Excited States in Bilayer Graphene Quantum Dots.

We report ground- and excited-state transport through an electrostatically defined few-hole quantum dot in bilayer graphene in both parallel and perpendicular applied magnetic fields. A remarkably clear level scheme for the two-particle spectra is found by analyzing finite bias spectroscopy data within a two-particle model including spin and valley degrees of freedom. We identify the two-hole ground state to be a spin-triplet and valley-singlet state. This spin alignment can be seen as Hund's rule for a valley-degenerate system, which is fundamentally different from quantum dots in carbon nanotubes, where the two-particle ground state is a spin-singlet state. The spin-singlet excited states are found to be valley-triplet states by tilting the magnetic field with respect to the sample plane. We quantify the exchange energy to be 0.35 meV and measure a valley and spin g factor of 36 and 2, respectively.

Congregate Meals: Opportunities to Help Vulnerable Older Adults Achieve Diet and Physical Activity Recommendations.

BACKGROUND: Through diet and exercise interventions, community centers offer an opportunity to address health-related issues for some of the oldest, most vulnerable members of our society. OBJECTIVES: The purpose of this investigation is to draw upon nationwide data to better characterize the population served by the congregate meals program and to gather more detailed information on a local level to identify opportunities for service enhancement to improve the health and well-being of older adults. DESIGN: We examined community center data from two sources: 2015 National Survey of Older Americans Act and surveys from two New York City community centers. To assess nationwide service delivery, we analyzed participant demographics, functional status defined by activities of daily living, and perceptions of services received. MEASUREMENTS: Participants from the two New York City community centers completed a four-day food record. Functional measures included the short physical performance battery, self-reported physical function, grip strength, and the Montreal Cognitive Assessment. RESULTS: Nationwide (n=901), most participants rated the meal quality as good to excellent (91.7%), and would recommend the congregate meals program to a friend (96.0%). Local level data (n=22) were collected for an in-depth understanding of diet, physical activity patterns, body weight, and objective functional status measures. Diets of this small, local convenience sample were higher in fat, cholesterol, and sodium, and lower in calcium, magnesium, and fiber than recommended by current United States Dietary Guidelines. Average time engaged in moderate physical activity was 254 minutes per week (SD=227), exceeding the recommended 150 minutes per week, but just 41% (n=9) and 50% (n=11) of participants engaged in strength or balance exercises, respectively. CONCLUSION: Research is warranted to test whether improvements in the nutritional quality of food served and access/supports for engaging in strength training within community centers could help older adults achieve diet and physical activity recommendations.

Optimized SESAMs for kilowatt-level ultrafast lasers.

We present a thorough investigation of surface deformation and thermal properties of high-damage threshold large-area semiconductor saturable absorber mirrors (SESAMs) designed for kilowatt average power laser oscillators. We compare temperature rise, thermal lensing, and surface deformation of standard SESAM samples and substrate-removed SESAMs contacted using different techniques. We demonstrate that for all cases the thermal effects scale linearly with the absorbed power, but the contacting technique critically affects the strength of the temperature rise and the thermal lens of the SESAMs (i.e. the slope of the linear change). Our best SESAMs are fabricated using a novel substrate-transfer direct bonding technique and show excellent surface flatness (with non-measureable radii of curvature (ROC), compared to astigmatic ROCs of up to 10 m for standard SESAMs), order-of-magnitude improved heat removal, and negligible deformation with absorbed power. This is achieved without altering the saturation behavior or the recovery parameters of the samples. These SESAMs will be a key enabling component for the next generation of kilowatt-level ultrafast oscillators.

10 GHz pulse repetition rate Er:Yb:glass laser modelocked with quantum dot semiconductor saturable absorber mirror.

Semiconductor saturable absorber mirror (SESAM) modelocked high pulse repetition rate (≥10 GHz) diode-pumped solid-state lasers are proven as an enabling technology for high data rate coherent communication systems owing to their low noise and high pulse-to-pulse optical phase-coherence. Compared to quantum well, quantum dot (QD)-based SESAMs offer potential advantages to such laser systems in terms of reduced saturation fluence, broader bandwidth, and wavelength flexibility. Here, we describe the first 10 GHz pulse repetition rate QD-SESAM modelocked laser at 1.55 µm, exhibiting 2 ps pulse width from an Er-doped glass oscillator (ERGO). The 10 GHz ERGO laser is modelocked with InAs/GaAs QD-SESAM with saturation fluence as low as 9 µJ/cm2.

