Miracle-dz/UniFAR-FTUs huggingface dataset:
Genetics of brain structure: Contributions from the vietnam era twin study of aging

Understanding the genetics of neuropsychiatric disorders requires an understanding of the genetics of brain structure and function. The Vietnam Era Twin Study of Aging (VETSA) is a longitudinal behavioral genetic study focused on cognitive and brain aging. Here, we describe basic science work carried out within the VETSA MRI study that provides meaningful contributions toward the study of neuropsychiatric disorders. VETSA produced the first comprehensive assessment of the heritability of cortical and subcortical brain structure sizes, all within the same individuals. We showed that neocortical thickness and surface area are largely genetically distinct. With continuous neocortical thickness maps, we demonstrated regional specificity of genetic influences, and that genetic factors did not conform to traditional regions of interest (ROIs). However, there was some evidence for different genetic factors accounting for different types of cortex, and for genetic relationships across cortical regions corresponding to anatomical and functional connectivity and brain maturation patterns. With continuous neocortical surface area maps, we confirmed the anterior–posterior gradient of genetic influences on cortical area patterning demonstrated in animal models. Finally, we used twin methods to create the first map of cortical ROIs based entirely on genetically informative data. We conclude that these genetically based cortical phenotypes may be more appropriate for genetic studies than traditional ROIs based on structure or function. Our results also suggest that cortical volume—the product of thickness and surface area—is a problematic phenotype for genetic studies because two independent sets of genes may be obscured. Examples supporting the validity of these conclusions are provided. © 2013 Wiley Periodicals, Inc.
Hepatocyte Growth Factor Promotes Motor Neuron Survival and Synergizes with Ciliary Neurotrophic Factor*

Hepatocyte growth factor (HGF) has been shown to function as a potent mitogen for a variety of cells, transducing its signal through the c-met tyrosine kinase receptor. Ciliary neurotrophic factor (CNTF) is a cytokine that has been shown to promote survival of motor neurons. We show here that c-met mRNA is present in the embryonic rat spinal cord. Peak expression of c-met (at E14) coincides with the period of naturally occurring cell death in motor neurons, suggesting a possible role of HGF in the regulation of this process. Utilizing a neuron-enriched culture system, we established that HGF, like CNTF, stimulates choline acetyltransferase (CAT) activity in motor neurons. When co-administered to motor neuron cultures, saturating concentrations of HGF and CNTF produced a synergistic increase in CAT levels. We show that this synergy reflects enhanced motor neuron survival. Exposure of motor neuron cultures to the cytostatic agent vincristine markedly decreased CAT levels; co-treatment with HGF and CNTF (but not either factor alone) restored CAT activity to control levels. Our findings indicate that HGF is a survival factor for motor neurons, that it acts synergistically with CNTF, and that HGF and CNTF can together be neuroprotective in the face of vincristine toxicity.
Concurrence of nivolumab‐induced interstitial lung disease and cancer invasion

Nivolumab improves overall survival rates of patients with advanced or recurrent non‐small‐cell lung cancer (NSCLC). Among immune‐related adverse events caused by nivolumab, interstitial lung disease (ILD) is a clinically serious and potentially life‐threatening toxicity, for which appropriate treatment is needed immediately. However, ILD is sometimes difficult to distinguish from invasive lung adenocarcinoma using only computed tomography (CT) findings. A 71‐year‐old man was diagnosed with advanced lung adenocarcinoma. The patient developed dyspnoea after eight cycles of nivolumab, when chest CT indicated ILD classified with a cryptogenic organizing pneumonia (COP) pattern. Although immunosuppressive therapies improved the CT findings temporarily, dyspnoea was re‐exacerbated 2 months later. The CT findings helped in making the diagnosis of a combination of ILD and invasive lung cancer, confirmed by a transbronchial lung biopsy. In conclusion, nivolumab‐related ILD and cancer invasion may concur and aggressive biopsy should be considered if nivolumab‐related ILD is refractory to immunosuppressive therapy.
Oncogenic roles of astrocyte elevated gene-1 (AEG-1) in osteosarcoma progression and prognosis

