Construction Of An Instrument For Doing Fast Time-Resolved Infrared Spectroscopy

We have designed and assembled a system for doing flash photochemical studies of organotransition metal carbonyl complexes with fast time-resolved infrared detection. Photolysis is with conventional xenon flashlamps (400J/flash) and time resolved infrared absorption spectra are measured with a diode laser (Laser Photonics, Inc.) and indium antimonide detector operating in the range 1700 - 2100 cm -1. Signals are collected and averaged on a digital oscilloscope (LeCroy 9410) for subsequent computer storage and analysis. The waveform is downloaded to the computer where calculations of percent transmittance and absorbance vs time are calculated. The information is then transferred to a spreadsheet where further calculations can be done and the information can be plotted. The spectral range of the probe laser corresponds to the CO stretching region in transition metal carbonyl complexes thus making it suitable for detailed time resolved studies of the kinetics and mechanisms of these species

Impacts of Policy Reforms on Labor Migration From Rural Mexico to the United States

Using new survey data from Mexico, a dynamic econometric model is estimated to test the effect of policy changes on the flow of migrant labor from rural Mexico to the United States and test for differential effects of policy changes on male and female migration. We find that both IRCA and NAFTA reduced the share of rural Mexicans working in the United States. Increased U.S. border enforcement had the opposite effect. The impacts of these policy variables are small compared with those of macroeconomic variables. The influence of policy and macroeconomic variables is small compared with that of migration networks, as reflected in past migration by villagers to the United States. The effects of all of these variables on migration propensities differ, quantitatively and in some cases qualitatively, by gender.

