Linear Analog Research Articles

Synthesis and morphological characterization of linear and miktoarm star poly(solketal methacrylate)-block-polystyrene copolymers

The synthesis, molecular characterization, and morphological evaluation of ABn, (n = 2,3) miktoarm star block copolymers consisting of poly(glycerol monomethacrylate) (PGMA) and polystyrene (PS) with varying molecular weights and compositions is described. The system is known to demonstrate a remarkably high Flory-Huggins interaction parameter. The corresponding linear diblock copolymer analogues, were synthesized as well, and comparisons with regard to feature dimensions and morphologies are provided. Well-ordered nanostructures of various morphologies were formed with domain spacing as low as 7.2 nm. Different morphologies were attained by some of the topological isomers indicating that in miktoarm star block copolymers the phase boundaries were strongly shifted. Additionally, a triblock ABA analogue was studied to investigate the effect of triblock copolymer conformations. Noteworthy is that for copolymers with different macromolecular architecture leading to similar morphology; different domain spacings were obtained. The synthesis of all the samples was carried out by high-vacuum anionic polymerization techniques. Molecular characterization with Size Exclusion Chromatography (SEC) and Proton Nuclear Magnetic Resonance Spectroscopy (1H NMR) confirmed well-defined copolymers obtained. The morphological characterization was accomplished by Small-Angle X-ray Scattering (SAXS). The observations from this study highlight the potential of incorporating macromolecular architecture in the self-assembly of strongly immiscible block copolymers to attain ultra-small nanofeatures with desired morphologies.

Improved Solid Electrolyte Conductivity via Macromolecular Self-Assembly: From Linear to Star Comb-like P(S-co-BzMA)-b-POEGA Block Copolymers.

Star block copolymer electrolytes with a lithium-ion conducting phase are investigated in the present work to assess the influence of this complex architecture compared to that of the linear one, on both, bulk morphology and ionic conductivity. For that purpose, the controlled synthesis of a series of poly(styrene-co-benzyl methacrylate)-b-poly[oligo(ethylene glycol) methyl ether acrylate] [P(S-co-BzMA)-b-POEGA] block copolymers (BCPs) by reversible addition-fragmentation transfer polymerization was performed from either a monofunctional or a tetrafunctional chain transfer agent containing trithiocarbonate groups. We emphasized how a small amount of styrene (6 mol %) drastically improved the control of the RAFT polymerization of benzyl methacrylate mediated by the tetrafunctional chain transfer agent. Transmission electron microscopy and small-angle X-ray scattering demonstrated a clear segregation of the BCPs in the presence of lithium salt. Interestingly, the star BCPs gave rise to highly ordered lamellar structures as compared to that of the linear analogues. Consequently, the reduced lamellae tortuosity of self-assembled star BCPs improved the lithium conductivity by more than 8 times at 30 °C for ∼30 wt % of the POEGA conductive phase.

Facile Synthesis of Helicene-Containing Arenes for Optical Limiting Devices.

A helicene-containing arene and its linear analogue have been successfully synthesized and characterized, where the single-crystal X-ray diffraction analysis indicates that the former can arrange in an offset packing style with a π-π overlap. The introduction of pentagon-rings into the parent skeletons in the resulting compounds can boost the stability, and such helicene-containing molecule possesses higher solubility in organic solvent than the linear analogue. The structural difference has significantly influenced the optical limiting performance. The former in solution and in doped gel glass presents higher optical limiting response towards 532 nm laser than the latter. This study can enrich the functionalization of helicene, which can possess a positive effect in terms of nonlinear optical property.

The Topology of Polymer Brushes Determines Their Nanoscale Hydration.

