Miracle-dz/UniFAR-FTUs huggingface dataset:
Sensitive detection of DNA modifications induced by cisplatin and carboplatin in vitro and in vivo using a monoclonal antibody.

An assay that is based upon a monoclonal antibody (ICR4) is described that enables the quantitation of cisplatin-induced adducts on DNA down to 3 nmol Pt/g DNA (i.e., 1 Pt adduct/10(6) bases), the level necessary to produce toxic effects in cells in vitro and in vivo, using just a few micrograms of DNA. Detection is possible below this level (although probably not necessary for in vivo studies) but the cross-reactivity of unmodified DNA sequences complicates absolute quantitation of adducts. Therefore, it will be possible to investigate the distribution of clinically useful platinum drugs in patients undergoing chemotherapy. Rats of strain F344 appeared to be the best, among several tested, for the production of antibodies to modified DNA, and they were used for the production of hybridomas. Fifteen hybridomas which secreted antibodies that bound to DNA that was highly modified with cisplatin but not to normal DNA were obtained. One (ICR4) was chosen for further characterization because of its relatively strong binding to DNA modified to a moderate level with cisplatin. The characterization included the development of a sensitive competitive enzyme-linked immunoabsorbent assay and the use of DNA that had been reacted with cisplatin both in vitro and in vivo. The levels of platination of both types of DNA samples were determined by atomic absorbance spectroscopy. For DNA that had been exposed to cisplatin in vitro, 50% inhibition of antibody binding was caused by about 15 fmol of total DNA-bound Pt/assay well. At moderate levels of platination, heating of the DNA solution at 100 degrees C for 5 min increased its immunoreactivity such that 50% inhibition was caused by 2.5 fmol Pt adducts/well. Pt adducts on DNA extracted from cells that had been treated with cisplatin were less immunoreactive than DNA treated with cisplatin in vitro, but after heating the immunoreactivity increased such that 50% inhibition in the assay was caused by 2 fmol Pt adduct/well. This sensitivity was invariant over a wide range of levels of platinum adduct frequency. DNA adducts formed by the second generation anticancer drug carboplatin were recognized similarly to the adducts formed by cisplatin, but those formed by the clinically inactive trans-diamminedichloroplatinum(II) or chloro(diethylenetriamine)-platinum(II)-chloride were not significantly immunoreactive. Control DNA cross-reacted in the competitive assay but the immunoreactivity per mol base was 10(7) times lower than the immunoreactivity of cisplatin adducts.
Red blood cell precursor mass as an independent determinant of serum erythropoietin level.

Serum erythropoietin (sEpo) concentration is primarily related to the rate of renal production and, under the stimulus of hypoxia, increases exponentially as hemoglobin (Hb) decreases. Additional factors, however, appear to influence sEpo, and in this work, we performed studies to evaluate the role of the red blood cell precursor mass. We first compared the relationship of sEpo with Hb in patients with low versus high erythroid activity. The first group included 27 patients with erythroid aplasia or hypoplasia having serum transferrin receptor (sTfR) levels < 3 mg/L (erythroid activity < 0.6 times normal), while the second one included 28 patients with beta-thalassemia intermedia having sTfR levels > 10 mg/L (erythroid activity > 2 times normal). There was no difference between the two groups with respect to Hb (8.3 +/- 1.6 v 8.0 +/- 1.3 g/dL, P > .05), but sEpo levels were notably higher in patients with low erythroid activity (1,601 +/- 1,542 v 235 +/- 143 mU/mL, P < . 001). In fact, multivariate analysis of variance (ANOVA) showed that, at any given Hb level, sEpo was higher in patients with low erythroid activity (P < .0001). Twenty patients undergoing allogeneic or autologous bone marrow transplantation (BMT) were then investigated. A marked increase in sEpo was seen in all cases at the time of marrow aplasia, disproportionately high when compared with the small decrease in Hb level. Sequential studies were also performed in five patients with iron deficiency anemia undergoing intravenous (IV) iron therapy. Within 24 to 72 hours after starting iron treatment, marked decreases in sEpo (up to one log magnitude) were found before any change in Hb level. Similar observations were made in patients with megaloblastic anemia and in a case of pure red blood cell aplasia. These findings point to an inverse relationship between red blood cell precursor mass and sEpo: at any given Hb level, the higher the number of red blood cell precursors, the lower the sEpo concentration. The most likely explanation for this is that sEpo levels are regulated not only by the rate of renal production, but also by the rate of utilization by erythroid cells.
Influence of binder component on kinetics of briquette gasification

