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Nucleosome-depleted regions (NDRs) at gene promoters support initiation of RNA polymerase II transcription. Interestingly, transcription often initiates in both directions, resulting in an mRNA and a divergent non-coding (DNC) transcript of unclear purpose. Here, we characterized the genetic architecture and molecular mechanism of DNC transcription in budding yeast. Using high-throughput reverse genetic screens based on quantitative single-cell fluorescence measurements, we identified the Hda1 histone deacetylase complex (Hda1C) as a repressor of DNC transcription. Nascent transcription profiling showed a genome-wide role of Hda1C in repression of DNC transcription. Live-cell imaging of transcription revealed that mutations in the Hda3 subunit increased the frequency of DNC transcription. Hda1C contributed to decreased acetylation of histone H3 in DNC transcription regions, supporting DNC transcription repression by histone deacetylation. Our data support the interpretation that DNC transcription results as a consequence of the NDR-based architecture of eukaryotic promoters, but that it is governed by locus-specific repression to maintain genome fidelity., (© 2021 The Authors. Published under the terms of the CC BY NC ND 4.0 license.)

Purpose: To evaluate the quality and content of internet-based information available for some of the most common orthopaedic sports medicine terms., Methods: A search of the PubMed, Embase, and Cochrane databases following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) guidelines was performed. All English-language literature published from 2010 to 2020 discussing information quality pertaining to orthopaedic sports medicine terms was included. Outcomes included the search engines used, number and type of websites evaluated, platform, and quality scoring metrics. Descriptive statistics are presented., Results: This review includes 21 studies. Of these, 3 evaluated both the upper and lower extremity. Twelve focused on either the upper or lower extremity, most commonly rotator cuff tears (3 of 12) and/or anterior cruciate ligament pathologies (7 of 12). The most common engines were Google (18 of 21), Bing (16 of 21), Yahoo (16 of 21), YouTube (3 of 21), Ask (3 of 21), and AOL (2 of 21). The average number of media files assessed per study was 87 ± 55. Website quality was assessed with DISCERN (7 of 21), Flesch-Kincaid (9 of 21), Health on the Net (7 of 21), and/or Journal of the American Medical Association Benchmark (7 of 21) scores. YouTube was evaluated with Journal of the American Medical Association Benchmark scores (1.74 ± 1.00). Image quality was reported in 2 studies and varied with search terminology., Conclusions: The results of this systematic review suggest that physicians should improve the quality of online information and encourage patients to access credible sources when conducting their own research., Clinical Relevance: Doctors can and should play an active role in closing the gap between the level of health literacy of their patients and that of most common online resources., (© 2021 by the Arthroscopy Association of North America. Published by Elsevier Inc.)

We demonstrate microfluidic automation and parallelization of Limulus amebocyte lysate (LAL)-based bacterial endotoxin testing using centrifugal microfluidics. LAL is the standard reagent to test for endotoxin contaminations in injectable pharmaceuticals. The main features of the introduced system are more than 90% reduction of LAL consumption, from 100 μL/reaction to 9.6 μL/reaction, automated liquid handling to reduce opportunities for contamination and manual handling errors, and microfluidic parallelization by integrating 104 reactions into a single centrifugal microplate. In a single Eclipse microplate, 21 samples and their positive product controls are tested in duplicate. In addition, a standard curve with up to five points is generated, resulting in a total of 104 reactions. Test samples with a defined concentration of 0.5 endotoxin units per milliliter were tested, resulting in a coefficient of variation below 0.75%. A key feature for achieving a small coefficient of variation is ensuring the same path length along the microfluidic channels to the final reaction chambers for each sample and the reagent, so that any unspecific adsorption to the polymer surfaces does not affect the accuracy and precision. Analysis of a sample containing naturally occurring endotoxin with the developed microfluidic microplate yielded comparable results to the conventional testing method. A test with eight commercially available pharmaceuticals was found to pass all requirements for bacterial endotoxin testing as specified in the United States Pharmacopeia. The automated endotoxin testing system reveals specific advantages of centrifugal microfluidics for analytical biochemistry applications. Small liquid volumes are handled (metered, mixed, and aliquoted) in a very precise, highly integrated, and highly parallel manner within mass-fabricated microplates.

The number of flowers and seed-bearing structures formed by the inflorescence meristem and the formation of ovules in the female reproductive part of the flowers are important yield-related traits of crop plants. It has been shown that cytokinin is a pivotal factor regulating these traits. Here, we explore the impact of mutation of CYTOKININ OXIDASE/DEHYDROGENASE (CKX) genes encoding cytokinin-degrading enzymes on these yield-related traits in oilseed rape (Brassica napus L.). We describe the identification of four BnCKX3 and two BnCKX5 genes as regulators of reproductive development in the allotetraploid B. napus. RNA-seq analysis and in situ hybridization showed expression of these genes in reproductive organs. Loss-of-function mutants for each of these CKX gene copies were identified by targeting induced local lesions in genomes (TILLING) and combined by crossing. Sextuple ckx3 ckx5 mutants showed an increased cytokinin concentration and larger and more active inflorescence meristems. They also produced up to 72% more flowers with gynoecia containing 32% more ovules and up to 54% more pods on the main stem. The weight of seeds harvested from the main stem of plants grown in the greenhouse or in the field was increased by 20-32%. Our results show that cytokinin regulates inflorescence meristem and placenta activity in oilseed rape. The work demonstrates the potential to achieve yield enhancement in a dicot crop plant by modulating the cytokinin status through mutagenesis of specific CKX genes., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

The investigation of influential parameters of the starching process on mechanical properties of yarns intended for multifunctional woven fabrics for thermal protective clothing was performed on four different yarn samples starched on an innovative starching machine, adapted to industrial starching conditions. The starching was conducted with two different processes with different starch mass concentrations: the standard starching process and a newer starching process (with yarn prewetting). Based on the results obtained, it can be concluded that starching positively affects all the properties of tested samples and that the increase of starch mass concentration is not accompanied by the improvement of those yarn properties. Synthetic polymer fibers that achieve satisfactory yarn strength need to be starched with lower starch mass concentrations in order to retain the breaking properties and to be protected from abrasion and static electricity, which occurs during the weaving process. The yarn prewetting starching process shows significantly better results than the standard starching process, especially for aramid yarns, where abrasion resistance increased from 42 to 135%. Therefore, we can conclude that the goal of starching such yarns is aimed at increasing the wear resistance. Linear regressions and correlations between the values of breaking properties and abrasion resistance obtained by the testing and their values that were estimated by the analysis show a high correlation coefficient.

