Manipulating the Properties of Poly(1,4‐Cyclohexylenedimethylene Terephthalate) (PCT) Just by Tuning Steric Configuration of 1.4‐Cyclohexanedimethanol (CHDM)

The properties of poly(1,4‐cyclohexylenedimethylene terephthalate) (PCT) are manipulated only by tuning the steric configuration of 1,4‐cyclohexanedimethanol (CHDM). The chemical structures and compositions of PCTs are confirmed by nuclear magnetic resonance (¹H NMR and ¹³C NMR) before their thermal and mechanical properties are investigated by differential scanning calorimeter, thermogravimetric analyzer, and dynamic mechanical analysis. Results show that the ratio of cis‐ to trans‐CHDM in PCTs has significant influences on their properties. The melting temperature of PCTs is varied from 251 to 313 °C, and the glass transition temperature is increased from 73 to 92 °C when the content of trans‐CHDM in PCTs is increased from 10% to 96%. In addition, the crystallizability of PCT is also increased with the content of trans‐CHDM. However, its thermal stability is decreased seriously when the melting temperature of PCT is higher than 280 °C. It is concluded that when the content of trans‐CHDM is lower than 50% (PCT‐10, PCT‐28, and PCT‐46), the balance of melting temperature, glass transition temperature, and thermal stability for PCT can be achieved. Just by varying the cis/trans ratio of CHDM, rather than the addition of other components, the properties of PCT can be manipulated.     

MR‐based measurements and simulations of the magnetic field created by a realistic transcranial magnetic stimulation (TMS) coil and stimulator

Transcranial magnetic stimulation (TMS) is an emerging technique that allows non‐invasive neurostimulation. However, the correct validation of electromagnetic models of typical TMS coils and the correct assessment of the incident TMS field (B_TMS) produced by standard TMS stimulators are still lacking. Such a validation can be performed by mapping B_TMS produced by a realistic TMS setup. In this study, we show that MRI can provide precise quantification of the magnetic field produced by a realistic TMS coil and a clinically used TMS stimulator in the region in which neurostimulation occurs. Measurements of the phase accumulation created by TMS pulses applied during a tailored MR sequence were performed in a phantom. Dedicated hardware was developed to synchronize a typical, clinically used, TMS setup with a 3‐T MR scanner. For comparison purposes, electromagnetic simulations of B_TMS were performed. MR‐based measurements allow the mapping and quantification of B_TMS starting 2.5 cm from the TMS coil. For closer regions, the intra‐voxel dephasing induced by B_TMS prohibits TMS field measurements. For 1% TMS output, the maximum measured value was ~0.1 mT. Simulations reflect quantitatively the experimental data. These measurements can be used to validate electromagnetic models of TMS coils, to guide TMS coil positioning, and for dosimetry and quality assessment of concurrent TMS‐MRI studies without the need for crude methods, such as motor threshold, for stimulation dose determination.     

Saturated Red Light‐Emitting Copolymers of Poly(aryleneethynylene)s with Narrow‐Band‐Gap (NBG) Units: Synthesis and Luminescent Properties

Summary: A series of novel poly(fluoreneethynylene) (PFE) copolymers containing a molar ratio less than or equal to 50% of narrow‐band‐gap (NBG) comonomers, 4,7‐dithienyl‐2,1,3‐benzothiadiazole (DBT), and 2,1,3‐benzothiadiazole (BT), is prepared by the Pd‐Cu‐catalyzed coupling reaction. The copolymers are soluble in common organic solvents. All the polymers are fluorescent in solution and in solid state. Chemical and photophysical properties of these copolymers were thoroughly studied. Devices based on the copolymers emit saturated red light, and the emission slightly red‐shifted gradually with increasing NBG comonomer content. The maximal external quantum efficiency of the polymer light‐emitting diodes (PLED) reaches 0.41% with the emission maximum at 638 nm.

Synthesis of PFE by Pd‐Cu‐catalyzed coupling reaction.     

