Miracle-dz/UniFAR-FTUs huggingface dataset:
Genetic Evidence for Function of the bHLH-PAS Protein Gce/Met As a Juvenile Hormone Receptor

Juvenile hormones (JHs) play a major role in controlling development and reproduction in insects and other arthropods. Synthetic JH-mimicking compounds such as methoprene are employed as potent insecticides against significant agricultural, household and disease vector pests. However, a receptor mediating effects of JH and its insecticidal mimics has long been the subject of controversy. The bHLH-PAS protein Methoprene-tolerant (Met), along with its Drosophila melanogaster paralog germ cell-expressed (Gce), has emerged as a prime JH receptor candidate, but critical evidence that this protein must bind JH to fulfill its role in normal insect development has been missing. Here, we show that Gce binds a native D. melanogaster JH, its precursor methyl farnesoate, and some synthetic JH mimics. Conditional on this ligand binding, Gce mediates JH-dependent gene expression and the hormone's vital role during development of the fly. Any one of three different single amino acid mutations in the ligand-binding pocket that prevent binding of JH to the protein block these functions. Only transgenic Gce capable of binding JH can restore sensitivity to JH mimics in D. melanogaster Met-null mutants and rescue viability in flies lacking both Gce and Met that would otherwise die at pupation. Similarly, the absence of Gce and Met can be compensated by expression of wild-type but not mutated transgenic D. melanogaster Met protein. This genetic evidence definitively establishes Gce/Met in a JH receptor role, thus resolving a long-standing question in arthropod biology.
Small-Signal Analysis of Naturally-Sampled Single-Edge PWM Control Loops

This paper presents a simple method to analyze the behavior of feedback loops that contain a naturally-sampled single-edge pulse-width modulator. A small-signal model is derived by means of simple geometric arguments. It is shown how this small-signal model can be used to analyze the stability of the continuous-time pulse-width modulated feedback loop by using standard <inline-formula><tex-math notation="LaTeX">$z$</tex-math></inline-formula>-domain techniques. The strategy relies on familiar concepts like transfer functions and small-signal gains and does not require any in-depth knowledge of nonlinear systems. A simple design process, where the continuous-time compensator is designed directly in the <inline-formula><tex-math notation="LaTeX">$z$</tex-math></inline-formula>-domain, is developed and detailed design equations are derived for a PI current regulator. It is shown how the proposed strategy can accurately predict instability that cannot be explained by means of the well-known average model of the pulse-width modulator. The theoretical analysis is confirmed by means of detailed time-domain simulations. The mechanisms that lead to instability are discussed and an equation for the critical loop gain is derived.
Molecular mechanics (MM4) calculations on conjugated hydrocarbons

The MM4 force field has been extended to conjugated hydrocarbon systems. It retains most of the formalism and computational schemes that were present in MM3. Several cross‐terms have been added in MM4 that were not present in MM3, mainly to improve vibrational frequencies, but also to improve structures and energies. Additional bond order dependence equations have been included. About 80 molecules have been examined, some in multiple conformations, and others with more complete experimental profiles. Conformational energy differences/barriers are generally fit to within 0.5 kcal/mol unless they are very large. The MM4 method for calculating heats of formation has been modified to include vibrational as well as steric energy contributions. The heats of formation for 35 alkenes and 57 conjugated hydrocarbons were determined to have an overall root mean square (rms) deviation of 0.68 kcal/mol from experiment (0.47 kcal/mol weighted rms). The vibrational frequency rms error for eight conjugated hydrocarbons is 31 cm1. Geometries are fit for the most part to within the following ranges: 0.004 Å for bond lengths, 1° for bond angles, 4° for torsion angles, and 0.5% for moments of inertia (r2). © 1996 by John Wiley & Sons, Inc.
Overhead power lines temperature measurements by a fiber optic Raman sensor

Temperature measures on overhead power lines are shown thanks to a Raman-based fiber optic distributed sensor. Monitoring performance on optical ground wires is compared to typical electric measurement in field. A large number of measurement cycles are performed over multiple days under various weather conditions. Monitoring performance on phase conductors is also evaluated and compared to electric measurement in realistic environment simulating solar irradiation and natural wind ventilation both on unloaded and loaded conductors.
Roles of JAK kinase in human GM-CSF receptor signals.

