bluuebunny/crossref_metadata_2025 huggingface dataset:
The role of nitric oxide synthase neurons in dorsal raphe nucleus stress circuitry
Authors:   , Vasudeva Rani Katherine , Waterhouse Barry D.
Published: July 2024

Anxiety afflicts approximately 20% of the US adult population, making it a prevalent disorder in our society. The serotonergic (5HT) dorsal raphe nucleus (DRN) has been implicated in this illness, and treatments targeting this system and brain structure typically alleviate anxiety symptoms. The DRN also contains neurons which produce a number of other transmitters, including nitric oxide. Cells expressing nitric oxide synthase (NOS) have a unique topographical relationship with 5HT cells of the DRN and contribute to the stress response of the rat, yet have not been extensively characterized. Our general hypothesis is that NOS neurons specifically located in the DRN lateral wing subregion constitute a unique contingent of cells that contribute to the stress response. Anatomical, pharmacological, and electrophysiological properties of NOS cells within the DRN lateral wing region were investigated in the rat. This group of neurons was found to project to brain regions involved in sensory processing, emotional regulation, and arousal/feeding behaviors. In addition, NOS lateral wing cells express the 5HT1A receptor and co-localize the neurotransmitter acetylcholine, associating them with the adjacent lateral dorsal tegmental nucleus (LDT) and not the DRN. Electrophysiological profiling of this group of NOS cells revealed distinguishing features compared to both the midline and rostral lateral wing DRN subregions. These properties were consistent with those expressed by NOS neurons of the LDT. Preliminary investigations of this DRN lateral wing/LDT group of NOS cells in the waking rat suggests a correlation between restraint stress and their pattern of discharge, further implicating a role for these cells during the stress response. Overall, our results indicate that NOS cells within the DRN lateral wing have connections to limbic brain regions, possess functional 5HT1A receptors, and co-localize acetylcholine. Previous studies and preliminary results from these studies indicate activation of this group of neurons as part of the stress response. Further examination into the role of this cell group during acute and chronic stressor exposure may provide insight into the mechanisms of current anxiety treatments and may lead to new targets for the management of this disorder.
Differential expression and regulation of lipooligosaccharide specific sialyltransferase in pathogenic neisseria
Authors:   , Packiam Mathanraj , Rest Richard F
Published: July 2024

Transfer of sialic acid onto the lipooligosaccharide (LOS) of Neisseria gonorrhoeae (Ng) and Neisseria meningitides (Nm), the two pathogenic species of neisseria, is catalyzed by the outer membrane enzyme [alpha]-2, 3-sialyltransferase (Lst). Sialylated LOS affects different facets of neisserial pathogenesis and is considered a key virulence factor. LOS sialylation interferes with neisserial (1) entry into epithelial cells, (2) killing by neutrophils, (3) killing by complement and (4) recognition by bactericidal antibodies against outer membrane structures. Very little is known about the gene regulation in neisseria and that of neisserial sialyltransferase (stase). Studies about distribution of stase activity in 16 random isolates of Ng and Nm revealed that Ng isolates contained varying amounts of stase activity, but, on average, 2.2-fold more stase activity than extracts of Nm isolates, representing seven serogroups and non-groupable strains (Mann-Whitney U test, p < 0.001). Ng isolates also express more lst transcript and Lst protein than most Nm isolates. Thus constitutive stase expression is higher in Ng isolates compared to Nm isolates. Promoter mapping studies revealed that Ng and Nm use different promoters to transcribe lst. In Ng a strong sigma 70 promoter 80 bp upstream of the translational start site is used to transcribe lst, whereas this promoter present in meningococci lst upstream region is inactive. In Nm a weak sigma 70 promoter at the 3' terminus of an 105 bp CREE insertion sequence element 99 bp upstream of the translational start site is used to transcribe lst. The differential constitutive stase expression between Ng and Nm is due, at least in part, to use of different promoters which have different strengths. Another factor that contributes to differential lst expression in Ng and Nm is differential half-life of the lst transcript. Ng F62 lst mRNA has a longer half-life (t1/2 = 90 to 120 sec) than Nm MC58 (t1/2 = 40 to 45 sec). Thus constitutive stase expression in pathogenic neisseria is affected by CREE insertion and differential half-life of lst transcript. Sequencing the Lst structural gene revealed many point mutations in isolates of Ng and Nm that could affect stase activity in those isolates. We also provide evidence for the existence of neisserial factors that affect stase activity. Besides regulation of constitutive expression, stase is regulated by environmental cues. Ng F62 downregulates expression of lst upon contact with cervical epithelial (ME-180) cells. In conclusion, the regulation of stase expression among and between pathogenic neisseria occurs by (1) differential gene transcription, (2) differential mRNA half life and (3) by sensing the environment. The presence of multiple gene regulatory mechanisms underscores the importance of this enzyme in neisserial pathogenesis.
Structural basis for autoantibody recognition of phosphatidylserine-[beta]2-glycoprotein I and apoptotic cells
Authors:   , Cocca Brian Anthony , Radic Marko Z
Published: July 2024

