Miracle-dz/UniFAR-FTUs huggingface dataset:
The Baseline and Longitudinal Changes of PCC Connectivity in Mild Cognitive Impairment: A Combined Structure and Resting-State fMRI Study

The baseline and longitudinal changes of the posterior cingulate cortex (PCC) connectivity were assessed in order to clarify the neural mechanism of mild cognitive impairment (MCI). Twenty-eight right-handed subjects (14 MCI patients and 14 healthy elders) participated in this study. Clinical and neuropsychological examinations were performed on all the subjects. PCC functional connectivity was studied by examining the correlation between low frequency fMRI signal fluctuations in the PCC and those in all the other brain regions. Additionally, we traced all the MCI patients and compared their PCC connectivity in the initial stage and that in 3 years later. We also explored the relationship between the PCC functional connectivity strength and cognitive performances. Our results are as follows: Functional connectivity between the PCC and a set of regions is decreased in MCI patients. Most of these regions are within the default mode network (DMN). Three years later, the regions of superior frontal gyrus (SFG) and middle frontal gyrus (MFG) presented further decreased connectivity to the PCC in MCI. In addition, we also find enhanced functional connectivity between PCC and medial prefrontal cortex (MPFC), PCC and anterior cingulate cortex (ACC) in MCI patients. At last, our research also shows that the PCC connectivity with some regions significantly correlates with the cognitive performances of patients as measured by mini-mental state examination (MMSE), and California verbal learning test (CVLT) scores. The baseline and longitudinal changes of the PCC connectivity in our study suggest that impairment and compensation coexist in the disease progress of MCI patients.
Problem solving support in constraint-based tutors

This paper discusses various ways problem-solving is supported in constraint-based tutors. We briefly discuss the underlying learning theory, and several constraint-based tutors developed at ICTG. We then discuss the various ways problem-solving is supported in these tutors. The interfaces play an important role, as they provide the student with domain-related information, describing the important domain concepts or providing means of obtaining additional information about problems. The interface also supports good practices in the domain, and visualizes the goal structure. Constraintbased tutor diagnose student’s solution, and provide feedback on the basis of this analysis. Feedback provides long and short-term learning advantages through revision of faulty knowledge in the context of learners’ errors. Our tutors provide progressive levels of feedback, with each new message specifying more detail about the error and the basic domain principle that was violated. Finally, we also engage the student in discussion about problem-solving actions, which support the learner to reflect on his/her actions and strengthen relationships between procedural and declarative knowledge.
Maternal family history of Alzheimer's disease predisposes to reduced brain glucose metabolism

Having a parent affected with late-onset Alzheimer's disease (AD) is a risk factor for developing AD among cognitively normal subjects. We examined whether cognitively normal subjects with a parental family history of AD show cerebral metabolic rate of glucose (CMRglc) reductions consistent with AD as compared with those without a family history and whether there are parent gender effects. Forty-nine 50- to 80-year-old normal subjects were examined who received clinical, neuropsychological, and 2-[18F]fluoro-2-deoxy-d-glucose–positron emission tomography examinations, including 16 subjects with a maternal (FHm) and eight with a paternal (FHp) family history of AD and 25 with no family history (FH−). FH groups were comparable for demographic and neuropsychological measures. As compared with both FH− and FHp groups, FHm subjects showed CMRglc reductions in the same regions as clinically affected AD patients, involving the posterior cingulate cortex/precuneus, parietotemporal and frontal cortices, and medial temporal lobes (P < 0.05, corrected for multiple comparisons). These effects remained significant after accounting for possible risk factors for AD, including age, gender, education, apolipoprotein E genotype, and subjective memory complaints. No CMRglc differences were found between FHp and FH− subjects. This study shows a relationship between reduced CMRglc in AD-vulnerable brain regions and a maternal family history of AD in cognitively normal individuals.
Cloning, in Vitro Expression, and Functional Characterization of a Novel Human CC Chemokine of the Monocyte Chemotactic Protein (MCP) Family (MCP-4) That Binds and Signals through the CC Chemokine Receptor 2B*

