Miracle-dz/UniFAR-FTUs huggingface dataset:
Genetic variability in the cytochrome P450–paraoxonase 1 (PON1) pathway for detoxication of organophosphorus compounds

Detoxication of organophosphorus (OP) compounds is affected by genetic and environmental modulation of a number of enzymes involved in the process. For organophosphorothioate insecticides, different P450 isozymes and variants carry out two reactions that have quite different consequences; (1) they bioactivate their parent compounds to highly toxic oxon forms that are many times more toxic than the parent compounds, and (2) concurrently, they dearylate the parent OP compounds, generating much less toxic metabolites. The ratios at which these different P450s carry out bioactivation versus dearylation differ among the P450 isozymes. The detoxication of the oxon forms of diazinon and chlorpyrifos is achieved by hydrolysis to the respective aromatic alcohols and diethyl phosphates primarily by paraoxonase 1 (PON1), a plasma enzyme tightly associated with high‐density lipoprotein particles and also found in liver. Stoichiometric binding to other targets also contributes to the detoxication of these oxons. PON1 is polymorphically distributed in human populations with an amino acid substitution (Gln/Arg) at position 192 of this 354‐amino acid protein (the initiator Met residue is cleaved on maturation) that determines the catalytic efficiency of hydrolysis of some substrates. In addition to the variable catalytic efficiency determined by the position 192 amino acid, protein levels of PON1 vary by as much as 15‐fold among individuals with the same PON1192 genotype (Q/Q; Q/R; R/R). The generation of PON1 null mice and transgenic mice, expressing each of the human PON1192 alloforms in place of mouse PON1, has allowed for the examination of the physiological function of the PON1192 alloforms in OP detoxication. Sensitivity to diazoxon exposure is primarily determined by the plasma level of PON1, whereas for chlorpyrifos oxon exposure, both the plasma PON1 level and the position 192 amino acid are important—PON1R192 is more efficient in inactivating chlorpyrifos oxon than is PON1Q192. The availability of PON1 null mice provides an opportunity to examine the contribution of other enzymes in the OP detoxication pathways without PON1 interference. © 2007 Wiley Periodicals, Inc. J Biochem Mol Toxicol 21:197–205, 2007; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.20181
Activation of autophagy and AMPK by gamma-tocotrienol suppresses the adipogenesis in human adipose derived stem cells.

SCOPE This study investigated the mechanistic details by which gamma-tocotrienol (γ-T3) manipulates adipocyte differentiation in human adipose derived stem cells (hASCs). METHODS AND RESULTS γ-T3 specifically inhibited the early stage of adipocyte differentiation by acting on downstream of C/EBP-β but upstream of C/EBP-α in hASCs. In searching a potential mechanism, we identified that γ-T3 promoted two catabolic signaling pathways: (i) AMP kinase (AMPK), and (ii) enhanced autophagy, as assessed by autophagic flux and cytosolic autophagosome (LC3II) accumulation. In addition, chronic exposure of γ-T3 induced caspase3-mediated apoptotic cell death. The blockage of AMPK by a dominant negative mutant of AMPK was insufficient to normalize γ-T3-mediated autophagy, suggesting that enhanced autophagic activity of γ-T3 is independent of AMPK activation. Intriguingly, AMPK inhibition significantly restored PPAR-γ activation, but marginally rescued lipid-loaded adipocyte morphology due to, at least partly, a lack of lipid droplet-coating protein. These data suggest that γ-T3 activates AMPK and autophagy signaling, which synergistically contributes to the suppression of adipogenic conversion of hASCs into adipocytes. CONCLUSION These results provide a novel insight into the molecular mechanism involved in anti-adipogenic action of γ-T3 in humans via AMPK and autophagy activation. Thus, γ-T3 may constitute a new dietary avenue to attenuate hyperplastic obesity in humans.
The LIMSI handwriting recognition system for the HTRtS 2014 contest

