Miracle-dz/UniFAR-FTUs huggingface dataset:
Acceleration of Crossbridge Kinetics by Protein Kinase A Phosphorylation of Cardiac Myosin Binding Protein C Modulates Cardiac Function

Normal cardiac function requires dynamic modulation of contraction. β1-Adrenergic–induced protein kinase (PK)A phosphorylation of cardiac myosin binding protein (cMyBP)-C may regulate crossbridge kinetics to modulate contraction. We tested this idea with mechanical measurements and echocardiography in a mouse model lacking 3 PKA sites on cMyBP-C, ie, cMyBP-C(t3SA). We developed the model by transgenic expression of mutant cMyBP-C with Ser-to-Ala mutations on the cMyBP-C knockout background. Western blots, immunofluorescence, and in vitro phosphorylation combined to show that non–PKA-phosphorylatable cMyBP-C expressed at 74% compared to normal wild-type (WT) and was correctly positioned in the sarcomeres. Similar expression of WT cMyBP-C at 72% served as control, ie, cMyBP-C(tWT). Skinned myocardium responded to stretch with an immediate increase in force, followed by a transient relaxation of force and finally a delayed development of force, ie, stretch activation. The rate constants of relaxation, krel (s-1), and delayed force development, kdf (s-1), in the stretch activation response are indicators of crossbridge cycling kinetics. cMyBP-C(t3SA) myocardium had baseline krel and kdf similar to WT myocardium, but, unlike WT, krel and kdf were not accelerated by PKA treatment. Reduced dobutamine augmentation of systolic function in cMyBP-C(t3SA) hearts during echocardiography corroborated the stretch activation findings. Furthermore, cMyBP-C(t3SA) hearts exhibited basal echocardiographic findings of systolic dysfunction, diastolic dysfunction, and hypertrophy. Conversely, cMyBP-C(tWT) hearts performed similar to WT. Thus, PKA phosphorylation of cMyBP-C accelerates crossbridge kinetics and loss of this regulation leads to cardiac dysfunction.
Outbreak of Shiga Toxin-Producing Escherichia coli (STEC) O157:H7 Associated with Romaine Lettuce Consumption, 2011

Background Shiga toxin-producing Escherichia coli (STEC) O157:H7 is the causal agent for more than 96,000 cases of diarrheal illness and 3,200 infection-attributable hospitalizations annually in the United States. Materials and Methods We defined a confirmed case as a compatible illness in a person with the outbreak strain during 10/07/2011-11/30/2011. Investigation included hypothesis generation, a case-control study utilizing geographically-matched controls, and a case series investigation. Environmental inspections and tracebacks were conducted. Results We identified 58 cases in 10 states; 67% were hospitalized and 6.4% developed hemolytic uremic syndrome. Any romaine consumption was significantly associated with illness (matched Odds Ratio (mOR) = 10.0, 95% Confidence Interval (CI) = 2.1–97.0). Grocery Store Chain A salad bar was significantly associated with illness (mOR = 18.9, 95% CI = 4.5–176.8). Two separate traceback investigations for romaine lettuce converged on Farm A. Case series results indicate that cases (64.9%) were more likely than the FoodNet population (47%) to eat romaine lettuce (p-value = 0.013); 61.3% of cases reported consuming romaine lettuce from the Grocery Store Chain A salad bar. Conclusions This multistate outbreak of STEC O157:H7 infections was associated with consumption of romaine lettuce. Traceback analysis determined that a single common lot of romaine lettuce harvested from Farm A was used to supply Grocery Store Chain A and a university campus linked to a case with the outbreak strain. An investigation at Farm A did not identify the source of contamination. Improved ability to trace produce from the growing fields to the point of consumption will allow more timely prevention and control measures to be implemented.
An improved wavelet-based corner detection technique

An improved, wavelet-based technique for corner detection, in 2-D planar curves, is presented. This boundary based technique is simple to implement and computationally efficient and exploits wavelet transform modulus maxima (WTMM) to detect corners. The proposed algorithm is robust with respect to object geometry. We also report results under additive white Gaussian noise (AWGN).
Human immunodeficiency virus type 1 nucleocapsid protein promotes efficient strand transfer and specific viral DNA synthesis by inhibiting TAR-dependent self-priming from minus-strand strong-stop DNA

