Paleoclimate reconstruction using LA-ICP-MS analyses of ostracods and stalagmite

Als paläoklimatische Archive können unter anderem Stalagmiten und Klappen von Ostrakoden herangezogen werden. Bisher gab es noch keine veröffentlichten Ergebnisse räumlich hochaufgelöster Spurenelementverteilungen in einzelnen Ostrakodenklappen. Das gleiche gilt für die Bestimmung radiogener Blei-Isotope in Stalagmiten. Um klimatische Prozesse vergangener Zeiten zu untersuchen, wurde eine neue LA-ICP-MS (Laserablations – Massenspektrometrie mit induktiv gekoppeltem Plasma) Technik für hochaufgelöste in-situ Messungen von Spurenelementen und Bleiisotopen entwickelt. rnrnZunächst wurden geeignete Materialien für die Kalibrierung der Technik untersucht; als Proben dienten die Silikatreferenzgläser BAM-S005-A und BAM-S005B der Bundesanstalt für Materialforschung und –prüfung (BAM). Die Homogenität dieser Referenzgläser wurde mit LA-ICP-MS und den anderen mikroanalytischen Methoden EPMA (Elektronenmikrosonde) und SIMS (Ionensonde) überprüft. Die Ergebnisse zeigten, dass alle Haupt- und die meisten Spurenelemente in beiden Gläsern selbst im Mikrometerbereich homogen verteilt sind. Ausnahmen sind einige Spurenelemente, wie Cs, Cl, Cr, Mo und Ni, die heterogen in den Gläsern verteilt sind. Die Hauptelementzusammensetzung von BAM-S005-A und BAM-S005-B wurde mit Hilfe der EPMA bestimmt, wobei die Ergebnisse die Referenzwerte des BAM-Zertifikats bestätigten. Mit Ausnahme von Sr, Ba, Ce und Pb, stimmten die LA-ICP-MS-Spurenelementwerte mit den zertifizierten Werten innerhalb der angegebenen Fehlergrenzen überein. Gründe für die Diskrepanz der vier oben erwähnten Elemente sind noch unklar, aber sind möglicherweise durch fehlerhafte Referenzwerte zu erklären. Zusätzlich wurden 22 Spurenelemente gemessen, deren Gehalte von BAM nicht zertifiziert wurden. Aufgrund dieser Untersuchungen konnte festgestellt werden, dass beide BAM-Gläser für mikroanalytische Anwendungen geeignet sind.rnrnUm neuartige paläoklimatische Proxies im Calcit von Ostrakoden aus tibetanischen Seesedimenten zu untersuchen, wurde die Spurenelementvariabilität in einzelnen Ostrakodenklappen durch eine neue LA-ICP-MS-Technik bestimmt. Klappen von Ostrakoden der drei Arten (Leucocytherella sinensis Huang, 1982, ?Leucocythere dorsotuberosa Huang, 1982 und ?L. dorsotuberosa f. postilirata sensu Pang, 1985) wurden aus zwei Sedimentkernen des Nam Co Sees auf dem Hochplateau von Tibet gewonnen. Zwei LA-ICP-MS-Varianten, Spot- bzw. Linienanalyse, wurden verwendet, um die Elementkonzentrationen der Spurenelemente Mg, Sr, Ba, U und die der Seltenen Erdelemente (SEE) in den Klappen einzelner Ostrakoden zu bestimmen. Die Ergebnisse zeigten, dass die Linienanalyse präzisere Daten als die Spotanalyse liefert und sie wurde daher vorgezogen. Signifikante Unterschiede in der Spurenelementzusammensetzung zwischen den verschiedenen Arten der Ostrakoden wurden nicht gefunden. Variationen der Elementverhältnisse Mg/Ca und Sr/Ca in den Klappen stimmen mit veröffentlichten Seenspiegelschwankungen während des Holozäns überein, was zeigt, dass Mg- und Sr-Messungen in den Ostrakoden zur Untersuchung paläohydrochemischer Prozesse in diesem Gebiet herangezogen werden kann. Die gute Korrelation, die in dieser Arbeit zwischen Ba/Ca und Sr/Ca gefunden wurde, ist ein Hinweis darauf, dass der Einbau von Ba und Sr in die Klappen durch den gleichen Mechanismus erfolgte. Eine mögliche Beziehung zwischen dem U/Ca-Verhältnis in den Ostrakoden und den Redoxbedingungen auf dem Boden des Sees in der Vergangenheit wird diskutiert. Relativ geringe und konstante La/Ca-Verhältnisse wurden festgestellt, deren Ursache möglicherweise entweder auf der SEE-Charakteristik des Seewassers, auf biologischen Prozessen in den Ostrakoden oder auf Kontamination von Fe-Mn und/oder organischen Substanzen beruhen. Weitere Untersuchungen an Proben aus diesem Gebiet, speziell Klappen von lebenden Ostrakoden, sind notwendig, um den Gehalt von Ba, U und den SEE in Ostrakoden als paläoklimatische Proxies von Umweltbedingungen zu verwenden.

