Flexible Profile Research Articles

Design and Fabrication of a Capacitance Based Wearable Pressure Sensor Using E-textiles

This paper addresses the methods used for the design and fabrication of a capacitance based wearable pressure sensor fabricated using neoprene and (SAC) plated Nylon Fabric. The experimental set up for the pressure sensor is comprised of a shielded grid of sensing modules, a 555 timer based transduction circuitry, and an Arduino board measuring the frequency of signal to a corresponding pressure. The fundamental design parameters addressed during the development of the pressure sensor presented in this paper are based on size, simplicity, cost, adaptability, and scalability. The design approach adopted in this paper results in a sensor module that is less obtrusive, has a thinner and flexible profile, and its sensitivity is easily scalable for ‘smart’ product applications across industries associated to sports performance, ergonomics, rehabilitation, etc.

Estimating seroprevalence of human papillomavirus type 16 using a mixture model with smoothed age-dependent mixing proportions.

The presence in serum of antibodies to viral antigens is generally considered a well-defined marker of past infection or vaccination. However, analyses of serological data that use a cut-off value to classify individuals as seropositive are prone to misclassification bias, in particular when studying infections with a weak serological response, such as the sexually transmitted human papillomavirus (HPV). We analyzed the serological concentrations of HPV type 16 (HPV16) antibodies in the general Dutch population in 2006-2007, before the introduction of mass vaccination against HPV. We used a 2-component mixture model to represent persons who were seronegative or seropositive for HPV16. Component densities were assumed to be log-normally distributed, with parameters possibly dependent on sex. The age-dependent mixing proportions were smoothed using penalized splines to obtain a flexible seroprevalence profile. Our results suggest that HPV16 seropositivity is associated with higher antibody concentrations in women as compared with men. Seroprevalence shows an increase starting from adolescence in men and women alike, coinciding with the age of sexual debut. Seroprevalence stabilizes in men around age 40, whereas it has a decreasing trend from age 50 onwards in women. Analyses that rely on a cut-off value to classify persons as seropositive yield substantially different seroprevalence profiles, leading to a qualitatively different interpretation of HPV16 infection dynamics. Our results provide a benchmark for examining the effect of HPV16 vaccination in future serological surveys. Our method may prove useful for estimating seroprevalence of other infections with a weak serological response.

Rational design of hyper-glycosylated interferon beta analogs: A computational strategy for glycoengineering

Glycoengineering has been successfully used to improve the physicochemical and pharmaceutical properties of therapeutics. One aspect of glycoengineering is to introduce new N-linked glycosylation consensus sequences (Asn, X, Thr/Ser) into desirable positions in the peptide backbone by mutational insertion to generate proteins with increased sialic acid content. In the current work, human interferon beta (huIFN-β) was used as a model to identify the potential positions for the addition of new N-glycosylation sites. A computational strategy was employed to predict the structural distortions and functional alterations that might be caused by the change in amino acid sequence. Accordingly, three-dimensional (3D) structures of the designed huIFN-β analogs were generated by comparative modeling. Molecular dynamics (MD) simulation was carried out to assess the molecular stability and flexibility profile of the structures. Subsequently, for the purpose of glycoengineering huIFN-β, analogs with 3D structures more similar to the wild-type huIFN-β and exposed Asn residue in the new N-glycosylation site were identified. These modeling procedures indicated that the addition of the new N-glycosylation site in the loop regions had lower constraining effects on the tertiary structure of the protein. This computational strategy can be applied to avoid alterations in the 3D structure of proteins caused by changes in the amino acid sequences, when designing novel hyper-glycosylated therapeutics. This in turn reduces labor-intensive experimental analyses of each analog.

