Miracle-dz/UniFAR-FTUs huggingface dataset:
Analysis of Auditory Evoked Responses Elicited by Gaps in Noise

of a dissertation at the University of Miami. Dissertation supervised by Professor Ozcan Ozdamar. No. of pages in text. (142) Psychophysical detection of gaps embedded in ongoing sounds is commonly used to measure temporal resolution in hearing tests. Cortical auditory responses to such gaps in noise are investigated as electrophysiological assessment of temporal resolution. This study was conducted to investigate the characteristics of auditory evoked potentials (AEPs) to gaps in broadband noise. Transient responses such as Auditory Brainstem (ABR), Middle Latency (MLR) and Late latency (LLR) were recorded as well as 40Hz Auditory Steady-State Responses (ASSR) and Quasi ASSR generated by jittered 40Hz gaps. Gaps of short and long durations were presented at different rates to study the effect of rate and duration on AEPs. Also, the influence of gap onset/offset on the transient evoked responses was examined. AEPs were elicited at four rates 0.5, 1, 5, and 40Hz. 0.5Hz responses showed cortical waves while 1 Hz responses showed ABR, MLR and LLR components. 40 and 5 Hz responses were characterized by ABR and MLR components with no LLRs likely. For short gaps, results suggest that amplitudes of MLR, LLR and QASSR were affected by gap duration; as the duration decreases the amplitudes diminish. For long gaps, two distinct onset and offset responses were observed. Waveform changes as the gap shortens from 300ms to 6ms suggest overlap of the onset and offset responses resulting in different AEP morphologies.
Epidermal fatty acid binding protein prevents chemical-induced skin tumorigenesis by regulation of TPA-induced IFN/p53/SOX2 pathway in keratinocytes

Skin lipids (e.g. fatty acids) are essential for normal skin functions. Epidermal fatty acid-binding protein (E-FABP) is the predominant FABP expressed in skin epidermis. However, the role of EFABP in skin homeostasis and pathology remains largely unknown. Herein, we utilized the 7,12dimethylbenz(a)anthracene (DMBA) and 12-O-tetradecanolyphorbol-13-acetate (TPA)-induced skin tumorigenesis model to assess the role of E-FABP in chemical-induced skin tumorigenesis. Compared to their wild type (WT) littermates, mice deficient in E-FABP, but not adipose FABP (A-FABP), developed more skin tumors with higher incidence. TPA functioning as a tumor promoter induced E-FABP expression and initiated extensive flaring inflammation in skin. Interestingly, TPA-induced production of IFNβ and IFNλ in the skin tissue was dependent on EFABP expression. Further protein and gene expression arrays demonstrated that E-FABP was critical in enhancing IFN-induced p53 responses and in suppressing SOX2 expression in keratinocytes. Thus, E-FABP expression in skin suppresses chemical-induced skin tumorigenesis through regulation of IFN/p53/SOX2 pathway. Collectively, our data suggest an unknown function of E-FABP in prevention of skin tumor development and offer E-FABP as a therapeutic target for improving skin innate immunity in chemical-induced skin tumor prevention. To whom correspondence should be ed: Bing Li, Department of Microbiology and Immunology, University of Louisville, 505 South Hancock Street, Louisville, KY, 40202. Telephone: 502-852-2678. Fax: 502-852-7531. b.li@louisville.edu. #These authors contributed equally to this work Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Disclosure of Potential Conflicts of Interest The authors state no conflict of interest. HHS Public Access Author manuscript J Invest Dermatol. Author manuscript; available in PMC 2019 September 01. Published in final edited form as: J Invest Dermatol. 2018 September ; 138(9): 1925–1934. doi:10.1016/j.jid. 2018.02. 041. A uhor M anscript
GPCRs as potential therapeutic targets in preeclampsia

Preeclampsia is an important obstetric complication that arises in 5% of women after the 20 th week of gestation, for which there is no specific therapy and no cure. Although much of the recent investigation in this field has focused on soluble forms of the angiogenic membrane receptor tyrosine kinase Flt1 and the transforming growth factor β co-receptor Endoglin, there is significant clinical potential for several GPCR targets and their agonists or antagonists in preeclampsia. In this review, we discuss several of the most promising candidates in this category, including calcitonin receptor-like receptor / receptor activity modifying protein 1 complexes, the angiotensin AT1, 2 and Mas receptors, and the relaxin receptor RXFP1. We also address some of the controversies surrounding the roles and therapeutic potential of these GPCRs and their (ant)agonists in preeclampsia.
The effect of a novel amplitude/phase binning algorithm on commercial 4DCT quality

