Absence of Low-Energy Shape Coexistence in

The ^{80}Ge structure was investigated in a high-statistics ß-decay experiment of ^{80}Ga using the GRIFFIN spectrometer at TRIUMF-ISAC through γ, ß-e, e-γ, and γ-γ spectroscopy. No evidence was found for the recently reported 0_{2}^{+} 639-keV level suggested as evidence for low-energy shape coexistence in ^{80}Ge. Large-scale shell model calculations performed in ^{78,80,82}Ge place the 0_{2}^{+} level in ^{80}Ge at 2 MeV. The new experimental evidence combined with shell model predictions indicate that low-energy shape coexistence is not present in ^{80}Ge.

Publisher's Note: Direct Lifetime Measurements of the Excited States in

This corrects the article DOI: 10.1103/PhysRevLett.116.122502.

Lifetime Measurements and Triple Coexisting Band Structure in

Lifetime measurements of excited states in the neutron-rich nucleus ^{43}S were performed by applying the recoil-distance method on fast rare-isotope beams in conjunction with the Gamma-Ray Energy Tracking In-beam Nuclear Array. The new data based on γγ coincidences and lifetime measurements resolve a doublet of (3/2^{-}) and (5/2^{-}) states at low excitation energies. Results were compared to the π(sd)-ν(pf) shell model and antisymmetrized molecular dynamics calculations. The consistency with the theoretical calculations identifies a possible appearance of three coexisting bands near the ground state of ^{43}S: the K^{π}=1/2^{-} band built on a prolate-deformed ground state, a band built on an isomer with a 1f_{7/2}^{-1} character, and a suggested excited band built on a newly discovered doublet state. The latter further confirms the collapse of the N=28 shell closure in the neutron-rich region.

Enhanced Electric Dipole Strength for the Weakly Bound States in

An enhanced low-energy electric dipole (E1) strength is identified for the weakly bound excited states of the neutron-rich isotope ^{27}Ne. The Doppler-shift lifetime measurements employing a combination of the γ-ray tracking array GRETINA, the plunger device, and the S800 spectrograph determine the lower limit of 0.030 e^{2} fm^{2} or 0.052 W.u. for the 1/2^{+}→3/2^{-} E1 transition in ^{27}Ne, representing one of the strongest E1 strengths observed among the bound discrete states in this mass region. This value is at least 30 times larger than that measured for the 3/2^{-} decay to the 3/2_{gs}^{+} ground state. A comparison of the present results to large-scale shell-model calculations points to an important role of core excitations and deformation in the observed E1 enhancement, suggesting a novel example of the electric dipole modes manifested in weakly bound deformed systems.

Isomeric Character of the Lowest Observed 4

Previous experiments observed a 4^{+} state in the N=28 nucleus ^{44}S and suggested that this state may exhibit a hindered E2-decay rate, inconsistent with being a member of the collective ground state band. We populate this state via two-proton knockout from a beam of exotic ^{46}Ar projectiles and measure its lifetime using the recoil distance method with the GRETINA γ-ray spectrometer. The result, 76(14)_{stat}(20)_{syst} ps, implies a hindered transition of B(E2;4^{+}→2_{1}^{+})=0.61(19) single-particle or Weisskopf units strength and supports the interpretation of the 4^{+} state as a K=4 isomer, the first example of a high-K isomer in a nucleus of such low mass.

Direct Lifetime Measurements of the Excited States in (72)Ni.

The lifetimes of the first excited 2^{+} and 4^{+} states in ^{72}Ni were measured at the National Superconducting Cyclotron Laboratory with the recoil-distance Doppler-shift method, a model-independent probe to obtain the reduced transition probability. Excited states in ^{72}Ni were populated by the one-proton knockout reaction of an intermediate energy ^{73}Cu beam. γ-ray-recoil coincidences were detected with the γ-ray tracking array GRETINA and the S800 spectrograph. Our results provide evidence of enhanced transition probability B(E2;2^{+}→0^{+}) as compared to ^{68}Ni, but do not confirm the trend of large B(E2) values reported in the neighboring isotope ^{70}Ni obtained from Coulomb excitation measurement. The results are compared to shell model calculations. The lifetime obtained for the excited 4_{1}^{+} state is consistent with models showing decay of a seniority ν=4, 4^{+} state, which is consistent with the disappearance of the 8^{+} isomer in ^{72}Ni.

Evolution of collectivity in 72Kr: evidence for rapid shape transition.

The transition rates from the yrast 2+ and 4+ states in the self-conjugate 72Kr nucleus were studied via lifetime measurements employing the GRETINA array with a novel application of the recoil-distance method. The large collectivity observed for the 4+→2+ transition suggests a prolate character of the excited states. The reduced collectivity previously reported for the 2+→0+ transition was confirmed. The irregular behavior of collectivity points to the occurrence of a rapid oblate-prolate shape transition in 72Kr, providing stringent tests for advanced theories to describe the shape coexistence and its evolution.

Sacral neuromodulation stimulation for IC/PBS, chronic pelvic pain, and sexual dysfunction.