The work described in this dissertation was undertaken to explore the nature of the autoantibody response in two antibody-mediated autoimmune diseases, systemic lupus erythematosus (SLE) and the antiphospholipid syndrome (APS). Mutant versions of a murine anti-DNA and anti-phospholipid autoantibody, 3H9, were constructed and expressed as recombinant single chain Fv (scFv) in Escherichia coli. Purified scFv were tested for binding to phosphatidylserine and to phosphatidylserine as a complex with [beta]2-glycoprotein I ([beta]2GPI) in ELISA, revealing that the 3H9 heavy (H) chain V gene encodes specificity for these antigens. Moreover, it was determined that higher affinity for phosphatidylserine-[beta]2GPI could be achieved by the introduction of arginine residues into the CDR1, CDR2, and FWR3 of the 3H9 H chain at positions previously shown to be important for DNA binding. Flow cytometric analysis of structurally diverse variants of 3H9 established that the autoantibodies preferentially recognize Jurkat cells in advancing stages of apoptosis as defined by positive binding of annexin V and staining with propidium idodide. Confocal fluorescence microscopy revealed that the scFv initially bind to the cell surface at positions that overlap with the binding of annexin V and that the binding of the scFv and annexin V begin to segregate as the cell undergoes blebbing. The segregation of binding was found to culminate in the exclusive localization of the scFv to surface blebs on the apoptotic cells, with annexin V bound to regions between adjacent blebs. The results of these experiments suggest that, in SLE, B cells that express Ig receptors reactive against phosphatidylserine bind to apoptotic blebs and may have implications for the processing of nuclear antigens and the regulation of immune tolerance to self.
The use of cyclodextrins for the study of intracellular cholesterol transport and metabolism
Authors:   , Christian Aimee Elizabeth , Rothblat George H.
Published: July 2024

Cyclodextrins have been used extensively in the pharmaceutical industry as vehicles for drug delivery. Their ability to interact with hydrophobic molecules and form host/guest inclusion complexes have been found to improve aspects of drug delivery such as solubility and dissolution rate, drug absorption and taste. Although, cyclodextrins have been widely used in industry, their use in basic science research has been limited. This dissertation project focuses on the ability of [beta]-cyclodextrins to complex with cholesterol and deliver this cholesterol to cells so that intracellular cholesterol transport and metabolism can be studied. Results from Aim 1 and 2 indicate that M[beta]CDs are preferred to deliver cholesterol to a variety of cells over a short period of time. We also demonstrate that M[beta]CD-delivered cholesterol is metabolically available as shown by an increase in esterified [3H]cholesterol over time. Furthermore, we indicate there are two protocols that can be employed for labeling and loading cells with CD-delivered cholesterol: the continuous labeling protocol and the pulse/chase protocol. Results from Aim 3 and 4 discuss the different applications for the study of cholesterol metabolism using cyclodextrins. Specifically, Aim 3 indicates that cyclodextrins, at low concentrations, have the ability to catalyze the exchange of free cholesterol from cells to serum lipoproteins. For this study, we screened several synthesized [beta]-cyclodextrin derivatives and double-decker cyclophane compounds for their cholesterol-shuttling ability. Aim 4 illustrates several other applications for CD-cholesterol delivery systems, including the use of metabolic inhibitors to explore the mechanism of cholesterol transport from the cell plasma membrane to the intracellular site of esterification. The ability of cyclodextrins to complex with sterols other than cholesterol and to supply these sterols to cells was also investigated. The results from all aims of this thesis project illustrate the usefulness of cyclodextrins as tools to study intracellular cholesterol transport and metabolism.
Psychological factors associated with anabolic steroid use in male body builders
Authors:   , Carter Tammy J. , Herbert James D
Published: July 2024

This study was designed to explore the relationship between various psychological factors and anabolic steroid use among male body builders. The main focus was to distinguish among variables that may be predisposing factors versus those that may be effects of current steroid use. The volunteer sample of 96 subjects recruited from health clubs compromised 30 current steroid users, 30 former steroid users, and 36 body builders who had no history of steroid use. Standardized measures of locus of control, psychopathology, personality traits, hostility, social anxiety, and competitiveness as well as a demographic questionnaire were completed by each of the subjects. Multivariate analyses of variance with follow-up univariate analyses were used to examine differences among the three groups. The following variables were found to be potential risk factors for steroid use: low levels of conscientiousness as well as high levels of neuroticism, global distress, phobic anxiety, somatization, assaultiveness, resentfulness, and verbalness. In addition, another set of variables, including high levels of depression, obsessive-compulsiveness, positive symptom distress, indirect hostility, and negativity seem to represent direct effects of steroid use. Finally, another set of variables, high levels of agreeableness, generalized anxiety, irritability, suspiciousness, panic anxiety, paranoia, and psychopathology seem to reflect a mixed effect. That is these variables may be predisposing factors which are exacerbated by steroid use. The clinical implications of these results are discussed, and directions for future research are outlined.
Influence of physical therapy on the motor and interactive behaviors of mothers and their children with motor delay during play
Authors:   , Chiarello Lisa Ann , Palisano Robert J
Published: July 2024

