Miracle-dz/UniFAR-FTUs huggingface dataset:
DrugPred: A Structure-Based Approach To Predict Protein Druggability Developed Using an Extensive Nonredundant Data Set

Judging if a protein is able to bind orally available molecules with high affinity, i.e. if a protein is druggable, is an important step in target assessment. In order to derive a structure-based method to predict protein druggability, a comprehensive, nonredundant data set containing crystal structures of 71 druggable and 44 less druggable proteins was compiled by literature search and data mining. This data set was subsequently used to train a structure-based druggability predictor (DrugPred) using partial least-squares projection to latent structures discriminant analysis (PLS-DA). DrugPred performed well in discriminating druggable from less druggable binding sites for both internal and external predictions. The method is robust against conformational changes in the binding site and outperforms previously published methods. The superior performance of DrugPred is likely due to the size and composition of the training set which, in contrast to most previously developed methods, only contains cavities that have evolved to bind a natural ligand.
Development of the Public-Private Wage Differential in the Netherlands 1979-2009

The public premium has disappeared during the 1980s when public-private wage linkages have been abandoned. Although the balance was partly restored recently when wages in Education improved, the public premium was still -2% in 2009. On average, public sector wages are unfavourable for men, people over 35 and higher educated. Most public-sector women also earn a premium over private-sector women, but not in all cases: not in 1989, nor higher educated women in recent years. This discussion paper documents in much detail the long-run evolution of the wage gap between the private and the public sector in the Netherlands.1 It estimates and decomposes wage equations for six different years stretching over a long period (1979, 1989, 1996, 2002, 2004 and 2009). The raw public wage advantage fell from 15 per cent in 1979 to 8 per cent in 1989, subsequently doubled to 16-17 per cent in 1996 and 2002, and then fell back again to 11-12 per cent in 2004 and 2009. This raw pay gap reflects both a composition effect (the two sectors are made up of different types of workers) and a reward effect (the sectors pay different rewards to the same type of workers). This reward effect is the prime focus of this paper. A positive reward effect means that public-sector workers are comparatively better paid, while a negative outcome implies a wage penalty for working in the public sector. Oaxaca-Blinder decomposition is used to split between the two above effects. The reward effect appears relatively high in 1979 (4 per cent) but falls considerably in the eighties and is actually negative in 1989 (minus 7 per cent), turning a premium into a considerable penalty in ten years’ time. In the 1990s the balance is restored as the public premium sticks around zero in 1996 and 2002. But then the public premium rapidly becomes negative again, resulting in a 3 per cent penalty in 2004. A slight improvement since then brings the public penalty back to around 2 per cent in 2009. A robustness check using other methods gives the same results.
Exchange Rate and Stock Price Interactions in European Emerging Financial Markets Before and after the Euro

In this paper, we investigate price interactions between two main components of European emerging financial markets, namely the foreign exchange market and the stock market, before and after the adoption of the Euro by most European Union (EU) economies. We estimate and test a bivariate vector autoregressive model using daily observations on the stock price index and nominal exchange rate for Hungary, Czech Republic and Poland, during 2/1/1995 - 31/12/1998 for the pre-Euro period and 1/1/1999 - 31/12/2003 for the Euro period. We find that for the pre-Euro period, stock prices unidirectionally Granger-cause exchange rates in Hungary only; in the Czech Republic and Poland, mutually reinforcing interactions between exchange rates and stock prices seem to exist. During the Euro period, exchange rates unidirectionally Granger-cause stock prices in all the three sample economies. We also find higher positive correlations among the stock markets in Hungary, Czech and Poland during the Euro period than is the case in the pre-Euro period. Similar results are obtained with respect to the foreign exchange markets. These findings are consistent with the dynamic nature of the transition process, suggesting that causality and correlations are much more easier to detect as the markets become more integrated with the EU.
Resource Allocation for Downlink NOMA Systems: Key Techniques and Open Issues