Time-of-flight neutron reflectometry (ToF-NR) performed under different relative humidity conditions demonstrates that polymer brushes constituted by hydrophilic, cyclic macromolecules exhibit a more compact conformation with lower roughness as compared to linear brush analogues, due to the absence of dangling chain ends extending at the polymer-vapor interface. In addition, cyclic brushes feature a larger swelling ratio and an increased solvent uptake with respect to their linear counterparts as a consequence of the increased interchain steric repulsions. It is proposed that differences in swelling ratios between linear and cyclic brushes come from differences in osmotic pressure experienced by each brush topology. These differences stem from entropic constraints. The findings suggest that to correlate the equilibrium swelling ratios at different relative humidity for different topologies a new form of the Flory-like expression for equilibrium thicknesses of grafted brushes is needed.

Greek Caregivers of Chronically Ill Patients Struggling in Everyday Life.

Caregivers of chronically ill geriatric patients face several problems throughout the disease progression of the patients under their care. This is a prospective crosssectional study conducted from September 2017 to September 2018, including 130 caregivers of geriatric patients from Attica, Greece. This study investigates caregivers' anxiety, perception of changes in their lives, and quality of life. The questionnaires administered were the revised Bakas Caregiving Outcomes Scale (rBCOS), the State-Trait Anxiety Inventory (STAI), and the Linear Analogue Scale Assessment (LASA). Influencing factors associated with rBCOS, STAI and LASA were care timespan and energy levels. Only the State Anxiety Scale and the Patient-caregiver Relationship rBCOS questionnaire seemed to be affected by a cancer diagnosis. Our findings revealed that anxiety, low quality of life, and perception of changes in the lives of caregivers are the underlying factors. Significant factors were time spent caring for the patient, the status of their relationship, the diagnosis, especially in life-threatening and life-limiting diseases, and the caregivers' energy levels. These results are important in order to comprehend the lives of caregivers and assess by what means could the healthcare system and society further assist them.

Flow-Based Fmoc-SPPS Preparation and SAR Study of Cathelicidin-PY Reveals Selective Antimicrobial Activity

Antimicrobial peptides (AMPs) hold promise as novel therapeutics in the fight against multi-drug-resistant pathogens. Cathelicidin-PY (NH2-RKCNFLCKLKEKLRTVITSHIDKVLRPQG-COOH) is a 29-residue disulfide-cyclised antimicrobial peptide secreted as an innate host defence mechanism by the frog Paa yunnanensis (PY) and reported to possess broad-spectrum antibacterial and antifungal properties, exhibiting low cytotoxic and low hemolytic activity. Herein, we detail the total synthesis of cathelicidin-PY using an entirely on-resin synthesis, including assembly of the linear sequence by rapid flow Fmoc-SPPS and iodine-mediated disulfide bridge formation. By optimising a synthetic strategy to prepare cathelicidin-PY, this strategy was subsequently adapted to prepare a bicyclic head-to-tail cyclised derivative of cathelicidin-PY. The structure-activity relationship (SAR) of cathelicidin-PY with respect to the N-terminally positioned disulfide was further probed by preparing an alanine-substituted linear analogue and a series of lactam-bridged peptidomimetics implementing side chain to side chain cyclisation. The analogues were investigated for antimicrobial activity, secondary structure by circular dichroism (CD), and stability in human serum. Surprisingly, the disulfide bridge emerged as non-essential to antimicrobial activity and secondary structure but was amenable to synthetic modification. Furthermore, the synthetic AMP and multiple analogues demonstrated selective activity towards Gram-negative pathogen E. coli in physiologically relevant concentrations of divalent cations.

