Direct observation of prefreezing at the interface melt–solid in polymer crystallization

Crystallization is almost always initiated at an interface to a solid. This observation is classically explained by the assumption of a reduced barrier for crystal nucleation at the interface. However, an interface can also induce crystallization by prefreezing (i.e., the formation of a crystalline layer that is already stable above the bulk melting temperature). We present an atomic force microscopy (AFM)-based in situ observation of a prefreezing process at the interface of a polymeric model system and a crystalline solid. Explicitly, we show an interfacial ordered layer that forms well above the bulk melting temperature with thickness that increases on approaching melt–solid coexistence. Below the melting temperature, the ordered layer initiates crystal growth into the bulk, leading to an oriented, homogeneous semicrystalline structure.The fundamental process of crystallization from the liquid or gaseous state is of importance in many areas of condensed matter physics and materials science. In practice, crystallization is, in most cases, initiated at an interface to a solid. Crystal growth on solid substrates from the gaseous state has been studied in depth, and detailed understanding of different growth modes as well as interfacial thermodynamics has been achieved (1–3). Much less experimental data are available for crystallization occurring at the interface from the solid to the melt. Generally, crystallization can be initiated at the solid–melt interface by two processes: heterogeneous nucleation or formation of a crystalline wetting layer (so-called prefreezing) (4–6). In terms of thermodynamics, these processes are very different. Whereas nucleation takes place under nonequilibrium conditions at finite supercooling below the melting temperature T_m of the bulk material, the formation of a wetting layer is an equilibrium phenomenon taking place above T_m (4). It is often assumed that heterogeneous nucleation is the more relevant process (7), but in simulations, nucleation as well as prefreezing have been shown to occur (4, 8). Prefreezing is expected for strongly attractive surfaces or epitaxial systems for which the lattices of the substrate and the crystallizing materials match well (9–12). In the case of polymers, prefreezing can also manifest itself in the conformational degrees of freedom, leading to an interfacial layer with nematic order, which was recently shown in simulations (13). Because of the difficult accessibility of the buried interface between a melt and a solid, direct observation of crystallization of molecular systems at the interface is lacking, and there is only limited, indirect evidence that, in some cases, prefreezing at the solid interface exists (e.g., for the growth of aluminum crystals on TiB₂ particles) (14, 15). Recently, it has been suggested that prefreezing also plays a role during epitaxial crystallization in some polymeric systems (16). It is well-known, however, that one or sometimes several ordered layers of organic molecules can form on suitable substrates at temperatures above the bulk melting point, which was observed for, for example, alkanes or similar molecules on graphite by scanning tunneling microscopy (17), atomic force microscopy (AFM) (18–20), or scattering methods (21, 22; review in ref. 23). A related but more special phenomenon is surface freezing of liquids (22). In some liquids, an ordered monolayer forms at the free surface in a finite temperature range above the bulk melting temperature [e.g., alkanes (24), alkylated side chain polymers (25), and AuSi alloys (26)]. It is an open question, however, which exact role all of these structures play for the initiation of crystal growth (27) and in most cases, the temperature range around melt–solid coexistence, where crystallization starts has not been studied in detail. Only for colloidal model systems has crystallization by prefreezing been directly observed (28) and studied in simulations (8, 10, 11).We here present direct AFM observations of an ordered wetting layer at the interface to a solid close to coexistence of the solid and the liquid phases of a polymeric model system. We show evidence for a temperature-dependent thickness of the wetting layer and its disappearance at a prewetting transition at finite superheating above T_m. Our observations are in line with a divergence of the layer thickness at the bulk melting temperature as expected for complete wetting. Below T_m, crystal growth into the film is initiated by the interfacial layer.     

Regulation of the human coronary microcirculation

Atherosclerosis of conduit epicardial arteries is the principal culprit behind the complications of coronary heart disease, but a growing body of literature indicates that the coronary microcirculation also contributes substantially to the pathophysiology of cardiovascular disease. An understanding of mechanisms regulating microvascular function in humans is an essential foundation for understanding the role in disease, especially since these regulatory mechanisms vary substantially across species and vascular beds. In fact all subjects whose coronary tissue was used in the studies described have medical conditions that warrant cardiac surgery, thus relevance to the normal human must be inferential and is based on tissue from subjects without known arteriosclerotic disease. This review will focus on recent advances in the physiological and pathological mechanisms of coronary microcirculatory control, describing a robust plasticity in maintaining endothelial control over dilation, including mechanisms that are most relevant to the human heart. This article is part of a Special Issue entitled "Coronary Blood Flow".     

