Miracle-dz/UniFAR-FTUs huggingface dataset:
Curcumin suppresses human papillomavirus oncoproteins, restores p53, rb, and ptpn13 proteins and inhibits benzo[a]pyrene‐induced upregulation of HPV E7

Curcumin has great potential as a chemopreventive and chemotherapeutic agent; however, its effects on human papillomavirus (HPV)‐associated molecular events are inadequately explored. This study examined the effects of curcumin on HPV‐associated pathways involved in developing cervical cancer. We demonstrate for the first time that curcumin treatment suppresses cervical cancer cell growth in a three‐dimensional raft culture system. Curcumin also inhibits tumorigenic characteristics as shown by decreases in both clonogenic potential and cell motility. Additionally, our findings show that curcumin treatment inhibits the transcription of HPV16 E6/E7 as early as 6 h posttreatment and restores the expression of tumor suppressor proteins p53, retinoblastoma protein, and PTPN13. While smoking is a recognized risk factor for cervical cancer, the molecular effects of smoke carcinogens on the expression of HPV E6/E7 oncogenes are not well known. We show for the first time that exposure to benzo[a]pyrene (BaP), a tobacco carcinogen, increases the expression of HPV E7 oncoprotein suggesting a molecular link between smoking and cervical cancer. Importantly, curcumin decreases the BaP induced increase in the expression of HPV E7 oncoprotein. The results of this study clearly demonstrate that curcumin alters HPV‐associated molecular pathways in cervical cancer cells. These novel findings imply that curcumin may be an effective chemopreventive and therapeutic agent for cervical cancer prevention and treatment. Mol. Carcinog. © 2010 Wiley‐Liss, Inc.
Differential Nuclear and Mitochondrial DNA Preservation in Post-Mortem Teeth with Implications for Forensic and Ancient DNA Studies

Major advances in genetic analysis of skeletal remains have been made over the last decade, primarily due to improvements in post-DNA-extraction techniques. Despite this, a key challenge for DNA analysis of skeletal remains is the limited yield of DNA recovered from these poorly preserved samples. Enhanced DNA recovery by improved sampling and extraction techniques would allow further advancements. However, little is known about the post-mortem kinetics of DNA degradation and whether the rate of degradation varies between nuclear and mitochondrial DNA or across different skeletal tissues. This knowledge, along with information regarding ante-mortem DNA distribution within skeletal elements, would inform sampling protocols facilitating development of improved extraction processes. Here we present a combined genetic and histological examination of DNA content and rates of DNA degradation in the different tooth tissues of 150 human molars over short-medium post-mortem intervals. DNA was extracted from coronal dentine, root dentine, cementum and pulp of 114 teeth via a silica column method and the remaining 36 teeth were examined histologically. Real time quantification assays based on two nuclear DNA fragments (67 bp and 156 bp) and one mitochondrial DNA fragment (77 bp) showed nuclear and mitochondrial DNA degraded exponentially, but at different rates, depending on post-mortem interval and soil temperature. In contrast to previous studies, we identified differential survival of nuclear and mtDNA in different tooth tissues. Futhermore histological examination showed pulp and dentine were rapidly affected by loss of structural integrity, and pulp was completely destroyed in a relatively short time period. Conversely, cementum showed little structural change over the same time period. Finally, we confirm that targeted sampling of cementum from teeth buried for up to 16 months can provide a reliable source of nuclear DNA for STR-based genotyping using standard extraction methods, without the need for specialised equipment or large-volume demineralisation steps.
Late-onset episodic ataxia type 2 due to an in-frame insertion in CACNA1A

Episodic ataxia type 2 (EA2) is caused by calcium channel (CACNA1A) mutations and typically begins before age 20 years. The molecular basis of late-onset EA2 is unclear. The authors describe a case of late-onset EA2 associated with the first multiple–base pair insertion in CACNA1A. Molecular expression revealed evidence of impaired calcium channel function, suggesting that genetically induced reduction in calcium channel function may associate with cases of late-onset EA2.
Molecular and functional characterization of two isoforms of chalcone synthase and their expression analysis in relation to flavonoid constituents in Grewia asiatica L

