Miracle-dz/UniFAR-FTUs huggingface dataset:
ROS-induced mitochondrial depolarization initiates PARK2/PARKIN-dependent mitochondrial degradation by autophagy

Reactive oxygen species (ROS) have been implicated as a signal for general autophagy. Both mitochondrial-produced and exogenous ROS induce autophagosome formation. However, it is unclear whether ROS are required for the selective autophagic degradation of mitochondria, a process called mitophagy. Recent work using carbonyl cyanide m-chlorophenylhydrazone (CCCP), a mitochondrial-uncoupling reagent, has been shown to induce mitophagy. However, CCCP treatment may not be biologically relevant since it causes the depolarization of the entire mitochondrial network. Since mitochondria are the main ROS production sites in mammalian cells, we propose that short bursts of ROS produced within mitochondria may be involved in the signaling for mitophagy. To test this hypothesis, we induced an acute burst of ROS within mitochondria using a mitochondrial-targeted photosensitizer, mitochondrial KillerRed (mtKR). Using mtKR, we increased ROS levels in the mitochondrial matrix, which resulted in the loss of membrane potential and the subsequent activation of PARK2-dependent mitophagy. Importantly, we showed that overexpression of the mitochondrial antioxidant protein, superoxide dismutase-2, can squelch mtKR-induced mitophagy, demonstrating that mitochondrial ROS are responsible for mitophagy activation. Using this assay, we examined the impact of mitochondrial morphology on mitophagy. It was shown recently that elongated mitochondria are more resistant to mitophagy through unknown mechanisms. Here, we show that elongated mitochondria are more resistant to ROS-induced damage and mitophagy compared with fragmented mitochondria, suggesting that mitochondrial morphology has an important role in regulating ROS and mitophagy. Together, our results suggest that ROS-induced mitochondrial damage may be an important upstream activator of mitophagy.
Are Unbundled and Self‐supplied Telecommunications Switching Substitutes? An Empirical Study

Abstract The Telecommunications Act of 1996 requires incumbent monopoly phone companies to lease elements of their networks to rivals. An important policy question is whether these unbundled elements are substitutes for entry modes that are more facilities‐based. In this article, we estimate demand curves for unbundled elements with the goal of assessing cross‐price effects between two of the more popular entry modes that differ in the mix of unbundled and self‐supplied inputs. As expected, we find downward sloping demand curves for unbundled elements. We also find own‐price elasticities in the elastic region of demand. What we do not find is evidence of substitution; we are able to reject the hypothesis of effective substitution between the two entry modes.
Controlling Imbalanced Error in Deep Learning with the Log Bilinear Loss

Deep learning has become the method of choice for many machine learning tasks in recent years, and especially for multi-class classiﬁcation. The most common loss function used in this context is the cross-entropy loss. While this function is insensitive to the identity of the assigned class in the case of misclassiﬁcation, in practice it very common to have imbalanced sensitivity to error, meaning some wrong assignments are much worse than others. Here we present the bilinear-loss (and related log-bilinear-loss) which diﬀerentially penalizes the diﬀerent wrong assignments of the model. We thoroughly test the proposed method using standard models and benchmark image datasets.
Assessing spatial equality of urban green spaces provision: a case study of Greater Doha in Qatar

Greater Doha is experiencing lack of sufficient urban green spaces (UGS) as a result of rapid urbanisation to cater for the fast population growth in the country. The availability of green spaces and the improvement of the green/built-up area ratio have been recognised by planners as a key factor in improving the life quality of city dwellers. This study aims at addressing the adequacy and spatial distribution of public parks in Greater Doha. The current status of public parks is assessed in relation to the population distribution using GIS and remote sensing techniques. The results show that the majority of administrative zones fell well below the adopted public parks standards. The park provision ratio ranged from 0 and 0.03 through 0.43 and 0.48 to 0.92 and 0.99 hectare (ha) per 1000 population, with an average of 0.37. After quantifying this deficiency in UGS, the study suggest remedy by identifying vacant parcels in each zone to match the adopted standards, taking into consideration their spatial distribution and minimum area criteria.
Relationship between haemoglobin and haematocrit in the definition of anaemia

