Miracle-dz/UniFAR-FTUs huggingface dataset:
Glycogen synthase kinase-3β (GSK-3β) inhibitors AR-A014418 and B6B3O prevent human immunodeficiency virus—mediated neurotoxicity in primary human neurons

Glycogen synthase kinase-3β (GSK3β) role in human immunodeficiency virus (HIV)-associated neurodegeneration has been evidenced by previous investigations. In this study, we investigated the specificity of two GSK3β-specific inhibitors, AR-A014418 (A) and B6B30 (B) to prevent direct neurotoxicity in primary human neurons exposed to HIV (BaL). Neurons were exposed to HIV (500 pg/ml) for 12-h and 6-day periods in the presence and absence of A (1 μM, 100 nM, 10 nM) and B (50 nM, 5 nM, 500 pM) to investigate acute and ongoing mechanisms of HIV neurotoxicity. Using an lactate dehydrogenase (LDH) assay to assess cytotoxicity, we observed a significant neurotoxic effect of HIV from control values (P <.01) that was not restored via coexposures of all concentrations of A and B. Additionally, no change in LDH levels were observed after 6 days. However, activity of the acute proapoptotic markers caspases 3 and 7 using a luminescence assay were measured and found to be increased by exposure to HIV (BaL) compared to controls (P=.022). This effect was ameliorated via coexposure to all concentrations of A and 50 nM B after 12 h (P <.01) and to all concentrations of A and B after 6 days (P < .01). Overall, the results from this study provide further evidence for the ability of GSK3β inhibition to be neuroprotective against HIV-associated neurotoxicity by reducing HIV associated procaspase induction. These data support a role for GSK3β as a potential therapeutic target and may have important clinical implications for treatment of HIV-associated neurocognitive disorder.
Robust image communication using bandwidth reducing and expanding mappings

Combined source-channel coding can be an efficient way to exploit a noisy channel for transmitting signals representing natural sources. In this paper, we propose a coding system for transmission of still images on a time discrete, amplitude continuous, additive white Gaussian noise channel. The coder is an extension of earlier work by Lervik and Ramstad (1996). We introduce a method for bandwidth expansion which gives extra protection to the most important symbols. An improvement of the PSNR up to 5 dB is demonstrated for the proposed coder compared to the reference coder.
Glatiramer acetate inhibition of tumor necrosis factor‐α‐induced RANTES expression and release from U‐251 MG human astrocytic cells

Glatiramer acetate is an approved drug for the treatment of multiple sclerosis (MS). RANTES is a β‐family chemokine that manifests chemoattractant activity for T lymphocytes and monocytes/macrophages implicated in the pathogenesis of MS lesions. However, the effect of glatiramer acetate on the regulation of RANTES secretion in glial cells is unknown. In the present study, we demonstrate for the first time that treatment of human U‐251 MG astrocytic cells with glatiramer acetate blocks tumor necrosis factor‐α (TNF‐α)‐induced RANTES mRNA and protein in a dose‐ and time‐dependent manner. This effect is attributed to inhibition of transcription and a 40% decrease in transcript stability. Furthermore, our electrophoretic mobility shift assays of nuclear extracts from TNF‐α‐treated cells reveal an increase in DNA‐binding activity specific for the nuclear factor‐kappa B (NF‐κB) binding site, in the 5′‐flanking promoter region of the human RANTES gene, and that this increase in NF‐κB binding activity is prevented by pretreatment with glatiramer acetate or the NF‐κB inhibitors. These findings suggest that glatiramer acetate may exert its therapeutic effect in MS partially through inhibiting NF‐κB activation and chemokine production.
Characterization of a partial prostaglandin endoperoxide H synthase‐1 deficiency in a patient with a bleeding disorder