Preparation and Characterization of a Novel Hyperbranched Polyester Polymers Using A2+B3 Monomers

Abstract Compared to linear analogs, hyperbranched polymers (HBPs) have gotten much attention in the last decade because of their intrinsic globular topologies and distinctive features like low viscosity, high solubility, and a high degree of functionality. In this work, four types of hyperbranched polyester polymer HBPs have been synthesized using the A2+B3 polycondensation methodology. Firstly, the starting material B3 monomer (Pyrimidine-2,4,6-triol) has been synthesized using urea and malonic acid with the presence of sodium Na as the catalyst for the reaction. Secondly, four types of materials (tartaric acid TA, adipic acid AD, maleic acid MA, and phthalic anhydride PA) as A2 monomers were added to the starting material B3 monomer in an oil bath to prepare the four types of HBP. The chemical structure of HBPs was characterized by FTIR, and 1H-NMR. The molecular weight of the prepared HBPs was characterized by gel permeation chromatography GPC, and thermal properties were characterized by differential scanning calorimetry DSC and thermal gravimetric analysis TGA. FTIR results showed that there are new bands, such as C-O-C between A2 and B3 monomers, as indicated by 1H-NMR. In addition, GPC shows that the prepared polymers have a narrow molecular weight distribution with good thermal stability, as indicated by DSC and TGA.

Synthesis and characterization of poly(tetramethylene oxide)-based segmented ionenes block copolymer with aliphatic or DABCO hard segments

In this study, the effects of the contents of the soft and hard segments as well as the type of hard segments (linear aliphatic and DABCO) on the properties of PTMO-based segmented ionenes were investigated. DSC revealed that soft segment weight fractions up to 75 wt% induced heterogeneous crystallization while the melting temperature decreased due to the lower degree of crystallization. DMA showed the formation of a higher degree of ionic aggregates in both linear aliphatic and DABCO-based PTMO ionenes with 25 wt% of soft segment resulting from strong Coulombic interactions between hard segments. DABCO-based ionenes showed a higher degree of phase separation compared to linear aliphatic analogs and displayed a long-range ordered lamellar structure. In contrast, linear aliphatic ionenes showed the formation of random ionic domains, which was confirmed by SAXS and AFM. TGA showed that the PTMO-based ionenes were thermally stable up to 250 °C and suggested that the DABCO hard segment has a weaker protective effect against the degradation of the PTMO soft segment at elevated temperatures compared to the linear aliphatic hard segment. Uniaxial tensile tests exhibited stress-induced crystallization of PTMO-based ionenes, high elongation at break with linear aliphatic hard segment compared to the DABCO hard segment, and the opposite trend of Young's modulus and ultimate tensile strength by changing the type of the hard segment.

Long-term 1,2-dimethylhydrazine triggers pathological remodeling of colon mucosa through repression of sestrin2, nuclear factor (erythroid-derived 2)-like 2, and sirtuin4 stimulating mitochondrial stress and metabolic reprogramming.

1,2-Dimethylhydrazine (DMH) is a plant toxicant that enters the food web through the diet. It is biotransformed into azoxymethane, a colon carcinogen, during the first hepatic passage. In mice, this study assessed the role of glutamate dehydrogenase (GDH), a key glutaminolysis enzyme in DMH-induced colorectal cancer (CRC). Colon samples were taken from mice given 6 or 15 weekly doses of 20mg/kg DMH and serially sacrificed. Repeated DMH doses induced early aberrant crypt foci that evolved into irreversible adenocarcinomas over 24weeks, along with an increase in GDH and lactate dehydrogenase activities (+ 122%, + 238%, P < 0.001), indicating a switch to aerobic glycolysis and glutaminolysis. Transcriptional downregulation of the endogenous GDH inhibitor, sirtuin4, and two redox regulators, mitochondrial sestrin2 and nuclear factor (erythroid derivative 2)-like 2 (- 26% and - 22%, P < 0, 05; and - 30%, P < 0.01), exacerbated mitochondrial stress by boosting mitochondrial superoxide dismutase activity (+ 240% (P < 0.001) while depressing catalase activity and GSH levels (- 57% and - 60%, P < 0.001). In vitro, allosteric GDH inhibition by 50µM epigallocatechin gallate decreased human carcinoma (HCT-116) cells' viability, clonogenicity, and migration (- 43% and - 57%, P < 0.001, 41%, P < 0.05), while stimulating ROS release (+ 57%, P < 0.001). Dimethylfumarate (DMF), a linear electrophile and mitochondrial fumarate analog, rebalanced ROS levels (- 34%, P < 0.05) and improved GDH activity, cell viability, and tumorogenic capacity (+ 20%, 20%, P < 0.001; and 33%, P < 0.05). Thus, the pathological remodeling of colon mucosa is supported by metabolic reprogramming bypassing uncoupled mitochondria. DMF highlights the critical role of electrophile response elements in modulating redox mithormesis and redox homeostasis during CRC.