This study aims to review the use of sacral neuromodulation in the patient population with painful bladder syndrome/interstitial cystitis (PBS/IC), chronic pelvic pain (CPP), and sexual dysfunction. A literature review of the current research was carried out. This article highlights the current research findings and uses of sacral neuromodulation in patients with PBS/IC, CPP, vulvar vestibulitis, and erectile dysfunction. Current research on sacral neuromodulation on the abovementioned patient population has shown potential efficacy in pilot studies, though larger, multi-centered trials with long-term follow-up are needed.

Depression, abuse and its relationship to interstitial cystitis.

This study evaluated the prevalence of depression, sexual abuse, and physical abuse among women diagnosed with interstitial cystitis (IC). One hundred forty-one subjects completed the validated Beck's Depression Inventory II Questionnaire (BDI-II) and the validated Drossman Abuse Questionnaire. Ninety-seven (69%) subjects scored 14 or higher on the BDI-II, corresponding to depression. When compared to the US prevalence of 9%, this was significantly higher. Fifty-one subjects (36%) reported sexual abuse which is higher than the US average. The prevalence of childhood sexual abuse in the sample was not significantly different than the US average. The prevalence of physical abuse in the sample was not statistically different than the US average. Women with IC appear to have a higher prevalence of depression and sexual abuse than the general population. Women with IC should be screened for depression and abuse and referred to a mental health expert as necessary for treatment.

Treatment of mice with IL-12 DNA constructs leads to augmented NK activity in lungs but low IFN-gamma release -- implications for Bordetella pertussis infections following aerosol challenge.

Interleukin-12 protein has been widely used experimentally in therapeutic and adjuvant settings in the treatment of different diseases including intra-cellular bacterial infections. The in vivo clearance of Bordetella pertussis infections in naive mice and in animals vaccinated with whole cell vaccine is considered to be a Th-1 dependent mechanism. Furthermore, the addition of IL-12 protein to an acellular pertussis vaccine increases the efficacy of this vaccine. Whilst the use of IL-12 protein is often beneficial, a number of problems there are associated with this cytokine including toxicities and down regulation of normal immune functions. The use of DNA constructs encoding this cytokine may be a way of achieving maximum therapeutic benefit with minimum toxicity. The aims of this study were to optimise the effects of two IL-12 DNA constructs, especially with respect to augmenting pulmonary immune responsiveness and to compare the effect of IL-12 DNA and IL-12 protein on bacterial colonisation of lungs following aerosol challenge with B. pertussis. We found that IL-12 DNA constructs augmented the activity of pulmonary NK cells but had little effect on the course of B. pertussis infections in mice. In contrast to IL-12 protein, the DNA constructs had no immunosuppressive effects on splenic lymphocyte mitogen responses.

High dose interleukin-12 exacerbates Bordetella pertussis infection and is associated with suppression of cell-mediated immunity in a murine aerosol challenge model.

The in-vivo clearance of Bordetella pertussis infections in murine models in naive mice and animals vaccinated with whole-cell vaccine is considered to be via a Th-1-dependent mechanism in which interleukin-12 (IL)-12 may play a prominent role. It has also been demonstrated clearly that the treatment of animals with macrophage-derived IL-12 administered with an acellular vaccine can increase the efficacy of this vaccine preparation to levels seen with the whole-cell vaccine. However, the effects of exogenously added IL-12 on immune responses in non-vaccinated B. pertussis-challenged mice remain unclear, with two studies giving contradictory findings. In this study we have treated mice with escalating doses of mIL-12 (0.1-10 microg/mouse) prior to challenge with B. pertussis (using an aerosol challenge model of infection). The ability of mice to clear infection was assessed in IL-12 treated and in phosphate buffered saline (PBS) control animals at days 6 and 13 post-challenge. Lymphoid cells were isolated from spleen and cell-mediated immune responses assessed at days 1, 6 and 13 post-challenge. In addition, the direct effects of high-dose IL-12 on challenged mice was assessed by checking natural killer (NK) activity from isolated lung and spleen lymphoid cells as well as interferon-gamma (IFN-gamma) generation from isolated cells and serum at day 1 post-challenge. The results from this study show that bacterial colonization of the lungs is actually enhanced following treatment with high-dose IL-12. This is associated with impaired cellular immune responses. The mechanisms associated with the immunosuppressive effects of IL-12 are discussed.

Phylogenetic conservation of the makorin-2 gene, encoding a multiple zinc-finger protein, antisense to the RAF1 proto-oncogene.

Natural endogenous antisense RNAs have been reported in multiple loci, with evidence in some cases supporting a regulatory role for the antisense transcript. Here, we describe a novel gene, makorin RING zinc finger-2 (MKRN2), that overlaps and is antisense to the gene RAF1 in mammals. Phylogenetic analysis of the 3' untranslated region of RAF1 orthologues suggests that this relationship may have existed for up to 450 million years. We have also identified MKRN2 orthologues in two species of fish. This places the gene duplication event that created this locus from an ancestral MKRN1 gene early in vertebrate evolution, over 450 million years ago. Northern blot analyses show that human MKRN2 and RAF1 are co-expressed in tissues and cell lines, raising the possibility of mRNA duplex formation. The encoded makorin-2 protein is likely a ribonucleoprotein of unknown function, but its conservation suggests an important cellular role. The data presented here describe a conserved vertebrate MKRN2 gene that is closely associated with the RAF1 locus.

