HIV-Associated Apathy/Depression and Neurocognitive Impairments Reflect Persistent Dopamine Deficits

Individuals living with human immunodeficiency virus type 1 (HIV-1) are often plagued by debilitating neurocognitive impairments and affective alterations;the pathophysiology underlying these deficits likely includes dopaminergic system dysfunction. The present review utilized four interrelated aims to critically examine the evidence for dopaminergic alterations following HIV-1 viral protein exposure. First, basal dopamine (DA) values are dependent upon both brain region andexperimental approach (i.e., high-performance liquid chromatography, microdialysis or fast-scan cyclic voltammetry). Second, neurochemical measurements overwhelmingly support decreased DA concentrations following chronic HIV-1 viral protein exposure. Neurocognitive impairments, including alterations in pre-attentive processes and attention, as well as apathetic behaviors, provide an additional line of evidence for dopaminergic deficits in HIV-1. Third, to date, there is no compelling evidence that combination antiretroviral therapy (cART), the primary treatment regimen for HIV-1 seropositive individuals, has any direct pharmacological action on the dopaminergic system. Fourth, the infection of microglia by HIV-1 viral proteins may mechanistically underlie the dopamine deficit observed following chronic HIV-1 viral protein exposure. An inclusive and critical evaluation of the literature, therefore, supports the fundamental conclusion that long-term HIV-1 viral protein exposure leads to a decreased dopaminergic state, which continues to persist despite the advent of cART. Thus, effective treatment of HIV-1-associated apathy/depression and neurocognitive impairments must focus on strategies for rectifying decreases in dopamine function.

Assessing Population Variation Using Heritable Nonmetric Traits

This research investigates the use of heritable nonmetric traits as a means for assessing population variation and biological relatedness within an archaeological sample using the commingled human skeletal tomb assemblage from the Bronze Age site of Tell Abraq, United Arab Emirates (2100-2000 BCE). A total of 410 individuals representing all ages and both sexes were interred in the Umm an-Nar period tomb. An analysis of sixteen heritable nonmetric traits was conducted on the adult human skeletal remains for both cranial and postcranial elements. Of the eight elements analyzed, one element in particular displayed anomalies rarely described in archaeological contexts. Seven patellae were identified as emarginated, six as bipartite and one as tripartite. The frequency of traits found here are inconclusive in suggesting biological homogeneity or heterogeneity. However, the baseline data provided here may be useful in investigating biological homogeneity in other studies in the future and may allow us to look at social practices such as marriage patterns. These data may also provide an additional line of evidence to the previous hypotheses concerning consanguineous marriage for this assemblage.

Efficacy of (R)-6-Adamantane-Derivatives of 1,3-Oxazinan-2-One and Piperidine-2,4-Dione in The Treatment of Mice Infected by the A/California/04/2009 influenza Virus

The World Health Organization (WHO) recommends antivirals as an additional line of defense against influenza. One of such drugs is rimantadine. However, most of the circulating strains of influenza A viruses are resistant to this drug. Thus, a search for analogs effective against rimantadine-resistant viruses is of the utmost importance. Here, we examined the efficiency of two adamantane azaheterocyclic rimantadine derivatives on a mouse model of pneumonia caused by the rimantadine-resistant influenza A virus /California/04/2009 (H1N1). BALB/c mice inoculated with the virus were treated with two doses (15 mg and 20 mg/kg a day) of tested analogs via oral administration for 5 days starting 4 hours before the infection. The efficacy was assessed by survival rate, mean day to death, weight loss, and viral titer in the lungs. Oral treatment with both compounds in both doses protected 60100% of the animals, significantly increased the survival rate, and abolished weight loss. The treatments also inhibited virus titer in the lungs in comparison to the control group. This treatment was more effective compared to rimantadine at the same scheme and dosage. Moreover, the study of the sensitivity of the virus isolated from the lungs of the treated mice and grown in MDCK cells showed that no resistance had emerged during the 5 days of treatment with both compounds.

