Miracle-dz/UniFAR-FTUs huggingface dataset:
DNA minor groove binding-directed poisoning of human DNA topoisomerase I by terbenzimidazoles.

We have employed a broad range of spectroscopic, calorimetric, DNA cleavage, and DNA winding/unwinding measurements to characterize the DNA binding and topoisomerase I (TOP1) poisoning properties of three terbenzimidazole analogues, 5-phenylterbenzimidazole (5PTB), terbenzimidazole (TB), and 5-(naphthyl[2,3-d]imidazo-2-yl)bibenzimidazole (5NIBB), which differ with respect to the substitutions at their C5 and/or C6 positions. Our results reveal the following significant features. (i) The overall extent to which the three terbenzimidazole analogues poison human TOP1 follows the hierarchy 5PTB > TB >> 5NIBB. (ii) The impact of the three terbenzimidazole analogues on the superhelical state of plasmid DNA depends on the [total ligand] to [base pair] ratio (rbp), having no effect on DNA superhelicity at rbp ratios < or = 0.1, while weakly unwinding DNA at rbp ratios > 0.1. This weak DNA unwinding activity exhibited by the three terbenzimidazoles does not appear to be correlated with the abilities of these compounds to poison TOP1. (iii) Upon complexation with both poly(dA). poly(dT) and salmon testes DNA, the three terbenzimidazole analogues exhibit flow linear dichroism properties characteristic of a minor groove-directed mode of binding to these host DNA duplexes. (iv) The apparent minor groove binding affinities of the three terbenzimidazole analogues for the d(GA4T4C)2 duplex follow a qualitatively similar hierarchy to that noted above for ligand-induced poisoning of human TOP1-namely, 5PTB > TB > 5NIBB. In the aggregate, our results suggest that DNA minor groove binding, but not DNA unwinding, is important in the poisoning of TOP1 by terbenzimidazoles.
Shifts in myocardial fatty acid and glucose metabolism in pulmonary arterial hypertension: a potential mechanism for a maladaptive right ventricular response.

AIMS We investigated the role of metabolic alterations in the development of a maladaptive right ventricular (RV) response in pulmonary arterial hypertension (PAH), which has not previously been undertaken. This study evaluated relationships between glucose and fatty acid metabolism obtained using PET with invasive pulmonary haemodynamics, RV measurements, and RV function to gain insight into the mechanism of RV maladaptation. METHODS AND RESULTS Seventeen consecutive PAH patients (mean age 56 ± 15) who underwent right heart catheterization [mean pulmonary arterial pressure (mPAP) 43 ± 12 mmHg] had cardiac 18F-fluoro-2-deoxyglucose (FDG) and (18)F-fluoro-6-thioheptadecanoic acid (FTHA) PET imaging. RV and left ventricular (LV) FDG and FTHA uptake standard uptake values (SUVs) were measured. The SUV was corrected for the partial volume effect (SUVPVE) based on cardiac magnetic resonance imaging (CMR). Right ventricular ejection fraction (RVEF) was determined by CMR. There was a significant positive correlation between mPAP and RV/LV FDG SUVPVE (r = 0.68, P = 0.003), and the ratio of RV/LV FDG SUV : RV/LV FTHA SUV (r = 0.60, P = 0.02). RVEF was negatively correlated with RV/LV FDG SUVPVE uptake (r = -0.56, P = 0.02) and RV/LV FTHA SUVPVE (r = -0.62, P = 0.019). CONCLUSION Increased pulmonary arterial pressures are associated with increases in the ratio of FDG/FTHA uptake in the RV. Inverse correlation between the uptake of the metabolic tracers and RV function may reflect a shift towards increased fatty acid oxidation and glycolysis associated with RV failure in maladaptive remodelling.
Tissue factor pathway inhibitors as a novel approach to antithrombotic therapy.