The IL-3 and GM-CSF (hGMR) receptors consist of two subunits, alpha and beta, both of which are members of the cytokine receptor superfamily. Phosphorylation of tyrosine residues of hGMR beta subunit and several cellular proteins are observed with hGM-CSF stimulation. We analyzed role of tyrosine residue of hGMR beta subunit and nature of tyrosine kinase, JAK2 in hGMR signals using several hGMR beta subunit mutants. In addition to box1 region, a membrane distal region (a.a. 544-589) of hGMR beta is required for c-fos activation. Only one tyrosine residue (Tyr577) exists within the region 544-589, and substitution of Tyr577 to phenylalanine in GMR beta 589 resulted in the loss of c-fos activation. In contrast, the same substitution in a wild type receptor did not affect GM-CSF-induced activities such as c-fos mRNA induction and proliferation but abolished Shc phosphorylation. These results suggest that the activation of Shc is not essential for c-fos activation and several tyrosine residues co-ordinate to activate c-fos activation. It is well documented that IL-3 or GM-CSF activates JAK2 in BA/F3 cells. However the role of JAK2 in IL-3/GM-CSF functions is largely unknown. We examined the role of JAK2 in GM-CSF-induced signaling pathways. Dominant negative JAK2 (delta JAK2) lacking the C-terminus kinase domain, suppressed IL-3/GM-CSF induced c-fos activation, c-myc activation and proliferation suggesting that JAK2 is involved in both signaling pathways. PTP1D and Shc are phosphorylated by IL-3/GM-CSF in BA/F3 cells, however these phosphorylation events were inhibited by expression of delta JAK2. Taken together, these results indicate that JAK2 is a primary kinase regulating all the known activities of GM-CSF. JAK2 mediates GM-CSF induced c-fos activation through receptor phosphorylation and Shc/PTP1D activation.
Stacking for Statistical Machine Translation

We propose the use of stacking, an ensemble learning technique, to the statistical machine translation (SMT) models. A diverse ensemble of weak learners is created using the same SMT engine (a hierarchical phrase-based system) by manipulating the training data and a strong model is created by combining the weak models on-the-fly. Experimental results on two language pairs and three different sizes of training data show significant improvements of up to 4 BLEU points over a conventionally trained SMT model.
Robust speaker's location detection in a vehicle environment using GMM models

Human-computer interaction (HCI) using speech communication is becoming increasingly important, especially in driving where safety is the primary concern. Knowing the speaker's location (i.e., speaker localization) not only improves the enhancement results of a corrupted signal, but also provides assistance to speaker identification. Since conventional speech localization algorithms suffer from the uncertainties of environmental complexity and noise, as well as from the microphone mismatch problem, they are frequently not robust in practice. Without a high reliability, the acceptance of speech-based HCI would never be realized. This work presents a novel speaker's location detection method and demonstrates high accuracy within a vehicle cabinet using a single linear microphone array. The proposed approach utilize Gaussian mixture models (GMM) to model the distributions of the phase differences among the microphones caused by the complex characteristic of room acoustic and microphone mismatch. The model can be applied both in near-field and far-field situations in a noisy environment. The individual Gaussian component of a GMM represents some general location-dependent but content and speaker-independent phase difference distributions. Moreover, the scheme performs well not only in nonline-of-sight cases, but also when the speakers are aligned toward the microphone array but at difference distances from it. This strong performance can be achieved by exploiting the fact that the phase difference distributions at different locations are distinguishable in the environment of a car. The experimental results also show that the proposed method outperforms the conventional multiple signal classification method (MUSIC) technique at various SNRs.
A New Development in Trypanosoma cruzi Detection

