Miracle-dz/UniFAR-FTUs huggingface dataset:
Nef Enhances Human Immunodeficiency Virus Replication and Responsiveness to Interleukin-2 in Human Lymphoid Tissue Ex Vivo

ABSTRACT The nef gene is important for the pathogenicity associated with simian immunodeficiency virus infection in rhesus monkeys and with human immunodeficiency virus type 1 (HIV-1) infection in humans. The mechanisms by which nef contributes to pathogenesis in vivo remain unclear. We investigated the contribution of nef to HIV-1 replication in human lymphoid tissue ex vivo by studying infection with parental HIV-1 strain NL4-3 and with anef mutant (ΔnefNL4-3). In human tonsillar histocultures, NL4-3 replicated to higher levels than ΔnefNL4-3 did. Increased virus production with NL4-3 infection was associated with increased numbers of productively infected cells and greater loss of CD4+ T cells over time. While the numbers of productively infected T cells were increased in the presence of nef, the levels of viral expression and production per infected T cell were similar whether the nefgene was present or not. Exogenous interleukin-2 (IL-2) increased HIV-1 production in NL4-3-infected tissue in a dose-dependent manner. In contrast, ΔnefNL4-3 production was enhanced only marginally by IL-2. Thus, Nef can facilitate HIV-1 replication in human lymphoid tissue ex vivo by increasing the numbers of productively infected cells and by increasing the responsiveness to IL-2 stimulation.
Colour and pattern selectivity of receptive fields in superior colliculus of marmoset monkeys

• In addition to supplying signals for conscious visual perception, the pathways from eye to brain serve visual functions such as reflex eye movements, which are controlled by a brain area called the superior colliculus (SC). • It is known that short‐wavelength sensitive (S or ‘blue’) cone photoreceptors serve an evolutionary ancient pathway for colour vision but whether S cones also contribute to reflex eye movements is poorly understood. • We show that in recordings from anaesthetised marmoset monkeys, S cones do not contribute to visual responses in the SC. Thus, although S cones are a primitive part of the visual system their signals are selectively directed to thalamo‐cortical pathways serving colour vision. • The result also implies that colour‐selective responses reported in SC of awake monkeys must arrive through indirect (non‐retinal) inputs to the SC.
The perspective of immunotherapy: new molecules and new mechanisms of action in immune modulation

Purpose of review Targeting CTLA-4, the patriarch of immune checkpoint modulators, is currently the only immunotherapeutic approach that has achieved significant clinical benefit in melanoma phase III trials. In this review, recent new ideas about the mechanism of action of anti-CTLA antibodies, other new molecules to target, and rationales for combination therapies will be discussed. Recent findings Although the clinical efficacy of the anti-CTLA-4 monoclonal antibody (mAb) ipilimumab is meanwhile without doubt, its mechanism of action is still not fully understood. Recent data indicate that, besides modulation of the TCR signal, CTLA-4 mAbs can mediate regulatory T-cell depletion in an Fc gamma receptor dependent manner. Blockade of the molecules PD-1 and PD-L1 has given promising clinical responses (and this beyond melanoma), whereas their complex expression and interaction pattern makes a clear statement about the mechanism of action challenging. Additional other co-inhibitory and co-stimulatory molecules have been identified recently. Combinations of immune checkpoint modulators themselves or with other therapies, such as adoptive cell therapy, targeted therapy or radiotherapy, will improve the outcomes further. Summary Immune checkpoint blockade is currently the most promising systemic therapeutic approach to achieve long-lasting responses or even cure in melanoma and other malignancies.
Hole Mobility in Germanium as a Function of Substrate and Channel Orientation, Strain, Doping, and Temperature

We present a comprehensive study of hole transport in germanium layers on “virtual” substrates using a full band Monte Carlo simulation approach, considering alternate “virtual” substrate and channel orientations and including the impact of the corresponding biaxial strain, doping, and lattice temperature. The superior mobility in strained germanium channels with orientation on a (110) “virtual” substrate is confirmed, and the factors leading to this enhancement are evaluated. The significant decrease in strain-and-orientation-induced mobility enhancement due to impurity scattering in doped material and at increasing lattice temperature is also demonstrated. Both factors determine how efficiently the mobility enhancement translates into transistor performance enhancement. Additionally, we shine light on the question of which factor has stronger impact in mediating the increase in mobility due to strain-the breaking of degeneracy for the heavy- and light-hole bands at the point or the reduction in the density of states.
Terms of Trade and Current Account