RNA polymerase (RNAP)II frequently transcribes non-protein-coding DNA sequences in eukaryotic genomes into long noncoding RNA (lncRNA). Distinct molecular mechanisms linked to the position of lncRNA relative to the coding gene illustrate how noncoding transcription controls gene expression. Here, we focus on the impact of the act of lncRNA transcription on nearby functional DNA units. We review the biological significance of the act of lncRNA transcription on DNA processing, highlighting common themes, such as mediating cellular responses to environmental changes. This review combines the background of chromatin signaling with examples in several organisms to clarify when functions of ncDNA can be interpreted through the act of RNAPII transcription., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

For the purpose of this research, six types of woven fabrics with different proportions of bicomponent carbon fibres (CF), differently distributed in the fabric, were woven and tested. Fibre composition in the core and sheath was determined with X-ray spectroscopy (EDS). Two types of bicomponent CF were selected which are characterised by different proportions of carbon and other polymers in the fibre core and sheath and different cross-sections of the fibres formed during chemical spinning. Physical-mechanical properties were investigated, as well as deformations of fabrics after 10,000, 20,000 and 30,000 cycles under biaxial cyclic stress on a patented device. Tests of the surface and vertical electrostatic resistance from fabric front to back side and from the back side to the fabric front were conducted. According to the obtained results and statistical analyses, it was concluded that the proportion of CF affects the fabric's physical and mechanical properties, the electrostatic resistance as well as the deformations caused by biaxial cyclic stresses. A higher proportion of CF in the fabric and a higher proportion of carbon on the fibre surface, gave lower electrostatic resistance, i.e., better conductivity, especially when CFs are woven in the warp and weft direction. The higher presence of CF on the front of the fabric, as a consequence of the weave, resulted in a lower surface electrostatic resistance.

Synaptically released glutamate is largely cleared by glutamate transporters localized on perisynaptic astrocyte processes. Therefore, the substantial variability of astrocyte coverage of individual hippocampal synapses implies that the efficacy of local glutamate uptake and thus the spatial fidelity of synaptic transmission is synapse dependent. By visualization of sub-diffraction-limit perisynaptic astrocytic processes and adjacent postsynaptic spines, we show that, relative to their size, small spines display a stronger coverage by astroglial transporters than bigger neighboring spines. Similarly, glutamate transients evoked by synaptic stimulation are more sensitive to pharmacological inhibition of glutamate uptake at smaller spines, whose high-affinity N-methyl-D-aspartate receptors (NMDARs) are better shielded from remotely released glutamate. At small spines, glutamate-induced and NMDAR-dependent Ca 2+ entry is also more strongly increased by uptake inhibition. These findings indicate that spine size inversely correlates with the efficacy of local glutamate uptake and thereby likely determines the probability of synaptic crosstalk., Competing Interests: Declaration of Interests The authors declare no competing interests., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

The subject of the paper focuses on the effect of weave architecture on microbial barrier properties of woven fabrics or more precisely on identifying crucial elements of weave architecture that dominantly influence bacteria penetration in dry condition. For that purpose, 12 samples of cotton fabrics were woven and examined. In their structure, all samples had the same yarns (36 tex) in warp and weft, same densities of warp (24 yarns/cm), two weft densities (24 and 20 yarns/cm) and six different basic weave structures. Microbial barrier permeability was determined according to a previously developed test method in cooperation with University Hospital Center Zagreb. Bacterial endospores of apathogenic species of the genus Bacillus: Geobacillus stearothermophilus and Bacillus atrophaeus were used. The effect of weave pattern on microbial barrier properties was significant. Weave patterns, decisively determined the number of influencing pores and its sizes in woven fabrics, as well as the yarn floating which jointly almost perfectly correlated with bacteria penetration through the woven fabric. Multiple linear regression of pore numbers and floating threads produced equations which correspond in 99% to the measuring results for densities 24/24 and 24/20, and more than 98% considering both densities of the set. Among compared weave patterns, satin weave had significantly lower permeability of microorganisms (six-seven times) than basket weave (the highest), for both densities., Competing Interests: The authors declare no conflict of interest.

Background: Few studies have investigated the relationship between the Patient-Reported Outcomes Measurement Information System (PROMIS) and legacy patient-reported outcome (PRO) measurements., Purpose: To compare patient-reported outcomes from the PROMIS physical function (PF) and upper extremity (UE) platforms against one another and against legacy PRO measurements to assess the potential strengths and weaknesses of the National Institutes of Health PROMIS initiative and expand on the use of PRO measurements in clinical orthopaedic practice., Study Design: Systematic review; Level of evidence, 4., Methods: A systematic search of the PubMed, Embase, and Cochrane Library databases was conducted following PRISMA (Preferred Reporting Items for Systematic Meta-Analyses) guidelines. All English-language studies published between 2017 and 2019 using PROMIS to evaluate patients for shoulder surgery were analyzed. PROs were compared based on survey administered and the shoulder condition being investigated. Study quality was evaluated using the Modified Coleman Methodology Score and the Methodological Index for Non-Randomized Studies score., Results: We included 9 studies (5 studies were level 2; 3 studies were level 3; 1 study was level 4) encompassing a total of 1130 patients (60.2% male; mean age, 52.6 ± 16.5 years; mean BMI, 29.8 ± 2.8 kg/m 2 ). Of these, 6 studies administered the PROMIS PF, and 6 studies administered the PROMIS UE. The strongest correlation was between PROMIS PF computer adaptive test and the 36-Item Short Form Health Survey Global Health (SF-36 GH) ( r = 0.75). The highest overall correlation with the PROMIS UE was found with the American Shoulder and Elbow Surgeons (ASES) Shoulder Score ( r = 0.70). The lowest correlations were found between PROMIS PF and the Marx Shoulder Activity Scale ( r = 0.08) and the PROMIS UE and the Marx Shoulder Activity Scale ( r = 0.18)., Conclusion: From available data, the PROMIS PF and PROMIS UE were most closely correlated with outcomes measured by the SF-36 GH. The PROMIS UE alone was most correlated with ASES Shoulder Score. Thus, either PROMIS PF or UE may provide a possible alternative to legacy PRO measurements but with a lower overall number of questions and higher generalizability. Future research should compare the time and question burden of the various PROMIS platforms with a more consistent evaluation of standard PRO measurements., Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: R.M.F. has received grant support from Arthrex; educational support from Arthrex, Medwest, and Smith & Nephew; speaking fees from Arthrex; and royalties from Elsevier. J.T.B. has received research support from Biomet and Stryker; consulting fees from DJO, Encore Medical, and Smith & Nephew; and royalties from Shukla Medical. E.C.M. has received research support from Arthrex, Biomet, Breg, Mitek, Ossur, Smith & Nephew, and Stryker; consulting fees from DePuy and Zimmer Biomet; speaking fees from Arthrex; and royalties from Elsevier and Zimmer Biomet. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto., (© The Author(s) 2020.)