Ottimizzazione di un controllo di temperatura per diodi laser

In questo lavoro di tesi si studia un processo sperimentale necessario alla realizza- zione di un esperimento di Fisica Atomica. L’attivit`a svolta consiste nell’ottimizzazione dei paramentri di un algoritmo di con- trollo PI (proporzionale-integrale) atto a stabilizzare la temperatura di un Diodo Laser entro 1mK. Nella branca dell’Ottica Non Lineare (dove la polarizzazione del mezzo ha una rispo- sta non lineare al campo elettrico) si possono presentare casi in cui la birifrangenza del mezzo ha una forte dipendenza dalla temperatura. Questa pu o ` essere control- lata per il raggiungimento delle condizioni di phase matching. Le fluttuazioni di temperatura possono minare tramite la dilatazione termica la precisione di una ca- vit`a Fabry-Perot, utilizzata per controllare e misurare la lunghezza d’onda della luce, dato che nominalmente ∆ν/ν = − ∆L/L. Negli esperimenti di Laser Cooling infi- ne si lavora spesso con transizioni la cui larghezza naturale Γ ∼ 1MHz , mentre la frequenza di un laser pu o ́ dipendere dalla temperatura con coefficienti tipicamente dell’ordine del GHz/K. Questa stabilizzazione risulta dunque fondamentale per una vasta classe di esperi- menti nei quali le derive termiche possono influenzare drammaticamente il processo di misura. La tesi, in particolare, si apre con un capitolo nel quale si tratta brevemente il con- testo matematico di riferimento per i sistemi di controllo a retroazione. Tra questi e ` di particolare interesse la regolazione proporzionale-integrale. Il secondo capitolo si concentra sulla caratterizzazione del sistema in oggetto al fine di trovare la sua funzione di trasferimento ad anello aperto. Nel terzo capitolo infine, si utilizzano gli strumenti matematici descritti precedente- mente per ottimizzare i parametri del regolatore e si discutono i risultati ottenuti e le misure finali.

Feasibility of image-guided radiotherapy based on tomotherapy for the treatment of locally advanced anal carcinoma

The standard of care for locally advanced anal cancer has been concurrent chemoradiation. However, conventional treatment with 3-dimensional radiotherapy is associated with significant toxicity. The feasibility of new radiotherapy techniques such as image-guided radiotherapy (IGRT) in combination with chemotherapy for the treatment of this malignancy was assessed.

Unpredicted adverse reaction to omalizumab

Despite promising reports of the use of omalizumab as add-on therapy in patients with systemic mastocytosis and recurrent anaphylaxis during specific venom immunotherapy (VIT), unpredicted adverse effects may lead to therapy failure. We present the case of a patient with systemic mastocytosis and Hymenoptera venom allergy who was administered omalizumab as add-on therapy to improve VIT tolerability after repeated severe adverse reactions despite H1/H2-antihistamine prophylaxis. We describe an unexpected discontinuation of omalizumab following successful initiation of VIT in a patient with systemic mastocytosis, with subsequent lack of tolerability of VIT. An interesting aspect of this case is the correlation of basophil activation test results with both clinical tolerability and VIT intolerance.

The Dual Ownership Structure: a Model to Connect the Cooperative Model With Financial Markets

In business literature, the conflicts among workers, shareholders and the management have been studied mostly in the frame of stakeholder theory. The stakeholder theory recognizes this issue as an agency problem, and tries to solve the problem by establishing a contractual relationship between the agent and principals. However, as Marcoux pointed out, the appropriateness of the contract as a medium to reduce the agency problem should be questioned. As an alternative, the cooperative model minimizes the agency costs by integrating the concept of workers, owners and management. Mondragon Corporation is a successful example of the cooperative model which grew into the sixth largest corporation in Spain. However, the cooperative model has long been ignored in discussions of corporate governance, mainly because the success of the cooperative model is extremely difficult to duplicate in reality. This thesis hopes to revitalize the scholarly examination of cooperatives by developing a new model that overcomes the fundamental problem in the cooperative model: the limited access to capital markets. By dividing the ownership interest into financial and control interest, the dual ownership structure allows cooperatives to issue stock in the capital market by making a financial product out of financial interest.

