Miracle-dz/UniFAR-FTUs huggingface dataset:
Regional and Developmental Expression of the Npc1 mRNA in the Mouse Brain

Abstract: Niemann‐Pick type C (NP‐C) disease is a fatal, autosomal recessive disorder of cholesterol metabolism that results in progressive central nervous system deterioration and premature death. Recently, a gene mutated in NP‐C disease (NPC1) was identified in both human patients and in the npcnih mouse model. Although the function of the NPC1 gene is at present unknown, determining the pattern of its expression in the brain may facilitate identification of the mechanisms underlying the neuropathology of this disease and in identifying relevant targets for any potential therapeutic intervention. We have used in situ hybridization techniques to characterize the pattern of Npc1 mRNA expression in both the wild‐type and the npcnih mutant mouse brain. In adult animals of both genotypes, the Npc1 mRNA was detected in the majority of neurons in nearly all regions, but at significantly higher levels in the cerebellum and in specific pontine nuclei. Analysis of Npc1 mRNA levels during development in the wild‐type mouse indicated that this transcript was expressed in neurons as early as embryonic day 15 and that a significant region‐specific pattern of expression was established by postnatal day 7. Our data suggest that whereas the NPC1 gene is widely expressed in neurons of the brain, the higher levels of expression in the cerebellum and pontine structures established by early postnatal ages may make these regions more susceptible to neuronal dysfunction in NP‐C disease.
Novel Chimeric Genotype 1b/2a Hepatitis C Virus Suitable for High-Throughput Screening

ABSTRACT A major obstacle in hepatitis C virus (HCV) research has been the lack of a permissive cell culture system that produces infectious viral particles. Significant breakthroughs have been achieved lately in establishing such culture systems. Yet to date, there are no reports of the applications of any of these systems in HCV drug screening. Here, we report the generation of two monocistronic, chimeric genotype 1 full-length HCV genome molecules. These molecules, C33J-Y835C-UBI and C33J-Y835C-FMDV2A, both contain the structural protein region from genotype 1 (subtype 1b, Con1) and the remaining region from the genotype 2a (JFH1) clone. Both contain the humanized Renilla luciferase reporter gene which is separated from the rest of the HCV open reading frame by two different cleavage sites. The viral RNAs replicated efficiently in transfected cells. Viral particles produced were infectious in naïve Huh7.5 cells, and the infectivity could be blocked by monoclonal antibody against a putative HCV entry cofactor, CD81. A pilot high-throughput screen of 900 unknown compounds was executed by both the genotype 2a subgenomic replicon system and the infectious system. Thirty-one compounds were identified as hits by both systems, whereas 78 compounds were identified as hits only for the infectious system, suggesting that the infectious system is capable of identifying inhibitors targeting the viral structural proteins and steps involving them in the viral life cycle. The infectious HCV system developed here provides a useful and versatile tool which should greatly facilitate the identification of HCV inhibitors currently not identified by the subgenomic replicon system.
Relationship between Nanohardness and Mineral Content of Artificial Carious Enamel Lesions

The aim of this study was to compare cross-sectional nanohardness, measured using an ultra-microindentation system, with mineral content, from transversal microradiography, of artificial enamel caries lesions. Sections (85 ± 10 µm) from 16 bovine enamel samples with artificial caries were prepared. The mineral content and cross-sectional nanohardness at known depths from the surface were compared. Both methods showed lesion profiles with a surface layer. The determination of nanohardness seems limited to lesions with a mineral content >45 vol%. There was a moderate linear relationship between mineral content and the square root of nanohardness (R2 = 0.81). It was concluded that the conversion of cross-sectional hardness into mineral content remains questionable and cannot be recommended.
Response of the rare biosphere to environmental stressors in a highly diverse ecosystem (Zodletone spring, OK, USA)

Within highly diverse ecosystems, the majority of bacterial taxa are present in low abundance as members of the rare biosphere. The rationale for the occurrence and maintenance of the rare biosphere, and the putative ecological role(s) and dynamics of its members within a specific ecosystem is currently debated. We hypothesized that in highly diverse ecosystems, a fraction of the rare biosphere acts as a backup system that readily responds to environmental disturbances. We tested this hypothesis by subjecting sediments from Zodletone spring, a sulfide- and sulfur-rich spring in Southwestern OK, to incremental levels of salinity (1, 2, 3, 4, and 10% NaCl), or temperature (28°, 30°, 32°, and 70 °C), and traced the trajectories of rare members of the community in response to these manipulations using 16S rRNA gene analysis. Our results indicate that multiple rare bacterial taxa are promoted from rare to abundant members of the community following such manipulations and that, in general, the magnitude of such recruitment is directly proportional to the severity of the applied manipulation. Rare members that are phylogenetically distinct from abundant taxa in the original sample (unique rare biosphere) played a more important role in the microbial community response to environmental disturbances, compared to rare members that are phylogenetically similar to abundant taxa in the original sample (non-unique rare biosphere). The results emphasize the dynamic nature of the rare biosphere, and highlight its complexity and non-monolithic nature.
A Model of the Joint Distribution of Purchase Quantity and Timing

