Inhibition of HIV derived lentiviral production by TAR RNA binding domain of TAT protein

BACKGROUND: A critical step in the production of new HIV virions involves the TAT protein binding to the TAR element. The TAT protein contains in close proximity its TAR RNA binding domain and protein transduction domain (PTD). The PTD domain of TAT has been identified as being instrumental in the protein's ability to cross mammalian cell and nuclear membranes. All together, this information led us to form the hypothesis that a protein containing the TAR RNA binding domain could compete with the native full length TAT protein and effectively block the TAR RNA binding site in transduced HIV infected cells. RESULTS: We synthesized a short peptide named Tat-P, which contained the TAR RNA binding and PTD domains to examine whether the peptide has the potential of inhibiting TAT dependent HIV replication. We investigated the inhibiting effects of Tat-P in vitro using a HIV derived lentiviral vector model. We found that the TAT PTD domain not only efficiently transduced test cells, but also effectively inhibited the production of lentiviral particles in a TAT dependent manner. These results were also supported by data derived from the TAT activated LTR-luciferase expression model and RNA binding assays. CONCLUSION: Tat-P may become part of a category of anti-HIV drugs that competes with full length TAT proteins to inhibit HIV replication. In addition, this study indicates that the HIV derived lentiviral vector system is a safe and reliable screening method for anti-HIV drugs, especially for those targeting the interaction of TAT and TAR RNAs

USE OF FUZZY LOGIC TO INVESTIGATE WEATHER PARAMETER IMPACT ON ELECTRICAL LOAD BASED ON SHORT TERM FORECASTING

Load forecasting guides the power company to make some decisions on generation, transmission and distribution of electrical power. This work presents a solution methodology, using fuzzy logic approach for short term load forecasting (STLF) for Adamawa State University, Mubi.  The proposed methodology utilized fuzzy reasoning decision rules that use the nonlinear relationships between inputs and outputs. The fuzzy logic model was developed in the Simulink environment of a MATLAB software. The model developed was able to forecast a day ahead load (kW) with a mean absolute error (MAPE) of 6.17% and it was observed that weather parameter (temperature) has significant impact on electrical load.  http://dx.doi.org/10.4314/njt.v35i3.1

Statin use and adverse effects among adults \u3e 75 years of age: Insights from the Patient and Provider Assessment of Lipid Management (PALM) registry

Background: Current statin use and symptoms among older adults in routine community practice have not been well characterized since the release of the 2013 American College of Cardiology/American Heart Association guideline. Methods and results: We compared statin use and dosing between adults \u3e75 and ≤75 years old who were eligible for primary or secondary prevention statin use without considering guideline-recommended age criteria. The patients were treated at 138 US practices in the Patient and Provider Assessment of Lipid Management (PALM) registry in 2015. Patient surveys also evaluated reported symptoms while taking statins. Multivariable logistic regression models examined the association between older age and statin use and dosing. Among 6717 people enrolled, 1704 (25%) were \u3e75 years old. For primary prevention, use of any statin or high-dose statin did not vary by age group: any statin, 62.6% in those \u3e75 years old versus 63.1% in those ≤75 years old (P=0.83); high-dose statin, 10.2% versus 12.3% in the same groups (P=0.14). For secondary prevention, older patients were slightly less likely to receive any statin (80.1% versus 84.2% [P=0.003]; adjusted odds ratio, 0.81; 95% confidence interval, 0.66-1.01 [P=0.06]), but were much less likely to receive a high-intensity statin (23.5% versus 36.2% [PP=0.0001]). Among current statin users, older patients were slightly less likely to report any symptoms (41.3% versus 46.6%; P=0.003) or myalgias (27.3% versus 33.3%; Conclusions: Overall use of statins was similar for primary prevention in those aged \u3e75 years versus younger patients, yet older patients were less likely to receive high-intensity statins for secondary prevention. Statins appear to be similarly tolerated in older and younger adult

Reliability of medical record abstraction by non-physicians for orthopedic research

