Miracle-dz/UniFAR-FTUs huggingface dataset:
CSF Biomarkers in Prediction of Cerebral and Clinical Change in Mild Cognitive Impairment and Alzheimer's Disease

Brain atrophy and altered CSF levels of amyloid β (Aβ42) and the microtubule-associated protein tau are potent biomarkers of Alzheimer's disease (AD)-related pathology. However, the relationship between CSF biomarkers and brain morphometry is poorly understood. Thus, we addressed the following questions. (1) Can CSF biomarker levels explain the morphometric differences between normal controls (NC) and patients with mild cognitive impairment (MCI) or AD? (2) How are CSF biomarkers related to atrophy across the brain? (3) How closely are CSF biomarkers and morphometry related to clinical change [clinical dementia rating sum of boxes (CDR-sb)]? Three hundred seventy participants (105 NC, 175 MCI, 90 AD) from the Alzheimer's Disease Neuroimaging Initiative were studied, of whom 309 were followed for 1 year and 176 for 2 years. Analyses were performed across the entire cortical surface, as well as for 30 cortical and subcortical regions of interest. Results showed that CSF biomarker levels could not account for group differences in brain morphometry at baseline but that CSF biomarker levels showed moderate relationships to longitudinal atrophy rates in numerous brain areas, not restricted to medial temporal structures. Baseline morphometry was at least as predictive of atrophy as were CSF biomarkers. Even MCI patients with levels of Aβ42 comparable with controls and of p-tau lower than controls showed more atrophy than the controls. Morphometry predicted change in CDR-sb better than did CSF biomarkers. These results indicate that morphometric changes in MCI and AD are not secondary to CSF biomarker changes and that the two types of biomarkers yield complementary information.
Sexually dimorphic neuronal responses to social isolation

Many species use social networks to buffer the effects of stress. The mere absence of a social network, however, may also be stressful. We examined neuroendocrine, PVN CRH neurons and report that social isolation alters the intrinsic properties of these cells in sexually dimorphic fashion. Specifically, isolating preadolescent female mice from littermates for <24 hr increased first spike latency (FSL) and decreased excitability of CRH neurons. These changes were not evident in age-matched males. By contrast, subjecting either males (isolated or grouped) or group housed females to acute physical stress (swim), increased FSL. The increase in FSL following either social isolation or acute physical stress was blocked by the glucocorticoid synthesis inhibitor, metyrapone and mimicked by exogenous corticosterone. The increase in FSL results in a decrease in the excitability of CRH neurons. Our observations demonstrate that social isolation, but not acute physical stress has sex-specific effects on PVN CRH neurons. DOI: http://dx.doi. org/10.7554/eLife.18726. 001
Long-term Follow-up Results of Adult Patients with Acute Lymphocytic Leukemia or Lymphoblastic Lymphoma Treated with Short-term, Alternating Non-cross-resistant Chemotherapy: Japan Clinical Oncology Group Study 8702

Background Patients with acute lymphocytic leukemia (ALL) and those with lymphoblastic lymphoma (LBL) have overlapping clinical and immunophenotypic features and they have been treated with the same or very similar chemotherapy regimens. The goal of this multi-institutional phase II trial was to evaluate the therapeutic efficacy of a short-term, six-drug chemotherapy regimen for adult patients with untreated ALL or LBL. Methods Forty-six eligible patients, 41 with ALL and five with LBL, were treated with a short-term (planned total therapy duration; 36-38 weeks), simplified chemotherapy program; two courses of VEPA-L (vincristine, cyclophosphamide, prednisolone, doxorubicin, I-asparaginase plus intrathecal methotrexate and prednisolone) followed by four courses of M-VEPA (methotrexate plus VEPA), without the traditional maintenance therapy using daily 6-mercaptopurine and weekly methotrexate. Results Thirty-six (78%; 95% confidence interval 64-89%) of the 46 eligible patients achieved complete remission (CR). Among the 36 patients who achieved CR, four (11%) died of treatment complications, 26 (72%) relapsed and six (17%) remain alive in continuous CR. The median survival for all 46 eligible patients is 14 months and the median disease-free survival (DFS) for the 36 patients who achieved CR is 11 months. The estimate of the proportion of survival at 7 years of all 46 eligible patients is 15% at a median follow-up time of 96 months and that of DFS of the 36 patients achieving CR is 17% at a median follow-up time of 93 months. Subgroup analysis showed that an elevated serum C-reactive protein (CRP) level, age of 30 years or older, the presence of B-symptom and T-cell phenotype were likely to be associated with shortened survival. Although the observed CR rate (78%) is within the range of satisfaction, the long-term survival rate (15%) is inferior to those of published programs incorporating maintenance therapy. Conclusions A fraction of adult patients with ALL or LBL are curable with a short-term, six-drug chemotherapy regimen. However, this simplified therapy of shorter duration cannot be recommended.
Financial Openness and Growth: Short-Run Gain, Long-Run Pain?

