Miracle-dz/UniFAR-FTUs huggingface dataset:
Distinct cysteine sulfhydryl environments detected by analysis of Raman S-hh markers of Cys-->Ser mutant proteins.

Very little is known about the character or functional relevance of hydrogen-bonded cysteine sulfhydryl (S-H) groups in proteins. The Raman S-H band is a unique and sensitive probe of the local S-H environment. Here, we report the use of Raman spectroscopy combined with site-specific mutagenesis to document the existence of five distinguishable hydrogen-bonded states of buried cysteine sulfhydryl groups in a native protein. The 666 residue subunit of the Salmonella typhimurium bacteriophage P22 tailspike contains eight cysteine residues distributed through the elongated structure. The tailspike cysteine residues display an unusual Raman S-H band complex (2500-2600 cm(-1) interval) indicative of diverse S-H hydrogen-bonding interactions in the native trimeric structure. To resolve specific Cys contributions to the complex Raman band we characterized a set of tailspike proteins with each cysteine replaced by a serine. The mutant proteins, once folded, were structurally and functionally indistinguishable from wild-type tailspikes, except for their Raman S-H signatures. Comparison of the Raman spectra of the mutant and wild-type proteins reveals the following hydrogen-bond classes for cysteine sulfhydryl groups. (i) Cys613 forms the strongest S-H.X bond of the tailspike, stronger than any heretofore observed for a protein. (ii) Cys267, Cys287 and Cys458 form robust S-H.X bonds. (iii) Moderate S-H.X bonding occurs for Cys169 and Cys635. (iv) Cys290 and Cys496 form weak hydrogen bonds. (v) It is remarkable that Cys287 contributes two Raman S-H markers, indicating the population of two distinct hydrogen-bonding states. The sum of the S-H Raman signatures of all eight mutants accurately reproduces the composite Raman band of the wild-type tailspike. The diverse cysteine states may be an outcome of the folding and assembly pathway of the tailspike, which though lacking disulfide bonds in the native state, utilizes transient disulfide bonds in the maturation pathway. This Raman study represents the first detailed assessment of local S-H hydrogen bonding in a native protein and provides information not obtainable directly by other structural probes. The method employed here should be applicable to a wide range of cysteine-containing proteins.
Interactions among subunits of human Arp2/3 complex: p20-Arc as the hub.

The Arp2/3 complex is critical for nucleation and crosslinking of actin filaments. To gain insight into its subunit topology and assembly pathway, we systematically examined interactions among subunits of human Arp2/3 complex by yeast two-hybrid assays. It was shown that p20-Arc was able to interact with p21-Arc, p34-Arc, and p16-Arc, respectively. In contrast, p41-Arc only interacted with p20-Arc/p16-Arc heterodimer. In addition, we found that structural integrity was important for association between p20-Arc and p21-Arc, while the N-terminal half of p34-Arc was dispensable for its binding to p20-Arc. Our data suggest a key role of p20-Arc and a multistep pathway for the complex formation.
Music as a diagnostic tool in low awareness states: Considering limbic responses

Primary objective: Examining the evidence from contrasting epistemological sources a case is made for the use of music as an assessment medium with patients in low awareness states. Profound brain damage can result in long-term states of altered consciousness such as vegetative and minimally conscious states. Differential diagnosis with this population is immensely complex requiring diverse approaches. Neuroimaging alone is not, as yet, sufficient to establish diagnosis in this population and must be supplemented by repeated behavioural observation methods from a skilled and diverse treatment team, as there are enormous medico-legal and ethical implications. Evidence from research in neuroimaging and the behavioural health sciences indicates that auditory stimulation can reveal residual functioning and elicit optimal behaviours in such patients, particularly when the stimulation has emotional significance. Main outcomes and results: Behavioural assessment is complicated by limbic behaviours which can be misinterpreted as purposeful emotional responses. A case vignette using music therapy in a complex case illustrates such complications. Conclusions: Given the evidence for residual auditory functioning in patients in low awareness states, music is recommended as a medium for assessment. However, professionals involved in diagnosis must take caution against misinterpreting limbic responses and attributing greater meaning to such behaviours.
Prejunctional and Postjunctional Inhibitory Actions of Eprosartan and Candesartan in the Isolated Rabbit Mesenteric Artery

