Miracle-dz/UniFAR-FTUs huggingface dataset:
Role of T‐Cell Derived Cytokines in the Downregulation of Immune Responses in Parasitic and Retroviral Infection

Parasitic infection is frequently accompanied by a downregulation in host cell-mediated immunity. Recent studies suggest that this modulation of helper T cells and effector cell function can at least in part be attributed to the action of a set of inhibitory cytokines produced by T lymphocytes as well as by a number of other cell types. The best characterized of these inhibitory lymphokines are IL-4, IL-10 and TGF-beta. Interestingly, both IL-4 and IL-10 are produced by the Th2 but not the Th1 subset of CD4+ helper cells. The former subset dominates in many situations of chronic or exacerbated parasitic infection and is thought to suppress Th1 function as a consequence of the cross-regulatory activity of these two cytokines. The latter hypothesis is supported by recent experiments demonstrating that mAb-mediated neutralization of IL-10 reverses suppressed IFN-gamma responses and/or disease susceptibility in mice with parasitic infections. In vivo neutralization of TGF-beta has also been reported to increase host resistance to parasite challenge. In addition to suppressing T-cell differentiation, function or proliferation, IL-4, IL-10 and TGF-beta each inhibit the ability of IFN-gamma to activate macrophages for killing of both intracellular and extracellular parasites. Moreover, the three cytokines are able to synergize with each other in downregulating these parasiticidal effects. Interestingly, each of the cytokines inhibits the production of reactive nitrogen oxides, an effector mechanism previously demonstrated to play a major role in parasite killing by activated macrophages. In the case of IL-10, this suppression of nitrogen oxide production appears to result from an inhibition of TNF-alpha synthesis leading to defective macrophage stimulation. While distant from parasites in their biology and phylogeny, some retroviruses also appear to induce an over-production in downregulatory cytokines which is closely associated with the onset of immunodeficiency. Thus, in an animal model involving infection of mice with LP-BM5 MuLV and in human HIV infection, Th2 (IL-10 and/or IL-4) cytokine synthesis is increased while Th1 (IFN-gamma and/or IL-2) cytokine production is suppressed. These observations suggest that cytokine-mediated cross-regulation may play a role in the pathogenesis of acquired immune deficiency disease, contributing both to the progression of retroviral infection and the increase in susceptibility to opportunistic infections and malignancy. Observations of similar cytokine cross-regulatory activities in organisms as diverse as helminths, protozoa and retroviruses predict that comparable mechanisms may operate in a wide variety of infectious diseases.
Domain Specificity of Oculomotor Learning after Changes in Sensory Processing

Humans visually process the world with varying spatial resolution and can program their eye movements optimally to maximize information acquisition for a variety of everyday tasks. Diseases such as macular degeneration can change visual sensory processing, introducing central vision loss (a scotoma). However, humans can learn to direct a new preferred retinal location to regions of interest for simple visual tasks. Whether such learned compensatory saccades are optimal and generalize to more complex tasks, which require integrating information across a large area of the visual field, is not well understood. Here, we explore the possible effects of central vision loss on the optimal saccades during a face identification task, using a gaze-contingent simulated scotoma. We show that a new foveated ideal observer with a central scotoma correctly predicts that the human optimal point of fixation to identify faces shifts from just below the eyes to one that is at the tip of the nose and another at the top of the forehead. However, even after 5000 trials, humans of both sexes surprisingly do not change their initial fixations to adapt to the new optimal fixation points to faces. In contrast, saccades do change for tasks such as object following and to a lesser extent during search. Our findings argue against a central brain motor-compensatory mechanism that generalizes across tasks. They instead suggest task specificity in the learning of oculomotor plans in response to changes in front-end sensory processing and the possibility of separate domain-specific representations of learned oculomotor plans in the brain. SIGNIFICANCE STATEMENT The mechanism by which humans adapt eye movements in response to central vision loss is still not well understood and carries importance for gaining a fundamental understanding of brain plasticity. We show that although humans adapt their eye movements for simpler tasks such as object following and search, these adaptations do not generalize to more complex tasks such as face identification. We provide the first computational model to predict where humans with central vision loss should direct their eye movements in face identification tasks, which could become a critical tool in making patient-specific recommendations. Based on these results, we suggest a novel theory for oculomotor learning: a distributed representation of learned eye-movement plans represented in domain-specific areas of the brain.
Prevalence of STDs among prostitutes in Czech border areas with Germany in 1997–2001 assessed in project “Jana”