Astrocyte elevated gene-1 (AEG-1) is overexpressed in several cancers and plays an important role in cancer progression. However, AEG-1 expression, biological function, and clinical significance in osteosarcoma have not been uncovered. Utilizing manipulated human osteosarcoma cell lines and osteosarcoma tissues, we found that increasing expression of AEG-1 enhanced osteosarcoma cell proliferation and invasion in vitro, and knockdown of AEG-1 significantly attenuated osteosarcoma cell malignancy. Moreover, AEG-1 was overexpressed in osteosarcoma tissues, and overexpression of AEG-1 was strongly associated with gender (p = 0.018), clinical stages (p < 0.001), classification (p < 0.001), metastasis (p = 0.013), differentiation (p < 0.001), and poor survival (p = 0.021). Mechanistic studies conducted in vitro and in vivo revealed that AEG-1-mediated carcinogenesis and invasiveness might be through upregulating MMP-2. Taken together, our data strongly suggest that AEG-1 plays a crucial role in osteosarcoma progression through MMP-2, and AEG-1 could be a useful biomarker for the prediction of osteosarcoma progression and prognosis.
Asymmetric Income Segregation

Income segregation is found to be a common phenomenon, which imposes far-reaching implications on housing and social policies. However, the focus has long been on its extent rather than on its distribution. This study investigates the asymmetric relationship between household income and income segregation in Hong Kong, by studying the census data in 2001 and in 2006, compiled by the Hong Kong SAR Government. The result shows that segregation is more intense among high household income districts, which cannot be explained by the existing theories. We put forward a novel hypothesis, based on a one-sided self-reinforcing and spatial-diffusing model, which helps explain the underlying cause of asymmetric income segregation. The model is well supported by both a theoretical simulation and an empirical test.
Cloning and Functional Characterization of a Formin-Like Protein (AtFH8) from Arabidopsis1

The actin cytoskeleton is required for many cellular processes in plant cells. The nucleation process is the rate-limiting step for actin assembly. Formins belong to a new class of conserved actin nucleator, which includes at least 2 formin homology domains, FH1 and FH2, which direct the assembly of unbranched actin filaments. The function of plant formins is quite poorly understood. Here, we provide the first biochemical study of the function of conserved domains of a formin-like protein (AtFH8) from Arabidopsis (Arabidopsis thaliana). The purified recombinant AtFH8(FH1FH2) domain has the ability to nucleate actin filaments in vitro at the barbed end and caps the barbed end of actin filaments, decreasing the rate of subunit addition and dissociation. In addition, purified AtFH8(FH1FH2) binds actin filaments and severs them into short fragments. The proline-rich domain (FH1) of the AtFH8 binds directly to profilin and is necessary for nucleation when actin monomers are profilin bound. However, profilin inhibits the nucleation mediated by AtFH8(FH1FH2) to some extent, but increases the rate of actin filament elongation in the presence of AtFH8(FH1FH2). Moreover, overexpression of the full-length AtFH8 in Arabidopsis causes a prominent change in root hair cell development and its actin organization, indicating the involvement of AtFH8 in polarized cell growth through the actin cytoskeleton.
Absence of arms in the axoneme of immobile human spermatozoa.

The spermiograms of an infertile man were unique in showing normal parameters except for the presence of total immotility in 100 per cent of the spermatozoa. In 100 per Cent of the axonemes of such spermatozoa there was a consistent lack of arms on the doublets of the axoneme. The same feature was found in all stages of spermatid formation. Other less consistent abnormalities were the occasional appearance of extra coarse fibers and axonemal microtubules, and an abnormal relationship between the longitudinal columns of the fibrous sheath and the doublets of the axoneme. All other ultrastructural details compared well with normal spermatozoa. Detailed descriptions of the substructural organization of axonemes from a wide variety of sources have to some extent helped to clarify our understanding of ciliary and flagellar motility. However, at the present time significant information at the molecular level is needed before a functional model comparable to the one known for muscle contraction can be achieved. The presence of a rather unique axonemal defect in the spermatozoa of a sterile man may help to throw some light on these problems. In this report the history of such a patient and the ultrastructural findings in his spermatozoa will be described.
Pathways of extrapancreatic perineural invasion by pancreatic adenocarcinoma: evaluation with 3D volume-rendered MDCT imaging.

