Miracle-dz/UniFAR-FTUs huggingface dataset:
Linifanib versus Sorafenib in patients with advanced hepatocellular carcinoma: results of a randomized phase III trial.

PURPOSE This open-label phase III trial evaluated efficacy and tolerability of linifanib versus sorafenib in patients with advanced hepatocellular carcinoma (HCC) without prior systemic therapy. PATIENTS AND METHODS Patients were randomly assigned in a 1:1 ratio to linifanib 17.5 mg once daily or sorafenib 400 mg twice daily. Patients were stratified by region (Outside Asia, Japan, and rest of Asia), Eastern Cooperative Oncology Group performance score (ECOG PS; 0 or 1), vascular invasion or extrahepatic spread (yes or no), and hepatitis B virus (HBV) infection (yes or no). The primary end point of the study was overall survival (OS). Secondary end points were time to progression (TTP) and objective response rate (ORR) per RECIST v1.1. RESULTS We randomly assigned 1,035 patients (median age, 60 years; Asian, 66.6%; ECOG PS 0, 65.2%; HBV, 49.1%; vascular invasion or extrahepatic spread, 70.1%). Median OS was 9.1 months on the linifanib arm (95% CI, 8.1 to 10.2) and 9.8 months on the sorafenib arm (95% CI, 8.3 to 11.0; hazard ratio [HR], 1.046; 95% CI, 0.896 to 1.221). For prespecified stratification subgroups, OS HRs ranged from 0.793 to 1.119 and the 95% CI contained 1.0. Median TTP was 5.4 months on the linifanib arm (95% CI, 4.2 to 5.6) and 4.0 months on the sorafenib arm (95% CI, 2.8 to 4.2; HR, 0.759; 95% CI, 0.643 to 0.895; P = .001). Best response rate was 13.0% on the linifanib arm versus 6.9% on the sorafenib arm. Grade 3/4 adverse events (AEs); serious AEs; and AEs leading to discontinuation, dose interruption, and reduction were more frequent with linifanib (all P < .001). CONCLUSION Linifanib and sorafenib had similar OS in advanced HCC. Predefined superiority and noninferiority OS boundaries were not met for linifanib and the study failed to meet the primary end point. TTP and ORR favored linifanib; safety results favored sorafenib.
Economic analysis of profitability and competitiveness of sugarcane enterprise in Nigeria

In Nigeria, cultivation of Industrial Sugarcane has suffered a serious setback due to poor performance of government established and owned sugar companies. Arising from over-dependence on sugar importation, development in the Nigerian sugar industry has been very slow for the past three decades while the domestic supply of sugar had lagged behind the demand for the product, inspite of the country’s comparative advantages for sugarcane production. This study is therefore necessary to examine profitability and competitiveness of sugarcane enterprises for attracting private investment and employment generation in the country. The study employed financial and economic indicators and the value chain approach in analyzing primary data collected in a sample survey of various actors across the sugarcane value chain. Results of the study revealed that every stage of the commodity chain is profitable. Domestic Resource Cost (DRC) Indices ranged from 1.8 for medium scale and 2.3for small scale operators. Thus sugarcane production is not internationally competitive. To develop the industry, investment in infrastructure and new innovative processing technology is required for the modernization and the expansion of local processing industries. Key words: Agro-processing, investment, employment, income.
Croonian Lecture: The Antidiuretic Hormone and the Factors which Determine Its Release