The use of synthesized natural starches for the sizing process in fabric production is primarily an environmental contribution. Synthesized corn starch is environmentally friendly and productive, showing good results in cotton yarn sizing. Acrylamide (AA) and 2-hydroxyethyl methacrylate (HEMA) were applied for the grafting process of corn starch, and the initiators azobisisobutyronitrile (AIBN), potassium persulfate (KPS), and benzoyl peroxide (BP) were chosen to form the grafted monomers more effectively. The application of synthesized corn starch has been confirmed, especially with the AIBIN initiator in the grafting process of HEMA onto starch. The FTIR analysis confirmed that new and efficient products for sizing cotton yarns based on natural raw material (corn) were developed. The research showed that the synthesized corn starch improved physical-mechanical yarn properties and abrasion resistance and reduced yarn surface hairiness. Ultrasonic desizing of yarn and the use of a lower size concentration led to better results than desizing by washing, and the Tegewa numbers confirmed that the desizing process was successful., Competing Interests: The authors declare no conflict of interest.

Resilience to stress is critical for the development of depression. Enhanced adenosine A 1 receptor (A 1 R) signaling mediates the antidepressant effects of acute sleep deprivation (SD). However, chronic SD causes long-lasting upregulation of brain A 1 R and increases the risk of depression. To investigate the effects of A 1 R on mood, we utilized two transgenic mouse lines with inducible A 1 R overexpression in forebrain neurons. These two lines have identical levels of A 1 R increase in the cortex, but differ in the transgenic A 1 R expression in the hippocampus. Switching on the transgene promotes robust antidepressant and anxiolytic effects in both lines. The mice of the line without transgenic A 1 R overexpression in the hippocampus (A1Hipp-) show very strong resistance towards development of stress-induced chronic depression-like behavior. In contrast, the mice of the line in which A 1 R upregulation extends to the hippocampus (A1Hipp+), exhibit decreased resilience to depression as compared to A1Hipp-. Similarly, automatic analysis of reward behavior of the two lines reveals that depression resistant A1Hipp-transgenic mice exhibit high sucrose preference, while mice of the vulnerable A1Hipp + line developed stress-induced anhedonic phenotype. The A1Hipp + mice have increased Homer1a expression in hippocampus, correlating with impaired long-term potentiation in the CA1 region, mimicking the stressed mice. Furthermore, virus-mediated overexpression of Homer1a in the hippocampus decreases stress resilience. Taken together our data indicate for first time that increased expression of A 1 R and Homer1a in the hippocampus modulates the resilience to stress-induced depression and thus might potentially mediate the detrimental effects of chronic sleep restriction on mood., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

The objective of this research was to verify the feasibility of the use of newly synthesized biopolymer materials for sizing cotton yarns based on the basic principles of chemical modification. Research included acid hydrolysis of potato starch up to controlled molar masses together with graft-polymerization and methacrylic acid onto hydrolyzed starch to improve hydrophilicity and solubility, to increase the capability of film forming, to increase adhesive potential and to avoid retrogradation phenomena. Research objectives were primarily focused on finding an appropriate, environmentally-friendly and productive sizing agent for cotton yarns via the analysis and systematization of a large number of synthesis methods in conjunction with the characterization and properties of graft-copolymers. The research results showed that potassium persulfate initiator was most efficient in grafting of methacrylic acid onto hydrolyzed starch, while azobisisobutyronitrile (AIBIN) initiator was most efficient in grafting of acrylic acid (AC). FTIR analysis confirmed that new and efficient products for sizing cotton yarns from synthetized potato starch were obtained. Research on rheological properties of copolymers shows a higher viscosity of grafted products indicating the good stability of potential starches. Ecological improvements have been established through high desizing degree as well as improvements in physical-mechanical properties of yarn, abrasion resistance and decrease in yarn surface hairiness were noticed. The use of new derivatives of potato starch, especially of hydrolyzed starch grafted with methacrylic acid (MAA), potassium persulfate (KPS) as initiator, was confirmed. Anova statistical analysis determined the influence of the entire sizing process on individual yarn parameters.

Core vocabulary lists obtained through the analyses of children's utterances include a variety of basic concept words. Supporting young children who use augmentative and alternative communication (AAC) to develop their understanding and use of basic concepts is an area of practice that has important ramifications for successful communication in a classroom environment. This study examined the availability of basic concept words across eight frequently used, commercially available AAC language systems, iPad© applications, and symbol libraries used to create communication boards. The accessibility of basic concept words was subsequently examined using two AAC language page sets and two iPad applications. Results reveal that the availability of basic concept words represented within the different AAC language programs, iPad applications, and symbol libraries varied but was limited across programs. However, there is no significant difference in the accessibility of basic concept words across the language program page sets or iPad applications, generally because all of them require sophisticated motor and cognitive plans for access. These results suggest that educators who teach or program vocabulary in AAC systems need to be mindful of the importance of basic concept words in classroom settings and, when possible, enhance the availability and accessibility of these words to users of AAC.

