Miracle-dz/UniFAR-FTUs huggingface dataset:
Towards Engineering Hormone-Binding Globulins as Drug Delivery Agents

The treatment of many diseases such as cancer requires the use of drugs that can cause severe side effects. Off-target toxicity can often be reduced simply by directing the drugs specifically to sites of diseases. Amidst increasingly sophisticated methods of targeted drug delivery, we observed that Nature has already evolved elegant means of sending biological molecules to where they are needed. One such example is corticosteroid binding globulin (CBG), the major carrier of the anti-inflammatory hormone, cortisol. Targeted release of cortisol is triggered by cleavage of CBG's reactive centre loop by elastase, a protease released by neutrophils in inflamed tissues. This work aimed to establish the feasibility of exploiting this mechanism to carry therapeutic agents to defined locations. The reactive centre loop of CBG was altered with site-directed mutagenesis to favour cleavage by other proteases, to alter the sites at which it would release its cargo. Mutagenesis succeeded in making CBG a substrate for either prostate specific antigen (PSA), a prostate-specific serine protease, or thrombin, a key protease in the blood coagulation cascade. PSA is conspicuously overproduced in prostatic hyperplasia and is, therefore, a good way of targeting hyperplastic prostate tissues. Thrombin is released during clotting and consequently is ideal for conferring specificity to thrombotic sites. Using fluorescence-based titration assays, we also showed that CBG can be engineered to bind a new compound, thyroxine-6-carboxyfluorescein, instead of its physiological ligand, cortisol, thereby demonstrating that it is possible to tailor the hormone binding site to deliver a therapeutic drug. In addition, we proved that the efficiency with which CBG releases bound ligand can be increased by introducing some well-placed mutations. This proof-of-concept study has raised the prospect of a novel means of targeted drug delivery, using the serpin conformational change to combat the problem of off-target effects in the treatment of diseases.
Suckers Are Born but Markets Are Made: Individual Rationality, Arbitrage, and Market Efficiency on an Electronic Futures Market

The Iowa Electronic Markets are specially designed futures markets that appear to aggregate information efficiently to predict events such as election outcomes. Yet, in theory, perfect information aggregation is impossible. Further, the markets are populated by a nonrepresentative sample of mistake-prone and biased traders. That is, traders are prone to the behavioral anomalies predicted by behavioral finance. How can this be reconciled with market efficiency? Here, we take a first step by analyzing the behavior of two self-selected types of traders. Dramatic differences in mistake rates across traders can help us answer the question. Market-making traders who set prices are less mistake prone and appear to be more rational than price-taking traders. This highlights an important feature of markets: marginal (in this case, market making), not average, traders set prices. This can drive the efficiency of market prices in spite of large numbers of traders who display patently suboptimal behavior.
Impairment on Cardiac Output and Blood Flow Adjustments to Exercise in L-NAME–induced Hypertensive Rats

The objective of the present study was to investigate cardiovascular adjustments at rest, during exercise, and 1 hour after exercise among nitric oxide (NO) blockade-induced hypertensive rats. Male Wistar rats (308±9 g) assigned as normotensive (n=9) and hypertensive (Nω-nitro-L-arginine methyl ester, n=11) underwent a bout of exercise. Arterial pressure (AP) and blood oxygen saturation were measured. Colored microspheres were used to evaluate blood flow and cardiac output (CO). Hypertensive rats (143±5 vs. 102±4 mmHg in normotensive rats), who presented reduced CO (57±6 vs. 102±7 mL/min in normotensive), also presented diminished blood flow in kidney, lung, and muscles at rest in comparison with normotensive rats. Exercise increased AP (20%), heart rate (40%), and CO (32%) among the normotensive rats, whereas the hypertensive rats presented an increased heart rate (40%) accompanied by a reduced venous oxygen saturation (45.5±2.1% vs. 75±0.7% in normotensive rats). Muscle vasodilatation, which was observed among the normotensive rats and is considered a hallmark adjustment to exercise, was not observed among the hypertensive rats. After a 1-hour interval from exercise most of the evaluated parameters returned to basal values. In conclusion, exercise did not cause an increase in CO, AP, or blood flow to skeletal muscle in hypertensive rats. However, it was associated with a significant increase in the arterio-venous oxygen content difference in NO-blocked rats, thus suggesting that hypertension associated with impairment in NO release induced different cardiovascular adjustments to exercise.
Body packing--the internal concealment of illicit drugs.