Purpose— Respiratory motion is a significant source of anatomic uncertainty in radiotherapy treatment planning, and may result in errors of portal size and subsequent radiation dose. While 4DCT allows for more accurate analysis of the respiratory cycle, breathing irregularities during data acquisition may cause considerable image distortions. The aim of this study was to examine the impact of respiratory irregularities on 4DCT imaging, and to evaluate a novel image reconstruction algorithm based upon percentile-based tagging of the respiratory cycle. Materials/Methods— Respiratory correlated helical CT was acquired on 11 consecutive patients. Inspiration and expiration datasets were reconstructed using the default phase based method as well as a novel respiration percentile based method using patient specific metrics to define ranges of the reconstruction. Image output was analyzed in a blinded fashion for both the phase and percentile based reconstructions to determine the prevalence and severity of image artifacts. Results— The percentile-based algorithm resulted in a significant reduction in artifact severity compared to the phase-based algorithm, although overall artifact prevalence did not differ between the two algorithms. The magnitude of differences in respiratory tag placement between the phase and percentile based algorithms was correlated with the presence of image artifacts. Conclusions— We conclude that our novel 4DCT reconstruction method may be useful to detect clinically relevant image distortions that may otherwise go unnoticed, and to reduce image distortion associated with some respiratory irregularities. Further work is necessary to assess the clinical impact on areas of possible irregular breathing.
Chapter 8. Tea and Cancer Prevention: Epidemiological Studies

Experimental studies have consistently shown the inhibitory activities of tea extracts on tumorigenesis in multiple model systems. Epidemiologic studies, however, have produced inconclusive results in humans. A comprehensive review was conducted to assess the current knowledge on tea consumption and risk of cancers in humans. In general, consumption of black tea was not associated with lower risk of cancer. High intake of green tea was consistently associated with reduced risk of upper gastrointestinal tract cancers after sufficient control for confounders. Limited data support a protective effect of green tea on lung and hepatocellular carcinogenesis. Although observational studies do not support a beneficial role of tea intake on prostate cancer risk, phase II clinical trials have demonstrated an inhibitory effect of green tea extract against the progression of prostate pre-malignant lesions. Green tea may exert beneficial effects against mammary carcinogenesis in premenopausal women and recurrence of breast cancer. There is no sufficient evidence that supports a protective role of tea intake on the development of cancers of the colorectum, pancreas, urinary tract, glioma, lymphoma, and leukemia. Future prospective observational studies with biomarkers of exposure and phase III clinical trials are required to provide definitive evidence for the hypothesized beneficial effect of tea consumption on cancer formation in humans.
LIGAND MODULATION OF GPCR LATERAL SEGREGATION INTO LIPID MICRODOMAINS IN SPHINGOMYELIN/ PHOSPHATIDYLCHOLINE SOLID-SUPPORTED BILAYERS

