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Nuclear charge radii are sensitive probes of different aspects of the nucleon-nucleon interaction and the bulk properties of nuclear matter; thus, they provide a stringent test and challenge for nuclear theory. The calcium region has been of particular interest, as experimental evidence has suggested a new magic number at $N = 32$ [1-3], while the unexpectedly large increases in the charge radii [4,5] open new questions about the evolution of nuclear size in neutron-rich systems. By combining the collinear resonance ionization spectroscopy method with $\beta$-decay detection, we were able to extend the charge radii measurement of potassium ($Z =19$) isotopes up to the exotic $^{52}$K ($t_{1/2}$ = 110 ms), produced in minute quantities. Our work provides the first charge radii measurement beyond $N = 32$ in the region, revealing no signature of the magic character at this neutron number. The results are interpreted with two state-of-the-art nuclear theories. For the first time, a long sequence of isotopes could be calculated with coupled-cluster calculations based on newly developed nuclear interactions. The strong increase in the charge radii beyond $N = 28$ is not well captured by these calculations, but is well reproduced by Fayans nuclear density functional theory, which, however, overestimates the odd-even staggering effect. These findings highlight our limited understanding on the nuclear size of neutron-rich systems, and expose pressing problems that are present in some of the best current models of nuclear theory., Comment: submitted version; revision accepted in Nature Physics

© 2019 This paper presents an overview of recent resonance ionization schemes used at the Collinear Resonance Ionization Spectroscopy (CRIS) setup located at ISOLDE, CERN. The developments needed to reach high spectral resolution and efficiency will be discussed. Besides laser ionization efficiency and high resolving power, experiments on rare isotopes also require low-background conditions. Ongoing developments that aim to deal with beam-related sources of background are presented. ispartof: Nuclear Instruments & Methods In Physics Research Section B-Beam Interactions With Materials And Atoms vol:463 pages:398-402 ispartof: location:SWITZERLAND, CERN, Geneva status: published

Isotope shifts of $^{223-226,228}$Ra$^{19}$F were measured for different vibrational levels in the electronic transition $A^{2}{}{\Pi}_{1/2}\leftarrow X^{2}{}{\Sigma}^{+}$. The observed isotope shifts demonstrate the particularly high sensitivity of radium monofluoride to nuclear size effects, offering a stringent test of models describing the electronic density within the radium nucleus. Ab initio quantum chemical calculations are in excellent agreement with experimental observations. These results highlight some of the unique opportunities that short-lived molecules could offer in nuclear structure and in fundamental symmetry studies., Comment: The paper was accepted for publication as a Letter in Physical Review Letters

This paper presents high-precision spectroscopic measurements of atomic tin using five different resonance-ionization schemes performed with the collinear resonance-ionization spectroscopy technique. Isotope shifts were measured for the stable tin isotopes from the $5{s}^{2}5{p}^{2}\phantom{\rule{0.28em}{0ex}}^{3}{P}_{0,1,2}$ and ${}^{1}{S}_{0}$ to the $5{s}^{2}5p6s\phantom{\rule{0.28em}{0ex}}^{1}{P}_{1},^{3}{P}_{1,2}$ and $5{s}^{2}5p7s{\phantom{\rule{0.28em}{0ex}}}^{1}{P}_{1}$ atomic levels. The magnetic dipole hyperfine constants ${A}_{\mathrm{hf}}$ have been extracted for six atomic levels with electron angular momentum $Jg0$ from the hyperfine structures of nuclear spin $I=1/2$ tin isotopes, $^{115,117,119}\mathrm{Sn}$. State-of-the-art atomic calculations using a relativistic Fock-space coupled-cluster method and the configuration interaction approach combined with many-body perturbation theory allow accurate and reliable calculations of both field- and mass-shift factors for the studied transitions, in addition to the hyperfine magnetic fields and electric-field gradients of the atomic levels. The excellent agreement with the experimental results highlights the accuracy of modern atomic theory and establishes an important foundation for precision measurements of nuclear moments and charge radii of the most exotic isotopes of tin.