Background: The STD problem emerged in the Czech Republic as a result of geopolitical and social and economic changes in the state. Prostitution is concentrated mainly around border areas with Austria and Germany, contributing to the increase in STDs. The Czech-German project “Jana,” based on a project umbrella network of the WHO, was organised. Objectives: To prevent STDs, including HIV/AIDS, and assessment of STD prevalence in the target group. Methods: Prostitutes working in night clubs and in the streets and roads of three districts in the West Bohemian Region of the Czech Republic bordering on Germany were studied. Interactions included street work, venereology check up, psychology and sociology counselling, psychological preparation on possible treatment, and continuous and regular contact. Results: The number of “love clubs” involved in project “Jana” increased from 46 in 1997 to 72 in 2000. Of 561 street girls registered in the project during 1997–2001, there was one HIV positive, every 11th prostitute had syphilis, and one in 93 women had gonorrhoea, whereas incidence of syphilis in the Czech Republic was 10.2/100 000 and that of gonorrhoea 9.5/100 000 inhabitants in 2001, 31 women had Chlamydia trachomatis urinary tract and genital infection, and 25 were HBsAg positives. STD frequency revealed in project participants significantly exceeds numbers of STDs in the other inhabitants of the Czech Republic. The majority of prostitutes were foreigners, mostly Ukrainians and Russians. Conclusion: The situation in the border areas is alarming. The priority must be to concentrate efforts on prevention of spread of venereal diseases in borders of economically disparate states.
Auditor‐Provided Nonaudit Services: Post‐Eu‐Regulation Evidence from Denmark

This survey study focuses on the relationship between the simultaneous provision of audit and nonaudit services and auditor independence&#8208;in&#8208;appearance as perceived by Danish stakeholders. Thereby, the perceived usefulness of the new EU public&#8208;interest entity regulation and audit directive is evaluated. Our findings indicate that the joint provision of nonaudit and audit services is negatively associated with perceived auditor independence. However, this differs according to the type of stakeholder group. Many individual services, even those not on the EU blacklist, are regarded as problematic. Nevertheless, the relation to independence&#8208;in&#8208;appearance differs by type of service. The EU cap on nonaudit services fees seems to be too high. The separation between audit firms' staff that provides auditing services and staff that provides nonaudit services, and an approval of nonaudit services by the audit committee, are not regarded as helpful in enhancing auditor independence. Finally, respondents see a need to expand the strict EU regulations for audits of public&#8208;interest entities to audits of large non&#8208;public&#8208;interest entities.
VASCULAR ENDOTHELIAL GROWTH FACTOR IS INCREASED DURING THE FIRST 48 HOURS OF HUMAN SEPTIC SHOCK AND CORRELATES WITH VASCULAR PERMEABILITY

Meningococcal septic shock is an important cause of morbidity and mortality in children and young adults worldwide and is the prototypical gram-negative septic shock. One of the key factors in the development of shock is increased microvascular permeability. Vascular endothelial growth factor (VEGF) is a central factor in angiogenesis and is an important mediator of vascular permeability. Thirteen patients with meningococcal infection (eight presenting with shock) were investigated in the early phase of invasive meningococcal disease. Cytokines, complement activation, and VEGF plasma concentrations were measured during the first 48 h on the pediatric intensive care unit. Increased cytokine concentrations and activation of the complement system were observed. VEGF plasma concentrations were increased (median 193 pg/mL, range 71-1082) and were highest in the presence of shock (208 pg/mL, 169-1082) compared with patients presenting without shock (92 pg/mL range 71-299). VEGF concentration at admission correlated with the severity of disease (pediatric risk of mortality score, R = 0.90 [Spearman], P = 0.0001) and the amount of fluids administered within the first 24 h (R = 0.90, P < 0.0001). In all patients, a decrease in VEGF was associated with a decrease in fluid intake during t = 24 to 48 h. The results suggest that apart from correlation with IL-1β, −10, −12, and complement activation, microvascular permeability in sepsis is also closely linked to the plasma concentration of VEGF. The role of VEGF in sepsis-associated increased microvascular permeability needs further exploration and may represent a new therapeutic target.
Structural brain abnormalities in adolescents with autism spectrum disorder and patients with attention deficit/hyperactivity disorder.

