Makespan Scheduling of Unit Jobs with Precedence Constraints in O(1.995n)O(1.995^n) time

In a classical scheduling problem, we are given a set of $n$ jobs of unitlength along with precedence constraints and the goal is to find a schedule ofthese jobs on $m$ identical machines that minimizes the makespan. This problemis well-known to be NP-hard for an unbounded number of machines. Using standard3-field notation, it is known as $P|\text{prec}, p_j=1|C_{\max}$. We present an algorithm for this problem that runs in $O(1.995^n)$ time.Before our work, even for $m=3$ machines the best known algorithms ran in$O^\ast(2^n)$ time. In contrast, our algorithm works when the number ofmachines $m$ is unbounded. A crucial ingredient of our approach is an algorithmwith a runtime that is only single-exponential in the vertex cover of thecomparability graph of the precedence constraint graph. This heavily relies oninsights from a classical result by Dolev and Warmuth (Journal of Algorithms1984) for precedence graphs without long chains.<br

BISON ontwerpgerichte evaluatie:criteria, indicatoren en instrumenten

Deze deliverable van het BISON project beschrijft de criteria en instrumenten die gebruikt zijn in de (formatieve) evaluatie van drie scenario's voor samenwerkend leren in de virtuele klas

Las instituciones científico-medicas en la Murcia del XVIII : un intento fracasado de renovación de la formación médica

Presentamos un estudio sobre dos intentos que, en la Murcia del siglo XVIII, pretendieron mejorar y actualizar la formación que recibían los profesionales sanitarios. Ambos fracasaron, aparentemente por falta de acuerdo entre sus promotores, si bien pensamos que las causas fueron más profundas y habría que buscarlas en la escasa actividad científica que se desarrolló en la ciudad, lo que hacía innecesaria la existencia de instituciones docentes o de otras como las Academias de Medicina

Detection and monitoring of cancers with biosensors in Vietnam

Biosensors are able to provide fast, accurate and reliable detec-tions and monitoring of cancer cells, as well as to determine the effectiveness of anticancer chemotherapy agents in cancer treatments. These have attracted a great attention of research communities, especially in the capabilities of detecting the path-ogens, viruses and cancer cells in narrow scale that the conven-tional apparatus and techniques do not have. This paper pre-sents technologies and applications of biosensors for detections of cancer cells and related diseases, with the focus on the cur-rent research and technology development about biosensors in Vietnam, a typical developing country with a very high number of patients diagnosed with cancers in recent years, but having a very low cancer survival rate. The role of biosensors in early detections of diseases, cancer screening, diagnosis and treat-ment, is more and more important; especially it is estimated that by 2020, 60-70% new cases of cancers and nearly 70% of cancer deaths will be in economically disadvantaged countries. The paper is also aimed to open channels for the potential R&D collaborations with partners in Vietnam in the areas of innovative design and development of biosensors in particular and medical technology devices in general

Analysis of Released Circulating Tumor Cells During Surgery for Non-Small Cell Lung Cancer:are they what they appear to be?

Purpose: Tumor cells from patients with lung cancer are expelled from the primary tumor into the blood, but difficult to detect in the peripheral circulation. We studied the release of circulating tumor cells (CTCs) during surgery to test the hypothesis that CTC counts are influenced by hemodynamic changes (caused by surgical approach) and manipulation. Experimental Design: Patients undergoing video-assisted thoracic surgery (VATS) or open surgery for (suspected) primary lung cancer were included. Blood samples were taken before surgery (T0) from the radial artery (RA), from both the RA and pulmonary vein (PV) when the PV was located (T1) and when either the pulmonary artery (T2 open) or the PV (T2VATS) was dissected. The CTCs were enumerated using the CellSearch system. Single-cell whole-genome sequencing was performed on isolated CTCs for aneuploidy. Results: CTCs were detected in 58 of 138 samples (42%) of 31 patients. CTCs were more often detected in the PV (70%) compared with the RA (22%, P <0.01) and in higher counts ( P <0.01). After surgery, the RA but not the PV showed less often CTCs (P = 0.02). Type of surgery did not influence CTC release. Only six of 496 isolated CTCs showed aneuploidy, despite matched primary tumor tissue being aneuploid. Euploid so-called CTCs had a different morphology than aneuploid. Conclusions: CTCs defined by CellSearch were identified more often and in higher numbers in the PV compared with the RA, suggesting central clearance. The majority of cells in the PV were normal epithelial cells and outnumbered CTCs. Release of CTCs was not influenced by surgical approach

