to disintegrate and die. Amongst EN subject, 10–15% had CFA indicating that few of them harbour filarial AWs, thus they might not be truly immune as has been conventionally believed. The specificity for antigen detection was 100% when tested with sera from various other protozoan and non-filarial helminthic infections.
Genetic Evolution of H9 Subtype Influenza Viruses from Live Poultry Markets in Shanghai, China

ABSTRACT H9N2 influenza viruses have become established and maintain long-term endemicity in poultry. The complete genomes of seven avian H9N2 influenza viruses were characterized. These seven influenza virus isolates were obtained from live poultry markets in Shanghai, China, in 2002 and from 2006 to 2008. Genetic analysis revealed that all seven isolates had an RSSR motif at the cleavage site of hemagglutinin (HA), indicating low pathogenicity in chickens. Phylogenetic analyses indicated that the seven avian H9N2 viruses belonged to the lineage represented by Duck/Hong Kong/Y280/97 (H9N2), a virus belonging to the Chicken/Beijing/1/94-like (H9N2) lineage, and that they are all quadruple reassortants consisting of genes from different lineages. The six internal genes of the isolates possessed H5N1-like sequences, indicating that they were reassortants of H9 and H5 viruses. All of the viruses had nonstructural (as well as HA and neuraminidase) genes derived from the Duck/Hong Kong/Y280/97-like virus lineage but also had other genes of mixed avian virus origin, including genes similar to those of H5N1 viruses (Gs/GD-like). The infected chickens showed no signs of disease. These results show the genetic and biological diversity of H9N2 viruses in Shanghai and support their potential role as pandemic influenza agents.
The projection structure of the low temperature K intermediate of the bacteriorhodopsin photocycle determined by electron diffraction.

Bacteriorhodopsin (bR) is an integral membrane protein which absorbs visible light and pumps protons across the cell membrane of Halobacterium salinarium. bR is one of the few membrane-bound pumps whose structure is known at atomic resolution. Changes in the protein structure of bR are a crucial element in the mechanism of proton pumping and can be followed by a variety of spectroscopic, and diffraction methods. A number of intermediates in the photocycle have been identified spectroscopically and a number of laboratories have been successful in reporting the structural changes taking place in the later stages of the photocycle over the millisecond time-scale using diffraction techniques. These studies have revealed significant changes in the protein structure, possibly involving changes in flexibility and/or movement of helices. Earlier intermediates which arise and decay on the picosecond to microsecond time-scale have proven more difficult to trap. Here, we report for the first time the successful trapping and diffraction analysis of bR in a low temperature state resembling the very early intermediate, K. We have calculated a projection difference map to 3.5 A resolution. The map reveals no significant structural changes in the molecule, despite having a very low background noise level. This does not rule out the possibility of movements in a direction perpendicular to the plane of the membrane. However, the data are consistent with other evidence that significant structural changes do not occur in the protein itself.
Run-time power estimation for mobile and embedded asymmetric multi-core CPUs

Significant energy savings can be made in mobile devices using intelligent run-time management software (RTM) that can e↵ectively trade o↵ performance and energy. For the RTM to make informed decisions, it needs accurate and responsive run-time knowledge of the power consumption. For desktop and server systems, hardware performance monitoring counters (PMCs) have been successfully used for runtime power estimation. However, for mobile devices there is little research on the topic. This paper presents a PMCbased power model for mobile devices and the associated methodology for identifying the best PMCs and their relationship with power consumption. However, for the majority of mobile devices experimented with, PMCs were di cult or impossible to obtain and so a utilisation-based power model was proposed as a more practical alternative. Both these models are validated, respectively, on an ARM Cortex-A8 and an asymmetric ARM big.LITTLE architecture, which can be found in recent tablets and smartphones, such as the Samsung Galaxy S5. A key feature of the utilisationbased model is that it can derive the power consumed per core and per individual task. Furthermore, the model can predict the likely power consumption if a task currently executing on a particular core/frequency (e.g. Cortex-A7 at 400 MHz) were to be migrated to a di↵erent core/frequency (e.g. Cortex-A15 at 1200 MHz). This allows an RTM to explore the consequences of changing to any frequency/core combination in advance. By comparing the two models, it was found that while the PMC model achieves greater accuracy (3.2%), the utilisation model still achieves an impressive accuracy of 5.6% and 7.2% on a Cortex-A7 and Cortex-A15, respectively. As it has a high accuracy and can be easily implemented on all mobile devices, we propose that the utilisation model represents an attractive choice for guiding an RTM to improved energy e ciency.
US-proofing the Paris Climate Agreement