Tissue factor is the initiator of the extrinsic pathway of the coagulation cascade. It is expressed by endothelial cells when stimulated by cytokines and other mediators. The effect of tissue factor is physiologically balanced by tissue factor pathway inhibitor. Atherosclerotic plaques are rich in tissue factor. It stimulates thrombus formation when plaques rupture. The emerging role of tissue factor in cellular signaling and in the pathogenesis of atherosclerosis has directed attention to inhibitors of tissue factor as a new antithrombotic approach. In comparison to currently used anticoagulants, tissue factor pathway inhibitors have the potential advantage of inhibiting the coagulation cascade at its earliest stage. These agents also act locally at the site of endothelial injury with minimal disturbance of systemic hemostasis. In addition, their inhibitory effect on neointimal formation and restenosis after vascular intervention are appealing features in the management of the complications of atherosclerosis.
Biochemical adaptations to endurance exercise in muscle.

Two quite distinct adaptive responses can be induced in skeletal muscle by regularly performed, strenuous exercise. The nature of the exercise stimulus determines the type of adaptation. One type of adaptation involves hypertrophy of the muscle cells with an increase in strength; it is exemplified in its most extreme form by the muscles of weight lifters and body builders. The second type of adaptation involves an increase in the capacity of muscle for aerobic metabolism with an increase in endurance and is found in its most highly developed form in the muscles of competi­ tive middleand long-distance runners, long-distance cross-country skiers, bicy­ clists, and swimmers. Although many types of physical activity can bring about varying degrees of both types of adaptation in the same muscle, it does appear that these adaptations can occur quite independently of each other in their most extreme forms. For example, the hypertrophied muscles of weight lifters do not appear to have an increased respiratory capacity (45), whereas the muscles of rodents trained by prolonged daily running, which have a large increase in respiratory capacity, are not hypertrophied (56, 92) and show no increase in strength (12). This review deals with the biochemical adaptations induced in skeletal muscle by the endurance type of exercise and with the physiological consequences of these adaptations.
American Diabetes Association annual meeting, 1999: dyslipidemia, endothelial dysfunction, and glycosylation.

tensive. Blood pre s s u re levels are well cont rolled in only 27% of U.S. patients. Eff e ctive control of blood pre s s u re levels is less f requent in We s t e rn Europe (only an estimated 6% of U.K. patients have good blood p re s s u re control), and effective hypert e nsion control in the developing world is even less frequent than that in We s t e rn E u rope (4). The fourth re p o rt of the Joint National Committee on the Pre v e n t i o n , Detection, Evaluation, and Treatment of High Blood Pre s s u re recommended the use of diuretics and -blockers as the first-line t reatment for all patients, the use of calcium-channel blockers (CCBs) for elderly patients, and the use of ACE inhibitors (ACEIs) for patients with diabetes. Other first-line agents are -blockers and angiotensin II receptor blockers (ARBs). The Hypertension Optimal Tre a t m e n t Study consisted of 19,000 patients who w e re randomized to achieve diastolic blood p re s s u res of 90, 85, and 80 mmHg. All of the study patients received aspirin. The risk of a major CVD-related incident d e c reased by 30% in the nondiabetic patients. Of the 1,501 patients with diabetes, 24, 18, and 11 patients of the 3 t reatment groups, re s p e c t i v e l y, experienced major CVD-related incidents, resulting in a risk reduction of 37% in the lowest blood p re s s u re group (5). In the hypert e n s i o n substudy of the U.K. Prospective Diabetes Study (UKPDS), 1,148 patients with hypertension were randomized to “tight” blood p re s s u re control with ACEIs or - b l o c k e r s or to “less tight” control, with an average blood pre s s u re reduction of 10/5 mmHg with tight control. The intervention gro u p experienced a 32% decrease in the pre v alence of diabetes-related deaths, a 44% d e c rease in the prevalence of stroke, a 37% d e c rease in the prevalence of micro v a s c u l a r disease, and a 56% decrease in the pre v alence of heart failure (6). The Captopril P revention Project evaluated 11,000 patients who were treated with either ACEIs or -blockers plus diuretic tre a tment and showed similarly that both tre a tments are equally effective, using at a somewhat higher blood pre s s u re goal than that of the UKPDS tight blood pre s s u re c o n t rol group. However, among the 700 patients with diabetes in the study, ACEI t reatment decreased rates of myocard i a l i n f a rction (MI), total CVD, and mort a l i t y (7). Intere s t i n g l y, the incidence of diabetes was 9% lower in the nondiabetic patients who were randomized to ACEIs; this find
Ehrlichia‐induced hemophagocytic lymphohistiocytosis in two children

