Background: Pathology of white matter in brains of patients with major depressive disorder (MDD) is well-documented, but the cellular and molecular basis of this pathology are poorly understood. Methods:Levels of DNA oxidation and gene expression of DNA damage repair enzymes were measured in Brodmann area 10 (BA10) and/or amygdala (uncinate fasciculus) white matter tissue from brains of MDD (n=10) and psychiatrically normal control donors (n=13). DNA oxidation was also measured in BA10 white matter of schizophrenia donors (n=10) and in prefrontal cortical white matter from control rats (n=8) and rats with repeated stress-induced anhedonia (n=8). Results:DNA oxidation in BA10 white matter was robustly elevated in MDD as compared to control donors, with a smaller elevation occurring in schizophrenia donors. DNA oxidation levels in psychiatrically affected donors that died by suicide did not significantly differ from DNA oxidation levels in psychiatrically affected donors dying by other causes (non-suicide). Gene expression levels of two base excision repair enzymes, PARP1 and OGG1, were robustly elevated in oligodendrocytes laser captured from BA10 and amygdala white matter of MDD donors, with smaller but significant elevations of these gene expressions in astrocytes. In rats, repeated stress-induced anhedonia, as measured by a reduction in sucrose preference, was associated with increased DNA oxidation in white, but not gray, matter. Conclusions:Cellular residents of brain white matter demonstrate markers of oxidative damage in MDD. Medications that interfere with oxidative damage or pathways activated by oxidative damage have potential to improve treatment for MDD.

This project investigates the effects of social identity and personal characteristics on foreign policy decision-making. The two main US political parties, Democrats and Republicans, were used as markers for social identity. Participants were first instructed to read a scenario regarding a hostile fictional country followed by a speech regarding the same fictional country. Two speeches were created using a content analysis of speeches from Democrats and Republicans prior to the 2003 invasion of Iraq. Participants were randomly placed into one of four conditions. One condition paired a Democratic-themed speech with a Republican speaker, another paired a Democratic speech with a Democratic speaker, the third paired a Republican speech with a Democratic speaker, and the last paired a Republican speech with a Republican speaker. Participants then answered a survey that asked about their policy preferences regarding the fictional country. Manipulated variables were found to be insignificant, whereas the personality characteristics presented different levels of significance based on models of regression analysis. The data indicates that personality characteristics may be a more salient predictor of foreign policy preferences than social identity.

No description available.