BACKGROUND Although autism spectrum disorder (ASD) and attention deficit/hyperactivity disorder (ADHD) are two distinct neurodevelopmental diseases, they share behavioural, neuropsychological and neurobiological characteristics. For the identification of endophenotypes across diagnostic categories, further investigations of phenotypic overlap between ADHD and autism at the behavioural, neurocognitive, and brain levels are needed. METHODS We examined regional grey matter differences and similarities in children and adolescents with ASD and ADHD in comparison to healthy controls using structural magnetic resonance imaging (MRI) and voxel-based morphometry. RESULTS With regard to clinical criteria, the clinical groups did not differ with respect to ADHD symptoms; however, only patients with ASD showed deficits in social communication and interaction, according to parental rating. Structural abnormalities across both clinical groups compared to controls became evident as grey matter reductions in the left medial temporal lobe and as higher grey matter volumes in the left inferior parietal cortex. In addition, autism-specific brain abnormalities were found as increased grey matter volume in the right supramarginal gyrus. CONCLUSIONS While the shared structural deviations in the medial temporal lobe might be attributed to an unspecific delay in brain development and might be associated with memory deficits, the structural abnormalities in the inferior parietal lobe may correspond to attentional deficits observed in both ASD and ADHD. By contrast, the autism-specific grey matter abnormalities near the right temporo-parietal junction may be associated with impaired 'theory of mind' abilities. These findings shed some light on both similarities and differences in the neurocognitive profiles of ADHD and ASD patients.
Roles of dopaminergic innervation of nucleus accumbens shell and dorsolateral caudate-putamen in cue-induced morphine seeking after prolonged abstinence and the underlying D1- and D2-like receptor mechanisms in rats

Drug-associated cues can elicit relapse to drug seeking after abstinence. Studies with extinction–reinstatement models implicate dopamine (DA) in the nucleus accumbens shell (NAshell) and dorsolateral caudate-putamen (dlCPu) in cocaine seeking. However, less is known about their roles in cue-induced opiate seeking after prolonged abstinence. Using a morphine self-administration and abstinence–relapse model, we explored the roles of NAshell and dlCPu DA and the D1/D2-like receptor mechanisms underlying morphine rewarding and/or seeking. Acquisition of morphine self-administration was examined following 6-Hydroxydopamine hydrobromide (6-OHDA) lesions of the NAshell and dlCPu. For morphine seeking, rats underwent 3 weeks’ morphine self-administration followed by 3 weeks’ abstinence from morphine and the training environment. Prior to testing, 6-OHDA, D1 antagonist SCH23390, or D2 antagonist eticlopride was locally injected; then rats were exposed to morphine-associated contextual and discrete cues. Results show that acquisition of morphine self-administration was inhibited by NAshell (not dlCPu) lesions, while morphine seeking was attenuated by lesions of either region, by D1 (not D2) receptor blockade in NAshell, or by blockade of either D1 or D2 receptors in dlCPu. These data indicate a critical role of dopaminergic transmission in the NAshell (via D1-like receptors) and dlCPu (via D1- and D2-like receptors) in morphine seeking after prolonged abstinence.
Modelling Exchange Rate Volatility Dynamics: Empirical Evidence From South Africa