Kinematic and kinetic changes in a hurdle hop task following athletic groin pain rehabilitation

in side-lying using an eccentric break test with a hand held dynamometer (HHD) and were normalized to body weight and lever arm. The squeeze test at 45◦ hip flexion was also performed using the HHD. Flexibility measures included hip internal rotation (IR) in both 90◦ flexion and prone, hip Abd in side-lying and bent knee fall out (BKFO). Demographic information was collected pertaining to age, height, weight, leg dominance, past history of hip and groin injury and ethnicity. Pain on each testing procedure was recorded using a numerical rating scale. The effect each of these variables had on the strength and flexibility profiles was analysed using statistical methods appropriate for the variable type. Results: Normative values for strength were as follows (mean± SD); hip Add non-dominant =3.2±0.6Nm/kg, dominant =3.1±0.6Nm/kg; hip Abd both legs 2.4±0.4Nm/kg; Add:Abd ratios non-dominant =1.4±0.3, dominant =1.3±0.3; squeeze test 3.2±0.8N/kg; hip IR in flexion both legs =37±8◦, hip IR in prone non-dominant =36±8◦, dominant =37±8◦, hip Abd in side lying both legs =47±8◦, BKFO non-dominant =13.5±4.1 cm, dominant =13.7±4.1 cm. Leg dominance and a past history of injury had no clinically relevant effect on the strength and flexibility profiles of the footballers. However, players with pain on squeeze testing recorded significantly lower scores (p≤0.05). Discussion: These reference profiles in footballers can now be used by clinicians in their assessment and management of footballers. The results demonstrate that a clinician can confidently compare the strength and flexibility profile with the non-injured leg when assessing a player with unilateral pain. Pain on clinical testing resulted in lower squeeze values, but a past history of hip or groin injury does not affect these profiles in a healthy group of footballers.

Conservation analysis of residues in the S4-S5 linker and the terminal part of the S5-P-S6 pore modulus in Kv and HCN channels: flexible determinants for the electromechanical coupling.

Protein mobility is important to achieve protein function. Intrinsic flexibility associated with motion underlies this important issue and the analysis of side chain flexibility gives insights to understand it. In this work, the S5-P-S6 pore modulus (PM) of members of Kv and HCN channels was examined by a combination of sequence alignment, residue composition analysis, and intrinsic side chain flexibility. The PM sequences were organized as a database that was used to reveal and correlate the functional diversity of each analyzed family. Specifically, we focused our attention on the crucial role of the S4-S5 linker and its well-described interaction with the S6 T during the electromechanical coupling. Our analysis suggests the presence of a Gly-hinge in the middle of the S4-S5 linkers. This apparent Gly-hinge links a flexible N-terminal segment with a rigid C-terminal one, although in Kv7 channels, the latter segment is even more flexible. Instead, HCN channels exhibit a putative Thr-hinge andis rich in aromatic residues, in consequence, their linker is more rigid. Concerning S6, we confirm the presence of the two flexible kinks previously described and we provide the complete segmental flexibility profiles for the different families. Our results are discussed in terms of the relation between residue composition, conservation, and local conformational flexibility. This provides important insights to understand and differentiate the characteristic gating properties of these channels as well as their implications in cell physiology.

The wheres and whys of protein translation

Local Translation Localized protein synthesis is important for a broad range of biological activities, from specifying the animal body plan to coordinating entry into the secretory pathway. Few tools are available that can investigate translation at specific subcellular sites. Jan et al. present a flexible ribosome profiling–based methodology to enable precise characterization of localized protein synthesis (see the Perspective by Shao and Hegde). Proximity-specific ribosome profiling provides a high-precision tool for looking at the mechanism of localized protein targeting and synthesis in living cells. The approach yielded a high-resolution systems-level view of cotranslational translocation at the endoplasmic reticulum. Williams et al. applied the technique to look at localized mRNA translation at the mitochondrial outer membrane. Science , this issue [10.1126/science.1257521][1], p. [701][2]; see also p. [748][3] [1]: /lookup/doi/10.1126/science.1257521 [2]: /lookup/doi/10.1126/science.1261602 [3]: /lookup/doi/10.1126/science.1257522

Coarse-grained modeling of DNA curvature.

