Temperature Tides Across the Mid-Latitude Summer Turbopause Measured by a Sodium Lidar and MIGHTI/ICON.

Local full diurnal coverage of temperature variations across the turbopause (~90-115 km altitude) is achieved by combining the nocturnal observations of a Sodium (Na) Doppler lidar on the Utah State University (USU) campus (41.7°N, 248.2°E) and NASA Michelson interferometer for global high-resolution thermospheric imaging (MIGHTI)/Ionospheric connection explorer (ICON) daytime observations made in the same vicinity. In this study, utilizing this hybrid data set during summer 2020 between June 12th and July 15th, we retrieve the temperature signatures of diurnal and semidiurnal tides in this region. The tidal amplitudes of both components have similar vertical variation with increasing altitude: less than 5 K below ~98 km but increase considerably above, up to 19 K near 104 km. Both experience significant dissipation near turbopause altitudes, down to ~12 K up to 113 km for the diurnal tide and ~13 K for the semidiurnal tide near 110 km. In addition, while the semidiurnal tidal behavior is consistent with the theoretical predictions, the diurnal amplitude is considerably larger than what is expected in the turbopause region. The tidal phase profile shows a dominance of tidal components with a long vertical wavelength (longer than 40 km) for the semidiurnal tide. On the other hand, the diurnal tide demonstrates close to an evanescent wave behavior in the turbopause region, which is absent in the model results and Thermosphere ionosphere mesosphere energetics and dynamics (TIMED)/Sounding of the atmosphere using broadband radiometry (SABER) observations.

The Ionospheric Connection Explorer Mission: Mission Goals and Design.

The Ionospheric Connection Explorer, or ICON, is a new NASA Explorer mission that will explore the boundary between Earth and space to understand the physical connection between our world and our space environment. This connection is made in the ionosphere, which has long been known to exhibit variability associated with the sun and solar wind. However, it has been recognized in the 21st century that equally significant changes in ionospheric conditions are apparently associated with energy and momentum propagating upward from our own atmosphere. ICON's goal is to weigh the competing impacts of these two drivers as they influence our space environment. Here we describe the specific science objectives that address this goal, as well as the means by which they will be achieved. The instruments selected, the overall performance requirements of the science payload and the operational requirements are also described. ICON's development began in 2013 and the mission is on track for launch in 2017. ICON is developed and managed by the Space Sciences Laboratory at the University of California, Berkeley, with key contributions from several partner institutions.

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

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

The role of self-control strength in the development of state anxiety in test situations.

Self-control strength may affect state anxiety because emotion regulation is impaired in individuals whose self-control strength has been temporarily depleted. Increases in state anxiety were expected to be larger for participants with depleted compared to nondepleted self-control strength, and trait test anxiety should predict increases in state anxiety more strongly if self-control strength is depleted. In a sample of 76 university students, trait test anxiety was assessed, self-control strength experimentally manipulated, and state anxiety measured before and after the announcement of a test. State anxiety increased after the announcement. Trait test anxiety predicted increases in state anxiety only in students with depleted self-control strength, suggesting that increased self-control strength may be useful for coping with anxiety.

Liver transplantation in a child with liver failure due to chronic graft-versus-host disease after allogeneic hematopoietic stem cell transplantation from the same unrelated living donor.

We report a case of a six-yr-old boy who developed chronic GVHD of the liver, intestines, and skin following allogeneic hematopoietic SCT. The boy received an allogeneic hematopoietic stem cell transplant at the age of two yr because of early recurrence of ALL. Chimerism analysis showed complete chimerism. In the following year, he developed GVHD despite adequate immunosuppressive therapy. Liver biopsy showed liver GVHD resulting in liver cirrhosis by the age of five yr. LTx was performed with a left liver lobe from the unrelated donor from whom the stem cells had been taken. Immunosuppressive therapy consisted of low-dose steroids and low-dose cyclosporine. The postoperative course was uneventful. Graft function was excellent, and we performed protocol biopsies at seven days and three wk as well as three, six, and nine months after transplantation; none of these showed any signs of rejection or GVHD. Immunosuppressive therapy was discontinued nine months after LTx. Three yr after transplantation, the boy is in good condition with normal graft function. To our knowledge, this is the first report on LTx following allogeneic hematopoietic SCT from the same unrelated living donor.

Cranio-lenticulo-sutural dysplasia associated with defects in collagen secretion.