Ultrafast and widely tuneable vertical-external-cavity surface-emitting laser, mode-locked by a graphene-integrated distributed Bragg reflector.

We report a versatile way of controlling the unsaturated loss, modulation depth and saturation fluence of graphene-based saturable absorbers (GSAs), by changing the thickness of a spacer between a single layer graphene (SLG) and a high-reflection mirror. This allows us to modulate the electric field intensity enhancement at the GSA from 0 up to 400%, due to the interference of incident and reflected light at the mirror. The unsaturated loss of the SLG-mirror-assembly can be reduced to ∼0. We use this to mode-lock a vertical-external-cavity surface-emitting laser (VECSEL) from 935 to 981 nm. This approach can be applied to integrate SLG into various optical components, such as output coupler mirrors, dispersive mirrors or dielectric coatings on gain materials. Conversely, it can also be used to increase the absorption (up to 10%) in various graphene based photonics and optoelectronics devices, such as photodetectors.

Low repetition rate SESAM modelocked VECSEL using an extendable active multipass-cavity approach.

Ultrafast VECSELs are compact pulsed laser sources with more flexibility in the emission wavelength compared to diode-pumped solid-state lasers. Typically, the reduction of the pulse repetition rate is a straightforward method to increase both pulse energy and peak power. However, the relatively short carrier lifetime of semiconductor gain materials of a few nanoseconds sets a lower limit to the repetition rate of passively modelocked VECSELs. This fast gain recovery combined with low pulse repetition rates leads to the buildup of multiple pulses in the cavity. Therefore, we applied an active multipass approach with which demonstrate fundamental modelocking at a repetition rate of 253 MHz with 400 mW average output power in 11.3 ps pulses.

Gain characterization and passive modelocking of electrically pumped VECSELs.

Linear and nonlinear gain characterization of electrically pumped vertical external cavity surface emitting lasers (EP-VECSELs) is presented with spectrally resolved measurements of the gain and with gain saturation measurements of two EP-VECSEL samples with different field enhancement in the quantum-well gain layers. The spectral bandwidth, small-signal gain and saturation fluence of the devices are compared. Using the sample with the larger bandwidth, we have demonstrated the shortest pulses generated from a passively modelocked EP-VECSEL to date. With a low-saturation-fluence SESAM for passive modelocking we have achieved 9.5-ps pulses with 7.6 mW average output power at a repetition rate of 1.4 GHz. With a higher output coupler transmission the pulse duration was increased to 31 ps with an average output power of 13.6 mW. The pulses were chirped mainly due to the group delay dispersion (GDD) introduced by the intermediate DBR, which compensates the optical loss in the structure.

1.55 µm InAs/GaAs quantum dots and high repetition rate quantum dot SESAM mode-locked laser.

High pulse repetition rate (≥ 10 GHz) diode-pumped solid-state lasers, modelocked using semiconductor saturable absorber mirrors (SESAMs) are emerging as an enabling technology for high data rate coherent communication systems owing to their low noise and pulse-to-pulse optical phase-coherence. Quantum dot (QD) based SESAMs offer potential advantages to such laser systems in terms of reduced saturation fluence, broader bandwidth, and wavelength flexibility. Here, we describe the development of an epitaxial process for the realization of high optical quality 1.55 µm In(Ga)As QDs on GaAs substrates, their incorporation into a SESAM, and the realization of the first 10 GHz repetition rate QD-SESAM modelocked laser at 1.55 µm, exhibiting ∼2 ps pulse width from an Er-doped glass oscillator (ERGO). With a high areal dot density and strong light emission, this QD structure is a very promising candidate for many other applications, such as laser diodes, optical amplifiers, non-linear and photonic crystal based devices.

Optimal experimental design with the sigma point method.

Using mathematical models for a quantitative description of dynamical systems requires the identification of uncertain parameters by minimising the difference between simulation and measurement. Owing to the measurement noise also, the estimated parameters possess an uncertainty expressed by their variances. To obtain highly predictive models, very precise parameters are needed. The optimal experimental design (OED) as a numerical optimisation method is used to reduce the parameter uncertainty by minimising the parameter variances iteratively. A frequently applied method to define a cost function for OED is based on the inverse of the Fisher information matrix. The application of this traditional method has at least two shortcomings for models that are nonlinear in their parameters: (i) it gives only a lower bound of the parameter variances and (ii) the bias of the estimator is neglected. Here, the authors show that by applying the sigma point (SP) method a better approximation of characteristic values of the parameter statistics can be obtained, which has a direct benefit on OED. An additional advantage of the SP method is that it can also be used to investigate the influence of the parameter uncertainties on the simulation results. The SP method is demonstrated for the example of a widely used biological model.