Chalcone synthase constitutes a functionally diverse gene family producing wide range of flavonoids by catalyzing the initial step of the phenylpropanoid pathway. There is a pivotal role of flavonoids in pollen function as they are imperative for pollen maturation and pollen tube growth during sexual reproduction in flowering plants. Here we focused on medicinally important fruit-bearing shrub Grewia asiatica. It is a rich repository of flavonoids. The fruits are highly acclaimed for various putative health benefits. Despite its importance, full commercial exploitation is hampered due to two drawbacks which include short shelf life of its fruits and larger seed volume. To circumvent these constraints, seed abortion is one of the viable options. Molecular interventions tested in a number of economic crops have been to impair male reproductive function by disrupting the chalcone synthase (CHS) gene activity. Against this backdrop the aim of the present study included cloning and characterization of two full-length cDNA clones of GaCHS isoforms from the CHS multigene family. These included GaCHS1 (NCBI acc. KX129910) and GaCHS2 (NCBI acc. KX129911) with an ORF of 1176 and 1170 bp, respectively. GaCHSs were heterologously expressed and purified in E. coli to validate their functionality. Functionality of CHS isoforms was also characterized via enzyme kinetic studies using five different substrates. We observed differential substrate specificities in terms of their Km and Vmax values. Accumulation of flavonoid constituents naringenin and quercetin were also quantified and their relative concentrations corroborated well with the expression levels of GaCHSs. Further, our results demonstrate that GaCHS isoforms show differential expression patterns at different reproductive phenological stages. Transcript levels of GaCHS2 were more than its isoform GaCHS1 at the anthesis stage of flower development pointing towards its probable role in male reproductive maturity.
The Role of Task in the Development of Academic Thinking through Reading and Writing in a College History Course

The purpose of this study was to examine how different writing tasks influence students’ thinking in reading and writing. The tasks used in this study, writing either a report or a problem-based essay, required students to integrate prior knowledge with information from six sources in order to create their own texts. The 15 undergraduates, enrolled in a seminar on European history, were randomly assigned to one of two task conditions, report or problem. Analyses focused on students’ acquisition of topic knowledge and the ways writers structured meaning as they organized and selected information. For insights into how writers approached these two tasks, all students provided think-aloud protocols and kept reading-writing logs. Classroom observations also provided information about contextual factors that can influence the strategies students use in reading to create their own texts. Comparisons made between the two groups revealed that they differed significantly in their interpretations of the two tasks and in their approaches to restructuring information from sources. However, there was no difference between the amount of prior knowledge that students writing reports and problem-based essays included in their essays, nor were there differences in learning. Both groups of students improved their understanding of a given historical event. Possible directions for future research are discussed.
Effect of choline chloride in allergen-induced mouse model of airway inflammation

The incidence of asthma has increased the world over, and current therapies for the disease suffer from potential side-effects. This has created an opportunity to develop novel therapeutic approaches. Here, the anti-inflammatory activity of choline was investigated in a mouse model of allergic airway inflammation. Choline (1 mg·kg−1) was administered via oral gavage or intranasally before and after ovalbumin (OVA) challenge in sensitised mice. Airway hyperresponsiveness (AHR) to methacholine was measured in the mice by whole-body plethysmography. Type-2 T-helper cell cytokine and leukotriene levels were estimated in bronchoalveolar lavage fluid (BALF) and spleen culture supernatant by ELISA. Eosinophil peroxidase activity was also determined in the BALF supernatant. Choline treatment in sensitised mice before OVA challenge via oral/intranasal routes significantly inhibited eosinophilic airway inflammation and eosinophil peroxidase activity. It also reduced immunoglobulin E and G1 production and inhibited the release of type-2 T-helper cell cytokines and leukotrienes. However, the development of AHR was prevented effectively by intranasal choline treatment. Most importantly, choline treatment after OVA challenge by both routes could reverse established asthmatic conditions in mice by inhibiting AHR, eosinophilic airway inflammation and other inflammatory parameters. This study provides a new therapeutic approach for controlling as well as preventing asthma exacerbations.
Hilltop inflation

