Miracle-dz/UniFAR-FTUs huggingface dataset:
Comprehensive Epitope Analysis of Human Immunodeficiency Virus Type 1 (HIV-1)-Specific T-Cell Responses Directed against the Entire Expressed HIV-1 Genome Demonstrate Broadly Directed Responses, but No Correlation to Viral Load

ABSTRACT Cellular immune responses play a critical role in the control of human immunodeficiency virus type 1 (HIV-1); however, the breadth of these responses at the single-epitope level has not been comprehensively assessed. We therefore screened peripheral blood mononuclear cells (PBMC) from 57 individuals at different stages of HIV-1 infection for virus-specific T-cell responses using a matrix of 504 overlapping peptides spanning all expressed HIV-1 proteins in a gamma interferon-enzyme-linked immunospot (Elispot) assay. HIV-1-specific T-cell responses were detectable in all study subjects, with a median of 14 individual epitopic regions targeted per person (range, 2 to 42), and all 14 HIV-1 protein subunits were recognized. HIV-1 p24-Gag and Nef contained the highest epitope density and were also the most frequently recognized HIV-1 proteins. The total magnitude of the HIV-1-specific response ranged from 280 to 25,860 spot-forming cells (SFC)/106 PBMC (median, 4,245) among all study participants. However, the number of epitopic regions targeted, the protein subunits recognized, and the total magnitude of HIV-1-specific responses varied significantly among the tested individuals, with the strongest and broadest responses detectable in individuals with untreated chronic HIV-1 infection. Neither the breadth nor the magnitude of the total HIV-1-specific CD8+-T-cell responses correlated with plasma viral load. We conclude that a peptide matrix-based Elispot assay allows for rapid, sensitive, specific, and efficient assessment of cellular immune responses directed against the entire expressed HIV-1 genome. These data also suggest that the impact of T-cell responses on control of viral replication cannot be explained by the mere quantification of the magnitude and breadth of the CD8+-T-cell response, even if a comprehensive pan-genome screening approach is applied.
Detecting mental EEG properties using detrended fluctuation analysis

Based on detrended fluctuation analysis (DFA), we explore the characteristics of multichannel electroencephalogram (EEG), which is recorded from many subjects performing different mental tasks. The results show that mental EEG exhibits long-range power-law correlations by calculating its scaling exponents (alpha), which can reflect the kinds of mental tasks. The scaling exponent of letter-composing is different from that of multiplication especially at positions C3 and C4, and at positions O1 and O2 the scaling exponent of rotation is also different distinctively from that of multiplication. Detrended fluctuation analysis exhibits its robustness against noises in our works. We could benefit more from the results of this paper in designing mental tasks and selecting brain areas in brain-computer interface systems
Multidrug resistance in epilepsy and polymorphisms in the voltage-gated sodium channel genes SCN1A, SCN2A, and SCN3A: correlation among phenotype, genotype, and mRNA expression

Objectives Many antiepileptic drugs (AEDs) prevent seizures by blocking voltage-gated brain sodium channels. However, treatment is ineffective in 30% of epilepsy patients, which might, at least in part, result from polymorphisms of the sodium channel genes. We investigated the association of AED responsiveness with genetic polymorphisms and correlated any association with mRNA expression of the neuronal sodium channels. Methods We performed genotyping of tagging and candidate single nucleotide polymorphisms (SNPs) of SCN1A, 2A, and 3A in 471 Chinese epilepsy patients (272 drug responsive and 199 drug resistant). A total of 27 SNPs were selected based on the HapMap database. Genotype distributions in drug-responsive and drug-resistant patients were compared. SCN2A mRNA was quantified by real-time PCR in 24 brain and 57 blood samples. Its level was compared between patients with different genotypes of an SCN2A SNP found to be associated with drug responsiveness. Results SCN2A IVS7-32A>G (rs2304016) A alleles were associated with drug resistance (odds ratio=2.1, 95% confidence interval: 1.2–3.7, P=0.007). Haplotypes containing the IVS7-32A>G allele A were also associated with drug resistance. IVS7-32A>G is located within the putative splicing branch site for splicing exons 7 and 9. PCR of reverse-transcribed RNA from blood or brain of patients with different IVS7-32A>G genotypes using primers in exons 7 and 9 showed no skipping of exon 8, and real-time PCR showed no difference in SCN2A mRNA levels among genotypes. Conclusion Results of this study suggest an association between SCN2A IVS7-32A>G and AED responsiveness, without evidence of an effect on splicing or mRNA expression.
Extinction of Oct-3/4 gene expression in embryonal carcinoma x fibroblast somatic cell hybrids is accompanied by changes in the methylation status, chromatin structure, and transcriptional activity of the Oct-3/4 upstream region

