Miracle-dz/UniFAR-FTUs huggingface dataset:
A multivalent minigene vaccine, containing B-cell, cytotoxic T-lymphocyte, and Th epitopes from several microbes, induces appropriate responses in vivo and confers protection against more than one pathogen

The development of safe and effective vaccines remains a major goal in the prevention, and perhaps treatment, of infectious diseases. Ideally, a single vaccine would confer protection against several pathogens and would induce both cellular and humoral arms of the immune response. We originally demonstrated that two virus-specific cytotoxic T-lymphocyte (CTL) epitopes, from the same virus but presented by different major histocompatibility complex alleles, when linked in tandem as minigenes in a recombinant vaccinia virus, could confer complete protection against subsequent viral challenge. In the study, we extended this approach, which we termed string of beads, expanding the immunogenic scope in two ways: first, by introduction of T helper (Th) and B-cell (antibody) epitopes alongside CTL epitopes and second, by including immunogenic sequences from a variety of infectious agents, five viruses and one bacterium. The vaccine (VV-sv) comprises CTL epitopes from Sendai virus, respiratory syncytial virus, and lymphocytic choriomeningitis virus (LCMV); Th epitopes from vesicular stomatitis virus and Mycobacterium tuberculosis; and an antibody epitope from mengovirus. The construct contains a single start codon, and the epitopes are linked directly, without intervening spacer amino acids. There was some concern that the combination of several normally immunodominant epitopes might result in a new hierarchy of dominance, in which certain epitopes predominated and others exhibited reduced immunogenicity. However we show that when analyzed in tissue culture and in vivo, all six epitopes are expressed. CTL and Th cells are induced in vivo, along with neutralizing antibody. The induced immunity is biologically relevant: after VV-sv immunization, the antimengovirus antibody confers protection against mengovirus challenge. Similarly, CTL induced by the LCMV epitope protected mice against challenge with this agent. Thus, a polyvalent, minigene-based vaccine can simultaneously induce several classes of immune response and thereby can confer protection against diverse pathogens.
Contribution of astroglia to functionally activated energy metabolism.

Studies of local glucose utilization in neural tissues in vivo with the autoradiographic [14C]deoxyglucose method have demonstrated that energy metabolism increases almost linearly with the degree of functional activation, i.e. spike frequency, in the terminal projection zones of activated pathways. The increased metabolism is found in neuropil and is minimal or undetectable in neuronal cell bodies. Electrical stimulation, increased extracellular [K+] ([K+]o), or opening of Na+ channels with veratridine stimulates metabolism in neutral tissues, and this increase is blocked by ouabain, a specific inhibitor of Na+,K(+)-ATPase. Activation of this enzyme to restore ionic gradients across cellular membranes appears to mediate the function-related increase in energy metabolism. The metabolic activation is, therefore, not directly related to the functional activity itself but to processes operating to recover from that activity. The limited spatial resolution of the [14C]DG method precludes identification of cellular elements in neuropil participating in the metabolic activation, e.g. axonal terminals, dendrites, or astrocytic processes enveloping the synapses. We have, therefore, attempted to stimulate in vitro conditions to be expected from functional activation and increased spike activity in vivo, e.g. increased extracellular [K+], intracellular [Na+], or extracellular neurotransmitter levels, and examined their effects on glucose metabolism in neurons and astroglia in culture. Increased [K+]o stimulated [14C]DG phosphorylation in neuronal and mixed neuronal-astroglial cultures, but not in astroglial cultures assayed in bicarbonate buffer; it did occasionally stimulate metabolism in astroglia when assayed in HEPES or phosphate buffers, but these effects were variable and inconsistent. Veratridine (75 microM) stimulated [14C]DG phosphorylation in neurons and astroglia; these stimulations were blocked by 1 mM ouabain or 10 microM tetrodotoxin (TTX), which blocks voltage-dependent Na+ channels. The Na+ ionophore monensin (10 microM) doubled the rate of metabolism, a stimulation that was only partially blocked by ouabain and unaffected by TTX. L-Glutamate (500 microM) stimulated [14C]DG phosphorylation in astroglia, but this stimulation was probably secondary to Na+ uptake into the cells via a sodium/glutamate co-transporter because it was not blocked by inhibitors of NMDA or non-NMDA receptors but was absent in Na(+)-free medium. These results indicate that astroglia contribute to the increased energy metabolism in neuropil during functional activation by mechanisms that promote Na+ entry into the cells.
Cobalt nanoparticles coated with graphitic shells as localized radio frequency absorbers for cancer therapy