The transportation of illicit drugs by concealment within the body is now a common practice, and it has implications for clinical care. Body packers may ingest dozens of packets containing life-threatening doses of heroin, cocaine, or amphetamines. These smugglers may then present to physicians for evaluation while in legal custody or because of drug-induced toxic effects or obstruction or perforation of the gastrointestinal tract. This review provides guidance for the recognition and management of this clinical problem, which often also poses ethical and legal challenges for the clinician.
Anchor Models and WCCN Normalization For Speaker Trait Classification

This paper presents an improved version of anchor model applied to solve the two-class classification tasks of the INTERSPEECH 2012 speaker trait Challenge. To build the anchor model space of each task, we include the class models of all tasks. The introduction of within-class covariance normalization (WCCN) applied to the log-likelihood scores of the anchor space not only improves the results compared to the unnormalized version but also exceeds the performance of GMM or GMM-UBM systems. Even if Euclidean distance gives worst performances compared to cosine metric, we find that after normalization both metrics give similar results so they can be used interchangeably.
Cdc42 - the centre of polarity

All cell types polarize, at least transiently, during division or to generate specialized shapes and functions. This capacity extends from yeast to mammals, and it is now clear that many features of the molecular mechanisms controlling polarization are conserved in all eukaryotic cells. At the centre of the action is Cdc42, a small GTPase of the Rho family. Its activity is precisely controlled both temporally and spatially, and this can be achieved by a wide variety of extracellular cues in multicellular organisms. Moreover, although the functional characteristics of cell polarity are extremely variable (depending on the cell type and the biological context), Cdc42 has an amazing capacity to co-ordinate the control of multiple signal transduction pathways.
Rate scalable image and video compression techniques

In this paper we describe embedded image and video compression techniques. An embedded zero tree-like approach is discussed that exploits the interdependency between color components that is known as Color Embedded Zero Tree Wavelet (CEZW). We also present a video compression technique, Scalable Adaptive Motion compensated Wavelet (SAMCoW) compression, that uses the CEZW data structure. It is shown that in addition to providing a wide range of rate scalability, SAMCoW achieves comparable performance to the more traditional hybrid video coders.
On the Abrasion of Rubber

The following theoretical results on the abrasion of rubber have been deduced from a few simple assumptions concerning the initiation of the surface damage. The abrasion is proportional to the normal load, independent of the particle size of the abrasive if the particles are polyhedral, and proportional to their mean radius of curvature if they can be approximated to hemispheres. The spacing of the abrasion pattern is proportional to the cube root of the normal load, proportional to the two-thirds power of the particle size on an abrasive with polyhedral particles, and directly proportional to the particle size on an abrasive with hemispherical particles. These predictions have been reasonably well confirmed by experiment.
The Associations Between Pain Intensity, Psychosocial Variables, and Pain Duration/Recurrence in a Large Sample of Persons With Nonspecific Spinal Pain