In this study we evaluate, for the first time, the molecular mechanism that underlies the extinction of a tissue-specific transcription factor, Oct-3/4, in somatic cell hybrids and compared it with its down-regulation in retinoic acid (RA)-treated embryonal carcinoma (EC) cells. The Oct-3/4 gene, which belongs to the POU family of transcription factors and is abundantly expressed in EC (OTF9-63) cells, provides an excellent model system with which to study the extinction phenomenon. Unlike other genes whose expression has been repressed in hybrid cells but not during in vivo differentiation, Oct-3/4 expression is dramatically repressed in OTF9-63 x fibroblast hybrids and also during embryogenesis. The ectopic expression of Oct-3/4 in hybrid cells under a constitutive promoter is sufficient for transcriptional activation of an octamer-dependent promoter. These results argue against the possibility that fibroblasts contain a direct repressor which binds directly to the octamer sequence and prevents Oct-3/4 protein from binding. The extinction of Oct-3/4 binding activity in the hybrid cells occurs at the level of mRNA transcription, similarly to the repression of Oct-3/4 transcription during in vivo differentiation. This shutdown of Oct-3/4 transcription in hybrid cells and in RA-treated EC cells is accompanied by de novo methylation of its 1.3-kb upstream region. In contrast to EC cells, in which this region is sensitive to MspI digestion, in hybrid cells and in RA-treated EC cells, the Oct-3/4 upstream region is resistant to MspI digestion, which suggests a change in its chromatin structure. Furthermore, extinction is not restricted to the endogenous Oct-3/4 gene but is also exerted upon a transiently transfected reporter gene driven by the Oct-3/4 upstream region. Thus, changes in the cellular activity of trans-acting factors acting on the upstream region also contribute to the inability of the hybrid and RA-treated EC cells to generate Oct-3/4 transcripts. In conclusion, this study draws a connection between the shutdown of Oct-3/4 expression in RA-differentiated EC cells and its extinction in hybrid cells. In both systems, repression of Oct-3/4 expression is achieved through changes in the methylation status, chromatin structure, and transcriptional activity of the Oct-3/4 upstream regulatory region.
Cryptate mediated nucleophilic 18F-fluorination without azeotropic drying

Summary The radiosynthesis of the vast majority of 18F-labeled tracers rely on azeotropic drying of [18F]fluoride and subsequent cryptate mediated introduction of [18F]fluoride by nucleophilic substitution. The aim of this study was to develop a method for simplification of this process, based on preparation of reactive [K+⊂2.2.2]18F- by solvent drying of [18F]fluoride adsorbed onto an anion exchange resin. Methods: Aqueous [18F]fluoride (0.5–1 ml) obtained from the 18O(p,n)18F nuclear reaction was trapped on a strong anion-exchange (SAX) cartridge. After washing the cartridge with dry CH3CN, [18F]fluoride was eluted with an anhydrous solution of [K+⊂2.2.2]OH- in CH3CN and directly used for nucleophilic fluorination reactions. Results: [18F]Fluoride from target water was quantitatively retained by the SAX cartridge, and water-free [18F] − fluoride recovered in an overall yield of 92 ± 5% (n = 10). [18F]Fluoride obtained by this procedure led to radiochemical yields of 70–90% for [18F]FDG, [18F]FET, [18F]FLT, [18F]FAZA and [18F]Fallypride. Conclusion: SAXresin adsorbed [18F]fluoride can be dried with non-aqueous solvents and eluted with [K+⊂2.2.2]OH- in CH3CN. The reactivity of [K+⊂2.2.2]F- generated by the new method is comparable to that of [18F]fluoride obtained by azeotropic drying. The described procedure facilitates the automated production of 18F-radiopharmaceuticals in general, and may also simplify the use of microfluidic devices for 18F-radiotracer production.
Effects of anaerobiosis and aerobiosis on interactions of human polymorphonuclear leukocytes with the dental plaque bacteria Streptococcus mutans, Capnocytophaga ochracea, and Bacteroides gingivalis

