Miracle-dz/UniFAR-FTUs huggingface dataset:
MHC Class II Compartments in Human Dendritic Cells Undergo Profound Structural Changes Upon Activation

Immature dendritic cells efficiently capture exogenous antigens in peripheral tissues. In an inflammatory environment, dendritic cells are activated and become highly competent antigen‐presenting cells. Upon activation, they lose their ability for efficient endocytosis and gain capability to migrate to secondary lymphoid organs. In addition, peptide loading of MHC class II molecules is enhanced and MHC class II/peptide complexes are redistributed from an intracellular location to the plasma membrane. Using immuno‐electron microscopy, we show that activation of human monocyte‐derived dendritic cells induced striking modifications of the lysosomal multilaminar MHC class II compartments (MIICs), whereby electron‐dense tubules and vesicles emerged from these compartments. Importantly, we observed that MHC class II expression in these tubules/vesicles transiently increased, while multilaminar MIICs showed a strongly reduced labeling of MHC class II molecules. This suggests that formation of the tubules/vesicles from multilaminar MIICs could be linked to transport of MHC class II from these compartments to the cell surface. Further characterization of endocytic organelles with lysosomal marker proteins, such as the novel dendritic cell‐specific lysosomal protein DC‐LAMP, HLA‐DM and CD68, revealed differential sorting of these markers to the tubules and vesicles.
Clinical and molecular genetics of Leber's congenital amaurosis: a multicenter study of Italian patients.

PURPOSE To identify the molecular basis of Leber's congenital amaurosis (LCA) in a cohort of Italian patients and to perform genotype-phenotype analysis. METHODS DNA samples from 95 patients with LCA were analyzed by using a microarray chip containing disease-associated sequence variants in eight LCA genes. In addition, all patients in whom no mutations were identified by microarray were subjected to sequence analysis of the CEP290 gene. Patients with mutations identified underwent a detailed ophthalmic evaluation. RESULTS Disease-causing mutations were identified in 28% of patients, and twelve novel variants were identified. Mutations occurred more frequently in the RPE65 (8.4%), CRB1 (7.4%), and GUCY2D (5.2%) genes. Mutations in CEP290 were found in only 4.2% of the patients analyzed. Clinical assessment of patients carrying RPE65 or CRB1 mutations revealed the presence of retained visual capabilities in the first decade of life. RPE65 mutations were almost always associated with normal macular thickness, as assessed by optical coherence tomography (OCT), whereas CRB1 mutations were associated with reduced retinal thickness and a coarsely laminated retina. Fundus autofluorescence was mostly observed in patients with RPE65 and GUCY2D mutations and was not elicitable in patients carrying CRB1. CONCLUSIONS RPE65 gene mutations represented a significant cause of LCA in the Italian population, whereas GUCY2D and CEP290 mutations had a lower frequency than that found in other reports. This finding suggests that the genetic epidemiology of LCA in Italy is different from that reported in the United States and in northern European countries. Autofluorescence in patients with RPE65 mutations was more frequently associated with preserved retinal thickness, which suggests that these mutations are not associated with progression of retinal degeneration. Therefore, normal retinal thickness (identified with OCT) and fundus autofluorescence may be the means with which to identify patients with LCA who carry RPE65 mutations, which are expected to be a potential gene therapy target in the near future.
Fast Semi-Lagrangian Schemes for the Eikonal Equation and Applications

We introduce and analyze a fast version of the semi-Lagrangian algorithm for front propagation originally proposed in [M. Falcone, “The minimum time problem and its applications to front propagation,” in Motion by Mean Curvature and Related Topics, A. Visintin and G. Buttazzo, eds., de Gruyter, Berlin, 1994, pp. 70-88]. The new algorithm is obtained using the local definition of the approximate solution typical of semi-Lagrangian schemes and redefining the set of “neighboring nodes” necessary for fast marching schemes. A new proof of convergence is needed since that definition produces a new narrow band centered at the interphase which is larger than the one used in fast marching methods based on finite differences. We show that the new algorithm converges to the viscosity solution of the problem and that its complexity is $O(N \log N_{nb})$, as it is for the fast marching method based on finite difference ($N$ and $N_{nb}$ being, respectively, the total number of nodes and the number of nodes in the narrow band). A new sufficient condition for the convergence of the standard finite difference fast marching method is also given. We present several tests comparing the two algorithms and other fast methods (e.g., fast sweeping) on a series of benchmarks which include the minimum time problem and the shape-from-shading problem.
Phase II trial of a 3-hour infusion of paclitaxel in previously untreated patients with advanced non-small-cell lung cancer.

