Miracle-dz/UniFAR-FTUs huggingface dataset:
Development of a quantitative method to analyse tumour cell invasion in organotypic culture

Tumour invasion is a dynamic process occurring in three dimensions and involving interactions between both tumour and stromal cells. Experimental analysis of squamous carcinoma cell invasion has often used the organotypic gel culture system, which is generated by plating tumour cells on to a synthetic stroma composed of a collagen gel embedded with fibroblasts. Unfortunately, quantitation of invasion in these organotypic gels has relied largely on subjective pathological opinion, which may be influenced by different patterns of tumour cell infiltration. Therefore a computer‐assisted digital image analysis system that assesses invasion objectively and provides a numerical ‘Invasion Index’ was developed. The Invasion Index, by combining depth and pattern of invasion in a single value, establishes a quantitative value that allows assessment of the influences of positive and negative regulation of tumour invasion. These data demonstrate that the organotypic gel system is a robust, accurate, and reproducible method for measuring tumour cell invasion. They also show that the Invasion Index can be used after organotypic gels have been implanted in mice for up to 6 weeks. Illustrative examples of how various factors influence the invasion of squamous carcinoma cells in three dimensions both in vitro and in vivo are provided. Copyright © 2005 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Revisiting the ENSO–SSW Relationship

AbstractStratospheric sudden warming (SSW) events exhibit pronounced interannual variability. Based on zonal wind reversals at 60°N and 10 hPa, it has been suggested that SSW events occur more preferentially during El Nino–Southern Oscillation (ENSO) winters (both El Nino and La Nina winters) than during ENSO-neutral winters. This relationship is reevaluated here by considering seven different SSW definitions. For all definitions, SSW events are detected more frequently during El Nino winters than during ENSO-neutral winters, in agreement with a strengthened planetary-scale wave activity. However, such a systematic relationship is not found during La Nina winters. While three SSW definitions, including the wind-reversal definition, show a higher SSW frequency during La Nina winters than during ENSO-neutral winters, other definitions show no difference or even lower SSW frequency during La Nina winters. This result, which is qualitatively insensitive to the choice of reanalysis datasets, ENSO indices, and .
Small Molecule Suppressors of Drosophila Kinesin Deficiency Rescue Motor Axon Development in a Zebrafish Model of Spinal Muscular Atrophy

Proximal spinal muscular atrophy (SMA) is the most common inherited motor neuropathy and the leading hereditary cause of infant mortality. Currently there is no effective treatment for the disease, reflecting a need for pharmacologic interventions that restore performance of dysfunctional motor neurons or suppress the consequences of their dysfunction. In a series of assays relevant to motor neuron biology, we explored the activities of a collection of tetrahydroindoles that were reported to alter the metabolism of amyloid precursor protein (APP). In Drosophila larvae the compounds suppressed aberrant larval locomotion due to mutations in the Khc and Klc genes, which respectively encode the heavy and light chains of kinesin-1. A representative compound of this class also suppressed the appearance of axonal swellings (alternatively termed axonal spheroids or neuritic beads) in the segmental nerves of the kinesin-deficient Drosophila larvae. Given the importance of kinesin-dependent transport for extension and maintenance of axons and their growth cones, three members of the class were tested for neurotrophic effects on isolated rat spinal motor neurons. Each compound stimulated neurite outgrowth. In addition, consistent with SMA being an axonopathy of motor neurons, the three axonotrophic compounds rescued motor axon development in a zebrafish model of SMA. The results introduce a collection of small molecules as pharmacologic suppressors of SMA-associated phenotypes and nominate specific members of the collection for development as candidate SMA therapeutics. More generally, the results reinforce the perception of SMA as an axonopathy and suggest novel approaches to treating the disease.
Therapeutic application of collateral ventilation with pulmonary drainage in the treatment of diffuse emphysema: report of the first three cases.

