Application of blood-based biomarkers of Alzheimer's disease in clinical practice: Recommendations from Taiwan Dementia Society.

Blood-based biomarkers (BBM) are potentially powerful tools that assist in the biological diagnosis of Alzheimer's disease (AD) in vivo with minimal invasiveness, relatively low cost, and good accessibility. This review summarizes current evidence for using BBMs in AD, focusing on amyloid, tau, and biomarkers for neurodegeneration. Blood-based phosphorylated tau and the Aß42/Aß40 ratio showed consistent concordance with brain pathology measured by CSF or PET in the research setting. In addition, glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) are neurodegenerative biomarkers that show the potential to assist in the differential diagnosis of AD. Other pathology-specific biomarkers, such as α-synuclein and TAR DNA-binding protein 43 (TDP-43), can potentially detect AD concurrent pathology. Based on current evidence, the working group from the Taiwan Dementia Society (TDS) achieved consensus recommendations on the appropriate use of BBMs for AD in clinical practice. BBMs may assist clinical diagnosis and prognosis in AD subjects with cognitive symptoms; however, the results should be interpreted by dementia specialists and combining biochemical, neuropsychological, and neuroimaging information. Further studies are needed to evaluate BBMs' real-world performance and potential impact on clinical decision-making.

PIP2 regulating calcium signal modulates actin cytoskeleton-dependent cytoadherence and cytolytic capacity in the protozoan parasite Trichomonas vaginalis.

Trichomonas vaginalis is a prevalent causative agent that causes trichomoniasis leading to uropathogenic inflammation in the host. The crucial role of the actin cytoskeleton in T. vaginalis cytoadherence has been established but the associated signaling has not been fully elucidated. The present study revealed that the T. vaginalis second messenger PIP2 is located in the recurrent flagellum of the less adherent isolate and is more abundant around the cell membrane of the adherent isolates. The T. vaginalis phosphatidylinositol-4-phosphate 5-kinase (TvPI4P5K) with conserved activity phosphorylating PI(4)P to PI(4, 5)P2 was highly expressed in the adherent isolate and partially colocalized with PIP2 on the plasma membrane but with discrete punctate signals in the cytoplasm. Plasma membrane PIP2 degradation by phospholipase C (PLC)-dependent pathway concomitant with increasing intracellular calcium during flagellate-amoeboid morphogenesis. This could be inhibited by Edelfosine or BAPTA simultaneously repressing parasite actin assembly, morphogenesis, and cytoadherence with inhibitory effects similar to the iron-depleted parasite, supporting the significance of PIP2 and iron in T. vaginalis colonization. Intriguingly, iron is required for the optimal expression and cell membrane trafficking of TvPI4P5K for in situ PIP2 production, which was diminished in the iron-depleted parasites. TvPI4P5K-mediated PIP2 signaling may coordinate with iron to modulate T. vaginalis contact-dependent cytolysis to influence host cell viability. These observations provide novel insights into T. vaginalis cytopathogenesis during the host-parasite interaction.

An Atypical F-Actin Capping Protein Modulates Cytoskeleton Behaviors Crucial for Trichomonas vaginalis Colonization.