PURPOSE To determine the antitumor activity and toxicity of paclitaxel administered as a 3-hour infusion in patients with advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS Fifty-one patients with advanced measurable or assessable NSCLC and performance status 0 to 2 who had not received prior chemotherapy were treated with paclitaxel 175 mg/m2 over 3 hours with premedication. Cycles were repeated every 3 weeks for a maximum of nine cycles. Most patients had prior radiotherapy (57%), extrathoracic metastatic disease (65%), and measurable disease (75%). Twenty-two percent had previously untreated stage III disease. RESULTS The objective response rate was five of 51 (10%; 95% confidence interval, 3% to 21%). No subgroup with a higher response rate could be identified. There were no complete responses (CRs) and all responses lasted less than 5 months. Treatment was well tolerated with brief World Health Organization (WHO) grade IV neutropenia in only 16% of patients. Grade III/IV myalgia/athralgia occurred in 22% of patients. No significant hypersensitivity reactions occurred. CONCLUSION The antitumor activity of this dose and schedule appears inferior to that reported in previously published phase II trials in NSCLC that used higher doses of paclitaxel infused over 24 hours, although confidence intervals for response overlap. Determining the optimal dose and schedule for using paclitaxel in NSCLC requires further investigation, and these results should caution against using shorter infusions outside appropriate clinical trials.
CDKN2A (P16INK4a) and CDK4 mutation analysis in 131 Australian melanoma probands: Effect of family history and multiple primary melanomas

Mutation analysis of two genes involved in melanoma susceptibility (CDKN2A/p16INK4a and CDK4) was undertaken in 131 probands with a family history of melanoma. Screening of all three exons of CDKN2A and exon 2 of CDK4 by single‐strand conformation polymorphism (SSCP) analysis and/or direct sequencing identified a total of 10 different CDKN2A germline mutations, including 6 not previously described in the germline. All but one has been previously proven to, or is likely to, affect the structure and function of p16INK4a. The incidence of CDKN2A mutation was 8.4% (11/131), but was significantly higher in families with three or more cases of melanoma (10/66, 15.1%) than in those in which only two relatives were affected (1/65, 1.5%). The incidence of CDKN2A mutation was also higher in families with three or more cases of melanoma and at least one member with multiple primary melanomas (6/19, 31.6%) than in similar families without multiple primary melanomas (4/47, 8.5%). One novel CDK4 variant of uncertain significance was found in a kindred that also carries a CDKN2A mutation. Genes Chromosomes Cancer 25:339–348, 1999. © 1999 Wiley‐Liss, Inc.
Research students and the Loughborough institutional repository

This article investigates the potential role for research students in an institutional repository (IR). Face-to-face interviews with 34 research students at Loughborough University were carried out. Using a mixture of closed and open questions, the interviews explored the students’ experiences and opinions of publishing, open access and the proposed Loughborough repository. As both authors and readers, students were most interested in access to complete theses, postprints and conference papers. The ability to disseminate their work and to receive feedback and commentary were the most important motivators to students depositing work in the IR, closely followed by the principle of open access. The greatest deterrents were the risk of being unable to publish elsewhere later, the ownership of copyright and plagiarism. Appropriate recommendations are made for the implementation of an institutional repository.
Is Strategic Proactivity a Driver of an Environmental Strategy? Effects of Innovation and Internationalization Leadership

