Miracle-dz/UniFAR-FTUs huggingface dataset:
Human lymphoid organ dendritic cell identity is predominantly dictated by ontogeny, not tissue microenvironment

Transcriptional identity of human dendritic cell subsets is mainly dictated by ontogeny rather than by signals derived from the cells’ final tissue microenvironment. Dendritic cell branches Dendritic cell (DC) subsets have been well studied in mice; however, the relative contribution of ontogeny and tissue microenvironment to DC function in humans is less clear. Now, Heidkamp et al. perform phenotypic and transcriptional profiling of three DC subtypes in different human tissues from a large number of individuals. They find that DC subpopulations in more lympho-hemaotopoietic organs (spleen, thymus, and blood) are more strongly influenced by ontogeny, whereas those from lung and skin may be influenced by the issue microenvironment. The data collected here provide an in depth look at the transcriptional profile of dendritic cell subsets in humans and inform our understanding of human DC biology. In mice, conventional and plasmacytoid dendritic cells (DCs) derive from separate hematopoietic precursors before they migrate to peripheral tissues. Moreover, two classes of conventional DCs (cDC1 and cDC2 DCs) and one class of plasmacytoid DCs (pDCs) have been shown to be transcriptionally and functionally distinct entities. In humans, these three DC subtypes can be identified using the cell surface markers CD1c (cDC2), CD141 (cDC1), and CD303 (pDCs), albeit it remains elusive whether DC functionality is mainly determined by ontogeny or the tissue microenvironment. By phenotypic and transcriptional profiling of these three DC subtypes in different human tissues derived from a large number of human individuals, we demonstrate that DC subpopulations in organs of the lymphohematopoietic system (spleen, thymus, and blood) are strongly defined by ontogeny rather than by signals from the microenvironment. In contrast, DC subsets derived from human lung or skin differed substantially, strongly arguing that DCs react toward modulatory signals from tissue microenvironments. Collectively, the data obtained in this study may serve as a major resource to guide further studies into human DC biology during homeostasis and inflammation.
SEMG feature extraction methods for pattern recognition of upper limbs

In this paper, a new feature of surface electromyo-graphy (sEMG) by using discrete wavelet transform (DWT) is proposed for motion recognition of upper limbs, and this method can be eventually used for rehabilitation robot control. Seven traditional features of sEMG are also extracted for comparative study, they are integral of absolute value (IAV), difference absolute mean value (DAMV), zero crossing (ZC), variance (VAR), mean power spectral density (MPSD), mean frequency (MF) and median frequency (MDF) respectively. For comparing the recognition rate of the different motions of the upper limb, each feature or their combination are used to construct the feature vectors, and the BP neural network with variable learning rate back propagation with momentum (GDX) algorithm is used to classify these motion modes. The experimental results summarize that the new feature extracted by using DWT presents a higher recognition rate (98.9%) than all of the traditional features, and the traditional features combination can also greatly improve the recognition rate (99%).
Impact of missing data due to drop‐outs on estimators for rates of change in longitudinal studies: a simulation study

Many cohort studies and clinical trials are designed to compare rates of change over time in one or more disease markers in several groups. One major problem in such longitudinal studies is missing data due to patient drop‐out. The bias and efficiency of six different methods to estimate rates of changes in longitudinal studies with incomplete observations were compared: generalized estimating equation estimates (GEE) proposed by Liang and Zeger (1986); unweighted average of ordinary least squares (OLSE) of individual rates of change (UWLS); weighted average of OLSE (WLS); conditional linear model estimates (CLE), a covariate type estimates proposed by Wu and Bailey (1989); random effect (RE), and joint multivariate RE (JMRE) estimates. The latter method combines a linear RE model for the underlying pattern of the marker with a log‐normal survival model for informative drop‐out process. The performance of these methods in the presence of missing data completely at random (MCAR), at random (MAR) and non‐ignorable (NIM) were compared in simulation studies. Data for the disease marker were generated under the linear random effects model with parameter values derived from realistic examples in HIV infection. Rates of drop‐out, assumed to increase over time, were allowed to be independent of marker values or to depend either only on previous marker values or on both previous and current marker values. Under MACR all six methods yielded unbiased estimates of both group mean rates and between‐group difference. However, the cross‐sectional view of the data in the GEE method resulted in seriously biased estimates under MAR and NIM drop‐out process. The bias in the estimates ranged from 30 per cent to 50 per cent. The degree of bias in the GEE estimates increases with the severity of non‐randomness and with the proportion of MAR data. Under MCAR and MAR all the other five methods performed relatively well. RE and JMRE estimates were more efficient(that is, had smaller variance) than UWLS, WLS and CL estimates. Under NIM, WLS and particularly RE estimates tended to underestimate the average rate of marker change (bias≈10 per cent). Under NIM, UWLS, CL and JMRE performed better in terms of bias (3–5 per cent) with the JMRE giving the most efficient estimates. Given that markers are key variables related to disease progression, missing marker data are likely to be at least MAR. Thus, the GEE method may not be appropriate for analysing such longitudinal marker data. The potential biases due to incomplete data require greater recognition in reports of longitudinal studies. Sensitivity analyses to assess the effect of drop‐outs on inferences about the target parameters are important. Copyright © 2001 John Wiley & Sons, Ltd.
Adding to the ends: what makes telomerase processive and how important is it?