The purpose of this study was to examine the effects of physical therapy on motor and interactive behaviors of mothers and their children with motor delay during play. The subjects were 38 mothers and their children, ages 6 to 34 months, enrolled in early intervention. The subjects were assigned to an experimental or control group. The experimental group received five home-based sessions of physical therapy. Conventional physical therapy intervention strategies were incorporated into play activities. Mothers were given the opportunity to interact with their children during the activities. Mother-child interactions were measured by a modified version of the Response Class Matrix. Two-factor repeated measures analyses of variance were used to analyze group differences in mother and child interactive behaviors. Children in the experimental group demonstrated more frequent changes in position at post-assessment compared with children in the control group (p =.06). The mothers in the experimental group demonstrated an increase in frequency of holding their children in an appropriate manner (p <.05). The mothers in the experimental group were more directive at post-assessment compared with the mothers in the control group (p <.01), but they were not less positive or more negative. The directive style of the mothers' in the experimental group appeared to be a consequence of their investment in the therapy program and desire for their children to perform optimally. The children and mothers in the control group demonstrated higher interactive summary scores when the children had higher levels of motor development. For the entire sample, child's mental age and mother's interactive ability accounted for 49% of the variance associated with child's interactive ability. Child's interactive ability, child's chronological age, and group membership accounted for 73% of the variance associated with mother's interactive ability. The mothers in the experimental group reported they were satisfied with the intervention program and that they learned to integrate gross motor activities into play. The integration of conventional physical therapy strategies within the context of interactive play was well received by the children and mothers and may promote the generalization and practice of motor skills during play without interfering with positive mother-child interactions.
Primate [alpha]1,3-Galactosyltransferase
Authors:   , Henion Timothy R. , Galili Uri
Published: July 2024

The glycosyltransferase enzyme [alpha]1,3-galactosyltransferase ([alpha]13GT) is active in nonprimate mammals and New World monkeys, but absent in Old World monkeys, apes, and humans. The latter species produce large amounts of natural antibody, termed anti-Gal, which interact specifically with [alpha]-galactosyl epitopes, the biosynthetic product of [alpha]13GT. Our objectives were to study structure-function relationships in this enzyme, and based on the information obtained, to express large amounts of recombinant [alpha]13GT. We planned to use this recombinant enzyme for modulation of the carbohydrate makeup of influenza virus vaccines to enhance their immunogenicity. Our basic hypothesis is that vaccine antigens which display de novo synthesized [alpha]-galactosyl epitopes can form in situ immune complexes with anti-Gal, and be effectively targeted for uptake, processing, and presentation by FcR-bearing antigen presenting cells. We have cloned the cDNA for [alpha]13GT from the marmoset, where the enzyme is active, and conducted a truncation analysis of the coding region. We show that up to 67 amino acids can be deleted from the N-terminal "stem region" of [alpha]13GT without affect on enzymatic activity. In contrast, the loss of as few as 3 amino acids from the carboxy terminus completely abrogated [alpha]13GT catalytic activity. Likewise, insertion of a coding frameshift common to all ape species, including humans, resulted in total loss of enzyme function. Sequence analysis of RACE and cDNA library PCR clones revealed that at least four isoforms of [alpha]13GT are expressed in the B958 marmoset cell line by alternative splicing of two noncoding exons within the 5' untranslated region of the enzyme, generating leader sequences which are heterogeneous in length. Based on our truncation analysis, we have been able to express a soluble recombinant form of the enzyme in the baculovirus system (r[alpha]13GT), which lacks the membrane anchoring domain. We show that r[alpha]13GT has the same acceptor specificity and similar kinetic properties compared to natural [alpha]13GT, and can readily synthesize [alpha]-galactosyl epitopes on influenza hemagglutinin which are bound by anti-Gal antibodies. In future studies we plan to use the method we have developed here to demonstrate the increased efficiency of vaccines which express de novo synthesized [alpha]-galactosyl epitopes.
The role of neurotrophin-trk receptor interactions in the development of pancreatic ductal adenocarcinoma
Authors:   , Miknyoczki Sheila Jean , Ruggeri Bruce A.
Published: July 2024

