Miracle-dz/UniFAR-FTUs huggingface dataset:
Role of IscX in Iron–Sulfur Cluster Biogenesis in Escherichia coli

The Escherichia coliisc operon encodes key proteins involved in the biosynthesis of iron–sulfur (Fe–S) clusters. Whereas extensive studies of most ISC proteins have revealed their functional properties, the role of IscX (also dubbed YfhJ), a small acidic protein encoded by the last gene in the operon, has remained in question. Previous studies showed that IscX binds iron ions and interacts with the cysteine desulfurase (IscS) and the scaffold protein for cluster assembly (IscU), and it has been proposed that IscX functions either as an iron supplier or a regulator of Fe–S cluster biogenesis. We have used a combination of NMR spectroscopy, small-angle X-ray scattering (SAXS), chemical cross-linking, and enzymatic assays to enlarge our understanding of the interactions of IscX with iron ions, IscU, and IscS. We used chemical shift perturbation to identify the binding interfaces of IscX and IscU in their complex. NMR studies showed that Fe2+ from added ferrous ammonium sulfate binds IscX much more avidly than does Fe3+ from added ferric ammonium citrate and that Fe2+ strengthens the interaction between IscX and IscU. We found that the addition of IscX to the IscU–IscS binary complex led to the formation of a ternary complex with reduced cysteine desulfurase activity, and we determined a low-resolution model for that complex from a combination of NMR and SAXS data. We postulate that the inhibition of cysteine desulfurase activity by IscX serves to reduce unproductive conversion of cysteine to alanine. By incorporating these new findings with results from prior studies, we propose a detailed mechanism for Fe–S cluster assembly in which IscX serves both as a donor of Fe2+ and as a regulator of cysteine desulfurase activity.
A large deviations approach to secure lossy compression

A Shannon cipher system for memoryless sources is considered, in which distortion is allowed at the legitimate decoder. The source is compressed using a rate distortion code secured by a shared key, which satisfies a constraint on the compression rate, as well as a constraint on the exponential rate of the excess-distortion probability at the legitimate decoder. Secrecy is measured by the exponential rate of the exiguous-distortion probability at the eavesdropper, rather than by the traditional measure of equivocation. The perfect secrecy exponent is defined as the maximal exiguous-distortion exponent achievable when the key rate is unlimited. Under limited key rate, it is proved that the maximal achievable exiguous-distortion exponent is equal to the minimum between the average key rate and the perfect secrecy exponent, for a fairly general class of variable key rate codes.
Effectiveness of Personalized Feedback Alone or Combined with Peer Support to Improve Physical Activity in Sedentary Older Malays with Type 2 Diabetes: A Randomized Controlled Trial

Introduction Regular physical activity is an important aspect of self-management among older people with type 2 diabetes but many remain inactive. Interventions to improve physical activity levels have been studied but few studies have evaluated the effects of personalized feedback (PF) or peer support (PS); and there was no study on older people of Asian heritage. Hence, this trial evaluated whether PF only or combined with PS improves physical activity among older Malays with type 2 diabetes (T2DM) compared to usual care only. Materials and methods A three-arm randomized controlled trial was conducted in a primary healthcare clinic in Malaysia. Sixty-nine sedentary Malays aged 60 years and older with T2DM who received usual diabetes care were randomized to PF or PS interventions or as controls for 12 weeks with follow-ups at weeks 24 and 36. Intervention groups performed unsupervised walking activity and received written feedback on physical activity. The PS group also received group and telephone contacts from trained peer mentors. The primary outcome was pedometer steps. Secondary outcomes were self-reported physical activity, cardiovascular risk factors, cardiorespiratory fitness, balance, quality of life, and psychosocial wellbeing. Results Fifty-two (75.4%) completed the 36-week study. The PS group showed greater daily pedometer readings than the PF and controls (p = 0.001). The PS group also had greater improvement in weekly duration (p < 0.001) and frequency (p < 0.001) of moderate intensity physical activity, scores on the Physical Activity Scale for Elderly (p = 0.003), 6-min walk test (p < 0.001), and social support from friends (p = 0.032) than PF and control groups. Conclusion The findings suggest that PF combined with PS in older Malays with T2DM improved their physical activity levels, cardiorespiratory fitness, and support from friends. Trial registration Current Controlled Trials ISRCTN71447000.
Comparing Clustered and Distributed Sampling for Random Subspace Brain Mapping