Telomerase is a cellular reverse transcriptase responsible for telomere maintenance in most organisms. It does so by adding telomere repeats onto pre‐existing ends using an integral RNA component as template. Compared to “prototypical” reverse transcriptases, telomerase is unique in being able to repetitively copy a short templating RNA segment, thus adding multiple copies of the repeat to the DNA substrate following a single binding event. This uniquely processive property hints at the intricate conformational alterations that the enzyme must choreograph during its reaction cycles. Recent studies have identified distinct structural elements within both the RNA and protein components of telomerase that modulate enzyme processivity. Pharmacological and genetic analysis suggest that telomerase processivity is a significant determinant of telomere length. Because telomere maintenance and the lack thereof have been linked to tumor progression and aging, further investigation of telomerase processivity may lead to novel medical intervention strategies. BioEssays 26:955–962, 2004. © 2004 Wiley Periodicals, Inc.
Suberoylanilide hydroxamic acid (vorinostat) represses androgen receptor expression and acts synergistically with an androgen receptor antagonist to inhibit prostate cancer cell proliferation

Growth of prostate cancer cells is initially dependent on androgens, and androgen ablation therapy is used to control tumor growth. Unfortunately, resistance to androgen ablation therapy inevitably occurs, and there is an urgent need for better treatments for advanced prostate cancer. Histone deacetylase inhibitors, such as suberoylanilide hydroxamic acid (SAHA; vorinostat), are promising agents for the treatment of a range of malignancies, including prostate cancer. SAHA inhibited growth of the androgen-responsive LNCaP prostate cancer cell line at low micromolar concentrations and induced caspase-dependent apoptosis associated with chromatin condensation, DNA fragmentation, and mitochondrial membrane depolarization at higher concentrations (≥5 μmol/L). Gene profiling and immunoblot analyses showed a decrease in androgen receptor (AR) mRNA and protein in LNCaP cells cultured with SAHA compared with control cells, with a corresponding decrease in levels of the AR-regulated gene, prostate-specific antigen. Culture of LNCaP cells in steroid-free medium markedly sensitized the cells to SAHA. Moreover, a combination of low, subeffective doses of SAHA and the AR antagonist bicalutamide resulted in a synergistic reduction in cell proliferation and increase in caspase-dependent cell death. Addition of exogenous androgen prevented the induction of cell death, indicating that suppression of androgen signaling was required for synergy. At the subeffective concentrations, these agents had no effect, alone or in combination, on proliferation or death of AR-negative PC-3 prostate cancer cells. Our findings indicate that SAHA is effective in targeting the AR signaling axis and that androgen deprivation sensitizes prostate cancer cells to SAHA. Consequently, combinatorial treatments that target different components of the AR pathway may afford a more effective strategy to control the growth of prostate cancer cells. [Mol Cancer Ther 2007;6(1):51–60]
Cortisol Measures Across the Weight Spectrum.