Two children presented with a history of fever and rash. Lab values revealed pancytopenia, elevated ferritin, coagulopathy, and elevated triglycerides. Both children quickly developed respiratory distress and hypotension requiring admission to the ICU. Bone marrow biopsies revealed hemophagocytosis. Studies for Ehrlichia returned positive. The patients were started on doxycycline and treated for hemophagocytic lymphohistiocytosis (HLH). Each made a full recovery. In both patients, testing for MUNC and perforin genes were found to have no mutation. These two cases demonstrate the importance of considering Ehrlichiosis as a possible trigger of HLH. Pediatr Blood Cancer 2011;56:661–663. © 2010 Wiley‐Liss, Inc.
Histochemical diagnosis of muscle phosphofructokinase deficiency.

MUSCLE phosphofructokinase (PFK) deficiency in man was first described by Tauri et al1in a biochemical investigation in 1965. In 1967, Layzer et al2reported additional biochemical and immunologic studies in a second family with this disease. This disorder may be regarded as a fourth type of muscle glycogenosis3in addition to deficiencies of phosphorylase, amylo-1,6-glucosidase (debrancher) and amylo-1,4-glucosidase (acid maltase). The PFK catalyzes the conversion of fructose-6-phosphate (F-6-P) to fructose-1,6-diphosphate (F-1,6-PP); in the absence of this enzyme, glycogen cannot be broken down to lactic acid (Fig 1). The clinical features of this disease are identical to muscle phosphorylase deficiency (McArdle's disease) and include muscle cramps, exercise intolerance, contracture following ischemic work, and myoglobinuria.4 At the present time, phosphorylase deficiency can be detected by histochemical means prior to biochemical studies,5,11but a histochemical method for the detection of muscle PFK deficiency is not
Application of Host-Specific Bacteriophages to the Surface of Chicken Skin Leads to a Reduction in Recovery of Campylobacter jejuni

ABSTRACT Retail poultry products are widely purported as the major infection vehicle for human campylobacteriosis. Numerous intervention strategies have sought to reduce Campylobacter contamination on broiler carcasses in the abattoir. This study reports the efficacy of bacteriophage in reducing the number of recoverable Campylobacter jejuni cells on artificially contaminated chicken skin.
Mitochondrial DNA sequence variation and phylogeography among Salmo trutta L. (Greek brown trout) populations

To investigate the phylogenetic relationships and geographical structure among brown trout S. trutta L. populations from the South Adriatic‐Ionian and Aegean sea basins, mitochondrial DNA nucleotide sequence comparisons were used. A 310‐base‐pair (bp) segment of the control region (D‐loop), and an additional 280‐bp segment of the cytochrome b gene were sequenced from representatives of 13 brown trout populations. Phylogenetic analyses, conducted after combining the data presented with published data from other Eurasian brown trout, revealed four major phylogenetic groups, three of which were found widely distributed within the southern Balkan region. The phylogeographical patterns revealed by mtDNA represent one of the few cases where phylogenetic discontinuity in a gene tree exists without obvious geographical localization within a species' range and has most likely resulted from the differentiation of the major mtDNA clades during Messinian or early Pleistocene times. Finally, the genetic relationships among the populations suggested by mtDNA were generally not in accordance with either allozyme or morphological data.
Size of the Permo-Triassic Bottleneck and Its Evolutionary Implications

Rarefaction analysis of extinctions in the Late Permian indicates that as many as 96 percent of all marine species may have died out, thus forcing the marine biosphere to pass through a small bottleneck. With such severity of extinction, chance elimination of certain biologic groups would have been probable. Some of the changes in biologic composition observed at the Permo-Triassic boundary may be explained as an evolutionary founder effect that followed the bottleneck.
An efficient dynamic protection scheme in integrated IP/WDM networks