The interaction of DNA with proteins occurs over a wide range of length scales, and depends critically on its local structure. In particular, recent experimental work suggests that the intrinsic curvature of DNA plays a significant role on its protein-binding properties. In this work, we present a coarse grained model of DNA that is capable of describing base-pairing, hybridization, major and minor groove widths, and local curvature. The model represents an extension of the recently proposed 3SPN.2 description of DNA [D. M. Hinckley, G. S. Freeman, J. K. Whitmer, and J. J. de Pablo, J. Chem. Phys. 139, 144903 (2013)], into which sequence-dependent shape and mechanical properties are incorporated. The proposed model is validated against experimental data including melting temperatures, local flexibilities, dsDNA persistence lengths, and minor groove width profiles.

A stochastic framework for the grid integration of wind power using flexible load approach

Wind power integration has always been a key research area due to the green future power system target. However, the intermittent nature of wind power may impose some technical and economic challenges to Independent System Operators (ISOs) and increase the need for additional flexibility. Motivated by this need, this paper focuses on the potential of Demand Response Programs (DRPs) as an option to contribute to the flexible operation of power systems. On this basis, in order to consider the uncertain nature of wind power and the reality of electricity market, a Stochastic Network Constrained Unit Commitment associated with DR (SNCUCDR) is presented to schedule both generation units and responsive loads in power systems with high penetration of wind power. Afterwards, the effects of both price-based and incentive-based DRPs are evaluated, as well as DR participation levels and electricity tariffs on providing a flexible load profile and facilitating grid integration of wind power. For this reason, novel quantitative indices for evaluating flexibility are defined to assess the success of DRPs in terms of wind integration. Sensitivity studies indicate that DR types and customer participation levels are the main factors to modify the system load profile to support wind power integration.

Solid-Phase Reactive Chromatographic Separation System: Optimization-Based Design and Its Potential Application to Biomass Saccharification via Acid Hydrolysis

A new reactive separation process concept termed solid-phase reactive separation system (SPRSS) is proposed which integrates the progressing batch reactor (PBR) and simulated moving bed (SMB) chromatography processes. The key idea of this new process is that both PBR and SMB employ similar principles of the movement of the liquid feed to imitate the countercurrent movement of solid and liquid phases. This concept may be applied to the reactive separation system that involves solid reactants. In this work, SPRSS is applied to the production of sugar from cellulosic materials which contain different amounts of cellulose and hemicellulose in which the kinetics of each hydrolysis reaction path are different. SPRSS enables the variation of these reaction parameters within the reactor system to hydrolyze different portions of the biomass, which allows more flexible acid catalyst concentration profiles. The overarching goal is to improve the total sugar yield and concentration while minimizing the sugar decomposition reaction and undesired product formation. An optimization strategy using a superstructure formulation is applied to find the optimal process design of SPRSS using a continuous moving-bed model. The optimal results show a potential improvement of the sugar yield as well as less byproduct formation by changing the acid concentration using the SPRSS configuration design. The effect of different kinetic parameters is investigated, which could significantly affect the performance of SPRSS. Several observations of the values of these kinetic parameters which could further enhance the advantages of SPRSS design are demonstrated.

Psychological flexibility is not a single dimension: The distinctive flexibility profiles of underweight, overweight, and obese people

Psychological flexibility interventions such as Acceptance and Commitment Therapy have been shown to be beneficial for weight management. Flexibility is often treated as a single, global construct, but it can also be described in terms of interrelated components (e.g., accepting, awareness, defusion, values). Are some components of flexibility of greater relevance to weight-related issues than others? We utilized a planned missing data design to assess weight status and a broad range of psychological flexibility components in a nationally representative sample of Americans (N=7884; 3748 males, 4136 females; age: M=47.9, SD=16). Profile analyses revealed that different weight and gender groups showed different configurations of inflexibility. Underweight men showed a “defensive but active” pattern, expressing high avoidance on multiple dimensions, high levels of fusion, but also showing high hope and willingness to experience distress when pursuing goals. Overweight and obese participants did not show elevated levels of inflexibility, and indeed there was some evidence that overweight men (but not obese and severely obese men) were more flexible than other males. Severely obese participants showed elevated patterns of inflexibility across multiple indices, but this pattern differed for men and women. We conclude that psychological flexibility should not be treated as a unitary construct, and make specific suggestions for future intervention research.