Here we describe the characterization of a novel human CC chemokine, tentatively named monocyte chemotactic protein (MCP-4). This chemokine was detected by random sequencing of expressed sequence tags in cDNA libraries. The full-length cDNA revealed an open reading frame for a 98-amino acid residue protein, and a sequence alignment with known CC chemokines showed high levels of similarity (59–62%) with MCP-1, MCP-3, and eotaxin. MCP-4 cDNA was cloned into Drosophila S2 cells, and the mature protein (residues 24–98) was purified from the conditioned medium. Recombinant MCP-4 induced a potent chemotactic response (EC50 = 2.88 ± 0.15 nm) and a transient rise in cytosolic calcium concentration in fresh human peripheral blood monocytes but not in neutrophils. Binding studies in monocytes showed that MCP-4 and MCP-3 were very potent in displacing high affinity binding of125I-MCP-1 (IC50 for MCP-4, MCP-3, and unlabeled MCP-1 of 2.1 ± 1.4, 0.85–1.6, and 0.7 ± 0.2 nm respectively), suggesting that all three chemokines interact with the CC chemokine receptor-2 (MCP-1 receptor). This was confirmed in binding studies with Chinese hamster ovary cells, stably transfected with the CC chemokine 2B receptor. Northern blot analysis in extracts of normal human tissues showed expression of mRNA for MCP-4 in small intestine, thymus, and colon, but the level of protein expression was too low to be detected in Western blot analysis. However, expression of MCP-4 protein was demonstrated by immunohistochemistry in human atherosclerotic lesion and found to be associated with endothelial cells and macrophages.
Flexible use of memory for replication/migration in cache-coherent DSM multiprocessors

Given the limitations of bus-based multiprocessors, CC-NUMA is the scalable architecture of choice for shared-memory machines. The most important characteristic of the CC-NUMA architecture is that the latency to access data on a remote node is considerably larger than the latency to access local memory. On such machines, good data locality can reduce memory stall time and is therefore a critical factor in application performance. In this paper we study the various options available to system designers to transparently decrease the fraction of data misses serviced remotely. This work is done in the context of the Stanford FLASH multiprocessor. FLASH is unique in that each node has a single pool of DRAM that can be used in a variety of ways by the programmable memory controller. We use the programmability of FLASH to explore different options for cache-coherence and data-locality in compute-server workloads. First, we consider two protocols for providing base cache-coherence, one with centralized directory information (dynamic pointer allocation) and another with distributed directory information (SCI). While several commercial systems are based on SCI, we find that a centralized scheme has superior performance. Next, we consider different hardware and software techniques that use some or all of the local memory in a node to improve data locality. Finally, we propose a hybrid scheme that combines hardware and software techniques. These schemes work on the same base platform with both user and kernel references from the workloads. The paper thus offers a realistic and fair comparison of replication/migration techniques that has not previously been feasible.
A Bayesian approach to estimate and model SINR in wireless networks

In wireless communications, the signal‐to‐interference‐plus‐noise ratio (SINR) is important in spectrum management and link scheduling. In cognitive radio and ad hoc networks, where the spectrum is shared between nodes, the SINR is required to measure the outage probability and the level of accumulated interference on a specific node from other nodes sharing the same band. Several techniques have been proposed to estimate and statistically model the SINR. However, most of these techniques do not account for uncertainty in factors such as the number of nodes and their locations, the distance between nodes, the transmission powers, and the frequencies. In addition, these methods are not able to learn from and adapt to the changes of the network. Therefore, there is a need for models able to dynamically deal with the uncertainty affecting the SINR and provide a modular framework for its estimation. In this article, a Bayesian model is proposed to probabilistically model the SINR and describe how variables affect its probability distribution. Simulation results confirm the validity and robustness of the proposed method.
Epigenetics in Schizophrenia: A Pilot Study of Global DNA Methylation in Different Brain Regions Associated with Higher Cognitive Functions

Attempts to discover genes that are involved in the pathogenesis of major psychiatric disorders have been frustrating and often fruitless. Concern is building about the need to understand the complex ways in which nature and nurture interact to produce mental illness. We analyze the epigenome in several brain regions from schizophrenic patients with severe cognitive impairment using high-resolution (450K) DNA methylation array. We identified 139 differentially methylated CpG sites included in known and novel candidate genes sequences as well as in and intergenic sequences which functions remain unknown. We found that altered DNA methylation is not restricted to a particular region, but includes others such as CpG shelves and gene bodies, indicating the presence of different DNA methylation signatures depending on the brain area analyzed. Our findings suggest that epimutations are not relatables between different tissues or even between tissues' regions, highlighting the need to adequately study brain samples to obtain reliable data concerning the epigenetics of schizophrenia.
Leveraging Optical Technology in Future Bus-based Chip Multiprocessors

Although silicon optical technology is still in its formative stages, and the more near-term application is chip-to-chip communication, rapid advances have been made in the development of on-chip optical interconnects. In this paper, we investigate the integration of CMOS-compatible optical technology to on-chip cache-coherent buses in future CMPs. While not exhaustive, our investigation yields a hierarchical opto-electrical system that exploits the advantages of optical technology while abiding by projected limitations. Our evaluation shows that, for the applications considered, compared to an aggressive all-electrical bus of similar power and area, significant performance improvements can be achieved using an opto-electrical bus. This performance improvement is largely dependent on the application's bandwidth demand and on the number of implemented wavelengths per optical waveguide. We also present a number of critical areas for future work that we discover in the course of our research
An exploration of loneliness: Communication and the social networks of older people with cerebral palsy

