Late-Stage Diazoester Installation via Arylthianthrenium Salts.

By leveraging the fast oxidative addition of arylthianthrenium salts (aryl-TT) to palladium(0), a regioselective diazoester installation has been developed. This approach enables the introduction of a diazo moiety to densely functionalized arenes at a late stage. The installed diazo group is amenable to facile further derivatization.

Quantum annealing for nearest neighbour compliance problem.

Quantum Computing has emerged as a promising alternative, utilising quantum mechanics for faster computations. This paper explores the nearest neighbour compliance (NNC) Problem in Gate-based Quantum Computers, where quantum gates are constrained to operate on physically adjacent qubits. The NNC problem aims to optimise the insertion of SWAP-gates to ensure compliance with these constraints while minimising their count.

Synthesis of α-Branched Enones via Chloroacylation of Terminal Alkenes.

Here, we show the conversion of unactivated alkenes into α-branched enones via regioselective chloroacylation with acyl chlorides. The method relies upon the initial in situ generation of chlorine radicals directly from the acyl chloride precursor under cooperative nickel/photoredox catalysis. Subsequent HCl elimination provides enones and α,β-unsaturated esters that are not accessible via the conventional acylation approaches that provide the other, linear constitutional isomer.

The EGFR phosphatase RPTPγ is a redox-regulated suppressor of promigratory signaling.

Spatially organized reaction dynamics between proto-oncogenic epidermal growth factor receptor (EGFR) and protein tyrosine phosphatases determine EGFR phosphorylation dynamics in response to growth factors and thereby cellular behavior within developing tissues. We show that the reaction dynamics of mutual inhibition between RPTPγ phosphatase and autocatalytic ligandless EGFR phosphorylation enable highly sensitive promigratory EGFR signaling responses to subnanomolar EGF levels, when < 5% receptors are occupied by EGF. EGF thereby triggers an autocatalytic phospho-EGFR reaction by the initial production of small amounts of phospho-EGFR through transient, asymmetric EGF-EGFR dimers.

Prophylactic effect of retromuscular mesh placement during loop ileostomy closure on incisional hernia incidence-a multicentre randomised patient- and observer-blind trial (P.E.L.I.O.N trial).

Background: Incisional hernia is a frequent complication following loop ileostomy reversal. Incisional hernias are associated with morbidity, loss of health-related quality of life and costs and warrant the investigation of prophylactic measures. Prophylactic mesh implantation at the time of surgical stoma reversal has shown to be a promising and safe method to prevent incisional hernias in this setting.

Nondirected Pd-catalyzed aerobic C-H alkenylation of ruthenocene and ferrocene.

Pd-catalyzed alkenylations of metallocenes C-H activation were developed using electronically tunable pyrazolonaphthyridine (PzNPy) ligands. Ferrocene was alkenylated using the most electron-deficient ligand in the series, whereas the less reactive ruthenocene needed balancing of the electrophilicity and stability of catalysts. Various alkenes were installed, allowing fine-tuning of redox potentials.

Exploiting RNA thermometer-driven molecular bioprocess control as a concept for heterologous rhamnolipid production.

A key challenge to advance the efficiency of bioprocesses is the uncoupling of biomass from product formation, as biomass represents a by-product that is in most cases difficult to recycle efficiently. Using the example of rhamnolipid biosurfactants, a temperature-sensitive heterologous production system under translation control of a fourU RNA thermometer from Salmonella was established to allow separating phases of preferred growth from product formation. Rhamnolipids as bulk chemicals represent a model system for future processes of industrial biotechnology and are therefore tied to the efficiency requirements in competition with the chemical industry.

Evaluating temperature-induced regulation of a ROSE-like RNA-thermometer for heterologous rhamnolipid production in Pseudomonas putida KT2440.