When water is given under specified conditions to the living dog, there is a lag of 15 min. between the peak of the animal's water load and the maximum rate of water excretion by the kidney. The diuresis is inhibited by emotional stress, the inhibition being of post-pituitary origin and itself suppressed by an immediately preceding injection of adrenaline or tyramine. Reasons are given for the view that this action of adrenaline is independent of any accompanying increase in arterial pressure or cerebral blood flow. The intracarotid injection (short period, 5 to 20 sec.) of 'hypertonic' solutions of sodium chloride (but not of urea) causes a similar inhibition, the response being diminished by some 90% after removal of the posterior lobe. The response to sodium chloride is shown to be osmotically determined, and the term 'osmoreceptors' has therefore been introduced as descriptive of the autonomic receptive elements with which the neurohypophysis is functionally linked. The receptors are somewhere in the vascular bed of the internal carotid artery. The results of long-period (10 and 40 min.) intracarotid infusions and of the short-period injections, show that the osmoreceptors are freely permeable to urea, less freely permeable to dextrose and relatively impermeable to sodium chloride and sucrose. The local increase in osmotic pressure required in the 40 min. infusions (unilateral) to reduce the urine flow during water diuresis to about 10% of its maximum, is some 2% only; and assay of such response shows it to have a post-pituitary extract equivalence of $1\mu \text{U/sec. }$ $(0.5\times 10^{-9}$ $\text{g./sec.}$ in terms of the standard powder). These facts give an intelligible interpretation to the time-lag between the peak of the water load and the peak of diuresis. Water diuresis, therefore, is fitly and accurately described as a condition of physiological diabetes insipidus, the antidiuretic secretion of the neurohypophysis being a hormone in the sense that its liberation is continually governed by the concentration of sodium chloride, and of other osmotically active substances, in the arterial plasma.
Nonparametric Bayesian Estimation of Reliabilities in a Class of Coherent Systems

Usually, methods evaluating system reliability require engineers to quantify the reliability of each of the system components. For series and parallel systems, there are limited options to handle the estimation of each component's reliability. This study examines the reliability estimation of complex problems of two classes of coherent systems: series-parallel, and parallel-series. In both of the cases, the component reliabilities may be unknown. We developed estimators for reliability functions at all levels of the system (component and system reliabilities). The main assumption required is that, for all the distributions of the components of a particular system, the sets of discontinuity points have to be disjoint. Nonparametric Bayesian estimators of all sub-distribution and distribution functions are derived, and a Dirichlet multivariate process as a prior distribution is considered for the nonparametric Bayesian estimation of all distributions. For illustration, two simulated numerical examples are presented. The estimators are s-consistent, and one may observe from the examples that they have good performance. Our estimator can accommodate continuous failure distributions, as well as distributions with mass points.
Learning Slowness in a Sparse Model of Invariant Feature Detection

Primary visual cortical complex cells are thought to serve as invariant feature detectors and to provide input to higher cortical areas. We propose a single model for learning the connectivity required by complex cells that integrates two factors that have been hypothesized to play a role in the development of invariant feature detectors: temporal slowness and sparsity. This model, the generative adaptive subspace self-organizing map (GASSOM), extends Kohonen’s adaptive subspace self-organizing map (ASSOM) with a generative model of the input. Each observation is assumed to be generated by one among many nodes in the network, each being associated with a different subspace in the space of all observations. The generating nodes evolve according to a first-order Markov chain and generate inputs that lie close to the associated subspace. This model differs from prior approaches in that temporal slowness is not an externally imposed criterion to be maximized during learning but, rather, an emergent property of the model structure as it seeks a good model of the input statistics. Unlike the ASSOM, the GASSOM does not require an explicit segmentation of the input training vectors into separate episodes. This enables us to apply this model to an unlabeled naturalistic image sequence generated by a realistic eye movement model. We show that the emergence of temporal slowness within the model improves the invariance of feature detectors trained on this input.
The Position-Aware-Market: Optimizing Freight Delivery for Less-Than-Truckload Transportation

The increasing competition faced by logistics carriers requires them to ship at lower cost and higher efficiency. In reality, however, many trucks are running empty or with a partial load. Bridging such residual capacity with real time transportation demand enhances the efficiency of the carriers. We therefore introduce the Position-Aware-Market (PAM), where transportation requests are traded in real time to utilize transportation capacities optimally. In this paper we mainly focus on the decision support system for the truck driver, which solves a profit- maximizing Pickup and Delivery Problem with Time Windows (PM-PDPTW). We propose a novel Recursive Branch-and-Bound algorithm that solves the problem optimally, and apply it to a Tabu-Search heuristic for larger problem instances. Simulations show that problems with up to 50 requests can be solved optimally within seconds. Larger problems with 200 requests can be solved approximately by Tabu-Search in seconds, retaining 60% of the optimal profit.
Bone Mass Cannot Be Predicted by Estimations of Frailty in Elderly Ambulatory Women

