Identifying characteristics of mentally ill homeless individuals who are successfully linked to health and social services post-incarceration via the jail inreach project

Healthcare for the Homeless—Houston (HHH) received a research grant from The Medallion Foundation, Inc. in March 2006 to pilot The Jail Inreach Project, an intensive “inreach” initiative to assess the impact of providing continuity of mental and primary health care services for homeless individuals who suffer from mental illness and/or substance abuse being released from jail. This pilot project was initiated by HHH, in collaboration with the Harris County Sheriff’s Office and the Mental Health Mental Retardation Authority of Harris County (MHMRA). Those who are flagged as “frequent flyers” and who are diagnosed with a mental illness are referred to the Jail Inreach Project. In order to maximize the effectiveness of the discharge plan, case managers offer the option of meeting the client at the time of release and bring them to the HHH clinic located four blocks from the jail. Participation in both the program and the option for direct release to the care of a case manager are voluntary.^ The purpose of this study is to determine the outcomes of the Jail Inreach Project and addresses the following objectives: (1) to evaluate the characteristics of inmates that chose to be released from jail to the direct care of an HHH case manager versus those who opt for self release and (2) to determine the number and percent of inmates that are linked to services and relationship with type of release (direct versus indirect), (3) to determine if there is a relationship between outcomes and characteristics and (4) to determine what outcomes are a function of release, controlling for characteristics. Statistical analysis, including frequencies, cross tabulations, chi-square and logistical regression, found that those who opt for self release are six times less likely to be successfully linked to services and that gender is the most significant predictor of choosing self release. Men are far more likely to opt for self release than women engaged in this program. These findings help inform policy and program design and development that addresses the difference in service utilization and successful linkage to services post-incarceration. Successful linkage to services, thus continuity of and access to care, further impact the effects of the revolving door phenomenon of mentally ill homeless individuals cycling between the streets, jails and hospital emergency centers.^

Endemic tuberculosis, the homeless, and public transportation: A merging of geographical information systems surveillance and the Houston Tuberculosis Initiative Surveillance project

To reach the goals established by the Institute of Medicine (IOM) and the Centers for Disease Control's (CDC) STOP TB USA, measures must be taken to curtail a future peak in Tuberculosis (TB) incidence and speed the currently stagnant rate of TB elimination. Both efforts will require, at minimum, the consideration and understanding of the third dimension of TB transmission: the location-based spread of an airborne pathogen among persons known and unknown to each other. This consideration will require an elucidation of the areas within the U.S. that have endemic TB. The Houston Tuberculosis Initiative (HTI) was a population-based active surveillance of confirmed Houston/Harris County TB cases from 1995–2004. Strengths in this dataset include the molecular characterization of laboratory confirmed cases, the collection of geographic locations (including home addresses) frequented by cases, and the HTI time period that parallels a decline in TB incidence in the United States (U.S.). The HTI dataset was used in this secondary data analysis to implement a GIS analysis of TB cases, the locations frequented by cases, and their association with risk factors associated with TB transmission. ^ This study reports, for the first time, the incidence of TB among the homeless in Houston, Texas. The homeless are an at-risk population for TB disease, yet they are also a population whose TB incidence has been unknown and unreported due to their non-enumeration. The first section of this dissertation identifies local areas in Houston with endemic TB disease. Many Houston TB cases who reported living in these endemic areas also share the TB risk factor of current or recent homelessness. Merging the 2004–2005 Houston enumeration of the homeless with historical HTI surveillance data of TB cases in Houston enabled this first-time report of TB risk among the homeless in Houston. The homeless were more likely to be US-born, belong to a genotypic cluster, and belong to a cluster of a larger size. The calculated average incidence among homeless persons was 411/100,000, compared to 9.5/100,000 among housed. These alarming rates are not driven by a co-infection but by social determinants. The unsheltered persons were hospitalized more days and required more follow-up time by staff than those who reported a steady housing situation. The homeless are a specific example of the increased targeting of prevention dollars that could occur if TB rates were reported for specific areas with known health disparities rather than as a generalized rate normalized over a diverse population. ^ It has been estimated that 27% of Houstonians use public transportation. The city layout allows bus routes to run like veins connecting even the most diverse of populations within the metropolitan area. Secondary data analysis of frequent bus use (defined as riding a route weekly) among TB cases was assessed for its relationship with known TB risk factors. The spatial distribution of genotypic clusters associated with bus use was assessed, along with the reported routes and epidemiologic-links among cases belonging to the identified clusters. ^ TB cases who reported frequent bus use were more likely to have demographic and social risk factors associated with poverty, immune suppression and health disparities. An equal proportion of bus riders and non-bus riders were cultured for Mycobacterium tuberculosis, yet 75% of bus riders were genotypically clustered, indicating recent transmission, compared to 56% of non-bus riders (OR=2.4, 95%CI(2.0, 2.8), p<0.001). Bus riders had a mean cluster size of 50.14 vs. 28.9 (p<0.001). Second order spatial analysis of clustered fingerprint 2 (n=122), a Beijing family cluster, revealed geographic clustering among cases based on their report of bus use. Univariate and multivariate analysis of routes reported by cases belonging to these clusters found that 10 of the 14 clusters were associated with use. Individual Metro routes, including one route servicing the local hospitals, were found to be risk factors for belonging to a cluster shown to be endemic in Houston. The routes themselves geographically connect the census tracts previously identified as having endemic TB. 78% (15/23) of Houston Metro routes investigated had one or more print groups reporting frequent use for every HTI study year. We present data on three specific but clonally related print groups and show that bus-use is clustered in time by route and is the only known link between cases in one of the three prints: print 22. (Abstract shortened by UMI.)^