Veterinary certificates have been an integral component of animal and animal product trade for many years. These certificates are agreed to by trading partners during bilateral or multilateral negotiations on the trade of animals and animal products, and provide assurance that goods are free from specific diseases. Many countries seek to implement or adopt a more streamlined and secure method of information exchange, with some implementing the electronic exchange of certificates for cross-border trade. Such an exchange of data has many advantages over its paper counterpart, including a streamlined business process, better accessibility to information (particularly in advance of shipment arrival) and the reduction of fraudulent certificates. Although there are some challenges related to this initiative and important considerations to be taken into account for its implementation, many countries are becoming aware of its efficiencies, leading to more productive and mutually beneficial trading-partner relationships.Les certificats vétérinaires sont une composante essentielle des échanges internationaux d’animaux et de produits d’origine animale depuis de nombreuses années. Il s’agit de certificats approuvés préalablement par les partenaires commerciaux lors de négociations bilatérales ou multilatérales relatives aux échanges d’animaux et de produits d’origine animale et qui apportent la garantie que les marchandises échangées sont indemnes de certaines maladies spécifiées. Plusieurs pays ont cherché à mettre en oeuvre ou à valider une procédure d’échange d’informations à la fois plus simple et plus sûre ; parmi eux certains ont mis en place un système de certification électronique pour les échanges transfrontaliers. Ce type de transmission de données présente de nombreux avantages par rapport à la délivrance de certificats papier : un processus opérationnel rationalisé, un meilleur accès à l’information (en particulier avant l’arrivée d’une cargaison) et un nombre réduit de certificats frauduleux. Bien que certains problèmes en lien avec cette initiative restent encore à résoudre et que plusieurs aspects importants devront être pris en compte lors de sa mise en oeuvre, un nombre croissant de pays prennent conscience du fait que les performances d’un tel système contribueront à des relations plus productives et mutuellement bénéfiques entre partenaires commerciaux.Hace ya muchos años que los certificados veterinarios son un componente intrínseco del comercio de animales y productos de origen animal. Estos certificados, acordados por las partes en el curso de negociaciones bilaterales o multilaterales sobre ese tipo de comercio, aportan la garantía de que las mercancías están exentas de una u otra enfermedad. Muchos países están tratando de aplicar o adoptar un método más ágil y seguro para intercambiar información, y algunos están implantando el intercambio de certificados por vía electrónica para operaciones comerciales transfronterizas. Esta modalidad de transmisión de datos presenta muchas ventajas con respecto al uso del papel, en particular porque agiliza los procesos de trabajo, facilita el acceso a la información (en particular, antes de que llegue la mercancía) y reduce los casos de certificados fraudulentos. Aunque esta iniciativa no deja de presentar dificultades y hay importantes consideraciones que es preciso tener en cuenta para llevarla adelante, muchos países van cobrando conciencia de que trae consigo procesos más eficientes y se traduce en relaciones más productivas y mutuamente beneficiosas entre los socios comerciales.

This work reports on the application of a novel electric field-ionization setup for high-resolution laser spectroscopy measurements on bunched fast atomic beams in a collinear geometry. In combination with multi-step resonant excitation to Rydberg states using pulsed lasers, the field ionization technique demonstrates increased sensitivity for isotope separation and measurement of atomic parameters over previous non-resonant laser ionization methods. The setup was tested at the Collinear Resonance Ionization Spectroscopy experiment at ISOLDE-CERN to perform high-resolution measurements of transitions in the indium atom from the $$\text {5s}^2\text {5d}\,^2\text {D}_{5/2}$$5s25d2D5/2 and $$\text {5s}^2\text {5d}\,^2\text {D}_{3/2}$$5s25d2D3/2 states to $$\text {5s}^2n$$5s2np $$^2$$2P and $$\text {5s}^2n\text {f}\,^2$$5s2nf2F Rydberg states, up to a principal quantum number of $$n=72$$n=72. The extracted Rydberg level energies were used to re-evaluate the ionization potential of the indium atom to be $$46,670.107(4)\,\hbox {cm}^{-1}$$46,670.107(4)cm-1. The nuclear magnetic dipole and nuclear electric quadrupole hyperfine structure constants and level isotope shifts of the $$\text {5s}^2\text {5d}\,^2\text {D}_{5/2}$$5s25d2D5/2 and $$\text {5s}^2\text {5d}\,^2\text {D}_{3/2}$$5s25d2D3/2 states were determined for $$^{113,115}$$113,115In. The results are compared to calculations using relativistic coupled-cluster theory. A good agreement is found with the ionization potential and isotope shifts, while disagreement of hyperfine structure constants indicates an increased importance of electron correlations in these excited atomic states. With the aim of further increasing the detection sensitivity for measurements on exotic isotopes, a systematic study of the field-ionization arrangement implemented in the work was performed at the same time and an improved design was simulated and is presented. The improved design offers increased background suppression independent of the distance from field ionization to ion detection.

Molecular spectroscopy offers opportunities for the exploration of the fundamental laws of nature and the search for new particle physics beyond the standard model1–4. Radioactive molecules—in which one or more of the atoms possesses a radioactive nucleus—can contain heavy and deformed nuclei, offering high sensitivity for investigating parity- and time-reversal-violation effects5,6. Radium monofluoride, RaF, is of particular interest because it is predicted to have an electronic structure appropriate for laser cooling6, thus paving the way for its use in high-precision spectroscopic studies. Furthermore, the effects of symmetry-violating nuclear moments are strongly enhanced5,7–9 in molecules containing octupole-deformed radium isotopes10,11. However, the study of RaF has been impeded by the lack of stable isotopes of radium. Here we present an experimental approach to studying short-lived radioactive molecules, which allows us to measure molecules with lifetimes of just tens of milliseconds. Energetically low-lying electronic states were measured for different isotopically pure RaF molecules using collinear resonance ionisation at the ISOLDE ion-beam facility at CERN. Our results provide evidence of the existence of a suitable laser-cooling scheme for these molecules and represent a key step towards high-precision studies in these systems. Our findings will enable further studies of short-lived radioactive molecules for fundamental physics research., Measurements of low-energy electronic states of radium monofluoride validate predictions of the use of this short-lived radioactive molecule in exploring fundamental physics and provide evidence of its suitability for laser cooling.

A higher than baseline atmospheric concentration of the radioactive fission product 85Kr is considered to be the best indicator of clandestine plutonium separation. Additionally, its high volatility makes it suitable for detecting leaks in nuclear waste containers and damaged fuel cladding. A spectrometer for ultra-trace analysis is currently under development and will be optimised for atmospheric monitoring of 85Kr. This device is based on an adapted form of collinear resonance ionisation spectroscopy, a technique developed at ISOLDE-CERN for performing precision measurements on exotic nuclei. The motivation for this device is explored, along with an overview of progress and future developments.