Randomized placebo-controlled trial of ursodeoxycholic acid with vitamin e in nonalcoholic steatohepatitis

BACKGROUND ; AIMS: Nonalcoholic steatohepatitis (NASH) is a frequent liver disease that can progress to cirrhosis and for which there is no recognized therapy. UDCA and vitamin E have been considered separately as therapeutic options and have not been shown to be effective. This study tested their combination. METHODS: Patients with elevated aminotransferase levels and drinking less than 40 g alcohol/week with biopsy-proven NASH were randomly assigned to receive UDCA 12-15 mg.kg-1.day-1 with vitamin E 400 IU twice a day (UDCA/Vit E), UDCA with placebo (UDCA/P), or placebo/placebo (P/P). After 2 years, they underwent a second liver biopsy. Biopsy specimens were collected, blinded, and scored by a single liver pathologist. RESULTS: Forty eight patients were included, 15 in the UDCA/Vit E group, 18 in the UDCA/P group, and 15 in the P/P group; 8 patients dropped out, none because of side effects. Baseline parameters were not significantly different between the 3 groups. Body mass index remained unchanged during the study. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels diminished significantly in the UDCA/Vit E group. Neither the AST nor the ALT levels improved in the P/P group and only the ALT levels in the UDCA/P group. Histologically, the activity index was unchanged at the end of the study in the P/P and UDCA/P groups, but it was significantly better in the UDCA/Vit E group, mostly as a result of regression of steatosis. CONCLUSIONS: Two years of treatment with UDCA in combination with vitamin E improved laboratory values and hepatic steatosis of patients with NASH. Larger trials are warranted.

Diagnostic approach to hypercalcemia: relevance of parathyroid hormone and parathyroid hormone-related protein measurements

Background: Parathyroid hormone (PTH) and parathyroid hormone-related protein (PTH-rP) are two potent hypercalcemic hormones that act on the same targets. Autonomous secretion of the former is involved in primary hyperparathyroidism (PHPT), whereas the latter is responsible for humoral hypercalcemia of malignancy (HHM). Methods: From 250 consecutive, hypercalcemic serum samples sent to our laboratory for assessment of intact PTH, we were able to obtain clinical information, as well as an additional plasma sample for PTH-rP measurement, in 134 patients. At the time of sampling, patients could be classified into seven groups: cancer without known bone metastases (CaNoMeta, n=36), cancer with bone metastases (CaMeta, n=9), no evidence of cancer (noEvCa, n=71), sarcoidosis (Sarc, n=3), end-stage renal disease (ESRD, n=12), vitamin D overdose (VIT-D, n=2), and hyperthyroidism (Thyr, n=1). Results: In the CaNoMeta group, 29/36 patients had elevated PTH-rP levels, 9/36 patients had inappropriately elevated PTH levels, and 5/36 had elevated levels of both hormones. In the CaMeta group, three of the nine patients had inappropriately elevated PTH levels, two of them with concomitantly elevated PTH-rP levels. In the NoEvCa group, 63/71 patients had an inappropriate elevation of PTH levels and were diagnosed as having PHPT. Four of the 71 patients had elevated levels of both PTH and PTH-rP; three of them were in poor health and died within a short period of time. All of the ESRD patients had very high PTH and normal PTH-rP levels, except for one woman with high PTH-rP and undetectable PTH levels; she died from what later turned out to be a recurrent bladder carcinoma. In the Sarc, Vit-D, and Thyr groups, both PTH and PTH-rP levels were normal. Conclusions: (1) Elevated PTH-rP levels are a common finding in cancer patients without bone metastases. Intact PTH, however, should always be measured in hypercalcemic patients with malignancy because concurrent primary hyperparathyroidism is not rare. (2) Primary hyperparathyroidism accounts for hypercalcemia in 90% of patients without evidence of cancer whose PTH-rP levels may also be found to be elevated in a few cases, even some with surgically demonstrated parathyroid adenoma.