Cytoadherence and migration are crucial for pathogens to establish colonization in the host. In contrast to a nonadherent isolate of Trichomonas vaginalis, an adherent one expresses more actin-related machinery proteins with more active flagellate-amoeboid morphogenesis, amoeba migration, and cytoadherence, activities that were abrogated by an actin assembly blocker. By immunoprecipitation coupled with label-free quantitative proteomics, an F-actin capping protein (T. vaginalis F-actin capping protein subunit α [TvFACPα]) was identified from the actin-centric interactome. His-TvFACPα was detected at the barbed end of a growing F-actin filament, which inhibited elongation and possessed atypical activity in binding G-actin in in vitro assays. TvFACPα partially colocalized with F-actin at the parasite pseudopod protrusion and formed a protein complex with α-actin through its C-terminal domain. Meanwhile, TvFACPα overexpression suppressed F-actin polymerization, amoeboid morphogenesis, and cytoadherence in this parasite. Ser2 phosphorylation of TvFACPα enriched in the amoeboid stage of adhered trophozoites was reduced by a casein kinase II (CKII) inhibitor. Site-directed mutagenesis and CKII inhibitor treatment revealed that Ser2 phosphorylation acts as a switching signal to alter TvFACPα actin-binding activity and the consequent actin cytoskeleton behaviors. Through CKII signaling, TvFACPα also controls the conversion of adherent trophozoites from amoeboid migration to the flagellate form with axonemal motility. Together, CKII-dependent Ser2 phosphorylation regulates TvFACPα binding to actin to fine-tune cytoskeleton dynamics and drive crucial behaviors underlying host colonization by T. vaginalis. IMPORTANCE Trichomoniasis is one of the most prevalent nonviral sexually transmitted diseases. T. vaginalis cytoadherence to urogenital epithelium cells is the first step in the colonization of the host. However, studies on the mechanisms of cytoadherence have focused mainly on the role of adhesion molecules, and their effects are limited when analyzed by loss- or gain-of-function assays. This study proposes an extra pathway in which the actin cytoskeleton mediated by a capping protein α-subunit may play roles in parasite morphogenesis, cytoadherence, and motility, which are crucial for colonization. Once the origin of the cytoskeleton dynamics could be manipulated, the consequent activities would be controlled as well. This mechanism may provide new potential therapeutic targets to impair this parasite infection and relieve the increasing impact of drug resistance on clinical and public health.

Triggering the Vapochromic Behavior in C60 via the Supramolecular Wrapping of st-PMMA.

Understanding the physicochemical modulation of functional molecules is the primary step in exploring novel stimuli-responsive materials, and preventing the π-π stacking configuration of π-conjugated molecules has been an effective strategy of vapochromic material development, such as of nanoporous frameworks. Nevertheless, the more complicated synthetic strategy should in fact be applied in many circumstances. In this study, we explore a facile supramolecular strategy where the commodity plastic, syndiotactic-poly(methyl methacrylate) (st-PMMA), is utilized to wrap C60 to form the inclusion complex. The structural characterization revealed that C60s in the st-PMMA supramolecular helix had a lower coordination number (CN = 2) compared to the face-centered-cubic packing of pure C60s (CN = 12). Since the st-PMMA/C60 helical complex has structural flexibility, the π-π stacking structure of C60 was further interrupted by the intercalation of toluene vapors, and the complete isolation of C60 in the complex induced the desired vapochromic behavior. Furthermore, the aromatic interaction between C60 and aromatic solvent vapors enabled the st-PMMA/C60 inclusion complex to selectively encapsulate chlorobenzene, toluene, etc., and induce the color change. The st-PMMA/C60 inclusion complex exhibited a transparent film of sufficient structural integrity such that it can still induce a reversible color change after several cycles. As a result, a new strategy has been discovered for the development of novel vapochromic materials via host-guest chemistry.

Atrophy, hypometabolism and implication regarding pathology in late-life major depression with suspected non-alzheimer pathophysiology (SNAP).

BACKGROUND: A substantial proportion of individuals with late-life major depression could be classified as having a suspected non-Alzheimer disease pathophysiology (SNAP), as indicated by a negative test for the biomarker ß-amyloid (Aß-) but a positive test for neurodegeneration (ND+). This study investigated the clinical features, characteristic patterns of brain atrophy and hypometabolism, and implications regarding pathology in this population. METHODS: Forty-six amyloid-negative patients with late-life major depressive disorder (MDD) patients, including 23 SNAP (Aß-/ND+) and 23 Aß-/ND- MDD subjects, and 22 Aß-/ND-healthy control subjects were included in this study. Voxel-wise group comparisons between the SNAP MDD, Aß-/ND- MDD and control subjects were performed, adjusting for age, gender and level of education. For exploratory comparisons, 8 Aß+/ND- and 4 Aß+/ND + MDD patients were included in the Supplementary Material. RESULTS: The SNAP MDD patients had atrophy extending to regions outside the hippocampus, predominately in the medial temporal, dorsomedial and ventromedial prefrontal cortex; hypometabolism involving a large portion of the lateral and medial prefrontal cortex in addition to the bilateral temporal, parietal and precuneus cortex within typical Alzheimer disease regions were observed. Metabolism ratios of the inferior to the medial temporal lobe were significantly elevated in the SNAP MDD patients. We further discussed the implications with regards to underlying pathologies. CONCLUSION: The present study demonstrated characteristic patterns of atrophy and hypometabolism in patients with late-life major depression with SNAP. Identifying individuals with SNAP MDD may provide insights into currently unspecified neurodegenerative processes. Future refinement of neurodegeneration biomarkers is essential in order to identify potential pathological correlates while in vivo reliable pathological biomarkers are not forthcoming.