Background: Medical record review (MRR) is one of the most commonly used research methods in clinical studies because it provides rich clinical detail. However, because MRR involves subjective interpretation of information found in the medical record, it is critically important to understand the reproducibility of data obtained from MRR. Furthermore, because medical record review is both technically demanding and time intensive, it is important to establish whether trained research staff with no clinical training can abstract medical records reliably. Methods: We assessed the reliability of abstraction of medical record information in a sample of patients who underwent total knee replacement (TKR) at a referral center. An orthopedic surgeon instructed two research coordinators (RCs) in the abstraction of inpatient medical records and operative notes for patients undergoing primary TKR. The two RCs and the surgeon each independently reviewed 75 patients’ records and one RC reviewed the records twice. Agreement was assessed using the proportion of items on which reviewers agreed and the kappa statistic. Results: The kappa for agreement between the surgeon and each RC ranged from 0.59 to 1 for one RC and 0.49 to 1 for the other; the percent agreement ranged from 82% to 100% for one RC and 70% to 100% for the other. The repeated abstractions by the same RC showed high intra-rater agreement, with kappas ranging from 0.66 to 1 and percent agreement ranging from 97% to 100%. Inter-rater agreement between the two RCs was moderate with kappa ranging from 0.49 to 1 and percent agreement ranging from 76% to 100%. Conclusion: The MRR method used in this study showed excellent reliability for abstraction of information that had low technical complexity and moderate to good reliability for information that had greater complexity. Overall, these findings support the use of non-surgeons to abstract surgical data from operative notes

Attosecond control of electrons emitted from a nanoscale metal tip

Attosecond science is based on steering of electrons with the electric field of well-controlled femtosecond laser pulses. It has led to, for example, the generation of XUV light pulses with a duration in the sub-100-attosecond regime, to the measurement of intra-molecular dynamics by diffraction of an electron taken from the molecule under scrutiny, and to novel ultrafast electron holography. All these effects have been observed with atoms or molecules in the gas phase. Although predicted to occur, a strong light-phase sensitivity of electrons liberated by few-cycle laser pulses from solids has hitherto been elusive. Here we show a carrier-envelope (C-E) phase-dependent current modulation of up to 100% recorded in spectra of electrons laser-emitted from a nanometric tungsten tip. Controlled by the C-E phase, electrons originate from either one or two sub-500as long instances within the 6-fs laser pulse, leading to the presence or absence of spectral interference. We also show that coherent elastic re-scattering of liberated electrons takes place at the metal surface. Due to field enhancement at the tip, a simple laser oscillator suffices to reach the required peak electric field strengths, allowing attosecond science experiments to be performed at the 100-Megahertz repetition rate level and rendering complex amplified laser systems dispensable. Practically, this work represents a simple, exquisitely sensitive C-E phase sensor device, which can be shrunk in volume down to ~ 1cm3. The results indicate that the above-mentioned novel attosecond science techniques developed with and for atoms and molecules can also be employed with solids. In particular, we foresee sub-femtosecond (sub-) nanometre probing of (collective) electron dynamics, such as plasmon polaritons, in solid-state systems ranging in size from mesoscopic solids via clusters to single protruding atoms.Comment: Final manuscript version submitted to Natur

Density-dependence of functional development in spiking cortical networks grown in vitro

During development, the mammalian brain differentiates into specialized regions with distinct functional abilities. While many factors contribute to functional specialization, we explore the effect of neuronal density on the development of neuronal interactions in vitro. Two types of cortical networks, dense and sparse, with 50,000 and 12,000 total cells respectively, are studied. Activation graphs that represent pairwise neuronal interactions are constructed using a competitive first response model. These graphs reveal that, during development in vitro, dense networks form activation connections earlier than sparse networks. Link entropy analysis of dense net- work activation graphs suggests that the majority of connections between electrodes are reciprocal in nature. Information theoretic measures reveal that early functional information interactions (among 3 cells) are synergetic in both dense and sparse networks. However, during later stages of development, previously synergetic relationships become primarily redundant in dense, but not in sparse networks. Large link entropy values in the activation graph are related to the domination of redundant ensembles in late stages of development in dense networks. Results demonstrate differences between dense and sparse networks in terms of informational groups, pairwise relationships, and activation graphs. These differences suggest that variations in cell density may result in different functional specialization of nervous system tissue in vivo.Comment: 10 pages, 7 figure

Quantitative Changes in Hydrocarbons over Time in Fecal Pellets of Incisitermes minor May Predict Whether Colonies Are Alive or Dead