Graphitic carbon-coated ferromagnetic cobalt nanoparticles (C–Co-NPs) with diameters of around 7 nm and cubic crystalline structures were synthesized by catalytic chemical vapor deposition. X-ray diffraction and x-ray photoelectron spectroscopy analysis indicated that the cobalt nanoparticles inside the carbon shells were preserved in the metallic state. Fluorescence microscopy images and Raman spectroscopy revealed effective penetrations of the C–Co-NPs through the cellular plasma membrane of the cultured HeLa cells, both inside the cytoplasm and in the nucleus. Low radio frequency (RF) radiation of 350 kHz induced localized heat into the metallic nanoparticles, which triggered the killing of the cells, a process that was found to be dependent on the RF application time and nanoparticle concentration. When compared to carbon nanostructures such as single-wall carbon nanotubes, these coated magnetic cobalt nanoparticles demonstrated higher specificity for RF absorption and heating. DNA gel electrophoresis assays of the HeLa cells after the RF treatment showed a strong broadening of the DNA fragmentation spectrum, which further proved the intense localized thermally induced damages such as DNA and nucleus membrane disintegration, under RF exposure in the presence of C–Co-NPs. The data presented in this report indicate a great potential of this new process for in vivo tumor thermal ablation, bacteria killing, and various other biomedical applications.
HIV vaccine acceptability and culturally appropriate dissemination among sexually diverse Aboriginal peoples in Canada

Abstract This study explored HIV vaccine acceptability and strategies for culturally appropriate dissemination among sexually diverse Aboriginal peoples in Canada, among those at highest HIV risk. We conducted four focus groups (n=23) with Aboriginal male (1) and female (1) service users, peer educators (1) and service providers (1) in Ontario, Canada. Transcripts were analysed with narrative thematic techniques from grounded theory, using NVivo. Participants’ mean age was 37 years; about half (52%) were female, half (48%) Two-spirit or lesbian, gay or bisexual (LGB)-identified, 48% had a high-school education or less and 57% were unemployed. Vaccine uptake was motivated by community survival; however, negative HIV vaccine perceptions, historically based mistrust of government and healthcare institutions, perceived conflict between western and traditional medicine, sexual prejudice and AIDS stigma within and outside of Aboriginal communities, and vaccine cost may present formidable obstacles to HIV vaccine acceptability. Culturally appropriate processes of engagement emerged on individual levels (i.e., respect for self-determination, explanations in Native languages, use of modelling and traditional healing concepts) and community levels (i.e., leadership by Aboriginal HIV advocates and political representatives, identification of gatekeepers, and procuring Elders’ endorsements). Building on cultural strengths and acknowledging the history and context of mistrust and social exclusion are fundamental to effective HIV vaccine dissemination.
The use of a fixed value of RPE during a ramp protocol. Comparison with the ventilatory threshold.

BACKGROUND The purpose of our investigation was to assess the use of a fixed value (12-13) of the Rating of Perceived Exertion (RPE) scale (6-20) as a valid method for the determination of the workload corresponding to the ventilatory threshold (VT) during a ramp protocol on a cycle ergometer. METHODS Eleven trained cyclists (22 +/- 3 years of age; VO2max: 65.2 +/- 12.4 ml.kg-1.min-1) were selected as subjects. DESIGN Each of the subjects performed a ramp protocol on a cycle ergometer (starting at 25 W, with increases of 25 W.min-1 until exhaustion). Gas exchange data were analysed continually during the test to detect the ventilatory threshold (VT) of the subjects. In addition values of RPE were obtained from each subject in the last 15 sec of each 2-minute-interval during the tests, and immediately after exhaustion. The RPE threshold (RPET) was defined as a constant value of 12-13. Mean values of VT and RPET were expressed as VO2 (ml.kg-1.min-1), %VO2max, heart rate (bpm) and power output (W), and were compared using a paired "t"-test. RESULTS No significant difference (p < 0.05) was found between mean values of VT and RPET, when both parameters where expressed either as VO2, %VO2max, heart rate, or power output. CONCLUSIONS In conclusion, a fixed value (12-13) of the RPE scale might be used to detect the exercise intensity corresponding to VT. Such parameter may therefore be used for exercise prescription in substitution to more sophisticated methodologies.
Effect of storage on breast milk antioxidant activity