ObjectivesThe aims of this study were: (1) to describe and compare pain intensity, disability, cognitive, physical, behavioral, and environmental variables in 4 predefined categories, on the basis of duration and recurrence of nonspecific spinal pain; and (2) to compare disability, cognitive, physical, behavioral, and environmental variables in these 4 predefined categories, after controlling for pain intensity. MethodsPostal questionnaires were sent to a random sample of 5000 persons, aged 20 to 50 years, in Sweden. The response rate was 39%. One thousand and twenty-four participants reporting spinal pain were divided into 4 predefined categories (n=100, 215, 172, and 537) based on duration and recurrence of pain. Multivariate analyses of variance and covariance were performed to investigate differences between the 4 pain duration/recurrence groups. ResultsThe first analyses revealed that the 4 pain duration/recurrence groups differed in pain intensity, disability, 7 cognitive variables, and perceived social support. After controlling for pain intensity, small but significant group differences were identified in depression, catastrophizing, pain expectations, and perceived social support. Higher levels of catastrophizing and pain expectations and lower levels of perceived social support were seen in groups with longer duration of pain. DiscussionAfter controlling for pain intensity, categories based on pain duration/recurrence differed in 3 cognitive variables and perceived social support. Pain expectations, catastrophizing and perceived social support were related to longer duration of pain. Between-group differences were small and pain duration/recurrence was not an important explanatory factor.
Designing beta basis function neural network for optimization using particle swarm optimization

Many methods for solving optimization problems, whether direct or indirect, rely upon gradient information and therefore may converge to a local optimum. Global optimization methods like evolutionary algorithms, overcome this problem. In this work it is investigated how to construct a quality BBF network for a specific application can be a time-consuming process as the system must select both a suitable set of inputs and a suitable BBF network structure. Evolutionary methodologies offer the potential to automate all or part of these steps. This study illustrates how a hybrid BBFN-PSO system can be constructed, and applies the system to a number of datasets. The utility of the resulting BBFNs on these optimization problems is assessed and the results from the BBFN-PSO hybrids are shown to be competitive against the best performance on these datasets using alternative optimization methodologies. The results show that within these classes of evolutionary methods, particle swarm optimization algorithms are very robust, effective and highly efficient in solving the studied class of optimization problems.
Care of patients with hepatitis C and HIV co-infection.

Liver disease caused by chronic hepatitis C virus (HCV) infection is now a leading cause of morbidity and mortality among HIV-infected patients in the developed world, where classic opportunistic complications of severe immunodeficiency have declined dramatically as a result of the widespread use of potent antiretroviral therapies [1]. Over the past few years, several consensus reports have addressed the issue of viral hepatitis and HIV infection [2,3]. In 2000, a group of experts in the field were invited to join the HCV– HIV International Panel. The first consensus conference took place in Paris [4]. Two years later, the large amount of new information on HCV and HIV, as well as important changes made in the guidelines for using antiretroviral drugs [5], prompted us to organize another consensus conference, which was held in Barcelona in the summer of 2002. Following international recommendations for the development of clinical guidelines [6], the meeting was planned as a full oneday workshop in which nine experts in the field of HIV and viral hepatitis discussed a total of nine questions, which were selected in advance as the most relevant and currently conflicting topics in the management of chronic viral hepatitis in the setting of HIV infection. A draft was written and circulated among panel members during the following months. Finally, in a second meeting that took place in February 2003, a final consensus was reached, and is presented here. The statements are graded according to the Infectious Diseases Society of America scoring system [6], with minor changes (see Table 1).
Enhancing network-on-chip components to support security of processing elements

Network-on-Chip (NoC) has emerged as a promising solution for scalable communication among steadily growing number of cores integrated in MultiProcessor System-on-Chips (MPSoCs). The increasing system heterogeneity together with the possibility of reconfiguration makes the overall system security one of the major concerns in MPSoC design. On the other hand, modular and scalable design of NoCs enables their enhancements in various directions for supporting services other than simple data routing. In this work we propose and implement a solution to secure attached processing units from a buffer overflow type of the attacks that comes in a form of a protection module that is embedded into the Network Interface of the NoC. At the same time, our solution prevents potential propagation of the attack through the NoC towards other processors. We prove feasibility via prototype realization in FPGA technology for a MicroBlaze processor on Xilinx Virtex-II Pro board.
Preference Inference Based on Lexicographic Models