The standard model of particle physics cannot currently explain the origin of neutrino masses and anomalies that have been observed at different experiments. One solution for this is to introduce a beyond the standard model origin for these issues, which introduces a coupling between neutrinos and dark matter. Such an interaction would have implications on cosmology and would be constrained by astrophysical neutrino sources. A promising astrophysical source to probe this interaction is core-collapse supernovae as they release ~3x10^53 erg in neutrinos for each transient. However, more observations that constrain the internal physics of core-collapse supernovae are needed in order to better understand their neutrino emission. This dissertation studies two probes of internal physics that allow for a better understanding of the neutrino emission from core-collapse supernovae. The first is a novel approach to try and detect more supernova neutrinos that do not come from galactic events nor from the diffuse supernova background. This is accomplished by doing an offline timing coincidence search at neutrino detectors with a search window determined by optical observations of core-collapse supernovae. With a two-tank Hyper-Kamiokande, this allows for ~1 neutrino detection every 10 years with a confidence level of ~2.6 sigma, resulting from low nearby core-collapse rates and large background rates in the energy range of interest. The second probe of internal physics is high energy gamma-rays from the decays of unstable nuclei in proto-magnetar jets. The abundance distribution of the unstable nuclei depends directly on the neutrino emission, which controls the electron fraction, as well as properties of the proto-magnetar. We find that different proto-magnetar properties produce gamma-ray signals that are distinguishable from each other, and multiple types of observations allow for estimations of the jet and proto-magnetar properties. These gamma-ray signals are detectable for on-axis jets out to extragalactic distances, ~35 Mpc in the best case, and for off-axis jets the signal is only detectable for galactic or local galaxies depending upon the viewing angle. This dissertation also studies a phenomenological constraint on the interactions between neutrinos and dark matter. Using the neutrino emission from supernovae and the inferred dark matter distributions in Milky Way dwarf spheroidals, we constrain the amount of energy the neutrinos can inject into the dark matter sub-halos. This then allows a constraint on the interaction cross-section between neutrinos and dark matter with assumptions about the interaction kinematics. Assuming Lambda-CDM to be correct, the neutrinos cannot interact with low mass dark matter too often as it will become gravitationally unbound, changing the mass of the core we see today. For high mass dark matter, neutrinos can only inject a fraction of ~6.8x10^-6 of their energy in order to not conflict with estimates of the current shapes of the dark matter sub-halos. The constraints we obtain are sigma_nu-DM(E_nu=15 MeV, m_DM>130 GeV) ~ 3.4x10^-23 cm^2 and sigma_nu-DM(E_nu=15 MeV, m_DM <130 GeV) ~ 3.2x10^-27} (m_DM/1 GeV)^2 cm^2, which is slightly stronger than previous bounds for these energies. Consideration of baryonic feedback or host galaxy effects on the dark matter profile can strengthen this constraint. / Doctor of Philosophy / In our current understanding of the physics of the particles that govern how the universe behaves, there is no way to explain the properties we observe for the neutrino. Neutrinos were originally theorized to have zero mass, however neutrino experiments suggests otherwise. The current model of particle physics cannot explain how the neutrinos have mass, therefore an viable way to explain it is to introduce new physics that can generate the neutrino masses. A way to do this is to allow the neutrinos to interact with dark matter, which is matter that does not interact with light and is therefore invisible to the human eye. We know dark matter should exist in the universe due to the gravitational effects it has, making things like galaxies much heavier than what the stars and gas we see can explain. If neutrinos and dark matter interact, we should be able to see the effects of these interactions in the universe, and also possibly at locations where many neutrinos are produced. One such source of neutrinos in the universe are core-collapse supernovae, which are the deaths of massive stars and produce copious amounts of neutrinos. This dissertation studies signals that allow us to better understand the neutrino emission from core-collapse supernovae. One of these signals comes from summing the neutrinos we detect from many distant core-collapse supernovae. This technique uses the optical observations of the supernovae to give us a time window around which we can go through neutrino detector data to find if there are any neutrino detections that cannot be explained as coming from background events. Another method is to observe gamma-rays, high energy photons, that come from the radioactive decay of elements in jets moving near the speed of light powered by rare core-collapse supernovae. The specific gamma-rays and the overall brightness of them allows for an estimation of the properties of the neutrino emission and properties of the central engine that accelerates the jet to near the speed of light. This dissertation also studies the implications of a possible interactions in small and dim satellite galaxies of the Milky Way known as dwarf spheroidals. The shape of the dark matter that is distributed in these dwarf spheroidals can be inferred from the motion of the stars in that dwarf spheroidal, and this shape disagrees with the prevailing theory of dark matter in the universe. We take advantage of this disagreement to place an upper limit on both the mass loss that can occur in this region and the energy that past core-collapse supernovae within the dwarf spheroidals can inject into the dark matter. The mass loss bound lets us place a constraint on how often neutrinos can interact with light dark matter particles. The energy injection limit and an assumption on the energy transfer in each interaction between dark matter and neutrinos allows us to constrain how often the interaction can occur for heavy dark matter particles.