OBJECTIVE To report the results obtained in three patients with diffuse pulmonary emphysema during the pre- and post-operative periods following a new surgical technique: collateral ventilation with lung parenchyma drainage. METHODS Patients suffering from pulmonary failure and disabling dyspnea, despite having received the gold standard treatment, including pulmonary rehabilitation, were selected for the evaluation of pulmonary drainage. During the pre- and post-operative periods, patients were submitted to plethysmography and six-minute walk tests, as well as completing the following quality of life questionnaires: Medical Outcomes Study 36-item Short-Form Health Survey, Saint George's Respiratory Questionnaire, Eastern Cooperative Oncology Group Performance Status and Medical Research Council Scale. In all three cases, the postoperative follow-up period was at least 300 days. The tests were performed at the following time points: during the pre-operative period; between post-operative days 30 and 40; and on post-operative day 300. Data were analyzed using profile plots of the means. RESULTS When the results obtained in the pre-operative period were compared to those obtained at the two post-operative time points evaluated, improvements were observed in all parameters studied. CONCLUSIONS The results suggest that the surgical technique proposed for the treatment of patients suffering from severe diffuse emphysema successfully reduces the debilitating symptoms of these patients, improving their quality of life considerably.
The nature and processing of errors in interactive behavior

Understanding the nature of errors in a simple, rule-based task—programming a VCR—required analyzing the interactions among human cognition, the artifact, and the task. This analysis was guided by least-effort principles and yielded a control structure that combined a rule hierarchy task-to-device with display-based difference-reduction. A model based on this analysis was used to trace action protocols collected from participants as they programmed a simulated VCR. Trials that ended without success (the show was not correctly programmed) were interrogated to yield insights regarding problems in acquiring the control structure. For successful trials (the show was correctly programmed), steps that the model would make were categorized as matches to the model; steps that the model would not make were violations of the model. The model was able to trace the vast majority of correct keystrokes and yielded a business-as-usual account of the detection and correction of errors. Violations of the model fell into one of two fundamental categories. The model provided insights into certain subcategories of errors; whereas, regularities within other subcategories of error suggested limitations to the model. Although errors were rare when compared to the total number of correct actions, they were important. Errors were made on 4% of the keypresses that, if not detected, would have prevented two-thirds of the shows from being successfully recorded. A misprogrammed show is a minor annoyance to the user. However, devices with the approximate complexity of a VCR are ubiquitous and have found their way into emergency rooms, airplane cockpits, power plants, and so on. Errors of ignorance may be reduced by training; however, errors in the routine performance of skilled users can only be reduced by design.
KIBRA gene polymorphism has no association with verbal or visual episodic memory performance

Inter-individual variability in memory performance has been suggested to result, in part, from genetic differences in the coding of proteins involved in long-term potentiation (LTP). The present study examined the effect of a single-nucleotide polymorphism (SNP) in the KIBRA gene (rs17070145) on episodic memory performance, using multiple measures of verbal and visual episodic memory. A total of 256 female and 130 male healthy, older adults (mean age = 60.86 years) were recruited from the Tasmanian Healthy Brain Project (THBP), undergoing both neuropsychological and genetic testing. The current study showed no significant effect of the KIBRA polymorphism on performance on the Rey Auditory Verbal Learning Task, Logical Memory test, Paired Associates Learning test or Rey Complex Figure Task. The results suggest there is little to no functional significance of KIBRA genotype on episodic memory performance, regardless of modality.
The Effect of Some Remineralization Materials and Resin Infiltration (ICON) on the Depth of White Spot Lesions