Human polymorphonuclear leukocytes (PMN) were able to generate and release superoxide anions upon stimulation of Streptococcus mutans, Bacteroides gingivalis, and Capnocytophaga ochracea when incubated aerobically but not when incubated anaerobically. Lysozyme release and phagocytosis by PMN were independent of oxygen, and no difference between PMN incubated aerobically or anaerobically was observed (PMN stimulated by B. gingivalis released 7.6% total lysozyme when aerobic and 6.9% when anaerobic). There were variations in lysozyme release and phagocytosis for the three organisms, particularly for phagocytosis. B. gingivalis and C. ochracea yielded lower phagocytosis values than those for S. mutans, e.g., at 1 h 67% of the initial inoculum of S. mutans was phagocytosed (versus only 40% for B. gingivalis). Transmission electron microscopy showed that both S. mutans and B. gingivalis were internalized into classical phagolysosomes. In contrast, C. ochracea showed two forms of internalization; C. ochracea either formed a classical phagolysosome or was tightly bound in the cytoplasm with no surrounding cell membrane. Intracellular killing of S. mutans and C. ochracea was unaffected by anaerobiosis, but killing of C. ochracea was much lower than that of S. mutans (1 x 10(7) to 2 x 10(7) bacteria killed compared with 5.1 x 10(7) bacteria killed at 6 h). In contrast, a greater number of B. gingivalis was killed in the presence of oxygen (5.3 x 10(7) bacteria were killed when aerobically incubated and 1.9 x 10(7) bacteria were killed when anaerobically incubated). These results suggest that the ability to survive anaerobically may enable some bacteria to evade PMN killing; however, abnormal phagocytosis may represent a more efficient way to evade both oxygen-dependent and -independent killing mechanisms, leading to enhanced virulence of the organism.
Advance Directives in Nursing Home Residents Aged ≥65 Years: United States 2004

In 1996, 53% of US nursing home residents had advance directives. This report defines documentation of advance directives in a nationally representative survey of US nursing home residents aged ! 65 years in 2004, as well as advance directive use in relation to demographic factors and receipt of specialty services including hospice/palliative care. In 2004, advance directives were documented in 69.9% of US nursing home residents aged ! 65 years and in 93.6% of residents receiving hospice/palliative care. Documentation of advance directives increased substantially between 1996 and 2004 and is nearly universal among residents receiving hospice/palliative care services. However in 2004, 3 of every 10 US nursing home residents did not have documentation of advance care plans. Continued efforts are needed to promote the importance of advance care planning among US nursing home residents.
Microdissection and transcriptional profiling

Prion diseases share common features on a sub-cellular level with many neurodegenerative diseases including Alzheimer disease; the most prevalent neurodegenerative disease world-wide. The most obvious similarity is the accumulation of misfolded forms of the host proteins which forms aggregates in the brains of patients. Remarkably, one of the earliest pathological changes detected in degenerating brain tissue, well before clinical symptoms are observed, is synaptic dysfunction and loss. This pathology was recently shown to be reversible in early stages of mouse prion disease suggesting that synaptic regeneration and reestablishment of neuronal function is possible. Determination of the molecular events that underlie synapse degeneration and how this eventually results in neuronal loss is therefore a research priority that may contribute to the search for new therapeutic interventions for neurodegenerative disorders. Functional genomic studies using unbiased whole genome expression analyses represent one method that can provide insights into these perplexing processes. However, transcriptional profiles from brain tissues are representative of a heterogeneous mixture of cell types that effectively mask the expression of low abundance transcripts, or molecular changes that occur only in a small population of affected neurons. One method that was recently applied to address these challenges was laser capture microdissection which was used to effectively isolate the CA1 neuronal rich region of the hippocampus prior to RNA extraction. Profiling of both mRNAs and microRNAs revealed previously unidentified neuronal-specific genes and expression signatures that are relevant to understanding the pathophysiological processes involved in preclinical stages of prion disease. In this review we will highlight these molecular signatures and discuss their implications with respect to prion-induced neurodegeneration.
Anaesthesia as a career choice in a developing country; effect of clinical clerkship.

