Miracle-dz/UniFAR-FTUs huggingface dataset:
IFI44L promoter methylation as a blood biomarker for systemic lupus erythematosus

Objective Systemic lupus erythematosus (SLE) is a clinically heterogeneous disease with limited reliable diagnostic biomarkers. We investigated whether gene methylation could meet sensitivity and specificity criteria for a robust biomarker. Methods IFI44L promoter methylation was examined using DNA samples from a discovery set including 377 patients with SLE, 358 healthy controls (HCs) and 353 patients with rheumatoid arthritis (RA). Two independent sets including 1144 patients with SLE, 1350 HCs, 429 patients with RA and 199 patients with primary Sjögren's syndrome (pSS) were used for validation. Results Significant hypomethylation of two CpG sites within IFI44L promoter, Site1 (Chr1: 79 085 222) and Site2 (Chr1: 79 085 250; cg06872964), was identified in patients with SLE compared with HCs, patients with RA and patients with pSS. In a comparison between patients with SLE and HCs included in the first validation cohort, Site1 methylation had a sensitivity of 93.6% and a specificity of 96.8% at a cut-off methylation level of 75.5% and Site2 methylation had a sensitivity of 94.1% and a specificity of 98.2% at a cut-off methylation level of 25.5%. The IFI44L promoter methylation marker was also validated in an European-derived cohort. In addition, the methylation levels of Site1 and Site2 within IFI44L promoter were significantly lower in patients with SLE with renal damage than those without renal damage. Patients with SLE showed significantly increased methylation levels of Site1 and Site2 during remission compared with active stage. Conclusions The methylation level of IFI44L promoter can distinguish patients with SLE from healthy persons and other autoimmune diseases, and is a highly sensitive and specific diagnostic marker for SLE.
Personality as a Predictor of Hooking Up Among College Students

Hookups—casual sexual encounters that may or may not include intercourse—are common on college campuses. Previous research has suggested that these casual sexual encounters may have serious health-related consequences. Understanding the relationships among multiple predictors of hooking up is important if high-risk prevention programming among college students is to be effective. This study considers each of the Big Five personality traits as predictors of hooking-up behaviors in a sample of Midwestern undergraduates (N = 247). Fifty-six percent of women and 63% of men reported engaging in a hookup. In general, Extraversion was positively associated with hooking up behaviors; Conscientiousness was negatively associated with hooking up. Relationships between personality and hooking up were significant while controlling for alcohol use. Implications for prevention programming on college campuses are discussed.
Histone Deacetylase Inhibitors for Cancer Therapy

The epigenome of cancer cells is determined by DNA methylation and an array of post-translational modifications of the core histones. Epigenetic abnormalities are commonly found in human tumors and importantly, they can be reversed by pharmacologic inhibitors. Histone deacetylase inhibitors (HDACIs) represent one of the most promising epigenetic treatments for cancer. HDACIs have emerged as promising targets for cancer therapy because they reactivate the transcription of multiple genes that are silenced in human tumors and they show pleiotropic anti-tumor effects selectively in cancer cells. HDACIs are well-tolerated and several show promising anti-tumor activity. While gene transcription has been considered to be the major target of HDACIs, inhibition of acetylation of non-histone proteins is now emerging as a novel basis for their anti-tumor effects. In this review, we discuss new insights into the molecular mechanism of HDACIs, their current status of clinical development, and possible future uses in cancer therapy.
Update on carbonic anhydrase inhibitors: a patent review (2008 – 2011)