In this paper, we extend the literature on modelling exchange rate v olatility in South Africa by estimating a range of models, including some that attempt to account for structural breaks and long memory. We examine the key nominal exchange rates of the South African rand and replicate common findings in the literature; particularly that volatility is ‘persistent’. We investigate whether this ‘persistence’ is due to structural breaks or long memory, and the extent of asymmetric responses of the rand to ‘good news’ and ‘bad news’. Our results show that while long memory is evident in the actual processes, a structural break analysis reveals that this feature is partially explained by unaccounted shifts in volatility regime; the most striking finding is the remarkable fall in the estimates of volatility persistence when considerably more structural breaks than those identified in recent studies are detected and integrated into the generalised autoregressive conditional heteroscedasticity (GARCH) framework. Furthermore, the asymmetric GARCH model results provide evidence of leverage effects, indicating that negative shocks imply a higher next period volatility than positive shocks. The empirical results also shed light on the timing and likely triggers of volatility regime switching.
Mechanism of enlargement of major cerebral collateral arteries in rabbits.

Major cerebral collateral arteries enlarge following bilateral ligation of the common and internal carotid arteries. The purpose of this investigation was to determine the relative contribution of cellular hypertrophy versus cellular hyperplasia to this vessel change in a morphometric analysis as well as the functional properties of remodeled vessels in an in vitro study. We assessed cell number and vessel dimensions by morphometric analysis of 16 perfusion-fixed rabbit basilar arteries. Results demonstrated significant increases in luminal diameter from 761 to 946 microns (p less than 0.01), medial cross-sectional area from 5.1 x 10(4) to 7.6 x 10(4) micron2 (p less than 0.005), smooth muscle cell volume from 9.19 x 10(5) to 1.44 x 10(6) micron3 (p less than 0.0005), and overall arterial length from 17.41 to 20.36 mm (p less than 0.005) in basilar arteries from the eight ligated rabbits compared with the eight sham-operated controls. Smooth muscle cell volume fraction and cell numerical density were unchanged whereas the number of cells per unit length of artery was increased significantly from 21.5 to 31.0 cells/micron (p less than 0.05). These data indicate that smooth muscle cell hyperplasia rather than hypertrophy contributes to increases in vessel mass. Functional properties of the basilar arteries from 10 ligated and 10 normal control rabbits were analyzed in vitro. Results showed increased contraction to potassium chloride (approximately 74%) (p less than 0.01) and increased sensitivity of smooth muscle to acetylcholine (p less than 0.05) while maximal relaxation was the same as control in the ligated animals. (ABSTRACT TRUNCATED AT 250 WORDS)
Climate Vulnerability and the Cost of Debt

We use indices from the Notre Dame Global Adaptation Initiative to investigate the impact of climate vulnerability on bond yields. Our methodology invokes panel ordinary least squares with robust standard errors and principal component analysis. The latter serves to address the multicollinearity between a set of vulnerability measures. We find that countries with higher exposure to climate vulnerability, such as the member countries of the V20 climate vulnerable forum, exhibit 1.174 percent higher cost of debt on average. This effect is significant after accounting for a set of macroeconomic controls. Specifically, we estimate the incremental debt cost due to higher climate vulnerability, for the V20 countries, to have exceeded USD 62 billion over the last ten years. In other words, for every ten dollars they pay in interest cost, they pay another dollar for being climate vulnerable. We also find that a measure of social readiness, which includes education and infrastructure, has a negative and significant effect on bond yields, implying that social and physical investments can mitigate climate risk related debt costs and help to stabilize the cost of debt for vulnerable countries.
Experimental study on gas desorption in surface flashover of solids in vacuum

The relation of desorbed gases and surface discharge in vacuum is a complex problem without reliable theory. The vacuum experimental platform of direct current and nanosecond pulse source was built, and the quadrupole mass spectrometer connected to vacuum cavity was used to analysis the out-gassing characteristics of insulation materials. Then the vacuum surface discharge experiments were done and the desorbed gases were measured in the process. By comparing the mass spectrum before discharges with ones after discharges, we obtained the out-gassing composition of several insulation materials. Meanwhile we analyzed the probable sources of different gases. Main gas components generated by vacuum surface flashover included H2O, N2, H2, O2, hydrocarbon fragment, CO, CO2 and sometimes high polymer fragment. C2H2 appeared in gas components when the filamentary discharge channel was formed between two electrodes. The results show that the high polymer surface may decompose and the dissolved gases may be extracted besides gas desorption in discharges. The discharge pattern has direct effect on their out-gassing characteristics. We'll thoroughly research their relation in subsequent work.
Cochlear implantation: osteoneogenesis, electrode-tissue impedance, and residual hearing.

