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Speech requires successful information transfer within cortical-basal ganglia loop circuits to produce the desired acoustic output. For this reason, up to 90% of Parkinson’s disease patients experience impairments of speech articulation. Deep brain stimulation (DBS) is highly effective in controlling the symptoms of Parkinson’s disease, sometimes alongside speech improvement, but subthalamic nucleus (STN) DBS can also lead to decreases in semantic and phonological fluency. This paradox demands better understanding of the interactions between the cortical speech network and the STN, which can be investigated with intracranial EEG recordings collected during DBS implantation surgery. We analyzed the propagation of high-gamma activity between STN, superior temporal gyrus (STG), and ventral sensorimotor cortices during reading aloud via event-related causality, a method that estimates strengths and directionalities of neural activity propagation. We employed a newly developed bivariate smoothing model based on a two-dimensional moving average, which is optimal for reducing random noise while retaining a sharp step response, to ensure precise embedding of statistical significance in the time–frequency space. Sustained and reciprocal neural interactions between STN and ventral sensorimotor cortex were observed. Moreover, high-gamma activity propagated from the STG to the STN prior to speech onset. The strength of this influence was affected by the lexical status of the utterance, with increased activity propagation during word versus pseudoword reading. These unique data suggest a potential role for the STN in the feedforward control of speech.

ObjectiveWe evaluated whether the combination of epileptiform spikes and ripples (spike ripples) outperformed other leading biomarkers in identifying the epileptogenic zone across subjects in a multicenter international study.MethodsWe validated and applied an automated spike ripple detector on intracranial EEG recordings in subjects from 4 centers who subsequently underwent surgical resection with known 1-year seizure outcomes. We evaluated the spike ripple rate in subjects cured after resection (ILAE 1 outcome) and those with persistent seizures (ILAE 2-5) across sites and recording types. We also evaluated spike, wideband HFO (80-500 Hz), fast ripple (250-500 Hz), and ripple (80-250 Hz) rates using validated automated detectors. The proportion of resected events was computed and compared across subject outcomes and biomarkers.Results109 subjects were included. The majority of spike ripples were removed in subjects with ILAE 1 outcome (p = 1e-6), and this was qualitatively observed across the four sites (p = 0.032, p = 0.092, p = 0.0005, p = 0.003) and the two electrode types (p = 0.01, p = 7e-6). A higher proportion of spike ripples were removed in subjects with ILAE 1 outcomes compared to ILAE 2-5 outcomes (p = 0.02). Among ILAE 1 subjects, the proportion of spike ripples removed was higher than the proportion of spikes (p = 0.0004), wideband HFOs (p = 0.0004), fast ripples (p = 0.008), and ripples (p = 0.008) removed. At the individual level, more subjects with ILAE 1 outcome had the majority of spike ripples removed (40/48, 83%) than spikes (69%, p = 0.04), wideband HFOs (63%, p = 0.009), fast ripples (36%, p = 2e-5), or ripples (45%, p = 0.0007) removed.InterpretationWhen surgical resection was successful, the majority of spike ripples were removed. Automatically detected spike ripples have improved specificity for epileptogenic tissue compared to spikes, wideband HFOs, fast ripples, and ripples.

No clear evidence‐based treatment paradigm currently exists for refractory and super‐refractory status epilepticus, which can result in significant mortality and morbidity. While patients are typically treated with antiepileptic drugs and anesthetics, neurosurgical neuromodulation techniques can also be considered. We present a novel case in which responsive neurostimulation was used to effectively treat a patient who had developed super‐refractory status epilepticus, later consistent with epilepsia partialis continua, that was refractory to antiepileptic drugs, immunomodulatory therapies, and transcranial magnetic stimulation. This case demonstrates how regional therapy provided by responsive neurostimulation can be effective in treating super‐refractory status epilepticus through neuromodulation of seizure networks.

Although micelles derived from the solution self-assembly of amphiphilic molecules and polymers have been prepared with a wide variety of shapes, examples with well-defined branched structures have remained elusive. We describe a divergent, directed self-assembly approach to low dispersity dendritic micelles with a high degree of structural perfection and tailorable branch numbers and generations. We use block copolymer amphiphiles as precursors and a crystallization-driven seeded growth approach whereby the termini of fiber-like micelles function as branching sites. Different dendrimeric generations are accessible by adjusting the ratio of added unimers to pre-existing seed micelles where the branch positions are determined by the reduced coronal chain grafting density on the surface of the micelle crystalline core. We demonstrate the spatially defined decoration of the assemblies with emissive nanoparticles and utility of the resulting hybrids as fluorescent sensors for anions where the dendritic architecture enables ultrahigh sensitivity.

SummarySubanesthetic doses of ketamine produce rapid and sustained anti-depressant effects in patients with treatment-resistant depression. Unfortunately, the usefulness of ketamine as a treatment is limited by its potential for abuse because of psychotropic side effects such as dissociation. Understanding the brain dynamics and the neural circuits involved in ketamine’s effects could lend insight into improved therapies for depression with fewer adverse effects. It is believed that ketamine acts via NMDA receptor and hyperpolarization-activated cyclic nucleotide-gated 1 (HCN1) channels to produce changes in oscillatory brain dynamics. Here we show, in humans, a detailed description of the principal oscillatory changes in cortical and subcortical structures by administration of a subanesthetic dose of ketamine. Using recordings from intracranial electrodes, we found that ketamine increased gamma oscillations within prefrontal cortical areas and the hippocampus--structures previously implicated in ketamine’s antidepressant effects. Furthermore, our studies provide direct evidence of a ketamine-induced 3 Hz oscillation in posteromedial cortex that has been proposed as a mechanism for its dissociative effects. By analyzing changes in neural oscillations after the addition of propofol, whose GABAergic activity antagonizes ketamine’s NMDA-mediated disinhibition alongside a shared HCN1 inhibitory effect, we identified brain dynamics that could be attributed to NMDA-mediated disinhibition versus HCN1 inhibition. Overall, our results imply that ketamine engages different neural circuits in distinct frequency-dependent patterns of activity to produce its antidepressant and dissociative sensory effects. These insights may help guide the development of novel brain dynamic biomarkers and therapeutics for depression.