A hallmark of pancreatic ductal adenocarcinoma (PDAC) is the aberrant expression of many growth factors and their corresponding receptors. This study examined the expression and the potential involvement of a novel growth factor-receptor axis (neurotrophins and Trk receptors) in the development of PDAC and the consequences of uncoupling this interaction. Using immunohistochemical and in situ hybridization analyses, we localized the expression of Trks A, B, and C mainly to the ducts of both normal and neoplastic specimens. In addition, there was an increased expression of the Trk receptors in PDAC specimens as compared to the normal controls. Conversely, NT (BDNF, NT-3, and NT-4/5) expression was mainly localized to the stromal compartment, with some expression observed in the normal acinar cells within the tumor. As determined using a modified Boyden chamber assay, in vitro invasiveness of four of six PDAC derived cell lines was significantly inhibited when the cells were incubated with 100 ng/ml NT. However, when select cell lines (Panc1, CFPAC, and ASPC1) were incubated with lower concentrations of NT-3 or BDNF invasiveness was stimulated significantly. These studies demonstrated a dose-dependent, biphasic response to specific NTs on the in vitro invasive behavior of select PDAC derived cells, and further confirmed that the Trk receptors present on PDAC are in fact functional biologically. The consequences of inhibiting NT-Trk receptor interactions on the development of PDAC was evaluated using several preclinical models (subcutaneous (s.c.) and rat trachea xenografts) of human PDAC in athymic nude mice and the BOP-induced PDAC model in Syrian golden hamsters. Treatment of s.c. xenografts with CEP-701 (10 mg/kg s.c. BID, five days/week; 21 to 28 days) revealed a statistically significant reduction in tumor growth volume in five of the six PDAC xenografts. These data were corroborated using the rat trachea model of in vivo invasiveness, which showed that at the identical dose of CEP-701 in the same xenografts, tumor cell invasiveness through the tracheal wall was inhibited as compared to vehicle controls. In further support of the antitumor efficacy of CEP-701, the incidence of BOP-induced pancreatic tumors in Syrian golden hamsters was significantly reduced when CEP-701 was administered (10 mg/kg s.c. qd) during the post-initiation phase of PDAC development. These collective data suggest that NT-Trk interactions play a role in the development of PDAC and indicate that further studies are warranted to evaluate CEP-701 as a potential therapeutic agent in the treatment and management of PDAC.
Diagnostic differentiation in the eating disorders
Authors:   , Murphy-Eberenz Kathleen P.
Published: July 2024

The current study investigated the distinctiveness of the eating disorders anorexia nervosa and bulimia nervosa. Apart from the diagnostic criteria for the disorders many other variables have been hypothesized to be consistently associated with these disorders. These variables include depression, personality disorders, personality traits, and family functioning. Self-report measures assessing these areas of functioning and psychopathology were administered to restricting anorexics, binge/purge anorexics, and bulimics. A discriminant function analysis was calculated and two significant functions resulted. The first function termed Self-Control/Body Image showed the greatest differentiation between restricting anorexics and bulimics. However, the clinical severity of the variables making up this function was not impressive. The second function termed General Psychopathology differentiated binge/purge anorexics from both restricting anorexics and bulimics. Examination of the functions provided little support for the continued separation of the eating disorder groups in the DSM diagnostic system. Suggestions for future research and refinements to the diagnostic definition of the eating disorders were provided.
Characterization of carotenoid transport and antioxidant function in humans
Authors:   , Romanchick Joelle Elizabeth , Harrison Gerald , Morel Diane W.
Published: July 2024

Carotenoids are dietary, lipophilic antioxidants transported in vivo with plasma lipoproteins. These antioxidants may help prevent atherosclerosis, a disease believed to involve the oxidation of LDL. One goal of this research was to characterize the transport of carotenoids with lipoproteins. The hypothesis that carotenoids inhibit LDL oxidation and that individual carotenoids vary in effectiveness as antioxidants, was also tested. Total carotenoid in fasted human plasma associated primarily with LDL (73%), as did the more non-polar [beta]-cryptoxanthin (68%), lycopene (79%), and [beta]-carotene (72%), in patterns similar to cholesteryl ester. The more polar lutein distributed equally between LDL (44%) and HDL (38%) in a pattern similar to phospholipid. Relative polarities of carotenoids appear to influence their distributions. However, bulk solubility does not, as only four carotenoid molecules associated with each VLDL, one with each LDL, while only 25 of every 1,000 HDL particles contained carotenoid. These amounts represent a small 0.02 to 0.04 mole % of major lipids. Lecithin cholesterol acyl transferase and cholesteryl ester transfer protein, factors responsible for major lipid distributions, do not appear to influence carotenoid distributions as net transfer of carotenoids among lipoproteins did not occur when plasma was incubated in vitro, unlike triglyceride and cholesteryl ester. When LDL were oxidized in vitro (0.25 mg protein/ml, 5[mu]M CuSO4, 37[degrees]C), lutein, [beta]-cryptoxanthin, lycopene, and [beta]-carotene were destroyed at different rates (7, 3, 17, 11 pmols/min) and before the formation of lipid peroxidation products. To test the hypothesis that carotenoids differ in their antioxidant abilities, amounts of carotenoids in LDL were increased by adding each carotenoid in solvent to either isolated LDL or serum. LDL were enriched 4-134, 2-15, and 4-28 fold with lutein, lycopene, or [beta]-carotene, respectively, increasing concentrations to 52, 9.3, and 7.5 nmols/mg protein. The onset of oxidation in LDL enriched with [beta]-carotene (65 min) was significantly delayed compared to controls (19 min) as was the destruction of lutein, lycopene, and [beta]-carotene (t1/2min = 85, 21, 19, respectively) compared to controls (20, 9, 10, respectively). However, increased concentrations of lutein and lycopene did not protect LDL from oxidation. Thus, [beta]-carotene is unique in its ability to alter LDL oxidation. In summary, these studies provide new information on the transport of carotenoids with lipoproteins and their potential for preventing the oxidation of LDL.
A study of the dosimetry of small field photon beams used in intensity modulated radiation therapy in inhomogeneous media
Authors:   , Jones Andrew Osler , Das Indra J. , Emrich Jacqueline
Published: July 2024

