Specifically regulated genes in malignant melanoma tissues identified by subtractive hybridization

A polymerase chain reaction (PCR)-based subtractive hybridization technique was used to identify transformation-related genes in malignant melanoma. Melanoma biopsies were compared with tissues of benign melanocytic naevi and 549 gene fragments were screened using arrayed filters. Thirty-eight clones were confirmed to be differentially expressed representing 30 different genes (18 melanoma-specific and 12 naevus-specific genes). To further confirm differential gene expression, Northern blot analyses with six of the 30 genes as probes were performed. All six were differentially expressed in benign and malignant melanocytic lesions, specifically dbpB/YB-1, 67-kDa laminin receptor, CAGH-3, 71-kDa heat shock protein and two unknown genes. The expression levels of these genes were then analysed in 50 different tissues to determine their overall expression profile. In conclusion, the technique of PCR-based subtractive hybridization in combination with arrayed filters allows detection of differences in gene expression even in tissues from which high-quality RNA is hard to isolate. The genes identified in this study are of interest because of their potential role in the pathogenesis of malignant melanoma. © 2000 Cancer Research Campaig

Analyzing the footprints of near-surface aqueous turbulence: An image processing-based approach

In this contribution, a detailed investigation of surface thermal patterns on the water surface is presented, with wind speeds ranging from 1 to 7 m s  − 1 and various surface conditions. Distinct structures can be observed on the surface—small-scale short-lived structures termed fish scales and larger-scale cold streaks that are consistent with the footprints of Langmuir circulations. The structure of the surface heat pattern depends strongly on wind-induced stress. Consistent behavior regarding the spacing of cold streaks can be observed in a range of laboratory facilities when expressed as a function of water-sided friction velocity, u * . This behavior systematically decreased until a point of saturation at u *  = 0.7 cm/s. We present a new image processing-based approach to the analysis of the spacing of cold streaks based on a machine learning approach to classify the thermal footprints of near-surface turbulence. Comparison is made with studies of Langmuir circulation and the following key points are found. Results suggest a saturation in the tangential stress, anticipating that similar behavior will be observed in the open ocean. A relation to Langmuir numbers shows that thermal footprints in infrared images are consistent with Langmuir circulations and depend strongly on wind wave conditions

Mid-Pliocene shifts in ocean overturning circulation and the onset of Quaternary-style climates

A major tipping point of Earth's history occurred during the mid-Pliocene: the onset of major Northern-Hemisphere Glaciation (NHG) and of pronounced, Quaternary-style cycles of glacial-to-interglacial climates, that contrast with more uniform climates over most of the preceding Cenozoic and continue until today (Zachos et al., 2001). The severe deterioration of climate occurred in three steps between 3.2 Ma (warm MIS K3) and 2.7 Ma (glacial MIS G6/4) (Lisiecki and Raymo, 2005). Various models (sensu Driscoll and Haug, 1998) and paleoceanographic records (intercalibrated using orbital age control) suggest clear linkages between the onset of NHG and the three steps in the final closure of the Central American Seaways (CAS), deduced from rising salinity differences between Caribbean and the East Pacific. Each closing event led to an enhanced North Atlantic meridional overturning circulation and this strengthened the poleward transport of salt and heat (warmings of +2–3°C) (Bartoli et al., 2005). Also, the closing resulted in a slight rise in the poleward atmospheric moisture transport to northwestern Eurasia (Lunt et al., 2007), which probably led to an enhanced precipitation and fluvial run-off, lower sea surface salinity (SSS), and an increased sea-ice cover in the Arctic Ocean, hence promoting albedo and the build-up of continental ice sheets. Most important, new evidence shows that the closing of the CAS led to greater steric height of the North Pacific and thus doubled the low-saline Arctic Throughflow from the Bering Strait to the East Greenland Current (EGC). Accordingly, Labrador Sea IODP Site 1307 displays an abrupt but irreversible EGC cooling of 6°C and freshening by ~2 psu from 3.25/3.16–3.00 Ma, right after the first but still reversible attempt of closing the CAS

Effects of the fibers distribution in the human eardrum: A biomechanical study

The eardrum separates the external ear from the middle ear and it is responsible to convert the acoustical energy into mechanical energy. It is divided by pars tensa and pars flaccida. The aim of this work is to analyze the susceptibility of the four quadrants of the pars tensa under negative pressure, to different lamina propria fibers distribution. The development of associated ear pathology, in particular the formation of retraction pockets, is also evaluated. To analyze these effects, a computational biomechanical model of the tympano-ossicular chain was constructed using computerized tomography images and based on the finite element method. Three fibers distributions in the eardrum middle layer were compared: case 1 (eardrum with a circular band of fibers surrounding all quadrants equally), case 2 (eardrum with a circular band of fibers that decreases in thickness in posterior quadrants), case 3 (eardrum without circular fibers in the posterior/superior quadrant). A static analysis was performed by applying approximately 3000Pa in the eardrum. The pars tensa of the eardrum was divided in four quadrants and the displacement of a central point of each quadrant analyzed. The largest displacements of the eardrum were obtained for the eardrum without circular fibers in the posterior/superior quadrant

Position statement on classification of basal cell carcinomas. Part 1: unsupervised clustering of experts as a way to build an operational classification of advanced basal cell carcinoma based on pattern recognition