In this paper, we find that a rise in the price of land-using commodity would lead to a decrease in the interest rate and hence the price of capital would decline. In addition, we also find that a rise in the price of land-using commodity would lead to an increase in the land rent and hence lead to a rise in the price of land. Finally, we reveal that the impact of terms of trade on current account is ambiguous
Comparison of pharmacokinetics and toxicity after high-dose methotrexate treatments in children with acute lymphoblastic leukemia

We carried out a detailed comparative study of the pharmacokinetics and toxicity of methotrexate (MTX) and 7-hydroxy-methotrexate (7-OH-MTX) after high-dose intravenous methotrexate (HD-MTX) in children with acute lymphoblastic leukemia (ALL). Overall, 65 children were treated with 5 g/m2/24 h MTX and 88 children were treated with 2 g/m2/24 h MTX according to ALL-BFM 95 and ALL IC-BFM 2002 protocols (mean age: 6.4 years, range 1.0–17.9 years). A total of 583 HD-MTX courses were analyzed. Serum MTX and 7-OH-MTX levels were measured at 24, 36, and 48 h, and cerebrospinal fluid (CSF) MTX levels were determined 24 h after the initiation of the infusion. The area under the concentration–time curve was calculated. Hepatotoxicity, nephrotoxicity, and bone marrow toxicity were estimated by routine laboratory tests. We investigated pharmacokinetics and toxicity in distinct age groups (<6 and >14 years). 5 g/m2/24 h treatments resulted in higher serum and CSF MTX and 7-OH-MTX levels (P<0.05). The CSF penetration rate of MTX was independent of the MTX dose [2.3% (95% confidence interval: 1.7–2.5%) vs. 2.8% (95% confidence interval: 2.4–3%)]. The CSF MTX concentration was correlated with the 24 h MTX serum level (r=0.38, P<0.0001). Repeated treatments did not alter MTX or 7-OH-MTX levels. 7-OH-MTX levels were correlated with nephrotoxicity (r=0.36, P<0.0001). Higher MTX levels and toxicity occurred more frequently in children aged older than 14 years (P<0.05). Therapeutic serum and CSF MTX concentrations can be achieved more reliably with 5 g/m2/24 h treatments. To predict the development of toxicity, monitoring of the level of the 7-OH-MTX is useful. Monitoring of pharmacokinetics is essential to prevent the development of severe adverse events in adolescents.
Sensory-motor integration for dexterous high-speed handling

In this paper, visuomotor integration in high-speed manipulation system is discussed, and ldquodynamic pen-spinningrdquo and ldquoone-handed knottingrdquo are proposed as the examples. These applications are based on not only the improvement of the vision and the multifingered hand but also new control strategies. The balanced development of the hardware and the control method can produce new capability of manipulation.
Role of protein F in maintaining structural integrity of the Pseudomonas aeruginosa outer membrane

To investigate the functional role of protein F of the outer membrane of Pseudomonas aeruginosa, we isolated mutants devoid of protein F, and the defective gene was transferred to a wild-type strain by plasmid FP5-mediated conjugation. Chemical analyses of the protein F-deficient outer membrane revealed that the amount of outer membrane protein was reduced to 72 to 74% of that of the protein F-sufficient strain and that lipopolysaccharides and phospholipids increased to 117 to 123% and 135 to 136%, respectively. The mutants and the transconjugant showed the following characteristics: (i) growth rates of protein F-deficient strains in low-osmolarity medium (e.g., L broth containing 0.1% NaCl) were less than 1/10 the rate of the protein F-sufficient strain; (ii) protein F-deficient cells were rounded, and the outer membrane formed large protruded blebs; and (iii) the outer membrane became physically fragile, since a significant amount of periplasmic proteins leaked out and the cells became highly sensitive to osmotic shock. The results suggested that protein F plays an important role in morphogenesis and in maintaining the integrity of the outer membrane. Determination of the diffusion rates of saccharides and beta-lactam antibiotics showed that the protein F-deficient outer membrane had no detectable transport defect compared with the protein F-sufficient outer membrane. The MICs of antibiotics for the protein F-deficient strains were nearly identical to those for the protein F-sufficient strain.
Rapid pharmacokinetics of intradermal insulin administered using microneedles in type 1 diabetes subjects.