A gas-filled linear Paul trap for the Collinear Resonance Ionisation Spectroscopy (CRIS) experiment at ISOLDE, CERN is currently under development. The trap is designed to accept beam from both ISOLDE target stations and the CRIS stable ion source. The motivation for the project along with the current design, simulations and future plans, will be outlined. peerReviewed

Rydberg positronium (Ps) atoms have been prepared in selected Stark states via two-step (1s→2p→nd/ns) optical excitation. Two methods have been used to achieve Stark-state selection: a field ionization filter that transmits the outermost states with positive Stark shifts, and state-selected photoexcitation in a strong electric field. The former is demonstrated for n=17 and 18 while the latter is performed for n=11 in a homogeneous electric field of 1.9 kV/cm. The observed spectral intensities and their dependence on the polarization of the laser radiation are in agreement with calculations that include the perturbations of the intermediate n=2 manifold. Our results pave the way for the generation of Rydberg Ps atoms with large electric dipole moments that are required for the realization of schemes to control their motion using inhomogeneous electric fields, an essential feature of some proposed Ps free-fall measurements requiring focused beams of long-lived atoms.

The incidence of atresia, concentrations of follicular fluid steroids, and circulating concentrations of estradiol, FSH, and progesterone were investigated to determine whether there was any evidence for a wave of follicular activity or atresia between Days 7 and 15 of the estrous cycle in pigs, Cyclic pigs (gilts) were slaughtered on Days 7, 9, 11, 13, and 15 (4, 4, 4, 4, and 3 pigs per day), and 287 follicles > 2 mm were dissected from ovaries to recover follicular fluid and granulosa cells. Apoptotic (Ao) granulosa cells were those containing sub-diploid DNA fluorescence as determined by flow cytometry. follicles with > or = 10% Ao granulosa cells were classified as atretic, and those with < 10% Ao granulosa cells were designated nonatretic. The percentage of atretic follicles (AF) per pig was 35.5 +/- 4.7 (mean +/- SEM), and while the percentage of AF ranged from 12% to 73%, means did not differ significantly among days. Mean follicular estradiol concentration was higher (p < 0.05) in nonatretic follicles (NAF) than in AF; in NAF, the concentration decreased (p < 0.05) from 15 ng/ml on Day 7 to 2.5 ng/ml on Day 11 and then increased (p < 0.05) to 10 ng/ml on Day 15 of the cycle. Mean follicular progesterone concentration was higher (p < 0.05) in AF than in NAF, while follicular androstenedione concentration (20 +/- 1.5 ng/ml, overall mean +/- SEM) did not differ between AF and NAF. Mean plasma estradiol, FSH, and progesterone concentrations did not differ among days of the cycle or differ significantly during the last 42 h before slaughter. Plasma estradiol and FSH concentrations were not significantly correlated with percentage of AF or with follicular steroid concentrations. These results support the notion of continuous growth and atresia of ovarian follicles in pigs independent of changes in plasma FSH and follicular steroid concentration, without evidence for a dominant cohort of follicles during the luteal phase of the estrous cycle.

Introduction: Maintenance therapy with lenalidomide (LEN) is considered standard of care in the US, supported by meta analysis showing that LEN maintenance is associated with significantly longer progression free survival (PFS) and overall survival (OS). In a previously reported study of MM patients (pts) treated with extended courses of LEN, we have described a polyclonal Ig and FLC elevation exceeding the upper limit of normal (up to 3-4 X the ULN) and associated with striking polyclonal bone marrow (BM) plasmacytosis (up to 20% of plasma cells (PCs)), occurring with a relatively high frequency (20% of pts) and associated with better outcome (Zamarin, Leukemia, 2013). Importantly, we cautioned about the risk of misinterpretation of this polyclonal Ig response and plasmacytosis. Since Immuno-histochemical staining (IHS) may often be an unreliable tool to distinguish between a reactive polyclonal plasmacytosis from monoclonal disease, especially when the percentage of PCs in the BM is relatively low (5 -15%), we aimed at confirming the polyclonal nature of this often unrecognized and paradoxical response to prolonged LEN exposure, and at validating the important role of BM assessment by flow cytometry (FACS) in this setting. Methods: Pts analyzed in this study were enrolled at MSKCC on three randomized, first line therapy, clinical trials (NCT01109004, NCT01208662, and NCT00807599). All pts were kept on LEN maintenance until POD, toxicity, or major event. BM aspirate and biopsy with IHS were performed as per standard of care. Eight-fluorochrome FACS method (minimum of 1 x 106 cells) was used for 2014 samples employing a surface marker cocktail (CD117 PC5.5, CD19 BV421, CD138 APC, CD56 PC7, CD45 APC-H7, CD38 BV510) and cytoplasmic Kappa FITC/Lambda PE staining. Ten-fluorochrome (minimum of 5 x 106 WBCs) method was used in 2015 and performed employing a surface marker cocktail (CD117 PC5.5, CD19 PC7, CD138 APC, CD56 APC-R700, CD45 APC-H7, CD81 Pacific Blue, CD38 BV510, CD27 BV605) and cytoplasmic Kappa FITC/Lambda PE staining. Results: Among 147 pts enrolled in the three trials, 55 achieved serologic CR after first line therapy. Of those, 46 had a BM biopsy with FACS analysis available. Among these 46 patients, bone marrow plasmacytosis as assessed by light microscopy of BM aspirate and biopsy ranged from 2% to 15% (32 pts had PCs ≤ 5%, 14 PCs > 5%). Among the 14 pts with > 5% PCs, 2 had PCs = 15%, 9 had PCs = 10%, and 3 between 6% and 9%. By FACS, 9 of 14 pts showed no clonal or phenotypically aberrant PCs. The percentage of aberrant PCs among all PCs in the other 5 pts remained low (≤7.3%). Among the 2 pts with PC = 15%, the percentage of aberrant PCs among all PCs was 0% and 7.3%. In pts with PC = 10%, the percentage of aberrant PCs among all PCs was 0% (6 pts), or ranged from 0.17% to 5.1% (3 pts). Figure 1 depicts representative pt cases with BM plasmacytosis estimated at 15% by light microscopy. PCs were gated based on CD38 and CD138 expression as well as forward and side scatter (not shown). Blue dots represent kappa LC expression; Red lambda LC. Proportion of aberrant PCs among total PCs in the sample is quantitated and shown using high sensitivity MRD detection with 10-color panel with 6-million event acquisitions. Panel A shows a pt with 15% PC in the BM with no residual disease confirming the polyclonal nature of the plasmacytosis. Panel B shows a pt with 15% PC exhibiting a low proportion of aberrant PCs (green) among a predominant background of normal polytypic PCs. In contrast, Panel C shows a pt with early relapsed disease with 15% PCs exhibiting a high proportion of aberrant PCs (99% of all PCs). Conclusions: These results confirm the common and striking polyclonal plasmacytosis (up to 15% PCs in this cohort) associated with prolonged LEN exposure, and the importance of FACS in the assessment of BM plasmacytosis in these MM pts. In the setting of current MM response criteria established by the IMWG and NCCN guidelines, mandating a BM plasmacytosis Figure 1 Figure 1. Disclosures Hassoun: Novartis: Consultancy; Binding Site: Research Funding; Celgene: Research Funding; Takeda: Consultancy, Research Funding. Roshal:BD Biosciences: Consultancy. Landau:Prothena: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Research Funding; Janssen: Consultancy; Spectrum Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees, Research Funding. Korde:Medscape: Honoraria. Landgren:Merck: Honoraria; BMS: Honoraria; Takeda: Honoraria; Amgen: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Medscape Myeloma Program: Honoraria.

