ABSTRACT
The dynamics of electron excitations associated with the initiation of laser-induced damage in hafnia and silica monolayer films are investigated using time-resolved damage testing involving a pair of 0.7 ps pulses with adjustable delay and laser pulse fluences. Results in hafnia indicate that the relaxation profile depends on the pump-pulse fluence (initial excitation), and as a result, it exhibits an effective lifetime that is variable. Analogous experiments in silica form two different types of damage morphologies that are observed on different ranges of delay times.
ABSTRACT
A sampling system for measuring emissions of nonvolatile particulate matter (nvPM) from aircraft gas turbine engines has been developed to replace the use of smoke number and is used for international regulatory purposes. This sampling system can be up to 35 m in length. The sampling system length in addition to the volatile particle remover (VPR) and other sampling system components lead to substantial particle losses, which are a function of the particle size distribution, ranging from 50 to 90% for particle number concentrations and 10-50% for particle mass concentrations. The particle size distribution is dependent on engine technology, operating point, and fuel composition. Any nvPM emissions measurement bias caused by the sampling system will lead to unrepresentative emissions measurements which limit the method as a universal metric. Hence, a method to estimate size dependent sampling system losses using the system parameters and the measured mass and number concentrations was also developed (SAE 2017; SAE 2019). An assessment of the particle losses in two principal components used in ARP6481 (SAE 2019) was conducted during the VAriable Response In Aircraft nvPM Testing (VARIAnT) 2 campaign. Measurements were made on the 25-meter sample line portion of the system using multiple, well characterized particle sizing instruments to obtain the penetration efficiencies. An agreement of ± 15% was obtained between the measured and the ARP6481 method penetrations for the 25-meter sample line portion of the system. Measurements of VPR penetration efficiency were also made to verify its performance for aviation nvPM number. The research also demonstrated the difficulty of making system loss measurements and substantiates the E-31 decision to predict rather than measure system losses.
ABSTRACT
The modifications of multilayer dielectric (MLD) gratings arising from laser-induced damage using 0.6-ps and 10-ps laser pulses at 1053 nm are investigated to better understand the damage-initiation mechanisms. Upon damage initiation, sections of the affected grating pillars are removed, thereby erasing the signature of the underlying mechanisms of laser damage. To address this issue, we performed paired studies using macroscopic grating-like features that are 5 mm in width to reveal the laser-damage morphology of the different grating sections: pillar side wall, sole, and pillar top. The results suggest that, similarly to MLD coatings, there are two damage-initiation mechanisms corresponding to the different pulse durations.
ABSTRACT
Owing to their relatively high resistance to laser-induced damage, hafnia and silica are commonly used in multilayered optical coatings in high-power laser facilities as high- and low-refractive-index materials, respectively. Here, we quantify the laser-induced-damage threshold (LIDT) at 1053 nm in the short-pulse regime of hafnia and silica monolayers deposited by different fabrication methods, including electron-beam evaporation, plasma ion-assisted deposition and ion-assisted deposition. The results demonstrate that nominally identical coatings fabricated by different deposition techniques and/or vendors can exhibit significantly different damage thresholds. A correlation of the LIDT performance of each material with its corresponding absorption edge is investigated. Our analysis indicates a weak correlation between intrinsic LIDT and the optical gap of each material (Tauc gap) but a much better correlation when considering the spectral characteristics in the Urbach tail spectral range. Spectrophotometry and photothermal absorption were used to provide evidence of the correlation between the strength of the red-shifted absorption tail and reduced LIDT at 1053 nm.
ABSTRACT
The propagation of 355-nm, nanosecond pulses in absorbing glasses is investigated for the specific case examples of the broadband absorbing glass SuperGrey and the Ce3+-doped silica glass. The study involves different laser irradiation conditions and material characterization methods to capture the transient material behaviors leading to laser-induced damage. Two damage-initiation mechanisms were identified: (1) melting of the surface as a result of increased temperature; and (2) self-focusing caused by a transient change in the index of refraction. Population of excited states greatly affects both mechanisms by increasing the transient absorption cross section via excited-state absorption and introducing a change of the refractive index to support the formation of graded-index lensing and self-focusing of the beam inside the material. The governing damage-initiation mechanism depends on the thermodynamic properties of the host glass, the electronic structure characteristics of the doped ion, and the laser-spot size.
