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Folk housing is one of the elements of material culture which geographers often employ in understanding the cultural aspects of regional studies. As one of the most obvious features of the cultural landscape, folk housing serves as a tool in the determination of culturogeographic regions, the final objective of this study. In this atomistic regional approach, geometry is the principle feature of interest. In other words, the one-dimensional plan type and the three-dimensional form class are the elements of focus in order to distinguish regionality. As opposed to other sub-systems of structural analysis, geometry, especially house from, distinguishes regions of influence and surpasses both environmental and socioeconomic barriers. Once a part of New Spain's vast northern frontier, the northeast Mexican borderlands—presently the states of Coahuila, Nuevo León, and Tamaulipas—became characterized as a buffer zone between two major colonizing cultures. The mixing of influences of these two nations, the Spanish—later the Mexicans—from the South and the Anglo-Americans—among other European immigrants—from the North, perhaps has become most apparent through time in the cultural landscape. To add to these two major ethnic groups are Native Americans, namely the Tlaxcalan and Huastec cultures, the latter a northern extension of the Maya-Quiché group. Northeastern Mexico's folk architecture clearly represents these major cultural elements. The purpose of this dissertation is to provide one important component that would contribute to an ultimate determination of northeastern Mexico's culturogeographic regions and, thus, to better understand the geographic expression of culture. Due to the persistence of traditional modes of life in this region, as in the rest of Mexico, the folk house seems to be an adequate tool in which to accomplish such a task. For these reasons, this can be considered a region worthy of regional culturogeographic research, as the existence of folk dwellings is still highly visible here, despite proximity to an industrialized nation such as the United States and the industrial zones of Mexico itself.

Does trade with non-market economies (NMEs) raise special welfare concerns for the importing market economy? Based on theoretical analysis, statistical testing and case studies, this dissertation concludes that the evidence does not support the hypothesis that NME trade is particularly destabilizing to importing countries. The thesis first shows that the importing country gains from trade even when foreign goods are priced \"artificially\" due to dumping or subsidies. Stressing that these results assume a reasonably steady pattern of import supply and pricing, the study asks whether an investigation into the exporting country's economic organization might help predict the relative stability of future exports. If the exporting country's allocation mechanism or systemic objectives suggest tendencies toward erratic fluctuations in export volume or price, a persuasive case can be made to limit imports from such countries. Analyzing the cost and pricing standards and foreign trade systems of NMEs, the thesis inquires whether discriminatory trade restrictions on NME exports are justified on welfare grounds. Theoretically the analysis demonstrates first, that charges of NME \"dumping\" are unfounded and second, why the phenomenon of \"crisis exports\"--forced selling at depressed prices--is unlikely. Furthermore, using United Nations data the study compares market share variations of NME exporters against other major exporters in world commodity markets. Rather than exhibiting a pronounced volatility for the period 1965-81, East European and Soviet market shares demonstrate greater stability than that of any other single exporting bloc. Therefore, the study concludes that NMEs do not appear to differ from market economies in a way detrimental to an importing country in their desire to, or demonstrated behavoir in, disrupting markets. The thesis then examines a secondary question: Regardless of injury to import-competing producers, do conceptually sound, objective tests exist for establishing the \"fair value\" of NME exports? An analysis of the arguments in Polish Golf Carts--in which the U.S. developed a \"constructed value\" basis for verifying dumping--and in the case of Chinese textiles--where the People's Republic is accused of subsidizing exports through the maintenance of dual exchange rates--shows these arguments to be theoretically weak and empirically unsubstantiated.

