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1.
Cyclic peptides have the potential to vastly extend the scope of druggable proteins and lead to new therapeutics for currently untreatable diseases. However, cyclic peptides often suffer from poor bioavailability. To uncover design principles for permeable cyclic peptides, a promising strategy is to analyze the conformational dynamics of the peptides using molecular dynamics (MD) and Markov state models (MSMs). Previous MD studies have focused on the conformational dynamics in pure aqueous or apolar environments to rationalize membrane permeability. However, during the key steps of the permeation through the membrane, cyclic peptides are exposed to interfaces between polar and apolar regions. Recent studies revealed that these interfaces constitute the free energy minima of the permeation process. Thus, a deeper understanding of the behavior of cyclic peptides at polar/apolar interfaces is desired. Here, we investigate the conformational and kinetic behavior of cyclic decapeptides at a water/chloroform interface using unbiased MD simulations and MSMs. The distinct environments at the interface alter the conformational equilibrium as well as the interconversion kinetics of cyclic peptide conformations. For peptides with low population of the permeable conformation in aqueous solution, the polar/apolar interface facilitates the interconversion to the closed conformation, which is required for membrane permeation. Comparison to unbiased MD simulations with a POPC bilayer reveals that not only the conformations but also the orientations are relevant in a membrane system. These findings allow us to propose a permeability model that includes both ‘prefolding’ and ‘non-prefolding’ cyclic peptides – an extension that can lead to new design considerations for permeable cyclic peptides.

This study uses molecular dynamics and Markov state models to analyse how interfaces interact with cyclic decapeptides and modulate their dynamic and equilibrium properties.  相似文献   

2.
3.
The introduction of ‘defects’ to the thermoset crosslinking network is one of the most applicable strategies for improving the modulus and toughness simultaneously. However, the reinforcement effect disappears when the ‘defects’ proportion exceeds the threshold. The speculated mechanism was that the aggregation and entanglement of the ‘defects’ chains changed the matrix topology, making the stacking structure more compact. However, the ‘defects’ are hardly directly observed in the experiment. As the result, the relationship between the ‘defects’ proportion and the package state of the matrix, and the effect on the material''s mechanical performance was not explored. Herein, the network of bisphenol-A diglycidyl (DGEBA) with diethyltoluenediamine (DETDA) as the hardener was constructed using MD simulation, and n-butylamine was decorated on the matrix by replacing a proportion of DETDA acting as the ‘defects’. The results indicated that the aliphatic chains aggregated and entangled at a low concentration, occupying the voids in the rigid aromatic crosslinking structure, thus lowering the free volume. The strong non-bonding interactions drew the matrix segments close together, thus reinforcing the resin. However, the microphases formed by the aliphatic chains no longer filled the voids but created a new free volume and loosened the network when the content increased, which reduced the mechanical performance of the material. The experimental results were consistent with the findings in the simulations. The moduli of the resin increased with the increase in the n-butylamine content first and then declined. The maximum moduli of the thermosets was 3.4 GPa in S30, which was about 25% higher compared with the control; the corresponding elongation at break was 8.9%, which was about 46% improved compared with the control.

The introduction of ‘defects’ to the thermoset crosslinking network is one of the most applicable strategies for improving the modulus and toughness simultaneously.  相似文献   

4.
Brain activity is continuously modulated, even at “rest”. The alpha rhythm (8–12 Hz) has been known as the hallmark of the brain's idle-state. However, it is still debated if the alpha rhythm reflects synchronization in a distributed network or focal generator and whether it occurs spontaneously or is driven by a stimulus. This EEG/fMRI study aimed to explore the source of alpha modulations and their distribution in the resting brain. By serendipity, while computing the individually defined power modulations of the alpha-band, two simultaneously occurring components of these modulations were found. An ‘induced alpha’ that was correlated with the paradigm (eyes open/ eyes closed), and a ‘spontaneous alpha’ that was on-going and unrelated to the paradigm. These alpha components when used as regressors for BOLD activation revealed two segregated activation maps: the ‘induced map’ included left lateral temporal cortical regions and the hippocampus; the ‘spontaneous map’ included prefrontal cortical regions and the thalamus. Our combined fMRI/EEG approach allowed to computationally untangle two parallel patterns of alpha modulations and underpin their anatomical basis in the human brain. These findings suggest that the human alpha rhythm represents at least two simultaneously occurring processes which characterize the ‘resting brain’; one is related to expected change in sensory information, while the other is endogenous and independent of stimulus change.  相似文献   