Thromboxane A2 (TXA2), synthesized in platelets, is a powerful aggregating agent and vasoconstrictor. To induce platelet aggregation, the platelets' enzyme, prostaglandin endoperoxide H synthase‐1 (PGHS‐1), first converts arachidonic acid (AA) into prostaglandin H2 (PGH2). PGH2 is then converted by the enzyme thromboxane synthase into TXA2. Finally, TXA2 is secreted and can activate the TXA2 receptor on the platelet surface. The importance of TXA2 in haemostasis has been demonstrated by the presence of a bleeding tendency in patients showing an inherited defect in the TXA2 production pathway. We studied an 18‐year‐old woman with a lifelong bleeding disorder, moderate thrombocytopenia (55–71 × 109/l) and a prolonged bleeding time (12·5 min). Her platelets aggregated in the presence of both PGH2 and a stable TXA2 analogue, but did not aggregate in the presence of AA. The activity of PGHS‐1 in platelets, measured using thin‐layer chromatography and radioactive counting of TXA2 formation from [14C]‐AA, was reduced to 13% of the activity measured in control subjects. PGHS‐1 protein levels, measured using Western blot analysis, were also markedly reduced to 10% of control values. Such levels of PGHS‐1 enzyme were too low to sustain platelet aggregation in the patient, even if the enzyme was active. The PGHS‐1 protein level was also reduced in the patient's immortalized B lymphocytes, suggesting a systemic expression defect. Northern blot analysis was then carried out with poly (A)+ RNA extracted from the patient's immortalized B lymphocytes. PGHS‐1 mRNA was detected as a 2·8‐kb band in both the patient and control. The intensity of the band representing the patient's PGHS‐1 mRNA was similar to that of the control subject. The Northern blot result suggests a normal transcriptional rate of the PGHS‐1 gene for the patient. Therefore, the defect responsible for the reduced levels of PGHS‐1 protein is probably post‐transcriptional.
Replacement therapy of secondary hypothyroidism in children born with low body weight improves mental development.

BACKGROUND Secondary hypothyroidism is observed in children after brain damage. The aim of the study was evaluation of the mental development in preterm-born children during replacement therapy with l-thyroxin because of secondary hypothyroidism. MATERIALS AND METHODS The motor and mental development of preterm newborns with secondary hypothyroidism treated with l-thyroxin since the second week of life were compared with the development of preterm newborns with secondary hypothyroidism treated since the fourth week, or later. Motor development was evaluated, and the mental development and IQ assessed by the Wechsler Intelligence Scale for Children in the seventh year of life. RESULTS Earlier achievement of the milestones of motor development, i.e. sitting, standing, and walking, was observed in children from the group who received early treatment with modest doses of l-thyroxin. In this group, all infants acquired the motor functions statistically significantly earlier in comparison to the infants from group with delayed treatment. In the seventh year of life, the IQs were significantly higher in group I treated since the second week of life, compared to group II. CONCLUSIONS The early replacement therapy with l-thyroxin initiated in the second week of life may improve long-term mental development in children.
Embryonic development and maternal regulation of murine circadian clock function

The importance of circadian clocks in the regulation of adult physiology in mammals is well established. In contrast, the ontogenesis of the circadian system and its role in embryonic development are still poorly understood. Although there is experimental evidence that the clock machinery is present prior to birth, data on gestational clock functionality are inconsistent. Moreover, little is known about the dependence of embryonic rhythms on maternal and environmental time cues and the role of circadian oscillations for embryonic development. The aim of this study was to test if fetal mouse tissues from early embryonic stages are capable of expressing endogenous, self-sustained circadian rhythms and their contribution to embryogenesis. Starting on embryonic day 13, we collected precursor tissues for suprachiasmatic nucleus (SCN), liver and kidney from embryos carrying the circadian reporter gene Per2::Luc and investigated rhythmicity and circadian traits of these tissues ex vivo. We found that even before the respective organs were fully developed, embryonic tissues were capable of expressing circadian rhythms. Period and amplitude of which were determined very early during development and phases of liver and kidney explants are not influenced by tissue preparation, whereas SCN explants phasing is strongly dependent on preparation time. Embryonic circadian rhythms also developed in the absence of maternal and environmental time signals. Morphological and histological comparison of offspring from matings of Clock-Δ19 mutant and wild-type mice revealed that both fetal and maternal clocks have distinct roles in embryogenesis. While genetic disruptions of maternal and embryonic clock function leads to increased fetal fat depots, abnormal ossification and organ development, Clock gene mutant newborns from mothers with a functional clock showed a larger body size compared to wild-type littermates. These data may contribute to the understanding of the ontogenesis of circadian clocks and the risk of disturbed maternal or embryonic circadian rhythms for embryonic development.
Restriction and modification activities from Streptococcus lactis ME2 are encoded by a self-transmissible plasmid, pTN20, that forms cointegrates during mobilization of lactose-fermenting ability

