Miracle-dz/UniFAR-FTUs huggingface dataset:
Synergistic CD40 signaling on APCs and CD8 T cells drives efficient CD8 response and memory differentiation

The role of CD4 help during CD8 response and memory differentiation has been clearly demonstrated in different experimental models. However, the exact mechanisms of CD4 help remain largely unknown and preclude replacement therapy to develop. Interestingly, studies have shown that administration of an agonist aCD40ab can substitute CD4 help in vitro and in vivo, whereas the targets of this antibody remain elusive. In this study, we address the exact role of CD40 expression on APCs and CD8 T cells using aCD40ab treatment in mice. We demonstrate that aCD40 antibodies have synergetic effects on APCs and CD8 T cells. Full efficiency of aCD40 treatment requires CD40 expression on both populations: if one of these cell populations is CD40‐deficient, the CD8 T cell response is impaired. Most importantly, direct CD40 signaling on APCs and CD8 T cells affects CD8 T cell differentiation differently. In our model, CD40 expression on APCs plays an important but dispensable role on CD8 T cell expansion and effector functions during the early phase of the immune response. Conversely, CD40 on CD8 T cells is crucial and nonredundant for their progressive differentiation into memory cells. Altogether, these results highlight that CD40–CD40L‐dependent and independent effects of CD4 help to drive a complete CD8 T cell differentiation.
Prostatic duct adenocarcinoma. Findings at radical prostatectomy

Previous studies of prostatic duct adenocarcinoma have reported a poor prognosis, but they included few patients treated by radical prostatectomy. The authors studied 15 cases treated with radical prostatectomy to define more completely their pathologic features and determine the clinical outcome in these surgically treated patients. The study included morphometry and DNA image analysis using the CAS‐200 system. The most common presentation was urinary outlet obstruction (n = 9), and most patients were clinical Stage B with palpable prostatic lesions (n = 12). Compared with acinar cancers of similar clinical stage, duct cancers were large (tumor volume, 8.4 ± 10.0 cc) and occupied a large portion of the gland (23 ± 21%). Duct cancers were in an advanced final pathologic stage with 93% having capsular penetration, 47% positive margins, 40% seminal vesicle invasion, and 27% positive pelvic lymph nodes. The DNA analysis on cells disaggregated from paraffin revealed that 54% of cases were diploid, 15% tetraploid, 8% aneuploid, and 23% tetraploid/aneuploid. On clinical follow‐up, eight patients had no evidence of tumor at intervals ranging from 1 to 28 months, and seven patients (47%) had persistent tumor at intervals of 3 to 18 months. This study demonstrates that duct cancers are in an advanced pathologic stage by the time of presentation and have a much higher short‐term failure rate after radical prostatectomy compared with acinar cancers.
High-power microwave 0.25-μm gate doped-channel GaN/AlGaN heterostructure field effect transistor

We report on the high-power performance of the 0.25-/spl mu/m gate Doped-Channel GaN/AlGaN Heterostructure Field Effect Transistors (DC-HFETs). At a drain bias voltage of 18 V and drain bias current of 46 mA, these 100-/spl mu/m wide devices exhibit high gain at 8.4 GHz with a power density reaching 1.73 W/mm. The devices also display high gain at moderate power over a wide range of frequencies. This high gain at high frequency is a result of an optimal doping level in the AlGaN layer that gives rise to a high sheet charge density while maintaining a high-channel electron mobility. These results demonstrate the excellent microwave power capability of the GaN/AlGaN based heterostructure field effect transistors.
Gene Expression Microarray Data Analysis for Toxicology Profiling

Abstract: When dealing with thousands of genes, all potentially interesting, it is desirable to rank the genes according to their degree of participation in a physiological process. Therefore, genes with the highest Shannon entropy and ERL can be selected as the best toxicity target candidates, permitting preclinical scientists to focus their research and resources on those genes.
Randomised trial on treatment of vaginal intraepithelial neoplasia—Imiquimod, laser vaporisation and expectant management

