JLab Measurements of the

The charge and magnetic form factors, F_{C} and F_{M}, respectively, of ^{3}He are extracted in the kinematic range 25 fm^{-2}≤Q^{2}≤61 fm^{-2} from elastic electron scattering by detecting ^{3}He recoil nuclei and scattered electrons in coincidence with the two High Resolution Spectrometers of the Hall A Facility at Jefferson Lab. The measurements find evidence for the existence of a second diffraction minimum for the magnetic form factor at Q^{2}=49.3 fm^{-2} and for the charge form factor at Q^{2}=62.0 fm^{-2}. Both minima are predicted to exist in the Q^{2} range accessible by this Jefferson Lab experiment. The data are in qualitative agreement with theoretical calculations based on realistic interactions and accurate methods to solve the three-body nuclear problem.

Publisher's Note: JLab Measurements of the

This corrects the article DOI: 10.1103/PhysRevLett.119.162501.

Feasibility and Preliminary Efficacy of an Internet Support Group for Parents of a Child with Neurofibromatosis Type 1: a Pilot Study.

This pilot study investigated the feasibility and preliminary efficacy of an Internet Support Group (ISG) for parents of children with NF1. Eligible parents were recruited by email and completed baseline questionnaires assessing social support, self-efficacy, depression, and anxiety. The ISG involved eight weekly 90-min chat sessions and a discussion forum open 24 h/day for 8 weeks. Follow-up measures were completed immediately post-intervention and 3 months later. Parents from 33 families (29 mothers, 4 fathers) completed baseline measures. Over half of parents (52 %) rated their child's disease severity as mild, 33 % moderate, and 15 % severe. Among 21 parents who completed post-intervention measures, ratings of perceived emotional (p = .0008) and informational (p = .0003) support increased. There were no significant changes in self-efficacy, depression, or anxiety (ps > .05). The mean satisfaction rating was moderately high (7.6/10; range 4-10). Some parents commented that the chat sessions were at inconvenient times, which may have limited participation. Preliminary evidence in this small sample of parents suggests that ISGs may be a feasible and potentially efficacious method of providing support to parents of children with NF1. Having multiple weekly chat sessions held at various days and times may improve accessibility and participation. Clinicians are encouraged to help parents access online support resources.

Light scattering study of the "pseudo-layer" compression elastic constant in a twist-bend nematic liquid crystal.

The nematic twist-bend (TB) phase, exhibited by certain achiral thermotropic liquid crystalline (LC) dimers, features a nanometer-scale, heliconical rotation of the average molecular long axis (director) with equally probable left- and right-handed domains. On meso to macroscopic scales, the TB phase may be considered as a stack of equivalent slabs or "pseudo-layers", each one helical pitch in thickness. The long wavelength fluctuation modes should then be analogous to those of a smectic-A phase, and in particular the hydrodynamic mode combining "layer" compression and bending ought to be characterized by an effective layer compression elastic constant Beff and average director splay constant K. The magnitude of K is expected to be similar to the splay constant of an ordinary nematic LC, but due to the absence of a true mass density wave, Beff could differ substantially from the typical value of ∼106 Pa in a conventional smectic-A. Here we report the results of a dynamic light scattering study, which confirms the "pseudo-layer" structure of the TB phase with Beff in the range 103-104 Pa. We show additionally that the temperature dependence of Beff at the TB to nematic transition is accurately described by a coarse-grained free energy density, which is based on a Landau-deGennes expansion in terms of a heli-polar order parameter that characterizes the TB state and is linearly coupled to bend distortion of the director.

Prevalence of cervical cancer and associated mortality in Grenada, 2000-2010.

Objective To assess cervical cancer prevalence and associated mortality in Grenada, West Indies during 2000-2010. Methods Records of visits to hospital and clinical facilities were obtained from the histopathology laboratory of the Grenada General Hospital. Records were de-identified and electronically compiled. Cervical cancer prevalence was assessed via cross-sectional analysis of this secondary data. Of a total 12 012 records, 2 527 were selected for analysis using sampling without replacement. Cases were matched to corresponding patient data from death registries, where possible, and used to calculate associated mortality rates. Results The observed prevalence of cervical cancer was 52.4 per 100 000 women (ages 15 and above). The highest rates of cervical cancer occurred in the 35-44 age group, with the second highest among 45-64-year-olds. A total of 65 deaths were attributable to cervical cancer during 2000-2010, more than 50% of which were among women > 65 years old. The observed mortality rate was 16.7 per 100 000, almost twice the rate estimated by WHO for the region. Conclusions This study demonstrates the need for a comprehensive cervical cancer-screening program in Grenada. Results should contribute to informing future studies on how to appropriately generate and execute public health policy for education, screening, prevention, and control of cervical cancer in Grenada.

