Miracle-dz/UniFAR-FTUs huggingface dataset:
The BBXB Motif of RANTES Is the Principal Site for Heparin Binding and Controls Receptor Selectivity*

The chemokine RANTES (regulated on activation normal T cell expressed and secreted; CCL5) binds selectively to glycosaminoglycans (GAGs) such as heparin, chondroitin sulfate, and dermatan sulfate. The primary sequence of RANTES contains two clusters of basic residues, 44RKNR47 and55KKWVR59. The first is a BBXB motif common in heparin-binding proteins, and the second is located in the loop directly preceding the C-terminal helix. We have mutated these residues to alanine, both as point mutations as well as triple mutations of the 40s and 50s clusters. Using a binding assay to heparin beads with radiolabeled proteins, the44AANA47 mutant demonstrated an 80% reduction in its capacity to bind heparin, whereas the55AAWVA59 mutant retained full binding capacity. Mutation of the 44RKNR47 site reduced the selectivity of RANTES binding to different GAGs. The mutants were tested for their integrity by receptor binding assays on CCR1 and CCR5 as well as their ability to induce chemotaxis in vitro. In all assays the single point mutations and the triple 50s cluster mutation caused no significant difference in activity compared with the wild type sequence. However, the triple 40s mutant showed a 80-fold reduction in affinity for CCR1, despite normal binding to CCR5. It was only able to induce monocyte chemotaxis at micromolar concentrations. The triple 40s mutant was also able to inhibit HIV-1 infectivity, but consistent with its abrogated GAG binding capacity, it no longer induced enhanced infectivity at high concentrations.
Exploring visitor experience at a mountain attraction

The study explores visitor experience while visiting a mountain attraction in the Alpine region of Tirol, Austria, through participant observations, informal conversations, and photography. A grounded theory approach was adopted to uncover the meaning of visitors’ overall experience and deduct a possible theory that may contribute to a better understanding of visitor experiences at mountain attractions. The data collected from 600 subjects at the attraction’s four stopovers concluded that the visiting experience was a process that involved a blend of events composed of material and human elements. Guest experiences were also practiced on a passive–active continuum, where some of the experiential consumption activities were focused beyond the mountain itself, primarily viewing the landscape and photography. The study affirms the importance of participant observation as a methodological tool to study visitors at a tourist attraction, discusses implications for management, and offers recommendations for enhancing the overall guest experience.
Sun Exposure, Sunscreens, and Skin Cancer Prevention: A Year-Round Concern

Objective To review the role of sunlight in skin aging and skin cancer formation, and to provide guidelines on the use of sunscreens to minimize the adverse effects of sun damage. Data Sources A MEDLINE search of applicable articles on ultraviolet (UV) radiation, melanoma, sunscreens, and skin cancer, evaluating both human and animal studies. Published and unpublished original research as well as clinical experience were also used. Data Synthesis The interaction of UV radiation and skin type plays a central role in melanoma formation. Mortality from melanoma is highest in geographic locations near the equator, where UV intensity is greatest. The incidence of melanomas in light-complected individuals (skin types I-III) is several times higher than those with darker skin types (types IV-VI), even in similar geographic regions. The UVB portion of the spectrum appears to be primarily responsible for skin cancer formation and photoaging, while short wave UVA rays play a significant contributing role. Regular sunscreen use has been shown to reduce the formation of precancerous actinic keratoses (AK) lesions by 36%. A dose-response relationship has also been found between the amount of sunscreen used and AK formation. Conclusions Sunscreens have now been shown to reduce the carcinogenic effects of sunlight in humans. Patients should be advised of the long-term consequences of sun exposure and the benefits of regular sunscreen use.
Immunoglobulin G expression in carcinomas and cancer cell lines

