Miracle-dz/UniFAR-FTUs huggingface dataset:
Cyclin D2 is a critical mediator of exercise-induced cardiac hypertrophy

A number of signaling pathways underlying pathological cardiac hypertrophy have been identified. However, few studies have probed the functional significance of these signaling pathways in the context of exercise or physiological pathways. Exercise studies were performed on females from six different genetic mouse models that have been shown to exhibit alterations in pathological cardiac adaptation and hypertrophy. These include mice expressing constitutively active glycogen synthase kinase-3β (GSK-3βS9A), an inhibitor of CaMK II (AC3-I), both GSK-3βS9A and AC3-I (GSK-3βS9A/AC3-I), constitutively active Akt (myrAkt), mice deficient in MAPK/ERK kinase kinase-1 (MEKK1−/−), and mice deficient in cyclin D2 (cyclin D2−/−). Voluntary wheel running performance was similar to NTG littermates for five of the mouse lines. Exercise induced significant cardiac growth in all mouse models except the cyclin D2−/− mice. Cardiac function was not impacted in the cyclin D2−/− mice and studies using a phospho-antibody array identified six proteins with increased phosphorylation (greater than 150%) and nine proteins with decreased phosphorylation (greater than 33% decrease) in the hearts of exercised cyclin D2−/− mice compared to exercised NTG littermate controls. Our results demonstrate that unlike the other hypertrophic signaling molecules tested here, cyclin D2 is an important regulator of both pathologic and physiological hypertrophy. Impact statement This research is relevant as the hypertrophic signaling pathways tested here have only been characterized for their role in pathological hypertrophy, and not in the context of exercise or physiological hypertrophy. By using the same transgenic mouse lines utilized in previous studies, our findings provide a novel and important understanding for the role of these signaling pathways in physiological hypertrophy. We found that alterations in the signaling pathways tested here had no impact on exercise performance. Exercise induced cardiac growth in all of the transgenic mice except for the mice deficient in cyclin D2. In the cyclin D2 null mice, cardiac function was not impacted even though the hypertrophic response was blunted and a number of signaling pathways are differentially regulated by exercise. These data provide the field with an understanding that cyclin D2 is a key mediator of physiological hypertrophy.
High-resolution manganese-enhanced MRI of experimental retinopathy of prematurity.

PURPOSE To test the hypothesis that in experimental retinopathy of prematurity (ROP), retinal neovascularization (NV) and vessel tortuosity have distinct spatial and temporal links with receptor and postreceptor ion demand. METHODS Newborn rats were raised in either room air (controls) or variable oxygen (50%/10% [50/10]). After 14 days, 50/10 rats were recovered in room air until postnatal day (P) 19 or P22. Peripheral retinal NV severity and incidence and panretinal arteriole and venule tortuosity indexes (TI(a), TI(v)) were measured from ADPase-stained retinal wholemounts. Intraretinal ion demand and retinal thickness were measured from high-resolution manganese-enhanced MRI (MEMRI). In separate experiments, intraretinal manganese uptake was also measured in adult rats pretreated with diltiazem, a Ca(2+) channel antagonist. RESULTS In 50/10 rats, peripheral retinal NV severity was significantly greater than in controls at P19 and was decreased by P22. Panretinal TI(a) and TI(v) were increased over control values at P19, but only TI(v) decreased by P22. Unlike control retinas at P19 that had a centroperipheral total retinal thickness gradient, 50/10 retinas had similar central and peripheral total retinal thickness. The 50/10 group also demonstrated a correlation between peripheral retinal NV and TI(a) and TI(v). Peripheral intraretinal uptake of manganese was significantly supernormal at P19 and decreased by P22. Increased peripheral intraretinal retinal manganese uptake was associated with peripheral NV severity and panretinal TI(a). In contrast, ion demand of central postreceptor, but not receptor, retina was significantly associated with peripheral NV severity and panretinal TI(a). Panretinal TI(v) was not correlated with intraretinal ion demand in any case. In adult rats, diltiazem suppressed (P < 0.05) intraretinal manganese uptake. CONCLUSIONS The present data raise the possibility that altered retinal layer-specific ion demand causes retinal circulation abnormalities in experimental ROP.
Dynamic 3D PET reconstruction for kinetic analysis using patch-based low-rank penalty