Precise timekeeping is critical to metrology, forming the basis by which standards of time, length, and fundamental constants are determined. Stable clocks are particularly valuable in spectroscopy because they define the ultimate frequency precision that can be reached. In quantum metrology, the qubit coherence time defines the clock stability, from which the spectral linewidth and frequency precision are determined. We demonstrate a quantum sensing protocol in which the spectral precision goes beyond the sensor coherence time and is limited by the stability of a classical clock. Using this technique, we observed a precision in frequency estimation scaling in time T as T -3/2 for classical oscillating fields. The narrow linewidth magnetometer based on single spins in diamond is used to sense nanoscale magnetic fields with an intrinsic frequency resolution of 607 microhertz, which is eight orders of magnitude narrower than the qubit coherence time., (Copyright © 2017, American Association for the Advancement of Science.)

While transplantation represents a key tool for assessing in vivo functionality of neural stem cells and their suitability for neural repair, little is known about the integration of grafted neurons into the host brain circuitry. Rabies virus-based retrograde tracing has developed into a powerful approach for visualizing synaptically connected neurons. Here, we combine this technique with light sheet fluorescence microscopy (LSFM) to visualize transplanted cells and connected host neurons in whole-mouse brain preparations. Combined with co-registration of high-precision three-dimensional magnetic resonance imaging (3D MRI) reference data sets, this approach enables precise anatomical allocation of the host input neurons. Our data show that the same neural donor cell population grafted into different brain regions receives highly orthotopic input. These findings indicate that transplant connectivity is largely dictated by the circuitry of the target region and depict rabies-based transsynaptic tracing and LSFM as efficient tools for comprehensive assessment of host-donor cell innervation., Competing Interests: O.B. is a co-founder and owns equity of LIFE & BRAIN GmbH. The remaining authors declare no competing financial interests.

The medial septum and diagonal band of Broca (MSDB) send glutamatergic axons to medial entorhinal cortex (MEC). We found that this pathway provides speed-correlated input to several MEC cell-types in layer 2/3. The speed signal is integrated most effectively by pyramidal cells but also excites stellate cells and interneurons. Thus, the MSDB conveys speed information that can be used by MEC neurons for spatial representation of self-location.

Alzheimer's disease (AD) is characterized by cognitive decline and neuronal network dysfunction, but the underlying mechanisms remain unknown. In the hippocampus, microcircuit activity during learning and memory processes is tightly controlled by O-LM interneurons. Here, we investigated the effect of beta-amyloidosis on O-LM interneuron structural and functional connectivity, combining two-photon in vivo imaging of synaptic morphology, awake Ca 2+ imaging, and retrograde mono-transsynaptic rabies tracing. We find severely impaired synaptic rewiring that occurs on the O-LM interneuron input and output level in a mouse model of AD. Synaptic rewiring that occurs upon fear learning on O-LM interneuron input level is affected in mice with AD-like pathology. This process requires the release of acetylcholine from septo-hippocampal projections. We identify decreased cholinergic action on O-LM interneurons in APP/PS1 mice as a key pathomechanism that contributes to memory impairment in a mouse model, with potential relevance for human AD., (Copyright © 2016 Elsevier Inc. All rights reserved.)

The oral allergy syndrome is one of the most common form of food allergy and manifests as contact urticaria of the oral mucosa after consumption of cross reacting foods. Whereas allergic contact stomatitis often occurs due to dental materials, allergic contact cheilitis is usually a reaction due to topical therapeutics like herpes ointments or lip care products. As late type reactions are more frequent than immediate type reactions in the anogenital mucosa, contact dermatitis in this area should be identified via epicutaneous testing. In case of contact urticaria at the genital mucosa, a semen allergy or a latex allergy should be given due consideration as a possible cause. Angioedemas, which are mostly common histamine mediated, usually prefer skin areas with loose connective tissue such as the oral or genital mucosa. Fixed drug eruption also occurs preferentially in these areas. Bullous drug-induced skin reactions (e.g., SJS and TEN) are characterized by severe hemorrhagic, erosive affections of mucous membranes.

Existing evidence suggests that children, when they first pass standard theory-of-mind tasks, still fail to understand the essential aspectuality of beliefs and other propositional attitudes: such attitudes refer to objects only under specific aspects. Oedipus, for example, believes Yocaste (his mother) is beautiful, but this does not imply that he believes his mother is beautiful. In three experiments, 3- to 6-year-olds' (N = 119) understanding of aspectuality was tested with a novel, radically simplified task. In contrast to all previous findings, this task was as difficult as and highly correlated with a standard false belief task. This suggests that a conceptual capacity more unified than previously assumed emerges around ages 4-5, a full-fledged metarepresentational scheme of propositional attitudes., (© 2014 The Authors. Child Development © 2014 Society for Research in Child Development, Inc.)

Cellular resolution three-dimensional (3D) visualization of defined, fluorescently labeled long-range neuronal networks in the uncut adult mouse brain has been elusive. Here, a virus-based strategy is described that allowed fluorescent labeling of centrifugally projecting neuronal populations in the ventral forebrain and their directly, monosynaptically connected bulbar interneurons upon a single stereotaxic injection into select neuronal populations. Implementation of improved tissue clearing combined with light-sheet fluorescence microscopy permitted imaging of the resulting connectivity maps in a single whole-brain scan. Subsequent 3D reconstructions revealed the exact distribution of the diverse neuronal ensembles monosynaptically connected with distinct bulbar interneuron populations. Moreover, rehydratation of brains after light-sheet fluorescence imaging enabled the immunohistochemical identification of synaptically connected neurons. Thus, this study describes a method for identifying monosynaptic connectivity maps from distinct, virally labeled neuronal populations that helps in better understanding of information flow in neural systems., (Copyright © 2012 The Authors. Published by Elsevier Inc. All rights reserved.)