New Nostocyclophanes from Nostoc linckia.

Six new nostocyclophanes and four known compounds have been isolated from Nostoc linckia (Nostocaceae) cyanobacterial strain UTEX B1932. The new compounds, nostocyclophanes E-J (1-6), were characterized by NMR and MS techniques. The known compounds were nostocyclophanes B-D, previously isolated from this strain, and dedichloronostocyclophane D. Structural modifications on the new [7.7]paracyclophane analogs 1-5, isolated from the 80% methanol fraction, range from simple changes such as the lack of methylation or halogenation to more unusual modifications such as those seen in nostocyclophane H (4), in which the exocyclic alkyl chains are of different length; this is the first time this modification has been observed in this family of natural products. In addition, nostocyclophane J (6) is a linear analog in which C-20 is chlorinated in preparation for the presumed enzymatic Friedel-Craft cyclization needed to form the final ring structure, analogous to the biosynthesis of the related cylindrocyclophanes. Nostocyclophane D, dedichloronostocyclophane D, and nostocyclophanes E-J demonstrated moderate to weak growth inhibition against MDA-MB-231 breast cancer cells.

Aerodynamic shape optimization based on discrete adjoint and RBF

This paper presents a new framework for Aerodynamic Shape Optimization (ASO) implemented inside the open-source software SU2. A parametrized surface is iteratively morphed to improve a desired aerodynamic coefficient. At each loop, the computational grid must be updated. The radial basis function (RBF) mesh deformation technique is introduced to extend the capability to explore the design space. RBF is implemented with some state-of-the-art data reduction systems to lower the computational cost. The Discrete Adjoint is adopted to compute the sensitivity in combination with Automatic Differentiation to calculate the required Jacobians. RBF is differentiated as well, resulting in a method-dependent surface sensitivity. The gradient-based algorithm “Sequential Least Squares Programming” drives the research of the minimum. The study demonstrates that the presented combination is more robust than an ASO, including linear elasticity analogy (ELA) as mesh deformation method. It can handle complex geometries and apply larger displacements, making possible the optimization of a wing-winglet configuration and a rotating wind turbine. Results are presented in two and three-dimensions for compressible and incompressible flows, showing a stronger reduction of the drag without affecting the lift.

Design of Analgesic Trivalent Peptides with Low Withdrawal Symptoms: Probing the Antinociceptive Profile of Novel Linear and Cyclic Peptides as Opioid Pan Ligands

The discovery of efficacious and safe analgesics with reduced side effects is the foremost challenge in the pain field. In this work, we report the in vitro and in vivo evaluation of linear and cyclic analogues of biphalin with the aim to complete the series of structural modifications previously applied in the development of opioid peptides incorporating a xylene bridge. Replacement of Tyr1,1' by Dmt (2,5-dimethyltyrosine) in the linear biphalin analogue AM94 and cyclic analogue MACE4 resulted in two new compounds (namely, MJ2 and MJ5) endowed with improved KOR/MOR/DOR binding affinity. Both compounds showed a strong antinociceptive profile in in vivo models of nociception, allodynia, and hyperalgesia via the tail flick, hot plate, and formalin tests after intracerebroventricular and subcutaneous administration. One of these ligands, MJ2, was also tested in tolerance and dependence studies, exhibiting very little withdrawal symptoms.

