Precision Measurement of sin^2 theta_W at a Reactor

This paper presents a strategy for measuring sin^2 theta_W to ~1% at a reactor-based experiment, using antineutrinos electron elastic scattering. This error is comparable to the NuTeV, SLAC E158, and APV results on sin^2 theta_W, but with substantially different contributions to the systematics. An improved method for identifying antineutrino proton events, which serve both as a background and as a normalization sample, is described. The measurement can be performed using the near detector of the presently proposed reactor-based oscillation experiments. We conclude that an absolute error of delta(sin^2 theta_W)=0.0019 may be achieved.Comment: To be Submitted to Phys. Rev.

Glucocorticoids rapidly inhibit oxytocin-stimulated adrenocorticotropin release from rat anterior pituitary cells, without modifying intracellular calcium transients

Glucocorticoid hormones suppress the secretion of ACTH evoked by secretagogues such as CRF and arginine vasopressin. In this study, we investigated the effects of glucocorticoids on ACTH release induced by oxytocin (OT) and on intracellular free calcium ion levels in corticotropes prepared from the adenohypophyses of female Wistar rats. Pulsatile additions of physiological concentration of OT (10 nM) to superfused anterior pituitary cells caused pulsatile ACTH release about 4-fold above basal secretion with similar peak amounts of ACTH during subsequent OT pulses. Exposure of the cells to corticosterone (100 nM) or to a selective glucocorticoid receptor agonist RU 28362 (100 nM) for 30 min suppressed OT-stimulated but not basal ACTH release by approximately 60%. Inhibition gradually disappeared during subsequent pulses of OT in the absence of corticosterone. Pretreatment with the selective antagonist RU 38486 (1 microM) completely blocked the inhibitory effect of corticosterone on OT-induced ACTH secretion. Changes in free cytosolic calcium levels in single cultured pituitary cells were measured using the calcium indicator Fura-2. OT caused calcium transients in corticotropes, which were identified by immunocytochemistry. They responded in a similar manner to a second OT stimulus when preincubated for 30 min with corticosterone (1 microM) or with RU 28362 (1 microM). Our data indicate that glucocorticoids, via glucocorticoid receptors, rapidly inhibit OT-stimulated ACTH secretion by corticotropes without affecting intracellular calcium transients due to OT. Therefore, we conclude that rapid inhibition of ACTH release by glucocorticoids interferes with cellular signal transduction beyond the step of calcium mobilization

Using Reactors to Measure θ13\theta_{13}

A next-generation neutrino oscillation experiment using reactor neutrinos could give important information on the size of mixing angle $\theta_{13}$. The motivation and goals for a new reactor measurement are discussed in the context of other measurements using off-axis accelerator neutrino beams. The reactor measurements give a clean measure of the mixing angle without ambiguities associated with the size of the other mixing angles, matter effects, and effects due to CP violation. The key question is whether a next-generation experiment can reach the needed sensitivity goals to make a measurement for $\sin^{2}2\theta_{13}$ at the 0.01 level. The limiting factors associated with a reactor disappearance measurement are described with some ideas of how sensitivities can be improved. Examples of possible experimental setups are presented and compared with respect to cost and sensitivity

Oxytocin at physiological concentrations evokes adrenocorticotropin (ACTH) release from corticotrophs by increasing intracellular free calcium mobilized mainly from intracellular stores. Oxytocin displays synergistic or additive effects on ACTH-releasing factor or arginine vasopressin-induced ACTH secretion, respectively

The potency of oxytocin (OT) in evoking ACTH secretion by isolated, superfused rat adenohypophyseal corticotrophs and its enhancement by CRF and arginine vasopressin (AVP) were analyzed. Each secretagogue effectively released ACTH from adenohypophyseal cells when added separately in pulsatile fashion in physiological concentrations based on hypophyseal portal blood (OT, 10 nM; AVP, 0.5 nM; CRF, 0.1 nM). OT released ACTH at concentrations as low as 1 nM. Moreover, a dose- response relationship up to 10 microM was revealed. Combinations of a constant amount of CRF (0.1 nM) with increasing concentrations of OT exerted a synergistic effect on ACTH release. In contrast, OT given in various concentrations in combination with AVP (0.5 nM) produced an additive effect on ACTH release. To study the mechanism of action of OT on ACTH secretion, cytosolic free calcium levels in single pituitary cells exposed to OT or AVP were measured using the calcium-sensitive fluorescent indicator Fura-2. Corticotrophs among mixed adenohypophyseal cell types in the primary cultures were identified by immunocytochemistry. More than 500 cells were individually stimulated with OT or AVP. Basal cytosolic free calcium levels ranged between 80- 130 nM free calcium. The addition of 100 nM OT or 1 microM AVP increased the cytosolic free calcium concentration within 3 sec to values ranging from 500-800 nM. An increase in intracellular calcium ranging from 200-500 nM due to OT could still be observed after extracellular calcium depletion. Taken together, our data demonstrate that physiological concentrations of OT stimulate ACTH secretion, independent of the other ACTH secretagogues, by mobilizing calcium mainly from intracellular stores

