Miracle-dz/UniFAR-FTUs huggingface dataset:
Subventricular zone neural progenitors from rapid brain autopsies of elderly subjects with and without neurodegenerative disease

In mice and in young adult humans, the subventricular zone (SVZ) contains multipotent, dividing astrocytes, some of which, when cultured, produce neurospheres that differentiate into neurons and glia. It is unknown whether the SVZ of very old humans has this capacity. Here, we report that neural stem/progenitor cells can also be cultured from rapid autopsy samples of SVZ from elderly human subjects, including patients with age‐related neurologic disorders. Histological sections of SVZ from these cases showed a glial fibrillary acidic protein (GFAP)‐positive ribbon of astrocytes similar to the astrocyte ribbon in human periventricular white matter biopsies that is reported to be a rich source of neural progenitors. Cultures of the SVZ contained 1) neurospheres with a core of Musashi‐1‐, nestin‐, and nucleostemin‐immunopositive cells as well as more differentiated GFAP‐positive astrocytes; 2) SMI‐311‐, MAP2a/b‐, and β‐tubulin(III)‐positive neurons; and 3) galactocerebroside‐positive oligodendrocytes. Neurospheres continued to generate differentiated progeny for months after primary culturing, in some cases nearly 2 years postinitial plating. Patch clamp studies of differentiated SVZ cells expressing neuron‐specific antigens revealed voltage‐dependent, tetrodotoxin‐sensitive, inward Na+ currents and voltage‐dependent, delayed, slowly inactivating K+ currents, electrophysiologic characteristics of neurons. A subpopulation of these cells also exhibited responses consistent with the kinetics and pharmacology of the h‐current. However, although these cells displayed some aspects of neuronal function, they remained immature, insofar as they did not fire action potentials. These studies suggest that human neural progenitor activity may remain viable throughout much of the life span, even in the face of severe neurodegenerative disease. J. Comp. Neurol. 515:269–294, 2009. © 2009 Wiley‐Liss, Inc.
Prevalence and prognosis of unclassifiable interstitial lung disease

To the Editor: We read with interest the recent article by Ryerson et al. [1], describing the prevalence and characteristics of patients with unclassifiable interstitial lung disease (ILD) presenting to a specialist centre. This study is the first to target specifically this newly defined disease category, in parallel with publication of the updated American Thoracic Society/European Respiratory Society classification of the idiopathic interstitial pneumonias (IIPs) [2]. The authors identified 10% of their ILD patient population as having unclassifiable ILD following multidisciplinary discussion (MDD). The major reasons for diagnostic uncertainty related to either inability or unwillingness of the patient to undergo surgical lung biopsy, or inadequacy of the tissue specimen sampled. Only a minority of cases remained ambiguous after a reasonable tissue sample had been obtained. The study detailed the clinical characteristics of this hybrid group, with many of the mean baseline demographics and disease behaviours falling between the two reference groups of patients with confirmed idiopathic pulmonary fibrosis (IPF) and non-IPF diagnoses. Multivariate analysis revealed low diffusing capacity of …
Theory of orientation tuning in visual cortex.

The role of intrinsic cortical connections in processing sensory input and in generating behavioral output is poorly understood. We have examined this issue in the context of the tuning of neuronal responses in cortex to the orientation of a visual stimulus. We analytically study a simple network model that incorporates both orientation-selective input from the lateral geniculate nucleus and orientation-specific cortical interactions. Depending on the model parameters, the network exhibits orientation selectivity that originates from within the cortex, by a symmetry-breaking mechanism. In this case, the width of the orientation tuning can be sharp even if the lateral geniculate nucleus inputs are only weakly anisotropic. By using our model, several experimental consequences of this cortical mechanism of orientation tuning are derived. The tuning width is relatively independent of the contrast and angular anisotropy of the visual stimulus. The transient population response to changing of the stimulus orientation exhibits a slow "virtual rotation. " Neuronal cross-correlations exhibit long time tails, the sign of which depends on the preferred orientations of the cells and the stimulus orientation.
Effects of applied load on bone tissue as observed by Raman spectroscopy