No empirical evidence has yet emerged for the existence of a robust positive relationship between financial openness and economic growth. This paper argues that a key reason for the elusive evidence is the presence of a time-varying relationship between openness and growth over time: countries tend to gain in the short-term, immediately following capital account liberalisation, but may not grow faster or even experience temporary growth reversals in the medium- to long-term. The paper finds substantial empirical evidence for the existence of such an intertemporal trade-off for 45 industrialised and emerging market economies. The acceleration of growth immediately after liberalisation is found to be often driven by an investment boom and a surge in portfolio and debt inflows. By contrast, the quality of domestic institutions, the size of FDI inflows and the sequencing of the liberalisation process are found to be important driving forces for growth in the medium to longer term. JEL Classification: F33, F34, F36, F43
Coupling Hidden Markov Models for the Discovery of Cis-Regulatory Modules in Multiple Species

Cis-regulatory modules (CRMs) composed of multiple transcription factor binding sites (TFBS's) control gene expression in eukaryotic genomes. Comparative genomic studies have shown that these regulatory elements are more conserved across species due to evolutionary constraints. We propose a statistical method to combine module structure and cross-species orthology in de novo motif discovery. We use a hidden Markov model (HMM) to capture the module structure in each species and couple these HMMs through multiple-species alignment. Evolutionary models are incorporated to consider correlated structures among aligned sequence positions across different species. Based on our model, we develop a Markov chain Monte Carlo approach, MultiModule, to discover CRMs and their component motifs simultaneously in groups of orthologous sequences from multiple species. Our method is tested on both simulated and biological data sets in mammals and Drosophila, where significant improvement over other motif and module discovery methods is observed.
Assessing the Distribution Consistency of Sequential Data

Given n observations, we study the consistency of a batch of k new observations, in terms of their distribution function. We propose a non-parametric, non-likelihood test based on Edgeworth expansion of the distribution function. The keypoint is to approximate the distribution of the n+k observations by the distribution of n-k among the n observations. Edgeworth expansion gives the correcting term and the rate of convergence. We also study the discrete distribution case, for which Cramer's condition of smoothness is not satisfied. The rate of convergence for the various cases are compared.
ADDRESSING PAIN AND PAIN-BASED BEHAVIOURS FOR CHILDREN AND YOUNG PEOPLE IN CHILD PROTECTION AND OUT-OF-HOME CARE

In this paper we discuss the concepts of physical and emotional pain and people’s reactions such as pain-based behaviours. We describe our work with children and young people in the Victorian (Australia) child protection and out-of-home care system who have experienced many painful experiences often resulting in pain-based behaviours. We describe our practice approach with a description of the “PAIN Relief” emotional first aid tool. We highlight implications for practice, and training in response to emotional pain and pain-based behaviours.
Effects of Fatigue on Balance and Mobility in Subjects with Multiple Sclerosis: A Brief Report