Effect of oxytocin on free intracellular Ca2+ levels and progesterone release by human granulosa-lutein cells

Oxytocin and its receptor are found in the corpus luteum in a variety of species, including the human. In the present study we used fura-2 microfluorimetry to investigate whether activation of the oxytocin receptor of cultured human granulosa-lutein cells causes intracellular calcium (Ca2+) signals and affects progesterone release. Although after 1 day in culture, cells were not responsive to oxytocin, the number of responsive cells increased steadily during the first 3 days in culture, reaching a maximum on days 4 and 5 (59-66%) and then declined again until day 8. Effective oxytocin concentrations were apparently independent of the culture day, and concentrations as low as 10 nmol/L increased intracellular free Ca2+ levels from 70-140 nmol/L (basal levels) to maximal peak levels of 800 nmol/L. The oxytocin-induced Ca2+ signal was not affected by removal of extracellular Ca2+ with EGTA. Moreover, depletion of intracellular Ca2+ stores by ionomycin treatment rendered the cells unresponsive to oxytocin, pointing also at the intracellular source of the oxytocin-inducible Ca2+ signal. Interestingly, after one single stimulation with oxytocin, cells became refractory to additional stimuli, and only extremely high concentrations of oxytocin induced a second increase in intracellular free Ca2+. To examine the possible effects of oxytocin on progesterone release by cultured cells, we incubated cells on culture day 2 (20% responsive cells in the fura measurements) and culture day 5 (66% responsive cells in the fura measurements) for 24 h with oxytocin (10 nmol/L) and hCG (10,000 IU/L). Although hCG significantly stimulated progesterone release, oxytocin alone was without a stimulatory effect on either day. However, a significant augmentation of the effect of hCG on progesterone release was found in incubations of cells on day 5. Interestingly, the effects of hCG also included stimulation of oxytocin release by cultured granulosa-lutein cells into the culture medium, as determined by RIA. In summary, our data indicate the presence of a functional oxytocin receptor on human granulosa-lutein cells that is linked to Ca2+ as a second messenger released from intracellular Ca2+ stores. The number of oxytocin-responsive cells increases during differentiation in culture. Moreover, oxytocin release induced by hCG and a stimulatory effect of oxytocin on the hCG-induced progesterone production during the period of maximal responsiveness of cultured cells were found. We, therefore, propose that oxytocin may have autocrine and/or paracrine functions in human granulosa-lutein cells, including fine-tuning of progesterone release

РАЗЛИЧИЕ РАКА ТОЛСТОЙ И ПРЯМОЙ КИШКИ С ТОЧКИ ЗРЕНИЯ ЭПИДЕМИОЛОГИИ, КАНЦЕРОГЕНЕЗА, МОЛЕКУЛЯРНОЙ БИОЛОГИИ, ПЕРВИЧНОЙ И ВТОРИЧНОЙ ПРОФИЛАКТИКИ: ДОКЛИНИЧЕСКИЕ ИССЛЕДОВАНИЯ