Sensitivity and specificity of antiproliferative factor, heparin-binding epidermal growth factor-like growth factor, and epidermal growth factor as urine markers for interstitial cystitis.

We previously determined that the urine of interstitial cystitis (IC) patients specifically contains a factor (antiproliferative factor [APF]) that inhibits primary bladder epithelial cell proliferation, and that it has significantly decreased levels of heparin-binding epidermal growth factor-like growth factor (HB-EGF) and increased levels of epidermal growth factor (EGF) compared with urine from asymptomatic controls and patients with bacterial cystitis. We sought to confirm the specificity of these findings for IC using a larger patient population, including control patients with a variety of urogenital disorders. Clean catch urine specimens were collected from 219 symptomatic IC patients, 113 asymptomatic controls without bladder disease, and 211 patients with various urogenital diseases including acute bacterial cystitis, vulvovaginitis, chronic nonbacterial prostatitis, overactive bladder, hematuria, stress incontinence, neurogenic bladder, benign prostatic hyperplasia, bladder or pelvic pain without voiding symptoms, bladder cancer, prostate cancer, or miscellaneous diagnoses including anatomic disorders. APF activity was determined by (3)H-thymidine incorporation into primary normal adult human bladder epithelial cells. HB-EGF and EGF levels were determined by enzyme-linked immunosorbent assay. APF activity was present significantly more often in IC than control urine specimens (P <0.005 for IC vs any control group; sensitivity = 94%, specificity = 95%, P <10(-82) for IC vs all controls). HB-EGF levels were also significantly lower and EGF levels significantly higher in IC urine than in specimens from controls (P <10(-84) and P <10(-36), respectively). These findings confirm the utility of APF, HB-EGF, and EGF as markers for IC. Understanding the reasons for altered levels of these markers may lead to understanding the pathogenesis of this disorder.

Psychometric validation of the O'leary-Sant interstitial cystitis symptom index in a clinical trial of pentosan polysulfate sodium.

The O'Leary-Sant Interstitial Cystitis Symptom Index (ICSI) has been proposed as a treatment outcome measure in interstitial cystitis (IC). The psychometric properties of the ICSI were assessed for reliability and validity in a randomized, double-blind clinical study of 300, 600, and 900 mg daily dose of pentosan polysulfate sodium (PPS) in patients with IC. The ICSI contains 4 items that measure urgency and frequency of urination, nighttime urination, and pain or burning. The ICSI index score is the sum of the item scores (range: 0-20). ICSI scores were obtained at baseline, 4, 8, 12, 16, 24, and 32 weeks of treatment. Patients' overall ratings of improvement of symptoms (PORIS) scores evaluating improvements in pain, urgency, and overall IC symptoms were also collected except at baseline. A total of 376 patients were included in the analysis. Psychometric properties evaluated included variability (range), test-retest reliability (intraclass correlation coefficient [ICC]), internal consistency (the Cronbach alpha), construct validity (convergent, discriminant), responsiveness, and clinically meaningful change. The ICSI items and index score had good variability and test-retest reliability. The ICSI demonstrated internal consistency reliability and was responsive to change. Participants indicating a 75% improvement in PORIS had a 48% mean reduction in the ICSI score, while participants reporting 100% improvement in PORIS had a 77% mean reduction in the ICSI score. The ICSI is a valid, reliable, and responsive measure of change in IC symptoms. This outcome measure should be utilized in future treatment outcomes studies in IC.

Interstitial cystitis and pelvic floor dysfunction: a comprehensive review.

Interstitial cystitis is a clinical condition occurring predominantly in women and is characterized by urinary frequency, urgency, and pain. Patient symptoms have the potential to significantly affect quality of life, posing a challenge to some to perform activities of daily living. This article comprehensively reviews the literature on the epidemiology, etiology, evaluation, and treatment of interstitial cystitis, and considers commonly associated pelvic floor dysfunction.

Cyclobutane carboxamide inhibitors of fungal melanin: biosynthesis and their evaluation as fungicides.

A new fungicide lead has been identified by enzyme screening of a focused combinatorial library. The lead compound 4, a potent inhibitor of scytalone dehydratase (SD), exhibits fungicidal activity upon foliar application but does not show systemic activity. The X-ray crystal structure of the enzyme-inhibitor complex and an appreciation for the relationship between physical properties and systemic activity enabled us to rapidly improve upon this initial lead. The geminal halogen-methyl group combination was found to be optimal for interaction with the bounding serine and asparagine side-chain residues. Replacement of CF3 with methyl was a key discovery, giving inhibitors with slightly diminished enzyme inhibition potency while significantly increasing systemic activity. Amides prepared from amines with 2,4-dichloro substitution on the phenyl ring gave the most potent enzyme inhibitors. Two compounds from this series showed systemic activity comparable to the commercial standard and were selected for outdoor testing in flooded plots which simulate rice paddies.