The traditional view that immunoglobulin is produced only by differentiated B lymphocytes has been challenged as immunoglobulin genes have been found to be expressed in nonhematopoietic human cancer cells. However, this phenomenon has not been widely accepted, and knowledge about this newly discovered concept is limited. In this study, we investigated the IgG1 heavy chain (IGHG1) constant region gene and IgG protein expression in 6 cell lines, including epithelial cancer cells, and in tissues from 66 hyperplasias, adenomas, and carcinomas. We also studied the mechanism of IgG production in these cells by examining the expression of RAG1 (recombination activating gene 1), RAG2, and AID (activation‐induced cytidine deaminase). In cancer cell lines, mRNA of the IGHG1 constant region and Iy‐Cy sterile transcript were detected by nested RT‐PCR, and Ig y and Ig κ proteins were detected by immunofluorescence and Western blot. In surgically resected carcinoma tissues, we detected mRNA of the IGHG1 constant region by in situ hybridization, and by laser microdissection‐assisted nested RT‐PCR. Ig y and Ig κ proteins were detected by immunohistochemistry. The V(D)J recombination of IgH and IgL loci, the Sy1/2‐Sμ switch circle, and the expression of RAG1 and RAG2 were also found in these cancer cell lines. These data suggest that cancer cells are capable of producing IgG. Because of its potential biological and clinical significance, this phenomenon warrants further investigation. —Chen Z. , and Gu J. Immunoglobulin G expression in carcinomas and cancer cell lines. FASEB J. 21, 2931–2938 (2007)
Steroids in the equine oviduct: synthesis, local concentrations and receptor expression.

Steroids play an important role in mammalian reproduction and early pregnancy. Although systemic changes in steroid concentrations have been well documented, it is not clear how these correlate with local steroid concentrations in the genital tract. We hypothesised that, in the horse, the preimplantation embryo may be subjected to high local steroid concentrations for several days. Therefore, we measured progesterone, 17-hydroxyprogesterone, 17? -oestradiol, testosterone and 17? -testosterone concentrations in equine oviductal tissue by ultra-HPLC coupled with tandem mass spectrometry, and progesterone, 17? -oestradiol, oestrone and testosterone concentrations in oviduct fluid by radioimmunoassay, with reference to cycle stage and side of ovulation. Progesterone concentrations were high in oviductal tissue and fluid ipsilateral to the ovulation side during dioestrus, whereas other steroid hormone concentrations were not influenced by the side of ovulation. These results suggest that the high ipsilateral progesterone concentration is caused by: (1) contributions from the follicular fluid in the oviduct and diffusion of follicular fluid steroids after ovulation; (2) local transfer of steroids via blood or lymph; (3) local synthesis of progesterone in the oviduct, as evidenced by the expression of steroidogenic enzymes; and (4) a paracrine contribution from follicular cells. These data provide a basis for the study of the importance of endocrine and paracrine signalling during early embryonic development in the horse.
[Detection of microembolus with transcranial doppler].

OBJECTIVES To review techniques and the most important clinical applications of microembolus detection with transcranial Doppler. DEVELOPMENT Technical aspects of microembolus detection are discussed initially; clinical circumstances in which embolus detection is currently used follow, such as carotid stenosis, cardiac pathology, monitoring during neuroangiography, coronary revascularization surgery and endarterectomy. Lastly, the potential clinical applications of this technique are reviewed: localization of an embolic source, risk of recurrent ischemia in patients with unstable atherosclerotic plaques, intraoperative monitoring and potential surgical technique modifications based on this information, contributions to the understanding of the pathophysiology of the fat embolism syndrome, and monitoring therapeutic efficacy of antithrombotics and thrombolytics. CONCLUSIONS The ability to detect cerebral emboli with transcranial ultrasound has increased significantly our understanding about the pathogenesis of cerebral ischemia. Microembolus detection with transcranial Doppler is a powerful and novel diagnostic technique that allows to study the embolic process in vivo and in real time, instead of using indirect indicators of embolism (clinical and radiological features, possible embolic sources, etc.).
A Decentralized Storage Strategy for Residential Feeders With Photovoltaics