Vaginal intraepithelial neoplasia (VAIN) is associated with human papillomavirus (HPV) infection. The most common treatment modality is laser vaporisation, but recurrences are common. Imiquimod is an immune response modulator which is used for the treatment of external condylomas and other HPV‐related genital neoplasias. The aim of the study was to evaluate the efficacy and tolerability of vaginally administered imiquimod in comparison with laser vaporisation and expectant management of high‐grade VAIN. This proof of principle pilot study was a prospective 16‐week randomised trial. We enrolled 30 patients with histologically confirmed VAIN 2 or 3 into three study arms: vaginally administered imiquimod, laser vaporisation and expectant management. Follow‐up colposcopy visits included high‐risk human papillomavirus (hrHPV) testing, cytology and punch biopsies. At baseline 77% (n = 20/26) of the patients were hrHPV positive. HPV clearance was significantly higher in the imiquimod arm (63%, n = 5/8) than in the laser arm (11%, n = 1/9) (p = 0.05) or in the expectant management arm (17%, n = 1/6) (p = 0.138). At baseline 25 patients (83%) had VAIN 2 and five (17%) had VAIN 3. None of the lesions progressed during the follow‐up. Histological regression (≤VAIN 1) was observed in 80% (n = 8/10) of patients in the imiquimod arm, 100% (n = 10/10) of the laser arm (p = 0.474) and 67% (n = 6/9) of the expectant management arm (p = 0.628). Vaginal imiquimod appears to be as effective as laser treatment in high‐grade VAIN.
Clinical experience utilizing a novel fluoroscopic technique for wire-guided nasojejunal tube placement in the dog: 26 cases (2006-2010).

OBJECTIVE To describe the clinical use of a novel, minimally invasive fluoroscopic technique for the wire-guided placement of nasojejunal tubes (NJT) in dogs. DESIGN Retrospective study (September 22, 2006-October 2, 2010). SETTING University veterinary teaching hospital. ANIMALS Twenty-six consecutive dogs with intolerance of, or contraindications to gastric feeding that underwent attempted fluoroscopic NJT placement. No dogs were excluded from analysis. INTERVENTIONS All dogs underwent attempted fluoroscopic NJT placement using a novel fluoroscopic wire-guided technique. MEASUREMENTS AND MAIN RESULTS Patient data were collected in concert with information about the NJT placement procedure as well as the maintenance and utilization of the tube. The primary diagnosis in dogs undergoing NJT placement was pancreatitis in 60%. The ability to achieve transpyloric passage of the tube was 92.3% (24/26) and the ability to achieve jejunal access was 78.2%. In the second half of the study period, the ability to achieve jejunal access was significantly higher than in the first half of the study period suggesting that technical proficiency improves over time. Mean duration of the procedure was 35.3±20 minutes. Significant oral migration was a complication of NJT placement in some dogs. The median duration of feeding was 3.3 days (range 0.3-10.5). CONCLUSIONS Fluoroscopic wire-guided NJT placement is a viable method for sustained postpyloric feeding in dogs. Success in acquiring jejunal access improves with experience. The NJT may be utilized as a strategy to provide enteral nutritional support to the population of dogs with contraindications to, or intolerance of gastric feeding.
Recrystallization phenomena in an IF steel observed by in situ EBSD experiments

In situ electron backscatter diffraction microstructural analysis of recrystallizing interstitial free steels deformed to strains of 0.75 and 1.6 has been carried out in a FEG‐SEM. The experimental procedures are discussed, and it is shown that there is no degradation of the electron backscatter diffraction patterns at temperatures up to 800°C. Analysis of the surface and interior microstructures of annealed samples shows only minor difference, which suggests that in situ annealing experiments are of value. In addition, it is shown that in situ measurements allow a detailed comparison between the same areas before and after annealing, thereby providing information about the recrystallization mechanisms. Sequential recrystallization phenomena, such as initiation and growth of new grains, are observed at temperatures over 740°C, and depending on the deformation histories, different recrystallization behaviour is observed. It is found that {111}〈123〉 recrystallized grains are preferentially formed in the highly deformed material, whereas no strong recrystallization texture is formed in the lower strained material.
“The transformative power of Europe” beyond enlargement: the EU’s performance in promoting democracy in its neighbourhood*