BACKGROUND This study compared the pharmacokinetics, postprandial glycemic response, and pain associated with intradermal lispro insulin delivery using a microneedle with that of a conventional catheter. SUBJECTS AND METHODS Five subjects with type 1 diabetes were administered a bolus infusion of lispro insulin using a 9-mm-long subcutaneous catheter (control treatment) and a 0.9-mm-long microneedle (study treatment), followed by consumption of a standardized meal. Blood samples were periodically assayed for plasma glucose and free insulin levels. RESULTS Intradermal insulin infusion using microneedles reached peak insulin concentrations in approximately half the time and led to greater reduction in plasma glucose levels than subcutaneous catheters. Microneedles were also significantly less painful than the catheters. CONCLUSION The rapid pharmacokinetics and minimally invasive nature of intradermal insulin infusion using microneedles provide significant potential for improved diabetes management.
Cyclohexylpiperazine derivative PB28, a σ2 agonist and σ1 antagonist receptor, inhibits cell growth, modulates P-glycoprotein, and synergizes with anthracyclines in breast cancer

σ Ligands have recently been shown to have cytotoxic activity, to induce ceramide-dependent/caspase-independent apoptosis, and to down-regulate P-glycoprotein (P-gp) mRNA levels in some mouse and human models. In this study, we verified whether a mixed σ2 agonist/σ1 antagonist, PB28, was able to have antitumor activity and to enhance anthracycline efficacy in two human breast cancer cell lines, MCF7 and MCF7 ADR, both characterized by significant σ2 receptor expression, by high and low σ1 receptor expression, and low and high P-gp expression, respectively. In both cell lines, PB28 showed high σ2 receptor affinity and low σ1 receptor affinity; furthermore, it inhibited cell growth with a clear effect at 48 hours (IC50 in nanomolar range), a consistent time exposure-independent increase of G0-G1-phase fraction (of ∼20% of both cell lines) and caspase-independent apoptosis (15% increased after 1-day drug exposure). PB28 also reduced P-gp expression in a concentration- and time-dependent manner (∼60% in MCF7 and 90% in MCF7 ADR). We showed also a strong synergism between PB28 and doxorubicin by adopting either simultaneous or sequential schedules of the two drugs. We suggest that this synergism could depend on PB28-induced increase of intracellular accumulation of doxorubicin (∼50% in MCF7 and 75% in MCF7 ADR by flow cytometry analysis). In conclusion, we suggest that the σ2 agonist PB28 could be an interesting antitumor agent either in monotherapy or in combination with conventional drugs. [Mol Cancer Ther 2006;5(7):1807–16]
On - Farm Apprenticeships: Labor Identities and Sociocultural Reproduction within Alternative Agrifood Movements

On-­‐‐farm apprenticeship is a site of sociocultural learning for beginning farmers, and also for identity politics, mediated by social movement learning processes. This critical ethnographic case study used cultural historical activity theory (CHAT) to illuminate ways in which institutions mediated this cultural work to both reinforce and challenge dominant narratives.
Impact of Fluctuations in the Prices of Crude Oil on Inflation: Evidence from Jordanian Economy

Inflation remains a major and lasting challenge for the economies of most countries in the world, because of its undesirable effects on economic units. The research aims mainly to study and analyze the impact of fluctuations in the prices of crude oil on inflation in the Jordanian economy. The researchers collect financial data for the period from 1/1/2000 until 31/12/2013 on a monthly basis. The study shows that the inflation rate in the Jordanian economy is not much affected by fluctuations taking place in crude oil prices and gold prices. The results show that the effect after the global financial crisis began in the relationship between the growth of oil prices and gold prices and inflation. This result may be attributable to changes in domestic and international investment environment. The study recommends studying other factors that affect the inflation rate in the Jordanian economy, such as interest rates.
Prospects of Transcript Profiling for mRNAs and MicroRNAs Using Formalin‐Fixed and Paraffin‐Embedded Dissected Autoptic Multiple Sclerosis Lesions

