Higgs physics at the CLIC electron-positron linear collider.

The Compact Linear Collider (CLIC) is an option for a future [Formula: see text] collider operating at centre-of-mass energies up to [Formula: see text], providing sensitivity to a wide range of new physics phenomena and precision physics measurements at the energy frontier. This paper is the first comprehensive presentation of the Higgs physics reach of CLIC operating at three energy stages: [Formula: see text], 1.4 and [Formula: see text]. The initial stage of operation allows the study of Higgs boson production in Higgsstrahlung ([Formula: see text]) and [Formula: see text]-fusion ([Formula: see text]), resulting in precise measurements of the production cross sections, the Higgs total decay width [Formula: see text], and model-independent determinations of the Higgs couplings. Operation at [Formula: see text] provides high-statistics samples of Higgs bosons produced through [Formula: see text]-fusion, enabling tight constraints on the Higgs boson couplings. Studies of the rarer processes [Formula: see text] and [Formula: see text] allow measurements of the top Yukawa coupling and the Higgs boson self-coupling. This paper presents detailed studies of the precision achievable with Higgs measurements at CLIC and describes the interpretation of these measurements in a global fit.

Mixture effects of azole fungicides on the adrenal gland in a broad dose range.

Consumers are exposed to low concentrations of a variety of pesticide residues in or on food. Some of them might interfere with the endocrine system. While each individual active substance has been extensively tested for toxicity and safety, potential combination effects possibly resulting from combined exposure to different pesticides have seldomly been tested so far, especially in vivo. Since the adrenal gland is a key endocrine organ, we investigated if and how substances of a group of fungicides presumed to interfere with the biosynthesis of steroid hormones affect this organ when applied individually and in combination in a broad dose range. A 28-day feeding study was conducted in Wistar rats by using three (tri)azole fungicides considered to potentially affect the endocrine system (cyproconazole, epoxiconazole and prochloraz) individually at five dose levels, ranging from 0.9ppm to 2400ppm, and in combination at three dose levels. The parameters analysed included classical toxicology (pathology, histopathology, clinical chemistry) and molecular toxicology endpoints (gene expression arrays and quantitative real time PCR e.g. of Star, HSD3ß, Cyp11a1, Cyp11b1, Cyp11b2, Cyp 21, ApoE), as well as hormone analysis. A dose-dependent decrease in the adrenal gland weight of rats treated with epoxiconazole alone, which was accompanied by an atrophy of the adrenal gland as well as by an increase in the serum cholesterol level and which only became statistically significant at the top dose levels, was observed. These effects were attenuated in the combination experiments, although the same epoxiconazole concentration was used.

General vulnerability to stuttering: The experience of stuttering and conditions bringing about invulnerability.

General vulnerability to stuttering is the broad awareness of stuttering and the ever-present, experiential sense of a person who stutters (PWS). It is defined by stuttering in all its forms and the awareness of its presence, both in moments of stuttering and moments of perceivably fluent speech. Under the heading of general vulnerability to stuttering is specific vulnerability to stuttering, which includes the actual events of stuttering (i.e., overt symptoms, covert symptoms, subperceptual stuttering, and anticipation of stuttering). The differentiation between the two is that specific vulnerability requires a specific moment of stuttering where general vulnerability does not.

Carry-over fluency induced by extreme prolongations: A new behavioral paradigm.