Gamma-zein, a proline-rich protein from corn endosperm, was investigated at the molecular level. Immunological and electrophoretic data indicated that gamma-zein was deposited into protein bodies in corn endosperm. Both isolated polysomes and poly(A)⁺ mRNA were found to direct in vitro synthesis of gamma-zein in a wheat germ system. In vitro synthesized gamma-zein was immunoprecipitated from the total in vitro translation products. A cDNA expression library was constructed by reverse transcription of total poly(A)⁺ mRNA using pUC8 plasmid as vector and <i>E. coli</i> strain DH1 as host. The library was screened for the expression of gamma-zein and alpha-zein by specific antibodies. The library was also screened with ³²P-labeled gamma-zein and alpha-zein cDNA probes. The results indicated that gamma-zein and its fragments were readily expressed in <i>E. coli</i> while alpha-zein was not. Seven independently selected clones, six of which were selected by antibody and one by a cDNA probe, were sequenced. A comparison of sequence information from seven clones revealed that their overlapping regions were identical. This suggests that gamma-zein is encoded by a single U gene. This finding is in conflict with what was expected on the basis of extensive charge heterogeneity of gamma-zein in isoelectric focusing. Individual bands cut from an IEF gel were rerun and shown to give several bands suggesting that the charge heterogeneity of gamma-zein may be an artifact. Sequence information of gamma-zein indicated that the gene encodes a mature protein whose primary structure includes 204 amino acids and has a molecular weight of 21,824 daltons. There are eight essentially identical tandem repeats of the hexapeptide Pro-Pro-Pro-Val-His-Leu and two of the octapeptide Gln-Pro-His-Pro-Cys-Pro-Cys-Gln in the N-terminal one-half of the polypeptide. The codon specifying the third proline in the hexapeptide repeating unit is identical, CCG, in all eight repeats. It is likely that these highly conserved tandem repeats are of critical importance to the function of gamma-zein which is presently unknown. Alternatively, it is conceivable that selective pressures responsible for conserving these tandem repeats may be operating at the nucleic acid level. / Ph. D. / incomplete_metadata

Circulating RNA was previously demonstrated through the identification of tumour-derived transcripts in the plasma and serum of cancer patients. This finding inspired the detection of cell-free fetal mRNA in maternal plasma which in turn facilitated the development of promising non-invasive prenatal assessment strategies applicable to pregnancies regardless of fetal sex. / Finally, in the last study, I implemented what I have learnt from the analysis of circulating fetal RNA into the development of brain-derived RNA transcripts for detection in the plasma of patients who had sustained brain injuries. A systematic approach based on gene expression microarray analysis was adopted to search for circulating brain-specific mRNA markers. Transcripts showing high expression levels in brain tissues but low expression levels in peripheral blood were identified. However, the detectability of these brain-derived mRNA markers in both peripheral and jugular plasma was found to be low. Instead, concentrations of these mRNA markers were found to be higher in cerebral spinal fluid (CSF) from brain-injured than non-brain-injured patients. / In section IV of this thesis, I reviewed and modified the blood sample processing and plasma RNA extraction protocols that were previously practised, in an attempt to enrich circulating fetal RNA in maternal plasma. Besides mRNA, extraction protocols for microRNAs (miRNAs), a new class of circulating nucleic acid markers, were also evaluated. The modifications in the protocols that I introduced led to significant improvements in RNA yield and enhanced the accuracy and reliability of circulating RNA detection in plasma, especially for those marginally detectable transcripts. / Recently, in addition to maternal plasma, there have been studies by other research groups reporting the presence of placental/fetal mRNA in maternal whole blood. In the first part of this thesis, I studied a list of previously identified placental mRNA transcripts, including chorionic somatomammotropin hormone 1 (CSH1), KiSS-1 metastasis-suppressor (KISS1), placenta-specific 4 (PLAC4) and placenta-specific 1 (PLAC1) in maternal whole blood and determined if this whole blood-based approach offered advantages over maternal plasma analysis. The presence of KISS1, PLAC4 and PLAC1 in non-pregnant and post-partum blood samples as well as the confirmed maternal contribution of PLAC4 mRNA in maternal blood proved that most of the detected 'placental' mRNA molecules in maternal whole blood were of maternal origin. To explore if more pregnancy-associated circulating mRNA markers could be developed for maternal whole blood analysis, candidates were mined after performing gene expression microarray comparison of whole blood samples from pregnant and non-pregnant individuals. The pregnancy-specificity of the identified gene candidates was further investigated. However, their presence in non-pregnant whole blood and lack of clearance after pregnancy indicated that they were not "pregnancy-specific" markers. These data suggested that pregnancy specific transcripts could be more readily identified from maternal plasma than whole blood. / The results presented in this thesis have not only provided a foundation facilitating the precise and accurate detection of fetal-specific RNA markers but have also improved the current understanding of the biology of circulating RNA. / Heung, May Sze. / Advisers: Dennis Lo; Rossa Wk Chiu. / Source: Dissertation Abstracts International, Volume: 72-11, Section: B, page: . / Thesis (Ph.D.)--Chinese University of Hong Kong, 2009. / Includes bibliographical references (leaves 212-239). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [201-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese.

