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Purpose: Although currently there are simplified methods to measure the pathophysiological traits that stimulate the occurrence and maintenance of obstructive sleep apnea–hypopnea (OSAH), they remain difficult to implement in routine practice. This pilot study aimed to find a simpler daytime approach to obtain a meaningful, similar pathophysiological phenotypic profile in patients with OSAH. Methods: After obtaining diagnostic polygraphy from a group of consecutive patients with OSAH, we performed the dial-down CPAP technique during nocturnal polysomnography and used it as reference method. This allowed assessment of upper airway collapsibility, loop gain (LG), arousal threshold (AT), and upper airway muscle gain (UAG). We compared these results with a daytime protocol based on negative expiratory pressure (NEP) technique for evaluating upper airway collapsibility and UAG, on maximal voluntary apnea for LG, and on clinical predictors for AT. Results: Of 15 patients studied, 13 patients with OSAH accurately completed the two procedures. There were strong (all r2 > 0.75) and significant (all p < 0.001) correlations for each phenotypic trait between the measurements obtained through the reference method and those achieved during wakefulness. Conclusion: It is possible to phenotype patients with OSAH from a pathophysiological point of view while they are awake. Using this approach, cutoff values corresponding to those usually adopted using the reference method can be identified to detect abnormal traits, achieving profiles similar to those obtained through the dial-down CPAP technique. [ABSTRACT FROM AUTHOR]

Purpose: BRCA1/2 founder pathogenic variants (PVs) occur in various populations, but data on the mutational spectrum in Africans are limited. We examined BRCA1/2 PVs in breast cancer patients of Ethiopian Jewish (EJ) origin. Methods: We retrospectively analyzed BRCA1/2 test results and clinical features of EJ breast cancer patients from seven medical institutions. We obtained heterozygote carrier rates in affected individuals from the laboratories of the largest Israeli HMO (Clalit). Population carrier frequency was determined in EJ controls. Results: We identified three recurrent BRCA2 PVs in 11 EJ breast cancer patients (9 females, 2 males): c.7579delG, c.5159C > A, and c.9693delA. Only c.5159C > A was previously reported in Africans. In women, mean age at diagnosis was 35.7y; 8/9 were diagnosed with advanced disease. All tumors were invasive, 4/9 were triple negative. Only 3/11 carriers had relevant family history. Carrier rate in high-risk breast cancer patients was 11% (3/28; 95%CI [2.3%, 28.2%]). Combined carrier rate among controls was 1.8% (5/280; 95%CI [0.6%, 4.1%]). Conclusion: EJs harbor 3 recurrent BRCA2 PVs presenting with relatively severe breast cancer morbidity. Combined with the high BRCA2 carrier rate in the EJ population, these findings merit increasing awareness in this community and suggest that a culturally adapted population screening approach may be warranted. [ABSTRACT FROM AUTHOR]

Lynch syndrome is an inherited cancer predisposition syndrome caused by germline defects in any of the mismatch repair (MMR) genes. Diagnosis of carriers makes precision prevention, early detection, and tailored treatment possible. Herein we report a novel founder deletion of 18,758 bp, mediated by Alu repeats on both sides, detected in Ethiopian Jews. The deletion, which encompasses exon 9–10 of the MSH2 coding sequence, is associated mainly with early-onset MSH2/MSH6-deficient colorectal cancer (CRC) and liposarcoma. Testing of 35 members of 5 seemingly unrelated families of Ethiopian origin yielded 10/21 (48%) carriers, of whom 9 had CRC. Age at first tumor diagnosis ranged from 16 to 89 years. Carriers from the oldest generations were diagnosed after age 45 years (mean 57), and carriers from the younger generation were diagnosed before age 45 years (mean 30). Awareness of this founder deletion is important to improve patient diagnosis, institute surveillance from an early age, and refer patients for genetic counseling addressing the risk of bi-allelic constitutional MMR deficiency syndrome. [ABSTRACT FROM AUTHOR]

The energy demand for heating and cooling buildings is changing with global warming. Using proxies of climate-driven energy demand based on the heating and cooling Degree-Days methodology applied to thirty global climate model simulations, we show that, over all continental areas, the climate-driven energy demand trends for heating and cooling were weak, changing by less than 10% from 1950 to 1990, but become stronger from 1990 to 2030, changing by more than 10%. With the multi-model mean, the increasing trends in cooling energy demand are more pronounced than the decreasing trends in heating. The changes in cooling, however, are highly variable depending on individual simulations, ranging from a few to several hundred percent in most of the densely populated mid-latitude areas. This work presents an example of the challenges that accompany future energy demand quantification as a result of the uncertainty in the projected climate. The energy demand for heating and cooling buildings is changing with global warming. Here the authors show that trends in cooling energy demands are increasing, although the magnitude is extremely uncertain, which highlights challenges for future energy demand quantification. [ABSTRACT FROM AUTHOR]