In this paper we present the handwriting recognition systems submitted by the LIMSI to the HTRtS 2014 contest. The systems for both the restricted and unrestricted tracks consisted of combination of several optical models. We extracted handcrafted features as well as pixels values with a sliding window. We trained Deep Neural Networks (DNNs) and Bidirectional Long Short-Term Memory Recurrent Neural Networks (BLSTM-RNNs), which where plugged as the optical model in Hidden Markov Models (HMMs). We propose a novel method to build language models that can cope with hyphenation in the text. The combination was performed from lattices generated from the different systems. We were the only team participating in both tracks and ranked second in each. The final Word Error Rates were 15.0% and 11.0% for the restricted (resp. unrestricted) track. We studied the impact of adding data for optical and language modeling. After the evaluation, we also used the same corpus for the language model as the winning team and obtained comparable results.
An evaluation of the POSSUM surgical scoring system

POSSUM (Physiological and Operative Severity Score for the enumeration of Morbidity and mortality) has been studied as a possible surgical audit system for a 9‐month interval using a sample of 28 per cent of the general surgical workload. Mortality or survival was analysed as an endpoint. In this sample the published POSSUM predictor equation for mortality overpredicted deaths by a factor of more than two. The bulk of the overprediction occurred in the group at lowest risk (predicted mortality 10 per cent or less), in which death was overpredicted by a factor of six. This is the most important group for audit purposes since it contains the majority of surgical patients and is composed of fit patients undergoing minor surgery. The published predictor equation for mortality returns a minimum predicted mortality of 1·08 per cent, clearly far higher than that expected for a fit patient having minor surgery. Logistic regression was done on a set of 1485 surgical episodes to generate a local predictor equation for mortality. This process gave a predictor equation that fitted well with the observed mortality rate and gave a minimum predicted risk of mortality of 0·20 per cent. The previously published POSSUM predictor equation for mortality performed badly when tested using a standard test of goodness of fit for logistic regression and must be modified.
Group environmental preference aggregation: the principle of environmental justice

The aggregation of group environmental preference presents a challenge of principle that has not, as yet, been satisfactorily met. One such principle, referred to as an environmental justice, is established based on a concept of social justice and axioms for rational choice under uncertainty. It requires that individual environmental choices be so decided that their supporters will least mind being anyone at random in the new environment. The application of the principle is also discussed. Its only information requirement is a ranking of alternative choices by each interested party. 25 references.
Local programming language barriers in stream-based systems

Stream-based data processing systems, such as Complex Event Processing or data stream mining systems, may be composed of several components which may be implemented in various programming languages. In distributed scenarios, computer networks typically represent important bottlenecks. However, the performance of data exchange in local contexts may be as important as the performance of data exchange via computer networks. Local programming language barriers may represent important bottlenecks for components that are located on the same computer system. In distributed scenarios, it may be beneficial to relocate components on a single physical host for exploiting the higher local data throughput. The properties of stream-based systems pose challenges like high throughput requirements but also open up optimization potential such as leveraging batched transfers. We performed an experimental analysis of ways for bridging local programming language barriers using the examples of C, Java, and Python and analyzed the impact of batched forwarding. While local data exchange can be expected to offer a higher throughput than exchange across networks, our results show that batch forwarding can increase the local throughput by factors of up to 47.6 and we measured net throughputs up to 39.5 Gbps.
Induction of a regular nuclear lattice by overexpression of NuMA.

Transient overexpression of nuclear mitotic apparatus protein (NuMA) in HeLa cells results in ordered lattices which can fill the nucleus and which are stable to detergent extraction. Electron microscopy reveals a quasi-hexagonal organization with an average spacing between the vertices of approximately 170 nm and short 6-nm-diameter rods connecting the vertices. Overexpression of a NuMA construct with an in-frame addition in the coiled-coil domain shows hexagons with the spacing increased by 42% while constructs with deletions in the coiled-coil domain yield hexagons with the spacing decreased by 40 and 19%. NuMA constructs truncated at residue 2005 or 2030 in the tail domain cause a drastic reorganization of nuclear components with relocation of the DNA, histone H1, and nucleoli to the nuclear rim. A construct lacking the head and much of the coiled-coil region also affects nuclear organization. In contrast, NuMA constructs truncated at residue 1950 or 1935 which lack the nuclear localization signal display normal nuclear structure but form cytoplasmic aggregates which also display hexagonal organization. Immunoelectron microscopy confirms that the nuclear lattices are built from NuMA. We discuss the importance of the different domains of NuMA for building the ordered in vivo lattices and whether NuMA could play a structural role in the architecture of the normal interphase nucleus.
The nurse's role in cancer rehabilitation: Review of the literature