During the first strand transfer in reverse transcription, minus-strand strong-stop DNA [(-) SSDNA] is annealed to the 3' end of the acceptor RNA in a reaction mediated by base-pairing between terminal repeat sequences in the RNA and their complement in the DNA. The large stem-loop structure in the repeat region known as TAR could interfere with this annealing reaction. We have developed an in vitro human immunodeficiency virus type 1 (HIV-1) system to investigate the effect of TAR on strand transfer. Mutational analysis demonstrates that the presence of TAR in the donor and acceptor templates inhibits strand transfer and is correlated with extensive synthesis of heterogeneous DNAs formed by self-priming from (-) SSDNA. These DNAs are not precursors to the transfer product. Interestingly, products of self-priming are not detected in HIV-1 endogenous reactions; this suggests that virions contain a component which prevents self-priming. Our results show that the viral nucleocapsid protein (NC), which can destabilize secondary structures, drastically reduces self-priming and dramatically increases the efficiency of strand transfer. In addition, the data suggest that the ability to eliminate self-priming is a general property of NC which is manifested during reverse transcriptase pausing at sites of secondary structure in the template. We conclude that this activity of NC is critical for achieving highly efficient and specific viral DNA synthesis. Our findings raise the possibility that inactivation of NC could provide a new approach for targeting reverse transcription in anti-HIV therapy.
Multivariate Approaches to the Detection of Leukemic Cells in Flow Cytometry Readouts

Background: Modern flow cytometers enable researchers to reliably measure four to eight variables, such as size, granularity and expression of extraand intracellular proteins, for thousands of cells per second. In cytometry readouts, leukemic cells can be identified by their display of abnormal surface-protein expression patterns, never observed in physiological blood cells and their precursors. However, dissemination and therapy response of leukemic cells are not fully understood to date. Established oneand two-dimensional analysis-techniques for the identification and investigation of leukemic cells are labor-intensive and fail to capture higherorder dependencies. Such dependencies are known to exist in the cytometry setting, due to properties of utilized materials and biological, superordinate regulatory mechanisms. So far, few multivariate methods, which potentially capture these higher-order interactions, have been proposed for the analysis of cytometry readouts. Methods: We have utilized multivariate analysis techniques for unsupervised clustering andsupervised classification to investigate leukemic cells in flow cytometry readouts. In the unsupervised approach, we employed model-based clustering, which allows us to interpret results in terms of probabilities. For classification, we used established techniques that have been successfully applied in a large number of different settings, namely classification treesandsupport vector machines . Classifiers were built on noisy, conventionally diagnosed training data, artificially contaminated to simulate experimental variations. We assessed classification performance on independent test data and analyzed marker expression of misclassified events. Conclusions: Multivariate classification techniques allow for automating diagnostic procedures on cytometry readouts. They potentially reduce time and costs associated with these procedures, shifting efforts to possible research extensions. Unsupervised cluster analysis of leukemic cells in multivariate space before and after chemo-therapy can provide insights on the characteristics of treatment response and leukemia relapse.
INFLUENCE OF FLOORING ON OBJECTIVE STANDING FATIGUE MEASURES

Flooring may play a role in standing fatigue, however previous studies of flooring on subjective and objective measures thought to be related to fatigue/discomfort, have had mixed results. The majority of the differences in the reported results are probably due to differences in procedures and analysis methods, particularly variations in testing duration and exposure time. The impact of flooring on discomfort/pain is still largely unknown.
The chromo shadow domain, a second chromo domain in heterochromatin-binding protein 1, HP1.

The chromo domain was originally identified as a protein sequence motif common to the Drosophila chromatin proteins, Polycomb (Pc) and heterochromatin protein 1 [HP1; Paro and Hogness (1991) Proc. Natl. Acad. Sci. USA, 88, 263-267; Paro (1990) Trends Genet. , 6, 416-421]. Here we describe a second chromo domain-like motif in HP1. Subsequent refined searches identified further examples of this chromo domain variant which all occur in proteins that also have an N-terminally located chromo domain. Due to its relatedness to the chromo domain, and its occurrence in proteins that also have a classical chromo domain, we call the variant the 'chromo shadow domain'. Chromo domain-containing proteins can therefore be divided into two classes depending on the presence, for example in HP1, or absence, for example in Pc, of the chromo shadow domain. We have also found examples of proteins which have two classical chromo domains. The Schizosaccharomyces pombe SWI6 protein, involved in repression of the silent mating-type loci, is a member of the chromo shadow group. The similar modular architecture of SpSW16, HP1 and HP1-like proteins supports the model that the specificity of action of chromatin proteins is generated by combinations of protein modules.
Personality and mortality salience Who ’ s Afraid of Death and Terrorists ? Investigating Moderating Effects of Sense of Coherence , Mindfulness , Neuroticism , and Meaning in Life on Mortality Salience