Random subspace sampling provides a simple and intuitive solution to the problem of the large dimensionality of functional magnetic resonance imaging (fMRI) data for brain state decoding. Recently proposed methods for estimating voxelwise contributions to the ensemble decoding task yield biologically plausible and interpretable maps, but their sensitivity may suffer since random sub sampling ignores the spatial smoothness typical of brain activity. We therefore compare random subspace maps with those generated with explicit modeling of spatial relationships through regionally clustered sampling. On realistic simulated data, clustered sampling dramatically boosted voxel detection sensitivities and specificities from an area under the receiver operating characteristic curve in the range of 0.6 to 0.9. These results suggest that future efforts in classifier ensemble approaches are devoted to accommodate the spatial organization of brain activation.
Volatility After-Effects: Evidence from the Field

We document significant distortions of S&P 500 options prices consistent with “after-effects” impacting perceptions of volatility. After prolonged exposure to high (low) volatility, the marginal trader under- (over-) estimates volatility. The longer the exposure and the stronger the volatility level, the larger the subsequent bias, consistent with after-effects theory and inconsistent with alternative explanations. Strikingly, the price distortions that we document occur in very actively traded financial securities. These results point to a systematic bias in investors’ risk perceptions, with implications for asset pricing, risk management, entrepreneurship, and corporate investment decisions.
Self-reflection and set-shifting mediate awareness in cognitively preserved schizophrenia patients

ABSTRACT Background: Poor insight in schizophrenia has been linked to poor cognitive functioning, psychological processes such as denial, or more recently with impaired metacognitive capacity. Few studies, however, have investigated the potential co-dependency of multiple factors in determining level of insight, but such a model is necessary in order to account for patients with good cognitive functioning who have very poor awareness. As evidence suggests that set-shifting and cognitive insight (self-reflection (SR) and self-certainty) are strong predictors of awareness we proposed that these factors are key mediators in the relationship between cognition and awareness. We hypothesised that deficits specifically in SR and set-shifting determine level of awareness in the context of good cognition. Methods: Thirty schizophrenia patients were stratified by high and low awareness of illness and executive functioning scores. Cognitive insight, cognition, mood and symptom measures were compared between sub-groups. Results: A low insight/high executive functioning (LI–HE) group, a high insight/high executive functioning (HI–HE) group and a low insight/low executive functioning (LI–LE) group were revealed. As anticipated, the LI–HE patients showed significantly lower capacity for SR and set-shifting than the HI–HE patients. Conclusions: This study indicates that good cognitive functioning is necessary but not sufficient for good awareness; good awareness specifically demands preserved capacity to self-reflect and shift-set. Results support Nelson and Narens’ [1990. Metamemory: A theoretical framework and new findings. The Psychology of Learning and Motivation, 26, 125–173] model of metacognition by which awareness is founded on control (set-shifting) and monitoring (SR) processes. These specific factors could be targeted to improve insight in patients with otherwise unimpaired cognitive function.
Discovery of Naturally Occurring Splice Variants of the Rat Histamine H3 Receptor That Act as Dominant-Negative Isoforms