Rehabilitative nursing is an integral part of all phases of patient-centered care. The role of the nurse in addressing rehabilitation issues for cancer patients is one of teaching, counseling, and coordination. Nurses have made significant contributions to educational programs available to cancer patients and their families. The program structure, content, and setting are as varied as the potential patient. Site-specific support programs, as well as programs that identify and support positive coping behaviors, have been developed by nurses. In their efforts to maximize resource allocation in a variety of settings, nurses have developed roles and programs that promote the process of rehabilitation. This review of nursing literature provides a source for nurses wishing to continue designing programs that enhance rehabilitation.
A common information model (CIM) toolkit framework implemented in Java

The common information model (CIM) is an object-oriented representation of a power system and is used primarily as a data exchange format for power system operational control systems. CIM has the potential to be used as much more than an intermediary exchange language. This paper explores the possible use of CIM as the core of a power systems analytical toolkit for storing, processing, extracting, and exchanging data directly from CIM objects. To this end, this paper discusses solutions to some of the challenges in storing and processing large power system network models as native Java objects without sacrificing reliability and robustness. This paper highlights the advantages provided by such a system when dealing with extensions to the CIM standard and overcoming the problems posed with simultaneously maintaining backward compatibility without sacrificing a higher level of detail. This paper also addresses the issue of data processing performance in contrast to other approaches.
ERK1/2/MAPK pathway-dependent regulation of the telomeric factor TRF2

Telomere stability is a hallmark of immortalized cells, including cancer cells. While the telomere length is maintained in most cases by the telomerase, the activity of a protein complex called Shelterin is required to protect telomeres against unsuitable activation of the DNA damage response pathway. Within this complex, telomeric repeat binding factor 2 (TRF2) plays an essential role by blocking the ataxia telangiectasia-mutated protein (ATM) signaling pathway at telomeres and preventing chromosome end fusion. We showed that TRF2 was phosphorylated in vitro and in vivo on serine 323 by extracellular signal-regulated kinase (ERK1/2) in both normal and cancer cells. Moreover, TRF2 and activated ERK1/2 unexpectedly interacted in the cytoplasm of tumor cells and human tumor tissues. The expression of non-phosphorylatable forms of TRF2 in melanoma cells induced the DNA damage response, leading to growth arrest and tumor reversion. These findings revealed that the telomere stability is under direct control of one of the major pro-oncogenic signaling pathways (RAS/RAF/MEK/ERK) via TRF2 phosphorylation.
Autophagy is a protective mechanism in normal cartilage, and its aging-related loss is linked with cell death and osteoarthritis.

OBJECTIVE Autophagy is a process for turnover of intracellular organelles and molecules that protects cells during stress responses. We undertook this study to evaluate the potential roles of Unc-51-like kinase 1 (ULK1), an inducer of autophagy, Beclin1, a regulator of autophagy, and microtubule-associated protein 1 light chain 3 (LC3), which executes autophagy, in the development of osteoarthritis (OA) and in cartilage cell death. METHODS Expression of ULK1, Beclin1, and LC3 was analyzed in normal and OA human articular cartilage and in knee joints of mice with aging-related and surgically induced OA, using immunohistochemistry and Western blotting. Poly(ADP-ribose) polymerase (PARP) p85 expression was used to determine the correlation between cell death and autophagy. RESULTS ULK1, Beclin1, and LC3 were constitutively expressed in normal human articular cartilage. ULK1, Beclin1, and LC3 protein expression was reduced in OA chondrocytes and cartilage, but these 3 proteins were strongly expressed in the OA cell clusters. In mouse knee joints, loss of glycosaminoglycans (GAGs) was observed at ages 9 months and 12 months and in the surgical OA model, 8 weeks after knee destabilization. Expression of ULK1, Beclin1, and LC3 decreased together with GAG loss, while PARP p85 expression was increased. CONCLUSION Autophagy may be a protective or homeostatic mechanism in normal cartilage. In contrast, human OA and aging-related and surgically induced OA in mice are associated with a reduction and loss of ULK1, Beclin1, and LC3 expression and a related increase in apoptosis. These results suggest that compromised autophagy represents a novel mechanism in the development of OA.
Radiofrequency heating at 9.4T: In vivo temperature measurement results in swine