Background/Methods: High biological age, or frailty, a possible risk factor for fragility fracture, and its relation to known risk factors for fracture (low bone mineral density (BMD), low muscle strength, poor gait performance and poor balance, previous falls, previous fractures and future risk of falls) were investigated in 993 randomly selected 75-year-old women. Frailty, which has no accepted definition, was here defined as a subjective immediate impression of an individual’s general health appearance and was transferred into an arbitrary scale. 993 individuals were scored by at least one of four observers. Results: The frailty score and BMD were not correlated. A high frailty score was significantly correlated to poor gait (r = 0.53–0.59, p < 0.0001), poor balance (r = –0.49, p < 0.0001), low muscle strength (r = –0.25 to –0.41, p < 0.0001), low activity level (r = –0.43, p < 0.0001) and a high risk of falling (r = 0.24, p < 0.0001). The group of women who had experienced at least one fall the previous year had a higher frailty score (p < 0.0001) compared to those who had not. Women who had sustained a hip or femoral fracture after the age of 70 had a higher frailty score than women with no earlier fracture at all. Conclusions: Bone mass cannot be predicted by our subjective frailty score in elderly, ambulant women. Since a high frailty score correlates with factors that affect or are likely to affect fall propensity, this could indicate that a high frailty score is a risk factor for fracture, independent of bone mass. Frailty may be regarded as a complex risk factor, including several assessments that can be objectively measured. Whether estimation of frailty is a method to improve the assessment of the patient at risk for a fragility fracture is yet to be proven and can only be shown in a prospective study of fracture occurrence.
State Child Welfare Spending at a Glance: A Supplemental Report to the Cost of Protecting Vulnerable Children

This supplement to the main report The Cost of Protecting Vulnerable Children: Understanding Federal, State, and Local Child Welfare Spending (Occasional Paper 20) provides state-by-state data on spending for child welfare services in state fiscal year 1996. Charts detail sources of funding for child welfare services and spending by type of service, type of out-of-home placement, and type of child welfare expenditure.
Cluster analysis using multivariate mixed effects models

A common situation in the biological and social sciences is to have data on one or more variables measured longitudinally on a sample of individuals. A problem of growing interest in these areas is the grouping of individuals into one of two or more clusters according to their longitudinal behavior. Recently, methods have been proposed to deal with cases where individuals are classified into clusters through a linear model of mixed univariate effects deriving from a longitudinally measured variable. The method proposed in the current work deals with the case of clustering and then classification based on two or more variables measured longitudinally, through the fitting of non‐linear multivariate mixed effect models, and with consideration given to parameter estimation for balanced and unbalanced data using an EM algorithm. The application of the method is illustrated with an example in which the clusters are identified and the classification into clusters is compared with the true membership of individuals in one of two groups, which is known at the end of the follow‐up period. Copyright © 2009 John Wiley & Sons, Ltd.
Arg/Abl‐binding protein, a Z‐body and Z‐band protein, binds sarcomeric, costameric, and signaling molecules

ArgBP2 (Arg/Abl‐Binding Protein) is expressed at high levels in the heart and is localized in the Z‐bands of mature myofibrils. ArgBP2 is a member of a small family of proteins that also includes vinexin and CAP (c‐Cbl‐associated protein), all characterized by having one sorbin homology (SOHO) domain and three C‐terminal SH3 domains. Antibodies directed against ArgBP2 also react with the Z‐bodies of myofibril precursors: premyofibrils and nascent myofibrils. Expression in cardiomyocytes of plasmids encoding Yellow Fluorescent Protein (YFP) fused to either full length ArgBP2, the SOHO, mid‐ArgBP or the SH3 domains of ArgBP2 led to Z‐band targeting of the fusion proteins, whereas an N‐terminal fragment lacking these domains did not target to Z‐bands. Although ArgBP2 is not found in skeletal muscle cells, YFP‐ArgBP2 did target to Z‐bodies and Z‐bands in cultured myotubes. GST‐ArgBP2‐SH3 bound actin, α‐actinin and vinculin proteins in blot overlays, cosedimentation assays, and EM negative staining techniques. Over‐expression of ArgBP2 and ArgBP2‐SH3 domains, but not YFP alone, led to loss of myofibrils in cardiomyocytes. Fluorescence recovery after photobleaching was used to measure the rapid dynamics of both the full length and some truncated versions of ArgBP2. Our results indicate that ArgBP2 may play an important role in the assembly and maintenance of myofibrils in cardiomyocytes. © 2010 Wiley‐Liss, Inc.
The Civic Culture at 50: Change, Continuity and Challenges in the Federal Republic of Germany

