Analysis of a Streptomyces coelicolor A3(2) locus containing the nucleoside diphosphate kinase (ndk) and folylpolyglutamate synthetase (folC) genes

A 3.6-kb DNA fragment from Streptomyces coelicolor A3(2) with the genes valS probably encoding a valyl-tRNA synthetase, folC encoding folylpolyglutamate synthetase, and ndk encoding a nucleoside diphosphate kinase was analysed. folC and ndk are separated by a small open reading frame of unknown function, orfX. The deduced folC gene product is a protein of 46 677 Da whose sequence is similar to other folylpolyglutamate synthetases and folylpolyglutamate synthetase-dihydrofolate synthetases from both Gram-positive and Gram-negative bacteria. After cloning folC behind the lacZ promoter, the Streptomyces folC complemented a folC mutant of Escherichia coli. An essential function for Streptomyces folC was suggested by the fact that it could not be mutated using a conventional gene disruption techniqu

Planar fiber-chip-coupling using angle-polished polarization maintaining fibers

We report on our latest developments of a planar fiber-chip-coupling scheme, using angle polished, polarization maintaining (PM) fibers. Most integrated photonic chip components are polarization sensitive and a suitable way to launch several wavelength channels with the same polarization to the chip is the use of PM fibers. Those impose several challenges at processing and handling to achieve a stable, permanent, and low-loss coupling. We present the processing of the fibers in detail and experimental results for our planar and compact fiber-chip-coupling technique.Comment: 6 pages, 8 figures, conference paper for TWEPP2022, submitted to and reviewed by Journal of Instrumentation (JINST), to be typeset and published in JINS

Signal-to-noise ratio of temperature measurement with Cernox sensors at various supply currents

The Karlsruhe Institute of Technology (KIT) has developed a new thermal method for flow measurement, which is particularly suitable for the application in cryogenic systems. In this method, the stability and the resolution of temperature measurement is important, rather than precision. In other words, constant offsets in temperature measurements can be ignored, and the temperature sensors can be operated at supply currents beyond their nominal design value in order to gain resolution. For this application, the performance of two Cernox TM type CX-1050-SD-HT-1.4L sensors was measured in a temperature range between 300 K and 4 K. The experiments were carried out in the calibration cryostat at the Institute for Technical Physics. Sensors were connected to a Lake Shore Model 121 current source and a Keithley 2701/E digital multimeter for voltage measurements. At constant calibration temperatures, the supply currents were varied such that the resulting voltage drops lay in-between 10 mV and 100 mV. The influence on both the noise and the temperature offset are presented

Population pharmacokinetics of intraperitoneal irinotecan and SN-38 in patients with peritoneal metastases from colorectal origin

Peritoneal metastases (PM) are common in patients with colorectal cancer. Patients with PM have a poor prognosis, and for those who are not eligible for cytoreductive surgery (CRS) with or without hyperthermic intraperitoneal chemotherapy (HIPEC), palliative chemotherapy is currently the only option. Recently, we conducted a phase I trial (INTERACT) in which irinotecan was administered intraperitoneally (IP) to 18 patients ineligible for CRS-HIPEC. The primary objective was to evaluate covariates influencing the PK profile of irinotecan and SN-38 after IP administration. Secondly, a population PK model was developed to support the further development of IP irinotecan by improving dosing in patients with PM. Patients were treated with IP irinotecan every 2 weeks in combination with systemic FOLFOX-bevacizumab. Irinotecan and SN-38 were measured in plasma (588 samples) and SN-38 was measured in peritoneal fluid (267 samples). Concentration-Time data were log-transformed and analyzed using NONMEM version 7.5 using FOCE+I estimation. An additive error model described the residual error, with inter-individual variability in PK parameters modeled exponentially. The final structural model consisted of five compartments. Weight was identified as a covariate influencing the SN-38 plasma volume of distribution and GGT was found to influence the SN-38 plasma clearance. This population PK model adequately described the irinotecan and SN-38 in plasma after IP administration, with weight and GGT as predictive factors. Irinotecan is converted intraperitoneal to SN-38 by carboxylesterases and the plasma bioavailability of irinotecan is low. This model will be used for the further clinical development of IP irinotecan by providing dosing strategies.</p

Silicon-organic hybrid photonics: Overview of recent advances, electro-optical effects and CMOS-integration concepts