ABSTRACT Chagas disease is caused by the parasite Trypanosoma cruzi and is an important cause of morbidity and mortality in areas of Latin America where Chagas disease is endemic and among infected individuals who have migrated to nonendemic areas of North America and Europe. There are many diagnostic tests that are employed in the serological diagnosis of this infection. In this issue of the Journal of Clinical Microbiology, Bautista-López et al. provide characterization of excretory vesicles (EVs) from Vero cells infected with T. cruzi and provide data on the EVs produced by trypomastigotes and amastigotes (N. L. Bautista-López et al., J Clin Microbiol 55:744–758, 2017, https://doi.org/10.1128/JCM.01649-16 ). Their proteomic study defines potential targets to evaluate for improved diagnostic tests, effects on host cell biology that contribute to the pathogenesis of infection, and vaccine candidates. If any of the EV-associated proteins identified were to be correlated to cure of infection, this would be a major advance.
Revisiting Stress Majorization as a Unified Framework for Interactive Constrained Graph Visualization

We present an improved stress majorization method that incorporates various constraints, including directional constraints without the necessity of solving a constraint optimization problem. This is achieved by reformulating the stress function to impose constraints on both the edge vectors and lengths instead of just on the edge lengths (node distances). This is a unified framework for both constrained and unconstrained graph visualizations, where we can model most existing layout constraints, as well as develop new ones such as the star shapes and cluster separation constraints within stress majorization. This improvement also allows us to parallelize computation with an efficient GPU conjugant gradient solver, which yields fast and stable solutions, even for large graphs. As a result, we allow the constraint-based exploration of large graphs with 10K nodes — an approach which previous methods cannot support.
Extracting seismic core phases with array interferometry

Seismic body waves that sample Earth's core are indispensable for studying the most remote regions of the planet. Traditional core phase studies rely on well‐defined earthquake signals, which are spatially and temporally limited. We show that, by stacking ambient‐noise cross‐correlations between USArray seismometers, body wave phases reflected off the outer core (ScS), and twice refracted through the inner core (PKIKP2) can be clearly extracted. Temporal correlation between the amplitude of these core phases and global seismicity suggests that the signals originate from distant earthquakes and emerge due to array interferometry. Similar results from a seismic array in New Zealand demonstrate that our approach is applicable in other regions and with fewer station pairs. Extraction of core phases by interferometry can significantly improve the spatial sampling of the deep Earth because the technique can be applied anywhere broadband seismic arrays exist.
Presenting the Students’ Academic Achievement Causal Model based on Goal Orientation

Introduction: Several factors play a role in academic achievement, individual's excellence and capability to do actions and tasks that the learner is in charge of in learning areas. The main goal of this study was to present academic achievement causal model based on the dimensions of goal orientation and learning approaches among the students of Medical Science and Dentistry courses in Guilan University of Medical Sciences in 2013. Methods: This study is based on a cross-sectional model. The participants included 175 first and second students of the Medical and Dentistry schools in Guilan University of Medical Sciences selected by random cluster sampling [121 persons (69%) Medical Basic Science students and 54 (30.9%) Dentistry students]. The measurement tool included the Goal Orientation Scale of Bouffard and Study Process Questionnaire of Biggs) and the students’ Grade Point Average. The study data were analyzed using Pearson correlation coefficient and structural equations modeling. SPSS 14 and Amos were used to analyze the data. Results: The results indicated a significant relationship between goal orientation and learning strategies (P<0.05). In addition, the results revealed that a significant relationship exists between learning strategies[Deep Learning (r=0.37, P<0.05), Surface Learning (r=-0.21,P<0.05)], and academic achievement.The suggested model of research is fitted to the data of the research. Conclusion: Results showed that the students' academic achievement model fits with experimental data, so it can be used in learning principles which lead to students’ achievement in learning.
Fundamental Molecular Mechanism for the Cellular Uptake of Guanidinium-Rich Molecules