The Cytotoxicity of Analogues Carnosine Dipeptide on Human Glioblastoma Multiforme

Background & Aims: The present study evaluated the effect of some synthesized linear and cyclic Carnosine analogues on the cells of human glioblastoma multiforme (GBM). The purpose of this research was to study the exposure of Carnosin analogues on astrocytoma using several experiments. Methods: The mass spectral measurements were performed on a 6410 Agilent LCMS triple quadrupole mass spectrometer (LCMS) with an electrospray ionization (ESI) interface. All tests were carried out six times. The concentration used for peptides (10 µg/mL) was selected based on MTT assay. The effect of peptides on the activity of SDH was assayed by MTT test. 100 μL mitochondrial suspension from GBM and normal groups were incubated with applied concentration of peptides (10μg/mL) at 37°C for 30 min. DCFH (final concentration, 10µM) was added to cells of both groups and incubated at 37°C for 15 min. The fluorescence intensity of DCFH which is an indicator of ROS concentration was then assayed by a Shimadzu RF-5000U fluorescence spectrophotometer. The cationic fluorescent dye, rhodamine 123 (concentration10 µM), from mitochondria into the cytosol have been used for the determination of MMP collapse. Mitochondria from astrocytoma and normal astocyte groups were suspended in corresponding assay buffer and incubated at 37°C with 10µg/mL peptides. The release was assayed by the Quantikine Cytochrome c. Carnosine peptide analogues on the activation of caspase-3 in the mitochondria isolated from GBM and normal groups using Sigma’s caspase-3 colorimetric assay kit. Results: Our study showed that a various range of toxicity on GBM cells was resulted by the linear and cyclic Carnosine analogues using MTT assay. Also, applying peptides on the mitochondria of GBM cells, a raise of mitochondrial reactive oxygen species (ROS) level, mitochondrial swelling, mitochondrial membrane potential (∆ψm) collapse, release of cytochrome c and caspase-3 activation of the affected mitochondria were detected. Conclusion: Based on the overall results, cyclic Carnosine analogues, especially compound 1c [Cyclo-(β-alanine-¬His-Pro-¬β-alanine-¬His)] showed more toxic activity than linear Carnosine analogues, which would be supporting to develop Carnosine cyclic peptide analogues as new anticancer and complementary therapeutic agents for the treatment of glioblastoma.

Multi-orbit cyclic subspace codes and linear sets

Cyclic subspace codes gained a lot of attention especially because they may be used in random network coding for correction of errors and erasures. Roth, Raviv and Tamo in 2018 established a connection between cyclic subspace codes (with certain parameters) and Sidon spaces. These latter objects were introduced by Bachoc, Serra and Zémor in 2017 in relation with the linear analogue of Vosper's Theorem. This connection allowed Roth, Raviv and Tamo to construct large classes of cyclic subspace codes with one or more orbits. In this paper we will investigate cyclic subspace codes associated to a set of Sidon spaces, that is cyclic subspace codes with more than one orbit. Moreover, we will also use the geometry of linear sets to provide some bounds on the parameters of a cyclic subspace code. Conversely, cyclic subspace codes are used to construct families of linear sets which extend a class of linear sets recently introduced by Napolitano, Santonastaso, Polverino and the author. This yields large classes of linear sets with a special pattern of intersection with the hyperplanes, defining rank metric and Hamming metric codes with only three distinct weights.

Non-Rouse behavior of short ring polymers in melts by molecular dynamics simulations.

Short ring polymers are expected to behave nearly Rouse-like due to the little effect of topological constraints of non-knot and non-concatenation. However, this notion is questioned because of several simulation and experiment findings in recent times, which requires a further more quantitative study. Therefore, we perform a deep investigation of statics and dynamics of flexible short ring polymers (N < 2Ne) in melts via molecular dynamics simulations by further taking linear analogues as well as all-crossing ring and linear polymers with switched off topological constraints for comparisons and demonstrate the noticeable deviations from the Rouse model in terms of local and global scales. Although the overall size is compact, the subchains are swollen, which is traced back to the deeper "segmental correlation hole" effect. The same scaling relationship of the non-Gaussian deviation of the static structure factor holds, but the deviation magnitude of rings is larger than that of linear analogues. By checking the non-Gaussian parameter and autocorrelation function of center-of-mass velocity, the physical origin of anomalous sub-diffusions of short rings is identified as unscreened viscoelastic hydrodynamic interactions and not correlation hole effects, like linear analogues.