HYPOTHESIS: Among other functions, mucins hydrate and protect biological interfaces from mechanical challenges. Mucins also attract interest as biocompatible coatings with excellent lubrication performance. Therefore, it is of high interest to understand the structural response of mucin films to mechanical challenges. We hypothesized that this could be done with Neutron Reflectometry using a novel sample environment where mechanical confinement is achieved by inflating a membrane against the films. EXPERIMENTS: Oral MUC5B mucin films were investigated by Force Microscopy/Spectroscopy and Neutron Reflectometry both at solid-liquid interfaces and under mechanical confinement. FINDINGS: NR indicated that MUC5B films were almost completely compressed and dehydrated when confined at 1 bar. This was supported by Force Microscopy/Spectroscopy investigations. Force Spectroscopy also indicated that MUC5B films could withstand mechanical confinement by means of steric interactions for pressures lower than ∼ 0.5 bar i.e., mucins could protect interfaces from mechanical challenges of this magnitude while keeping them hydrated. To investigate mucin films under these pressures by means of the employed sample environment for NR, further technological developments are needed. The most critical would be identifying or developing more flexible membranes that would still meet certain requirements like chemical homogeneity and very low roughness.

Consciousness is not explained by a single mechanism, rather it involves multiple specialized neural systems overlapping in space and time. We hypothesize that synergistic, large-scale subcortical and cortical attention and signal processing networks encode conscious experiences. To identify brain activity in conscious perception without overt report, we classified visual stimuli as perceived or not using eye measurements. Report-independent event-related potentials and functional magnetic resonance imaging (fMRI) signals both occurred at early times after stimuli. Direct recordings revealed a novel thalamic awareness potential linked to conscious visual perception based on report. fMRI showed thalamic and cortical detection, arousal, attentional salience, task-positive, and default mode networks were involved independent of overt report. These findings identify a specific sequence of neural mechanisms in human conscious visual perception.One-Sentence SummaryHuman conscious visual perception engages large-scale subcortical and cortical networks even without overt report.

Speaking precisely is important for effective verbal communication, and articulatory gain is one component of speech motor control that contributes to achieving this goal. Given that the basal ganglia have been proposed to regulate the speed and size of limb movement, that is, movement gain, we explored the basal ganglia contribution to articulatory gain, through local field potentials (LFP) recorded simultaneously from the subthalamic nucleus (STN), precentral gyrus, and postcentral gyrus. During STN deep brain stimulation implantation for Parkinson’s disease, participants read aloud consonant-vowel-consonant syllables. Articulatory gain was indirectly assessed using the F2 Ratio, an acoustic measurement of the second formant frequency of/i/vowels divided by/u/vowels. Mixed effects models demonstrated that the F2 Ratio correlated with alpha and theta activity in the precentral gyrus and STN. No correlations were observed for the postcentral gyrus. Functional connectivity analysis revealed that higher phase locking values for beta activity between the STN and precentral gyrus were correlated with lower F2 Ratios, suggesting that higher beta synchrony impairs articulatory precision. Effects were not related to disease severity. These data suggest that articulatory gain is encoded within the basal ganglia-cortical loop.

The importance of the basal ganglia in modulating cognitive and motor behaviors is well known, yet how the basal ganglia participate in the uniquely human behavior of speech is poorly understood. The subthalamic nucleus (STN) is well positioned to facilitate two basal ganglia functions critical for speech: motor learning and gain modulation. Using a novel paradigm to study cortical-subcortical interactions during speech in patients undergoing awake DBS surgery, we found evidence for a left opercular hyperdirect pathway in humans by stimulating in the STN and examining antidromic evoked activity in the left temporal, parietal and frontal opercular cortex. These high resolution cortical and subcortical mapping data provided evidence for hyperdirect connectivity between Broca’s area (typically corresponding to pars triangularis and pars opercularis of the inferior frontal gyrus) and the STN. In addition, we observed evoked potentials consistent with the presence of monosynaptic projections from areas of opercular speech cortex that are primarily sensory, including auditory cortex, to the STN. These connections may be unique to humans, evolving alongside the ability for speech.SIGNIFICANCEUsing intracranial recordings from the basal ganglia and cortex in subjects undergoing deep brain stimulation, this study provides evidence for monosynaptic cortical inputs from motor planning, motor sensory, and auditory sensory cortices to the subthalamic nucleus. These observations suggest that in humans, the cortical-basal ganglia hyperdirect pathway is uniquely positioned to participate in speech production. Moreover, the existence of a monosynaptic connection between human sensory cortical areas and the subthalamic nucleus indicates a need to update traditional models of information transfer within cortical-basal ganglia-thalamocortical circuitry, which has significant implications for understanding other human cognitive behavior or dysfunction.

There is great interest in identifying the neurophysiological underpinnings of speech production. Deep brain stimulation (DBS) surgery is unique in that it allows intracranial recordings from both cortical and subcortical regions in patients who are awake and speaking. The quality of these recordings, however, may be affected to various degrees by mechanical forces resulting from speech itself. Here we describe the presence of speech-induced artifacts in local-field potential (LFP) recordings obtained from mapping electrodes, DBS leads, and cortical electrodes. In addition to expected physiological increases in high gamma (60-200 Hz) activity during speech production, time-frequency analysis in many channels revealed a narrowband gamma component that exhibited a pattern similar to that observed in the speech audio spectrogram. This component was present to different degrees in multiple types of neural recordings. We show that this component tracks the fundamental frequency of the participant’s voice, correlates with the power spectrum of speech and has coherence with the produced speech audio. A vibration sensor attached to the stereotactic frame recorded speech-induced vibrations with the same pattern observed in the LFPs. No corresponding component was identified in any neural channel during the listening epoch of a syllable repetition task. These observations demonstrate how speech-induced vibrations can create artifacts in the primary frequency band of interest. Identifying and accounting for these artifacts is crucial for establishing the validity and reproducibility of speech-related data obtained from intracranial recordings during DBS surgery.

A new sample environment is introduced for the study of soft matter samples in electric fields using small-angle neutron scattering instruments. The sample environment is temperature controlled and features external electrodes, allowing standard quartz cuvettes to be used and conducting samples or samples containing ions to be investigated without the risk of electrochemical reactions occurring at the electrodes. For standard 12.5 mm quartz cuvettes, the maximum applied field is 8 kV/cm, and the applied field may be static or alternating (up to 10 kHz for 8 kV/cm and up to 60 kHz for 4 kV/cm). The electric fields within the sample are calculated and simulated under a number of different conditions, and the capabilities of the setup are demonstrated using a variety of liquid crystalline samples. Measurements were performed as a function of temperature and time spent in the electric field. Finally, the advantages, drawbacks, and potential optimization of the sample environment are discussed with reference to applications in the fields of complex soft matter, biology, and electrorheology.