Face-to-face communication is always complemented with non-verbal signals that give us clues as to how a message shall be interpreted, but as communication is moved online the possibilities to express oneself becomes more limited. This paper focuses on the instant messaging client Windows Live Messenger and three of the non-verbal functions that it provides (nudges, winks and emotes). The purpose of the paper and its underlying study is to compare the senders' intentions with the receivers' conceptions when it comes to these functions. The study was done as a questionnaire with two different versions of the questions, one looking at the senders' intentions and the other at the receivers' conceptions. The results were then compared in order to look for tendencies. The results showed that the most common intention among the senders was also the most common conception among the receivers, but that the rest of the attitudes didn't match at all. The functions that are supposed to help the conversation flow often create ambiguity instead and lead to vagueness, misconceptions and annoyance. / Kommunikation som sker ansikte mot ansikte kompletteras alltid med icke-verbala signaler som ger ledtrådar till hur ett budskap ska tolkas, men i och med att kommunikationen flyttas online begränsas möjligheterna att uttrycka sig. Uppsatsen fokuserar på chatt-tjänsten Windows Live Messenger och tre av de icke-verbala funktioner som den tillhandahåller (vibbar, blinkningar och uttryckssymboler). Syftet med uppsatsen och dess bakomliggande studie är att jämföra avsändarnas avsikter med mottagarnas uppfattningar när det gäller dessa funktioner. Studien utfördes med kvantitativ metod i form av en enkätundersökning. Respondenterna fördelades jämnt mellan två olika enkäter vilka behandlade avsändarnas avsikter och mottagarnas uppfattningar var för sig. Resultaten av de två enkäterna jämfördes sedan med varandra i ett försök att avläsa vissa tendenser. Analysen visade att den vanligaste avsikten hos avsändarna också var den vanligaste uppfattningen hos mottagarna, men att resterande åsikter inte alls stämde överens. Funktionerna som ska hjälpa konversationen framåt visar sig istället vara mångtydiga och leda till så väl oklarheter som missförstånd och irritation.

Thesis (M.S.)--West Virginia University, 2002. / Title from document title page. Document formatted into pages; contains viii, 100 p. : ill. (some col.). Vita. Includes abstract. Includes bibliographical references (p. 80-96).