ABSTRACT
BACKGROUND: Alemtuzumab administration is known to cause secondary autoimmune disease but has not been associated with the development of neurologic autoimmune conditions. Lambert-Eaton myasthenic syndrome (LEMS) is caused by autoantibodies directed against calcium channels on the neuromuscular junction. CASE REPORT: We report a case of a patient with relapsing-remitting multiple sclerosis (RRMS) treated with alemtuzumab who develop generalized weakness initially attributed to progression of MS but eventually determined to be due to LEMS. CONCLUSION: Alemtuzumab treatment can result in the development of neurologic autoimmune conditions that could mimic MS progression.
Subject(s)
Alemtuzumab/adverse effects , Immunologic Factors/adverse effects , Lambert-Eaton Myasthenic Syndrome/chemically induced , Multiple Sclerosis, Relapsing-Remitting/drug therapy , Humans , Male , Middle AgedABSTRACT
Hafnium oxide thin films with varying oxygen content were investigated with the goal of finding the optical signature of oxygen vacancies in the film structure. It was found that a reduction of oxygen content in the film leads to changes in both, structural and optical characteristics. Optical absorption spectroscopy, using nanoKelvin calorimetry, revealed an enhanced absorption in the near-ultraviolet (near-UV) and visible wavelength ranges for films with reduced oxygen content, which was attributed to mid-gap electronic states of oxygen vacancies. Absorption in the near-infrared was found to originate from structural defects other than oxygen vacancy. Luminescence generated by continuous-wave 355-nm laser excitation in e-beam films showed significant changes in the spectral profile with oxygen reduction and new band formation linked to oxygen vacancies. The luminescence from oxygen-vacancy states was found to have microsecond-scale lifetimes when compared with nanosecond-scale lifetimes of luminescence attributed to other structural film defects. Laser-damage testing using ultraviolet nanosecond and infrared femtosecond pulses showed a reduction of the damage threshold with increasing number of oxygen vacancies in hafnium oxide films.
ABSTRACT
Changes in muscle fascicle mechanics have been postulated to underpin the repeated bout effect (RBE) observed following exercise-induced muscle damage (EIMD). However, in the medial gastrocnemius (MG), mixed evidence exists on whether fascicle stretch amplitude influences the level of EIMD, thus questioning whether changes in fascicle mechanics underpin the RBE. An alternative hypothesis is that neural adaptations contribute to the RBE in this muscle. The aim of this study was to investigate the neuromechanical adaptations during and after repeated bouts of a highly controlled muscle lengthening exercise that aimed to maximize EIMD in MG. In all, 20 subjects performed two bouts of 500 active lengthening contractions (70% of maximal activation) of the triceps surae, separated by 7 days. Ultrasound constructed fascicle length-torque (L-T) curves of MG, surface electromyography (EMG), maximum torque production, and muscle soreness were assessed before, 2 hours and 2 days after each exercise bout. The drop in maximum torque (4%) and the increase in muscle soreness (24%) following the repeated bout were significantly less than following the initial bout (8% and 59%, respectively), indicating a RBE. However, neither shift in the L-T curve nor changes in EMG parameters were present. Furthermore, muscle properties during the exercise were not related to the EIMD or RBE. Our results show that there are no global changes in gastrocnemius mechanical behavior or neural activation that could explain the observed RBE in this muscle. We suggest that adaptations in the non-contractile elements of the muscle are likely to explain the RBE in the triceps surae.