This article presents advances in resource allocation for downlink non-orthogonal multiple access (NOMA) systems, focusing on user pairing and power allocation algorithms. The former pairs the users to obtain high capacity gain by exploiting the channel gain difference between the users, while the latter allocates power to users in each cluster to balance system throughput and user fairness. Additionally, the article introduces the concept of cluster fairness and proposes the divide-and-next-largest-difference-based user pairing algorithm to distribute the capacity gain among the NOMA clusters in a controlled manner. Furthermore, performance comparison between multiple-input multiple-output NOMA (MIMO-NOMA) and MIMO orthogonal multiple access (MIMO-OMA) is conducted when users have pre-defined quality of service. Simulation results are presented, which validate the advantages of NOMA over OMA. Finally, the article provides avenues for further research on resource allocation for downlink NOMA.
Doxorubicin induces expression of multidrug resistance‐associated protein 1 in human small cell lung cancer cell lines by the c‐jun N‐terminal kinase pathway

Multidrug resistance (MDR) is a major impediment to successful chemotherapy for lung cancer. Overexpression of multidrug resistance‐associated protein 1 (MRP1) appears to be involved in MDR development in lung cancer cells. A number of chemotherapeutic agents including doxorubicin (DOX) were reported to induce MRP1 expression in human lung cancer cells. In our study, we investigated the mechanism by which DOX induces MRP1 expression in human small cell lung cancer (SCLC) cell lines, GLC4 and NCI‐H82. These cells expressed MRP1 protein at low levels and were sensitive to DOX. Doxorubicin at 50 nM induced a marked increase in MRP1 expression in 24 hr, and stimulated c‐jun N‐terminal kinase (JNK) activity. Treatment with a JNK inhibitor, SP600125, significantly inhibited MRP1 induction. Furthermore, transfection with JNK1 and JNK2 antisense oligonucleotides markedly inhibited DOX‐induced MRP1 expression. Chromatin immunoprecipitation assays revealed an enhanced recruitment of phosphorylated c‐jun to the MRP1 promoter containing the AP‐1 site upon DOX stimulation, which was inhibited by pretreatment with SP600125. Surprisingly, GLC4 cells exposed to DOX for 24 hr maintained increased MRP1 expression and resistance to DOX for at least 3 weeks. Pretreatment with SP600125 before DOX stimulation blocked the appearance of the MDR phenotype as well as MRP1 induction in GLC4 cells. These findings suggest that JNK activation may play an essential role for the induction of MRP1 protein in human SCLC cells by chemotherapeutic agents and that combined treatment of a JNK inhibitor with anticancer drugs may prevent the development of MDR by the abrogation of MRP1 induction. © 2005 Wiley‐Liss, Inc.
Forecasting Fiji's Exports and Imports, 2003-2020

Purpose - The purpose of this paper is to forecast Fiji's exports and imports for the period 2003-2020. Design/methodology/approach - To achieve the goal of this paper, the autoregressive moving average with explanatory variables (ARMAX) model was applied. To this end, the paper drew on the published export demand model and the import demand model of Narayan and Narayan for Fiji. Findings - The paper's main findings are: Fiji's imports will outperform exports over the 2003-2020 period; and current account deficits will escalate to be around F$934.4 million on average over the 2003-2020 period. Originality/value - Exports and imports are crucial for macroeconomic policymaking. It measures the degree of openness of a country and it signals the trade balance and current account balances. This has implications for inflation and exchange rate. By forecasting Fiji's exports and imports, the paper provides policy makers with a set of information that will be useful for devising macroeconomic policies.
Redundant and Nonredundant Functions of ATM and H2AX in αβ T-Lineage Lymphocytes