Effects of angiotensin II type 1 (AT1) receptor antagonists eprosartan and candesartan and AT2 receptor antagonist PD123319 on Ang II-induced facilitation of noradrenergic neurotransmission were investigated in isolated rabbit mesenteric artery under isometric conditions. Sympathoinhibitory potency of AT1 blockers was compared with their potency concerning inhibition of direct vasoconstrictor effect of Ang II. To investigate blockade of presynaptic AT1 and AT2 receptors, effects of Ang II on electrical field stimulation (EFS)–induced contractions in presence or absence of eprosartan, candesartan, or PD123319 were studied. To investigate blockade of postsynaptic AT1 receptors, effects of either eprosartan or candesartan on concentration-response curves of Ang II were studied. In addition, effect of Ang II on postsynaptic &agr;-adrenoceptor-mediated responses was studied using noradrenaline. EFS (1, 2, and 4 Hz) caused an increase of contractile force. At stimulation frequencies of 1, 2, and 4 Hz, a subpressor concentration of Ang II (0.5 n M) increased stimulation-induced vasoconstrictor responses by 2.8 ± 0.5, 2.4 ± 0.4, and 1.6 ± 0.1 of control values, respectively (p < 0.05 compared with control for all frequencies). The enhancement could be antagonized by eprosartan (1 n M–0.1 &mgr;M) and candesartan (1 n M–0.1 &mgr;M). The AT2 antagonist PD123319 (10 n M) did not influence Ang II-induced facilitation of stimulation-induced contractions. Contractile responses to exogenous noradrenaline were unaltered in presence of Ang II 0.5 n M. Ang II (1 n M–0.3 &mgr;M) caused a concentration-dependent increase in contractile force, which could be antagonized by eprosartan (pD2´ 8.8 ± 0.19) and candesartan (pD2´ 11.3 ± 0.23). Thus, the facilitating effect of Ang II on noradrenergic neurotransmission is mediated by presynaptically located AT1 receptors and not by AT2 receptors. For eprosartan, sympathoinhibition was achieved at concentrations that also block AT1 receptors on vascular smooth muscle. In contrast, for candesartan, presynaptic inhibitory concentrations were considerably higher than those required for postsynaptic inhibition.
High-resolution threshold photodetachment spectroscopy of OH–

Relative photodetachment cross sections for rotational thresholds of the hydroxide anion were measured using a coaxial laser-ion beam spectrometer. The thresholds correspond to transitions from the J51 and J52 states of X 1 S 1 OH 2 to the J53/2 state of X 2 P 3/2 OH. Best fits of the data give cross sections that scale with energy above threshold as ( E2Eth) 0.1860. 06 and (E2Eth) 0.2160. 05 for the two thresholds, respectively. This non-Wigner law energy dependence of the cross section results from the long-range r 22 interaction between the dipole and the departing electron. Experimental results were compared with the predictions of a strong-coupling model of charge-dipole interaction devised by Engelking and good qualitative agreement was observed. When the resolution and range of the data for transitions that terminate in the lower L-doublet component is such that the L-doublet splitting is resolved, one observes the ( E2Eth) 1/2 behavior predicted by the Wigner law. This result is explained in terms of the effect of the L doubling upon the r 22 charge-dipole interaction. From the threshold frequencies, an OH electron affinity of 14 741.02~3! cm 21 was determined. @S1050-2947~97! 04803-8# PACS number~s! : 33.80. Eh
Efficient simulation of the impulse response of the indoor wireless optical channel