Background: Human milk, which contains compounds beneficial to infants, is often expressed and stored before use. Changes in its antioxidant activity with storage have not been studied. Objectives: To measure antioxidant activity of fresh, refrigerated (4°C), and frozen human milk (−20°C), stored for two to seven days; to compare the antioxidant activity of milk from mothers delivering prematurely and at term; to compare the antioxidant activity of infant formulas and human milk. Methods: Sixteen breast milk samples (term and preterm) were collected from mothers within 24 hours of delivery and divided into aliquots. Fresh samples were immediately tested for antioxidant activity, and the rest of the aliquots were stored at −20°C or 4°C to be analysed at 48 hours and seven days respectively. The assay used measures the ability of milk samples to inhibit the oxidation of 2,2′-azino-di-3-(ethylbenzthiazolinesulphonate) to its radical cation compared with Trolox. Results: Antioxidant activity at both refrigeration and freezing temperatures was significantly decreased. Freezing resulted in a greater decrease than refrigeration, and storage for seven days resulted in lower antioxidant activity than storage for 48 hours. There was no difference in milk from mothers who delivered prematurely or at term. Significantly lower antioxidant activity was noted in formula milk than in fresh human milk. Conclusions: To preserve the antioxidant activity of human milk, storage time should be limited to 48 hours. Refrigeration is better than freezing and thawing.
Wavelet energy distribution with PCA & DBSCAN for partial discharge pulse extraction

Condition monitoring based on partial discharge diagnostics has seen a very rapid increase of interest from high voltage industry. Condition monitoring is an asset monitoring tool that can inform the user of real time health of their high voltage equipment / plant, which has now become a necessity in ageing networks that still have equipment in operation that has fulfilled its rated life. Partial discharge pulse detection and extraction is the first step of condition monitoring. This research is focused on assessing the capability of wavelet energy distribution for pulse extraction with the help of principle component analysis (PCA) and density based spatial clustering algorithm (DBSCAN). One problem that every pulse extraction method faces is that their efficiency is highly affected when a signal with high noise is processed through them. This research will also assess the robustness of the aforementioned procedure on signals with different signal to noise ratio by comparing results of each signal. Moreover, this procedure will also be vetted on its level of intrusiveness to see if it can be used for online condition monitoring.
Vibronic effects on the low-lying electronic excitations in N2O induced by electron impact

We report a theoretical study on the valence-shell electronic excitations of N2O induced by electron impact. Momentum transfer–dependent generalized oscillator strengths (GOSs) or GOS profiles have been calculated for the low-lying electronic excitations using theoretical wave functions at the equation-of-motion coupled-cluster singles and doubles level. In the calculation, Herzberg–Teller vibronic effects are taken into account. The computed results are in overall agreement with experimental GOS profiles reported in the literature and reveal prominent roles of the bending vibration of N2O in the B1Δ and C1Π transitions.
CAMs and FGF cause a local submembrane calcium signal promoting axon outgrowth without a rise in bulk calcium concentration

Binding of basic fibroblast growth factor (bFGF) and cell adhesion molecules to the nerve cell membrane promotes axon outgrowth. This response can be blocked by antagonists of voltage‐gated calcium channels, yet no change of cytosolic calcium concentration in the growth cone can be detected upon binding of the growth factor bFGF or the cell adhesion molecule L1. Using barium as a charge carrier, we show that bFGF and L1 open a calcium influx pathway in growth cones of rat sensory neurons without changing the membrane voltage. L1 does not activate influx in cells expressing a dominant negative mutant of the fibroblast growth factor receptor (FGFR) tyrosine kinase. FGFR‐activated influx is blocked by specific antagonists of L‐ and N‐type voltage‐gated calcium channels and by an inhibitor of diacylglycerol lipase. We propose that both L1 and bFGF act via the FGFR to generate polyunsaturated fatty acids which in turn cause calcium channels to flicker open and shut. Short‐lived domains of raised calcium at the cytosolic mouth of open channels activate axon outgrowth without raising bulk cytosolic calcium concentration. In confirmation of this model, the rapidly‐acting calcium buffer BAPTA is significantly more effective at blocking FGF‐induced axon outgrowth when compared with the slower buffer EGTA. Generation of short‐lived calcium domains may provide a crucial mechanism for axon guidance during development and for promoting regeneration of damaged axons.
2-Tetradecylglycidic acid, an inhibitor of carnitine palmitoyltransferase-1, induces myocardial hypertrophy via the AT1 receptor.