Key message: The first report presenting successful and efficient carrot genome editing using CRISPR/Cas9 system.Abstract: Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/CRISPR-associated (Cas9) is a powerful genome editing tool that has been widely adopted in model organisms recently, but has not been used in carrot—a model species for in vitro culture studies and an important health-promoting crop grown worldwide. In this study, for the first time, we report application of the CRISPR/Cas9 system for efficient targeted mutagenesis of the carrot genome. Multiplexing CRISPR/Cas9 vectors expressing two single-guide RNA (gRNAs) targeting the carrot flavanone-3-hydroxylase (F3H) gene were tested for blockage of the anthocyanin biosynthesis in a model purple-colored callus using Agrobacterium-mediated genetic transformation. This approach allowed fast and visual comparison of three codon-optimized Cas9 genes and revealed that the most efficient one in generating F3H mutants was the Arabidopsis codon-optimized AteCas9 gene with up to 90% efficiency. Knockout of F3H gene resulted in the discoloration of calli, validating the functional role of this gene in the anthocyanin biosynthesis in carrot as well as providing a visual marker for screening successfully edited events. Most resulting mutations were small Indels, but long chromosome fragment deletions of 116-119 nt were also generated with simultaneous cleavage mediated by two gRNAs. The results demonstrate successful site-directed mutagenesis in carrot with CRISPR/Cas9 and the usefulness of a model callus culture to validate genome editing systems. Given that the carrot genome has been sequenced recently, our timely study sheds light on the promising application of genome editing tools for boosting basic and translational research in this important vegetable crop. [ABSTRACT FROM AUTHOR]

This paper considers the dynamic coupled problem of harmonic vibrations of a layeredinhomogeneous electromagnetoelastic medium subjected to an oscillating mechanical or electrical load under various electric and magnetic field conditions specified on the surface and internal boundaries of this medium. Green's function of the medium is constructed. Dispersion curves and phase velocities for different boundary conditions and materials are obtained. [ABSTRACT FROM AUTHOR]

Although much is known about the migration of T cells from blood to lymph nodes, less is known about the mechanisms regulating the migration of T cells from tissues into lymph nodes through afferent lymphatics. Here we investigated T cell egress from nonlymphoid tissues into afferent lymph in vivo and developed an experimental model to recapitulate this process in vitro. Agonism of sphingosine 1-phosphate receptor 1 inhibited the entry of tissue T cells into afferent lymphatics in homeostatic and inflammatory conditions and caused the arrest, mediated at least partially by interactions of the integrin LFA-1 with its ligand ICAM-1 and of the integrin VLA-4 with its ligand VCAM-1, of polarized T cells at the basal surface of lymphatic but not blood vessel endothelium. Thus, the increased sphingosine 1-phosphate present in inflamed peripheral tissues may induce T cell retention and suppress T cell egress. [ABSTRACT FROM AUTHOR]

In a previous study, Mg–Sn–Zn-based alloys showed insufficient structural stability at elevated temperatures. In order to improve the castability and corrosion resistance 2.1%wt Al was added to the Mg–5.6%Sn–4.4%Zn base alloy. At the as-cast condition, SEM micrographs indicate a very fine microstructure (Dendritic Arm Spacing—DAS—smaller than 17 μm). The study focuses on precipitation hardening, phase formation and structural stability, during the aging of solution treated samples at elevated temperatures. After solution treatment and aging at 225 °C, Vickers hardness measurements show that this alloy maintains a constant increase of 30% in hardness for periods of up to 32 days. EDS (SEM & STEM), XRD, and Auger characterization methods were applied to identify the phases presented in the alloy. There is no evidence for the presence of the deleterious γ-Al12 Mg17 phase. SAXS measurement and STEM micrographs reveal very fine precipitations (less than 100 nm) after 32 days of aging, along with homogenously distributed larger precipitations (up to 500 nm). [ABSTRACT FROM AUTHOR]