We described previously the cDNA cloning of three functional rat histamine H3 receptor (rH3R) isoforms as well as the differential brain expression patterns of their corresponding mRNAs and signaling properties of the resulting rH3A, rH3B, and rH3C receptor isoforms (Mol Pharmacol 59:1–8). In the current report, we describe the cDNA cloning, mRNA localization in the rat central nervous system, and pharmacological characterization of three additional rH3R splice variants (rH3D, rH3E, and rH3F) that differ from the previously published isoforms in that they result from an additional alternative-splicing event. These new H3R isoforms lack the seventh transmembrane (TM) helix and contain an alternative, putatively extracellular, C terminus (6TM-rH3 isoforms). After heterologous expression in COS-7 cells, radioligand binding or functional responses upon the application of various H3R ligands could not be detected for the 6TM-rH3 isoforms. In contrast to the rH3A receptor (rH3AR), detection of the rH3D isoform using hemagglutinin antibodies revealed that the rH3D isoform remains mainly intracellular. The expression of the rH3D-F splice variants, however, modulates the cell surface expression-levels and subsequent functional responses of the 7TM H3R isoforms. Coexpression of the rH3AR and the rH3D isoforms resulted in the intracellular retention of the rH3AR and reduced rH3AR functionality. Finally, we show that in rat brain, the H3R mRNA expression levels are modulated upon treatment with the convulsant pentylenetetrazole, suggesting that the rH3R isoforms described herein thus represent a novel physiological mechanism for controlling the activity of the histaminergic system.
Multiproxy evidence of the Neoglacial expansion of Atlantic Water to eastern Svalbard: Does ancient environmental DNA complement sedimentary and microfossil records?

Abstract. The main goal of this study was to reconstruct the paleoceanographic development of Storfjorden during the Neoglacial (~ 4 cal ka BP). A multiproxy approach was applied to provide evidence for interactions between the inflow of Atlantic Water (AW) and sea-ice coverage, which are the major drivers of environmental changes in Storfjorden. The sedimentary and microfossil records indicate that a major reorganization of oceanographic conditions in Storfjorden occurred at ~ 2.7 cal ka BP. A general cooling and the less pronounced presence of AW in Storfjorden during the early phase of the Neoglacial are prerequisite conditions for the formation of an extensive sea-ice cover. The period after ~ 2.7 cal ka BP was characterized by alternating short-term cooling and warming intervals. Warming was associated with pulsed inflows of AW and sea-ice melting that stimulated phytoplankton blooms and organic matter supply to the bottom. The cold phases were characterized by heavy and densely packed sea ice resulting in a decrease in productivity. The ancient environmental DNA (aDNA) records of foraminifera and diatoms reveal the timing of the major pulses of AW (~ 2.3 and ~ 1.7 cal ka BP) and the variation in sea-ice cover. The AW inflow was marked by an increase in the percentage of DNA sequences of monothalamous foraminifera associated with the presence of fresh phytodetritus, while cold and less productive intervals were marked by an increased proportion of monothalamous taxa known only from environmental sequencing. The diatom aDNA record indicates that primary production was continuous during the Neoglacial regardless of sea-ice conditions. However, the colder periods were characterized by the presence of diatom taxa associated with sea ice, whereas the present-day diatom assemblage is dominated by open-water taxa.
Laziness and Stinginess Th e Negative Effi cacy of Care and the Dynamics of Kinship in the Orinoco Delta, Venezuela

: Care, in lowland South America, is an ethical practice that is constitutive of kinship relations. Drawing on the case of the Warao, an indigenous people of Venezuela, I complicate this link between care and kinship in two interrelated ways: fi rst, by focusing on the impossibility of perfect care (the particularising orientation of care makes neglect inevitable); and second, by acknowledging that kinship must not only be made, but also unmade. Both strands of this argument contribute to an eff ort to show that the dark side of the care/kinship nexus is relationally productive. Since kinship relations are constituted by the memory of past acts of care and nurture, quarrels that arise from reciprocal accusations of laziness and stinginess trigger dynamics of separation with long-term implications. Care is remembered but its limits are also acknowledged, especially at death, and such refl exivity contributes to its properly ethical character.
Hepatitis C Virus (HCV) Evades NKG2D-Dependent NK Cell Responses through NS5A-Mediated Imbalance of Inflammatory Cytokines