Amplification and Bandwidth Recovery of Chirped Super-Gaussian Pulses by Use of Gain Shaping in Ytterbium-Doped Fiber Amplifiers

We demonstrate a simple passive method to generate broadband chirped super-Gaussian pulses from high-gain ytterbium-doped fiber amplification system without obvious bandwidth degradation. By use of the inherent gain shaping effect of fiber amplifiers, pulses can recover the initial Super-Gaussian profile and bandwidth with large gain and optical signal-to-noise ratio (OSNR). In this method, fiber amplifier itself works as a spectral filter with flexible transmission profiles and gain, which can be optimized by pump power and fiber length. A spectrally resolved numerical model with amplified spontaneous emission (ASE) is developed for broadband ytterbium-doped double-clad fiber pulse amplifiers. In a proof-of-principle two-stage amplification system, with a shorter fiber preamplifier working in the gain-narrowing region as a pre-shaper, broadband Super-Gaussian pulses resemble themselves after the second amplification stage with the largest total gain and OSNR. Experimental results quantitatively confirm the numerical predictions. The proposed gain shaping method also provides a new way to compensate the pulse deformation and bandwidth narrowing in high-gain fiber chirped pulse amplification systems.

Dopamine DRD2/ANKK1 Taq1A and DAT1 VNTR polymorphisms are associated with a cognitive flexibility profile in pathological gamblers.

Like drug addiction, pathological gambling (PG) has been associated with impairments in executive functions and alterations in dopaminergic functioning; however, the role of dopamine (DA) in the executive profile of PG remains unclear. The aim of this study was to identify whether the DRD2/ANKK1 Taq1A-rs1800497 and the DAT1-40 bp VNTR polymorphisms are associated with cognitive flexibility (measured by Wisconsin Card Sorting Test (WCST) and Trail Making Test (TMT)) and inhibition response (measured by Stroop Color and Word Test (SCWT)), in a clinical sample of 69 PG patients. Our results showed an association between DA functioning and cognitive flexibility performance. The Taq1A A1+ (A1A2/A1A1) genotype was associated with poorer TMT performance (p<0.05), while DAT1 9-repeat homozygotes displayed better WCST performance (p<0.05) than either 10-repeat homozygotes or heterozygotes. We did not find any association between the DRD2 or DAT1 polymorphisms and the inhibition response. These results suggested that pathological gamblers with genetic predispositions toward lower availability of DA and D2 receptor density are at a higher risk of cognitive flexibility difficulties. Future studies should aim to shed more light on the genetic mechanisms underlying the executive profile in PG.

Chain interdigitation in DPPC bilayers induced by HgCl2: Evidences from continuous wave and pulsed EPR

Continuous-wave electron paramagnetic resonance (CW-EPR) spectroscopy and electron spin echo methods of pulsed EPR of phosphatidylcholine spin-labeled at different positions, n, in the sn-2 chain (n-PCSL, n=5, 7, 10, 12, 14, and 16) are used to study the interaction of inorganic mercury chloride HgCl2 with multilamellar vesicles of dipalmitoylphosphatidylcholine (DPPC). For temperatures through the gel phase of DPPC multilayers, the CW-EPR spectra show that an increase of HgCl2 content in the dispersion medium slightly increases the rotational mobility of 5-PCSL and markedly restricts the motion of 16-PCSL. Mercury chloride at 100mM (HgCl2/lipid molar ratio=2:1) removes the gradient of increasing mobility along the chain found in DPPC bilayers in the gel phase. In contrast, HgCl2 does not influence the DPPC chain flexibility profile in the fluid phase. It also suppresses the pre-transition and moderately downshifts the main transition temperature of DPPC membranes. These findings indicate that HgCl2 affects the lipid chain packing of DPPC bilayers and are consistent with the induction of an interdigitated gel phase. Further, D2O-electron spin echo envelope modulation spectroscopy indicates that in the interdigitated phase a higher water permeation is favored at any chain position and the sigmoidal transmembrane water accessibility profile of DPPC bilayers is abolished. Accordingly, the positional dependence of 14N-hyperfine splitting, 2Azz, shows that the typical hydrophobic barrier of DPPC is significantly altered in the interdigitated phase and all the segments of the lipid chains result to be in a more polar environment.