This paper proposes a decentralized storage strategy to support voltage control in low-voltage (LV) residential feeders with high photovoltaic (PV) capacity installed. The proposed strategy is capable of preventing overvoltage situations during high PV generation periods, by the use of locally controlled battery energy storage systems (ESS) at the PV system grid interface. The traditional way of operating a domestic ESS is based on charging the battery as soon as the PV generation exceeds the consumption, without taking into account overvoltage events during high PV generation hours; the proposed storage concept improves the traditional approach, thanks to the provision of voltage support. A novel method, based on voltage sensitivity analysis, identifies a common power threshold that triggers the ESSs activation in the feeder. A Belgian residential LV feeder is used as a case study. Time-series simulations based on 1-year load and generation profiles verify the method findings and quantify the ESS size in terms of storage power and energy level.
NATO's Post-Cold War Relevance in Counter Terrorism

From the end of the Cold War, through the process of globalization, national security has transitioned from an idea of purely state versus state interaction into a concept including both state and non-state actors. The North Atlantic Treaty Organization (NATO), once the counter balance to the Soviet Union, has evolved into an alliance that has expanded its attention to include non-state actors, such as international terrorist organizations. Scholars have theorized on the lifespan of NATO post-Cold War, however the majority of these theories have focused on state versus state issues, a common paradigm of the 20 th century, and not included state versus non-state issues, such as international terrorism. As NATO continues to be a post-Cold War, state alliance has it been able to transition to a relevant counter terrorism force and reduce the number of terrorist attacks within each member state, the alliance as a whole, and/or in the international community? With statistical data of terrorist attacks within NATO member states from the Global Terrorism Database this study focuses on each new member that joined during three influential time periods before and after the end of the Cold War in order to determine if becoming a member correlates to an increase or decrease in the number of terrorist attacks. Complementing the statistical data is a content analysis of NATO Summit Declarations in order to determine the combined strategies of each member state in reference to international terrorism. According to the findings of the statistical data, I hypothesize that each state will have experienced a decrease in terrorist attacks within their borders after becoming a member of NATO. The content analysis will illustrate that the alliance has continued to evolve its existence by increasing attention and resources to the fight against international terrorism.
Frequency of Amantadine-Resistant Influenza A Viruses during Two Seasons Featuring Cocirculation of H1N1 and H3N2

ABSTRACT In two influenza seasons during which H1N1 and H3N2 cocirculated, resistance was more frequent in H3N2 strains than in H1N1 strains after amantadine treatment. Predominant amino acid substitutions in M2 protein occurred at position 31 (serine to asparagine) in H3N2 strains and at position 27 (valine to alanine) in H1N1 strains.
Earlier versus later start of antiretroviral therapy in HIV-infected adults with tuberculosis.

BACKGROUND Tuberculosis remains an important cause of death among patients infected with the human immunodeficiency virus (HIV). Robust data are lacking with regard to the timing for the initiation of antiretroviral therapy (ART) in relation to the start of antituberculosis therapy. METHODS We tested the hypothesis that the timing of ART initiation would significantly affect mortality among adults not previously exposed to antiretroviral drugs who had newly diagnosed tuberculosis and CD4+ T-cell counts of 200 per cubic millimeter or lower. After beginning the standard, 6-month treatment for tuberculosis, patients were randomly assigned to either earlier treatment (2 weeks after beginning tuberculosis treatment) or later treatment (8 weeks after) with stavudine, lamivudine, and efavirenz. The primary end point was survival. RESULTS A total of 661 patients were enrolled and were followed for a median of 25 months. The median CD4+ T-cell count was 25 per cubic millimeter, and the median viral load was 5.64 log(10) copies per milliliter. The risk of death was significantly reduced in the group that received ART earlier, with 59 deaths among 332 patients (18%), as compared with 90 deaths among 329 patients (27%) in the later-ART group (hazard ratio, 0.62; 95% confidence interval [CI]; 0.44 to 0.86; P=0.006). The risk of tuberculosis-associated immune reconstitution inflammatory syndrome was significantly increased in the earlier-ART group (hazard ratio, 2.51; 95% CI, 1.78 to 3.59; P<0.001). Irrespective of the study group, the median gain in the CD4+ T-cell count was 114 per cubic millimeter, and the viral load was undetectable at week 50 in 96.5% of the patients. CONCLUSIONS Initiating ART 2 weeks after the start of tuberculosis treatment significantly improved survival among HIV-infected adults with CD4+ T-cell counts of 200 per cubic millimeter or lower. (Funded by the French National Agency for Research on AIDS and Viral Hepatitis and the National Institutes of Health; CAMELIA ClinicalTrials.gov number, NCT01300481.).
A two‐stage approach for dynamic prediction of time‐to‐event distributions