Introduction Anaemia is the most frequent haematological disorder in childhood. The notion that defines naemia does not change throughout life, although parameters used for its evaluation show significant variations during childhood. Haematocrit (Hct) (%) is usually defined as three times the value of haemoglobin (Hgb) (g/dl), while the clinical definition of anaemia is related to either an abnormal Hct or Hgb value.
The relationship between output and unemployment in Scotland: A regional analysis

The relationship between unemployment and growth (i.e., the so-called Okun’s Law) has long standing in macroeconomics and regional economics. In this paper we estimate such a relationship for Scotland and at the Nomenclature of Territorial Units for Statistics (NUTS) level 3 regions using a panel dataset. The main motivations behind this interest are twofold: first, to test whether such a relationship exists in Scotland and how different these estimates are from those produced for the UK. Second, whether there exist regional differences in the estimates. The latter is particularly important in the context of the current budgetary cuts, which may affect both GDP growth and unemployment in different ways rural and urban areas. Results indicate that the Okun’s coefficient for Scotland is slightly higher than the one computed for the UK (1.7 Scotland versus 1.39 and 1.45 for the UK), and although an Okun relationship seemed to be valid for most of the regions, there were no statistical differences between rural and urban areas. However, as regards the effect of economic growth on unemployment, the results indicate a different and stronger effect in urban areas than in rural areas.
Family ties and the crowding out of long-term care insurance

Insurance for long-term care (LTC) has developed only moderately compared to other areas of welfare, which has been explained variously as the result of market failures, public misconceptions of the risk of LTC needs, and intergenerational contracts. This paper offers a cultural explanation for the limited LTC insurance development in Europe. It argues that family ties, by enhancing informal care-giving duties, inhibit individuals' expected (public and private) insurance coverage. The empirical analysis of the paper exploits cross-country and sub-group variability of a representative database of European Union member states, containing records on LTC coverage and family structure. Drawing upon two measures of familistic culture or family ties, we find a negative association between family ties and expected coverage of LTC for different sub-samples. These results are robust to a set of checks for different definitions of family ties and controls, and for a sub-sample of first- and second-generation migrants. Policy implications suggest that widespread expansion of LTC coverage might need to accommodate existing familistic cultural norms to avoid insurance crowding out. Copyright 2010, Oxford University Press.
Chemical Proteomics for Target Discovery of Head-to-Tail Cyclized Mini-Proteins

Target deconvolution is one of the most challenging tasks in drug discovery, but a key step in drug development. In contrast to small molecules, there is a lack of validated and robust methodologies for target elucidation of peptides. In particular, it is difficult to apply these methods to cyclic and cysteine-stabilized peptides since they exhibit reduced amenability to chemical modification and affinity capture; however, such ribosomally synthesized and post-translationally modified peptide natural products are rich sources of promising drug candidates. For example, plant-derived circular peptides called cyclotides have recently attracted much attention due to their immunosuppressive effects and oral activity in the treatment of multiple sclerosis in mice, but their molecular target has hitherto not been reported. In this study, a chemical proteomics approach using photo-affinity crosslinking was developed to determine a target for the circular peptide [T20K]kalata B1. Using this prototypic nature-derived peptide enabled the identification of a possible functional modulation of 14-3-3 proteins. This biochemical interaction was validated via competition pull down assays as well as a cellular reporter assay indicating an effect on 14-3-3-dependent transcriptional activity. As proof of concept, the presented approach may be applicable for target elucidation of various cyclic peptides and mini-proteins, in particular cyclotides, which represent a promising class of molecules in drug discovery and development.
Transport and Economic Performance, a Survey of Developing Countries

