Absolute phase control of intense few-cycle pulses and steering the atomic-scale motion of electrons

In the past few years, ultrafast laser technology has developed to such a degree that the phase of a pulse under its envelope is now a meaningful measurable quantity. Many experiments now require the use of pulses with a fixed phase. The reliable production of such pulses, over extended periods of time, is of key importance to many areas of science. The central theme of this thesis is the generation of intense phase-controlled few-cycle optical pulses and their applications. This thesis reports on substantial improvements made in the generation of carrier-envelope phase-controlled pulses. Measurements performed show the accuracy to which absolute phase can be controlled has been improved to a unpreceded level. Also, the period of time over which such high accuracy measurements could be performed was extended by more than a factor of five, such that carrier-envelope phase-sensitive measurements that take longer than 24 hours without any breaks are now possible. With these tools at hand, physical processes that take place on sub-femtosecond time scales can be precisely measured, and control over the motion of bound electrons is possible. In this thesis, a report on the first demonstration of the latter is presented: In the dissociation of the D_2^+ -ion, control over the localisation of the remaining electron is demonstrated

Мінливість дуже сильних дощів і сильних злив в Україні

Розглянуто міжрічну мінливість кількості випадків стихійних гідрометеорологічних явищ (СГЯ), а саме: дуже сильних дощів і сильних злив – в Україні та її регіонах у другій половині ХХ – на початку ХХІ ст. Використавши методи сезонної декомпозиції, встановлено тенденцію динаміки цих рядів протягом досліджуваного періоду. Шляхом автокореляційного та спектрального аналізів визначено циклічні компоненти у структурі рядів річної кількості випадків СГЯ та їх особливості в періоди, коли спостерігали тенденцію до зменшення і збільшення інтенсивності цих явищ.Рассмотрена межгодовая изменчивость количества случаев очень сильных дождей и сильных ливней в Украине и ее регионах во второй половине ХХ - в начале ХХІ в. Установлена тенденция динамики этих рядов на протяжении исследуемого периода. Определены циклические компоненты в структуре рядов годового количества случаев стихийных осадков (СГЯ) и их особенности в периоды, когда наблюдали тенденцию к уменьшению и увеличению интенсивности этих явлений

A transcriptomic approach for evaluating the relative potency and mechanism of action of azoles in the rat Whole Embryo Culture.

We evaluated the effect of six azoles on embryonic development in the rat whole embryo culture (WEC). Using the total morphological scoring system (TMS), we calculated the ID10concentration (effective dose for 10% decrease in TMS). For evaluating gene specific responses, we combined previously and newly collected transcriptomics data of rat WEC exposed to a total of twelve azoles at their ID10for 4h. Results revealed shared expressions responses in genes involved in the retinoic acid (RA) and sterol biosynthesis pathways, which are respectively representatives of developmental toxicity and targeted fungicidal action of the azoles. Azoles with more pronounced effects on the regulation of RA-associated genes were generally characterized as more potent embryotoxicants. Overall, compounds with strong sterol biosynthesis related responses and low RA related responses were considered as more favourable candidates, as they specifically regulated genes related to a desired target response. Among the identified sterol associated genes, we detected that methylsterol monooxygenase 1 (Msmo1) was more sensitively induced compared to Cyp51, a classical biomarker of this pathway. Therefore, we suggest that Msmo1 could be a better biomarker for screening the fungicidal value of azoles. In summary, we conclude that the embryonic regulation of RA and sterol metabolic pathways could be indicators for ranking azoles as embryotoxicants and determining their drug efficacy

Luteinizing hormone (LH)-responsive Cushing's syndrome: the demonstration of LH receptor messenger ribonucleic acid in hyperplastic adrenal cells, which respond to chorionic gonadotropin and serotonin agonists in vitro

In a substantial part of adrenal adenomas and hyperplasias from patients with Cushing's syndrome, cortisol production is controlled by the expression of aberrant hormone receptors on adrenocortical cells. We present in vivo and in vitro data of two patients with a LH-responsive Cushing's syndrome based on ACTH-independent bilateral adrenal hyperplasia. Patients 1 and 2 are women who presented with Cushing's syndrome and bilateral adrenal hyperplasia. Endocrine testing demonstrated absence of cortisol diurnal rhythm, insufficient cortisol suppression after 1 mg dexamethasone orally, and undetectable ACTH levels in both patients. Both patients were treated by laparoscopic biadrenalectomy. In in vivo testing, in patients 1 and 2, a profound cortisol rise was found after administration of GnRH [change in cortisol (Delta F), 118 and 106%, respectively], human CG (Delta F, 133 and 44%), LH (Delta F, 73 and 43%), ACTH (Delta F, 89 and 181%), and the 5-hydroxy-tryptamine receptor type 4 (5-HT(4)) agonists cisapride (Delta F, 141 and 148%) and metoclopramide (Delta F, 189 and 95%). In in vitro testing, adrenal cells from patient 2 responded, in a dose-dependent fashion, with cortisol production after exposure to human CG (Delta F, 45%), cisapride (Delta F, 68%), and metoclopramide (Delta F, 81%). ACTH induced cortisol production by cells from both patients (Delta F, 135 and 159%). In receptor studies, LH receptor mRNA was demonstrated in adrenal tissue of both patients but also in control adrenal tissue of two patients with persisting pituitary-dependent Cushing's syndrome treated by biadrenalectomy. In neither patient were mutations found in the ACTH receptor gene. LH-responsive Cushing's syndrome associated with bilateral adrenal hyperplasia may result from aberrant (or possibly increased) adrenal LH receptor expression. This variant is further characterized by adrenal responsiveness to 5-HT4 receptor agonists, po