PCR/DGGE and 16S rRNA gene library analysis of the colonic microbiota of HLA-B27/beta2-microglobulin transgenic rats.

AIMS: To determine the phylogenetic composition of the colonic microbiota of transgenic (TG) HLA-B27 rats using 16S ribosomal RNA (rRNA) gene sequences obtained from denaturing gradient gel electrophoresis (DGGE) gels and sequences from a 16S rRNA gene library. METHODS AND RESULTS: Colonic microbiota of TG and nontransgenic (NT) rats harboured by 10-week-old and 6-month-old animals was screened using PCR/DGGE. Six months old TG rats had marked inflammation of the colon compared with 10-week-old TG and NT rats. The DGGE profiles of rats with inflamed colon were similar from rat to rat (Dice's Similarity Coefficient proximal colon 73%, distal colon 83%) whereas profiles from animals without inflammation were dissimilar (52-64%). Identifications of bacterial origins of 16S rRNA gene sequences obtained from DGGE gels (200 bp) and from 16S rRNA clones (450 bp) of the colonic microbiota of diseased rats gave sequences most closely phylogenetically affiliated with uncultured or unknown bacteria. CONCLUSIONS: PCR/DGGE was shown to be an effective method to compare the colonic microbiota composition of TG and NT rats relative to the progression of inflammatory disease. Sequencing of 16S rRNA gene fragments from DGGE gels or 16S rRNA gene clones from a random library showed that uncultured or unknown bacteria were most commonly detected by both methods. It can be concluded that it would be better in future studies to search for the antigens produced by the gut microbiota against which the dysfunctional immune system reacts rather than seek phylogenetic associations. SIGNIFICANCE AND IMPACT OF THE STUDY: PCR/DGGE can be used as a rapid initial screening method to compare the composition of bacterial communities of initially unknown composition that are associated with the development of intestinal disease.

Complex phenotype of mice homozygous for a null mutation in the Sp4 transcription factor gene.

BACKGROUND: Sp4 is a zinc finger transcription factor which is closely related to Sp1 and Sp3. All three proteins recognize the same DNA elements and can act as transcriptional activators through glutamine-rich activation domains. Unlike Sp1 and Sp3, which are ubiquitous proteins, Sp4 is highly abundant in the central nervous system, but also detectable in many other tissues. RESULTS: We have disrupted the mouse Sp4 gene by a targeted deletion of the exons encoding the N-terminal activation domains. Sp4 knockout mice show a complete absence of Sp4 expression. They develop until birth without obvious abnormalities. After birth, two-thirds die within 4 weeks. Surviving mice are growth retarded. Male Sp4null mice do not breed. The cause for the breeding defect remains obscure since they show complete spermatogenesis. In addition, pheromone receptor genes in the vomeronasal organ appear unaffected. Female Sp4null mice have a smaller thymus, spleen and uterus. In addition, they exhibit a pronounced delay in sexual maturation. CONCLUSIONS: The phenotype of the Sp4null mice differs significantly from those described for Sp1-/- and Sp3-/- mice. Thus, the structural similarities, the common recognition motif and the overlapping expression pattern of these three transcription factors do not reflect similar physiological functions.

Characterization and promoter analysis of the mouse gene for transcription factor Sp4.

Transcription factor Sp4 is a member of the Sp1 family. It functions differently from other members of this family, such as Sp1 and Sp3, and the gene for Sp4 is transcribed in a tissue-specific manner. Recent studies in mice suggest that Sp4 might play an important role in growth, viability, and male fertility. We report here the isolation and characterization of the gene for Sp4 from a mouse genomic library. The mouse gene for Sp4 was about 80 kb in length and it consisted of six exons and five introns. The promoter was found in a CpG island and had a high G+C content. The proximal promoter contained multiple putative binding sites for the transcription factors Sp1 and MAZ but lacked a consensus TATA box. Multiple sites for the initiation of transcription were mapped in a GC-rich region from 286 bp to 211 bp upstream of the ATG triplet at the site of initiation of translation, and all of the sites were either C or G. Transfection experiments and deletion analysis allowed us to localize the promoter to a region that was no more than 93 bp upstream from the first site of initiation of transcription. We also found that ectopic expression of Sp1 and of MAZ, but not of Sp3, suppressed expression of the Sp4 promoter in a dose-dependent manner.