OBJECTIVE To explore the fourth year medical student's knowledge regarding anaesthesia as a specialty, their attitude towards anaesthesia as a career choice and the effect of clinical clerkship on these. METHODS This survey was conducted in the Department of Anaesthesia of a university medical centre in a developing country. One hundred and fifty year four medical students rotating in anaesthesia were enrolled. They were asked to fill a structured questionnaire before (pre) and after (post) their anaesthesia rotation. The questionnaire sought information on their perception of anaesthesia as a specialty, role of anaesthetists clerkship duration, and reasons for considering or not considering anaesthesia. RESULTS Prior to anaesthesia clerkship 12 students (8%) included anaesthesia in their first three career choices (2 as first preference). Post clerkship 36 (24%) included it in their first 3 career choices (3 as first preference). There was a change in perception of specialty for 57 participants. CONCLUSION The findings support the positive influence of anaesthesia clerkship on changing the attitude of medical students towards anaesthesia specialty in a developing country with shortage of anaesthesia personnel.
Role of β-Cells in Type 1 Diabetes Pathogenesis

Whether autoimmunity results primarily from a defect of the immune system, target organ dysfunction, or both remains an open issue in most human autoimmune diseases. The highly multigenic background on which diabetes develops in the NOD mouse and in the human suggests that numerous gene variants associate in contributing to activation of autoimmunity to β-cells. Both immune genes and islet-related genes are involved. The presence of β-cells is required for initiation of diabetes autoimmunity to proceed. Available experiments in the NOD mouse and epidemiological evidence in the human point to proinsulin as a key autoantigen in diabetes. The functional importance of insulin, the high number of autoantigens characterized at different stages of diabetes, and their clustering within β-cell subparticles point to the islet as a starting point in the initiation phase of the disease. Genes that direct the autoimmune reaction toward the β-cell target, autoantigens that are recognized by autoreactive B- and T-cells along the autoimmune process, the importance of β-cells in the activation of autoreactive lymphocytes, and the expression level of key β-cell molecules along diabetes development are successively considered in this review.
Recent trends in user studies: action research and qualitative methods

This paper was commissioned by Professor Gernot Wersig of the Freie Universitat, Berlin in 1980, as part of his Project, Methodeninstrumentarium zur Benutzforschung in Information und Dokumentation. It attempted to set out what was, for the time, a novel perspective on appropriate methodologies for the study of human information seeking behaviour, focusing on qualitative methods and action research, arguing that the application of information research depended up its adoption into the managerial processes of organizations, rather than its self-evident relationship to any body of theory.
Atypical Basal Cell Hyperplasia of the Prostate: Immunophenotypic Profile and Proposed Classification of Basal Cell Proliferations

Prostatic basal cell proliferations range from focal basal cell hyperplasia (BCH) to florid adenoid basal cell tumor (ABCT). We reviewed 36 cases of basal cell proliferation to evaluate the architectural and cytologic spectrum of these lesions and identified four distinct patterns by light microscopy: BCH, 12 cases, including two cases with stromal sclerosis; atypical BCH with nucleolomegaly, eight cases; basal cell adenoma (BCA), nine cases; and ABCT, seven cases. Twenty-three cases were evaluated immunohistochemically, and all displayed cytoplasmic immunoreactivity in basal cells with basal-cell-specific high-molecular-weight keratin 34βE12 but with increased staining in BCH compared with that in BCA and ABCT. Prostate-specific antigen and prostatic acid phosphatase reactivity were seen at least focally in all cases except two cases each of BCA and ABCT. Chromogranin, S-100 protein, and neuron-specific enolase reactivity were rare or negative in all cases. Nucleolar diameter, measured in 18 of the 36 cases, was significantly greater in atypical BCH (mean, 1.96 µm) than in other forms of basal cell proliferation (mean, <1.0 µm) (P<0.05). These results indicate that on the basis of light microscopic, immunohistochemical, and morphometric findings, the spectrum of basal cell proliferations in the prostate can be separated into four distinct groups: BCH, atypical BCH, BCA, and ABCT.
Time Dependent Vehicle Routing Problems: Formulations, Properties and Heuristic Algorithms