The ataxia telangiectasia mutated (ATM) kinase and H2AX histone tumor suppressor proteins are each critical for maintenance of cellular genomic stability and suppression of lymphomas harboring clonal translocations. ATM is the predominant kinase that phosphorylates H2AX in chromatin around DNA double-strand breaks, including along lymphocyte Ag receptor loci cleaved during V(D)J recombination. However, combined germline inactivation of Atm and H2ax in mice causes early embryonic lethality associated with substantial cellular genomic instability, indicating that ATM and H2AX exhibit nonredundant functions in embryonic cells. To evaluate potential nonredundant roles of ATM and H2AX in somatic cells, we generated and analyzed Atm-deficient mice with conditional deletion of H2ax in αβ T-lineage lymphocytes. Combined Atm/H2ax inactivation starting in early-stage CD4–/CD8– thymocytes resulted in lower numbers of later-stage CD4+/CD8+ thymocytes, but led to no discernible V(D)J recombination defect in G1 phase cells beyond that observed in Atm-deficient cells. H2ax deletion in Atm-deficient thymocytes also did not affect the incidence or mortality of mice from thymic lymphomas with clonal chromosome 14 (TCRα/δ) translocations. Yet, in vitro-stimulated Atm/H2ax-deficient splenic αβ T cells exhibited a higher frequency of genomic instability, including radial chromosome translocations and TCRβ translocations, compared with cells lacking Atm or H2ax. Collectively, our data demonstrate that both redundant and nonredundant functions of ATM and H2AX are required for normal recombination of TCR loci, proliferative expansion of developing thymocytes, and maintenance of genomic stability in cycling αβ T-lineage cells.
Why Do Insiders Hedge Their Ownership? An Empirical Examination

type="main"> We examine different types of derivative instruments used by corporate insiders. These instruments are more likely to be used when there is greater insider ownership and greater capital market scrutiny. While these instruments may be allowed by boards to mitigate agency problems relating to overvalued equity and high equity-based pay, our evidence regarding forwards and collars is more consistent with the strategic timing of transactions by insiders. Exchange funds appear to be primarily used for diversification and are associated with higher personal tax rates. Collectively, our results suggest that there is significant heterogeneity in the motivation to use these instruments.
Correlated Demand Shocks and Price Wars During Booms

The supergame-theoretic model of price competition (Rotemberg and Saloner (1986)) is re-examined in the case of serially correlated demand shocks. The equilibrium price is shown to exhibit the same counter-cyclical movement as in the i.i. d. case, if the discount factor and the number of firms satisfy certain relationship.
PET of Adoptively Transferred Chimeric Antigen Receptor T Cells with 89Zr-Oxine

Chimeric antigen receptor (CAR) T cell therapy is a promising clinical approach for reducing tumor progression and prolonging patient survival. However, improvements in both the safety and the potency of CAR T cell therapy demand quantitative imaging techniques to determine the distribution of cells after adoptive transfer. The purpose of this study was to optimize 89Zr-oxine labeling of CAR T cells and evaluate PET as a platform for imaging adoptively transferred CAR T cells. Methods: CAR T cells were labeled with 0–1.4 MBq of 89Zr-oxine per 106 cells and assessed for radioactivity retention, viability, and functionality. In vivo trafficking of 89Zr-oxine–labeled CAR T cells was evaluated in 2 murine xenograft tumor models: glioblastoma brain tumors with intracranially delivered IL13Rα2-targeted CAR T cells, and subcutaneous prostate tumors with intravenously delivered prostate stem cell antigen (PSCA)–targeted CAR T cells. Results: CAR T cells were efficiently labeled (75%) and retained more than 60% of the 89Zr over 6 d. In vitro cytokine production, migration, and tumor cytotoxicity, as well as in vivo antitumor activity, were not significantly reduced when labeled with 70 kBq/106 cells. IL13Rα2-CAR T cells delivered intraventricularly were detectable by PET for at least 6 d throughout the central nervous system and within intracranial tumors. When intravenously administered, PSCA-CAR T cells also showed tumor tropism, with a 9-fold greater tumor-to-muscle ratio than for CAR-negative T cells. Conclusion: 89Zr-oxine can be used for labeling and imaging CAR T cells while maintaining cell viability and function. On the basis of these studies, we conclude that 89Zr-oxine is a clinically translatable platform for real-time assessment of cell therapies.
Identification of Coxiella burnetii Type IV Secretion Substrates Required for Intracellular Replication and Coxiella-Containing Vacuole Formation

