Probing the mechanism of electron capture and electron transfer dissociation using tags with variable electron affinity

Electron capture dissociation (ECD) and electron transfer dissociation (ETD) of doubly protonated electron affinity (EA)-tuned peptides were studied to further illuminate the mechanism of these processes. The model peptide FQpSEEQQQTEDELQDK, containing a phosphoserine residue, was converted to EA-tuned peptides via β-elimination and Michael addition of various thiol compounds. These include propanyl, benzyl, 4-cyanobenzyl, perfluorobenzyl, 3,5-dicyanobenzyl, 3-nitrobenzyl, and 3,5-dinitrobenzyl structural moieties, having a range of EA from −1.15 to +1.65 eV, excluding the propanyl group. Typical ECD or ETD backbone fragmentations are completely inhibited in peptides with substituent tags having EA over 1.00 eV, which are referred to as electron predators in this work. Nearly identical rates of electron capture by the dications substituted by the benzyl (EA = −1.15 eV) and 3-nitrobenzyl (EA = 1.00 eV) moieties are observed, which indicates the similarity of electron capture cross sections for the two derivatized peptides. This observation leads to the inference that electron capture kinetics are governed by the long-range electron−dication interaction and are not affected by side chain derivatives with positive EA. Once an electron is captured to high-n Rydberg states, however, through-space or through-bond electron transfer to the EA-tuning tags or low-n Rydberg states via potential curve crossing occurs in competition with transfer to the amide π* orbital. The energetics of these processes are evaluated using time-dependent density functional theory with a series of reduced model systems. The intramolecular electron transfer process is modulated by structure-dependent hydrogen bonds and is heavily affected by the presence and type of electron-withdrawing groups in the EA-tuning tag. The anion radicals formed by electron predators have high proton affinities (approximately 1400 kJ/mol for the 3-nitrobenzyl anion radical) in comparison to other basic sites in the model peptide dication, facilitating exothermic proton transfer from one of the two sites of protonation. This interrupts the normal sequence of events in ECD or ETD, leading to backbone fragmentation by forming a stable radical intermediate. The implications which these results have for previously proposed ECD and ETD mechanisms are discussed

A Prospective Study of Venous Thromboembolic Prophylaxis Using Foot Pumps Following Total Knee Replacement in a Chinese Population

AbstractPurposeThe purpose of this study was to evaluate foot pumps as mechanical prophylaxis for deep vein thrombosis (DVT) following total knee replacement (TKR) in a Chinese population.MethodsAll consecutive patients following TKR during 2002–2006 received routine duplex ultrasound surveillance for DVT 9 days postoperatively. The demographic data and risk factors were recorded. No medication was given for DVT prophylaxis in all patients.ResultsWe evaluated 91 consecutive TKRs in 85 patients. Although 44 knee replacements (Group 1) done before December 2004 were not given foot pumps, 47 knee replacements (Group 2) done afterwards were given foot pumps. All patients were followed up for more than 6 months. DVT was detected in three cases (6.8%) in Group 1 compared with four knees (8.5%) in Group 2. Proximal thrombosis was observed in two knees (4.5%) in Group 1 compared with two knees (4.3%) in Group 2. No patient had pulmonary embolism. Six out of 59 (10.2%) patients who underwent the operations under general anaesthesia suffered from DVT, whereas one in 28 (3.6%) patients operated under spinal anaesthesia had DVT. All had no statistical significance.ConclusionThe rate of proximal DVT after TKR was low (4.5%) without pharmacological prophylaxis. We advise against the use of pharmacological prophylaxis in Chinese population for TKRs because of the low risk of proximal DVT and its possible bleeding complications. Foot pump did not lower the rate of DVTfurther, and its use for DVT prophylaxis in TKR is not necessary

An algorithm for decoherence analyses of lights through three-dimensional periodic microstructures