Subject(s)
Adaptation, Physiological , Exercise/physiology , Muscle Contraction , Muscle, Skeletal/physiology , Adult , Biomechanical Phenomena , Electromyography , Female , Humans , Male , Myalgia , Torque , Ultrasonography , Young AdultABSTRACT
Preliminary evidence suggests that postoperative cognitive dysfunction (POCD) is common after lung transplantation. The impact of POCD on clinical outcomes has yet to be studied. The association between POCD and longer-term survival was therefore examined in a pilot study of posttransplantation survivors. Forty-nine participants from a prior randomized clinical trial underwent a neurocognitive assessment battery pretransplantation and 6 months posttransplantation, including assessments of the domains of Executive Function (Trail Making Test, Stroop, Digit Span), Processing Speed (Ruff 2 and 7 Test, Digit Symbol Substitution Test), and Verbal Memory (Verbal Paired Associates, Logical Memory, Animal Naming, and Controlled Oral Word Association Test). During a 13-year follow-up, 33 (67%) participants died. Greater neurocognition was associated with longer survival (hazard ratio [HR] = 0.49 [0.25-0.96], P = .039), and this association was strongest on tests assessing Processing Speed (HR = 0.58 [0.36-0.95], P = .03) and Executive Function (HR = 0.52 [0.28-0.97], P = .040). In addition, unadjusted analyses suggested an association between greater Memory performance and lower risk of CLAD (HR = 0.54 [0.29-1.00], P = .050). Declines in Executive Function tended to be predictive of worse survival. These preliminary findings suggest that postoperative neurocognition is predictive of subsequent mortality among lung transplant recipients. Further research is needed to confirm these findings in a larger sample and to examine mechanisms responsible for this relationship.
Subject(s)
Cognition Disorders/mortality , Graft Rejection/mortality , Lung Transplantation/adverse effects , Postoperative Complications , Quality of Life , Cognition Disorders/etiology , Female , Follow-Up Studies , Graft Rejection/etiology , Graft Survival , Humans , Male , Middle Aged , Neuropsychological Tests , Pilot Projects , Prognosis , Risk Factors , Survival RateABSTRACT
The purpose of this investigation was to determine whether the magnitude of adaptation to integrated ballistic training is influenced by initial strength level. Such information is needed to inform resistance training guidelines for both higher- and lower-level athlete populations. To this end, two groups of distinctly different strength levels (stronger: one-repetition-maximum (1RM) squat = 2.01 ± 0.15 kg·BM-1 ; weaker: 1.20 ± 0.20 kg·BM-1 ) completed 10 weeks of resistance training incorporating weightlifting derivatives, plyometric actions, and ballistic exercises. Testing occurred at pre-, mid-, and post-training. Measures included variables derived from the incremental-load jump squat and the 1RM squat, alongside muscle activity (electromyography), and jump mechanics (force-time comparisons throughout the entire movement). The primary outcome variable was peak velocity derived from the unloaded jump squat. It was revealed that the stronger group displayed a greater (P = .05) change in peak velocity at mid-test (baseline: 2.65 ± 0.10 m/s, mid-test: 2.80 ± 0.17 m/s) but not post-test (2.85 ± 0.18 m/s) when compared to the weaker participants (baseline 2.43 ± 0.09, mid-test. 2.47 ± 0.11, post-test: 2.61 ± 0.10 m/s). Different changes occurred between groups in the force-velocity relationship (P = .001-.04) and jump mechanics (P ≤ .05), while only the stronger group displayed increases in muscle activation (P = .05). In conclusion, the magnitude of improvement in peak velocity was significantly influenced by pre-existing strength level in the early stage of training. Changes in the mechanisms underpinning performance were less distinct.
Subject(s)
Adaptation, Physiological , Athletic Performance/physiology , Muscle, Skeletal/physiology , Resistance Training/methods , Weight Lifting/physiology , Electromyography , Humans , MaleABSTRACT
AIM: To determine the accuracy of the susceptible vessel sign (SVS) in the detection of arterial occlusion and its clinical implication in acute ischaemic stroke. MATERIALS AND METHODS: Consecutive ischaemic stroke patients who underwent magnetic resonance imaging (MRI) with susceptibility-weighted imaging (SWI) within 24 hours of symptom onset or time last-seen-well were included. Two independent neuroradiologists reviewed the SWI for evidence of the SVS. Admission stroke severity was determined by the National Institute of Health Stroke Scale (NIHSS) scores, and poor clinical outcome was defined by a 3-months modified Rankin scale (mRS) score >2. RESULTS: The SVS was identified in 26 (12%) of 213 patients with substantial inter-reviewer agreement. The SVS had 99% specificity, 88% negative predictive value (NPV), 51% sensitivity, and 92% positive predictive value (PPV) for detection of acute arterial occlusions. In consecutive stroke patients, the presence of SVS was associated with higher admission NIHSS scores (median 9 versus 3, p<0.001), arterial occlusion (92% versus 12%, p<0.001), larger infarct volume (162±180 ml versus 25±48 ml, p=0.001), and higher rate of poor clinical outcome at 3-months follow-up (58% versus 25%, p=0.001). In the subset of patients with acute arterial occlusion (n=47), the SVS was associated with higher admission NIHSS scores (median of 10 versus 3, p=0.038) and larger infarct volumes (173±184 ml versus 76±112 ml, p=0.034). CONCLUSIONS: The SVS is a highly specific sign of occlusive arterial thrombus, and is associated with larger infarct volume and more severe presentation in a series of consecutive stroke patients, as well as in the subgroup of patients with acute arterial occlusion.