Dynamic positron emission tomography (PET) is widely used to identify metabolism over time. However, conventional reconstruction algorithm provides a noisy reconstruction due to the lack of photon counts in each frame. Therefore, the main goal of this paper is to develop a novel spatio-temporal regularization approach that exploits inherent similarities within intra- and inter- frames. One of the main contributions of this paper is to demonstrate that such correlations can be exploited using a low rank constraint of overlapping similarity blocks. The resulting optimization framework is, however, non-smooth and non Lipschitz due to the low-rank penalty terms and Poisson log-likelihood. Therefore, we propose a novel globally convergent optimization method using the concave-convex procedure (CCCP) by exploiting Legendre-Fenchel transform.We confirm that the proposed algorithm can provide significantly improved image quality.
Placental vessel adaptation during gestation and to high altitude: changes in diameter and perivascular cell coverage.

The objective of this study was to determine how human placental vascular structures change during gestation and whether this would be altered by external factors such as reduced ambient oxygen. To achieve this, several experiments were carried out: Vessel profile diameter was measured and the presence of perivascular cells (pericytes or smooth muscle cells) noted. This was carried out in normal human first trimester and term placentae, and in term placentae obtained from high altitude and an ethnically matched lowland population. In addition, to characterize endothelial cells in human placenta a panel of endothelial markers anti-CD 105, CD31, CD34, Von Willebrand factor (vWF), Ulex europaeus agglutinin 1 (UEA I), Peanut agglutinin (PNA), Dolichos biflorus agglutinin (DBA) and Bandeieraea simplicifolia agglutinin 1 (BS 1) was used. The proportion of vessels associated with perivascular cells rises during gestation from 37 per cent in the first trimester to 63 per cent at term (P<0.0001) and vessels with perivascular cells have a larger median diameter at term. In placentae obtained at high altitude, the vessels are dilated and are less frequently associated with perivascular cells. The absence of perivascular cells may allow remodelling of capillaries and this is likely to be physiological important in the first trimester but also under physiological or pathological stress.
A dual three-phase induction machine based flywheel storage system driven by modular multilevel converters for fault ride through in HVDC systems

One of the main challenges of voltage source converter based high voltage direct current (VSC-HVDC) transmission systems is the AC faults at the grid side. This work introduces the integration of multiphase induction machine (IM) based flywheel energy storage systems (FESS) with VSC-HVDC systems for AC side fault ride through purposes employing modular multilevel converters (MMC). MMCs have become suitable candidates for medium/high power energy conversion systems due to the capability of simply extending the levels of the converter while retaining high levels of reliability. In order to enhance the storage system reliability, a dual three phase IM is used to drive the FESS due to its fault tolerance capability. In this paper, the performance of the FESS is investigated under the operation of a dual three phase IM being driven by two three-phase MMCs. To step-down the DC-link voltage of the HVDC system to a proper voltage level for IMs, the DC-link voltage is divided into two series connected capacitor, and each capacitor voltage is fed as an input DC voltage for each three- phase MMC. The control strategies of the MMCs and the IM are presented, in addition to the IM mathematical model. Simulation case studies are performed using MATLAB/Simulink to validate the proposed system.
[Tumor necrosis factor-alpha enhances the effect of endothelin on renal vasoconstriction in isolated perfused rat kidney].