We study ‘hilltop’ inflation, in which inflation takes place near a maximum of the potential. Viewed as a model of inflation after the observable Universe leaves the horizon (observable inflation), hilltop inflation is rather generic. If the potential steepens monotonically, observable hilltop inflation gives a tiny tensor fraction . The usual F- and D-term models may easily be transmuted to hilltop models by Planck-suppressed terms, making them more natural. The only commonly considered model of observable inflation which is definitely not hilltop is tree-level hybrid inflation. Viewed instead as an initial condition, we explain that hilltop inflation is more generic than seems to have been previously recognized, adding thereby to the credibility of the idea that eternal inflation provides the pre-inflationary initial condition.
Negotiated A* Routing for FPGAs ∗

In the next few years, logic capacities for fieldprogrammable gate arrays are expected to exceed one million gates per device. While this expansion of FPGA device resources offers the promise of exceptional finegrained performance for developing technologies such as ASIC prototyping and FPGA computing, supporting computer-aided design tools have yet to be developed to target these devices rapidly and efficiently. This paper addresses the compilation time issue for routing array FPGAs with segmented routing architectures. By treating the routing problem as an A∗ search, it is possible to trade additional device routing resources for decreased router run-time by converting an exhaustive breadth-first maze route into a shorter depth-first route. It is shown that for the depth-first case, the sparse nature of FPGA routing switches in commerical architectures, such as the Xilinx XC4000 family, necessitates an additional localized search near net inputs, called domain negotiation, to aid in directing the route of each design net onto a set of routing resources most likely to lead to a successful route. For a set of large FPGA benchmarks, a route time speedup of over an order of magnitude for an iterative maze router configured for depth-first routing is shown when compared to the same router configured for a breadth-first search.
Establishment of Myotis myotis Cell Lines - Model for Investigation of Host-Pathogen Interaction in a Natural Host for Emerging Viruses

Bats are found to be the natural reservoirs for many emerging viruses. In most cases, severe clinical signs caused by such virus infections are normally not seen in bats. This indicates differences in the virus-host interactions and underlines the necessity to develop natural host related models to study these phenomena. Due to the strict protection of European bat species, immortalized cell lines are the only alternative to investigate the innate anti-virus immune mechanisms. Here, we report about the establishment and functional characterization of Myotis myotis derived cell lines from different tissues: brain (MmBr), tonsil (MmTo), peritoneal cavity (MmPca), nasal epithelium (MmNep) and nervus olfactorius (MmNol) after immortalization by SV 40 large T antigen. The usefulness of these cell lines to study antiviral responses has been confirmed by analysis of their susceptibility to lyssavirus infection and the mRNA patterns of immune-relevant genes after poly I:C stimulation. Performed experiments indicated varying susceptibility to lyssavirus infection with MmBr being considerably less susceptible than the other cell lines. Further investigation demonstrated a strong activation of interferon mediated antiviral response in MmBr contributing to its resistance. The pattern recognition receptors: RIG-I and MDA5 were highly up-regulated during rabies virus infection in MmBr, suggesting their involvement in promotion of antiviral responses. The presence of CD14 and CD68 in MmBr suggested MmBr cells are microglia-like cells which play a key role in host defense against infections in the central nervous system (CNS). Thus the expression pattern of MmBr combined with the observed limitation of lyssavirus replication underpin a protective mechanism of the CNS controlling the lyssavirus infection. Overall, the established cell lines are important tools to analyze antiviral innate immunity in M. myotis against neurotropic virus infections and present a valuable tool for a broad spectrum of future investigations in cellular biology of M. myotis.
Screening of rotavirus and adenovirus infections during prolonged hospitalization in a neonatal unit