The influence of PVA on the gasification was studied from macro and micro angles. In this paper, briquette gasificaition was operated with thermal analyzer. The experimental data showed that with the increase of binder content, the reaction rate increased and the reaction time and activation energy reduced. Starch and PVA increased the linear molecular structure of briquette and improved the reaction rate. CaO inhibited graphite process of briquette. The shrinking core model can better describe the gasification reaction of briquette-CO2.
On some Hochschild cohomology classes of fusion algebras

The obstructions for an arbitrary fusion algebra to be a fusion algebra of some semisimple monoidal category are constructed. Those obstructions lie in groups which are closely related to the Hochschild cohomology of fusion algebras with coefficients in theK-theory of the ground (algebraically closed) field. The special attention is devoted to the case of fusion algebra of invariants of finite group action on the group ring of abelian group.
Tumor cell heterogeneity.

: The paper deals with the analysis of literary data on the tumor cell heterogeneity. Phenotypic, genetic and epigenetic mechanisms of heterogeneity are considered. The heterogeneity of metastasis is considered too. The importance for the biology of populations of tumor cells and the sensitivity of tumors to therapeutic treatment are discussed.
Mechanisms of Liver and Muscle Insulin Resistance Induced by Chronic High-Fat Feeding

To elucidate cellular mechanisms of insulin resistance induced by excess dietary fat, we studied conscious chronically high-fat–fed (HFF) and control chow diet-fed rats during euglycemic-hyperinsulinemic (560 pmol/1 plasma insulin) clamps. Compared with chow diet feeding, fat feeding significantly impaired insulin action (reduced whole body glucose disposal rate, reduced skeletal muscle glucose metabolism, and decreased insulin suppressibility of hepatic glucose production [HGP]). In HFF rats, hyperinsulinemia significantly suppressed circulating free fatty acids but not the intracellular availability of fatty acid in skeletal muscle (long chain fatty acyl-CoA esters remained at 230% above control levels). In HFF animals, acute blockade of β-oxidation using etomoxir increased insulin-stimulated muscle glucose uptake, via a selective increase in the component directed to glycolysis, but did not reverse the defect in net glycogen synthesis or glycogen synthase. In clamp HFF animals, etomoxir did not significantly alter the reduced ability of insulin to suppress HGP, but induced substantial depletion of hepatic glycogen content. This implied that gluconeo-genesis was reduced by inhibition of hepatic fatty acid oxidation and that an alternative mechanism was involved in the elevated HGP in HFF rats. Evidence was then obtained suggesting that this involves a reduction in hepatic glucokinase (GK) activity and an inability of insulin to acutely lower glucose-6-phos-phatase (G-6-Pase) activity. Overall, a 76% increase in the activity ratio G-6-Pase/GK was observed, which would favor net hepatic glucose release and elevated HGP in HFF rats. Thus in the insulin-resistant HFF rat 1) acute hyperinsulinemia fails to quench elevated muscle and liver lipid availability, 2) elevated lipid oxidation opposes insulin stimulation of muscle glucose oxidation (perhaps via the glucose-fatty acid cycle) and suppression of hepatic gluconeogenesis, and 3) mechanisms of impaired insulin-stimulated glucose storage and HGP suppressibility are not dependent on concomitant lipid oxidation; in the case of HGP we provide evidence for pivotal involvement of G-6-Pase and GK in the regulation of HGP by insulin, independent of the glucose source.
1 Screening for Chronic Kidney Disease