With personalisation becoming more prevalent, it can often be useful to be able to infer additional preferences from input user preferences. Preference inference techniques assume a set of possible user preference models, and derive inferences that hold in all models satisfying the inputs; the more restrictive one makes the set of possible user preference models, the more inferences one gets. Sometimes it can be useful to have an adventurous form of preference inference when the input information is relatively weak, for example, in a conversational recommender system context, to give some justification for showing some options before others. This paper considers an adventurous inference based on assuming that the user preferences are lexicographic, and also an inference based on an even more restrictive preference model. We show how preference inference can be efficiently computed for these cases, based on a relatively general language of preference inputs.
On the Inherent Sequentiality of Concurrent Objects

We present $\Omega(n)$ lower bounds on the worst case time to perform a single instance of an operation in any nonblocking implementation of a large class of concurrent data structures shared by n processes. Time is measured by the number of stalls a process incurs as a result of contention with other processes. For standard data structures such as counters, stacks, and queues, our bounds are tight. The implementations considered may apply any primitives to a base object. No upper bounds are assumed on either the number of base objects or their size.
Macular thickness decreases with age in normal eyes: a study on the macular thickness map protocol in the Stratus OCT

Background/aim: Retinal and retinal nerve fibre layer (RNFL) thinning with age have been described in histological studies. In vivo techniques like optical coherence tomography (OCT) have shown thinning of optic nerve RNFL and the retina in specific areas. One would expect thinning of the total macula, but so far, no correlation with the quantitative OCT macular map tool and age has been found. Methods: Sixty-seven healthy individuals underwent three repeated scans in both eyes with the macular thickness map protocol in the Stratus OCT. That protocol divides the macula area into nine ETDRS fields. The RNFL was measured in one specific location close to the optic disc. Correlations between retinal, RNFL thickness, macular volume and age were determined. Results: We found a statistically significant negative relationship between retinal thickness and age for all ETDRS areas, total macular volume and RNFL thickness. Retinal thickness decreased by 0.26–0.46 μm, macula volume 0.01 mm3 and RNFL 0.09 μm per year. Conclusion: Retinal thickness within the area covered by the macular map significantly decreases with age. In the area examined in the papillomacular bundle, 20% of the retinal thinning is due to the RNFL, and 80% is due to thinning of other layers of the retina.
Computational Design of Targeted Inhibitors of Polo-Like Kinase 1 (Plk1)

Computational design of small molecule putative inhibitors of Polo-like kinase 1 (Plk1) is presented. Plk1, which regulates the cell cycle, is often over expressed in cancers. Down regulation of Plk1 has been shown to inhibit tumor progression. Most kinase inhibitors interact with the ATP binding site on Plk1, which is highly conserved. This makes the development of Plk1-specific inhibitors challenging, since different kinases have similar ATP sites. However, Plk1 also contains a unique region called the polo-box domain (PBD), which is absent from other kinases. In this study, the PBD site was used as a target for designed Plk1 putative inhibitors. Common structural features of several experimentally known Plk1 ligands were first identified. The findings were used to design small molecules that specifically bonded Plk1. Drug likeness and possible toxicities of the molecules were investigated. Molecules with no implied toxicities and optimal drug likeness values were used for docking studies. Several molecules were identified that made stable complexes only with Plk1 and LYN kinases, but not with other kinases. One molecule was found to bind exclusively the PBD site of Plk1. Possible utilization of the designed molecules in drugs against cancers with over expressed Plk1 is discussed.
Local and average filtration properties of kraft softwood lignin