OBJECTIVE To explore the role of tumor necrosis factor-alpha (TNF-alpha) in the pathogenesis of hepatorenal syndrome. METHODS By isolated perfused kidney technique, rat kidneys were perfused at a constant flow. Changes in perfusion pressure (mmHg) were consecutively measured with multi-functional physiology recorder. After TNF-alpha or heparin treated 90 minutes, the perfusion pressure stimulated by endothelin-1 (ET-1) was detected. RESULTS TNF-alpha and heparin didn't modify the baseline perfusion pressure. When ET-1 was added at 2 nmol/L, the perfusion pressures increased to (47+/-9) mmHg, (97+/-36) mm Hg and (11+/-6) mm Hg in control, TNF-alpha and heparin (10mg/L) treated group, respectively, which were different among the three groups (t>or=3.811, P<0.01). No pathological damages were found in kidney tissues from all the groups after being stained with hematoxylin/eosin. CONCLUSION TNF-alpha plays an important role in the pathogenesis of hepatorenal syndrome by promoting renal vasoconstriction.
Feasibility and effectiveness of a cognitive remediation programme with original computerised cognitive training and group intervention for schizophrenia: a multicentre randomised trial

ABSTRACT Devising new methods to improve neurocognitive impairment through cognitive remediation is an important research goal. We developed an original computer programme termed the Japanese Cognitive Rehabilitation Programme for Schizophrenia (JCORES) that provides cognitive practice across a broad range of abilities. The current study examined for the first time whether a cognitive remediation programme, including both computerised cognitive training using JCORES and group intervention such as enhancing meta-cognition and teaching strategies, is more effective than treatment as usual for improving neurocognitive and social functioning. Sixty-two outpatients with schizophrenia were randomised to either a cognitive remediation group or a control group. Participants engaged in two computerised cognitive training sessions and one group meeting per week for 12 weeks. The average number of total sessions attended (computerised cognitive practice + group intervention) was 32.3 (89.7%). The cognitive remediation group showed significantly more improvements in verbal memory, composite score of the Brief Assessment of Cognition in Schizophrenia, Japanese version (BACS-J), and general psychopathology on the Positive and Negative Syndrome Scale (PANSS) than the control group. These findings demonstrate that a cognitive remediation programme is feasible in Japan and is a more effective way to improve neurocognitive functioning and psychiatric symptoms.
Outcomes generated by patients with rheumatoid arthritis: how important are they?

BACKGROUND It has been shown previously that patients with rheumatoid arthritis (RA) can generate a wide range of outcomes that they consider important in treatment. It is not known if these outcomes are generally important in the wider RA patient community. OBJECTIVES (1) To examine whether recent patient-generated outcomes are generalizable within a wider RA population; (2) to assess the relative importance of each outcome; and(3) to explore whether any important outcomes have been omitted. METHODS A questionnaire, listing 23 outcomes previously generated by RA patients, was distributed through three rheumatology centres in the UK. Patients gave an importance score to each outcome (0-3), selected their top three most important outcomes, and then listed any outcomes of personal importance that were missing. RESULTS 323 questionnaires were returned (65%). All outcomes were deemed important. Independence, pain, and mobility were most frequently selected by patients in their top three outcomes but were not chosen by 61-66% of patients. The next most commonly chosen outcomes related to feeling well and fatigue. Factor analysis revealed six reasonably distinct groupings: general well-being (11.9% explained variance), day-to-day functioning(10.6%), emotional and psychological well-being (10.6%), social role and confidence (10%), physical symptoms (9.5%) and medication issues (7.9%). CONCLUSION Outcomes generated by patients as important in RA, are generalizable and inclusive. The most important (independence, pain and mobility) are routinely treated and measured. The next most important (feeling well, fatigue) are infrequently addressed and deserve urgent consideration for measurement, treatment and research.
AutoMFIS: Fuzzy Inference System for multivariate time series forecasting

A time series is the most commonly used representation for the evolution of a given variable over time. In a time series forecasting problem, a model aims at predicting the series' future values, assuming that all information needed to do so is contained in the series' past behavior. Since the phenomena described by the time series does not always exist in isolation, it is possible to enhance the model with historical data from other related time series. The structure formed by several different time series occurring in parallel, each featuring the same interval and dimension, is called a multivariate time series. This paper presents a methodology for the generation of a Fuzzy Inference System (FIS) for multivariate time series forecasting from historical data, aiming at good performance in both forecasting accuracy and rule base interpretability - in order to extract knowledge about the relationship between the modeled time series. Several aspects related to the operation and construction of such a FIS are investigated regarding complexity and semantic clarity. The model is evaluated by applying it to multivariate time series obtained from the complete M3 competition database and by comparing it to other methods in terms of accuracy. In addition knowledge extraction possibilities from the resulting rule base are explored.
Genomic profiling of malignant pleural mesothelioma with array‐based comparative genomic hybridization shows frequent non‐random chromosomal alteration regions including JUN amplification on 1p32