Chronic kidney disease (CKD), defined as reduced excretory kidney function (glomerular filtration rate (GFR) <60 mL/min/1.73m2) or evidence of kidney damage (such as proteinuria) for a period of at least 3 months, is considered a major global public health problem (Levey, Atkins et al. 2007). The prevalence of CKD has been estimated at between 10-15% in industrialised countries and is increasing, likely as a result of population ageing and the increasing incidence of diabetes, vascular disease and obesity (Chadban, Briganti et al. 2003; Coresh, Astor et al. 2003; Coresh, Selvin et al. 2007; Stevens, O'Donoghue et al. 2007). A definition and staging system for CKD was introduced in 2002 and has been widely accepted (Table 1) (K/DOQI 2002).
Pricing Security Software: Theory and Evidence

This paper presents a model of multi-product pricing for consumer security software. It highlights two aspects unique to this kind of software. The first is a supply-side effect relating to the security software update process that alters its cost structure, and the second is a demand-side effect relating to the fact that customers often get free substitutes for components of security software suites, which are bundled with products unrelated to computer security. We develop an analytical model that captures each of these effects. In contrast with prior results, this model predicts the optimality of mixed bundling as a pricing strategy; we show how removing the effects we highlight leads to the optimality of pure bundling, which is consistent with past work on information goods. The analytical model also predicts that the “discount" on a bundled software suite increases as the variable cost of high-quality updates goes up. We test the predictions of our model using data on security software demand and pricing we have gathered from Amazon.com, and find preliminary support for our theory. There are a number of aspects of security software that make its economics somewhat different from those of traditional consumer software. First, the quality of security software depends less on the range of end-user features incorporated into the software, and more on the reliability and
Is Difficulty Overrated?: The Effects of Choice, Novelty and Suspense on Intrinsic Motivation in Educational Games

Many game designers aim to optimize difficulty to make games that are "not too hard, not too easy. " However, recent experiments have shown that even moderate difficulty can reduce player engagement. The present work investigates other design factors that may account for the purported benefits of difficulty, such as choice, novelty and suspense. These factors were manipulated in three design experiments involving over 20,000 play sessions of an online educational game. The first experiment (n=10,472) randomly assigned some players to a particular level of difficulty but allowed other players to freely choose their difficulty. Moderately difficult levels were most motivating when self-selected; yet, when difficulty was blindly assigned, the easiest games were most motivating. The second experiment (n=5,065) randomly assigned players to differing degrees of novelty. Moderate novelty was optimal, while too much or too little novelty reduced intrinsic motivation. A final experiment (n=6,511) investigated the role of suspense in "close games", where it was found to be beneficial. If difficulty decreases motivation while novelty and suspense increase it, then an implication for educational game designers is to make easy, interesting games that are "not too hard, not too boring. "
Nonuniform Discretization for Kinodynamic Motion Planning and its Applications

The first main result of this paper is a novel nonuniform discretization approximation method for the kinodynamic motion-planning problem. The kinodynamic motion-planning problem is to compute a collision-free, time-optimal trajectory for a robot whose accelerations and velocities are bounded. Previous approximation methods are all based on a uniform discretization in the time space. On the contrary, our method employs a nonuniform discretization in the configuration space (thus also a nonuniform one in the time space). Compared to the previously best algorithm of Donald and Xavier, the running time of our algorithm reduces in terms of $1/\varepsilon$, roughly from $O((1/\varepsilon)^{6d-1})$ to $O((1/\varepsilon)^{4d-2})$, in computing a trajectory in a $d$-dimensional configuration space, such that the time length of the trajectory is within a factor of $(1+\varepsilon)$ of the optimal. More importantly, our algorithm is able to take advantage of the obstacle distribution and is expected to perform much better than the analytical result. This is because our nonuniform discretization has the property that it is coarser in regions that are farther from all obstacles. So for situations where the obstacles are sparse, or the obstacles are unevenly distributed, the size of the discretization is significantly smaller. Our second main result is the first known polynomial-time approximation algorithm for the curvature-constrained shortest-path problem in three and higher dimensions. We achieved this by showing that the approximation techniques for the kinodynamic motion-planning problem are applicable to this problem.
Risk Management in Smallholder Cattle Farming: A Hypothetical Insurance Approach in Western Kenya

