Subclinical Photoreceptor Disruption in Response to Severe Head Trauma

Commotio retinae is a transient opacification of the retina due to outer retinal disruption occurring in a contrecoup fashion after blunt trauma.Histological studies in animals and humans after ocular blunt trauma have revealed that disruption occurs at the level of the photoreceptor outer segments and retinal pigment epithelium.Recent reports using optical coherence tomography (OCT) have shown detectable disruption at the level of the photoreceptor inner segment/outer segment junction and retinal pigment epithelium and that these changes may be reversible over time with restoration of normal outer retinal architecture.However, the resolution of existing OCT technology may not be sensitive enough to detect photoreceptor disruption. Adaptive optics (AO) imaging systems enable cellular-resolution imaging of the human retina, and there is a growing number of cases where deficits have been visible on AO images but not on OCT. Herein, we report a case of subclinical photoreceptor disruption after head trauma as seen by an AO scanning ophthalmoscope (AOSO) but not apparent clinically or on spectral-domain OCT (SD-OCT)

Study of localization in the quantum sawtooth map emulated on a quantum information processor

Quantum computers will be unique tools for understanding complex quantum systems. We report an experimental implementation of a sensitive, quantum coherence-dependent localization phenomenon on a quantum information processor (QIP). The localization effect was studied by emulating the dynamics of the quantum sawtooth map in the perturbative regime on a three-qubit QIP. Our results show that the width of the probability distribution in momentum space remained essentially unchanged with successive iterations of the sawtooth map, a result that is consistent with localization. The height of the peak relative to the baseline of the probability distribution did change, a result that is consistent with our QIP being an ensemble of quantum systems with a distribution of errors over the ensemble. We further show that the previously measured distributions of control errors correctly account for the observed changes in the probability distribution.Comment: 20 pages, 9 figure

Robust Control of Quantum Information

Errors in the control of quantum systems may be classified as unitary, decoherent and incoherent. Unitary errors are systematic, and result in a density matrix that differs from the desired one by a unitary operation. Decoherent errors correspond to general completely positive superoperators, and can only be corrected using methods such as quantum error correction. Incoherent errors can also be described, on average, by completely positive superoperators, but can nevertheless be corrected by the application of a locally unitary operation that ``refocuses'' them. They are due to reproducible spatial or temporal variations in the system's Hamiltonian, so that information on the variations is encoded in the system's spatiotemporal state and can be used to correct them. In this paper liquid-state nuclear magnetic resonance (NMR) is used to demonstrate that such refocusing effects can be built directly into the control fields, where the incoherence arises from spatial inhomogeneities in the quantizing static magnetic field as well as the radio-frequency control fields themselves. Using perturbation theory, it is further shown that the eigenvalue spectrum of the completely positive superoperator exhibits a characteristic spread that contains information on the Hamiltonians' underlying distribution.Comment: 14 pages, 6 figure

Peaks in the Cosmic Microwave Background: flat versus open models

We present properties of the peaks (maxima) of the CMB anisotropies expected in flat and open CDM models. We obtain analytical expressions of several topological descriptors: mean number of maxima and the probability distribution of the gaussian curvature and the eccentricity of the peaks. These quantities are calculated as functions of the radiation power spectrum, assuming a gaussian distribution of temperature anisotropies. We present results for angular resolutions ranging from 5' to 20' (antenna FWHM), scales that are relevant for the MAP and COBRAS/SAMBA space missions and the ground-based interferometer experiments. Our analysis also includes the effects of noise. We find that the number of peaks can discriminate between standard CDM models, and that the gaussian curvature distribution provides a useful test for these various models, whereas the eccentricity distribution can not distinguish between them.Comment: 13 pages latex file using aasms4.sty + 3 tables + 2 postscript figures, to appear in ApJ (March 1997

Mutation signature analysis identifies increased mutation caused by tobacco smoke associated DNA adducts in larynx squamous cell carcinoma compared with oral cavity and oropharynx.