What can be done if a future US President withdraws from the Paris Climate Agreement? This is a critical question for an agreement which relies on universal participation for legitimacy. The US can and likely will ratify the Paris Agreement via a presidential-executive agreement. However, this could be easily reversed by a future President or an antagonistic Congress. A non-party US operating outside of the Paris climate architecture is a real threat, especially given Republican opposition to international climate policy. This article explores both what tools are available for addressing a non-party US in any climate agreement and what the Paris Agreement in particular can do. The Paris Agreement is extremely vulnerable to the withdrawal of the US, or any other major party. It possesses no non-party measures, although it can be amended to help avoid this Achilles heel. Through amendments to Article 6 a market link between subnational states in a renegade US and international carbon markets could be created. Ideally, a more semi-global approach with punitive carbon border tax adjustments could be taken to help US-proof an alternative climate agreement. The Paris Agreement will be fatally susceptible to a US dropout unless amendments to the treaty are made. Relying on the good will of a single president is short-sighted. Longer-term climate governance needs to take seriously the threat of non-parties, particularly if they are superpowers. Policy relevance This article explores how to craft an effective climate treaty without US ratification, including through reforms to the Paris Agreement. While the US is likely to be able to be able legally adopt the Paris Agreement through a presidential-executive agreement there is a distinct possibility of the US withdrawing and repealing such an agreement due to a change in president. This article suggests that the Paris Agreement is vulnerable to such an occurrence and thus the insights of this research are both timely and relevant to delegations and others involved with the UNFCCC. It will be of use to domestic US actors, as well as international negotiators and scholars in dealing with a non-party US and non-parties in general.
Primary afferent projections from the upper respiratory tract in the muskrat

The central projections of the ethmoidal, glossopharyngeal, and superior laryngeal nerves were determined in the muskrat by use of the transganglionic transport of a mixture of horseradish peroxidase (HRP) and wheat germ agglutinin (WGA)‐HRP. The ethmoidal nerve projected to discrete areas in all subdivisions of the ipsilateral trigeminal sensory complex. Reaction product was focused in ventromedial portions of the principal nucleus, subnucleus oralis, and subnucleus interpolaris. The subnucleus oralis also contained sparse reaction product in its dorsomedial part. Projections were dense to ventrolateral parts of laminae I and II of the rostral medullary dorsal horn, with sparser projections to lamina V. Label in laminae I and V extended into the cervical dorsal horn. A few labeled fibers were followed to the contralateral dorsal horn. The interstitial neuropil of the ventral paratrigeminal nucleus was densely labeled.
How can a simulation game support the development of computational problem-solving strategies?

Game-based learning using interactive environments to impart theoretical and applied knowledge for introductory programming courses is divided in two popular approaches: “game making” and “game playing”. Various studies have been conducted following greatly the former approach in secondary and tertiary education with controversial results. However, there has been relatively little research shown about how game playing can be associated with the development of computational thinking and how fundamental programming concepts can be supported by playing games. This work investigates how a simulation game should be designed to support the development of computational problem-solving strategies through the medium of learning fundamental computer science concepts, by proposing a theoretical game playing framework.
Co-stimulation of mGluR5 and N-Methyl-D-aspartate Receptors Is Required for Potentiation of Excitatory Synaptic Transmission in Hippocampal Neurons*