Prediction of purchase timing and quantity decisions of a household is an important element for success of any retailer. This is especially so for an online retailer, as the traditional brick-and-mortar retailer would be more concerned with total sales. A number of statistical models have been developed in the marketing literature to aid traditional retailers in predicting sales and analyzing the impact of various marketing activities on sales. However, there are two important differences between traditional retail outlets and the increasingly important online retail/delivery companies, differences that prevent these firms from using models developed for the traditional retailers: (1) the profits of the online retailer/delivery company depend on purchase frequency and on purchase quantity, whereas the profits of traditional retailers are simply tied to total sales, and (2) customers in the tails of the frequency distribution are more important to the delivery company than to the retail outlet. Both of these differences are due to the fact that the delivery companies incur a delivery cost for each sale, whereas customers themselves travel to retail outlets when buying from traditional retailers. These differences in costs translate directly into needs that a model must address. For a model intended to be useful to online retailers, the dependent variable should be a bivariate distribution of frequency and quantity, and the frequency distribution must accurately represent consumers in the tails. In this article we develop such a model and apply it to predicting the consumer's joint decision of when to shop and how much to spend at the store. Our approach is to model the marginal distribution of purchase timing and the distribution of purchase quantity co nditional on purchase timing. We propose a hierarchical Bayes model that disentangles the weekly and daily components of the purchase timing. The daily component has a dependence on the weekly component, thereby accounting for strong observed periodicity in the data. For the purchase times, we use the Conway-Maxwell-Poisson distribution, which we find useful to fit data in the tail regions (extremely frequent and infrequent purchasers).
Effect of perceived anonymity in assessments of eating disordered behaviors and attitudes.

OBJECTIVE The present study assessed the effect of perceived anonymity on endorsements of eating disordered behaviors and attitudes across multiple response formats. METHOD Four hundred sixty-nine undergraduate women responded using one of three questionnaire formats: a nominally anonymous true/false condition, an unmatched count condition, or a randomized-response condition. Both the unmatched count and randomized response conditions provided complete response anonymity. RESULTS Significantly different endorsement rates were found for the majority of items when comparing the standard and unmatched count conditions, whereas differences were found for fewer items when comparing the standard and randomized response conditions. Perceived anonymity significantly differed across conditions, with the highest and lowest perceptions of anonymity found for the unmatched count and standard conditions, respectively. DISCUSSION Perceived anonymity and response format affect endorsements of eating disordered behaviors and attitudes, highlighting the necessity of understanding factors that contribute to response bias.
Human T-cell leukemia-lymphoma virus type I (HTLV-I) expression in fresh peripheral blood mononuclear cells from patients with tropical spastic paraparesis/HTLV-I-associated myelopathy

Tropical spastic paraparesis/human T-cell leukemia-lymphoma virus type I (HTLV-I)-associated myelopathy (TSP/HAM) is a chronic neurological illness epidemiologically associated with HTLV-I infection. We investigated the role of HTLV-I in the pathogenesis of this disease by studying viral expression in fresh uncultured peripheral blood mononuclear cells (PBMCs) of six patients of Caribbean origin with TSP/HAM. The PBMC genomic DNA of all the patients studied carried HTLV-I provirus, but viral expression was not detected by Northern (RNA) blot analysis of total cellular PBMC RNA. When the reverse transcriptase polymerase chain reaction technique was used with primers specific for the tax-rex mRNA, all of the samples were positive for this viral mRNA species, regardless of the duration of the illness (range, 2 to 13 years). The splice junctions for the tax-rex mRNA described in cases of HTLV-I-induced adult T-cell leukemia (position 5183 of the envelope and position 7302 of the pX region) were identical in three TSP/HAM cases studied. To ascertain whether viral expression occurred at a low level in many cells or at a high level in a few permissive cells, we performed in situ hybridization on fresh PBMCs from two patients (2 and 7 years after clinical diagnosis), seeking HTLV-I RNA sequences. Our finding indicated that in vivo HTLV-I expression occurred at a high level in a few cells (1 of every 5,000 PBMCs) in both cases studied. The fact that cells of all six patients with TSP/HAM were positive for viral expression, regardless of the time lag from diagnosis, suggests that persistent expression of a viral product(s) may be pivotal in the pathogenesis of TSP/HAM.
A study of the psychological distress in family caregivers of patients with prolonged disorders of consciousness during in-hospital rehabilitation

