The presence of elafin, SLPI, IL1-RA and STNFalpha RI in head and neck squamous cell carcinomas and their relation to the degree of tumour differentiation.

Biopsy samples of head and neck carcinomas were investigated with regard to elafin, secretory leukocyte protease inhibitor (SLPI), interleukin 1-receptor antagonist [(IL)1-RA] and soluble tumour necrosis factor alpha receptor antagonist (STNFalpha RI). SLPI and elafin are serine protease inhibitors produced in the serous cells of the upper respiratory airways and in the keratinocytes, respectively. We have now found the presence of elafin and SLPI in squamous cell carcinomas of the upper respiratory tract (tonsillar, hypopharyngeal, tongue, mouth floor, gingival and laryngeal cancer). Significantly higher amounts of SLPI and elafin are present in well-differentiated and moderately differentiated tumours than in poorly differentiated tumours (p < 0.0001 and p < 0.0015). Tumour necrosis factor-alpha and IL-1beta have been shown to stimulate the production of SLPI and elafin. Since these cytokines can both be difficult to detect, we chose to study their inhibitors, STNFalpha RI and IL1-RA, instead. IL1-RA was expressed in highly differentiated tumours as well as in poorly differentiated ones. No significant difference was seen between the groups. STNFalpha RI was only found in very small amounts, sparsely distributed in the tumours, and was not related to the degree of differentiation

Quantum Fluctuations around the Electroweak Sphaleron

We present an analysis of the quantum fluctuations around the electroweak sphaleron and calculate the associated determinant which gives the 1--loop correction to the sphaleron transition rate. The calculation differs in various technical aspects from a previous analysis by Carson et al. so that it can be considered as independent. The numerical results differ also -- by several orders of magnitude -- from those of this previous analysis; we find that the sphaleron transition rate is much less suppressed than found previously.Comment: DO-TH-93/19 39 pages, 5 figures (available on request as Postscript files or via Fax or mail), LaTeX, no macros neede

Breast cancer incidence after the start of mammography screening in Denmark

Mammography screening may lead to overdiagnosis of asymptomatic breast cancers, that would otherwise not have given rise to clinical symptoms. This aspect was studied in three regional screening programmes in Denmark, which started in Copenhagen municipality, Fyn county, and Frederiksberg municipality in 1991, 1993, and 1994, respectively. In these regions, we compared time trends in incidence of invasive breast cancer with the rest of Denmark. Since the number of clinical mammograms was relatively low, it was reasonable to assume that the breast cancer incidence outside the three screening regions represented the incidence of a population with low-intensity opportunistic screening. In Copenhagen and Fyn, a prevalence peak in incidence was seen during the first invitation round. During the subsequent invitation rounds, the incidence dropped to a level in line with the incidence expected without screening. The pattern was different in the small municipality of Frederiksberg, where the sensitivity was low during the first invitation round. Inclusion of screen-detected ductal carcinoma in situ cases did not change these results. The experiences from Copenhagen and Fyn show that organised mammography screening can operate without overdiagnosis of breast cancer

Deep Eyedentification: Biometric Identification using Micro-Movements of the Eye

We study involuntary micro-movements of the eye for biometric identification. While prior studies extract lower-frequency macro-movements from the output of video-based eye-tracking systems and engineer explicit features of these macro-movements, we develop a deep convolutional architecture that processes the raw eye-tracking signal. Compared to prior work, the network attains a lower error rate by one order of magnitude and is faster by two orders of magnitude: it identifies users accurately within seconds

Ecological speciation in European whitefish is driven by a large-gaped predator

Lake-dwelling fish that form species pairs/flocks characterized by body size divergence are important model systems for speciation research. Although several sources of divergent selection have been identified in these systems, their importance for driving the speciation process remains elusive. A major problem is that in retrospect, we cannot distinguish selection pressures that initiated divergence from those acting later in the process. To address this issue, we studied the initial stages of speciation in European whitefish (Coregonus lavaretus) using data from 358 populations of varying age (26-10,000 years). We find that whitefish speciation is driven by a large-growing predator, the northern pike (Esox lucius). Pike initiates divergence by causing a largely plastic differentiation into benthic giants and pelagic dwarfs: ecotypes that will subsequently develop partial reproductive isolation and heritable differences in gill raker number. Using an eco-evolutionary model, we demonstrate how pike's habitat specificity and large gape size are critical for imposing a between-habitat trade-off, causing prey to mature in a safer place or at a safer size. Thereby, we propose a novel mechanism for how predators may cause dwarf/giant speciation in lake-dwelling fish species.Peer reviewe

SerpinB2 regulates stromal remodelling and local invasion in pancreatic cancer

Pancreatic cancer has a devastating prognosis, with an overall 5-year survival rate of ~8%, restricted treatment options and characteristic molecular heterogeneity. SerpinB2 expression, particularly in the stromal compartment, is associated with reduced metastasis and prolonged survival in pancreatic ductal adenocarcinoma (PDAC) and our genomic analysis revealed that SERPINB2 is frequently deleted in PDAC. We show that SerpinB2 is required by stromal cells for normal collagen remodelling in vitro, regulating fibroblast interaction and engagement with collagen in the contracting matrix. In a pancreatic cancer allograft model, co-injection of PDAC cancer cells and SerpinB2(-/-) mouse embryonic fibroblasts (MEFs) resulted in increased tumour growth, aberrant remodelling of the extracellular matrix (ECM) and increased local invasion from the primary tumour. These tumours also displayed elevated proteolytic activity of the primary biochemical target of SerpinB2-urokinase plasminogen activator (uPA). In a large cohort of patients with resected PDAC, we show that increasing uPA mRNA expression was significantly associated with poorer survival following pancreatectomy. This study establishes a novel role for SerpinB2 in the stromal compartment in PDAC invasion through regulation of stromal remodelling and highlights the SerpinB2/uPA axis for further investigation as a potential therapeutic target in pancreatic cancer