CONTEXT There are conflicting reports of increased vs decreased hypothalamic-pituitary-adrenal (HPA) activation in obesity; the most consistent finding is an inverse relationship between body mass index (BMI) and morning cortisol. In anorexia nervosa (AN), a low-BMI state, cortisol measures are elevated. OBJECTIVE This study aimed to investigate cortisol measures across the weight spectrum. DESIGN AND SETTING This was a cross-sectional study at a clinical research center. PARTICIPANTS This study included 60 women, 18-45 years of age: overweight/obese (OB; N = 21); AN (N = 18); and normal-weight controls (HC; N = 21). MEASURES HPA dynamics were assessed by urinary free cortisol, mean overnight serum cortisol obtained by pooled frequent sampling every 20 minutes from 2000-0800 h, 0800 h serum cortisol and cortisol-binding globulin, morning and late-night salivary cortisol, and dexamethasone-CRH testing. Body composition and bone mineral density (BMD) were assessed by dual-energy x-ray absorptiometry. RESULTS Cortisol measures demonstrated a U-shaped relationship with BMI, nadiring in the overweight-class I obese range, and were similarly associated with visceral adipose tissue and total fat mass. Mean cortisol levels were higher in AN than OB. There were weak negative linear relationships between lean mass and some cortisol measures. Most cortisol measures were negatively associated with postero-anterior spine and total hip BMD. CONCLUSIONS Cortisol measures are lowest in overweight-class I obese women-lower than in lean women. With more significant obesity, cortisol levels increase, although not to as high as in AN. Therefore, extreme underweight and overweight states may activate the HPA axis, and hypercortisolemia may contribute to increased adiposity in the setting of caloric excess. Hypercortisolemia may also contribute to decreased BMD and muscle wasting in the setting of both caloric restriction and excess.
Focus-immunoassay for Borna disease virus-specific antigens.

Summary Borna Disease virus and its antigens have been assayed by the fluorescence antibody technique. A focus-immunoassay, termed PELISA, was established. It is based on fixation of the cells with 3% formaldehyde, treatment with 1% Triton X-100, incubation with antibodies and the corresponding species-specific antibodies coupled to horseradish peroxidase followed by the enzyme/substrate (3-amino-9-ethyl-carbazole, H202) reaction. This assay can be applied to detect antigens. It allows quantitation of virus as well as titration of antibodies. It greatly facilitates studies on Borna Disease virus and its antigens and is approx. 10 to 100-fold more sensitive than the fluorescence antibody test used previously. Zusammenfassung Focus-Immuntest zum Nachweis von virus-spezifischen Antigenen bei der Borna Krankheit Eine Borna Virus Infektion sowie Borna Virus-spezifische Antigene wurden bisher mittels der Fluoreszenzantikorper-Technik nachgewiesen. Es wird uber einen empfindlichen Focus-Immuntest, genannt PELISA, berichtet. Er basiert auf der Fixation von Zellen mit 3% Formaldehyd, Behandlung mit 1% Triton X-100, Inkubation mit Antikorpern und den entsprechenden speziesspezifischen, Peroxidase markierten Antikorpern. Die Antikorperbindung wird durch eine Enzym/Substrat (3-Amino-9-Ethyl-Carbazol, H202) Reaktion nachgewiesen. Dieser Test kann zur Antigendarstellung genutzt werden. Er erlaubt die Quantifizierung von Virus ebenso wie die Titration von Antikorpern und ist etwa 10–100fach empfindlicher als der bis jetzt verwendete Fluoreszenzantikorpertest. Untersuchungen am Virus der Borna Krankheit sowie seiner Antigene werden mit diesem Test erheblich vereinfacht. Resumen La prueba inmunitaria focal para los antigenos especificos del virus de la enfermedad de Borna Hasta la fecha se ponian en evidencia una infeccion por virus Borna y los antigenos especificos del mismo virus mediante la tecnica de anticuerpos fluorescentes. Se informa sobre una prueba inmunitaria focal sensible, llamada PELISA. Esta tecnica se basa en la fijacion de celulas con un 3% de aldehido metilico, tratamiento con 1% de Triton X-100, incubacion con anticuerpos y con los anticuerpos correspondientes especificos de especie, marcados con peroxidasa de rabano rusticano. La fijacion de anticuerpos se pone en evidencia por medio de una reaccion de enzima/substrato (3-amino-9-etil-carbazol, H202). Esta prueba se puede utilizar para detectar antigenos. Permite cuantificar virus, titular anticuerpos y es de 10–100 veces mas sensible que la prueba de anticuerpos fluorescentes que se venia utilizando hasta ahora. Con esta prueba se han simplificado mucho los estudios referentes al virus de la enfermedad de Borna y a sus antigenos.
Modelling and forecasting the demolition market in shipping