There is an increasing interest in the use of inhomogeneity corrections for lung, air, and bone in radiotherapy treatment planning. Traditionally, corrections based on physical density have been used. Modern algorithms use the electron density derived from CT images. Small fields are used in both conformal radiotherapy and IMRT, however their beam characteristics in inhomogeneous media have not been extensively studied. This work compares traditional and modern treatment planning algorithms to Monte Carlo simulations in and near low-density inhomogeneities. Field sizes ranging from 0.5 cm to 5 cm in diameter are projected onto a phantom containing inhomogeneities and depth dose curves are compared. Comparisons of the Dose Perturbation Factors (DPF) are presented as functions of density and field size. Dose Correction Factors (DCF), which scale the algorithms to the Monte Carlo data, are compared for each algorithm. Physical scaling algorithms such as Batho and Equivalent Pathlength (EPL) predict an increase in dose for small fields passing through lung tissue, where Monte Carlo simulations show a sharp dose drop. The physical model-based collapsed cone convolution (CCC) algorithm correctly predicts the dose drop, but does not accurately predict the magnitude. Because the model-based algorithms do not correctly account for the change in backscatter, the dose drop predicted by CCC occurs further downstream compared to that predicted by the Monte Carlo simulations. Beyond the tissue inhomogeneity all of the algorithms studied predict dose distributions in close agreement with Monte Carlo simulations. Dose-volume relationships are important in understanding the effects of radiation to the lung. Dose within the lung is affected by a complex function of beam energy, lung tissue density, and field size. Dose algorithms vary in their abilities to correctly predict the dose to the lung tissue. A thorough analysis of the effects of density, and field size on dose to the lung and how modern dose calculation algorithms compare to Monte Carlo data is presented in this research project. This work can be used as a basis to further refine an algorithm's accuracy in low-density media or to correct prior dosimetric results.
Acousto-optically controlled beamsteering techniques for MMIC-based phased array antennas
Authors:   , Jemison William D. , Herczfeld Peter R
Published: July 2024

Future phased array antenna systems for radar and communications will utilize MMIC phase shifters and optical distribution techniques within a subarrayed antenna architecture. While significant progress has been made in the areas of photonic signal distribution in the last decade, relatively little effort has been directed towards compatibility with MMIC technology. This thesis presents both a theoretical and experimental investigation of two acousto-optically controlled array beamsteering techniques which are compatible with MMIC technology and subarrayed antenna architectures. The first technique explores the application of parallel optical signal processing within an acousto-optic cell to generate and distribute MMIC phase shifter control commands for array beamsteering control. This technique is analyzed from both a subsystem and system point of view and theory is developed which quantifies beamsteering performance with respect to noise, dynamic range requirements in both the microwave and optical domains, channel capacity, and the non-linearity of the acousto-optic cell driver. An experimental demonstration of the beamsteering control system was performed to validate the theory. The experiment was performed at L-band using a three bit MMIC phase shifter operating at 1300 MHz. Radiation patterns computed from experimental data show the correct steered responses. The second techniques explores the application of acousto-optic deflection in conjunction with high speed intensity modulation to generate programmable microwave time delays for true time delay beamsteering. Theory is developed which shows that there is no interaction between the optical sidebands generated in the intensity modulation process and the Doppler shift generated in the acousto-optic cell. The number of achievable delays as a function the acousto-optic cell parameters and the desired isolation between delays is also quantified. Experimental results are presented which validate the theory, showing 10 and 20 ns delays using external intensity modulation of a 1310 nm diode pumped solid state laser at 650 MHz.
Developmental growth trajectories of infants and toddlers in the child welfare system
Authors:   , Christian-Parilla Rebecca , Turner Ralph M.
Published: July 2024