Squamous cell carcinomas of the head and neck (HNSCC) arise from mucosal keratinocytes of the upper aero-digestive tract. Despite a common cell of origin and similar driver-gene mutations which divert cell fate from differentiation to proliferation, HNSCC are considered a heterogeneous group of tumors categorized by site of origin within the aero-digestive mucosa, and the presence or absence of HPV infection. Tobacco use is a major driver of carcinogenesis in HNSCC and is a poor prognosticator that has previously been associated with poor immune cell infiltration and higher mutation numbers. Here, we study patterns of mutations in HNSCC that are derived from the specific nucleotide changes and their surrounding nucleotide context (also known as mutation signatures). We identify that mutations linked to DNA adducts associated with tobacco smoke exposure are predominantly found in the larynx. Presence of this class of mutation, termed COSMIC signature 4, is responsible for the increased burden of mutation in this anatomical sub-site. In addition, we show that another mutation pattern, COSMIC signature 5, is positively associated with age in HNSCC from non-smokers and that larynx SCC from non-smokers have a greater number of signature 5 mutations compared with other HNSCC sub-sites. Immunohistochemistry demonstrates a significantly lower Ki-67 proliferation index in size matched larynx SCC compared with oral cavity SCC and oropharynx SCC. Collectively, these observations support a model where larynx SCC are characterized by slower growth and increased susceptibility to mutations from tobacco carcinogen DNA adducts

Application of scaled nucleation theory to metallic vapor condensation

In this paper we report that scaled nucleation theory (SNT) can describe moderately well the observed nucleation behavior of a significant number of refractory materials if a more appropriate value of a quantity commonly referred to as the excess surface entropy is used. With the availability of more reliable critical point and liquid property data, we are better able to calculate this quantity and we find that for refractory materials it can be as small as one half to one third the quantity traditionally used in its approximation. As a result of using more accurate values, we find considerably better agreement between SNT and experiment than what was originally determined. We also explain why using surface tension slope information to determine the excess surface entropy can lead to substantial errors in the SNT supersaturation prediction

Prevalence of Abnormal Systemic Hemodynamics in Veterans with and without Spinal Cord Injury

Advances in the clinical management of patients with acute and chronic spinal cord injury (SCI) have contributed to extended life expectancies; however longevity in those with SCI remains below that of the general population.(1) Reduced longevity in the SCI population has been attributed to increased incidence of age-associated chronic illnesses,(2) premature cardiovascular aging,(3) and increased prevalence of heart disease, stroke (4) and diabetes mellitus, (5) compared to the general population. In fact, cardiovascular disease (CVD) is now a leading cause of morbidity and mortality in the SCI population, which may be amplified due to increased risk factors such as inactivity, chronic inflammation, and impairment in autonomic cardiovascular control.(6) The American Spinal Injury Association (ASIA) impairment scale (AIS) is used to document remaining motor and sensory function following SCI; (7, 8) however, the degree of autonomic nervous system impairment is not considered within this classification schema.(9, 10) That said, impaired autonomic control of the cardiovascular system after SCI results in measurable changes in heart rate (HR) and blood pressure (BP) that loosely reflect the level and completeness of SCI documented using the AIS classification, (11, 12) but may also reflect orthostatic positioning.(6, 12, 13) The impact of these changes in HR and BP on cardiovascular health and longevity is not fully appreciated in the SCI population; however, prior to identifying the consequences of these cardiovascular abnormalities, prevalence rates of HR and BP values which fall outside the expected normal range should be documented. The International Standards to Document Autonomic Function (post-SCI) initially established guidelines for the assessment of HR and BP abnormalities in 2009, (10) which was updated in 2012, but the thresholds remained consistent. (14) Specifically, bradycardia is defined as a HR ≤ 60 beats/minute (bpm) and tachycardia as a HR ≥ 100 bpm. (14) Hypotension is defined as a systolic BP (SBP) ≤ 90 mmHg and a diastolic BP (DBP) ≤ 60 mmHg; hypertension is SBP ≥ 140 and/or DBP ≥ 90 mmHg. (14) While these definitions comply with standards established in the non-SCI population, due to decentralized cardiovascular control, they may not be appropriate for use in the SCI population. In addition, relatively recent evidence has emerged which associates adverse outcomes in the general population using other HR (15, 16) and BP (17-21) thresholds. Beyond the clinical consequences of alterations in HR and BP, persons with SCI may experience loss of independence and life quality related to the inability to adequately maintain cardiovascular homeostasis; however, until we gain a better understanding of the prevalence of these abnormalities, the development and testing of effective treatment strategies will not be a priority. Therefore, the goal of this investigation was to assess HR and BP in veterans with (SCI) and without SCI (non SCI). Similar to a recent report, (6) we hypothesized that level of SCI (i.e., the higher the lesion level the greater the prevalence of abnormal HR and BP recordings) and orthostatic positioning (i.e., increased prevalence of abnormal HR and BP recordings in the seated versus the supine position) would influence the prevalence of HR and BP abnormalities. In addition, we hypothesized that the prevalence of comorbid cardiovascular medical conditions, current smoking status, age and use of prescription anti-hypertensive (anti-HTN) medications would influence the prevalence of HR and BP abnormalities in veterans with and without SCI

