Miracle-dz/UniFAR-FTUs huggingface dataset:
A Drosophila melanogaster Model of Diastolic Dysfunction and Cardiomyopathy Based on Impaired Troponin-T Function

Rationale: Regulation of striated muscle contraction is achieved by Ca2+-dependent steric modulation of myosin cross-bridge cycling on actin by the thin filament troponin–tropomyosin complex. Alterations in the complex can induce contractile dysregulation and disease. For example, mutations between or near residues 112 to 136 of cardiac troponin-T, the crucial TnT1 (N-terminal domain of troponin-T)–tropomyosin-binding region, cause cardiomyopathy. The Drosophila upheld101 Glu/Lys amino acid substitution lies C-terminally adjacent to this phylogenetically conserved sequence. Objective: Using a highly integrative approach, we sought to determine the molecular trigger of upheld101 myofibrillar degeneration, to evaluate contractile performance in the mutant cardiomyocytes, and to examine the effects of the mutation on the entire Drosophila heart to elucidate regulatory roles for conserved TnT1 regions and provide possible mechanistic insight into cardiac dysfunction. Methods and Results: Live video imaging of Drosophila cardiac tubes revealed that the troponin-T mutation prolongs systole and restricts diastolic dimensions of the heart, because of increased numbers of actively cycling myosin cross-bridges. Elevated resting myocardial stiffness, consistent with upheld101 diastolic dysfunction, was confirmed by an atomic force microscopy–based nanoindentation approach. Direct visualization of mutant thin filaments via electron microscopy and 3-dimensional reconstruction resolved destabilized tropomyosin positioning and aberrantly exposed myosin-binding sites under low Ca2+ conditions. Conclusions: As a result of troponin–tropomyosin dysinhibition, upheld101 hearts exhibited cardiac dysfunction and remodeling comparable to that observed during human restrictive cardiomyopathy. Thus, reversal of charged residues about the conserved tropomyosin-binding region of TnT1 may perturb critical intermolecular associations required for proper steric regulation, which likely elicits myopathy in our Drosophila model.
The Transcriptional Repressor ZFM1 Interacts with and Modulates the Ability of EWS to Activate Transcription*

The ZFM1 protein is both a transcriptional repressor and identical to the splicing factor SF1. ZFM1 was shown to interact with and repress transcription from the glycine, glutamine, serine, and threonine-rich transcription activation domain of the sea urchin transcription factor, stage-specific activator protein (SSAP). EWS, a human protein involved in cellular transformation in Ewing’s sarcoma tumors, contains an NH2-terminal transcriptional activation domain (NTD) which resembles that of SSAP in both amino acid composition and the ability to drive transcription to levels higher than VP16 in most cell types. Here we report that ZFM1 also interacts with EWS in both two-hybrid assays and glutathioneS-transferase pull-down experiments. The region on EWS which interacts with ZFM1 maps to 37 amino acids within its NTD. Overexpression of ZFM1 in HepG2 cells represses the transactivation of reporter gene expression driven by Gal4-EWS-NTD fusion protein and this repression correlates with ZFM1 binding to EWS. Furthermore, two proteins, TLS and hTAFII68, which have extensive homology to EWS, also interact with ZFM1. Recently, it was discovered that EWS/TLS/hTAFII68 are each present in distinct TFIID populations and EWS and hTAFII68 were also found to be associated with the RNA polymerase II holoenzyme. The association of ZFM1 with these proteins implies that one normal cellular function for ZFM1 may be to negatively modulate transcription of target genes coordinated by these cofactors.
Serum ischemia-modified albumin levels in an experimental acute mesenteric ischemia model.

