Performance of Pyridylthiourea-Polyethylenimine Polyplex for siRNA-Mediated Liver Cancer Therapy in Cell Monolayer, Spheroid, and Tumor Xenograft Models

Medical application of siRNAs relies on methods for delivering nucleic acids into the cytosol. Synthetic carriers, which assemble with nucleic acids into delivery systems, show promises for cancer therapy but efficiency remains to be improved. In here, the effectiveness of pyridylthiourea‐polyethylenimine (πPEI), a siRNA carrier that favors both polyplex disassembly and endosome rupture upon sensing the acidic endosomal environment, in 3 experimental models of hepatocellular cancer is tested. The πPEI‐assisted delivery of a siRNA targeting the polo‐like kinase 1 into Huh‐7 monolayer produces a 90% cell death via a demonstrated RNA interference mechanism. Incubation of polyplex with Huh‐7 spheroids leads to siRNA delivery into the superficial first cell layer and a 60% reduction in spheroid growth compared to untreated controls. Administration of polyplexes into mice bearing subcutaneous implanted Huh‐7Luc tumors results in a reduced tumor progression, similar to the one observed in the spheroid model. Altogether, these results support the in vivo use of synthetic and dedicated polymers for increasing siRNA‐mediated gene knockdown, and their clinical promise in cancer therapeutics

Acute bacterial prostatitis: heterogeneity in diagnostic criteria and management. Retrospective multicentric analysis of 371 patients diagnosed with acute prostatitis

<p>Abstract</p> <p>Background</p> <p>There is currently a lack of consensus for the diagnosis, investigations and treatments of acute bacterial prostatitis (AP).</p> <p>Methods</p> <p>The symptoms, investigations and treatments of 371 inpatients diagnosed with AP were analyzed through a retrospective study conducted in four departments – Urology (U), Infectious Diseases (ID), Internal Medicine (IM), Geriatrics (G) – of two French university hospitals.</p> <p>Results</p> <p>The cause of admission, symptoms, investigations and treatments depended markedly on the department of admission but not on the hospital. In U, patients commonly presented with a bladder outlet obstruction, they had a large imaging and functional check-up, and received alpha-blockers and anti-inflammatory drugs. In ID, patients were febrile and received longer and more appropriate antibiotic treatments. In G, patients presented with cognitive disorders and commonly had post-void urine volume measurements. In IM, patients presented with a wide range of symptoms, and had very diverse investigations and antibiotic regimen.</p> <p>Overall, a 3:1 ratio of community-acquired AP (CA-AP) to nosocomial AP (N-AP) was observed. Urine culture isolated mainly <it>E. coli </it>(58% of AP, 68% of CA-AP), with venereal agents constituting less than 1%. The probabilistic antibiotic treatments were similar for N-AP and CA-AP (58% bi-therapy; 63% fluoroquinolone-based regimen). For N-AP, these treatments were more likely to be inadequate (42% <it>vs. </it>8%, p < 0.001) and had a higher rate of bacteriological failure (48% <it>vs. </it>19%, p < 0.001).</p> <p>Clinical failure at follow-up was more common than bacteriological failure (75% versus 24%, p < 0.001). Patients older than 49 had more underlying urinary tract disorders and a higher rate of clinical failure (30% versus 10%, p < 0.0001).</p> <p>Conclusion</p> <p>This study highlights the difficulties encountered on a daily basis by the physicians regarding the diagnosis and management of acute prostatitis.</p

Construction and test of a fine-grained liquid argon preshower prototype

A separate liquid argon preshower detector consisting of two layers featuring a fine granularity of 2.5~10$^{\mathrm{-3}}$ was studied by the RD3 collaboration. A prototype covering approximately 0.8 in pseudo-rapidity and 9 degrees in azimuth was built and tested at CERN in July 94. CMOS and GaAs VLSI preamplifiers were designed and tested for this occasion. The combined response of this detector and an accordion electromagnetic calorimeter prototype to muons, electrons and photons is presented. For minimum ionizing tracks a signal-to-noise ratio of 4.5 per preshower layer was measured. Above 150~GeV the space resolution for electrons is better than 250~$\mu$m in both directions. The precision on the electromagnetic shower direction, determined together with the calorimeter, is better than 4 mrad above 50~GeV. It is concluded that the preshower detector would adequately fulfil its role for future operation at CERN Large Hadron Collider

