Miracle-dz/UniFAR-FTUs huggingface dataset:
Functional Attributions and Functional Architecture A Reply to Axel Kohler

In his commentary (Kohler this collection) on my target article (Anderson this collection), Axel Kohler suggests that componential mechanism (Craver 2008) in fact suffices as a framework for understanding function-structure relationships, even in complex cases such as direction selectivity in Starburst Amacrine Cells. Here I’ll argue that while Kohler is correct that the framework can accommodate such cases, this approach misses an opportunity to draw important distinctions between what appear to be different sorts of relationships between functioning systems and the mechanisms in virtue of which they function. I tentatively suggest further that the avenue that one prefers may turn on whether one expects the functional architecture of the brain to be primarily componential and hierarchical (Craver 2008; this collection) or typically more complex than that (Pessoa 2014).
Arabidopsis ROOT HAIR DEFECTIVE3 is involved in nitrogen starvation-induced anthocyanin accumulation.

Anthocyanin accumulation is a common phenomenon seen in plants under environmental stress. In this study, we identified a new allele of ROOT HAIR DEFECTIVE3 (RHD3) showing an anthocyanin overaccumulation phenotype under nitrogen starvation conditions. It is known that ethylene negatively regulates light- and sucrose-induced anthocyanin biosynthesis. We hypothesized that RHD3 achieves its negative effect on anthocyanin biosynthesis via an ethylene-regulating pathway. In support of this, similar to rhd3 mutants, the Arabidopsis ethylene signaling mutants etr1, ein2, and ein3/eil1 showed an anthocyanin overaccumulation phenotype under nitrogen starvation conditions. The ethylene precursor ACC strongly suppressed anthocyanin accumulation, dependent on ETR1, EIN2, EIN3/EIL1, and, partially, RHD3. In addition, inactivating RHD3 partially reversed the suppressive effect of ETO1 inactivation-evoked endogenous ethylene production on anthocyanin accumulation. The expression of nitrogen starvation-induced anthocyanin biosynthesis genes was negatively regulated by RHD3, but ethylene response genes were positively regulated by RHD3. Wild-type seedlings overexpressing RHD3 showed similar phenotypes to rhd3 mutants, indicating the existence of a fine-tuned relationship between gene expression and function. RHD3 was initially identified as a gene involved in root hair development. This study uncovered a new physiological function of RHD3 in nitrogen starvation-induced anthocyanin accumulation and ethylene homeostasis. [Correction added on 6 August 2015, after first online publication: "RND3" corrected to "RHD3". ].
Non-alcoholic fatty liver disease is associated with early left ventricular dysfunction in childhood acute lymphoblastic leukaemia survivors.

BACKGROUND Childhood acute lymphoblastic leukaemia (ALL) survivors have an increased risk of metabolic and cardiovascular disease. We aimed to assess the presence of non-alcoholic fatty liver disease (NAFLD) in childhood ALL and if it is associated with early cardiovascular dysfunction. METHODS In total, 53 childhood ALL survivors and 34 controls underwent auxological evaluation, biochemical assay, liver, heart and vascular ultrasound study. RESULTS NAFLD was more frequent in ALL patients than in controls (39.6% vs 11.7%, P < 0.01). Patients with NAFLD were more obese and insulin resistant than patients without NAFLD. Flow-mediated dilatation and interventricular septum were lower in the ALL group than those in the control group (P < 0.001 for both). The patients with NAFLD showed lower left ventricular ejection fraction than those without NAFLD (P = 0.011). In ALL survivors, BMI-SDS and subcutaneous fat were the strongest predictors of NAFLD, whereas preperitoneal adipose tissue and C-reactive protein were the strongest predictors of left ventricular ejection fraction. CONCLUSIONS Childhood ALL survivors had higher prevalence of NAFLD than healthy controls, which is associated with early left ventricular impairment. In the case of fatty liver, a comprehensive heart evaluation is mandatory. We strongly recommend to prevent visceral adiposity in ALL survivors, to search for metabolic syndrome or its components and to reinforce the need of intervention on diet and lifestyle during the follow-up of these patients.
Efficacy of bivalirudin sequential dose therapy in patients with ST-segment elevation myocardial infarction undergoing emergency intervention during the perioperative period