ABSTRACT We model the demolition market, an integral part of the international shipping industry. It is shown through the implementation of a Vector Autoregressive (VAR) model that international steel-scrap prices contribute decisively towards price discovery in the ship-demolition industry. Our finding is explained and attributed to the fact that the growth models of Southeast Asian countries, where the ship-demolition market is primarily located, rely on scrap metal imports. These are mainly obtained from the developed economies rather than the recycling of vessels. We then proceed to test the forecasting ability of our model and use it for price prediction in the ship-demolition market. We establish that it provides the decision-makers with a useful prediction tool which enables all stakeholders involved, the ship owner, the recycler and the cash buyer alike, to gain valuable insights of the underlying trend in the sector.
A Prospective Study to Validate an Impairment Questionnaire for Major Trauma Survivors

Marshall SC, Gray D, Wilson KG, Yelle J-D, Hébert P, O'Rourke K, Jamshidi M: A prospective study to validate an impairment questionnaire for major trauma survivors. Am J Phys Med Rehabil 2007;86:114–124. Objective:To develop and validate an impairment questionnaire that will provide an estimate of whole-person impairment in patients who have suffered major trauma. Design:This was a multicenter prospective study involving a convenience sample of 43 volunteer participants who had sustained major trauma within 1 yr of study commencement. Patients were recruited from two trauma centers in Ontario, Canada. The impairment questionnaire was developed as a self-administered questionnaire based on the American Medical Association's Guides to the Evaluation of Permanent Impairment, Fourth Edition. Results:Clinician assessments of whole-person impairment showed adequate interrater (r ≥ 0.55, P ≤ 0.03) and intrarater (r ≥ 0.62, P ≤ 0.055) reliabilities across dimensions. The impairment questionnaire correlated significantly with clinician assessments at the initial visit (r ≥ 0.57, P < 0.001) and at follow-up (r > 0.60, P < 0.001). Comparison of the physical and emotional subcategories of the impairment questionnaire, whole-person impairment ratings by physicians, and the Short Form 36 demonstrated good convergent and divergent validity of the impairment questionnaire. Conclusions:The impairment questionnaire is a reliable and valid self-administered tool that can be used to evaluate physical impairment after major trauma.
Patient reported outcomes in benign multiple sclerosis

Background: Benign MS patients have a mild course of disease and show no or minimal accumulation of disability over time. Little is known about the patient reported outcomes (PROs) in benign MS. Objective: The objective of the study was to compare PROs in benign MS patients and patients with similar disease duration or disability status, and to investigate how the definition of benign MS affected this outcome. Methods: Two groups of Benign MS patients (disease duration ≥15 years, Expanded Disability Status Scale [EDSS] score ≤1.5 [Benign-1.5], or ≤3.0 [Benign-3]) were compared with four other MS groups: disease duration ≥15 years, EDSS score >3.0 (Late-MS); disease duration <15 years, and EDSS score ≤1.5 (Low-EDSS-1.5), or ≤3.0 (Low-EDSS-3); disease duration ≤5 years (Early-MS). PROs included measures of QOL, fatigue, depression, and social support. Cognitive function was also assessed. Results: Both benign groups had better PROs than Late MS patients on all measures (p < 0.05). QOL, depression, and fatigue were significantly different between Benign-1.5 and Early-MS groups (p < 0.01). Benign-1.5 had higher mental health QOL than Low EDSS-1.5, but was otherwise similar. Benign-3 patients had worse depression than Early-MS (p < 0.01), and worse cognition compared with Low-EDSS-3 (p = 0.033). Benign-1.5 had higher QOL and lower fatigue (p < 0.005) than Benign-2-3, and showed a marginally significant difference in cognitive functioning (p = 0.055). Conclusions: Patients with benign MS had better PROs than other groups of MS patients, suggesting that both disease duration and disability influence PROs. The study also showed a difference in PROs based on the way benign MS was defined.
Review of sunscreen and the emergence of non‐conventional absorbers and their applications in ultraviolet protection