Increasing evidence supports the idea that the plasma membrane bilayer is characterized by a laterally inhomogeneous mixture of lipids, having an organized structure in which lipid molecules segregate into small domains or patches. Such microdomains are characterized by high contents of sphingolipids that form thicker liquid-ordered regions having resistance to extraction with nonionic detergents. The existence of lipid lateral segregation has been demonstrated in both model and biological membranes, although its role in protein sorting and membrane function still remains unclear. In the present studies, plasmon-waveguide resonance (PWR) spectroscopy was employed to investigate the properties of microdomains in a model system consisting of a solid-supported lipid bilayer composed of a 1:1 mixture of palmitoyloleoylphosphatidylcholine (POPC) and brain sphingomyelin (SM), and their influence on the partitioning and functioning of the human delta opioid receptor (hDOR; a G-protein coupled receptor, GPCR). Resonance signals corresponding to two microdomains (POPC-rich and SM-rich) were observed in such bilayers, and the sorting of the receptor into each domain was highly dependent on the type of ligand that was bound. When no ligand was bound, the receptor incorporated preferentially into the POPC-rich domain; when an agonist or an antagonist was bound, the receptor incorporated preferentially into the SM-rich component, although with a two-fold greater propensity for this microdomain in the case of the agonist. G-protein binding to the agonist-bound receptor in the SM-rich domain occurred with a 30-fold higher affinity than to the receptor in the PC-rich domain. The binding of agonist to an unliganded receptor in the bilayer produced receptor trafficking from the PC-rich into the SM-rich component. Since the SM-rich domain is thicker than the PC-rich domain, and previous studies with the hDOR have shown that the receptor elongates upon agonist-activation, we propose that hydrophobic matching between the receptor and the lipid is a driving force for receptor trafficking to the SM-rich component.
INFLUENCE OF NON-COMPLIANCE WITH RADIATION THERAPY PROTOCOL GUIDELINES AND OPERATIVE BED RECURRENCES FOR CHILDREN WITH RHABDOMYOSARCOMA AND MICROSCOPIC RESIDUAL DISEASE: A REPORT FROM THE CHILDREN’S ONCOLOGY GROUP

Purpose— Post-operative radiation therapy (RT) is recommended for patients with rhabdomyosarcoma (RMS) having microscopic disease. Sometimes RT dose/volume is reduced or omitted in an attempt to avoid late effects, particularly in young children. We reviewed operative bed recurrences to determine if non-compliance with RT protocol guidelines, influenced localregional control. Methods— All operative bed recurrences among 695 Group II RMS patients on IRS I-IV were reviewed for deviation from RT protocol. Major/minor dose deviation was defined as > 10% or 6– 10% of the prescribed dose (40–60 Gy), respectively. Major/minor volume deviation was defined as tumor excluded from the RT field or treatment volume not covered by the specified margin (pre-operative tumor volume and 2–5 cm margin), respectively. No RT was a major deviation. Results— Forty-six of 83 (55%) patients with operative bed recurrences did not receive the intended RT (39 major and 7 minor deviations). RT omission was the most frequent RT protocol deviation (19/46 – 41%), followed by dose (17/46 – 37%), volume (9/46 – 20%), dose and volume deviation (1/46 – 2%). Only 7 operative bed recurrences occurred on IRS IV (5% local-regional failure) with only 3 RT protocol deviations. 63 (76%) patients with a recurrence died of disease despite retrieval therapy, including 13 of 19 non-irradiated children. Conclusion— Over half the operative bed recurrences were associated with non-compliance; omission of RT was the most common protocol deviation. Three-fourths of children die when local-regional disease is not controlled, emphasizing the importance of RT in Group II RMS.
Transposable elements in response to environmental stressors &

Transposable elements (TEs) comprise a group of repetitive sequences that bring positive, negative, as well as neutral effects to the host organism. Earlier considered as “junk DNA,” TEs are now well-accepted driving forces of evolution and critical regulators the of expression of genetic information. Their activity is regulated by epigenetic mechanisms, including methylation of DNA and histone modifications. The loss of epigenetic control over TEs, exhibited as loss of DNA methylation and decondensation of the chromatin structure, may result in TEs reactivation, initiation of their insertional mutagenesis (retrotransposition) and has been reported in numerous human diseases, including cancer. Accumulating evidence suggests that these alterations are not the simple consequences of the disease, but often may drive the pathogenesis, as they can be detected early during disease development. Knowledge derived from the in vitro, in vivo , and epidemiological studies, clearly demonstrates that exposure to ubiquitous environmental stressors, many of which are carcinogens or suspected carcinogens, are capable of causing alterations in methylation and expression of TEs and initiate retrotransposition events. Evidence summarized in this review suggests that TEs are the sensitive endpoints for detection of effects caused by such environmental stressors, as ionizing radiation (terrestrial, space, be detected early during disease development and even shortly after exposure to a given environmental stressor. These findings suggest that TEs may potentially be introduced into safety and risk assessment and serve as biomarkers of exposure to environmental stressors, as well as surrogate biomarkers in clinic and possible targets for therapeutic modalities for disease treatment and prevention.
Post-Traumatic Stress Disorder, Neighborhood Residency and Satisfaction, and Social Network Characteristics among Underserved Women in Baltimore, MD 1

