Syllabus: Urban Policies

This class focuses on a significant and far-reaching federal policy, The Fair Housing Act (FHA), as a springboard to explore many facets of urban life and policy. The purpose of the FHA is to enable all people, regardless of race, religion, disability, national origin, sex, age or the presence of children under 18 in the family (plus other characteristics enacted by states and municipalities) the right to rent, buy and enjoy housing in any neighborhood they can afford. We explore how US cities and towns became segregated as a context for exploring other social policies including, but not limited to, housing, education, health, immigration, zoning, transportation, environmental justice, food security, industrial development, voting and predatory lending. With this foundation, we complete a project with the Massachusetts Fair Housing Center (MFHC). MFHC will use our work to inform their fair housing program. In addition, MFHC will train everyone to be a fair housing tester as a precursor to doing testing for them and helping with the analysis of those tests. In the Spring 2014 semester, students from this class organized, and got approved, a new UMass Registered Student Organization (RSO), Students for Fair Housing. We will help carry on that work. By the end of the term you will have a firm understanding of the implicit and explicit policies that created the ethnic and racial demographic distributions of the U.S., the importance of access to housing of choice, jobs, recreation, etc. and the profound implications of not having access. You will also have the satisfaction of knowing your class work will help inform the work of MFHC and provide you with valuable experience for your resume

Identification and characterisation of a novel mechanism of antibiotic resistance

Daptomycin is a bactericidal antibiotic of last resort for serious infections caused by methicillin-resistant Staphylococcus aureus (MRSA). Although resistance is rare, treatment failure can occur in >20% of cases and so there is a pressing need to identify and mitigate factors that contribute to poor therapeutic outcomes. Work described in this thesis revealed that loss of the Agr quorum-sensing system, which frequently occurs in clinical isolates, enhanced S. aureus survival during daptomycin treatment. Wild-type S. aureus was killed rapidly by daptomycin but Agr-defective mutants survived antibiotic exposure by releasing membrane phospholipid, which bound and inactivated the antibiotic. Although wild-type bacteria also released phospholipid in response to daptomycin, Agr-triggered secretion of small cytolytic toxins, known as phenol soluble modulins, prevented antibiotic inactivation. Phospholipid release by S. aureus occurred via an active process that appears to involve the VraUTRS regulon, and was inhibited by the β-lactam antibiotic oxacillin, which slowed inactivation of daptomycin and enhanced bacterial killing. Subsequent work revealed that next-generation lipid biosynthesis inhibitors completely blocked phospholipid release, whilst the presence of host-associated fatty acids enhanced the release of membrane phospholipids. Future work will determine the molecular mechanism by which S. aureus releases phospholipids, and exploit this information to develop new therapeutic approaches that enhance daptomycin treatment efficacy.Open Acces

Selective activation of oxidized PTP1B by the thioredoxin system modulates PDGF-ß receptor tyrosine kinase signaling

The inhibitory reversible oxidation of protein tyrosine phosphatases (PTPs) is an important regulatory mechanism in growth factor signaling. Studies on PTP oxidation have focused on pathways that increase or decrease reactive oxygen species levels and thereby affect PTP oxidation. The processes involved in reactivation of oxidized PTPs remain largely unknown. Here the role of the thioredoxin (Trx) system in reactivation of oxidized PTPs was analyzed using a combination of in vitro and cell-based assays. Cells lacking the major Trx reductase TrxR1 (Txnrd1-/-) displayed increased oxidation of PTP1B, whereas SHP2 oxidation was unchanged. Furthermore, in vivo-oxidized PTP1B was reduced by exogenously added Trx system components, whereas SHP2 oxidation remained unchanged. Trx1 reduced oxidized PTP1B in vitro but failed to reactivate oxidized SHP2. Interestingly, the alternative TrxR1 substrate TRP14 also reactivated oxidized PTP1B, but not SHP2. Txnrd1-depleted cells displayed increased phosphorylation of PDGF-ß receptor, and an enhanced mitogenic response, after PDGF-BB stimulation. The TrxR inhibitor auranofin also increased PDGF-ß receptor phosphorylation. This effect was not observed in cells specifically lacking PTP1B. Together these results demonstrate that the Trx system, including both Trx1 and TRP14, impacts differentially on the oxidation of individual PTPs, with a preference of PTP1B over SHP2 activation. The studies demonstrate a previously unrecognized pathway for selective redox-regulated control of receptor tyrosine kinase signaling