5.
Wuyi rock tea is a typical and famous oolong tea in China and roasting is an important manufacturing procedure for its flavor formation. This work aimed to explore the effect of roasting on non-volatiles and volatiles of 12 Wuyi rock tea samples at three roasting levels (low, moderate and sufficient), made from four tea cultivars (Shuixian, Qizhong, Dahongpao, Rougui). Results show that different roasting had not caused significant difference on contents of soluble solids, total polyphenols, flavonoids, soluble sugar, thearubigins and theabrownins, while it slightly regulated caffeine, proteins and theaflavins, and remarkably reduced catechins and free amino acids. The ratio of polyphenol content/amino acid content, a negative-correlated indicator of fresh and brisk taste, significantly increased with the increase of roasting degree. High-level roasting not only decreased the fresh and brisk taste of the tea infusion, but also reduced the amount of bioactive ingredients including catechins and theanine. A total of 315 volatiles were detected and analyzed with OPLS-DA and HCA methods, in which 99 volatiles were found with variable importance in the projection (VIP) values greater than 1.00. Tea samples at different roasting degrees were successfully separated by this model of roasting-level discrimination. ‘Naphthalene, 1,2,3,4-tetrahydro-1,6,8-trimethyl-’, ‘1,1,5-trimethyl-1,2-dihydronaphthalene’, ‘p-Xylene’, ‘alpha.-methyl-.alpha.-[4-methyl-3-pentenyl]oxiranemethanol’, ‘hydrazinecarboxylic acid, phenylmethyl ester’, and ‘3-buten-2-one, 4-(2,6,6-trimethyl-2-cyclohexen-1-yl)-’ might be key characteristic markers for the roasting process of Wuyi rock tea.

Wuyi rock tea is a typical and famous oolong tea in China and roasting is an important manufacturing procedure for its flavor formation.  相似文献   

6.
Correction for ‘Reactions of nitroxides 16. First nitroxides containing tellurium atom’ by Jerzy Zakrzewski et al., RSC Adv., 2016, 6, 98829–98834, https://doi.org/10.1039/c6ra15880c.

The authors regret that incorrect text concerning names of specific chemical compounds were included in the original article.In the subheading “3-(Phenyltellanyl)ethylamine 3a, 3-(phenyltellanyl)propylamine 3b (according to a known procedure20 with some modifications)” on page 98831, ‘3-(Phenyltellanyl)ethylamine 3a’ should read as ‘2-(Phenyltellanyl)ethylamine 3a’.In the subheading “3-(Phenyltellanyl)ethylamine 3a (M = 248.6)” on page 98831, ‘3-(Phenyltellanyl)ethylamine 3a’ should read as ‘2-(Phenyltellanyl)ethylamine 3a’.In the subheading “3-(Phenyltellanyl)ethyl isothiocyanate 4a, and 3-(phenyltellanyl)propyl isothiocyanate 4b. General procedure” on page 98831, ‘3-(Phenyltellanyl)ethyl isothiocyanate 4a’ should read as ‘2-(Phenyltellanyl)ethyl isothiocyanate 4a’.Following the subheading “Tellurium nitroxides 6a–6f, general procedure” on page 98832, in the sentence reading “2-(Phenyltellanyl)ethyl isothiocyanate (4a, 0.111 g, 0.382 mmol) or 2-(phenyltellanyl)propyl isothiocyanate”, ‘2-(phenyltellanyl)propyl isothiocyanate’ should read as ‘3-(phenyltellanyl)propyl isothiocyanate’.The Royal Society of Chemistry apologises for these errors and any consequent inconvenience to authors and readers.  相似文献   

7.

Objective

To evaluate the use of palpation of the coccyx (the coccygeal movement test, CMT) as a possible objective screening tool for the assessment of adequate localization of the pelvic floor muscles (PFMs).