Rotavirus and adenovirus infections in 308 infants hospitalized for longer than 1 wk, and cases with necrotizing enterocolitis, were screened in a neonatal unit during a 15 mo period, covering two rotavirus epidemics in the community. Altogether, 1020 stool samples were collected weekly until hospital discharge, and in necrotizing enterocolitis cases at the onset of symptoms, and tested for rotavirus and adenovirus by means of enzyme‐linked immunosorbent assay. The positive samples were further analysed by polymerase chain reaction. Enzyme‐linked immunosorbent assay revealed five adenovirus‐positive cases, which were tested negative by polymerase chain reaction. Out of 16 necrotizing enterocolitis cases, one was adenovirus‐ and another rotavirus positive when tested by polymerase chain reaction, the latter having a concomitant Candida albicans septicaemia.
An Infeasible Bundle Method for Nonsmooth Convex Constrained Optimization without a Penalty Function or a Filter

Global convergence in constrained optimization algorithms has traditionally been enforced by the use of parametrized penalty functions. Recently, the filter strategy has been introduced as an alternative. At least part of the motivation for using filter methods consists of avoiding the need for estimating a suitable penalty parameter, which is often a delicate task. In this paper, we demonstrate that the use of a parametrized penalty function in nonsmooth convex optimization can be avoided without using the relatively complex filter methods. We propose an approach which appears to be more direct and easier to implement, in the sense that it is closer in spirit and structure to the well-developed unconstrained bundle methods. Preliminary computational results are also reported.
Alternative splicing of Myb-related genes MYR1 and MYR2 may modulate activities through changes in dimerization, localization, or protein folding

Arabidopsis genes MYR1 and MYR2 are regulators of flowering time under low light intensity. These Myb-related genes are expressed as alternative splice variants affected in their coiled-coil and DNA-binding domains. We tested whether alternative splicing could affect dimerization and localization of MYR1 and MYR2, thereby potentially affecting their activity. Using MYR1 as a model for variants within the coiled-coil region, we detected 2 types of homodimers. For MYR2, alternative splicing in the DNA-binding Myb-like domain abolished the ability of MYR2 to dimerize. Alternative splicing in the coiled-coil domain did not affect nuclear localization, as determined by transient expression in tobacco, while alternative splicing in the DNA-binding domain of MYR2 yielded a distinct intranuclear localization pattern that may reflect changes in phosphorylation-dependent protein folding. Thus alternative splicing of these genes may result in changes in dimerization or protein folding resulting in changes in activity and abundance of MYR1 or MYR2 protein.
Increased tryptophan hydroxylase immunoreactivity in the dorsal raphe nucleus of alcohol‐dependent, depressed suicide subjects is restricted to the dorsal subnucleus

Considerable evidence suggests that alcoholics with co‐occurring depressive disorder are at greater risk for developing psychosocial problems particularly suicidal behavior. Moreover, dysfunction in serotonin (5‐HT) neurotransmission has been implicated in depression, suicide and alcoholism. In the present study, we measured the levels of tryptophan hydroxylase (TPH), the main synthetic enzyme of 5‐HT synthesis, in specific nuclei of the dorsal raphe (DR) in depressed suicide victims with alcohol dependence and matched psychiatrically normal controls. TPH immunoreactivity (IR) was quantified in frozen tissue sections containing the DR from 8 suicide victims with a diagnosis of major depression and alcohol dependence, and 8 psychiatrically normal control subjects by using immunoautoradiographic methods. We found that the levels of TPH‐IR were significantly increased by 46% in the dorsal subnucleus of the DR in depressed suicide victims with alcohol dependence when compared with controls. In contrast, TPH‐IR levels did not significantly differ in the other DR subnuclei between depressed, alcoholic suicide subjects, and controls. Our results indicate that abnormalities in 5‐HT biosynthesis in the brain of depressed alcoholic suicide subjects are restricted within distinct regions of the DR. Synapse 60:81–85, 2006. © 2006 Wiley‐Liss, Inc.
Sequence Classification for

