Home rule: the creation of local historic districts in the New Boston, 1953 to 1983

As large-scale, modernist urban renewal projects advanced following World War II, residents of Boston’s historic neighborhoods pushed back, asserting the value of the existing built environment and enlisting new strategies, like local historic districts, to mediate change. Over time, these defenders of traditional urbanism changed from relatively conventional 1950s home- and business-owners to more countercultural, back-to-the-city technocrats, the advance guard of a new middle class. Employing previously unexplored government archives and public documents, extensive contemporaneous newspaper reports, and interviews with current and former neighborhood activists, “Home Rule” analyzes historic districting as a social movement, tracing how adherents of this cause mobilized resources to effect the policy changes they sought. While the growth of the historic preservation movement in the interwar South has been well documented, the adoption of preservation planning techniques in the post-war North is less well studied. The first chapter investigates the effort to create the first historic district in the urban North on Beacon Hill, a campaign that took place against the backdrop of a destructive urban-renewal project in the nearby West End. A neighborhood association spearheaded the effort, carefully building support, consistent with the consensus culture of the 1950s. The chapter also examines the expansion of the district and challenges to its authority. The highly contested movement to designate the Back Bay occupies the second chapter, pitting a powerful mayor and his deep-pocketed allies determined to insert high-rise towers in a historically low-rise area against a large and well-heeled neighborhood association. The third chapter examines the drive to create a statutory Landmarks Commission to regulate historic resources citywide. The chapter also explores two attempts to designate historic districts after the creation of the new agency, one effort on Ashmont Hill that failed and another in West Back Bay that succeeded. The movement to designate three contiguous historic districts – the St. Botolph Street area, Bay Village, and the South End – constitutes the fourth and last chapter. These efforts exemplify the rediscovery of urban life by an educated, progressive middle class who negotiated with various ethnic and racial minorities, transformed the city, and reinvented urban renewal.2018-08-11T00:00:00

What is missing from Minkowski's "Raum und Zeit" lecture

This contribution tries to highlight the importance of Minkowski's ``Raum und Zeit'' lecture in a ``negative'' way, where {\it negative} is taken in the photographic sense of reversing lights and shades. Indeed, we focus on the ``shades'' of Minkowski's text, i.e. what is missing, or misunderstood. In particular, we focus on two issues: (i) why are Poincar\'e's pioneering contributions to four-dimensional geometry not quoted by Minkowski (while he abundantly quoted them a few months before the Cologne lecture)?, and (ii) did Minkowski fully grasp the physical (and existential) meaning of ``time'' within spacetime? We think that this ``negative'' approach (and the contrast between Poincar\'e's and Minkowski's attitudes towards physics) allows one to better grasp the boldness of the {\it revolutionary} step taken by Minkowski in his Cologne lecture.Comment: 18 pages, to appear in the special (Sept/Oct 2008) issue of Annalen der Physik (Berlin) commemorating H. Minkowski's 1908 lecture in Cologn

Cytotoxic effects of curcumin on osteosarcoma cell lines

Summary: Curcumin (diferuloylmethane), one of the main components of the Indian spice turmeric, is known to possess potent anti-inflammatory and anti-oxidant properties. In addition, curcumin has also been shown to have in vitro and in vivo efficacy against a variety of malignancies. In the current study we examined the cytotoxic effect of curcumin on seven osteosarcoma (OS) cell lines with varying degrees of in vivo metastatic potential. Curcumin inhibited the growth of all OS cell lines tested with half-maximal inhibitory concentration values ranging from 14.4 to 24.6μM. Growth inhibition was associated with a dose dependent increase in the number of apoptotic cells and accumulation of cells in the G2/M phase of the cell cycle. Curcumin treatment also resulted in cleavage of caspase-3 and poly adenosine diphosphate-ribose polymerase. Moreover, curcumin treatment was associated with an increase in cellular levels of the apoptotic B-cell leukemia/lymphoma 2 (Bcl-2)-associated X protein and a decrease in cellular content of the anti-apoptotic protein Bcl-2. In addition, curcumin treatment also inhibited the migration of OS cell lines. These data indicate that the potent cytotoxic activity of curcumin on OS cell lines is mediated by induction of apoptotic processes. Thus, curcumin has potential to be a novel OS chemotherapeutic agen

Cytotoxic effects of curcumin on osteosarcoma cell lines

Summary: Curcumin (diferuloylmethane), one of the main components of the Indian spice turmeric, is known to possess potent anti-inflammatory and anti-oxidant properties. In addition, curcumin has also been shown to have in vitro and in vivo efficacy against a variety of malignancies. In the current study we examined the cytotoxic effect of curcumin on seven osteosarcoma (OS) cell lines with varying degrees of in vivo metastatic potential. Curcumin inhibited the growth of all OS cell lines tested with half-maximal inhibitory concentration values ranging from 14.4 to 24.6μM. Growth inhibition was associated with a dose dependent increase in the number of apoptotic cells and accumulation of cells in the G2/M phase of the cell cycle. Curcumin treatment also resulted in cleavage of caspase-3 and poly adenosine diphosphate-ribose polymerase. Moreover, curcumin treatment was associated with an increase in cellular levels of the apoptotic B-cell leukemia/lymphoma 2 (Bcl-2)-associated X protein and a decrease in cellular content of the anti-apoptotic protein Bcl-2. In addition, curcumin treatment also inhibited the migration of OS cell lines. These data indicate that the potent cytotoxic activity of curcumin on OS cell lines is mediated by induction of apoptotic processes. Thus, curcumin has potential to be a novel OS chemotherapeutic agen