Proceedings of the Fifth Biochemical Engineering Symposium

This report presents the proceedings of the Biochemical Engineering Symposium held at Kansas State University, April 26, 1975. Since a number of the contributions will be published in detail elsewhere, only brief summaries of each contribution are included here. Requests for additional information on projects conducted at Iowa State University should be directed to Dr. Peter J. Reilly, and those at Kansas State University to the editors. Contents"Enzymatic Breakdown of Hemicellulose," Alfred R. Fratzke, Iowa State University "Biochemical Aspects of Hydrocarbon Uptake in Hydrocarbon Fermentations," Tadaatsu Nakahara, Kansas State University "Optimal Concentration Profiles for Bifunctional Catalysts with Langmuir-Hinshelwood Kinetics and Varying Effectiveness Factors," Ho Nam Chang, Iowa State University "Single Cell Protein Production from Hydrocarbons in Tower Systems," J. R. Gutierrez, Kansas State University "Effect of Temperature and pH on the Stability and Activity of Immobilized Glucoamylase and Glucose Isomerase," Gene K. Lee, Iowa State University "Oxygen Transfer in a Tower System with Two Liquid Phases," G. T. MacLean, Kansas State University "Continuous Production of Glucose from Dextrin by Glucoamylase Immlobilized on Porous Silica," Douglas D. Lee, Iowa State University

Solar wind dynamic pressure effect on planetary wave propagation and synoptic-scale Rossby wave breaking

We provide statistical evidence of the effect of the solar wind dynamic pressure (Psw) on the northern winter and spring circulations. We find that the vertical structure of the Northern Annular Mode (NAM), the zonal mean circulation, and Eliassen-Palm (EP)-flux anomalies show a dynamically consistent pattern of downward propagation over a period of ~45 days in response to positive Psw anomalies. When the solar irradiance is high, the signature of Psw is marked by a positive NAM anomaly descending from the stratosphere to the surface during winter. When the solar irradiance is low, the Psw signal has the opposite sign, occurs in spring, and is confined to the stratosphere. The negative Psw signal in the NAM under low solar irradiance conditions is primarily governed by enhanced vertical EP-flux divergence and a warmer polar region. The winter Psw signal under high solar irradiance conditions is associated with positive anomalies of the horizontal EP-flux divergence at 55°N–75°N and negative anomalies at 25°N–45°N, which corresponds to the positive NAM anomaly. The EP-flux divergence anomalies occur ~15 days ahead of the mean-flow changes. A significant equatorward shift of synoptic-scale Rossby wave breaking (RWB) near the tropopause is detected during January–March, corresponding to increased anticyclonic RWB and a decrease in cyclonic RWB. We suggest that the barotropic instability associated with asymmetric ozone in the upper stratosphere and the baroclinic instability associated with the polar vortex in the middle and lower stratosphere play a critical role for the winter signal and its downward propagation.

Molecular mechanism by which the Escherichia coli nucleoid occlusion factor, SlmA, keeps cytokinesis in check

Cell division or cytokinesis is one of the most fundamental processes in biology and is essential for the propagation of all living species. In Escherichia coli, cell division occurs by ingrowth of the membrane envelope at the cell center and is orchestrated by the FtsZ protein. FtsZ self-assembles into linear protofilaments in a GTP dependent manner to form a cytoskeletal scaffold called the Z-ring. The Z-ring provides the framework for the assembly of the division apparatus and determines the site of cytokinesis. The total amount of FtsZ molecules in a cell significantly exceeds the concentration required for Z-ring formation. Hence, Z-ring formation must be highly regulated, both temporally and spatially. In particular, the assembly of Z-rings at the cell poles and over chromosomal DNA must be prevented. These inhibitory roles are played by two key regulatory systems called the Min and nucleoid occlusion (NO) systems. In E. coli, Min proteins oscillate from pole to pole; the net result of this oscillatory process is the formation of a zone of FtsZ inhibition at the cell poles. However, the replicated nucleoid DNA near the midcell must also be protected from bisection by the Z-ring which is ensured by NO. A protein called SlmA was shown to be the effector of NO in E. coli. SlmA was identified in a screen designed to isolate mutations that were lethal in the absence of Min, hence the name SlmA (synthetic lethal with a defective Min system). Furthers SlmA was shown to bind DNA and localize to the nucleoid fraction of the cell. Additionally, light scattering experiments suggested that SlmA interacts with FtsZ-GTP and alters its polymerization properties. Here we describe studies that reveal the molecular mechanism by which SlmA mediates NO in E. coli. Specifically, we determined the crystal structure of SlmA, identified its DNA binding site specificity, and mapped its binding sites on the E. coli chromosome by chromatin immuno-precipitation experiments. We went on to determine the SlmA-FtsZ structure by small angle X-ray scattering and examined the effect of SlmA-DNA on FtsZ polymerization by electron microscopy. Our combined data show how SlmA is able to disrupt Z-ring formation through its interaction with FtsZ in a specific temporal and spatial manner and hence prevent nucleoid guillotining during cell division.

