A model measurements comparison of atmospheric forcing and surface fluxes of the Baltic Sea

Observed basic meteorological quantities, heat and radiation fluxes from three different measurement stations in the Baltic Sea are compared with model data of the coupled sea-ice-ocean model BSIOM in order to evaluate the atmospheric forcing, corresponding surface fluxes and the sea surface response. Observational data were made available from the BASIS winter campaigns in 1998 and 2001 as well as from the r/v "Alkor" cruise in June 2001. Simulated fluxes were calculated from prescribed atmospheric forcing provided from the SMHI meteorological database and modelled sea surface temperatures. The comparison of these fluxes with observations demonstrates a strong correlation, even though mean differences in sensible heat fluxes range from 4 to 12 W m-2 in winter and -25 W m-2 in the June experiment. Differences in latent heat fluxes range from -10 to 23 W m-2. The short-wave radiation flux used as model forcing is on average 15 W m-2 less than the corresponding observations for the winter experiments and 40 W m-2 for the June experiment. Differences in net long-wave radiation fluxes range from -5 to 12 W m-2 in winter and -62 W m-2 for the June experiment. The correspondence between measured and calculated momentum fluxes is very high, which confirms the usability of our model component for calculating surface winds and wind stresses from the atmospheric surface pressure

A model-measurements comparison of atmospheric forcing and surface fluxes of the Baltic Sea

Die Quantifizierung des Energie- und Wasserkreislaufs im Einzugsgebiet der Ostsee stellt ein wesentliches Ziel des internationalen BALTEXProgramms dar. Eine genaue Bestimmung des Wasser- und Energiebudgets kann aber nur durch den kombinierten Einsatz von gekoppelten Modellen und Beobachtungen erreicht werden. Dies erfordert eine detaillierte Validierung der Modellkomponenten bei umfangreicher Nutzung bereits vorhandener Beobachtungs-und Satellitendaten, einschließlich der genauen Analyse der Kopplungsmechanismen und Antriebsfunktionen, d. h. der Oberflächenflüsse bzw. der Wechselwirkung Ozean und Atmosphäre. In dieser Arbeit werden der atmosphärische Antrieb, die Wärmeflüsse und der Oberflächenresponse des 3dimensionalen gekoppelten Meereis-Ozean Modells (BSIOM) näher untersucht und unter Verwendung meteorologischer Basisdaten Wärme- und Strahlungsflußdaten von verschiedenen Stationen in der Ostsee, Vergleiche mit Modelldaten angestellt. Die Beobachtungsdaten stammen aus der BASIS Messkampagne im Winter 1998 und 2001 sowie von den RV Alkor Reisen in den Jahren 2000 und 2001. Zusätzlich werden die meteorologischen Messdaten vom Kieler Leuchtturm und vom Institutsdach des IFM-GEOMAR genutzt, um einen statistischen Vergleich der meteorologischen Größen mit den berechneten Modelldaten durchzuführen. Der simulierte kurzwellige Strahlungsfluß über Eis ist im Durchschnitt 15 Wm-2 geringer, als die entsprechenden Beobachtungen in den Winterexperimenten; in den Sommerexperimenten findet sich sogar eine Abweichung von ca. 40 Wm-2, was auf unterschiedliche Bedeckungsgrade in dem vorgeschriebenen atmosphärischen Antrieb und Beobachtungen hindeutet. Die Berechnung der Wärmeflüsse erfolgt mit modellierten SSTs und vorgegebenem atmosphärischen Antrieb (meteorologischen Datenbank des SMHI). Der Vergleich der Wärmeflüsse mit Beobachtungen zeigt eine gute Korrelation, wenn auch die mittleren Differenzen des sensiblen Wärmeflusses zwischen 4 und 12 Wm-2 im Winter und ca. 25 Wm-2 im Sommer schwanken. Differenzen der latenten Wärme liegen zwischen 10 und 70 Wm-2. Der Vergleich der beobachteten und modellierten Windschubspannungen zeigt hohe Übereinstimmungen. Dies deutet darauf hin, dass die gewählte Berechnung des Oberflächenwindes aus dem Bodendruckfeld und der gewählten Parametrisierung zur Berechnung der Windschubspannung geeignet ist, den Impulsfluß zwischen Ozean und Atmosphäre realistisch zu beschreiben. Die gewählten Parametrisierungen (Bulkformeln) zur Berechnung der Strahlungs, Wärme- und Impulsflüsse liefern gute Ergebnisse und erscheinen somit als Antrieb für das Ostseemodell (BSIOM) bei vorgegebenen atmospärischen Parametern geeignet

