Miracle-dz/UniFAR-FTUs huggingface dataset:
Sarcocystis neurona Merozoites Express a Family of Immunogenic Surface Antigens That Are Orthologues of the Toxoplasma gondii Surface Antigens (SAGs) and SAG-Related Sequences

ABSTRACT Sarcocystis neurona is a member of the Apicomplexa that causes myelitis and encephalitis in horses but normally cycles between the opossum and small mammals. Analysis of an S. neurona expressed sequence tag (EST) database revealed four paralogous proteins that exhibit clear homology to the family of surface antigens (SAGs) and SAG-related sequences of Toxoplasma gondii. The primary peptide sequences of the S. neurona proteins are consistent with the two-domain structure that has been described for the T. gondii SAGs, and each was predicted to have an amino-terminal signal peptide and a carboxyl-terminal glycolipid anchor addition site, suggesting surface localization. All four proteins were confirmed to be membrane associated and displayed on the surface of S. neurona merozoites. Due to their surface localization and homology to T. gondii surface antigens, these S. neurona proteins were designated SnSAG1, SnSAG2, SnSAG3, and SnSAG4. Consistent with their homology, the SnSAGs elicited a robust immune response in infected and immunized animals, and their conserved structure further suggests that the SnSAGs similarly serve as adhesins for attachment to host cells. Whether the S. neurona SAG family is as extensive as the T. gondii SAG family remains unresolved, but it is probable that additional SnSAGs will be revealed as more S. neurona ESTs are generated. The existence of an SnSAG family in S. neurona indicates that expression of multiple related surface antigens is not unique to the ubiquitous organism T. gondii. Instead, the SAG gene family is a common trait that presumably has an essential, conserved function(s).
Plasmid DNA malaria vaccine: the potential for genomic integration after intramuscular injection.

Plasmid-based (naked DNA) genetic vaccines are now entering clinical trials to test their safety and efficacy in healthy human volunteers. A safety concern unique to this new class of vaccines is the potential risk of deleterious integration into host cell genomic DNA following direct intramuscular injection. To address this issue experimentally, a preclinical safety study was conducted in mice to determine the structural nature of plasmid DNA sequences persisting in total muscle DNA at both 30 and 60 days following a single intramuscular injection of a plasmid expressing the Plasmodium falciparum circumsporozoite protein. In a protocol described for the first time, total DNA was extracted from muscle tissue and was subsequently linearized with a restriction endonuclease to enable agarose gel size fractionation of all extrachromosomal plasmid DNAs from high molecular weight mouse genomic DNA. Using PCR assays to quantitate plasmid-specific sequences, it was found that the amount of plasmid DNA persisting in muscle tissue varied but averaged about 10 fg per microgram of genomic DNA (in the range of 1500 copies per 150,000 genomes). In two of four separate experimental injections of mouse muscle, PCR assays of genomic DNA fractions indicated that agarose gel purification removed plasmid DNA down to a level of < or =3 copies per 150,000 mouse genomes. In the two other experimental samples, 3-30 copies of plasmid DNA remained associated with purified genomic DNA. The time following injection (i.e., 30 or 60 days) was not a factor in the number of copies of plasmid associating with genomic DNA and it was not possible to conclude if such sequences were covalently linked to genomic DNA or simply adventitiously associated with the genomic DNA. However, if an assumption is made that the highest level plasmid DNA found associated with genomic DNA (i.e., 30 copies) represented covalently integrated plasmid inserts and that each insert resulted in a mutational event, the calculated rate of mutation would be 3000 times less than the spontaneous mutation rate for mammalian genomes. This level of integration, if it should occur, was not considered to pose a significant safety concern.
Physiologically Based Modeling of n-Hexane Kinetics in Humans Following Inhalation Exposure at Rest and Under Physical Exertion: Impact on Free 2,5-Hexanedione in Urine and on n-Hexane in Alveolar Air