Hydrocarbon mixtures extracted from fecal pellets of drywood termites are species-specific and can be characterized to identify the termites responsible for damage, even when termites are no longer present or are unable to be recovered easily. In structures infested by drywood termites, it is common to find fecal pellets, but difficult to sample termites from the wood. When fecal pellets appear after remedial treatment of a structure, it is difficult to determine whether this indicates that termites in the structure are still alive and active or not. We examined the hydrocarbon composition of workers, alates, and soldiers of Incisitermes minor (Hagen) (family Kalotermitidae) and of fecal pellets of workers. Hydrocarbons were qualitatively similar among castes and pellets. Fecal pellets that were aged for periods of 0, 30, 90, and 365 days after collection were qualitatively similar across all time periods, however, the relative quantities of certain individual hydrocarbons changed over time, with 19 of the 73 hydrocarbon peaks relatively increasing or decreasing. When the sums of the positive and negative slopes of these 19 hydrocarbons were indexed, they produced a highly significant linear correlation (R2 = 0.89). Consequently, the quantitative differences of these hydrocarbons peaks can be used to determine the age of worker fecal pellets, and thus help determine whether the colony that produced them is alive or dead

Transplantation of canine olfactory ensheathing cells producing chondroitinase ABC promotes chondroitin sulphate proteoglycan digestion and axonal sprouting following spinal cord injury

Olfactory ensheathing cell (OEC) transplantation is a promising strategy for treating spinal cord injury (SCI), as has been demonstrated in experimental SCI models and naturally occurring SCI in dogs. However, the presence of chondroitin sulphate proteoglycans within the extracellular matrix of the glial scar can inhibit efficient axonal repair and limit the therapeutic potential of OECs. Here we have used lentiviral vectors to genetically modify canine OECs to continuously deliver mammalian chondroitinase ABC at the lesion site in order to degrade the inhibitory chondroitin sulphate proteoglycans in a rodent model of spinal cord injury. We demonstrate that these chondroitinase producing canine OECs survived at 4 weeks following transplantation into the spinal cord lesion and effectively digested chondroitin sulphate proteoglycans at the site of injury. There was evidence of sprouting within the corticospinal tract rostral to the lesion and an increase in the number of corticospinal axons caudal to the lesion, suggestive of axonal regeneration. Our results indicate that delivery of the chondroitinase enzyme can be achieved with the genetically modified OECs to increase axon growth following SCI. The combination of these two promising approaches is a potential strategy for promoting neural regeneration following SCI in veterinary practice and human patients

Direct observation of active material concentration gradients and crystallinity breakdown in LiFePO4 electrodes during charge/discharge cycling of lithium batteries

The phase changes that occur during discharge of an electrode comprised of LiFePO4, carbon, and PTFE binder have been studied in lithium half cells by using X-ray diffraction measurements in reflection geometry. Differences in the state of charge between the front and the back of LiFePO4 electrodes have been visualized. By modifying the X-ray incident angle the depth of penetration of the X-ray beam into the electrode was altered, allowing for the examination of any concentration gradients that were present within the electrode. At high rates of discharge the electrode side facing the current collector underwent limited lithium insertion while the electrode as a whole underwent greater than 50% of discharge. This behavior is consistent with depletion at high rate of the lithium content of the electrolyte contained in the electrode pores. Increases in the diffraction peak widths indicated a breakdown of crystallinity within the active material during cycling even during the relatively short duration of these experiments, which can also be linked to cycling at high rate

Genetic determinants of co-accessible chromatin regions in activated T cells across humans.

Over 90% of genetic variants associated with complex human traits map to non-coding regions, but little is understood about how they modulate gene regulation in health and disease. One possible mechanism is that genetic variants affect the activity of one or more cis-regulatory elements leading to gene expression variation in specific cell types. To identify such cases, we analyzed ATAC-seq and RNA-seq profiles from stimulated primary CD4+ T cells in up to 105 healthy donors. We found that regions of accessible chromatin (ATAC-peaks) are co-accessible at kilobase and megabase resolution, consistent with the three-dimensional chromatin organization measured by in situ Hi-C in T cells. Fifteen percent of genetic variants located within ATAC-peaks affected the accessibility of the corresponding peak (local-ATAC-QTLs). Local-ATAC-QTLs have the largest effects on co-accessible peaks, are associated with gene expression and are enriched for autoimmune disease variants. Our results provide insights into how natural genetic variants modulate cis-regulatory elements, in isolation or in concert, to influence gene expression