Miracle-dz/UniFAR-FTUs huggingface dataset:
Dual blockade of FAAH and MAGL identifies behavioral processes regulated by endocannabinoid crosstalk in vivo

Δ9-Tetrahydrocannabinol (THC), the psychoactive component of marijuana, and other direct cannabinoid receptor (CB1) agonists produce a number of neurobehavioral effects in mammals that range from the beneficial (analgesia) to the untoward (abuse potential). Why, however, this full spectrum of activities is not observed upon pharmacological inhibition or genetic deletion of either fatty acid amide hydrolase (FAAH) or monoacylglycerol lipase (MAGL), enzymes that regulate the two major endocannabinoids anandamide (AEA) and 2-arachidonoylglycerol (2-AG), respectively, has remained unclear. Here, we describe a selective and efficacious dual FAAH/MAGL inhibitor, JZL195, and show that this agent exhibits broad activity in the tetrad test for CB1 agonism, causing analgesia, hypomotilty, and catalepsy. Comparison of JZL195 to specific FAAH and MAGL inhibitors identified behavioral processes that were regulated by a single endocannabinoid pathway (e.g., hypomotility by the 2-AG/MAGL pathway) and, interestingly, those where disruption of both FAAH and MAGL produced additive effects that were reversed by a CB1 antagonist. Falling into this latter category was drug discrimination behavior, where dual FAAH/MAGL blockade, but not disruption of either FAAH or MAGL alone, produced THC-like responses that were reversed by a CB1 antagonist. These data indicate that AEA and 2-AG signaling pathways interact to regulate specific behavioral processes in vivo, including those relevant to drug abuse, thus providing a potential mechanistic basis for the distinct pharmacological profiles of direct CB1 agonists and inhibitors of individual endocannabinoid degradative enzymes.
Update on the EUVL mask blank activity at Schott Lithotec

Schott Lithotec has introduced all relevant technology steps to manufacture EUV mask blanks in its advanced quality mask blank manufacturing line -- ranging from Low Thermal Expansion Material (LTEM) high quality substrate polishing to low defect blank manufacturing. New polishing and cleaning technologies, improved sputter technology and updated metrology enable us to produce EUVL mask blanks meeting already some of the roadmap requirements. Further R&D is ongoing to path the way to the pilot production of EUV blanks which meet the beta-specifications end of 2005. We present the status of our EUVL substrate program and report on the recent results of our activities for low defect multilayer, buffer and absorber coating including new absorber materials. Recent results from the production of full LTEM EUV blanks with multilayer, buffer and absorber coatings will be presented. Process steps in the EUVL mask blank fabrication in a production environment were characterized in terms of defects; the process improvement potential is discussed. We will also throw a light on the aspects of changed layer properties after a longer period of storage. In addition, special metrology methods for EUVL components are currently being developed within the program. The status of the high throughput EUV-Reflectometer for mask blanks will be presented. We developed new processes to achieve EUVL requirements.
Hepcidin antagonists for potential treatments of disorders with hepcidin excess

The discovery of hepcidin clarified the basic mechanism of the control of systemic iron homeostasis. Hepcidin is mainly produced by the liver as a propeptide and processed by furin into the mature active peptide. Hepcidin binds ferroportin, the only cellular iron exporter, causing the internalization and degradation of both. Thus hepcidin blocks iron export from the key cells for dietary iron absorption (enterocytes), recycling of hemoglobin iron (the macrophages) and the release of storage iron from hepatocytes, resulting in the reduction of systemic iron availability. The BMP/HJV/SMAD pathway is the major regulator of hepcidin expression that responds to iron status. Also inflammation stimulates hepcidin via the IL6/STAT3 pathway with a support of an active BMP/HJV/SMAD pathway. In some pathological conditions hepcidin level is inadequately elevated and reduces iron availability in the body, resulting in anemia. These conditions occur in the genetic iron refractory iron deficiency anemia and the common anemia of chronic disease (ACD) or anemia of inflammation. Currently, there is no definite treatment for ACD. Erythropoiesis-stimulating agents and intravenous iron have been proposed in some cases but they are scarcely effective and may have adverse effects. Alternative approaches aimed to a pharmacological control of hepcidin expression have been attempted, targeting different regulatory steps. They include hepcidin sequestering agents (antibodies, anticalins, and aptamers), inhibitors of BMP/SMAD or of IL6/STAT3 pathway or of hepcidin transduction (siRNA/shRNA) or ferroportin stabilizers. In this review we summarized the biochemical interactions of the proteins involved in the BMP/HJV/SMAD pathway and its natural inhibitors, the murine and rat models with high hepcidin levels currently available and finally the progresses in the development of hepcidin antagonists, with particular attention to the role of heparins and heparin sulfate proteoglycans in hepcidin expression and modulation of the BMP6/SMAD pathway.
Breast Milk Protects Against Gastrointestinal Symptoms in Infants at High Risk for Autism During Early Development