The formation of dense arrays of nanospikes occurs under laser ablation of bulk silver immersed in liquids such as water or ethanol. The average height of spikes is 50 nm and their density on the target amounts to 1010 cm-2. This effect is observed with sufficiently short laser pulses. In particular, either a 350 ps or a 90 ps Nd:YAG lasers are used operating in their fundamental harmonics. These nanospikes are characterized by UV–visible reflection spectrometry and atomic force microscopy. The oscillations of electrons within Ag nanospikes results in a permanent coloration of the surface and a modification of the optical reflection spectra of the metal. Nanospikes show a peak of plasmon resonance around 380 nm, which shifts to the visible range upon oxidation in air. The initial spectrum may be restored by reduction of the oxidized Ag surface through processing in an ammonia aqueous solution. Scanning the laser beam along the metal surface allows its nanostructuring over extended areas (∼1 cm2). The nanostructured Ag surface shows enhanced Raman scattering of acridine molecules at a concentration of 10-5 M/l, whereas initial Ag target do not show any signal within the accuracy of measurements. [ABSTRACT FROM AUTHOR]

High temperature sessile drop experiments were conducted to evaluate the wetting (contact angle, surface/interface energies) on the basal C and prismatic A surfaces of sapphire by pure liquid Ni, and Ni alloyed with Al or S. After solidification of the drops, inspection of samples showed the presence of millimetre-sized voids at the interface between pure nickel and the basal surface of the sapphire substrate. However, no voids were found at the interfaces of pure Ni with the prismatic surface of sapphire, or at the interfaces of sapphire with Ni alloyed with 0.03at.%S or 2at.%Al, or if the pure Ni drops were significantly smaller in size. It is proposed that the voids form to release strain energy stored in the system, due to the dissimilar thermal expansion coefficients of Ni relative to sapphire. Alloying with Al and/or S retards interfacial void formation by enhancing the metal-ceramic interfacial wetting and adhesion. [ABSTRACT FROM AUTHOR]

Based on thermodynamic calculations, four alloys in the system Mg-Ca-Zn produced by gravity die casting were solution treated and aged at 175 °C for different times. The scanning electron microscopy and X-ray diffraction analyses of the solutionized alloys were in good agreement with the thermodynamic calculations. In these Mg-Ca-Zn alloys, the hardness increases with aging time up to 8 hours followed by typical overaging, during which the hardness decreases. According to the calculations and scanning transmission electron microscopy analyses, the change in the hardness can be correlated to the precipitation of Ca2Mg6Zn3. [ABSTRACT FROM AUTHOR]

Highway traffic as simulated with a simple cellular automata model has been analysed in a search for self-similarity in the behaviour of car density and car flow as a function of space. Fractal dimensions between 1.5 and 1.6, depending on the simulation characteristics, have been measured with a box counting algorithm. The self-similarity spans over about 2 orders of magnitude. A comparison with experimental data is suggested. [ABSTRACT FROM AUTHOR]

We present results relative to a simple cellular automata model without periodic boundary conditions for an highway with on-ramps. Simulations performed with this model reproduce experimental phenomena observed in traffic such as free flow, synchronized flow, congested flow, lane inversion, forward and backward propagating waves. On-ramps play the important role of nucleation points for the dynamic features of traffic. [ABSTRACT FROM AUTHOR]

Intravenous administration could become a delivery route of choice for prophylactic and curative gene therapies on condition that genes cross the capillary barrier and reach target tissues without being degraded. We investigated the kinetics and process of transgene delivery through mouse lung capillaries following DNA complexation with linear polyethylenimine (L-PEI) and intravenous injection. Using digoxin-labeled DNA we followed the cellular localization of DNA at different times after injection and correlated these findings with cell markers and transgene expression. At 2 h after injection some DNA was still localized on the interior of the capillary lumen, but other complexes had already crossed the barrier and resulted in gene expression. At 24 h after injection most labeled DNA was localised in pulmonary cells, as was transgene expression. Only rarely was transgene expression found in endothelial cells, suggesting that the complexes cross the capillary barrier rapidly. Levels of caspase-1-like activity did not increase following transfection implying that L-PEI/DNA complexes are transported across cellular barriers by a non-damaging, physiological process, without causing inflammation. The high levels of expression of different transgenes in pneumocytes indicates that transport of LPEI/DNA complexes through the endothelial barrier does not affect their transfection capacity. These findings open up new possibilities for gene delivery and its application to the lung. [ABSTRACT FROM AUTHOR]

Copyright of Archives of Oto-rhino-laryngology is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

In this note the problem is considered of finding maximal common subgraphs of two given graphs. A technique is described by which this problem can be stated as a problem of deriving maximal compatibility classes. A known «maximal compatibility classes» algorithm can then be used to derive maximal common subgraphs. The same technique is shown to apply to the classical subgraph isomorphism problem. [ABSTRACT FROM AUTHOR]