We used a modified physiologically based pharmacokinetic (PBPK) to describe/predict n-hexane (HEX) alveolar air concentrations and free 2,5-HD urinary concentrations in humans exposed to n-HEX by inhalation during a typical workweek. The effect of an increase in workload intensity on these two exposure indicators was assessed and, using Monte Carlo simulation, the impact of biological variability was investigated. The model predicted HEX alveolar air concentrations at rest of 19.0 ppm (25 ppm exposure) and 38.7 ppm (50 ppm exposure) at the end of the last working day (day 5), while free 2,5-HD urinary concentrations of 3.4 μ mol/L (25 ppm) and 6.3 μ mol/L (50 ppm) were predicted for the same period (last 4.5 hours of Day 5). Monte Carlo simulations showed that the range of values expected to occur in a group of 1000 individuals exposed to 50 ppm of HEX (95% confidence interval) for free 2,5-HD (1.7–14.7 μ mol/L) is much higher compared with alveolar air HEX (33.4–46 ppm). Simulations of exposure at 50 ppm with different workloads predicted that an increase in workload intensity would not greatly affect both indicators studied. However, the alveolar air HEX concentration is more sensitive to modifications of workload intensity and time of sampling, after the end of exposure, compared with 2,5-HD. The PBPK model successfully described the HEX alveolar air concentrations and free 2,5-HD urinary concentrations measured in human volunteers and is the first, to our knowledge, to describe the excretion kinetics of free 2,5-HD in humans over a 5-day period.
Antecedents of national park knowledge in Tanzania

ABSTRACT Over time, national park knowledge has come to constitute the gap between the full social freedom and individual consciousness of the ecological conditions inside a park. While other visitors have a rigorous knowledge of transportation, nature, and culture, some visitors naively enter the area in order to enjoy their tourism rights. Theoretically, our model proposes that national park knowledge can change as a result of knowing about eco-tourist attractions; also, knowledge of public infrastructure and accessibility is strongly correlated to knowledge of what you can and cannot do in the protected area. Eco-tourist attractions include natural resources, cultural attractions, and recreational facilities. The argument is that all the infrastructure is developed around these, as that these are the sources of attraction. Based on the literature, we link these variables with the ecotourism concept, thus positioning our paper as an ecotourism study. A total of 103 questionnaires were returned on the basis of convenience sampling. A satisfying underlying factor structure was confirmed by CFA and EFA, in which four hypotheses were tested. With 103 observations, the model sufficiently met the minimum sample size for SEM. This paper provides some evidence for its cross validity and may inspire more studies in future.
Entrepreneurial orientation in family firms: New drivers and the moderating role of the strategic involvement of the board

In this study, we examine new drivers that generate a disposition toward entrepreneurial activity in family firms and how the strategic involvement of the board of directors (SIBD) moderates the relationships between these drivers (image of the firm, willingness to change, and access to financial resources) and entrepreneurial orientation (EO). Using a sample of 230 family small and medium-sized enterprises (SMEs), our results confirm that a good family firm image and willingness to change may be powerful tools that stimulate a firm to develop entrepreneurial activities. The negative relationship between access to financial resources and EO may relate to the false belief that financial resources help firms be more creative and to maintaining family control of the firm and the socioemotional endowment. Contrary to our expectations, we also find that the SIBD negatively influences the relationship between the above drivers and EO, pointing to the need for more open boards of directors in family SMEs in order to develop and implement entrepreneurial strategies. JEL Classification: L2, M1
Economic Integration and State Responses: Change in European Industrial Relations Since Maastricht

The article analyses industrial relations change in the six largest EU countries since 1992 in relation to increased internationalization pressures. Based on qualitative and quantitative analysis, it distinguishes between associational and state governance, and detects that despite a predominant, but not universal, trend of weakening trade unions and collective bargaining, no overall liberalization has occurred in the political regulation of employment (employment policies, welfare state, labour law, state support to collective bargaining, public sector). Rather than converging towards neoliberalism, industrial relations emerge as more politically contingent and dependent on multiple forms of power, which are affected by internationalization in different ways.
Design of a half-bridge bootstrap circuit for grid inverter application controled by PIC24FJ128GA010