This study analyses strategic proactivity as a driving factor in the implementation of an advanced environmental strategy in a firm. Strategic proactivity is defined as a firm’s tendency to initiate voluntary changes instead of reacting to events in the environment and according to previous literature, can be interpreted as a combination of internal factors that characterise a firm’s business strategy as that of a prospector firm. In this study, we measured this through innovation, with two variables related to the firm’s entire production cycle: R&D expenditure and patents. However, we also considered two more strategic proactivity indicators: innovation proactivity and internationalisation proactivity. These two proactivity variables take into account the innovative and international actions of the firms, going beyond the actions usually taken by firms in the same sector. Using panel data methodology, we obtained results that show that firms who invest in R&D and patent their innovations achieve more advanced positions in their environmental strategies. Empirical evidence also shows that firms with a greater innovation effort throughout the production cycle (product, process, organisation and marketing) than their competitors also attain more advanced positions (proactivity) in environmental matters. In other words, innovation proactivity is a driver of environmental strategy. In relation to internationalization, the results also showed that firms that operate in a larger geographical area than their competitors adapt to the most demanding environmental legislation, placing them in a position of environmental leadership in their respective sectors. The inclusion of internationalization as an indicator of strategic proactivity, the measurement of proactivity variables and the correction of firms’ specific unobserved aspects are some of this paper’s contributions.
Simultaneous determination of alpha-fetoprotein and free beta-human chorionic gonadotropin by element-tagged immunoassay with detection by inductively coupled plasma mass spectrometry.

BACKGROUND An inductively coupled plasma mass spectrometry (ICP-MS)-based immunoassay has been proposed independently by Baranov et al. (Anal Chem 2002;74:1629-36) and our group, but the applicability of this method for multianalyte analysis in clinical samples has not been fully illustrated. We developed a dual-label immunoassay method for the simultaneous determination of alpha-fetoprotein (AFP) and free beta-human chorionic gonadotropin (hCGbeta) in human serum. METHODS Monoclonal antibodies immobilized on microtiter plates captured AFP and hCGbeta, which were detected by use of Eu(3+)-labeled anti-AFP and Sm(3+)-labeled anti-hCGbeta monoclonal antibodies. Eu(3+) and Sm(3+) were dissociated from the immunocomplex with HNO(3) solution (10 mL/L) and delivered by peristaltic pump to the ICP mass spectrometer. RESULTS The measurable ranges of AFP and hCGbeta were 4.6-500 and 5.0-170 microg/L, respectively, with detection limits of 1.2 and 1.7 microg/L (3 SD above mean of zero calibrator), respectively. The intraassay imprecision (CV) for AFP was 8.3%, 4.0%, and 2.7% at 16.3, 86, and 354 microg/L, respectively, and the interassay CV was 10%, 5.7%, and 3.5%. For hCGbeta, the intraassay CV was 5.4%, 6.4%, and 3.1%, respectively, at 10.5, 45.2, and 105 microg/L, and the interassay CV was 7.2%, 8.0%, and 3.7%. Comparison with IRMAs for AFP and hCGbeta yielded correlation coefficients (r(2)) of 0.97 and 0.95. CONCLUSIONS Two proteins can be measured simultaneously by immunoassays using two rare earth elemental tags (Eu(3+) and Sm(3+)) and ICP-MS detection. The multielement capability and the multiple potential elemental labels make ICP-MS attractive for multianalyte immunoassays. Implementation of ICP-MS-linked immunoassays may be relatively straightforward because the labeling and immunoreaction procedures have been well developed for clinical time-resolved immunofluorometric assays.
Applications of Artificial Neural Networks (ANNs) in Food Science

Artificial neural networks (ANNs) have been applied in almost every aspect of food science over the past two decades, although most applications are in the development stage. ANNs are useful tools for food safety and quality analyses, which include modeling of microbial growth and from this predicting food safety, interpreting spectroscopic data, and predicting physical, chemical, functional and sensory properties of various food products during processing and distribution. ANNs hold a great deal of promise for modeling complex tasks in process control and simulation and in applications of machine perception including machine vision and electronic nose for food safety and quality control. This review discusses the basic theory of the ANN technology and its applications in food science, providing food scientists and the research community an overview of the current research and future trend of the applications of ANN technology in the field.
Disparities in colorectal cancer screening rates among Asian Americans and non‐Latino whites