Background : TheHevylite assay (HLC Assay) is a novel assay using antibodies that recognize unique conformational epitopes presented by the association of the heavy and light chain constant regions of intact immunoglobulins (Ig) allowing quantitative measurement of each Ig class concentration and generating ratios for each pair (e.g. IgGK/IgGL). Recent studies indicate that HLC Assay can enhance the ability to detect and quantify monoclonal Ig, potentially providing greater sensitivity for detection of minimal residual disease or early relapse after treatment and providing a prognostic indicator of progression free survival (Ludwig, H. et al. Leukemia (2013) 27, 213-219; Kraj, M. et al. Adv Clin Exp Med 2014, 23, 1, 127-133). While HLC Assay could simplify and enhance the assessment of monoclonal protein response in multiple myeloma (MM), its utility as compared to standard assays (SA) (Serum Protein Electrophoresis (SPEP) and Immunofixation (IF)) is not well established. The goal of this retrospective study was to compare the performance of these tests in patients with MM seen at Memorial Sloan Kettering Cancer Center. Methods : We have previously reported on the patterns of relapse and/or progression (R/POD) in 179 patients with MM transplanted between 2001 and 2009 at MSKCC and determined the precise date of R/POD based on IMWG standard clinical criteria using serum and urine PEP and IF, as well as Free Light Chain Assay (FLCA) (Zamarin, Bone Marrow Transplant, 2013). Serum samples from 63 of these patients, collected at the time of R/POD and/or at time points preceding R/POD were analyzed by HLC Assay and compared to results obtained by SA. Results : Among the 63 patients, 22 had IgA and 41 had IgG isotype. Overall, 207 samples were available for all 63 patients, including 72 IgA and 135 IgG samples. Figure 1 shows the concordance of Hevylite ratio (on the Y-axis) with the results obtained by SA (on the X-axis), for IgA and IgG samples, respectively. These graphs reveal an excellent association between HLC Assay and SA results in the IgA samples: all IgA samples revealing an M spike by SPEP had an abnormal HLC ratio even for low M spike levels (between 0 and 0.5 g/dL). Among IgA samples with a monoclonal band detectable by IF, 43 out of 48 samples also had an abnormal ratio by HLC Assay; and among samples with no detectable band by IF, 18 out of 24 had a normal ratio by HLC Assay (sensitivity 90%, specificity 75%, p< 0.001) (Table 1, Panel 1). Interestingly, when looking at samples taken prior to relapse in IgA patients having achieved CR, HLC Assay was abnormal in 4 out of 7 patients while SA was still reported as normal. In contrast, the lack of association between the SA and HLC Assay is striking for the IgG samples, with poor sensitivity for the HLC Assay to detect monoclonal gammopathies with M spikes below 1 g/dL on SPEP. Among IgG samples with a monoclonal band detectable by IF, only 48 out of 89 samples also had an abnormal ratio by HLC Assay; while among samples with no detectable band by IF, 40 out of 46 had a normal ratio by HLC Assay (sensitivity 53% and specificity of 86% , p < 0.001) (Table 1, Panel 2). Conclusions: Although retrospective, this analysis suggests the following: 1) HLC Assay may be more sensitive than IF or SPEP in patients with IgA disease, as it can detect an abnormal HLC ratio at a time prior to relapse by SA, when IF and SPEP are still normal; 2) HLC Assay appears to be less useful in IgG patients, as its sensitivity in these patients appears much lower than IF; 3) There is a need for further detailed analysis on larger prospective cohorts to test the utility of HLC Assay compared to SA in the management of multiple myeloma patients, especially those with IgA disease. Figure 1 Association between HLC Assay and SA (SPEP/IF) results in patients with IgA disease. Figure 1. Association between HLC Assay and SA (SPEP/IF) results in patients with IgA disease. Figure 2 Association between HLC Assay and SA (SPEP/IF) results in patients with IgG disease. Figure 2. Association between HLC Assay and SA (SPEP/IF) results in patients with IgG disease. Disclosures Hassoun: Celgene: Research Funding; Binding Site: Research Funding; Novartis: Consultancy; Takeda: Consultancy, Research Funding. Kazunori:Binding Site: Research Funding. Landau:Prothena: Honoraria, Membership on an entity's Board of Directors or advisory committees; Onyx/Amgen: Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Consultancy; Spectrum Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees. Korde:Medscape: Honoraria. Landgren:Takeda: Honoraria; Amgen: Honoraria, Research Funding; BMS: Honoraria; Medscape Myeloma Program: Honoraria; Merck: Honoraria; Celgene: Honoraria, Research Funding.