The document addresses the relationship between transport and economic performance and considers the implications of these linkages for sector policy. It reviews the existing literature on the linkages between transport and economic performance in developing countries and identifies some of the areas where World Bank policy interventions need rethinking. Section 1 discusses a number of methodological issues which arise in analyzing the linkages between transport and production. Section II reviews the literature on the linkages between transport and production. Section III shifts the focus to how transport affects personal welfare. Section IV looks at the evidence concerning the role of transport in international trade. Section V turns to the input linkages and looks at the public finance effects of the transport sector. The paper ends with a discussion of the policy implications in Section VI.
A mutation in the putative Mg(2+)-binding site of Gs alpha prevents its activation by receptors

The properties of a Gs alpha mutant with an Asn substituted for Ser at position 54, designated mutant 54Asn alpha s, were studied after expression in S49 alpha s-deficient (cyc-) cells. Ser-54 in alpha s is comparable to Ser-17 in Ras, which is involved in binding Mg2+ associated with bound nucleotide. 54Asn alpha s did not restore either hormone-induced cyclic AMP production in intact cyc- cells or hormone-induced adenylyl cyclase activation in membranes isolated from these cells. The defect was a failure of ligand-bound receptor to activate 54Asn alpha s, since the mutant protein retained the ability to activate adenylyl cyclase in isolated membranes in the presence of GTP or GTP gamma S. Guanine nucleotide regulation of mutant alpha s suggested that it has increased guanine nucleotide exchange rates and an increased preference for diphosphates over triphosphates. Hormone stimulation magnified the preference of 54Asn alpha s for diphosphates, which could account for its inability to be activated by receptor. The properties of this mutant are discussed in terms of similarities to and differences with the analogous RasH mutant, which has been shown to interfere with endogenous Ras function in cells.
Risk and Uncertainty in Central Bank Signals: An Analysis of Monetary Policy Committee Minutes

This paper considers the signalling aspect of monetary policy. We introduce a heuristic framework for the study of signal uncertainty, and use this to analyse the signal uncertainty implicit in the communications of the Bank of England's Monetary Policy Committee (MPC). Our findings suggest that frequencies of key terms expressing signal uncertainty in MPC minutes may either reflect the degree of confidence implicit in MPC deliberations, or offer evidence for the presence of an irreducible kind of signal uncertainty that shows up as white noise, casting doubt on the soundness of the various qualitative uncertainty indices found in the literature.
Functional and structural implications of the complement factor H Y402H polymorphism associated with age-related macular degeneration.

PURPOSE A Tyr-to-His (Y402H) sequence variant in the factor H (FH) and factor H-like protein (FHL-1) gene is strongly associated with an increased susceptibility for age-related macular degeneration (AMD). The purpose of this study was to understand how the Y402H variant in FH/FHL-1 contributes to the pathogenesis of AMD and, in particular, whether interactions mediated by FH/FHL-1, including binding to C-reactive protein (CRP), group A streptococcal M protein (GAS M6), heparin, and retinal pigment epithelial cells (RPE), are affected. METHODS FH was purified from sera of patients homozygous for FH(Y402) or (H402), and recombinant FH fragments representing FHL-1 were generated. Proteins were analyzed for binding to CRP, GAS M6, heparin, and RPE cells. RESULTS Binding of the FH and FH1 to seven polymorphic variants to CRP and M protein was reduced. The variant did not influence the interaction of FH with heparin but did reduce binding of FHL-1. Binding of the FH and FHL-1 polymorphic variant to RPE cells was not affected. CONCLUSIONS The FH Y402H polymorphism associated with AMD causes a reduction in binding of FH and FHL-1 to CRP and M protein. Both variants show comparable binding to RPE cells, indicating that AMD is unlikely to manifest as a result of impaired host cell-surface recognition. The decreased interaction between FH and CRP, which is essential for the anti-inflammatory function of CRP, provides a possible pathophysiological explanation for the association of the Y402H variant with AMD.
In vitro virulence marker: growth of dengue-2 virus in human leukocyte suspension cultures

