Electromagnetically induced transparency in cold 85Rb atoms trapped in the ground hyperfine F = 2 state

We report electromagnetically induced transparency (EIT) in cold 85Rb atoms, trapped in the lower hyperfine level F = 2, of the ground state 5$^{2}S_{1/2}$ (Tiwari V B \textit{et al} 2008 {\it Phys. Rev.} A {\bf 78} 063421). Two steady state $\Lambda$-type systems of hyperfine energy levels are investigated using probe transitions into the levels F$^{\prime}$ = 2 and F$^{\prime}$ = 3 of the excited state 5$^{2}P_{3/2}$ in the presence of coupling transitions F = 3 $\to$ F$^{\prime}$ = 2 and F = 3 $\to$ F$^{\prime}$ = 3, respectively. The effects of uncoupled magnetic sublevel transitions and coupling field's Rabi frequency on the EIT signal from these systems are studied using a simple theoretical model.Comment: 12 pages, 7 figure

Towards a single step process to create high purity gold structures by electron beam induced deposition at room temperature

Highly pure metallic structures can be deposited by electron beam induced deposition and they have many important applications in different fields. The organo-metallic precursor is decomposed and deposited under the electron beam, and typically it is purified with post-irradiation in presence of O2. However, this approach limits the purification to the surface of the deposit. Therefore, 'in situ' purification during deposition using simultaneous flows of both O2 and precursor in parallel with two gas injector needles has been tested and verified. To simplify the practical arrangements, a special concentric nozzle has been designed allowing deposition and purification performed together in a single step. With this new device metallic structures with high purity can be obtained more easily, while there is no limit on the height of the structures within a practical time frame. In this work, we summarize the first results obtained for 'in situ' Au purification using this concentric nozzle, which is described in more detail, including flow simulations. The operational parameter space is explored in order to optimize the shape as well as the purity of the deposits, which are evaluated through scanning electron microscope and energy dispersive x-ray spectroscopy measurements, respectively. The observed variations are interpreted in relation to other variables, such as the deposition yield. The resistivity of purified lines is also measured, and the influence of additional post treatments as a last purification step is studied.EMPA is acknowledged for providing the original code for the GIS simulator model, which was extended by Stan de Muijnck (TU Delft) with the new geometry. Pleun Dona (FEI) is acknowledged for helping in the design of the concentric nozzle and in getting a working prototype. Patricia Peinado is also acknowledged for help on experimental activities. This work was supported by NanoNextNL program, a Dutch national research and technology program for micro- and nano-technology

Glucosylceramide synthase upregulates MDR1 expression in the regulation of cancer drug resistance through cSrc and β-catenin signaling