Specificity of signaling by STAT1 depends on SH2 and C-terminal domains that regulate Ser727 phosphorylation, differentially affecting specific target gene expression.

Complete activation of signal transducer and activator of transcription 1 (STAT1) requires phosphorylation at both Y701 and a conserved PMS(727)P sequence. S727 phosphorylation of STAT1 in interferon-gamma (IFN-gamma)-treated mouse fibroblasts occurred without a need for p38 mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinases 1 and 2 or c-Jun kinases, and required both an intact SH2 domain and phosphorylation of Y701. In contrast, UV irradiation-induced STAT1 phosphorylation on S727 required p38MAPK, but no SH2 domain- phosphotyrosine interactions. Mutation of S727 differentially affected IFN-gamma target genes, at the level of both basal and induced expression. Particularly strong effects were noted for the GBP1 and TAP1 genes. The PMS(727)P motif of STAT3 was phosphorylated by stimuli and signaling pathways different from those for STAT1 S727. Transfer of the STAT3 C-terminus to STAT1 changed the stimulus and pathway specificity of STAT1 S727 phosphorylation to that of STAT3. Our data suggest that STAT C-termini contribute to the specificity of cellular responses by linking individual STATs to different serine kinase pathways and through an intrinsically different requirement for serine phosphorylation at different target gene promoters.

NGF ligand alters NGF signaling via p75(NTR) and trkA.

Nerve growth factor (NGF) binds to two neurotrophin receptors: p75(NTR) and p140(Trk) (TrkA). Both receptors dimerize in response to NGF binding. TrkA homodimers and heteromers of TrkA and p75(NTR) promote cell survival whereas homodimers of p75(NTR) mediate apoptosis upon binding of NGF. The interaction between receptor and NGF can be inhibited either on the level of the ligand by altering NGF conformation so that NGF is no longer recognized by the receptor or on the level of the receptor by blocking the binding site of p75(NTR) or TrkA. The effect of altering NGF conformation on NGF signaling was investigated in two neuron-like cell lines: in human SK-N-MC cells that express only p75(NTR) and in rat PC12 cells that express both p75(NTR) and TrkA. In the present study we demonstrate that Ro 08-2750 binds to the NGF dimer thereby probably inducing a change in its conformation such that NGF cannot bind to p75(NTR) anymore. In SK-N-MC cells this leads to inhibition of NGF-induced programmed cell death. In PC12 cells enhanced signaling through TrkA was observed.

Psychometric evaluation of the Gothenburg Profile for measurement of experienced hearing disability and handicap: applications with new hearing aid candidates and experienced hearing aid users.

The Gothenburg Profile (GP) for measurement of experienced hearing disability and handicap was developed with content partly taken from the shortened Hearing Measurement Scale (HMS25). The GP consists of 20 items divided into two subscales. The first subscale measures Experienced Disability as to hearing speech (items 1-5) and sound localization (items 6-10). The second subscale targets the Experienced Handicap in social settings (items 11-15) and the personal reactions to the experienced handicap (items 16-20). In this study, data are presented for new hearing aid candidates (NewHA) (n=441) and for experienced hearing aid users (ExpHA) (n=476). Principal components factor analyses were conducted and a three-factor solution was obtained, supporting the two factors of the Experienced Disability subscale, but just confirming one factor in the Experienced Handicap subscale. The internal consistency reliability (coefficient alpha) was good (0.85 to 0.95) for the subscales as was the test-retest reliability. The ExpHA group expressed significantly greater disability (first subscale) as well as experienced handicap (second subscale). However, when controlling for hearing level the differences disappeared. The clinical use of the GP for assessment of rehabilitation needs is recommended.

The subjective meaning of illness in severe otosclerosis: a descriptive study in three steps based on focus group interviews and written questionnaire.