The extraction of lignin from black liquor is of interest in order to increase the overall material yield when producing paper pulp by the kraft process. The extracted lignin can be used either as a solid biofuel or a potential alternative raw material to fossil oil for the production of various green chemicals and high valuable products such as carbon fibres. The LignoBoost process is a new approach in which the kraft lignin extracted reaches a high level of purity. In this study, the local and average dead-end filtration properties during dewatering of a softwood lignin extracted from black liquor using the LignoBoost process were investigated; the material was also characterized. It was found that the investigated lignin was an easy to filter material that formed weakly compressible filter cakes in the solid compressive pressure range of 0.03 to 1.5 MPa. The concentration of the lignin slurry did not influence the filtration properties; the resulting cakes final heights were in the industrial size range. Moreover, the two different filter media used yielded similar results. Semi-empirical relationships were fitted successfully to the experimental local data and a good estimation of the average filtration properties was also obtained using the relationships fitted parameters. This indicates a good agreement between the local and average experimental data.
Eye and Brain Giant cell arteritis : a review

Correspondence: Bhaskar Dasgupta Southend University Hospital, Prittlewell Chase, Westcliff-on-sea, Essex, SS0 0RY, United Kingdom Tel +44 17 0222 1048 Fax +44 17 0238 5909 Email bhaskar.dasgupta@southend.nhs. uk Abstract: Giant cell arteritis is the most common vasculitis in Caucasians. Acute visual loss in one or both eyes is by far the most feared and irreversible complication of giant cell arteritis. This article reviews recent guidelines on early recognition of systemic, cranial, and ophthalmic manifestations, and current management and diagnostic strategies and advances in imaging. We share our experience of the fast track pathway and imaging in associated disorders, such as large-vessel vasculitis.
The Effects of Increasing Openness and Integration to the Mercosur on the Uruguayan Labor Market: A CGE Modeling Analysis

Uruguay is a small economy. Its integration into MERCOSUR has increased its exposure to regional macroeconomic instability. The aim of this paper is to assess the impact of regional integration on the country's labour market and poverty. We estimated wage differentials between labour categories, finding a 60 percent wage gap between formal and informal workers. A CGE model with an efficiency wage specification for unskilled labour was built, with results showing that regional shocks deeply affect the Uruguayan economy. The consideration of an efficiency wage model is particularly important when shocks lead to a reallocation of resources towards sectors intensive in unskilled labour. A subsidy on formal, unskilled labour could contribute to decrease informality and therefore increase GDP, but this type of policy needs to be carefully implemented because it may have negative effects on investment. Finally, the effects on poverty and income distribution obtained through microsimulations are consistent with the results of the CGE experiments.
Inflation Targets in a Global Context

Inflation targeting has become a global framework, used by countries of many different types and in all the continents of the world. To assess its global contribution, this paper uses one of the broadest ever surveys of monetary policy frameworks to construct an overall picture from the individual jigsaw pieces of framework characteristics. The jigsaw is made of targets and other measures of policy reaction, institutional characteristics such as independence, accountability and transparency, and analytical capacities within the central bank. The paper notes that the use of inflation targets has spread very rapidly in the 1990s, far more so than has the number of "inflation targeting" frameworks. The analysis focuses on the flexible use of inflation (and money) targets, and how these relate to indicators of each of central bank reaction functions, independence, accountability, transparency, and analytical methods. The use of targets appears to have built a strong momentum towards explanation of policy, and the use of inflation targets in particular has provided a vehicle for communication between central banks and governments and the private sector.
Lighting quality recommendations for VDT offices: a new method of derivation

An experiment in a mock-up office space gave occupants control over dimmable lighting circuits after a day working under pseudo-random lighting conditions. Data analysis indicated that the lighting experienced during the day influenced the changes in lighting made at the end of the day. Occupants chose to reduce screen glare if any existed. Even after allowing for the effect of glare, desktop illuminance at day’s end varied with the illuminance experienced during the day. Regression of these end-of-day choices relative to the illuminance experienced during the day can yield a preferred illuminance, equivalent to the daytime illuminance at which no change was preferred at day’s end. Using this method, preferred illuminances in the range 200-500 lux were derived. Preferences for luminance ratio were also derived. Interestingly, the deviation between participants’ lighting preferences and the lighting they experienced during the day was a significant predictor of participant mood and satisfaction.