OBJECTIVE The purpose of this article is to familiarize radiologists with the common pathways of extrapancreatic perineural invasion of pancreatic adenocarcinoma and to highlight the potential value of 3D volume-rendered MDCT in its diagnosis. CONCLUSION The perineural plexuses closely follow peripancreatic vessels, which are well depicted by contrast-enhanced 3D volume-rendered imaging, thus facilitating the diagnosis of extrapancreatic perineural invasion of pancreatic adenocarcinoma.
Iron accumulation, iron‐mediated toxicity and altered levels of ferritin and transferrin receptor in cultured astrocytes during incubation with ferric ammonium citrate

The cellular uptake and storage of iron have to be tightly regulated in order to provide iron for essential cellular functions while preventing the iron‐catalysed generation of reactive oxygen species (ROS). In contrast to cells in other organs, little is known about the regulation of iron metabolism in brain cells, particularly in astrocytes. To investigate the regulation of iron metabolism in astrocytes we have used primary astrocyte cultures from the brains of newborn rats. After application of ferric ammonium citrate (FAC), cultured astrocytes accumulated iron in a time‐ (0–48 h) and concentration‐dependent (0.01–1 mm) manner. This accumulation was prevented if FAC was applied in combination with the iron‐chelator deferoxamine (DFX). Application of FAC to astrocyte cultures caused a strong increase in the cellular content of the iron storage protein ferritin and a decrease in the amount of transferrin receptor (TfR), which is involved in the transferrin‐mediated uptake of iron into cells. In contrast, application of DFX strongly increased the level of TfR. Both up‐regulation of ferritin content by iron application and up‐regulation of TfR content by DFX were prevented by the protein synthesis inhibitor cycloheximide (CHX). During incubation of astrocytes with FAC, a mild and transient increase in the extracellular activity of the cytosolic enzyme lactate dehydrogenase and in the concentration of intracellular ROS was observed. In contrast, prevention of protein synthesis by CHX during incubation with FAC resulted in significantly more cell loss and a persistent and intense increase in the production of intracellular ROS. These results demonstrate that both iron accumulation and deprivation modulate the synthesis of ferritin and TfR in astrocytes and that protein synthesis is required to prevent iron‐mediated toxicity in astrocytes.
Latent transforming growth factor β1 activation in situ: quantitative and functional evidence after low‐dose γ‐irradiation 1

The biological activity of transforming growth factor β1 (TGF‐β) is controlled by its secretion as a latent complex in which it is noncovalently associated with latency‐associated peptide (LAP). Activation is the extracellular process in which TGF‐β is released from LAP, and is considered to be a primary regulatory control. We recently reported rapid and persistent changes in TGF‐β immunoreactivity in conjunction with extracellular matrix remodeling in γ‐irradiated mouse mammary gland. Our hypothesis is that these specific changes in immunoreactivity are indicative of latent TGF‐β activation. In the present study, we determined the radiation dose response and tested whether a functional relationship exists between radiation‐induced TGF‐β and collagen type III remodeling. After radiation exposures as low as 0.1 Gy, we detected increased TGF‐β immunoreactivity in the mammary epithelium concomitant with decreased LAP immunostaining, which are events consistent with activation. Quantitative image analysis demonstrated a significant (P= 0.0005) response at 0.1 Gy without an apparent threshold and a linear dose response to 5 Gy. However, in the adipose stroma, loss of LAP demonstrated a qualitative threshold at 0.5 Gy. Loss of LAP paralleled induction of collagen III immunoreactivity in this tissue compartment. We tested whether TGF‐β mediates collagen III expression by treating animals with TGF‐β panspecific monoclonal antibody, 1D11.16, administered i.p. shortly before irradiation. Radiation‐induced collagen III staining in the adipose stroma was blocked in an antibody dose‐dependent manner, which persisted through 7 days postirradiation. RN‐ase protection assay revealed that radiation‐induced elevation of total gland collagen III mRNA was also blocked by neutralizing antibody treatment. These data provide functional confirmation of the hypothesis that radiation exposure leads to latent TGF‐β activation, support our interpretation of the reciprocal shift in immunoreactivity as evidence of activation, and implicate TGF‐β as a mediator of tissue response to ionizing radiation. The sensitivity of activation to low radiation doses points to a potential role for TGF‐β in orchestrating tissue response to oxidative stress. As such, radiation may be useful as a probe to delineate the consequences of latent TGF‐β activation in situ. —Ehrhart, E. J., Segarini, P., Tsang, M. L. ‐S. , Carroll, A. G. , Barcellos‐Hoff, M. H. Latent transforming growth factor‐β1 activation in situ: quantitative and functional evidence after low‐dose γ‐irradiation. FASEB J. 11, 991–1002 (1997)
Nuclear Localization of Enzymatically Active Green Fluorescent Protein-CTP:Phosphocholine Cytidylyltransferase α Fusion Protein Is Independent of Cell Cycle Conditions and Cell Types*

