Neural abnormalities underlying tinnitus and hyperacusis

Thesis (Ph. D.)--Harvard-MIT Division of Health Sciences and Technology, 2011.Cataloged from PDF version of thesis.Includes bibliographical references (p. 83-90).Tinnitus, the ongoing perception of sound in the absence of a physical stimulus, and hyperacusis, the intolerance of sound intensities considered comfortable by most people, are two often co-occurring clinical conditions lacking effective treatments. This thesis identified neural correlates of these poorly understood disorders using functional magnetic resonance imaging (fMRI) and auditory brainstem responses (ABRs) to measure sound-evoked activity in the auditory pathway. Subjects with clinically normal hearing thresholds, with and without tinnitus, underwent fMRI or ABR testing and behavioral assessment of sound-level tolerance (SLT). The auditory midbrain, thalamus, and primary auditory cortex (PAC) showed elevated fMRI activation related to reduced SLT (i.e. hyperacusis). PAC, but not midbrain or thalamus, showed elevated fMRI activation related to tinnitus, perhaps reflecting undue attention to the auditory domain. In contrast to fMRI activation, ABRs showed relationships only to tinnitus, not SLT. Wave I of the ABR, which reflects auditory nerve activity, was reduced in tinnitus subjects, while wave V, reflecting input activity to the midbrain, was elevated. Wave I reduction in tinnitus subjects suggests that auditory nerve dysfunction apparent only above threshold is a factor in tinnitus. Because ABRs reflect activity in only one of multiple pathways from cochlear nucleus to midbrain, the wave V elevation implicates this particular pathway in tinnitus. The results directly link tinnitus and hyperacusis to hyperactivity within the central auditory system. Because fMRI and ABRs reflect different aspects of neural activity, the dependence of fMRI activation on SLT and ABR activity on tinnitus in the midbrain raises the possibility that tinnitus and hyperacusis arise in parallel from abnormal activity in separate brainstem pathways.by Jianwen Wendy Gu.Ph.D

The regulation of angular momentum during human walking

Thesis (S.B.)--Massachusetts Institute of Technology, Dept. of Physics, 2003.Includes bibliographical references (p. 47-48).The conservation of angular momentum provides an elegant model for human walking and might be used to generate stable robotic locomotion if employed by a control algorithm. To examine the extent to which the body regulates angular momentum, a force model was developed to predict horizontal ground reaction forces assuming perfect angular momentum conservation. These model forces closely matched experimental forces, suggesting that the body does indeed regulate angular momentum. To determine how various links of the body contribute to total angular momentum, link angular momenta were calculated. Angular momenta in the medial-lateral and vertical directions showed evident cancellation of link angular momenta whereas angular momentum in the anterior-posterior direction did not. Link by link, angular momentum in the medial-lateral direction was much larger than angular momenta in the anterior-posterior and vertical directions, which makes it more likely to cause stability problems. Hence, angular momentum in the medial-lateral direction is the key angular momentum to regulate.by Jianwen Wendy Gu.S.B

Col11a2 Deletion Reveals the Molecular Basis for Tectorial Membrane Mechanical Anisotropy

The tectorial membrane (TM) has a significantly larger stiffness in the radial direction than other directions, a prominent mechanical anisotropy that is believed to be critical for the proper functioning of the cochlea. To determine the molecular basis of this anisotropy, we measured material properties of TMs from mice with a targeted deletion of Col11a2, which encodes for collagen XI. In light micrographs, the density of TM radial collagen fibers was lower in Col11a2 –/– mice than wild-types. Tone-evoked distortion product otoacoustic emission and auditory brainstem response measurements in Col11a2 –/– mice were reduced by 30–50 dB independent of frequency as compared with wild-types, showing that the sensitivity loss is cochlear in origin. Stress-strain measurements made using osmotic pressure revealed no significant dependence of TM bulk compressibility on the presence of collagen XI. Charge measurements made by placing the TM as an electrical conduit between two baths revealed no change in the density of charge affixed to the TM matrix in Col11a2 –/– mice. Measurements of mechanical shear impedance revealed a 5.5 ± 0.8 dB decrease in radial shear impedance and a 3.3 ± 0.3 dB decrease in longitudinal shear impedance resulting from the Col11a2 deletion. The ratio of radial to longitudinal shear impedance fell from 1.8 ± 0.7 for TMs from wild-type mice to 1.0 ± 0.1 for those from Col11a2 –/– mice. These results show that the organization of collagen into radial fibrils is responsible for the mechanical anisotropy of the TM. This anisotropy can be attributed to increased mechanical coupling provided by the collagen fibrils. Mechanisms by which changes in TM material properties may contribute to the threshold elevation in Col11a2 –/– mice are discussed.National Institutes of Health (U.S.) (Grant R01-DC00238