Management of borderline change in endocervical cells: a more dependable approach.

BACKGROUND: There are limited data and guidance from the UK on borderline nuclear change in endocervical cells (BNCs). The objective of this study is to determine the clinical outcome of women with BNCs, to determine the accuracy of colposcopy and propose a more robust management algorithm. METHODS: This is a retrospective review of all BNC referrals between January 2006 and December 2011 at the Northumbria Healthcare Trust. Histological diagnosis was based on high-grade histology (CIN 2 or worse). Any high-grade histology in the first year of follow-up was included in the final diagnosis. RESULTS: Of the 9001 new referrals, 167 women had BNCs. Thirty-seven (22%) were diagnosed with high-grade histology on initial assessment. Sixty women had satisfactory and negative colposcopy, out of which 7 (12%) were detected with high-grade histology/cytology in the first year of follow-up. Overall, 50 high-grade histology (30%), including two invasive carcinomas were detected. CONCLUSIONS: Current follow-up of BNCs relies heavily on colposcopic assessment. A significant proportion of women with negative colposcopy was found to have high-grade histology in the first year of follow-up. We propose a more robust management algorithm to lower the probability of missed high-grade histology in this subgroup of women.

JLab measurement of the 4He charge form factor at large momentum transfers.

The charge form factor of 4He has been extracted in the range 29 fm(-2) ≤ Q2 ≤ 77 fm(-2) from elastic electron scattering, detecting 4He recoil nuclei and electrons in coincidence with the high resolution spectrometers of the Hall A Facility of Jefferson Lab. The measurements have uncovered a second diffraction minimum for the form factor, which was predicted in the Q2 range of this experiment. The data are in qualitative agreement with theoretical calculations based on realistic interactions and accurate methods to solve the few-body problem.

Effects of elevated atmospheric CO2 on competition between the mosquitoes Aedes albopictus and Ae. triseriatus via changes in litter quality and production.

Elevated atmospheric CO2 can alter aquatic communities via changes in allochthonous litter inputs. We tested effects of atmospheric CO2 on the invasive Aedes albopictus (Skuse) and native Aedes triseriatus (Say) (Diptera: Culicidae) via changes in competition for microbial food or resource inhibition/toxicity. Quercus alba L. litter was produced under elevated (879 ppm) and ambient (388 ppm) atmospheric CO2. Saplings grown at elevated CO2 produced greater litter biomass, which decayed faster and leached more tannins than saplings at ambient CO2. Competition was tested by raising larvae in different species and density combinations provisioned with elevated- or ambient-CO2 litter. Species-specific performance to water conditions was tested by providing single-species larval cohorts with increasing amounts of elevated- or ambient-CO2 litter, or increasing concentrations of tannic acid. Larval densities affected some fitness parameters of Ae. albopictus and Ae. triseriatus, but elevated-CO2 litter did not modify the effects of competition on population growth rates or any fitness parameters. Population growth rates and survival of each species generally were affected negatively by increasing amounts of both elevated- and ambient-CO2 litter from 0.252 to 2.016 g/liter, and tannic acid concentrations above 100 mg/liter were entirely lethal to both species. Aedes albopictus had consistently higher population growth rates than Ae. triseriatus. These results suggest that changes to litter production and chemistry from elevated CO2 are unlikely to affect the competitive outcome between Ae. albopictus and Ae. triseriatus, but that moderate increases in litter production increase population growth rates of both species until a threshold is exceeded that results in resource inhibition and toxicity.

Use of X-ray micro tomography to study the microstructure of loose-packed and compacted milk powders.