In vivo temperatures were correlated to the whole head average specific absorption rate (SARavg) at 9.4T using 12 anesthetized swine (mean animal weight = 52 kg, standard deviation = 6.7 kg). Correlating the temperatures and SARavg is necessary to ensure safe levels of human heating during ultra‐high field MR exams. The temperatures were measured at three depths inside the brain, in the rectum, and at the head‐skin of swine. A 400 MHz, continuous wave RF power was deposited to the head using a volume coil. The SARavg values were varied between 2.7–5.8 W/kg. The RF power exposure durations were varied between 1.4–3.7 hr. To differentiate the temperature response caused by the RF from that of the anesthesia, the temperatures were recorded in four unheated swine. To study the effect of the spatial distribution of the RF and tissue properties, the temperature probes were placed at two brain locations (n = 4 swine for each location). Results showed that the in vivo brain temperatures correlated to the SARavg in a geometry‐dependent manner. Additionally, 1) the skin temperature change was not the maximum temperature change; 2) the RF heating caused an inhomogeneous brain temperature distribution; and 3) the maximum temperature occurred inside the brain. Magn Reson Med, 2007. © 2007 Wiley‐Liss, Inc.
Vitamin D receptor polymorphisms: no association with type 1 diabetes in the Finnish population.

OBJECTIVE The effect of polymorphisms of the vitamin D receptor (VDR) gene on susceptibility to type 1 diabetes has recently been investigated extensively. Several findings on positive disease associations have been observed and, in addition, a protective effect of vitamin D supplementation has been reported. DESIGN We studied the effect of three vitamin D receptor gene polymorphisms (VDRA, VDRB, VDRF) on susceptibility to type 1 diabetes in a large case-control series (more than 2000 controls and about 1000 patients) from the Finnish population. METHODS A combination of case-control and affected-family based approaches was used. Subjects were genotyped for VDRA (ApaI), VDRB (BsmI) and VDRF (FokI) single nucleotide polymorphisms using a minisequencing reaction. RESULTS A few borderline significant associations were observed with both approaches used. In the case-control association analyses we found significant differences between cases and controls in frequencies of VDRB (P=0.024, all subjects and P=0.016, HLA DQB1*0302-positive subjects) and VDRF (P=0.0063, Turku cohort). In the total family set a decreased (39.3%) transmission of the VDRA-VDRB-VDRF haplotype 1-1-2 and an increased (60.3%) transmission of haplotype 2-1-2 to sons was seen (P=0.0059 and P=0.024 respectively). Transmission of the haplotype 2-2-1 to daughters was decreased (37.6%, P=0.022). Interestingly, we also observed significant differences in allele frequencies of the polymorphisms studied between populations from three different regions in Finland. CONCLUSIONS All these differences disappeared after correction for multiple testing. We conclude that the single nucleotide polymorphisms analysed are unlikely to be associated with type 1 diabetes in the Finnish population.
Coordinate expression of c-fos and jun B is induced in the rat striatum by cocaine