Understanding how hepatitis C virus (HCV) induces and circumvents the host's natural killer (NK) cell-mediated immunity is of critical importance in efforts to design effective therapeutics. We report here the decreased expression of the NKG2D activating receptor as a novel strategy adopted by HCV to evade NK-cell mediated responses. We show that chronic HCV infection is associated with expression of ligands for NKG2D, the MHC class I-related Chain (MIC) molecules, on hepatocytes. However, NKG2D expression is downmodulated on circulating NK cells, and consequently NK cell-mediated cytotoxic capacity and interferon-γ production are impaired. Using an endotoxin-free recombinant NS5A protein, we show that NS5A stimulation of monocytes through Toll-like Receptor 4 (TLR4) promotes p38- and PI3 kinase-dependent IL-10 production, while inhibiting IL-12 production. In turn, IL-10 triggers secretion of TGFβ which downmodulates NKG2D expression on NK cells, leading to their impaired effector functions. Moreover, culture supernatants of HCV JFH1 replicating Huh-7.5. 1 cells reproduce the effect of recombinant NS5A on NKG2D downmodulation. Exogenous IL-15 can antagonize the TGFβ effect and restore normal NKG2D expression on NK cells. We conclude that NKG2D-dependent NK cell functions are modulated during chronic HCV infection, and demonstrate that this alteration can be prevented by exogenous IL-15, which could represent a meaningful adjuvant for therapeutic intervention.
Hardware-Enhanced Association Rule Mining with Hashing and Pipelining

Generally speaking, to implement Apriori-based association rule mining in hardware, one has to load candidate itemsets and a database into the hardware. Since the capacity of the hardware architecture is fixed, if the number of candidate itemsets or the number of items in the database is larger than the hardware capacity, the items are loaded into the hardware separately. The time complexity of those steps that need to load candidate itemsets or database items into the hardware is in proportion to the number of candidate itemsets multiplied by the number of items in the database. Too many candidate itemsets and a large database would create a performance bottleneck. In this paper, we propose a HAsh-based and Pipelined (abbreviated as HAPPI) architecture for hardware- enhanced association rule mining. We apply the pipeline methodology in the HAPPI architecture to compare itemsets with the database and collect useful information for reducing the number of candidate itemsets and items in the database simultaneously. When the database is fed into the hardware, candidate itemsets are compared with the items in the database to find frequent itemsets. At the same time, trimming information is collected from each transaction. In addition, itemsets are generated from transactions and hashed into a hash table. The useful trimming information and the hash table enable us to reduce the number of items in the database and the number of candidate itemsets. Therefore, we can effectively reduce the frequency of loading the database into the hardware. As such, HAPPI solves the bottleneck problem in a priori-based hardware schemes. We also derive some properties to investigate the performance of this hardware implementation. As shown by the experiment results, HAPPI significantly outperforms the previous hardware approach and the software algorithm in terms of execution time.
The Thai

The significantly high similarity of karyotypes were shown between Bos taurus and B. indicus except for morphology of the Y-chromosome. The B. taurus-Y (BTA-Y) is submetacentric whereas the B. indicus -Y (BIN-Y) is acrocentic. Based on the hybridization of the chromosome painting technique, the difference between Y chromosomes in B. taurus and B. indicus was proposed to be originated from the pericentric inversion between these two species. However, hybridization of SRY to the sub-centromeric end of BIN-Y indicated a double pericentric inversion found between B. taurus and B. indicus . We suggested that BTA-Y and BIN-Y were originated from a common ancestor submetacentric Y chromosome with a short p-arm. The BTA-Y was formed by pericentric inversion of a major segment of q-arm and a centromere of the ancestor chromosome whereas the BIN-Y was generated from the ancestor Y chromosome by pericentric inversion of the complete p-arm together with the centromere. A proposed model of a common ancestor sub-metacentric Y of B. taurus and B. indicus had provided a new insight into the evolution of the Y chromosome in the family of Bovidae.
Information use by humans during dynamic route choice in virtual crowd evacuations