In recent decades, much research effort has been invested in the development of photonic integrated circuits, and silicon-on-insulator technology has been established as a reliable platform for highly scalable silicon-based electro-optical modulators. However, the performance of such devices is restricted by the inherent material properties of silicon. An approach to overcoming these deficiencies is to integrate organic materials with exceptionally high optical nonlinearities into a silicon-on-insulator photonic platform. Silicon–organic hybrid photonics has been shown to overcome the drawbacks of silicon-based modulators in terms of operating speed, bandwidth, and energy consumption. This work reviews recent advances in silicon–organic hybrid photonics and covers the latest improvements to single components and device concepts. Special emphasis is given to the in-device performance of novel electro-optical polymers and the use of different electro-optical effects, such as the linear and quadratic electro-optical effect, as well as the electric-field-induced linear electro-optical effect. Finally, the inherent challenges of implementing non-linear optical polymers on a silicon photonic platform are discussed and a perspective for future directions is given

Intraperitoneal pharmacokinetics of systemic oxaliplatin, 5-fluorouracil and bevacizumab in patients with colorectal peritoneal metastases

Background: Peritoneal metastases (PM) commonly occur in colorectal cancer patients. Systemic chemotherapy yields poor outcomes for these patients. It is hypothesised that traditional systemic chemotherapy is not very effective for this patient population. This study investigates to what extent systemic anti-cancer therapy crosses the peritoneal barrier. Methods: In a Phase I study, eighteen patients received systemic oxaliplatin, 5-FU, and bevacizumab. Plasma and peritoneal fluid samples were collected to measure drug concentrations. A non-compartmental analysis determined the Area Under the Curve (AUC) for oxaliplatin and 5-FU in both matrices. Intraperitoneal (IP) and intravenous (IV) exposure ratios were calculated, along with the bevacizumab concentration IP/IV ratio. The relationship between tumour load and IP/IV ratios and the correlation between the IP/IV ratios of different treatments were assessed statistically. Results: A total of 438 5-FU samples and 578 oxaliplatin samples were analysed in plasma and peritoneal fluid. Bevacizumab was quantified with 17 measurements in plasma and 15 measurements IP. Median IP/IV ratios were 0.143, 0.352 and 0.085 for 5-FU, oxaliplatin and bevacizumab, respectively. Oxaliplatin exhibited a longer IP half-life than 5-FU. A correlation was found between oxaliplatin and bevacizumab IP/IV ratios (R=0.69, p=0.01). No statistical correlations were found between the other investigated drugs. Conclusions: Our findings indicate that only a small percentage of systemically administered anti-cancer treatment reaches the IP cavity, questioning their efficacy against PM. This strengthens the hypothesis for repeated intraperitoneal chemotherapy to reach adequate anti-cancer drug levels.</p

Intraperitoneal pharmacokinetics of systemic oxaliplatin, 5-fluorouracil and bevacizumab in patients with colorectal peritoneal metastases

Background: Peritoneal metastases (PM) commonly occur in colorectal cancer patients. Systemic chemotherapy yields poor outcomes for these patients. It is hypothesised that traditional systemic chemotherapy is not very effective for this patient population. This study investigates to what extent systemic anti-cancer therapy crosses the peritoneal barrier. Methods: In a Phase I study, eighteen patients received systemic oxaliplatin, 5-FU, and bevacizumab. Plasma and peritoneal fluid samples were collected to measure drug concentrations. A non-compartmental analysis determined the Area Under the Curve (AUC) for oxaliplatin and 5-FU in both matrices. Intraperitoneal (IP) and intravenous (IV) exposure ratios were calculated, along with the bevacizumab concentration IP/IV ratio. The relationship between tumour load and IP/IV ratios and the correlation between the IP/IV ratios of different treatments were assessed statistically. Results: A total of 438 5-FU samples and 578 oxaliplatin samples were analysed in plasma and peritoneal fluid. Bevacizumab was quantified with 17 measurements in plasma and 15 measurements IP. Median IP/IV ratios were 0.143, 0.352 and 0.085 for 5-FU, oxaliplatin and bevacizumab, respectively. Oxaliplatin exhibited a longer IP half-life than 5-FU. A correlation was found between oxaliplatin and bevacizumab IP/IV ratios (R=0.69, p=0.01). No statistical correlations were found between the other investigated drugs. Conclusions: Our findings indicate that only a small percentage of systemically administered anti-cancer treatment reaches the IP cavity, questioning their efficacy against PM. This strengthens the hypothesis for repeated intraperitoneal chemotherapy to reach adequate anti-cancer drug levels.</p