A photospheric and chromospheric activity analysis of the quiescent retrograde-planet host ν Octantis A

ABSTRACT The single-lined spectroscopic binary ν Octantis provided evidence of the first conjectured circumstellar planet demanding an orbit retrograde to the stellar orbits. The planet-like behaviour is now based on 1437 radial velocities (RVs) acquired from 2001 to 2013. ν Oct’s semimajor axis is only 2.6 au with the candidate planet orbiting $\nu ~{\rm Oct\, A}$ about mid-way between. These details seriously challenge our understanding of planet formation and our decisive modelling of orbit reconfiguration and stability scenarios. However, all non-planetary explanations are also inconsistent with numerous qualitative and quantitative tests including previous spectroscopic studies of bisectors and line-depth ratios, photometry from Hipparcos and the more recent space missions TESS and Gaia (whose increased parallax classifies $\nu ~{\rm Oct\, A}$ closer still to a subgiant, ∼K1 IV). We conducted the first large survey of $\nu ~{\rm Oct\, A}$’s chromosphere: 198 $\rm Ca\,{\small II}$ H-line and 1160 $\rm {H}\, \alpha$ indices using spectra from a previous RV campaign (2009–2013). We also acquired 135 spectra (2018–2020) primarily used for additional line-depth ratios, which are extremely sensitive to the photosphere’s temperature. We found no significant RV-correlated variability. Our line-depth ratios indicate temperature variations of only ±4 K, as achieved previously. Our atypical $\rm Ca\,{\small II}$ analysis models the indices in terms of S/N and includes covariance significantly in their errors. The $\rm {H}\, \alpha$ indices have a quasi-periodic variability that we demonstrate is due to telluric lines. Our new evidence provides further multiple arguments realistically only in favour of the planet.

Suppression of Supply Current Harmonics of 18-Pulse Diode Rectifier by Series Active Power Filter with LC Coupling

The reported research aims at improving the quality of three-phase rectifier supply currents. An effective method consists of adding properly formed booster voltages to the fundamental supply voltages using a series active filter. In the proposed solution, the booster voltages are generated by three single-phase systems consisting of inverters, LC filters, and single-phase transformers. The application of LC couplings ensures low emission of disturbances, but may provoke compensator stability problems. The article presents the current control system for a series active filter designed to suppress the dominant harmonics in the supply currents of an 18-pulse rectifier, without interference into fundamental current components. A proportional control is proposed in combination with integral terms implemented in the orthogonal coordinate systems, which synchronically rotate with frequencies equal to those of the harmonic components to be eliminated. The use of complex gains in integral terms allows a simple phase correction of the output signals. A description is given of the method to determine controller parameters based on the mathematical model of the control object. Sample results of experimental tests performed in steady-state and transient conditions are included to illustrate the quality of performance of the series active filter as compared to the results recorded for the rectifier alone, and for the rectifier with additional line reactor. The applied control method of active filter significantly reduces harmonic distortion of the grid current, which is particularly advantageous at nonideal supply voltage and low loads.

An Efficient Design for Testability Approach of Reversible Logic Circuits

Reversible circuits have been extensively investigated because of their applications in areas of quantum computing or low-power design. A reversible circuit is composed of only reversible gates and allow computations from primary inputs to primary outputs and vice-versa. In the last decades, synthesis of reversible circuits received significant interest. Additionally, testing of these kinds of circuits has been studied which included different fault models and test approaches dedicated for reversible circuits only. The analysis of testability issues in a reversible circuit commonly involves the detection of the missing gate faults that may occur during the physical realizations of the reversible gates. In this paper, we propose a design for testability (DFT) technique for reversible circuits in which the gates of a circuit are clustered into different sets and the gates from each cluster are then connected to an additional input line where, the additional line acts as an extra control input to the corresponding gate. Such arrangement makes it possible to achieve [Formula: see text] fault detection in any reversible circuit with a small increase in quantum cost. Experimental evaluations confirm that the proposed DFT technique incurs less quantum cost overhead with [Formula: see text] fault detection compared to existing DFT techniques for reversible circuits.

Comprehensive Genetic Analysis of 128 Candidate Genes in a Cohort With Idiopathic, Severe, or Familial Osteoporosis