Teaching politics after the practice turn

The ‘practice turn’ and its associated ontology, epistemology and methodology are now well established in political research. In this article, we identify and explore a corollary pedagogy. After outlining the principal components of practice theory, we compare case- and placement-based approaches to learning, designed to develop skills for use in practice. We introduce and describe our own rather different course, which we designed to develop an understanding of the nature of practice as such. We discuss its scope and dynamics, particularly with regard to power in the classroom, and identify broader opportunities and challenges for the development of practice-based pedagogy

Welfare in horse breeding

Welfare problems related to the way horses are bred, whether by coitus or by the application of artificial reproduction techniques (ARTs), have been given no discrete consideration within the academic literature. This paper reviews the existing knowledge base about welfare issues in horse breeding and identifies areas in which data is lacking. We suggest that all methods of horse breeding are associated with potential welfare problems, but also that the judicious use of ARTs can sometimes help to address those problems. We discuss how negative welfare effects could be identified and limited and how positive welfare effects associated with breeding might be maximised. Further studies are needed to establish an evidence base about how stressful or painful various breeding procedures are for the animals involved, and what the lifetime welfare implications of ARTs are for future animal generations

Microfluidic Intracranial Pressure Monitoring Sensor

This thesis presents the design of a novel microfluidic sensor for continuous monitoring of intracranial pressure (ICP), intended as a less invasive alternative to current monitoring techniques. The sensor targets patients with critical and chronic neurological conditions, aiming to provide real-time data on ICP fluctuations. The microfluidic intracranial pressure sensor is designed for implantation beneath the skull, on the dura mater, and integrates a PDMS-based microfluidic strain sensor with wireless data transmission. Initial testing focuses on optimizing sensor design and integration with a microcontroller. Preliminary benchtop testing demonstrates the sensor\u27s capability to detect ICP with a minimum sensitivity of 5 mbar. Wireless data transmission was integrated by using a microcontroller to turn resistance measurements into readable pressure values using a voltage divider circuit and calibration equation. This cost effective alternative to ICP detection gives real-time data which may improve clinical decisionmaking, enable early detection of ICP changes, and reduce the need for invasive procedures and MRI-associated complications

Characterization of thioredoxin related protein of 14 kDa and its role in redox signaling