Extreme prolongations, which can be generated via extreme delayed auditory feedback (DAF) (e.g., 250-500 ms) or mediated cognitively with timing applications (e.g., analog stopwatch) at 2 s per syllable, have long been behavioral techniques used to inhibit stuttering. Some therapies have used this rate solely to establish initial fluency, while others use extremely slowed speech to establish fluency and add other strategic techniques such as easy onsets and diaphragmatic breathing. Extreme prolongations generate effective, efficient, and immediate forward flowing fluent speech, removing the signature behaviors of discrete stuttering (i.e., syllable repetitions and audible and inaudible postural fixations). Prolonged use of extreme prolongations establishes carry-over fluency, which is spontaneous, effortless speech absent of most, if not all, overt and covert manifestations of stuttering. The creation of this immediate fluency and the immense potential of extreme prolongations to generate long periods of carry-over fluency have been overlooked by researchers and clinicians alike. Clinicians depart from these longer prolongation durations as they attempt to achieve the same fluent results at a near normal rate of speech. Clinicians assume they are re-teaching fluency and slow rates will give rise to more normal rates with less control, but without carry-over fluency, controls and cognitive mediation are always needed for the inherently unstable speech systems of persons who stutter to experience fluent speech. The assumption being that the speech system is untenable without some level of cognitive and motoric monitoring that is always necessary. The goal is omnipresent "near normal rate sounding fluency" with continuous mediation via cognitive and motoric processes. This pursuit of "normal sounding fluency" continues despite ever-present relapse. Relapse has become so common that acceptance of stuttering is the new therapy modality because relapse has come to be understood as somewhat inevitable. Researchers and clinicians fail to recognize that immediate amelioration of stuttering and its attendant carry-over fluency are signs of a different pathway to fluency. In this path, clinicians focus on extreme prolongations and the extent of their carry-over. While fluency is automatically generated under these extreme prolongations, the realization is that communication at this rate in routine speaking tasks is not feasible. The perceived solution is a systematic reduction in the duration of these prolongations, which attempts to approximate "normal speech." Typically, the reintroduction of speech at a normalized rate precipitates a laborious style that is undesirable to the person who stutters (PWS) and is discontinued, once departed from the comforts of the clinical setting. The inevitable typically occurs; the well-intentioned therapist instructs the PWS to focus on the techniques while speaking at a rate that is nearest normal speech, but the overlooked extreme prolongations are unlikely to ever be revisited. The foundation of this hypothesis is that the departure from fluency generators (e.g. extreme prolongations) is the cause of regression to the stuttering set point. In turn, we postulate that the continued use of extreme prolongations, as a solitary practice method, will establish and nurture different neural pathways that will create a modality of fluent speech, able to be experienced without cognitive or motoric mediation. This would therefore result in fewer occurrences of stuttering due to a phenomenon called carry-over fluency. Thus, we hypothesize that the use of extreme prolongations fosters neural pathways for fluent speech, which will result in carry-over fluency that does not require mediation by the speaker.

Physics at the [Formula: see text] linear collider.

A comprehensive review of physics at an [Formula: see text] linear collider in the energy range of [Formula: see text] GeV-3 TeV is presented in view of recent and expected LHC results, experiments from low-energy as well as astroparticle physics. The report focusses in particular on Higgs-boson, top-quark and electroweak precision physics, but also discusses several models of beyond the standard model physics such as supersymmetry, little Higgs models and extra gauge bosons. The connection to cosmology has been analysed as well.

Ab initio and semi-empirical Molecular Dynamics simulations of chemical reactions in isolated molecules and in clusters.

Recent progress in "on-the-fly" trajectory simulations of molecular reactions, using different electronic structure methods is discussed, with analysis of the insights that such calculations can provide and of the strengths and limitations of the algorithms available. New developments in the use of both ab initio and semi-empirical electronic structure algorithms are described. The emphasis is on: (i) calculations of electronic properties along the reactive trajectories and the unique insights this can contribute to the processes; (ii) electronic structure methods recently introduced to this topic to improve accuracy, extend applicability or enhance computational efficiency. The methods are presented with examples, including new results, of reactions of both isolated molecules and of molecules in media, mostly clusters. Possible future directions for this fast growing field are suggested.

Overview of the Shenzhen Emergency Medical Service Call Pattern / 世界急诊医学杂志（英文）

BACKGROUND: In Shenzhen, the Emergency Medical Service (EMS) system has been in service since 1997. This study aims to examine the operation of Shenzhen 120 EMS center and to identify the reasons of calling EMS. METHODS: In this retrospective quantitative descriptive study, the data from the Shenzhen 120 EMS registry in 2011 were analyzed. RESULTS: Shenzhen 120 EMS center is a communication command center. When the number of 120 are dialed, it is forwarded to the closest appropriate hospital for ambulance dispatch. In 2011, the Shenzhen 120 EMS center received 153160 ambulance calls, with an average of 420 calls per day. Calling emergency services was mainly due to traffic accidents. Trauma and other acute diseases constituted a majority of ambulance transports. The adult patients aged 15–60 years are the principal users of EMS. There are no recognized 'paramedic' doctors and nurses. The pre-hospital emergency service is under the operation of emergency departments of hospitals. Shenzhen at present does not have specialized pre-hospital training for doctors and nurses in post-trauma management. Moreover, specialized pre-hospital training, financial support, and public health education on proper use of EMS should be emphasized. CONCLUSION: The Shenzhen 120 EMS center has its own epidemiology characteristics. Traumatic injury and traffic accident are the main reasons for calling ambulance service. In-depth study emphasizing the distribution and characteristics of trauma patients is crucial to the future development of EMS.