To determine if simultaneous bilateral scalp EEG (scEEG) can accurately detect a contralateral seizure onset in patients with unilateral intracranial EEG (IEEG) implantation.We evaluated 39 seizures from 9 patients with bitemporal epilepsy who underwent simultaneous scEEG and IEEG (SSIEEG). To simulate conditions of unilateral IEEG implantation with a missed contralateral seizure onset, we analyzed the IEEG recording contralateral to the seizure onset (CL- IEEG), in conjunction with simultaneous scEEG. The following criteria were evaluated between scEEG and CL- IEEG (1) latency: the time to onset of EEG seizure (2) location: concordance of ictal onset zones and (3) pattern: congruence of EEG morphology and frequency.SSIEEG correctly lateralized 36/39 (92.3%) seizures compared to 13/39 (33.3%) seizures using CL- IEEG alone (OR = 24.0, p 0.01), 33 (84.6%) seizures using scEEG alone (OR = 2.2, p = 0.29) and 26 (66.9%) seizures using time of clinical onset alone (OR = 6.0, p = 0.01). For the three criteria evaluated, (1) 22/39 (56.4%) seizures had an earlier onset on the scEEG, compared to CL- IEEG; (2) lack of congruence of location of seizure onset was noted in 33/39 (84.6%) of the seizures; and (3) 22/39 (56.4%) seizures did not have a congruent ictal pattern.The chronological, topographic and morphologic features of SSIEEG can accurately detect the hemisphere of seizure onset in most cases with unilateral IEEG implantation. SSIEEG is significantly better than, IEEG, scEEG or clinical onset alone in this scenario. We propose that SSIEEG should be considered in all cases of intractable focal epilepsy undergoing unilateral IEEG evaluation.

Quantum-sized metallic clusters protected by biological ligands represent a new class of luminescent materials; yet the understanding of structural information and photoluminescence origin of these ultrasmall clusters remains a challenge. Herein we systematically study the surface ligand dynamics and ligand–metal core interactions of peptide-protected gold nanoclusters (AuNCs) with combined experimental characterizations and theoretical molecular simulations. We show that the peptide sequence plays an important role in determining the surface peptide structuring, interfacial water dynamics and ligand–Au core interaction, which can be tailored by controlling peptide acetylation, constituent amino acid electron donating/withdrawing capacity, aromaticity/hydrophobicity and by adjusting environmental pH. Specifically, emission enhancement is achieved through increasing the electron density of surface ligands in proximity to the Au core, discouraging photoinduced quenching, and by reducing the amount of surface-bound water molecules. These findings provide key design principles for understanding the surface dynamics of peptide-protected nanoparticles and maximizing the photoluminescence of metallic clusters through the exploitation of biologically relevant ligand properties.

Background: A number of centers across the world offer short daily hemodialysis (SDHD) treatments. To date, cefazolin pharmacokinetics have not been described in patients undergoing SDHD. Objective: The purpose of this study was to investigate the effect of SDHD on the pharmacokinetics of cefazolin. Methods: This was a prospective, open-label, pharmacokinetic study of cefazolin during SDHD in 10 noninfected patients. Participants received a 1-g intravenous (IV) infusion of cefazolin after SDHD on study day 1 and a second dose after SDHD on study day 2. To determine the concentration of cefazolin, 6 blood samples were drawn at 0, 1, 2, 2.3, 4, and 24 hours after initiation of dialysis on day 2, and 2 dialysate samples were drawn at 1 and 2 hours after initiation of dialysis on day 2. Samples were analyzed using high-performance liquid chromatography, and pharmacokinetic parameters were determined. Results: Median interdialysis clearance was 0.16 L/h (interquartile range [IQR]: 0.11-0.21 L/h), and median intradialysis clearance was 1.95 L/h (IQR: 1.66-2.45 L/h). Median interdialysis half-life was 28.2 hours (IQR: 23.5-59.3 hours) as compared with a median intradialysis half-life of 2.3 hours (IQR: 1.7-2.7 hours). The median percentage removal of cefazolin during dialysis was 41% (IQR: 35%-53%). Conclusion and Relevance: Estimated cefazolin dialysis clearance is similar to previous estimates with conventional thrice-weekly regimens. Current dosing recommendations of 1 g IV post-SDHD achieve total serum drug concentrations greater than 40 mg/L in all patients, which is the total drug concentration required for bactericidal activity against Staphylococcus species.

The mechanism of action of deep brain stimulation (DBS) for Parkinson’s disease remains unclear. Studies have shown that DBS decreases pathological beta hypersynchrony between the basal ganglia and motor cortex. However, little is known about DBS’s effects on long range corticocortical synchronization. Here, we use machine learning combined with spectral graph theory to compare resting-state cortical connectivity between the off and on-stimulation states and compare these differences to healthy controls. We found that turning DBS on increased high beta and gamma band coherence in a cortical circuit spanning the motor, occipitoparietal, middle temporal, and prefrontal cortices. We found no significant difference between DBS-off and controls in this network with multivariate pattern classification showing that the brain connectivity pattern in control subjects is more like those during DBS-off than DBS-on. These results show that therapeutic DBS increases spontaneous high beta-gamma synchrony in a network that couples motor areas to broader cognitive systems.

The textile industry is resource-intensive, which has a significant impact on global emissions and waste pollution. To meet the demand of textiles over a third of fibres used in manufacturing are sourced from fossil fuels. As the global demand for textiles continues to grow, manufacturers are having to seek innovative approaches to providing sustainable and regenerative cellulose fibres. However, the latest climate change pressures on the textile industry have uncovered grave environmental issues associated with traditional regenerative cellulose production, such as the viscose manufacturing process. The viscose process requires intensive use of hazardous chemicals which leads to water pollution and ecotoxicity. In addition, if forestry products are unsustainably sourced for this process, this can lead to resource scarcity and deforestation. To provide a holistic solution for mitigating these challenges this study uses the by-products of paper manufacturing dissolved in an ionic liquid to produce regenerated cellulose filaments. Paper mill sludge (PMS) is a cellulosic by-product typically used on animal bedding and land spreading. The material has been dissolved in an ionic liquid - 1-ethyl-3-methylimidazolium diethyl phosphate - with the aid of a co-solvent dimethyl sulfoxide (DMSO) - and spun into continuous filaments for textile production. The mechanical properties of paper sludge filaments are found to be competitive with commercial viscose, which is promising for their drop-in replacement. It is also demonstrated that by increasing the concentration of the PMS from 9% to 12.4%, an improvement of the filament properties can be achieved; an increase in modulus from ∼19 GPa to ∼26 GPa and strength from ∼223 MPa to ∼282 MPa. These values are shown to be competitive with other commercial, less sustainable, regenerated cellulose fibres.