Application of Survival Analysis Methods to Long Term Care Insurance

With the introduction of compulsory long term care (LTC) insurance in Germany in 1995, a large claims portfolio with a significant proportion of censored observations became available. In first part of this paper we present an analysis of part of this portfolio using the Cox proportional hazard model (Cox, 1972) to estimate transition intensities. It is shown that this approach allows the inclusion of censored observations as well as the inclusion of time dependent risk factors such as time spent in LTC. This is in contrast to the more commonly used Poisson regression with graduation approach (see for example Renshaw and Haberman 1995) where censored observations and time dependent risk factors are ignored. In the second part we show how these estimated transition intensities can be used in a multiple state Markov process (see Haberman and Pitacco, 1999) to calculate premiums for LTC insurance plans

Achromatopsia: Genetics and Gene Therapy

Achromatopsia (ACHM), also known as rod monochromatism or total color blindness, is an autosomal recessively inherited retinal disorder that affects the cones of the retina, the type of photoreceptors responsible for high-acuity daylight vision. ACHM is caused by pathogenic variants in one of six cone photoreceptor-expressed genes. These mutations result in a functional loss and a slow progressive degeneration of cone photoreceptors. The loss of cone photoreceptor function manifests at birth or early in childhood and results in decreased visual acuity, lack of color discrimination, abnormal intolerance to light (photophobia), and rapid involuntary eye movement (nystagmus). Up to 90% of patients with ACHM carry mutations in CNGA3 or CNGB3, which are the genes encoding the alpha and beta subunits of the cone cyclic nucleotide-gated (CNG) channel, respectively. No authorized therapy for ACHM exists, but research activities have intensified over the past decade and have led to several preclinical gene therapy studies that have shown functional and morphological improvements in animal models of ACHM. These encouraging preclinical data helped advance multiple gene therapy programs for CNGA3- and CNGB3-linked ACHM into the clinical phase. Here, we provide an overview of the genetic and molecular basis of ACHM, summarize the gene therapy-related research activities, and provide an outlook for their clinical application

Accounting of vehicles

Актуальность исследования определяется возросшей необходимостью наличия транспортного средства для каждой компании. Автомобиль - это всегда большие затраты, учет которых «ложится на плечи» бухгалтерии. В организации должны быть разработаны внутренние положения, инструкции, иные организационно-распорядительные документы, необходимые для организации учета основных средств, включая автотранспортные средства, и контроля за их использованием. Методы ведения бухгалтерского учета в организации - это один из сложных вопросов управления компанией. Цель работы: установление статей расходов на транспортное средство в бухгалтерском учете. Методы исследования: методы эмпирического исследования (наблюдение, сравнение) и методы теоретического исследования (абстрагирование, анализ и синтез, индукция и дедукция, мысленное моделирование, восхождение от абстрактного к конкретному). Результаты. Рассмотрены основные затраты на содержание автомобильного транспорта, проанализированы имеющиеся теоретические материалы по выбранной тематике, государственные законодательные акты. Принимая во внимание изменения в законодательстве 2017 года, выбрана методика внесения затрат на автомобильный транспорт в бухгалтерский учет.The relevance of the study is determined by the increased need for each company in a vehicle. A car is always a big expense, which should be recorded by accountant. A company should develop internal regulations, instructions, other organizational and administrative documents required for accounting fixed assets, including vehicles, and control over their use. Method of accounting in the organization is one of the complex issues of company management. The aim of the study is to determine the items of expenses for a vehicle in accounting. Methods of research: methods of empirical research (observation, comparison) and methods of theoretical research (abstraction, analysis and synthesis, induction and deduction, mental modeling, climbing from the abstract to the concrete). Results. The paper considers the main expenses for maintaining motor transport. The authors have analyzed the theoretical materials on the chosen subjects, state legislative acts and selected the method of entering the costs for road transport into accounting taking into account the changes in the legislation of 2017

Vitamin B12 in Leber hereditary optic neuropathy mutation carriers: a prospective cohort study

Background Leber hereditary optic neuropathy (LHON) is the most common mitochondrial disorder, frequently resulting in acute or subacute severe bilateral central vision loss. Vitamin B12 deficiency is also a known cause of optic neuropathy through mitochondrial dysfunction. Here we evaluated the prevalence and clinical significance of vitamin B12 deficiency in a large cohort of LHON patients and asymptomatic mutation carriers from a tertiary referral center. Methods From the Munich LHON prospective cohort study, participants included all LHON patients and asymptomatic LHON mutation carriers, who were recruited between February 2014 and March 2020 and consented to participate. Neurological, general, and ophthalmological examinations were regularly performed, as were laboratory tests. Vitamin B12 deficiency was diagnosed if serum vitamin B12 was below 201 pg/mL, or if 201–339 pg/mL plus low serum holotranscobalamin or elevated serum methylmalonic acid or elevated total plasma homocysteine. Results We analyzed 244 subjects, including 147 symptomatic LHON patients (74% males) and 97 asymptomatic mutation carriers (31% males). Median age at study baseline was 34 years (range 5–82 years). The prevalence of vitamin B12 deficiency was higher for LHON mutation carriers than for the general population in all age categories. This was statistically significant for the LHON mutation carriers under 65 years (21% vs. 5–7%, p = 0.002). While vitamin B12 deficiency prevalence was not statistically different between LHON patients and asymptomatic mutation carriers, its clinical correlates, e.g., macrocytosis and polyneuropathy, were more frequent in the subgroup of LHON patients. Excessive alcohol consumption was a significant predictor of vitamin B12 deficiency (p < 0.05). Conclusions The high prevalence of vitamin B12 deficiency in LHON mutation carriers, both asymptomatic mutation carriers and LHON patients, highlights the need for regular vitamin B12 screening in this population, in order to ensure early treatment, aiming for better outcomes. Our study is not conclusive regarding vitamin B12 deficiency as determinant for disease conversion in LHON, and further research is warranted to disentangle the role of vitamin B12 in the pathophysiology and prognosis of LHON