Many psychosocial stressors, such as foster care, abuse, neglect, and parental drug use have been theorized to impact negatively upon a child's development. Additionally, there is a growing body of evidence to suggest that it is the multiplicity of risk factors that have the most impact upon a child's development. Understanding the relationships between these risk factors and the development of very young at-risk children is crucial because the number of children under the age of five who are in the child welfare system is growing dramatically. Therefore, this project attempts to address this problem by employing individual risk variables as predictors of initial status and growth on four measures of development in a sample of infants and toddlers in the child welfare system who repeatedly attended an evaluation program for at-risk children. Additionally, this project created three indices of risk comprised of multiple risk factors. The indices of risk represented three spheres of the child's experience: Home Environment, Drug Exposure, and Foster Care Experience. These indices were then also employed to predict initial status and developmental growth in this sample of at-risk children. It was found that no individual variable of risk predicted initial status or growth in this sample of children. However, the "Foster Care Experience" factor significantly predicted higher initial scores on a measure of gross motor skills, and the "Home Environment" factor predicted significantly lower initial scores on a measure of receptive and expressive language. No factor was found to significantly predict growth, although the growth rates were found to be relatively homogeneous for this sample of children.
Neuropsychological tests of executive function in predicting instrumental activities of daily living
Authors:   , Bell Sandra Lee , Williams Joseph M
Published: July 2024

Older adults are at risk for functional impairment in performing instrumental activities of daily living. Previous research has demonstrated that poor functional performance is associated with executive dysfunction. The current study investigated neuropsychological tests of executive function in determining functional ability in older adults. Fifty study participants consisted of community-dwelling and nursing home volunteers, and subjects referred for a neuropsychological. evaluation for assessment of dementia. Executive function tests accounted for 58% of the variance in functional status, with Trail Making Test-Part B demonstrating the strongest predictive power. Results also suggested that tests of executive function contribute significantly to the prediction of functional status, even after statistically controlling for memory function and global cognitive function. Depression had a low, statistically significant association with functional ability. In conclusion, results supported the hypothesis that common clinical measures of executive control predict functional status in older adults.
Cancer, coping, and readiness to change
Authors:   , DelliCarpini Lisa Anne
Published: July 2024

The stages of "readiness to change" were developed as a way of explaining how people change addictive behaviors. Research in this area has shown empirical support for the model as a viable theory for understanding the mechanism of change, not only in this context, but in general. The purpose of this study was to examine the applicability of this theory with cancer patients who were learning problem-solving therapy to improve coping skills. Analyses of scores from the 71 subjects indicated that these subjects were more "ready to change" than samples of individuals changing addictive behaviors. Problem-solving therapy, specifically the Problem Orientation component, was found to be an effective way of facilitating readiness to change among those 26 subjects who completed treatment. Further, pre-treatment scores on the four stages of change contributed to a significant amount of the variance in post-treatment problem-solving scores. Comparisons between the treatment group and wait-list control group indicated that there was a significant Time x Group interaction, and a significant main effect for time. Individual contrasts revealed that the treatment group had significantly lower depression and cancer-related distress scores at post-treatment.
The Impact of Stressors on Sensory Signal Processing Regulated by the Nucleus Locus Coeruleus
Authors:   , Zitnik Gerard A. , Waterhouse Barry D.
Published: July 2024

Stress is an adaptive response to adverse and challenging [behavioral or physiological] circumstances. The neurological cascade of events that follow stressor exposure results in a state of preparedness to respond to bodily demands or environmental challenges. Hypothalamic and extrahypothalamic release of the neuropeptide corticotropin releasing factor (CRF) is important for coordinating the physiological and behavioral responses during stress. A major target for the CRF system is the brainstem nucleus locus coeruleus (LC). The LC is the primary source of norepinephrine (NE) for the entire forebrain and exhibits a range of output that correlate with target NE release. Changes in LC output modulate neuronal responses to salient stimuli, including sensory driven activity within the thalamus. Stress causes a CRF-mediated increase in LC discharge that is dependent upon the nature and intensity of the stress[ors]. However, these effects on downstream target sensory cell physiology remain unclear. To that end, this work examines how different degrees of CRF-mediated LC activation modulate individual neurons responsible for sensory signal processing. The dorsal lateral geniculate nucleus (dLGN) of the thalamus is the primary relay for visual information from the retina to the cortex and is innervated by the LC. Using in vivo extracellular recording in the anesthetized rat, we monitored light-evoked responses from single dLGN neurons before and after CRF-mediated activation of the LC. Exposure to a physiological stressor suppressed dLGN evoked activity, which was blocked in animals pretreated locally with CRF-antagonist. Administration of CRF augmented dLGN neuron sensory evoked responses in an inverted-U dose-response relationship. Together, these data suggest that stressor exposure and subsequent CRF release can alter early stage sensory signal processing via activation of the LC. However, stressor-induced changes in sensory neurons cannot be defined in terms of a singular modulatory effect, but rather exists along a continuum that is dictated by the degree of activation of the CRF-LC-NE pathway. The present findings also suggest a physiological basis for disruption in sensory processing that occurs during intense periods of acute stress or in conjunction with stress disorders associated with dysregulation of the CRF system, e.g. anxiety and post-traumatic stress disorder (PTSD).
Evaluation of techniques for drowsiness detection
Authors:   , Mallis Melissa Mercedes , Dinges David F.
Published: July 2024