Subject(s)
Intracranial Thrombosis/diagnostic imaging , Intracranial Thrombosis/epidemiology , Magnetic Resonance Angiography/statistics & numerical data , Stroke/diagnostic imaging , Stroke/epidemiology , Comorbidity , Disease Susceptibility/diagnostic imaging , Disease Susceptibility/epidemiology , Female , Humans , Incidence , Magnetic Resonance Angiography/methods , Male , Middle Aged , Minnesota/epidemiology , Prognosis , Reproducibility of Results , Risk Factors , Sensitivity and SpecificityABSTRACT
BACKGROUND AND PURPOSE: Recent studies demonstrated superiority of CTP to NCCT/CTA at detecting lacunar infarcts. This study aimed to assess CTP's capability to identify lacunae in different intracranial regions. MATERIALS AND METHODS: Over 5.5 years, 1085 CTP examinations were retrospectively reviewed in patients with acute stroke symptoms with CTP within 12 hours and MRI within 7 days of symptom onset. Patients had infarcts ≤2 cm or no acute infarct on DWI; patients with concomitant infarcts >2 cm on DWI were excluded. CTP postprocessing was automated by a delay-corrected algorithm. Three blinded reviewers were given patient NIHSS scores and symptoms; infarcts were recorded based on NCCT/CTA, CTP (CBF, CBV, MTT, and TTP), and DWI. RESULTS: One hundred thirteen patients met inclusion criteria (53.1% female). On DWI, lacunar infarcts were present in 37 of 113 (32.7%), and absent in 76 of 113 (67.3%). On CTP, lacunar infarcts typically appeared as abnormalities larger than infarct size on DWI. Interobserver κ for CTP ranged from 0.38 (CBF) (P < .0001) to 0.66 (TTP) (P < .0001); interobserver κ for DWI was 0.88 (P < 0.0001). In all intracranial regions, sensitivity of CTP ranged from 18.9% (CBV) to 48.7% (TTP); specificity ranged from 97.4% (CBF and TTP) to 98.7% (CBV and MTT). CTP's sensitivity was highest in the subcortical white matter with or without cortical involvement (21.7%-65.2%) followed by periventricular white matter (12.5%-37.5%); sensitivity in the thalami or basal ganglia was 0%. CONCLUSIONS: CTP has low sensitivity and high specificity in identifying lacunar infarcts. Sensitivity is highest in the subcortical white matter with or without cortical involvement, but limited in the basal ganglia and thalami.
Subject(s)
Neuroimaging/methods , Stroke, Lacunar/diagnostic imaging , Adult , Aged , Computed Tomography Angiography/methods , Diffusion Magnetic Resonance Imaging/methods , Female , Humans , Male , Middle Aged , Perfusion Imaging/methods , Retrospective Studies , Sensitivity and Specificity , Stroke, Lacunar/pathology , Tomography, X-Ray Computed/methodsABSTRACT
Diabetes is a chronic disease that results from the body's inability to properly control circulating blood glucose levels. The loss of glucose homoeostasis can arise from a loss of ß-cell mass because of immune-cell-mediated attack, as in type 1 diabetes, and/or from dysfunction of individual ß-cells (in conjunction with target organ insulin resistance), as in type 2 diabetes. A better understanding of the transcriptional pathways regulating islet-cell survival is of great importance for the development of therapeutic strategies that target ß-cells for diabetes. To this end, we previously identified the transcription factor Myt3 as a pro-survival factor in islets following acute suppression of Myt3 in vitro. To determine the effects of Myt3 suppression on islet-cell survival in vivo, we used an adenovirus to express an shRNA targeting Myt3 in syngeneic optimal and marginal mass islet transplants, and demonstrate that suppression of Myt3 impairs the function of marginal mass grafts. Analysis of grafts 5 weeks post-transplant revealed that grafts transduced with the shMyt3 adenovirus contained ~20% the number of transduced cells as grafts transduced with a control adenovirus. In fact, increased apoptosis and significant cell loss in the shMyt3-transduced grafts was evident after only 5 days, suggesting that Myt3 suppression sensitizes islet cells to stresses present in the early post-transplant period. Specifically, we find that Myt3 suppression sensitizes islet cells to high glucose-induced cell death via upregulation of the pro-apoptotic Bcl2 family member Bim. Taken together these data suggest that Myt3 may be an important link between glucotoxic and immune signalling pathways.