Objective: This study aimed to observe the efficacy and safety of bivalirudin sequential dose therapy in patients with ST-segment elevation myocardial infarction (STEMI) undergoing emergency percutaneous coronary intervention (PCI). Methods: A total of 86 patients that were diagnosed with STEMI and underwent emergency PCI, from January 2012 to March 2017, were retrospectively analyzed. Main observational indexes included in-stent thrombosis rate and incidence of various bleeding events within 30 days postoperatively. Other observational indexes included incidence of major adverse cardiac and cerebrovascular events (MACCE) and thrombocytopenia within 30 days. Results: Enrolled patients had an average age of 62.56±12.97 years old. The percentage of males was 82.6% and percentage of PCI was 97.7%. During the 30 days of follow-up, no patients had in-stent thrombosis. Incidence of total bleeding events, MACCE, and postoperative thrombocytopenia were 3.49%, 2.26%, and 2.26%, respectively. Conclusion: Bivalirudin sequential dose therapy can be safely and effectively applied in patients with STEMI undergoing emergency PCI. This therapy can effectively control perioperative risk of bleeding during emergency PCI, with good anticoagulant effects.
Quaternary structure of the severe acute respiratory syndrome (SARS) coronavirus main protease.

SARS (severe acute respiratory syndrome) has been one of the most severe viral infectious diseases last year and still remains as a highly risky public health problem around the world. Exploring the types of interactions responsible for structural stabilities of its component protein molecules constitutes one of the approaches to find a destabilization method for the virion particle. In this study, we performed a series of experiments to characterize the quaternary structure of the dimeric coronavirus main protease (M(pro), 3CL(pro)). By using the analytical ultracentrifuge, we demonstrated that the dimeric SARS coronavirus main protease exists as the major form in solution at protein concentration as low as 0.10 mg/mL at neutral pH. The enzyme started to dissociate at acidic and alkali pH values. Ionic strength has profound effect on the dimer stability indicating that the major force involved in the subunit association is ionic interactions. The effect of ionic strength on the protease molecule was reflected by the drastic change of electrostatic potential contour of the enzyme in the presence of NaCl. Analysis of the crystal structures indicated that the interfacial ionic interaction was attributed to the Arg-4.Glu-290 ion pair between the subunits. Detailed examination of the dimer-monomer equilibrium at different pH values reveals apparent pK(a) values of 8.0 +/- 0.2 and 5.0 +/- 0.1 for the Arg-4 and Glu-290, respectively. Mutation at these two positions reduces the association affinity between subunits, and the Glu-290 mutants had diminished enzyme activity. This information is useful in searching for substances that can intervene in the subunit association, which is attractive as a target to neutralize the virulence of SARS coronavirus.
Fabrication of biocompatible ordered iron oxide nanopillars for the observation of cell behavior

In this study we present a novel substrate for the investigation of cell response, behavior and attachment to the surface of iron oxide nanopillars. The material was fabricated using an anodic aluminum oxide template to electroform nanopillars of iron oxide. The lengths of the rods were controlled by the electroforming time and this has a direct influence on the stiffness of the nanopillars. The material surface roughness was analyzed using atomic force microscopy, while the lengths were analyzed using field emission scanning electron microscopy. The surface roughness was found to be not significantly different for various nanopillar lengths used in this study (p < 0.05). The biocompatibility of the substrate was confirmed through culturing of murine neural stem/progenitor KT98 cells. The substrates were sterilized and placed into 24-well cell culture plates then seeded with 1 × 104 cells and cultured for 48 h. The cultured cells were immunostained after 48 h, and it was revealed that the cultured cells on flat and different length nanopillar arrays had different morphologies. The cells were observed to be more spread on the flat substrate than on the nanopillars. It was also found that the cell adhesion area on the shorter nanopillar substrate was greater than the longer nanopillar substrate. The use of this ferromagnetic substrate, due to the metallic iron, to physically stimulate cell cultures and induce differentiation without the addition of chemical growth factors is a future possibility.
Individual variation in temporal relationships between exposure to radiofrequency electromagnetic fields and non-specific physical symptoms