Background— Post-traumatic stress disorder (PTSD) prevalence is high, but not well-understood, among women living in urban, impoverished areas. While previous studies have established social support as an important factor in PTSD development and maintenance, little is known about how perceptions of neighborhood are linked to PTSD. This study examined the the between and health behaviors. research explores networks among populations at risk for HIV/ STIs. She has also developed, tested, and disseminated HIV prevention interventions into the community. and community-driven stated preference methods, health, and disadvantaged approaches qualitative and quantitative methods, including social network analysis. relationship between PTSD and social network and neighborhood factors among women with a low socioeconomic status. Basic procedures— We analyzed cross-sectional data collected from an HIV/STI peer network study in Baltimore, Maryland (n=438). We used bivariate analyses to examine the associations between PTSD and social network characteristics and time in neighborhood and satisfaction. We then constructed multivariable regression models that controlled for with PTSD: homelessness, cocaine/heroin use, and unemployment. Main finding— Overall, 30% of women had PTSD symptom severity consistent with a clinical diagnosis. In the multivariable model, dissatisfaction with neighborhood block (OR=1.80, p=0.03) and living in one’s neighborhood >5 years (OR=1.69, p=0.03) were associated with PTSD. Social network factors that were significantly associated with PTSD included a higher number of network members in conflict with the participant (OR=1.28, p=0.02), presence of a network member who would let the participant stay with them (OR=0.4, p=0.004), and the number of network members with whom the participant socialized (OR=0.6, p=0.04). Principal conclusions— In this sample of impoverished urban women with a high prevalence of PTSD, duration of residency, satisfaction with neighborhood, and network characteristics were found to be strongly associated with PTSD symptom severity.
Seizures and MRI brain injury in newborns cooled for hypoxic ischemic encephalopathy

Objective— To describe the association between electrographic seizures and brain injury judged from magnetic resonance imaging (MRI) in newborns treated with hypothermia. Study design— 56 newborns treated with hypothermia were monitored using video-EEG through cooling and rewarming, and imaged at a median of 5 days. EEGs were reviewed for seizures and status epilepticus. Moderate-severe injury on MRI was measured using a classification similar to one predicting abnormal outcome in an analogous population. Results— Seizures were recorded in 17 newborns, five withstatus epilepticus. Moderate-severe injury was more common in newborns with seizures (RR 2.9; 95%CI 1.2-4.5; P=0.02), and present in all with status epilepticus. Children with moderate-severe injury had seizures that were multifocal, later onset, and more likely to have ongoing seizures following 20mg/kg phenobarbital. Newborns with only subclinical seizures were as likely to have injury as compared with those whose seizures had a clinical correlate (57% vs. 60%). Conclusions— Seizures remain a risk factor for brain injury in the setting of therapeutic hypothermia, especially in neonates with status epilepticus, multifocal onset seizures, and need for multiple medications.However, 40% were spared from brain injury, suggesting that the outcome following seizures is not uniformly poor in children treated with therapeutic hypothermia.
Nitric Oxide Signaling Is Disrupted in the Yeast Model for Batten Disease □ D

The juvenile form of neuronal ceroid lipofuscinoses (JNCLs), or Batten disease, results from mutations in the CLN3 gene, and it is characterized by the accumulation of lipopigments in the lysosomes of several cell types and by extensive neuronal death. We report that the yeast model for JNCL ( btn1- (cid:1) ) that lacks BTN1 , the homologue to human CLN3, has increased resistance to menadione-generated oxidative stress. Expression of human CLN3 complemented the btn1- (cid:1) phenotype, and equivalent Btn1p/Cln3 mutations correlated with JNCL severity. We show that the previously reported decreased levels of L -arginine in btn1- (cid:1) limit the synthesis of nitric oxide ( (cid:2) NO) in both physiological and oxidative stress conditions. This defect in (cid:2) NO synthesis seems to suppress the signaling required for yeast menadione-induced apoptosis, thus explaining btn1- (cid:1) phenotype of increased resistance. We propose that in JNCL, a limited capacity to synthesize (cid:2)
Expression of Tumor Necrosis Factor-a and Its mRNA in the Endometrial Mucosa During the Menstrual Cycle