In the central nervous system, excitatory synaptic transmission is mediated by the neurotransmitter glutamate and its receptors. Interestingly, stimulation of group I metabotropic glutamate receptors (mGluRs) can either enhance or depress synaptic transmission at CA1 hippocampal synapses. Here we report that co-activation of mGluR5, a member of the group I mGluR family, and N-methyl-d-aspartate receptors (NMDARs) potentiates NMDAR currents and induces a long lasting enhancement of excitatory synaptic transmission in primary cultured hippocampal neurons. Unexpectedly, activation of mGluR5 alone fails to enhance evoked NMDAR currents and synaptic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptor (AMPAR) AMPAR currents. The observed potentiation requires an mGluR5-induced, inositol 1,4,5-trisphosphate receptor-mediated mobilization of intracellular Ca2+, which acts in concert with a protein kinase C, calcium-activated tyrosine kinase cascade to induce a long lasting enhancement of NMDAR and AMPAR currents.
Impact of prompt catheter withdrawal and adequate antimicrobial therapy on the prognosis of hospital-acquired parenteral nutrition catheter-related bacteraemia.

Catheter-related bacteraemia (CRB) is a cause of death in hospitalized patients, and parenteral nutrition (PN) is a risk factor. We aim to describe the prognosis of PN-CRB and the impact of catheter extraction within 48 h from bacteraemia. All consecutive hospitalized adult patients with CRB (2007-2012) were prospectively enrolled. Factors associated with 30-day mortality were determined by logistic regression analysis. Among 847 episodes of CRB identified, 291 (34%) episodes were associated with short-term catheter use for PN. Cure was achieved in 236 (81%) episodes, 42 (14.5%) patients died within the first 30 days, 7 (2.5%) relapsed, and 6 (2%) had re-infection. On multivariate analysis, previous immunosuppressive therapy (OR 5.62; 95% CI 1.69-18.68; p 0.0048) and patient age (OR 1.05; 95% CI 1.02-1.07; p 0.0009) were predictors of 30-day mortality, whereas catheter removal within 48 h of bacteraemia onset (OR 0.26; 95% CI 0.12-0.58; p 0.0010) and adequate empirical antibiotic treatment (OR 0.36; 95% CI 0.17-0.77; p 0.0081) were protective factors. Incidence of PN-CRB decreased from 5.36 episodes/1000 days of PN in 2007 to 2.9 in 2012, yielding a 46.1% rate reduction (95% CI 15.7-65.5%), which may be attributable to implementation of a multifaceted prevention strategy. In conclusion, short-term PN-CRB accounted for one-third of all episodes of CRB in our setting, and 14.5% of patients died within 30 days following bacteraemia. Our findings suggest that prompt catheter removal and adequate empirical antibiotic treatment could be protective factors for 30-day mortality. Concomitantly with implementation of a multifaceted prevention strategy, PN-CRB incidence was reduced by half.
The effect of water film thickness and conductivity on discharge initiation and propagation over an ice surface

Experimental studies were carried out to analyze and better understand the effect of water film thickness and applied water conductivity on arc propagation process over an ice surface. The thickness of the water film was found to be a determinant factor for discharge initiation and initial current level. As concerns the conductivity of the water used for ice formation it was found that it has a decisive role on the rate of current increase.
Islet Allograft Rejection by Contact‐Dependent CD8+ T cells: Perforin and FasL Play Alternate but Obligatory Roles 1