To address the recent controversy about the subcellular localization of CTP:phosphocholine cytidylyltransferase α (CTα), this study was designed to visualize green fluorescent protein (GFP)·CTα fusion proteins directly and continuously under different conditions of cell cycling and in various cell lines. The GFP·CTα fusion proteins were enzymatically active and capable of rescuing mutant cells with a temperature-sensitive CT. The expressed GFP·CTα fusion protein was localized to the nucleus in all cell lines and required the N-terminal nuclear targeting sequence. Serum depletion/replenishment did not cause shuttling of CTα between the nucleus and cytoplasm. Moreover, the subcellular localization of CTα was examined continuously through all stages of the cell cycle in synchronized cells. No shuttling of CTα between the nucleus and cytoplasm was observed at any stage of the cell cycle. Stimulation of cells with oleate had no effect on the localization of CTα. The GFP·CTα lacking the nuclear targeting sequence stayed exclusively in the cytoplasm. Regardless of their localization, the GFP·CTα fusion proteins were equally active for phosphatidylcholine synthesis and mutant rescue. We conclude that the nuclear localization of CTα is a biological event independent of cell cycle in most mammalian cells and is unrelated to activation of phosphatidylcholine synthesis.
Stage I Lung Cancer Survivorship: Risk of Second Malignancies and Need for Individualized Care Plan

Background: Survivors of stage I lung cancer are at increased risk of subsequent malignancies. Specific data on risk of subsequent malignancies are underreported in the literature. We studied the incidence of stage I lung cancer and the incidence of all second malignancies in survivors. Methods: Data from the Surveillance, Epidemiology and End Results 9 database were analyzed to calculate the incidence of stage I lung cancer and subsequent malignancies from 1998 to 2007. The risk of subsequent malignancies is reported as a standardized incidence ratio (observed incidence [O]/expected incidence [E]). Results: The incidence rate of stage I lung cancer increased slowly from 1988 (8, confidence interval [CI]: 7.6–8.4) to 2003 (9.2, CI: 8.9–9.6) and more rapidly from 2003 to 2007 (11.2, CI: 10.8–11.7). The risk of developing a second lung cancer is highest in the first year with the O/E at 6.78 (CI: 6.29–7.31) and continues to be high at 10 years (O/E 4.12; CI: 4.44–4.80). Laryngeal cancer has the highest incidence in the first year (O/E 9.78; CI: 7.51–12.51) and continues to be high at 10 years (O/E 3.55; CI: 1.77–6.34). For gastrointestinal cancers, there is increased risk of colon (O/E 1.33; CI: 1.22–1.44), esophagus (O/E 2.29; CI: 1.85–2.89), and stomach (O/E 1.43; CI: 1.15–1.75) cancers. The increased risk of bladder cancer (O/E 1.83; CI: 1.65–2.03) remains high even at 10 years after the diagnosis of stage I lung cancer. Conclusions: There is increasing incidence of stage I lung cancer. Survivors of stage I are at increased risk of certain second malignancies.
Towards a Reappraisal of Henge Monuments

The definition and classification of ‘henges’ and ‘hengiform’ sites are reconsidered. A new classification is proposed based on the nature of the perimeter, the number of entrances, and a range of features within or concentric to the perimeter. It is suggested that there is no valid distinction between sites termed ‘henge’ or ‘hengiform’. The site, distribution and chronology of these sites are also considered. Some of the associated features have close parallels in earlier neolithic sites.
Cognitive‐motor profile, clinical characteristics and diagnosis of CHARGE syndrome: An Italian experience