Exciton quenching in emitter blends for organic light emitting devices probed by electric field-dependent time-resolved luminescence.

We investigate quenching mechanisms of excited states in emitter layers for organic light emitting diodes (LEDs). An extensive study of a strong electric field-induced modulation (over 50%) of the time-resolved luminescence in a diamine derivative (TPD): polycarbonate blend films doped with an organic complex of europium are presented as a typical example of an important class of emitters for organic monochromatic LEDs. Using this method allowed us to identify the quenched species as the excited ligand precursors of the emissive europium ion states. Manipulating the electrode materials and their electrical bias, the electric field-enhanced dissociation, and interaction with injected charge could be separated and found as principal quenching mechanisms. We show the first one to follow the three-dimensional Onsager theory of geminate recombination, and the second one raised by their interaction with the TPD-transported holes. The interaction rate constant is found to be underlain by the three-dimensional diffusion of excited ligand singlets, combining the exciton diffusion coefficient and long-range (Forster type) energy transfer parameters. The dynamic parameters of the hole-precursor excitons interactions, extracted from the experimental data, allow us to establish the criteria for identifying useful ligands and matrices in the optimized design of electrophosphorescent, linelike emitting molecules, and device structure for organic LEDs.

Analysis of subcellular surface structure, function and dynamics.

Analytics of single biological cells allows quantitative investigation from a structural, functional and dynamical point of view and opens novel possibilities to an unamplified subcellular analysis. In this article, we report on three different experimental methods and their applications to single cellular systems with a subcellular sensitivity down to the single molecule level. First, the subcellular surface structure of living bacteria (Corynebacterium glutamicum) was investigated with atomic force microscopy (AFM) at the resolution of individual surface layer (S-layer) proteins; discrimination of bacterial strains that lack the expression of hexagonally packed surface layer proteins was possible. Second, quantitative measurement of individual recognition events of membrane-bound receptors on living B-cells was achieved in single cell manipulation and probing experiments with optical tweezers (OT) force spectroscopy. And third, intracellular dynamics of translocating photoactivatable GFP in plant protoplasts (Nicotiana tabacum BY-2) was quantitatively monitored by two-photon laser scanning microscopy (2PLSM).

Role of the ssu and seu genes of Corynebacterium glutamicum ATCC 13032 in utilization of sulfonates and sulfonate esters as sulfur sources.

Corynebacterium glutamicum ATCC 13032 was found to be able to utilize a broad range of sulfonates and sulfonate esters as sulfur sources. The two gene clusters potentially involved in sulfonate utilization, ssuD1CBA and ssuI-seuABC-ssuD2, were identified in the genome of C. glutamicum ATCC 13032 by similarity searches. While the ssu genes encode proteins resembling Ssu proteins from Escherichia coli or Bacillus subtilis, the seu gene products exhibited similarity to the dibenzothiophene-degrading Dsz monooxygenases of Rhodococcus strain IGTS8. Growth tests with the C. glutamicum wild-type and appropriate mutant strains showed that the clustered genes ssuC, ssuB, and ssuA, putatively encoding the components of an ABC-type transporter system, are required for the utilization of aliphatic sulfonates. In C. glutamicum sulfonates are apparently degraded by sulfonatases encoded by ssuD1 and ssuD2. It was also found that the seu genes seuA, seuB, and seuC can effectively replace ssuD1 and ssuD2 for the degradation of sulfonate esters. The utilization of all sulfonates and sulfonate esters tested is dependent on a novel putative reductase encoded by ssuI. Obviously, all monooxygenases encoded by the ssu and seu genes, including SsuD1, SsuD2, SeuA, SeuB, and SeuC, which are reduced flavin mononucleotide dependent according to sequence similarity, have SsuI as an essential component. Using real-time reverse transcription-PCR, the ssu and seu gene cluster was found to be expressed considerably more strongly during growth on sulfonates and sulfonate esters than during growth on sulfate.

Photophysics of an electrophosphorescent platinum (II) porphyrin in solid films.