INTRODUCTION This study was undertaken to find out how new bone is produced in the implanted cochlea, and the effects of fibrous tissue and new bone growth on electrode-tissue impedance. This knowledge is essential, as bone and fibrous tissue in the cochlea could account for variations in patients' speech perception performance. The study was also carried out to examine the effects of implantation on residual hearing. This information is also important, as cochlear implant speech perception results in profoundly deaf people are now better on average than severely or profoundly deaf people obtain with a hearing aid. Consequently, more people will need to be considered for cochlear implantation in ears with some residual hearing. In this case we need to know to what extent residual hearing is affected by implantation.
Translocation or membrane disintegration? Implication of peptide–membrane interactions in pep‐1 activity

The Cell membrane is impermeable for most peptides, proteins, and oligonucleotides. Moreover, some cationic peptides, the so‐called cell‐penetrating peptides (CPPs), are able to translocate across the membrane. This observation has attracted much attention because these peptides can be covalently coupled to different macromolecules, which are efficiently delivered inside the cell. The mechanism used by these peptides to pass across the membrane is a controversial matter of debate. It has been suggested that endocytosis is the main mechanism of internalization and this was confirmed by several studies for different peptides. Pep‐1 is an exception worthy of attention for its ability to translocate cargo macromolecules without the need to be covalently attached to them. A preferential internalization by an endocytosis‐independent mechanism was demonstrated both in vitro and in vivo. Pep‐1 has a high affinity to lipidic membranes, it is able to insert and induce local destabilization in the lipidic bilayer, although without pore formation. No cytotoxic effects were found for pep‐1 concentrations where translocation is fully operative. At much higher concentrations, membrane disintegration takes place by a detergent‐like mechanism that resembles anti‐microbial peptide activity. In this review, the ability of pep‐1 to transverse the membrane by an endocytosis‐independent mechanism, not mediated by pores as well as an ability to induce membrane disintegration at high peptide concentration, is demonstrated. Copyright © 2008 European Peptide Society and John Wiley & Sons, Ltd.
On the limiting density of field emission current from metals

The present work considers the problem of the field emission characteristics of metals for the range of external electric fields 10/sup 8/-10/sup 9/ V/cm. It has been shown that, as far as the field emission is considered, ultrahigh fields are the electric fields at which the decrease of the height of the potential barrier due to the Schottky effect is greater than the work function of the emitter. In this case, the penetration of the external electric field into the metal emitter results in a substantial increase in electron density near the emission boundary. It has also been shown that the Fowler-Nordheim relation that describes the electric field dependence of the current density does not hold at ultrahigh fields. Analytical expressions for this dependence have been obtained taking into account the perturbation of the electronic structure of the emitter by the external electric field both in the WKB and in the Miller-Good approximation in the low-temperature limit. Based on the results obtained, it has been shown that the saturation of the FE current density does not happen, as supposed earlier, and the current density practically linearly increases with electric field.
The Performance of Angel-Backed Companies

We provide empirical evidence of the post-investment performance and survivorship profile of angel-backed companies, filling a long-standing gap within the entrepreneurial finance literature. Using a unique database of 111 angel-backed companies that received angel investments between 2008 and 2012 and at least 3 years of post-investment financial data, we develop an innovative performance metric and show that the performance and the probability of survival of investee companies are positively affected by the presence of angel syndicates and the hands-on involvement of business angels, while they are negatively related to the intensity of angel monitoring and the time structure of equity provision. Our results are robust to several endogeneity tests and provide insights on the multifaceted contributions of angel investors to the performance and survival of new ventures.