Two different strains of HIV-1, the lymphotropic HIV-IIIB and the monocytotropic HIV-Ba-L, were able to infect tertiary cultures of astrocytes established from the human embryonic brain. The infection did not require contact with infected cells, as astrocytes were exposed to infectious cell-free supernatants. Except for an early transient peak of p24 consistently observed after infection with HIV-Ba-L, the infection of astrocytes appeared to be nonproductive. However, viral production was always observed when infected astrocytes were cocultured with permissive cells (CEM-SS or monocytes). To exclude the possibility that undetectable levels of virus are chronically produced by astrocytes, we exposed permissive cells to p24 negative supernatants taken from infected cultures. In such conditions permissive cells were never infected. Infection of astrocytes by HIV-1 was further supported by the finding that provirus persisted in these cells. Indeed, by a nested PCR, we detected HIV-1 DNA even one month after infection. Moreover, at the transcriptional level we observed expression of the multiply spliced RNA ( tat) and nef primers). Noteworthy, this pattern of HIV-1 expression did not change appreciably when astrocytes were pretreated and cultivated in the presence of IL-1β. Altogether, our data support the concept that astrocytes may play a role in the spread of HIV-1 infection within the brain and in the pathogenesis of neuro-AIDS. [ABSTRACT FROM AUTHOR]

Generally, cationic vector-based intravenous delivery of DNA is hindered by interactions of positively charged complexes with serum proteins. However, if optimally formulated, cationic vectors can provide reasonable levels of transfection in the lung either by intravenous or intrapulmonary routes. We investigated the in vivo transfection capacity of a cationic polymer: linear, 22 kDa polyethylenimine. PEI/DNA complexes were formulated in 5% glucose and delivered into adult mice through the tail vein. Two marker genes were used, β-galactosidase and luciferase. High levels of luciferase expression (107 RLU/mg protein) were found in the lung when DNA was complexed with PEI at a ratio of 4 nitrogen equivalents per DNA phosphate. Lower levels of transfection were found in the heart, spleen, liver and kidney. Expression was dose- and time-dependent in all tissues examined. In the lung, β-galactosidase staining showed transgene expression in clusters of 10 or more pulmonary cells including the alveolar endothelium, squamous and great alveolar epithelial cells (type I and II pneumocytes) and septal cells. These findings indicate that the complexes pass the capillary barrier in the lung. Although the delivery mechanism requires elucidation, linear PEI has promise as a vector for intravenous transfer of therapeutic genes. [ABSTRACT FROM AUTHOR]

Currently in vivo gene delivery by synthetic vectors is hindered by the limited diffusibility of complexes in extracellular fluids and matrices. Here we show that certain formulations of plasmid DNA with linear polyethylenimine (22 kDa PEI, ExGene 500) can produce complexes that are sufficiently small and stable in physiological fluids so as to provide high diffusibility. When plasmid DNA was formulated with 22 kDa PEI in 5% glucose, it produced a homogeneous population of complexes with mean diameters ranging from 30 to 100 nm according to the amount of PEI used. In contrast, formulation in physiological saline produced complexes an order of magnitude greater (1 μm). Intraventricular injection of complexes formulated in glu-cose showed the complexes to be highly diffusible in the cerebrospinal fluid of newborn and adult mice, diffusing from a single site of injection throughout the entire brain ventricular spaces. Transfection efficiency was followed by histochemistry of β-galactosidase activity and double immunocytochemistry was used to identify the cells transfected. Transgene expression was found in both neurons and glia adjacent to ventricular spaces. Thus, this method of formulation is promising for in vivo work and may well be adaptable to other vectors and physiological models. [ABSTRACT FROM AUTHOR]

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The extension of a known technique for graph embedding is presented for the solution of a class of problems arising in computer aided circuit layout. The embedding of a weighted graph X onto another weighted graph Y is studied, with concurrent minimization of a cost function whose value depends on node and are associations. The embedding process is based on a partially enumerative covering technique on a Node Correspondence Table. Two applications are described, namely the placement of electrical components on a card in printed circuit design, and the allocation of a cards in a rack for the optimal design of backboard connections. An example of this latter problem is discussed in detail. [ABSTRACT FROM AUTHOR]

Copyright of Zeitschrift Für Wissenschaftliche Biologie - Abteilung B: Zeitschrift Für Zellforschung und Mikroskopische Anatomie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Zeitschrift für Physik is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

An introduction to the journal is presented in which the editor discusses a study on the postnatal role of homeobox protein DLX-3 in the appendicular skeleton.

Elementary phosphorus is formed when a catalyst of phosphoric acid on activated charcoal comes in contact with hydrogen or vapors of organic substances, beginning at 400° and above, and also when the catalyst is treated with nitrogen at ∼600° and above. A hypothetical explanation was presented for this phenomenon. [ABSTRACT FROM AUTHOR]