The time dependent vehicle routing problem (TDVRP) is defined as follows. A vehicle fleet of fixed capacities serves customers of fixed demands from a central depot. Customers are assigned to vehicles and the vehicles routed so that the total time of the routes is minimized. The travel time between two customers or between a customer and the depot depends on the distance between the points and time of day. Time windows for serving the customers may also be present. The time dependent traveling salesman problem (TDTSP) is a special case of the TDVRP in which only one vehicle of infinite capacity is available. Mixed integer linear programming formulations of the TDVRP and the TDTSP are presented that treat the travel time functions as step functions. The characteristics and properties of the TDVRP preclude modification of most of the algorithms that have been developed for the vehicle routing problem. Several simple heuristic algorithms are given for the TDTSP and TDVRP without time windows based on the nearest-neighbor heuristic. A mathematical-programming-based heuristic for the TDTSP without time windows using cutting planes is also briefly discussed. Test results on small, randomly generated problems are reported.
Transferability of Dual-Task Coordination Skills after Practice with Changing Component Tasks

Recent research has demonstrated that dual-task performance with two simultaneously presented tasks can be substantially improved as a result of practice. Among other mechanisms, theories of dual-task practice-relate this improvement to the acquisition of task coordination skills. These skills are assumed (1) to result from dual-task practice, but not from single-task practice, and (2) to be independent from the specific stimulus and response mappings during the practice situation and, therefore, transferable to new dual task situations. The present study is the first that provides an elaborated test of these assumptions in a context with well-controllable practice and transfer situations. To this end, we compared the effects of dual-task and single-task practice with a visual and an auditory sensory-motor component task on the dual-task performance in a subsequent transfer session. Importantly, stimulus and stimulus-response mapping conditions in the two component tasks changed repeatedly during practice sessions, which prevents that automatized stimulus-response associations may be transferred from practice to transfer. Dual-task performance was found to be improved after practice with the dual tasks in contrast to the single-task practice. These findings are consistent with the assumption that coordination skills had been acquired, which can be transferred to other dual-task situations independently on the specific stimulus and response mapping conditions of the practiced component tasks.
Synergistic interaction between PPAR ligands and salbutamol on human bronchial smooth muscle cell proliferation

An important objective in asthma therapy is to prevent the accelerated growth of airway smooth muscle cells which leads to hyperplasia and bronchial hyperreactivity. We investigated the effect of combination of salbutamol and PPARγ agonists on growth factor‐stimulated human bronchial smooth muscle cell (BSMC) proliferation.
Renoprotective effects of VPI versus ACEI in normotensive nephrotic rats on different sodium intakes.

BACKGROUND Control of blood pressure (BP) and optimal reduction of proteinuria (Uprot) are necessary for long-term renoprotection. Unfortunately, angiotensin-converting enzyme inhibitors (ACEI) and angiotensin II (Ang II) antagonists are not effective during sodium repletion. Vasopeptidase inhibitors (VPI) cause dual inhibition of ACE and neutral endopeptidase, the latter resulting in decreased atrial natriuretic peptide (ANP) breakdown and thus enhanced natriuresis. Therefore, in contrast with ACEI, VPI may be effective during high sodium intake. METHODS To test this hypothesis, the renoprotective actions of the new VPI gemopatrilat (GEM) were studied during low (0.05% NaCl) and high (3.0% NaCl) sodium diets in normotensive Wistar rats with established adriamycin nephrosis. The ACEI lisinopril (LIS) was used as control. Rats received either GEM (0.3 mg/g chow), an equihypotensive dose of LIS (75 mg/L drinking water), or vehicle (VEH) from week 6 (that is, established Uprot) until sacrifice. The effect of therapy was monitored by measuring systolic BP and Uprot (weekly) and structural renal damage at the end of study (week 16). RESULTS During low sodium, GEM effectively reduced Uprot (-48 +/- 4%), but LIS was more effective (-80 +/- 2%), while Uprot slightly increased in VEH (+23 +/- 2%). The focal glomerulosclerosis (FGS) score after GEM (38 +/- 14) was lower than in the VEH group (79 +/- 27), although this was not significant. LIS (18 +/- 6) reduced FGS significantly. Remarkably, on high sodium, GEM was completely ineffective in reducing BP, Uprot and structural renal injury, just like LIS. CONCLUSIONS The renoprotective actions of VPI depend on dietary sodium intake in normotensive nephrotic rats: therapeutic efficacy is fully blunted by a high sodium diet. During a low sodium diet, gemopatrilat was renoprotective, but less effective than lisinopril. Whether higher doses of the VPI could improve its renoprotective efficacy remains to be elucidated.