The incidence of atresia in the first group of follicles grown after ovulation was investigated in the pig. At slaughter, 113 follicles 3-6 mm in diameter were dissected from the ovaries of four pregnant pigs per day on Days 5, 6, and 7 after the onset of estrus. Granulosa cells were isolated from each follicle. The percentage of granulosa cells containing sub-diploid amounts of DNA (%Ao cells), a measure of apoptosis, was determined for each follicle by DNA fluorescence flow cytometry of propidium iodide (PI) stained nuclei of ethanol-fixed cells. Granulosa cell DNA condition was used to classify follicles. Follicles with > or = 10% Ao cells (n = 33) were designated biochemically atretic (BA), and follicles with or = 0.90, N = 22, p < 0.001). The incidence of pigs with BA follicles was 2 of 4, 3 of 4, and 4 of 4 on Days 5, 6, and 7, respectively. The %BA follicles per pig (mean +/- SEM) increased (p < or = 0.01) between Days 5 and 7; values were 6.2 +/- 3.6, 28.1 +/- 13.5, and 50.0 +/- 7.1, respectively, on Days 5, 6, and 7.(ABSTRACT TRUNCATED AT 250 WORDS)

Granulosa cells of individual follicles were analyzed by DNA fluorescence flow cytometry to determine how the percentage of cells with degraded DNA and the distribution of cells in the phases of the cell cycle (Go/G,, S,, G,/M) related to the incidence of morphological atresia and to changes in follicular steroid concentrations. Follicles were dissected from ovaries recovered at slaughter on Days 1, 3, 5, or 7 of altrenogest-synchronized preovulatory maturation. Twenty-one follicles with debris among their isolated granulosa cells were classified as morphologically atretic (MA); 92 follicles with debris-free granulosa cells were classified as morphologically healthy (MH). Granulosa cells were prepared for flow cytometry by fixation in 80% ethanol and staining with propidium iodide (PI) containing RNase. DNA fluorescence intensity was determined by use of the 488-nm line of an argon laser. A subpopulation of granulosa cells with degraded DNA (Ao cells), containing less fluorescence than the Go/G, peak, was found in the DNA histogram of every follicle. The percentage of A cells ranged from 0.02 to 83.6% per follicle. The percentage of Ao cells was inversely related to the percentage of Go/G, cells (r = -0.9611,p = 0.0001). The percentage of Ao cells (mean ± SEM) was greater (p = 0.0001) in MA (45.9 6.3%) than in MH follicles (5.3 + 1.6%). Follicular estradiol-171 was less in MA than in MH follicles, but androstenedione or progesterone did not differ significantly. A follicle biochemical health classification was derived from the percentage of Ao granulosa cells in the DNA histogram; 27 follicles were biochemically atretic (BA) with 10% Ao cells (mean 44.5 5.0%), while 86 follicles were biochemically healthy (BH) with < 10% Ao cells (mean 2.2 + 0.4% ). The percentage of BA follicles per pig was greater (p = 0.0001) on Day 5 (47%) than on any other day (10-22% ). Compared to BH follicles, BA follicles contained a reduced percentage of Go/G, and S+G2 /M cells and less estradiol-17[ and androstenedione (p s 0.05). The increased incidence of granulosa cells with low DNA fluorescence, measured by flow cytometry, is a new, biochemical marker for atretic follicles in the pig.

Many organisms modify their physiological functions by acclimating to changes in their environment. Recent studies of thermal physiology have been influenced by verbal models that fail to consider the selective advantage of acclimation and thus make no predictions about variation in acclimation capacity. We used a quantitative model of optimal plasticity to generate predictions about the capacity of Drosophila melanogaster to acclimate to developmental temperature. This model predicts that the ability to acclimate thermal sensitivity should evolve when temperature varies greatly among generations. Based on the model, we expected that flies from the highly seasonal environment of New Jersey would acclimate thermal sensitivity more than would flies from the less seasonal environment of Florida. When raised at constant and fluctuating temperatures, flies from these populations failed to adjust their thermal optima in the way predicted by the model, suggesting that current assumptions about functional and genetic constraints should be reconsidered.

