Miracle-dz/UniFAR-FTUs huggingface dataset:
MACULAR DYSTROPHY ASSOCIATED WITH MONOGENIC ARG172TRP MUTATION OF THE PERIPHERIN/RDS GENE IN A JAPANESE FAMILY

Objective Mutations of the peripherin/RDS gene have been reported in several kinds of retinal dystrophy, and they show variation of manifestation. In some pedigrees, the same mutation can produce different phenotypic features, a factor that makes it difficult to deduce certain rules for genotype-phenotype correlations in the peripherin/RDS gene. The authors report the phenotypic features of a Japanese family with a mutation in codon 172 of the peripherin/RDS gene and compare them to previously reported ocular findings in British pedigrees with the same mutation. Patients and Methods A 45-year-old man and his 15-year-old son were screened for mutations in the peripherin/RDS gene and the ROM1 gene. Clinical features were characterized by visual acuity and visual field testing, fundus examination, fluorescein angiography, and electroretinography. Results Both patients had the same mutation in codon 172 of the peripherin/RDS gene designated as Arg172Trp. No mutation was found in the ROM1 gene in either patient. Clinical features were summarized as autosomal dominant macular dystrophy. The father had sharply demarcated chorioretinal atrophy in the macula. The son showed mild granularity in the macular area in ophthalmoscopic appearances. Conclusions The Arg172Trp mutation was confirmed to produce autosomal dominant macular dystrophy. This particular phenotype was caused by the monogenic mutation in the peripherin/RDS gene.
Pharmacological Evidence for A1 and A2 Adenosine Receptors in the Skin Microcirculation

To characterize adenosine-mediated vascular responses, synthetic A1 and A2 receptor agonists (N-ethyl carboxamido adenosine [NECA], 2-chloro adenosine [2CA], or cyclohexyl adenosine [CHA]), the parent compound (adenosine [ADO]), an uptake inhibitor (dipyridamole [DIPYRID]) or a nonselective, competitive antagonist (8-phenyl theophylline [8pTHEO]) were topically applied to 20–60 μm arterioles in the subcutaneous microcirculation of the hamster. Blood flow was calculated from arteriolar diameter and red blood cell velocity using intravital microscopy. At >10−8 M, the potency order for vasodilation (maximum, 170–190% of control) was NECA>2CA>ADO; these responses were attenuated by 10−5 M 8pTHEO. From 10−8 to 10−6 M, 2CA evoked vasodilation whereas ADO, which has an identical affinity at A1 and A2 receptors, evoked lesser responses. ADO-induced vasodilation was potentiated by 10−5 M DIPYRID; this response was similar to that evoked by 2CA alone or 2CA+DIPYRID. In contrast to ADO, 2CA is a poor substrate for cellular uptake, which suggests that uptake reduces the A2 effect of exogenous ADO. From 10−10 to 10−8 M, CHA and ADO were equipotent for causing vasoconstriction (minimum, 80–90% of control); these responses were completely antagonized by SpTHEO. Norepinephrine was a more potent vasoconstrictor and 8pTHEO did not alter these responses. Since ADO is a metabolic substrate and a nonselective receptor agonist, while CHA is Arselective and a poor substrate for cellular uptake, neither A2 activation nor cellular uptake altered expression of the A1 effect of exogenous ADO. Furthermore, DIPYRID had no effect on the A1 response. Thus, depending on agonist concentration, stimulation of high affinity A1 receptors or low affinity A2 receptors can cause opposite responses in the skin microcirculation. The precise location or physiological role of these receptors is unknown.
Midlife vs late-life depressive symptoms and risk of dementia: differential effects for Alzheimer disease and vascular dementia.