Purpose. People with Multiple Sclerosis (PwMS) tent to have increased levels of fatigue which can impact on their balance and increase risk of falls. However, the relationship between fatigue and balance is poorly understood. The aim of the present study was to assess if an experimentally induced fatigue had an immediate effect on balance. Methods. 37 inpatients with multiple sclerosis were recruited; the mean age (standard deviation) was 48.7 (9.6) years. The average onset of the pathology was 15.3 (9.8) years before the start of the study. The median (1°–3° quartile) Expanded Disability Status Scale (EDSS) score was 5.5 (4.5–6.0). Before and after a fatiguing treadmill, session, subjects were assessed with the Berg Balance Scale and Dynamic Gait Index. Results. After the treadmill, no statistically significant differences were found in balance before and after a treadmill session (monopodalic stance: before 5.3s (10.3) and after 7.7s (13.9); walk with horizontal head turns: before 11.6 (6.9) seconds and after 11.3 (7.7)). There was no correlation between the EDSS score and the difference in balance skills before and after treadmill. Conclusion. After treadmil PwMS were mentally and physically fatigued; however, their balance performance did not change, indicating no increase in risk of falling with fatigue.
Estimation in Large and Disaggregated Demand Systems: An Estimator for Conditionally Linear Systems

Empirical demand systems that do not impose unreasonable restrictions on preferences are typically non-linear. We show, however, that all popular systems possess the property of conditional linearity. A computationally attractive iterated linear least squares estimator (ILLE) is proposed for large non-linear simultaneous equation systems which are conditionally linear in unknown parameters. The estimator is shown to be consistent and its asymptotic efficiency properties are derived. An application is given for a 22-commodity quadratic demand system using household-level data from a time series of repeated cross-sections.
Pace, rhythm and scope: Process dependence in building a profitable multinational corporation

Many potential benefits of foreign expansion have been identified in the literature, yet empirical support that multinational firms perform better than domestic firms is mixed. This paper takes a longitudinal perspective and argues that how much a firm benefits from having foreign subsidiaries depends on its process of internationalization. We argue that a firm's capacity to absorb expansion is subject to constraints: some expansion patterns increase profitability less than others, owing to diseconomies of time compression. We hypothesize that the speed of internationalization, the spread of the geographical and product markets entered, and the irregularity of the expansion pattern negatively moderate a firm's increase in profitability resulting from international expansion. Model estimations based on panel data raised strong support for these predictions.
Lattices which are good for (almost) everything

Using random coding techniques, we show that, in high dimensions, there exist lattices which are simultaneously good as sphere packings, sphere coverings, AWGN channel and MSE quantization codes. These lattices are produced by a construction, similar to construction A (Conway, J.H. and Sloane, N.J.A., 1988), and a randomly chosen set of generating vectors.
On the Morgan's problem for neutral time delay systems via dynamic controllers with application to a test case central heating system

The Morgan's problem is investigated, using a realizable controller with dynamic measurement output feedback and dynamic precompensator for the general class of linear neutral multi delay systems. It is proven that the necessary and sufficient condition for the solvability of the problem via a realizable controller is independent of the realizability requirement and it is the right invertibillity of the open loop transfer matrix. A class of controllers solving the problem is explicitly determined. The proposed technique is applied to a test case central heating system to achieve thermal autonomy. Based on the dynamic model of the heating system the performance of the proposed control scheme is successfully illustrated through computational experiments.
Glutamatergic synaptic transmission participates in generating the hippocampal EEG