Ovarian tissues were collected from 5 pigs on each of days 1, 3, 5, and 7 after withdrawal of an orally active progestin to determine changes in follicular inhibin subunit mRNAs during preovulatory maturation. Follicles (N = 146) were aspirated for fluid and homogenized in guanidinium isothiocyanate for RNA isolation. Follicular RNA and inhibin a andA subunit mRNA standards were dot-blotted, hybridized with (32Pj-cDNA probes, and quantified by densitometry. Mean concentrations of a mRNA (pg/i'g of RNA) increased (p � 0.05) by 140% as healthy follicles grew from medium (3-5 mm) to large (>5 mm). Inhibin immunoactivity was greater (p � 0.05) in large than medium follicles. In contrast, mean concentrations of Inhibinsubunit mRNA did not differ between healthy medium and large follicles. However, both a mRNA andmRNA increased (p � 0.05) linearly as foflicular diameter increased from 3 to 5 mm on Day I and from 3 to 9 mm on Day 3. On Day 5, a mRNA remained elevated, but was not significantly correlated with diameter. In contrast, �A mRNA decreased linearly (p < 0.05) as diameter increased from 6 to 11 mm on Day 5-The molar ratio a mRNA toA mRNA was 20:1 in healthy, large follicles on Days 3 and 5. Mean concentration of a mRNA in large follicles decreased (p

Thymocytes and granulosa cells (GC) were cultured up to 48 h to determine the effect of dexamethasone (DEX) on apoptosis in culture (in RPMI containing 10% fetal bovine serum [FBS] at 38 degrees C in a 5% CO2:95% air atmosphere). In experiment 2, GC were cultured for 24 h at a density of 0.5 x 10(6) cells/0.5 ml in Dulbecco's Modified Eagle's medium:Hams F-12 (1:1) containing 1% FBS to determine whether porcine FSH and insulin-like growth factor-I (IGF-I) attenuated apoptosis and to compare two methods of measuring apoptosis: 1) flow cytometry of dispersed cells for subdiploid DNA fluorescence and 2) densitometry of internucleosomal DNA fragments. The percentages of apoptotic (%A0) thymocytes and GC increased (p0.01) during 48 h of culture. Compared to no DEX, 0.1 or 1.0 microM DEX in thymocytes caused a 33% further increase (p0.01) in %A0 cells but had no effect in GC. In experiment 2, apoptosis, measured by %A0 GC and amount of internucleosomal fragments, decreased (p0.01) by 50% during culture in the presence of FSH (4 NIH-S1 mU/ml) or IGF-I (50 ng/ml); results from these techniques were correlated (r = 0.829, n = 44, por = 0.0001). We conclude that 1) porcine GC and thymocytes undergo spontaneous apoptosis in culture, 2) two methods of analyzing apoptosis were in excellent agreement, and 3) FSH and IGF-I attenuated spontaneous apoptosis in cultured porcine GC.

The Kimmeridge Clay Formation and its equivalents of Callovian to early Ryazanian age are by far the most important oil source rocks of the northern North Sea area. The source rocks comprise marine claystones which were deposited in waters of increased salinity with short episodes of high salinity, during which uranium-enriched shales accumulated. Much of the sedimentary sequence in the inner parts of the basin comprises mass-flow deposits and storm-activated reworked deposits. The mineralogy and quantity and quality of the organic content is extremely varied, both regionally and in vertical sequence. A comparison of the biomarker and other geo-chemical characteristics leads to a conclusion that at least eight definable kerogen types contribute to the organic content, and a knowledge of their distributions is necessary before oil to source rock correlation can be performed with confidence. However, such interpretations require a large database and computer-based multivariate analysis.

Granulosa cells of individual follicles were analyzed by DNA fluorescence flow cytometry to determine how the percentage of cells with degraded DNA and the distribution of cells in the phases of the cell cycle (Go/G1, S1, G2/M) related to the incidence of morphological atresia and to changes in follicular steroid concentrations. Follicles were dissected from ovaries recovered at slaughter on Days 1, 3, 5, or 7 of altrenogest-synchronized preovulatory maturation. Twenty-one follicles with debris among their isolated granulosa cells were classified as morphologically atretic (MA); 92 follicles with debris-free granulosa cells were classified as morphologically healthy (MH). Granulosa cells were prepared for flow cytometry by fixation in 80% ethanol and staining with propidium iodide (PI) containing RNase. DNA fluorescence intensity was determined by use of the 488-nm line of an argon laser. A subpopulation of granulosa cells with degraded DNA (Ao cells), containing less fluorescence than the Go/G1 peak, was found in the DNA histogram of every follicle. The percentage of Ao cells ranged from 0.02 to 83.6% per follicle. The percentage of Ao cells was inversely related to the percentage of Go/G1 cells (r = -0.9611, p = 0.0001). The percentage of Ao cells (mean +/- SEM) was greater (p = 0.0001) in MA (45.9 +/- 6.3%) than in MH follicles (5.3 +/- 1.6%). Follicular estradiol-17 beta was less in MA than in MH follicles, but androstenedione or progesterone did not differ significantly.(ABSTRACT TRUNCATED AT 250 WORDS)