We conducted a computer-based experiment with over 450 human participants and used a Bayesian model selection approach to explore dynamic exit route choice mechanisms of individuals in simulated crowd evacuations. In contrast to previous work, we explicitly explore the use of time-dependent and time-independent information in decision-making. Our findings suggest that participants tended to base their exit choices on time-dependent information, such as differences in queue lengths and queue speeds at exits rather than on time-independent information, such as differences in exit widths or exit route length. We found weak support for similar decision-making mechanisms under a stress-inducing experimental treatment. However, under this treatment participants were less able or willing to adjust their original exit choice in the course of the evacuation. Our experiment is not a direct test of behaviour in real evacuations, but it does highlight the role different types of information and stress play in real human decision-making in a virtual environment. Our findings may be useful in identifying topics for future study on real human crowd movements or for developing more realistic agent-based simulations.
PRAXIS Project: Final Report

Applaud is The Open University’s institutional scheme for Accrediting & Promoting Professional Learning & Academic Development. It is accredited by the Advance HE and it is offered fully online to OU staff in teaching and supporting learning roles. The scheme gives individuals the opportunity to gain external recognition as an Associate Fellow, Fellow or Senior Fellow of the HEA. This report explores the evaluation of the Applaud scheme
Spatial heterogeneity in the effects of climate and density-dependence on dispersal in a house sparrow metapopulation

Dispersal plays a key role in the response of populations to climate change and habitat fragmentation. Here, we use data from a long-term metapopulation study of a non-migratory bird, the house sparrow (Passer domesticus), to examine the influence of increasing spring temperature and density-dependence on natal dispersal rates and how these relationships depend on spatial variation in habitat quality. The effects of spring temperature and population size on dispersal rate depended on the habitat quality. Dispersal rate increased with temperature and population size on poor-quality islands without farms, where house sparrows were more exposed to temporal fluctuations in weather conditions and food availability. By contrast, dispersal rate was independent of spring temperature and population size on high-quality islands with farms, where house sparrows had access to food and shelter all the year around. This illustrates large spatial heterogeneity within the metapopulation in how population density and environmental fluctuations affect the dispersal process.
Pay-as-bid versus marginal pricing-part I:Strategic generator offers

As the arguments for and against the use of pay-as-bid (PAB) or marginal pricing (MP) in electricity pools tend to be qualitative, we compare the quantitative behavior of the two markets assuming that generators submit the best strategic offers that correspond to the specified pricing method. In Part I of this two-part study, assuming that the system marginal costs for PAB and MP are random with known probability density functions, we develop generator strategic offers by maximizing the corresponding expected values of the generator profits over the offer parameters. In Part II relations are established between the SMCs for each market type and a common random demand, thus allowing the two markets to be compared through the expected values and variances of the individual generation profits and of the consumer payments. This comparison demonstrates both theoretically and through simulation that: 1) the expected values of the individual generator profits as well as of the consumer payments are the same under MP and PAB and 2) the variances of the individual generator profits and of the consumer payments however are larger under MP than under PAB. The primary conclusion is then that although MP and PAB yield identical expected generator profits and consumer payments, the risk of not meeting these expected values is greater under MP than under PAB.
Newly identified biologically active and proteolysis-resistant VEGF-A isoform VEGF111 is induced by genotoxic agents

Ultraviolet B and genotoxic drugs induce the expression of a vascular endothelial growth factor A (VEGF-A) splice variant (VEGF111) encoded by exons 1–4 and 8 in many cultured cells. Although not detected in a series of normal human and mouse tissue, VEGF111 expression is induced in MCF-7 xenografts in nude mice upon treatment by camptothecin. The skipping of exons that contain proteolytic cleavage sites and extracellular matrix–binding domains makes VEGF111 diffusible and resistant to proteolysis. Recombinant VEGF111 activates VEGF receptor 2 (VEGF-R2) and extracellularly regulated kinase 1/2 in human umbilical vascular endothelial cells and porcine aortic endothelial cells expressing VEGF-R2. The mitogenic and chemotactic activity and VEGF111's ability to promote vascular network formation during embyonic stem cell differentiation are similar to those of VEGF121 and 165. Tumors in nude mice formed by HEK293 cells expressing VEGF111 develop a more widespread network of numerous small vessels in the peritumoral tissue than those expressing other isoforms. Its potent angiogenic activity and remarkable resistance to proteolysis makes VEGF111 a potential adverse factor during chemotherapy but a beneficial therapeutic tool for ischemic diseases.