A self-transmissible (Tra+) plasmid encoding determinants for restriction and modification activities (R+/M+) from Streptococcus lactis ME2 was isolated and characterized. The 28-kilobase (kb) plasmid (pTN20) was detected in lactose-fermenting (Lac+) transconjugants generated from matings between S. lactis N1, and ME2 variant, and a plasmid-free recipient, S. lactis LM2301. The plaquing efficiencies of prolate- and small isometric-headed phages were reduced on transconjugants containing either pTN20 (R+/M+ Tra+) or 100-kb plasmids encoding Lac+, R+/M+, and Tra+. Lac+ transconjugants which harbored pTR1040 (Lac+) and pTN20 (R+/M+) were phenotypically R-/M- and transferred Lac+ at low frequency in subsequent matings to give rise to 100-kb R+/M+ plasmids. R+/M+ activities and high-frequency conjugal transfer ability were detected in Lac+ transconjugants that contained pTR1041 (Lac+) and pTN20 (R+/M+). No 100-kb R+/M+ plasmids were recovered after these matings, suggesting that pTR1041 was mobilized by pTN20 through a process that resembled plasmid donation. pTR1041 was identical to pTR1040 but contained an additional 3.3-kb DNA fragment. These data suggested that phenotypic expression of R+/M+ and Tra+ is affected by coresident Lac+ plasmids. Restriction enzyme analysis and hybridization reactions demonstrated that the 100-kb R+/M+ plasmid was formed by a cointegration event between pTR1040 (Lac+) and pTN20 (R+/M+ Tra+) during conjugal transfer via a conductive-type process. This is the first report that defines self-transmissible restriction and modification plasmids in the lactic streptococci.
Children placed in alternate care in Norway: A review of mental health needs and current official measures to meet them

Children and youth placed in alternate care have often suffered detrimental care conditions before placement and the rupture of attachment bonds both before and during alternate care. In this article, we review the knowledge base on the prevalence of mental disorders, and access to mental health services, of children and youth in alternate care in Norway. Due to the increasing knowledge of this group's needs, official measures are now taken to improve service provision and cooperation between types and levels of services for children and youth in alternate care. We review the recent Norwegian official reports aiming to improve access to mental health services for children placed in alternate care and discuss their recommendations in light of empirical findings from our own research.
Relationship between morphotypes of Atelognathus patagonicus (Anura, Neobatrachia) and environmental conditions: evidence and possible explanation

Relationship between morphotypes of Atelognathus patagonicus (Anura, Neobatrachia) and environmental conditions: evidence and possible explanation. The frog Atelognathus patagonicus (Gallardo, 1962) is endemic to an endorheic pond system in basaltic basins, in Laguna Blanca National Park and its surroundings, in northwest Argentinean Patagonia. The species has two morphotypes, aquatic and littoral, which were studied in Laguna Batea, a semi permanent pond. Aquatic and terrestrial samples were taken over a period of 31 months, including periods of drought and periods of normal precipitation. Evidence was found of the reversible character of the two morphotypes. The changes in the phenotype were consistent with the water level and limnological conditions in the pond. We believe that the change and subsequent reversal of the somatic features in these frogs are an opportunistic alternative showing remarkable plasticity of the species, which can thus inhabit both permanent and temporary ponds. Therefore, the two morphotypes, aquatic and littoral, cannot be considered as "fixed forms" within a given population, as other authors have speculated, and do not correspond to ontogenetic states.
THE SEASONAL EFFECT ON THE BODY CONDITION OF DAIRY COWS IN EASTERN ALGERIA