Cranio-lenticulo-sutural dysplasia (CLSD) is a rare autosomal recessive syndrome manifesting with large and late-closing fontanels and calvarial hypomineralization, Y-shaped cataracts, skeletal defects, and hypertelorism and other facial dysmorphisms. The CLSD locus was mapped to chromosome 14q13-q21 and a homozygous SEC23A F382L missense mutation was identified in the original family. Skin fibroblasts from these patients exhibit features of a secretion defect with marked distension of the endoplasmic reticulum (ER), consistent with SEC23A function in protein export from the ER. We report an unrelated family where a male proband presented with clinical features of CLSD. A heterozygous missense M702V mutation in a highly conserved residue of SEC23A was inherited from the clinically unaffected father, but no maternal SEC23A mutation was identified. Cultured skin fibroblasts from this new patient showed a severe secretion defect of collagen and enlarged ER, confirming aberrant protein export from the ER. Milder collagen secretion defects and ER distention were present in paternal fibroblasts, indicating that an additional mutation(s) is present in the proband. Our data suggest that defective ER export is the cause of CLSD and genetic element(s) besides SEC23A may influence its presentation.

Synergistic effects of growth and differentiation factor-5 (GDF-5) and insulin on expanded chondrocytes in a 3-D environment.

OBJECTIVE: To investigate the effects of growth and differentiation factor-5 (GDF-5) alone or in combination with insulin on engineered cartilage from primary or expanded chondrocytes during 3-dimensional in vitro culture. DESIGN: Juvenile bovine chondrocytes were seeded either as primary or as expanded (passage 2) cells onto polyglycolic acid fiber meshes and cultured for 3 weeks in vitro. Additionally, adult human chondrocytes were grown in pellet culture after expansion (passage 2). The culture medium was supplemented either with GDF-5 in varying concentrations or insulin alone, or with combinations thereof. RESULTS: For primary chondrocytes, the combination of GDF-5 and insulin led to increased proliferation and construct weight, as compared to either factor alone, however, the production of glycosaminoglycans (GAG) and collagen per cell were not affected. With expanded bovine chondrocytes, the use of GDF-5 or insulin alone led to only very small constructs with no type II collagen detectable. However, the combination of GDF-5 (0.01 or 0.1 microg/ml) and insulin (2.5 microg/ml) yielded cartilaginous constructs and, in contrast to the primary cells, the observed redifferentiating effects were elicited on the cellular level independent of proliferation (increased production of GAG and collagen per cell, clear shift in collagen subtype expression with type II collagen observed throughout the construct). The synergistic redifferentiating effects of the GDF-5/insulin combination were confirmed with expanded adult human cells, also exhibiting a clear shift in collagen subtype expression on the mRNA and protein level. CONCLUSIONS: In combination with insulin, GDF-5 appears to enable the redifferentiation of expanded chondrocytes and the concurrent generation of cartilaginous constructs. The demonstration of these synergistic effects also for adult human chondrocytes supports the clinical relevance of the findings.

[Sports and activities after achilles tendon injury of the recreational athlete]. / Freizeit- und Sportverhalten nach Achillessehnenruptur des Breitensportlers.

BACKGROUND: There is abundant literature on the treatment of Achilles tendon rupture; however data on sports and recreational activities after this injury is scarce. PATIENTS AND METHODS: 71 patients were assessed in a prospective cross-sectional study after an average of 3 years after Achilles tendon rupture. 44 patients were treated non-operatively, using a functional algorithm, and 23 patients were treated operatively. Outcome parameters were the AOFAS-Score and the SF-36 Score. The strength of plantar-flexion was measured using the Isomed 2000 system, the structural integrity of the tendon was assessed sonografically. RESULTS: Patients treated operatively had a higher complication rate than patients treated non-operatively (p = 0.05). Re-rupture rate was identically in both groups. No difference was noted between the two groups for the AOFAS score (92 vs. 90). Moreover the SF-36 score did not show any significant difference between the groups. However, if compared to the age-adjusted normative population significant lower scores were achieved. A significant reduction in practicing sports was detected, as well as a reduction of plantar flexion of the affected foot (p = 0.04). CONCLUSION: Except for complication rate no significant difference could be detected between the groups. Thus operative treatment in the recreational athlete should only be considered, if no adaptation of the ends of the tendon is diagnosed during the initial or repeated ultrasound. Regardless of the therapeutic intervention chosen an Achilles tendon rupture leads to marked changes in sports- and recreational activities.