An enduring neuroscientific debate concerns the extent to which neural representation is restricted to networks of patches specialized for particular domains of perceptual input (Kaniwsher et al., 1997; Livingstone et al., 2019), or distributed outside of these patches to broad areas of cortex as well (Haxby et al., 2001; Op de Beeck, 2008). A critical level for this debate is the localization of the neural representation of the identity of individual images, (Spiridon & Kanwisher, 2002) such as individual-level face or written word recognition. To address this debate, intracranial recordings from 489 electrodes throughout ventral temporal cortex across 17 human subjects were used to assess the spatiotemporal dynamics of individual word and face processing within and outside cortical patches strongly selective for these categories of visual information. Individual faces and words were first represented primarily only in strongly selective patches and then represented in both strongly and weakly selective areas approximately 170 milliseconds later. Strongly and weakly selective areas contributed non-redundant information to the representation of individual images. These results can reconcile previous results endorsing disparate poles of the domain specificity debate by highlighting the temporally segregated contributions of different functionally defined cortical areas to individual level representations. Taken together, this work supports a dynamic model of neural representation characterized by successive domain-specific and distributed processing stages. SIGNIFICANCE STATEMENT The visual processing system performs dynamic computations to differentiate visually similar forms, such as identifying individual words and faces. Previous models have localized these computations to 1) circumscribed, specialized portions of the brain, or 2) more distributed aspects of the brain. The current work combines machine learning analyses with human intracranial recordings to determine the neurodynamics of individual face and word processing in and outside of brain regions selective for these visual categories. The results suggest that individuation involves computations that occur first in primarily highly selective parts of the visual processing system, then later recruits highly and non-highly selective regions. These results mediate between extant models of neural specialization by suggesting a dynamic domain specificity model of visual processing.

Despite ongoing advances in our understanding of local single-cellular and network-level activity of neuronal populations in the human brain, extraordinarily little is known about their “intermediate” microscale local circuit dynamics. Here, we utilized ultra-high-density microelectrode arrays and a rare opportunity to perform intracranial recordings across multiple cortical areas in human participants to discover three distinct classes of cortical activity that are not locked to ongoing natural brain rhythmic activity. The first included fast waveforms similar to extracellular single-unit activity. The other two types were discrete events with slower waveform dynamics and were found preferentially in upper cortical layers. These second and third types were also observed in rodents, nonhuman primates, and semi-chronic recordings from humans via laminar and Utah array microelectrodes. The rates of all three events were selectively modulated by auditory and electrical stimuli, pharmacological manipulation, and cold saline application and had small causal co-occurrences. These results suggest that the proper combination of high-resolution microelectrodes and analytic techniques can capture neuronal dynamics that lay between somatic action potentials and aggregate population activity. Understanding intermediate microscale dynamics in relation to single-cell and network dynamics may reveal important details about activity in the full cortical circuit.

BACKGROUND: Despite the impact of Parkinson disease (PD) on speech communication, there is no consensus regarding the effect of lead location on voice-related outcomes in subthalamic nucleus (STN) deep brain stimulation (DBS). OBJECTIVE: To determine the relationship of stimulation location to changes in cepstral analyses of voice following STN DBS. METHODS: Speech pathology evaluations were obtained from 14 PD subjects, before and after STN DBS, including audio-perceptual voice ratings (overall severity, loudness, hoarseness changes), measured indices of dysphonia (cepstral peak prominence and cepstral spectral index of dysphonia), and phonatory aerodynamics. The contact locations used for active stimulation at the time of postoperative voice evaluations were determined and assessed in relation to voice outcomes. RESULTS: Voice outcomes remained relatively unchanged on average. Stimulation locations in the anterior portion of the sensorimotor region of the left STN, however, were associated with improvements in voice severity scores, cepstral spectral index of dysphonia, shortness of breath, and phonatory airflow during connected speech. Posterior locations were associated with worsening of these outcomes. Variation in the medial-lateral or dorsal-ventral position on the left, and in any direction on the right, did not correlate with any voice outcome. CONCLUSION: Active contact placement within the anterior sensorimotor STN was associated with improved perceptual and acoustic-aerodynamic voice-related outcomes. These findings suggest an STN topography for improving airflow for speech, in turn improving how PD patients’ voices sound.

Cortico-basal ganglia interactions continuously shape the way we move. Ideas about how this circuit works are based largely on models those consider only firing rate as the mechanism of information transfer. A distinct feature of neural activity accompanying movement, however, is increased motor cortical and basal ganglia gamma synchrony. To investigate the relationship between neuronal firing in the basal ganglia and cortical gamma activity during movement, we analysed human ECoG and subthalamic nucleus (STN) unit activity during hand gripping. We found that fast reaction times were preceded by enhanced STN spike-to-cortical gamma phase coupling, indicating a role in motor preparation. Importantly, increased gamma phase coupling occurred independent of changes in mean STN firing rates, and the relative timing of STN spikes was offset by half a gamma cycle for ipsilateral vs. contralateral movements, indicating that relative spike timing is as relevant as firing rate for understanding cortico-basal ganglia information transfer.

Background: Understanding the structure of hybrid nanoparticle-lipid multilayers is of fundamental importance to their bioanalytical applications and nanotoxicity, where nanoparticle-membrane interactions play an important role. Poly(amidoamine) (PAMAM) dendrimers are branched polymeric nanoparticles with potential biomedical applications due to precise tunability of their physicochemical properties. Here, the effect of PAMAM dendrimers (2.9–4.5 nm) with either a hydrophilic amine (NH2) or a hydrophobic C12 chain surface termination on the 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) multilayers has been studied for the first time. Methods: DOPC multilayers were created by the liposome-rupture method via drop-casting dendrimer-liposome dispersions with the dendrimers added at different concentrations and at three different stages. The multilayer structure was evaluated via the analysis of the synchrotron X-ray reflectivity (XRR) curves, obtaining the bilayer d-spacing, the coherence length from the Scherrer (Ls) analysis of the Bragg peaks, and the paracrystalline disorder parameter (g). Results: Dendrimer addition led to lipid bilayer thinning and more disordered multilayer structures. Larger hydrophobic dendrimers caused greater structural disruption to the multilayers compared to the smaller dendrimers. The smallest, positively charged dendrimers at their highest concentration caused the most pronounced bilayer thinning. The dendrimer-liposome mixing method also affected the multilayer structure due to different dendrimer aggregation involved. Conclusions: These results show the complexity of the effect of dendrimer physicochemical properties and the addition method of dendrimers on the structure of mixed dendrimer-DOPC multilayers. General significance: These insights are useful for fundamental understanding of nanotoxicity and future biomedical application of nanocomposite multilayer materials in which nanoparticles are added for enhanced properties and functionality.