A Unique Meta‐Form Structure in the Stereocomplex of Poly(D‐lactic acid) with Low‐Molecular‐Weight Poly(L‐lactic acid)

The crystalline structure and crystallization behavior of PLLA crystals in a 1:1 w/w mixture of low‐MW PLLA with high‐MW PDLA were analyzed using WAXD, DSC, and SAXS. Under cold crystallization, homopolymeric PLLA, appearing as a meta crystal, was discovered in the PDLA/LMW‐PLLA blend. The meta‐ and α′ crystal forms of PLLA were found to form on crystallization at a T_cc of 85–95 °C and the α crystal PLLA formed at 100 ≤ T_cc < 120 °C. The meta‐crystal PLLA may be incorporated in the stereocomplexed PDLA/LMW‐PLLA lamellar region. During heating, the meta‐crystal PLLA first partially melted and then repacked directly into the α crystal PLLA without going through the less‐stable α′ form.

     

Mechanical Properties of Blends of Double‐Fullerene End‐Capped Poly(ethylene oxide) and Poly(L‐lactic acid)

Summary: The crystallization behavior and mechanical properties of composites of PLLA and FPEOF were studied using DSC, DMA and tensile strength measurements. For PLLA/FPEOF composites aged at room temperature, when PLLA was amorphous, an astonishing around 100 times increase in the fracture strain with a high modulus was observed. For PLLA/FPEOF composites aged at 90 °C, the mechanical performance of the composites was greatly decreased and the fracture strain did not show much of an increase compared with pure PLLA. A mechanism for the large changes in the mechanical properties of PLLA/FPEOF blends aged at different temperatures was proposed.

Strain‐stress curves of the PLLA/FPEO20F6 composite aged at 90 °C and room temperature.     

Linking non‐invasive parametric MRI with invasive physiological measurements (MR‐PHYSIOL): towards a hybrid and integrated approach for investigation of acute kidney injury in rats

Acute kidney injury of various origins shares a common link in the pathophysiological chain of events: imbalance between renal medullary oxygen delivery and oxygen demand. For in vivo assessment of kidney haemodynamics and oxygenation in animals, quantitative but invasive physiological methods are established. A very limited number of studies attempted to link these invasive methods with parametric Magnetic Resonance Imaging (MRI) of the kidney. Moreover, the validity of parametric MRI (pMRI) as a surrogate marker for renal tissue perfusion and renal oxygenation has not been systematically examined yet. For this reason, we set out to combine invasive techniques and non‐invasive MRI in an integrated hybrid setup (MR‐PHYSIOL) with the ultimate goal to calibrate, monitor and interpret parametric MR and physiological parameters by means of standardized interventions. Here we present a first report on the current status of this multi‐modality approach. For this purpose, we first highlight key characteristics of renal perfusion and oxygenation. Second, concepts for in vivo characterization of renal perfusion and oxygenation are surveyed together with the capabilities of MRI for probing blood oxygenation‐dependent tissue stages. Practical concerns evoked by the use of strong magnetic fields in MRI and interferences between MRI and invasive physiological probes are discussed. Technical solutions that balance the needs of in vivo physiological measurements together with the constraints dictated by small bore MR scanners are presented. An early implementation of the integrated MR‐PHYSIOL approach is demonstrated including brief interventions of hypoxia and hyperoxia.     

Differences Between Stereocomplex Spherulites Obtained in Equimolar and Non‐Equimolar Poly(L‐lactide)/Poly(D‐lactide) Blends

PLLA/PDLA blends were crystallized between 120 and 195 °C. The stereocomplex spherulites acquired in equimolar and non‐equimolar blends were compared using POM, WAXD, DSC, and AFM. For equimolar blends, stereocomplex crystals show spherulites with positive birefringence, which is ascribed to the existence of domains made up of tangentially oriented lamellae. For PLLA‐rich (or PDLA‐rich) blends, the signs of the birefringence changed from a positive spherulite to a mixed spherulite and then to a negative spherulite. In negative spherulites, most lamellae orient radially. Radial and tangential cracks were observed in equimolar blends when crystallization took place above 175 °C whereas no cracks formed for non‐equimolar blends.