Mortality of cardiovascular diseases in patients with type 1 diabetes is increased 2- to 20-fold compared to non-diabetic individuals. In young adults with type 1 diabetes, cardiovascular events are more often the cause of premature death than nephropathy. The aim of this study was to evaluate the prevalence and extent of cardiovascular risk factors in children and adolescents with type 1 diabetes in Austria. In a cross sectional study data of children with type 1 diabetes <18 years of age treated at the Children's department of the University Hospitals of Vienna and Graz were collected. We recorded body mass index, waist circumference, blood pressure, HbA1c, triglycerides, total cholesterol, high-density lipoprotein cholesterol and low-density lipoprotein cholesterol according to age, sex, age at manifestation, diabetes duration, and insulin requirement. From 264 patients (49.4% male) complete data were available. Of all patients, 76.1% had one or more risk factors, 20.8% had two or more, 10.2% had three or more, and 4.9% had four or more risk factors. Insufficient glycemic control was the most frequent risk factor, present in 60.6% of our patients, followed by elevated triglycerides (22.7%) and increased body mass index (20.1%). Higher prevalence of risk factors was correlated with increasing age, diabetes duration, HbA1c, and insulin requirement. In conclusion, children and adolescents with type 1 diabetes have a much higher prevalence of cardiovascular risk factors compared to non-diabetic individuals. To prevent future cardiovascular events, achieving the best possible glycemic control, early detection of further risk factors, and adequate intervention are highly important.

Hippocampal NMDA receptors (NMDARs) and NMDAR-dependent synaptic plasticity are widely considered crucial substrates of long-term spatial memory, although their precise role remains uncertain. Here we show that Grin1(ΔDGCA1) mice, lacking GluN1 and hence NMDARs in all dentate gyrus and dorsal CA1 principal cells, acquired the spatial reference memory water maze task as well as controls, despite impairments on the spatial reference memory radial maze task. When we ran a spatial discrimination water maze task using two visually identical beacons, Grin1(ΔDGCA1) mice were impaired at using spatial information to inhibit selecting the decoy beacon, despite knowing the platform's actual spatial location. This failure could suffice to impair radial maze performance despite spatial memory itself being normal. Thus, these hippocampal NMDARs are not essential for encoding or storing long-term, associative spatial memories. Instead, we demonstrate an important function of the hippocampus in using spatial knowledge to select between alternative responses that arise from competing or overlapping memories.

Ground states of spin lattices can serve as a resource for measurement-based quantum computation. Ideally, the ability to perform quantum gates via measurements on such states would be insensitive to small variations in the Hamiltonian. Here, we describe a class of symmetry-protected topological orders in one-dimensional systems, any one of which ensures the perfect operation of the identity gate. As a result, measurement-based quantum gates can be a robust property of an entire phase in a quantum spin lattice, when protected by an appropriate symmetry.

We present an intuitive reasoning and derivation leading to an approximated, simple closed-form model for predicting and explaining the general emergence of enhanced transmission resonances through rectangular, optically thick metallic gratings in various configurations and polarizations. This model is based on an effective index approximation and it unifies in a simple way the underlying mechanism of enhanced transmission as emerging from standing wave resonances of the different diffraction orders of periodic structures. The model correctly predicts the conditions for the enhanced transmission resonances in various geometrical configurations, for both TE and TM polarizations, and in both the subwavelength and non-subwavelength spectral regimes, using the same underlying mechanism and one simple closed-form equation, and does not require explicitly invoking specific polarization dependent mechanisms. The known excitation of surface plasmons polaritons or slit cavity modes, emerge as limiting cases of a more general condition. This equation can be used to easily design and analyze the optical properties of a wide range of rectangular metallic transmission gratings.

We consider a theoretical model for a binary mixture of colloidal particles and spherical emulsion droplets. The hard sphere colloids interact via additional short-ranged attraction and long-ranged repulsion. The droplet-colloid interaction is an attractive well at the droplet surface, which induces the Pickering effect. The droplet-droplet interaction is a hard-core interaction. The droplets shrink in time, which models the evaporation of the dispersed (oil) phase, and we use Monte Carlo simulations for the dynamics. In the experiments, polystyrene particles were assembled using toluene droplets as templates. The arrangement of the particles on the surface of the droplets was analyzed with cryogenic field emission scanning electron microscopy. Before evaporation of the oil, the particle distribution on the droplet surface was found to be disordered in experiments, and the simulations reproduce this effect. After complete evaporation, ordered colloidal clusters are formed that are stable against thermal fluctuations. Both in the simulations and with field emission scanning electron microscopy, we find stable packings that range from doublets, triplets, and tetrahedra to complex polyhedra of colloids. The simulated cluster structures and size distribution agree well with the experimental results. We also simulate hierarchical assembly in a mixture of tetrahedral clusters and droplets, and find supercluster structures with morphologies that are more complex than those of clusters of single particles.

We demonstrate a directional beaming of photons emitted from nanocrystal quantum dots that are embedded in a subwavelength metallic nanoslit array with a divergence angle of less than 4°. We show that the eigenmodes of the structure result in localized electromagnetic field enhancements at the Bragg cavity resonances, which could be controlled and engineered in both real and momentum space. The photon beaming is achieved using the enhanced resonant coupling of the quantum dots to these Bragg cavity modes, which dominates the emission properties of the quantum dots. We show that the emission probability of a quantum dot into the narrow angular mode is 20 times larger than the emission probability to all other modes. Engineering nanocrystal quantum dots with subwavelength metallic nanostructures is a promising way for a range of new types of active optical devices, where spatial control of the optical properties of nanoemitters is essential, on both the single and many photons level.

We show a large enhancement of two-photon absorption processes in nanocrystal quantum dots and of light upconversion efficiency from the IR to the near-IR spectral regime, using a hybrid optical device in which near-IR emitting InAs quantum dots were embedded on top a metallic nanoslit array. The resonant enhancement of these nonlinear optical processes is due to the strong local electromagnetic field enhancements inside the nanoslit array structure at the extraordinary transmission resonances. A maximal two-photon absorption enhancement of more than 20 was inferred. Different high field regions were identified for different polarizations, which can be used for designing and optimizing efficient nonlinear processes in such hybrid structures. Combining nanocrystal quantum dots with subwavelength metallic nanostructures is therefore a promising way for a range of possible nonlinear optical devices.