Introduction: Carbonic anhydrases (CA) are a family of zinc metalloenzymes (EC 4.2.1.1) found in all organisms, catalyzing the reversible reaction of CO2 hydration to bicarbonate and a proton. CAs are involved in various physiological reactions including respiration, pH regulation, Na+ retention, calcification, tumorigenesis, electrolyte secretion, gluconeogenesis, ureagenesis, and lipogenesis. Hence CA inhibitors (CAIs) have long been studied as various classes of systemic anticonvulsants, anti-obesity, anti-pain, anti-tumor and topically acting anti-glaucoma agents, and agents for treating altitude sickness. In addition, CA isozyme IX (CA IX) has been shown to play a critical role in cancer proliferation, with CA IX overexpression in certain types of cancers leading to its use as a biomarker for cancer diagnosis and prognosis. Areas covered: Recently, the structures of all the catalytic α-CAs have been determined and with better understanding of gene-based RNA interference (RNAi) therapy, many patents on CA have been filed in the past few years. More new inhibitors are being tested in various labs around the world, in pursuit of designing high-affinity compounds that bind to specific isozymes of CA, thereby reducing side effects caused by off-target binding. This is a review on the patents filed related to CAs during 2008 – 2011. Expert opinion: Structural knowledge regarding CA isozymes offers great opportunity to explore and design inhibitors that will specifically bind to CA IX, avoid off-target binding with other CA isozymes and thus reduce side effects. Various in silico and kinetic studies to test and characterize novel and preexisting inhibitors for isozyme specificity are currently being conducted. However, there remains a need for more research to be carried out to develop better and more specific CAIs with lesser off-target inhibition.
Selection bias correction for species sensitivity distribution modeling and hazardous concentration estimation

The species sensitivity distribution (SSD) has been an important development in ecotoxicology, and despite numerous concerns having been raised over many years, it remains the preferred (and often mandated) technique for establishing “safe” concentrations of contaminants in receiving water bodies by jurisdictions around the world. Although universally recognized as a crucial prerequisite for the statistical validity of the procedure, the assumption of random selection of species for SSD modeling is invariably violated. It is shown in the present study that, under very minimal assumptions, nonrandom species selection can result in hazardous concentration estimation errors of a factor of 20 or more. Importantly, if the toxicity data are biased toward the more sensitive species, then the conventional practice of using the lower confidence interval limit for the estimated hazardous concentration may be compensating in the wrong direction. Environ Toxicol Chem 2015;34:2555–2563. © 2015 SETAC
Moral Hazard in High Office and the Dynamics of Aristocracy

Both aristocratic privileges and constitutional constraints in traditional monarchies can be derived from a ruler's incentive to minimize expected costs of moral-hazard rents for high officials. We consider a dynamic moral-hazard model of governors serving a sovereign prince, who must deter them from rebellion and hidden corruption which could cause costly crises. To minimize costs, a governor's rewards for good performance should be deferred up to the maximal credit that the prince can be trusted to pay. In the long run, we find that high officials can become an entrenched aristocracy with low turnover and large claims on the ruler. Dismissals for bad performance should be randomized to avoid inciting rebellions, but the prince can profit from reselling vacant offices, and so his decisions to dismiss high officials require institutionalized monitoring. A soft budget constraint that forgives losses for low-credit governors can become efficient when costs of corruption are low.
Dual Role for Transactivator Protein C in Activation of mom Promoter of Bacteriophage Mu*

Transactivator C protein of bacteriophage Mu activates the mom gene of the phage by an unusual mechanism. DNA binding by C to its site results in unwinding of the neighboring sequences, realigning the out-of-phase promoter elements to facilitate RNA polymerase (RNAP) binding. High level stimulation of a C-independent constitutive promoter mutant (where RNAP is already bound) by the transactivator suggested an additional mechanism of transcription activation at a step after RNAP recruitment. In this study, we have investigated the various steps of promoter-polymerase interactions during transcription initiation by using both the promoter mutant and a positive control (pc) mutant of C protein. The transactivator does not influence formation of the open complex or its stability after facilitating the RNAP binding. However, at a subsequent step, the protein exerts an important role, enhancing the promoter clearance by increasing the productive RNAP·promoter complex. The pc mutant of the transactivator C is compromised at this step, supporting the additional downstream role for C in mom transcription activation. We suggest that this unusual multistep activation of Pmom has evolved to ensure irreversibility of the switch during the late lytic cycle of the phage.
Automatic motion segmentation using random walks

