232 research outputs found
THE KINGDOM OF SAUDI ARABIAāS OPPOSITION TO NORMALIZATION WITH ISRAEL
This thesis addresses the Kingdom of Saudi Arabiaās refusal to normalize relations with Israel. The United States is the facilitator of normalization between Arab states and Israel and possesses an interest in successful rapprochement for regional stability and peace. KSAās opposition to formal diplomatic relations with Israel presents a challenge to U.S. interests of regional stability and peace. To determine why KSA refused normalization, this thesis analyzes international, domestic, and individual factors. The main findings of the research are that each level holds explanatory power, and combined, these factors help one understand why KSA did not normalize relations with Israel. I argue that the international factor that explains KSAās refusal is its offensive realist foreign policy approach. The domestic factors that dissuade KSA from normalization create fear for KSA regime survival. These domestic factors include public opinion, internal government opposition, and resistance from the Muslim world. The individual factors analysis sheds light on the historical opposition to normalization with Israel in the Saud family. To meet U.S. interests of peace and stability in the Arab world, it is paramount to understand why KSA did not normalize relations with Israel.Second Lieutenant, United States Air ForceApproved for public release. Distribution is unlimited
Enhanced DNA binding affinity of RecA protein from Deinococcus radiodurans
Ā© 2015 Elsevier B.V. Deinococcus radiodurans (Dr) has a significantly more robust DNA repair response than Escherichia coli (Ec), which helps it survive extremely high doses of ionizing radiation and prolonged periods of desiccation. DrRecA protein plays an essential part in this DNA repair capability. In this study we directly compare the binding of DrRecA and EcRecA to the same set of short, defined single (ss) and double stranded (ds) DNA oligomers. In the absence of cofactors (ATPĪ³S or ADP), DrRecA binds to dsDNA oligomers more than 20 fold tighter than EcRecA, and binds ssDNA up to 9 fold tighter. Binding to dsDNA oligomers in the absence of cofactor presumably predominantly monitors DNA end binding, and thus suggests a significantly higher affinity of DrRecA for ds breaks. Upon addition of ATPĪ³S, this species-specific affinity difference is nearly abolished, as ATPĪ³S significantly decreases the affinity of DrRecA for DNA. Other findings include that: (1) both proteins exhibit a dependence of binding affinity on the length of the ssDNA oligomer, but not the dsDNA oligomer; (2) the salt dependence of binding is modest for both species of RecA, and (3) in the absence of DNA, DrRecA produces significantly shorter and/or fewer free-filaments in solution than does EcRecA. The results suggest intrinsic biothermodynamic properties of DrRecA contribute directly to the more robust DNA repair capabilities of D. radiodurans
Immune features that afford protection from clinical disease versus sterilizing immunity to Bordetella pertussis infection in a nonhuman primate model of whooping cough
The respiratory bacterial infection caused by Bordetella pertussis (whooping cough) is the only vaccine-preventable disease whose incidence has been increasing over the last 3 decades. To better understand the resurgence of this infection, a baboon animal model of pertussis infection has been developed. NaĆÆve baboons that recover from experimental pertussis infection are resistant both to clinical disease and to airway colonization when re-challenged. In contrast, animals vaccinated with acellular pertussis vaccine and experimentally challenged do not develop disease, but airways remain colonized for 4-6 weeks. We explored the possibility that the IgG antibody response to pertussis infection is qualitatively different from antibodies induced by acellular pertussis vaccination.
IgG was purified from pertussis-convalescent baboons shown to be resistant to pertussis disease and airway colonization. Purified IgG contained high titers to pertussis toxin, pertactin, and filamentous hemagglutinin. This pertussis-immune IgG or control IgG was passively transferred to naĆÆve, juvenile baboons before experimental airway pertussis inoculation. The control animal that received normal IgG developed a typical symptomatic infection including leukocytosis, cough and airway colonization for 4 weeks. In contrast, baboons that received convalescent IgG maintained normal WBC counts and were asymptomatic. However, despite remaining asymptomatic, their airways were colonized for 4-6 weeks with B. pertussis. All animals developed IgG and IgA anti-pertussis antibody responses. Interestingly, the clearance of B. pertussis from airways coincided with the emergence of a serum anti-pertussis IgA response.
These studies demonstrate that passive administration of pertussis-specific IgG from previously infected animals can prevent clinical disease but does not affect prolonged airway colonization with B. pertussis. This outcome is similar to that observed following acellular pertussis vaccination. Understanding immune mechanismsāother than IgGāthat are capable of preventing airway colonization with B. pertussis will be critical for developing more effective vaccines to prevent whooping cough
The Energetics of Halogenated Ethylenes (Ethynes) and 1,3-Butadienes (Butadiynes): A Computational and Conceptual Study of Substituent Effects and āDimerizationā
The energetics of ethylenes and 1,3-butadienes may be interrelated by the reaction:
RHC=CH2 + H2C=CHR\u27 ā RHC=CHāCH=CHR\u27 + H2.