Ovarian tissues were collected from 5 pigs on each of days 1, 3, 5, and 7 after withdrawal of an orally active progestin to determine changes in follicular inhibin subunit mRNAs during preovulatory maturation. Follicles (N = 146) were aspirated for fluid and homogenized in guanidinium isothiocyanate for RNA isolation. Follicular RNA and inhibin alpha and beta A subunit mRNA standards were dot-blotted, hybridized with [32P]-cDNA probes, and quantified by densitometry. Mean concentrations of alpha mRNA (pg/micrograms of RNA) increased (por = 0.05) by 140% as healthy follicles grew from medium (3-5 mm) to large (5 mm). Inhibin immunoactivity was greater (por = 0.05) in large than medium follicles. In contrast, mean concentrations of inhibin beta A subunit mRNA did not differ between healthy medium and large follicles. However, both alpha mRNA and beta A mRNA increased (por = 0.05) linearly as follicular diameter increased from 3 to 5 mm on Day 1 and from 3 to 9 mm on Day 3. On Day 5, alpha mRNA remained elevated, but was not significantly correlated with diameter. In contrast, beta A mRNA decreased linearly (p0.05) as diameter increased from 6 to 11 mm on Day 5. The molar ratio alpha mRNA to beta A mRNA was 20:1 in healthy, large follicles on Days 3 and 5. Mean concentration of alpha mRNA in large follicles decreased (p0.05) by 72% between Days 5 and 7, while beta A mRNA decreased to non-detectable levels on Day 7.(ABSTRACT TRUNCATED AT 250 WORDS)

In the pig, preovulatory follicle maturation is accompanied by increased immunoreactive plasma inhibin (1), decreased plasma FSH (1, 2), and increased atresia of nonovulatory follicles (2). Preovulatory follicles may be the major source of inhibin because granulosa cells cultured from large follicles, >5 mm in diameter, produced more inhibin than those from small follicles

Sodium benzyl penicillin, procaine penicillin and benethamine penicillin were applied into the bovine conjunctival sac as an aqueous solution or in ointment form in order to study the concentration-time profiles. The series of treatments was repeated in five animals in a random sequence. Penicillin concentration in conjunctival sac fluid (CF) was determined using the agar-well-diffusion assay technique. The data obtained were transformed to linear regression slopes. Similarity of the slopes within treatments (in five different eyes) enabled the construction of four common lines by co-variance analysis to represent each treatment. The regression coefficients of the four common lines were then compared to study the difference between treatments. Topical application of 5,000 iu sodium benzylpenicillin in aqueous solution at a concentration isotonic with 0.9% saline, produced a duration of therapeutic concentration (DTC) in CF of 12.6 +/- 1.5 h. When the same salt or other less water-soluble ones were formulated at the same concentration in an ointment base, the DTC was significantly prolonged. For all treatments, peak concentrations in CF were recorded at the first sampling and ranged between 7 iu/ml and 14 iu/ml. Sodium benzylpenicillin or procaine penicillin, both in the ointment base, produced DTCs of 38.8 +/- 2.1 h and 37 +/- 4.0 h, respectively, while the ointment formulation of benethamine penicillin produced a DTC of 56 +/- 4.5 h. The prolonged duration observed in the eye ointments can be partly accounted for by the viscous nature of the base. Other differences may be dependent on relative water solubility of each penicillin product and complexity of the surface mucosae of the eye.

Single dose, subconjunctival injections of procaine penicillin using either skin or conjunctival routes of administration were evaluated in order to compare the duration of antibacterial concentrations at the site of Moraxella bovis infection. Samples of conjunctival sac fluid (CF) were collected using blunted capillary tubes and were periodically assayed for penicillin by an agar-well-diffusion technique. Linear regression lines were constructed for concentration of penicillin-time profiles. Similarity of the regression slopes for each treatment enabled the construction of three common lines by the method of co-variance analysis in order to represent each treatment. Treatments were thereafter compared by the slopes of the common regression lines. A subconjunctival injection of procaine penicillin at a dose of 6 X 10(5) iu in 2 ml, administered either through the skin or through the conjunctiva, produced a peak penicillin concentration in the CF of approximately 8 iu/ml for either route and a duration of therapeutic concentration (DTC) of 67.6 +/- 4.9 and 40 +/- 2.7 h respectively. A dose of 3 X 10(5) iu in 1 ml, administered through the conjunctiva, produced a similar peak but the DTC was reduced to 35 +/- 4.2 h. The results of this study support field practices, as adequate penicillin concentrations were maintained by both techniques investigated.

Coals are oil source rocks in many of the Tertiary basins of Southeast Asia. The precursors of these hydrogen rich and oxygen poor coals are coastal plain peats which have mainly developed in an everwet and tropical climate. In these environments water flow and reworking can concentrate liptinitic kerogen in preference to vitrinitic kerogen. The distribution, petrography and chemistry of the coaly Miocene source rocks present in the Kutai Basin are described. The recognition of environmental controls on the accumulation of potentially oil-prone coals and coaly shales in deltaic environments is an aid to predictive source bed recognition in petroleum exploration. Comments on the environment of deposition of coaly sediments in the basins of the Norwegian Sea are discussed with reference to their possible oil and/or gas sourcing potential. The Triassic - Jurassic coals of the Haltenbanken area may become more oil-prone towards the delta margins, and facies mapping could aid oil exploration in this area.

When a dc arc is used for trace analysis on a spectrometer, calibration curves with a pronounced toe due to spectral background are found. For analysis of high purity materials it is most important that linear relationships should be established to ultra-trace levels when total impurity content is specified within the ppm level. A solution to this problem is outlined and the linear relationships obtained for copper, bismuth, and cadmium in high purity silver to 0.1 ppm are shown. An electronic circuit is described that enables these background corrections to be made.