Among Asian Americans, colorectal cancer (CRC) is the second most commonly diagnosed cancer, and it is the third highest cause of cancer‐related mortality. The 2001 California Health Interview Survey (CHIS 2001) was used to examine 1) CRC screening rates between different Asian‐American ethnic groups compared with non‐Latino whites and 2) factors related to CRC screening. The CHIS 2001 was a population‐based telephone survey that was conducted in California. Responses about CRC screening were analyzed from 1771 Asian Americans age 50 years and older (Chinese, Filipino, South Asian, Japanese, Korean, and Vietnamese). The authors examined two CRC screening outcomes: individuals who ever had CRC screening and individuals who were up to date for CRC screening. For CRC screening, fecal occult blood test (FOBT), sigmoidoscopy/colonoscopy, and any other form of screening were examined. CRC screening of any kind was low in all populations, and Koreans had the lowest rate (49%). Multivariate analysis revealed that, compared with non‐Latino whites, Koreans were less likely to undergo FOBT (odds ratio [OR], 0.40; 95% confidence interval [95% CI], 0.25–0.62), and Filipinos were the least likely to undergo sigmoidoscopy/colonoscopy (OR, 0.62; 95% CI, 0.44–0.88) or to be up to date with screening (OR, 0.68; 95% CI, 0.48–0.97). Asian Americans were less likely to undergo screening if they were older, male, less educated, recent immigrants, living with ≥ 3 individuals, poor, or uninsured. Asian‐American populations, especially Koreans and Filipinos, are under‐screened for CRC. Outreach efforts could be more focused on helping Asian Americans to understand the importance of CRC screening, providing accurate information in different Asian languages. Other strategies for increasing CRC screening may include using a more family‐centered approach and using qualified translators. Cancer 2005. © 2005 American Cancer Society.
Attenuation-Corrected 99 mTc-Tetrofosmin Single-Photon Emission Computed Tomography in the Detection of Viable Myocardium : Comparison With Positron Emission Tomography Using 18 F-Fluorodeoxyglucose

Objectives. The purpose of this study was to assess the efficacy of attenuation-corrected (AC) technetium-99m (Tc)tetrofosmin single-photon emission computed tomography (SPECT) in detecting viable myocardium compared to Ffluorodeoxyglucose (FDG) positron emission tomography (PET). Background. The role of Tc-labeled perfusion tracers in the assessment of myocardial viability remains controversial. Attenuation artifacts affect the diagnostic accuracy of SPECT images. Methods. Twenty-four patients with coronary artery disease (mean left ventricular ejection fraction 30%) underwent resting Tc-tetrofosmin SPECT and FDG PET imaging. Both AC and non–attenuation-corrected (NC) SPECT images were generated. Results. Using a 50% threshold for viability by FDG PET, the percentage of concordant segments of viability between Tctetrofosmin and FDG on the patient basis increased from 79.8% 6 14.0% (mean 6 SD) on the NC images to 90.8% 6 10.6% on the AC images (p 5 0.002). The percentage of Tc-tetrofosmin defect segments within PET-viable segments, an estimate for the degree of underestimation of viability, decreased from 19.8% 6 15.2% on the NC images to 9.7% 6 12.6% on the AC images (p 5 0.01). Similar results were obtained when a 60% threshold was used to define viability by FDG PET. When the anterior-lateral and inferior-septal regions were separately analyzed, the effect of attenuation correction was significant only in the inferior-septal region. Conclusions. The results indicate that AC Tc-tetrofosmin SPECT improves the detection of viable myocardium mainly by decreasing the underestimation of viability particularly in the inferior-septal region, although some underestimation/ overestimation of viability may still occur even with attenuation correction. (J Am Coll Cardiol 1998;32:927–35) ©1998 by the American College of Cardiology
Infliximab in the treatment of extra‐intestinal manifestations of Crohn's disease