A transfer-matrix algorithm is presented herein as a beginning to study the transmission characteristics of coherent light through three-dimensional periodic microstructures, in which the structures are treated as two-dimensional-layer stacks and multiple reflections are considered negligible. The spatial-correlated noise is further introduced layer by layer to realize the actual decoherence of the light and allows for statistical investigation of the partial spatially coherent optics in transparent mediums. Numerical analyses show comparable results to the Gaussian Schell model in free-space cases, indicating the validity of the algorithms.Comment: 15 pages, 7 figure

Imaging findings in coronavirus infections : SARS-CoV, MERS-CoV, and SARS-CoV-2

During the first two decades of the 21st century, there have been three coronavirus infection outbreaks raising global health concerns by severe acute respiratory syndrome coronavirus (SARS-CoV), the Middle East respiratory syndrome coronavirus (MERS-CoV), and the SARS-CoV-2. Although the reported imaging findings of coronavirus infection are variable and non-specific, the most common initial chest radiograph (CXR) and CT findings are ground-glass opacities and consolidation with peripheral predominance and eventually spread to involve both lungs as the disease progresses. These findings can be explained by the immune pathogenesis of coronavirus infection causing diffuse alveolar damage. Although it is insensitive in mild or early coronavirus infection, the CXR remains as the first-line and the most commonly used imaging modality. That is because it is rapid and easily accessible and helpful for monitoring patient progress during treatment. CT is more sensitive to detect early parenchymal lung abnormalities and disease progression, and can provide an alternative diagnosis. In this pictorial review, various coronavirus infection cases are presented to provide imaging spectrums of coronavirus infection and present differences in imaging among them or from other viral infections, and to discuss the role of imaging in viral infection outbreaks

Effects of loading positions on the activation of trunk and hip muscles during flywheel and dumbbell single-leg Romanian deadlift exercises

Objective: The study compared the activities of the surface electromyography (sEMG) of trunk and hip muscles during single-leg Romanian deadlift (SLRDL) exercises using a flywheel and dumbbell with different loading positions (ipsilateral and contralateral).Method: Twelve active male subjects with at least 2 years of strength training experience (age: 26.7 ± 3.3 years; weight: 73.9 ± 6.2 kg) participated in this study. sEMG in the percentage of maximum voluntary isometric contraction of four SLRDL exercises (ipsilateral and contralateral loading position for dumbbell and flywheel) in a randomized order for superior gluteus maximus (SGM), inferior gluteus maximus (IGM), gluteus medius (GM), biceps femoris (BF), erector spinae (ES), external oblique (EO), and adductor longus (AL) were measured. One-way repeated measure ANOVA with Bonferroni adjustment (statistical significance at 0.05) and the non-clinical magnitude-based decision with a standardized difference were performed for statistical analysis.Results: The overall results demonstrated a very high level of SGM (105.4%–168.6%) and BF (69.6%–122.4%) muscle activities. A significant moderate increase of sEMG signals in GM, IGM, and ES (dominant side) and a large increase in SGM activity during concentric action when the loading position of flywheel SLRDL was changed from ipsilateral to the contralateral side. No significant difference was observed between flywheel and dumbbell SLRDL exercises.Conclusion: Strength coaches may adopt dumbbell or flywheel SLRDL exercises using the contralateral loading position to simultaneously strengthen the hip extensors and trunk stabilizers effectively

Responsiveness of the EuroQoL 5-Dimension (EQ-5D) questionnaire in patients with spondyloarthritis.