This paper presents an efficient protection scheme to dynamically allocate restorable bandwidth-guaranteed paths in integrated IP-over-WDM networks. A restorable bandwidth-guaranteed path implies an active path and another link-disjoint backup path both with the required bandwidth. Dynamic traffic where connection requests arrive one by one with no knowledge about future requests is assumed. We consider integrated IP/WDM networks with generalized multi-protocol label switching (GMPLS) capabilities. To optimize the network resources, we provide the protection at the multi-protocol label switching (MPLS) layer and backup resources are judiciously shared among different requests at the label switched path (LSP) level. To allocate the restorable bandwidth-guaranteed paths, we propose two integrated routing algorithms: hop-based integrated routing algorithm (HIRA) and bandwidth-based integrated routing algorithm (BIRA). We use connection blocking probability and number of optical-electrical-optical (o-e-o) conversions as performance metrics to evaluate these two algorithms. Through extensive simulation experiments, we demonstrate that our algorithms perform better in terms of the above two metrics than other existing approaches.
Ultrastructure of Paired Helical Filaments of Alzheimer's Neurofibrillary Tangle

Isolated paired helical filaments (PHF) of Alzheimer's disease and senile dementia of the Alzheimer type (AD/SDAT) were studied by negative stain techniques and electron microscopy (EM). The helical structure of the PHF was confirmed by tilt analysis of negatively stained isolated PHF. A substructure of four protofilaments, each 3–5 nm in diameter, was also observed. A comparison of PHF substructure, neurofilaments and microtubules, revealed no similarity among the three structures.
View Planning and Refractive Modeling for Structure and Motion

This thesis presents contributions to structure-and-motion estimation, a central topic in the field of geometric computer vision. In particular, the problem of view planning is considered, and continuous and discrete optimization-based algorithms are given for how to plan the path of a sensor to its destination, while balancing the competing goals of path length and reconstruction accuracy. The same concepts are then applied to the problem of sequential 3D reconstruction from unordered image sequences. By propagating reconstruction uncertainties and actively selecting the order in which images are used via view planning, significant gains in robustness and computational efficiency are achieved. The second topic of the thesis is refractive structure-and-motion, specifically the problem of absolute pose estimation when the camera and structure are separated by an optically refracting plane. Using methods from algebraic geometry for solving multivariate polynomial systems, efficient minimal and near-minimal solvers are constructed. Finally, a practical method for calibrating a set of cameras under refraction is given, including an algorithm for efficient refractive bundle adjustment.
GFP is the way to glow: bioimaging of the plant endomembrane system

It is less than a decade that the green fluorescent protein (GFP) and its spectral variants have changed the approach to studying the dynamics of the plant secretory pathway. GFP technology has in fact shed new light on secretory events by allowing bioimaging in vivo right to the heart of a plant cell. This review highlights exciting discoveries and the most recent developments in the understanding of morphology and dynamics of the plant secretory pathway achieved with the application of fluorescent proteins.
Magnetic carbon nanotubes: preparation, physical properties, and applications in biomedicine

Abstract Magnetic carbon nanotubes (MCNTs) have been widely studied for their potential applications in medicine, diagnosis, cell biology, analytical chemistry, and environmental technology. Introduction of MCNTs paved the way for the emergence of new approaches in nanobiotechnology and biomedicine as a result of their multifarious properties embedded within either the carbon nanotubes (CNTs) or magnetic parts. Numerous preparation techniques exists for functionalizing CNTs with magnetic nanoparticles, and these versatile strategies lay the ground for the generation of novel and versatile systems which are applicable to many industries and biological areas. Here, we review and discuss the recent papers dealing with MCNTs and their application in biomedical and industrial fields.
Rab8, a Vesicular Traffic Regulator, Is Involved in Dengue Virus Infection in HepG2 Cells

Objective: The pathogenesis of dengue virus (DV) has not been completely clarified. Rab8 regulates vesicular traffic from Golgi to plasma membrane where DV is matured and then delivered by exocytosis. In this study, involvement of Rab8 in DV serotype 2 (DV2) infection was investigated in HpeG2 cells. Methods: Distributions of Rab8 and DV2, and the number of infection cells were observed by immunostaining. HepG2Rab8AM and HepG2Rab8DN cells were constructed to stably express a constitutively active mutant of Rab8 and a dominant negative mutant, respectively, which were assessed by flow cytometry. Production of infectious virions and the amounts of DV2 entry were detected by standard plaque assay. Viral RNA replication was detected by real-time RT-PCR. Results: Rab8 showed high co-localization with DV2 in HpeG2 cells and the amount of DV antigen-positive cells decreased in HepG2Rab8AM and HepG2Rab8DN cells. Also, progeny virus released from those cells was drastically reduced. Infectious virions produced in cells were also significantly reduced, while the viral RNA replication was down-regulated by a different level. Furthermore, viral entry into those cells was reduced by about 80%. Conclusions: Our data suggest that the function of Rab8 is important for DV2 infection, and Rab8 may be involved in DV2 infection.
Active perception for 3D range-only simultaneous localization and mapping with UAVs