Protection against ultraviolet (UV) radiation is the major function of sunscreen lotions and UV‐protective coatings for vehicles, homes, equipment and clothing. Sunscreen formulations have been optimized to become protective over a broader spectrum of UV radiation and maintain greater photostability. They are comprised of organic and inorganic components that act as chemical and physical UV protectors, respectively. Some of the organic components are limited by their spectrum of protection and photostability. Studies using solid lipid nanoparticles, recently explored organic molecules, inorganic components and antioxidants attempt to further optimize UV protection. In this review, we examine traditional and emerging nanoparticle components and highlight novel ideas in UV protection which may provide pathways for future studies.
Encoding of anisotropic diffusion with tetrahedral gradients: A general mathematical diffusion formalism and experimental results

A diffusion imaging method with a tetrahedral sampling pattern has been developed for high‐sensitivity diffusion analysis. The tetrahedral gradient pattern consists of four different combinations of x, y, and z gradients applied simultaneously at full strength to uniformly measure diffusion in four different directions. Signal‐to‐noise can be increased by up to a factor of about three using this approach, compared with diffusion measurements made using separately applied x, y, and z gradients. A mathematical formalism is presented describing six fundamental parameters: the directionally averaged diffusion coefficient D and diffusion element anisotropies η and ε which are rotationally invariant, and diffusion ellipsoid orientation angles θ, ϕ, and Ψ which are rotationally variant. These six parameters contain all the information in the symmetric diffusion tensor D. Principal diffusion coefficients, reduced anisotropies, and other rotational invariants are further defined. It is shown that measurement of off‐diagonal tensor elements is essential to assess anisotropy and orientation, and that the only parameter which can be measured with the orthogonal method is D. In cases of axial diffusion symmetry (e.g., fibers), the four tetrahedral diffusion measurements efficiently enable determination of D, η, θ, and ϕ which contain all the diffusion information. From these four parameters, the diffusion parallel and perpendicular to the symmetry axis (D1 and D1) and the axial anisotropy A can be determined. In more general cases, the six fundamental parameters can be determined with two additional diffusion measurements. Tetrahedral diffusion sequences were implemented on a clinical MR system. A muscle phantom demonstrates orientation independence of D, D1, D1, and A for large changes in orientation angles. Sample background gradients and diffusion gradient imbalances were directly measured and found to be insignificant in most cases.
Carbon-11-cocaine binding compared at subpharmacological and pharmacological doses: a PET study.

UNLABELLED We have characterized cocaine binding in the brain to a high-affinity site on the dopamine transporter using PET and tracer doses of [11C]cocaine in the baboon in vivo. The binding pattern, however, of cocaine at tracer (subpharmacological) doses may differ from that observed when the drug is taken in behaviorally active doses particularly since in vitro studies have shown that cocaine also binds to low affinity binding sites. METHODS PET was used to compare and characterize [11C]cocaine binding in the baboon brain at low subpharmacological (18 micrograms average dose) and at pharmacological (8000 micrograms) doses. Serial studies on the same day in the same baboon were used to assess the reproducibility of repeated measures and to assess the effects of drugs which inhibit the dopamine, norepinephrine and serotonin transporters. Time-activity curves from brain and the arterial plasma input function were used to calculate the steady-state distribution volume (DV). RESULTS At subpharmacological doses, [11C]cocaine had a higher binding and slower clearance in striatum than in other brain regions. At pharmacological doses, [11C]cocaine had a more homogeneous distribution. Bmax/Kd for sub-pharmacological [11C]cocaine corresponded to 0.5-0.6 and for pharmacological [11C]cocaine it corresponded to 0.1-0.2. Two-point Scatchard analysis gave Bmax = 2300 pmole/g and Kd' = 3600 nM. Bmax/Kd for sub-pharmacological doses of [11C]cocaine was decreased by cocaine and drugs that inhibit the dopamine transporter, to 0.1-0.2, but not by drugs that inhibit the serotonin or the norepinephrine transporter. None of these drugs changed Bmax/Kd for a pharmacological dose of [11C]cocaine. CONCLUSION At subpharmacological doses, [11C]cocaine binds predominantly to a high-affinity site on the dopamine transporter.