Introduction. Colon and rectal cancer (CC, RC) are different entities from a clinical and tumor biological point of view. Up to now, both, CC and RC, are synonymously called  “Colorectal Cancer” (CRC). With our experience in basic and clinical research and routine  work in this field we now have come to the opinion, that the term “CRC” should definitely be questioned, and if justified, be abandoned.Materials/Methods. We analyzed the actual available data from the literature and our own  results from the Ulm based study group FOGT to proof or reject our hypothesis.Results. The following evident differences were recognized: Anatomically, the risk to  develop RC is 4× higher than for CC. Molecular changes in carcinogenesis in CC are different from RC. Physical activity helps to prevent CC, not RC. Pathologically there are differences between RC and CC. In addition, there are also major clinical differences  between CC and RC, such as in surgical topography and– procedures, multimodal treatment  (MMT) approaches (RC in MMT is less sensitive to chemotherapy than CC), and prognostic  factors for the spontaneous course and for success of MMT (e.g. TS or DPD ). Discussion. CC ´sand RC´s definitely are different in parameters of causal and formal carcinogenesis, effectivity of primary prevention by physical activity, conventional and  molecular pathology.According to our findings we can demand from the preclinical point of  view that CC and RC are two different tumor entities in terms of various representative  biological characteristics.CC and RC are also differing substantially in many clinical features, as outlined in a separate paper from our group.Conclusion. “CRC” should no longer be used in basic and clinical research and other fields  of cancer classification as a single disease entity. CC is not the same as RC. CC might even be divided into right and left CC.Введение. Рак толстой и прямой кишки – разные опухоли с клинической и биологической точек зрения. В  настоящее время рак толстой и прямой кишки синонимично называют колоректальным раком. Основываясь  на нашем опыте в фундаментальных и клинических исследованиях в этой области, мы пришли к выводу, что  термин «колоректальный рак» необходимо пересмотреть, его нельзя использовать как обобщающее понятие.Материал и методы. Были проанализировали данные литературы и собственные результаты исследований, чтобы доказать или отклонить эту гипотезу.Результаты. Выявлены следующие очевидные различия: риск развития рака прямой кишки в 4 раза выше,  чем рака толстой кишки; молекулярный канцерогенез при раке толстой кишки отличается от рака прямой  кишки; физическая активность помогает предотвратить рак толстой кишки, но не прямой кишки;  существуют патогистологические различия между раком прямой и толстой кишки. Кроме того, имеются  значительные клинические отличия между этими злокачественными новообразованиями, такие как  различная хирургическая топография и объемы операций, разные показания для назначения  комбинированного лечения, поскольку рак прямой кишки менее чувствителен к химиотерапии, чем рак  толстой кишки, и отличаются прогностические факторы эффективности мультимодальной терапии  (например, тимидилат синтетаза и дигидропиримидин дегидрогеназа).Дискуссия. Рак толстой и прямой кишки определенно различаются по этиологии и формальному  канцерогенезу, эффективности первичной профилактики, связанной с физической активностью, обычной и  по параметрам молекулярной патологии. Согласно нашим данным, можно утверждать, что с доклинической  точки зрения рак толстой и прямой кишки являются двумя разными опухолями, поскольку обладают  различными репрезентативными биологическими характеристиками. Рак толстой и прямой кишки также  существенно различаются по многим клиническим признакам, что было указано в отдельной статье,  представленной нашей исследовательской группой. Заключение. Термин «колоректальный рак» не должен  использоваться в фундаментальных и клинических исследованиях, как определение единого заболевания.  Рак толстой кишки не одно и то же, что и рак прямой кишки. Злокачественные новообразования толстой  кишки могут быть разделены на рак правой и левой половины ободочной кишки

Evolution of a fluorinated green fluorescent protein

The fluorescence of bacterial cells expressing a variant (GFPm) of the green fluorescent protein (GFP) was reduced to background levels by global replacement of the leucine residues of GFPm by 5,5,5-trifluoroleucine. Eleven rounds of random mutagenesis and screening via fluorescence-activated cell sorting yielded a GFP mutant containing 20 amino acid substitutions. The mutant protein in fluorinated form showed improved folding efficiency both in vivo and in vitro, and the median fluorescence of cells expressing the fluorinated protein was improved {approx}650-fold in comparison to that of cells expressing fluorinated GFPm. The success of this approach demonstrates the feasibility of engineering functional proteins containing many copies of abiological amino acid constituents

Barriers Inhibiting Industry from Partnering with Universities: Evidence from the Advanced Technology Program

A small sample of 38 Advanced Technology Projects funded between 1993 and 1996 are surveyed to explore the reasons for university non-participation, or, in the cases where they did participate, whether the partnerships encountered any difficulties from their participation. 32 percent report that intellectual property issues were an insurmountable barrier to university participation. Such barriers are more likely when the ATP share of funding is high and when the expected duration of the research is relatively short. They are also somewhat more likely for projects involving chemical technology, and when industrial participants have had previous experience with universities as research partners. These difficulties over IP may arise because the cultures in the two institutional forms differ, or because the original ATP guidelines do not recognize the existence of the Bayh-Dole Act (which grants universities title to inventions made by their employees using outside funding).

Universities as Research Partners

Universities are a key institution in the US innovation system and an important aspect of their involvement is the role they play in Private-Public Partnering activities. This study seeks to gain a better understanding of the performance of university-industry research partnerships using a sample survey of pre-commercial research projects funded the U.S. government's Advanced Technology Program. Although results must be interpreted cautiously due to the small size of the sample, the study finds that projects with university involvement tend to be in areas involving "new" science and therefore experience more difficulty and delay but also are more likely not to be aborted prematurely. We interpret this finding to imply that universities are contributing to basic research awareness and insight among the partners in ATP-funded projects.