Discriminatively trained classification techniques have been shown to out-perform generative techniques on many speech and natural language processing problems. However, most of the research in machine translation has been based on generative modeling techniques. The application of classification techniques to machine translation requires scaling classifiers to deal with very large label sets (the vocabulary of the target language). In this paper, we present a method to scale classifiers to very large label sets and apply it to train classifiers for machine translation. We contrast this approach to a generatively trained machine translation model represented as a weighted finite-state transducer. We show translation accuracy results on spoken language corpora in English to Spanish and English to Japanese translation tasks.
Real-Time Evolution of Neural Networks in the NERO Video Game

A major goal for AI is to allow users to interact with agents that learn in real time, making new kinds of interactive simulations, training applications, and digital entertainment possible. This paper describes such a learning technology, called real-time NeuroEvolution of Augmenting Topologies (rtNEAT), and describes how rtNEAT was used to build the NeuroEvolving Robotic Operatives (NERO) video game. This game represents a new genre of machine learning games where the player trains agents in real time to perform challenging tasks in a virtual environment. Providing laymen the capability to effectively train agents in real time with no prior knowledge of AI or machine learning has broad implications, both in promoting the field of AI and making its achievements accessible to the public at large.
A comparison of the prevalence of the metabolic syndrome using two proposed definitions.

OBJECTIVE To compare the prevalence of the metabolic syndrome using two definitions: one proposed by the Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III [ATP III]) and one by the World Health Organization (WHO). RESEARCH DESIGN AND METHODS We used data from a nationally representative sample of the noninstitutionalized civilian population of the U.S. from the Third National Health and Nutrition Examination Survey, a cross-sectional health examination survey (1988-1994). RESULTS Among 8608 participants aged >or=20 years, the age-adjusted prevalence was 23.9% using the ATP III definition and 25.1% using the WHO definition. Among all participants, 86.2% were classified as either having or not having the metabolic syndrome under both definitions. Estimates differed substantially for some subgroups, however. For example, in African-American men, the WHO estimate was 24.9%, compared with the ATP III estimate of 16.5%. CONCLUSIONS A universally accepted definition of the metabolic syndrome is needed.
Prevalence of hydrogen cyanide and carboxyhaemoglobin in victims of smoke inhalation during enclosed-space fires: a combined toxicological risk

Background. Hydrogen cyanide (HCN) is one of the most toxic components of fire smoke, but insufficient attention is paid to its potential role as a cause of injury or death in victims (alive or dead) of enclosed-space fires. Objective. To analyse the prevalence of toxic HCN exposure in fire victims and factors that may influence its toxicity, particularly the co-presence of carbon monoxide (CO) and ethanol. Materials and methods. Blood samples from fire victims and persons rescued from fires were analysed. Results. A positive result for HCN (mean concentration 16.83 mg/l) was detected in blood samples from 169 of 285 fire-related deaths (59%). Ethanol was present in 91 (65%) of 139 samples with coincident presence of HCN and carboxyhaemoglobin (COHb). HCN (mean 4.0 mg/l) was also detected in 20 of 40 (50%) fire survivors. Discussion. The high prevalence of coincident CO and HCN in enclosed-space, fire-related deaths should alert clinicians to suspect toxic HCN exposure in all persons rescued from fire with signs and symptoms of respiratory distress. Conclusions. Medical procedures in persons rescued from enclosed-space fires, especially in the pre-hospital setting, should be augmented to cover the possibility of toxic HCN exposure, particularly in individuals who do not respond to standard supportive therapy. Likewise, post-mortem investigations should routinely include assays for HCN when determining probable cause of death.