Background No simple classification system has emerged for 'advanced basal cell carcinomas', and more generally for all difficult-to-treat BCCs (DTT-BCCs), due to the heterogeneity of situations, TNM inappropriateness to BCCs, and different approaches of different specialists. Objective To generate an operational classification, using the unconscious ability of experts to simplify the great heterogeneity of the clinical situations into a few relevant groups, which drive their treatment decisions. Method Non-supervised independent and blinded clustering of real clinical cases of DTT-BCCs was used. Fourteen international experts from different specialties independently partitioned 199 patient cases considered 'difficult to treat' into as many clusters they want (<= 10), choosing their own criteria for partitioning. Convergences and divergences between the individual partitions were analyzed using the similarity matrix, K-mean approach, and average silhouette method. Results There was a rather consensual clustering of cases, regardless of the specialty and nationality of the experts. Mathematical analysis showed that consensus between experts was best represented by a partition of DTT-BCCs into five clusters, easily recognized a posteriori as five clear-cut patterns of clinical situations. The concept of 'locally advanced' did not appear consistent between experts. Conclusion Although convergence between experts was not granted, this experiment shows that clinicians dealing with BCCs all tend to work by a similar pattern recognition based on the overall analysis of the situation. This study thus provides the first consensual classification of DTT-BCCs. This experimental approach using mathematical analysis of independent and blinded clustering of cases by experts can probably be applied to many other situations in dermatology and oncology

Temozolomide plus pegylated interferon alfa-2b as first-line treatment for stage IV melanoma: a multicenter phase II trial of the Dermatologic Cooperative Oncology Group (DeCOG)

Background: Combination of temozolomide (TMZ) with nonpegylated interferon alfa is associated with increased efficacy in terms of response rates compared with monotherapy. A multicenter phase II study was carried out to assess the activity and toxicity of TMZ plus pegylated interferon alfa-2b (peg-IFNα-2b), hypothesizing improved efficacy due to modified pharmacokinetic properties of the novel interferon (IFN) formulation. Patients and methods: In all, 124 patients with stage IV melanoma without prior chemotherapy and no cerebral metastases were treated with 100 μg peg-IFNα-2b s.c. per week and oral TMZ 200 mg/m2 (days 1-5, every 28 days). Primary study end point was objective response, and secondary end points were overall and progression-free survival (PFS) and safety. Results: In all, 116 patients were assessable for response: 2 (1.7%) had a complete response and 19 (16.4%) a partial response (overall response rate 18.1%). Of total, 25.0% achieved disease stabilization and 56.9% progressed. Overall survival was 9.4 months; PFS was 2.8 months. Grade 3/4 thrombocytopenia occurred in 20.7% and grade 3/4 leukopenia in 23.3%. Conclusions: The efficacy of TMZ plus peg-IFNα-2b in this large phase II study is moderate and comparable to published results of the combination of TMZ with non-peg-IFN. Likewise, the safety profile of peg-IFNα-2b seems to be similar to non-peg-IFN when combined with TM

Ctenophore population recruits entirely through larval reproduction in the central Baltic Sea

The comb jelly Mertensia ovum, widely distributed in Arctic regions, has recently been discovered in the northern Baltic Sea. We show that M. ovum also exists in the central Baltic but that the population consists solely of small-sized larvae (less than 1.6 mm). Despite the absence of adults, eggs were abundant. Experiments revealed that the larvae were reproductively active. Egg production and anticipated mortality rates suggest a self-sustaining population. This is the first account of a ctenophore population entirely recruiting through larval reproduction (paedogenesis). We hypothesize that early reproduction is favoured over growth to compensate for high predation pressure

Time Course and Pattern of Metastasis of Cutaneous Melanoma Differ between Men and Women

Background: This study identified sex differences in progression of cutaneous melanoma. Methodology/Principal Findings: Of 7,338 patients who were diagnosed as an invasive primary CM without clinically detectable metastases from 1976 to 2008 at the University of Tuebingen in Germany, 1,078 developed subsequent metastases during follow up. The metastatic pathways were defined in these patients and analyzed using the Kaplan-Meier method. Multivariate survival analysis was performed using Cox modeling. In 18.7 % of men and 29.2 % of women (P,0.001) the first metastasis following diagnosis of primary tumor was locoregional as satellite/in-transit metastasis. The majority of men (54.0%) and women (47.6%, P = 0.035) exhibited direct regional lymph node metastasis. Direct distant metastasis from the stage of the primary tumor was observed in 27.3 % of men and 23.2 % of women (P = 0.13). Site of first metastasis was the most important prognostic factor of survival after recurrence in multivariate analysis (HR:1.3; 95 % CI: 1.0–1.6 for metastasis to the regional lymph nodes vs. satellite/in-transit recurrence, and HR:5.5; 95 % CI: 4.2–7.1 for distant metastasis vs. satellite/ in-transit recurrence, P,0.001). Median time to distant metastasis was 40.5 months (IQR, 58.75) in women and 33 months (IQR, 44.25) in men (P = 0.002). Five-year survival after distant recurrence probability was 5.2 % (95 % CI: 1.4–2.5) for men compared with 15.3 % (95 % CI: 11.1–19.5; P = 0.008) for women. Conclusions/Significance: Both, the pattern of metastatic spread with more locoregional metastasis in women, and th