The use of X-rays to evaluate food microstructure has developed considerably in recent years. In this work we used X-ray micro tomography (XMT) to visualize the microstructure of loose-packed and compacted samples of spray-dried skim milk powder (SMP) and whole milk powder (WMP) and to quantify the proportion of both interstitial and occluded air voids in each sample. Visual scrutiny of the acquired XMT images showed details of the microstructure of the milk powders such as the spherical morphology of the particles, the size of the particles and internal air voids of various sizes. Within loose-packed powders, the proportion of air voids was higher (13% average) in WMP than in SMP. This was reversed in the compacted powders, in which the proportion of air voids was higher in SMP. The disparity in the proportion of air voids in both loose-packed and compacted samples of SMP and WMP was attributed to the size, shape and surface properties of the particles.

Multilocus sequence types of invasive Corynebacterium diphtheriae isolated in the Rio de Janeiro urban area, Brazil.

Invasive infections caused by Corynebacterium diphtheriae in vaccinated and non-vaccinated individuals have been reported increasingly. In this study we used multilocus sequence typing (MLST) to study genetic relationships between six invasive strains of this bacterium isolated solely in the urban area of Rio de Janeiro, Brazil, during a 10-year period. Of note, all the strains rendered negative results in PCR reactions for the tox gene, and four strains presented an atypical sucrose-fermenting ability. Five strains represented new sequence types. MLST results did not support the hypothesis that invasive (sucrose-positive) strains of C. diphtheriae are part of a single clonal complex. Instead, one of the main findings of the study was that such strains can be normally found in clonal complexes with strains related to non-invasive disease. Comparative analyses with C. diphtheriae isolated in different countries provided further information on the geographical circulation of some sequence types.

Acute pain-related depression of operant responding maintained by social interaction or food in male and female rats.

RATIONALE: Clinically relevant pain is often associated with functional impairment and behavioral depression, including depression of social behavior. Moreover, recovery of function is a major goal in pain treatment. We used a recently developed model of operant responding for social interaction in rats to evaluate the vulnerability of social behavior to an experimental pain manipulation and the sensitivity of pain-depressed social behavior to treatment with clinically effective analgesics. METHODS: Sprague-Dawley male and female rats were trained to lever press for social access to another rat, and responding was evaluated after treatment with (a) intraperitoneal injection of dilute lactic acid (IP acid; 0.18-5.6%) administered alone as a visceral noxious stimulus, (b) the mu-opioid receptor (MOR) agonist morphine (0.32-10 mg/kg) or nonsteroidal anti-inflammatory drug (NSAID) ketoprofen (10 mg/kg) administered alone, or (c) morphine or ketoprofen administered before IP acid. For comparison, the same treatments were evaluated in separate rats trained to lever press for food delivery. RESULTS: Both IP acid alone and morphine alone more potently decreased responding maintained by social interaction than by food, whereas ketoprofen did not affect responding for either reinforcer. In general, analgesics were most effective to rescue operant responding when relatively low IP acid concentrations produced significant but submaximal behavioral depression; however, morphine was not effective to rescue responding for social interaction. CONCLUSIONS: Operant responding maintained by social interaction was more sensitive to pain-related disruption and less responsive to opioid analgesic rescue than food-maintained operant responding. Social behavior may be especially vulnerable to depression by pain states.

Control of inducible chemoresistance: enhanced anti-tumor therapy through increased apoptosis by inhibition of NF-kappaB.

Programmed cell death (apoptosis) seems to be the principal mechanism whereby anti-oncogenic therapies such as chemotherapy and radiation effect their responses. Resistance to apoptosis, therefore, is probably a principal mechanism whereby tumors are able to overcome these cancer therapies. The transcription factor NF-kappaB is activated by chemotherapy and by irradiation in some cancer cell lines. Furthermore, inhibition of NF-kappaB in vitro leads to enhanced apoptosis in response to a variety of different stimuli. We show here that inhibition of NF-kappaB through the adenoviral delivery of a modified form of IkappaBalpha, the inhibitor of NF-kappaB, sensitizes chemoresistant tumors to the apoptotic potential of TNFalpha and of the chemotherapeutic compound CPT-11, resulting in tumor regression. These results demonstrate that the activation of NF-kappaB in response to chemotherapy is a principal mechanism of inducible tumor chemoresistance, and establish the inhibition of NF-kappaB as a new approach to adjuvant therapy in cancer treatment.