CONTEXT Depression and dementia are common in older adults and often co-occur, but it is unclear whether depression is an etiologic risk factor for dementia. OBJECTIVE To clarify the timing and nature of the association between depression and dementia. DESIGN We examined depressive symptoms assessed in midlife (1964-1973) and late life (1994-2000) and the risks of dementia, Alzheimer disease (AD), and vascular dementia (VaD) (2003-2009) in a retrospective cohort study. Depressive symptoms were categorized as none, midlife only, late life only, or both. Cox proportional hazards models (age as timescale) adjusted for demographics and medical comorbidities were used to examine depressive symptom category and risk of dementia, AD, or VaD. SETTING Kaiser Permanente Medical Care Program of Northern California. PARTICIPANTS Thirteen thousand five hundred thirty-five long-term Kaiser Permanente members. MAIN OUTCOME MEASURE Any medical record diagnosis of dementia or neurology clinic diagnosis of AD or VaD. RESULTS Subjects had a mean (SD) age of 81.1 (4.5) years in 2003, 57.9% were women, and 24.2% were nonwhite. Depressive symptoms were present in 14.1% of subjects in midlife only, 9.2% in late life only, and 4.2% in both. During 6 years of follow-up, 22.5% were diagnosed with dementia (5.5% with AD and 2.3% with VaD). The adjusted hazard of dementia was increased by approximately 20% for midlife depressive symptoms only (hazard ratio, 1.19 [95% CI, 1.07-1.32]), 70% for late-life symptoms only (1.72 [1.54-1.92]), and 80% for both (1.77 [1.52-2.06]). When we examined AD and VaD separately, subjects with late-life depressive symptoms only had a 2-fold increase in AD risk (hazard ratio, 2.06 [95% CI, 1.67-2.55]), whereas subjects with midlife and late-life symptoms had more than a 3-fold increase in VaD risk (3.51 [2.44-5.05]). CONCLUSIONS Depressive symptoms in midlife or in late life are associated with an increased risk of developing dementia. Depression that begins in late life may be part of the AD prodrome, while recurrent depression may be etiologically associated with increased risk of VaD.
Lactate in the Cerebrospinal Fluid and Pressure‐Flow Relationships in Canine Cerebral Circulation

In 11 dogs, lactate and pH in the cerebrospinal fluid and in the arterial and the venous blood were measured during stepwise reductions of the arterial blood pressure by controlled bleeding. Increase in lactate and decrease in pH of the cerebrospinal fluid occurred with lowering of the mean arterial blood pressure even within the pressure ranges of 110 to 50 mm Hg, where autoregulation was fairly observed. Reductions of the blood pressure by 20 to 40 mm Hg led to a significant increase in lactate, and reductions by 60 mm Hg led to a significant decrease in pH of the cerebrospinal fluid. The relation of decrease in pH and increase in lactate was linear, suggesting that lactacidosis occurred. In the arterial and the venous blood, a marked increase in lactate and decrease in pH also were observed. Lactate concentrations of the cerebral venous blood were significantly higher than those of the arterial blood until the arterial blood pressure had been reduced below 70 mm Hg. Therefore, it was suggested that increase in lactate of the cerebrospinal fluid might be attributed solely to increase in lactate of the brain tissue, so far as the blood pressure was not lowered below 70 mm Hg at least. The possibility of participation of the cerebrospinal fluid lactacidosis in autoregulation of the cerebral blood flow was discussed.
A Model of Global Supply Chain Agility and its Impact on Competitive Performance

During the past few years, organizational agility has gained prominence as a competitive weapon in both the academic and business communities. Although much discussion has taken place, little research exists which explains the relationship between organizational agility, organizational strategies and performance. Using sound theory-building methods, this study proposes related constructs and a model of global supply chain agility. For this study, global supply chain agility is defined as a measure of the supply chain's ability to efficiently adapt to a rapidly changing global competitive environment to provide products and/or services. We posit that global supply chain agility is determined by four flexibility components; product development flexibility, sourcing flexibility, manufacturing flexibility, and logistics flexibility. Each flexibility is composed of two dimensions which we call range and adaptability. We also posit that an organization's information technology flexibility and its industry's global competitive environment influence its level of global supply chain agility. To study the effects of global supply chain agility on performance, two additional constructs called supply chain performance and global competitive performance are included in the model. Our primary goal is the development of a framework for future research on global supply chain agility.
Sensory Deprivation Alters Aggrecan and Perineuronal Net Expression in the Mouse Barrel Cortex