     

Regulatory role of leukocyte common antigen‐related molecule (LAR) in thymocyte differentiation

The strength of interaction between the antigenic peptide‐loaded MHC (MHC/p) and the TCR determines T‐cell fate in the thymus. A high avidity interaction between the TCR and the MHC/p induces apoptosis of self‐reactive T cells (negative selection), whereas a moderate avidity interaction rescues thymocytes from apoptosis and permits further differentiation to mature T cells (positive selection). Leukocyte common antigen‐related molecule (LAR), a receptor‐like protein tyrosine phosphatase, is expressed on immature thymocytes, but its role in thymocyte differentiation has not yet been fully elucidated. We analyzed LAR‐deficient mice and demonstrated that LAR deficiency affected the differentiation and expansion of immature thymocytes as well as positive and negative selection. Furthermore, LAR deficiency resulted in a lower Ca²⁺ response. The results indicate that LAR is an important modulator of TCR signaling that controls thymocyte differentiation.     

Crystallization of Poly(vinylidene fluoride) in Blends with Poly(methyl methacrylate‐co‐methacrylic acid) Copolymers

A series of poly(methyl methacrylate‐co‐methacrylic acid) (PMMA‐co‐MAA) random copolymers ranging in MAA content from 0–15 mol% is synthesized and blended with poly(vinylidene fluoride) (PVDF). Using infrared spectroscopy, it is observed that the absorption bands attributed to hydrogen‐bonded carbonyl groups increase in intensity as the amount of MAA in the copolymer increases. In DSC analysis, the crystallization temperature of the PVDF in the blend initially decreases by ca. 12 °C with MAA contents ranging from 0 to 5.5 mol%; however, a PVDF blend with a 15 mol% MAA copolymer has a crystallization temperature that is only ca. 3 °C below that of pure PVDF. Similarly, spherulitic growth rate analysis initially shows a decrease in radial growth rate for PVDF in blends with PMMA‐co‐MAA copolymers containing less than 5.5 mol% MAA. At higher MAA copolymer contents, the spherulitic growth rate approaches that of pure PVDF. It is concluded that the presence of the MAA comono­mer in the PMMA‐co‐MAA copolymer initially (<5.5 mol% MAA) increases the intermolecular interactions between the copoly­mer and the PVDF. However, as the MAA content of the copolymer rises above 5.5 mol%, intramolecular hydrogen bonding interactions within the PMMA‐co‐MAA copolymer cause the copoly­mer to be less compatible with PVDF.

     

Effect of Temperature on the Mobility of Core‐Shell‐Type Nanoparticles Composed of Poly(γ‐benzyl‐L‐glutamate) and Poly(N‐isopropylacrylamide)

Summary: Core‐shell‐type nanoparticles composed of PBLG and PNIPAAm were prepared in an attempt to study the effects of temperature on the dynamic behavior of temperature‐sensitive polymeric shell, PNIPAAm, in the nanoparticles by ¹H NMR spectroscopy. Spin‐lattice relaxation time (T₁) and line halfwidth in D₂O and CDCl₃ were measured to monitor the change of the chain mobility of PNIPAAm in the GN nanoparticles within the temperature range encompassing its LCST. The molecular motion of PBLG segment in GN nanoparticles in CDCl₃ was also examined and compared with that of the PNIPAAm. The morphology, size distribution, and effect of temperature on the sizes of the GN nanoparticles were also investigated. The temperature dependence of T₁ and line halfwidth suggests that the N‐isopropyl group turns gradually into the solid‐like aggregates at temperatures higher than the LCST of PNIPAAm due to the collapsed coil‐globule transition. T₁ values of N‐isopropyl groups decreased with increasing PBLG content in GN diblock copolymer, suggesting the mobility of PNIPAAm chain, as the shell, becomes more restricted at higher PBLG core content.

Changes in the mobility of PNIPAAm shell in the core‐shell‐type nanoparticles composed of PBLG and PNIPAAm.     

Melt Properties of Poly(styrene‐co‐acrylonitrile) and Poly(butylene terephthalate) and their Interfacial Tension

Pressure‐volume‐temperature and surface tension behaviour were studied for random copolymers of styrene and acrylonitrile (SAN) and for poly(butylene terephthalate) (PBT). Results served to determine reduction parameters for the equation‐of‐states by Flory‐Orwoll‐Vrij and by Simha‐Somcynsky as well. Surface tension as a function of copolymer composition displays negative deviation from additivity. It indicates surface excess of styrene units. Similar behaviour with respect to copolymer composition was found for variation of interfacial tension between SAN and PBT. Thickness of surface region is around 1 nm and does not change with copolymer composition whereas extension of interfacial region between PBT and SAN copolymers varies strongly with copolymer composition between around 2 and 60 nm.

