Miracle-dz/UniFAR-FTUs huggingface dataset:
Molecular biology of Hodgkin's and Reed/Sternberg cells in Hodgkin's lymphoma

Hodgkin's and Reed/Sternberg (HRS) cells, the tumour cells in classical Hodgkin's lymphoma (HL), represent transformed B cells in nearly all cases. The detection of destructive somatic mutations in the rearranged immunoglobulin (Ig) genes of HRS cells in classical HL indicated that they originate from preapoptotic germinal centre (GC) B cells that lost the capacity to express a high‐affinity B‐cell receptor (BCR). Several aberrantly activated signalling pathways and transcription factors have been identified that contribute to the rescue of HRS cells from apoptosis. Among the deregulated signalling pathways, activation of multiple receptor tyrosine kinases in HRS cells appears to be a specific feature of HL. In about 40% of cases of classical HL the HRS cells are infected by Epstein‐Barr virus (EBV), indicating an important role of EBV in HL pathogenesis. Interestingly, nearly all cases of HL with destructive Ig gene mutations eliminating BCR expression (e.g. nonsense mutations) are EBV‐positive, suggesting that EBV‐encoded genes have a particular function to prevent apoptosis of HRS‐cell precursors that acquired such crippling mutations. This idea is further supported by the recent demonstration that isolated human GC B cells harbouring crippled Ig genes can be rescued by EBV from cell death, giving rise to lymphoblastoid cell lines. The molecular analysis of composite Hodgkin's and non‐Hodgkin's lymphomas indicated that many cases develop from a common GC B‐cell precursor in a multistep transformation process with both shared and distinct oncogenic events. © 2005 Wiley‐Liss, Inc.
Stachybotrys, a mycotoxin-producing fungus of increasing toxicologic importance.

BACKGROUND Stachybotrys as a fungus has been implicated as a source of mycotoxins. While the toxicity of several well-known mycotoxins (aflatoxins) is well documented, recent studies on Stachybotrys have raised the question that mycotoxins produced by this fungus may be responsible for the health effects of occupants in water-damaged buildings. METHODS Published articles regarding Stachybotrys-related mycotoxins were reviewed with particular focus on human toxicity. RESULTS A critical review of papers, reports, and studies on Stachybotrys mycotoxins revealed only descriptive reports of suspected animal and human poisoning secondary to consumption of mold-contaminated food products. No studies of good toxicologic and epidemiologic designs answer whether airborne mycotoxins produced by Stachybotrys could produce specific human toxicity. CONCLUSIONS Current data on the toxicology of mycotoxins produced by Stachybotrys demonstrate that this group of mycotoxins is capable of producing immunosuppression and inflammatory insults to gastrointestinal and pulmonary systems. Case control study and case reports have suggested a possible association with environmental exposure to Stachybotrys mycotoxins, although a firm causal relationship has not been firmly established. Additional studies are needed to document that humans with sufficient exposure to these mycotoxins develop compatible clinical and pathologic pictures as demonstrated in animal models.
Albendazole: a review of anthelmintic efficacy and safety in humans

This comprehensive review briefly describes the history and pharmacology of albendazole as an anthelminthic drug and presents detailed summaries of the efficacy and safety of albendazole's use as an anthelminthic in humans. Cure rates and % egg reduction rates are presented from studies published through March 1998 both for the recommended single dose of 400mg for hookworm (separately for Necator americanus and Ancylostoma duodenale when possible), Ascaris lumbricoides, Trichuris trichiura, and Enterobius vermicularis and, in separate tables, for doses other than a single dose of 400mg. Overall cure rates are also presented separately for studies involving only children 2–15 years. Similar tables are also provided for the recommended dose of 400mg per day for 3 days in Strongyloides stercoralis, Taenia spp. and Hymenolepis nana infections and separately for other dose regimens. The remarkable safety record involving more than several hundred million patient exposures over a 20 year period is also documented, both with data on adverse experiences occurring in clinical trials and with those in the published literature and/or spontaneously reported to the company. The incidence of side effects reported in the published literature is very low, with only gastrointestinal side effects occurring with an overall frequency of just >1%. Albendazole's unique broad-spectrum activity is exemplified in the overall cure rates calculated from studies employing the recommended doses for hookworm (78% in 68 studies: 92% for A. duodenale in 23 studies and 75% for N. americanus in 30 studies), A. lumbricoides (95% in 64 studies), T. trichiura (48% in 57 studies), E. vermicularis (98% in 27 studies), S. stercoralis (62% in 19 studies), H. nana (68% in 11 studies), and Taenia spp. (85% in 7 studies). The facts that albendazole is safe and easy to administer, both in treatment of individuals and in treatment of whole communities where it has been given by paramedical and nonmedical personnel, have enabled its use to improve general community health, including the improved nutrition and development of children.
[The application of multiple breath nitrogen washout in chronic obstructive pulmonary disease].

