Многолетнее изменение водного стока р. Черный Иртыш и условий его формирования (Республика Казахстан)

Выполнен статистический анализ многолетнего изменения расходов воды р. Черный Иртыш в створе с. Буран (Республика Казахстан, Восточно-Казахстанская область) и климатических условий формирования водного стока по данным гидрологических и метеорологических наблюдений за период с 1938 по 2008 гг. Выявлено уменьшение расходов воды р. Черный Иртыш в июле и августе и увеличение в марте, общее увеличение температуры атмосферного воздуха в равнинной части бассейна р. Иртыш (метеостанция г. Омск). Значимые изменения температуры воздуха горных районов не выявлены (метеостанция г. Змеиногорск)

Über das tumorigene Potential eines konstitutiv aktivierten Wnt-Signalwegs im Riechepithel der Maus

Dem kanonischen Wnt-Signalweg kommt eine entscheidende Bedeutung in der riechepithelialen Neurogenese zu, wo er die Proliferation und Expansion neuronaler Vorläuferzellen ausgehend von riechepithelialen Stammzellen fördert. Eine pathologische Aktivierung des Wnt-Signalwegs stellt eine Schüsselalteration in der Tumorigenese verschiedener humaner Neoplasien dar. Das Olfaktoriusneuroblastom (ONB) ist ein Malignom, welches vermutlich von Zellen des Riechepithels ausgeht – über die molekulare Pathogenese dieses Tumors ist jedoch bislang wenig bekannt. Die vorliegende Arbeit untersucht das tumorigene Potential eines aberrant aktivierten Wnt-Signalwegs im Riechepithel der Maus. Zu diesem Zwecke stand ein Sox2-creERT2::Ctnnb1(ex3)Fl/+-Mausmodell zu Verfügung, welches eine konstitutive Aktivierung des kanonischen Wnt-Signalwegs in Sox2-positiven Zellen des Riechepithels an verschiedenen Altersstufe erlaubt. Es kann gezeigt werden, dass eine embryonale Induktion dieses Modells an Tag 14,5 der Embryonalentwicklung zur Entstehung von Tumor-artigen Läsionen führt, welche invasives Wachstum als Kennzeichen von Malignität aufweisen. Ein früh-postnatale Induktion des Modells führt zur Entstehung riechepithelialer Polypen ohne malignen Charakter, wohingegen eine späte Induktion am Postnataltag 21 keine offensichtlichen morphologischen Alterationen des murinen Riechepithels mehr hervorruft. Diese Ergebnisse suggerieren zusammenfasend ein altersabhängiges tumorigenes Potential einer aberranten Aktivierung des Wnt-Signalwegs im murinen Riechepithel. Humane Olfaktoriusneuroblastome ähneln histomorphologisch und immunohistochemisch den beschriebenen Wnt-abhängigen, Tumor-artigen riechepithelialen Läsionen im Mausmodell, bieten jedoch keinen überzeugenden Anhalt auf eine Bedeutung einer pathologischen Aktivierung des kanonischen Wnt-Signalwegs für ihre Pathogenese. In welchem Maße eine pathologische Aktivierung des Wnt-Signalwegs für die Entstehung humaner Neoplasien des Nasen-Rachenraums eine entscheidende Rolle spielt und im Besonderen eine neoplastische Transformation im Riechepithel des Menschen bewirken kann, muss in zukünftigen Forschungsprojekten weiter evaluiert werden

Über das tumorigene Potential eines konstitutiv aktivierten Wnt-Signalwegs im Riechepithel der Maus

Dem kanonischen Wnt-Signalweg kommt eine entscheidende Bedeutung in der riechepithelialen Neurogenese zu, wo er die Proliferation und Expansion neuronaler Vorläuferzellen ausgehend von riechepithelialen Stammzellen fördert. Eine pathologische Aktivierung des Wnt-Signalwegs stellt eine Schüsselalteration in der Tumorigenese verschiedener humaner Neoplasien dar. Das Olfaktoriusneuroblastom (ONB) ist ein Malignom, welches vermutlich von Zellen des Riechepithels ausgeht – über die molekulare Pathogenese dieses Tumors ist jedoch bislang wenig bekannt. Die vorliegende Arbeit untersucht das tumorigene Potential eines aberrant aktivierten Wnt-Signalwegs im Riechepithel der Maus. Zu diesem Zwecke stand ein Sox2-creERT2::Ctnnb1(ex3)Fl/+-Mausmodell zu Verfügung, welches eine konstitutive Aktivierung des kanonischen Wnt-Signalwegs in Sox2-positiven Zellen des Riechepithels an verschiedenen Altersstufe erlaubt. Es kann gezeigt werden, dass eine embryonale Induktion dieses Modells an Tag 14,5 der Embryonalentwicklung zur Entstehung von Tumor-artigen Läsionen führt, welche invasives Wachstum als Kennzeichen von Malignität aufweisen. Ein früh-postnatale Induktion des Modells führt zur Entstehung riechepithelialer Polypen ohne malignen Charakter, wohingegen eine späte Induktion am Postnataltag 21 keine offensichtlichen morphologischen Alterationen des murinen Riechepithels mehr hervorruft. Diese Ergebnisse suggerieren zusammenfasend ein altersabhängiges tumorigenes Potential einer aberranten Aktivierung des Wnt-Signalwegs im murinen Riechepithel. Humane Olfaktoriusneuroblastome ähneln histomorphologisch und immunohistochemisch den beschriebenen Wnt-abhängigen, Tumor-artigen riechepithelialen Läsionen im Mausmodell, bieten jedoch keinen überzeugenden Anhalt auf eine Bedeutung einer pathologischen Aktivierung des kanonischen Wnt-Signalwegs für ihre Pathogenese. In welchem Maße eine pathologische Aktivierung des Wnt-Signalwegs für die Entstehung humaner Neoplasien des Nasen-Rachenraums eine entscheidende Rolle spielt und im Besonderen eine neoplastische Transformation im Riechepithel des Menschen bewirken kann, muss in zukünftigen Forschungsprojekten weiter evaluiert werden