Most localization approaches do not take into account the possibility of controlling the robot to improve the perception, instead, the robot is just commanded with a predefined path. Active sensing strategies may lead to more efficient exploration and mapping approaches. The robot can adapt its trajectory, avoiding for instance non-observable motions or following those paths which are most informative. In the case of Range-only Simultaneous Localization and Mapping (RO-SLAM), this means selecting the path which is likely to produce the highest reduction in the uncertainty on the landmarks' positions. This paper proposes an active sensing approach able to command the UAV to more informative areas from the RO-SLAM point of view, allowing a faster filter convergence and better mapping accuracy.
Late Holocene climate: Natural or anthropogenic?

For more than a decade, scientists have argued about the warmth of the current interglaciation. Was the warmth of the preindustrial late Holocene natural in origin, the result of orbital changes that had not yet driven the system into a new glacial state? Or was it in considerable degree the result of humans intervening in the climate system through greenhouse gas emissions from early agriculture? Here we summarize new evidence that moves this debate forward by testing both hypotheses. By comparing late Holocene responses to those that occurred during previous interglaciations (in section 2), we assess whether the late Holocene responses look different (and thus anthropogenic) or similar (and thus natural). This comparison reveals anomalous (anthropogenic) signals. In section 3, we review paleoecological and archaeological syntheses that provide ground truth evidence on early anthropogenic releases of greenhouse gases. The available data document large early anthropogenic emissions consistent with the anthropogenic ice core anomalies, but more information is needed to constrain their size. A final section compares natural and anthropogenic interpretations of the δ13C trend in ice core CO2.
[Fuzzy cluster analysis of therapeutic effects of electro-acupuncture at different parameters].

OBJECTIVE To probe into the application of fuzzy cluster in analysis of therapeutic effects of electro-acupuncture at different parameters on adjuvant-induced arthritis (AA) in rats. METHODS One hundred Wistar rats were randomly divided into ten groups: normal control group, untreated group and eight electro-acupuncture groups at different parameters. There were ten rats in each group. AA rats were treated by electro-acupuncture at different frequencies (2 Hz or 100 Hz), waveforms (successive wave or intermittent wave) and current intensities (0.1 mA or 0.2 mA). Firstly, the anti-inflammatory and analgesic effects of electro-acupuncture at different parameters were compared with orthogonal experiment, and then with the application of fuzzy mathematics, the data of joint swelling, pain threshold and the contents of beta-endorphin (beta-EP) and interleukin-1beta (IL-1beta) after the treatment in all groups were standardized by the method of data range normalization. Programming and solution were done by MATLAB. The methods of fuzzy similar matrix and the transitive closure were used in similarity evaluation of therapeutic effects of electro-acupuncture at different parameters. RESULTS Based on index determination and variance analysis, both the normal control group and untreated group were clustered to one category as lambda equaled to 0.72. Electro-acupuncture at 100 Hz, successive wave, 0.2 mA, electro-acupuncture at 100 Hz, intermittent wave, 0.1 mA and electro-acupuncture at 100 Hz, intermittent wave, 0.2 mA were clustered to one category and had similar good anti-inflammatory and analgesic effects. The therapeutic effects of the remaining electro-acupuncture types were similar. CONCLUSION Fuzzy cluster analysis provides a better method for evaluating the overall therapeutic effects of electro-acupuncture with multiple factors.
Isolated Central Diabetes Insipidus in a Newborn with Congenital Toxoplasmosis

We present a 5 day-old male newborn with isolated central diabetes insipidus due to congenital toxoplasmosis. This patient was referred to us for hydrocephalus. As we investigated the aetiology of the hydrocephalus, the patient's serum and cerebrospinal fluid tested positive for toxoplasmosis via ELISA and polymerase chain reaction. Computed tomography showed obstructive hydrocephalus and disseminated cranial calcifications. Central diabetes insipidus developed on the 10th day, apparently as a result of the toxoplasmosis infection, and was treated successfully with oral desmopressin.