The elaboration of novel pathogenic aspects of multiple sclerosis (MS) requires the analysis of well‐defined stages of lesion development. However, specimens of certain stages and lesion types are either present in small brain biopsies, insufficient in size for further molecular studies or available as formalin‐fixed and paraffin‐embedded (FFPE) material only. Therefore, application of current molecular biology techniques to FFPE tissue is warranted. We compared FFPE and frozen tissue by using quantitative polymerase chain reaction and report: (1) FFPE material is highly heterogeneous regarding the utility for transcript profiling of mRNAs; well‐preserved FFPE samples had about a 100‐fold reduced sensitivity compared with frozen tissue, but gave similar results for genes of sufficient abundance; (2) FFPE samples not suitable for mRNA analysis are still highly valuable for miRNA quantification; (3) the length of tissue fixation greatly affects utility for mRNA but not for miRNA analysis; (4) FFPE samples can be processed via a hot water bath for dissection of defined lesion areas; and (5) in situ hybridization for proteolipid protein (PLP) helps to identify samples not suitable for mRNA amplification. In summary, we present a detailed protocol how to use autoptic FFPE tissue for transcript profiling in dissected tissue areas.
Fuzzy logic based hybrid approach for sentiment analysisl of Malayalam movie reviews

In this paper, Sentence level Sentiment Analysis of Malayalam movie reviews is done by classifying the polarity of opinions obtained from the user as positive, negative and neutral. Sentiment analysis is an application of Natural Language Processing and text analysis which helps to identify the emotions in a given context. In this work a hybrid approach for Sentiment Analysis is used in which Machine Learning method is used for tagging and Fuzzy Logic is used to find the membership of the review in each sentiment class. Fuzzy logic can be used to handle the vagueness in natural language. Manually tagged data are trained using TnT and Fuzzy rules are incorporated for identifying and classifying the emotions. Certain other rules are also incorporated to handle certain special cases. The fuzzy rules yield output that varies in degree between 0 and 1.
The tyrosine kinase inhibitor bafetinib inhibits PAR2‐induced activation of TRPV4 channels in vitro and pain in vivo

Protease‐activated receptor 2 (PAR2) is expressed on nociceptive neurons, and can sensitize transient receptor potential (TRP) ion channels to amplify neurogenic inflammation and pain. The mechanisms by which this occurs are not fully understood. PAR2 causes receptor‐operated activation of TRPV4 channels and TRPV4 null mice have attenuated PAR2‐stimulated neurogenic inflammation and mechanical hyperalgesia. Here we investigate the intracellular signalling mechanisms underlying PAR2‐induced TRPV4 channel activation and pain.
Analysis Method of the Dynamic Force and Torque Distribution in the Magnet Array of a Commutated Magnetically Levitated Planar Actuator

This paper concerns the analysis of the dynamic forces and torques acting on the magnets in a Halbach permanent magnet array of a magnetically levitated moving-magnet planar actuator. A new analysis tool is presented which predicts the dynamic force and torque distribution on the magnet array. This design tool uses lookup table data, which are generated by numerically solving the Lorentz force and torque integral, to describe the force and torque between each magnet and coil in the topology. It offers a fast and accurate solution for the analysis of magnetically levitated planar actuators. The results for two different commutation methods are presented.
Long-term controlled release of PLGA microparticles containing antidepressant mirtazapine

Abstract The aim of the study was to prepare PLGA microparticles for prolonged release of mirtazapine by o/w solvent evaporation method and to evaluate effects of PVA concentration and organic solvent choice on microparticles characteristics (encapsulation efficiency, drug loading, burst effect, microparticle morphology). Also in vitro drug release tests were performed and the results were correlated with kinetic model equations to approximate drug release mechanism. It was found that dichloromethane provided microparticles with better qualities (encapsulation efficiency 64.2%, yield 79.7%). Interaction between organic solvent effect and effect of PVA concentration was revealed. The prepared samples released the drug for 5 days with kinetics very close to that of zero order (R2 = 0.9549 – 0.9816). According to the correlations, the drug was probably released by a combination of diffusion and surface erosion, enhanced by polymer swelling and chain relaxation.
Are female leaders more efficient in family firms than in non-family firms?