An important role for the neural extracellular matrix in modulating cortical activity-dependent synaptic plasticity has been established by a number of recent studies. However, identification of the critical molecular components of the neural matrix that mediate these processes is far from complete. Of particular interest is the perineuronal net (PN), an extracellular matrix component found surrounding the cell body and proximal neurites of a subset of neurons. Because of the apposition of the PN to synapses and expression of this structure coincident with the close of the critical period, it has been hypothesized that nets could play uniquely important roles in synapse stabilization and maturation. Interestingly, previous work has also shown that expression of PNs is dependent on appropriate sensory stimulation in the visual system. Here, we investigated whether PNs in the mouse barrel cortex are expressed in an activity-dependent manner by manipulating sensory input through whisker trimming. Importantly, this manipulation did not lead to a global loss of PNs but instead led to a specific decrease in PNs, detected with the antibody Cat-315, in layer IV of the barrel cortex. In addition, we identified a key activity-regulated component of PNs is the proteoglycan aggrecan. We also demonstrate that these Cat-315-positive neurons virtually all also express parvalbumin. Together, these data are in support of an important role for aggrecan in the activity-dependent formation of PNs on parvalbumin-expressing cells and suggest a role for expression of these nets in regulating the close of the critical period.
Incentive Networks

In a basic economic system, each participant receives a (financial) reward according to his own contribution to the system. In this work, we study an alternative approach — Incentive Networks — in which a participant's reward depends not only on his own contribution; but also in part on the contributions made by his social contacts or friends. We show that the key parameter effecting the efficiency of such an Incentive Network-based economic system depends on the participant's degree of directed altruism. Directed altruism is the extent to which someone is willing to work if his work results in a payment to his friend, rather than to himself. Specifically, we characterize the condition under which an Incentive Network-based economy is more efficient than the basic "pay-for-your-contribution" economy. We quantify by how much incentive networks can reduce the total reward that needs to be paid to the participants in order to achieve a certain overall contribution. Finally, we study the impact of the network topology and various exogenous parameters on the efficiency of incentive networks. Our results suggest that in many practical settings, Incentive Network-based reward systems or compensation structures could be more efficient than the ubiquitous 'pay-for-your-contribution' schemes.
Ten Years of Pathway Analysis: Current Approaches and Outstanding Challenges

Pathway analysis has become the first choice for gaining insight into the underlying biology of differentially expressed genes and proteins, as it reduces complexity and has increased explanatory power. We discuss the evolution of knowledge base–driven pathway analysis over its first decade, distinctly divided into three generations. We also discuss the limitations that are specific to each generation, and how they are addressed by successive generations of methods. We identify a number of annotation challenges that must be addressed to enable development of the next generation of pathway analysis methods. Furthermore, we identify a number of methodological challenges that the next generation of methods must tackle to take advantage of the technological advances in genomics and proteomics in order to improve specificity, sensitivity, and relevance of pathway analysis.
Development and preliminary evaluation of the caregiver assistive technology outcome measure.

INTRODUCTION Assistive technology is often recommended with the aim of increasing user independence and reducing the burden on informal caregivers. However, until now, there has been no tool to measure the outcomes of this process for caregivers. OBJECTIVES To describe the development of the Caregiver Assistive Technology Outcome Measure (CATOM), a tool developed to measure the impact of assistive technology interventions on the burden experienced by informal caregivers, and to undertake preliminary evaluation of its psychometric properties. METHODS Based on an existing conceptual framework, existing measures were reviewed to identify potential items in a preliminary version of the measure. Cognitive interviewing was used to identify items needing clarification. A revised CATOM and manual were then reviewed by clinicians. After revising some items based on the interview findings, the measure was piloted as part of an intervention study examining the impact of assistive technology on the users' informal caregivers (n = 44). RESULTS Based on a review of 12 existing measures, a 3-part measure was developed and questions were refined based on cognitive interviews with informal caregivers and feedback experienced assistive technology practitioners. For the activity-specific and overall portions of the measure, the 6-week, test-retest intraclass correlations coefficients were 0.88 (95% CI 0.64-0.96) and 0.86 (95% CI 0.60-0.95), respectively. The CATOM data correlated as hypothesized with other measures. CONCLUSION The CATOM is a promising measure with good content validity and encouraging psychometric properties.
Serum Levels of Several Organochlorine Pesticides in Farmers Correspond With Dietary Exposure and Local Use History