Reversible reduction/oxidation (redox) reactions play key roles in cellular signaling pathways. Particularly cysteine residues in proteins can be modified by reactive oxygen-, nitrogen- or sulfur species (ROS, RNS, RSS), thereby altering the functions of the respective proteins. These modifications can be reversed by two major reductive systems in mammalian cells – the thioredoxin (Trx) and glutathione (GSH) systems. Both contain various representatives of the Trx fold family of proteins, among them the name-giving Trxs being the most prominent. In the cytosolic Trx system, electrons are transferred from NADPH to Trx reductase 1 (TrxR1) and subsequently to Trx1, which reduces a multitude of cellular substrates. Thioredoxin-related protein of 14 kDa (TRP14, TXNDC17) is a sparsely characterized, but evolutionarily well-conserved member of the Trx system. The studies comprising this thesis examined TRP14 in several aspects of redox signaling. In Paper I we investigated the inhibition of TrxR1 by noble metal compounds and their effect on cancer cell survival. Inhibition of the Trx system as anti-cancer strategy is thought to attenuate the antioxidant capacity of cancer cells, thereby leading to cell death. We found that gold (Au), platinum (Pt), and palladium (Pd) compounds all inhibited TrxR1 in vitro, but in a cellular context, the inhibition and cytotoxicity were mainly dependent on the ligand substituents and cellular uptake. Furthermore, we found a covalent crosslink between TrxR1 and TRP14 upon treatment of cells with the antitumor agent cisplatin. We concluded that noble metals are potent TrxR1 inhibitors but Pt compounds, especially cisplatin, trigger highly specific cellular effects, including the covalent complex formation. In Paper II we studied the role of the Trx system in reactivation of oxidized protein tyrosine phoshatases (PTPs) in platelet derived growth factor (PDGF) signaling. Using fibroblasts that lacked TrxR1 (Txnrd1 -/-), we found both an increased oxidation of PTP1B and phosphorylation of the PDGF β receptor (PDGF βR). Consequently, we showed that both Trx1 and TRP14, coupled to TrxR1, are able to reduce oxidized PTP1B in vitro. This study demonstrated that the Trx system, including both Trx1 and TRP14, impacts the oxidation of specific PTPs and can thereby modulate PDGF signaling. In Paper III we established TRP14 as an efficient TrxR1-dependent reductase and denitrosylase. Using several low molecular weight disulfide compounds, we found that, dependent on the substrate, TRP14 can be at least as efficient as Trx1. We also suggested TRP14 instead of Trx1 to be a major intracellular cystine reductase, because Trx1 does not reduce cystine once a preferred substrate such as insulin is present. Acting in parallel with Trx1, we also provide evidence of TRP14 being an efficient cellular reductase for nitrosylated proteins and concluded that TRP14 should be considered as an integral part of the Trx system. In Paper IV we developed a novel method for the detection of protein persulfides named Protein Persulfide Detection Protocol, ProPerDP. The formation of persulfide (-SSH) moieties at regulatory cysteine residues is emerging as a major pathway of hydrogen sulfide (H2S) mediated redox signaling. Using ProPerDP we discovered that both the Trx and the GSH system are potent reduction pathways for poly- and persulfides in cells. These studies reinforce the notion that TrxR1-dependent pathways are not only mediated via its wellknown substrate Trx1. We show that TRP14 is yet another cytosolic oxidoreductase with various intracellular functions, including reduction of PTPs, disulfides, nitrosothiols and persulfides. TRP14 is thereby potentially involved in a variety of different redox signaling pathways

Evaluation d une technique de castration du cheval par laparoscopie

Ce travail vise à comparer les ratios bénéfices / risques des techniques actuelles de castration des équidés, classiques et laparoscopiques. La première partie rappelle les bases anatomo-fonctionnelles de la reproduction de l'étalon. Les techniques de castration et de cryptorchidectomie, classiques et laparoscopiques, leurs avantages, leurs inconvénients et leurs complications respectives sont ensuite décrits de façon approfondie. La troisième partie présente les moyens d évaluation de l'efficacité de la castration. Une dernière partie est consacrée à l'évaluation d une technique laparoscopique de castration du cheval debout, visant à laisser les testicules en place et réalisée chez 10 chevaux entre Août 2005 et Mars 2006. Les avantages et les inconvénients, les données légales concernant la castration sans orchidectomie, la faisabilité et l'efficacité de cette méthode chirurgicale sont discutés en détail au cours de ce travail

‘Sons of athelings given to the earth’: Infant Mortality within Anglo-Saxon Mortuary Geography

FOR 20 OR MORE YEARS early Anglo-Saxon archaeologists have believed children are underrepresented in the cemetery evidence. They conclude that excavation misses small bones, that previous attitudes to reporting overlook the very young, or that infants and children were buried elsewhere. This is all well and good, but we must be careful of oversimplifying compound social and cultural responses to childhood and infant mortality. Previous approaches have offered methodological quandaries in the face of this under-representation. However, proportionally more infants were placed in large cemeteries and sometimes in specific zones. This trend is statistically significant and is therefore unlikely to result entirely from preservation or excavation problems. Early medieval cemeteries were part of regional mortuary geographies and provided places to stage events that promoted social cohesion across kinship systems extending over tribal territories. This paper argues that patterns in early Anglo-Saxon infant burial were the result of female mobility. Many women probably travelled locally to marry in a union which reinforced existing social networks. For an expectant mother, however, the safest place to give birth was with experience women in her maternal home. Infant identities were affected by personal and legal association with their mother’s parental kindred, so when an infant died in childbirth or months and years later, it was their mother’s identity which dictated burial location. As a result, cemeteries central to tribal identities became places to bury the sons and daughters of a regional tribal aristocracy