The Cstf2t Polyadenylation Gene Plays a Sex-Specific Role in Learning Behaviors in Mice

Polyadenylation is an essential mechanism for the processing of mRNA 30 ends. CstF-64 (the 64,000 Mr subunit of the cleavage stimulation factor; gene symbol Cstf2) is an RNAbinding protein that regulates mRNA polyadenylation site usage. We discovered a paralogous form of CstF-64 called τCstF-64 (Cstf2t). The Cstf2t gene is conserved in all eutherian mammals including mice and humans, but the τCstF-64 protein is expressed only in a subset of mammalian tissues, mostly testis and brain. Male mice that lack Cstf2t (Cstf2t-/- mice) experience disruption of spermatogenesis and are infertile, although female fertility is unaffected. However, a role for τCstF-64 in the brain has not yet been determined. Given the importance of RNA polyadenylation and splicing in neuronal gene expression, we chose to test the hypothesis that τCstF-64 is important for brain function. Male and female 185-day old wild type and Cstf2t-/- mice were examined for motor function, general activity, learning, and memory using rotarod, open field activity, 8-arm radial arm maze, and Morris water maze tasks. Male wild type and Cstf2t-/- mice did not show differences in learning and memory. However, female Cstf2t-/- mice showed significantly better retention of learned maze tasks than did female wild type mice. These results suggest that τCstf-64 is important in memory function in female mice. Interestingly, male Cstf2t-/- mice displayed less thigmotactic behavior than did wild type mice, suggesting that Cstf2t may play a role in anxiety in males. Taken together, our studies highlight the importance of mRNA processing in cognition and behavior as well as their established functions in reproduction

TP53-inducible Glycolysis and Apoptosis Regulator (TIGAR) Metabolically Reprograms Carcinoma and Stromal Cells in Breast Cancer.

A subgroup of breast cancers has several metabolic compartments. The mechanisms by which metabolic compartmentalization develop in tumors are poorly characterized. TP53 inducible glycolysis and apoptosis regulator (TIGAR) is a bisphosphatase that reduces glycolysis and is highly expressed in carcinoma cells in the majority of human breast cancers. Hence we set out to determine the effects of TIGAR expression on breast carcinoma and fibroblast glycolytic phenotype and tumor growth. The overexpression of this bisphosphatase in carcinoma cells induces expression of enzymes and transporters involved in the catabolism of lactate and glutamine. Carcinoma cells overexpressing TIGAR have higher oxygen consumption rates and ATP levels when exposed to glutamine, lactate, or the combination of glutamine and lactate. Coculture of TIGAR overexpressing carcinoma cells and fibroblasts compared with control cocultures induce more pronounced glycolytic differences between carcinoma and fibroblast cells. Carcinoma cells overexpressing TIGAR have reduced glucose uptake and lactate production. Conversely, fibroblasts in coculture with TIGAR overexpressing carcinoma cells induce HIF (hypoxia-inducible factor) activation with increased glucose uptake, increased 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase-3 (PFKFB3), and lactate dehydrogenase-A expression. We also studied the effect of this enzyme on tumor growth. TIGAR overexpression in carcinoma cells increases tumor growth in vivo with increased proliferation rates. However, a catalytically inactive variant of TIGAR did not induce tumor growth. Therefore, TIGAR expression in breast carcinoma cells promotes metabolic compartmentalization and tumor growth with a mitochondrial metabolic phenotype with lactate and glutamine catabolism. Targeting TIGAR warrants consideration as a potential therapy for breast cancer