OBJECTIVE We investigated ventilation inhomogeneity indices (Sacin, Scond) in patients with chronic obstructive pulmonary disease (COPD) using the multiple breath nitrogen washout test (MBNW) and determined the correlation between the 2 indices ( Scond and Sacin, as a measure of ventilation inhomogeneity in conductive and acinar zones of the lungs, respectively) and lung function to investigate the significance of assessing the COPD severity with ventilation inhomogeneity indices. METHODS Forty-three stable COPD patients and 56 non-smoking healthy subjects were recruited from November 2014 to February 2015. The differences of ventilation inhomogeneity indices (Sacin, Scond) between the 2 groups were compared, and the correlation between ventilation inhomogeneity indices and traditional parameters of lung function were determined using Pearson linear correlation. According to the FEV1%pred=50%, COPD patients were divided into 2 groups and ventilation inhomogeneity indices (Sacin, Scond) were compared between groups. RESULTS Compared with the healthy control group,Sacin [0.320 (0.238, 0.432) vs 0.097 (0.073, 0.144), u=144.5, P<0.001], and Scond [0.082 (0.043, 0.103) vs 0.018 (0.007, 0.028), u=103.5, P<0.001] in COPD patients were significantly increased, and the difference was statistically significant. Sacin and Scond were negatively correlated with FVC%pred (r=-0.686, -0.551, both P<0.001), FEV1%pred (r=-0.681, -0.475, both P<0.01), FEV1/FVC (r=-0.458, -0.210, both P<0.01). Sacin was negatively correlated with DLCO (r=0.413, P<0.01). With the increase in the severity of the disease, Sacin and Scond increased gradually. CONCLUSION Sacin and Scond in COPD patients increased significantly, which was significantly correlated with lung function. COPD has ventilation inhomogeneity in conductive and acinar zones and ventilation inhomogeneity indices can be used to evaluate the severity of COPD.
Automotive hybrid voltage regulator design with adaptive LDO dropout using load-sense technique

A switching converter (DC-DC) cascaded with a low dropout regulator (LDO) gives the best trade off in terms of high system efficiency and low output ripple for automotive power management applications. The dropout voltage of the LDO is fixed based on its peak load. An adaptive LDO dropout technique, based on LDO load-current sensing, has been proposed to improve the moderate and light load system efficiency of the cascaded DC-DC and LDO combination. The feedback from LDO output to DC-DC output is stable and has minimal overhead (<; 2%) in terms of area and current consumption. The 1V LDO with adaptive dropout gives an efficiency improvement of 74% for 1A load to 81.6% for 100uA load across input voltage range of 6V to 18V. The overall hybrid regulator efficiency improvement upto 5% is achieved in simulations using 0. 35μm AMS H35 process.
Inferring Extinction of Mammals from Sighting Records, Threats, and Biological Traits