Dynamic prediction uses longitudinal biomarkers for real‐time prediction of an individual patient's prognosis. This is critical for patients with an incurable disease such as cancer. Biomarker trajectories are usually not linear, nor even monotone, and vary greatly across individuals. Therefore, it is difficult to fit them with parametric models. With this consideration, we propose an approach for dynamic prediction that does not need to model the biomarker trajectories. Instead, as a trade‐off, we assume that the biomarker effects on the risk of disease recurrence are smooth functions over time. This approach turns out to be computationally easier. Simulation studies show that the proposed approach achieves stable estimation of biomarker effects over time, has good predictive performance, and is robust against model misspecification. It is a good compromise between two major approaches, namely, (i) joint modeling of longitudinal and survival data and (ii) landmark analysis. The proposed method is applied to patients with chronic myeloid leukemia. At any time following their treatment with tyrosine kinase inhibitors, longitudinally measured BCR‐ABL gene expression levels are used to predict the risk of disease progression. Copyright © 2016 John Wiley & Sons, Ltd.
MAPping out distribution routes for kinesin couriers

In the crowded environment of eukaryotic cells, diffusion is an inefficient distribution mechanism for cellular components. Long‐distance active transport is required and is performed by molecular motors including kinesins. Furthermore, in highly polarised, compartmentalised and plastic cells such as neurons, regulatory mechanisms are required to ensure appropriate spatio‐temporal delivery of neuronal components. The kinesin machinery has diversified into a large number of kinesin motor proteins as well as adaptor proteins that are associated with subsets of cargo. However, many mechanisms contribute to the correct delivery of these cargos to their target domains. One mechanism is through motor recognition of sub‐domain‐specific microtubule (MT) tracks, sign‐posted by different tubulin isoforms, tubulin post‐translational modifications, tubulin GTPase activity and MT‐associated proteins (MAPs). With neurons as a model system, a critical review of these regulatory mechanisms is presented here, with a particular focus on the emerging contribution of compartmentalised MAPs. Overall, we conclude that – especially for axonal cargo – alterations to the MT track can influence transport, although in vivo, it is likely that multiple track‐based effects act synergistically to ensure accurate cargo distribution.
Development of Unscented Kalman filter algorithm for 3-D point based rigid registration

This paper proposes an effective algorithm for estimating the transformation parameters which align two data sets belonging to the rigid objects. This point based algorithm uses unscented Kalman filter for estimating the state vector of transformation which is a nonlinear function of translation and rotation. It is also assumed that the Gaussian noise is added to the fixed data set. In this paper, firstly we investigate the newest algorithm performance for point based rigid body registration using UKF and then we show the drawback of this algorithm in estimating of high range rotations. It is shown that the UKF algorithm is sensitive to selecting the appropriate initial sate vector. For solving limitation of the UKF algorithm, we propose an extended unscented kalman filter algorithm. It is shown that by exploiting this new algorithm which uses pre-registration, we can find an appropriate initial state vector. In this paper, we compare the results of EUKF algorithm with the previous UKF algorithm for different rotations. We demonstrate the effectiveness of the EUKF algorithm for estimation of high transformations between two data sets.
Retransplantation After Post‐Transplant Lymphoproliferative Disorders: An OPTN/UNOS Database Analysis