The microbial production of rhamnolipids has been in the focus of research for the last decades. Today, mainly heterologous production systems are targeted due to the advantage of non-pathogenic hosts as well as uncoupling from complex quorum sensing regulatory networks compared to their natural producer Pseudomonas aeruginosa. In the recent past, the presence and function of a ROSE-like RNA-thermometer located in the 5'UTR of the rhamnosyltransferase genes rhlAB has been reported in wild type P.

Factors predicting hypocalcemia after total thyroidectomy - A retrospective cohort analysis.

Background: Hypocalcemia after total thyroidectomy is the most frequent complication resulting in prolongation of hospitalisation. Therefore we aimed to analyse clinical risk factors predictive for hypocalcemia and its long term persistence after total thyroidectomy.

Methods: Retrospective analysis of patients undergoing total thyroidectomy from 2005 until 2013.

Evaluation of self-educational training methods to learn laparoscopic skills - a randomized controlled trial.

Background: Evaluation of two different self-educational methods (video assisted learning versus video assisted learning plus a nodal point operation primer) on learning laparoscopic suturing and intracorporal knotting.

Methods: Randomized controlled trial at the laparoscopic surgical training center, University of Tubingen with 45 surgical novices first year medical students being pretested for dexterity. After self-educational training for 90 min with either method (Group A: video assisted learning, Group B: video assisted learning plus a nodal point operation primer) participants had to perform five laparoscopic intracorporal knots.

Primary squamous cell carcinoma of the thyroid: Case report and systematic review of the literature.

Background: Primary squamous cell cancer (PSCC) of thyroid is a rare malignancy with poor prognosis. It is mandatory to exclude secondary involvement of the thyroid by panendoscopy, CT-scan and immunohistochemical analysis. As treatment surgery, radiation and rarely chemotherapy is employed.

Comparative studies of TIMP-1 immunohistochemistry, TIMP-1 FISH analysis and plasma TIMP-1 in glioblastoma patients.

Tissue inhibitor of metalloproteinases-1 (TIMP-1) has been associated with poor prognosis and resistance towards chemotherapy in several cancer forms. In a previous study we found an association between a low TIMP-1 tumor immunoreactivity and increased survival for glioblastoma patients, when compared to moderate and high TIMP-1 tumor immunoreactivity. The aim of the present study was to further evaluate TIMP-1 as a biomarker in gliomas by studying TIMP-1 gene copy numbers by fluorescence in situ hybridization (FISH) on 33 glioblastoma biopsies and by measuring levels of TIMP-1 in plasma obtained pre-operatively from 43 patients (31 gliomas including 21 glioblastomas) by enzyme-linked immunosorbent assay (ELISA).

Compliance of Clinical Pathways in Elective Laparoscopic Cholecystectomy: Evaluation of Different Implementation Methods.

Background: Clinical pathways aim to standardize perioperative and postoperative care of surgical procedures and are shown to result in a significant optimization associated with cost reduction. The aim of this study was to establish the impact of two different implementations forms of clinical pathways on the pathway compliance and resulting costs.

Methods: Data of patients undergoing elective cholecystectomy for symptomatic cholecystolithiasis were collected over two different periods: using a clinical pathway in the form of a paper-based checklist, or a clinical pathway integrated into the paper-based medical treatment and nursing documentation.

Rapid thyroid nodule growth is not a marker for well-differentiated thyroid cancer.

Background: Rapid growth of thyroid nodules is described as being associated with thyroid cancer. The objective of the study was to determine how the growth rate of thyroid nodules during follow-up is associated with the risk of thyroid cancer.

Methods: Retrospective analysis of patients undergoing thyroid surgery for nodular disease and a repetitive preoperative ultrasound work-up of at least 6 months was done.

Diagnostic accuracy of hyperbilirubinaemia in anticipating appendicitis and its severity.

Background: Hyperbilirubinaemia is reported to be a positive predictor in diagnosing appendicitis and especially appendiceal perforation. We, therefore, analysed the diagnostic accuracy of serum bilirubin in anticipating appendicitis and its severity.