Much political science is ephemeral. Academic studies of government spawn countless fads and fashions that vanish in a time interval that varies somewhere between a scholarly conference and a generation. On rare occasions, however, a text appears that is sufficiently influential in its ideas and methods to contribute to shaping the development of the discipline. These studies are neither faultless in design nor detail, but the way in which they cast new light on ancient subjects stimulates the imagination of successive generations of scholars. The Civic Culture is one such example. It has attained enduring relevance through its claim that the evolution and persistence of democracy depends not only on the constitutional and institutional structure of democracy, but upon the emergence of a judicious blend of attitudes and values – a political culture. This insight elevated the social prerequisites of democracy to the apex of twentieth-century political science, triggered countless successor studies and provided important momentum to the comparative research and behavioural traditions. Yet while The Civic Culture has enjoyed enormous longevity, some now regard it as an old-fashioned concept from a bygone era – as a simplistic anachronism incapable of corresponding to the complexity of modern democratic life. As 2013 marked the 50th anniversary of the publication of The Civic Culture, it thus represented a timely juncture at which to revisit the claims of the text, to reassess the findings and to engage in the kind of unsentimental reflection that is necessary if the debate is to be successfully reframed for future generations of scholars.
Oral contraceptives and risk of ovarian cancer and breast cancer among high-risk women: a systematic review and meta-analysis.

PURPOSE To estimate the risks of ovarian cancer and breast cancer associated with oral contraceptive (OC) use among women at elevated risk owing to mutations in BRCA1/2 or a strong family history. METHODS We searched PubMed, Embase, the Cochrane Database of Systematic Reviews, and ClinicalTrials.gov for studies published 2000 to 2012 that evaluated associations between OC use and breast or ovarian cancer among women who are carriers of a BRCA1/2 mutation or have a family history of breast or ovarian cancer. RESULTS From 6,476 unique citations, we identified six studies examining ovarian cancer risk in BRCA1/2 mutation carriers and eight studies examining breast cancer risk in BRCA1/2 mutation carriers. For BRCA1/2 mutation carriers combined, meta-analysis showed an inverse association between OC use and ovarian cancer (odds ratio [OR], 0.58; 95% CI, 0.46 to 0.73) and a nonstatistically significant association with breast cancer (OR, 1.21; 95% CI, 0.93 to 1.58). Findings were similar when examining BRCA1 and BRCA2 mutation carriers separately. Data were inadequate to perform meta-analyses examining duration or timing of use. For women with a family history of ovarian or breast cancer, we identified four studies examining risk for ovarian cancer and three for breast cancer, but differences between studies precluded combining the data for meta-analyses, and no overall pattern could be discerned. CONCLUSION Our analyses suggest that associations between ever use of OCs and ovarian and breast cancer among women who are BRCA1 or BRCA2 mutation carriers are similar to those reported for the general population.
Energy Harvesting and Spectrum Sharing Protocol for Wireless Sensor Networks

In this letter, a novel approach for solving the power and spectrum issues in wireless sensor network (WSN) has been proposed. Typically, a deployed sensor node is programmed to periodically send the data to the central base station (CBS). Moreover, most of the sensor nodes are deployed in a hostile environment where replacing a power supply may not be feasible. In the proposed work, we intend to solve the dual problem of spectrum and power for WSN by utilizing techniques such as cooperative spectrum sharing (CSS) and RF (radio frequency) energy harvesting, respectively. Specifically, by characterizing the WSN as an energy constrained secondary user, which will harvest power and spectrum from the primary user, we have shown that significant performance gains can be obtained for both primary and secondary users. Closed form expressions for outage probability under a Nakagami fading channel have been derived for both primary and secondary users. Furthermore, the theoretical results have been compared with simulation results to validate the proposed analysis.
Amino Acids in Segment IVS6 and β-Subunit Interaction Support Distinct Conformational Changes during Cav2.1 Inactivation*