Genome‐wide array‐based comparative genomic hybridization analysis of malignant pleural mesotheliomas (MPM) was carried out to identify regions that display DNA copy number alterations. Seventeen primary tumors and nine cell lines derived from 22 individuals were studied, some of them originating from the same patients. Regions of genomic aberrations observed in >20% of individuals were 1q, 5p, 7p, 8q24 and 20p with gains, and 1p36.33, 1p36.1, 1p21.3, 3p21.3, 4q22, 4q34‐qter, 6q25, 9p21.3, 10p, 13q33.2, 14q32.13, 18q and 22q with losses. Two regions at 1p32.1 and 11q22 showed a high copy gain. The 1p32.1 region contained a protooncogene, JUN, and we further demonstrated overexpression of JUN with real‐time polymerase chain reaction analysis. As MPM cell lines did not overexpress JUN, our findings suggested that induction of JUN expression was involved in the development of MPM cells in vivo, which also might result in gene amplification in a subset of MPM. Meanwhile, the most frequent alteration was the 9p21.3 deletion, which includes the p16INK4a/p14ARF locus. With polymerase chain reaction analysis, we determined the extent of the homozygous deletion regions of the p16INK4a/p14ARF locus in MPM cell lines, which indicated that the deletion regions varied among cell lines. Our results with array comparative genomic hybridization analysis provide new insights into the genetic background of MPM, and also give some clues to develop a new molecular target therapy for MPM. (Cancer Sci 2007; 98: 438–446)
Effect of stretching on the elastic characteristics and the contractile component of frog striated muscle

1. The force—velocity relationship and the stress—strain curve of the so‐called series elastic component (s.e.c.) of frog sartorius, semitendinosus and gastrocnemius have been determined during shortening against a given force (isotonic quick‐release) and at high speed (controlled release): (a) from a state of isometric contraction and (b) after stretching of the contracted muscle. In both cases the muscle was released from the same length: this was usually slightly greater than the muscle's resting length.
Dendritic Cells Charged with Apoptotic Tumor Cells Induce Long-Lived Protective CD4+ and CD8+ T Cell Immunity against B16 Melanoma 1

Dendritic cells (DCs) are potent APCs and attractive vectors for cancer immunotherapy. Using the B16 melanoma, a poorly immunogenic experimental tumor that expresses low levels of MHC class I products, we investigated whether DCs loaded ex vivo with apoptotic tumor cells could elicit combined CD4+ and CD8+ T cell dependent, long term immunity following injection into mice. The bone marrow-derived DCs underwent maturation during overnight coculture with apoptotic melanoma cells. Following injection, DCs migrated to the draining lymph nodes comparably to control DCs at a level corresponding to ∼0.5% of the injected inoculum. Mice vaccinated with tumor-loaded DCs were protected against an intracutaneous challenge with B16, with 80% of the mice remaining tumor-free 12 wk after challenge. CD4+ and CD8+ T cells were efficiently primed in vaccinated animals, as evidenced by IFN-γ secretion after in vitro stimulation with DCs loaded with apoptotic B16 or DCs pulsed with the naturally expressed melanoma Ag, tyrosinase-related protein 2. In addition, B16 melanoma cells were recognized by immune CD8+ T cells in vitro, and cytolytic activity against tyrosinase-related protein 2180–188-pulsed target cells was observed in vivo. When either CD4+ or CD8+ T cells were depleted at the time of challenge, the protection was completely abrogated. Mice receiving a tumor challenge 10 wk after vaccination were also protected, consistent with the induction of tumor-specific memory. Therefore, DCs loaded with cells undergoing apoptotic death can prime melanoma-specific helper and CTLs and provide long term protection against a poorly immunogenic tumor in mice.
Gait and Cognition: A Complementary Approach to Understanding Brain Function and the Risk of Falling