[Treatment of lower limb osteomyelitis by a local bone substitute supplemented with antibiotics]. / Osteitisbehandlung an Unterschenkeln mit Knochenersatzmaterial als lokalem Antibiotikumträger.

A seriously injured tsunami victim with complicated osteomyelitis is presented. The patient was treated with a new resorbable bone substitute, which can be loaded with different antibiotics. The successful treatment is illustrated by the clinical, radiological and histological features. Bilateral open fractures of the lower leg with open elbow fracture led to a bilateral amputation of the lower legs and the right arm because of a beginning sepsis. The following intramedullary osteitis with multiresistant Pseudomonas aeruginosa, Escherichia coli and Enterococcus faecium was treated with the bone substitute PerOssal combined with systemic and local application of vancomycin and systemic application of ceftazidime and meropenem. This case report illustrates the concept of an additional local antibiotic treatment of osteomyelitis by a bone substitute also functioning as a drug delivery system.

T-peel test for the analysis of articular cartilage integration.

A central aim of current research is to determine the molecular mechanisms of articular cartilage repair. One major issue of articular cartilage repair is the achievable mechanical strength which has been correlated with the collagen metabolism, deposition and collagen cross-linking. Current in vitro techniques, leading to cartilage integration used a shear test to failure. Another well established in vitro method to investigate articular cartilage integration is the insert-ring push out model which is mainly utilized investigating the integration of tissue engineered cartilage to native cartilage. Finite element modeling illustrates at least for the shear test to failure that the contact area is not homogeneously loaded. For the mechanical analysis of articular cartilage integration in regard to its inhomogeneous integration a higher mechanical resolution method is needed. Furthermore the shear test to failure as well as the ring-insert model lacks a comparison to in situ trauma situation, where ruptured or fractured articular cartilage surfaces are opposed after surgical reduction. Considering all these a T-peel test has been introduced in literature but never been experimentally performed. This project deals with the establishment of a T-peel test as a topographical sensitive tool in mechanical analysis of T-peel data and its potential to investigate articular cartilage in vitro integration in comparison to articular cartilage rupture strength.

[Conductive bone substitute material with variable antibiotic delivery]. / Konduktives Knochenersatzmaterial mit variabler Antibiotikaversetzung.

BACKGROUND: A new bone substitute, consisting of hydroxylapatite and calcium sulphate, was prepared in two formulations and analysed for its mechanical strength and antibiotic elution. MATERIAL AND METHODS: The bone substitute PerOssal has osteoconductive and degradable properties. The material has a built-in capillary structure, which results in an immediate fluid uptake. Antibiotics absorbed to the bone substitute resulted in a prolonged release rate. Mechanical strength was investigated by an unconfined compression test up to failure under both wet and dry conditions for both formulations of the bone substitute. Antibiotic release was analysed microbiologically for two antibiotics, vancomycin and gentamicin, over an elution period of 10 days using the agar diffusion method. RESULTS: The drug release analysis resulted in a prolonged release rate of both antibiotics over 10 days. In vitro the amount of gentamicin and vancomycin eluted at day 10. From one pellet still exceeded the minimal inhibitory concentration of most aetiologically important pathogens. Formulation two of the present bone substitute is significantly harder in both wet and dry conditions when compared to formulation one. Both formulations lose strength in the wet condition relative to their performance in the dry condition. However, formulation two is as hard under wet conditions as formulation one is when dry. CONCLUSION: PerOssal is a suitable new degradable osteoconductive bone substitute that can be loaded with antibiotic solutions, which are released in effective doses over 10 days. The mechanical strength of PerOssal is sufficient to support cancellous bone defects in non-weight-bearing areas or in combination with osteosynthesis.

WT1-mediated gene regulation in early urogenital ridge development.