Neue zellpenetrierende Phosphopeptide für die molekulare Bildgebung

Im Kontext komplexer zellulärer Prozesse stellen Phosphopeptide essentielle bioaktive Verbindungen dar, die mit Phosphorylierungs- und Dephosphorylierungsreaktionen eng verbunden sind. Diese Prozesse sind in die Regulation nahezu jeder zellulären Funktion involviert und spielen damit ebenso im Falle von Erkrankungen eine tragende Rolle. Synthetische Phosphopeptide könnten in Form molekularer Sonden zur Charakterisierung dieser physiologisch fundamentalen Prozesse beitragen. Die radiopharmazeutische Forschung brachte in den letzten zwei Jahrzehnten zahlreiche radiomarkierte Peptide für das Peptidrezeportargeting im Rahmen der Tumordiagnose und -therapie hervor. Unter diesen regulatorischen Peptiden mit vorwiegend neuroendokrinem Ursprung sind bisher keine radiomarkierten Phosphopeptide für die Anwendung in der molekularen Bildgebung bekannt. Das Anliegen dieser Arbeit ist es, grundlegende Erkenntnisse zur Synthese und Markierung von Phosphopeptiden zu erlangen. Neben der Etablierung der Radiomarkierung von Phosphopeptiden mit dem kurzlebigen Positronenstrahler Fluor-18 und deren radiopharmakologischen Charakterisierung steht auch die Fluoreszenzmarkierung mit dem Fluorophor 5(6)-Carboxyfluorescein (CF) im Fokus. Phosphopeptidliganden der kürzlich identifizierten Polo-Box-Domäne (PBD) als Phosphopeptid-bindende Proteindomäne der Zellzykluskinase Plk1, die ebenso ein interessantes onkologisches Target darstellt, wurden für diese Arbeit als Model ausgewählt. Es stand ein Repertoire verschiedenster Methoden zur Verfügung, welche molekulare Bildgebung mittels Kleintier-PET, wie auch optische Bildgebung und die Radiomarkierung mittels klassischer und Mikrofluidik-Technik beinhalten. Im ersten Abschnitt der Promotion wurden kürzlich vorgestellte Plk1-PBD-gerichtete Phosphopeptide mit einer Ser-pThr-Kernsequenz ausgewählt und deren Darstellung mit der Fmoc-gestützten orthogonalen Festphasenpeptidsynthese (SPPS) vollzogen. Dabei erfolgt die Umsetzung nach dem Prinzip des Synthon-basierten Ansatzes, der den Einsatz des monobenzylierten Phosphothreonin-Bausteines involviert. Das Uronium-basierte Kupplungs- und Aktivierungsreagenz HBTU/HOBt/DIPEA, sowie das Abspaltreagenz TFA/Wasser/Thioanisol/EDT als eine modifizierte Variante des Reagenz K garantiert die zuverlässige Synthese von Phosphopeptiden unter Erhalt der Phosphatfunktion. Zur Charakterisierung der Peptide wurden HPLC und Massenspektrometrie als geeignete Methoden herangezogen. An die erfolgreiche Darstellung von Phosphopeptiden schloss sich im Weiteren die Ausarbeitung einer zuverlässigen Radiomarkierungsstrategie mit dem kurzlebigen Positronenstrahler Fluor-18 an. Das bifunktionelle, aminogruppenselektive Agenz N-Succinimidyl-4-[18F]fluorbenzoat ([18F]SFB) ist für eine indirekte und milde Markierung von Peptiden geeignet. Durch Optimierung der N-terminalen 18F-Fluorbenzoylierung des Phosphopeptides MQSpTPL 2 hinsichtlich der Verwendung eines 0,05 M Na2HPO4-Puffers (pH 9) als Reaktionsmedium bei geringer Peptidmenge (0,5 mg), sowie 40°C Reaktionstemperatur und 30 min Reaktionszeit kann das 18F-markierte Phosphopeptid [18F]FBz-MQSpTPL [18F]4 in guten radiochemischen Ausbeuten von 25-28%, mit entsprechender radiochemischer Reinheit >95% mittels HPLC-Reinigung und guter spezifischer Aktivität (20-40 GBq/µmol) hergestellt werden. Der Einsatz von Peptiden ist für die molekulare Bildgebung besonders attraktiv, jedoch oftmals durch ihre Instabilität in vivo, ausgelöst durch ubiquitär vorhandene endogene Peptidasen, limitiert. Beispielsweise besitzt ein N-terminal 18F-fluorbenzoyliertes Neurotensin(8-13) eine biologische Halbwertszeit von weniger als 5 min in vivo. Mit dem neuartigen 18F-markierten Phosphopeptid [18F]FBz-MQSpTPL [18F]4 wurde ein Peptid geschaffen, das in vitro und besonders in vivo außerordentlich hohe Stabilität von > 50% nach 60 min aufweist und damit wegweisende Eigenschaften für die Entwicklung neuer stabiler Radiopeptide für die molekulare Bildgebung aufzeigt. Da Phosphopeptiden aufgrund ihrer negativgeladenen Phosphatfunktionalität ein intrazellulärer Zugang verwehrt bleibt, wie auch in dieser Arbeit an den Tumorzelllinien HT-29 und FaDu nachgewiesen wurde, steht die Realisierung einer verbesserten intrazellulären Internalisierung von Phosphopeptiden im Blickfeld des zweiten Teils der Promotion. Der Versuch einer gezielten Zellaufnahme über rezeptorinternalisierende Peptide wurde mit dem Neuropeptidhormon Neurotensin(8-13) (NT(8-13)), welches über einen G-Protein-gekoppelten Mechanismus in die Zelle gelangt, beschritten. Jedoch zeigte ein Triazol-verbrücktes Konjugat 8 aus NT(8-13) als molekularer Transporter und dem Phosphopeptid MQSpTPL 2, welches auf Basis der Azid-Alkin-Click-Chemie synthetisiert wurde, anhand seiner niedrigen Bindungsaffinität (IC50 = 8,33 µM) kein Potential zu einer erfolgreichen Zellinternalisierung des Phosphopeptides. Vermittler eines rezeptorunabhängigen molekularen Zelltransportes stellen zellpenetrierende Peptide (CPP) dar. Versuche mit den derzeit kürzesten CPPs, den zellpenetrierenden Pentapeptiden (CPP5) oder auch Bax-Inhibitoren genannt, waren nicht erfolgreich. Zwei weitere, in dieser Arbeit verwendete, potente CPPs sind sC18, abgeleitet aus dem antimikrobiellen Peptid Cathelicidin, sowie hCT(18-32)-k7, einem verzweigten Calcitonin-Derivat. Mit den Phosphopeptid-CPP-konjugierten Verbindungen MQSpTPL-sC18 2-CPP1 und MQSpTPL-hCT(18-32)-k7 2-CPP2 wurden nicht-toxische Konstrukte geschaffen, die eine definierte Aufnahme in HeLa, MCF-7 und HT-29 Zellen aufweisen, wie nach Markierung mit dem Fluoreszenzfarbstoff 5(6)-Carboxfluorescein (CF) mittels optischer Bildgebung nachgewiesen werden konnte. Die Integration und Anwendung der Mikrofluidik-Technik im Rahmen der Darstellung der N-terminal 18F-fluorbenzoylierten Phosphopeptid-CPP-Konjugate [18F]FBz-MQSpTPL-sC18 [18F]2-CPP3 und [18F]FBz-MQSpTPL-hCT(18-32)-k7 [18F]2-CPP4 weist im Vergleich zur konventionellen Radiomarkierung entscheidende Vorteile auf. In Anwesenheit der für die [18F]SFB-Markierung reaktiven ε-NH2-Gruppen in den CPP-Fragmenten zeichnet sich im Rahmen der mikrofluiden Markierung entscheidende Selektivität für den N-Terminus der Peptide ab. Die radiochemischen Markierungsausbeuten betragen 21% für [18F]2-CPP3 und 26% für [18F]2-CPP4, im Vergleich zu 2-4% für [18F]2-CPP3 und [18F]2-CPP4 bei klassischer Markierung. In Zellaufnahmestudien wurde ebenfalls eine Internalisierung der 18F-markierten Konjugate in FaDu, HT-29 und MCF-7 Zellen bestätigt, die in allen drei Zelllinien vergleichbar ist und um 40% ID/mg Protein liegt. Wie auch das 18F-markierte Hexaphosphopeptid selbst in Wistar-Unilever-Ratten, zeigten die 18F-markierten Phosphopeptid-CPP-Konjugate in Kleintier-PET-Untersuchungen in Balb/C-Mäusen (Normaltiere) die für ein radiomarkiertes Peptid typische Bioverteilung. Hierbei ist eine renale Exkretion eingeschlossen. Im Rahmen dieser Arbeit ist es gelungen, erstmals 18F-markierte Phosphopeptide mit zellpenetrierenden Eigenschaften für die molekulare Bildgebung zu entwickeln. Diese neuen zellpenetrierenden Phosphopeptide stehen für die Untersuchung intrazellulärer Prozesse, die auf Phosphorylierungs-/Dephosphorylierungsprozessen basieren, zur Verfügung