Sense of coherence (SOC) is thought to be a stress-buffering personality construct. We explored if SOC has a moderating effect on the distress experienced following mortality salience. SOC, mindfulness, neuroticism, and meaning in life were measured as potential moderators. Participants reported on death anxiety and completed a worldview defense task. Results indicated that all potential moderators were correlated with death anxiety, but not with worldview defense. Yet despite a large sample no main effect for the mortality salience induction could be found. Results highlight the importance of various personality variables on death anxiety.
Effectiveness of Tyrosine Kinase Inhibitors on “Uncommon” Epidermal Growth Factor Receptor Mutations of Unknown Clinical Significance in Non–Small Cell Lung Cancer

Purpose: Clinical features of epidermal growth factor receptor (EGFR) mutations, L858R, deletions in exon 19, T790M, and insertions in exon 20, in non–small cell lung cancer (NSCLC) are well known. The clinical significance of other uncommon EGFR mutations, such as their association with the effectiveness of EGFR tyrosine kinase inhibitors (TKI), is not well understood. This study aimed to improve the understanding of these uncommon EGFR mutations of unknown clinical significance. Patients and Methods: Specimens from 1,261 patients were tested for EGFR mutations. We surveyed the clinical data and the effectiveness of gefitinib and erlotinib in NSCLC patients with uncommon EGFR mutations. Results: Of the 1,261 patients, 627 (49.8%) had EGFR mutations. This included 258 patients with deletions in exon 19, 260 patients with L858R, 25 patients with insertions or duplications in exon 20, 6 patients with de novo T790M, and 78 (12.4%) patients with uncommon mutations. Of the 78 patients, 62 received either gefitinib or erlotinib treatment. The response rate of TKIs treatment was 48.4%, and the median progression-free survival (PFS) was 5.0 months. Mutations on G719 and L861 composed a major part (28 of 62) of uncommon mutations, and were associated with a favorable effectiveness of EGFR TKIs (response rate, 57.1%; median PFS, 6.0 months). Mutations other than G719 and L861 led to a worse response to EGFR TKIs (response rate, 20.0%; median PFS, 1.6 months). Conclusions: Uncommon EGFR mutations constituted a distinct part of the whole group of EGFR mutations. Their composition was heterogeneous, and their associations with EGFR TKIs differed. Clin Cancer Res; 17(11); 3812–21. ©2011 AACR.
Prepaying the entropic cost for allosteric regulation in KIX

Significance Understanding how proteins are regulated through the binding of an effector molecule at a nonoverlapping site is a central problem in protein allostery. However, connecting the changes in structural dynamics to changes in the binding affinity can be challenging. Here, we investigate the allosteric mechanism involving a promiscuous protein that serves as a hub for a variety of intrinsically disordered proteins (IDPs). By using a coarse-grained model to simulate the interactions between the protein and two IDPs, we were able to recapitulate experimental binding affinities, capture relevant structural dynamics, and provide a thermodynamic and kinetic description of the allosteric mechanism. It is presumable that the features identified in this allosteric mechanism are conserved between the central protein and other IDPs. The kinase-inducible domain interacting (KIX) domain of the CREB binding protein (CBP) is capable of simultaneously binding two intrinsically disordered transcription factors, such as the mixed-lineage leukemia (MLL) and c-Myb peptides, at isolated interaction sites. In vitro, the affinity for binding c-Myb is approximately doubled when KIX is in complex with MLL, which suggests a positive cooperative binding mechanism, and the affinity for MLL is also slightly increased when KIX is first bound by c-Myb. Expanding the scope of recent NMR and computational studies, we explore the allosteric mechanism at a detailed molecular level that directly connects the microscopic structural dynamics to the macroscopic shift in binding affinities. To this end, we have performed molecular dynamics simulations of free KIX, KIX-c-Myb, MLL-KIX, and MLL-KIX-c-Myb using a topology-based Gō-like model. Our results capture an increase in affinity for the peptide in the allosteric site when KIX is prebound by a complementary effector and both peptides follow an effector-independent folding-and-binding mechanism. More importantly, we discover that MLL binding lowers the entropic cost for c-Myb binding, and vice versa, by stabilizing the L12-G2 loop and the C-terminal region of the α3 helix on KIX. This work demonstrates the importance of entropy in allosteric signaling between promiscuous molecular recognition sites and can inform the rational design of small molecule stabilizers to target important regions of conformationally dynamic proteins.
Acute dietary nitrate supplementation improves cycling time trial performance.