Subject(s)
Bcl-2-Like Protein 11/genetics , Diabetes Mellitus, Experimental/genetics , Glucose/toxicity , Insulin-Secreting Cells/metabolism , Islets of Langerhans Transplantation , Transcription Factors/genetics , Adenoviridae/genetics , Adenoviridae/metabolism , Animals , Bcl-2-Like Protein 11/agonists , Bcl-2-Like Protein 11/metabolism , Cell Death/drug effects , Diabetes Mellitus, Experimental/chemically induced , Diabetes Mellitus, Experimental/mortality , Diabetes Mellitus, Experimental/therapy , Female , Gene Expression Regulation , Glucose/metabolism , Glucose Tolerance Test , Insulin-Secreting Cells/cytology , Insulin-Secreting Cells/drug effects , Mice , Mice, Inbred C57BL , Primary Cell Culture , RNA, Small Interfering/genetics , RNA, Small Interfering/metabolism , Signal Transduction , Streptozocin , Survival Analysis , Transcription Factors/antagonists & inhibitors , Transcription Factors/metabolism , Transplantation, IsogeneicABSTRACT
Lung transplantation has become an increasingly common treatment for patients with end-stage lung disease. Few studies have examined psychosocial risk factors for mortality in transplant recipients, despite evidence suggesting that elevated levels of negative affect are associated with greater mortality following major cardiac surgery. We therefore examined the relationship between negative affect early after lung transplantation and long-term survival in a sample of 132 lung transplant recipients (28 cystic fibrosis, 64 chronic obstructive pulmonary disease, 26 idiopathic pulmonary fibrosis, 14 other) followed for up to 13.5 years (median 7.4 years) following transplantation. Patients underwent both medical and psychosocial assessments 6 months following transplantation, which included the Beck Depression Inventory-II (BDI-II), Spielberger Anxiety Inventory, and General Health Questionnaire (GHQ). Over the course of follow-up, 80 (61%) participants died. Controlling for demographic factors, native lung disease, disease severity, family income, education level, social support, and frequency of posttransplant rejection, elevated symptoms of depression (BDI-II: HR = 1.31, p = 0.011) and distress (GHQ: HR = 1.28, p = 0.003) were associated with increased mortality. Higher levels of depression and general distress, but not anxiety, measured 6 months following lung transplantation are associated with increased mortality, independent of background characteristics and medical predictors.