Characterization of ERG, AR and PTEN gene status in circulating tumor cells from patients with castration-resistant prostate cancer

Hormone-driven expression of the ERG oncogene after fusion with TMPRSS2 occurs in 30% to 70% of therapy-naive prostate cancers. Its relevance in castration-resistant prostate cancer (CRPC) remains controversial as ERG is not expressed in some TMPRSS2-ERG androgen-independent xenograft models. However, unlike these models, CRPC patients have an increasing prostate-specific antigen, indicating active androgen receptor signaling. Here, we collected blood every month from 89 patients (54 chemotherapy-naive patients and 35 docetaxel-treated patients) treated in phase I/phase II clinical trials of an orally available, highly specific CYP17 inhibitor, abiraterone acetate, that ablates the synthesis of androgens and estrogens that drive TMPRSS2-ERG fusions. We isolated circulating tumor cells (CTC) by anti-epithelial cell adhesion molecule immunomagnetic selection followed by cytokeratin and CD45 immunofluorescence and 4',6diamidino-2-phenylindole staining. We used multicolor fluorescence in situ hybridization to show that CRPC CTCs, metastases, and prostate tissue invariably had the same ERG gene status as therapy-naive tumors (n = 31). We then used quantitative reverse transcription-PCR to show that ERG expression was maintained in CRPC. We also observed homogeneity in ERG gene rearrangement status in CTCs (n = 48) in contrast to significant heterogeneity of AR copy number gain and PTEN loss, suggesting that rearrangement of ERG may be an earlier event in prostate carcinogenesis. We finally report a significant association between ERG rearrangements in therapy-naive tumors, CRPCs, and CTCs and magnitude of prostate-specific antigen decline (P = 0.007) in CRPC patients treated with abiraterone acetate. These data confirm that CTCs are malignant in origin and indicate that hormone-regulated expressio

Single tube liquid biopsy for advanced non-small cell lung cancer

The need for a liquid biopsy in non-small cell lung cancer (NSCLC) patients is rapidly increasing. We studied the relation between overall survival (OS) and the presence of four cancer biomarkers from a single blood draw in advanced NSCLC patients: EpCAM(high) circulating tumor cells (CTC), EpCAM(low) CTC, tumor-derived extracellular vesicles (tdEV) and cell-free circulating tumor DNA (ctDNA). EpCAM(high) CTC were detected with CellSearch, tdEV in the CellSearch images and EpCAM(low) CTC with filtration after CellSearch. ctDNA was isolated from plasma and mutations present in the primary tumor were tracked with deep sequencing methods. In 97 patients, 21% had >= 2 EpCAM(high) CTC, 15% had >= 2 EpCAM(low) CTC, 27% had >= 18 tdEV and 19% had ctDNA with >= 10% mutant allele frequency. Either one of these four biomarkers could be detected in 45% of the patients and all biomarkers were present in 2%. In 11 out of 16 patients (69%) mutations were detected in the ctDNA. Two or more unfavorable biomarkers were associated with poor OS. The presence of EpCAM(high) CTC and elevated levels of tdEV and ctDNA was associated with a poor OS; however, the presence of EpCAM(low) CTC was not. This single tube approach enables simultaneous analysis of multiple biomarkers to explore their potential as a liquid biopsy