ABSTRACT This paper argues that the European Union’s (EU) performance in promoting democracy in its neighbourhood is not only compromised by the lack of a membership perspective but the selective sanctioning of non-compliance with democracy standards caused by conflicting foreign policy objectives. We identify two conditions for the EU’s consistent application of democratic conditionality: the absence of a stability-democratisation dilemma and the presence of pro-democratic reform coalitions. If neither of these conditions is present, the EU is more likely to act as a status-quo than a transformative power prioritising (authoritarian) stability over uncertain (democratic) change.
Effect of Single Nucleotide Polymorphisms in Cytochrome P450 Isoenzyme and N-Acetyltransferase 2 Genes on the Metabolism of Artemisinin-Based Combination Therapies in Malaria Patients from Cambodia and Tanzania

ABSTRACT The pharmacogenetics of antimalarial agents are poorly known, although the application of pharmacogenetics might be critical in optimizing treatment. This population pharmacokinetic-pharmacogenetic study aimed at assessing the effects of single nucleotide polymorphisms (SNPs) in cytochrome P450 isoenzyme genes (CYP, namely, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP3A4, and CYP3A5) and the N-acetyltransferase 2 gene (NAT2) on the pharmacokinetics of artemisinin-based combination therapies in 150 Tanzanian patients treated with artemether-lumefantrine, 64 Cambodian patients treated with artesunate-mefloquine, and 61 Cambodian patients treated with dihydroartemisinin-piperaquine. The frequency of SNPs varied with the enzyme and the population. Higher frequencies of mutant alleles were found in Cambodians than Tanzanians for CYP2C9*3, CYP2D6*10 (100C→T), CYP3A5*3, NAT2*6, and NAT2*7. In contrast, higher frequencies of mutant alleles were found in Tanzanians for CYP2D6*17 (1023C→T and 2850C→T), CYP3A4*1B, NAT2*5, and NAT2*14. For 8 SNPs, no significant differences in frequencies were observed. In the genetic-based population pharmacokinetic analyses, none of the SNPs improved model fit. This suggests that pharmacogenetic data need not be included in appropriate first-line treatments with the current artemisinin derivatives and quinolines for uncomplicated malaria in specific populations. However, it cannot be ruled out that our results represent isolated findings, and therefore more studies in different populations, ideally with the same artemisinin-based combination therapies, are needed to evaluate the influence of pharmacogenetic factors on the clearance of antimalarials.
Abnormal Movements in Children With Migraine

The cause and treatment of functional movement disorders and nonepileptic spells in children is poorly understood, and an association with migraine has not previously been reported. We retrospectively reviewed children diagnosed with chronic or episodic migraine at our institution from 2006 to 2013 to determine the proportion with nonorganic movement disorders, their phenomenology, provoking factors, and natural history. Thirty-two patients were identified, representing 4.3% of patients with chronic migraine and 0.9% of patients with episodic migraine. Twenty-four of the 32 (75%) had chronic migraine, whereas 8 (25%) had episodic migraine. Nonepileptic spells was the most common phenomenon in both cohorts, followed by tremor and functional gait disorders. Severe migraine attacks preceded these movements in the majority of patients. With appropriate migraine therapy, significant reduction or resolution of these movements was reported. We conclude that nonorganic movement disorders are observed in pediatric migraine, are more prevalent among chronic migraineurs, and can resolve with improved pain control.
Parietal area BA7 integrates motor programs for reaching, grasping, and bimanual coordination.

Skillful interaction with the world requires that the brain uses a multitude of sensorimotor programs and subroutines, such as for reaching, grasping, and the coordination of the two body halves. However, it is unclear how these programs operate together. Networks for reaching, grasping, and bimanual coordination might converge in common brain areas. For example, Brodmann area 7 (BA7) is known to activate in disparate tasks involving the three types of movements separately. Here, we asked whether BA7 plays a key role in integrating coordinated reach-to-grasp movements for both arms together. To test this, we applied transcranial magnetic stimulation (TMS) to disrupt BA7 activity in the left and right hemispheres, while human participants performed a bimanual size-perturbation grasping task using the index and middle fingers of both hands to grasp a rectangular object whose orientation (and thus grasp-relevant width dimension) might or might not change. We found that TMS of the right BA7 during object perturbation disrupted the bimanual grasp and transport/coordination components, and TMS over the left BA7 disrupted unimanual grasps. These results show that right BA7 is causally involved in the integration of reach-to-grasp movements of the two arms. NEW & NOTEWORTHY Our manuscript describes a role of human Brodmann area 7 (BA7) in the integration of multiple visuomotor programs for reaching, grasping, and bimanual coordination. Our results are the first to suggest that right BA7 is critically involved in the coordination of reach-to-grasp movements of the two arms. The results complement previous reports of right-hemisphere lateralization for bimanual grasps.
Stress modulates the enzymatic inducibility by benzo[alpha]pyrene in the rat liver.