Efficacy and safety of low concentration hydrogen peroxide as nasopharyngeal lavage fluid in the treatment for nasopharyngeal carcinoma radiotherapy: a pilot cohort study.

Purpose: This study aimed to evaluate and analyze the efficacy and safety of low concentration (0.15%) hydrogen peroxide as nasopharyngeal lavage fluid in the treatment for nasopharyngeal carcinoma radiotherapy. Methods: Patients with nasopharyngeal carcinoma from Jiangxi cancer hospital were randomly divided into two cohorts. The training cohort (n= 50) received low concentration (0.15%) hydrogen peroxide as nasopharyngeal lavage fluid in the treatment for nasopharyngeal carcinoma radiotherapy, and the control cohort (n= 50) received 0.02% nitrofurazone lavage fluid. The primary endpoint of the study was result of short-term efficacy. Second endpoints were assessment of the linear visual analogue scale score and the incidences rate of nasopharyngeal radiation related toxicity. Results: All patients had completed the scheduled nasopharyngeal radiotherapy except two patients in control cohort. The complete response, partial response, stable disease and disease objective response of nasopharyngeal primary tumor observed in the training cohort included 18 cases, 23 cases, 9 cases and 41 cases respectively, while in the control cohort 20 cases, 25 cases, 5 cases and 45 cases were recorded, respectively. The study showed a significant discrepancy in the incidence rate of radiation-related mucosa damage between the two. Specifically, Grade 1 and 2 included 37 cases (74.0%) in the training cohort, while in the control cohort the cases were 20 (40.0%). Grade 3 and 4 damage however reported an incidence of 26.0% and 60%, respectively, which clearly constitutes a significant statistical difference (P = 0.002). The assessment of linear visual analogue scale showed that the patients self-conscious comfortable feeling in the training cohort were significantly higher than in the control cohort (P = 0.003). Conclusions: low concentration (0.15%) hydrogen peroxide as nasopharyngeal lavage fluid in the treatment for nasopharyngeal carcinoma patients is effective and safe, and can reduce nasopharyngeal local mucosa radiation related toxicity after radiotherapy.

Resistance is futile: targeting multidrug-resistant bacteria with de novo Cys-rich cyclic polypeptides.

The search for novel antimicrobial agents to combat microbial pathogens is intensifying in response to rapid drug resistance development to current antibiotic therapeutics. The use of disulfide-rich head-to-tail cyclized polypeptides as molecular frameworks for designing a new type of peptide antibiotics is gaining increasing attention among the scientific community and the pharmaceutical industry. The use of macrocyclic peptides, further constrained by the presence of several disulfide bonds, makes these peptide frameworks remarkably more stable to thermal, biological, and chemical degradation showing better activities when compared to their linear analogs. Many of these novel peptide scaffolds have been shown to have a high tolerance to sequence variability in those residues not involved in disulfide bonds, able to cross biological membranes, and efficiently target complex biomolecular interactions. Hence, these unique properties make the use of these scaffolds ideal for many biotechnological applications, including the design of novel peptide antibiotics. This article provides an overview of the new developments in the use of several disulfide-rich cyclic polypeptides, including cyclotides, θ-defensins, and sunflower trypsin inhibitor peptides, among others, in the development of novel antimicrobial peptides against multidrug-resistant bacteria.

Engineering of ion permeable planar membranes and polymersomes based on β-cyclodextrin-cored star copolymers.