Relationships of flow and basin variables on the island of Newfoundland, Canada with a regional application

A hydrological study of the island of Newfoundland (Canada) was carried out to identify the key basin characteristics associated with a range of flow measures and to assess the potential for improving flow estimates at ungauged sites using various regionalization methods. The data set was the natural flow records of 40 stations on the island with record lengths of more than ten years. The research included a detailed assessment of the flow records, selection and computation or abstraction of appropriate flow and basin variables, analysis of the relationships of the flow measures to basin characteristics, grouping of the basins (for flood analysis only) into regions of geographic and basin characteristic dataspace, development of predictive equations for all groups, and assessment of the effectiveness of the regionalization methods. A procedure was developed in this work for estimating the effective precipitation in ungauged basins from geographic and topographic variables. -- The most important explanatory variables were found to be drainage area, area controlled by lakes and swamps, fraction of barren area in the basin, and distance of the basins north and/or southwest of defined lines. A detailed assessment of five methods of regional subdivision carried out using the mean annual maximum daily flow as the measure of interest found that dividing the island into regions generally improves the estimates at ungauged sites. Clustering based on basin characteristics is a promising method of regionalization

Visioning services for children affected by HIV and AIDS through a family lens

The HIV epidemic continues to place a great burden on children, from loss of parents and income to severe disruptions of their homes and families. Underpinned by the understanding that a healthy family constitutes the foundation for a child's wellbeing, the importance of family-centred care and services for children is increasingly recognized. It is not enough to merely provide antiretrovirals: it is of pivotal importance that treatment and care for children are integrated into the broader context of family-support schemes. However, despite growing evidence of the benefits of family-centred services, reforms in favour of family oriented HIV interventions have been slow to emerge. Treatment, prevention and care interventions often target individuals, and not families and communities

Is It Attachment Style or Socio-Demography: Singlehood in a Representative Sample

Since the percentage of single adults is steadily increasing, the reasons for this development have become a matter of growing interest. Hereby, an individual’s attachment style may have a connection to the partnership status. In the following analysis, attachment style, gender, age, education, and income were compared in regard to the partnership status. Furthermore, an analysis of variance was computed to compare the attachment style within different groups. In 2012, a sample of 1,676 representative participants was used. The participants were aged 18 to 60 (M = 41.0, SD = 12.3); 54% of the sample were female, and 40% were single. Attachment-related attitudes were assessed with the German version of the adult attachment scale (AAS). Single adult males did not show a more anxious attachment style than single adult females or females in relationships. Younger, i.e., 18 to 30 years old, paired individuals showed greater attachment anxiety than single individuals, whereby single individuals between the ages of 31 to 45 showed greater attachment anxiety than individuals in relationships. In addition, single individuals more frequently had obtained their high school diploma in contrast to individuals in relationships. Concerning attachment style, the individuals who had not completed their high school diploma showed less faith in others independent of singlehood or being in a relationship. Concerning age, older single individuals, i.e., 46 to 60 years, felt less comfortable in respect to closeness and showed less faith in others compared to paired individuals. Logistic regression showed that individuals were not single if they did not mind depending on others, showed high attachment anxiety, were older, and had lower education. An income below € 2000/month was linked to a nearly 13-fold increase of likelihood of being single. In sum, the attachment style had a differential age-dependent association to singlehood versus being in a relationship. Education played also a role, exclusively concerning faith in others