Predictive value of MRI-detected extramural vascular invasion in stage T3 rectal cancer patients before neoadjuvant chemoradiation

PURPOSE:We set out to explore the probability of MRI-detected extramural vascular invasion (mr-EMVI) before chemoradiation to predict responses to chemoradiation and survival in stage T3 rectal cancer patients. METHODS:A total of 100 patients with T3 rectal cancer who underwent MRI examination and received neoadjuvant chemoradiation and surgery were enrolled. The correlation between mr-EMVI and other clinical factors were analyzed by chi-square. Logistic regression model was performed to select the potential factors influencing tumor responses to neoadjuvant chemoradiation. A Cox proportional hazards regression model was performed to explore potential predictors of survival.RESULTS:The positive mr-EMVI result was more likely to be present in patients with a higher T3 subgroup (T3a+b = 7.1% vs. T3c+d = 90.1%, P < 0.001) and more likely in patients with mesorectal fascia involvement than in those without MRF (65% vs. 38.8%, P = 0.034). Compared with mr-EMVI (+) patients, more mr-EMVI (-) patients showed a good response (staged ≤ ypT2N0) (odds ratio [OR], 3.020; 95% confidence interval [CI], 1.071–8.517; P = 0.037). In univariate analysis, mr-EMVI (+) (hazard ratio [HR], 5.374; 95% CI, 1.210–23.872; P = 0.027) and lower rectal cancers (HR, 3.326; 95% CI, 1.135–9.743; P = 0.028) were significantly associated with decreased disease-free survival. A positive mr-EMVI status (HR, 5.727; 95% CI, 1.286–25.594; P = 0.022) and lower rectal cancers (HR, 3.137; 95% CI, 1.127–8.729; P = 0.029) also served as prognostic factors related to decreased disease-free survival in multivariate analysis.CONCLUSION:The mr-EMVI status before chemoradiation is a significant prognostic factor and could be used for identifying T3 rectal cancer patients who might benefit from neoadjuvant chemoradiation

FREPA: An Automated and Formal Approach to Requirement Modeling and Analysis in Aircraft Control Domain

Formal methods are promising for modeling and analyzing system requirements. However, applying formal methods to large-scale industrial projects is a remaining challenge. The industrial engineers are suffering from the lack of automated engineering methodologies to effectively conduct precise requirement models, and rigorously validate and verify (V&V) the generated models. To tackle this challenge, in this paper, we present a systematic engineering approach, named Formal Requirement Engineering Platform in Aircraft (FREPA), for formal requirement modeling and V\&V in the aerospace and aviation control domains. FREPA is an outcome of the seamless collaboration between the academy and industry over the last eight years. The main contributions of this paper include 1) an automated and systematic engineering approach FREPA to construct requirement models, validate and verify systems in the aerospace and aviation control domain, 2) a domain-specific modeling language AASRDL to describe the formal specification, and 3) a practical FREPA-based tool AeroReq which has been used by our industry partners. We have successfully adopted FREPA to seven real aerospace gesture control and two aviation engine control systems. The experimental results show that FREPA and the corresponding tool AeroReq significantly facilitate formal modeling and V&V in the industry. Moreover, we also discuss the experiences and lessons gained from using FREPA in aerospace and aviation projects.Comment: 12 pages, Published by FSE 202

Absence of metallicity and bias-dependent resistivity in low-carrier-density EuCd2As2

EuCd2As2 was theoretically predicted to be a minimal model of Weyl semimetals with a single pair of Weyl points in the ferromagnet state. However, the heavily p-doped EuCd2As2 crystals in previous experiments prevent direct identification of the semimetal hypothesis. Here we present a comprehensive magneto-transport study of high-quality EuCd2As2 crystals with ultralow bulk carrier density (10^13 cm-3). In contrast to the general expectation of a Weyl semimetal phase, EuCd2As2 shows insulating behavior in both antiferromagnetic and ferromagnetic states as well as surface-dominated conduction from band bending. Moreover, the application of a dc bias current can dramatically modulate the resistance by over one order of magnitude, and induce a periodic resistance oscillation due to the geometric resonance. Such nonlinear transport results from the highly nonequilibrium state induced by electrical field near the band edge. Our results suggest an insulating phase in EuCd2As2 and put a strong constraint on the underlying mechanism of anomalous transport properties in this system.Comment: 13 pages, 4 figure