This article describes the purpose and application of an essential functions rubric for prospective and current students engaged in the study of communication sciences and disorders. Adopted in 2007 by the Council on Academic Programs in Communication Sciences and Disorders (CAPCSD), the essential functions rubric identifies core skills and attributes in five areas: communication, motor, intellectual-cognitive, sensory/observational, and behavioral/social. CAPCSD does not intend the rubric to be prescriptive but rather expects that it will be adapted to reflect the unique mission or circumstances of each academic program. The value of an essential functions rubric for academic programs is the opportunity it provides to educate students about the roles and responsibilities of the disciplines. A rubric also allows academic programs an objective basis for counseling students about professional expectations. Importantly, an essential functions rubric gives both students and programs opportunities to determine what, if any, accommodations might be employed to allow students who are otherwise qualified to help them succeed both academically and clinically.

Cinnamon and vinegar or acetic acid were reported to reduce the postprandial blood glucose response. We hypothesized that the combination of these substances might result in an additive effect. Therefore, we determined the 2-hour postprandial blood glucose and satiety response to a milk rice meal supplemented with either cinnamon or acetic acid on their own or in combination. Subjects (n = 27) consumed the meal on 4 occasions as either pure (control trial), with 4 g cinnamon, 28 mmol acetic acid, or the combination of cinnamon + acetic acid. Blood glucose and satiety were assessed before eating and 15, 30, 45, 60, 90, and 120 minutes postprandially. At 15 minutes, the combination of cinnamon + acetic acid resulted in a significantly reduced blood glucose concentration compared with the control meal (P = .021). The incremental area under the blood glucose response curve over 120 minutes did, however, not differ between the trials (P = .539). The satiety score of the cinnamon + acetic acid trial was significantly higher than that in the control trial at 15 (P = .024) and 30 minutes (P = .024), but the incremental area under the curve of the satiety response did not differ (P = .116) between the trials. In conclusion, the significant effect of the combination of cinnamon and acetic acid on blood glucose and satiety immediately after meal intake indicated an additive effect of the 2 substances. Whether larger doses of cinnamon and acetic acid may result in a more substantial additive effect on blood glucose or satiety remains to be investigated.

We apply the Lieb-Robinson bounds technique to find the maximum speed of interaction in a spin model with topological order whose low-energy effective theory describes light [see X.-G. Wen, Phys. Rev. B 68, 115413 (2003)10.1103/PhysRevB.68.115413]. The maximum speed of interactions in two dimensions is bounded from above by less than e times the speed of emerging light, giving a strong indication that light is indeed the maximum speed of interactions. This result does not rely on mean field theoretic methods. In higher spatial dimensions, the Lieb-Robinson speed is conjectured to increase linearly with the dimension itself. The implications for the horizon problem in cosmology are discussed.

We compared the effect n-3 polyunsaturated fatty acids (PUFAs) with direct renin inhibition on electrophysiological remodeling in angiotensin II-induced cardiac injury. We treated double-transgenic rats expressing the human renin and angiotensinogen genes (dTGRs) from week 4 to 7 with n-3 PUFA ethyl-esters (Omacor; 25-g/kg diet) or a direct renin inhibitor (aliskiren; 3 mg/kg per day). Sprague-Dawley rats were controls. We performed electrocardiographic, magnetocardiographic, and programmed electrical stimulation. Dietary n-3 PUFAs increased the cardiac content of eicosapentaenoic and docosahexaenoic acid. At week 7, mortality in dTGRs was 31%, whereas none of the n-3 PUFA- or aliskiren-treated dTGRs died. Systolic blood pressure was modestly reduced in n-3 PUFA-treated (180+/-3 mm Hg) compared with dTGRs (208+/-5 mm Hg). Aliskiren-treated dTGRs and Sprague-Dawley rats were normotensive (110+/-3 and 119+/-6 mm Hg, respectively). Both n-3 PUFA-treated and untreated dTGRs showed cardiac hypertrophy and increased atrial natriuretic peptide levels. Prolonged QRS and QT(c) intervals and increased T-wave dispersion in dTGRs were reduced by n-3 PUFAs or aliskiren. Both treatments reduced arrhythmia induction from 75% in dTGRs to 17% versus 0% in Sprague-Dawley rats. Macrophage infiltration and fibrosis were reduced by n-3 PUFAs and aliskiren. Connexin 43, a mediator of intermyocyte conduction, was redistributed to the lateral cell membranes in dTGRs. n-3 PUFAs and aliskiren restored normal localization to the intercalated disks. Thus, n-3 PUFAs and aliskiren improved electrical remodeling, arrhythmia induction, and connexin 43 expression, despite a 70-mm Hg difference in blood pressure and the development of cardiac hypertrophy.

Fibromyalgia (FM) is an incurable common syndrome of non-articular origin, and with no effective treatment by now. A great deal of research has sought to assess the efficacy of different therapies, especially non-pharmacological and low-cost ones, in the reduction of the intensity of symptoms. Despite the availability of a wide range of alternative therapies nowadays, there is little scientific evidence of the potential benefits of most of them, with results being contradictories. The purpose of this paper is to review some of the less well known alternative therapies in FM treatment, to describe the more relevant clinical studies published in this matter, and to analyze the potential effects of the main alternative therapies, in order to verify their efficacy.

Objectives: To evaluate the efficacy of the Lidcombe programme of early stuttering intervention by comparison to a control group., Design: A pragmatic, open plan, parallel group, randomised controlled trial with blinded outcome assessment., Setting: Two public speech clinics in New Zealand., Participants: Stuttering preschool children who presented to the speech clinics for treatment. Inclusion criteria were age 3-6 years and frequency of stuttering of at least 2% syllables stuttered. Exclusion criteria were onset of stuttering during the six months before recruitment and treatment for stuttering during the previous 12 months. 54 participants were randomised: 29 to the Lidcombe programme arm and 25 to the control arm. 12 of the participants were girls., Intervention: Lidcombe programme of early stuttering intervention., Main Outcome Measures: Frequency of stuttering was measured as the proportion of syllables stuttered, from audiotaped recordings of participants' conversational speech outside the clinic. Parents in both arms of the trial collected speech samples in three different speaking situations before randomisation and at three, six, and nine months after randomisation., Results: Analysis showed a highly significant difference (P = 0.003) at nine months after randomisation. The mean proportion of syllables stuttered at nine months after randomisation was 1.5% (SD 1.4) for the treatment arm and 3.9% (SD 3.5) for the control arm, giving an effect size of 2.3% of syllables stuttered (95% confidence interval 0.8 to 3.9). This effect size was more than double the minimum clinically worthwhile difference specified in the trial protocol., Conclusions: The results provide evidence from a randomised controlled trial to support early intervention for stuttering. The Lidcombe programme is an efficacious treatment for stuttering in children of preschool age.