Das IceCube Neutrino Observatory, das größte Neutrino-Observatorium der Welt, entdeckte 2013 erstmals einen Fluss hochenergetischer Neutrinos. Diese Neutrinos müssen von astrophysikalischen Beschleunigern erzeugt werden, aber ihr genauer Ursprung ist bisher unbekannt. Vorgeschlagene Neutrinoquellen sind Gezeitenkatastrophen (Tidal Disruption Events, TDEs), Ereignisse bei denen Sterne zerfallen, wenn sie supermassiven Schwarzen Löchern zu nahe kommen. In dieser Doktorarbeit wurde erstmals nach Korrelationen zwischen Neutrinos und TDEs gesucht, wobei eine Zusammenstellung veröffentlichter TDEs und ein IceCube-Datensatz von einer Million Myon-Neutrinos mit GeV-PeV-Energien von verwendet wurde. Es wurde keine signifikante Korrelation gefunden, sodass der Beitrag von TDEs ohne relativistische Jets auf 0-38,0% des gesamten astrophysikalischen Neutrinoflusses begrenzt werden kann. Der Beitrag von TDEs mit relativistischen Jets wurde auf 0-3,0% des Gesamtflusses begrenzt. IceCube veröffentlicht auch hochenergetische (>100 TeV) Myon-Neutrino-Ereignisse in Form von automatischen, öffentlichen Echtzeit-‘Neutrinoalerts’. Im Rahmen dieser Arbeit wurde die Lokalisierung von 22 solcher Neutrinoalerts mit dem optischen Zwicky Transient Facility (ZTF) Teleskop beobachtet, um nach möglichen elektromagnetischen Gegenstücken zu Neutrinos zu suchen. Mit diesem Neutrino-Nachfolgebeobachtungsprogramm wurde die helle TDE AT2019dsg als mutmaßliche Neutrinoquelle identifiziert. Die Wahrscheinlichkeit, solch eine helle TDE zufällig zu finden, beträgt 0,2%. Die Assoziation bedeutet, dass TDEs 3-100% der astrophysikalischen Neutrino-Alerts von IceCube ausmachen. Zusammengenommen deuten diese beiden Ergebnisse darauf hin, dass TDEs einen subdominanten Anteil des astrophysikalischen Neutrinoflusses bei hohen Energien emittieren. Die Assoziation des Neutrinoalerts IC191001A mit AT2019dsg ist erst das zweite Mal, dass ein hochenergetisches Neutrino mit einer mutmaßlichen astrophysikalischen Quelle in Verbindung gebracht werden konnte. / The IceCube Neutrino Observatory, the world’s largest neutrino observatory, first discovered a flux of high-energy neutrinos in 2013. These neutrinos must be produced by astrophysical accelerators, but their exact origin remains unknown. One proposed source of neutrinos are Tidal Disruption Events (TDEs), which occur when stars disintegrate after passing sufficiently close to supermassive black holes. In this thesis, the first search for neutrino-TDE correlations was performed, using a compilation of published TDEs and a dataset of one million muon neutrino events of GeV-PeV energies from IceCube. No significant correlation was found, limiting the contribution of TDEs without relativistic jets to 0-38.0% of the total astrophysical neutrino flux. The contribution of TDEs with relativistic jets was limited to 0-3.0% of the total flux. IceCube also publishes high-energy (>100 TeV) probable astrophysical muon neutrino events automatically, in the form of public realtime alerts. As part of this thesis, the location of 22 such neutrino alerts were observed by the Zwicky Transient Facility (ZTF), an optical telescope, in order to search for possible electromagnetic counterparts to neutrinos. With this neutrino follow-up program, the bright TDE AT2019dsg was identified as a probable neutrino source. The probability of finding such a bright TDE by chance is 0.2%. The association implies that TDEs contribute 3-100% of the astrophysical neutrino alerts issued by IceCube. Taken together, these two results suggest that TDEs emit a subdominant fraction of the astrophysical neutrino flux at high energies. The association of neutrino alert IC191001A with AT2019dsg represents only the second time that a high-energy neutrino has been matched to a probable astrophysical source.

Sucrose fading was used to initiate self-administration of ethanol on an FR4 schedule in male Fischer 344 rats. Rats showed low response rates for ethanol alone. After administration of liquid diet containing ethanol, ethanol intake increased over levels prior to administration of the liquid diet. In situ hybridization compared mRNA for the inducible or constitutive 70 kD heat shock proteins in ethanol and nonethanol rats. Both inducible and constitutive mRNAs were found in nonethanol and ethanol tissues. In peripheral organs, radiolableling was higher in ethanol tissue. In brain regions, nonethanol tissues showed higher radiolabeling.