In response to reported increased cancer risks among farmers, the Agricultural Health Study (AHS) was designed to examine health outcomes and environmental exposures among farm families in the United States. In the pilot phase of the AHS, food, beverage, air, dermal, dust, surface wipe, and biological specimens (blood and urine) were collected and analyzed for six farm families in two states (IA and NC). In addition, questionnaires were administered to examine previous pesticide use. This paper reports the organochlorine pesticide results of the serum and dietary analyses as well as questionnaire results from the pilot exposure study of farmers and their families. Note, no organochlorine pesticides were reported as currently being applied to the study farms. In all human serum samples examined, typical U.S. population levels were found for the majority of the pesticides. In addition, human serum levels of organochlorine pesticides showed no significant daily or seasonal variation. However, serum trans-nonachlor levels were found to be higher in people living on the two farms in North Carolina than
Reproductive Asynchrony in Spatial Population Models: How Mating Behavior Can Modulate Allee Effects Arising from Isolation in Both Space and Time

Mate finding, which is essential to both population growth and gene exchange, involves both spatial and temporal components. From a population dynamics perspective, spatial mate‐finding problems are well studied, and decreased mate‐finding efficiency at low population densities is a well‐recognized mechanism for the Allee effect. Temporal aspects of mate finding have been rarely considered, but reproductive asynchrony may engender an Allee effect in which some females go mateless by virtue of temporal isolation. Here we develop and explore a model that unifies previously disparate theoretical considerations of spatial and temporal aspects of mate finding. Specifically, we develop a two‐sex reaction‐diffusion system to examine the interplay between reproductive asynchrony and the dispersal of individuals out of a patch. We also consider additional behavioral complications, including several alternative functional forms for mating efficiency and advective movements in which males actively seek out females. By calculating the fraction of females expected to go mateless as a joint function of reproductive asynchrony and patch size, we find that the population‐level reproductive rates necessary to offset female matelessness may be quite high. These results suggest that Allee effects engendered by reproductive asynchrony will be greatly exacerbated in spatially isolated populations.
A 12.5Gb/s CMOS BER test using a jitter-tolerant parallel CDR

Implemented in a 0.13 /spl mu/m CMOS process, pulse pattern generation and BER test functions are integrated in a chip. A parallel CDR (clock data recovery) circuit provides 12.5 Gb/s operation and wide tolerance of over 0.5 UIpp for 4 to 80 MHz sinusoidal jitter.
The prepilin peptidase is required for protein secretion by and the virulence of the intracellular pathogen Legionella pneumophila

Prepilin peptidases cleave, among other substrates, the leader sequences from prepilin‐like proteins that are required for type II protein secretion in Gram‐negative bacteria. To begin to assess the importance of type II secretion for the virulence of an intracellular pathogen, we examined the effect of inactivating the prepilin peptidase (pilD ) gene of Legionella pneumophila. Although the pilD mutant and its parent grew similarly in bacteriological media, they did differ in colony attributes and recoverability from late stationary phase. Moreover, at least three proteins were absent from the mutant's supernatant, indicating that PilD is necessary for the secretion of Legionella proteins. The absence of both the major secreted protein and a haemolytic activity from the mutant signalled that the L. pneumophila zinc metalloprotease is excreted via type II secretion. Most interestingly, the pilD mutant was greatly impaired in its ability to grow within Hartmannella vermiformis amoebae and the human macrophage‐like U937 cells. As reintroduction of pilD into the mutant restored infectivity and as a mutant lacking type IV pilin replicated like wild type, these data suggested that the intracellular growth of L. pneumophila is promoted by proteins secreted via a type II pathway. Intratracheal inoculation of guinea pigs revealed that the LD50 for the pilD mutant is at least 100‐fold greater than that for its parent, and the culturing of bacteria from infected animals showed a rapid clearance of the mutant from the lungs. This is the first study to indicate a role for PilD and type II secretion in intracellular parasitism.
The Bunny Dilemma: Stepping between Agents and Avatars