ABSTRACT Coxiella burnetii, the etiological agent of acute and chronic Q fever in humans, is a naturally intracellular pathogen that directs the formation of an acidic Coxiella-containing vacuole (CCV) derived from the host lysosomal network. Central to its pathogenesis is a specialized type IVB secretion system (T4SS) that delivers effectors essential for intracellular replication and CCV formation. Using a bioinformatics-guided approach, 234 T4SS candidate substrates were identified. Expression of each candidate as a TEM-1 β-lactamase fusion protein led to the identification of 53 substrates that were translocated in a Dot/Icm-dependent manner. Ectopic expression in HeLa cells revealed that these substrates trafficked to distinct subcellular sites, including the endoplasmic reticulum, mitochondrion, and nucleus. Expression in Saccharomyces cerevisiae identified several substrates that were capable of interfering with yeast growth, suggesting that these substrates target crucial host processes. To determine if any of these T4SS substrates are necessary for intracellular replication, we isolated 20 clonal T4SS substrate mutants using the Himar1 transposon and transposase. Among these, 10 mutants exhibited defects in intracellular growth and CCV formation in HeLa and J774A.1 cells but displayed normal growth in bacteriological medium. Collectively, these results indicate that C. burnetii encodes a large repertoire of T4SS substrates that play integral roles in host cell subversion and CCV formation and suggest less redundancy in effector function than has been found in the comparative Legionella Dot/Icm model.
Exploring Temporal Preservation Networks for Precise Temporal Action Localization

Temporal action localization is an important task of computer vision. Though a variety of methods have been proposed, it still remains an open question how to predict the temporal boundaries of action segments precisely. Most works use segment-level classifiers to select video segments pre-determined by action proposal or dense sliding windows. However, in order to achieve more precise action boundaries, a temporal localization system should make dense predictions at a fine granularity. A newly proposed work exploits Convolutional-Deconvolutional-Convolutional (CDC) filters to upsample the predictions of 3D ConvNets, making it possible to perform per-frame action predictions and achieving promising performance in terms of temporal action localization. However, CDC network loses temporal information partially due to the temporal downsampling operation. In this paper, we propose an elegant and powerful Temporal Preservation Convolutional (TPC) Network that equips 3D ConvNets with TPC filters. TPC network can fully preserve temporal resolution and downsample the spatial resolution simultaneously, enabling frame-level granularity action localization with minimal loss of time information. TPC network can be trained in an end-to-end manner. Experiment results on public datasets show that TPC network achieves significant improvement in both per-frame action prediction and segment-level temporal action localization.
Resource Allocation for OFDM Based Cognitive Radio System

Cognitive Radio (CR) is a novel concept for improving the utilization of the radio spectrum. It is a software controlled radio that senses the unused frequency spectrum at any time from the wide but congested wireless radio spectrum. This promises the efficient use of scarce radio resources. Orthogonal Frequency Division Multiplexing (OFDM) is a reliable transmission scheme for Cognitive Radio Systems which provides flexibility in allocating the radio resources in dynamic environment. It also assures no mutual interference among the CR radio channels which are just adjacent to each other, making it one of the best schemes to be used in CR systems. Allocation of radio resources is a major challenge in cognitive radio systems. In a dynamic environment, many parameters and situations have to be considered which affect the total data rate of the system. A Secondary users (CRUs/SUs) may coexist with the Primary user (PU) either on Conservative basis or on a more aggressive basis which allows secondary transmissions as long as the induced interference to the PU is below acceptable level. In this we have considered Uplink cognitive radio system heaving one PU coexists with M SUs and A Downlink of an Multi User Orthogonal Frequency Division Multiplexing CR system with one base station (BS) serving one PU and K SUs. We focused on the design on the design and analysis of subcarrier and power allocation scheme under imperfect CSI for cognitive OFDM systems. A two – step Algorithm for bit rate is proposed to obtain the (1) subcarrier allocation to secondary users and (2) bits, power allocation on subcarriers. The algorithms attempt to maximize the total throughput of the CR system (secondary users) subject to the total power constraint of the CR system and tolerable interference from and to the licensed band (primary users).
POWER AND POLICY MAKING: THE DEVELOPMENT OF AN R & D STANDARD