Subject(s)
Anxiety/mortality , Depressive Disorder, Major/mortality , Lung Transplantation/psychology , Postoperative Complications , Transplant Recipients/psychology , Anxiety/diagnosis , Anxiety/psychology , Depressive Disorder, Major/diagnosis , Depressive Disorder, Major/psychology , Female , Follow-Up Studies , Graft Rejection , Graft Survival , Humans , Lung Transplantation/adverse effects , Lung Transplantation/mortality , Male , Middle Aged , Prognosis , Risk FactorsABSTRACT
Extensive muscle damage can be induced in isolated muscle preparations by performing a small number of stretches during muscle activation. While typically these fiber strains are large and occur over long lengths, the extent of exercise-induced muscle damage (EIMD) observed in humans is normally less even when multiple high-force lengthening actions are performed. This apparent discrepancy may be due to differences in muscle fiber and tendon dynamics in vivo; however, muscle and tendon strains have not been quantified during muscle-damaging exercise in humans. Ultrasound and an infrared motion analysis system were used to measure medial gastrocnemius fascicle length and lower limb kinematics while humans walked backward, downhill for 1 h (inducing muscle damage), and while they walked briefly forward on the flat (inducing no damage). Supramaximal tibial nerve stimulation, ultrasound, and an isokinetic dynamometer were used to quantify the fascicle length-torque relationship pre- and 2 h postexercise. Torque decreased ~23%, and optimal fascicle length shifted rightward ~10%, indicating that EIMD occurred during the damage protocol even though medial gastrocnemius fascicle stretch amplitude was relatively small (~18% of optimal fascicle length) and occurred predominantly within the ascending limb and plateau region of the length-torque curve. Furthermore, tendon contribution to overall muscle-tendon unit stretch was ~91%. The data suggest the compliant tendon plays a role in attenuating muscle fascicle strain during backward walking in humans, thus minimizing the extent of EIMD. As such, in situ or in vitro mechanisms of muscle damage may not be applicable to EIMD of the human gastrocnemius muscle.
Subject(s)
Gait/physiology , Muscle Contraction/physiology , Muscle Strength/physiology , Muscle, Skeletal/diagnostic imaging , Muscle, Skeletal/physiology , Physical Conditioning, Human/methods , Walking/physiology , Adult , Humans , Male , Muscle, Skeletal/injuries , Physical Conditioning, Human/adverse effects , Physical Exertion/physiology , UltrasonographyABSTRACT
Autophagy is a lysosomal degradation pathway important for cellular homeostasis, mammalian development, cancer and immunity. Many molecular components of autophagy have been identified, but little is known about regulatory mechanisms controlling their effector functions. Here, we show that, in contrast to other p38 MAP kinase activators, the growth arrest and DNA damage 45 beta (Gadd45ß)-MAPK/ERK kinase kinase 4 (MEKK4) pathway specifically directs p38 to autophagosomes. This process results in an accumulation of autophagosomes through p38-mediated inhibition of lysosome fusion. Conversely, autophagic flux is increased in p38-deficient fibroblasts and Gadd45ß-deficient cells. We further identified the underlying mechanism and demonstrate that phosphorylation of the autophagy regulator autophagy-related (Atg)5 at threonine 75 through p38 is responsible for inhibition of starvation-induced autophagy. Thus, we show for the first time that Atg5 activity is controlled by phosphorylation and, moreover, that the spatial regulation of p38 by Gadd45ß/MEKK4 negatively regulates the autophagic process.
Subject(s)
Antigens, Differentiation/metabolism , Autophagy , MAP Kinase Kinase Kinase 4/metabolism , Microtubule-Associated Proteins/metabolism , p38 Mitogen-Activated Protein Kinases/metabolism , Animals , Antigens, Differentiation/genetics , Autophagy/drug effects , Autophagy-Related Protein 5 , Cell Line , Lipopolysaccharides/toxicity , Mice , Microtubule-Associated Proteins/genetics , Mutagenesis, Site-Directed , NIH 3T3 Cells , Phosphorylation , RNA Interference , RNA, Small Interfering/metabolism , Signal Transduction , p38 Mitogen-Activated Protein Kinases/antagonists & inhibitors , p38 Mitogen-Activated Protein Kinases/geneticsABSTRACT
AIMS/HYPOTHESIS: The paucity of information on the epigenetic barriers that are blocking reprogramming protocols, and on what makes a beta cell unique, has hampered efforts to develop novel beta cell sources. Here, we aimed to identify enhancers in pancreatic islets, to understand their developmental ontologies, and to identify enhancers unique to islets to increase our understanding of islet-specific gene expression. METHODS: We combined H3K4me1-based nucleosome predictions with pancreatic and duodenal homeobox 1 (PDX1), neurogenic differentiation 1 (NEUROD1), v-Maf musculoaponeurotic fibrosarcoma oncogene family, protein A (MAFA) and forkhead box A2 (FOXA2) occupancy data to identify enhancers in mouse islets. RESULTS: We identified 22,223 putative enhancer loci in in vivo mouse islets. Our validation experiments suggest that nearly half of these loci are active in regulating islet gene expression, with the remaining regions probably poised for activity. We showed that these loci have at least nine developmental ontologies, and that islet enhancers predominately acquire H3K4me1 during differentiation. We next discriminated 1,799 enhancers unique to islets and showed that these islet-specific enhancers have reduced association with annotated genes, and identified a subset that are instead associated with novel islet-specific long non-coding RNAs (lncRNAs). CONCLUSIONS/INTERPRETATIONS: Our results indicate that genes with islet-specific expression and function tend to have enhancers devoid of histone methylation marks or, less often, that are bivalent or repressed, in embryonic stem cells and liver. Further, we identify a subset of enhancers unique to islets that are associated with novel islet-specific genes and lncRNAs. We anticipate that these data will facilitate the development of novel sources of functional beta cell mass.