The role of stress on the inducibility by benzo[alpha]pyrene (B[alpha]P), a representative polycyclic aromatic hydrocarbon, of several drug-metabolizing enzymes was investigated in rats, using restraint stress and mild unpredictable stress as models of psychological stress. Restraint stress was found to significantly suppress basal ethoxyresorufin 7-dealkylase (EROD) and pentoxyresorufin 7-dealkylase (PROD) activities (two-fold). In contrast, mild unpredictable stress markedly increased basal EROD activity, while PROD activity was not affected. In addition, both types of stress resulted in a significant reduction of basal p -nitrophenol hydroxylation (PNP). It is worth noting that restraint stress greatly enhanced the inducibility of EROD, methoxyresorufin 7-dealkylase (MROD) and to a lesser extent PROD activities by B[alpha]P, while mild unpredictable stress had no, or only a mild effect on the inducibility of cytochrome P450s (CYPs) by B[alpha]P. In conclusion, psychological stress may modulate different enzymatic systems which are vital elements of the detoxification mechanisms of the body. The two distinct types of psychological stress used in this study appear to affect the enzymatic systems under investigation in a stress-specific manner at the basal level and at the induced state by B[alpha]P.
Driving Performance and Psychomotor Function in Depressed Patients Treated with Agomelatine or Venlafaxine

Abstract Objective: We conducted a randomized case-control study in depressive inpatients to assess the effects of agomelatine and venlafaxine on psychomotor functions related to driving skills and on driving performance in an on-road driving test. Method: 40 depressed inpatients treated with agomelatine (n=20) or venlafaxine (n=20) were tested before pharmacological treatment (t0), and on days 14 (t1) and 28 (t2). 20 healthy subjects were examined in the same time schedule to control for retest effects in psychomotor measures. Additionally, participants were rated in a standardized on-road driving test on day 28 by a licensed driving instructor, who was blind with respect to treatment, diagnosis and test results. Results: After 4 weeks of treatment (t2) with agomelatine or venlafaxine, patients showed a significant reduction in depressive symptoms, and a distinct improvement in psychomotor functions. Controlling for retest effects in psychomotor measures, data indicate, that both patient groups significantly improved in tests measuring reactivity and stress-tolerance. Furthermore, prior discharge to outpatient treatment (day 28), 72.5% of patients were labeled abundantly fit to drive in the on-road driving test by a licensed driving instructor. However, patients did not reach the performance level of healthy controls in functional domains tested. Significant differences between treatment groups were not observed. Conclusion: Our results indicate that depressed inpatients treated with agomelatine or venlafaxine show a better test performance on tasks related to driving skills than do untreated depressives and could predominantly be rated as fit to drive on an actual driving test prior discharge to outpatient treatment.
Specificity in Receptor Usage by T-Cell-Tropic Feline Leukemia Viruses: Implications for the In Vivo Tropism of Immunodeficiency-Inducing Variants