<p>Abstract</p> <p>Background</p> <p>Drug resistance is the outcome of multiple-gene interactions in cancer cells under stress of anticancer agents. <it>MDR1 </it>overexpression is most commonly detected in drug-resistant cancers and accompanied with other gene alterations including enhanced glucosylceramide synthase (GCS). <it>MDR1 </it>encodes for P-glycoprotein that extrudes anticancer drugs. Polymorphisms of <it>MDR1 </it>disrupt the effects of P-glycoprotein antagonists and limit the success of drug resistance reversal in clinical trials. GCS converts ceramide to glucosylceramide, reducing the impact of ceramide-induced apoptosis and increasing glycosphingolipid (GSL) synthesis. Understanding the molecular mechanisms underlying <it>MDR1 </it>overexpression and how it interacts with GCS may find effective approaches to reverse drug resistance.</p> <p>Results</p> <p><it>MDR1 </it>and <it>GCS </it>were coincidently overexpressed in drug-resistant breast, ovary, cervical and colon cancer cells; silencing <it>GCS </it>using a novel mixed-backbone oligonucleotide (MBO-asGCS) sensitized these four drug-resistant cell lines to doxorubicin. This sensitization was correlated with the decreased <it>MDR1 </it>expression and the increased doxorubicin accumulation. Doxorubicin treatment induced GCS and <it>MDR1 </it>expression in tumors, but MBO-asGCS treatment eliminated "in-vivo" growth of drug-resistant tumor (NCI/ADR-RES). MBO-asGCS suppressed the expression of <it>MDR1 </it>with GCS and sensitized NCI/ADR-RES tumor to doxorubicin. The expression of P-glycoprotein and the function of its drug efflux of tumors were decreased by 4 and 8 times after MBO-asGCS treatment, even though this treatment did not have a significant effect on P-glycoprotein in normal small intestine. GCS transient transfection induced <it>MDR1 </it>overexpression and increased P-glycoprotein efflux in dose-dependent fashion in OVCAR-8 cancer cells. GSL profiling, silencing of globotriaosylceramide synthase and assessment of signaling pathway indicated that GCS transfection significantly increased globo series GSLs (globotriaosylceramide Gb3, globotetraosylceramide Gb4) on GSL-enriched microdomain (GEM), activated cSrc kinase, decreased β-catenin phosphorylation, and increased nuclear β-catenin. These consequently increased <it>MDR1 </it>promoter activation and its expression. Conversely, MBO-asGCS treatments decreased globo series GSLs (Gb3, Gb4), cSrc kinase and nuclear β-catenin, and suppressed <it>MDR-1 </it>expression in dose-dependent pattern.</p> <p>Conclusion</p> <p>This study demonstrates, for the first time, that GCS upregulates <it>MDR1 </it>expression modulating drug resistance of cancer. GSLs, in particular globo series GSLs mediate gene expression of <it>MDR1 </it>through cSrc and β-catenin signaling pathway.</p

Dynamics of coherently pumped lasers with linearly polarized pump and generated fields

The influence of light polarization on the dynamics of an optically pumped single-mode laser with a homogeneously broadened four-level medium is theoretically investigated in detail. Pump and laser fields with either parallel or crossed linear polarizations are considered, as are typical in far-infrared-laser experiments. Numerical simulations reveal dramatically different dynamic behaviors for these two polarization configurations. The analysis of the model equations allows us to find the physical origin of both behaviors. In particular, the crossed-polarization configuration is shown to be effective in decoupling the pump and laser fields, thus allowing for the appearance of Lorenz-type dynamics

Clinical and cost effectiveness of single stage compared with two stage revision for hip prosthetic joint infection (INFORM):pragmatic, parallel group, open label, randomised controlled trial

OBJECTIVES: To determine whether patient reported outcomes improve after single stage versus two stage revision surgery for prosthetic joint infection of the hip, and to determine the cost effectiveness of these procedures. DESIGN: Pragmatic, parallel group, open label, randomised controlled trial. SETTING: High volume tertiary referral centres or orthopaedic units in the UK (n=12) and in Sweden (n=3), recruiting from 1 March 2015 to 19 December 2018. PARTICIPANTS: 140 adults (aged ≥18 years) with a prosthetic joint infection of the hip who required revision (65 randomly assigned to single stage and 75 to two stage revision). INTERVENTIONS: A computer generated 1:1 randomisation list stratified by hospital was used to allocate participants with prosthetic joint infection of the hip to a single stage or a two stage revision procedure. MAIN OUTCOME MEASURES: The primary intention-to-treat outcome was pain, stiffness, and functional limitations 18 months after randomisation, measured by the Western Ontario and McMasters Universities Osteoarthritis Index (WOMAC) score. Secondary outcomes included surgical complications and joint infection. The economic evaluation (only assessed in UK participants) compared quality adjusted life years and costs between the randomised groups. RESULTS: The mean age of participants was 71 years (standard deviation 9) and 51 (36%) were women. WOMAC scores did not differ between groups at 18 months (mean difference 0.13 (95% confidence interval -8.20 to 8.46), P=0.98); however, the single stage procedure was better at three months (11.53 (3.89 to 19.17), P=0.003), but not from six months onwards. Intraoperative events occurred in five (8%) participants in the single stage group and 20 (27%) in the two stage group (P=0.01). At 18 months, nine (14%) participants in the single stage group and eight (11%) in the two stage group had at least one marker of possible ongoing infection (P=0.62). From the perspective of healthcare providers and personal social services, single stage revision was cost effective with an incremental net monetary benefit of £11 167 (95% confidence interval £638 to £21 696) at a £20 000 per quality adjusted life years threshold (£1.0; $1.1; €1.4). CONCLUSIONS: At 18 months, single stage revision compared with two stage revision for prosthetic joint infection of the hip showed no superiority by patient reported outcome. Single stage revision had a better outcome at three months, fewer intraoperative complications, and was cost effective. Patients prefer early restoration of function, therefore, when deciding treatment, surgeons should consider patient preferences and the cost effectiveness of single stage surgery. TRIAL REGISTRATION: ISRCTN registry ISRCTN10956306.RD&E staff can access the full-text of this article by clicking on the 'Additional Link' above and logging in with NHS OpenAthens if prompted.Unknow