Molecular mechanism by which the nucleoid occlusion factor, SlmA, keeps cytokinesis in check.

In Escherichia coli, cytokinesis is orchestrated by FtsZ, which forms a Z-ring to drive septation. Spatial and temporal control of Z-ring formation is achieved by the Min and nucleoid occlusion (NO) systems. Unlike the well-studied Min system, less is known about the anti-DNA guillotining NO process. Here, we describe studies addressing the molecular mechanism of SlmA (synthetic lethal with a defective Min system)-mediated NO. SlmA contains a TetR-like DNA-binding fold, and chromatin immunoprecipitation analyses show that SlmA-binding sites are dispersed on the chromosome except the Ter region, which segregates immediately before septation. SlmA binds DNA and FtsZ simultaneously, and the SlmA-FtsZ structure reveals that two FtsZ molecules sandwich a SlmA dimer. In this complex, FtsZ can still bind GTP and form protofilaments, but the separated protofilaments are forced into an anti-parallel arrangement. This suggests that SlmA may alter FtsZ polymer assembly. Indeed, electron microscopy data, showing that SlmA-DNA disrupts the formation of normal FtsZ polymers and induces distinct spiral structures, supports this. Thus, the combined data reveal how SlmA derails Z-ring formation at the correct place and time to effect NO.

Role of Urbanization, Land-Use Diversity, and Livestock Intensification in Zoonotic Emerging Infectious Diseases

Emerging infectious diseases (EIDs) continue to significantly threaten human and animal health. While there has been some progress in identifying underlying proximal driving forces and causal mechanisms of disease emergence, the role of distal factors is most poorly understood. This article focuses on analyzing the statistical association between highly pathogenic avian influenza (HPAI) H5N1 and urbanization, land-use diversity and poultry intensification. A special form of the urban transition—peri-urbanization—was hypothesized as being associated with ‘hot-spots’ of disease emergence. Novel metrics were used to characterize these distal risk factors. Our models, which combined these newly proposed risk factors with previously known natural and human risk factors, had a far higher predictive performance compared to published models for the first two epidemiological waves in Viet Nam. We found that when relevant risk factors are taken into account, urbanization is generally not a significant independent risk factor. However, urbanization spatially combines other risk factors leading to peri-urban places being the most likely ‘hot-spots’. The work highlights that peri-urban areas have highest levels of chicken density, duck and geese flock size diversity, fraction of land under rice, fraction of land under aquaculture compared to rural and urban areas. Land-use diversity, which has previously never been studied in the context of HPAI H5N1, was found to be a significant risk factor. Places where intensive and extensive forms of poultry production are collocated were found to be at greater risk.

Steroidogenesis of the testis - new genes and pathways

Defects of androgen biosynthesis cause 46,XY disorder of sexual development (DSD). All steroids are produced from cholesterol and the early steps of steroidogenesis are common to mineralocorticoid, glucocorticoid and sex steroid production. Genetic mutations in enzymes and proteins supporting the early biosynthesis pathways cause adrenal insufficiency (AI), DSD and gonadal insufficiency. The classic androgen biosynthesis defects with AI are lipoid CAH, CYP11A1 and HSD3B2 deficiencies. Deficiency of CYP17A1 rarely causes AI, and HSD17B3 or SRD5A2 deficiencies only cause 46,XY DSD and gonadal insufficiency. All androgen biosynthesis depends on 17,20 lyase activity of CYP17A1 which is supported by P450 oxidoreductase (POR) and cytochrome b5 (CYB5). Therefore 46,XY DSD with apparent 17,20 lyase deficiency may be due to mutations in CYP17A1, POR or CYB5. Illustrated by patients harboring mutations in SRD5A2, normal development of the male external genitalia depends largely on dihydrotestosterone (DHT) which is converted from circulating testicular testosterone (T) through SRD5A2 in the genital skin. In the classic androgen biosynthetic pathway, T is produced from DHEA and androstenedione/-diol in the testis. However, recently found mutations in AKR1C2/4 genes in undervirilized 46,XY individuals have established a role for a novel, alternative, backdoor pathway for fetal testicular DHT synthesis. In this pathway, which has been first elucidated for the tammar wallaby pouch young, 17-hydroxyprogesterone is converted directly to DHT by 5α-3α reductive steps without going through the androgens of the classic pathway. Enzymes AKR1C2/4 catalyse the critical 3αHSD reductive reaction which feeds 17OH-DHP into the backdoor pathway. In conclusion, androgen production in the fetal testis seems to utilize two pathways but their exact interplay remains to be elucidated.