The Wilms tumor protein WT1 is involved in the development of several organs, including the gonads. WT1 mutations in humans lead to syndromes associated with impaired sexual development and Wt1 knockout mice show regression of gonad anlagen. As a transcription factor, WT1 fulfills its function by regulating a set of target genes. With respect to gonad development only few in vivo WT1 targets, e.g. steroidogenic factor 1 (SF1) have been identified so far. To get a comprehensive view of WT1 targets in the gonad, we compared gene expression in urogenital ridges of wild-type and Wt1(-/-) embryos. We found almost 150 genes differentially expressed higher than factor three, using microarray analysis. To confirm these results we performed quantitative real-time RT-PCR for many genes and observed a high degree of concordance between microarray and real-time RT-PCR results. Employing in situ hybridization we found 'WT1 activated genes' to be expressed in gonads, mesonephroi and coelomic epithelium--those parts of the urogenital ridge with Wt1 expression. Interestingly, many of the differentially expressed genes are known to show sex-specific expression at later time-points. These results provide a basis for investigation of developmental pathways in the urogenital ridge downstream of WT1 and for identification of new candidate genes involved in early urogenital ridge development. For example we provide a first potential target of WT1 in the coelomic epithelium--Muc16, and a gene regulated by the WT1 target SF1--Gata4.

The Müllerian duct: recent insights into its development and regression.

Several recent publications have contributed to our understanding of the processes involved in development of the Müllerian ducts in both sexes and regression of these structures in male embryos. Additionally, new insights in the regulation of the anti-Müllerian hormone (AMH) signaling pathway, the pathway, which mediates the male specific degeneration of Müllerian ducts, have been gained. It has become clear that the Müllerian duct is formed by invagination of the coelomic epithelium and elongates primarily by proliferation. Later on cells of the coelomic epithelium perform epithelial to mesenchymal transition and move around the epithelium of the Müllerian duct to induce degeneration of this structure in male embryos. Besides AMH and its specific type II receptor AMHR2 two different type I receptors as well as different SMAD family members have been shown to be involved in the AMH signaling cascade. Other factors including WT1, WNT7a, beta-catenin and MMP2 act upstream and downstream of AMH signaling. Here we try to draw an overall picture of Müllerian duct formation and regression by integrating the recent literature in the field.

Biomechanical properties of articular cartilage as a standard for biologically integrated interfaces.

Articular cartilage integration has been described in in-vitro models, which compare mechanical to biochemical behaviour and histological analysis, respectively. The emphasis of these findings is mainly on the biochemical and histological analysis, rather than on the mechanical performance. The complex in vitro loading conditions and high deviations in the mechanical results due to the biological variance, make interpretations difficult. The aim of this study is to analyse and define the mechanical stress and strain distribution in a single lap configuration by means of an optical strain measurement system. Supportive finite element computation is performed to indicate the heterogeneous stress strain distribution in the integration area. The optical failure analysis of the experiment reveals crack propagation through the integration area comparable to plane shear in fracture mode two. Using the optical strain measurement set up a direct estimation of the shear modulus is achievable by analysing the relative displacement within the bonded joint before the onset of delamination in the adhesive layer. This result lead to a better interpretation of the mechanical behaviour of articular cartilage integration in vitro.

Lipidic implants for controlled release of bioactive insulin: effects on cartilage engineered in vitro.

Controlled release systems for growth factors and morphogens are potentially powerful tools for the engineering or the treatment of living tissues. However, due to possible instabilities of the protein during manufacture, storage, and release, in the development of new release systems it is paramount to investigate into the maintenance of bioactivity of the protein. Within this study, recently developed protein releasing lipid matrix cylinders of 2 mm diameter and 2 mm height made from glycerol tripalmitate were manufactured in a compression process without further additives. Insulin in different concentrations (0.2%, 1%, and 2%) served as model protein. The bioactivity of the protein released from the matrices was investigated in a long-term cartilage engineering culture for up to four weeks; additionally, the release profiles were determined using ELISA. Insulin released from the matrices increased the wet weights of the cartilaginous cell-polymer constructs (up to 3.2-fold), the amount of GAG and collagen in the constructs (up to 2.4-fold and 3.2-fold, respectively) and the GAG and collagen content per cell (1.8-fold and 2.5-fold, respectively), compared to the control. The dose-dependent effects on tissue development correlated well with release profiles from the matrices with different insulin loading. In conclusion, the lipid matrices, preserving the bioactivity of incorporated and released protein, are suggested as a suitable carrier system for use in tissue engineering or for the localized treatment of tissues with highly potent protein drugs such as used in the therapy of brain cancer or neurodegenerative CNS diseases.

Hypogammaglobulinemia in pediatric liver transplant recipients.

