Miracle-dz/UniFAR-FTUs huggingface dataset:
Adelaide Stroke Incidence Study: Declining Stroke Rates but Many Preventable Cardioembolic Strokes

Background and Purpose— Stroke incidence rates are in flux worldwide because of evolving risk factor prevalence, risk factor control, and population aging. Adelaide Stroke Incidence Study was performed to determine the incidence of strokes and stroke subtypes in a relatively elderly population of 148 000 people in the Western suburbs of Adelaide. Methods— All suspected strokes were identified and assessed in a 12-month period from 2009 to 2010. Standard definitions for stroke and stroke fatality were used. Ischemic stroke pathogenesis was classified by the Trial of ORG 10172 in Acute Stroke Treatment criteria. Results— There were 318 stroke events recorded in 301 individuals; 238 (75%) were first-in-lifetime events. Crude incidence rates for first-ever strokes were 161 per 100 000 per year overall (95% confidence interval [CI], 141–183), 176 for men (95% CI, 147–201), and 146 for women (95% CI, 120–176). Adjusted to the world population rates were 76 overall (95% CI, 59–94), 91 for men (95% CI, 73–112), and 61 for women (95% CI, 47–78). The 28-day case fatality rate for first-ever stroke was 19% (95% CI, 14–24); the majority were ischemic (84% [95% CI, 78–88]). Intracerebral hemorrhage comprised 11% (8–16), subarachnoid hemorrhage 3% (1–6), and 3% (1–6) were undetermined. Of the 258 ischemic strokes, 42% (95% CI, 36–49) were of cardioembolic pathogenesis. Atrial fibrillation accounted for 36% of all ischemic strokes, of which 85% were inadequately anticoagulated. Conclusions— Stroke incidence in Adelaide has not increased compared with previous Australian studies, despite the aging population. Cardioembolic strokes are becoming a higher proportion of all ischemic strokes.
Distinct functions of H‐Ras and K‐Ras in proliferation and survival of primary hepatocytes due to selective activation of ERK and PI3K

Ras proteins mediate signals both via extracellular signal‐regulated kinase 1 and 2 (ERK), and phosphoinositide 3‐kinase (PI3K). These signals are key events in cell protection and compensatory cell growth after exposure to cell damaging and pro‐apoptotic stimuli, thus maintaining homeostasis. By transfection techniques, we found that both H‐Ras and K‐Ras were expressed and appeared functionally active in primary hepatocytes. We compared the ability of H‐Ras and K‐Ras homologues to preferentially activate one of the two pathways, thereby differentially controlling cell survival and growth. We found that ectopic expression of dominant negative (DN) H‐RasN17, but not DN K‐RasN17, efficiently inhibited both phosphorylation and translocation of ERK to the nuclear compartment, which are prerequisites for cell cycle progression. Furthermore, ectopic expression of constitutive active (CA) H‐RasV12, but not CA K‐RasV12, potentiated EGF‐induced proliferation. We also found that expression of CA mutants of either H‐Ras or K‐Ras protected hepatocytes from transforming growth factor‐β1 (TGF‐β1)‐induced apoptosis. However, H‐Ras‐induced survival was mediated by ERK/RSK as well as by PI3K, whereas K‐Ras‐induced survival was mediated by PI3K only. In conclusion, H‐Ras and K‐Ras had differential functions in proliferation and survival of primary hepatocytes. H‐Ras was the major mediator of ERK‐induced proliferation and survival, whereas H‐Ras and K‐Ras both mediated PI3K‐induced survival. J. Cell. Physiol. 215: 818–826, 2008. © 2007 Wiley‐Liss, Inc.
Cannabis controversies: how genetics can inform the study of comorbidity.

AIMS To review three key and controversial comorbidities of cannabis use-other illicit drug use, psychosis and depression, as well as suicide, from a genetically informed perspective. DESIGN Selective review. RESULTS Genetic factors play a critical role in the association between cannabis use, particularly early-onset use and use of other illicit drugs, psychosis and depression, as well as suicide, albeit via differing mechanisms. For other illicit drugs, while there is strong evidence for shared genetic influences, residual association that is attributable to causal or person-specific environmental factors cannot be ruled out. For depression, common genetic influences are solely responsible for the association with cannabis use but for suicidal attempt, evidence for person-specific factors persists. Finally, even though rates of cannabis use are inordinately high in those with psychotic disorders, there is no evidence of shared genetic etiologies underlying this comorbidity. Instead, there is limited evidence that adolescent cannabis use might moderate the extent to which diathesis influences psychosis. CONCLUSIONS Overlapping genetic influences underlie the association between early-onset cannabis use and other illicit drug use as well as depression and suicide. For psychosis, mechanisms other than shared genetic influences might be at play.
RTBC: A Simple CNS-like Routing Protocol for Target Detection in Wireless Sensor Networks