Purpose The aim of this study is to investigate whether female leaders are more efficient in family firms than in non-family firms. Design/methodology/approach This paper uses a unique database of ownership and leadership in private Swedish firms that makes it possible to analyze differences in firm performance due to female leadership in family and non-family firms. The analysis is based on survey data merged with micro-level data on Swedish firms. Only firms with five or more employees are included in the analysis. The sample contains more than 1,000 firms. Findings The descriptive statistics show that there are many more male than female corporate leaders. However, the regression analysis indicates that female leadership has a much more positive impact on the performance of family firms than on that for non-family firms, where the effect is ambiguous. Originality/value Comparative studies examining the impact of female leadership on firm-level performance in family and non-family firms are rare, and those that exist are most often either qualitative or focused on large, listed firms. By investigating the role of female directors in family and non-family firms, the study adds to the literature on management, corporate governance and family firms.
NEURAL DIFFERENTIATION POTENTIAL OF RAT AMNIOTIC EPITHELIAL CELLS

Amniotic epithelial cells (AEC) are thought to represent a stem-like cell population and to be an attractive cell source for regenerative medicine, because abundant cells can be obtained noninvasively at delivery. The authors investigated the neural differentiation potential of rat AEC. Rat AEC expressed vimentin and nestin, but not c-kit, oct-4, or nanog. The expression of the neural lineage markers, including βIII-tubulin, neuron specific enolase (NSE), neurofilament-M, neuroD, glial fibrillary acidic protein (GFAP), myelin basic protein (MBP), tyrosine hydroxylase (TH), acetylcholinesterase (AChE), cholin acetyltransferase (ChAT), and mammalian achaete-scute homolog1 (MASH1), was detected by RT-PCR in the cultured rat AEC. After neural induction, rat AEC dramatically changed their shapes, projecting dendrite-like structures. Immunocytochemically, ∼20% of the induced cells expressed an immature neuronal marker, βIII-tubulin. Our findings suggested that rat AEC might be already committed to differentiate to various neural lineages and that they could differentiate to immature neurons in vitro.
SatR Is a Repressor of Fluoroquinolone Efflux Pump SatAB

ABSTRACT Streptococcus suis is an emerging zoonotic agent responsible for high-mortality outbreaks among the human population in China. In this species, the ABC transporter SatAB mediates fluoroquinolone resistance when overexpressed. Here, we describe and characterize satR, an open reading frame (ORF) encoding a MarR superfamily regulator that acts as a repressor of satAB. satR is cotranscribed with satAB, and its interruption entails the overexpression of the pump, leading to a clinically relevant increase in resistance to fluoroquinolones.
Early epitope- and isotype-specific humoral immune responses to GAD65 in young children with genetic susceptibility to type 1 diabetes.

OBJECTIVE The pattern of the humoral immunity to disease-associated autoantigens may reflect the severity of the autoimmune disease process. The purpose of this study was to delineate the maturation of the humoral immunity to one of the main autoantigens in type 1 diabetes (T1D), glutamic acid decarboxylase (GAD65). DESIGN AND METHODS Serum samples were obtained for the detection of epitope- and isotype-specific antibodies sequentially with short intervals from 36 young children with HLA-conferred genetic susceptibility to T1D starting from the first appearance of GAD65Ab. During prospective observation, ten children developed T1D. Antibodies were analyzed using biotinylated anti-human immunoglobulin (Ig) antibodies and chimeric GAD molecules in radio-binding assays. RESULTS The immune response to GAD65 started as reactivity to the middle region and spread rapidly to the C-terminal region. IgG1 antibodies dominated among the isotypes from the first appearance of GAD65Ab, while other IgG subclasses were observed to a lesser extent. IgG4 antibodies emerged clearly as the last IgG subclass. A broad initial response comprising three to four IgG subclasses and the lack of an emerging IgG4 response during follow-up was associated with increased risk for progression to clinical diabetes (P<0.05). CONCLUSIONS The humoral response to GAD65 epitope clusters is relatively uniform in young children, whereas there is conspicuous individual variation in IgG subclass responses except for IgG1. A narrow initial IgG subclass response to GAD65 and the emergence of IgG4 antibodies were characteristic of those who remained non-diabetic over the first few years of GAD65 autoimmunity.