The aim of this study is to evaluate the body condition of dairy cows at different stages of lactation and analysis of the effect of the seasons on the body condition. From 2011 to 2015, we realized 1210 scoring on 564 lactations of 656 dairy cows. The average values are low; they are between 2.1 ± 0.4 to 2.7 ± 0.4 in the dry and calving periods and 1.2 ± 0.4 to 1.4 ± 0.4 in early lactation and 1.7 ± 0.5 to 2.2 ± 0.5 in mid-lactation. The differences in body condition scoring between seasons spring-summer and fall-winter are highly significant (P<0.01) in the middle of lactation, and significant (P<0.05) in the early lactation. These results show the need for the establishment of a monitoring body condition and fed rations related to the physiological state of cows to improve the performance of milk production.
Extracellular ATP induces the rapid release of HIV-1 from virus containing compartments of human macrophages

Significance A major obstacle to the eradication of HIV-1 by combination antiretroviral therapy (cART) is the formation of cellular reservoirs in CD4+ T lymphocytes (carrying latently integrated provirus) and tissue macrophages. Infected macrophages assemble new virions in subcellular vacuoles known as virus-containing compartments (VCC), hiding them from the immune system and, in part, from antiretroviral agents. Here we report that extracellular ATP is capable of inducing the rapid release of virions accumulated in VCC via interaction with the P2X7 receptor and without inducing cell death, whereas the antidepressant agent Imipramine blocks the release. Thus, our study identifies two “druggable” targets affecting the release of stored virions from infected human macrophages that could bear relevance for purging HIV-1 reservoirs in individuals receiving cART. HIV type 1 (HIV-1) infects CD4+ T lymphocytes and tissue macrophages. Infected macrophages differ from T cells in terms of decreased to absent cytopathicity and for active accumulation of new progeny HIV-1 virions in virus-containing compartments (VCC). For these reasons, infected macrophages are believed to act as “Trojan horses” carrying infectious particles to be released on cell necrosis or functional stimulation. Here we explored the hypothesis that extracellular ATP (eATP) could represent a microenvironmental signal potentially affecting virion release from VCC of infected macrophages. Indeed, eATP triggered the rapid release of infectious HIV-1 from primary human monocyte-derived macrophages (MDM) acutely infected with the CCR5-dependent HIV-1 strain. A similar phenomenon was observed in chronically infected promonocytic U1 cells differentiated to macrophage-like cells (D-U1) by costimulation with phorbol esters and urokinase-type plasminogen activator. Worthy of note, eATP did not cause necrotic, apoptotic, or pyroptotic cell death, and its effect on HIV-1 release was suppressed by Imipramine (an antidepressant agent known to inhibit microvesicle formation by interfering with membrane-associated acid sphingomyelinase). Virion release was not triggered by oxidized ATP, whereas the effect of eATP was inhibited by a specific inhibitor of the P2X7 receptor (P2X7R). Thus, eATP triggered the discharge of virions actively accumulating in VCC of infected macrophages via interaction with the P2X7R in the absence of significant cytopathicity. These findings suggest that the microvesicle pathway and P2X7R could represent exploitable targets for interfering with the VCC-associated reservoir of infectious HIV-1 virions in tissue macrophages.
The Growth Factor Granulin Interacts with Cyclin T1 and Modulates P-TEFb-Dependent Transcription

ABSTRACT Cyclin T1, together with the kinase CDK9, is a component of the transcription elongation factor P-TEFb which binds the human immunodeficiency virus type 1 (HIV-1) transactivator Tat. P-TEFb facilitates transcription by phosphorylating the carboxy-terminal domain (CTD) of RNA polymerase II. Cyclin T1 is an exceptionally large cyclin and is therefore a candidate for interactions with regulatory proteins. We identified granulin as a cyclin T1-interacting protein that represses expression from the HIV-1 promoter in transfected cells. The granulins, mitogenic growth factors containing repeats of a cysteine-rich motif, were reported previously to interact with Tat. We show that granulin formed stable complexes in vivo and in vitro with cyclin T1 and Tat. Granulin bound to the histidine-rich domain of cyclin T1, which was recently found to bind to the CTD, but not to cyclin T2. Binding of granulin to P-TEFb inhibited the phosphorylation of a CTD peptide. Granulin expression inhibited Tat transactivation, and tethering experiments showed that this effect was due, at least in part, to a direct action on cyclin T1 in the absence of Tat. In addition, granulin was a substrate for CDK9 but not for the other transcription-related kinases CDK7 and CDK8. Thus, granulin is a cellular protein that interacts with cyclin T1 to inhibit transcription.
Will 10-Gigabit Ethernet Have a Bright Future?