Objectives: Parents of children with autism spectrum disorders (ASDs) often report gastrointestinal (GI) dysfunction in their children. The objectives of the present study were to determine whether infants at high risk for developing ASD (ie, siblings of children diagnosed as having ASD) show greater prevalence of GI problems and whether this prevalence is associated with diet and age at weaning from breast milk. Methods: Using questionnaires, diet history and GI problems were tracked prospectively and retrospectively in 57 high-risk infants and for comparison in 114 low-risk infants (infants from families without ASD history). Results: In low-risk infants, prevalence of GI symptoms, in aggregate, did not vary with diet or age of weaning. By contrast, high-risk infants with GI symptoms were weaned earlier than those without symptoms (P < 0.04), and high-risk infants showed greater prevalence of GI symptoms, in aggregate, on a no breast milk diet than on an exclusive breast milk diet (P < 0.017). Constipation, in particular, was more prevalent in high-risk infants compared with low-risk infants (P = 0.01), especially on a no breast milk diet (P = 0.002). High-risk infants who completed weaning earlier than 6 months showed greater prevalence of constipation (P = 0.001) and abdominal distress (P = 0.004) than those fully weaned after 6 months. Conclusions: The greater prevalence of GI symptoms in high-risk infants suggests that GI dysfunction during early infant development may be a part of the ASD endophenotype. Late weaning and exclusive breast milk were associated with protection against GI symptoms in high-risk infants.
Cognitive Limitations in Aging and Psychopathology: Working Memory Capacity in Hot and Cold Cognition

Much has been said about the relationship between measures of Work­ ing Memory Capacity (WMC) and higher order cognition. Indeed, what exactly accounts for this relationship has been a major topic of inquiry in cognitive psychology for over 20 years (Engle & Oransky, 1999). Attempts to better understand this problem have shed considerable light on the role of WMC in a wide array of research domains. Specifically, research has shown that measures of WMC are related to complex learning (Kyllonen & Stephens, 1990), following directions (Engle, Carullo, & Collins, 1991), rea­ soning ability (Engle, Tuholski, Laughlin, & Conway, 1999; Kyllonen & Christal, 1990), and vocabulary learning (Daneman & Green, 1986). Addi­ tionally, not only has WMC been implicated in higher order cognition indeed, these correlations point to the utility of such a concept in the first placebut also now WMC is being implicated in other research domains. Working memory measures not only predict reading comprehension scores (Daneman & Carpenter, 1980), performance on standard achievement tests (i.e., SAT: Engle et al., 1999), and reasoning, but also seem to predict early onset Alzheimer's (Rosen, Bergeson, Putnam, Harwell, & Sunderland, 2002), the effects of alcohol consumption (Finn, 2002), and one's ability to deal with life-event stress (Klein & Boals, 2001). Thus, the utility of WMC is not merely limited to performance on high-level cognitive tasks, but is also important in a variety of situations that impact people on a day-to-day basis. Working Memory Capacity is important in situations requiring both rational or cold cognition such as selective attention and reasoning (Engle et al., 1999; Kane & Engle, 2003) and is also important under conditions of emotional or hot cognition, such as stress and depression (Arnett et al., 1999; Klein & Boals, 2001). The present chapter will focus on the WMC's role in these situations in terms of our view that the basis for WMC is the ability to control attention.
Hearing loss prevalence and risk factors among older adults in the United States.