Activation of the antiogensin II, type 1 (AT1) receptor mediates the myocardial response to numerous hypertrophic stimuli. This study tested the hypothesis that 2-tetradecylglycidic acid (TDGA), an oxirane carboxylate inhibitor of mitochondrial carnitine plamitoyltransferase-1, induces myocardial hypertrophy via the AT1 receptor system. Male Sprague-Dawley rats treated with 10 mg TDGA/kg/day for 7 days had a heart wet weight:body weight ratio of 3. 58+/-0.16 mg/g compared with a ratio of 2.79+/-0.07 for rats treated with vehicle (P<0.05). The plasma level of antiogensin II was 117. 75+/-17.39 pg/ml in rats treated with 10 mg TDGA/kg/day compared with 54.0+/-11.38 pg/ml for rats treated with vehicle (P<0.05). The plasma level of angiotensin I in these two groups of rats was not different statistically. Rats treated with TDGA and given drinking water containing 1 mg losartan/ml had a heart wet weight:body weight ratio of 2.84+/-0.05 mg/g. This value was not statistically different from the value measured in rats given drinking water containing 1 mg losartan/ml and treated with vehicle alone. No significant difference in the heart wet weight:dry weight ratio occurred among these groups of rats. Finally, treating rats with TDGA or giving rats drinking water that contained 1 mg losartan/ml altered neither their heart rate nor their mean arterial blood pressure when compared with untreated rats. This data, therefore, suggests that oxirane carboxylates induce myocardial hypertrophy by activating the AT1 receptor independent of changes in systemic hemodynamics.
Physiologic smoothing of blood time-activity curves for PET data analysis.

UNLABELLED Blood or plasma time-activity curves (TACs) are used as the input function for mathematical models of tracer kinetics in several applications including PET. Uncertainty associated with both the blood data and the PET tissue data can result in uncertainty in the estimates of metabolic rates, blood flow, etc. METHODS This article presents an approach to reduce the uncertainty in the blood TAC by fitting a model to the curve. The model includes a choice of bolus or infusion input and has three compartments (plasma, interstitial fluid and tissue fluid) with exchange between them. There is a parameter for loss from the plasma compartment. To test the utility of smoothing blood TACs with this approach, a program was set up, using the fluorodeoxyglucose (FDG) model, with simulated noisy blood and tissue TACs. The smoothed blood TAC was compared to a linearly interpolated TAC as the input function with a compartmental model parameter estimation program and with graphical analysis. RESULTS With a well sampled blood TAC (19 points), the model approach is somewhat more accurate than linear interpolation if the s.d. of noise added to the data exceeded 10%. With sparsely sampled blood TACs (five points) or with a large gap in the blood TAC, the modeled approach was markedly better. For graphical analysis, the model smoothed TAC was also more accurate, although, in general, the results were not as sensitive to the input function. CONCLUSION This approach, using a physiologically reasonable model to smooth the blood TAC, is a useful aid in PET data analysis, particularly when the data are quite noisy or when there are large gaps in the data.
Long resonator micromachined tunable GaAs-AlAs Fabry-Perot filter

We present novel concepts for tunable optical filters. Long resonant cavities of about 30-/spl mu/m length have been realized with two-chip designs. GaAs technology has been applied to filters that are designed for the use in dense wavelength-division multiplexing (WDM) at wavelengths around 1550 nm. A finesse of 46.7, a full-width at half-maximum (FWHM) of 1.2 nm and electrostatic tuning over a range of 103 nm with an applied voltage of 35 V has been achieved. An alternative tuning concept that allows to tune the resonator length 4 /spl mu/m by heating Ni-Cr resistors placed on the suspending beams of a membrane with an applied voltage of 2.7 V has been realized.
Over-segmentation of handwriting Arabic scripts using an efficient heuristic technique