Endometrial biopsies, collected at various phases of the menstrual cycle, were examined for the presence of tumor necrosis factor- a (TNF- a) by histochemistry, and TNF-a mRNA by in situ hybridization and Northern blotting. During the proliferativephase, TNF- a and TNF- a mRNA were not detected or were at low levels. During the secretory phase, the TNF-a mRNA level was in-creased and observed in the wall of coiled arteries. TNF-a was detected both in the wall of the coiled arteries and, in highest concentration, within the epithelial cells. In regard to the capac-ity of TNF-a to induce a hemorrhagic necrosis in various tissues, this study suggests that an overproduction of TNF-a within the small arteries of the endometrial mucosa might be responsiblefor menstruation. (Am J Pathol 1993, 143:480-486) Tumor necrosis activated
Two- Ph a se Flow and Pressure Drop

Two-phase flow experiments were performed with air/water mixtures in a small rectangular channel measuring 9.52 x 1.59 mm (aspect ratio equal to 6), for application to compact heat exchangers. Pressure drop and flow pattern definition data were obtained over a large range of mass qualities (0.0002 to 1) and, in the case of flow pattern data, a large range of mass fluxes (50 to 2,0000 kg/m2s). A flow pattern map, based on visual observations and photographs of the flow patterns, is presented and compared with a map developed for a rectangular channel of the same aspect ratio but with dimensions twice those of the test channel, and with a map developed for a circular tube with the same hydraulic diameter of 3 mm. Pressure drop data are presented as a function of both mass quality and Martinelli parameter and are compared with state-of-the-art correlations and a modified Chisholm correlation.
r-VKORC1 expression in factor IX BHK cells increases factor IX carboxylation but is limited by saturation of another carboxylation component or by a shift in the rate limiting step†

Carboxylation of vitamin K-dependent (VKD) proteins is required for their activity and depends upon reduced vitamin K generated by vitamin K oxidoreductase (VKOR) and a redox protein that regenerates VKOR activity. VKD protein carboxylation is inefficient in mammalian cells, and to understand why carboxylation becomes saturated we developed an approach that directly measures intracellular VKD protein carboxylation. Analysis of factor IX (fIX)-expressing BHK cells indicated that slow fIX egress from the endoplasmic reticulum and preferential secretion of the carboxylated form contribute to secreted fIX being more fully-carboxylated. The analysis also revealed the first reported in vivo VKD protein turnover, which was 14-fold faster than occurs in vitro, suggesting facilitation of this process in vivo. r-VKORC1 expression increased the rate of fIX carboxylation and extent of carboxylated fIX ~2-fold, which shows that carboxylation is the rate-limiting step in fIX turnover and which was surprising because turnover in vitro is limited by release of carboxylated fIX. Interestingly, the increases were significantly less than the amount of VKOR overexpression (15-fold). However, when cell extracts were tested in single turnover experiments in vitro, where redox protein is functionally substituted by dithiothreitol, VKOR overexpression increased the fIX carboxylation rate 14-fold, showing r-VKORC1 is functional for supporting fIX carboxylation. These data indicate that the effect of VKOR overexpression is limited in vivo, possibly because a carboxylation component like the redox protein becomes saturated or because another step is now rate-limiting. The studies illustrate the complexity of carboxylation and potential importance of component stoichiometry to overall efficiency.
Involute Gear Tooth Stresses Analysis Using Finite Element Modeling

The bending and surface stresses of gear tooth are major factor for failure of gear. Pitting is a surface fatigue failure due to repetitions of high contact stresses. This paper presented analysis of bending and contact stresses of involute teeth of spur gear in meshing. The involute profile of spur gear has been modeled and the simulation is carried out for analysis of stresses and deformation. 2D and 3D models are simulated. The tooth involute is designed from which the tooth is extruded to form the 3D models of spur gear. The simulation is done by finite element software package ANSYS Workbench 16.2. These stresses are also estimated using AGMA bending and contact stresses equations for comparison. The results show that the 2D model is more accurate than the 3D. Care must be taken when selecting the type of contact condition since the results are very sensitive to it. Also it is found that the elastic modulus of the material is greatly affecting the contact stresses. Poor accuracy is achieved for the bending stresses while the contact stress shows very accurate results.