Most evidence of the association between maternal depression and children's development is limited by being cross-sectional. To date, few studies have modelled trajectories of maternal depressive symptoms from pregnancy through the early postpartum years and examined their association with social emotional and behavior functioning in preschool children. The objectives of this study were to: 1) identify distinct groups of women defined by their trajectories of depressive symptoms across four time points from mid-pregnancy to one year postpartum; and 2) examine the associations between these trajectories and child internalizing and externalizing behaviors. We analyzed data from the All Our Families (AOF) study, a large, population based pregnancy cohort of mother-child dyads in Alberta, Canada. The AOF study is an ongoing pregnancy cohort study designed to investigate relationships between the prenatal and early life period and outcomes for children and mothers. Maternal depressive symptoms were assessed using the Edinburgh Postnatal Depression Scale. Children's behavioral functioning at age 3 was assessed using the Behavior Scales developed for the Canadian National Longitudinal Survey of Children and Youth. Longitudinal latent class analysis was conducted to identify trajectories of women's depressive symptoms across four time points from pregnancy to 1 year postpartum. We used multivariable logistic regression to assess the relationship between trajectories of maternal depressive symptoms and children's behavior, while adjusting for other significant maternal, child and psychosocial factors. 1983 participants met eligibility criteria. We identified four distinct trajectories of maternal depressive symptoms: low level (64.7%); early postpartum (10.9%); subclinical (18.8%); and persistent high (5.6%). In multivariable models, the proportion of children with elevated behavior symptoms was highest for children whose mothers had persistent high depressive symptoms, followed by mothers with moderate symptoms (early postpartum and subclinical trajectories) and lowest for minimal symptoms. After accounting for demographic, child and psychosocial factors, the relationships between depression trajectories and child hyperactivity/inattention, physical aggression (subclinical trajectory only) and separation anxiety symptoms remained significant. These findings suggest both externalizing and internalizing children's behaviors are associated with prolonged maternal depressive symptoms. There is a good case for the need to move beyond overly simplistic clinical cutoff approaches of depressed/not depressed in screening for perinatal depression. Women with elevated depressive symptoms at clinical and subclinical levels need to be identified, provided with evidence-based treatment, and monitored with repeat screening to improve maternal mental health outcomes and reduce the risk of associated negative outcomes on children's early social-emotional and behavior development.

Abstract Rationale Simvastatin inhibits inflammatory responses in vitro and in murine models of lung inflammation in vivo. As simvastatin modulates a number of the underlying processes described in acute lung injury (ALI), it may be a potential therapeutic option. Objectives To investigate in vivo if simvastatin modulates mechanisms important in the development of ALI in a model of acute lung inflammation induced by inhalation of lipopolysaccharide (LPS) in healthy human volunteers. Methods Thirty healthy subjects were enrolled in a double-blind, placebo-controlled study. Subjects were randomized to receive 40 mg or 80 mg of simvastatin or placebo (n = 10/group) for 4 days before inhalation of 50 μg LPS. Measurements were performed in bronchoalveolar lavage fluid (BALF) obtained at 6 hours and plasma obtained at 24 hours after LPS challenge. Nuclear translocation of nuclear factor-κB (NF-κB) was measured in monocyte-derived macrophages. Measurements and Main Results Pretreatment with simvastatin reduced LPS-induced BALF neutrophilia, myeloperoxidase, tumor necrosis factor-α, matrix metalloproteinases 7, 8, and 9, and C-reactive protein (CRP) as well as plasma CRP (all P < 0.05 vs. placebo). There was no significant difference between simvastatin 40 mg and 80 mg. BALF from subjects post-LPS inhalation induced a threefold up-regulation in nuclear NF-κB in monocyte-derived macrophages (P < 0.001); pretreatment with simvastatin reduced this by 35% (P < 0.001). Conclusions Simvastatin has antiinflammatory effects in the pulmonary and systemic compartment in humans exposed to inhaled LPS. Clinical trial registered with www.controlled-trials.com (ISRCTN21056528).

The vast boreal biome plays an important role in the global carbon cycle but is experiencing particularly rapid climate warming, threatening the integrity of valued ecosystems and their component species. We developed a framework and taxonomy to identify climate-change refugia potential in the North American boreal region, summarizing current knowledge regarding mechanisms, geographic distribution, and landscape indicators. While “terrain-mediated” refugia will mostly be limited to coastal and mountain regions, the ecological inertia (resistance to external fluctuations) contained in some boreal ecosystems may provide more extensive buffering against climate change, resulting in “ecosystem-protected” refugia. A notable example is boreal peatlands, which can retain high surface soil moisture and water tables even in the face of drought. Refugia from wildfire are also especially important in the boreal region, which is characterized by active disturbance regimes. Our framework will help identify areas of high refugia potential, and inform ecosystem management and conservation planning in light of climate change.