Background: White spot lesions (WSLs) are subsurface enamel demineralization manifested as white opacities which had an esthetic problem. The purpose of this in-vitro study was to evaluate the lesion depth improvement of WSLs following application of fluoride varnish, tooth mousse and resin infiltration (ICON). Materials and methods: Artificial WSLs were created on 120 premolar teeth using demineralization solution with pH (44.5). Samples randomly allocated into four groups; fluoride varnish, tooth mousse, ICON and untreated group. Groups were discolored in Cola and orange juice for 24 hours. Teeth were ground sectioned by longitudinal cutting then these sections examined and photographed under stereomicroscope at 12X magnification then analyzed for lesion depth measurements using Image Pro Plus computer software to record the average lesion depth (μm). Results: The mean values of lesion depth for WSLs groups in DDW, Cola and orange juice increased after formation of WSLs then decreased with the fluoride varnish, tooth mousse and ICON. There was a statistically significant difference between the WSLs, fluoride and Mousse group in DDW and Cola, while there was no statistically significant effect of ICON on WSL in DDW (p=0.341)and Cola (p=0.210). Conclusions: Formation of WSLs is associated with significant lesion depth changes and the use of fluoride varnish, tooth mousse and ICON could return minerals or resin to subsurface enamel of WSLs and improve lesion depth in different soft drinks.
A prospective study of weight training and risk of type 2 diabetes mellitus in men.

BACKGROUND The role of weight training in the primary prevention of type 2 diabetes mellitus (T2DM) is largely unknown. METHODS To examine the association of weight training with risk of T2DM in US men and to assess the influence of combining weight training and aerobic exercise, we performed a prospective cohort study of 32 002 men from the Health Professionals Follow-up Study observed from 1990 to 2008. Weekly time spent on weight training and aerobic exercise (including brisk walking, jogging, running, bicycling, swimming, tennis, squash, and calisthenics/rowing) was obtained from questionnaires at baseline and biennially during follow-up. RESULTS During 508 332 person-years of follow-up (18 years), we documented 2278 new cases of T2DM. In multivariable-adjusted models, we observed a dose-response relationship between an increasing amount of time spent on weight training or aerobic exercise and lower risk of T2DM (P < .001 for trend). Engaging in weight training or aerobic exercise for at least 150 minutes per week was independently associated with a lower risk of T2DM of 34% (95% CI, 7%-54%) and 52% (95% CI, 45%-58%), respectively. Men who engaged in aerobic exercise and weight training for at least 150 minutes per week had the greatest reduction in T2DM risk (59%; 95% CI, 39%-73%). CONCLUSIONS Weight training was associated with a significantly lower risk of T2DM, independent of aerobic exercise. Combined weight training and aerobic exercise conferred a greater benefit.
Dietary Adequacy in Older Adult Nursing Home Residents of the Northern Iberian Peninsula

According to the latest data, Spain (19.4%) and Portugal (21.8%) are the two European countries with the highest percentage of older adults. Concerns about diet quality are increasing, especially among institutionalized older people, who are at the greatest risk of malnutrition. To assess the adequacy of dietary intake of 186 older adults (>65 y) institutionalized in public nursing homes (NH) in Galicia (Northwest Spain) and the Porto district (Northern Portugal), a cross-sectional study has been carried out. The double-weighing method and a country-specific food composition database were employed for nutritional assessment. Nutritional adequacy was assessed based on the recommendations of the EFSA and WHO. Caloric intake in Spanish NHs was higher than in Portuguese facilities; 20.3% and 35.8% of Spanish and Portuguese residents, respectively, had a protein intake below the EFSA recommendation, and 46.2% and 44.9% of residents in Portugal and Spain, respectively, had lipid intakes below the reference intake range. Further, 45.5% of the residents in Portugal and 66.9% in Spain had a carbohydrate intake within the recommended range. Salt intake was higher than the recommendation for 67.0% and 32.3% of the residents in Spain and Portugal, respectively. This study supports the notion that institutionalized older adults are prone to significant nutritional inadequacies.
Response of the ITCZ to Northern Hemisphere cooling