OBJECTIVES This experimental study aimed to assess the changes in the levels of serum ischemia-modified albumin (IMA) and interleukin-6 (IL-6) by time in cases of acute mesenteric ischemia due to superior mesenteric artery occlusion. METHODS Twenty-one New Zealand rabbits were randomly divided into three groups. Blood samples were collected at hours 0, 1, 3, and 6 from animals in a control group; a sham group following a simple laparotomy; and in an ischemia group following superior mesenteric artery ligation. All blood samples were analyzed for serum IMA and IL-6 levels, and then the time-dependent changes of biomarkers were investigated. RESULTS The serum IMA levels of the ischemia group at hours 3 and 6 were significantly higher than those of the control and sham groups (hour 3, p = 0.017; hour 6, p = 0.001). The increase in serum IL-6 levels in the ischemia group at hours 1, 3, and 6 compared to the control and sham groups was also significant (hour 1, p = 0.002; hour 3, p = 0.003; hour 6, p = 0.003). CONCLUSIONS IMA may be helpful as a marker in the diagnosis of acute mesenteric ischemia; however, its diagnostic value and use as a routine biochemical test should be assessed in further studies.
Association of ACE genotype and predominantly diastolic hypertension: a preliminary study

Background. The insertion/deletion (I/D) angiotensin-converting enzyme (ACE) polymorphism has been established as a cardiovascular risk factor in some populations, but the association with essential hypertension is controversial. Predominantly diastolic hypertension (PDH), or narrow pulse pressure hypertension, has been shown to have increased peripheral resistance. Because a DD genotype has been associated with higher plasma ACE levels and angiotensin II activity, we genotyped PDH patients for ACE I/D polymorphism. Methods. Ninety-three patients with systolic blood pressure (BP) < 140 mmHg systolic and diastolic BP > 90 mmHg, or BP > 140/90 mmHg with a pulse pressure < 45 mmHg, were defined as PDH. The II, ID and DD genotype variants of ACE were characterised by the triple primer nested-PCR method. Results were compared to 75 normotensive control individuals. Statistical significance was assessed by the Chi square test. Results. The genotype distribution among PDH patients was II=20 (21.5%), ID=34 (36.5%), DD=39 (42%), while the distribution among normotensive controls was II= O 16 (21.4%), ID=42 (56%), DD=17 (22.6%). The difference in genotype distribution between PDH patients and controls was significant (p<0.02). ACE allele frequencies in PDH patients and controls were D=0.60, I=0.40 and D=0.51, and controls were D=0.60, 1=0.40 and D=0.51, I=0.49, respectively, statistically non-significant (ns). Conclusion. These results suggest an association between ACE genotype DD and predominantly diastolic hypertension.
Design of compact monolithically integrated semiconductor spot-size converters for efficient laser-fiber coupling

A rigorous numerical approach, based on the full vectorial finite element method, is used to design various types of monolithically integrated spot-size converters for efficient coupling to an industry-standard optical fiber. Spot-size converters with a tapered core, using uniform directional couplers and MMI structures are discussed and the predicted performance of the system reported.
Intravenous and intrapulmonary recombinant tissue-type plasminogen activator in the treatment of acute massive pulmonary embolism.

Eight centers participated in a study in which intrapulmonary and intravenous administration of recombinant tissue-type plasminogen activator (rt-PA) were compared in 34 patients with acute massive pulmonary embolism. All patients received intravenous heparin in a bolus of 5,000 IU followed by 1,000 IU/hr. After 50 mg rt-PA given over 2 hr the severity of embolism, determined from pulmonary angiograms, declined by 12% in the intrapulmonary drug group (p less than .005) and 15% in the intravenous drug group (p less than .005); mean pulmonary arterial pressure fell from 31 +/- 7 to 22 +/- 6 mm Hg (p less than .005) and from 31 +/- 12 to 21 +/- 9 mm Hg (p less than .005) in the respective groups. After a further 50 mg given over 5 hr (22 patients), the angiographically determined severity of embolism had decreased by 38% from baseline in the intrapulmonary drug group and by 38% in the intravenous drug group. The mean pulmonary arterial pressure further declined to 18 +/- 7 and 12 +/- 5 mm Hg in the respective groups. Fibrinogen levels dropped to 48% of baseline after 50 mg and to 36% of baseline after 100 mg rt-PA. Some degree of bleeding at puncture and/or operation sites was noted in 16 patients, including four who required a transfusion of two or more units of blood and had been operated on an average of 7.5 days (range 2 to 13) before thrombolytic treatment was started. (ABSTRACT TRUNCATED AT 250 WORDS)
How representative are the known structures of the proteins encoded by (AU:OK?) a complete genome? A comprehensive structural census