Decreased Cerebral Amyloid-ß Depositions in Patients With a Lifetime History of Major Depression With Suspected Non-Alzheimer Pathophysiology.

Cerebral amyloid-ß (Aß) depositions in depression in old age are controversial. A substantial proportion of individuals with late-life major depressive disorder (MDD) could be classified as having suspected non-Alzheimer's disease pathophysiology (SNAP) by a negative test for the biomarker amyloid-ß (Aß-) but positive neurodegeneration (ND+). This study aimed to evaluate subthreshold Aß loads in amyloid-negative MDD, particularly in SNAP MDD patients. This study included 46 amyloid-negative MDD patients: 23 SNAP (Aß-/ND+) MDD and 23 Aß-/ND- MDD, and 22 Aß-/ND- control subjects. All subjects underwent 18F-florbetapir PET, FDG-PET, and MRI. Regions of interest (ROIs) and voxel-wise group comparisons were performed with adjustment for age, gender, and level of education. The SNAP MDD patients exhibited significantly deceased 18F-florbetapir uptakes in most cortical regions but not the parietal and precuneus cortex, as compared with the Aß-/ND- MDD and control subjects (FDR correction, p < 0.05). No correlations of neuropsychological tests or depression characteristics with global cortical uptakes, but significant positive correlations between cognitive functions and adjusted hippocampal volumes among different groups were observed. The reduced Aß depositions in the amyloid-negative MDD patients might be attributed mainly to the SNAP MDD patients. Our results indicated that meaningfully low amounts of subclinical Aß might contain critical information on the non-amyloid-mediated pathogenesis.

Dual-Axis Alignment of Bulk Artificial Water Channels by Directional Water-Induced Self-Assembly.

Approaching single-crystal-like morphology has always been important in driving materials toward their optimal properties. With only orientational order, liquid crystal (LC) materials require dual-axis orientational control to optimize their structural order in the bulk phase. However, current external guiding fields such as electrical, magnetic, and mechanical guiding fields are less effective in aligning amphiphilic LCs. In this study, water is developed as an excellent structural stabilizer and orientation-directing agent of an amphiphilic discotic molecule (AD) in the water-induced self-assembly (WISA) process. Thermal analysis and structural characterization results show that water increases the stability and domain sizes of the hexagonal columnar (Colh) phase of the AD by co-assembling with the ADs to form bulk artificial water channels (AWCs). Moreover, through control over the nucleation conditions (degree of supercooling and location of nucleation), dual-axis alignment in both the planar and vertical growth of the AWCs is achieved by applying water as the guiding field in the directional WISA. With precise control over the hierarchical structures, the bulk AWC array of the AD delivers excellent salt rejection properties and water permeability. Considering that all the amphiphilic LCs have hydrophilic segments, these new roles of water in the WISA process could launch the further development of functional amphiphilic LCs by providing a dynamic interaction and a readily available guiding field.

GAGE mediates radio resistance in cervical cancers via the regulation of chromatin accessibility.