We wished to find a simple, biologically relevant method to evaluate the virulence of dengue viruses for human beings. Since cells of mononuclear phagocyte lineage may be important sites of dengue infection in primates, we evaluated the permissiveness of these cells to dengue virus as a correlate of virus virulence. Two wild-type, large-plaque, monkey-virulent dengue-2 virus strains and two small-plaque, monkey-avirulent dengue-2 virus strains were evaluated for their ability to replicate in human peripheral blood leukocyte cultures supplemented with enhancing antibody. One of the small-plaque strains was demonstrated to have reduced virulence for man. Wild-type dengue-2 viruses replicated readily in peripheral blood leukocyte suspension cultures, whereas small-plaque dengue-2 strains did not. Differences between our data and results obtained by other workers employing adherent peripheral blood leukocytes are discussed. Antibody-enhanced growth of dengue virus in suspension cultures of human peripheral blood leukocytes gives promise of being a simple in vitro system for characterizing dengue virus virulence.
Context‐Dependent Intergenerational Effects: The Interaction between Past and Present Environments and Its Effect on Population Dynamics

Intergenerational effects arise when parents’ actions influence the reproduction and survival of their offspring and possibly later descendants. Models suggest that intergenerational effects have important implications for both population dynamical patterns and the evolution of life‐history traits. However, these will depend on the nature and duration of intergenerational effects. Here we show that manipulating parental food environments of soil mites produced intergenerational effects that were still detectable in the life histories of descendents three generations later. Intergenerational effects varied in different environments and from one generation to the next. In low‐food environments, variation in egg size altered a trade‐off between age and size at maturity and had little effect on the size of eggs produced in subsequent generations. Consequently, intergenerational effects decreased over time. In contrast, in high‐food environments, variation in egg size predominantly influenced a trade‐off between fecundity and adult survival and generated increasing variation in egg size. As a result, the persistence and significance of intergenerational effects varied between high‐ and low‐food environments. Context‐dependent intergenerational effects can therefore have complex but important effects on population dynamics.
Going Public: An Empirical Investigation of U.S. Bound Israeli IPOs

Between 1985–2003, more than 120 Israeli companies went public in the U.S., bringing the accumulated number of U.S. bound, Israeli initial public offerings (IPOs) to a figure greater than all other foreign countries combined. In this study, we compare the short and long run performance of Israeli IPOs to that of similar international and U.S. IPOs. Holding all else equal, we find that Israeli IPOs are significantly less underpriced than their local and foreign counterparts. As we examine the characteristics of Israeli issuers, we find that they differ than those of other foreign and local issuers in some important dimensions that compensate investors for information asymmetry and risk. First, compared to their home market capitalization size, U.S. bound Israeli IPOs, are significantly larger than the IPOs conducted by their foreign counterparts. Second, Israeli issuers tend to perform better than other foreign and U.S. local IPOs during our entire period of observation. Third, to a large extent, the Israeli firms in our sample have products, licensing or franchising relationships or venture capital funds with strong roots in the U.S. prior to the IPO. And fourth, the relevant investor community of Israeli IPOs, at least at the early stages, is small and overwhelmingly American. Our findings are consistent with prior studies documenting that firms raising capital outside of their domicile country are typically a select group of high quality firms in need of external financing that cannot be sufficiently provided in their home market.
Femto-to-Femto (F2F) communication: The next evolution step in 5G wireless backhauling