BACKGROUND Hearing loss has been associated with cognitive and functional decline in older adults and may be amenable to rehabilitative interventions, but national estimates of hearing loss prevalence and hearing aid use in older adults are unavailable. METHODS We analyzed data from the 2005-2006 cycle of the National Health and Nutritional Examination Survey, which is the first cycle to ever incorporate hearing assessment in adults aged 70 years and older. Audiometry was performed in 717 older adults, and data on hearing aid use, noise exposure, medical history, and demographics were obtained from interviews. Analyses incorporated sampling weights to account for the complex sampling design and yield results that are generalizable to the U.S. population. RESULTS The prevalence of hearing loss defined as a speech frequency pure tone average of more than 25 dB in the better ear was 63.1% (95% confidence interval: 57.4-68.8). Age, sex, and race were the factors most strongly associated with hearing loss after multivariate adjustment, with black race being substantially protective against hearing loss (odds ratio 0.32 compared with white participants [95% confidence interval: 0.19-0.53]). Hearing aids were used in 40.0% (95% confidence interval: 35.1-44.8) of adults with moderate hearing loss, but in only 3.4% (95% confidence interval: 0.8-6.0) of those with a mild hearing loss. CONCLUSION Hearing loss is prevalent in nearly two thirds of adults aged 70 years and older in the U.S. population. Additional research is needed to determine the epidemiological and physiological basis for the protective effect of black race against hearing loss and to determine the role of hearing aids in those with a mild hearing loss.
Connecting time-oriented data and information to a coherent interactive visualization

In modern intensive care units (ICUs), the medical staff has to monitor a huge amount of high-dimensional and time-oriented data, which needs to be visualized user- and task-specifically to ease diagnosis and treatment planning. Available visual representations, like diagrams or charts neglect the implicit information as well as a-priory or associated knowledge about the data and its meaning (for example, 38.5°C (101.3°F) is moderate fever and 41°C (105.8°F) is critical fever). Another challenge is to provide appropriate interaction techniques to explore and navigate the data and its temporal dimensions. In this context one major challenge is to connect time-oriented data and information to a coherent interactive visualization. In this paper we present different interactive visualization techniques which enable the users to reveal the data at several levels of detail and abstraction, ranging from a broad overview to the fine structure. We will also introduce a time visualization and navigation technique that connects overview+detail, pan+zoom, and focus+context features to one powerful time-browser.
Early and late onset ulcerative colitis: distinct clinical features.

A review of 93 patients with ulcerative colitis revealed that in 47 (50.5%) symptoms first appeared between 21 and 30 years of age--"early-onset"--and in 26 (27.9%) at the age of 51 years or above--"late-onset. " Proctocolitis was more common in late-onset patients (p = 0.077) and in males of both age groups (p = 0.002). Extensive colitis was significantly more common in females (p = 0.002). Patients with late-onset proctocolitis had more bowel movements/day and liver involvement than patients with early-onset disease. The first episode of proctocolitis was more protracted and the ensuing remission of shorter duration in late-onset patients. Most patients with early-onset disease improved on steroid enemas, whereas most patients with late-onset disease required systemic corticosteroid therapy (p = 0.0028). Female patients with early-onset proctocolitis tended to be more severely afflicted than males, with an increased incidence of weight loss, leukocytosis, increased erythrocyte sedimentation rate (ESR), and need for systemic corticosteroid therapy. We conclude that late-onset ulcerative colitis is distinct from early-onset disease in its relative refractoriness to therapy and its predilection for distal colonic involvement.
Diagnostic Value of Facial Nerve Antidromic Evoked Potential in Patients With Bell's Palsy: A Preliminary Study