High aboveground carbon stock of African tropical montane forests

Tropical forests store 40-50 per cent of terrestrial vegetation carbon(1). However, spatial variations in aboveground live tree biomass carbon (AGC) stocks remain poorly understood, in particular in tropical montane forests(2). Owing to climatic and soil changes with increasing elevation(3), AGC stocks are lower in tropical montane forests compared with lowland forests(2). Here we assemble and analyse a dataset of structurally intact old-growth forests (AfriMont) spanning 44 montane sites in 12 African countries. We find that montane sites in the AfriMont plot network have a mean AGC stock of 149.4 megagrams of carbon per hectare (95% confidence interval 137.1-164.2), which is comparable to lowland forests in the African Tropical Rainforest Observation Network(4) and about 70 per cent and 32 per cent higher than averages from plot networks in montane(2,5,6) and lowland(7) forests in the Neotropics, respectively. Notably, our results are two-thirds higher than the Intergovernmental Panel on Climate Change default values for these forests in Africa(8). We find that the low stem density and high abundance of large trees of African lowland forests(4) is mirrored in the montane forests sampled. This carbon store is endangered: we estimate that 0.8 million hectares of old-growth African montane forest have been lost since 2000. We provide country-specific montane forest AGC stock estimates modelled from our plot network to help to guide forest conservation and reforestation interventions. Our findings highlight the need for conserving these biodiverse(9,10) and carbon-rich ecosystems. The aboveground carbon stock of a montane African forest network is comparable to that of a lowland African forest network and two-thirds higher than default values for these montane forests.Peer reviewe

Search for the bcb_c meson in hadronic Z decays

A search for the Bc meson decaying into the channels J/psi pi+ and J/psi l nu (l = e or mu) is performed in a sample of 3.9 million hadronic Z decays collected by the ALEPH detector. This search results in the observation of 0 and 2 candidates in each of these channels, respectively, while 0.44 and 0.81 background events are expected. The following 90\% confidence level upper limits are derived: Br(Z->Bc X)/Br(Z->q q )*Br(Bc->J/psi pi+) 3.6 10^-5 Br(Z->Bc X)/Br(Z->q q )*Br(Bc->J/psi l nu) 5.2 10^-5 An additional Bc->J/psi(e+e-) mu nu candidate with very low background probability, found in an independent analysis, is also described in detail

Measurement of the tau lepton lifetime with the three-dimensional impact parameter method.

A new method is presented for the measurement of the mean $\tau$ lepton lifetime using events in which $\tau$'s are pair-produced and both $\tau$'s decay to hadrons and $\nu_\tau$. Based on the correlation between the two $\tau$'s produced at a symmetric $e^+ e^-$ collider, the 3DIP method relies on the three-dimensional information from a double-sided vertex detector and on kinematic constraints for the precise measurement of the $\tau$ decay angles. Using the data collected from 1992 to 1994 with the ALEPH detector at LEP, a $\tau$ lifetime of $288.0 \pm 3.1 \pm 1.3$\fs is obtained from the sample in which both $\tau$'s decay to one charged track, and $292.8 \pm 5.6 \pm 3.0$\fs from the sample in which one $\tau$ decays to one prong and the other to three prongs. The results show small statistical correlations with those derived from other methods. When combined with the previously published ALEPH measurements, the resulting $\tau$ lifetime is $291.2 \pm 2.0 \pm 1.2$\fs

Measurement of the tau lepton lifetime with the three-dimensional impact parameter method.

A new method is presented for the measurement of the mean $\tau$ lepton lifetime using events in which $\tau$'s are pair-produced and both $\tau$'s decay to hadrons and $\nu_\tau$. Based on the correlation between the two $\tau$'s produced at a symmetric $e^+ e^-$ collider, the 3DIP method relies on the three-dimensional information from a double-sided vertex detector and on kinematic constraints for the precise measurement of the $\tau$ decay angles. Using the data collected from 1992 to 1994 with the ALEPH detector at LEP, a $\tau$ lifetime of $288.0 \pm 3.1 \pm 1.3$\fs is obtained from the sample in which both $\tau$'s decay to one charged track, and $292.8 \pm 5.6 \pm 3.0$\fs from the sample in which one $\tau$ decays to one prong and the other to three prongs. The results show small statistical correlations with those derived from other methods. When combined with the previously published ALEPH measurements, the resulting $\tau$ lifetime is $291.2 \pm 2.0 \pm 1.2$\fs

Measurement of the tau lepton lifetime with the three-dimensional impact parameter method.

A new method is presented for the measurement of the mean $\tau$ lepton lifetime using events in which $\tau$'s are pair-produced and both $\tau$'s decay to hadrons and $\nu_\tau$. Based on the correlation between the two $\tau$'s produced at a symmetric $e^+ e^-$ collider, the 3DIP method relies on the three-dimensional information from a double-sided vertex detector and on kinematic constraints for the precise measurement of the $\tau$ decay angles. Using the data collected from 1992 to 1994 with the ALEPH detector at LEP, a $\tau$ lifetime of $288.0 \pm 3.1 \pm 1.3$\fs is obtained from the sample in which both $\tau$'s decay to one charged track, and $292.8 \pm 5.6 \pm 3.0$\fs from the sample in which one $\tau$ decays to one prong and the other to three prongs. The results show small statistical correlations with those derived from other methods. When combined with the previously published ALEPH measurements, the resulting $\tau$ lifetime is $291.2 \pm 2.0 \pm 1.2$\fs