Post‐transplant lymphoproliferative disorders (PTLD) are a life‐threatening complication of immunosuppressive therapy. Retransplantation of survivors remains controversial. The Organ Procurement and Transplant Network/United Network for Organ Sharing database was reviewed for individuals who developed PTLD and underwent retransplant from 1987 through 2004. Sixty‐nine retransplants have been performed: 27 kidney, 22 liver, 9 lung, 6 heart, 4 intestine and 1 pancreas. At first transplant, most subjects (63.8%) were <17 years of age and was similar at retransplant with 50.7% less than 17 years. Time from transplant to PTLD was <1 year in 33.3%, 1–3 years in 21.7%, 3–5 years in 21.7%, 5–10 years in 21.7% and >10 years in 1.4%. Time from PTLD to retransplant was <1 year in 24.6%, 1–3 years in 37.7%, 3–5 years in 17.4% and 5–10 years in 20.3%. Induction agents were used in 21.7% of first and 47.8% of retransplants. Immunosuppression for first transplant was cyclosporine (CSA) in 55.1%, tacrolimus (TAC) in 27.5% versus CSA in 26.1%, TAC in 66.7% of retransplants. At last follow‐up, patient and graft survival are 85.5% and 73.9%, respectively. Most subjects retransplanted after PTLD are <17 years on TAC‐based immunosuppression. Patient/graft survival is excellent and retransplantation in PTLD subjects should be considered acceptable.
Platelet membrane receptor glycoprotein IIb/IIIa antagonism in unstable angina. The Canadian Lamifiban Study.

BACKGROUND Ligand binding to the platelet membrane receptor glycoprotein (GP) IIb/IIIa, the final and obligatory step to platelet aggregation, can now be inhibited by pharmacological agents. This study was designed to evaluate the potential of lamifiban, a novel nonpeptide antagonist of GP IIb/IIIa, for the management of unstable angina. METHODS AND RESULTS In a prospective, dose-ranging, double-blind study, 365 patients with unstable angina were randomized to an infusion of 1, 2, 4, or 5 micrograms/min of lamifiban or of placebo. Treatment was administered for 72 to 120 hours. Outcome events were measured during the infusion period and after 1 month. Concomitant aspirin was administered to all patients and heparin to 28% of patients. Lamifiban, all doses combined, reduced the risk of death, nonfatal myocardial infarction, or the need for an urgent revascularization during the infusion period from 8.1% to 3.3% (P = .04). The rates were 2.5%, 4.9%, 3.3%, and 2.4% with increasing doses. At 1 month, death or nonfatal infarction occurred in 8.1% of patients with placebo and in 2.5% of patients with the two high doses (P = .03). The highest dose of lamifiban additionally prevented the need for an urgent intervention. Lamifiban dose-dependently inhibited platelet aggregation. Bleeding times were significantly prolonged with platelet inhibition of > 80%. Major (but neither life-threatening nor intracranial) bleedings occurred in 0.8% of patients with placebo and 2.9% with lamifiban. CONCLUSIONS The nonpeptide GP IIb/IIIa antagonist lamifiban protected patients with unstable angina from severe ischemic events during a 3- to 5-day infusion and reduced the incidence of death and infarction at 1 month, suggesting considerable promise for this new therapeutic approach.
Early Islet Damage after Direct Exposure of Pig Islets to Blood: Has Humoral Immunity Been Underestimated?

Currently, islet transplantation as a cell therapeutic option for type 1 diabetes occurs via islet injection into the portal vein. Direct contact between islets and blood is a pathophysiological “provocation” that results in the instant blood-mediated inflammatory reaction (IBMIR) and is associated with early islet loss. However, the nature of the various insults on the islets in the blood stream remains mostly unknown. To gain insight into the mechanisms, we utilized a simplified in vitro model in which islets were exposed to blood in different clinically relevant but increasingly challenging, autologous, allogeneic, and xenogeneic combinations. Irrespective of the blood type and species compatibility, islets triggered blood clotting. Islet damage was worse as islet, and blood compatibility diminished, with substantial islet injury after exposure of porcine islets to human blood. Islet damage involved membrane leakage, antibody deposition, complement activation, positive staining for the membrane attack complex, and mitochondrial dysfunction. Islet damage occurred even after exposure to plasma only, and specific complement inactivation and neutralization of IgM substantially prevented islet damage, indicating the importance of humoral immunity. Efficacious measures are needed to reduce this injury, especially in view of a potential clinical use of porcine islets to treat diabetes.