Since 2005, the Pediatric Clinic of Maternal‐Infantile Sciences Institute in Ancona, in collaboration with the Lega del Filo d'Oro in Osimo, has been taking care of 35 patients with clinical and molecular diagnosis of CHARGE syndrome. Our investigation is the largest Italian cohort study of CHARGE patients. CHARGE syndrome is a multiple malformation syndrome involving ocular coloboma, heart defects, choanal atresia, retardation of growth and\or development, genital anomalies and\or urinary and ear abnormalities which leads to visual–auditory disabilities, cognitive impairment and behavioral abnormalities. Our purpose is to expand the knowledge of this syndrome by reviewing this group of affected patients in order to delineate in detail the natural history of the disease, and in particular to define the cognitive and motor profiles using an Italian questionnaire called “Progress Guide”. Our main results show that Italian CHARGE patients have more delayed development in their physical abilities or skills with respect to normal patients. In particular, the delay is statistically significant in regard to self‐care skills (worse toileting, better washing) and the communication skill (language). On the other hand, the expressive skills are still preserved. When patients are considered according to their age (≤3 years) and (>3 years), the older ones have more delayed development than the younger ones when compared with healthy individuals of the same age. © 2014 Wiley Periodicals, Inc.
Social Capital among Indian and Iranian Youth and their Families

The social capital, conceptualized into different aspects, i.e. scope of social relations and level of social trust, was studied among 600 cases of Indian and Iranian students and their parents, in two cities of Chandigarh and Tehran, in India and Iran. The results showed that the scope of social relations in India was higher than Iran. One of the variables which could affect the scope of social relation network was the distance or closeness of the person with his relatives. Normally, in villages or small towns, the relatives live close to each other. It is this closeness factor which results in the increased interactions of relatives and neighbors. Contrary to this, in large or metropolitan cities, the closeness people's with their relatives is not available to such an extent.
On a posteriori error estimates

Consider a sequence {xn}nfl0 in a normed space X converging to some x* E X. It is shown that the sequence satisfies a condition of the type Ix* xnI 1, if the associated null sequence {en}n=0, en = x*xn, is uniformly decreasing in norm or if it is alternating with respect to any ordering whose cone of positive elements is acute.
NPLs — The Solution Recipe for Albania

The quality of the loan portfolio in Albanian banking system is facing many obstacles during the last decade. In this paper we look at possible determinants of assets quality. During the recent financial crisis commercial banks were confronted with deteriorating asset quality that threatened not only the banking industry, but also the stability of the entire financial system. This study aims to examine the correlation between non-performing loans and the macroeconomic determinants in Albania during the last decade. NPLs are considered to be of a high importance as they represent the high risk exposure of banking system. A solid bank with healthy assets increases the market efficiency. Our approach is based on a panel data regression analysis technique from 2005-2015. Within this methodology this study finds robust evidence on the existing relationship between lending interest rate, real GDP growth and NPLs. We expect to find a negative relationship between lending interest rate and asset quality. Further we assume an inverse relationship between GDP growth and non-performing loans, suggesting that NPLs decrease if the economy is growing. Furthermore this study proposes a solution platform, which looks deeper into the possibility of creating a secondary active market for troubled loans, restructuring the banking system or implementing the Podgorica model. This research paper opens a new lieu of discussion in terms of academic debates and decision-making policies.
End users creating effective software

Is it possible to bring the benefits of rigorous software engineering methodologies to end users? End users create software when they use spreadsheet systems, web authoring tools and graphical languages, when they write educational simulations, spreadsheets, and dynamic e-business web applications. Unfortunately, however, errors are pervasive in end-user software, and the resulting impact is sometimes enormous. A growing number of researchers and developers are working on ways to make the software created by end users more reliable. This special interest group meeting will help support the community of researchers who are addressing this topic.
Automated data capture from free‐text radiology reports to enhance accuracy of hospital inpatient stroke codes

Much potentially useful clinical information for pharmacoepidemiological research is contained in unstructured free‐text documents and is not readily available for analysis. Routine health data such as Scottish Morbidity Records (SMR01) frequently use generic ‘stroke’ codes. Free‐text Computerised Radiology Information System (CRIS) reports have potential to provide this missing detail. We aimed to increase the number of stroke‐type‐specific diagnoses by augmenting SMR01 with data derived from CRIS reports and to assess the accuracy of this methodology.