Guanidinium-rich molecules, such as cell-penetrating peptides, efficiently enter living cells in a non-endocytic energy-independent manner and transport a wide range of cargos, including drugs and biomarkers. The mechanism by which these highly cationic molecules efficiently cross the hydrophobic barrier imposed by the plasma membrane remains a fundamental open question. Here, a combination of computational results and in vitro and live-cell experimental evidence reveals an efficient energy-independent translocation mechanism for arginine-rich molecules. This mechanism unveils the essential role of guanidinium groups and two universal cell components: fatty acids and the cell membrane pH gradient. Deprotonated fatty acids in contact with the cell exterior interact with guanidinium groups, leading to a transient membrane channel that facilitates the transport of arginine-rich peptides toward the cell interior. On the cytosolic side, the fatty acids become protonated, releasing the peptides and resealing the channel. This fundamental mechanism appears to be universal across cells from different species and kingdoms.
Recent advances in fluorination techniques and their anticipated impact on drug metabolism and toxicity

Introduction: Fluorine’s unique physicochemical properties make it a key element for incorporation into pharmacologically active compounds. Its presence in a drug can alter a number of characteristics that affect ADME-Tox, which has prompted efforts at improving synthetic fluorination procedures. Areas covered: This review describes the influence of fluorine on attributes such as potency, lipophilicity, metabolic stability and bioavailablility and how the effects observed are related to the physicochemical characteristics of the element. Examples of more recently used larger scale synthetic methods for introduction of fluorine into drug leads are detailed and the potential for using biological systems for fluorinated drug production is discussed. Expert opinion: The synthetic procedures for carbon-fluorine bond formation largely still rely on decades-old technology for the manufacturing scale and new reagents and methods are required to meet the demands for the preparation of structurally more complex drugs. The improvement of in vitro and computational methods should make fluorinated drug design more efficient and place less emphasis on approaches such as fluorine scanning and animal studies. The introduction of new fluorinated drugs, and in particular those that have novel fluorinated functional groups, should be accompanied by rigorous environmental assessment to determine the nature of transformation products that may cause ecological damage.
Cell-probe bounds for online edit distance and other pattern matching problems

We give cell-probe bounds for the computation of edit distance, Hamming distance, convolution and longest common subsequence in a stream. In this model, a fixed string of n symbols is given and one δ-bit symbol arrives at a time in a stream. After each symbol arrives, the distance between the fixed string and a suffix of most recent symbols of the stream is reported. The cell-probe model is perhaps the strongest model of computation for showing data structure lower bounds, subsuming in particular the popular word-RAM model. • We first give an Ω((δ log n)/(w+log log n)) lower bound for the time to give each output for both online Hamming distance and convolution, where w is the word size. This bound relies on a new encoding scheme and for the first time holds even when w is as small as a single bit. • We then consider the online edit distance and longest common subsequence problems in the bit-probe model (w = 1) with a constant sized input alphabet. We give a lower bound of Ω([EQUATION]log n/(log log n)3/2) which applies for both problems. This second set of results relies both on our new encoding scheme as well as a carefully constructed hard input distribution. • Finally, for the online edit distance problem we show that there is an O((log2n)/w) upper bound in the cell-probe model. This bound gives a contrast to our new lower bound and also establishes an exponential gap between the known cell-probe and RAM model complexities.
Evidence for the subsynaptic zone as a preferential site for CHRN recycling at neuromuscular junctions