Living crystallization-driven self-assembly (CDSA) is a seeded growth method for crystallizable block copolymers (BCPs) and related amphiphiles in solution and has recently emerged as a highly promising and versatile route to uniform core-shell nanoparticles (micelles) with control of dimensions and architecture. However, the factors that influence the rate of nanoparticle growth have not been systematically studied. Using transmission electron microscopy, small- and wide-angle X-ray scattering, and super-resolution fluorescence microscopy techniques, we have investigated the kinetics of the seeded growth of poly(ferrocenyldimethylsilane)-b-(polydimethylsiloxane) (PFS-b-PDMS), as a model living CDSA system for those employing, for example, crystallizable emissive and biocompatible polymers. By altering various self-assembly parameters including concentration, temperature, solvent, and BCP composition our results have established that the time taken to prepare fiber-like micelles via the living CDSA method can be reduced by decreasing temperature, by employing solvents that are poorer for the crystallizable PFS core-forming block, and by increasing the length of the PFS core-forming block. These results are of general importance for the future optimization of a wide variety of living CDSA systems. Our studies also demonstrate that the growth kinetics for living CDSA do not exhibit the first-order dependence of growth rate on unimer concentration anticipated by analogy with living covalent polymerizations of molecular monomers. This difference may be caused by the combined influence of chain conformational effects of the BCP on addition to the seed termini and chain length dispersity.

PAMAM dendrimers have been conjectured for a wide range of biomedical applications due to their tuneable physicochemical properties. However, their application has been hindered by uncertainties in their cytotoxicity, which is influenced by dendrimer generation (i.e. size and surface group density), surface chemistry, and dosage, as well as cell specificity. In this review, biomedical applications of polyamidoamine (PAMAM) dendrimers and some related cytotoxicity studies are first outlined. Alongside these in vitro experiments, lipid membranes such as supported lipid bilayers (SLBs), liposomes, and Langmuir monolayers have been used as cell membrane models to study PAMAM dendrimer-membrane interactions. Related experimental and theoretical studies are summarized, and the physical insights from these studies are discussed to shed light on the fundamental understanding of PAMAM dendrimer-cell membrane interactions. We conclude with a summary of some questions that call for further investigations.

Fiber-like micelles based on biodegradable and biocompatible polymers exhibit considerable promise for applications in nanomedicine, but until recently no convenient methods were available to prepare samples with uniform and controllable dimensions and spatial control of functionality. "Living" crystallization-driven self-assembly (CDSA) is a seeded growth method of growing importance for the preparation of uniform 1D and 2D core-shell nanoparticles from a range of crystallizable polymeric amphiphiles. However, in the case of poly(l-lactide) (PLLA), arguably the most widely utilized biodegradable polymer as the crystallizable core-forming block, the controlled formation of uniform fiber-like structures over a substantial range of lengths by "living" CDSA has been a major challenge. Herein, we demonstrate that via simple modulation of the solvent conditions via the addition of trifluoroethanol (TFE), DMSO, DMF and acetone, uniform fiber-like nanoparticles from PLLA diblock copolymers with controlled lengths up to 1 μm can be prepared. The probable mechanism involves improved unimer solvation by a reduction of hydrogen bonding interactions among PLLA chains. We provide evidence that this minimizes undesirable unimer aggregation which otherwise favors self-nucleation that competes with epitaxial crystallization from seed termini. This approach has also allowed the formation of well-defined segmented block comicelles with PLLA cores via the sequential seeded-growth of PLLA block copolymers with different corona-forming blocks.

Epilepsy is a chronic brain disorder, and for at least one- third of epilepsy patients, medications do not adequately control seizures and surgery is the only potential cure. An automated seizure detector that requires a short period of normal EEG would shorten the seizure monitoring durations, decrease the need for manual assessment of large amount of recorded EEG data, and accordingly assist the neurologists focus on improving quality of care. In this work, we propose a novel approach based on the extended cumulative sum test to detect seizures using intracranial EEG. Different than the existing machine learning approaches, this method requires only a short period of normal EEG for training. In addition to a new proposed feature based on partial directed coherence and random graph theory, in this work, previously developed features used to characterize seizures are used as features in cumulative sum test for seizure detection. A total of 33 intracranial EEG recordings collected from a total of 9 patients corresponding to three different datasets have been used for the analysis purposes: (i) the first dataset includes 11 recorded EEG files (~12.5 min) from 4 patients; (ii) the second dataset includes 20 recorded EEG files (~30 min) from 4 patients; and (iii) two 24-hour long EEG files from a single patient. The proposed detector achieved a mean sensitivity and mean specificity for the first (0.77, 0.86), second (0.88, 0.9) and third datasets (0.92, 0.94) respectively. Statistical detection of seizures has shown success in detecting seizures without the need for highly customizable parameters or previously labelled EEG data. The proposed method could be used in real-time at hospital settings with a minimum requirement of training data.

Many language functions are traditionally assigned to cortical brain areas, leaving the contributions of subcortical structures to language processing largely unspecified. The present study examines a potential role of the subthalamic nucleus (STN) in lexical processing, specifically, reading aloud of words (e.g., 'fate') and pseudowords (e.g., 'fape'). We recorded local field potentials simultaneously from the STN and the cortex (precentral, postcentral, and superior temporal gyri) of 13 people with Parkinson's disease undergoing awake deep brain stimulation and compared STN's lexicality-related neural activity with that of the cortex. Both STN and cortical activity demonstrated significant task-related modulations, but the lexicality effects were different in the two brain structures. In the STN, an increase in gamma band activity (31-70 Hz) was present in pseudoword trials compared to word trials during subjects' spoken response. In the cortex, a greater decrease in beta band activity (12-30 Hz) was observed for pseudowords in the precentral gyrus. Additionally, 11 individual cortical sites showed lexicality effects with varying temporal and topographic characteristics in the alpha and beta frequency bands. These findings suggest that the STN and the sampled cortical regions are involved differently in the processing of lexical distinctions.

Current knowledge of the functional anatomy of the subthalamic nucleus and globus pallidus, discovered through microelectrode recording and postoperative imaging, justifies purely anatomic targeting for deep brain stimulation (DBS). Interventional MRI (iMRI)-DBS is more anatomically accurate than traditional awake procedures and has similar clinical outcomes without increased risk or increased operative times. iMRI lead implantation allows patients to receive DBS therapy who cannot tolerate or do not agree to undergo an awake procedure. This article describes considerations for iMRI-DBS implantation in the subthalamic nucleus and globus pallidus, including patient selection, technique of electrode placement, expected outcomes, and potential complications.