The future 5G cellular networks are expected to support several-fold increase in data traffic and number of devices, and provide a very low latency and gigabit-rate data services. millimeter Wave (mmWave) communication (30–300 GHz) is proposed to be an important part of the 5G cellular networks to fulfill these requirements. With most of the high data rate demands originating from indoor User Equipments (UEs), conventional wired backhaul links prove to be a major bottleneck. Hence, mmWave wireless backhaul links are explored at Femto Base Stations (FBSs). In order to derive maximum benefit of mmWave backhaul links, efficient resource (data slots) utilization is necessary. Proper scheduling of mmWave backhaul links will help to achieve the same. In this paper, we propose a novel FBS-to-FBS (F2F) communication scheme which not only helps in offloading the data traffic from the Micro Base Station (MiBS) but also can act as a relay link for the other FBSs for routing the backhaul traffic to the MiBS. We also propose a solution to concurrently schedule mmWave wireless backhaul links to increase the resource utilization considering the coexistence of both FBS-to-MiBS (F2M) and F2F links. Our proposed solution consists of two parts — first, it determines which backhaul links can be scheduled concurrently by finding the upper bound for the interfering distance based on the alignment of different lobes of the directional antennas. Second, the transmit power is throttled to match the Quality of Service (QoS) requirements of each link aiming to further control the interference and to increase the number of concurrent transmissions. The benefits of the proposed solution are studied and compared with the Time Division Multiple Access (TDMA) and random scheduling schemes using extensive simulations.
Safe Guidance for a Walking-Assistant Robot Using Gait Estimation and Obstacle Avoidance

This paper presents a motion control design for a walking-assistant robot by combining passive-compliant behavior and active obstacle avoidance. The proposed method recognizes the intended motion for a user using gait movement and the applied force of a hand. A passive-compliant motion control is developed that allows the user to safely walk with the robot. The obstacle avoidance controller actively controls the velocity to guide the user in a direction that avoids collisions. A shared-control scheme combines active obstacle avoidance and passive-compliant motion commands. The experimental results verify the effectiveness of the proposed method and show that the robot allows a user to walk safely in a complex environment. A questionnaire survey of elderly users shows that the proposed design for a walking-assistant robot gives satisfactory performance.
ERP system implementation announcements: does the market cheer or jeer the adopters and vendors?

Purpose - – The purpose of the study is to examine the implementation of Enterprise Resource Planning (ERP) on the announcement of firms’ stock market returns. The authors investigate the stock market reaction on ERP adopters and ERP vendor firms in the USA during 1990-2010. The study examines firm- and non-firm-specific factors including the role of the financial analyst in explaining the determinants of the cumulative abnormal returns surrounding ERP announcements of adopting firms. Design/methodology/approach - – Data on ERP system implementation announcements of 112 US firms for the period 1990-2010 were collected from LexisNexis Academics. The authors estimate abnormal returns using an event study methodology for each of the ERP announcements based on the Fama–French three-factor and Fama–French-momentum four-factor models for ERP adopters and for vendors. Subsequently, the authors explain the determinants of abnormal returns in terms of firm and non-firm behavioral variables using cross-section regression methodology. Findings - – The empirical results establish that cumulative abnormal returns of US firms on ERP system implementation announcements are positive, signifying that investors view this decision positively and that ERP implementation contributes to enhanced business value in the future. On the contrary, the impact of ERP announcements on vendors is muted. We find that the extent of financial analyst coverage negatively impacts abnormal returns, while the extent of stock market liquidity has a significant positive impact on abnormal returns. Research limitations/implications - – This study is based on a sample of ERP implementing firms which are predominantly large firms and on technology provided by one vendor that is predominantly monopolistic. Practical implications - – Firms’ attitudes toward implementing an ERP system for future efficiency gains and the implications on the stock market (and indirectly, on the cost of equity of adopters) provide valuable insights for firms and stock markets. Originality/value - – This study brings clarity to the debate on stock market impacts of ERP implementation announcements – stock markets cheer such announcements. The study also contributes to the literature by examining firm-specific factors (such as performance, size and leverage) and non-firm-specific factors (such as market risk and analyst coverage) in explaining the determinants of abnormal returns of firms announcing ERP investment.