The use of wireless local area networks (WLANs) is experiencing a significant growth. Infrared technology has an extensive bandwidth of free use, and has the potential to be the support of high-baud rate WLANs. For that, it is necessary to understand the propagation characteristics of the indoor optical channel. This paper presents a computationally efficient algorithm for the simulation of indoor optical channels, considering multiple reflections of the emitted signal. The models used to approximate the emitter pattern, the propagation environment and the receiver pattern are described. Two new procedures (called time-delay agglutination and time and space indexed tables) are introduced to increase the efficiency of the simulation of the impulse response of the indoor wireless optical channel. The structure of the algorithm is presented and the approaches used are discussed. The new algorithm was implemented in a simulation package, named SCOPE, which is very efficient and allows the evaluation of the main parameters of indoor optical channels considering multiple reflections of the emitted signal. Results obtained for several channels are compared with experimental and published values, and good agreement is verified. Copyright © 2000 John Wiley & Sons, Ltd.
References values for forced spirometry

The European Coal and Steel Community (ECSC) prediction equations exemplify a significant effort carried out approximately 15 yrs ago to provide uniform standards for lung function testing, but this set of equations has not been properly validated as yet. The present study evaluates the ECSC reference values and four other sets of prediction equations, using spirometric data collected in 12,900 nonasthmatic subjects (43% lifetime nonsmokers and 36% active smokers) aged 20-44 yrs from the European Community Respiratory Health Survey (ECRHS). Standardized spirometric measurements were obtained using a common protocol in 34 centres in 14 countries. For each prediction equation, the prediction deviations (i.e. observed minus predicted value) for forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) were examined for the whole study population and for each centre. For the age range included, the errors about the ECSC equations showed the most prominent underestimation of both predicted FVC (+355 and +360 mL on average in males and females, respectively) and predicted FEV1 (+211 and +200 mL, respectively) among the five studies examined. As expected, FVC and FEV1 in active smokers from the ECRHS were significantly lower than in lifetime nonsmokers (each p<0.01). We conclude that the present European recommendations on lung function reference values should be reconsidered, but further data for nonsymptomatic subjects above the age of 44 yrs are needed.
Targeting c-FLICE-like inhibitory protein (CFLAR) in cancer

Introduction: Evasion of apoptosis (programmed cell death) is one of the characteristic hallmarks of human cancers and may be caused by aberrant expression of antiapoptotic proteins. Among those is c-FLICE-like inhibitory protein (c-FLIP), a protein that not only blocks apoptosis signaling but also regulates additional cell death pathways. Areas covered: Because c-FLIP is regulated both at the transcriptional and posttranscriptional level by various mechanisms and is a short-lived protein with a rapid turnover, the regulation of c-FLIP expression represents a versatile tool to modulate cell death signaling pathways. Because c-FLIP is aberrantly expressed in various cancers, it represents a promising target for therapeutic intervention. Expert opinion: Therefore, insights into the molecular events that regulate c-FLIP expression and activity in human cancers will provide the basis for the development of new strategies to target c-FLIP expression in human cancers.
Modern antiepileptic drug development has failed to deliver: Ways out of the current dilemma

Despite the development of various new antiepileptic drugs (AEDs) since the early 1990s, the available evidence indicates that the efficacy and tolerability of drug treatment of epilepsy has not substantially improved. What are the reasons for this apparent failure of modern AED development to discover drugs with higher efficacy? One reason is certainly the fact that, with few exceptions, all AEDs have been discovered by the same conventional animal models, particularly the maximal electroshock seizure test (MES) in rodents, which served as a critical gatekeeper. These tests have led to useful new AEDs, but obviously did not help developing AEDs with higher efficacy in as yet AED‐resistant patients. This concern is not new but, surprisingly, has largely been unappreciated for several decades. A second—admittedly speculative—reason is that progress in pharmacologic treatment of drug‐resistant epilepsy will not be made unless and until we develop drugs that specifically target the underlying disease. Although better preclinical approaches will not be able to circumvent regulatory requirements, more efficacious drugs may allow us to abandon clinically questionable trials with intentionally less efficacious controls and noninferiority designs, and require evidence for comparative effectiveness. The failure of AED development has led to increasing disappointment among clinicians, basic scientists, and industry and may halt any further improvement in the treatment of epilepsy unless we find ways out of this dilemma. Therefore, we need new concepts and fresh thinking about how to radically change and improve AED discovery and development. In this respect, the authors of this critical review will discuss several new ideas that may hopefully lead to more efficacious drug treatment of epilepsy in the future.
MEMS Resonant Strain Sensor Integration