In recent years, wireless sensor networks have become a very hot research area, and are going to find lots of applications in ubiquitous monitoring and information collecting. Routing in wireless sensor networks is an important problem. It is also very different from that in traditional wireless networks. In this paper, a new CNS-like routing protocol, RTBC (random time-choosing based clustering routing protocol), is proposed for mobile targets detection in wireless sensor networks. In RTBC, a random time-choosing based CH select algorithm is introduced. It is a new distributed algorithm, with the ability of dynamically forming clusters on-demand for reactive sensor networks. It requires only one local broadcast for CH select and intra-cluster communication schedule. We then compare RTBC with ideal CNS, which is the theoretical optimal routing scheme for our system model, in terms of communication energy costs, and find that RTBC introduces a quite small overhead. Thus, it is very energy-efficient
Role of tissue C-reactive protein in atrial cardiomyocytes of patients undergoing catheter ablation of atrial fibrillation: pathogenetic implications.

AIMS Histological studies support the important role of inflammation in the initiation and maintenance of atrial fibrillation (AF). We describe a novel and safe technique of atrial biopsy during AF radiofrequency catheter ablation (RFCA) to investigate the role of atrial tissue inflammation. METHODS AND RESULTS We enrolled 70 consecutive patients (age 60 ± 12 years, 49 males) undergoing RFCA for AF. The control group was represented by 10 patients with Wolff-Parkinson-White syndrome undergoing trans-septal puncture. Atrial biopsies were obtained by washing the dilator and needle used for trans-septal puncture with 20 mL sterile phosphate-buffered saline. The presence of intracytoplasmic C-reactive protein was assessed in formalin-fixed atrial specimens by immunohistochemistry. A sufficient amount of atrial tissue was obtained in 23/70 (32%) patients with AF and in 4/10 (40%) of the control group. Intracytoplasmic localization of C-reactive protein was found in isolated atrial cardiomyocytes in 11 (73%) of 15 patients with paroxysmal AF as compared with 2 (25%) of eight patients with persistent AF (P= 0.02). CONCLUSION In this study, we demonstrate the safety and feasibility of a novel technique to obtain atrial specimens during routine trans-septal puncture. Local inflammation assessed by atrial tissue localization of C-reactive protein is more likely involved in paroxysmal rather than in persistent AF.
Efficacy and Dose Response of Soil-Applied Neem Formulations in Substrates with Different Amounts of Organic Matter, in the Control of Whiteflies, Aleyrodes proletella and Trialeurodes vaporariorum (Hemiptera: Aleyrodidae)

ABSTRACT Neem products have been used frequently as an alternative to synthetic pesticides, because of their insecticidal, insect antifeedant, and growth-regulating effects. Moreover, new formulations are continually being developed and therefore, they have to be evaluated for their efficacy and persistence. In this regard, two soil-applied products—a liquid-based drenching solution NeemAzal-T and NeemAzal granules—were evaluated against two whitefly species, Aleyrodes proletella L. and Trialeurodes vaporariorum (West) on Brussels sprout and tomatoes, respectively. The plants were grown in two substrates: one was a commercial substrate (CS) composed of 15% humus, 35% clay, and 50% peat, and the other was a commercial substrate and sand mixture in 1:1 ratio. The main objective of the study was to evaluate the efficacy, persistence, and dose response of the two soil-applied NeemAzal formulations in substrates with different amount of organic matter. The results show that the efficacy of neem formulations was dose dependent, with the highest doses of NeemAzal granules (300 mg/kg = 21 mg azadirachtin [AZA]/kg of substrate) and NeemAzal T (2 ml/kg = 20 mg AZA/kg of substrate) achieving up to 100% mortality of immature stages of whiteflies. NeemAzal caused significantly higher mortality in immature stages of both whitefly species with CS + sand mixture than with pure CS. Persistence of the NeemAzal formulations was not influenced by the substrate type but rather by time span between treatment application and infestation, with significant decrease in efficacy when whiteflies were exposed 10 d after treatments.
On the non‐respect of the thermodynamic cycle by DsbA variants