For polymersome-based nanoreactor purposes, we herein present the synthesis and characterization of well-defined star amphiphilic copolymers composed of a beta-cyclodextrin (βCD) core and seven poly(butylene oxide)-block-polyglycidol (PBO-PGL) arms per side (βCD-(PBO-PGL)14). The self-assembly behavior of 14-armed βCD-(PBO-PGL)14 and PGL-PBO-PGL (linear analogues without the βCD segment) was investigated using scattering techniques for comparison. The morphologies, including vesicles and micelles, are governed by the hydrophobic-to-hydrophilic (weight) ratio, regardless of the polymer architecture (linear or star). Interestingly, despite notable differences in polymer conformation, the produced supramolecular structures were evidenced to be fairly similar on the structural point of view. We subsequently investigated the ion permeability of the membranes of the self-assemblies focusing on the impact of the presence of βCD. The results demonstrated that the βCD-containing vesicular membranes are less permeable to H+, compared with βCD-free vesicular membranes. The presence of βCD in planar membranes also influences the K+Cl- permeability to some extent. Thus, βCD-containing membranes can be considered as potential candidates in designing nano-containers towards applications where precise changes in environmental pH are required.

Baseline Quality of Life is a Strong and Independent Prognostic Factor for Overall Survival in Metastatic Colorectal Cancer.

Previous studies have established that higher baseline quality of life (QOL) scores are associated with improved survival in patients with metastatic colorectal cancer (mCRC). We examined the relationship between overall survival (OS) and baseline QOL. A total of 1 247 patients with mCRC participating in N9741 (comparing bolus 5-FU/LV, irinotecan [IFL] vs infusional 5-FU/leucovorin [LV]/oxaliplatin [FOLFOX] vs. irinotecan/oxaliplatin [IROX]) provided data at baseline on overall QOL using a single-item linear analogue self-assessment (LASA) 0-100 point scale. The association of OS according to clinically deficient (defined as CD-QOL, score 0-50) vs not clinically deficient (nCD-QOL, score 51-100) baseline QOL scores was tested. A multivariable analysis using Cox proportional hazards modeling was performed to adjust for the effects of multiple baseline factors. An exploratory analysis was performed evaluating OS according to baseline QOL status among patients who did or did not receive second-line therapy. Baseline QOL was a strong predictor of OS for the whole cohort (CD-QOL vs nCD-QOL: 11.2months vs 18.4months, P < .0001), and in each arm IFL 12.4 vs 15.1months, FOLFOX 11.1 months vs 20.6months, and IROX 8.9months vs 18.1months. Baseline QOL was associated with baseline performance status (PS) (P < .0001). After adjusting for PS and treatment arm, baseline QOL was still associated with OS (P = .017). Baseline QOL is an independent prognostic factor for OS in patients with mCRC. The demonstration that patient-assessed QOL and PS are independent prognostic indicators suggests that these assessments provide important complementary prognostic information.

Hydrodynamic radius of dendrimers in solvents.

The diffusion properties and hydrodynamic radius, Rh, of macromolecules are important for theoretical studies and practical application. Moreover, comparison of Rh values obtained from simulation and experimental data is used to check the correctness of simulation results. Here, we study the translation mobility of poly(butylcarbosilane) dendrimers in chloroform solution using molecular dynamics simulations and consider simulation details that may influence the accuracy of the result. Different methods to estimate Rh for a dendrimer are discussed with comparison to our experimental data. It was shown that the traditional MD simulation method for extraction of the diffusion coefficient (and calculation of Rh) of dendrimers as a rule faces difficulties and requires simulation resources several times greater than, for example, the same for a linear analogue. In the majority of MD simulation papers, the diffusion coefficient and/or Rh are calculated incorrectly. Also, we establish that correction of Rh according to the simulation box or estimation of Rh by using the gyration radius does not give values close to experimental data. To avoid the mentioned problems, we found an alternative way: to consider rotational diffusion, which gives an Rh similar to that from experiment and is practically independent of the size of the simulation box and other simulation parameters.