Targeting AKT/mTOR Signaling Pathways During Murine Skin Tumor Promotion and the Impact of Dietary Energy Balance Manipulation

The prevalence of obesity has continued to rise over the last several decades in the United States lending to overall increases in risk for chronic diseases including many types of cancer. In contrast, reduction in energy consumption via calorie restriction (CR) has been shown to be a potent inhibitor of carcinogenesis across a broad range of species and tumor types. Previous data has demonstrated differential signaling through Akt and mTOR via the IGF-1R and other growth factor receptors across the diet-induced obesity (DIO)/CR spectrum. Furthermore, mTORC1 is known to be regulated directly via nutrient availability, supporting its role in the link between epithelial carcinogenesis and diet-induced obesity. In an effort to better understand the importance of mTORC1 in the context of both positive and negative energy balance during epithelial carcinogenesis, we have employed the use of specific pharmacological inhibitors, rapamycin (mTORC1 inhibitor) and metformin (AMPK activator) to target mTORC1 or various components of this pathway during skin tumor promotion. Two-stage skin carcinogenesis studies demonstrated that mTORC1 inhibition via rapamycin, metformin or combination treatments greatly inhibited skin tumor development in normal, overweight and obese mice. Furthermore, mechanisms by which these chemopreventive agents may be exerting their anti-tumor effects were explored. In addition, the effect of these compounds on the epidermal proliferative response was analyzed and drastic decreases in epidermal hyperproliferation and hyperplasia were found. Rapamycin also inhibited dermal inflammatory cell infiltration in a dose-dependent manner. Both compounds also blocked or attenuated TPA-induced signaling through epidermal mTORC1 as well as several downstream targets. In addition, inhibition of this pathway by metformin appeared to be, at least in part, dependent on AMPK activation in the skin. Overall, the data indicate that pharmacological strategies targeting this pathway offset the tumor-enhancing effects of DIO and may serve as possible CR mimetics. They suggest that mTORC1 contributes significantly to the process of skin tumor promotion, specifically during dietary energy balance effects. Exploiting the mechanistic information underlying dietary energy balance responsive pathways will help translate decades of research into effective strategies for prevention of epithelial carcinogenesis.