The skeleton is certainly essential to our physiology. Yet, surprisingly little is understood about how bone responds when a load is applied. This is particularly true at the ultrastructural level, where neither the behavior under stress of the collagenous matrix nor that of the calcium phosphate mineral has been explored. Most standard techniques used in the investigation of the biomechanical properties of bone tissue are unable to obtain information at this level. Raman spectroscopy, however, is capable of probing biological specimens at the molecular level, without interference from water or common histological stains. Using this technique, we are able to observe changes in both the mineral and the matrix of bone during and after the application of load. These changes manifest themselves as band shifts in the bone Raman spectrum. We utilize this ability in this study. Two-dimensional Raman imaging is used to investigate the effect of macroscopic fracture on the mineral in sections of femora from 4-month-old and 18-month-old mice. Changes are seen in the mineral around fractured areas that indicate the fracture process may be causing a phase transformation in the bone mineral, similar to the 'transformation toughening' process that is observed in many ceramics. We discuss the physiological implications of these results.
Document Writer Analysis with Rejection for Historical Arabic Manuscripts

Determining the individuality of handwriting in ancient manuscripts is an important aspect of the manuscript analysis process. Automatic identification of writers in historical manuscripts can support historians to gain insights into manuscripts with missing metadata such as writer name, period, and origin. In this paper writer classification and retrieval approaches for multi-page documents in the context of historical manuscripts are presented. The main contribution is a learning-based rejection strategy which utilizes writer retrieval and support vector machines for rejecting a decision if no corresponding writer can be found for a query manuscript. Experiments using different feature extraction methods demonstrate the abilities of our proposed methods. A dedicated data set based on a publicly available database of historical Arabic manuscripts was used and the experiments show promising results.
Formation of lipofuscin in cultured retinal pigment epithelial cells exposed to pre‐oxidized photoreceptor outer segments

Accumulation of lipofuscin in the retinal pigment epithelium (RPE) with increasing age may affect essential supportive functions for the photoreceptors. Earlier, we described a model system for the study of lipofuscinogenesis in RPE cell cultures and showed that mild oxidative stress enhances lipofuscin formation from phagocytized photoreceptor outer segments (POS). In the present study, bovine POS were photo‐oxidized, and turned into a lipofuscin‐like material, by irradiation with UV light. Transmission electron microscopy of irradiated POS showed loss of the normal stacks of the disk membranes with conversion into an amorphous osmiophilic electron‐dense mass. The formation of thiobarbituric acid reactive substances (TBARS), estimated during the irradiation process, indicated lipid peroxidation. Irradiated POS also showed a strong granular yellow autofluorescence. RPE cell cultures, kept at 21% ambient oxygen, were fed daily for 3, 5 or 7 days with either (i) UV‐peroxidized POS, (ii) native POS or (iii) culture medium only. RPE cells fed irradiated POS showed significantly higher levels of lipofuscin‐ specific autofluorescence compared to cells exposed to native POS after 3 days (p = 0.0056), 5 days (p = 0.0037) and 7 days (p = 0.0020), and to the non‐exposed control cells (3 days: p = 0.005, 5 days: p = 0.0037, 7 days: p = 0.0094). The lipofuscin content of cells exposed to irradiated POS increased significantly between days 3 and 7 (p = 0.0335). Ultrastructural studies showed much more numerous and larger lipofuscin‐like inclusions in RPE cells fed irradiated POS compared to cells exposed to native POS. In the control cells, lipofuscin‐like granules were small and sparse. It appears that exposing RPE cells to previously peroxidized POS, thus artificially converted to lipofuscin and obviously not digestible by the lysosomal enzymes, accelerates the formation of severely lipofuscin‐loaded cells. The results will be useful for further studies of possible harmful effects of lipofuscin in heavily loaded RPE cells.
Spectral signatures of characteristic spatial scales and nonfractal structure in landscapes