MIP models for resource-constrained project scheduling with flexible resource profiles

This paper addresses the resource-constrained project scheduling problem with flexible resource profiles (FRCPSP). Such a problem often arises in many real-world applications, in which the resource usage of an activity is not merely constant, but can be adjusted from period to period. The FRCPSP is, therefore, to simultaneously determine the start time, the resource profile, and the duration of each activity in order to minimize the makespan, subject to precedence relationships, limited availability of multiple resources, and restrictions on resource profiles. We propose four discrete-time model formulations and compare their model efficiency in terms of solution quality and computational times. Both preprocessing and priority-based heuristic methods are also applied to compute both upper and lower bounds of the makespan. Our comparative results show significant dominance of one of the models, the so-called “variable-intensity-based” model, in both solution quality and runtimes.

Redistribution of flexibility in stabilizing antibody fragment mutants follows Le Châtelier's principle.

Le Châtelier’s principle is the cornerstone of our understanding of chemical equilibria. When a system at equilibrium undergoes a change in concentration or thermodynamic state (i.e., temperature, pressure, etc.), La Châtelier’s principle states that an equilibrium shift will occur to offset the perturbation and a new equilibrium is established. We demonstrate that the effects of stabilizing mutations on the rigidity ⇔ flexibility equilibrium within the native state ensemble manifest themselves through enthalpy-entropy compensation as the protein structure adjusts to restore the global balance between the two. Specifically, we characterize the effects of mutation to single chain fragments of the anti-lymphotoxin-β receptor antibody using a computational Distance Constraint Model. Statistically significant changes in the distribution of both rigidity and flexibility within the molecular structure is typically observed, where the local perturbations often lead to distal shifts in flexibility and rigidity profiles. Nevertheless, the net gain or loss in flexibility of individual mutants can be skewed. Despite all mutants being exclusively stabilizing in this dataset, increased flexibility is slightly more common than increased rigidity. Mechanistically the redistribution of flexibility is largely controlled by changes in the H-bond network. For example, a stabilizing mutation can induce an increase in rigidity locally due to the formation of new H-bonds, and simultaneously break H-bonds elsewhere leading to increased flexibility distant from the mutation site via Le Châtelier. Increased flexibility within the VH β4/β5 loop is a noteworthy illustration of this long-range effect.

Flexibility of cold- and heat-adapted subtilisin-like serine proteinases evaluated with fluorescence quenching and molecular dynamics

The subtilisin-like serine proteinases, VPR, from a psychrotrophic Vibrio species and aqualysin I (AQUI) from the thermophile Thermus aquaticus, are structural homologues, but differ significantly with respect to stability and catalytic properties. It has been postulated that the higher catalytic activity of cold adapted enzymes when compared to homologues from thermophiles, reflects their higher molecular flexibility. To assess a potential difference in molecular flexibility between the two homologous proteinases, we have measured their Trp fluorescence quenching by acrylamide at different temperatures. We also investigated protein dynamics of VPR and AQUI at an atomic level by molecular dynamics simulations. VPR contains four Trp residues, three of which are at corresponding sites in the structure of AQUI. To aid in the comparison, a Tyr at the fourth corresponding site in AQUI was mutated to Trp (Y191W). A lower quenching effect of acrylamide on the intrinsic fluorescence of the thermophilic AQUI_Y191W was observed at all temperatures measured (10–55°C), suggesting that it possesses a more rigid structure than VPR. The MD analysis (Cα rmsf profiles) showed that even though VPR and AQUI have similar flexibility profiles, the cold adapted VPR displays higher flexibility in most regions of the protein structure. Some of these regions contain or are in proximity to some of the Trp residues (Trp6, Trp114 and Trp208) in the proteins. Thus, we observe an overall agreement between the fluorescence quenching data and the flexibility profiles obtained from the MD simulations to different flexibilities of specific regions in the proteins.