Evidence that lymphokine -activated killer (LAK) cell function is regulated by both serine and tyrosine kinase pathways

Signal transduction pathways operative in lymphokine activated killer (LAK) cells during execution of cytolytic function have never been characterized. Based on ubiquitous involvement of protein phosphorylation in activation of cytolytic mechanisms used by CTL and NK cells, it was hypothesized that changes in protein phosphorylation should occur when LAK encounter tumor targets. It was further hypothesized that protein kinases would regulate LAK-mediated cytotoxicity. Exposure to either SK-Mel-1 (melanoma) or Raji (lymphoma) targets consistently led to increased phosphorylation of two 65-kD LAK proteins pp65a and -b, with isoelectric points (pI) of 5.1 and 5.2 respectively. Increased p65 phosphorylation was initiated between 1 and 5 min after tumor coincubation, occurred on Ser residues, required physical contact between LAK and tumors, correlated with target recognition, and also occurred after crosslinking Fc$\gamma$RIIIA in the absence of tumors. Both pp65a and -b were tentatively identified as phosphorylated forms of the actin-bundling protein L-plastin, based on pI, molecular weight, and cross-reactivity with specific antiserum. The known biochemical properties of L-plastin suggest it may be involved in regulating adhesion of LAK to tumor targets. The protein tyrosine kinase-specific inhibitor Herb A did not block p65 phosphorylation, but blocked LAK killing of multiple tumor targets at a post-binding stage. Greater than 50% inhibition of cytotoxicity was observed after a 2.5-h pretreatment with 0.125 $\mu$g/ml Herb A. Inhibition occurred over a period in pretreatment which LAK were not dependent upon IL-2 for maintenance of killing activity, supporting the conclusion that the drug interfered with mobilization of cytotoxic function. Granule exocytosis measured by BLT-esterase release from LAK occurred after coincubation with tumors, and was inhibited by Herb A LAK cytotoxicity was dependent upon extracellular calcium, suggesting that granule exocytosis rather than Fas ligand was the principal pathway leading to target cell death. The data indicate that protein tyrosine kinases play a pivotal role in LAK cytolytic function by regulating granule exocytosis, and that tumor targets can activate an adhesion dependent Ser kinase pathway in LAK resulting in phosphorylation of L-plastin. ^

Activation of matrix metalloproteinase -9 (MMP-9) by heregulin in human breast cancer cells involves multiple signaling pathways

Matrix metalloproteinase-9 (MMP-9) plays an important role in tumor invasion and angiogenesis. Secretion of MMP-9 has been reported in various cancer types including lung cancer, brain cancer, colon cancer, and breast cancer. Heregulin is a growth factor that regulates growth and differentiation of normal breast cells as well as mammary tumor cells. To study the role of heregulin in breast cancer metastasis, we tested whether heregulin may regulate MMP-9 secretion. By screening a panel of breast cancer cell line for their ability to respond to heregulin and produce MMP-9, we have found that MMP-9 secretion can be induced by heregulin-β1 in two breast cancer cell lines, SKBr3 and MCF-7. In both cell lines, increase of MMP-9 activity as shown by zymography was accompanied by increased protein level as well as mRNA level of MMP-9. Using a reporter luciferase assay, we have identified that proximal −670bp promoter of MMP-9 had similar activity to a 2.2kb MMP-9 promoter in response to heregulin stimulation. Heregulin treatment of SKBr3 and MCF-7 activated multiple signaling pathways inside cells. These include the Erk pathway, the p38 kinase pathway, PKC pathway, and PI-3K pathway. To examine which pathways are involved in MMP-9 activation by heregulin, we have used a panel of chemical inhibitors to specifically inhibit each one of these pathways. Ro-31-8220 (PKC inhibitor) and SB203580 (p38 kinase inhibitor) completely blocked heregulin activation of MMP-9. On the other hand, PD098059 (MEK-1 inhibitor) partially blocked MMP-9 activation, whereas PI-3K inhibitor, wortmannin, had no effect. Therefore, at least three signaling pathways are involved in activation of MMP-9 by heregulin. Since MMP-9 is tightly associated with metastatic potential, our study also suggests that heregulin may enhance breast tumor metastasis through induction of MMP-9 expression. ^