[1] Landscapes are sometimes argued to be scale-invariant or random surfaces, yet qualitative observations suggest that they contain characteristic spatial scales. We quantitatively investigate the existence of characteristic landscape scales by analyzing two-dimensional Fourier power spectra derived from high-resolution topographic maps of two landscapes in California. In both cases, we find that spectral power declines sharply above a frequency that corresponds roughly to hillslope length, implying that the landscape is relatively smooth at finer scales. The spectra also show that both landscapes contain quasiperiodic ridge-and-valley structures, and we derive a robust measure of the ridge-valley wavelength. By comparing the spectra with the statistical properties of spectra derived from randomly generated topography, we show that such uniform valley spacing is unlikely to occur in a random surface. We describe several potential applications of spectral analysis in geomorphology beyond the identification of characteristic spatial scales, including a filtering technique that can be used to measure topographic attributes, such as local relief, at specific scales or in specific orientations.
Prospective study of social and other risk factors for incidence of type 2 diabetes in the Whitehall II study.

BACKGROUND Social inequalities in the incidence of type 2 diabetes and the relation of health behaviors and psychosocial factors to the incidence of type 2 diabetes are not well established. METHODS Prospective occupational cohort study of 10 308 civil servants aged 35 to 55 years at baseline in phase 1 (1985-1988). Diagnosis of diabetes was ascertained by questionnaire at baseline and follow-up at phases 2 (1989), 3 (1992-1993), 4 (1995), and 5 (1997-1999) and glucose tolerance tests in phases 3 and 5. RESULTS Participants working in the lower employment grades had a higher incidence of diabetes than those in higher employment grades (men: odds ratio [OR], 2.9; 95% confidence interval [CI], 1.9-4.4; women: OR, 1.7 [95% CI, 0.8-3.7]). Body mass index and other risk factors considered traditional for type 2 diabetes were found to be so in this cohort. In men, of the psychosocial risk factors examined, only effort-reward imbalance was related to incidence of diabetes (OR, 1.7 [95% CI, 1.0-2.8]). The General Health Questionnaire depression subscale was related to incidence of diabetes and impaired glucose tolerance (OR, 1.25 [95% CI, 1.0-1.6]). These associations remained after adjustment for other confounding factors. In men only, social difference in incidence of diabetes was reduced but still significant after adjustment for conventional risk factors. CONCLUSIONS An inverse relationship exists between social position and incidence of diabetes that is partly explained by health behaviors and other risk factors. Effort-reward imbalance, which is reportedly associated with coronary heart disease, is also associated with type 2 diabetes.
Health Endowments and Parental Investments in Infancy and Early Childhood

This paper tests whether parents reinforce or compensate for child endowments. The authors employ birth weight as a proxy for endowments and estimate how the difference in birth weight across siblings impacts specific parental investments, including breastfeeding initiation and duration, well-baby visits, immunizations, preschool attendance, and kindergarten entry age. They also examine whether parental investment in a child is impacted by her siblings' endowments. Their results indicate that heavier birth weight children receive higher levels of most parental investment than their lower birth weight siblings suggesting that parental investments in infancy and early childhood reinforce differences in endowments. In one exception, they find weak evidence that lower birth weight children enter kindergarten slightly later than their normal birth weight siblings, which could be interpreted as a compensating parental investment. Presence of a low birth weight sibling in the household increases the likelihood of investments such as well-baby visits and immunizations.
The Case for Conservative Management of Venous Angiomas

ABSTRACT: Venous angiomas (developmental venous anomalies) are vascular malformations increasingly recognized in general neurosurgical or neurological practice. They are associated with intracranial hemorrhage, seizures, or progressive neurological deficits or found as incidental findings in patients who present with headaches or have neuroimaging studies for investigation of unrelated neurological disorders. Since venous angiomas drain normal cerebral tissue within a functionally normal arterial territory, resection can lead to venous infarction. This report studies 27 patients with venous angiomas, all of whom had conservative treatment. The venous angioma was considered to be responsible for the onset of neurological symptoms in 14 patients (7 with hemorrhage, 3 with hemorrhage and seizures, 2 with seizures, one with an extrapyramidal movement disorder, and one with motor deficit). Thirteen patients had incidental lesions (8 with headache, and 5 with unrelated neurological symptoms). Ten venous angiomas were in the posterior fossa; seven in the cerebellum. Location did not correlate with symptomatic presentation. No patient with hemorrhage required surgical evacuation of the hematoma. No patient died or had significant morbidity during the follow-up interval (mean of 3.7 years). Venous angiomas are low flow, low resistance vascular malformations, many of which are not associated with neurological sequelae. Our series supports the concept that surgical removal or radiosurgical obliteration should not be performed unless a patient has a second life threatening hemorrhage.
Kinetic studies of Escherichia coli AlkB using a new fluorescence-based assay for DNA demethylation