Characterizing the solid hydrolysis product, UF4(H2O)2.5, generated from neat water reactions with UF4 at room temperature.

Uranium tetrafluoride (UF4) is an important intermediate in the production of UF6 and uranium metal. Room temperature hydrolysis of UF4 was investigated using a combination of Fluorine-19 nuclear magnetic resonance spectroscopy (19F NMR), Raman and infrared spectroscopy, powder X-ray diffraction, and microscopy measurements. UF4(H2O)2.5 was identified as the primary solid hydrolysis product when anhydrous UF4 was stirred in deionized water. Static NMR and 19F magic angle spinning NMR measurements revealed that a small amount of uranyl fluoride can also form when anhydrous UF4 is left in water, although this species comprises less than 5% of the total sample with the remaining parts being UF4(H2O)2.5. Since UF4 is generally considered to be stable under ambient conditions, these findings mark the first time that a room temperature reaction between UF4 and water has been detected and analyzed without interference from additional chemical reagents. The Raman characterization of UF4(H2O)2.5 presented herein is the first on record. Since UF4 is one of the most used intermediates during chemical conversion of uranium ore to uranium metal for nuclear fuel and weapons, the results presented herein are applicable to numerous nuclear science fields where solid state detection of uranium is of value, including nuclear nonproliferation, nuclear forensics, and environmental remediation.

Involvement of Egr-1/RelA synergy in distinguishing T cell activation from tumor necrosis factor-alpha-induced NF-kappa B1 transcription.

NF-kappa B is an important transcription factor required for T cell proliferation and other immunological functions. The NF-kappa B1 gene encodes a 105-kD protein that is the precursor of the p50 component of NF-kappa B. Previously, we and others have demonstrated that NF-kappa B regulates the NF-kappa B1 gene. In this manuscript we have investigated the molecular mechanisms by which T cell lines stimulated with phorbol 12-myristate 13-acetate (PMA) and phytohemagglutin (PHA) display significantly higher levels of NF-kappa B1 encoding transcripts than cells stimulated with tumor necrosis factor-alpha, despite the fact that both stimuli activate NF-kappa B. Characterization of the NF-kappa B1 promoter identified an Egr-1 site which was found to be essential for both the PMA/PHA-mediated induction as well as the synergistic activation observed after the expression of the RelA subunit of NF-kappa B and Egr-1. Furthermore, Egr-1 induction was required for endogenous NF-kappa B1 gene expression, since PMA/PHA-stimulated T cell lines expressing antisense Egr-1 RNA were inhibited in their ability to upregulate NF-kappa B1 transcription. Our studies indicate that transcriptional synergy mediated by activation of both Egr-1 and NF-kappa B may have important ramifications in T cell development by upregulating NF-kappa B1 gene expression.

Ex vivo inhibition of NF-kappaB signaling in alloreactive T-cells prevents graft-versus-host disease.

The ex vivo induction of alloantigen-specific hyporesponsiveness by costimulatory pathway blockade or exposure to immunoregulatory cytokines has been shown to inhibit proliferation, IL-2 production, and the graft-versus-host disease (GVHD) capacity of adoptively transferred T-cells. We hypothesized that inhibition of the intracellular NF-kappaB pathway in alloreactive T-cells, which is critical for T-cell activation events including IL-2 transcription, could lead to alloantigen hyporesponsiveness and loss of GVHD capacity. We demonstrate that treatment of mixed lymphocyte reaction (MLR) cultures with PS1145, a potent inhibitor of NF-kappaB activation, can induce T-cell hyporesponsiveness to alloantigen in primary and secondary responses while preserving in vitro responses to potent mitogenic stimulation. GVHD lethality in recipients of ex vivo PS1145-treated cells was profoundly inhibited. Parking of control or PS1145-treated MLR cells in syngeneic Rag(-/-) recipients resulted in intact contact hypersensitivity (CHS) responses. However, GVHD lethality capacity also was restored, suggesting that lymphopenic expansion uncoupled alloantigen hyporesponsiveness. These results indicate that the NF-kappaB pathway is a critical regulator of alloresponses and provide a novel small molecule inhibitor based approach that is effective in preventing early posttransplant GVHD lethality but that also permits donor T-cell responses to recover after a period of lymphopenic expansion.