Radiotherapy (RT) resistance is a major cause of treatment failure in cancers that use definitive RT as their primary treatment modality. This study identifies the cancer/testis (CT) antigen G antigen (GAGE) as a mediator of radio resistance in cervical cancers. Elevated GAGE expression positively associates with de novo RT resistance in clinical samples. GAGE, specifically the GAGE12 protein variant, confers RT resistance through synemin-dependent chromatin localization, promoting the association of histone deacetylase 1/2 (HDAC1/2) to its inhibitor actin. This cumulates to elevated histone 3 lysine 56 acetylation (H3K56Ac) levels, increased chromatin accessibility, and improved DNA repair efficiency. Molecular or pharmacological disruption of the GAGE-associated complex restores radiosensitivity. Molecularly, this study demonstrates the role of GAGE in the regulation of chromatin dynamics. Clinically, this study puts forward the utility of GAGE as a pre-screening biomarker to identify poor responders at initial diagnosis and the therapeutic potential of agents that target GAGE and its associated complex in combination with radiotherapy to improve outcomes.

Water-Induced Self-Assembly of Amphiphilic Discotic Molecules for Adaptive Artificial Water Channels.

Inspired by the induced-fit mechanism in nature, we developed the process of water-induced self-assembly (WISA) to make water an active substrate that regulates the self-assembly and function of amphiphilic discotic molecules (ADMs). The ADM is an isotropic liquid that self-assembles only when in contact with water. Characterization results indicate that water fits into the hydrophilic core of the ADMs and induces the formation of a hexagonal columnar phase (Colh), where each column contains a hydrated artificial water channel (AWC). The hydrated AWCs are adaptive rather than static; the dynamic incorporation/removal of water results in the reversible assembly/disassembly of the adaptive AWCs (aAWCs). Furthermore, its dynamic characteristics can enable water to act as an orientation-directional guest molecule that controls the growth direction of the aAWCs. Well-aligned aAWC arrays that showed the ability of water transport were obtained via a "directional WISA" method. In WISA, water thus governs the supramolecular chemistry and function of synthetic molecules as it does with natural materials. By making water an active component in adaptive chemistry and enabling host molecules to dynamically interact with water, this adaptive aquatic material may motivate the development of synthetic molecules further toward biomaterials.

Investigation of reactive astrogliosis effect on post-stroke cognitive impairment.

BACKGROUND: The aim of this study is to investigate the associations between post-stroke cognitive impairment (PSCI) severity and reactive astrogliosis (RA) extent on normalized 18F-THK-5351 positron-emission tomography (PET) imaging in amyloid-negative patients with first-ever stroke. METHODS: We prospectively enrolled 63 amyloid-negative patients with first-ever stroke. Neurocognitive evaluation, MRI, 18F-THK-5351, and 18F-florbetapir PET were performed around 3 months after stroke. The 18F-THK-5351 uptake intensity was normalized using a signal distribution template to obtain the Z-SUM scores as the RA extent in the whole brain and cerebral hemisphere ipsilateral to stroke lesion. We evaluated stroke volume, leukoaraiosis, and brain atrophy on MRI. We used a comprehensive neurocognitive battery to obtain composite cognitive scores, and defined PSCI as a general cognitive function score < - 1. We analyzed the influence of Z-SUM scores on PSCI severity after adjusting for demographic, vascular, and neurodegenerative variables. RESULTS: Twenty-five of 63 stroke patients had PSCI. Patients with PSCI had older age, lower education, and more severe cortical atrophy and total Z-SUM scores. Total Z-SUM scores were significantly associated with general cognitive and executive functions at multiple regression models. Path analyses showed that stroke can exert cognitive influence directly by stroke itself as well as indirectly through RA, including total and ipsilateral Z-SUM scores, in patients with either right or left hemisphere stroke. CONCLUSION: The patterns and intensity of 18F-THK-5351 uptake in amyloid-negative patients with first-ever stroke were associated with PSCI manifestations, which suggests that RA presents a modulating effect in PSCI development.

Author Correction: Plasma Aß analysis using magnetically-labeled immunoassays and PET 18F-florbetapir binding in non-demented patients with major depressive disorder.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

Unique Supramolecular Liquid-Crystal Phases with Different Two-Dimensional Crystal Layers.