Shown earlier to be nearly enthalpically thermoneutral for a variety of hydrocarbon cases, we are now interested in the related energetics of halogenated alkenes and alkynes. Using quantum chemical calculations, we have studied this as recast as the isodesmic reactions:
2(H2C=CHX) + H2C=CHāCH=CH2 ā p,q-di-X-1,3-butadiene + 2H2C=CH2
2(HCā”CX) + HCā”CāCā”CH ā di-X-butadiyne + 2HCā”CH.
Here p,q- = 1,3-; 1,4- and 2,3- with X = F, Cl, Br, and I. The halogen and location-dependent deviations from near enthalpic thermoneutrality are discussed
Impaired Mitochondrial Fat Oxidation Induces FGF21 in Muscle
SummaryFatty acids are the primary fuel source for skeletal muscle during most of our daily activities, and impaired fatty acid oxidation (FAO) is associated with insulin resistance. We have developed a mouse model of impaired FAO by deleting carnitine palmitoyltransferase-1b specifically in skeletal muscleĀ (Cpt1bmā/ā). Cpt1bmā/ā mice have increased glucose utilization and are resistant to diet-induced obesity. Here, we show that inhibition of mitochondrial FAO induces FGF21 expression specifically in skeletal muscle. The induction of FGF21 in Cpt1b-deficient muscle is dependent on AMPK and Akt1 signaling but independent of the stress signaling pathways. FGF21 appears to act in a paracrine manner to increase glucose uptake under low insulin conditions, but it does not contribute to the resistance to diet-induced obesity
Ion acoustic wave experiments in a high school plasma physics laboratory
We describe a successful alliance between a university and several high schools. The alliance is centered on a laboratory experiment constructed by students and faculty. The experiment involves sophisticated concepts and equipment not readily available in high schools. Much of the experiment is directly related to the science and mathematics learned in high school, with opportunities to extend their understanding by applying it to a research experience. The experiment is in plasma physics, but a similar alliance can be implemented in any area of science. Although the number of high school students affected by any one alliance is small, the impact is potentially large in the scientific life of a participating student or teacher
Splenic peliosis with spontaneous splenic rupture: report of two cases
BACKGROUND: Peliosis is a rare condition characterised by multiple cyst-like, blood-filled cavities within the parenchyma of solid organs. Most commonly affecting the liver, isolated splenic peliosis is an even more unique phenomenon. Patients with the condition are often asymptomatic. However, this potentially lethal condition can present with spontaneous organ rupture. We present two such cases, discuss their management and review what is currently known in the existing literature. CASE PRESENTATION: A previously well twenty-six year old woman presented with abdominal pain following a trivial episode of coughing. A diagnosis of spontaneous splenic rupture was made following clinical and radiological examination. She underwent emergency splenectomy and made a full, uneventful recovery. Histopathological examination confirmed splenic peliosis. The second case describes an eighty six year old lady who sustained a trivial fall and developed pain in her left side. A CT confirmed splenic rupture. She became haemodynamically unstable during her admission and underwent emergency splenectomy. Histopathological examination revealed splenic peliosis. She went on to make an uneventful recovery. CONCLUSION: Splenic peliosis is very rare. It has a number of associations including immunosuppression, drug therapy and infection. Although patients are often asymptomatic, life-threatening spontaneous organ rupture may occur. If the diagnosis of peliosis is confirmed, additional investigations should be considered to detect its presence in other organs. Furthermore, the presence of the condition may be relevant if further medical or surgical intervention is planned
Role of N-Terminal Amino Acids in the Potency of Anthrax Lethal Factor
Anthrax lethal factor (LF) is a Zn+2-dependent metalloprotease that cleaves several MAPK kinases and is responsible for the lethality of anthrax lethal toxin (LT). We observed that a recombinant LF (LF-HMA) which differs from wild type LF (LF-A) by the addition of two residues (His-Met) to the native Ala (A) terminus as a result of cloning manipulations has 3-fold lower potency toward cultured cells and experimental animals. We hypothesized that the āN-end ruleā, which relates the half-life of proteins in cells to the identity of their N-terminal residue, might be operative in the case of LF, so that the N-terminal residue of LF would determine the cytosolic stability and thereby the potency of LF. Mutational studies that replaced the native N-terminal residue of LF with known N-end rule stabilizing or destabilizing residues confirmed that the N-terminal residue plays a significant role in determining the potency of LT for cultured cells and experimental animals. The fact that a commercially-available LF preparation (LF-HMA) that is widely used in basic research studies and for evaluation of vaccines and therapeutics is 3-fold less potent than native LF (LF-A) should be considered when comparing published studies and in the design of future experiments
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