Results: The known structures are compared to the proteins encoded by eight complete microbial genomes in terms of simple statistics such as sequence length, composition and secondary structure. The known structures are represented by a collection of nonhomologous domains from the PDB and a smaller list of ‘biophysical proteins’ on which folding experiments have concentrated. The proteins encoded by the genomes are considered as a whole and divided into various regions, such as known-structure homologue, low complexity (nonglobular), transmembrane or linker. Various tests are performed to assess the significance of the reported differences, in both a practical and a statistical sense. Conclusions: The proteins encoded by the genomes are significantly different from those in the PDB. Their sequence lengths, which follow an extreme value distribution, are longer than the PDB proteins and much longer than the biophysical proteins. Their composition differs from the PDB proteins in having more Lys, Ile, Asn and Gln and less Cys and Trp. This is true overall and especially for the regions corresponding to soluble proteins of as yet unknown fold. Secondary-structure prediction on these uncharacterized regions indicates that they contain on average more helical structure than the PDB; differences about this mean are small, with yeast having slightly more β structure and Haemophilus influenzae and Helicobacter pylori more α structure. Further information is available through the GeneCensus system at
Mining Negative Sequential Patterns in Transaction Databases

Sequential pattern is an important research topic in data mining and knowledge discovery. Sequential pattern is traditionally formed as (A, B) where A and B are frequent sequence in a transaction database. We extend this definition to include sequential patterns of forms (A, notB), (notA, B) and (notA, notB), which present negative sequential patterns among sequences. We call patterns of the form (A, B) positive sequential patterns, and patterns of the other forms negative patterns. Negative sequential patterns can also provide very useful insight view into the data set although they are different from positive ones. We put forward a discovery algorithm for mining negative sequential patterns from large transaction database in this paper.
Turnpike and dissipativity properties in dynamic real-time optimization and economic MPC

We investigate the turnpike and dissipativity properties of continuous-time optimal control problems. These properties play a key role in the analysis and design of schemes for dynamic real-time optimization and economic model predictive control. We show in a continuous-time setting that dissipativity of a system with respect to a steady state implies the existence of a turnpike at this steady state and optimal stationary operation at this steady state. Furthermore, we investigate the converse statements: We show that the existence of a turnpike at a steady state implies (a) that this steady state is the optimal steady state; and (b) that over an infinite horizon the system is optimally operated at this steady state. We draw upon a numerical example to illustrate our findings.
A Biomimetic Carbon Nanotube Synapse Circuit

A neural synapse circuit design is presented here. The circuit models the result of an action potential applied to a biological synapse, including neurotransmitter action, membrane potentials, and ion pumps. The output of the circuit is an Excitatory PostSynaptic Potential (EPSP). The circuit is simulated using carbon nanotube SPICE models.
MRF-Based Fast HEVC Inter CU Decision With the Variance of Absolute Differences

The newly developed High Efficiency Video Coding (HEVC) Standard has improved video coding performance significantly in comparison to its predecessors. However, more intensive computation complexity is introduced by implementing a number of new coding tools. In this paper, a fast coding unit (CU) decision based on Markov random field (MRF) is proposed for HEVC inter frames. First, it is observed that the variance of the absolute difference (VAD) is proportional with the rate-distortion (R-D) cost. The VAD based feature is designed for the CU selection. Second, the decision of CU splittings is modeled as an MRF inference problem, which can be optimized by the Graphcut algorithm. Third, a maximum a posteriori (MAP) approach based on the R-D cost is conducted to evaluate whether the unsplit CUs should be further split or not. Experimental results show that the proposed algorithm can achieve about 53% reduction of the coding time with negligible coding performance degradation, which outperforms the state-of-the-art algorithms significantly.
Synaptic Islands Defined by the Territory of a Single Astrocyte