Subjects and Methods

Twenty-four healthy female volunteers, known to be able to locate their PFMs, were given instructions (allocated at random) to perform a ‘correct contraction’, ‘straining’ or ‘nothing’ when examined by six independent assessors using the CMT. The assessors were blinded to the instructions and to the test results recorded by other assessors. Data were available for 137 observations, and these were dichotomized into either ‘able to contract’ (‘correct contraction’) or ‘not able to contract’ (‘straining’ or ‘nothing’). This information was used to calculate the sensitivity, specificity and positive and negative predictive values for the CMT.

Results

The CMT correctly identified 56/58 observations when women did not perform the contraction of the PFMs compared to 61/79 observations when they did. Hence, the sensitivity and specificity were 97 and 77%, respectively.

Conclusion

This study showed that the CMT was a useful test to identify women who were able to localize their PFMs compared to those who were not, making it a potentially useful initial screening test in structured training programmes for the PFMs.Key Words: Pelvic floor, Incontinence, Coccygeal movement test, Pelvic floor muscle training  相似文献   

8.
Combinatorial material science crucially depends on robust, high-throughput characterization methods. While X-ray photoelectron spectroscopy (XPS) may provide detailed information about chemical and electronic properties, it is a time-consuming technique and, therefore, is not viewed as a high-throughput method. Here we present preliminary XPS data of 169 measurement spots on a combinatorial 72 × 72 cm2 CuxNi1−xOy compositional library to explore how characterization and evaluation routines can be optimized to improve throughput in XPS for combinatorial studies. In particular, two quantification approaches are compared. We find that a simple integration (of XPS peak regions) approach is suited for fast evaluation of, in the example system, the [Cu]/([Cu] + [Ni]) ratio. Complementary to that, the time-consuming (XPS peak-) fit approach provides additional insights into chemical speciation and oxidation state changes, without a large deviation of the [Cu]/([Cu] + [Ni]) ratio. This insight suggests exploiting the fast integration approach for ‘real time’ analysis during XPS data collection, paving the way for an ‘on-the-fly’ selection of points of interest (i.e., areas on the sample where sudden composition changes have been identified) for detailed XPS characterization. Together with the envisioned improvements when going from laboratory to synchrotron-based excitation sources, this will shorten the analysis time sufficiently for XPS to become a realistic characterization option for combinatorial material science.

Methods for fast quantification of XPS data of a CuxNi1−xOy combinatorial material library were evaluated in a step towards high-throughput analysis.  相似文献   

9.
Visible and near infrared (Vis-NIR) hyperspectral imaging was used for fast detection and visualization of soluble solid content (SSC) in ‘Beijing 553’ and ‘Red Banana’ sweet potatoes. Hyperspectral images were acquired from 420 ROIs of each cultivar of sliced sweet potatoes. There were 8 and 10 outliers removed from ‘Beijing 553’ and ‘Red Banana’ sweet potatoes by Monte Carlo partial least squares (MCPLS). The optimal spectral pretreatments were determined to enhance the performance of the prediction model. Successive projections algorithm (SPA) and competitive adaptive reweighted sampling (CARS) were employed to select characteristic wavelengths. SSC prediction models were developed using partial least squares regression (PLSR), support vector regression (SVR) and multivariate linear regression (MLR). The more effective prediction performances emerged from the SPA–SVR model with Rp2 of 0.8581, RMSEP of 0.2951 and RPDp of 2.56 for ‘Beijing 553’ sweet potato, and the CARS–MLR model with Rp2 of 0.8153, RMSEP of 0.2744 and RPDp of 2.09 for ‘Red Banana’ sweet potato. Spatial distribution maps of SSC were obtained in a pixel-wise manner using SPA–SVR and CARS–MLR models for quantifying the SSC level in a simple way. The overall results illustrated that Vis-NIR hyperspectral imaging was a powerful tool for spatial prediction of SSC in sweet potatoes.