We investigated the effect of physiologic variations in sex hormone levels during the menstrual cycle on biomarkers of bone turnover. Blood and 24-h and fasting urine samples were obtained in nine women (age, 25.1+/-3.0 yr) with regular menstrual cycles during the early follicular period (t1), 3 days before ovulation (t2), 3 days after ovulation (t3), at the midluteal period (t4) and again during the early follicular period of the next cycle (t5). All subjects had a calcium intake covering current dietary recommendations (above 1,000 mg/day, standardized food record). Serum calcium, phosphorus, calcitriol, 24-h and 2-h fasting urinary calcium, and phosphorus excretion remained constant during the menstrual cycle. Serum 25-hydroxyvitamin D3 levels decreased slightly from the beginning until the end of the study (P<0.05), indicating low cutaneous vitamin D synthesis during wintertime. The serum levels of sex hormones showed typical monthly variations, with the lowest estradiol (E2) levels at t1 and t5. Fasting 2-h pyridinoline (Pyd) concentrations (a marker of bone resorption) fell from t1 to t3 and rose again at t5 (P<0.01). Similar variations were observed for the resorption marker deoxypyridinoline (Dpd; P<0.05). The amplitude of the two biomarkers was 32% and 33%, respectively. The serum levels of the carboxyterminal propeptide of type I collagen (a marker of bone formation) showed an inverse cyclic pattern, as compared with the pyridinium cross-links. Low concentrations were observed at t1; a rise occurred until t3 and was followed by a decrease until t5 (P<0.05). A similar cyclic pattern was observed for serum PTH levels, with the highest concentrations at t3 (P<0.05). Dpd and Pyd values were significantly correlated with serum E2 levels (r = 0.52; P<0.0001 and r = 0.50; P<0.001, respectively). Neither progesterone nor LH nor FSH was correlated with Pyd or Dpd levels. The data suggest that normal menstrual cycling in young women is associated with monthly fluctuations in bone turnover. This physiological effect of the menstrual cycle is most probably related to variations in serum E2 concentrations.

CD97 is a dimeric glycoprotein belonging to the secretin receptor superfamily and is abundantly expressed in cells of hematopoietic origin. The aim of this study was to analyze the expression of the CD97 protein in thyroid carcinomas and the role of all-trans-retinoic acid (RA) in the regulation of CD97 protein in monolayer culture of the human follicular thyroid carcinoma cell line FTC-133. In normal thyroid tissue, no immunoreactivity of CD97 could be found, whereas in differentiated thyroid carcinomas, CD97 expression was either lacking or low. Undifferentiated anaplastic thyroid carcinomas revealed high CD97 expression. The expression of CD97 protein seems to be correlated to the postoperative histopathological classification staging. Approximately 50% of FTC-133 cells expressed the CD97 protein under basal culture conditions. No differences were found in the number of CD97-positive cells after TSH, forskolin, and insulin treatment compared to control values. Epidermal growth factor treatment led to an increase in CD97 immunostaining (up to 90%), whereas phorbol 12-myristate 13-acetate slightly decreased the immunoreactivity of CD97 (from 50% to 30%). Under basal conditions, RA treatment for 72 h led to a decrease in total cell number by 33% and in CD97-positive cells from 50% to 30%. TSH, forskolin, phorbol 12-myristate 13-acetate, and insulin showed no effect after 72-h pretreatment with RA, whereas epidermal growth factor treatment led to a slight increase in the number of the CD97-positive cells (from 30% to 40%) compared to the control value. These data suggest that CD97 expression may play an important role in the dedifferentiation of thyroid tumors, and RA might interfere with this process in thyroid carcinoma by suppressing the dedifferentiation marker CD97.

Background: Patients with upper gastrointestinal ulceration may be treated with misoprostol, but it is not recommended for pregnant women because it may stimulate uterine contractions and cause vaginal bleeding and miscarriage. Recent data from Brazil, where misoprostol is used orally and vaginally as an abortifacient, have suggested a relation between the use of misoprostol by women in an unsuccessful attempt to terminate pregnancy and Möbius' syndrome (congenital facial paralysis) in their infants., Methods: We compared the frequency of misoprostol use during the first trimester by mothers of infants in whom Möbius' syndrome was diagnosed and mothers of infants with neural-tube defects in Brazil. All diagnoses in infants were made between January 16, 1990, and May 31, 1996, by clinical geneticists at seven hospitals who also interviewed the mothers and recorded information about the administration of misoprostol, among other data., Results: We identified 96 infants with Möbius' syndrome and matched them with 96 infants with neural-tube defects. The mean age at the time of the diagnosis of Möbius' syndrome was 16 months (range, 0.5 to 78), and the diagnosis of neural-tube defects was made within 1 week of birth in most cases. Among the mothers of the 96 infants with Möbius' syndrome, 47 (49 percent) had used misoprostol in the first trimester of pregnancy, as compared with 3 (3 percent) of the mothers of the 96 infants with neural-tube defects (odds ratio, 29.7; 95 percent confidence interval, 11.6 to 76.0). Twenty of the mothers of the infants with Möbius' syndrome had taken misoprostol only orally (odds ratio, 38.8; 95 percent confidence interval, 9.5 to 159.4), 20 had taken misoprostol both orally and vaginally, 3 had taken the drug vaginally, and 4 did not report how they took the drug., Conclusions: Attempted abortion with misoprostol is associated with an increased risk of Möbius' syndrome in infants.