Subject(s)
Islets of Langerhans/metabolism , Animals , Basic Helix-Loop-Helix Transcription Factors/metabolism , Chromatin Immunoprecipitation , Enhancer Elements, Genetic/genetics , Hepatocyte Nuclear Factor 3-beta/metabolism , Homeodomain Proteins/metabolism , Mice , Nerve Tissue Proteins/metabolism , Trans-Activators/metabolismABSTRACT
Human length-tension curves are traditionally constructed using a model that assumes passive tension does not change during contraction (model A) even though the animal literature suggests that passive tension can decrease (model B). The study's aims were threefold: 1) measure differences in human medial gastrocnemius length-tension curves using model A vs. model B, 2) test the reliability of ultrasound constructed length-tension curves, and 3) test the robustness of fascicle length-generated length-tension curves to variations between the angle and fascicle length relationship. An isokinetic dynamometer manipulated and measured ankle angle while ultrasound was used to measure medial gastrocnemius fascicle length. Supramaximal tibial nerve stimulation was used to evoke resting muscle twitches. Length-tension curves were constructed using model A {angle-torque [A-T((A))], length-torque [L-T((A))]} or model B {length-torque [L-T((B))]} in three conditions: baseline, heel-lift (where the muscle was shortened at each angle), and baseline repeated 2 h later (+2 h). Length-tension curves constructed from model B differed from those produced via model A, indicated by a significant increase in maximum torque (≈23%) when using L-T((B)) vs. L-T((A)). No parameter measured was different between baseline and +2 h for any method, indicating good reliability when using ultrasound. Length-tension curves were unaffected by the heel-lift condition when using L-T((A)) or L-T((B)) but were affected when using A-T((A)). Since the muscle model used significantly alters human length-tension curves, and given animal data indicate model B to be more accurate when passive tension is present, we recommend that model B should be used when constructing medial gastrocnemius length-tension curves in humans in vivo.
Subject(s)
Muscle, Skeletal/physiology , Tibial Nerve/physiology , Adult , Ankle/physiology , Elasticity/physiology , Electric Stimulation , Female , Humans , Male , Models, Biological , Muscle Contraction/physiology , Muscle, Skeletal/diagnostic imaging , Reproducibility of Results , Tendons/physiology , Torque , Ultrasonography , Young AdultABSTRACT
Although neurocognitive impairment is relatively common among patients with advanced lung disease, little is known regarding changes in neurocognition following lung transplantation. We therefore administered 10 tests of neurocognitive functioning before and 6 months following lung transplantation and sought to identify predictors of change. Among the 49 study participants, native diseases included chronic obstructive pulmonary disease (n = 22), cystic fibrosis (n = 12), nonfibrotic diseases (n = 11) and other (n = 4). Although composite measures of executive function and verbal memory scores were generally within normal limits both before and after lung transplantation, verbal memory performance was slightly better posttransplant compared to baseline (p < 0.0001). Executive function scores improved in younger patients but worsened in older patients (p = 0.03). A minority subset of patients (29%) exhibited significant cognitive decline (i.e. >1 standard deviations on at least 20% of tests) from baseline to posttransplant. Patients who declined were older (p < 0.004) and tended to be less educated (p = 0.07). Lung transplantation, like cardiac revascularization procedures, appears to be associated with cognitive decline in a subset of older patients, which could impact daily functioning posttransplant.