Visible and near infrared (Vis-NIR) hyperspectral imaging was used for fast detection and visualization of soluble solid content (SSC) in ‘Beijing 553’ and ‘Red Banana’ sweet potatoes.  相似文献   

10.
The meta-analysis of early goal-directed therapy (EGDT) by Gu and colleagues in the previous issue of Critical Care adds to the ongoing controversy about the value of EGDT for resuscitating patients with severe sepsis and septic shock. The results of the ProCESS (protocolized care for early septic shock) and ARISE (Australasian resuscitation in sepsis evaluation) trials failed to demonstrate any benefit of EGDT or protocolized resuscitation when compared with ‘usual care’. The questions are the following: What is ‘usual’ care? What is ‘real world’ care? Do the results of a robust and well-conducted randomized controlled trial - in which many patients may be excluded for a variety of reasons - reflect the care given to patients on a daily basis in our emergency departments and intensive care units? Of course, there are no obvious answers to these questions, and many clinicians look forward to managing these patients without protocols. For now, the data do seem to support the management of patients with septic shock without mandated central lines or protocols. Does this mean we should go back to the era of ‘do whatever you want’? No consensus exists among clinicians regarding optimal hemodynamic monitoring, and to date no method has been proven to be superior. Given the amount of fluids given prior to randomization in the ProCESS and ARISE trials, ‘usual care’ appears to now include aggressive, early fluid resuscitation with at least 20 mL/kg of crystalloid and rapid administration of appropriate antibiotics. Certainly, this reflects the impact of the original trial by Rivers and colleagues and the broad-based implementation of the Surviving Sepsis Campaign Guidelines and bundles. If this continues to define ‘usual care’, then perhaps it is no longer necessary to mandate specific protocols for resuscitation, as it appears that standard sepsis management has evolved to be consistent with published protocols.  相似文献   

11.
Herein, we report the covalent functionalization of graphene oxide (GO) through ‘‘click’’ reaction and its applications towards ammonia sensing. This inimitable method of covalent functionalization involves linking GO with azide moiety and click coupling of different derivatives of aryl propargyl ether, which enhances the sensitivity towards ammonia. The functionalized GO were characterized using NMR, XRD, SEM, FT-IR, Raman, UV-Vis, TGA and DSC. Compared to pristine GO, the GO functionalized with Ar samples (GO-Ar) exhibit excellent room temperature ammonia sensing properties with good response/recovery characteristics. It has been observed that 2,3-difluoro and 2,3,4-trifluoro substituted aryl propargyl ether functionalized GO (GO-Ar2 and GO-Ar3) shows superior ammonia sensing with response/recovery of 63%/∼90% and 60%/100%, respectively at 20 ppm. The GO-Ar3 exhibits high sensitivity towards ammonia at 20–100 ppm. Computational studies supports the high sensitivity of GO-Ar towards ammonia due to its high adsorption energy.

Covalent functionalization of graphene oxide (GO) through ‘‘click’’ reaction and its applications towards ammonia sensing has been demonstrated.  相似文献   

12.
13.
Purpose of ReviewSoft tissue imbalance, presenting as instability or stiffness, is an important cause of revision total knee arthroplasty (TKA). Traditional methods of determining soft tissue balance of the knee lack precision and are not reliable between operators. Use of intra-operative pressure sensors offers the potential to identify and avoid soft tissue imbalance following TKA. This review aims to summarise the literature supporting the clinical indication for the use of intra-articular pressure sensors during TKA.Recent FindingsAnalytical validation studies suggest that intra-operative pressure sensors demonstrate ‘moderate’ to ‘good’ intra-observer reliability and ‘good’ to ‘excellent’ interobserver reliability throughout the flexion arc. However, there are important errors associated with measurements when devices are used out-with the stated guidelines and clinicians should be aware of the limitations of these devices in isolation. Current evidence regarding patient benefit is conflicting. Despite positive early results, several prospective studies have subsequently failed to demonstrate significant differences in overall survival, satisfaction, and patient-reported outcome measures within 1 year of surgery.SummarySurgeon-defined soft tissue stability appears to be significantly different from the absolute pressures measured by the intra-operative sensor. Whilst it could be argued that this confirms the need for intra-articular sensor guidance in TKA; the optimal ‘target’ balance remains unclear and the relationship with outcome in patients is not determined. Future research should (1) identify a suitable reference standard for comparison; (2) improve the accuracy of the sensor outputs; and (3) demonstrate that sensor-assisted TKA leads to patient benefit in patient-reported outcome measures and/or enhanced implant survival.  相似文献   