In the mammalian brain, astrocytes modulate neuronal function, in part, by synchronizing neuronal firing and coordinating synaptic networks. Little, however, is known about how this is accomplished from a structural standpoint. To investigate the structural basis of astrocyte-mediated neuronal synchrony and synaptic coordination, the three-dimensional relationships between cortical astrocytes and neurons was investigated. Using a transgenic and viral approach to label astrocytes with enhanced green fluorescent protein, we performed a three-dimensional reconstruction of astrocytes from tissue sections or live animals in vivo. We found that cortical astrocytes occupy nonoverlapping territories similar to those described in the hippocampus. Using immunofluorescence labeling of neuronal somata, a single astrocyte enwraps on average four neuronal somata with an upper limit of eight. Single-neuron dye-fills allowed us to estimate that one astrocyte contacts 300–600 neuronal dendrites. Together with the recent findings showing that glial Ca2+ signaling is restricted to individual astrocytes in vivo, and that Ca2+ signaling leads to gliotransmission, we propose the concept of functional islands of synapses in which groups of synapses confined within the boundaries of an individual astrocyte are modulated by the gliotransmitter environment controlled by that astrocyte. Our description offers a new structurally based conceptual framework to evaluate functional data involving interactions between neurons and astrocytes in the mammalian brain.
Social Effects in the Diffusion of solar Photovoltaic Technology in the UK

The main research question in this paper is whether the installation rate of solar pv technology is affected by social spillovers from spatially close households. The installed base, defined as the cumulative number of solar v installations within a neighbourhood by the end of a particular month, serves as a measure for the social effects of interest. Motivated by the technology-specific time lag between the decision to adopt a solar Pv panel and the completion of the installation, the third lag of the installed base serves as main regressor of interest in the panel data model employed. The results suggest small, but positive and significant social effects that can be exploited to promote adoption: at the average installation rate of 0.7 installations per 1,000 owner-occupied households, one more solar PV panel in the postcode district increases the installation rate three months later by one percent. At the average number of 6,629 owner—occupied households within a postcode district, this implies an increase in the number of new installations in the neighbourhood by 0.005. Projects involving a high number of installations could hence promote diffusion. A major limitation of the model is that social spillovers are assumed to spread within defined neighbourhoods, only. spatial econometric methods could allow for social effects across these borders.
Selective gene activation by spatial segregation of insulin receptor B signaling

Insulin exerts pleiotropic effects at the cellular level. Signaling via the two isoforms of the insulin receptor (IR) may explain the activation of different signaling cascades, while it remains to be explored how selectivity is achieved when utilizing the same IR isoform. We now demonstrate that insulin‐stimulated transcription of c‐fos and glucokinase genes is activated simultaneously in the insulin‐producing β‐cell via IR‐B localized in different cellular compartments. Insulin activates the glucokinase gene from plasma membrane‐standing IR‐B, while c‐fos gene activation is dependent on clathrin‐mediated IR‐B‐endocytosis and signaling from early endosomes. Moreover, glucokinase gene up‐regulation requires the integrity of the jux‐tamembrane IR‐B NPEY‐motif and signaling via PI3K‐C2α‐like/PDK1/PKB, while c‐fos gene activation requires the intact C‐terminal YTHM‐motif and signaling via PI3K Ia/Shc/MEK1/ERK. By using IR‐B as an example it is thus possible to demonstrate how spatial segregation allows simultaneous and selective signaling via the same receptor isoform in the same cell. —Uhles S. , Moede T. , Leibiger B. , Berggren P.‐O. , and Leibiger I. B. Selective gene activation by spatial segregation of insulin receptor B signaling. FASEB J. 21, 1609–1621 (2007)
Induction of foxP3+ Regulatory T Cells in the Periphery of T Cell Receptor Transgenic Mice Tolerized to Transplants1