We report herein a series of tetrablock-mimic azobenzene-containing [60]fullerene dyads that form supramolecular liquid crystals (LCs) from phase-segregated two-dimensional (2D) crystals. The unique double-, triple-, and quadruple-layer packing structure of fullerenes in the 2D crystals leads to different smectic supramolecular LC phases, and novel LC phase transitions were observed upon changes in the fullerene packing layer number in the 2D crystals. Interestingly, by combining the LC properties with 2D crystals, these materials show excellent electron mobility in the order of 10-3  cm2 V-1 s-1 , despite their relatively low fullerene content. Our results provide a novel method to manipulate 2D crystal layer thickness, with promising applications in optoelectronic devices.

Diversity of neurodegenerative pathophysiology in nondemented patients with major depressive disorder: Evidence of cerebral amyloidosis and hippocampal atrophy.

BACKGROUND: Patients with late-life depression may be at the preclinical stage of dementia. However, the neurodegenerative processes in late-life depression are poorly understood. This study aimed to investigate the distribution patterns of amyloid pathology and neurodegeneration in a depressive population without dementia. METHODS: The study recruited 63 middle-aged and elderly patients with major depressive disorder (MDD) and 22 control subjects. The MDD patients were further subdivided into those with mild cognitive impairment (MCI) (n = 24) and non-MCI (n = 39) patients. We used the global standardized uptake value ratio of 18 F-florbetapir (AV-45/Amyvid) positron emission tomography imaging as a biomarker of cerebral amyloidosis and the hippocampal volume as a biomarker for neurodegeneration. Cutoff points of brain amyloid positivity and hippocampal atrophy were determined using independent data obtained from clinically diagnosed Alzheimer's disease (AD) patients in a previous study. RESULTS: Most of the control subjects (81.8%) were biomarker-negative, in contrast to the MCI MDD patients (37.5%). A relatively high proportion of the MCI MDD patients (12.5%) exhibited both amyloid positivity and hippocampal atrophy as compared to the control subjects (4.5%) and non-MCI patients (5.1%). However, a considerable proportion of the MCI MDD patients (29.2%) were categorized into the group with hippocampal atrophy alone, and negative amyloid deposition, as compared to the control subjects (0%) and non-MCI patients (5.1%). CONCLUSIONS: This study highlights the expected heterogeneity of the processes of neurodegeneration in MDD patients. The diverse neurodegenerative processes may have important etiologic and therapeutic implications regarding neurodegenerative pathophysiology in late-life depression.

Influences of Conjugation Length on Organic Field-Effect Transistor Performances and Thin Film Structures of Diketopyrrolopyrrole-Oligomers.

Here, two diketopyrrolopyrrole (DPP)-based oligomers, DPP-4T and DPP-6T, are studied to reveal the influences of conjugation length on thin-film morphology and organic field-effect transistor (OFET) performances. PDMS-assisted crystallization in a solvent-annealing chamber is applied to prepare crystal arrays of DPP-4T and DPP-6T to optimize the quality of charge channels for OFET characterizations. To deliver insights into microstructure and morphology of thin films, a characterization procedure for determining molecular packing in thin film and crystallinity of the crystal arrays is presented via grazing incidence wide-angle X-ray scattering, electron diffraction, and lattice simulation software package (Cerius2). With the lattice parameters derived from analyses of grazing incidence wide-angle X-ray scattering (GIWAXS) and electron diffraction (ED), the lattice modeling results indicate that the inferior organic field-effect transistor (OFET) performances of DPP-6T are attributed to longer π-stacking distance. Also, less-ordered molecular arrangement and lower continuity of crystalline domains, both of which are revealed from crystallinity results, lead to lower mobility of DPP-6T. In this case, longer conjugated backbones with more conformational degrees of freedom thus cause inherent crystal defects during the crystal growth process, despite the potential to enhance intermolecular π-orbital overlap. Therefore, to achieve better OFET performance, suitable backbone length makes conjugated oligomers give high intermolecular π-orbital overlap and low density of structural disorder, which are the priorities for constructing good charge channel.