PURPOSE Dietary nitrate supplementation has been shown to reduce the O2 cost of submaximal exercise and to improve high-intensity exercise tolerance. However, it is presently unknown whether it may enhance performance during simulated competition. The present study investigated the effects of acute dietary nitrate supplementation on power output (PO), VO2, and performance during 4- and 16.1-km cycling time trials (TT). METHODS After familiarization, nine club-level competitive male cyclists were assigned in a randomized, crossover design to consume 0.5 L of beetroot juice (BR; containing ∼ 6.2 mmol of nitrate) or 0.5 L of nitrate-depleted BR (placebo, PL; containing ∼ 0.0047 mmol of nitrate), ∼ 2.5 h before the completion of a 4- and a 16.1-km TT. RESULTS BR supplementation elevated plasma [nitrite] (PL = 241 ± 125 vs BR = 575 ± 199 nM, P < 0.05). The VO2 values during the TT were not significantly different between the BR and PL conditions at any elapsed distance (P > 0.05), but BR significantly increased mean PO during the 4-km (PL = 279 ± 51 vs BR = 292 ± 44 W, P < 0.05) and 16.1-km TT (PL = 233 ± 43 vs BR = 247 ± 44 W, P < 0.01). Consequently, BR improved 4-km performance by 2.8% (PL = 6.45 ± 0.42 vs BR = 6.27 ± 0.35 min, P < 0.05) and 16.1-km performance by 2.7% (PL = 27.7 ± 2.1 vs BR = 26.9 ± 1.8 min, P < 0.01). CONCLUSIONS These results suggest that acute dietary nitrate supplementation with 0.5 L of BR improves cycling economy, as demonstrated by a higher PO for the same VO2 and enhances both 4- and 16.1-km cycling TT performance.
Monolysocardiolipins accumulate in Barth syndrome but do not lead to enhanced apoptosis Published, JLR Papers in Press, April 1, 2005. DOI 10.1194/jlr.M500056-JLR200

Barth syndrome (BTHS) is an X-linked recessive disorder that is biochemically characterized by low cellular levels of the mitochondrial phospholipid cardiolipin (CL). Previously, we discovered that the yeast disruptant of the TAZ ortholog in Saccharomyces cerevisiae not only displays CL deficiency but also accumulates monolysocardiolipins (MLCLs), which are intermediates in CL remodeling. Therefore, we set out to investigate whether MLCL accumulation also occurs in BTHS. Indeed, we observed MLCL accumulation in heart, muscle, lymphocytes, and cultured lymphoblasts of BTHS patients; however, only very low levels of these lysophospholipids were found in platelets and fibroblasts of these patients. Although the fatty acid composition of the MLCLs was different depending on the tissue source, it did parallel the fatty acid composition of the (remaining) CLs. The possible implications of these findings for the two reported CL remodeling mechanisms, transacylation and deacylation/reacylation, are discussed. Because MLCLs have been proposed to be involved in the initiation of apoptosome-mediated cell death by the sequestration of the proapoptotic protein (t)BH3-interacting domain death agonist (Bid) to the mitochondrial membrane, we used control and BTHS lymphoblasts to investigate whether the accumulation of MLCLs results in higher levels of apoptosis. We found no differences in susceptibility to death receptor-mediated apoptosis or in cellular distribution of Bid, cytochrome c, and other parameters, implying that MLCL accumulation does not lead to enhanced apoptosis in cultured BTHS lymphoblasts.
Implementation of the Natura 2000 Network in Poland – an Opportunity or a Threat to Sustainable Development of Rural Areas? Study on Local Stakeholders’ Perception