This paper explains a design of a bootstrap circuit to drive a half-bridge inverter circuit, The standard bootstrap circuit consists of a driver IC and three external components (RBoot, DBoot and CBoot) for inverter application. However, the bootstrap circuits had shown some weakness such as having adequate components to allow a high performance. This article shows how to select the bootstrap driver circuit parameters and using IR2112 to drive a power IGBTs inverter with a low energy consumption. In this paper, the PWM signal is generated by using a PIC24FJ128GA010 microcontroller and interfaced to the bootstrap circuit. The paper discusses the advantage and disadvantages of the bootstrap.
A 31P NMR investigation into the effects of repeated vascular occlusion on uterine metabolites, intracellular pH and force, in vivo

Little is known about the metabolic effects of ischaemia on high energy phosphates in vivo in smooth muscle. We have developed a method for reversibly occluding the uterine artery, which allows simultaneous measurement of uterine metabolites using 31P NMR spectroscopy, and intra‐uterine pressure, in vivo during ischaemia. We have investigated the effects of repeated ischaemia on metabolites, intracellular pH and contractions in anaesthetized rats. Occlusion produced an immediate drop in uterine blood flow and decreased contractions. Although contractions recovered upon reperfusion after both occlusions, the contractile activity was less after the second period of occlusion, suggesting less resistance after a prior ischaemic period. Significant falls in [ATP] and [phosphocreatine] and an increase in [Pi] occurred during both occlusions. These were all reversed within 30 min of reperfusion. There was a large drop in intracellular pH produced by occlusion, which was rapidly reversed upon reperfusion. The changes in metabolites and intracellular pH were similar during the repeated ischaemic period, to those occurring during the first ischaemic period suggesting no alteration in energy production or utilization had occurred, with prior exposure to ischaemia. The significance of these results to the functioning of the uterus in labour is briefly discussed.
A method for reversible drug delivery to internal tissues of Drosophila embryos

Drosophila melanogaster is a powerful model organism to elucidate basic cellular mechanisms of development. Indeed, much of our understanding of genetic pathways comes from work in Drosophila. However, mutations in many critical genes cause early embryonic lethality; thus, it is difficult to study the role of proteins that are required for early fundamental processes during later embryonic stages. We have therefore developed a method to reversibly deliver drugs to internal tissues of stage 15–16 Drosophila embryos using a 1:1 combination of D-limonene and heptane (LH). Specifically, delivery of Nocodazole was shown to be effective as evidenced by the significant decrease in microtubule density seen in muscle cells. Following complete depolymerization of the microtubule cytoskeleton, removing the Nocodazole and washing for 10 min was sufficient for the microtubule network to be re-established, indicating that drug delivery is reversible. Additionally, the morphology of LH-treated embryos resembled that of untreated controls, and embryo viability post-treatment with LH was significantly increased compared with previously reported permeabilization techniques. These advances in embryo permeabilization provide a means to disrupt protein function in vivo with high temporally specificity, bypassing the complications associated with genetic disruptions as they relate to the study of late-stage developmental mechanisms.
An optomechanical transducer in the blue light receptor phototropin from Avena sativa

The PHOT1 (NPH1) gene from Avena sativa specifies the blue light receptor for phototropism, phototropin, which comprises two FMN-binding LOV domains and a serine/threonine protein kinase domain. Light exposure is conducive to autophosphorylation of the protein kinase domain. We have reconstituted a recombinant LOV2 domain of A. sativa phototropin with various 13C/15N-labeled isotopomers of the cofactor, FMN. The reconstituted protein samples were analyzed by NMR spectroscopy under dark and light conditions. Blue light irradiation is shown to result in the addition of a thiol group (cysteine 450) to the 4a position of the FMN chromophore. The adduct reverts spontaneously in the dark by elimination. The light-driven flavin adduct formation results in conformational modification, which was diagnosed by 1H and 31P NMR spectroscopy. This conformational change is proposed to initiate the transmission of the light signal via conformational modulation of the protein kinase domain conducive to autophosphorylation of NPH1.
Induction and Repair of DNA DSB as Revealed by H2AX Phosphorylation Foci in Human Fibroblasts Exposed to Low- and High-LET Radiation: Relationship with Early and Delayed Reproductive Cell Death