Coupled oscillatory activity recorded between sensorimotor regions of the basal ganglia-thalamocortical loop is thought to reflect information transfer relevant to movement. A neuronal firing-rate model of basal ganglia-thalamocortical circuitry, however, has dominated thinking about basal ganglia function for the past three decades, without knowledge of the relationship between basal ganglia single neuron firing and cortical population activity during movement itself. We recorded activity from 34 subthalamic nucleus (STN) neurons, simultaneously with cortical local field potentials and motor output, in 11 subjects with Parkinson's disease (PD) undergoing awake deep brain stimulator lead placement. STN firing demonstrated phase synchronization to both low- and high-beta-frequency cortical oscillations, and to the amplitude envelope of gamma oscillations, in motor cortex. We found that during movement, the magnitude of this synchronization was dynamically modulated in a phase-frequency-specific manner. Importantly, we found that phase synchronization was not correlated with changes in neuronal firing rate. Furthermore, we found that these relationships were not exclusive to motor cortex, because STN firing also demonstrated phase synchronization to both premotor and sensory cortex. The data indicate that models of basal ganglia function ultimately will need to account for the activity of populations of STN neurons that are bound in distinct functional networks with both motor and sensory cortices and code for movement parameters independent of changes in firing rate. NEW & NOTEWORTHY Current models of basal ganglia-thalamocortical networks do not adequately explain simple motor functions, let alone dysfunction in movement disorders. Our findings provide data that inform models of human basal ganglia function by demonstrating how movement is encoded by networks of subthalamic nucleus (STN) neurons via dynamic phase synchronization with cortex. The data also demonstrate, for the first time in humans, a mechanism through which the premotor and sensory cortices are functionally connected to the STN.

Square-planar platinum(II) complexes often stack cofacially to yield supramolecular fiber-like structures with interesting photophysical properties. However, control over fiber dimensions and the resulting colloidal stability is limited. We report the self-assembly of amphiphilic Pt(II) complexes with solubilizing ancillary ligands based on polyethylene glycol [PEGn, where n = 16, 12, 7]. The complex with the longest solubilizing PEG ligand, Pt-PEG16, self-assembled to form polydisperse one-dimensional (1D) nanofibers (diameters 16 complex, underwent elongation in a "living supramolecular polymerization" process to yield relatively uniform fibers of length up to ca. 400 nm. The fiber lengths were dependent on the Pt-PEG16 complex to seed mass ratio in a manner analogous to a living covalent polymerization of molecular monomers. Moreover, the fiber lengths were unchanged in solution after 1 week and were therefore "static" with respect to interfiber exchange processes on this time scale. In contrast, similarly formed near-uniform fibers of Pt-PEG12 exhibited dynamic behavior that led to broadening of the length distribution within 48 h. After aging for 4 weeks in solution, Pt-PEG12 fibers partially evolved into 2D platelets. Furthermore, self-assembly of Pt-PEG7 yielded only transient fibers which rapidly evolved into 2D platelets. On addition of further fiber-forming Pt complex (Pt-PEG16), the platelets formed assemblies via the growth of fibers selectively from their short edges. Our studies demonstrate that when interfiber dynamic exchange is suppressed, dimensional control and hierarchical structure formation are possible for supramolecular polymers through the use of kinetically controlled seeded growth methods.

Understanding interactions between nanoparticles and model membranes is relevant to functional nano-composites and the fundamentals of nanotoxicity. In this study, the effect of polyamidoamine (PAMAM) dendrimers as model nanoparticles (NP) on the mesophase behaviour of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine (POPE) has been investigated using high-pressure small-angle X-ray scattering (HP-SAXS). The pressure-temperature ( p − T ) diagrams for POPE mesophases in excess water were obtained in the absence and presence of G2 and G4 polyamidoamine (PAMAM) dendrimers (29 A and 45 A in diameter, respectively) at varying NP-lipid number ratio (ν = 0.0002–0.02) over the pressure range p = 1–3000 bar and temperature range T = 20–80 °C. The p − T phase diagram of POPE exhibited the Lβ, Lα and HII phases. Complete analysis of the phase diagrams, including the relative area pervaded by different phases, phase transition temperatures (Tt) and pressures (pt), the lattice parameters (d-spacing), the pressure-dependence of d-spacing (Δd/Δp), and the structural ordering in the mesophase as gauged by the Scherrer coherence length (L) permitted insights into the size- and concentration-dependent interactions between the dendrimers and the model membrane system. The addition of dendrimers changed the phase transition pressure and temperature and resulted in the emergence of highly swollen lamellar phases, dubbed Lβ-den and Lα-den. G4 PAMAM dendrimers at the highest concentration ν = 0.02 suppressed the formation of the HII phase within the temperature range studied, whereas the addition of G2 PAMAM dendrimers at the same concentration promoted an extended mixed lamellar region in which Lα and Lβ phases coexisted. Statement of Significance Using high pressure small angle X-ray scattering in the pressure range 1–3000 bar and temperature range 20–60 °C, we have studied interactions between PAMAM dendrimers (as model nanoparticles) and POPE lipid mesophases (as model membranes). We report the pressure-temperature phase diagrams for the dendrimer-lipid mesophases for the first time. We find that the dendrimers alter the phase transition temperatures (Tt) and pressures (pt), the lattice parameters (d-spacing), and the structural order in the mesophase. We interpret these unprecedented results in terms of the fluidity of the lipid membranes and the interactions between the dendrimers and the membranes. Our findings are of fundamental relevance to the field of nanotoxicity and functional nanomaterials that integrate nanoparticles and organized lipid structures.

The sensorimotor cortex is somatotopically organized to represent the vocal tract articulators such as lips, tongue, larynx, and jaw. How speech and articulatory features are encoded at the subcortical level, however, remains largely unknown. We analyzed LFP recordings from the subthalamic nucleus (STN) and simultaneous electrocorticography recordings from the sensorimotor cortex of 11 human subjects (1 female) with Parkinson´s disease during implantation of deep-brain stimulation (DBS) electrodes while they read aloud three-phoneme words. The initial phonemes involved either articulation primarily with the tongue (coronal consonants) or the lips (labial consonants). We observed significant increases in high-gamma (60?150 Hz) power in both the STN and the sensorimotor cortex that began before speech onset and persisted for the duration of speech articulation. As expected from previous reports, in the sensorimotor cortex, the primary articulators involved in the production of the initial consonants were topographically represented by high-gamma activity. We found that STN high-gamma activity also demonstrated specificity for the primary articulator, although no clear topography was observed. In general, subthalamic high-gamma activity varied along the ventral?dorsal trajectory of the electrodes, with greater high-gamma power recorded in the dorsal locations of the STN. Interestingly, the majority of significant articulator-discriminative activity in the STN occurred before that in sensorimotor cortex. These results demonstrate that articulator-specific speech information is contained within high-gamma activity of the STN, but with different spatial and temporal organization compared with similar information encoded in the sensorimotor cortex. Fil: Chrabaszcz, Anna. University of Pittsburgh; Estados Unidos Fil: Neumann, Wolf Julian. Universität zu Berlin; Alemania Fil: Stretcu, Otilia. University of Pittsburgh; Estados Unidos Fil: Lipski, Witold J.. University of Pittsburgh; Estados Unidos Fil: Dastolfo Hromack, Christina A.. University of Pittsburgh; Estados Unidos Fil: Bush, Alan. University of Pittsburgh; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Física de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Física de Buenos Aires; Argentina Fil: Wang, Dengyu. Tsinghua University; China. University of Pittsburgh; Estados Unidos Fil: Crammond, Donald J.. University of Pittsburgh; Estados Unidos Fil: Shaiman, Susan. University of Pittsburgh; Estados Unidos Fil: Dickey, Michael W.. University of Pittsburgh; Estados Unidos Fil: Holt, Lori L.. University of Pittsburgh; Estados Unidos Fil: Turner, Robert S.. University of Pittsburgh; Estados Unidos Fil: Fiez, Julie A.. University of Pittsburgh; Estados Unidos Fil: Richardson, R. Mark. University of Pittsburgh; Estados Unidos