Methods: All consecutive patients undergoing appendectomy for suspected appendicitis from May 2009 to August 2011 were analysed.

Silicide induced ion beam patterning of Si(001).

Low energy ion beam pattern formation on Si with simultaneous co-deposition of Ag, Pd, Pb, Ir, Fe or C impurities was investigated by in situ scanning tunneling microscopy as well as ex situ atomic force microscopy, scanning electron microscopy, transmission electron microscopy and Rutherford backscattering spectrometry. The impurities were supplied by sputter deposition. Additional insight into the mechanism of pattern formation was obtained by more controlled supply through e-beam evaporation.

An explorative analysis of ERCC1-19q13 copy number aberrations in a chemonaive stage III colorectal cancer cohort.

Background: Platinum-based chemotherapy has long been used in the treatment of a variety of cancers and functions by inducing DNA damage. ERCC1 and ERCC4 are involved in the removal of this damage and have previously been implicated in resistance to platinum compounds. The aim of the current investigation is to determine the presence, frequency and prognostic impact of ERCC1 or ERCC4 gene copy number alterations in colorectal cancer (CRC).

Beam position and energy monitoring in compact linear accelerators for radiotherapy.

The experimental verification of a novel sensor topology capable of measuring both the position and energy of an electron beam inside a compact electron linear accelerator for radiotherapy is presented. The method applies microwave sensing techniques and allows for the noninterceptive monitoring of the respective beam parameters within compact accelerators for medical or industrial purposes. A state space feedback approach is described with the help of which beam displacements, once detected, can be corrected within a few system macropulses.

Mechanisms of topoisomerase I (TOP1) gene copy number increase in a stage III colorectal cancer patient cohort.

Background: Topoisomerase I (Top1) is the target of Top1 inhibitor chemotherapy. The TOP1 gene, located at 20q12-q13.1, is frequently detected at elevated copy numbers in colorectal cancer (CRC).

Prognostic and predictive value of tumor vascular endothelial growth factor gene amplification in metastatic breast cancer treated with paclitaxel with and without bevacizumab; results from ECOG 2100 trial.

Purpose: Clinically validated biomarkers for anti-angiogenesis agents are not available. We have previously reported associations between candidate VEGFA single-nucleotide polymorphisms (SNP) and overall survival (OS) in E2100. The associations between tumor VEGFA amplification and outcome are evaluated here.

MSH2 and CXCR4 involvement in malignant VIPoma.

Background: Vasoactive intestinal polypeptide secreting tumors(VIPomas) are rare endocrine tumors of the pancreas with an estimated incidence of 0.1 per million per year. The molecular mechanisms that mediate development of VIPomas are poorly investigated and require definition.

Topoisomerase 1(TOP1) gene copy number in stage III colorectal cancer patients and its relation to prognosis.

Purpose: A Topoisomerase 1 (Top1) poison is frequently included in the treatment regimens for metastatic colorectal cancer (mCRC). However, no predictive biomarkers for Top1 poisons are available. We here report a study on the TOP1 gene copy number in CRC patients and its association with patient prognosis and tumor cell proliferation.

Utility of routine ultrasound after laparoscopic cholecystectomy to detect early postoperative complication.

Background And Aim: In up to 3% of laparoscopic cholecystectomies, procedure-related complications occur. Routine postoperative ultrasound is one means of screening for these complications. The aim of this study was to determine the utility of this practice after laparoscopic cholecystectomy.

ESR1 gene status correlates with estrogen receptor protein levels measured by ligand binding assay and immunohistochemistry.

The Estrogen Receptor (ER) is an established predictive marker for the selection of adjuvant endocrine treatment in early breast cancer. During the 1990s Immunohistochemistry (IHC) replaced cytosol based assays for determination of ER status. This study examined the association between ER protein level determined by two different methods and ESR1 gene copy number.