A 28-day oral dose toxicity study enhanced to detect endocrine effects of hexabromocyclododecane in wistar rats

A 28-day repeated dose study in rats (OECD407) enhanced for endocrine and immune parameters was performed with hexabromocyclododecane (HBCD). Rats were exposed by daily gavage to HBCD dissolved in corn oil in 8 dose groups with doses ranging between 0 and 200 mg/kg bw per day (mkd). Evaluation consisted of dose-response analysis with calculation of a benchmark dose at the lower 95% one-sided confidence bound (BMDL) at predefined critical effect sizes (CESs) of 10-20%. The most remarkable findings were dose-related effects on the thyroid hormone axis, that is, decreased total thyroxin (TT4, BMDL 55.5 mkd at CES--10%), increased pituitary weight (29 mkd at 10%) and increased immunostaining of TSH in the pituitary, increased thyroid weight (1.6 mkd at 10%), and thyroid follicle cell activation. These effects were restricted to females. Female rats also showed increased absolute liver weights (22.9 mkd at 20%) and induction of T4-glucuronyl transferase (4.1 mkd at 10%), suggesting that aberrant metabolization of T4 triggers feedback activation of the thyroid hormone system. These effects were accompanied by possibly secondary effects, including increased cholesterol (7.4 mkd at 10%), increased tibial bone mineral density (> 49 mkd at 10%), both in females, and decreased splenocyte counts (0.3-6.3 mkd at 20%; only evaluated in males). Overall, female rats appeared to be more sensitive to HBCD than male rats, and an overall BMDL is proposed at 1.6 mkd, based on a 10% increase of the thyroid weight, which was the most sensitive parameter in the sequence of events

Transcriptomic Analysis of Neurulation and Early Organogenesis in Rat Embryos: An In Vivo and Ex Vivo Comparison

Cultured embryos mimic the morphological developmental progression of embryos (in vivo) undergoing neurulation and early organogenesis. Using available genomics technologies, comparative molecular-based assessments between cultured embryos and in vivo models may further clarify commonalities and dissimilarities, which contribute to differences between systems. Therefore, in this study, using a transcriptomic approach, we compared cultured whole rat embryos and embryos in vivo at comparable time points in development (gestational day (GD) 10 + 2-48 h, GD 0 = copulatory plug) to assess for commonalities and differences in gene expression in relation to morphology. We reveal strong parallels in time-dependent expression of genes in terms of magnitude, directionality, and functionality between whole embryo culture (WEC) and in vivo (rat). Genes changing in expression over time resemble previously hypothesized mechanisms underlying early development in mammalian systems. Furthermore, at the gene and functional level, we identify genes, which differ in expression between models, including genes related to development, oxygen transport, and metabolism. In summary, our results support the use of WEC for toxicological studies aimed at representing in vivo development during this time window at the molecular level. Additionally, we indicate genes, which differ in expression between models, providing possible insights for improvement of culture conditions

Optical Detection Of Attosecond Ionization Induced By A Few-Cycle Laser Field In A Transparent Dielectric Material

We observe an optical signature induced by the modulation of electron density inside a bulk transparent solid that is quasiperiodically ionized on an attosecond time scale by electric field peaks of a focused few-cycle laser pulse. The emitted optical signal resulting from the attosecond ionization dynamics is spatially, temporally and spectrally isolated from concomitant optical responses through the use of a noncollinear pump-probe technique. The method holds promise for developing an attosecond metrology for bulk solids, in which, unlike in the established attosecond metrology of gases and surfaces, direct detection of charged particles is unfeasible. © 2011 American Physical Society

Developmental immunotoxicity in male rats after juvenile exposure to ethanol

The aim of the present study was to determine the sensitivity of the developing immune system to ethanol (EtOH) after exposure from postnatal day (PND) 10 onward. Adult Wistar dams and litters were exposed to EtOH via drinking water (0, 0.25, 1.5, 2.75, 4, 5.25, or 6.5% (w/v) EtOH ad libitum) and drinking water exposure of the F-1 was continued from weaning until sacrifice. Immune assessments were performed at postnatal days (PNDs) 21, 42, and 70. Furthermore, Keyhole Limpet Hemocyanin (KLH) specific immune responses were evaluated following subcutaneous immunizations on PNDs 21 and 35. EtOH exposure affected innate immune responses, such as LPS-induced NO-production by adherent splenocytes, as well as adaptive immune responses as represented by KLH-specific parameters. The most sensitive developmental parameters included effects on maternal and pup bodyweight with calculated BMDs of 4.0% and 4.3% EtOH, respectively. The most sensitive immune parameters were affected at dose levels lower than those affecting developmental parameters and included KLH-specific immune responses, LPS-induced NO production by adherent splenocytes, and IL-10 production by ConA stimulated splenocytes. Calculated BMDs for these parameters were between 0.01% and 0.1% EtOH. A comparison of the results of this juvenile study with an extended one-generation reproductive toxicity study revealed that the juvenile study design may result in a higher sensitivity related to differences in the exposure design. These findings demonstrate the relative sensitivity of the developing immune system for EtOH exposure, the additional value of assessing functional immune parameters, and the importance of the juvenile window in developmental immunotoxicity testing