This paper addresses the question of policy-making by such bodies as the UK Accounting Standards Committee (ASC) and suggests that an understanding of the nature of power is a necessary prerequisite to rigorous analysis of the political process. Using the example of SSAP 13, the paper investigates the applicability of political methodologies to attempt to understand and analyse ASC behaviour. The paper attempts to provide: (a) a deeper understanding of the issues which determined the outcome of the R & D standard; (b) support for the importance of the political science experience in this field; and (c) suggestions on how future research may be formulated and developed.
On the Change in the Austrian Business Cycle

This paper analyses the change in the Austrian business cycle over time using data back to 1954. The change in the cyclical pattern is captured using a non-linear univariate structural time series model where the time of the break point is estimated. Results for GDP series suggest a break in the frequency of the cycle and in the parameter covering the variance of the disturbances of the cycle taking place in the mid 1970s and early 1980s, respectively. Using data for GDP components a break in these variables is found too, but the timing of the break differs among the series. In a further step the paper assesses the relevance of these findings for forecasting purposes. It is shown that during certain periods the out-of-sample forecasting performance of GDP does improve when a break in one of the two parameters is explicitly modelled.
Private foreign asset accumulation, not just capital flight: Evidence from the Philippines

External debt problems have been accompanied in many developing countries with large private capital outflows. The latter phenomenon is usually identified in the literature as ‘capital flight’. This article argues that private foreign asset accumulation is a more appropriate term and compares a great variety of definitions and measurement methods and applies these to Philippine data for 1971–88. Outcomes show striking differences in assessment of the magnitude of the phenomenon. In the preferred definition of this study applied to the Philippines, unrecorded workers remittances from abroad, a factor omitted in other studies, represent a major source of foreign exchange earnings which indirectly support private foreign asset accumulation. Other definitions appear to severely underestimate private capital outflows. Econometric evidence on the causes of private foreign asset acquisition shows a strong sensitivity to the applied definition. Regression analysis for six alternative definitions shows that the ex.
Evidence-Based Guideline of the German Nutrition Society: Carbohydrate Intake and Prevention of Nutrition-Related Diseases

The relative contribution of nutrition-related chronic diseases to the total disease burden of the society and the health care costs has risen continuously over the last decades. Thus, there is an urgent necessity to better exploit the potential of dietary prevention of diseases. Carbohydrates play a major role in human nutrition – next to fat, carbohydrates are the second biggest group of energy-yielding nutrients. Obesity, type 2 diabetes mellitus, dyslipoproteinaemia, hypertension, metabolic syndrome, coronary heart disease and cancer are wide-spread diseases, in which carbohydrates could have a pathophysiologic relevance. Correspondingly, modification of carbohydrate intake could have a preventive potential. In the present evidence-based guideline of the German Nutrition Society, the potential role of carbohydrates in the primary prevention of the named diseases was judged systematically. The major findings were: a high carbohydrate intake at the expense of total fat and saturated fatty acids reduces the concentrations of total, LDL and HDL cholesterol. A high carbohydrate consumption at the expense of polyunsaturated fatty acids increases total and LDL cholesterol, but reduces HDL cholesterol. Regardless of the type of fat being replaced, a high carbohydrate intake promotes an increase in the triglyceride concentration. Furthermore, a high consumption of sugar-sweetened beverages increases the risk of obesity and type 2 diabetes mellitus, whereas a high dietary fibre intake, mainly from whole-grain products, reduces the risk of obesity, type 2 diabetes mellitus, dyslipoproteinaemia, cardiovascular disease and colorectal cancer at varying evidence levels. The practical consequences for current dietary recommendations are presented.
Household production and taxation in the stochastic growth model

We estimate a dynamic general equilibrium model of the U.S. economy that includes an explicit household production sector. We use these estimates to investigate two issues. First, we analyze how well the model accounts for aggregate fluctuations. Second, we use the model to study the effects of fiscal policy. We find household production has a significant impact, and reject a nested specification in which changes in the home production technology do not matter for market variables. The model generates very different predictions for the effects of tax changes than similar models without home production.