Climate simulations, using models with different levels of complexity, indicate that the north‐south position of the intertropical convergence zone (ITCZ) responds to changes in interhemispheric temperature contrast. Paleoclimate data on a variety of timescales suggest a similar behavior, with southward displacements of the ITCZ and associated changes in tropical atmospheric circulation during cold periods in the Northern Hemisphere. To identify a mechanism by which ITCZ displacements can be forced from the extratropics, we use a climate model with idealized geography and a simple slab ocean. We cool the northern extratropics and warm the southern extratropics to represent the asymmetric temperature changes associated with glacial‐interglacial and millennial‐scale climate variability. A southward shift in the ITCZ occurs, along with changes in the trade winds and an asymmetric response of the Hadley circulation. Changes in atmospheric heat exchange between the tropics and midlatitudes are the likely cause of this response, suggesting that this mechanism may play an important role in ITCZ displacements on timescales from decadal to glacial‐interglacial.
Epidemiology of hepatitis B virus in Africa, its genotypes and clinical associations of genotypes

Of approximately 360 million people in the world chronically infected with hepatitis B virus (HBV), 65 million reside in Africa. Thus, Africa, with 12% of the world's population, carries approximately 18% of the global burden of HBV infection, with hepatocellular carcinoma and cirrhosis accounting for 2% of the continent's annual deaths. Despite HBV being endemic or hyperendemic in Africa, there is a paucity of data on the genotypes and their distribution. Genotype A is found mainly in southern, eastern and central Africa. Most African genotype A strains belong to subgenotype A1, with subgenotype A3 found in western Africa. Genotype D prevails in northern countries and genotype E in western and central Africa. Ithas become increasingly evident that heterogeneity in the global distribution of HBV genotypes may be responsible for differences in the clinical outcomes of HBV infections and the response to antiviral treatment and vaccination. A limited number of studies have been published relating genotypes to clinical outcomes in African countries. Because observations from other regions of the world can not be extrapolated from one locale to another, the HBV strains circulating in Africa should be studied and related to clinical outcomes.
Relative-Error CUR Matrix Decompositions

Many data analysis applications deal with large matrices and involve approximating the matrix using a small number of “components. ” Typically, these components are linear combinations of the rows and columns of the matrix, and are thus difficult to interpret in terms of the original features of the input data. In this paper, we propose and study matrix approximations that are explicitly expressed in terms of a small number of columns and/or rows of the data matrix, and thereby more amenable to interpretation in terms of the original data. Our main algorithmic results are two randomized algorithms which take as input an $m\times n$ matrix $A$ and a rank parameter $k$. In our first algorithm, $C$ is chosen, and we let $A'=CC^+A$, where $C^+$ is the Moore-Penrose generalized inverse of $C$. In our second algorithm $C$, $U$, $R$ are chosen, and we let $A'=CUR$. ($C$ and $R$ are matrices that consist of actual columns and rows, respectively, of $A$, and $U$ is a generalized inverse of their intersection.) For each algorithm, we show that with probability at least $1-\delta$, $\|A-A'\|_F\leq(1+\epsilon)\,\|A-A_k\|_F$, where $A_k$ is the “best” rank-$k$ approximation provided by truncating the SVD of $A$, and where $\|X\|_F$ is the Frobenius norm of the matrix $X$. The number of columns of $C$ and rows of $R$ is a low-degree polynomial in $k$, $1/\epsilon$, and $\log(1/\delta)$. Both the Numerical Linear Algebra community and the Theoretical Computer Science community have studied variants of these matrix decompositions over the last ten years. However, our two algorithms are the first polynomial time algorithms for such low-rank matrix approximations that come with relative-error guarantees; previously, in some cases, it was not even known whether such matrix decompositions exist. Both of our algorithms are simple and they take time of the order needed to approximately compute the top $k$ singular vectors of $A$. The technical crux of our analysis is a novel, intuitive sampling method we introduce in this paper called “subspace sampling. ” In subspace sampling, the sampling probabilities depend on the Euclidean norms of the rows of the top singular vectors. This allows us to obtain provable relative-error guarantees by deconvoluting “subspace” information and “size-of-$A$” information in the input matrix. This technique is likely to be useful for other matrix approximation and data analysis problems.
Exploring Challenges Forefront to Family Business Leaders: A Perspective of Family Business Owners