To resolve the apparent conflict between a lubricating glycoprotein, 'lubricin', as the active ingredient in synovial fluid (SF) and surface-active phospholipid (SAPL) present in SF (and adsorbed to articular cartilage) as the boundary lubricant reducing friction to such low physiological levels, lubricin was isolated from bovine SF following the original procedure of Swann et al. (Arthritis Rheum 1981;24:22-30). Analysis of the lipid extract by thin-layer chromatography and phosphorus determination demonstrated a phospholipid component of 11.1 +/- 1.7% (N = 5) which corresponds very closely to the 9.2-13.0% of lubricin which had hitherto remained unidentified and which has previously been shown to be transferable to the articular surface to impart lubrication. These results would appear to resolve any theoretical conflict in that lubricin is, indeed, an active ingredient within SF. Yet, as a large water-soluble molecule, it really functions as a carrier for the highly insoluble SAPL which it deposits on the articular surface as the oligolamellar layer visualized in previous studies. However, it is this deposited SAPL, rather than lubricin, which actually lubricates.

A proverb explanation task consisting of 24 low-familiarity expressions was administered to 353 individuals ranging in age from 13 through 79 years. Half the proverbs were composed of concrete nouns ("A caged bird longs for the clouds") and half were composed of abstract nouns ("Humility often gains more than pride"). The task was designed to examine how patterns of language growth in adults compare to those observed in adolescents. It also served as a tool for examining the "metasemantic hypothesis," the view that complex semantic units, such as proverbs, are learned through active analysis of the words they contain. Performance on the task improved markedly during adolescence and into early adulthood. It reached a plateau during the 20s, remained stable during the 30s, 40s, and 50s, and began a slight decline during the 60s that reached statistical significance during the 70s. Concrete proverbs were easier to explain than abstract proverbs for adolescents and for adults in their 20s, but the two proverb types did not differ for adults in their 30s and older. Thus, the metasemantic hypothesis was supported for adolescents and young adults. For the adults, performance on the proverb explanation task was related to the number of years of formal education they had completed.

We investigated retrograde labelling with tritiated glycine injected into the inferior colliculus of the chicken. Tracer deposits were placed in the central nucleus of the inferior colliculus at positions yielding unit activity with best frequencies between 0.4 and 4 kHz. Most neuron systems known to project to the inferior colliculus in birds were unlabelled, whereas strongly labelled cells were found in three nuclei, only on the ipsilateral side. The nucleus lemnisci lateralis pars ventralis contained numerous small glycine-transporting cells. The superior olivary nucleus contained few such cells of similar size in its peripheral region. The nucleus of the trapezoid body contained a group of larger labelled neurons. The observed specificity suggests that we labelled glycinergic neurons projecting to the inferior colliculus.

There is increasing evidence for the role of basophils in allergic bronchial asthma. We studied the potential role of basophils in the pathogenesis of post-exercise-induced bronchoconstriction by measuring the histamine release from basophils both spontaneously and following ConA, FMLP, anti-IgE and TPA treatment. Two groups of patients with allergic asthma were studied: group I consisted of 8 patients with an exercise-induced fall in FEV1 of 20% or more, and group II had 7 patients with bronchial asthma who had less than a 5% fall in FEV1 following exercise. The mean spontaneous histamine release (SHR%) from basophils for group I was significantly larger than that of group II both before as well as at 5-10 and 60 min following exercise. The SHR% at baseline was 25 +/- 10 in group I (mean +/- SD) and 15 +/- 5 in group II (mean +/- SD). At 5-10 min following exercise it was 24 +/- 6 in group I and 11 +/- 2 in group II, while at 60 min following exercise it was 24 +/- 6 in group I and 17 +/- 2 in group II. There was no significant difference between the two groups in the effect of ConA, FMLP, anti-IgE or TPA treatment on basophil histamine release. The enhanced bronchoconstriction by exercise did not affect histamine release either spontaneously or following those 4 stimuli. It was concluded that, although patients with exercise-induced asthma have a greater degree of spontaneous histamine release, this is not affected by induced bronchoconstriction, a finding which does not support a role for basophils in exercise-induced asthma.

The chicken's auditory brainstem nuclei from the cochlear nuclei to the nuclei of the lateral leminiscus were studied with cytochrome oxidase histochemistry. A strong reactivity in the cochlear and laminar nuclei was confirmed. Additional structures displaying high activity levels include the superior olive and both partitions of the nucleus intermedius lemnisci lateralis. Unilateral cochlea removal led to a strong reduction of activity in the cochlear nuclei and the nucleus laminaris, whereas there was no remarkable effect in higher brainstem centers. After bilateral cochlea extirpation auditory structures still displayed higher enzyme levels than most other nuclei. These observations point to the extraordinary metabolic activity in the ascending auditory pathway which is largely independent of sensory input from the auditory nerve.

The chicken's central auditory nuclei from the inferior colliculus to field L in the forebrain were studied with cytochrome oxidase histochemistry. All stations of the ascending pathway displayed high activity levels, including the inferior colliculus, the nucleus ovoidalis of the thalamus, and field L1 to L3 and the hyperstriatum ventrale caudale which correspond to primary and secondary auditory cortex. In the inferior colliculus a moderately active external nucleus could be distinguished from a more intensely stained central and superficial nucleus. In the central nucleus there was a lateral shell displaying stronger neuropil reactivity than a central core. Unilateral cochlea removal caused no remarkable effect in tectum and thalamus. The auditory forebrain contralateral to the lesion displayed reduced CO reactivity compared with the ipsilateral side. After bilateral cochlea extirpation auditory structures still displayed higher enzyme levels than most other nuclei.

94 patients with malignant melanoma or soft tissue sarcoma of the extremities were submitted to isolated cytostatic limb perfusion. With palliative indication for treatment of malignant melanoma, the 5 year survival rate was 25% after perfusion with methotrexate and 50% after perfusion with melphalan. The adjuvant perfusion showed very good results, too. Furthermore, the authors report on their first experiences in regional cytostatic perfusion of soft tissue sarcoma and bone sarcoma.