The mechanism of the disulfide‐bond forming enzyme DsbA depends on the very low pKa of a cysteine residue in its active‐site and on the relative instability of the oxidized enzyme compared to the reduced one. A thermodynamic cycle has been used to correlate its redox properties to the difference in the free energies of folding (ΔΔGred/ox) of the oxidized and reduced forms. However, the relation was proved unsatisfied for a number of DsbA variants. In this study, we investigate the thermodynamic and redox properties of a highly destabilized variant DsbAP151A (substitution of cis‐Pro151 by an alanine) by the means of intrinsic tryptophan fluorescence and by high‐sensitivity differential scanning calorimetry (HS‐DSC). When the value of ΔΔGred/ox obtained fluorimetrically for DsbAP151A does not correlate with the value expected from its redox potential, the value of ΔΔGred/ox provided by HS‐DSC are in perfect agreement with the predicted thermodynamic cycle for both wild‐type and variant. HS‐DSC data indicate that oxidized wild‐type enzyme and the reduced forms of both wild‐type and variant unfold according to a two‐state mechanism. Oxidized DsbAP151A shows a deviation from two‐state behavior that implies the loss of interdomain cooperativity in DsbA caused by Pro151 substitution. The presence of chaotrope in fluorimetric measurements could facilitate domain uncoupling so that the fluorescence probe (Trp76) does not reflect the whole unfolding process of DsbAP151A anymore. Thus, theoretical thermodynamic cycle is respected when an appropriate method is applied to DsbA unfolding under conditions in which protein domains still conserve their cooperativity.
Osteoblasts induce osteopontin expression in response to attachment on fibronectin: Demonstration of a common role for integrin receptors in the signal transduction processes of cell attachment and mechanical stimulation

Osteopontin is a predominant integrin binding protein of bone and its expression has been shown to be induced by mechanical stimuli within osteoblasts (Toma et al. [1997] J. Bone Miner. Res. 12:1626–1636). The present studies examined if the cell adhesion would mimic the mechano‐transduction that stimulated opn mRNA expression and whether integrin receptors were involved in these processes. Osteopontin mRNA expression was induced three‐ to four‐fold, 24 hours after embryonic chicken calvaria osteoblast attachment to fibronectin (FN), however no induction was observed if the cells were plated on tissue culture plastic alone. Osteopontin mRNA induction in response to cell attachment on FN was dependent on new protein synthesis and the activation of a tyrosine protein kinase(s) but unlike mechano‐induction was independent of the maintenance of the cell's microfilament structure. Integrin receptor(s) were shown to be involved in mediating the signal transduction processes of both cell attachment and mechanical stimulation since incubation of osteoblasts with the integrin binding peptide RGDS partially blocked the induction of opn expression in response to both stimuli. Interestingly, incubation of the osteoblasts that were adherent on tissue culture plastic alone with the RGDS peptide lead to an induction in opn expression suggesting that integrin occupancy by itself was sufficient to initiate the signal transduction process that induced opn expression. In order to assess the role of integrin occupancy vs. focal adhesion complex formation that accompanies cell attachment, in the signal transduction process that induces opn expression, receptor clustering was stimulated pharmacologically with bombesin or lysophasphatidic acid in osteoblasts attached to tissue culture plastic. Neither compound in the absence of occupancy of the integrin receptors was capable of stimulating opn expression in attached cells, however if the cells were placed in suspension pharmacological mediation of receptor clustering and integrin occupancy were additive in their effect of inducing opn expression. These data demonstrate that induction of opn expression by mechanical stimuli and cell attachment are commonly mediated through integrin receptor(s). However, when cells are attached receptor clustering alone which accompanies focal adhesion formation was incapable of mediating signal transduction suggesting that receptor occupancy was a prerequisite to the signal transduction process that leads to the induction of opn mRNA expression. J. Cell. Biochem. 70:376–390. © 1998 Wiley‐Liss, Inc.
Rolle der von Willebrand-Faktor-spaltenden-Protease ADAMTS-13 bei Patienten mit systemischer Inflammation