Until recently, clinicians and researchers have performed gait assessments and cognitive assessments separately when evaluating older adults, but increasing evidence from clinical practice, epidemiological studies, and clinical trials shows that gait and cognition are interrelated in older adults. Quantifiable alterations in gait in older adults are associated with falls, dementia, and disability. At the same time, emerging evidence indicates that early disturbances in cognitive processes such as attention, executive function, and working memory are associated with slower gait and gait instability during single‐ and dual‐task testing and that these cognitive disturbances assist in the prediction of future mobility loss, falls, and progression to dementia. This article reviews the importance of the interrelationship between gait and cognition in aging and presents evidence that gait assessments can provide a window into the understanding of cognitive function and dysfunction and fall risk in older people in clinical practice. To this end, the benefits of dual‐task gait assessments (e.g., walking while performing an attention‐demanding task) as a marker of fall risk are summarized. A potential complementary approach for reducing the risk of falls by improving certain aspects of cognition through nonpharmacological and pharmacological treatments is also presented. Untangling the relationship between early gait disturbances and early cognitive changes may be helpful in identifying older adults at risk of experiencing mobility decline, falls, and progression to dementia.
The Relationship Between Social Anxiety and Online Communication Among Adolescents in the City of Isfahan, Iran

Background: The internet is a phenomena that changes human, specially the younger generation's, life in the 21st century. Online communication is a common way of interacting among adolescents who experience feelings of social anxiety. The aim of this study was to investigate the relationship between social anxiety and online communication in adolescents. Methods: Three hundred and thirty students aged 13-16 years were selected from eight middle and high schools in Isfahan by multistage cluster sampling. Each of them completed a survey on the amount of time they spent communicating online, the topics they discussed, the partners they engaged with and their purpose for communicating over the internet. They also completed the social anxiety scale of adolescents. Data were analyzed using Pearson correlation and multiple regression. Results: Results of the Pearson analysis showed that online communication has a significant positive relationship with apprehension and fear of negative evaluation (AFNE), and a significant negative relationship with tension and inhibition in social contact (TISC) (P < 0.01). The results of regression analysis showed that the best predictor of online communication is AFNE, TISC. Conclusions: It is suggested that students from middle school get assessed in terms of the level of social anxiety. Then, the quality and quantity of their online communication should be moderated through group training and consulting and referral to medical centers, if needed. The results of this study may lead to optimal use of online communications and reduce the personal, social and psychological problems of adolescents.
Short-term laryngeal electromyography and histopathological findings after primary reconstruction of the inferior laryngeal nerve in rabbits: prospective study

Abstract Introduction: The recurrent laryngeal nerve can be injured during surgery. This study investigated recurrent laryngeal nerve reinnervation. Objective: To study the short-term effects of primary anastomosis of the recurrent laryngeal nerve, by laryngeal electromyography and histopathological analysis, in a rabbit model. Method: Twenty Zealand rabbits underwent either right recurrent laryngeal nerve (1) transection with excision of 1 cm or (2) transection and end-to-end primary anastomosis. Vocal fold movements, laryngeal electromyography results and histological changes were recorded. Results: Vocal fold analysis showed a paramedian vocal fold in both groups, with perceptible vibratory movements in group two. Electromyography revealed total denervation potentials in group one, but denervation and regeneration signs in group two. Histopathologically, hyperkeratosis and parakeratosis of the vocal fold mucosa were seen in group one, and signs of parakeratosis and hyperplasia in group two. Conclusion: Even under ideal conditions for primary recurrent laryngeal nerve anastomosis, a return to normal muscle function is unlikely. However, such anastomosis prevents muscle atrophy, and should be performed as soon as possible. The degree of nerve recovery is associated with the number, amplitude and myelination level of fibrils returning to the original motor end-plaque.