The spatial distribution of radiation-induced DNA breaks within the cell nucleus depends on radiation quality in terms of energy deposition pattern. It is generally assumed that the higher the radiation linear energy transfer (LET), the greater the DNA damage complexity. Using a combined experimental and theoretical approach, we examined the phosphorylation-dephosphorylation kinetics of radiation-induced γ-H2AX foci, size distribution and 3D focus morphology, and the relationship between DNA damage and cellular end points (i.e., cell killing and lethal mutations) after exposure to gamma rays, protons, carbon ions and alpha particles. Our results showed that the maximum number of foci are reached 30 min postirradiation for all radiation types. However, the number of foci after 0.5 Gy of each radiation type was different with gamma rays, protons, carbon ions and alpha particles inducing 12.64 ± 0.25, 10.11 ± 0.40, 8.84 ± 0.56 and 4.80 ± 0.35 foci, respectively, which indicated a clear influence of the track structure and fluence on the numbers of foci induced after a dose of 0.5 Gy for each radiation type. The γ-H2AX foci persistence was also dependent on radiation quality, i.e., the higher the LET, the longer the foci persisted in the cell nucleus. The γ-H2AX time course was compared with cell killing and lethal mutation and the results highlighted a correlation between cellular end points and the duration of γ-H2AX foci persistence. A model was developed to evaluate the probability that multiple DSBs reside in the same gamma-ray focus and such probability was found to be negligible for doses lower than 1 Gy. Our model provides evidence that the DSBs inside complex foci, such as those induced by alpha particles, are not processed independently or with the same time constant. The combination of experimental, theoretical and simulation data supports the hypothesis of an interdependent processing of closely associated DSBs, possibly associated with a diminished correct repair capability, which affects cell killing and lethal mutation.
T‐cell intrinsic effects of GITR and 4‐1BB during viral infection and cancer immunotherapy

Summary: GITR [glucocorticoid inducible tumor necrosis factor receptor (TNFR)‐related protein] and 4‐1BB are costimulatory TNFR family members that are expressed on regulatory and effector T cells as well as on other cells of the immune system. Here we discuss the role of GITR and 4‐1BB on T cells during viral infections and in cancer immunotherapy. Systemic treatment with agonistic anti‐4‐1BB antibody leads to a number of immune system abnormalities, and clinical trials of anti‐4‐1BB have been terminated. However, other modes of 4‐1BB ligation may be less toxic. To date, similar toxicities have not been reported for anti‐GITR treatment of mice, although anti‐GITR antibodies can exacerbate mouse autoimmune models. Intrinsic effects of GITR and 4‐1BB on effector T cells appear to predominate over their effects on other cell types in some models. Despite their similarities in enhancing T‐cell survival, 4‐1BB and GITR are clearly not redundant, and both pathways are required for maximal CD8+ T‐cell responses and mouse survival following severe respiratory influenza infection. GITR uses TNFR‐associated factor (TRAF) 2 and TRAF5, whereas 4‐1BB recruits TRAF1 and TRAF2 to mediate survival signaling in T cells. The differential use of signaling adapters combined with their differential expression may explain the non‐redundant roles of GITR and 4‐1BB in the immune system.
IoT devices: The quest for energy security

Analysts predict that by 2020, more than 50 billion devices to be deployed and interconnected to serve Internet of Things (IoT) applications. However, battery powered devices are vulnerable to periodic battery replacement as their operating time gets limited, and this indicates a high operational and maintenance cost which will affect the economic viability to deploy devices. As a consequence, the energy procurement and energy usage are key factors for sustainability. This paper tackles the energy issue for the IoT devices, and it presents an overview of energy sources and energy harvesting challenges. The paper also proposes recommendations to operate the networked IoT devices in a self-sufficient manner and to acquire the “Place-and-Forget” functionality.
Serum immunoreactive-leptin concentrations in normal-weight and obese humans.