Background: Crohn's disease (CD) is frequently associated with extra‐intestinal manifestations (EIMs) and infliximab has been recently proposed for the treatment of CD with EIMs. Our aim was to evaluate the short‐term efficacy of infliximab in this treatment. Patients and methods: Thirty CD patients were treated with infliximab. Fifteen patients (50%) showed EIMs before starting therapy. Ten patients presented an arthritis (five sacroiliitis, five spondylitis), with six also reporting peripheral arthralgias. Four patients presented cutaneous EIMs while three patients had an ocular EIM. Results: At week 10, all patients reported an improvement in EIMs. Regarding arthritis, ASAS20 and ASAS40 improvement was observed in 80% and 60% of patients, respectively. In the four patients with cutaneous EIMs and in the three with ocular EIMs, complete healing was observed. Recurrence was observed in 10 out of 15 patients (66%) and a second course of treatment with infliximab was required. This proved to be effective in all cases except for one patient who stopped treatment because of a severe adverse reaction. Conclusions: Infliximab is an effective drug in the short‐term treatment of EIMs complicating CD. Although relapse of EIMs occurs frequently, retreatment ensures effective control of the symptoms.
Non-local diffusion-weighted image super-resolution using collaborative joint information

Due to the clinical durable scanning time and other physical constraints, the spatial resolution of diffusion-weighted magnetic resonance imaging (DWI) is highly limited. Using a post-processing method to improve the resolution of DWI holds the potential to improve the investigation of smaller white-matter structures and to reduce partial volume effects. In the present study, a novel non-local mean super-resolution method was proposed to increase the spatial resolution of DWI datasets. Based on a non-local strategy, joint information from the adjacent scanning directions was taken advantage of through the implementation of a novel weighting scheme. Besides this, an efficient rotationally invariant similarity measure was introduced for further improvement of high-resolution image reconstruction and computational efficiency. Quantitative and qualitative comparisons in synthetic and real DWI datasets demonstrated that the proposed method significantly enhanced the resolution of DWI, and is thus beneficial in improving the estimation accuracy for diffusion tensor imaging as well as high-angular resolution diffusion imaging.
A Dietary Agonist of Transient Receptor Potential Cation Channel V3 Elicits Endothelium-Dependent Vasodilation

The Mediterranean diet may be responsible for lower cardiovascular disease rates in Southern versus Northern European countries. Oregano is used abundantly in Mediterranean cooking, but potential cardiovascular benefits have not been investigated. Carvacrol, present in oregano, activates the transient receptor potential (TRP) cation channels TRPA1 and TRPV3. We hypothesized that chemosensing of this dietary molecule by TRP channels in the endothelium promotes arterial relaxation. TRPA1 and TRPV3 were detected in the endothelium of intact arteries. Carvacrol causes concentration-dependent increases in the intracellular [Ca2+] of native cerebral artery endothelial cells and is more potent (EC50 = 34 μM) than the TRPA1 agonist allyl isothiocyanate (EC50 = 400 μM) or the TRPV3 agonist eugenol (EC50 = 2.3 mM). Carvacrol also activates TRPV3-like cation currents in cerebral artery endothelial cells. Carvacrol elicits vasodilation of intact cerebral arteries (EC50 = 4.1 μM) that is accompanied by smooth muscle hyperpolarization and a decrease in the intracellular [Ca2+] of arterial myocytes. Endothelium disruption inhibits carvacrol-induced vasodilation, but block of nitric-oxide synthase and cyclooxygenase activity does not alter the response. Vasodilation in response to carvacrol is inhibited when blockers of Ca2+-activated K+ channels are present in the lumen or when the inwardly rectifying K+ channel blocker BaCl2 is present in the superfusion bath. Carvacrol-induced dilation is not diminished by a TRPA1 antagonist but is inhibited by the TRPV blocker ruthenium red. Our findings show that oregano can relax arteries by activating TRPV3 channels in the endothelium. This effect may account for some of the cardioprotective effects of the Mediterranean diet.
Outcome evaluation of the 1997 American Joint Committee on Cancer staging system for prostate carcinoma treated by radiation therapy

The 1997 American Joint Committee on Cancer (AJCC) staging system condensed unilobular tumors into one entity and continues the use of both imaging and biopsy to alter classification status in T2 and T3 carcinomas. This study analyzes the biochemical freedom from disease recurrence (bNED) outcome in a large database to determine whether these changes reflect outcome differences.