Cav2.1 mediates voltage-gated Ca2+ entry into neurons and the release of neurotransmitters at synapses of the central nervous system. An inactivation process that is modulated by the auxiliary β-subunits regulates Ca2+ entry through Cav2.1. However, the molecular mechanism of this α1-β-subunit interaction remains unknown. Herein we report the identification of new determinants within segment IVS6 of the α12. 1-subunit that markedly influence channel inactivation. Systematic substitution of residues within IVS6 with amino acids of different size, charge, and polarity resulted in mutant channels with rates of fast inactivation (k inact) ranging from a 1.5-fold slowing in V1818I (k inact = 0.98 ± 0.09 s− 1 compared with wild type α12.1/α2-δ/β1a k inact = 1.35 ± 0.25 s− 1) to a 75-fold acceleration in mutant M1811Q (k inact = 102 ± 3 s− 1). Coexpression of mutant α12. 1-subunits with β2a resulted in two different phenotypes of current inactivation: 1) a pronounced reduction in the rate of channel inactivation or 2) an attenuation of a slow component in I Ba inactivation. Simulations revealed that these two distinct inactivation phenotypes arise from a β2a-subunit-induced destabilization of the fast-inactivated state. The IVS6- and β2a-subunit-mediated effects on Cav2.1 inactivation are likely to occur via independent mechanisms.
CrmA/SPI-2 Inhibition of an Endogenous ICE-related Protease Responsible for Lamin A Cleavage and Apoptotic Nuclear Fragmentation*

CrmA, a poxvirus gene product with a serpin-like structure, blocks a variety of apoptotic death events in cultured cells. Based on the ability of CrmA to inhibit the interleukin-1β converting enzyme in vitro, it has been speculated that interleukin-1β converting enzyme-related proteases (caspases) essential for apoptosis are the cellular targets of CrmA. Here we found that rabbitpox virus CrmA/SPI-2 inhibits the cleavage of lamin A mediated by a caspase in our cell-free system of apoptosis. In the presence of CrmA/SPI-2, nuclear apoptosis in vitro was blocked at an intermediate stage after collapse of the chromatin against the nuclear periphery and before nuclear shrinkage and disintegration into apoptotic body-like fragments. Using N-(acetyltyrosinylvalinyl-Nε-biotinyllysyl) aspartic acid [(2,6-dimethylbenzoyl)oxy] methyl ketone, which derivatizes the active forms of caspases, we could show that one of five caspases active in the extracts is inhibited both by CrmA/SPI-2 and by a peptide spanning the lamin A apoptotic cleavage site. These results reveal that CrmA/SPI-2 can inhibit a caspase responsible both for lamin A cleavage and for the nuclear disintegration characteristic of apoptosis.
Evaluation of the anti-proliferative and cytostatic effect of Citrus sinensis (orange) fruit juice

Aim: This work has been designed to evaluate the anti-proliferative and cytostatic effects of Citrus sinensis (orange) fruit juice on rapidly proliferating cells. Materials and Methods: The study was carried out on the seeds of Sorghum bicolor for 72 h. The mean radicle length (mm) of the seeds was taken at 48 and 72 h. Result: The result showed that when compared with the control, methotrexate, the standard drug showed a significant (P < 0.001) anti-proliferative effect throughout the experiment. The inhibition of the radicle growth was more after 72 h (87.42%). At a dose of 5% (v/v), the juice showed a slightly significant (P < 0.05) effect affect after 72 h; however, there was no significant effect at 48 h. The juice at doses of 10% and 20% (v/v) showed a highly significant (P < 0.001) anti-proliferative effect throughout the experiment; however, the percentage inhibitions were higher at 72 h. At 72 h, the percentage inhibition for juice at 10% (v/v) was 72.37% and at 20% (v/v) was 91.96%. The concentrations of 40% and 60% (v/v) showed cytostatic effects as no appreciable growth of the radicles of the seeds was observed throughout the experiment. The percentage inhibition for 40% (v/v) was 100% and 99.72% for 48 and 72 h, respectively, while that for the juice concentration of 60% (v/v) was 100% throughout the study. Conclusion: The experiment has shown that C. sinensis fruit juice has a potential for causing both anti-proliferative and cytostatic effects on fast proliferating cells and hence cancerous cells.