BACKGROUND Leptin, the product of the ob gene, is a hormone secreted by adipocytes. Animals with mutations in the ob gene are obese and lose weight when given leptin, but little is known about the physiologic actions of leptin in humans. METHODS Using a newly developed radioimmunoassay, wer measured serum concentrations of leptin in 136 normal-weight subjects and 139 obese subjects (body-mass index, > or = 27.3 for men and > or = 27.8 for women; the body-mass index was defined as the weight in kilograms divided by the square of the height in meters). The measurements were repeated in seven obese subjects after weight loss and during maintenance of the lower weight. The ob messenger RNA (mRNA) content of adipocytes was determined in 27 normal-weight and 27 obese subjects. RESULTS The mean (+/- SD) serum leptin concentrations were 31.3 +/- 24.1 ng per milliliter in the obese subjects and 7.5 +/- 9.3 ng per milliliter in the normal-weight subjects (P < 0.001). There was a strong positive correlation between serum leptin concentrations and the percentage of body fat (r = 0.85, P < 0.001). The ob mRNA content of adipocytes was about twice as high in the obese subjects as in the normal-weight subjects (P < 0.001) and was correlated with the percentage of body fat (r = 0.68, P < 0.001) in the 54 subjects in whom it was measured. In the seven obese subjects studied after weight loss, both serum leptin concentrations and ob mRNA content of adipocytes declined, but these measures increased again during the maintenance of the lower weight. CONCLUSIONS Serum leptin concentrations are correlated with the percentage of body fat, suggesting that most obese persons are insensitive to endogenous leptin production.
Effects of Spinal Analgesics on Spinal Circulation: The Safety Standpoint

Administration of spinal analgesics around the spinal cord requires safety assessment due to the possibility of inflicting neurotoxic damage. Thus, neurotoxicologic evaluation should be performed for effective, safer spinal antinociception. Every potential agent for spinal administration should be studied in animals for its effects on spinal blood flow or vessels before any attempt is made to administer the drug to humans. As the spinal cord normally has a marginal blood flow, excessive vasoconstriction might produce spinal cord ischemia and consequent neurologic dysfunction. This review therefore focuses on the effects on the spinal circulation induced by well-known spinal analgesics employed in the treatment of acute and chronic pain disorders.
SOYA: SSD-based RAID systems reliability simulator

The use of Solid State Drives (SSDs) has been increased in storage systems due to high performance and low power consumption. However, some inherent properties of SSDs result in different behavior for SSDs in comparison with Hard Disk Drives (HDDs). As an inherent property, the Bit Error Rate (BER) of SSDs increases, when the number of Program/Erase (P/E) cycles arises. This increment leads to two effects in an array of SSDs during its operation: (1) different BER on different SSDs of the system (SSD-variant BER), and (2) different BER in different time moments (time-variant BER). With respect to these two effects, the reliability evaluation of SSD-based RAIDs would be different from HDD-based RAlDs. This paper introduces a simulator called SOYA for evaluating the reliability of RAH) systems regarding different BER of SSDs. Both time-variant BER and SSD-variant BER have been considered in the evaluation process of this simulator. This simulator provides the ability to compare the reliability of SSD-based RAID systems considering arbitrary parameters in the evaluation such as disk failure rate, disk repair time, RAID-controller failure rate, RAID-controller repair time, and different levels of reliability. SOYA is the first SSD-based reliability simulator for SSD-bases RAID systems which can consider all the above-mentioned parameters together in its reliability evaluation.