Transplantation tolerance can be induced in mice by grafting under the cover of nondepleting CD4 plus CD8 or CD154 mAbs. This tolerance is donor Ag specific and depends on a population of CD4+ regulatory T cells that, as yet, remain poorly defined in terms of their specificity, origin, and phenotype. Blocking of the Ag-specific response in vitro with an anti-CD4 mAb allowed T cells from monospecific female TCR-transgenic mice against the male Ag Dby, presented by H-2Ek, to express high levels of foxP3 mRNA. foxP3 induction was dependent on TGF-β. The nondepleting anti-CD4 mAb was also able to induce tolerance in vivo in such monospecific TCR-transgenic mice, and this too was dependent on TGF-β. As in conventional mice, acquired tolerance was dominant, such that naive monospecific T cells were not able to override tolerance. Splenic T cells from tolerant mice proliferated normally in response to Ag, and secreted IFN-γ and some IL-4, similar to control mice undergoing primary or secondary graft rejection. High levels of foxP3 mRNA, and glucocorticoid-induced TNFR superfamily member 18 (GITR)+ CD25+ T cells were found within the tolerated skin grafts of long-term tolerant recipients. These data suggest that regulatory T cells maintaining transplantation tolerance after CD4 Ab blockade can be induced de novo through a TGF-β-dependent mechanism, and come to accumulate in tolerated grafts.
Robust Synchronization via Homogeneous Parameter-Dependent Polynomial Contraction Matrix

Robust synchronization problem is a key issue in chaotic circuits and nonlinear systems. This paper is concerned with robust synchronization problem of polynomial nonlinear system affected by time-varying uncertainties on topology, i.e., structured uncertain parameters constrained in a bounded-rate polytope. Via partial contraction analysis, novel conditions, both for robust exponential synchronization and for robust asymptotical synchronization, are proposed by using parameter-dependent contraction matrices. In addition, for polynomial nonlinear system, this paper introduces a new class of contraction matrix, i.e., homogeneous parameter-dependent polynomial contraction matrix (HPD-PCM), by which tractable conditions of linear matrix inequalities (LMIs) are provided via affine space parametrizations. Furthermore, the variant rate margin for robust asymptotical synchronization is, for the first time, proposed and investigated via handling generalized eigenvalue problems (GEVPs). A set of representative examples demonstrate the effectiveness of proposed method.
Optimal Energy Management for a Residential Microgrid Including a Vehicle-to-Grid System

An optimization model is proposed to manage a residential microgrid including a charging spot with a vehicle-to-grid system and renewable energy sources. In order to achieve a realistic and convenient management, we take into account: (1) the household load split into three different profiles depending on the characteristics of the elements considered; (2) a realistic approach to owner behavior by introducing the novel concept of range anxiety; (3) the vehicle battery management considering the mobility profile of the owner and (4) different domestic renewable energy sources. We consider the microgrid operated in grid-connected mode. The model is executed one-day-ahead and generates a schedule for all components of the microgrid. The results obtained show daily costs in the range of 2.82 C = to 3.33 C =; the proximity of these values to the actual energy costs for Spanish households validate the modeling. The experimental results of applying the designed managing strategies show daily costs savings of nearly 10%.
Neural Features of Processing the Enforcement Phrases Used during Occupational Health and Safety Inspections: An ERP Study

The appropriate enforcement phrases used during occupational health and safety (OHS) inspection activities is a crucial factor to guarantee the compliance with OHS regulations in enterprises. However, few researchers have empirically investigated the issue of how enforcement phrases are processed. The present study explored the neural features of processing two types of enforcement phrases (severe-and-deterrent vs. mild-and-polite phrases) used during OHS inspections by applying event-related potentials (ERP) method. Electroencephalogram data were recorded while the participants distinguished between severe-and-deterrent phrases and mild-and-polite phrases depicted in written Chinese words. The ERP results showed that severe-and-deterrent phrases elicited significantly augmented P300 amplitude with a central-parietal scalp distribution compared with mild-and-polite phrases, indicating the allocation of more attention resources to and elaborate processing of the severe-and-deterrent phrases. It reveals that humans may consider the severe-and-deterrent phrases as more motivationally significant and elaborately process the severity and deterrence information contained in the enforcement phrases for the adaptive protection. The current study provides an objective and supplementary way to measure the efficiency of different enforcement phrases at neural level, which may help generate appropriate enforcement phrases and improve the performance of OHS inspections.