Phase II trial of preoperative radiochemotherapy with concurrent bevacizumab, capecitabine and oxaliplatin in patients with locally advanced rectal cancer

Background: Preoperative radiochemotherapy (RCT) with 5-FU or capecitabine is the standard of care for patients with locally advanced rectal cancer (LARC). Preoperative RCT achieves pathological complete response rates (pCR) of 10-15%. We conducted a single arm phase II study to investigate the feasibility and efficacy of addition of bevacizumab and oxaliplatin to preoperative standard RCT with capecitabine. Methods: Eligible patients had LARC (cT3-4; N0/1/2, M0/1) and were treated with preoperative RCT prior to planned surgery. Patients received conventionally fractionated radiotherapy (50.4 Gy in 1.8 Gy fractions) and simultaneous chemotherapy with capecitabine 825 mg/m2 bid (d1-14, d22-35) and oxaliplatin 50 mg/m2 (d1, d8, d22, d29). Bevacizumab 5 mg/kg was added on days 1, 15, and 29. The primary study objective was the pCR rate. Results: 70 patients with LARC (cT3-4; N0/1, M0/1), ECOG < 2, were enrolled at 6 sites from 07/2008 through 02/2010 (median age 61 years [range 39–89], 68% male). At initial diagnosis, 84% of patients had clinical stage T3, 62% of patients had nodal involvement and 83% of patients were M0. Mean tumor distance from anal verge was 5.92 cm (± 3.68). 58 patients received the complete RCT (full dose RT and full dose of all chemotherapy). During preoperative treatment, grade 3 or 4 toxicities were experienced by 6 and 2 patients, respectively: grade 4 diarrhea and nausea in one patient (1.4%), respectively, grade 3 diarrhea in 2 patients (3%), grade 3 obstipation, anal abscess, anaphylactic reaction, leucopenia and neutropenia in one patient (1.4%), respectively. In total, 30 patients (46%) developed postoperative complications of any grade including one gastrointestinal perforation in one patient (2%), wound-healing problems in 7 patients (11%) and bleedings in 2 patients (3%). pCR was observed in 12/69 (17.4%) patients. Pathological downstaging (ypT < cT and ypN ≤ cN) was achieved in 31 of 69 patients (44.9%). All of the 66 operated patients had a R0 resection. 47 patients (68.1%) underwent sphincter preserving surgery. Conclusions: The addition of bevacizumab and oxaliplatin to RCT with capecitabine was well tolerated and did not increase perioperative morbidity or mortality. However, the pCR rate was not improved in comparison to other trials that used capecitabine or capecitabine/oxaliplatin in preoperative radiochemotherapy

Dynamics of neural cryptography

Synchronization of neural networks has been used for novel public channel protocols in cryptography. In the case of tree parity machines the dynamics of both bidirectional synchronization and unidirectional learning is driven by attractive and repulsive stochastic forces. Thus it can be described well by a random walk model for the overlap between participating neural networks. For that purpose transition probabilities and scaling laws for the step sizes are derived analytically. Both these calculations as well as numerical simulations show that bidirectional interaction leads to full synchronization on average. In contrast, successful learning is only possible by means of fluctuations. Consequently, synchronization is much faster than learning, which is essential for the security of the neural key-exchange protocol. However, this qualitative difference between bidirectional and unidirectional interaction vanishes if tree parity machines with more than three hidden units are used, so that those neural networks are not suitable for neural cryptography. In addition, the effective number of keys which can be generated by the neural key-exchange protocol is calculated using the entropy of the weight distribution. As this quantity increases exponentially with the system size, brute-force attacks on neural cryptography can easily be made unfeasible.Comment: 9 pages, 15 figures; typos correcte