Objective To assess the practical diagnostic value of facial nerve antidromic evoked potential (FNAEP), we compared it with the diagnostic value of the electroneurography (ENoG) test in Bell's palsy. Methods In total, 20 patients with unilateral Bell's palsy were recruited. Between the 1st and 17th days after the onset of facial palsy, FNAEP and ENoG tests were conducted. The degeneration ratio and FNAEP latency difference between the affected and unaffected sides were calculated in all subjects. Results In all patients, FNAEP showed prolonged latencies on the affected side versus the unaffected side. The difference was statistically significant. In contrast, there was no significant difference between sides in the normal control group. In 8 of 20 patients, ENoG revealed a degeneration ratio less than 50%, but FNAEP show a difference of more than 0.295±0.599 ms, the average value of normal control group. This shows FNAEP could be a more sensitive test for Bell's palsy diagnosis than ENoG. In particular, in 10 patients tested within 7 days after onset, an abnormal ENoG finding was noted in only four of them, but FNAEP showed a significant latency difference in all patients at this early stage. Thus, FANEP was more sensitive in detecting facial nerve injury than the ENoG test (p=0.031). Conclusion FNAEP has some clinical value in the diagnosis of facial nerve degeneration. It is important that FNAEP be considered in patients with facial palsy at an early stage and integrated with other relevant tests.
Digital Technology and the Allocation of Ownership in the Music Industry1

We apply the property rights theory of Grossman-Hart-Moore in the music industry and study the optimal allocation of copyright between the artists who create music and the labels who promote and distribute it. Digital technology opens up a role for new intermediaries. We nd that entry of online platforms occurs only if they are su¢ ciently more productive in distribution than the incumbent label. Furthermore, entry leads to a change in bargaining positions and it can become optimal for the copyright to be shifted from the label to the artist. JEL classi cation: D23, L22, L23, L82, L86
Inclusion criteria provide heterogeneity in baseline profiles of patients with mild cognitive impairment: comparison of two prospective cohort studies

Background Mild cognitive impairment (MCI) is considered to represent a transitional stage between ageing and Alzheimer's disease (AD). To aim at identifying neuroimaging measures associated with cognitive changes in healthy elderly and MCI patients, longitudinal multicentre studies are ongoing in several countries. The patient profiles of each study are based on unique inclusion criteria. Objectives The purpose of the study is to clarify differences in baseline profiles of MCI patients between Studies on Diagnosis of Early Alzheimer's Disease—Japan (SEAD-J) and Alzheimer's Disease Neuroimaging Initiative (ADNI) and to examine the association between baseline profiles and risk of early conversion to AD. Design Prospective cohort study. Setting and participants SEAD-J recruited 114 patients from nine facilities in Japan. A total of 200 patients in ADNI with fluorodeoxyglucose–positron emission tomography (FDG-PET) were enrolled from the USA. Methods Baseline profiles were statistically analysed. For FDG-PET at a time of inclusion, associations between each profile and cerebral metabolic rate for glucose (CMRgl) were examined using SPM5 software. In each study, the ratio of conversion to AD within the 1-year and 2-year period after inclusion was investigated and differences in baseline profiles between AD converters and non-converters were analysed. Results SEAD-J included MCI patients with more severe verbal memory deficits and extracted patients with higher depressive tendencies. These differences were likely to be associated with criteria. SEAD-J exhibited a higher rate of conversion within 1 year compared with ADNI (24.5% vs 13.5%). In FDG-PET analyses of SEAD-J, AD converters within 1 year showed more severe decrease of FDG uptake in bilateral inferior parietal regions compared with non-converters. Conclusions Different inclusion criteria provided differences in baseline profiles. The severity of memory deficit might cause increase of the AD conversion within 1 year. Clinical outcomes of multicentre studies for early diagnosis of AD should be interpreted carefully considering profiles of patients.
Peroxisome Proliferator-Activated Receptor-γ Ligands Ameliorate Experimental Autoimmune Myocarditis Associated with Inhibition of Self-Sensitive T Cells