Plasma Aß analysis using magnetically-labeled immunoassays and PET 18F-florbetapir binding in non-demented patients with major depressive disorder.

An increased level of brain amyloid deposition and a decreased level of cerebral spinal fluid (CSF) Aß42 are currently considered reliable biomarkers of Alzheimer's disease (AD); however, the usefulness of plasma Aß levels are not well-established. This study investigated the relationships between plasma Aß levels and cerebral amyloidosis in 36 non-demented patients with major depressive disorder (MDD). All participants underwent 18F-florbetapir PET imaging and provided a blood sample at the same time for immunomagnetic reduction assay to measure the plasma levels of Aß40 and Aß42. We found inverse associations of the plasma Aß42 level and the Aß42/Aß40 ratio, and a positive association of the plasma Aß40 level, with cerebral amyloid deposition in the precuneus, parietal and posterior cingulate cortex. Subgroup analyses in subjects with higher 18F-florbetapir uptake values or MDD with amnestic mild cognitive impairment revealed more pervasive relationships of plasma Aß measures with 18F-florbetapir binding across the brain regions examined. The study suggested that regional brain amyloid deposition in terms of 18F-florbetapir PET uptake had weak-to-moderate associations with plasma Aß42 and Aß40 levels, and the Aß42/Aß40 ratio. Validation in a larger population of subjects of known cerebral amyloidosis status is needed. Careful interpretation of plasma data is warranted.

Cylindrical micelles of a POSS amphiphilic dendrimer as nano-reactors for polymerization.

A low generation amphiphilic dendrimer, POSS-AD, which has a POSS core and eight amphiphilic arms, was synthesized and used as a nano-reactor to produce well-defined polymer nano-cylinders. Confirmed by small-angle X-ray scattering (SAXS), Raman and NMR spectrometry, monodispersed cylindrical micelles that contain a hydrophilic cavity with a diameter of 2.09 nm and a length of 4.26 nm were produced via co-assembling POSS-AD with hydrophilic liquids, such as H2O and HEMA in hydrophobic solvents. Taking the HEMA/POSS-AD cylindrical micelles as nano-reactors, polymerization of HEMA within the micelles results in polymer nano-cylinders (POSS-ADNPs) with a diameter of 2.24 nm and a length of 5.02 nm. The study confirmed that despite the inability to maintain specific shape in solution, low generation dendrimers form well-defined nano-containers or nano-reactors, which relies on co-assembling with hydrophilic guest molecules. These nano-reactors are robust enough to maintain their shape during the polymerization of the guest molecules. Polymer nano-cylinders with dimensions less than 10 nm can thus be produced from the HEMA/POSS-AD micelles. Since the chemical structure of low-generation dendrimers and the contents of the co-assembled nano-reactors can be easily adjusted, the concept holds the potential for the further developments of low-generation amphiphilic dendrimers.

Psychotropic use and risk of stroke among patients with bipolar disorders: 10-year nationwide population based study.

OBJECTIVES: To investigate the association between psychotropic agents (including antipsychotics, antidepressants and mood stabilizers) and risk of stroke among patients with bipolar disorders. METHODS: We conducted a disease risk score-matched nested case-control study and identified patients with bipolar disorders (ICD-9 codes: 296.0x, 296.1x, 296.4x, 296.5x, 296.6x, 296.7x, 296.80, 296.81 or 296.89) from the National Health Insurance Research Database in Taiwan. Among them, we identified 1232 cases (981 were ischemic stroke and 251 were hemorrhagic stroke) and 5314 disease risk score-matched controls. Conditional logistic regression model equations were applied to determine the effect of psychotropic agents on stroke risk among patients with bipolar disorders. RESULTS: The results indicated that overall use of psychotropic agents was associated with an increased risk of stroke (adjusted odds ratio [AOR] = 1.82; 95% confidence interval [CI]: 1.56-2.13). When classifying psychotropic agents into antipsychotics, antidepressants and mood stabilizers, respectively, a significant positive association was found for users of antipsychotics (AOR = 1.98; 95% CI = 1.53-2.56), antidepressants (AOR = 1.44; 95% CI = 1.16-1.79), and mood stabilizers (AOR = 1.89; 95% CI = 1.22-2.93). Combined use of psychotropic agents was associated with higher risk of stroke than monotherapy (AOR = 2.62; 95% CI = 1.98-3.45). DISCUSSIONS: The results support our hypothesis that psychotropic use is associated with increased risk of stroke among patients with bipolar disorders. The stroke risks are higher among patients with polypharmacy than those with monotherapy. These findings warrant further investigation to confirm and replicate the findings using different methodologies and populations, and to mitigate residual confounding.