Despite commercial availability since the 1950's, silicon strain sensors have not experienced the same success as other microdevices, such as accelerometers, pressure sensors, and inkjet heads. Strain sensors measure mechanical deformation and could be used in many structural components, improving safety, controls, and manufacturing tolerances. This thesis examines major strain sensing techniques and highlights both advantages and disadvantages of each. MEMS resonant strain gauges are identified to have superior performance over many traditional strain gauges in terms of sensitivity, resolution, stability, and size. To use these gauges, additional issues such as harsh environment survivability, strain transfer, temperature stability, and encapsulation must be solved, as detailed in this thesis.Concerning harsh environment survivability, this work presents a MEMS resonant strain gauge fabricated from silicon carbide, which operates at 600dC, and has been tested to 64,000 G, while still resolving 0.01 microstrain in a 10 kHz bandwidth. Specific details on how to create harsh environment testing equipment are presented. Additionally, this original work identifies a unique temperature stability method based on purposely mismatched device and substrate layers. Full analytical equations are presented, and experimental confirmation of the scheme shows that temperature stability is improved from 23 ppm/dC to 3.6 ppm/dC. All MEMS devices are created on flat substrates, which are useful when integrating electronics, but can be difficult to use when measuring strain in structural components, especially round objects. Furthermore, no work has been presented for gauges operating at high strain. To address this issue, this thesis contains the first demonstration of a MEMS resonant strain gauge operating at 1000 microstrain on a static automobile halfshaft. Details on joining the substrate to the circular halfshaft are presented, as well as how to treat the issue of strain transfer. To protect the device, encapsulation is designed specifically to not change the strain sensitivity of the gauge. The encapsulation utilizes directional ion beam sputtering, which is experimentally shown to deposit spatially confined, extremely thin material through the release holes. Typical depositions were nanometers in thickness (<0.5% of deposited material) and on the order of tens to hundreds of femtograms.
Pseudo-Randomness of Round-Off Errors in Discretized Linear Maps on the Plane

We analyze the sequences of round-off errors of the orbits of a discretized planar rotation, from a probabilistic angle. It was shown [Bosio & Vivaldi, 2000] that for a dense set of parameters, the discretized map can be embedded into an expanding p-adic dynamical system, which serves as a source of deterministic randomness. For each parameter value, these systems can generate infinitely many distinct pseudo-random sequences over a finite alphabet, whose average period is conjectured to grow exponentially with the bit-length of the initial condition (the seed). We study some properties of these symbolic sequences, deriving a central limit theorem for the deviations between round-off and exact orbits, and obtain bounds concerning repetitions of words. We also explore some asymptotic problems computationally, verifying, among other things, that the occurrence of words of a given length is consistent with that of an abstract Bernoulli sequence.
CSF 5-HIAA and family history of antisocial personality disorder in newborns.

OBJECTIVE The relationship between genetic liability for antisocial behavior and CSF 5-hydroxyindoleacetic acid (5-HIAA) in newborns was explored. METHOD The authors assayed 5-HIAA in "leftover" CSF from 193 neurologically normal newborns and obtained family psychiatric histories of the newborns' first- and second-degree relatives. RESULTS Levels of 5-HIAA were significantly lower in the infants with family histories of antisocial personality disorder than in the newborns without such family histories. CONCLUSIONS These findings support the possibility that serotonin mediates one component of genetic liability to antisocial outcome, but the magnitude of that component may be less than what has been inferred from previously published reports.
An Integrated Derived Boost-Flyback Converter for fuel cell hybrid electric vehicles