Modelling Dominant Tree Heights of Fagus sylvatica L. Using Function-on-Scalar Regression Based on Forest Inventory Data

European beech (Fagus sylvatica L.) is an important tree species throughout Europe but shifts in its suitable habitats are expected in the future due to climate change. Finding provenances that are still economically viable and ecologically resilient is an ongoing field of research. We modelled the dominant tree heights of European beech as a trait reflecting growth performance dependent on provenance, climate and soil conditions. We derived dominant tree heights from national forest inventory (NFI) data from six European countries spanning over large ecological gradients. We performed function-on-scalar regression using hierarchical generalized additive models (HGAM) to model both the global effects shared among all provenances and the effects specific to a particular provenance. By comparing predictions for a reference period of 1981-2010 and 2071-2100 in a RCP 8.5 scenario, we showed that changes in growth performance can be expected in the future. Dominant tree heights decreased in Southern and Central Europe but increased in Northern Europe by more than 10 m. Changes in growth performance were always accompanied by a change in beech provenances, assuming assisted migration without dispersal limitations. Our results support the concept of assisted migration for the building of resilient future forests and emphasize the use of genetic data for future growth predictions

Mutation analysis in a German family identified a new cataract-causing allele in the CRYBB2 gene

The study demonstrates the functional candidate gene analysis in a cataract family of German descent. METHODS: We screened a German family, clinically documented to have congenital cataracts, for mutation in the candidate genes CRYG (A to D) and CRYBB2 through polymerase chain reaction analyses and sequencing. RESULTS: Congenital cataract was first observed in a daughter of healthy parents. Her two children (a boy and a girl) also suffer from congenital cataracts and have been operated within the first weeks of birth. Morphologically, the cataract is characterized as nuclear with an additional ring-shaped cortical opacity. Molecular analysis revealed no causative mutation in any of the CRYG genes. However, sequencing of the exons of the CRYBB2 gene identified a sequence variation in exon 5 (383 A&gt;T) with a substitution of Asp to Val at position 128. All three affected family members revealed this change but it was not observed in any of the unaffected persons of the family. The putative mutation creates a restriction site for the enzyme TaiI. This mutation was checked for in controls of randomly selected DNA samples from ophthalmologically normal individuals from the population-based KORA S4 study (n=96) and no mutation was observed. Moreover, the Asp at position 128 is within a stretch of 12 amino acids, which are highly conserved throughout the animal kingdom. For the mutant protein, the isoelectric point is raised from pH 6.50 to 6.75. Additionally, the random coil structure of the protein between the amino acids 126-139 is interrupted by a short extended strand structure. In addition, this region becomes hydrophobic (from neutral to +1) and the electrostatic potential in the region surrounding the exchanged amino acid alters from a mainly negative potential to an enlarged positive potential. CONCLUSIONS: The D128V mutation segregates only in affected family members and is not seen in representative controls. It represents the first mutation outside exon 6 of the human CRYBB2 gene

Fat-pad impingement after total knee arthroplasty with the LCS A/P-Glide system

Early follow-up (15.8 months;1-48) of 230 knee replacements with an LCS A/P Glide component indicated an increased occurrence of anterior knee pain due to a fat-pad impingement, necessitating early revision surgery. Unsatisfactory results were observed in 28 knees (12.2%). Thirteen knees (5.7%) were revised on finding the fat-pad impingement, and four knees (1.7%) were scheduled for later revision surgery; the remaining 11 subjects (4.8%) had revision surgery for a different reason. Twenty-six subjects (11.3%) complained about milder but typical symptoms of a fat-pad impingement, and 22 subjects (9.6%) had unspecific mild symptoms. 151 knees (65.7%) were free of pain and demonstrated an excellent result. The total revision rate of 10.4% (24 knees) is higher than described for other implant systems. However, the revision needed to treat the fat-pad impingement (5.7%) consisted of minor surgery only, such as exchange of the mobile bearing or reduction of the fat pad by arthroscopy. The femoral and tibial components were able to be left untouched. Resection of the Hoffa's fat pad is recommended when such an implant system is used, and possible impingement should be investigated intraoperatively before closur

Genetic attack on neural cryptography

Different scaling properties for the complexity of bidirectional synchronization and unidirectional learning are essential for the security of neural cryptography. Incrementing the synaptic depth of the networks increases the synchronization time only polynomially, but the success of the geometric attack is reduced exponentially and it clearly fails in the limit of infinite synaptic depth. This method is improved by adding a genetic algorithm, which selects the fittest neural networks. The probability of a successful genetic attack is calculated for different model parameters using numerical simulations. The results show that scaling laws observed in the case of other attacks hold for the improved algorithm, too. The number of networks needed for an effective attack grows exponentially with increasing synaptic depth. In addition, finite-size effects caused by Hebbian and anti-Hebbian learning are analyzed. These learning rules converge to the random walk rule if the synaptic depth is small compared to the square root of the system size.Comment: 8 pages, 12 figures; section 5 amended, typos correcte