In Part I it was shown how the values of the transmission and reflection of a sheet of a medium containing particles in suspension can he calculated. First the amounts of light scattered in the forward and forward directions from a single particle were determined; from these results the transmission 1 and rejection R for diffuse incident light were found for a layer of the disusing medium, when the effects of boundary reflections are negligible. At this stage, the expressions developed apply to a mist or fog consisting of particles suspended in air. Finally it was shown how, if the particles are suspended in some other medium, having a different refractive index from that of air, the transmission and reflection ז and p can be expressed in terms of T and R and the surface rejection coefficients. The more general expressions, for the case when the incident light is a parallel beam, were also developed. We shall now show how the absorption coefficient μ can be determined from photometric observations. As a check on the theory, we shall deduce the diameter D of the particles and the number N present per unit volume and compare these calculated values with those found by direct observation, Finally, the necessary modifications of the theory will be made to cover the case when the diffusing medium is in the form of a spherical shell.

To determine the effect of an IUD on the bactericidal capabilities of the rabbit uterus plastic spiral IUDs were implanted in 1 horn of each of 78 New Zeland white rabbits. After 1 month 1 horn of each of these rabbits and 32 sham-operated controls was ligated at each end and innoculated with Escherichia coli. The horns were flushed 2 4 or 8 hours later and E-coli colony counts done. Bactericidal activity was due to leukocytic debris around the IUD or to intensified acute responses to the bacteria both uterine horns of 14 rabbits were stimulated to produce a leukocytic response with an injection of egg albumin. After 18 hours the uteri of the 14 rabbits 10 of which had an IUD in 1 horn and 14 control rabgits were removed separated innoculated and incubated in the body cavity. Leukocytic responses were greater in the IUD-bearing horn suggesting that most of the increased bactericidal capabilities of intact IUD horns were due to an intensified response to the bacteria.

Extract Professional opinion was sought by a Taupo district farmer when he noticed what he took to be advanced cases of scabby mouth amongst one group of 3- to 4-month-old Romney lambs. These affected animals, and other groups of clinically normal lambs, had a 1 been “inoculated” with scab-by mouth vaccine by the farmer, at docking time 11 weeks previously. Most grazing on the farm was improved and in good condition after a wet and warm spring. Only the affected group of lambs and their ewes had been grazing on an unusually fibrous pasture.

Coals are oil source rocks in many of the Tertiary basins of Southeast Asia. The precursors of these hydrogen-rich and oxygen-poor coals are coastal plain peats which have mainly developed in an everwet and tropical climate. In these environments water flow and reworking can concentrate liptinitic kerogen in preference to vitrinitic kerogen. The distribution, petrography and chemistry of the coaly Miocene source rocks present in the Kutai Basin are described. Studies of Tertiary and contemporaneous coastal plain deposits can be applied to trends in source rock distribution in offshore Norway. Comments on the environment of deposition of coaly sediments in the basins of the Norwegian Sea are discussed with reference to their possible oil and/or gas sourcing potential. The Triassic—Jurassic coals of the Haltenbanken area may become more oil-prone towards the delta margins, and facies mapping could aid oil exploration in this area.

In and out of government, determining the cost of illness is a major concern. The allocation of health care resources and the evaluation of current research and program efforts depend in large measure on such information. This article updates the 1963 benchmark study of the cost of illness. For the 16 major diagnostic categories of illnesses, the cost is presented in terms of the direct costs for prevention,detection, and treatment; the morbidity losses due to disability; and the mortality losses resulting from premature death. The method of calculating the cost of any illness is described, and data necessary for the calculation are provided. In 1972, the estimated total cost of illness was $188 billion: $75 billion for direct costs, $42 billion for morbidity, and $71 billion for mortality. Diseases of the circulatory system were the most costly, representing about one-fifth of all costs of illness.

Right ventricular hypertrophy in elastase-induced emphysema in the System hamster was assessed by either the weight of the right ventricle as a fraction of body-weight or by the ratio of the weight of the right to the left ventricle. Right ventricular hypertrophy accompanies elastase-induced emphysema and is more severe in hamsters injected with elastase while fed a diet containing 0.5% beta-aminopropionitrile (BAPN), a combination that causes more severe emphysema. Measurements of arterial blood oxygen pressures showed that emphysematous animals were hypoxemic. Treatment of emphysematous animals with 35% O2 either during the development of right ventricular hypertrophy or after it had developed produced measurable amelioration of the hypertrophy in those groups with the more severe emphysema (elastase plus BAPN diet) but did not completely prevent it. The oxygen had no effect on the severity of the emphysema measured morphometrically. These results indicate that the cor pulmonale in elastase-induced emphysema is probably multifactorial, but hypoxia appears to be one of the major factors.

Regional studies of the petroleum geochemistry of the central and northern North Sea have been based on analyses of field sections and samples from approximately 150 released well sections available to Robertson Research International Limited. They show that hydrocarbon source rocks may occur at many levels from Cambrian to Recent, but that the principal source rock is the Kimmeridge Clay Formation and equivalent formations of Late Jurassic to Early Cretaceous age. Methods of evaluating the quality and quantity of this source rock are described and have been integrated with maturity data to obtain estimates of oil productivity. Potentially oil-generating organic matter preserved in the Kimmeridge Clay Formation is derived from both waxy plant detritus and algal material o iginating in the marine environment. The two important oil provinces of the East Shetland Basin and the Ekofish Complex contain examples of oil derived from "waxy" land plant and marine algal type source rocks, respectively. We also discuss the presence of gas in this important oil province and the distribution of low gravity oil.