Structure of a 13-fold superhelix (almost) determined from first principles.

Nuclear hormone receptors are cytoplasm-based transcription factors that bind a ligand, translate to the nucleus and initiate gene transcription in complex with a co-activator such as TIF2 (transcriptional intermediary factor 2). For structural studies the co-activator is usually mimicked by a peptide of circa 13 residues, which for the largest part forms an α-helix when bound to the receptor. The aim was to co-crystallize the glucocorticoid receptor in complex with a ligand and the TIF2 co-activator peptide. The 1.82 Å resolution diffraction data obtained from the crystal could not be phased by molecular replacement using the known receptor structures. HPLC analysis of the crystals revealed the absence of the receptor and indicated that only the co-activator peptide was present. The self-rotation function displayed 13-fold rotational symmetry, which initiated an exhaustive but unsuccessful molecular-replacement approach using motifs of 13-fold symmetry such as α- and β-barrels in various geometries. The structure was ultimately determined by using a single α-helix and the software ARCIMBOLDO, which assembles fragments placed by PHASER before using them as seeds for density modification model building in SHELXE. Systematic variation of the helix length revealed upper and lower size limits for successful structure determination. A beautiful but unanticipated structure was obtained that forms superhelices with left-handed twist throughout the crystal, stabilized by ligand interactions. Together with the increasing diversity of structural elements in the Protein Data Bank the results from TIF2 confirm the potential of fragment-based molecular replacement to significantly accelerate the phasing step for native diffraction data at around 2 Å resolution

Age‐dependent retinal neuroaxonal degeneration in children and adolescents with Leber hereditary optic neuropathy under idebenone therapy

Background The aim of this study was to investigate the neuroretinal structure of young patients with Leber hereditary optic neuropathy (LHON). Methods For this retrospective cross-sectional analysis, the peripapillary retinal nerve fiber layer (pRNFL) thickness and the macular retinal layer volumes were measured by optical coherence tomography. Patients aged 12 years or younger at disease onset were assigned to the childhood-onset (ChO) group and those aged 13–16 years to the early teenage-onset (eTO) group. All patients received treatment with idebenone. The same measurements were repeated in age-matched control groups with healthy subjects. Results The ChO group included 11 patients (21 eyes) and the eTO group 14 patients (27 eyes). Mean age at onset was 8.6 ± 2.7 years in the ChO group and 14.8 ± 1.0 years in the eTO group. Mean best-corrected visual acuity was 0.65 ± 0.52 logMAR in the ChO group and 1.60 ± 0. 51 logMAR in the eTO group (p < 0.001). Reduced pRNFL was evident in the eTO group compared to the ChO group (46.0 ± 12.7 μm vs. 56.0 ± 14.5 μm, p = 0.015). Additionally, a significantly lower combined ganglion cell and inner plexiform layer volume was found in the eTO compared to the ChO group (0.266 ± 0.0027 mm3 vs. 0.294 ± 0.033 mm3, p = 0.003). No difference in these parameters was evident between the age-matched control groups. Conclusion Less neuroaxonal tissue degeneration was observed in ChO LHON than in eTO LHON, a finding that may explain the better functional outcome of ChO LHON

DMSO increases efficiency of genome editing at two non-coding loci

Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/CRISPR-associated protein-9 (Cas9) has become the tool of choice for genome editing. Despite the fact that it has evolved as a highly efficient means to edit/replace coding sequence, CRISPR/Cas9 efficiency for “clean” editing of non-coding DNA remains low. We set out to introduce a single base-pair substitution in two intronic SNPs at the FTO locus without altering nearby non-coding sequence. Substitution efficiency increased up to 10-fold by treatment of human embryonic stem cells (ESC) with non-toxic levels of DMSO (1%) before CRISPR/Cas9 delivery. Treatment with DMSO did not result in CRISPR/Cas9 off-target effects or compromise the chromosomal stability of the ESC. Twenty-four hour treatment of human ESC with DMSO before CRISPR/Cas9 delivery may prove a simple means to increase editing efficiency of non-coding DNA without incorporation of undesirable mutations