This paper presents a method two segment moving objects from video sequences by combining spatial and temporal information. The segmentation is performed in two steps : automatic seeds detection, and random walk segmentation. In the first step, seeds are detected by using optical flow in specific pixels so in every d × d grid there is one pixel to represent the grid, then initial seeds are chosen automatically by thresholding the distance of estimated motion vector of the sparse pixels. In the second step, we treat our motion segmentation as a graph based problem, then an energy function is defined to evaluate spatial and temporal smoothness, and we apply random walk algorithm to solve the energy minimization problem, the solution leads to affecting a label to every pixel in sequences video and get the final segmentation. The experimental results illustrate its promising performance and can be integrated in real-time application.
A Production Function for Dental Services: Estimation and Economic Implications

the pricing of physicians' services [4; 6; 10; 16; 18]. For dentistry, Newhouse [16] has found that the price of services is positively related to the number of dentists per capita, a result which suggests some sort of satisficing behavior. Evans [4] has thoroughly discussed the problems and prospects of such models for economic analysis. Elsewhere [13] the authors have presented empirical results for dental prices which confirm the findings of Newhouse and add to the weight of evidence for target-oriented behavior. In the apparent absence of the usual sorts of pricing, it is natural to ask what power economic theory in general retains for explaining behavior. For instance, it is of interest to know whether inputs are used in a least-cost fashion. Another question is whether, for given prices, behavior can be
Microeconometric analysis of household saving in Estonia: income, wealth, financial exposure

This paper ascertains the determinants of household saving in Estonia based on a microeconometric analysis of household budget surveys from 2002 to 2005. Higher income leads to more saving, but the effect is largest for unanticipated income shocks. Ownership of real estate does not affect saving, while possession of durable goods like cars is associated with lower savings. A number of variables reflecting the households' financial exposure are of importance. Deposits, other forms of financial assets and access to liquidity reduce household saving. Surprisingly, debt and leasing liabilities and existing debt servicing payments also lead to lower savings. Young and in particular older households have a higher propensity to save than middle-aged households, while higher education is associated with lower savings. The results are robust to changes in the specification of the saving measure and the choice of estimation method.
Texture Analysis, Bone Mineral Density, and Cortical Thickness of the Proximal Femur: Fracture Risk Prediction

Objective: The objectives of this study were to perform a clinical study analyzing bone quality in multidetector computed tomographic images of the femur using bone mineral density (BMD), cortical thickness, and texture algorithms in differentiating osteoporotic fracture and control subjects; to differentiate fracture types. Methods: Femoral head, trochanteric, intertrochanteric, and upper and lower neck were segmented (fracture, n = 30; control, n = 10). Cortical thickness, BMD, and texture analysis were obtained using co-occurrence matrices, Minkowski dimension, and functional and scaling index method. Results: Bone mineral density and cortical thickness performed best in the neck region, and texture measures performed best in the trochanter. Only cortical thickness and texture measures differentiated femoral neck and intertrochanteric fractures. Conclusions: This study demonstrates that differentiation of osteoporotic fracture subjects and controls is achieved with texture measures, cortical thickness, and BMD; however, performance is region specific.
INFORMATION, SOCIAL MOBILITY AND THE DEMAND FOR REDISTRIBUTION

We study the consensus for redistribution in a framework where the voters consider their income Perspectives Of Upward Mobility (POUM effect) and test it to the Italian case. We propose a theoretical model where individuals, according to their personal characteristics, may discriminate to belong to a particular population group. These individual characteristics affect the future perspectives of mobility through different income dynamics. This general framework let us to explain how, individuals with the same current income, may have different preferences for redistribution. We show, by examples and estimations, that in the case people have better information on their future perspectives, an assumption of concavity on the aggregate income transition function as required by Ok and Benabou [2000], is neither sufficient nor necessary for a Poum effect.
Prevalence and genomic characterization of porcine parvoviruses detected in Chiangmai area of Thailand in 2011