Biomarkers for Type 2 Diabetes and Impaired Fasting Glucose Using a Nontargeted Metabolomics Approach

Using a nontargeted metabolomics approach of 447 fasting plasma metabolites, we searched for novel molecular markers that arise before and after hyperglycemia in a large population-based cohort of 2,204 females (115 type 2 diabetic [T2D] case subjects, 192 individuals with impaired fasting glucose [IFG], and 1,897 control subjects) from TwinsUK. Forty-two metabolites from three major fuel sources (carbohydrates, lipids, and proteins) were found to significantly correlate with T2D after adjusting for multiple testing; of these, 22 were previously reported as associated with T2D or insulin resistance. Fourteen metabolites were found to be associated with IFG. Among the metabolites identified, the branched-chain keto-acid metabolite 3-methyl-2-oxovalerate was the strongest predictive biomarker for IFG after glucose (odds ratio [OR] 1.65 [95% CI 1.39–1.95], P = 8.46 × 10⁻⁹) and was moderately heritable (h² = 0.20). The association was replicated in an independent population (n = 720, OR 1.68 [ 1.34–2.11], P = 6.52 × 10⁻⁶) and validated in 189 twins with urine metabolomics taken at the same time as plasma (OR 1.87 [1.27–2.75], P = 1 × 10⁻³). Results confirm an important role for catabolism of branched-chain amino acids in T2D and IFG. In conclusion, this T2D-IFG biomarker study has surveyed the broadest panel of nontargeted metabolites to date, revealing both novel and known associated metabolites and providing potential novel targets for clinical prediction and a deeper understanding of causal mechanisms.Currently, stratification of individuals at risk for type 2 diabetes (T2D) within the general population is based on well-established factors such as age, BMI, and fasting glucose (1). Although these factors contribute considerably to disease risk, they may not identify at-risk individuals before the disease process is well under way.Recently, a number of studies have found several metabolites to be correlated with insulin resistance and T2D (2–6), and T2D-associated metabolic profiles have been identified 10–15 years before the diagnosis/onset of the disease (7–9). To help preventive strategies, and maximize the potential for existing effective interventions, it is important to characterize the molecular changes that take place in the development of T2D.We aim to understand other biochemical changes, in addition to hyperglycemia, that take place at the onset of T2D using the largest metabolomic screening approach to date. We assessed >400 metabolites to determine which metabolomic profiles are correlated with T2D and impaired fasting glucose (IFG) in a large cohort of females from TwinsUK with independent replication.     

Oncological,functional and perioperative outcomes in transplant patients after radical prostatectomy

Purpose

Oncological surgery in immunosuppressed patients with solid organ transplantation (Tx) is challenging. These patients are thought to have higher postoperative morbidity and an increased rate of tumour progression. The aim of the present study was to analyse oncological, functional and perioperative outcomes in Tx patients following radical prostatectomy (RP).

Materials and methods

Between 1996 and 2014, 30 patients diagnosed with prostate cancer underwent RP at our institution following Tx (kidney: n = 20, heart: n = 5, liver: n = 5). Functional, oncological and perioperative follow-ups were analysed. Postoperative complications were assessed using the Clavien–Dindo classification.

Results

Median follow-up was 45 months. Median PSA was 5.3 ng/ml. Intraoperative blood loss was 600 ml at a median operating time of 180 min. Surgery in kidney Tx patients was technically feasible. Major complications occurred in 3 patients (ureteral injury, lymphocele and haematoma). Histological evaluation revealed n = 18 ≤pT2 tumours (60.0 %), n = 7 pT3a tumours (23.3 %) and n = 5 ≥pT3b tumours (16.7 %). Continence rate 12 months after surgery, defined as no or one safety pad use, was 73.3 %, while 93.3 % of the patients used ≤2 pads/24 h. After the median follow-up of 45 months, BCR-free survival was 69.0 %. In recurrent men, there was suspicion of metastasis in one patient. No cancer-specific death was observed. Five-year overall survival was 94.4 %.

Conclusion

The complication rate in patients with solid organ transplantation after RP was low. While histopathological evaluation revealed disease characteristics comparable to non-transplant patients from current RP series, postoperative continence was worse. Immunosuppressive therapy does not seem to lead to an increased rate of tumour progression.