14.
Postoperative cognitive problems and delirium are not uncommon in the elderly. We reported four cases in which auricular acupunctures on the ‘Shenmen’ and ‘Point Zero’ points successfully managed postoperative problematic behaviors of the three patients with dementia and the one patient postoperatively demonstrating an agitated behavior.  相似文献   

15.
BackgroundSouth Africa has made enormous progress in reducing mother-to-child transmission (MTCT) of human immunodeficiency virus (HIV), however, MTCT and AIDS related death persist among children particularly in the rural areas. Lack of adherence to health policies and guidelines implementation remain one of the contributory factors to poor management of HIV-exposed children. Hence, the need to deeply explore the complexity of the problems and understand the barriers to the management of HIV exposed children in the rural areas.ObjectivesTo explore and synthesise the barriers to the management of children under 5 years old exposed to HIV in rural areas in South Africa.MethodAn integrative literature review was conducted. An electronic search was conducted on several databases. The researchers applied the Boolean ‘ AND’/‘OR’ in combination with phrases such as ‘HIV infection*’, ‘HIV transmission’, ‘HIV-exposed infant*, child*, and neonate*’ and ‘South Africa*’. Included studies were limited to South Africa, and articles were written in English and published in peer-reviewed journals from 2005 to 2018. Both qualitative and quantitative studies between 2005 and 2018 were utilised.ResultsThe findings highlighted that healthcare institution-related barriers, healthcare provider-related barriers, patient-related barriers and Socio-economic-related barriers were the significant barriers to the management of HIV-exposed children in the rural areas.ConclusionContinuous engagement with all relevant stakeholders should remain a priority in protecting HIV-exposed children. It is evident that there exist gaps in the current implementation of prevention of mother-to-child transmission (PMTCT), especially in rural areas. Therefore, intervention strategies that could improve implementation of PMTCT policy guidelines for HIV-exposed children in rural areas are needed.  相似文献   

16.
BackgroundMothers are regarded as primary care givers. The experience of having a child with congenital abnormality may have an impact on their psychological well-being. It was observed that the psychological well-being of mothers is often unattended by health professionals, including nurses and their families. Mothers make adjustments in their daily lives to ensure the child’s activities of daily living are attended. Therefore, this raises the need for the experience of mothers who have children with congenital abnormalities in the Gert Sibande district to be explored. Gert Sibande was chosen because it has been observed that several mothers who visit the clinic and outpatient department have children with congenital abnormalities.ObjectivesThe purpose of this study was to explore and describe the lived experiences of mothers who have children with congenital abnormalities.MethodA phenomenological study was conducted. Purposive sampling of 12 participants was done. The study used adjusted ecological model of health for guidance. Data gathering was done by self-report using unstructured face-to-face interviews until data saturation was reached.ResultsFive themes emerged from the study, which include ‘being hurt emotionally’, ‘sense of guilt’, ‘acceptance’, ‘support from family’ and ‘community reaction to the congenital abnormality’. The findings show that mothers were affected by having children with congenital abnormalities.ConclusionThe study revealed that mothers of children with congenital abnormalities experienced devastation, denial, guilt and lack of acceptance of their child’s condition. The study indicates that mothers require support from health care professionals, family and the community.  相似文献   