Porcine parvovirus (PPV) causes reproductive failure in sows and has spread worldwide. Several new types of porcine parvoviruses have recently been identified in pig herds. The prevalence of five porcine parvoviruses in the Chiangmai area of Thailand was studied. The prevalence in 80 pigs was 53% for PPV (PPV‐Kr or ‐NADL2 being the new abbreviations), 83% for PPV2 (CnP‐PARV4), 73% for PPV3 (P‐PARV4), 44% for PPV4 (PPV4), and 18% for PBo‐likeV (PBoV7). Over 60% of the pigs carried more than three of the five porcine parvoviruses and occurrence together of the two pairs of viral genes, PPV1/PPV3 and PPV2/PBo‐likeV were observed. Phylogenetic analyses for PPV2 and PPV3 indicated the existence of only two major clades of PPV2 and one major clade of PPV3.
Development and Scale‐up of a Microsphere Protein Delivery System

This paper reviews the development path for the ProLease injectable microsphere delivery system for proteins using human growth hormone as an example. The process consists of four stages, the selection of a lead formulation for clinical testing, the preclinical evaluation of the lead formulation including toxicology and stability studies, the manufacture of phase I clinical supplies, and the scale‐up for phase II and phase III clinical trials. The approaches used to overcome obstacles during each stage are summarized including ways of stabilizing the protein, obtaining desirable release kinetics, and manufacturing sterile batches for clinical testing. Stability, release, toxicology, and scale‐up results for ProLease recombinant human growth hormone (rhGH) are given. The phase I clinical data show that bioactive rhGH was released for about 1 month in humans. This work shows that processes and procedures have been developed that enable the production of microsphere sustained release formulations for proteins suitable for clinical trails and commercialization.
The Topography of Brain Microstructural Damage in Amyotrophic Lateral Sclerosis Assessed Using Diffusion Tensor MR Imaging

BACKGROUND AND PURPOSE: ALS leads to macrostructural (ie, cortical atrophy and hyperintensities along the corticospinal tract) and microstructural (ie, gray matter intrinsic damage) central nervous system abnormalities. We used a multimodal voxelwise imaging approach to assess microstructural changes independent of macrostructural volume loss in patients with ALS compared with HCs. MATERIALS AND METHODS: Twenty-three patients with ALS and 14 HCs were studied. Conventional imaging and DTI were performed. Images were processed by using SPM5 to assess measures of gray and white matter atrophy as well as microstructural damage (ie, MD and FA). DTI alterations independent of volume loss were investigated. RESULTS: When we accounted for both gray and white matter atrophy, patients with ALS showed increased MD values in several gray and white matter areas mainly located in the orbitofrontal and frontotemporal regions bilaterally, in the right genu of the corpus callosum, and in the right posterior limb of the internal capsule. When we accounted for white matter volume loss, patients with ALS showed decreased FA along the corticospinal tract bilaterally and in the left inferior frontal lobe relative to HCs. The MD of the orbitofrontal regions bilaterally was associated significantly with disease duration. CONCLUSIONS: In patients with ALS, DTI detects microstructural changes independent of brain tissue loss. The affected regions included both motor and extramotor areas. The extent of ALS-related DTI abnormalities was greater than that disclosed by the volumetric analysis.
Down‐regulation of the Notch pathway mediated by a γ‐secretase inhibitor induces anti‐tumour effects in mouse models of T‐cell leukaemia

Background and purpose: γ‐Secretase inhibitors (GSIs) block NOTCH receptor cleavage and pathway activation and have been under clinical evaluation for the treatment of malignancies such as T‐cell acute lymphoblastic leukaemia (T‐ALL). The ability of GSIs to decrease T‐ALL cell viability in vitro is a slow process requiring >8 days, however, such treatment durations are not well tolerated in vivo. Here we study GSI's effect on tumour and normal cellular processes to optimize dosing regimens for anti‐tumour efficacy.
A 2.4 GHz 0.18 /spl mu/m CMOS self-biased cascode power amplifier with 23 dBm output power

A two-stage self-biased cascode power amplifier in 0.18 /spl mu/m CMOS process for Class 1 Bluetooth application provides 23 dBm output power with 31 dB gain and 42% PAE at 2.4 GHz. The power amplifier die occupies 0.46 mm/sup 2/.
On the Noise-Enhancing Ability of Stochastic Hodgkin-Huxley Neuron Systems

