34 research outputs found
Excess-noise-enhanced parametric down conversion
We calculate the influence of excess noise on parametric down conversion in an unstable optical parametric oscillator (OPO), using a quantum quasimode description. We find a strongly enhanced pair photon generation rate below threshold as compared to a conventional stable cavity setup of comparable gain and loss. In addition, the oscillation threshold is lowered due to the influence of the excess noise and the squeezing properties of the emitted light are significantly changed. In general, the maximal quantum-noise suppression in one quadrature component is reduced, which poses strong limitations for the practical usefulness of a geometrically unstable OPO source. The analytical results from our quasimode description are in good agreement with numerical simulations using a positive-P representation of the field in mode space and in position space
Neoadjuvant Chemoradiation Combined with Regional Hyperthermia in Locally Advanced or Recurrent Rectal Cancer
Background: To prospectively analyze feasibility and pathological complete response (pCR) rates of neoadjuvant chemoradiotherapy combined with regional hyperthermia (RHT) in patients with locally advanced (LARC) or recurrent (LRRC) rectal cancer. Methods: between 2012 and 2018, 111 patients with UICC stage IIB-IV or any locally recurrent rectal cancer were included (HyRec-Trial, ClinicalTrials.gov Identifier: NCT01716949). Patients received radiotherapy with concurrent 5-Fluororuracil (5-FU)/Capecitabine and Oxaliplatin, and RHT. Stage 1 feasibility analysis evaluated dose-limiting toxicities (DLT) after 19 patients, stage 2 after 59 evaluable patients. Analysis of the pCR rate was based on histopathological reports. Results: the feasibility rates for stages 1 and 2 were 90% (17/19) and 73% (43/59), respectively. In the intention-to-treat population the pCR rate was 19% (20/105; 90% confidence interval (CI) 13.0–26.5). In the per-protocol-analysis, complete tumor regression was seen in 28% (18/64) and 38% (3/8) of the patients with LARC and LRRC, respectively. Complete resection rates (R0) among patients with LARC and LRRC who received surgery were 99% (78/84) and 67% (8/12). Conclusions: the intensified neoadjuvant and multimodality treatment schedule was feasible and led to comparable early toxicity rates as described by other trials that used the similar chemoradiation protocol. The presented treatment regimen resulted in a very high pCR rate and appears as a promising option for patients with LRRC
Genomic loss of the putative tumor suppressor gene E2A in human lymphoma
The transcription factor E2A is essential for lymphocyte development. In this study, we describe a recurrent E2A gene deletion in at least 70% of patients with Sézary syndrome (SS), a subtype of T cell lymphoma. Loss of E2A results in enhanced proliferation and cell cycle progression via derepression of the protooncogene MYC and the cell cycle regulator CDK6. Furthermore, by examining the gene expression profile of SS cells after restoration of E2A expression, we identify several E2A-regulated genes that interfere with oncogenic signaling pathways, including the Ras pathway. Several of these genes are down-regulated or lost in primary SS tumor cells. These data demonstrate a tumor suppressor function of E2A in human lymphoid cells and could help to develop new treatment strategies for human lymphomas with altered E2A activity
Early and reversible changes to the hippocampal proteome in mice on a high-fat diet
Funding LMW, FMC, CG, ACM and C-DM were funded by the Scottish Government’s Rural and Environment Science and Analytical Services Division (RESAS). FHM was supported by an EASTBIO DTP BBSRC studentship. DS was supported by a SULSA studentship.Peer reviewedPublisher PD
Bovine colostrum increases pore-forming claudin-2 protein expression but paradoxically not ion permeability possibly by a change of the intestinal cytokine milieu
An impaired intestinal barrier function is involved in the pathogenesis of inflammatory bowel disease (IBD). Several nutritional factors are supposed to be effective in IBD treatment but scientific data about the effects on the intestinal integrity remain scarce. Bovine colostrum was shown to exert beneficial effects in DSS-induced murine colitis, and the present study was undertaken to explore the underlying molecular mechanisms. Western blot revealed increased claudin-2 expression in the distal ileum of healthy mice after feeding with colostrum for 14 days, whereas other tight junction proteins (claudin-3, 4, 10, 15) remained unchanged. The colostrum-induced claudin-2 induction was confirmed in differentiated Caco-2 cells after culture with colostrum for 48 h. Paradoxically, the elevation of claudin-2, which forms a cation-selective pore, was neither accompanied by increased ion permeability nor impaired barrier function. In an in situ perfusion model, 1 h exposure of the colonic mucosa to colostrum induced significantly increased mRNA levels of barrier-strengthening cytokine transforming growth factor-beta, while interleukine-2, interleukine-6, interleukine-10, interleukine-13, and tumor-necrosis factor-alpha remained unchanged. Thus, modulation of the intestinal transforming growth factor-beta expression might have compensated the claudin-2 increase and contributed to the observed barrier strengthening effects of colostrum in vivo and in vitro
BC influences intestinal cytokine milieu.
<p>RNA-transcript levels of TGF-β but not IL- 6, 2, 13, 10, and TNF-α were significantly elevated in mouse proximal colon exposed to BC compared to Hank’s balanced salt solution control group (HBSS) *p<0.05, n = 4–6.</p
Bovine colostrum increases claudin-2 expression in the distal ileum of healthy mice.
<p>(A) Representative western blot of elevated claudin-2 protein expression in whole tissue extracts from the distal ileum of mice after 14 days feeding with bovine colostrum (BC) and untreated controls. β-actin was used as internal control for equal protein loading. (B) Increased relative expression of claudin-2 protein upon BC-feeding compared to untreated controls. *p<0.05 vs. untreated, n = 5–6.</p
Increased claudin-2 expression is not paralled by decreased transepithelial electrical resistance.
<p>Apical stimulation of filter-grown differentiated 14 days postconfluent Caco-2 cells with IL-6 (50 ng/ml) decreased transepithelial electrical resistance (TER) after 24 h compared to unstimulated controls (complete media, CM). Incubation with bovine colostrum (BC) or fetal bovine serum (FBS) increased TER. TER in the presence of CM at the beginning of the incubation was set as 100%. *p<0.05, n = 3–4.</p