Eine generalisierte Inflammationsreaktion steht haufig im Zusammenhang mit einer gesteigerten Gerinnungsaktivierung. Bei der sepsis-assoziierten endothelialen Dysfunktion kommt es zur vermehrten Freisetzung des Akutphase-Proteins von Willebrand-Faktor (VWF). Native ultralange VWF-Multimere (ULVWF) werden vorwiegend durch die VWF spaltende Protease ADAMTS-13 gespalten. ULVWF-Multimere fuhren bei verminderter Enzymaktivitat zur spontanen Aktivierung der Thrombozyten und bilden die molekulare Basis der thrombotischen Mikroangiopathie. Es wurde untersucht, ob eine verminderte ADAMTS-13 Aktivitat bei Patienten mit systemischer Inflammation auftritt, sowie ob eine mogliche Prasenz von ULVWF-Multimeren fur die Entwicklung des septischen Organversagens relevant sein konnte. In einer prospektiven Longitudinalstudie fanden wir im Citratplasma von 11 thrombozytopenischen Patienten mit septischem Schock eine erniedrigte ADAMTS13 Aktivitat im gesamten Tagesverlauf. Hierbei traten Unterschiede zwischen Uberlebenden und Nicht-Uberlebenden auf, indem die ADAMTS13 Aktivitat bei den Uberlebenden im Zeitverlauf anstieg. Bei einem weiteren Patientenkollektiv von 22 Patienten mit postoperativem systemischem Inflammationssyndrom war die ADAMTS-13 Aktivitat an den ersten 5 postoperativen Tagen erniedrigt. Eine erniedrigte ADAMTS-13 Aktivitat war in beiden Kollektiven sowohl mit dem Auftreten von ULVWF-Multimeren als auch mit erhohten inflammationsrelevanten Parametern und erhohtem „Sequential Organ Failure Assessment“-(SOFA)-Score assoziiert. Die uber ULVWF-Multimere vermittelte Thrombozytenaggregation spielt eine potentielle Rolle bei der Entstehung eines Organversagens im Rahmen von systemischen Inflammationsreaktionen.
Effects of congenital stationary night blindness type 2 mutations R508Q and L1364H on Cav1.4 L‐type Ca2+ channel function and expression

At least 48 mutations in the CACNA1F gene encoding retinal Cav1.4 L‐type Ca2+ channels have been linked to X‐linked recessive congenital stationary night blindness type 2 (CSNB2). A large number of these are missense mutations encoding full‐length α1‐subunits that can potentially form functional channels. We have previously shown that such missense mutations can confer their phenotype by different pathological mechanisms, such as complete lack of α1 subunit protein expression or dramatic changes in channel gating. Here we investigated the functional consequences of CSNB2 missense mutations R508Q and L1364H. We found no (R508Q) or only minor (L1364H) changes in the gating properties of both mutants after heterologous expression in Xenopus laevis oocytes (at 20°C). However, both mutants resulted in altered expression density of Cav1.4 currents. When expressed in the mammalian cell line tsA‐201, the current amplitude of L1364H channels was reduced when cells were grown at 30°C and both mutations affected total α1 protein expression. This effect was temperature dependent. Our data provide evidence that, in contrast to previously characterized CSNB2 missense mutations, the clinical phenotype of R508Q and L1364H is unlikely to be explained by changes in channel gating. Instead, these mutations affect the protein expression of Cav1.4 Ca2+ channels.
Identification and Characterization of GONST1, a Golgi-Localized GDP-Mannose Transporter in Arabidopsis

Transport of nucleotide sugars across the Golgi apparatus membrane is required for the luminal synthesis of a variety of plant cell surface components. We identified an Arabidopsis gene encoding a nucleotide sugar transporter (designated GONST1) that we have shown by transient gene expression to be localized to the Golgi. GONST1 complemented a GDP-mannose transport–defective yeast mutant (vrg4-2), and Golgi-rich vesicles from the complemented strain displayed increased GDP-mannose transport activity. GONST1 promoter::β-glucuronidase studies suggested that this gene is expressed ubiquitously. The identification of a Golgi-localized nucleotide sugar transporter from plants will allow the study of the importance of this class of proteins in the synthesis of plant cell surface components such as cell wall polysaccharides.
Making small spaces feel large: infinite walking in virtual reality