ABSTRACT Cytopathic, T-cell-tropic feline leukemia viruses (FeLV-T) evolve from FeLV-A in infected animals and demonstrate host cell specificities that are distinct from those of their parent viruses. We recently identified two cellular proteins, FeLIX and Pit1, required for productive infection by these immunodeficiency-inducing FeLV-T variants (M. M. Anderson, A. S. Lauring, C. C. Burns, and J. Overbaugh, Science 287:1828–1830, 2000). FeLV-T is the first example of a naturally occurring type C retrovirus that requires two proteins to gain entry into target cells. FeLIX is an endogenous protein that is highly related to the N-terminal portion of the FeLV envelope protein, which includes the receptor-binding domain. Pit1 is a multiple-transmembrane phosphate transport protein that also functions as a receptor for FeLV-B. The FeLV-B envelope gene is derived by recombination with endogenous FeLV-like sequences, and its product can functionally substitute for FeLIX in facilitating entry through the Pit1 receptor. In the present study, we tested other retrovirus envelope surface units (SUs) with their cognate receptors to determine whether they also could mediate infection by FeLV-T. Cells were engineered to coexpress the transmembrane form of the envelope proteins and their cognate receptors, or SU protein was added as a soluble protein to cells expressing the receptor. Of the FeLV, murine leukemia virus, and gibbon ape leukemia virus envelopes tested, we found that only those with receptor-binding domains derived from endogenous FeLV could render cells permissive for FeLV-T. We also found that there is a strong preference for Pit1 as the transmembrane receptor. Specifically, FeLV-B SUs could efficiently mediate infection of cells expressing the Pit1 receptor but could only inefficiently mediate infection of cells expressing the Pit2 receptor, even though these SUs are able to bind to Pit2. Expression analysis of feline Pit1 and FeLIX suggests that FeLIX is likely the primary determinant of FeLV-T tropism. These results are discussed in terms of current models for retrovirus entry and the interrelationship among FeLV variants that evolve in vivo.
Childhood Sexual Abuse: A Gender Perspective on Context and Consequences

Literature on gender and child sexual abuse (CSA) has highlighted patterns of similarity and difference among survivors and the need for further research. This study relied on gender analysis of 128 women and 69 men, obtained through an examination of childhood hospital records, to further examine gender differences in mental health outcomes among abuse survivors and correlates of mental health outcomes including professional help seeking, family environment, and other trauma exposure. Overall, men and women were similar in the context and consequences of CSA. The role of the characteristics of CSA and contextual variables in explaining variance in mental health for 106 male victims and nonvictims was also examined. Among male participants, number of incidents of sexual abuse, injury at the hands of a caregiver, and exposure to other traumas significantly explained higher levels of an array of mental health symptoms. Implications for future research are discussed.
Expression of Eukaryotic Initiation Factor 4E in Astrocytic Tumors

Upregulation of expression of the eukaryotic initiation factor 4E (eIF4E) has been identified in breast carcinomas, squamous cell carcinomas in the head and neck regions, and transitional cell carcinomas of urinary bladder. In this immunohistochemical study, eIF4E protein expression was investigated in human brain tissue from patients without central nervous system diseases and brain biopsy tissues from patients with anaplastic astrocytoma and glioblastoma multiforme. Expression of eIF4E protein was observed in normal pyramidal neurons but not in neuroglial components. In anaplastic astrocytoma and glioblastoma multiforme, there was diffuse uniform expression of eIF4E immunoreactivity in malignant astrocytes. A similar pattern of immunoreactivity was also present in proliferative endothelial cells and vascular lining endothelial cells in glioblastoma multiforme. This study provides evidence that eIF4E is upregulated in high-grade astrocytic tumors. As in other malignancies, a high level of eIF4E may play an important role in the neoplastic transformation, angiogenesis, and tumor growth in astrocytic tumors. Because eIF4E is crucial in regulation of tumor growth, eIF4E could be a potential target for inhibitors as an adjuvant therapy for brain tumors.
Global Turkey in Europe: political, economic, and foreign policy dimensions of Turkey's evolving relationship with the EU

The EU is changing, Turkey too, and - above all - there is systemic change and crisis all round, ranging from economics, the spread of democratic norms and foreign policy. This research paper explores how the EU and Turkey can enhance their cooperation in the political, economic, and foreign policy domains and how they can find a way out of the stalemate EU-Turkey relations have reached with the lack of progress in accession negotiations and the increasing uncertainty over both the future of the European project after the Eurozone crisis and Turkey's role in it.
Urinary growth hormone following exercise to assess growth hormone production in adults

OBJECTIVE The insulin stress test (IST) is the most commonly used test to assess the GH reserve in children and adults. It is a time‐consuming, expensive and potentially dangerous test. We investigated whether measurement of urinary growth hormone excretion following exercise would prove a reliable method to diagnose adult GH deficiency.