Background: Everyday exposure to radiofrequency electromagnetic fields (RF-EMF) emitted from wireless devices such as mobile phones and base stations, radio and television transmitters is ubiquitous. Some people attribute non-specific physical symptoms (NSPS) such as headache and fatigue to exposure to RF-EMF. Most previous laboratory studies or studies that analyzed populations at a group level did not find evidence of an association between RF-EMF exposure and NSPS. Objectives: We explored the association between exposure to RF-EMF in daily life and the occurrence of NSPS in individual self-declared electrohypersensitive persons using body worn exposimeters and electronic diaries. Methods: We selected seven individuals who attributed their NSPS to RF-EMF exposure. The level of and variability in personal RF-EMF exposure and NSPS were determined during a three-week period. Data were analyzed using time series analysis in which exposure as measured and recorded in the diary was correlated with
Implementation of Marine Protected Areas Program in Indonesia : a Case Study of The Marine Recreational Park of Gili Meno , Gili Ayer , and Gili Trawangan , West Nusa Tenggara , Indonesia

This paper examines TWP Gili Matra as a case study to illustrate the current situation of MPAs in Indonesia. It will use qualitative approach to discuss the extant government policies through key informant interviews and reviews of documents with the consideration of different factors that impede such program which was then analyzed using the policy implementation analysis framework developed by Najam (1995). The result of the study shows that implementation of MPAs policy in TWP Gili Matra has not well implemented yet because of some constraining factors explained by the Najam’s framework. Thus, it need several clear action to be considered in suppressing such constraining factors and improving supporting factor of the management and development of TWP Gili Matra.
Reversibility of Hypertensive Vascular Changes after Coarctation Repair in Dogs

ABSTRACT: A silk ligature was tied around the aorta at the site of the ligamentum arteriosum in beagle puppies aged 8 wk, and the aortic coarctation was corrected 8 mo later, when the aortic peak-to-peak systolic pressure gradient was 6.0 (SD 0.7) kPa. Similar thoracotomy was performed as a sham operation on the control animals on both occasions. One y after the coarctation repair, there was practically no systolic pressure gradient across the aortoplasty site at rest [0.5 (1.0) kPa]. Histologic examination 12 mo after the correction operation showed the medial and intimal layers of the aortic arch in the aortoplasty group (n = 8) were significantly thicker than those in the control group (n = 7) [media 1.86 (0.06) versus 1.78 (0.08) mm and intima 53.2 (13.3) versus 38.3 (10.9) $mUm, respectively, p < 0.05 for both]. The thicknesses of both intima and media of the left anterior descending and circumflexing coronary arteries and descending aorta distal to the aortoplasty site were similar in both groups. The increased vascular wall thickness may cause reduced compliance of the vascular bed above the coarctation site and hypertension after correction of the coarctation. Our results support the finding that patients with repaired aortic coarctation have an increased risk of permanent vascular changes.
Modified whirlpool hash based bloom filter for networking and security applications