In recent years, an increasing number of fatigue-tracking technologies have become available with the widespread hope that they will be a key component in the prevention of fatigue-related accidents. To obtain estimates of the current scientific validity of six promising fatigue detection technologies, a double-blind, controlled laboratory validation experiment was undertaken. The six technologies tested included a video-based scoring of eye closure by trained observers; two EEG algorithms; a head tracking device; and two eye-blink monitors. Psychomotor vigilance task (PVT) performance lapses were selected as the validation criterion variable. Fourteen healthy adult males remained awake in the laboratory for 42-hr and performed a computerized test battery every 2-hr that included a 20-min PVT task, the criterion variable. Each technology was time-locked to PVT performance to test coherence between vigilance lapses and each technology's specific drowsiness metric, over both 1-min and 20-min intervals. All technologies performed better when predicting lapses over a 20-min period than over a 1-min period and all of the technologies showed potential for the detection of drowsiness-induced hypovigilance by accurately tracking the relative profile of PVT lapses in at least one subject or a subset of subjects. However, only one technology, PERCLOS-the video-based scoring of slow eye closure by trained observers (Wierwille et al., 1994; Wierwille & Ellsworth, 1994)-correlated highly with PVT lapses both within and between subjects (mean r = 0.875, p = 0.00001). PERCLOS also correlated more highly with PVT lapses than subjects' own ratings of their sleepiness (t = -3.9, p = 0.003). The results of this study revealed that although all of the technologies tested had potential to predict hypovigilant performance on a continuous visual vigilance task of sustained attention, only PERCLOS actually performed with a high level of validity and reliability, suggesting that PERCLOS has the greatest potential to be used as a valid fatigue-tracking device since it was able to consistently track the relative profile of PVT lapses of attention for all subjects.
The effects of ryanodine receptor mutations on sodium channel transcription
Authors:   , Stewart Sherri L. , Fletcher Jeffrey E.
Published: July 2024

Malignant hyperthermia (MH) is a genetic, anesthesia-induced rhabdomyolytic disorder of skeletal muscle. A mutation in the ryanodine receptor (RYR1) has been shown to cause all known cases of MH in swine. To date, nineteen mutations in the RYR1 have been associate with human MH. A mutation in the dihydropyridine receptor (DHPR) has been recently identified in one MH family. The objective of these experiments is to further clarify the roles of three key proteins of excitation-contraction coupling in skeletal muscle, the RYR1, DHPR, and Na + channel, in the pathophysiology of MH. The central hypothesis is that MH mutations lead to altered expression of sodium channel isoforms, specifically down-regulation of SkM2. It is further hypothesized that the changes observed with the specific RYR1 mutations are similar to what is observed in vivo in a population of heterogenotic subjects. In order to test this hypothesis, three specific aims were pursued. The first aim focused on screening DNA from a large North American population for the presence of a RYR1 MH mutation, Gly341Arg. The North American population was also screened for the DHPR MH mutation Arg1086His. The second aim, the main thrust of this work, was to characterize sodium channel transcript levels in an isolated system in which a known MH mutation is the only variable. In the third aim, sodium channel isoform transcript levels were measured in a different model of rhabdomyolysis (horses with chronic intermittent rhabdomyolysis [CIR]) to compare with those in MH. The results demonstrate that the RYR1 Gly341Arg mutation is not present in the large MH population described here and the DHPR Arg1086His mutation was present in approximately 1% of our MH population. Results from the second aim conclusively demonstrate that the SkM2 isoform of the sodium channel is significantly down-regulated secondarily in response to transfection with mutant forms of the RYR1. And in aim 3, it was determined that the SkM1 isoform of the sodium channel may have a role in the pathophysiology of the rhabdomyolytic disorder CIR. In summary, currently identified MH mutations account for a very small percentage of MH in our population. Therefore, the population frequency estimates for known human MH mutations are inconsistent with the data obtained in this North American population. SkM2 is the first transcript that has been shown to be downregulated by a specific MH mutation. This is the first clear demonstration of this cause-effect relationship phenomenon and establishes a model system in which to examine the previously reported association of SkM2 down-regulation with muscle from MH susceptible humans. The results of this work suggest that the many factors that regulate the expression of MH and this effect may contribute to the pathophysiology of the disease. (Abstract shortened by UMI.).
Rate of forgetting in chronic schizophrenia in relation to positive and negative typologies of schizophrenia
Authors:   , Steed Carl Alan
Published: July 2024