Smallholder cattle farming is an important livelihood strategy in most developing countries like Kenya. However, tropical diseases in Africa often wipe out these valuable assets. This paper focuses on mitigation of cattle disease risks through a hypothetical insurance scheme. The study is based on data from a survey conducted on a purposive sample of 300 smallholder cattle farmers in Kakamega and Siaya districts of Western Kenya. Descriptive measures and a regression model were used in the analysis. Results of the study showed that most farmers (91.3%) were willing to participate in the cattle insurance scheme. Also, the farmers observed that the scheme would enable them to increase their herd sizes and change their breed composition. The farmer's mean Willingness To Pay (WTP) for the scheme would be determined by their gender, income, cultural norms, cattle breed and economic value/price of the animal kept. This paper recommends establishment of a formal cattle insurance scheme; and economic empowerment of both male and female farmers to encourage adoption of the scheme, as well as educating the farmers on how to integrate the scheme within their cultural norms to ensure it's sustainability.
Btk29A-Mediated Tyrosine Phosphorylation of Armadillo/β-Catenin Promotes Ring Canal Growth in Drosophila Oogenesis

Drosophila Btk29A is the ortholog of mammalian Btk, a Tec family nonreceptor tyrosine kinase whose deficit causes X-linked agammaglobulinemia in humans. The Btk29AficP mutation induces multiple abnormalities in oogenesis, including the growth arrest of ring canals, large intercellular bridges that allow the flow of cytoplasm carrying maternal products essential for embryonic development from the nurse cells to the oocyte during oogenesis. In this study, inactivation of Parcas, a negative regulator of Btk29A, was found to promote Btk29A accumulation on ring canals with a concomitant increase in the ring canal diameter, counteracting the Btk29AficP mutation. This mutation markedly reduced the accumulation of phosphotyrosine on ring canals and in the regions of cell-cell contact, where adhesion-supporting proteins such as DE-cadherin and β-catenin ortholog Armadillo (Arm) are located. Our previous in vitro and in vivo analyses revealed that Btk29A directly phosphorylates Arm, leading to its release from DE-cadherin. In the present experiments, immunohistological analysis revealed that phosphorylation at tyrosine 150 (Y150) and Y667 of Arm was diminished in Btk29AficP mutant ring canals. Overexpression of an Arm mutant with unphosphorylatable Y150 inhibited ring canal growth. Thus Btk29A-induced Y150 phosphorylation is necessary for the normal growth of ring canals. We suggest that the dissociation of tyrosine-phosphorylated Arm from DE-cadherin allows dynamic actin to reorganize, leading to ring canal expansion and cell shape changes during the course of oogenesis.
Clinical profile of patients with nascent alcohol related seizures

Aim: The aim of this study is to characterize the clinical profile of patients with alcohol related seizures (ARS) and to identify the prevalence of idiopathic generalized epilepsy (IGE) in the same. Materials and Methods: 100 consecutive male patients presenting to a tertiary care center in South India with new onset ARS were analyzed with alcohol use disorders identification test (AUDIT) score. All underwent 19 channel digital scalp electroencephalography (EEG) and at least computed tomography (CT) scan. Results: A total of 27 patients (27%) who had cortical atrophy on CT had a mean duration of alcohol intake of 23.62 years compared with 14.55 years in patients with no cortical atrophy (P < 0.001). Twenty-two patients (22%) had clustering in the current episode of whom 18 had cortical atrophy. Nearly, 88% patients had generalized tonic clonic seizures while 12% who had partial seizures underwent magnetic resonance imaging (MRI), which identified frontal focal cortical dysplasia in one. Mean lifetime duration of alcohol intake in patients presenting with seizures within 6 hours (6H-gp) of intake of alcohol was significantly lower (P = 0.029). One patient in the 6H-gp with no withdrawal symptoms had EEG evidence for IGE and had a lower AUDIT score compared with the rest. Conclusion: CT evidence of cortical atrophy is related to the duration of alcohol intake and portends an increased risk for clustering. Partial seizures can be a presenting feature of ARS and those patients may benefit from MRI to identify underlying symptomatic localization related epilepsy (8.3% of partial seizures). IGE is more likely in patients presenting with ARS within first 6 hours especially if they do not have alcohol withdrawal symptoms and scalp EEG is helpful to identify this small subgroup (~1%) who may require long-term anti-epileptic medication.
Is Friedewald formula a good estimation for low density lipoprotein level in Iranian population?