Bloom is an efficient data structure technique. Initially it was used in intelligent dictionaries and spell check applications. Its ability for dynamic membership querying and information compaction attracted huge research. Various optimization models of bloom filter for diverse applications were suggested and hence many bloom filter variants emerged. Network security has become an important factor in the recent years. In this paper, we propose a new variant of bloom filter in which a standard cryptographic hash function whirlpool is modified into a non cryptographic form and deployed in the bloom filter to improve the network security. We also suggest a suitable mapping scheme. A cryptographic hash function is one which converts an input data of arbitrary length into a fixed-length output. Bloom Filters are hash based structures which have a certain degree of accuracy for considerable savings in memory and are used to support membership queries. Bloom Filters allow probability of False Positive Ratios and the aim of this paper is to reduce FPR by modifying the structure of bloom filter and enabling it to operate in the increasing network speed. The design has been implemented and tested using a Xilinx 65 nm field programmable gate array as the target technology and the results are compared with replacing the housing unit with widely used universal H3 hash function and also relatively compared with the other possible hash functions and bloom filters in literature. The performance matrices of the proposed design are false positive ratio and speed. The design is hardware based and suitable for networking and security querying applications.
High-b value diffusion-weighted MRI for detecting pancreatic adenocarcinoma: preliminary results.

OBJECTIVE The objective of our study was to evaluate the usefulness of high-b value diffusion-weighted MRI (DWI) in the detection of pancreatic adenocarcinoma. SUBJECTS AND METHODS Twenty-six patients with pancreatic adenocarcinoma were included in the study. Twenty-three other patients who were being followed up due to pancreatic diseases other than adenocarcinoma were included as control subjects. All patients and subjects underwent DWI, and the images were evaluated by three blinded radiologists. RESULTS Receiver operating characteristic (ROC) curve analysis yielded A(z) values (i.e., area under the ROC curve) of 0.998, 0.998, and 0.995 for the three radiologists. The mean sensitivity and specificity for the detection of pancreatic adenocarcinoma were 96.2% and 98.6%, respectively. The kappa values indicating interobserver agreement between different pairs of radiologists were in the category of excellent. CONCLUSION High-b value DWI allows the detection of pancreatic adenocarcinoma with a high sensitivity and specificity.
Pulsed addition of limiting-carbon during Aspergillus oryzae fermentation leads to improved productivity of a recombinant enzyme.

Fungal morphology in many filamentous fungal fermentations leads to high broth viscosity which limits oxygen mass transfer, and often results in reduced productivity. The objective in this study was to determine if a simple, fed-batch, process strategy-pulsed addition of limiting-carbon source-could be used to reduce fungal broth viscosity, and increase productivity of an industrially relevant recombinant enzyme (glucoamylase). As a control, three Aspergillus oryzae fed-batch fermentations were carried out with continuous addition of limiting-carbon. To determine the effect of pulse-feeding, three additional fermentations were carried out with limiting-carbon added in 90-second pulses, during repeated five-minute cycles. In both cases, overall carbon feed-rate was used to control dissolved oxygen concentration, such that increased oxygen availability led to increased addition of limiting-carbon. Pulse-fed fermentations were found to have smaller fungal mycelia, lower broth viscosity, and improved oxygen mass transfer. As a result, more carbon was added to pulse-fed fermentations that led to increased enzyme productivity by as much as 75%. This finding has significant implications for the bioprocessing industry, as a simple process modification which is likely to cost very little to implement in most production facilities, has the potential to substantially increase productivity.
Propionyl-l-Carnitine Improves Postischemic Blood Flow Recovery and Arteriogenetic Revascularization and Reduces Endothelial NADPH-Oxidase 4–Mediated Superoxide Production