Researchers, engineers, and vendors are readying the newest Ethernet standard which promises not only faster speeds than previous versions but also important new features. The proposed 10-Gigabit Ethernet (10 GbE) standard, known as IEEE 802.3ae, would not only provide data rates of 10 Gbits per second but would also work with metropolitan and wide area networks (MANs and WANs), where ATM (asynchronous transfer mode) and Sonet (synchronous optical network) currently dominate. Ethernet and Fast Ethernet were designed to work primarily with local area networks (LANs), where they are the dominant technologies. The IEEE expects to formally adopt the 802.3ae standard this year.
A multi-institutional survey of internal medicine residents’ learning habits

Background: Resident physicians are expected to demonstrate medical knowledge. However, little is known about the residents' reading habits and learning preferences. Aim: To assess residents’ reading habits and preferred educational resources. Methods: Residents at five internal medicine training programs were surveyed regarding their reading and learning habits and preferences. Results: The majority (77.7%) of residents reported reading less than 7 h a week. Most residents (81.4%) read in response to patient care encounters. The preferred educational format was electronic; 94.6% of residents cited UpToDate® as the most effective resource for knowledge acquisition, and 88.9% of residents reported that UpToDate® was their first choice for answering clinical questions. Conclusions: Residents spent little time reading and sought knowledge primarily from electronic resources. Most residents read in the context of patient care. Future research should focus on strategies for helping resident physicians learn in the electronic age.
Theoretical basis for separation of multiple linked gene effects in mapping quantitative trait loci.

It is now possible to use complete genetic linkage maps to locate major quantitative trait loci (QTLs) on chromosome regions. The current methods of QTL mapping (e.g., interval mapping, which uses a pair or two pairs of flanking markers at a time for mapping) can be subject to the effects of other linked QTLs on a chromosome because the genetic background is not controlled. As a result, mapping of QTLs can be biased, and the resolution of mapping is not very high. Ideally when we test a marker interval for a QTL, we would like our test statistic to be independent of the effects of possible QTLs at other regions of the chromosome so that the effects of QTLs can be separated. This test statistic can be constructed by using a pair of markers to locate the testing position and at the same time using other markers to control the genetic background through a multiple regression analysis. Theory is developed in this paper to explore the idea of a conditional test via multiple regression analysis. Various properties of multiple regression analysis in relation to QTL mapping are examined. Theoretical analysis indicates that it is advantageous to construct such a testing procedure for mapping QTLs and that such a test can potentially increase the precision of QTL mapping substantially.
Sectoral Effects of News Shocks

This paper argues that an aggregate news shock reveals news about technological improvements in the durable goods sector. Better technological prospects translate into large responses of the fundamentals in the durable goods sector; much larger than the responses of the fundamentals in the non‐durable goods sector. These better technological prospects, contrary to common belief, do not induce short‐run comovement among fundamentals within either of the two sectors. The behaviour of inventories, an important margin that durable goods producers can use to buffer news shocks, proves to be crucial for reconciling the effects of news shocks in a two‐sector model with the data.
A Grey Relation Analysis Method to Vibration Fault Diagnosis of Hydroelectric Generating Set

Aiming to the complexity of vibration fault cause, the great many of fault parameters in hydroelectric generating set, and the superiority of grey relation analysis for its no strict requirement to fault sample capacity and regularity, the weighted grey relation model is built to look for the vibration fault type. The fuzzy matrix's transformation arithmetic is used to obtain the weight vectors of the grey relation coefficient, thus the weighted coefficient is the weighted grey relation model. The relation coefficient between reference sequence and compare sequence in vibration fault sample is provided by synthetic arithmetic of fuzzy weight to diagnose the vibration fault type. The grey relation coefficient weighted by fuzzy synthetic arithmetic, which is not only made the established weight be a scientific basis, but also can “sensitive” highlight the vibration fault type of hydroelectric generating set. Thus the problem of looking for every fault types is better resolved. By analyzing the practical example, it proved that the weighted grey relation model in the paper can effectively diagnose the vibration fault type of hydroelectric generating set and it has definite applicability.