Canadian River Salinity Sources, UTE Reservoir, New Mexico, to Lake Meredith, Texas: Evaporate Dissoultion Patterns and Results of February 1992 Water Quality Survey

In February 1992, the Bureau of Economic Geology (BEG) joined representatives of the Canadian River Municipal Water Authority (CRMWA) and Lee Wilson & Associates (LWA) in conducting a survey of water quality along the Canadian River between Ute Reservoir, New Mexico, and Lake Meredith, Texas (fig. 1). This report describes evaporite dissolution patterns in Permian salt-bearing strata in the Ute Reservoir area, discusses conductivity and flow trends observed during the river survey, and concludes with a discussion of chemical analyses of waters sampled from the Canadian River, its tributaries, and adjacent pools and seeps.Bureau of Economic Geolog

Distinct Contributions of Eroding and Depositional Profiles to Land-Atmosphere CO2 Exchange in Two Contrasting Forests

This work is licensed under a Creative Commons Attribution 4.0 International License.Lateral movements of soil organic C (SOC) influence Earth's C budgets by transporting organic C across landscapes and by modifying soil-profile fluxes of CO2. We extended a previously presented model (Soil Organic C Erosion Replacement and Oxidation, SOrCERO) and present SOrCERODe, a model with which we can project how erosion and subsequent deposition of eroded material can modify biosphere-atmosphere CO2 fluxes in watersheds. The model permits the user to quantify the degree to which eroding and depositional profiles experience a change in SOC oxidation and production as formerly deep horizons become increasingly shallow, and as depositional profiles are buried. To investigate the relative importance of erosion rate, evolving SOC depth distributions, and mineralization reactivity on modeled soil C fluxes, we examine two forests exhibiting distinct depth distributions of SOC content and reactivity, hydrologic regimes and land use. Model projections suggest that, at decadal to centennial timescales: (1) the quantity of SOC moving across a landscape depends on erosion rate and the degree to which SOC production and oxidation at the eroding profile are modified as deeper horizons become shallower, and determines the degree to which depositional profile SOC fluxes are modified; (2) erosional setting C sink strength increases with erosion rate, with some sink effects reaching more than 40% of original profile SOC content after 100 y of a relatively high erosion rate (i.e., 1 mm y−1); (3) even large amounts of deposited SOC may not promote a large depositional profile C sink even with large gains in autochthonous SOC post-deposition if oxidation of buried SOC is not limited; and (4) when modeled depositional settings receive a disproportionately large amount of SOC, simulations of strong C sink scenarios mimic observations of modest preservation of buried SOC and large SOC gains in surficial horizons, suggesting that C sink scenarios have merit in these forests. Our analyses illuminate the importance of cross-landscape linkages between upland and depositional environments for watershed-scale biosphere-atmosphere C fluxes, and emphasize the need for accurate representations and observations of time-varying depth distributions of SOC reactivity across evolving watersheds if we seek accurate projections of ecosystem C balances

The Cost of Improving Nutritional Outcomes Through Food‐Assisted Maternal and Child Health and Nutrition Programmes in Burundi and Guatemala

Evidence on the cost‐effectiveness of multisectoral maternal and child health and nutrition programmes is scarce. We conducted a prospective costing study of two food‐assisted maternal and child health and nutrition programmes targeted to pregnant women and children during the first 1,000 days (pregnancy to 2 years). Each was paired with a cluster‐randomized controlled trial to evaluate impact and compare the optimal quantity and composition of food rations (Guatemala, five treatment arms) and their optimal timing and duration (Burundi, three treatment arms). We calculated the total and per beneficiary cost, conducted cost consequence analyses, and estimated the cost savings from extending the programme for 2 years. In Guatemala, the programme model with the lowest cost per percentage point reduction in stunting provided the full‐size family ration with an individual ration of corn–soy blend or micronutrient powder. Reducing family ration size lowered costs but failed to reduce stunting. In Burundi, providing food assistance for the full 1,000 days led to the lowest cost per percentage point reduction in stunting. Reducing the duration of ration eligibility reduced per beneficiary costs but was less effective. A 2‐year extension could have saved 11% per beneficiary in Guatemala and 18% in Burundi. We found that investments in multisectoral nutrition programmes do not scale linearly. Programmes providing smaller rations or rations for shorter durations, although less expensive per beneficiary, may not provide the necessary dose to improve (biological) outcomes. Lastly, delivering effective programmes for longer periods can generate cost savings by dispersing start‐up costs and lengthening peak operating capacity