The O-glycosylated stalk domain is required for apical sorting of neurotrophin receptors in polarized MDCK cells.

Delivery of newly synthesized membrane-spanning proteins to the apical plasma membrane domain of polarized MDCK epithelial cells is dependent on yet unidentified sorting signals present in the luminal domains of these proteins. In this report we show that structural information for apical sorting of transmembrane neurotrophin receptors (p75(NTR)) is localized to a juxtamembrane region of the extracellular domain that is rich in O-glycosylated serine/threonine residues. An internal deletion of 50 amino acids that removes this stalk domain from p75(NTR) causes the protein to be sorted exclusively of the basolateral plasma membrane. Basolateral sorting stalk-minus p75(NTR) does not occur by default, but requires sequences present in the cytoplasmic domain. The stalk domain is also required for apical secretion of a soluble form of p75(NTR), providing the first demonstration that the same domain can mediate apical sorting of both a membrane-anchored as well as secreted protein. However, the single N-glycan present on p75(NTR) is not required for apical sorting of either transmembrane or secreted forms.

Heterogeneous atmospheric reactions: sulfuric Acid aerosols as tropospheric sinks.

The collisional reaction probabilities of several atmospheric species on bulk sulfuric acid surfaces indicate that heterogeneous processes may be important in tropospheric chemistry.

TNF- and cancer therapy-induced apoptosis: potentiation by inhibition of NF-kappaB.

Many cells are resistant to stimuli that can induce apoptosis, but the mechanisms involved are not fully understood. The activation of the transcription factor nuclear factor-kappa B (NF-kappaB) by tumor necrosis factor (TNF), ionizing radiation, or daunorubicin (a cancer chemotherapeutic compound), was found to protect from cell killing. Inhibition of NF-kappaB nuclear translocation enhanced apoptotic killing by these reagents but not by apoptotic stimuli that do not activate NF-kappaB. These results provide a mechanism of cellular resistance to killing by some apoptotic reagents, offer insight into a new role for NF-kappaB, and have potential for improvement of the efficacy of cancer therapies.

Role of transcriptional activation of I kappa B alpha in mediation of immunosuppression by glucocorticoids.

Glucocorticoids are potent immunosuppressive drugs, but their mechanism is poorly understood. Nuclear factor kappa B (NF-kappa B), a regulator of immune system and inflammation genes, may be a target for glucocorticoid-mediated immunosuppression. The activation of NF-kappa B involves the targeted degradation of its cytoplasmic inhibitor, I kappa B alpha, and the translocation of NF-kappa B to the nucleus. Here it is shown that the synthetic glucocorticoid dexamethasone induces the transcription of the I kappa B alpha gene, which results in an increased rate of I kappa B alpha protein synthesis. Stimulation by tumor necrosis factor causes the release of NF-kappa B from I kappa B alpha. However, in the presence of dexamethasone this newly released NF-kappa B quickly reassociates with newly synthesized I kappa B alpha, thus markedly reducing the amount of NF-kappa B that translocates to the nucleus. This decrease in nuclear NF-kappa B is predicted to markedly decrease cytokine secretion and thus effectively block the activation of the immune system.

NF-kappaB-induced loss of MyoD messenger RNA: possible role in muscle decay and cachexia.

MyoD regulates skeletal muscle differentiation (SMD) and is essential for repair of damaged tissue. The transcription factor nuclear factor kappa B (NF-kappaB) is activated by the cytokine tumor necrosis factor (TNF), a mediator of skeletal muscle wasting in cachexia. Here, the role of NF-kappaB in cytokine-induced muscle degeneration was explored. In differentiating C2C12 myocytes, TNF-induced activation of NF-kappaB inhibited SMD by suppressing MyoD mRNA at the posttranscriptional level. In contrast, in differentiated myotubes, TNF plus interferon-gamma (IFN-gamma) signaling was required for NF-kappaB-dependent down-regulation of MyoD and dysfunction of skeletal myofibers. MyoD mRNA was also down-regulated by TNF and IFN-gamma expression in mouse muscle in vivo. These data elucidate a possible mechanism that may underlie the skeletal muscle decay in cachexia.