Objectives: To study psychological distress in a sample of caregivers of patients affected by prolonged disorders of consciousness during hospital stay in the Neurorehabilitation Unit. Materials and methods: Twenty-four caregivers of 22 patients affected by prolonged disorders of consciousness admitted to postacute rehabilitation center, completed self-reported questionnaires for assessment of depressive symptoms, state and trait anxiety, psychophysiological disturbances, prolonged grief disorder, psychological coping strategies, quality of perceived needs, perceived social support, and caregiver burden; at admission, and after four and eight months. Results: At admission depressive symptoms were found in 20/24 caregivers, high levels of anxiety in 16, and relevant psychophysiological disturbances in 10 participants; eight caregivers (32%) met criteria for prolonged grief disorder. The scores on questionnaires did not differ as a function of relatives’ diagnosis (vegetative state vs. minimally conscious state). The longitudinal study (n = 18) showed a progressive and statistically significant increase of “emotional burden” during the hospital stay, whereas the remaining variables did not change significantly. Conclusions: Data confirmed the presence of severe psychological problems in caregivers of patients with prolonged disorders of consciousness. The levels of psychological distress tend to be constant over time, while the emotional burden increases.
Atypical Croup

Objective To report on airway endoscopic findings and gastrointestinal and atopic conditions in a large consecutive series of atypical croup. Study Design Case series with chart review. Setting Tertiary pediatric referral center. Subjects and Methods A surgical database was searched for all children who underwent full airway endoscopy to investigate atypical croup. The primary outcome measure was the prevalence of large airway lesions in patients with atypical croup undergoing endoscopy. Demographics, secondary diagnoses, and rate of positive findings were documented. Age and atopy were correlated using Spearman’s correlation coefficient, and multivariate analysis identified predictors of large airway lesions. Results Eighty patients were identified over a period of 8 years (58 boys; mean [SD] age 4.8 [3.8] years; range, 46 days to 13.7 years). Of the 80 children, 31 had positive airway findings, with 33 large airway lesions demonstrated, including 10 subglottic stenosis, 7 laryngeal clefts, 6 subglottic hemangiomas, 4 tracheomalacia, and 3 laryngomalacia. Esophagitis was diagnosed in 36 children, 5 of whom had eosinophilic esophagitis. Thirty-five children had an atopic condition including asthma, allergic rhinitis, eosinophilic esophagitis, and food allergies. Age correlated with associated atopy (coefficient 0.4, P < .0001) and predicted the presence of any airway lesion (coefficient −0.0625, P < .001) and subglottic stenosis in particular (coefficient −0.0362, P = .001). Prior intubation predicted subglottic stenosis (coefficient 0.267, P = .011). Conclusion Thirty-nine percent of airway endoscopies demonstrated large airway lesions. When eosinophilic esophagitis was sought, it was confirmed in over 1:10 patients. The findings bolster the case for airway endoscopy coupled with allergy and gastrointestinal investigations.
Chemical and Structural Changes in Blood Undergoing Laser Photocoagulation¶

Abstract The treatment of cutaneous vascular lesions (port wine stains etc.) using lasers has been guided by theories based on the “cold” or room-temperature optical properties of the hemoglobin target chromophore. We have recently presented evidence showing that under the influence of laser irradiation, the optical properties of blood in vitro are time and temperature dependent. Such complications are not currently subsumed into the in vivo theory. Here, we study the time-domain optical properties of blood undergoing photocoagulation in vitro using two newly developed time-resolved techniques. We also study the asymptotic effect of laser photocoagulation on the chemical and structural properties of the components of the blood matrix. We present evidence showing that the photocoagulation process involves significant changes in the optical absorption and scattering properties of blood, coupled with photothermally induced chemical and structural changes. We demonstrate the first use of a laser to deliberately generate magnetic resonance imaging contrast in vitro. We show that this technique offers significant potential advantages to in vivo intravenous chemical contrast agent injection.
The atherogenic effect of excess methionine intake

Methionine is the precursor of homocysteine, a sulfur amino acid intermediate in the methylation and transsulfuration pathways. Elevated plasma homocysteine (hyperhomocysteinemia) is associated with occlusive vascular disease. Whether homocysteine per se or a coincident metabolic abnormality causes vascular disease is still an open question. Animals with genetic hyperhomocysteinemia have so far not displayed atheromatous lesions. However, when methionine-rich diets are used to induce hyperhomocysteinemia, vascular pathology is often observed. Such studies have not distinguished the effects of excess dietary methionine from those of hyperhomocysteinemia. We fed apolipoprotein E-deficient mice with experimental diets designed to achieve three conditions: (i) high methionine intake with normal blood homocysteine; (ii) high methionine intake with B vitamin deficiency and hyperhomocysteinemia; and (iii) normal methionine intake with B vitamin deficiency and hyperhomocysteinemia. Mice fed methionine-rich diets had significant atheromatous pathology in the aortic arch even with normal plasma homocysteine levels, whereas mice fed B vitamin-deficient diets developed severe hyperhomocysteinemia without any increase in vascular pathology. Our findings suggest that moderate increases in methionine intake are atherogenic in susceptible mice. Although homocysteine may contribute to the effect of methionine, high plasma homocysteine was not independently atherogenic in this model. Some product of excess methionine metabolism rather than high plasma homocysteine per se may underlie the association of homocysteine with vascular disease.
Hemodynamic Responses to DOCA in Young Pigs