Signaling pathways in the transcriptional and post-translational regulation of the human glutathione S -transferase P1 gene

The human glutathione S-transferase P1 (GSTP1) protein is an endogenous inhibitor of c-jun N-terminal kinases (JNKs) and an important phase II detoxification enzyme. ^ Recent identification of a cAMP response element (CRE) in the 5 ′-region of the human GSTP1 gene and several putative phosphorylation sites for the Ser/Thr protein kinases, including, cAMP-dependent protein kinases (PKAs), protein kinases C (PKCs), and JNKs in the GSTP1 protein raised the possibility that signaling pathways may play an important role in the transcriptional and post-translational regulation of GSTP1 gene. This study examined (a) whether the signaling pathway mediated by CAMP, via the GSTP1 CRE, is involved in the transcriptional regulation of the GSTP1 gene, (b) whether signaling pathways mediated by the Ser/Thr protein kinases (PKAs, PKCs, and JNKs) induce post-translational modification, viz. phosphorylation of the GSTP1 protein, and (c) whether such phosphorylation of the GSTP1 protein alters its functions in metabolism and in JNK signaling. ^ The first major finding in this study is the establishment of the human GSTP1 gene as a novel CAMP responsive gene in which transcription is activated via an interaction between PKA activated CRE binding protein-1 (CREB-1) and the CRE in the 5′-regulatory region. ^ The second major finding in this study is the observation that the GSTP1 protein undergoes phosphorylation and functionally activated by second messenger-activated protein kinases, PKA and PKC, in tumor cells with activated signaling pathways. Following phosphorylation by PKA or PKC, the catalytic activity of the GSTP1 protein was significantly enhanced, as indicated by a decrease in its Km (2- to 3.6-fold) and an increase in Kcat/ Km (1.6- to 2.5-fold) for glutathione. Given the frequent over-expression of GSTP1 and the aberrant PKA/PKC signaling cascade observed in tumors, these findings suggest that phosphorylation of GSTP1 may contribute to the malignant progression and drug-resistant phenotype of these tumors. ^ The third major finding in this study is that the GSTP1 protein, an inhibitor of JNKs, undergoes significant phosphorylation in tumor cells with activated JNK signaling pathway and in those under oxidative stress. Following phosphorylation by JNK, the ability of GSTP1 to inhibit JNK downstream function, i.e. c-jun phosphorylation, was significantly enhanced, suggesting a feedback mechanism of regulation of JNK-mediated cellular signaling. (Abstract shortened by UMI.) ^

Constitutively active cAMP receptor mutants dominantly inhibit receptor-mediated signaling pathways in Dictyostelium discoideum

Dictyostelium, a soil amoeba, is able to develop from free-living cells to multicellular fruiting bodies upon starvation using extracellular cAMP to mediate cell-cell communication, chemotaxis and developmental gene expression. The seven transmembrane G protein-coupled cAMP receptor-1 (cAR1) mediated responses, such as the activation of adenylyl cyclase and guanylyl cyclase, are transient, due to the existence of poorly understood adaptation mechanisms. For this dissertation, the powerful genetics of the Dictyostelium system was employed to study the adaptation mechanism of cAR1-mediated cAMP signaling as well as mechanisms intrinsic to cAR1 that regulate its activation. ^ We proposed that constitutively active cAR1 would cause constant adaptation, thus inhibiting downstream pathways that are essential for aggregation and development. Therefore, a screen for dominant negative cAR1 mutants was undertaken to identify constitutively active receptor mutants. Three dominant negative cAR1 mutants were identified. All appear to be constitutively active receptor mutants because they are constitutively phosphorylated and possess high affinity for cAMP. Biochemical studies showed that these mutant receptors prevented the activation of downstream effectors, including adenylyl and guanylyl cyclases. In addition, these cells also were defective in cAMP chemotaxis and cAR1-mediated gene expression. These findings suggest that the mutant receptors block development by constantly activating multiple adaptation pathways. ^ Sequence analysis revealed that these mutations (I104N, L100H) are clustered in a conserved region of the third transmembrane helix (TM3) of cAR1. To investigate the role of this region in receptor activation, one of these residues, I104, was mutated to all the other 19 possible amino acids. We found that all but the most conservative substitutions increase the receptor's affinity about 20- to 70-fold. However, only highly polar substitutions of I104, particularly basic residues, resulted in receptors that are constitutively phosphorylated and dominantly inhibit development, suggesting that highly polar substitutions not only disrupt an interaction constraining the receptor in its low-affinity, inactive state but also promote an additional conformational change that resembles the ligand-bound conformation. Our findings suggest that I104 plays a specific role in constraining the receptor in its inactive state and that substituting it with highly polar residues results in constitutive activation. ^