Recently noise has been shown to be useful in enhancing neuron sensitivity by stochastic resonance. In this study, in order to measure the noise-enhancing factor (NEF), a nonlinear stochastic model is introduced for the Hodgkin-Huxley (HH) neuron system with synaptic noise input stimulation and channel noises in the sodium and potassium channels. The enhancing factor of the HH neuron system is measured from the point of view of the noise-exploiting level of nonlinear stochastic H signal processing. Since the nonlinear stochastic-enhancing measure problem of HH neuron systems requires a solution for the difficulty presented by the Hamilton Jacobi inequality (HJI), a fuzzy interpolation of locally linearized systems is employed to simplify the nonlinear noise-enhancing problems by solving only a set of linear matrix inequalities. The NEF of the HH neuron system is found to be related to the locations of eigenvalues of linearized HH neuron systems and can be estimated through the H signal processing method. Based on a stochastic fuzzy linearized HH neuron system, we found that channel noises are enhanced by the active eigenvalues of ionic channels while synaptic noises are attenuated by the passive eigenvalues of synaptic process.
Hepatocyte senescence induced by radiation and partial hepatectomy in rat liver

Abstract Purpose: Exposure to radiation primes the liver for extensive replacement of the resident parenchymal cells by transplanted hepatocytes. The mechanisms underlying this repopulation remain to be clarified. In these studies, we examined the possible occurrence of cell senescence in vivo following radiation-associated preconditioning of the host liver. Materials and methods: Fischer 344 rats underwent external-beam, computed-tomography-based partial liver irradiation. A single dose of 25 Gy was delivered to the right liver lobes (40% of liver mass). An additional group of animals received a 1/3 partial hepatectomy (removal of the left anterior lobe) four days after irradiation. Non-irradiated groups served as controls. All rats were sacrificed four weeks after the initial treatment. Results: The irradiated livers displayed several markers of cell senescence, including expression of senescence-associated-β-galactosidase (SA-β-gal), increase in cell size, and up-regulation of cyclin-dependent kinase inhibitors (CDK-I) p16 and p21. Furthermore, quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) analysis revealed activation of the senescence-associated secretory phenotype (SASP), including the cytokines interleukin 6 (IL6) and 1α (IL1α). The senescence-related changes were more prominent in rats undergoing partial hepatectomy (PH) following irradiation (IR). Conclusions: We conclude that priming with radiation for liver repopulation results in the induction of cell senescence and the up-regulation of a senescence-associated secretory phenotype. The latter can contribute to the extensive growth of transplanted cells in this system.
Image constrained finite element modelling for real-time surgical simulation and guidance

Accurate physically based biomechanical modelling of tissue deformation is important to surgical simulation and image guided intervention. Achieving real-time performance whilst maintaining relatively accurate simulation result has been a challenging problem to resolve. The purpose of this paper is to describe a novel yet practical image constrained finite element modelling framework for real-time tissue deformation modelling. The accuracy of the proposed framework is validated with respiratory motion modelling and the proposed framework is incorporated into the Open Source SOFA framework, thus facilitating its use for other subject-specific motion modelling and real-time surgical simulation tasks.
Pride and Prejudice: Links between the Nominal Exchange Rates of Indian and Pakistani Currencies During 1957-1997

In theory, the exchange rate is assumed to respond to a number of economic factors such as the inflation rate differential, interest rate differential, and a number of other factors affecting expectations about the future. In practice, models of exchange rate that include economic variables tend to perform poorly against naive random walk models. In the case of developing countries, their nominal exchange rate against powerful currencies such as the US dollar is sometimes seen as a symbol of pride and used as a source of political leverage. In this paper, we test this theory using the exchange rate data for two rival countries with a shared history: India and Pakistan. These two countries have no trade between them and their import and export patterns are completely different. Hence one would not expect any influence of one currency. But we find that Indian exchange rate influences Pakistan's and vice-versa, supporting the pride theory.