We examine electronic processes in platinum (II) octaethyl porphyrin (PtOEP) embedded in an organic solid state matrix and in the form of vacuum-evaporated neat films in conjunction with potential applications of this compound to organic photovoltaic and electrophosphorescent devices. Absorption, photoexcitation, and luminescence spectra indicate the excitonic dimers to be dominant excited states, and their dissociation underlies the charge photogeneration process. Different charge separation distance (1.5 nm and 2.6 nm) in opposite charge carrier pairs preceding dissociation can be distinguished based on the fit of the three-dimensional Onsager theory of geminate recombination to electromodulated luminescence and photoconduction measurements. The near-positive electrode concentrated triplet dimer excitons, produced by strongly 370 nm absorbed light in neat PtOEP films, are efficiently quenched by electron transfer to the metal (Al), generating the positive charge with an efficiency eta+ exceeding 0.15 at high electric fields and dominating the measured photocurrent. Their dissociation efficiency in the bulk, eta- (negatively biased illuminated electrode), is more than one order of magnitude lower than eta+. The dissociation of singlet dimer states dominates the bulk photogeneration process induced by the weakly-absorbed light at 450 nm, with comparable eta+ and eta-. The "hot excited state" underlying the temperature-increasing emission at 540 nm has been attributed to the upper excitonic component Q+ of the first absorption band Q consistent with the exciton concept applied successfully to the interpretation of all dimer-underlain spectroscopic features of PtOEP samples studied.

Genome-wide analysis of the L-methionine biosynthetic pathway in Corynebacterium glutamicum by targeted gene deletion and homologous complementation.

The genome sequence of Corynebacterium glutamicum, a gram-positive soil bacterium widely used as an amino acid producer, was analyzed by a similarity-based approach to elucidate the pathway for the biosynthesis of L-methionine. The functions of candidate ORFs were derived by gene deletion and, if necessary, by homologous complementation of suitable mutants. Of nine candidate ORFs (four of which were known previously), seven ORFs (cg0754 (metX), cg0755 (metY), cg1290 (metE), cg1702 (metH), cg2383 (metF), cg2536 (aecD), and cg2687 (metB)) were demonstrated to be part of the pathway while two others (cg0961 and cg3086) could be excluded. C. glutamicum synthesizes methionine in three, respectively four steps, starting from homoserine. C. glutamicum possesses two genes with similarity to homoserine acetyltransferases but only MetX can act as such while Cg0961 catalyzes a different, unknown reaction. For the incorporation of the sulfur moiety, the known functions of MetY and MetB could be confirmed and AecD was proven to be the only functional cystathionine beta-lyase in C. glutamicum, while Cg3086 can act neither as cystathionine gamma-synthase nor as cystathionine beta-lyase. Finally, MetE and MetH, which catalyze the conversion of L-homocysteine to L-methionine, could be newly identified, together with MetF which provides the necessary N(5)-methyltetrahydrofolate.

Self-reported efficacy of an all in-the-ear-canal prosthetic device to inhibit stuttering during one hundred hours of university teaching: an autobiographical clinical commentary.

This manuscript outlines the lifelong battle with severe stuttering and describes a new modality of effective amelioration of the disorder from the standpoint of a university professor and researcher in the field of stuttering. Childhood reactions to stuttering are discussed, along with the educational and vocational impact of stuttering. Ongoing therapy was received throughout the formative years and into adulthood, emphasizing reduced rates of speech. The use of Delayed Auditory Feedback (DAF) was found to induce fluent speech, but was considered only as a tool for decreasing the speech rate to achieve fluency. When fluency under DAF was discovered to be possible at faster speech rates, the possibility that the use of DAF and other forms of altered auditory feedback could themselves have an inhibitory effect on stuttering, without concomitant rate reduction was investigated. An In-The-Canal (ITC) fluency-enhancing device was used that provided DAF and Frequency Altered Feedback (FAF) to produce more fluent speech. After 10 months of use, the author was relatively free from stuttering. Speech was natural sounding, relatively spontaneous and unlaboured with an absence of fear. However, further testing (that is currently underway at various centres) is necessary before generalizations can be made.

The end-product of behavioural stuttering therapy: three decades of denaturing the disorder.