The aim of this study of otosclerosis patients was to highlight the circumstances specific to an operable middle ear disease and to describe the psychologically unique aspects accompanying this disorder. In a first step five subjects participated in four focus group interviews, from which emanated a questionnaire answered in a second step by 28 randomly chosen subjects. Finally a second series of supplementary focus interviews were conducted with another group of subjects, after which the interview material was subjected to code-mapping, agreement and validation. The study results indicate that ear surgery was a very important occurrence in the lives of the patients and a unique aspect was that they were burdened by a sense of responsibility for deciding in favour of or against the ear surgery and in choosing the time for operation. An event as tangible as an operation impacts on the individual's psychological processing of the fact that one of his or her senses is damaged. The message to the person's surroundings is very clear: the operation makes others understand how serious the situation is, gives rise to a sense of sympathy. These factors together may promote adaptation to the handicap, or alternately, at least for some persons, may impede adaptation to the necessary hearing aids. To some individuals hearing aids were strongly associated with periods of deteriorating hearing and therefore had negative connotations. Thus the hearing aid was used while waiting for surgery or instead of surgery. The constant hope of regaining one's hearing through ear surgery, although not totally realistic in these cases of severe otosclerosis, always makes the hearing aid the second best solution. The overall conclusion from this study is that there are specific circumstances of an operable ear disease which have great impact upon quality of life, well-being and adaptation. The psychological situation is one of instability, feelings of responsibility and at times of anxiety. Patients with otosclerosis are sometimes told that they are better off than others with impaired hearing, because surgery can improve their hearing and because good amplification through hearing aids can be achieved in persons with conductive hearing losses. It is our hope that this study has helped to provide a fuller picture of the facts of life for persons with severe otosclerosis.

Ménière's disease: trauma, distress and adaptation studied through focus interview analyses.

In order to investigate, in depth, the role of psychological factors in Ménière's disease, i.e. how the patients experience and interpret their symptoms during the process of this illness, a qualitative method "focus group interviews" was used as a study design. The focus group included four subjects; one woman and three men. In addition, semi-structured interviews were performed with each of four more subjects having the disease, three women and one man, in order to guarantee representativity in terms of gender and age. Through the focus interview analyses eight final codes and a number of sub-codes were developed. Results clearly pointed out the significance of the first traumatic attack of the disease as well as early signs; different "psychosomatic" symptoms prior to the attacks. The recognition of fear and phobic reactions in the manifestation of the vertigo attack was considered as an important observation, as attacks often were triggered by distressing thoughts as well as by sensory sensations. Other areas, touched upon for future investigation, were crisis adaptation and illness function.

Perceived sound quality of three bone-anchored hearing aid models.

Eighteen patients judged the sound quality of the new Classic 300 and the existing HC 100 or HC 200 on 4 five-stage sound quality scales. Two of the scales relate to the perceptual dimensions softness and clarity, one relates to interference or noise and one relates to the overall impression. The evaluations were made, based on a questionnaire, in the patients' own homes and comprised the listening situations: TV news, music, conversation with two to three people in a noisy environment and one optional choice. The patients also stated which hearing aid was best in each situation and made a confidence rating for their selection. The patients were accustomed to wearing the HC 100 or HC 200. In these comparisons of the different bone-anchored hearing aid models, the Classic 300 received the best ratings overall. Seventeen patients changed their previously fitted hearing aid to a Classic 300 and satisfactory sound quality was undoubtedly one of the principal reasons. When it came to the confidence rating for their selections, some two-thirds of the patients stated that it was without hesitation or with little hesitation. Our overall conclusion is that the sound quality of bone-anchored hearing aids is satisfactory when it comes to clarity and overall impression. However, it may be expected that these patients with conductive losses get a better sound quality than other patients with sensorineural losses if the same type of aid is used.

Protein kinase inhibitor H-7 differentially affects early and delayed nerve growth factor responses in PC12 cells.

The effects of the protein kinase inhibitor H-7 on early and delayed responses to nerve growth factor (NGF) were investigated in PC12 cells. H-7 reduced the NGF-induced expression of c-Fos in a dose-dependent manner without affecting the time course of c-Fos appearance. Conversely, H-7 potentiated delayed NGF effects, i.e., neurite outgrowth and Ca2+/phospholipid-dependent protein kinase (PKC) induction, but not choline acetyltransferase induction. Long-term treatment with NGF resulted in an increase of at least four tyrosine-phosphorylated protein bands with molecular masses between 39 and 48 kDa, which was also potentiated by H-7. In the absence of NGF, H-7 had no significant effect on c-Fos expression, tyrosine phosphorylation of the 45 kDa protein, or choline acetyltransferase activity. However, 4 days of exposure to H-7 alone induced PKC activity and tyrosine phosphorylation of the 39-kDa protein. The action of H-7 derivatives on neurite outgrowth did not correlate with their inhibition profile of cyclic nucleotide-dependent protein kinases. Down-regulation of PKC activity by prolonged exposure to phorbol ester did not completely abolish the effects of NGF and H-7 on induction of c-Fos, choline acetyltransferase activity, and neurite outgrowth, indicating that PKC-independent pathways contribute to these actions. These results suggest that additional pathway(s) sensitive to H-7 may exist, which induce immediate early gene expression and suppress neuronal differentiation of PC12 cells.