BACKGROUND: Spondyloarthritis (SpA) has a significant impact on patients' quality of life due to functional impairments. Generic health instruments like the EuroQoL 5-dimension (EQ-5D) is important for cost-utility analysis of health care interventions and calculation of quality-adjusted life-years. It has been validated in patients with SpA. However, its responsiveness property is unclear. Hence, the aim of study is to test the responsiveness properties of the EQ-5D health measure for Chinese patients with SpA. METHODS: Prospective and consecutive recruitment of 151 Chinese patients with SpA was conducted with follow-up assessments 6 months later. Demographic data including smoking and drinking habits, education level, income and occupation was collected. Disease-associated data including disease duration, presence of back pain, peripheral arthritis, dactylitis, enthesitis, uveitis, psoriasis, and inflammatory bowel disease was also recorded. Questionnaires regarding disease activity and functional disability (BASDAI, BASFI, BASGI, BASMI, ASDAS), mental health (HADS) and the EQ-5D scores were recorded. Responsiveness was tested against the global rating of change scale (GRC) and changes in disease activity using BASDAI and ASDAS-CRP. RESULTS: A total of 113 (74.8%) patients completed the follow-up assessments. Most patients (61.6%) had low disease activity level with BASDAI <4 and 39.7% of patients had inactive disease by ASDAS-CRP. EQ-5D scores was well discriminated along with BASDAI and BASFI scores. EQ-5D scores also correlated well with HADS. The GRC was not able to discriminate adequately. No significant ceiling or floor effect was observed. CONCLUSIONS: EQ-5D demonstrates satisfactory responsiveness property for assessment of changes in SpA disease activity. LEVEL OF EVIDENCE: II

Electrical Abnormalities in Dopaminergic Neurons of the Substantia Nigra in Mice With an Aromatic L-Amino Acid Decarboxylase Deficiency

Aromatic L-acid decarboxylase (AADC) deficiency causes severe motor disturbances in affected children. A putamen-targeted gene therapy improves the motor function of patients. The present study investigated the electrical properties of dopaminergic (DA) neurons in the substantia nigra compacta (SNc) of mice with an AADC deficiency (DdcKI). The basal firing of DA neurons, which determines DA release in the putamen, was abnormal in the DdcKI mice, including a low frequency and irregular firing pattern, because of a decrease in the after-hyperpolarization (AHP) amplitude of action potentials (APs). The frequency of spontaneous excitatory postsynaptic currents (sEPSCs) increased and that of spontaneous inhibitory PSCs (sIPSCs) decreased in the SNc DA neurons from the DdcKI mice, suggesting an elevation in glutamatergic excitatory stimuli and a reduction in GABAergic inhibitory stimuli, respectively. Altered expression patterns of genes encoding receptors and channels were also observed in the DdcKI mice. Administration of a widespread neuron-specific gene therapy to the brains of the DdcKI mice partially corrected these electric abnormalities. The overexcitability of SNc DA neurons in the presence of generalized dopamine deficiency likely underlies the occurrence of motor disturbances

Clinical Evaluation of Acupuncture as Treatment for Complications of Cerebrovascular Accidents: A Randomized, Sham-Controlled, Subject- and Assessor-Blind Trial

Background and Purpose. The effect of acupuncture as treatment for poststroke complications is questionable. We performed a randomized, sham-controlled double-blind study to investigate it. Methods. Patients with first-time acute stroke were randomized to receive 24 sessions of either real or sham acupuncture during an eight-week period. The primary outcome measure was change in National Institute of Health Stroke Scale (NIHSS) score. Secondary outcome measures included changes in Barthel Index (BI), Instrumental Activities of Daily Living (IADL), Hamilton Depression Rating Scale (HAM-D), and Visual Analogue Scale (VAS) for pain scores. Results. Of the 52 patients who were randomized to receive acupuncture (n=28) or placebo (n=24), 10 patients in the acupuncture group and 9 patients in the placebo group failed to complete the treatment. In total, 18 patients in the acupuncture group and 15 patients in the control group completed the treatment course. Reduction in pain was significantly greater in the acupuncture group than in the control group (p value = 0.04). There were no significant differences in the other measures between the two groups. Conclusions. Acupuncture provided more effective poststroke pain relief than sham acupuncture treatment. However, acupuncture had no better effect on neurological, functional, and psychological improvement