Fiber-like block copolymer (BCP) micelles offer considerable potential for a variety of applications, however, uniform sam-ples of controlled length and with spatially tailored chemistry have not been accessible. Recently, a seeded growth method, termed ‘living’ crystallization-driven self-assembly (CDSA), has been developed to allow the formation of 1D micelles and block comicelles of precisely controlled dimensions from BCPs with a crystallizable segment. An expansion of the range of core forming blocks that participate in living CDSA is necessary for this technique to be compatible with a broad range of applications. Few examples currently exist of well-defined, water-dispersible BCP micelles prepared using this approach, especially from biocompatible and biodegradable polymers. Herein, we demonstrate that BCPs containing a crystallizable polycarbonate, poly(spiro[fluorene-9,5’-[1,3]dioxin]-2’-one) (PFTMC), can readily undergo living CDSA processes. PFTMC b poly(ethylene glycol) (PEG) BCPs with PFTMC:PEG block ratios of 1:11 and 1:25 were shown to undergo liv-ing CDSA to form near monodisperse fiber like micelles of precisely controlled lengths of up to ~1.6 m. Detailed structur-al characterization of these micelles by TEM, AFM, SAXS and WAXS, revealed that they comprise a crystalline, chain folded PFTMC core with a rectangular cross-section that is surrounded by a solvent swollen PEG corona. PFTMC b PEG fiber-like micelles were shown to be dispersible in water to give colloidally stable solutions. This allowed an assessment of the toxicity of these structures towards WI-38 and HeLa cells. From these experiments, we observed no discernable cytotoxi-city from a sample of 119 nm fiber-like micelles to either the healthy (WI-38) or cancerous (HeLa) cell types. The living CDSA process was extended to PFTMC-b-poly(2-vinylpyridine) (P2VP), and addition of this BCP to PFTMC-b-PEG seed micelles led to the formation of well-defined segmented fibers with spatially localized coronal chemistries.

Hydrogels are promising materials for mimicking the extra-cellular environment. Here, we present a simple methodology for the formation of a free-standing viscoelastic hydrogel from the abundant and low cost protein serum albumin. We show that the mechanical properties of the hydrogel exhibit a complicated behaviour as a function of the weight fraction of the protein component. We further use X-ray scattering to shed light on the mechanism of gelation from the formation of a fibrillary network at low weight fractions to interconnected aggregates at higher weight fractions. Given the match between our hydrogel elasticity and that of the myocardium, we investigated its potential for supporting cardiac cells in vitro. Interestingly, these hydrogels support the formation of several layers of myocytes and significantly promote the maintenance of a native-like gene expression profile compared to those cultured on glass. When confronted with a multicellular ventricular cell preparation, the hydrogels can support macroscopically contracting cardiac-like tissues with a distinct cell arrangement, and form mm-long vascular-like structures. We envisage that our simple approach for the formation of an elastic substrate from an abundant protein makes the hydrogel a compelling biomedical material candidate for a wide range of cell types.

We have developed a novel process to convert low molecular weight microcrystalline cellulose into stiff regenerated cellulose fibers using a dry-jet wet fiber spinning process. Highly aligned cellulose fibers were spun from optically anisotropic microcrystalline cellulose/1-ethyl-3-methylimidazoliumdiethyl phosphate (EMImDEP) solutions. As the cellulose concentration increased from 7.6 to 12.4 wt %, the solution texture changed from completely isotropic to weakly nematic. Higher concentration solutions (>15 wt %) showed strongly optically anisotropic patterns, with clearing temperatures ranging from 80 to 90 °C. Cellulose fibers were spun from 12.4, 15.2, and 18.0 wt % cellulose solutions. The physical properties of these fibers were studied by scanning electron microscopy (SEM), wide angle X-ray diffraction (WAXD), and tensile testing. The 18.0 wt % cellulose fibers, with an average diameter of ∼20 μm, possessed a high Young’s modulus up to ∼22 GPa, moderately high tensile strength of ∼305 MPa, as well as high alignment of cellulose chains along the fiber axis confirmed by X-ray diffraction. This process presents a new route to convert icrocrystalline cellulose, which is usually used for low mechanical performance applications (matrix for pharmaceutical tablets and food ingredients, etc.) into stiff fibers which can potentially be used for high-performance composite materials.

Positron Annihilation Lifetime Spectroscopy (PALS) has been employed to characterize the temperature dependence of the local free volume of hydrophobically-modified starch (HMS) – sucrose (S) blends as a function of blend composition and water content. The findings from PALS support the conclusions drawn from thermodynamic characterization using Differential Scanning Calorimetry (DSC) showing evidence of limited phase separation between the HMS and S phases, inferred from the drastic change in the temperature dependence of the average size of the local free volume element as a function of blend composition. The effect of water content on the average local free volume element size is in good agreement with previous studies on simpler carbohydrate polymer/low molecular weight inclusion blends, however, the width of the free volume distribution is also observed to be affected by water content. This is interpreted to be related to the heterogeneity of the free volume holes, which is higher for phase-separated systems comprising phases of different composition and molecular weight distribution. Wide angle X-ray scattering (WAXS) was employed to study the crystallinity of the blends, showing limited crystallinity is present in the blends at the highest water contents with origin in the corn starch (CS) added during processing, and not the HMS and S phases.