In cells in culture, specific stimuli induce selective patterns of immediate-early gene induction. In the present study, we tested for such selectivity of stimulated gene expression by monitoring the expression of fos/jun gene mRNAs in the striatum in rats treated in vivo with the indirect dopamine agonist cocaine. We found by Northern blot and in situ hybridization analysis that cocaine induces the coordinate expression of c-fos and jun B mRNAs in neurons of the rat's striatum. By contrast, another immediate-early gene of the leucine- zipper family, c-jun, was not induced in striatal neurons by cocaine at any time tested from 1 to 24 hr after treatment. With the same probe, we could detect the induction of c-jun mRNA (as well as that of c-fos and jun B mRNAs) in the hippocampus following administration of pentylenetetrazol. The induction of expression of c-fos and jun B was rapid and transient, with peak expression occurring at approximately 1 hr after cocaine administration, and the induction of the two genes was in similar striatal sites. These results establish that differential patterns of expression of fos/jun genes occur in striatal neurons following exposure to cocaine, a potent psychomotor stimulant. We suggest that these tissue-specific patterns of gene expression may contribute to the response specificity of striatal neurons to stimulation by monoamines including dopamine.
Backpacker travel and graduates' future employability

This research aims to identify whether or not post-university backpacking has a positive or negative effect on future employability. Questionnaires were distributed to students and telephone interviews were conducted with graduate employers. The main findings from the study show that students and employers share the view that independence is developed whilst backpacking and yet they differ in terms of which skills are important to the workplace. Overall, there is a significant difference between the two samples in terms of the overall effect that backpacking has on future employability chances.
Traumatic brain injury: Risks of epilepsy and implications for medicolegal assessment

Traumatic brain injury (TBI) is a potentially preventable cause of epilepsy. Increasing incidence among army personnel and the high incidence among children and young people raise concern. This article presents a review of selected studies dealing with the risks of TBI and the risk of posttraumatic epilepsy in humans. The incidence of persons admitted to hospital with TBI has decreased in developed countries in recent years. However, there is little change in TBI‐associated deaths, and the decrease in hospitalization may merely reflect that more people with head injury are cared for on an outpatient basis. It is clear that epilepsy is a frequent consequence of brain injury, even many years after the injury. However, several well‐controlled studies have been unable to identify therapies that prevent the development of epilepsy after TBI. Posttraumatic epilepsy has significant implications for the affected individuals, family, and society. Despite several interventions used to prevent posttraumatic epilepsy, the only proven “intervention” to date is to prevent TBI from occurring.
Separation accuracy of free flow electrophoresis as proved by flow cytometry

The separation accuracy of the free flow electrophoresis ACE 710 device was proved by immunological methods. Several cell populations of human peripheral blood were purified using physical cell isolation methods such as countercurrent centrifugal elutriation and cell electrophoresis. The purified cell fractions were treated with fluoresceinisothiocyanate‐labelled antibodies. The percentages of cells in each fraction binding the antibodies of interest were determined by flow cytometry. The analyses revealed that with the help of free flow electrophoresis, given cell population of human peripheral blood can be highly enriched and that preenrichment of minor cell populations enhances the efficacy of a flow cytometer.
Computational model-informed design and bioprinting of cell-patterned constructs for bone tissue engineering

Three-dimensional (3D) bioprinting is a rapidly advancing tissue engineering technology that holds great promise for the regeneration of several tissues, including bone. However, to generate a successful 3D bone tissue engineering construct, additional complexities should be taken into account such as nutrient and oxygen delivery, which is often insufficient after implantation in large bone defects. We propose that a well-designed tissue engineering construct, that is, an implant with a specific spatial pattern of cells in a matrix, will improve the healing outcome. By using a computational model of bone regeneration we show that particular cell patterns in tissue engineering constructs are able to enhance bone regeneration compared to uniform ones. We successfully bioprinted one of the most promising cell-gradient patterns by using cell-laden hydrogels with varying cell densities and observed a high cell viability for three days following the bioprinting process. In summary, we present a novel strategy for the biofabrication of bone tissue engineering constructs by designing cell-gradient patterns based on a computational model of bone regeneration, and successfully bioprinting the chosen design. This integrated approach may increase the success rate of implanted tissue engineering constructs for critical size bone defects and also can find a wider application in the biofabrication of other types of tissue engineering constructs.