The Escherichia coli AlkB protein catalyzes the direct reversal of alkylation damage to DNA; primarily 1-methyladenine (1mA) and 3-methylcytosine (3mC) lesions created by endogenous or environmental alkylating agents. AlkB is a member of the non-heme iron (II) α-ketoglutarate-dependent dioxygenase superfamily, which removes the alkyl group through oxidation eliminating a methyl group as formaldehyde. We have developed a fluorescence-based assay for the dealkylation activity of this family of enzymes. It uses formaldehyde dehydrogenase to convert formaldehyde to formic acid and monitors the creation of an NADH analog using fluorescence. This assay is a great improvement over the existing assays for DNA demethylation in that it is continuous, rapid and does not require radioactively labeled material. It may also be used to study other demethylation reactions including demethylation of histones. We used it to determine the kinetic constants for AlkB and found them to be somewhat different than previously reported values. The results show that AlkB demethylates 1mA and 3mC with comparable efficiencies and has only a modest preference for a single-stranded DNA substrate over its double-stranded DNA counterpart.
Peritubular Capillary Changes and C4d Deposits Are Associated with Transplant Glomerulopathy But Not IgA Nephropathy

We examined our renal transplant population for glomerular diseases demonstrated on biopsy between January 1993 and April 2002, focusing on transplant glomerulopathy (TGP). Of 1156 patients followed in our clinics during this period, glomerular disease was diagnosed in 132 cases (11.4%). Glomerulonephritis was diagnosed in 86 transplants (7.4%), with IgA nephropathy (IgAN) being the commonest diagnosis [32 cases (2.8%)]. Thirty‐one cases (2.7%) of biopsy‐proven TGP were analyzed for associated factors compared with 27 cases (2.3%) of recurrent IgAN. Transplant glomerulopathy was less frequent with mycophenolate mofetil (MMF) and/or tacrolimus, whereas recurrent IgAN showed no such tendency (P= 0.02). Peritubular capillary (PTC) C4d deposition was observed in six of 24 cases (25%) with TGP but none with recurrent IgAN (P= 0.02). Peritubular capillary basement membrane (BM) multilayering was significantly greater in TGP (4.92 ± 2.94) than in recurrent IgAN (1.86 ± 1.04) (P < 0.001). The graft survival of TGP was worse than recurrent IgAN (P= 0.05). The association of TGP with BM multilayering and C4d deposits in PTC suggests a generalized disorder of the graft microcirculation and its BM, owing to antibody‐mediated rejection in at least some cases. Transplant glomerulopathy has a serious prognosis but is less frequent in patients on newer immunosuppression, unlike recurrent IgAN.
Flash-Sinterforging of Nanograin Zirconia: Field Assisted Sintering and Superplasticity