Recent electrocorticography data have demonstrated excessive coupling of beta-phase to gamma-amplitude in primary motor cortex and that deep brain stimulation facilitates motor improvement by decreasing baseline phase-amplitude coupling. However, both the dynamic modulation of phase-amplitude coupling during movement and the general cortical neurophysiology of other movement disorders, such as essential tremor, are relatively unexplored. To clarify the relationship of these interactions in cortical oscillatory activity to movement and disease state, we recorded local field potentials from hand sensorimotor cortex using subdural electrocorticography during a visually cued, incentivized handgrip task in subjects with Parkinson’s disease ( n = 11), with essential tremor ( n = 9) and without a movement disorder ( n = 6). We demonstrate that abnormal coupling of the phase of low frequency oscillations to the amplitude of gamma oscillations is not specific to Parkinson’s disease, but also occurs in essential tremor, most prominently for the coupling of alpha to gamma oscillations. Movement kinematics were not significantly different between these groups, allowing us to show for the first time that robust alpha and beta desynchronization is a shared feature of sensorimotor cortical activity in Parkinson’s disease and essential tremor, with the greatest high-beta desynchronization occurring in Parkinson’s disease and the greatest alpha desynchronization occurring in essential tremor. We also show that the spatial extent of cortical phase-amplitude decoupling during movement is much greater in subjects with Parkinson’s disease and essential tremor than in subjects without a movement disorder. These findings suggest that subjects with Parkinson’s disease and essential tremor can produce movements that are kinematically similar to those of subjects without a movement disorder by reducing excess sensorimotor cortical phase-amplitude coupling that is characteristic of these diseases. * Abbreviations : DBS : deep brain stimulation ECoG : electrocorticography

Despite the hard-wired structural connectivity of neural pathways, neural circuits allow context-dependent reactions to sensory cues by triggering the desired movement. Cortico-basal-ganglia circuits seem particularly important for flexible motor control as this is impaired in Parkinson’s disease (PD). We analysed subthalamic nucleus (STN) spike and cortical ECoG activity from PD patients performing a visually-cued hand grip task. Fast reaction times were preceded by enhanced STN spike-to-cortical gamma phase coupling irrespective of firing rate changes, suggesting a role of gamma coupling in motor preparation. STN spike timing was offset by half a cycle when comparing ipsilateral with contralateral movements. Additionally, cortical high-frequency activity increased more steeply within each gamma cycle at the sites that showed the strongest coupling with STN spikes. Cortico-basal-ganglia gamma coupling may thus help shape neural activity to facilitate selective motor control. The observation that this effect occurs independent of changes in mean firing rate has far-reaching implications.HighlightsFast RTs were preceded by enhanced STN spike-to-cortical gamma phase couplingSTN spike probability was significantly modulated relative to the gamma cycleDuring ipsilateral movement, spikes were more likely at the opposite part of the cycleSTN output may thus help shape cortical gamma for selective motor control

Why does closed-loop invasive brain stimulation improve seizure control in some patients with epilepsy, but not others? The RNS System, the only FDA-approved bi-directional brain-computer interface, has been shown to improve seizure control in patients with refractory epilepsy, although the mechanisms behind this success are undefined. We analyzed recordings from the RNS System and discovered two main categories of electrophysiological signatures of stimulation-induced modulation of the seizure network. Direct effects included ictal inhibition and early frequency modulation but did not correlate with improved clinical outcomes. Only indirect effects, those occurring remote from triggered stimulation, predicted improved clinical outcomes. These indirect effects, which included spontaneous ictal inhibition, frequency modulation, fragmentation, and ictal duration modulation, may reflect progressive local epileptogenic network compartmentalization that hinders the spread of pathological synchrony from recruiting neuronal populations. Our findings suggest that responsiveness to RNS may be explained by chronic stimulation-induced modulation of seizure network activity, rather than direct effects on each detected seizure.

Chiral polymers are ubiquitous in nature, and the self-assembly of chiral materials is a field of widespread interest. In this paper, we describe the formation of chiral metallopolymers based on poly(cobaltoceniumethylene) ([PCE]n+), which have been prepared through oxidation of poly(cobaltocenylethylene) (PCE) in the presence of enantiopure N-acyl-amino-acid-derived anionic surfactants, such as N-palmitoyl-l-alanine (C16-l-Ala) and N-palmitoyl-d-alanine (C16-d-Ala). It is postulated that the resulting metallopolymer complexes [PCE][C16-l/d-Ala]n contain close ionic contacts, and exhibit chirality through the axially chiral ethylenic CH2-CH2 bridges, leading to interaction of the chromophoric [CoCp2]+ units through chiral space. The steric influence of the long palmitoyl (C16) surfactant tail is key for the transmission of chirality to the polymer, and results in a brushlike amphiphilic macromolecular structure that also affords solubility in polar organic solvents (e.g., EtOH, THF). Upon dialysis of these solutions into water, the hydrophobic palmitoyl surfactant substituents aggregate and the complex assembles into superhelical ribbons with identifiable "handedness", indicating the transmission of chirality from the molecular surfactant to the micrometer length scale, via the macromolecular complex.

Professor Alan James Leadbetter passed away peacefully on 11 March 2019 in Exeter, aged 84, leaving his wife Brenda, two adult children, Andrew and Jane and two grandchildren. 1. Alan pointing out ...

We report a novel manufacturing method for bio renewable regenerated cellulose fibres modified with curcumin, a molecule is known for its medicinal properties. Ionic liquid namely 1-Ethyl 3-Methyl Imidazolium diethyl phosphate (emim DEP) was found to be capable of dissolving cellulose as well as curcumin. Regenerated cellulose/curcumin composites fibres with curcumin concentration ranging from 1 to 10 wt% were manufactured using dry jet wet fibres spinning process using three different winding speeds. All the cellulose and curcumin composite fibres showed distinct yellow colour imparted by curcumin. The resultant fibres were characterised using scanning electron microscopy (SEM), infrared spectroscopy, mechanical testing, and X-Ray diffraction studies. Scanning electron microscopy of cellulose/curcumin fibres cross-section did not show curcumin aggregates in cellulose fibres indicating uniform dispersion of curcumin in cellulose matrix. The cellulose chain alignment in cellulose/curcumin composite fibres resulted in tensile strength ranging from 223 to 336 MPa and Young’s modulus ranging from 13 to 14.9 GPa. The mechanical properties of cellulose/curcumin composite fibres thus obtained are better than some of the commercially available regenerated cellulose viscose fibres. The wide-angle X-ray diffraction analysis of cellulose/curcumin composite fibres showed good alignment of cellulose chains along the fibre axis. Thus, our findings are a major step in manufacturing strong cellulose fibres with a pharmacologically potent drug curcumin which in future could be used for medicinal, cosmetic and food packaging applications.

We describe the case of a 30-year-old man with HIV with an elevated creatinine and three litres per day of urine output. Using this patient as a framework, we review a diagnostic approach to acute kidney injury with polyuria. This case emphasizes the importance of a complete diagnostic evaluation of acute kidney injury. Without this approach, it would have been easy to attribute the patient’s acute kidney injury to his HIV and necrotizing peri-anal infection, instead of the true life- threatening cause.