ABSTRACT Vertebrate skeletal muscle contraction is mediated by nicotinic acetylcholine receptors (CHRN). Endocytosis and recycling of CHRN regulate their proper abundance at nerve-muscle synapses, i.e. neuromuscular junctions. Recent work showed that RAB5 is essential for CHRN endocytosis. Here, using in vivo-imaging of endocytosed CHRN and RAB-GFP fusion proteins, we deliver evidence for differential effects of RAB5-GFP, RAB4-GFP, and RAB11-GFP on CHRN endocytosis. Furthermore, while newly endocytosed CHRN colocalized with RAB5-GFP over large stretches of muscle fibers, RAB4-GFP and RAB11-GFP colocalized with endocytosed CHRN almost exclusively at neuromuscular junctions. In agreement with previous findings, this data suggests the existence of a specialized subsynaptic zone that is particularly relevant for CHRN recycling.
Self-Administered Computer Therapy for Apraxia of Speech: Two-Period Randomized Control Trial With Crossover

Background and Purpose— There is currently little evidence on effective interventions for poststroke apraxia of speech. We report outcomes of a trial of self-administered computer therapy for apraxia of speech. Methods— Effects of speech intervention on naming and repetition of treated and untreated words were compared with those of a visuospatial sham program. The study used a parallel-group, 2-period, crossover design, with participants receiving 2 interventions. Fifty participants with chronic and stable apraxia of speech were randomly allocated to 1 of 2 order conditions: speech-first condition versus sham-first condition. Period 1 design was equivalent to a randomized controlled trial. We report results for this period and profile the effect of the period 2 crossover. Results— Period 1 results revealed significant improvement in naming and repetition only in the speech-first group. The sham-first group displayed improvement in speech production after speech intervention in period 2. Significant improvement of treated words was found in both naming and repetition, with little generalization to structurally similar and dissimilar untreated words. Speech gains were largely maintained after withdrawal of intervention. There was a significant relationship between treatment dose and response. However, average self-administered dose was modest for both groups. Future software design would benefit from incorporation of social and gaming components to boost motivation. Conclusions— Single-word production can be improved in chronic apraxia of speech with behavioral intervention. Self-administered computerized therapy is a promising method for delivering high-intensity speech/language rehabilitation. Clinical Trial Registration— URL: http://orcid.org/0000-0002-1278-0601. Unique identifier: ISRCTN88245643.
Cell Concentration Systems for Enhanced Biosensor Sensitivity

Concentration processes for analytical systems based on different types of biosensors are very important for many applications. The sample conditioning is oriented to enhance the sensitivity or directly to make the detection or analysis possible. Processes that may be used for concentration and conditioning of original samples are very diverse, depending on applications that may range from clinical diagnostics to industrial processes control, and there are different strategies to achieve the final goal. This chapter presents an overview of the most important and relevant microscale techniques to produce an effective separation and concentration of cells, mostly bacterial cells. The main focus is put on the separation mechanisms as a tool for biosensing toward the development of complete devices in a lab-on-a-chip format by integrating the concentration, sample conditioning, and detection subsystems.
Children's Developing Understanding of Spatial Metaphors for Time

Children’s Developing Understanding of Spatial Metaphors for Time Lauren Stites Georgia State University ¨ cali¸skan Seyda Oz¸ Georgia State University Abstract: Adult speakers of English use three different metaphor types to describe time, including moving-time (’summer approaches’), moving-ego (’we approach summer’), and sequence-as-relative-position-on-a-path (’autumn follows summer’). When do children grasp the meaning of these three metaphors for time and what cognitive and/or linguistic factors account for this understanding? To explore these questions, we interviewed 60 three- to six-year-old children as they participated in experimental tasks testing comprehension and production of time metaphors. We found that children could understand all three time metaphors by age five and verbally explain their meanings by age 6. Children’s comprehension also varied by metaphor type, with moving-time and moving- ego metaphors being learned earlier than sequence-as-relative-position-on-a-path metaphors. Moreover , children’s metaphor comprehension was strongly correlated with their time concept understanding. Overall, these results suggest that comprehension of time metaphors is an early emerging linguistic ability that is closely associated with children’s cognitive understanding of the time concept.