Abstract Background There is a large body of research focusing on the experiences of loneliness of older adults, yet little is known about the loneliness experiences of older adults with lifelong disability. In this paper, the authors present some findings from a larger qualitative study on the loneliness experiences of older people with cerebral palsy. Method Seven older adults with cerebral palsy participated in in‐depth interviews. Analysis of the interviews identified overarching themes and recurrent topics in the data. These topics were coded and then grouped under the overarching themes. Results Six themes were identified. All participants agreed that the themes of communication and social networks are most important when considering loneliness. In this paper, the participants' discussion of these two themes and their related topics are presented. Conclusions The results demonstrate the need to provide support and training in communication to older people with cerebral palsy who experience communication difficulty, as well as to their communication partners. They also indicate the need for policy development to assist older adults with cerebral palsy to develop and maintain their social networks and form relationships that are rewarding and enriching.
Validation of the Functional Assessment of Chronic Illness Therapy Fatigue Scale relative to other instrumentation in patients with rheumatoid arthritis.

OBJECTIVE This study validated a brief measure of fatigue in rheumatoid arthritis (RA), the Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Scale. METHODS The FACIT Fatigue was tested along with measures previously validated in RA: the Multidimensional Assessment of Fatigue (MAF) and Medical Outcomes Study Short-Form 36 (SF-36) Vitality. The sample included 636 patients with RA enrolled in a 24 week double blind, randomized clinical trial (RCT) of adalimumab versus placebo. RESULTS The FACIT Fatigue showed good internal consistency (alpha = 0.86 to 0.87), strong association with SF-36 Vitality (r = 0.73 to 0.84) and MAF (r = -0.84 to -0.88), and the ability to differentiate patients according to clinical change using the American College of Rheumatology (ACR) response criteria (ACR 20/50/70). Psychometric performance of the FACIT Fatigue scale was comparable to that of the other 2 fatigue measures. A minimally important difference in FACIT Fatigue change score of 3-4 points was confirmed in a separate sample of 271 patients with RA enrolled in a second double blind RCT of adalimumab versus placebo. CONCLUSION The FACIT Fatigue is a brief, valid measure for monitoring this important symptom and its effects on patients with RA.
Wage Inequality, Minimum Wage Effects and Spillovers

This paper investigates possible spillover effects of the UK minimum wage. The halt in the growth in inequality in the lower half of the wage distribution (as measured by the 50:10 percentile ratio) since the mid 1990s, in contrast to the continued inequality growth in the upper half of the distribution, suggests the possibility of a minimum wage effect and spillover effects on wages above the minimum. This paper analyses individual wage changes, using both a difference-in-differences estimator and a specification involving cross-uprating comparisons, and concludes that there have not been minimum wage spillovers. Since the UK minimum wage has always been below the 10th percentile, this lack of spillovers implies that minimum wage changes have not had an effect on the 50:10 percentile ratio measure of inequality in the lower half of the wage distribution. JEL classification: J31 ; J38 ; J08.
Universal Induction Motor Model With Low-to-High Frequency-Response Characteristics

A three-phase induction motor model that depicts the motor behavior over a wide range of frequencies from 10 Hz to 10 MHz is presented in this paper. The model is universal in the sense that common-mode, differential-mode, and bearing circuit models are combined into one three-phase equivalent circuit model. The proposed model is basically an extension of the low-frequency IEEE Standard 112 circuit model. The proposed model was experimentally simulated and verified with results presented.
Mapping Functional Brain Activation Using [14C]-Iodoantipyrine in Male Serotonin Transporter Knockout Mice