     

Stratification of the aggressiveness of prostate cancer using pre‐biopsy multiparametric MRI (mpMRI)

Risk stratification, based on the Gleason score (GS) of a prostate biopsy, is an important decision‐making tool in prostate cancer management. As low‐grade disease may not need active intervention, the ability to identify aggressive cancers on imaging could limit the need for prostate biopsies. We assessed the ability of multiparametric MRI (mpMRI) in pre‐biopsy risk stratification of men with prostate cancer. One hundred and twenty men suspected to have prostate cancer underwent mpMRI (diffusion MRI and MR spectroscopic imaging) prior to biopsy. Twenty‐six had cancer and were stratified into three groups based on GS: low grade (GS ≤ 6), intermediate grade (GS = 7) and high grade (GS ≥ 8). A total of 910 regions of interest (ROIs) from the peripheral zone (PZ, range 25–45) were analyzed from these 26 patients. The metabolite ratio [citrate/(choline + creatine)] and apparent diffusion coefficient (ADC) of voxels were calculated for the PZ regions corresponding to the biopsy cores and compared with histology. The median metabolite ratios for low‐grade, intermediate‐grade and high‐grade cancer were 0.29 (range: 0.16, 0.61), 0.17 (range: 0.13, 0.32) and 0.13 (range: 0.05, 0.23), respectively (p = 0.004). The corresponding mean ADCs (×10^–3 mm²/s) for low‐grade, intermediate‐grade and high‐grade cancer were 0.99 ± 0.08, 0.86 ± 0.11 and 0.69 ± 0.12, respectively (p < 0.0001). The combined ADC and metabolite ratio model showed strong discriminatory ability to differentiate subjects with GS ≤ 6 from subjects with GS ≥ 7 with an area under the curve of 94%. These data indicate that pre‐biopsy mpMRI may stratify PCa aggressiveness noninvasively. As the recent literature data suggest that men with GS ≤ 6 cancer may not need radical therapy, our data may help limit the need for biopsy and allow informed decision making for clinical intervention. Copyright © 2015 John Wiley & Sons, Ltd.     

Synthesis and Characterisation of Poly[oligo(ε‐caprolactone)L‐malate‐graft‐poly(L‐lactide)]

Graft copolyesters with a PCL backbone and PLLA side chains were successfully prepared in three steps avoiding transesterification. First ε‐caprolactone was polymerised with 1,6‐hexane diol as initiator to obtain hydroxytelechelic oligo(ε‐caprolactone)s. These diols were then subjected—in the second step—to polycondensation with L ‐malic acid yielding in linear poly[oligo(ε‐caprolactone)L ‐malate] having secondary hydroxyl functions in the side chain. For both reactions scandium triflate Sc(OTf)₃ was used as a catalyst. In the third step various amounts of L ‐lactide were grafted from the polymer backbone using Zn(oct)₂ as catalyst. The successful reaction was confirmed by NMR and SEC (size exclusion chromatography) analysis. Further the thermal properties of the graft copolymers with different graft lengths were determined via differential scanning calorimetry.

     

Hepatitis B virus (HBV) reactivation—The potential role of direct‐acting agents for hepatitis C virus (HCV)

Hepatitis C virus (HCV) is known to inhibit hepatitis B virus (HBV) replication in patients with HBV/HCV coinfection. Reactivation of HBV in patients treated for HCV with direct‐acting agents (DAAs) has emerged recently as an important clinical consideration. A growing number of case reports and case series support the association between new HCV treatments and HBV reactivation. Yet, very little is known about the specific viral characteristics that facilitate reactivation as functional characterization of the reactivated HBV has been conducted only rarely. This review provides the most recent data on HBV reactivation in the context of DAA initiation and highlights the existing viral genomic data from reactivating viruses. Current functional studies of HBV reactivation are largely limited by the retrospective identification of cases, no standardization of genomic regions that are studied with respect to HBV reactivation, and the lack of inclusion of nonreactivating controls to establish specific viral mutations that are associated with HBV reactivation. Importantly, none of these sequencing studies included cases of HBV reactivation after initiation of DAAs. While new HCV treatments have revolutionized care for HCV infected patients, HBV reactivation will likely increase in frequency, as DAAs are more commonly prescribed. Pretreatment determination of HBV status and thoughtful management of HBV coinfections will be necessary and lead to improved patient safety and yield optimal treatment results.     