Objective—The beneficial effect of the natural compound propionyl-l-carnitine (PLC) on intermittent claudication in patients with peripheral arterial disease is attributed to its anaplerotic function in ischemic tissues, but inadequate information is available concerning action on the vasculature. Methods and Results—We investigated the effects of PLC in rabbit hind limb collateral vessels after femoral artery excision, mouse dorsal air pouch, chicken chorioallantoic membrane, and vascular cells by angiographic, Doppler flow, and histomorphometrical and biomolecular analyses. PLC injection accelerated hind limb blood flow recovery after 4 days (P<0.05) and increased angiographic quadriceps collateral vascularization after 7 days (P<0.001) Histomorphometry confirmed the increased vascular area (P<0.05), with unchanged intramuscular capillary density. PLC-induced dilatative adaptation, and growth was found associated with increased inducible nitric oxide synthase and reduced arterial vascular endothelial growth factor and intracellular adhesion molecule-1 expression. PLC also increased vascularization in air pouch and chorioallantoic membrane (P<0.05), particularly in large vessels. PLC increased endothelial and human umbilical vascular endothelial cell proliferation and rapidly reduced inducible nitric oxide synthase and NADPH-oxidase 4–mediated reactive oxygen species production in human umbilical vascular endothelial cells; NADPH-oxidase 4 also regulated NF-&kgr;B–independent intracellular adhesion molecule-1 expression. Conclusion—Our results provided strong evidence that PLC improves postischemic flow recovery and revascularization and reduces endothelial NADPH-oxidase–related superoxide production. We recommend that PLC should be included among therapeutic interventions that target endothelial function.
University of Dundee Neural differentiation , selection and transcriptomic profiling of human neuromesodermal progenitor-like cells in vitro

Robust protocols for directed differentiation of human pluripotent cells are required to determine whether mechanisms operating in model organisms are relevant to our own development. Recent work in vertebrate embryos has identified neuromesodermal progenitors as a bipotent cell population that contributes to paraxial mesoderm and spinal cord. However, precise protocols for in vitro differentiation of human spinal cord progenitors are lacking. Informed by signalling in amniote embryos, we show here that transient dual-SMAD inhibition, together with retinoic acid (dSMADi-RA), provides rapid and reproducible induction of human spinal cord progenitors from neuromesodermal progenitor-like cells. Using CRISPRCas9 to engineer human embryonic stem cells with a GFP-reporter for neuromesodermal progenitor-associated gene Nkx1.2 we facilitate selection of this cell population. RNAsequencing was then used to identify human and conserved neuromesodermal progenitor transcriptional signatures, validate this differentiation protocol and implicate new pathways/processes in human neural differentiation. This optimised protocol, novel reporter line and transcriptomic data are useful resources with which to dissect molecular mechanisms regulating human spinal cord generation and allow scale-up of distinct cell populations for global analyses, including proteomic, biochemical and chromatin interrogation. D ev el o pm en t • A cc ep te d m an us cr ip t
Silicon insulator‐based dielectrophoresis devices for minimized heating effects

Concentration of biological specimens that are extremely dilute in a solution is of paramount importance for their detection. Microfluidic chips based on insulator‐based DEP (iDEP) have been used to selectively concentrate bacteria and viruses. iDEP biochips are currently fabricated with glass or polymer substrates to allow for high electric fields within the channels. Joule heating is a well‐known problem in these substrates and can lead to decreased throughput and even device failure. In this work, we present, for the first time, highly efficient trapping and separation of particles in DC iDEP devices that are fabricated on silicon using a single‐etch‐step three‐dimensional microfabrication process with greatly improved heat dissipation properties. Fabrication in silicon allows for greater heat dissipation for identical geometries and operating conditions. The 3D fabrication allows for higher performance at lower applied potentials. Thermal measurements were performed on both the presented silicon chips and previously published PDMS devices comprised of microposts. Trapping and separation of 1 and 2 μm polystyrene particles was demonstrated. These results demonstrate the feasibility of high‐performance silicon iDEP devices for the next generation of sorting and concentration microsystems.
Impact of Window Shading Devices on Energy Performance of Prototypical Buildings

External window shading, in its variety of forms, is an important measure for reducing air conditioning energy consumption. How to quickly evaluate and select effective external shading shapes to suit different climate zones and building types is of great significance towards promoting building energy conservation in China. In this paper, firstly, benchmarking models of four prototypical buildings in five climate zones in China are established and calibrated with EnergyPlus. Secondly, four common types of external shading are applied to the established benchmarking models which provide energy-saving rates and economies of the external shading modes in different building types and climate zones. Finally, after a comprehensive analysis of the energy-saving rates and economies, we can determine appropriate external shading devices for different building types in different climate zones, providing a design basis and theoretical support for actual projects.