Pathways leading to apoptosis resistance in a murine B -cell lymphoma cell system

The aberrant activation of signal transduction pathways has long been linked to uncontrolled cell proliferation and the development of cancer. The activity of one such signaling module, the Mitogen-Activated Protein Kinase (MAPK) pathway, has been implicated in several cancer types including pancreatic, breast, colon, and lymphoid malignancies. Interestingly, the activation of MAP-Kinase-Kinase-Kinase proteins often leads to the additional activation of NF-κB, a transcription factor that acts as a cell survival signal through its control of antiapoptotic genes. We have investigated the role of a specific dimer form of the NF-κB transcription factor family, NF-κB1 (p50) homodimers, in its control of the proto-oncogene, Bcl-2, and we have identified the MEK/ERK (MAPK) signaling cascade as a mediator of NF-κB1 activity. ^ Two murine B cell lymphoma cell lines were used for these studies: LY-as, an apoptosis proficient line with low Bcl-2 protein expression and no nuclear NF-κB activity, and LY-ar, a nonapoptotic line with constitutive p50 homodimer activity and 30 times more Bcl-2 protein expression than LY-as. Experiments modulating p50 activity correlated the activation of p50 homodimers with Bcl-2 expression and additional gel shift experiments demonstrated that the Bcl-2 P1 promoter had NF-κB sites with which recombinant p50 was able to interact. In vitro transcription revealed that p50 enhanced the production of transcripts derived from the Bcl-2 P1 promoter. These data strongly suggest that Bcl-2 is a target gene for p50-mediated transcription and suggest that the activation of p50 homodimers contributes to the expression of Bcl-2 observed in LY-ar cells. ^ Studies of upstream MAPK pathways that could influence NF-κB activity demonstrated that LY-ar cells had phosphorylated ERK proteins while LY-as cells did not. Treatment of LY-ar cells with the MEK inhibitors PD 98059, U0126, and PD 184352 led to a loss of phosphorylated ERK, a reversal of nuclear p50 homodimer DNA binding, and a decrease in the amount of Bcl-2 protein expression. Similarly, the activation of the MEK/ERK pathway in LY-as cells by phorbol ester led to Bcl-2 expression that could be blocked by PD 98059. Furthermore, treatment of LY-ar cells with TNFα, an IKK activator, did not change the suppressive effect of PD 98059 on p50 homodimer activity, suggesting an IKK-independent pathway for p50 homodimer activation. Lastly, all three MEK inhibitors sensitized LY-ar cells to radiation-induced apoptosis. ^ These data indicate that the activation of the MEK/ERK MAP-Kinase signaling pathway acts upstream of p50 homodimer activation and Bcl-2 expression in this B cell lymphoma cell system and suggest that the activation of MEK/ERK may be a key step in the progression of lymphoma to advanced-staged disease. Other researchers have used MEK inhibitors to inhibit cell growth and sensitize a number of tumors to chemotherapies. In light of our data, MEK inhibitors may additionally be useful clinically to radiosensitize cancers of lymphoid origin. ^

Using K5 Myc transgenic mice to delineate *Myc's apoptotic and tumorigenic pathways