In this paper, An Integrated Derived Boost-Flyback Converter with high voltage gain and reduced switch stress is proposed. It was used by fuel cell for hybrid electric vehicle applications. The proposed topology combines derived boost and flyback converters with a coupling inductor technique, which is able to achieve high voltage gain. The proposed converter extends the voltage gain without an extreme switch duty cycle by the three-winding coupled inductor and a voltage multiplier capacitor. The energy stored in leakage inductor of the coupled inductor can be recycled to the output capacitor to achieve high efficiency. The operational principles and steady-state analysis in continuous-conduction mode are described in detail to verify the performance of the proposed converter.
Novel method of analog circuit schematic synthesis

In this paper, we present a novel method of analog circuit schematic synthesis, which bridges topology synthesis and circuit sizing & layout synthesis in analog synthesis flow. Compared with traditional schematic synthesis, it brings templates-in, functionality analysis and partitioning for new hierarchy, constraint generation, port analysis, and analog-aware constraint identification into the new schematic synthesis, and enable analog-aware symbol generation for cells, symbol placement, and wire routing based on the functionality, new hierarchy, port types, and other constraints, also the constraints for sizing, floor-planning, and layout optimization are identified on the schematic. Experimental results show that designers can get analog functionality, structural feature, and constraints from the schematic intuitively, which is helpful to designers for sizing, floor-planning, and layout optimization.
Black-Box Composition : a Dynamic Approach

A core issue in component-based software engineering is represented by automatic component adaptation and composition. At behavioural level, an adaptor is an appropriate environment for two or more software components to correctly interoperate with respect to a certain desired behavioural property. This, however, requires for the behavioural interfaces of all components to be well-specified, which is not always the case in industrial practice. What happens if these components are black-boxes: incomplete specification, no provided models and no source code to extract interfaces from? How could we integrate them? Our approach interleaves online monitoring, verification-driven execution and model refinement in order to infer models of the black-box components, provide early access to a part of the system functionality whenever possible and synthesize permissive adaptors. We present both a centralized and a distributed technique, the last one directed towards the exploration and control of remote components.
The Development of Polymeric Devices as Dielectrophoretic Separators and Concentrators

Efficient and reliable particle separators and concentrators are needed to support a wide range of analytical functions including pathogen detection, sample preparation, high-throughput particle sorting, and biomedical diagnostics. The advent of lab-on-a-chip devices based on the phenomenon of dielectrophoresis offers advantages that can meet several of the challenges associated with cell sorting and detection. The majority of the devices presented in the scientific literature have used glass-based devices for these applications, but there has been recent activity that indicates that polymer-based devices can operate as effectively as their glass progenitors. Processing and operational advantages motivate the transition from glass and silicon to polymer microdevices: mechanical robustness, economy of scale, ease of thermoforming and mass manufacturing, and the availability of numerous innate chemical polymer compositions for tailoring performance. We present here a summary of the developments toward, and results obtained from, these polymeric dielectrophoretic devices in the selective trapping, concentration, and gated release of a range of biological organisms and particles.
Seismic tomography with irregular meshes

The current state of seismic tomography using irregular parameterizations is described. A review is given of previous work in the area covering local, regional and global seismic applications. The potential advantage of an irregular parameterization over a regular (uniform) one is that, by introducing higher resolution grids in particular parts of the model, one can maximize the information extracted from the data. Although irregular parameterizations have only recently been used in 3-D mantle tomography, their origins can be traced back more than twenty years. The use of irregular meshes in two and three dimensional tomographic imaging creates a number of 'implementation' issues, not seen with uniform grids. An outline of algorithms for solving all of these bookkeeping problems arising in cubic, tetrahedral or polygonal meshes is included, and references given to more detailed descriptions. Some recent implementations of tomography are discussed where the parameterization is refined during the course of the inversion process. Two examples of adaptive tomography in non-seismic problems suggest that the gradual refinement of the parameterization may be an effective way to regularize the inverse problem. The intention here is to point out the potential advantages and pitfalls of using an irregular parameterization in tomography. At present experience with seismic problems is rather limited (especially in 3-D) and an optimal approach is yet to emerge.