Abstract: For species with five or more sightings, quantitative techniques exist to test whether a species is extinct on the basis of distribution of sightings. However, 70% of purportedly extinct mammals are known from fewer than five sightings, and such models do not include some important indicators of the likelihood of extinction such as threats, biological traits, search effort, and demography. Previously, we developed a quantitative method that we based on species’ traits in which we used Cox proportional hazards regression to calculate the probability of rediscovery of species regarded as extinct. Here, we used two versions of the Cox regression model to determine the probability of extinction in purportedly extinct mammals and compared the results of these two models with those of stationary Poisson, nonparametric, and Weibull sighting‐distribution models. For mammals with five or more sightings, the stationary Poisson model categorized all but two critically endangered (flagged as possibly extinct) species in our data set as extinct, and results with this model were consistent with current categories of the International Union for the Conservation of Nature. The scores of probability of rediscovery for individual species in one version of our Cox regression model were correlated with scores assigned by the stationary Poisson model. Thus, we used this Cox regression model to determine the probability of extinction of mammals with sparse records. On the basis of the Cox regression model, the most likely mammals to be rediscovered were the Montane monkey‐faced bat (Pteralopex pulchra), Armenian myotis (Myotis hajastanicus), Alcorn's pocket gopher (Pappogeomys alcorni), and Wimmer's shrew (Crocidura wimmeri). The Cox model categorized two species that have recently disappeared as extinct: the baiji (Lipotes vexillifer) and the Christmas Island pipistrelle (Pipistrellus murrayi). Our new method can be used to test whether species with few records or recent last‐sighting dates are likely to be extinct.
Activation of serotonin receptor‐2B rescues small‐for‐size liver graft failure in mice

The implantation of grafts below 30% of the normal liver volume is associated with a high risk of failure known as small‐for‐size (SFS) syndrome. Strategies to rescue small grafts may have a dramatic impact on organ shortage. Serotonin is a potent growth factor for the liver. The goal of this study was to determine whether enhanced serotonin signaling could prevent the deleterious effects of SFS syndrome. We performed 30% normal liver volume transplantations in wild‐type C57/BL6 and interleukin‐6 (IL‐6)−/− mice. Some animals received α‐methyl‐5‐HT (DOI), an agonist of serotonin receptor‐2 (5‐HT2B). Endpoints included long‐term survival, serum and hepatic markers of liver injury and regeneration, assessment of hepatic microcirculation by intravital fluorescence microscopy and scanning electron microscopy, and transcript levels of a variety of serotonin receptors, tumor necrosis factor α, and IL‐6. All recipients of small grafts (controls) died within 2‐4 days of transplantation, whereas half of those receiving DOI survived permanently. Control animals disclosed major liver injury, including diffuse microvesicular steatosis in hepatocytes, impairment of microcirculation, and a failure of regeneration, whereas these parameters were dramatically improved in animals subjected to DOI. Blockage of 5‐HT2B blunted the protective effects of DOI. Whereas IL‐6 levels were higher in DOI‐treated animals, IL‐6−/− mice were still protected by DOI, suggesting a protective pathway independent of IL‐6. Conclusion: Serotonin through its action on receptor‐2B protects SFS liver grafts from injury and prevents microcirculation and regeneration. The mechanism of hepato‐protection is independent of IL‐6. (Hepatology 2011;)
Distribution pricing based on yardstick regulation

Summary form only given as follows. Transmission and distribution (T&D) pricing has been one of the keystones of the ongoing deregulation and privatization process in the power industry. The electricity market has been established based on the assumption of open access and nondiscriminatory use of the T&D assets. As T&D business remains as a monopoly, it is necessary to provide economic regulation. Many papers have dealt with transmission pricing and certain maturity has been reached in this area, but this is not true in the case of distribution services. This paper focuses on the distribution pricing methods and suggests one that is currently under development in Brazil. This method is based on incremental costs derived from the aggregated expansion plan of a particular utility, named model utility. This utility was obtained by comparisons among the real distribution companies. The method follows the fundamentals of the yardstick regulation.
Protectionism and international diplomacy