The c-myc oncogene has the unusual ability to induce proliferation and apoptosis. Transgenic mice have been generated in which the expression of Myc is under the control of an epithelial-specific keratin 5 (K5) promoter. These mice have increased levels of proliferation and p53-dependent apoptosis, and are predisposed to developing spontaneous tumors in epithelial tissues. In this study, various knockout mice were bred to K5 Myc transgenic mice to identify factors involved in the aberrant apoptosis, hyperproliferation, and spontaneous tumorigenesis present in these mice. Consistent with in vitro studies, Myc-induced, p53-dependent apoptosis in transgenic epidermis was found to be partially dependent on p19ARF, a p53 regulator that inhibits mdm2. Additionally, the rate of tumorigenesis was increased when p19ARF was absent in Myc transgenic mice. Consistent with previous reports that some E2F family members may function as tumor suppressors, inactivation of either E2f1 or E2f2 was found to accelerate tumor development in the K5 Myc transgenic mice. Acceleration of tumorigenesis in the absence of E2F1 occurred despite the fact that apoptotic levels were increased in transgenic tissue and tumors null for E2f1 , whereas hyperproliferation was unaffected. In contrast, inactivation of E2f2 was found to increase hyperproliferation in the K5 Myc transgenic mice, while having no effect on apoptosis. The lack of E2f1 in the Myc transgenic mice increased the expression of several p53 transcription target genes, which may explain the increased apoptosis in these mice. In transgenic epidermis, p53 is phosphorylated at serine 18, a site of phosphorylation by ATM. Inactivation of ATM in K5 Myc transgenic mice impaired Myc-induced apoptosis, identifying ATM as having an important role in Myc-induced apoptosis. Moreover, the absence of ATM accelerates tumorigenesis in K5-expressing tissues. However, p53 accumulation and phosphorylation at serine 18 induced by Myc occurs independent of ATM. Therefore, another activity of ATM appears to be important for Myc-induced apoptosis. These findings show that acceleration of tumorigenesis in K5 Myc transgenic mice, as in the case of p53, p19ARF, E2F1, E2F2, and ATM absence, does not necessarily correlate with suppression of Myc-induced apoptosis, as seen only when p53, p19ARF or ATM was absent. ^

Molecular mechanism of the relaxin signaling pathways: Activation of cAMP, PI3K, and PKCzeta

Relaxin is a polypeptide hormone that has diverse effects on reproductive and non-reproductive tissues. Relaxin activates the G-protein coupled receptors, LGR7 and LRG8. Early studies described increased cAMP and protein kinase A activity upon relaxin treatment, but cAMP accumulation alone could not account for all of the relaxin-mediated effects. We utilized the human monocyte cell line THP-1 to study the mechanism of relaxin-stimulated CAMP production. ^ Relaxin treatment in THP-1 cells produces a biphasic time course in cAMP accumulation, where the first peak appears as early as 1–2 minutes with a second peak at 10–20 minutes. Selective inhibitors for phosphoinositide 3-kinase (P13K), such as wortmannin and LY294002, show a dose-dependent inhibition of relaxin-stimulated cAMP accumulation, specific for the second peak of the relaxin time course. Neither the effects of relaxin nor the inhibition of relaxin by LY294002 is mediated by the activity of phosphodiesterases. Furthermore, LY294002 blocks upregulation of vascular endothelial growth factor transcript levels by relaxin. ^ To further delineate relaxin signaling pathways, we searched for downstream targets of PI3K that could activate adenylyl cyclase (AC). Protein kinase C ζ (PKCζ) was a prime candidate because it activates types II and V AC. Chelerythrine chloride (a general PKC inhibitor) inhibits relaxin-induced cAMP production to the same degree as LY294002 (∼40%). Relaxin stimulates PKCζ translocation to the plasma membrane in THP-1, MCF-7, PHM1-31, and MMC cells, as shown by immunocytochemistry. PKCζ translocation is P13K-dependent and independent of cAMP production. Antisense PKCζ oligodeoxynucleotides (PKCζ-ODNs) deplete both PKCζ transcript and protein levels in THP-1 cells. PKCζ-ODNs abolish relaxin-mediated PKCζ translocation and inhibit relaxin stimulation of cAMP by 40%, as compared to mock and random ODN controls. Treatment with LY294002 in the presence of PKCζ-ODNs results in little further inhibition. Taken together, we present a novel role for PI3K and PKCζ in relaxin stimulation of cAMP and provide the first example of the PKCζ regulation of AC in an endogenous system. Furthermore, we have identified higher order complexes of AC isoforms and PKA anchoring proteins in attempts to explain the differential coupling of relaxin to cAMP and PI3K-signaling pathways in various cell types. ^