The purpose of the current research was to examine the relatively unexplored aspect of memory functioning in schizophrenia known as savings scores. Positive and negative symptoms of schizophrenia were evaluated with the Schedule for the Assessment of Negative Symptoms (SANS) and the Schedule for the Assessment of Positive Symptoms (SAPS) and compared to savings scores. Positive symptoms reflect over-productive mental activities such as hallucinations, delusions, formal thought disorder, and bizarre or disorganized behavior. Negative symptoms reflect under-productive mental functions such as marked poverty of speech, poverty of content of speech, flat affect, an inability to experience pleasure, and impairments in attention. There is a growing body of evidence that implicates portions of the limbic system (i.e., hippocampus, parahippocampal gyrus, and amygdala) in the neuropathology of schizophrenia. These neuroanatomical structures are thought to be responsible for encoding, storing and retaining new information. Deficient savings scores have been linked to dysfunction of this hippocampal circuit. In the present study, 50 normal controls and 50 inpatients diagnosed with chronic schizophrenia were administered a battery of standardized memory tests and rating scales for positive and negative symptoms. The current study was unique as it systematically evaluated savings scores in relation to positive and negative symptoms. It was predicted that negative symptoms would predict savings scores on memory testing. It was also predicted that there would be a negative relationship between savings scores and negative symptoms. Higher negative symptom scores were predicted to be associated with lower savings scores. A comparison of SANS and SAPS scores was made between the schizophrenic group and control soup. Next, the two groups were compared on savings scores using a MANCOVA. There were significant differences between the groups on SANS/SAPS and savings scores. Multiple Regressions revealed there were certain core negative symptoms of schizophrenia which predicted savings scores. Implications for the neuropsychology of schizophrenia were discussed.
New class of parameter identification algorithms and their application to robot control
Authors:   , Ahmad Ziauddin
Published: July 2024

A system performs various tasks over its lifetime. The problem of optimal tracking performance for the entire lifetime of a robotic system with parametric uncertainty is considered. The classical adaptive control methods minimize the tracking error of the current task without making an effort to learn about the system parameters. We show that knowledge of the desired future tasks and the system parameters is necessary for design of the optimum controller. Therefore, identification of system parameters is a crucial task to be accomplished. In adaptive robot control if the input signal for a task is persistently exciting (PE), in accordance with the classical definition, then the parameters estimated by the classical methods of adaptive control/parameter estimation are guaranteed to converge to their true values. This PE signal is required for infinite horizon. This has been the case for the plants considered here which have constant parameters linearly related to the computable variables. A class of algorithms is proposed, both in open and closed loop, that guarantees identification of the parameters while requiring less stringent conditions on the input. The closed loop algorithm ensures asymptotic stable tracking of the desired trajectory as well. These algorithms are derived and demonstrated. We are specifically interested in robot control, where the state of the art algorithms employ gradient based methods. We show that the model based controller (e.g. Slotine and Li (2)) has the structure of optimal tracking controller. Examples providing quantitative results from robotics and linear time invariant systems are demonstrated, comparing the results with an enhancement of a classical approach of gradient type algorithm and least squares algorithm respectively. The overall effect is superior tracking performance over the lifetime of the system resulting in reduced cost of operation through improved quality of product, less wear tear, low input energy levels, longer life of the plant etc. We also discuss and demonstrate application of the proposed algorithms in case of step changes in plant parameters. It is expected that the results presented here will be applicable to a large class of dynamic systems, including discrete time systems and sampled data systems.
Stretch-evoked motor unit activation patterns in the decerebrate cat
Authors:   , Dacko Stan M.
Published: July 2024

The way in which muscle forces are generated and controlled for functional primarily on the recruitment and firing pattern of motor units within a muscle or groups of muscles. There is a wide range of anatomic and unit properties that covary with specific unit type. It is possible then, that the nervous system exploits these attributes in recruiting motor units. For most functional activities involving the cat hindlimb, there is a "usual" progression of motor unit activation as synergist muscles are mutually excited. Under certain conditions however, a divergence of whole muscle activity between anatomic synergists is seen and may reflect an alternative scheme of motor unit recruitment based on physiologic properties such as motor unit type. The force at which a motor unit is recruited, known as recruitment threshold, and is commonly used as a measure for comparing the relative excitability of units within a motor pool. A large deviation in recruitment threshold for motor units during repeated contractions would suggest that the recruitment process is variable and cannot be predicted by a particular level of muscle force. Therefore, the purpose of this dissertation was to study the organization of motor unit activation during stretch-evoked contractions under steady-state conditions in isolated muscle and during periods of divergent whole muscle behavior, specifically to investigate if the "usual" motor unit recruitment pattern is violated. Behavior of type-identified motor units from the ankle extensors in the cat was studied via intra-axonal penetration during 2-8mm stretch-hold-release perturbations. Force from selected hindlimb muscles and motor unit firing rate responses were recorded. Relationships between unit activity and muscle force were analyzed to assess organizational schemes. There was no evidence for selective recruitment based on motor unit type across motor pools other than the "usual" pattern, during conditions where divergent whole muscle behavior was seen. Instead motor unit recruitment was specific and ordered for each muscle within a synergist pair. The force threshold for recruitment under relatively stable conditions was minimally variable for most units. Mechanical elements contributing to muscle force only partially explain the variation in recruitment thresholds. Under all conditions examined, the "usual" motor recruitment pattern was consistently observed without any evidence for alternative recruitment schemes.