Just three decades after the fall of the Berlin Wall signifying the end of Cold War aggression and the ascendancy of international liberalism, the world faces even greater uncertainty. In every region of the world, geopolitical shifts are taking place that have brought offensive trade agendas to the fore. The US has withdrawn from underwriting the post-World War Two international economic and foreign policy architecture, instead proposing to build a wall between itself and neighbouring Mexico, imposing unilateral tariff increases while refusing to negotiate new international agreements. In Europe, the project of ever greater integration has been attacked by Brexit, as well as other populist sentiment against the perceived power of EU institutions and the forces of globalisation. The breakdown of the western coalition advocating global governance has left a power vacuum that other key players such as China are forced to respond to. These current tectonic shifts in power and foreign policy positions impact on every country and every individual in the early 21st century. While many governments strive to maintain international cooperation and further integration, it is an unpredictable era. For trade policy has established itself firmly within the arena of high foreign diplomacy and as a result, traditional assumptions and adherence to international norms can no longer be assumed in such a state of political and economic flux. Yet when trade policy becomes a tool of diplomacy and foreign policy, sound economic reasoning can be lost to political decision making. This report shines a spotlight on the rise of protectionism in the 21st century. It examines the diplomatic dynamics behind economic nationalism and its attack on the established liberal international institutions that were created after the second World War to settle disputes without recourse to war. Before focusing on the US, UK, EU and China, the first chapter centers on the threat to economic integration and cooperation in promoting sustainable development through the multilateral rules-based system established under the World Trade Organization.
Responsive Neuromodulators Based on Artificial Neural Networks Used to Control Seizure-like Events in a Computational Model of Epilepsy

Deep brain stimulation (DBS) has been noted for its potential to suppress epileptic seizures. To date, DBS has achieved mixed results as a therapeutic approach to seizure control. Using a computational model, we demonstrate that high-complexity, biologically-inspired responsive neuromodulation is superior to periodic forms of neuromodulation (responsive and non-responsive) such as those implemented in DBS, as well as neuromodulation using random and random repetitive-interval stimulation. We configured radial basis function (RBF) networks to generate outputs modeling interictal time series recorded from rodent hippocampal slices that were perfused with low Mg²⁺/high K⁺ solution. We then compared the performance of RBF-based interictal modulation, periodic biphasic-pulse modulation, random modulation and random repetitive modulation on a cognitive rhythm generator (CRG) model of spontaneous seizure-like events (SLEs), testing efficacy of SLE control. A statistically significant improvement in SLE mitigation for the RBF interictal modulation case versus the periodic and random cases was observed, suggesting that the use of biologically-inspired neuromodulators may achieve better results for the purpose of electrical control of seizures in a clinical setting.
cDNA‐AFLP analysis unravels a genome‐wide hrpG‐regulon in the plant pathogen Xanthomonas campestris pv. vesicatoria

The Hrp type III protein secretion system is essential for pathogenicity of the Gram‐negative plant pathogen Xanthomonas campestris pv. vesicatoria. Expression of the hrp gene cluster is controlled by HrpG, a two‐component response regulator, and HrpX, an AraC‐type transcriptional activator. Using the cDNA‐AFLP technique, 30 hrpG‐induced (hgi) and five hrpG‐repressed (hgr) cDNA fragments were identified, defining a large hrpG‐regulon in X. campestris pv. vesicatoria. Expression of most genes in the hrpG‐regulon was dependent on hrpX. Seven cDNA fragments map to the known hrp gene cluster and flanking regions. All other genes appear to be scattered over the chromosome and endogenous plasmids. Sequence analysis identified genes encoding putative extracellular proteases, a putative transcriptional regulator and XopJ and XopB (Xanthomonas outer proteins), homologues of YopJ from Yersinia spp. and the avirulence protein AvrPphD of Pseudomonas syringae respectively. XopB is secreted by the Hrp type III secretion system. Analysis of deletion mutants in several hgi genes revealed a new virulence locus. This study demonstrates that cDNA‐AFLP is a powerful tool to study prokaryotic transcriptomes and to identify genes contributing to Xanthomonas virulence and putative effector proteins.
High-Mobility Group A (HMGA) Proteins and Breast Cancer

The high-mobility group A (HMGA) protein family includes HMGA1a, HMGA1b and HMGA1c, which are encoded by the same gene through alternative splicing, and the closely related HMGA2 protein. HMGA proteins have been found to be abundant in several malignant neoplasias, including colorectal, prostate, cervical, lung, thyroid and breast carcinoma. HMGA proteins can be ideal candidates for the identification of new prognosis and diagnosis factors with non-invasive methods. To provide some clarity regarding the abundance of articles on this topic, here we focus on the relationship between HMGA proteins and breast cancer and their clinical perspective in the development of new therapeutic strategies.
Functional radiography of the lumbar spine.