A Reference-Pulse Generator for Motion Control System

This paper introduces a reference-pulse interpolator motion control system, which can be applied for computer numerical control (CNC) machine tools. The interpolation is calculated in DSP and the independent pulse generator modules are performed in FPGA, which can generate precise reference velocity profile and eliminate the path error of reference pulse interpolation. The proposed methodology has many advantages over existing reference-pulse interpolator controller, such as: real-time, extensibility, high flexibility and high precision motion profile planning.

Synthesis and evaluation of 4-substituted piperidines and piperazines as balanced affinity μ opioid receptor (MOR) agonist/δ opioid receptor (DOR) antagonist ligands

In this letter, we describe a series of 4-substituted piperidine and piperazine compounds based on tetrahydroquinoline 1, a compound that shows balanced, low nanomolar binding affinity for the mu opioid receptor (MOR) and the delta opioid receptor (DOR). We have shown that by changing the length and flexibility profile of the side chain in this position, binding affinity is improved at both receptors by a significant degree. Furthermore, several of the compounds described herein display good efficacy at MOR, while simultaneously displaying DOR antagonism. The MOR agonist/DOR antagonist has shown promise in the reduction of negative side effects displayed by selective MOR agonists, namely the development of dependence and tolerance.

Comparison of the flexibility and torsional resistance of nickel-titanium rotary instruments

Introduction: This study compared the flexibility and tor sional resistance of two types of instruments manufactured with special NiTi alloys, and one with conventional NiTi. Methods: Twisted File (TF) instruments manufactured with the R-phase of NiTi (SybronEndo, Orange, CA), and ProFile Vortex instruments (Dentsply Tulsa Dental, Tulsa, OK, USA) made of M-Wire NiTi were compared with RaCe (FKG Dentaire, La Chaux-de-Fonds, Switzerland) instruments made of conventional NiTi. Flexibility and torsion assays were carried out using twenty 25/0.06 instruments from each manufacturer. Statistical analysis was performed by ANOVA. Results: The mechanical resistance of the instruments tested was significantly different. TF were the most flexible instruments, followed by RaCe and ProFile Vortex (P < 0.01). In the torsion assay, ProFile Vortex instruments endured the greatest maximum load and maximum torque values prior to fracture, followed by RaCe and TF (P < 0.01). The torsional resistance values of RaCe and TF were not significantly different (P = 0.061). Conclusion: We observed a relationship between flexibility and torsional resistance (maximum torque and maximum angular deflection in torsion). The most flexible instrument (TF) was the least resistant to torsion, while the least flexible (ProFile Vortex) was the most resistant to torsion. RaCe presented intermediate results for both flexibility and torsional resistance.

Exclusion of an Internal Iliac Artery Aneurysm Using Stacked Aorto-uni-iliac Converters over a Femoro-femoral Pullthrough Wire

An endovascular solution for treating internal iliac artery aneurysms (IIAAs) with tortuous iliac anatomy and intraprocedural complications is presented. An 85-year-old male presented with a 7-cm left IIAA causing hydronephrosis. Following inability to deploy a standard aorto-uni-iliac converter and subsequent iliac dissection, two low-profile aorto-uni-iliac converters were deployed from the external to common iliac artery over a femoro-femoral pullthrough wire, achieving a stacked configuration and successful aneurysm exclusion. Iliac artery tortuosity may preclude successful iliac coverage and predispose to dissection. A pullthrough wire allows arterial straightening; use of flexible low profile devices facilitates procedural success.