Effect of Smoking on Circulating Angiogenic Factors in High Risk Pregnancies

Objective: Changes in maternal concentrations of the anti-angiogenic factors, soluble fms-like tyrosine kinase 1 (sFlt1) and soluble endoglin (sEng), and the pro-angiogenic placental growth factor (PlGF) precede the development of preeclampsia in healthy women. The risk of preeclampsia is reduced in women who smoke during pregnancy. The objective of this study was to investigate whether smoking affects concentrations of angiogenic factors (sFlt1, PlGF, and sEng) in women at high risk for developing preeclampsia. Study Design: We performed a secondary analysis of serum samples from 993 high-risk women (chronic hypertension, diabetes, multifetal gestation, and previous preeclampsia) in a preeclampsia prevention trial. sFlt1, sEng and PlGF were measured in serum samples obtained at study entry, which was prior to initiation of aspirin (median 19.0 weeks' [interquartile range of 16.0-22.6 weeks']). Smoking status was determined by self-report. Results: sFlt1 was not significantly different in smokers from any high-risk groups compared to their nonsmoking counterparts. PlGF was higher among smokers compared to nonsmokers among diabetic women (142.7 [77.4-337.3] vs 95.9 [48.5-180.7] pg/ml, p = 0.005) and women with a history of preeclampsia (252.2 [137.1-486.0] vs 152.2 [73.6-253.7] pg/ml, p = 0.001). sEng was lower in smokers with multifetal gestations (5.8 [4.6-6.5] vs 6.8 [5.5-8.7] ng/ml, p = 0.002) and trended lower among smokers with diabetes (4.9 [3.8-5.6] vs 5.3 [4.3-6.3] ng/ml, p = 0.05). Smoking was not associated with a lower incidence of preeclampsia in any of these groups. Conclusions: In certain high-risk groups, smoking is associated with changes in the concentrations of these factors towards a pro-angiogenic direction during early pregnancy; however, there was no apparent association between smoking and the development of preeclampsia in our cohort

Stigmatizing attitudes and low levels of knowledge but high willingness to participate in HIV management: A community-based survey of pharmacies in Pune, India