The participation of ionotropic glutamatergic synapses in the generation of hippocampal electroencephalography (EEG) of behaving rats has not been systematically studied. In this study, field potentials in hippocampal CA1 were recorded following injection of N‐methyl‐D‐aspartate (NMDA) and α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA) receptor antagonists, or vehicle control, either into the lateral ventricles or directly into the hippocampus or the medial septum. Intraventricular (i.c.v.) AMPA receptor antagonist 6,7‐dinitroquinoxaline‐2,3,dione (DNQX, 5–10 μg) decreased the commissural evoked potential and the amplitude of the hippocampal EEG, including the theta rhythm. Theta frequency was decreased by 10 μg, but not 5 μg DNQX i.c. v. Unilateral intrahippocampal injection of DNQX (5 μg) only decreased the amplitude, but not the frequency, of the theta rhythm near the site of injection, without affecting theta amplitude or frequency at the opposite hippocampus. Other than theta, the large irregular activity (with a delta frequency peak at 1–2 Hz) and gamma EEG (30–100 Hz) were also decreased by i.c. v. and intrahippocampal injections of DNQX. Intrahippocampal injection of NMDA receptor antagonist D‐2‐amino‐5‐phosphonovaleric acid (D‐APV, 2.5 μg) decreased the amplitude of the theta rhythm and, less consistently, the gamma EEG. The frequency of the theta rhythm and the peak of the commissural evoked potential were not significantly affected by intrahippocampal D‐APV injection. Medial septal injections of D‐APV or D,L‐APV (2.24 μg in 0.4 μl), but not DNQX (10 μg in 0.4 μl), decreased the amplitude of the hippocampal theta significantly, but theta frequency was not significantly affected. It is concluded that both NMDA and AMPA receptors in the hippocampus are involved in generating the amplitude of the hippocampal EEG of theta and gamma frequencies, while NMDA receptors in the medial septum are involved in controlling the amplitude of theta and gamma EEG in the hippocampus. Excitatory glutamatergic synaptic currents, activated by afferents from the entorhinal cortex and CA3, are suggested to participate in hippocampal EEG activities. © 2004 Wiley‐Liss, Inc.
Expression of Ccl11 Associates with Immune Response Modulation and Protection against Neuroinflammation in Rats

Multiple sclerosis (MS) is a polygenic disease characterized by inflammation and demyelination in the central nervous system (CNS), which can be modeled in experimental autoimmune encephalomyelitis (EAE). The Eae18b locus on rat chromosome 10 has previously been linked to regulation of beta-chemokine expression and severity of EAE. Moreover, the homologous chemokine cluster in humans showed evidence of association with susceptibility to MS. We here established a congenic rat strain with Eae18b locus containing a chemokine cluster (Ccl2, Ccl7, Ccl11, Ccl12 and Ccl1) from the EAE- resistant PVG rat strain on the susceptible DA background and utilized myelin oligodendrocyte glycoprotein (MOG)-induced EAE to characterize the mechanisms underlying the genetic regulation. Congenic rats developed a milder disease compared to the susceptible DA strain, and this was reflected in decreased demyelination and in reduced recruitment of inflammatory cells to the brain. The congenic strain also showed significantly increased Ccl11 mRNA expression in draining lymph nodes and spinal cord after EAE induction. In the lymph nodes, macrophages were the main producers of CCL11, whereas macrophages and lymphocytes expressed the main CCL11 receptor, namely CCR3. Accordingly, the congenic strain also showed significantly increased Ccr3 mRNA expression in lymph nodes. In the CNS, the main producers of CCL11 were neurons, whereas CCR3 was detected on neurons and CSF producing ependymal cells. This corresponded to increased levels of CCL11 protein in the cerebrospinal fluid of the congenic rats. Increased intrathecal production of CCL11 in congenic rats was accompanied by a tighter blood brain barrier, reflected by more occludin+ blood vessels. In addition, the congenic strain showed a reduced antigen specific response and a predominant anti-inflammatory Th2 phenotype. These results indicate novel mechanisms in the genetic regulation of neuroinflammation.
Cognitive Flexibility and Clinical Severity in Eating Disorders