Over the past few years, virtual reality has experienced a resurgence. Fueled by a proliferation of consumer-level head-mounted display and motion tracking devices, an unprecedented quantity of immersive experiences and content are available for both desktop and mobile platforms. However, natural locomotion in immersive virtual environments remains a significant challenge. Many of the VR applications available to date require seated use or limit body movement within a small area, instead relying a gamepad or mouse/keyboard for movement within the virtual world. Lacking support for natural walking, these virtual reality experiences do not fully replicate the physical and perceptual cues from the real world, and often fall short in maintaining the illusion that the user has been transported to another place. We present a virtual reality demonstration that supports infinite walking within a confined physical space. This is achieved using redirected walking, a class of techniques that introduce subtle discrepancies between physical and virtual motions [Razzaque et al. 2001]. When employed properly, redirected walking can be stunningly effective. Previous research has made users believe that they walked in a straight line when they actually traveled in a wide circle, or that they walked between waypoints in a long virtual hallway when in fact they went back and forth between the same two points in the real world. While perceptually compelling, redirected walking is challenging to employ effectively in an unconstrained scenario because users' movements may often be unpredictable. Therefore, our recent research has focused on dynamic planning and optimization of redirected walking techniques, enabling the system to intelligently apply redirection as users explore virtual environments of arbitrary size and shape [Azmandian et al. 2014b] [Azmandian et al. 2014a]. In this Emerging Technologies exhibit, attendees will explore a large-scale, outdoor immersive virtual environment in a head-mounted display (see Figure 1). The demonstration will support natural walking within a physical area of at least 6x6m, using a wide-area motion tracking system provided by PhaseSpace Inc. The virtual reality scenario will instruct users to scout the environment while stopping to take panoramic photos at various locations in the virtual world. As users explore the environment, our automated planning algorithm will dynamically apply redirection to optimally steer them away from the physical boundaries of the exhibit, thus enabling the experience of limitless walking in a potentially infinite virtual world (see Figure 2).
Molecular Basis of Arabinobio-hydrolase Activity in Phytopathogenic Fungi

The phytopathogenic fungus Fusarium graminearum secretes a very diverse pool of glycoside hydrolases (GHs) aimed at degrading plant cell walls. α-l-Arabinanases are essential GHs participating in the complete hydrolysis of hemicellulose, a natural resource for various industrial processes, such as bioethanol or pharmaceuticals production. Arb93A, the exo-1,5-α-l-arabinanase of F. graminearum encoded by the gene fg03054.1, belongs to the GH93 family, for which no structural data exists. The enzyme is highly active (1065 units/mg) and displays a strict substrate specificity for linear α-1,5-l-arabinan. Biochemical assays and NMR experiments demonstrated that the enzyme releases α-1,5-l-arabinobiose from the nonreducing end of the polysaccharide. We determined the crystal structure of the native enzyme and its complex with α-1,5-l-arabinobiose, a degradation product of α-Me-1,5-l-arabinotetraose, at 1.85 and 2.05Å resolution, respectively. Arb93A is a monomeric enzyme, which presents the six-bladed β-propeller fold characteristic of sialidases of clan GHE. The configuration of the bound arabinobiose is consistent with the retaining mechanism proposed for the GH93 family. Catalytic residues were proposed from the structural analysis, and site-directed mutagenesis was used to validate their role. They are significantly different from those observed for GHE sialidases.
Genomic Organization and Chromosomal Localization of the Gene Encoding Human P-selectin Glycoprotein Ligand (*)

The gene for P-selectin glycoprotein ligand (PSGL-1) has been cloned from a human placenta genomic DNA library. A single intron of approximately 9 kilobases was found in the 5′-untranslated region and the complete coding region resides in exon 2. The genomic clone differs from the cDNA clone isolated from HL-60 cells in that it encodes an extra copy of the decameric repeat located in the extracellular domain of PSGL-1. Further analysis indicated that the PSGL-1 genes of HL-60 and U-937 cells contain 15 repeats, whereas the PSGL-1 genes of polymorphonuclear leukocytes, monocytes, and several other cell lines contain 16 repeats. Transfection experiments did not indicate a functional difference between these two variants of PSGL-1. The two previously observed PSGL-1 mRNA species of 2.5 and 4 kilobases most likely arise from differential utilization of polyadenylation signal sequences. The organization of the PSGL-1 gene closely resembles those of CD43 and human platelet glycoprotein GPIbα, both of which have an intron in the 5′-noncoding region, a long second exon containing the complete coding region, and TATA-less promoters. The gene for human PSGL-1, which has been designated SELPLG by the Human Gene Nomenclature Committee, was mapped to chromosome 12q24 using Southern blot analysis of DNA from a set of human-mouse cell hybrids, and fluorescent in situ hybridization on metaphase chromosome spreads.