17.
‘Ki-energy’, which can be enhanced through the practice of Nishino Breathing Method, was reported to have beneficial health effects. Although Ki-energy can play an important role in complementary and alternative medicine (CAM), as yet it is unknown how Ki-energy is generated, transmitted through air and received by another individual. We previously proposed that Ki-energy may include near-infrared radiation, and that the wavelength was between 800 and 2700 nm. Since Ki-energy is reflected by a mirror, we believe that the ‘Ki-beam’ has a small divergence angle. It can also be guided in a desired direction. The acrylic mirror reflection experiment suggests that the wavelength may be between 800 and 1600 nm. Using a linear variable interference filter, we found that Ki-energy may have a peak around 1000 nm. We have also observed that ‘sensitive’ practitioners responded to Ki sent from a distance of 100 m. All of these results suggest that (i) Ki-energy can be guided as a directional ‘beam’ with a small divergence angle; (ii) the beam can be reflected by a mirror and (iii) Ki-energy may have a specific wavelength. Since these properties are characteristics of the laser radiation, we propose a quantum physics-based mechanism of ‘Light Amplification by the Stimulated Emission of Radiation’ (i.e. LASER) for the generation of Ki-energy. Volunteers responded to Ki even with a blindfold. This suggests that the skin must be detecting Ki-energy. We propose that the detector at the skin level may also have the stimulated emission mechanism, which amplifies the weak incident infrared radiation.  相似文献   

18.
IntroductionNurses often recognize deterioration in patients through intuition rather than through routine measurement of vital signs. Adding the ‘worry or concern’ sign to the Rapid Response System provides opportunities for nurses to act upon their intuitive feelings. Identifying what triggers nurses to be worried or concerned might help to put intuition into words, and potentially empower nurses to act upon their intuitive feelings and obtain medical assistance in an early stage of deterioration. The aim of this systematic review is to identify the signs and symptoms that trigger nurses’ worry or concern about a patient’s condition.MethodsWe searched the databases PubMed, CINAHL, Psychinfo and Cochrane Library (Clinical Trials) using synonyms related to the three concepts: ‘nurses’, ‘worry/concern’ and ‘deterioration’. We included studies concerning adult patients on general wards in acute care hospitals. The search was performed from the start of the databases until 14 February 2014.ResultsThe search resulted in 4,006 records, and 18 studies (five quantitative, nine qualitative and four mixed-methods designs) were included in the review. A total of 37 signs and symptoms reflecting the nature of the criterion worry or concern emerged from the data and were summarized in 10 general indicators. The results showed that worry or concern can be present with or without change in vital signs.ConclusionsThe signs and symptoms we found in the literature reflect the nature of nurses’ worry or concern, and nurses may incorporate these signs in their assessment of the patient and their decision to call for assistance. The fact that it is present before changes in vital signs suggests potential for improving care in an early stage of deterioration.

Electronic supplementary material

The online version of this article (doi:10.1186/s13054-015-0950-5) contains supplementary material, which is available to authorized users.  相似文献   

19.
CoNiP nanosheet array catalysts were successfully prepared on three-dimensional (3D) graphene foam using hydrothermal synthesis. These catalysts were prepared using 3D Ni–graphene foam (Ni/GF), comprising nickel foam as the ‘skeleton’ and reduced graphene oxide as the ‘skin’. This unique continuous modified ‘skeleton/skin’ structure ensure that the catalysts had a large surface area, excellent conductivity, and sufficient surface functional groups, which promoted in situ CoNiP growth, while also optimizing the hydrolysis of sodium borohydride. The nanosheet arrays were fully characterized and showed excellent catalytic performance, as supported by density functional theory calculations. The hydrogen generation rate and activation energy are 6681.34 mL min−1 g−1 and 31.2 kJ mol−1, respectively, outperforming most reported cobalt-based catalysts and other precious metal catalysts. Furthermore, the stability of mockstrawberry-like CoNiP catalyst was investigated, with 74.9% of the initial hydrogen generation rate remaining after 15 cycles. The catalytic properties, durability, and stability of the catalyst were better than those of other catalysts reported previously.

Schematic diagram of the preparation, cycles and the kinetics of the Ni/GF/CoNiP nanosheet catalyst.  相似文献   

20.
The first year of life traditionally refers to the growth and development of an infant. Recent studies have disclosed the powerful effects exerted by young babies upon their parents. These influences depend upon distinct, measurable personality and temperamental factors present in the infant from birth. Parent/child attachment has been observed, in both normal nurseries and premature intensive-care units, and appears to comprise a series of species-specific behaviors. Inadequate or incomplete bonding has been strongly correlated with subsequent ‘disorders of parenting’, including non-organic ‘failure to thrive’ and the abused child syndrome. The implications of these current discoveries for family physicians are discussed.  相似文献   

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