Therapeutics based on short interfering RNAs (siRNAs) delivered to hepatocytes have been approved, but new delivery solutions are needed to target additional organs. Here we show that conjugation of 2′- O -hexadecyl (C16) to siRNAs enables safe, potent and durable silencing in the central nervous system (CNS), eye and lung in rodents and non-human primates with broad cell type specificity. We show that intrathecally or intracerebroventricularly delivered C16-siRNAs were active across CNS regions and cell types, with sustained RNA interference (RNAi) activity for at least 3 months. Similarly, intravitreal administration to the eye or intranasal administration to the lung resulted in a potent and durable knockdown. The preclinical efficacy of an siRNA targeting the amyloid precursor protein was evaluated through intracerebroventricular dosing in a mouse model of Alzheimer’s disease, resulting in amelioration of physiological and behavioral deficits. Altogether, C16 conjugation of siRNAs has the potential for safe therapeutic silencing of target genes outside the liver with infrequent dosing. Lipophilic siRNA conjugates exert therapeutic activity in the mouse CNS.

Abstract Patients who undergo surgical resection of brain metastases are at significant risk of cavity local recurrence without additional radiation therapy. Postoperative stereotactic radiosurgery (SRS) is a method of focal treatment to the cavity to maximize local control while minimizing the risk of neurocognitive detriment associated with whole brain radiation therapy. Recently published randomized trials have demonstrated the benefit of postoperative SRS in terms of cavity tumor control and preserving neurocognition. However, there are several potential drawbacks with postoperative SRS including a possible increase in symptomatic radiation necrosis because of the need for cavity margin expansion due to target delineation uncertainty, the variable postoperative clinical course and potential delay in administering postoperative SRS, and the theoretical risk of tumor spillage into cerebrospinal fluid at the time of surgery. Preoperative SRS is an alternative paradigm wherein SRS is delivered prior to surgical resection, which may effectively address some of these potential drawbacks. The goal of this review is to examine the rationale, technique, outcomes, evidence, and future directions for the use of SRS as an adjunct to surgical resection. This can be delivered as either preoperative or postoperative SRS with potential advantages and disadvantages to both approaches that will be discussed.

Activating mutations in cytokine receptors and transcriptional regulators govern aberrant signal transduction in T‐cell lineage acute lymphoblastic leukemia (T‐ALL). However, the roles played by suppressors of cytokine signaling remain incompletely understood. We examined the regulatory roles of suppressor of cytokine signaling 5 (SOCS5) in T‐ALL cellular signaling networks and leukemia progression. We found that SOCS5 was differentially expressed in primary T‐ALL and its expression levels were lowered in HOXA‐deregulated leukemia harboring KMT2A gene rearrangements. Here, we report that SOCS5 expression is epigenetically regulated by DNA methyltransferase‐3A‐mediated DNA methylation and methyl CpG binding protein‐2‐mediated histone deacetylation. We show that SOCS5 negatively regulates T‐ALL cell growth and cell cycle progression but has no effect on apoptotic cell death. Mechanistically, SOCS5 silencing induces activation of JAK‐STAT signaling, and negatively regulates interleukin‐7 and interleukin‐4 receptors. Using a human T‐ALL murine xenograft model, we show that genetic inactivation of SOCS5 accelerates leukemia engraftment and progression, and leukemia burden. We postulate that SOCS5 is epigenetically deregulated in T‐ALL and serves as an important regulator of T‐ALL cell proliferation and leukemic progression. Our results link aberrant downregulation of SOCS5 expression to the enhanced activation of the JAK‐STAT and cytokine receptor‐signaling cascade in T‐ALL. Suppressor of cytokine signaling 5 (SOCS5) is differentially expressed in T‐cell lineage acute lymphoblastic leukemia (T‐ALL), and its expression levels are lowered in HOXA‐deregulated leukemia harboring KMT2A gene rearrangements. SOCS5 is epigenetically regulated by DNA methyltransferase‐3A‐mediated DNA methylation and methyl CpG binding protein‐2‐mediated histone deacetylation. Epigenetic silencing of SOCS5 potentiates interleukin‐7 receptor/JAK‐STAT signal transduction and T‐ALL progression.