Functional methods utilising the effects of gravity on the upright lordotic spine were developed for both static and dynamic radiography. Static standing orthoradiography of the lumbar spine and weight-bearing joints of the lower extremities shows constitutional and functional abnormalities not visible in conventional recumbent radiography, e.g., postural scoliosis, hypo- or hyperlordosis, "kissing spine"-syndrome and signs of segmental instability. In dynamic traction-compression radiography segmental instability is provoked by axial traction and compression of the spine. With this method translatory instability of 5 to 15 mm was found in about half of the patients with lytic spondylolisthesis of L5 for which flexion-extension radiography had consistently failed to produce any abnormal movement. The amount of anterior spondylolisthetic and posterior retro-olisthetic instability correlated significantly with the severity of back pain symptoms, the degree of maximal static slip, however, being without significance. Functional radiography showed positive findings in most patients suffering from chronic low back pain of otherwise unknown aetiology.
Characterization of white matter alterations in phenylketonuria by magnetic resonance relaxometry and diffusion tensor imaging

A multimodal MR study including relaxometry, diffusion tensor imaging (DTI), and MR spectroscopy was performed on patients with classical phenylketonuria (PKU) and matched controls, to improve our understanding of white matter (WM) lesions. Relaxometry yields information on myelin loss or malformation and may substantiate results from DTI attributed to myelin changes. Relaxometry was used to determine four brain compartments in normal‐appearing brain tissue (NABT) and in lesions: water in myelin bilayers (myelin water, MW), water in gray matter (GM), water in WM, and water with long relaxation times (cerebrospinal fluid [CSF]‐like signals). DTI yielded apparent diffusion coefficients (ADCs) and fractional anisotropies. MW and WM content were reduced in NABT and in lesions of PKU patients, while CSF‐like signals were significantly increased. ADC values were reduced in PKU lesions, but also in the corpus callosum. Diffusion anisotropy was reduced in lesions because of a stronger decrease in the longitudinal than in the transverse diffusion. WM content and CSF‐like components in lesions correlated with anisotropy and ADC. ADC values in lesions and in the corpus callosum correlated negatively with blood and brain phenylalanine (Phe) concentrations. Intramyelinic edema combined with vacuolization is a likely cause of the WM alterations. Correlations between diffusivity and Phe concentrations confirm vulnerability of WM to high Phe concentrations. Magn Reson Med 58:1145–1156, 2007. © 2007 Wiley‐Liss, Inc.
Treatment of leg veins with indocyanine green and lasers investigated with mathematical modelling

Purpose: The treatment of leg veins is routinely performed in clinical practice using near infrared (NIR) lasers. However, due to low absorption of NIR light in blood vessels, the clinical results are still suboptimal. The absorption of the NIR light can be significantly increased with intravenous introduction of an indocyanine green (ICG) dye. In this work a mathematical model was used to delineate clinically valid settings for ICG and NIR lasers for the treatment of leg veins. Methods: A finite element commercial package was used to simulate light propagation and absorption and heat generation in a skin-like geometry. The simulations were conducted for 755 nm and 810 nm light wavelengths, which are emitted by alexandrite and diode lasers, respectively. Five different laser settings, six different vessel diameters (0.1-2 mm) and three ICG concentrations (0, 1 or 2 mg/kg body weight (BW)) were used to calculate the temperature field spatial distribution as a function of time. Results: The diameter of the blood vessels affects the temperature distribution during and following laser irradiation, with and without ICG. Adding 1 or 2 mg/kg bw of ICG will cause significant temperature increase (15–35°C, p ≤ 0.001) in blood vessels with a diameter of 0.1–1 mm and steep temperature gradients in 1.5–2 mm diameter blood vessels. Conclusions: Intravenous application of ICG at 1–2 mg/kg may improve coagulation of blood vessels with 0.1–1 mm diameter irradiated with either a diode or alexandrite laser. This should be confirmed with clinical trials in the near future.