Background Serotonin transporter knockout mice have been a powerful tool in understanding the role played by the serotonin transporter in modulating physiological function and behavior. However, little work has examined brain function in this mouse model. We tested the hypothesis that male knockout mice show exaggerated limbic activation during exposure to an emotional stressor, similar to human subjects with genetically reduced transcription of the serotonin transporter. Methodology/Principal Findings Functional brain mapping using [14C]-iodoantipyrine was performed during recall of a fear conditioned tone. Regional cerebral blood flow was analyzed by statistical parametric mapping from autoradiographs of the three-dimensionally reconstructed brains. During recall, knockout mice compared to wild-type mice showed increased freezing, increased regional cerebral blood flow of the amygdala, insula, and barrel field somatosensory cortex, decreased regional cerebral blood flow of the ventral hippocampus, and conditioning-dependent alterations in regional cerebral blood flow in the medial prefrontal cortex (prelimbic, infralimbic, and cingulate). Anxiety tests relying on sensorimotor exploration showed a small (open field) or paradoxical effect (marble burying) of loss of the serotonin transporter on anxiety behavior, which may reflect known abnormalities in the knockout animal's sensory system. Experiments evaluating whisker function showed that knockout mice displayed impaired whisker sensation in the spontaneous gap crossing task and appetitive gap cross training. Conclusions This study is the first to demonstrate altered functional activation in the serotonin transporter knockout mice of critical nodes of the fear conditioning circuit. Alterations in whisker sensation and functional activation of barrel field somatosensory cortex extend earlier reports of barrel field abnormalities, which may confound behavioral measures relying on sensorimotor exploration.
Astrocytic control of synaptic NMDA receptors

Astrocytes express a wide range of G‐protein coupled receptors that trigger release of intracellular Ca2+, including P2Y, bradykinin and protease activated receptors (PARs). By using the highly sensitive sniffer‐patch technique, we demonstrate that the activation of P2Y receptors, bradykinin receptors and protease activated receptors all stimulate glutamate release from cultured or acutely dissociated astrocytes. Of these receptors, we have utilized PAR1 as a model system because of favourable pharmacological and molecular tools, its prominent expression in astrocytes and its high relevance to neuropathological processes. Astrocytic PAR1‐mediated glutamate release in vitro is Ca2+ dependent and activates NMDA receptors on adjacent neurones in culture. Activation of astrocytic PAR1 in hippocampal slices induces an APV‐sensitive inward current in CA1 neurones and causes APV‐sensitive neuronal depolarization in CA1 neurones, consistent with release of glutamate from astrocytes. PAR1 activation enhances the NMDA receptor‐mediated component of synaptic miniature EPSCs, evoked EPSCs and evoked EPSPs in a Mg2+‐dependent manner, which may reflect spine head depolarization and consequent reduction of NMDA receptor Mg2+ block during subsequent synaptic currents. The release of glutamate from astrocytes following PAR1 activation may also lead to glutamate occupancy of some perisynaptic NMDA receptors, which pass current following relief of tonic Mg2+ block during synaptic depolarization. These results suggest that astrocytic G‐protein coupled receptors that increase intracellular Ca2+ can tune synaptic NMDA receptor responses.
Coordination and Consensus of Networked Agents with Noisy Measurements: Stochastic Algorithms and Asymptotic Behavior

This paper considers the coordination and consensus of networked agents where each agent has noisy measurements of its neighbors' states. For consensus seeking, we propose stochastic approximation-type algorithms with a decreasing step size, and introduce the notions of mean square and strong consensus. Although the decreasing step size reduces the detrimental effect of the noise, it also reduces the ability of the algorithm to drive the individual states towards each other. The key technique is to ensure a trade-off for the decreasing rate of the step size. By following this strategy, we first develop a stochastic double array analysis in a two-agent model, which leads to both mean square and strong consensus, and extend the analysis to a class of well-studied symmetric models. Subsequently, we consider a general network topology, and introduce stochastic Lyapunov functions together with the so-called direction of invariance to establish mean square consensus. Finally, we apply the stochastic Lyapunov analysis to a leader following scenario.
A Modified Chi2 Algorithm for Discretization

Since the ChiMerge algorithm was first proposed by Kerber (1992), it has become a widely used and discussed discretization method. The Chi2 algorithm is a modification to the ChiMerge method. It automates the discretization process by introducing an inconsistency rate as the stopping criterion and it automatically selects the significance value. In addition, it adds a finer phase aimed at feature selection to broaden the applications of the ChiMerge algorithm. However, the Chi2 algorithm does not consider the inaccuracy inherent in ChiMerge's merging criterion. The user-defined inconsistency rate also brings about inaccuracy to the discretization process. These two drawbacks are first discussed in this paper and modifications to overcome them are then proposed. By comparison, results with the original Chi2 algorithm using C4.5, the modified Chi2 algorithm, performs better than the original Chi2 algorithm. It becomes a completely automatic discretization method.
Endoscopic stent placement throughout the gastrointestinal tract

In this thesis we focussed our research on stent placement throughout the GI tract. In search for ideal stents for treatment of malignant oesophageal stenosis and gastric outlet obstruction we evaluated new stent designs in prospective cohort studies. Smaller research projects mainly aimed to investigate safety and feasibility of new treatment modalities for relatively new indications in the upper GI tract. Finally retrospective cohort and comparative studies aimed to provide insight into the benefits and pitfalls of colonic stent placement as treatment for acute malignant colonic obstruction.