Topologically Directed Assemblies of Semiconducting Sphere-Rod Conjugates.

Spontaneous organizations of designed elements with explicit shape and symmetry are essential for developing useful structures and materials. We report the topologically directed assemblies of four categories (a total of 24) of sphere-rod conjugates, composed of a sphere-like fullerene (C60) derivative and a rod-like oligofluorene(s) (OF), both of which are promising organic semiconductor materials. Although the packing of either spheres or rods has been well-studied, conjugates having both shapes substantially enrich resultant assembled structures. Mandated by their shapes and topologies, directed assemblies of these conjugates result not only in diverse unconventional semiconducting supramolecular lattices with controlled domain sizes but also in tunable charge transport properties of the resulting structures. These results demonstrate the importance of persistent molecular topology on hierarchically assembled structures and their final properties.

Series elastic actuation of an elbow rehabilitation exoskeleton with axis misalignment adaptation.

Powered exoskeletons can facilitate rehabilitation of patients with upper limb disabilities. Designs using rotary motors usually result in bulky exoskeletons to reduce the problem of moving inertia. This paper presents a new linearly actuated elbow exoskeleton that consists of a slider crank mechanism and a linear motor. The linear motor is placed beside the upper arm and closer to shoulder joint. Thus better inertia properties can be achieved while lightweight and compactness are maintained. A passive joint is introduced to compensate for the exoskeleton-elbow misalignment and intersubject size variation. A linear series elastic actuator (SEA) is proposed to obtain accurate force and impedance control at the exoskeleton-elbow interface. Bidirectional actuation between exoskeleton and forearm is verified, which is required for various rehabilitation processes. We expect this exoskeleton can provide a means of robot-aided elbow rehabilitation.

Hierarchical Self-Organization of AB n Dendron-like Molecules into a Supramolecular Lattice Sequence.

To understand the hierarchical self-organization behaviors of soft materials as well as their dependence on molecular geometry, a series of AB n dendron-like molecules based on polyhedral oligomeric silsesquioxane (POSS) nanoparticles were designed and synthesized. The apex of these molecules is a hydrophilic POSS cage with 14 hydroxyl groups (denoted DPOSS). At its periphery, there are different numbers (n = 1-8) of hydrophobic POSS cages with seven isobutyl groups (denoted BPOSS), connected to the apical DPOSS via flexible dendron type linker(s). By varying the BPOSS number from one to seven, a supramolecular lattice formation sequence ranging from lamella (DPOSS-BPOSS), double gyroid (space group of Ia3̅d, DPOSS-BPOSS2), hexagonal cylinder (plane group of P6mm, DPOSS-BPOSS3), Frank-Kasper A15 (space group of Pm3̅n, DPOSS-BPOSS4, DPOSS-BPOSS5, and DPOSS-BPOSS6), to Frank-Kasper sigma (space group of P42/mnm, DPOSS-BPOSS7) phases can be observed. The nanostructure formations in this series of AB n dendron-like molecules are mainly directed by the molecular geometric shapes. Furthermore, within each spherical motif, the spherical core consists hydrophilic DPOSS cages with flexible linkages, while the hydrophobic BPOSS cages form the relative rigid shell, and contact with neighbors to provide decreased interfaces among the spherical motifs for constructing final polyhedral motifs in these Frank-Kasper lattices. This study provides the design principle of molecules with specific geometric shapes and functional groups to achieve anticipated structures and macroscopic properties.