Ocean acidification weakens the immune response of blood clam through hampering the NF-kappa beta and toll-like receptor pathways

The impact of pCO2 driven ocean acidification on marine bivalve immunity remains poorly understood. To date, this impact has only been investigated in a few bivalve species and the underlying molecular mechanism remains unknown. In the present study, the effects of the realistic future ocean pCO2 levels (pH at 8.1, 7.8, and 7.4) on the total number of haemocyte cells (THC), phagocytosis status, blood cell types composition, and expression levels of twelve genes from the NF-kappa beta signaling and toll-like receptor pathways of a typical bottom burrowing bivalve, blood clam (Tegillarca granosa), were investigated. The results obtained showed that while both THC number and phagocytosis frequency were significantly reduced, the percentage of red and basophil granulocytes were significantly decreased and increased, respectively, upon exposure to elevated pCO2. In addition, exposure to pCO2 acidified seawater generally led to a significant down-regulation in the inducer and key response genes of NF-kappa beta signaling and toll-like receptor pathways. The results of the present study revealed that ocean acidification may hamper immune responses of the bivalve T. granosa which subsequently render individuals more susceptible to pathogens attacks such as those from virus and bacteria.

Reaction pathways in the solid state synthesis of multiferroic BiFeO 3

The obtaining of multiferroicBiFeO3 as a pure single-phase product is particularly complex since the formation of secondary phases seems to be unavoidable. The process by which these secondary impurities are formed is studied by analyzing the diffusion and solidstate reactivity of the Bi2O3–Fe2O3 system. Experimental evidence is reported which indicates that the progressive diffusion of Bi3+ ions into the Fe2O3 particles governs the solidstatesynthesis of the perovskite BiFeO3 phase. However a competition is established between the diffusion process which tends to complete the formation of BiFeO3, and the crystallization of stable Bi2Fe4O9 mullite crystals, which tend to block that formation reaction.

Sources and pathways of trace elements in urban environments: A multielemental qualitative approach

A geochemical model of an urban environment is presented in which multielemental tracers are used to characterise the circulation of trace elements in particulate matter_atmospheric aerosol, street dust and urban soil, within a city.

Reaction pathways in the solid state synthesis of multiferroic BiFeO3

The obtaining of multiferroic BiFeO3 as a pure single-phase product is particularly complex since the formation of secondary phases seems to be unavoidable. The process by which these secondary impurities are formed is studied by analyzing the diffusion and solid state reactivity of the Bi2O3?Fe2O3 system. Experimental evidence is reported which indicates that the progressive diffusion of Bi3+ ions into the Fe2O3 particles governs the solid state synthesis of the perovskite BiFeO3 phase. However a competition is established between the diffusion process which tends to complete the formation of BiFeO3, and the crystallization of stable Bi2Fe4O9 mullite crystals, which tend to block that formation reaction.

Pathways towards the integration of periurban agrarian ecosystems into the spatial planning system

The potential of periurban agrarian ecosystems is recognized as one of the cornerstones for improving urban sustainability; however, this potential has been disregarded in spatial planning and decision making. The main goal of the PAEc-SP project was to assess the feasibility of integrating periurban agricultural areas into spatial planning by developing a viable ecosystem services-based methodology