Hypogammaglobulinemia has been reported after solid organ transplantation in adults, however immunoglobulin replacement [intravenous immunoglobulins (IVIG)] is only necessary in a minority of affected patients. We here present three pediatric patients with severe post-transplant hypogammaglobulinemia following liver transplantation (LTx) receiving a cyclosporine-based standard immunosuppression. Patient 1 was transplanted at the age of 10 months for biliary atresia. Eight weeks post-Ltx the serum IgG was 1.7 g/L. Patient 2 was transplanted at the age of 12 yr for acute liver failure. Four weeks post-Ltx the IgG dropped to 2.6 g/L. Patient 3 was transplanted at the age of 4 months for biliary atresia. Ten weeks post-Ltx severe hypogammaglobulinemia (IgG < 1.48 g/L) was diagnosed during a severe infectious complication. Patients 1 and 3 received a steroid bolus therapy for acute graft rejection. All patients had normal IgG concentrations prior to Ltx and lymphocyte subsets were post-operatively in the normal range. There was no extensive loss of protein by ascites. IGIV were replaced in the three patients monthly without further complications. In two of the patients (1 and 3) IVIG therapy was discontinued 8 and 10 months after Ltx when the immunosuppression has been reduced and serum IgG concentrations were found in the normal range without further immunoglobulin replacement. Severe hypogammaglobulinemia is a rare phenomenon following pediatric LTx and seems to be mainly caused by immunosuppressive drugs, however, the exact underlying mechanisms are unclear. A screening for hypogammaglobulinemia is useful after pediatric LTx, especially in patients with an intensified immunosuppression. Moreover, further immunologic research in affected patients is necessary.

[Embryonic and adult stem cells]. / Embryonale und adulte Stammzellen.

Stem cells possess an unlimited potential to regenerate and can acquire the identity of various differentiated cells. In the case of embryonic stem cells all the different cells of an organism can be generated. Recently the hitherto underestimated differentiation potential of adult stem cells has also taken center stage. These findings have opened up new perspectives in transplantation medicine and cell therapy for degenerative diseases. Before these possibilities can be realized, however, a number of ethical and scientific-technical obstacles have to be overcome. The latter are caused for example by the low abundance of the cell material as well as by possible immunological rejection reactions.

The murine Wilms tumor suppressor gene (wt1) locus.

The Wilms tumor suppressor gene WT1 plays a crucial role in the etiology of various human diseases as well as in the development of specific organs including the kidneys, gonads and the spleen. At present the human as well as the Fugu wt1 locus have been characterized. We have used a PAC clone to analyze the murine wt1 locus and report here the structure of the wt1 gene as well as a characterization of the nine wt1 introns regarding their size and sequence at the exon/intron and intron/exon boundaries. In addition we provide a restriction map of the murine wt1 locus which should prove useful for the cloning of various constructs designed for the generation of mouse models. Prompted by the existence of a WT1 antisense transcript in humans we also examined strand-specific transcription at the murine wt1 locus. Our analysis suggests that there is no detectable antisense transcription of sequences within or immediately downstream of wt1 exon 1. We find, however, evidence for a divergent transcript which encompasses sequences at and around minor transcriptional initiation sites of wt1 and which is transcribed in the opposite direction. Despite the very high degree of similarity between the human and the murine wt1 sequence and expression as well as the presence of divergent transcripts in both cases, the existence of antisense transcription does not seem to be conserved between the two species.

The speckling domain of the Wilms tumor suppressor WT1 overlaps with the transcriptional repression domain.

The Wilms tumor suppressor gene WT1 encodes a zinc finger protein, expressed as different splicing variants, that has all the hallmarks of a transcription factor. The -KTS form of WT1 displays a homogeneous localization within the nucleus and has been shown to activate or repress the activity of various target genes. In contrast, the WT1(+KTS) variant demonstrates a speckled pattern of expression within the nucleus. This and its association with factors of the splicing machinery has led to the hypothesis that WT1(+KTS) might play a role in post-transcriptional processes. By the generation of a series of deletion constructs and subsequent immunofluorescence analysis, we have identified and characterized the domain which is responsible for the localization of WT1 variants in nuclear speckles. The speckling domain comprises amino acids 76-120 within the N-terminus of WT1 and is sufficient to target other proteins into distinct nuclear domains. Interestingly the WT1 speckling domain does not overlap with the domain required for interaction with the splicing factor U2AF65 but overlaps with the transcriptional repression domain. Thus our data challenge the view that association of WT1 with spliceosomes is responsible for the speckling phenotype.