<p>Abstract</p> <p>Background</p> <p>The World Health Organization (WHO) recommends that the role of pharmacists in low-income settings be expanded to address the increasing complexity of HIV antiretroviral (ARV) and co-infection drug regimens. However, in many such settings including in India, many pharmacists and pharmacy workers are often neither well trained nor aware of the intricacies of HIV treatment. The aims of our study were; to determine the availability of ARVs, provision of ARVs, knowledge about ARVs, attitudes towards HIV-infected persons and self-perceived need for training among community-based pharmacies in an urban area of India.</p> <p>Methods</p> <p>We performed a survey of randomly selected, community-based pharmacies located in Pune, India, in 2004-2005 to determine the availability of ARVs at these pharmacies, how they were providing ARVs and their self-perceived need for training. We also assessed knowledge, attitudes and perceptions on HIV and ARVs and factors associated with stocking ARVs.</p> <p>Results</p> <p>Of 207 pharmacies included in the survey, 200 (96.6%) were single, private establishments. Seventy-three (35.3%) pharmacies stocked ARVs and 38 (18.4%) ordered ARVs upon request. The reported median number of ARV pills that patients bought at one time was 30, a two week supply of ARVs (range: 3-240 pills). Six (2.9%) pharmacy respondents reported selling non-allopathic medicines (i.e. Ayurvedic, homeopathy) for HIV. Ninety (44.2%) pharmacy respondents knew that ARVs cannot cure HIV, with those stocking ARVs being more likely to respond correctly (60.3% vs. 34.8%, p = 0.001). Respondents of pharmacies which stocked ARVs were also more likely to believe it was a professional obligation to provide medications to HIV-infected persons (91.8% vs. 78.8%, p = 0.007) but they were also more likely to believe that HIV-infected persons are unable to adhere to their medicines (79.5% vs. 40.9%, p < 0.01). Knowledge of the most common side effects of nevirapine, abnormal liver enzyme profile and skin rash, was reported correctly by 8 (3.9%) and 23 (11.1%) respondents, respectively. Seven (3.4%) respondents reported that they had received special training on HIV, 3 (1.5%) reported receipt of special training on ART and 167 (80.7%) reported that they believed that pharmacy staff should get special training on ART.</p> <p>Conclusion</p> <p>There is a high willingness to participate in HIV management among community-based pharmacies but there is a tremendous need for training on HIV therapies. Furthermore, stigmatizing attitudes towards HIV-infected persons persist and interventions to reduce stigma are needed, particularly among those that stock ARVs.</p

In Search of the Optimal Surgical Treatment for Velopharyngeal Dysfunction in 22q11.2 Deletion Syndrome: A Systematic Review

<div><h3>Background</h3><p>Patients with the 22q11.2 deletion syndrome (22qDS) and velopharyngeal dysfunction (VPD) tend to have residual VPD following surgery. This systematic review seeks to determine whether a particular surgical procedure results in superior speech outcome or less morbidity.</p> <h3>Methodology/ Principal Findings</h3><p>A combined computerized and hand-search yielded 70 studies, of which 27 were deemed relevant for this review, reporting on a total of 525 patients with 22qDS and VPD undergoing surgery for VPD. All studies were levels 2c or 4 evidence. The methodological quality of these studies was assessed using criteria based on the Cochrane Collaboration's tool for assessing risk of bias. Heterogeneous groups of patients were reported on in the studies. The surgical procedure was often tailored to findings on preoperative imaging. Overall, 50% of patients attained normal resonance, 48% attained normal nasal emissions scores, and 83% had understandable speech postoperatively. However, 5% became hyponasal, 1% had obstructive sleep apnea (OSA), and 17% required further surgery. There were no significant differences in speech outcome between patients who underwent a fat injection, Furlow or intravelar veloplasty, pharyngeal flap pharyngoplasty, Honig pharyngoplasty, or sphincter pharyngoplasty or Hynes procedures. There was a trend that a lower percentage of patients attained normal resonance after a fat injection or palatoplasty than after the more obstructive pharyngoplasties (11–18% versus 44–62%, p = 0.08). Only patients who underwent pharyngeal flaps or sphincter pharyngoplasties incurred OSA, yet this was not statistically significantly more often than after other procedures (p = 0.25). More patients who underwent a palatoplasty needed further surgery than those who underwent a pharyngoplasty (50% versus 7–13%, p = 0.03).</p> <h3>Conclusions/ Significance</h3><p>In the heterogeneous group of patients with 22qDS and VPD, a grade C recommendation can be made to minimize the morbidity of further surgery by choosing to perform a pharyngoplasty directly instead of only a palatoplasty.</p> </div

The Bergen proton CT system

The Bergen proton Computed Tomography (pCT) is a prototype detector under construction. It aims to have the capability to track and measure ions’ energy deposition to minimize uncertainty in proton treatment planning. It is a high granularity digital tracking calorimeter, where the first two layers will act as tracking layers to obtain positional information of the incoming particle. The remainder of the detector will act as a calorimeter. Beam tests have been performed with multiple beams. These tests have shown that the ALPIDE chip sensor can measure the deposited energy, making it possible for the sensors to distinguish between the tracks in the Digital Tracking Calorimeter (DTC)