SUMMARY Hemodynamic variables were measured in 20 young pigs; thirteen received subcutaneous implantations of desoxycorticosterone acetate (DOCA) impregnated in Sllastic strips, seven received implants of Silastic strips alone and served as controls. No salt was added to the standard diet of either group. Mean arterial pressure (MAP) rose in a regular pattern in the DOCA-treated pigs, reaching on the average a level significantly greater than that of the control group 48 hours after the implantation. Pressure continued to rise, reaching a plateau 38% above tbat of the preimpiant value 2 weeks later. In some pigs the MAP elevation was caused by an increase in cardiac output (CO); in others it was caused by an increase in total peripheral resistance (TPR). An increase in central venous pressure occurred in many DOCA-treated pigs regardless of whether the increase in MAP was caused by an increase in CO or in TPR. The results indicate that it is arterial pressure per se that is the regulated variable in this model of mineralocorticoid hypertension. The regulating system, whether it resides in the kidney or in the central nervous system, elevates pressure by effecting increases in either CO or TPR.
ICE: A General and Validated Energy Complexity Model for Multithreaded Algorithms

Like time complexity models that have significantly contributed to the analysis and development of fast algorithms, energy complexity models for parallel algorithms are desired as crucial means to develop energy efficient algorithms for ubiquitous multicore platforms. Ideal energy complexity models should be validated on real multicore platforms and applicable to a wide range of parallel algorithms. However, existing energy complexity models for parallel algorithms are either theoretical without model validation or algorithm-specific without ability to analyze energy complexity for a wide-range of parallel algorithms. This paper presents a new general validated energy complexity model for parallel (multithreaded) algorithms. The new model abstracts away possible multicore platforms by their static and dynamic energy of computational operations and data access, and derives the energy complexity of a given algorithm from its work, span and I/O complexity. The new model is validated by different sparse matrix vector multiplication (SpMV) algorithms and dense matrix multiplication (matmul) algorithms running on high performance computing (HPC) platforms (e.g., Intel Xeon and Xeon Phi). The new energy complexity model is able to characterize and compare the energy consumption of SpMV and matmul kernels according to three aspects: different algorithms, different input matrix types and different platforms. The prediction of the new model regarding which algorithm consumes more energy with different inputs on different platforms, is confirmed by the experimental results. In order to improve the usability and accuracy of the new model for a wide range of platforms, the platform parameters of ICE model are provided for eleven platforms including HPC, accelerator and embedded platforms.
Does the combined use of class and sequence diagrams improve the source code comprehension?: results from a controlled experiment

We present the results of a controlled experiment aimed to investigate whether the source code comprehension increases when participants are provided with UML class and sequence diagrams produced in the software design phase. The experiment has been conducted with Master students in Computer Science at the University of Salerno. The data analysis shows that the participants significantly better comprehend source code when it is added with class and sequence diagrams together.
Are patients discharged with care? A qualitative study of perceptions and experiences of patients, family members and care providers

Background Advocates for quality and safety have called for healthcare that is patient-centred and decision-making that involves patients. Objective The aim of the paper is to explore the barriers and facilitators to patient-centred care in the hospital discharge process. Methods A qualitative study using purposive sampling of 192 individual interviews and 26 focus group interviews was conducted in five European Union countries with patients and/or family members, hospital physicians and nurses, and community general practitioners and nurses. A modified Grounded Theory approach was used to analyse the data. Results The barriers and facilitators were classified into 15 categories from which four themes emerged: (1) healthcare providers do not sufficiently prioritise discharge consultations with patients and family members due to time restraints and competing care obligations; (2) discharge communication varied from instructing patients and family members to shared decision-making; (3) patients often feel unprepared for discharge, and postdischarge care is not tailored to individual patient needs and preferences; and (4) pressure on available hospital beds and community resources affect the discharge process. Conclusions Our findings suggest that involvement of patients and families in the preparations for discharge is determined by the extent to which care providers are willing and able to accommodate patients’ and families’ capabilities, needs and preferences. Future interventions should be directed at healthcare providers’ attitudes and their organisation's leadership, with a focus on improving communication among care providers, patients and families, and between hospital and community care providers.