Though CD8+ T lymphocytes are important cellular mediators of islet allograft rejection, their molecular mechanism of rejection remains unidentified. Surprisingly, while it is generally assumed that CD8+ T cells require classic cytotoxic mechanisms to kill grafts in vivo, neither perforin nor FasL (CD95L) are required for acute islet allograft rejection. Thus, it is unclear whether such contact‐dependent cytotoxic pathways play an essential role in islet rejection. Moreover, both perforin and CD95L have been implicated in playing roles in peripheral tolerance, further obscuring the role of these effector pathways in rejection. Therefore, we determined whether perforin and/or FasL (CD95L) were required by donor MHC‐restricted (‘direct’) CD8+ T cells to reject islet allografts in vivo. Islet allograft rejection by primed, alloreactive CD8+ T cells was examined independently of other lymphocyte subpopulations via adoptive transfer studies. Individual disruption of T‐cell‐derived perforin or allograft Fas expression had limited impact on graft rejection. However, simultaneous disruption of both pathways prevented allograft rejection in most recipients despite the chronic persistence of transferred T cells at the graft site. Thus, while there are clearly multiple cellular pathways of allograft rejection, perforin and FasL comprise alternate and necessary routes of acute CD8+ T‐cell‐mediated islet allograft rejection.
Phosphatase PTEN is inactivated in bovine aortic endothelial cells exposed to cyclic strain

Hemodynamic forces, including cyclic strain (CS) and shear stress (SS), have been recognized as important modulators of vascular cell morphology and function. PTEN (also known as MMAC1/TEP1) is a lipid phosphatase that leads to a decrease in intracellular phosphatidylinositol 3,4,5 trisphosphate (PIP3) and therefore can modulate the stimulating effect of phosphatidylinositol 3‐kinase (PI3K). In this study, we focused on the upstream regulators of the PI3K‐Akt pathway by assessing Akt, PTEN, casein kinase 2 (CK2) (a kinase that catalyzes phosphorylation of PTEN), and PI3K activity in endothelial cells (EC) exposed to CS. The activity of phospho‐PTEN (n = 4) and phospho‐CK2 (n = 4) increased in a time‐dependent fashion, reaching maximal activity by 10 min of CS stimulation. The peak of phospho‐Akt activity (n = 4) occurred later, at 60 min. Akt activity was altered by transfection of EC with dominant negative PTEN plasmids. Furthermore, CS increased PIP3 immunoreactivity in a time‐dependent manner, reaching maximal activity after 60 min of CS stimulation, and these effects were affected by transfection of EC with dominant negative PTEN plasmids. Inhibition of PTEN activity had no effect on CS‐mediated cell proliferation but inhibited CS‐mediated suppression of apoptosis. J. Cell. Biochem. 100: 515–526, 2007. © 2006 Wiley‐Liss, Inc.
Association of PNPLA3 Polymorphism with Hepatocellular Carcinoma Development and Prognosis in Viral and Non-Viral Chronic Liver Diseases.

BACKGROUND The aim of this study was to evaluate any association between a single nucleotide polymorphism (SNP) in the patatin-like phospholipase domain containing 3 (PNPLA3) (rs738409, C>G) and the development and prognosis in patients with hepatocellular carcinoma (HCC). MATERIALS AND METHODS Two hundred heathy controls and 388 HCC cases were included: 211 with HBV, 98 patients with HCV, 29 with alcoholic steatohepatitis (ASH) and 52 with non-alcoholic steatohepatitis (NASH). The SNP was determined by real-time PCR based on TaqMan assays. RESULTS The prevalence of rs738409 genotypes CC, CG and GG in controls was 91 (45.5%), 88 (44.0%), and 21 (10.5%), respectively, while the corresponding genotypes in all patients with HCC was 158 (40.7%), 178 (45.9%), and 52 (13.4%). The GG genotype had significantly higher distribution in patients with ASH/NASH-related HCC compared with controls (OR=2.34, 95% CI=1.16-4.71, P=0.018), and viral-related HCC cases (OR=2.15, 95% CI=1.13-4.08, P=0.020). However, the frequency of the GG genotype was similar between controls and patients with viral-related HCC. At initial diagnosis, HBV-related HCC were larger and at more advanced BCLC stage than the other HCC groups. There were no significant differences between the GG and non-GG groups regarding clinical characteristics, tumor stage and overall survival. CONCLUSIONS These data suggest an influence of the PNPLA3 polymorphism on the occurrence of HCC in patients with ASH/NASH but not among those with chronic viral hepatitis. However, the polymorphism was not associated with the prognosis of HCC.