Objective: Recent evidence has suggested that peroxisome proliferator-activated receptor-γ (PPAR-γ) serves as a negative regulator in the immune system. In the present study, we investigated the expression of PPAR-γ and the effect of PPAR-γ ligands on experimental autoimmune myocarditis (EAM). Methods and Results: Experimental autoimmune myocarditis was induced in Lewis rats by immunization with porcine cardiac myosin. PPAR-γ ligands 15-deoxy-Δ 12,14 -PGJ2 200 μg · kg−1 · d−1 by ip and pioglitazone 10 mg · kg−1 · d−1 by oral were administered for 3 weeks. PPAR-γ expression was upregulated in myocarditis and the enhanced PPAR-γ expression was prominently stained in the nuclear and perinuclear regions of the positive-stained cells in the inflammatory lesions. Administration of PPAR-γ ligands markedly reduced the severity of myocarditis, as indicated by the heart weight/body weight ratio, pericardial effusion scores, macroscopic scores, and microscopic scores. The upregulated PPAR-γ expression was also reduced by PPAR-γ ligands treatment. In addition, PPAR-γ ligands suppressed the proliferative response and interferon-γ production of T cell-enriched splenocytes from rats with EAM. Furthermore, the cytotoxic activity and myocarditogenic potential of these T cells were inhibited by PPAR-γ ligands treatment. Conclusions: PPAR-γ ligands ameliorate EAM associated with inhibition of expansion and activation of the self-sensitive T cells. These results suggest that PPAR-γ ligands may have the potential to modulate human inflammatory heart diseases as myocarditis.
Upper-Limb Position Sense Deficits in Adults with Cerebral Palsy

ObjectiveThe aim of this study was to examine proprioceptive performance in adults with hemiplegic cerebral palsy and the possibility that a home-based sensorimotor training program could improve proprioceptive performance. DesignThis study is a preintervention/postintervention assessment of 12 adults participating in a home-based program consisting of targeted unilateral and bilateral reaching movements, hand manipulation tasks, tactile discrimination, and stereognosis. It did not specifically include proprioceptive tasks. Training sessions were 45 mins, 5 days per week, for 8 wks. Limb position sense was assessed using three conditions: ipsilateral remembered (same arm used for reference and matching targets), contralateral concurrent (reference arm moved and held at target position while opposite arm matched reference position), and contralateral remembered (reference arm moved to target position and then returned to start position before opposite arm matching position). ResultsThe participants demonstrated greater absolute and constant error when the more affected arm served as the reference arm, and matching was performed by the less affected arm, particularly in the contralateral remembered condition. After training, the participants demonstrated less absolute error across matching tasks and no change in constant error. ConclusionsThe results suggest an important role for the reference arm in bilateral position matching tasks and the potential for improved proprioceptive performance after training in movement and unrelated sensory tasks.
Thermal boundary resistance predictions from molecular dynamics simulations and theoretical calculations

The accuracies of two theoretical expressions for thermal boundary resistance are assessed by comparing their predictions to independent predictions from molecular dynamics MD simulations. In one expression RE, the phonon distributions are assumed to follow the equilibrium, Bose-Einstein distribution, while in the other expression RNE, the phonons are assumed to have nonequilibrium, but bulk-like distributions. The phonon properties are obtained using lattice dynamics-based methods, which assume that the phonon interface scattering is specular and elastic. We consider i a symmetrically strained Si/Ge interface, and ii a series of interfaces between Si and “heavy-Si,” which differs from Si only in mass. All of the interfaces are perfect, justifying the assumption of specular scattering. The MD-predicted Si/Ge thermal boundary resistance is temperature independent and equal to 3.1 10 �9 m 2 -K/ W below a temperature of 500 K, indicating that the phonon scattering is elastic, as required for the validity of the theoretical calculations. At higher-temperatures, the MD-predicted Si/Ge thermal boundary resistance decreases with increasing temperature, a trend we attribute to inelastic scattering. For the Si/Ge interface and the Si/heavy-Si interfaces with mass ratios greater than two, RE is in good agreement with the corresponding MD-predicted values at temperatures where the interface scattering is elastic. When applied to a system containing no interface, RE is erroneously nonzero due to the assumption of equilibrium phonon distributions on either side of the interface. While RNE is zero for a system containing no interface, it is 40%–60% less than the corresponding MD-predicted values for the Si/Ge interface and the Si/heavy-Si interfaces at temperatures where the interface scattering is elastic. This inaccuracy is attributed to the assumption of bulk-like phonon distributions on either side of the interface.