We report on the influence of a uniaxial applied stress on flash-sintering and field assisted superplastic behavior of cylindrical powder preforms of 3 mol% tetragonal-stabilized zirconia. The experiments use the sinterforging method, where, in addition to pressure, a dc electrical field is applied by metal electrodes sandwiched between the push-rods and the specimen. The axial and radial strains in the experiment provide simultaneous measurement of the time-dependent densification and shear strains. Large effects of the electric field on sintering and superplasticity are observed. We see flash-sintering which is characterized by a threshold level of temperature and electric field. With higher applied fields, the sample sinters at a lower furnace temperature. Surprisingly, the applied stress further lowers this critical temperature: a sample, which sinters at 915°C under a stress of 1.5 MPa, densifies at only 850°C when the stress is raised to 12 MPa. This stress induced reduction in sintering temperature maybe related to the additional electrical fields generated within the specimen by the electro-chemo-mechanical mechanism described by Pannikkat and Raj [Acta Mater. , 47 (1999) 3423]. Remarkably, we also show that the sample deforms in pure shear to 30% strain in just a few seconds at anomalously low temperatures. The specimen temperature was measured with a pyrometer, during the flash sintering, as a check on Joule heating. A reading of 1000°C–1100°C was obtained, up to 200° above the furnace temperature. This temperature is still too low to explain the sintering in just a few seconds. It is suggested that the electric field can nucleate a defect avalanche that enhances diffusion kinetics not by changing the activation energy but by increasing the pre-exponential factor for the diffusion coefficient, noting that the pre-exponential factor depends on concentration of defects, and not upon their mobility.
Sampled differential dynamic programming

We present SaDDP, a sampled version of the widely used differential dynamic programming (DDP) control algorithm. We contribute through establishing a novel connection between two major branches of robotics control research, that is, gradient-based methods such as DDP, and Monte Carlo methods such as path integral control (PI) that utilize random simulated trajectory rollouts. One of our key observations is that the Taylor-expansion, central to DDP, can be reformulated in terms of second-order statistics computed of the sampled trajectories. SaDDP makes few assumptions about the controlled system and works with black-box dynamics simulations with non-smooth contacts. Our simulation results show that the method outperforms PI and CMA-ES in both a simple linear-quadratic problem, and a multilink arm reaching task with obstacles.
Evaluating Software Architectures for Stability and Evolution

: Architectural stability refers to the extent an architecture is flexible to endure evolutionary changes in stakeholders’ requirements and the environment, while leaving the architecture intact. We report an early result in an emerging discipline of software engineering, the economic-driven software engineering research. We propose a novel approach for evaluating the stability of software architectures using a synergy of real options theory and viewpoints. Specifically, we contribute to a novel model that exploits options theory to predict architectural stability. The model is predictive: it provides “insights” on the evolution of the software system based on valuing the extent an architecture can endure a set of likely evolutionary changes. The model builds on Black and Scholes financial options theory (Noble Prize wining) to value such extent. We show how we have derived the model: the analogy and assumptions made to reach the model, its formulation, and possible interpretations. We refer to this model as ArchOptions. ArchOptions requires the estimation of several parameters. The estimation necessarily involves many parties- each with their own perspective on the system defined by their valuation objectives, assessment “regime”, skills, responsibilities, knowledge, and expertise. The problem associated with how to guide the estimation in this setting, we term as a multiple perspectives valuation problem. We describe the problem from a value-based software engineering perspective. We suggest a viewpoints-oriented framework as a solution. The framework appears to promote flexibility in implementing the model through aligning the estimation needs with value objectives, valuation strategy, expertise, tools, and/or the development (evolution) process. The contribution of this framework demonstrates the ability to evolve robust approaches in software engineering to solve problems in an emerging discipline, the value-based software engineering.
Histomorphometric Evaluation of Anorganic Bovine Bone Coverage to Reduce Autogenous Grafts Resorption: Preliminary Results

Physiologic resorption due to remodeling processes affects autogenous corticocancellous grafts in the treatment of atrophic jawbone alveolar ridges. Such a situation in the past made overgrafting of the recipient site mandatory to get enough bone support to dental implants in order to perform a prosthetic rehabilitation. Anorganic bovine bone, conventionally used to treat alveolar bone deficiencies in implant surgery, showed a high osteoconductive property thanks to its micro and macrostructure very similar to that of human hydroxyapatite. An original technique provides for the application of a thin layer of anorganic bovine bone granules and a collagen membrane on the top of the corticocancellous onlay bone grafts to reduce in a remarkable way the graft resorption due to remodeling. The results of a clinical prospective study and a histomorphometric analysis done on autogenous grafts harvested from the iliac crest showed that the proposed technique is able to maintain the original bone volume of the corticocancellous blocks.