Family businesses, owing to their unique blend of family dynamics and business operations, often face distinctive hurdles that can significantly impact their sustainability and growth. This qualitative study delves into the multifaceted challenges that confront family business leaders, as seen through the eyes of family business owners, which is a missing aspect in the extant literature database. Through in-depth interviews and thematic analysis, this study aims to shed light on the key challenges family business leaders encounter. The findings of the study reveal that the family business leaders have challenges related to the succession planning, financial management, conflict resolution, communication breakdown, governance, HRM, and the evolving business environment in the day-to-day business operation. These findings further echoed the need for a personalized approach and support systems to face the challenges and to be successful in the long run. These results not only contribute to the existing literature related to the management of family business, but also provide a very practical use to the practitioners in increasing the strength of both the family and business while operating within the context with such complexity.
The transcription factor B-Myb is essential for S-phase progression and genomic stability in diploid and polyploid megakaryocytes

The cell-cycle-regulated Myb-family transcription factor B-Myb is crucial during S phase in many diploid cell types. We have examined the expression and function of B-Myb in megakaryocytic differentiation, during which cells progress from a diploid to a polyploid state. In contrast to terminal differentiation of most haematopoietic cells, during which B-myb is rapidly downregulated, differentiation of megakaryocytes is accompanied by continued B-myb RNA and protein expression. Overexpression of B-Myb in a megakaryoblastic cell line resulted in an increase in the number of cells entering S phase and, upon induction of differentiation, the fraction of cells actively endoreplicating increased. By contrast, reduction of B-Myb levels using short interfering (si)RNA resulted in a decline in S-phase progression during both normal and endoreplicative DNA synthesis. This effect correlated with aberrant localisation of initiation of DNA replication within the nucleus and an increased fraction of cells in mitosis. Chromosomal fragmentation and other aberrations, including shorter, thicker chromatids, end-to-end fusion, and loss of a chromatid, suggest that reduced B-Myb activity is also associated with structural chromosomal instability.
The Motion Picture Industry: Critical Issues in Practice, Current Research, and New Research Directions

Laminar articles are disclosed comprising a heterogeneous melt of (a) a polyolefin, (b) a barrier resin comprising a blend of a condensation polymer incompatible with the polyolefin such as a polyamide and a phenol-formaldehyde resin, and (c) a compatibilizer. A process for making such laminar articles is also disclosed. Multilayer structures incorporating this barrier resin are also disclosed.
FoldGPCR: Structure prediction protocol for the transmembrane domain of G protein‐coupled receptors from class A

Building reliable structural models of G protein‐coupled receptors (GPCRs) is a difficult task because of the paucity of suitable templates, low sequence identity, and the wide variety of ligand specificities within the superfamily. Template‐based modeling is known to be the most successful method for protein structure prediction. However, refinement of homology models within 1–3 Å Cα RMSD of the native structure remains a major challenge. Here, we address this problem by developing a novel protocol (foldGPCR) for modeling the transmembrane (TM) region of GPCRs in complex with a ligand, aimed to accurately model the structural divergence between the template and target in the TM helices. The protocol is based on predicted conserved inter‐residue contacts between the template and target, and exploits an all‐atom implicit membrane force field. The placement of the ligand in the binding pocket is guided by biochemical data. The foldGPCR protocol is implemented by a stepwise hierarchical approach, in which the TM helical bundle and the ligand are assembled by simulated annealing trials in the first step, and the receptor‐ligand complex is refined with replica exchange sampling in the second step. The protocol is applied to model the human β2‐adrenergic receptor (β2AR) bound to carazolol, using contacts derived from the template structure of bovine rhodopsin. Comparison with the X‐ray crystal structure of the β2AR shows that our protocol is particularly successful in accurately capturing helix backbone irregularities and helix‐helix packing interactions that distinguish rhodopsin from β2AR. Proteins 2010. © 2010 Wiley‐Liss, Inc.