MDM: A Mode Diagram Modeling Framework

Periodic control systems used in spacecrafts and automotives are usually period-driven and can be decomposed into different modes with each mode representing a system state observed from outside. Such systems may also involve intensive computing in their modes. Despite the fact that such control systems are widely used in the above-mentioned safety-critical embedded domains, there is lack of domain-specific formal modelling languages for such systems in the relevant industry. To address this problem, we propose a formal visual modeling framework called mode diagram as a concise and precise way to specify and analyze such systems. To capture the temporal properties of periodic control systems, we provide, along with mode diagram, a property specification language based on interval logic for the description of concrete temporal requirements the engineers are concerned with. The statistical model checking technique can then be used to verify the mode diagram models against desired properties. To demonstrate the viability of our approach, we have applied our modelling framework to some real life case studies from industry and helped detect two design defects for some spacecraft control systems.Comment: In Proceedings FTSCS 2012, arXiv:1212.657

Proteomics analysis of serum protein profiling in pancreatic cancer patients by DIGE: up-regulation of mannose-binding lectin 2 and myosin light chain kinase 2

<p>Abstract</p> <p>Background</p> <p>Pancreatic cancer has significant morbidity and mortality worldwide. Good prognosis relies on an early diagnosis. The purpose of this study was to develop techniques for identifying cancer biomarkers in the serum of patients with pancreatic cancer.</p> <p>Methods</p> <p>Serum samples from five individuals with pancreatic cancer and five individuals without cancer were compared. Highly abundant serum proteins were depleted by immuno-affinity column. Differential protein analysis was performed using 2-dimensional differential in-gel electrophoresis (2D-DIGE).</p> <p>Results</p> <p>Among these protein spots, we found that 16 protein spots were differently expressed between the two mixtures; 8 of these were up-regulated and 8 were down-regulated in cancer. Mass spectrometry and database searching allowed the identification of the proteins corresponding to the gel spots. Up-regulation of mannose-binding lectin 2 and myosin light chain kinase 2, which have not previously been implicated in pancreatic cancer, were observed. In an independent series of serum samples from 16 patients with pancreatic cancer and 16 non-cancer-bearing controls, increased levels of mannose-binding lectin 2 and myosin light chain kinase 2 were confirmed by western blot.</p> <p>Conclusions</p> <p>These results suggest that affinity column enrichment and DIGE can be used to identify proteins differentially expressed in serum from pancreatic cancer patients. These two proteins 'mannose-binding lectin 2 and myosin light chain kinase 2' might be potential biomarkers for the diagnosis of the pancreatic cancer.</p

The ALMA-QUARKS survey: -- I. Survey description and data reduction

This paper presents an overview of the QUARKS survey, which stands for `Querying Underlying mechanisms of massive star formation with ALMA-Resolved gas Kinematics and Structures'. The QUARKS survey is observing 139 massive clumps covered by 156 pointings at ALMA Band 6 ($\lambda\sim$ 1.3 mm). In conjunction with data obtained from the ALMA-ATOMS survey at Band 3 ($\lambda\sim$ 3 mm), QUARKS aims to carry out an unbiased statistical investigation of massive star formation process within protoclusters down to a scale of 1000 au. This overview paper describes the observations and data reduction of the QUARKS survey, and gives a first look at an exemplar source, the mini-starburst Sgr B2(M). The wide-bandwidth (7.5 GHz) and high-angular-resolution (~0.3 arcsec) observations of the QUARKS survey allow to resolve much more compact cores than could be done by the ATOMS survey, and to detect previously unrevealed fainter filamentary structures. The spectral windows cover transitions of species including CO, SO, N$_2$D$^+$, SiO, H$_{30}\alpha$, H$_2$CO, CH$_3$CN and many other complex organic molecules, tracing gas components with different temperatures and spatial extents. QUARKS aims to deepen our understanding of several scientific topics of massive star formation, such as the mass transport within protoclusters by (hub-)filamentary structures, the existence of massive starless cores, the physical and chemical properties of dense cores within protoclusters, and the feedback from already formed high-mass young protostars.Comment: 9 figures, 4 tables, accepted by RA