Context The genetic bases of osteoporosis (OP), a disorder with high heritability, are poorly understood at an individual level. Cases of idiopathic or familial OP have long puzzled clinicians as to whether an actionable genetic cause could be identified. Objective We performed a genetic analysis of 28 cases of idiopathic, severe, or familial osteoporosis using targeted massively parallel sequencing. Design Targeted sequencing of 128 candidate genes was performed using Illumina NextSeq. Variants of interest were confirmed by Sanger sequencing or SNP array. Patients and Setting Thirty-seven patients in an academic tertiary hospital participated (54% male; median age, 44 years; 86% with fractures), corresponding to 28 sporadic or familial cases. Main Outcome Measure The identification of rare stop-gain, indel, splice site, copy-number, or nonsynonymous variants altering protein function. Results Altogether, we identified 28 variants of interest, but only 3 were classified as pathogenic or likely pathogenic variants: COL1A2 p.(Arg708Gln), WNT1 p.(Gly169Asp), and IDUA p.(His82Gln). An association of variants in different genes was found in 21% of cases, including a young woman with severe OP bearing WNT1, PLS3, and NOTCH2 variants. Among genes of uncertain significance analyzed, a potential additional line of evidence has arisen for GWAS candidates GPR68 and NBR1, warranting further studies. Conclusions While we hope that continuing efforts to identify genetic predisposition to OP will lead to improved and personalized care in the future, the likelihood of identifying actionable pathogenic variants in intriguing cases of idiopathic or familial osteoporosis is seemingly low.

Pyrexia of unknown origin associated with a non-infected vaginal shelf pessary

An 82-year-old female was admitted with pyrexia and rigors. Bloods showed a raised C-reactive protein and she was commenced on empirical intravenous antibiotics. Chest X-ray, urine microscopy and computed tomography scan of the patient’s abdomen and pelvis did not demonstrate a source of infection, and blood cultures did not grow a microorganism. A collateral history was taken from the patient’s husband who raised concerns regarding her vaginal shelf pessary and it was therefore removed. Subsequently the patient’s fever subsided, her inflammatory markers improved and she was discharged 2 days later. We believe this is the first reported case of pyrexia secondary to a non-infected vaginal pessary, and may provide clinicians with an additional line of enquiry when presented with patients with pyrexia of unknown origin.

Taxonomic study on Lindernia All. (Linderniaceae) from some parts of South Eastern Nigeria

The morpho-anatomical characteristics of Lindernia diffusa var. diffusa-in E. & P., L. oliveriana (Benth.) Wettst. and L. crustacea (L.) F. Muell.) were investigated with a view of providing additional line of evidence in the delimitation of the species in Nigeria. The specimens were subjected to microtomy. The anatomy, fruit morphology, leaf shape, number of fruits per node and, flower colour differed among the species. The species have two trichome types (glandular and non-glandular) with varying number of gland head and basal cells. The glandular trichomes have 4-7 gland heads and 4-8 basal cells while the non-glandular type-1 and 2 trichomes with 5-10 basal cells. Type-1 non-glandular trichome occurred in L. crustacean and L. diffusa var. diffusa while type-2 occurred in L. oliveriana. The palisade and spongy mesophylls are 1-layer and 3-5 layers respectively in L. diffusa var. diffusa, 1-2 layers and 4-6 layers in L. oliveriana and 2-3 layers and3 layers in L. crustacea. The palisade and spongy mesophylls are poorly differentiated. Two to five vascular bundles at the basal and distal ends of the petioles were observed in the Lindernia species with the main vascular bundle forming circular-united or fussed vascular bundles in L. diffusa var. diffusa and L. crustacea and arced or horizontally elongated vascular bundle separated by parenchymatous rays in L. oliveriana. In L. diffusa var. diffusa, the pith covered 55.99% of the stem, 24.27% in L. crustacea and 72.74% in L. oliveriana. These characters could be used to delimit the species studied.

An Active-Clamp Forward Inverter Featuring Soft Switching and Electrical Isolation

Traditional photovoltaic (PV) grid-connection inverters with sinusoidal pulse-width modulation (SPWM) control suffer the problem of buck-typed conversion. Additional line-frequency transformers or boost converters are required to step-up output voltage, leading to low system efficiency and high circuit complexity. Therefore, many flyback inverters with electrical isolation have been proposed by adopting a flyback converter to generate a rectified sine wave, and then connecting with a bridge unfolder to control polarity. However, all energy of a flyback inverter must be temporarily stored in the magnetizing inductor of transformer so that the efficiency and the out power are limited. This paper presents a high-efficiency active-clamp forward inverter with the features of zero-voltage switching (ZVS) and electrical isolation. The proposed inverter circuit is formed by adopting a forward converter to generate a rectified sine wave, and combining with the active-clamp circuit to reset the residual magnetic flux of the transformer. Due to the boost capability of the transformer, this inverter is suitable for the PV grid-connection power systems with wide input-voltage variation. The operation principles at steady-state are analyzed, and the mathematical equations for circuit design are conducted. Finally, a laboratory prototype is built as an illustration example according to proper analysis and design. Based on the experimental results, the feasibility and satisfactory performance of the proposed inverter circuit are verified.