Conflicts related to the implementation of the Natura 2000 network can be found in Poland and other European countries. The general causes of those conflicts are known. Some of them lie in the habitat directive itself, and others are related to the transposition of the directive into national environmental law and management systems. The designation of Natura 2000 sites in Poland involved strong protests on a local level, mainly due to the lack of consultations with the stakeholders, or at least with the local governments. In those days, the common argument against the implementation of Natura 2000 was one of severe restrictions on the conduct of economic activities and infrastructure development. Eight years after the official implementation of Natura 2000 in Poland, we would like to state the research question as follows: “Is Natura 2000 a constraint on local development? ”
Passively aligned hybrid integration of 8 x 1 micromachined micro-Fresnel lens arrays and 8 x 1 vertical-cavity surface-emitting laser arrays for free-space optical interconnect

Surface micromachining technique has been successfully applied to the fabrications of a three-dimensional 8/spl times/1 micro-Fresnel lens array and other novel three-dimensional alignment structures. With the help of these three-dimensional structures, self-aligned integration of the micro-Fresnel lens array and an 8/spl times/1 vertical-cavity surface-emitting laser (VCSEL) array is realized for the first time with passive alignment. Individual addressing of the VCSEL/micro-lens element is also successfully demonstrated. With their three-dimensional and array structural characteristics, they are very attractive for free-space optical interconnect and other integrated micro-optical systems. <<ETX>>
A 20-b $\pm$ 40-mV Range Read-Out IC With 50-nV Offset and 0.04% Gain Error for Bridge Transducers

This paper presents a 20-b read-out IC with ±40-mV full-scale range that is intended for use with bridge transducers. It consists of a current-feedback instrumentation amplifier (CFIA) followed by a switched-capacitor incremental ΔΣ ADC. The CFIA's offset and 1/f noise are mitigated by chopping, while its gain accuracy and gain drift are improved by applying dynamic element matching to its input and feedback transconductors. Their mismatch is reduced by a digitally assisted correction loop, which further reduces the CFIA's gain drift. Finally, bulk-biasing and impedance-balancing techniques are used to reduce the common-mode dependency of these transconductors, which would otherwise limit the achievable gain accuracy. The combination of these techniques enables the read-out IC to achieve 140-dB CMRR, a worst-case gain error of 0.04% over a 0-2.5 V common-mode range, a maximum gain drift of 0.7 ppm/°C and an INL of 5 ppm. After applying nested-chopping, the read-out IC achieves 50-nV offset, 6-nV/°C offset drift, a thermal noise floor of 16.2 nV/√Hz and a 0.1-mHz 1/f noise corner. Implemented in a 0.7-μm CMOS technology, the prototype read-out IC consumes 270 μA from a 5-V supply.
Improving sleep quality using weighted blankets among young children with an autism spectrum disorder

Background/Aims: Sleep and rest disturbances in children with an autism spectrum disorder and sensory over-responsivity are challenging issues to address. These are important self-care challenges that are commonly faced by many individuals with an autism spectrum disorder, with a high percentage of individuals with an an autism spectrum disorder reporting sleep disturbances. Many health-related professions, including occupational therapy, use weighted blankets to assist children with an autism spectrum disorder to calm, fall asleep and remain asleep. The purpose of this study was to explore the efficacy of weighted blankets with children with an autism spectrum disorder and sleep disturbances using a single case, multiple baseline design. Methods: This pilot study included two children with an autism spectrum disorder and sensory over-responsivity. Results: Using a single subject design found that there were minimal changes reported via caregivers, indicating that weighted blankets assisted in improving t.
Navigation of Mobile Robots in Natural Environments : Using Sensor Fusion in Forestry

Navigation using GPS is a common strategy which cannot provide the desired accuracy in forests. In the forestry of North RhineWestphalia (Germany) algorithms are developed to delineate single trees from remote sensing data. These generated tree maps can be used to create a virtual testbed. Different kinds of sensor data can be merged to form a “visual GPS” system which improves accuracy for the navigation of autonomous vehicles in the forest. Algorithms were developed, which provide localization results accurate enough to allow navigation to a single tree.