Objective: Serum low density lipoprotein (LDL) level is an important biomarker for coronary artery disease (CAD). As direct LDL measurement is expensive and not cost effective, especially in a large population, it is estimated by Friedewald formula. Therefore, we decided to compare the direct LDL measurement method with LDL measured by Friedewald formula in a large general population for the first time in Iran. Furthermore, we examined the association of total cholesterol (TCh), triglyceride (TG), and high density lipoprotein (HDL) with LDL. Subjects and Methods: This study was conducted on the subjects, aged 11–97 years, in the third phase of Isfahan Healthy Heart Program (IHHP) from three cities: Isfahan, Najafabad, and Arak. A fasting blood sample was taken from all subjects and referred to Isfahan Cardiovascular Research Center (ICRC) laboratory (central laboratory of IHHP) to assess TCh, TG, HDL, and LDL directly. Also, the LDL level was calculated by Friedewald formula, in addition. Results: The mean level of LDL by direct method was lower than that calculated by Friedewald formula. The mean difference between the two methods was significant, which was 6.6 ± 15.5 mg/dl difference (t = -42.925, P < 0.0001). There was strong correlation between direct and calculated LDL levels (adjusted R2 = 80.4%). Using regression model, a new formula was found for the estimation of LDL. Conclusion: It is concluded that the Friedewald formula overestimates the LDL level compared to the direct method in general Iranian population. It is suggested that LDL measurement be carried out directly, especially in high-risk people. If a formula is necessary for LDL estimation, it is better to obtain an especial formula for each population.
Rhizome of life, catastrophes, sequence exchanges, gene creations, and giant viruses: how microbial genomics challenges Darwin

Darwin's theory about the evolution of species has been the object of considerable dispute. In this review, we have described seven key principles in Darwin's book The Origin of Species and tried to present how genomics challenge each of these concepts and improve our knowledge about evolution. Darwin believed that species evolution consists on a positive directional selection ensuring the “survival of the fittest. ” The most developed state of the species is characterized by increasing complexity. Darwin proposed the theory of “descent with modification” according to which all species evolve from a single common ancestor through a gradual process of small modification of their vertical inheritance. Finally, the process of evolution can be depicted in the form of a tree. However, microbial genomics showed that evolution is better described as the “biological changes over time. ” The mode of change is not unidirectional and does not necessarily favors advantageous mutations to increase fitness it is rather subject to random selection as a result of catastrophic stochastic processes. Complexity is not necessarily the completion of development: several complex organisms have gone extinct and many microbes including bacteria with intracellular lifestyle have streamlined highly effective genomes. Genomes evolve through large events of gene deletions, duplications, insertions, and genomes rearrangements rather than a gradual adaptative process. Genomes are dynamic and chimeric entities with gene repertoires that result from vertical and horizontal acquisitions as well as de novo gene creation. The chimeric character of microbial genomes excludes the possibility of finding a single common ancestor for all the genes recorded currently. Genomes are collections of genes with different evolutionary histories that cannot be represented by a single tree of life (TOL). A forest, a network or a rhizome of life may be more accurate to represent evolutionary relationships among species.
An XML Format Proposal for the Description of Weighted Automata, Transducers and Regular Expressions

We present an XML format that allows to describe a large class of finite weighted automata and transducers. Our design choices stem from our policy of making the implementation as simple as possible. This format has been tested for the communication between the modules of our automata manipulation platform Vaucanson, but this document is less an experiment report than a position paper intended to open the discussion among the community of automata software writers.
Digital taste & smell for remote multisensory interactions: poster abstract

This poster presents an approach to enhance remote multisensory interactions through digital taste (gustation) and smell (olfaction) senses on human. This approach mainly facilitates the digital actuation of taste and smell sensations on human. It utilizes electrical, thermal, and magnetic stimulation technologies to stimulate taste and smell sensations digitally. First, we present the initial prototype for digital taste actuation and then discuss the method for digital smell actuation.