As the Internet has become a global medium for communication, virtual environments are consolidating as the arena where users can interact with each others in a synchronous, threedimensional way. However, the poor behaviour usually shown by the avatars that inhabit these worlds, makes it difficult to achieve an acceptable level of immersion of their users in
Regulation of the Telomerase Reverse Transcriptase Subunit through Epigenetic Mechanisms

Chromosome-shortening is characteristic of normal cells, and is known as the end replication problem. Telomerase is the enzyme responsible for extending the ends of the chromosomes in de novo synthesis, and occurs in germ cells as well as most malignant cancers. There are three subunits of telomerase: human telomerase RNA (hTERC), human telomerase associated protein (hTEP1), or dyskerin, and human telomerase reverse transcriptase (hTERT). hTERC and hTEP1 are constitutively expressed, so the enzymatic activity of telomerase is dependent on the transcription of hTERT. DNA methylation, histone methylation, and histone acetylation are basic epigenetic regulations involved in the expression of hTERT. Non-coding RNA can also serve as a form of epigenetic control of hTERT. This epigenetic-based regulation of hTERT is important in providing a mechanism for reversibility of hTERT control in various biological states. These include embryonic down-regulation of hTERT contributing to aging and the upregulation of hTERT playing a critical role in over 90% of cancers. Normal human somatic cells have a non-methylated/hypomethylated CpG island within the hTERT promoter region, while telomerase-positive cells paradoxically have at least a partially methylated promoter region that is opposite to the normal roles of DNA methylation. Histone acetylation of H3K9 within the promoter region is associated with an open chromatin state such that transcription machinery has the space to form. Histone methylation of hTERT has varied control of the gene, however. Mono- and dimethylation of H3K9 within the promoter region indicate silent euchromatin, while a trimethylated H3K9 enhances gene transcription. Non-coding RNAs can target epigenetic-modifying enzymes, as well as transcription factors involved in the control of hTERT. An epigenetics diet that can affect the epigenome of cancer cells is a recent fascination that has received much attention. By combining portions of this diet with epigenome-altering treatments, it is possible to selectively regulate the epigenetic control of hTERT and its expression.
A Novel micro-Blog Sentiment Analysis Approach by Longest Common sequence and k-Medoids

This paper introduced a clustering-based Chinese sentiment analysis approach which is a new method to sentiment analysis appropriated for short text such as Sina Weibo. By building Sentiment Sequence from Weibo text, we apply the Longest Common Sequence algorithms to measure the sentiment different from two Sentiment Sequence, and K-Medoids clustering method to break a mass of Sentiment Sequences into groups. It has great advantages over the existing sentiment analysis method such as classification by supervised learning algorithms. The experiment result shows the sentiment distribution and groups of a mass of Weibo data aggregated by a given topic, and in a specific period. The method is well performed, efficient, and non-human participating, and appropriated for Chinese short text.
Automatic compositional minimization in CTL model checking

A method for reducing the complexity of CTL model checking on a system of interacting finite state machines is described. The method consists essentially of reducing each component machine with respect to the property to be verified, and then verifying the property on the composition of the reduced components. The procedure is fully automatic and produces an exact result. The potential of the approach is assessed on real-world examples, and the method is demonstrated on a circuit. <<ETX>>
Quick and easy CMOS amplifier design and optimization

This paper presents a quick and easy method for establishing the design conditions for a CMOS amplifier such that the design achieves near-optimum performance with respect to gain, bandwidth, noise, distortion, power and cost. The method is based on re-formulating the small-signal equations of circuit behavior in terms of an independent set of physically accessible design parameters. These new equations will enable one to easily identify a design and optimization procedure for any amplifier.