As is well known, good segmentation is one reason for high accuracy of character recognition; this paper proposes and investigates a new technique for segmentation of handwritten Arabic scripts. A new Arabic heuristic segmenter (AHS) has been implemented. The AHS employs three new features to locate a Prospected Segmentation Point (PSP) based on shape of the word image, first, remove the punctuation marks (dots), second, ligature detection, and third, additional techniques. Remove the punctuation marks technique has been used to avoid the overlap of the ligature to decrease errors of "missed" and "bad" segmentation points. Ligature detection technique has been used to improve locate the segmentation points that calculated based on distance between local minima and maxima of histogram, the technique calculated based on the distance between foreground and background pixels of word image histogram. An additional technique that contains the average character width technique, and close/open holes detection technique has also been investigated to enhance the overall results of segmentation.
Purification and Characteristics of Sorbitol-6-phosphate Dehydrogenase from Loquat Leaves.

To study the role of sorbitol-6-phosphate dehydrogenase in sorbitol synthesis in leaves of Rosaceous plants, properties of the enzyme and its presence in several plants in the family was investigated. The activity of the enzyme, which catalyzes an NADP-dependent oxidation of the substrate to glucose-6-phosphate, was detected in leaves of Prunus mume, Prunus persica, Rhaphiolepsis indica, Sorbus aucuparia, Cydonia oblonga, Photinia glabra, Sorbaria kirilowii, and Spiraea thunbergii.The enzyme was purified about 60-fold from leaves of loquat (Eriobotrya japonica) using affinity chromatography with Blue Sepharose. Neither mannitol-1-phosphate nor fructose-6-phosphate served as substrate. Molecular weight of the enzyme was calculated to be 65,000 at pH 8.0 by gel filtration. Since sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed a peptide of 33,000 daltons, the enzyme was assumed to be a dimer at pH 8.0 K(m) values for sorbitol-6-phosphate, glucose-6-phosphate, NADP, and NADPH were 2.22 millimolar, 11.6 millimolar, 13.5 micromolar, and 1.61 micromolar, respectively. Equilibrium constant for sorbitol-6-phosphate oxidation was 5.12 x 10(-10). Optimal pH for sorbitol-6-phosphate oxidation was 9.8. The enzyme showed its maximum activity within a broad pH range between 7 and 9 for glucose-6-phosphate reduction. The enzyme was more effective in the direction of glucose-6-phosphate reduction than in the reverse direction at neutral pH. Thus, it is suggested that the enzyme catalyzes sorbitol synthesis from glucose-6-phosphate during photosynthesis in leaves of Rosaceous plants.
The Unliganded Glucocorticoid Receptor Positively Regulates the Tumor Suppressor Gene BRCA1 through GABP Beta

Loss of BRCA1 tumor suppressor function is a critical event in breast tumorigenesis. We have previously identified the stress hormone hydrocortisone as a negative regulator of BRCA1 expression in nonmalignant mammary cells. Here, we have identified a direct role for the unliganded glucocorticoid receptor (GR) in BRCA1 upregulation in the absence of hydrocortisone. The positive regulatory effect of GR is lost upon the addition of hydrocortisone. We have shown that GR interacts with the BRCA1 promoter only in the absence of hydrocortisone, and that this interaction is mediated through the β-subunit of the ets transcription factor GA-binding protein (GABP) at the RIBS promoter element. GR and GABPβ interact in both coimmunoprecipitation and mammalian two-hybrid assays, and this interaction involves the N-terminal to central regions of both proteins. This work presents the first evidence of a ligand-independent role for GR as a positive regulator of gene expression, and loss of GR from the BRCA1 promoter in response to stress hormones leads to decreased BRCA1 expression. Because low levels of BRCA1 have been implicated in the development of sporadic breast cancer, this may represent a novel mechanism through which prolonged stress signaling increases breast cancer risk. Mol Cancer Res; 10(4); 558–69. ©2012 AACR.