A Novel Macroinitiator for the Synthesis of Triblock Copolymers via Atom Transfer Radical Polymerization: Polystyrene‐block‐poly(bisphenol A carbonate)‐block‐polystyrene and Poly(methyl methacrylate)‐block‐poly(bisphenol A carbonate)‐block‐poly(methyl methacrylate)

Summary: Bis(hydroxy)telechelic bisphenol A polycarbonate (PC) was prepared via melt polycondensation of bisphenol A (BPA) and diphenyl carbonate (DPC) using lanthanum(III ) acetylacetonate as a catalyst for transesterification. Subsequently, the polycarbonate was converted to a bifunctional macroinitiator for atom transfer radical polymerization (ATRP) with the reagent, α‐chlorophenylacetyl chloride. The macroinitiator was used for the polymerization of styrene (S) and methyl methacrylate (MMA) to give PS‐block‐PC‐block‐PS and PMMA‐block‐PC‐block‐PMMA triblock copolymers. These block copolymers were characterized by NMR and GPC. When styrene and methyl methacrylate were used in large excess, significant shifts toward high molecular weights were observed with quantitative consumption of the macroinitiator. Several ligands were studied in combination with CuCl as the ATRP catalyst. Kinetic studies reveal the controlled nature of the polymerization reaction for all the ligands used.

Formation of a bifunctional ATRP macroinitiator by esterification of bis(hydroxy)telechelic PC with α‐chlorophenylacetyl chloride.     

Synthesis and Characterization of Comb‐Like Copolymers Based on Poly(ε‐caprolactone) and Poly(α‐olefin)

Comb‐like copolymers based on a polyolefin backbone of poly(10‐undecene‐1‐ol) (PUol) with poly(ε‐caprolactone) (PCL) side chains are synthesized in two steps. After synthesis of PUol by metallocene‐catalyzed polymerization, the side‐chain hydroxyl functionalities of this polar polyolefin are used as an initiator for the ring‐opening polymerization (ROP) of ε‐caprolactone (CL). In this context, copolymers with different lengths of PCL grafts are prepared. The chemical structure and the composition of the synthesized copolymers are characterized by ¹H and ¹³C NMR spectroscopy. It is shown that the hydroxyl end groups of PUol act effectively as initiating sites for the CL ROP. Size‐exclusion chromatography (SEC) measurements confirm the absence of non‐attached PCL and the expected increase in molar mass after grafting. The thermal and decomposition behaviors are investigated by DSC and thermogravimetric analysis (TGA). The effect of the length of the PCL grafts on the crystallization behavior of the comb‐like copolymers is investigated by DSC and wide‐angle X‐ray scattering (WAXS).

     

Homo and Block Copolymers of Poly(β‐benzyl‐L‐aspartate)s and Poly(γ‐benzyl‐L‐glutamate)s of Different Architectures

Homopolypeptides of linear and star‐like architectures were prepared by polymerizing benzylic‐protected L ‐glutamic acid and L ‐aspartic acid N‐carboxyanhydrides (Glu NCA, Asp NCA) in DMF. The polymerization rate of the Glu NCA is faster than that of Asp NCA. Using a simple monoamino initiator, its hydrochloride, di‐, tri‐, and tetraamino functional initiators, homopolypeptides with well‐defined structures and molar masses were obtained. The molar‐mass averages of the poly(γ‐benzyl‐L ‐glutamate)s lie very close to calculated values, according to the initial [M]:[I] ratios, while those of the linear poly(β‐benzyl‐L ‐aspartate)s were lower than the predicted ones. PBAs had somewhat broader molar‐mass distributions than PBGs.