ISSUE: The state of stuttering therapy continues to be of great concern in the field of speech-language pathology. Despite decades of research and clinical practical, stuttering is still treated by ineffective and inefficient means. PROPOSAL: Our research group suggests that therapy failures stem from the use behavioural approaches; procedures that have resulted in only temporary and unnatural alleviation from the symptomatology by masking the disorder. These procedures 'denature' the disorder and induce pseudofluency rather than true fluency. It is proposed that in order to truly provide relief to those who stutter, professionals need to view both the overt and covert components of the disorder from the standpoint of attaining true fluency. Only then can the true syndrome-like nature of stuttering be addressed. In order to achieve true fluency the use of stuttering inhibitors must be incorporated such as choral speech and its permutations to derive natural sounding, stable and effortless speech in those who stutter. CONCLUSION: By doing so, the goal is to not only derive stable and natural-sounding speech, but also to help remove such factors as the expectancy, anticipation and the fear of stuttering that generally continue to shackle most people who stutter following behavioural therapy.

A common element in the immediate inducement of effortless, natural-sounding, fluent speech in people who stutter: 'the second speech signal'.

Recent attempts to find a common element in the inducement of fluent speech have focused on Wingate's notion that fluency can be induced via an altered manner of speaking by placing an emphasis on phonation. The problem with this notion of fluency enhancement is that it appears to be too expansive a scheme of fluency. The schemata allows for any forward flowing speech or speech-like act to be considered fluent despite the increased cognitive mediation, the extra effort involved in implementing the procedure, the unnaturalness of the resultant end product, and a lack of stability over time. It is proposed that the only significant characteristics of 'true fluency' are that it is indistinguishable from the typical fluent speech of people who do not stutter, and that it is effortless in nature. This is achieved via the use of a second speech signal which is not cognitive in nature, is operationally delineated, and is easy to manipulate.

Reduction of stuttering: the dual inhibition hypothesis.

Treatment for stuttering attempts to reduce or eliminate the observable core markers of the disorder, specifically repetitions and prolongation. In this hypothesis, it is proposed that stuttering may be inhibited by two distinct yet related procedures: active inhibition and passive inhibition. Active inhibition is brought about when the person who stutters makes volitional changes to his or her speaking pattern, such as when employing behavioral modification techniques. Passive inhibition automatically inhibits the involuntary stuttering block and can be induced from an external source, such as altered auditory feedback, or by the use of sufficient active inhibition. It is suggested that passively inhibiting stuttering results in speech that is more automatic, natural sounding, and truly fluent speech than the speech that is derived primarily from active inhibition. Evidence of passive inhibition resulting from active inhibition can be seen when people who stutter exhibit uncontrolled fluency following behavioral therapy.

Relaxed rrn expression and amino acid requirement of a Corynebacterium glutamicum rel mutant defective in (p)ppGpp metabolism.

The stringent response in Corynebacterium glutamicum was investigated. Sets of rrn-cat fusions were constructed in their native chromosomal position to examine the effects of amino acid starvation in a rel(+) strain and a Deltarel mutant defective in (p)ppGpp metabolism. The expression of the six rrn operons in the rel(+) control was stringently regulated and reduced to 79% upon induction of amino acid starvation. The Deltarel mutant displayed a relaxed regulation and was unable to reduce the rrn expression under amino acid depletion conditions. In addition, the Deltarel mutant grew more slowly in minimal medium than a rel(+) control. This growth effect was restored by a plasmid-encoded copy of rel or, alternatively, by supplementation of the minimal medium with the amino acid mixture casamino acids. In particular, the Deltarel strain of C. glutamicum displayed a requirement for the amino acids histidine and serine.

Proteome analysis of Corynebacterium glutamicum.

By the use of different Corynebacterium glutamicum strains more than 1.4 million tons of amino acids, mainly L-glutamate and L-lysine, are produced per year. A project was started recently to elucidate the complete DNA sequence of this bacterium. In this communication we describe an approach to analyze the C. glutamicum proteome, based on this genetic information, by a combination of two-dimensional (2-D) gel electrophoresis and protein identification via microsequencing or mass spectrometry. We used these techniques to resolve proteins of C. glutamicum with the aim to establish 2-D protein maps as a tool for basic microbiology and for strain improvement. In order to analyze the C. glutamicum proteome, methods were established to fractionate the C. glutamicum proteins according to functional entities, i.e., cytoplasm, membranes, and cell wall. Protein spots of the cytoplasmic and membrane fraction were identified by N-terminal sequencing, immunodetection, matrix assisted laser desorption/ionization-time of flight-mass spectrometry (MALDI-TOF-MS) and electrospray ionization-mass spectrometry (ESI-MS). Additionally, a protocol to analyze proteins secreted by C. glutamicum was established. Approximately 40 protein spots were observed on silver-stained 2-D gels, 12 of which were identified.