Objectives The aim of this study was to explore cognitive flexibility in a large dataset of people with Eating Disorders and Healthy Controls (HC) and to see how patient characteristics (body mass index [BMI] and length of illness) are related to this thinking style. Methods A dataset was constructed from our previous studies using a conceptual shift test - the Brixton Spatial Anticipation Test. 601 participants were included, 215 patients with Anorexia Nervosa (AN) (96 inpatients; 119 outpatients), 69 patients with Bulimia Nervosa (BN), 29 Eating Disorder Not Otherwise Specified (EDNOS), 72 in long-term recovery from AN (Rec AN) and a comparison group of 216 HC. Results The AN and EDNOS groups had significantly more errors than the other groups on the Brixton Test. In comparison to the HC group, the effect size decrement was large for AN patients receiving inpatient treatment and moderate for AN outpatients. Conclusions These findings confirm that patients with AN have poor cognitive flexibility. Severity of illness measured by length of illness does not fully explain the lack of flexibility and supports the trait nature of inflexibility in people with AN.
Chemicals and Nutritional Composition of Four Botanicals with Fungitoxic Properties

Evaluation of four botanicals Vernonia amygdalina L. , Bryophyllum pinnatum L. , Eucalyptus globules Labill and Ocimum gratissimum Kurz (Clocimum) for chemical and nutritional properties was conducted at Ago Iwoye in South-western Nigeria. The results from the investigation showed that V. amygdalina contained large quantity of Thiamine, Pyridoxine, Ascorbic acid, Glycine, Cysteine and Casein hydrolysate significantly more than other botanicals. Similarly, all the botanicals contained carbohydrates, proteins and lipids. However, the acid contents of B. pinnatum and E. globules were significantly higher than those of V. amygdalina and O. gratissimum. Similarly, the hydrocyanic acid and oxalic acid contents of B. pinnatum and E. globules were significantly (p = 0.05) higher than those of O. gratissimum. Moreover, the four botanicals contained mineral nutrients and sugars; hence, if the botanicals were used to treat cowpea plants, all these would be supplied to cowpea plants and so enhance their performances
Compression wood in Scots pine and Norway spruce

This thesis gives a summary and discussion of results from five studies concerned with: the distribution of compression wood in relation to external stem and log geometry and the impact of the compression wood distribution on deformations of sawn timber. Moreover the straightening process of trees is discussed. In order to study the distribution of compression wood in stems and logs, 63 trees of Norway spruce and Scots pine representing different age and curvature categories were sliced into 621 discs. In order to study the impact of compression wood on deformations of sawn timber, 146 logs of Scots pine and Norway spruce were processed into studs and battens. Before crosscutting, the external geometry of stems and logs were assessed. A 3D-logscanner was used for the assessment of logs. Deformations such as bow, spring and twist were measured on studs and battens at green condition, at 18% moisture content and at 12% moisture content. Compression wood content in thin cross sections of discs, studs and battens were analysed using transmitted light and image analysis. The analyses showed that a majority of all discs and cross sections contained compression wood. In all studies, the pith eccentricity was significantly correlated to the discs´ compression wood content. For the 6-year-old Scots pine trees, the compression wood content was significantly correlated to the size of basal sweep but not to out-of-roundness. For the 22-year-old Scots pine trees, the compression wood content was not correlated to either bow height or size of basal sweep. For the 60-year-old Norway spruce trees, the compression wood content was significantly correlated to compression wood content in log ends, pith eccentricity and bow height. For sawn timber, the compression wood content and its position was significantly correlated to bow and spring but not twist. Twist was significantly correlated to grain angle measured on tangential faces of studs and spiral grain angle measured under bark on the surface of logs. Results indicate that eccentric growth and compression wood formation play major roles in the development of stem straightness. Moreover, young trees with basal sweep will be straighter over time. Consequently, the straightness of a log is not a reliable measure of the compression wood content within the stem. By combining data describing external geometry with information regarding compression wood content and pith eccentricity obtained from log ends it is possible to detect logs that are prone to contain compression wood. The results also indicate that the distribution of compression wood in sawn timber influences the direction and size of bow and spring.
Latch divergency in microprocessor failure analysis

This paper presents an approach for analysis of system state differences observable through the scan chain for the debug of functional failures. A novel methodology for Latch Divergence Analysis (LDA) is proposed for creating stable failure signatures and reducing system noise. The methodology and processing flow have been integrated into the normal debug flow for the UltraSPARCTM family processors and have been successfully applied in numerous debugs in the bring-up of new products.