Taurolidine: a novel anti-neoplastic agent induces apoptosis of osteosarcoma cell lines

Summary: Taurolidine, the active agent of Taurolin®, is a broad spectrum anti-biotic that has been used for over 15years for the treatment of severe surgical infections. Recently, taurolidine has been shown to possess anti-neoplastic properties in vitro and in vivo against a variety of cancers including ovarian, colon and prostate. In this study we assessed the cytotoxic activity of taurolidine against human osteosarcoma (OS) cell lines and normal human bone cells. Treatment with taurolidine inhibited the growth of all ten osteosarcoma cell lines tested and taurolidine was equally potent against cell lines with and without distinct genetic defects (i.e. p53, Rb). Moreover, taurolidine-induced growth inhibition was found to be associated with a dose dependent increase in the number of apoptotic cells and apoptosis was shown to be caspase-dependent. Taurolidine treatment was also found to inhibit adhesion of OS cell lines. Compared to OS cell lines, normal bone cells in primary culture were found to be less sensitive to the cytotoxic and anti-adhesive effects of taurolidine. These data indicate that taurolidine possesses potent anti-neoplastic activity against osteosarcoma cell lines and may have potential as a novel OS chemotherapeutic agen

Targeting αvβ3 and αvβ5 integrins inhibits pulmonary metastasis in an intratibial xenograft osteosarcoma mouse model

Osteosarcoma is an aggressive bone cancer that has a high propensity for metastasis to the lungs. Patients with metastatic disease face a very poor prognosis. Therefore, novel therapeutics, efficiently suppressing the metastatic process, are urgently needed. Integrins play a pivotal role in tumor cell adhesion, motility and metastasis. Here, we evaluated αvβ3 and αvβ5 integrin inhibition with cilengitide as a novel metastasis-suppressive therapeutic approach in osteosarcoma. Immunohistochemical analysis of αvβ3 and αvβ5 integrins expression in a tissue microarray of tumor specimens collected from osteosarcoma patients revealed that αvβ5 integrin is mainly found on tumor cells, whereas αvβ3 is predominantly expressed by stromal cells. In vitro functional assays demonstrated that cilengitide dose-dependently inhibited de novo adhesion, provoked detachment and inhibited migration of osteosarcoma cell lines. Cilengitide induced a decline in cell viability, blocked the cell cycle in the G1 phase and caused anoikis by activation of the Hippo pathway. In a xenograft orthotopic mouse model cilengitide minimally affected intratibial primary tumor growth but, importantly, suppressed pulmonary metastasis. The data demonstrate that targeting αvβ3 and αvβ5 integrins in osteosarcoma should be considered as a novel therapeutic option for patients with metastatic disease

Do norms unintentionally increase stereotypical expressions? A randomised controlled trial

INTRODUCTION: Implicit biases of health professionals could cause biased judgements. Many anti‐bias interventions seem to be ineffective, and some even counterproductive. People tend to be compliant to standards describing what the majority of people finds or does, and this could cause people to think in a stereotype‐consistent manner. This study examines whether descriptive social norms such as ‘the majority of people have stereotypes’ (majority message), as often stated in interventions, actually increase people's stereotypes. To examine the effect of descriptive social norms (Hypothesis 1) and the effect of individual perceptions and preferences (Hypothesis 2a and 2b) on stereotypical expressions towards medical students. METHODS: First, we determined which ethic stereotypes regarding medical students prevail in Dutch medical education (N = 52). Next, two similar randomised controlled trials, both with teachers and students, were carried out (N = 158 and N = 123, respectively), one with an East Asian student picture (ethnic minority) and one with a native Dutch student picture (ethnic majority). Participants were randomly assigned to either a majority‐message, minority‐message or no‐message condition, and rated the presented minority or majority picture on specific stereotypical features. Subsequently, participants described a typical day of that same student's life. These descriptions were rated for stereotypicality by two independent raters, who were blind for condition and stimulus. Inclusive work environment (IWC) and social dominance orientation (SDO) of participants were measured as indicators of individual perceptions and preferences. RESULTS: Stereotypes were expressed towards both picture stimuli, yet message condition did not affect stereotypical expressions. SDO positively related to stereotypical expressions towards the East Asian student, whereas IWC positively related to stereotypical expressions towards the native Dutch student. CONCLUSION: Interventions do not unintentionally increase stereotypes by communicating what the majority of people thinks or does. Individual perceptions and preferences are predictive of stereotypes, whereas descriptive social norms are not

The Physics and Mathematics of the Second Law of Thermodynamics

The essential postulates of classical thermodynamics are formulated, from which the second law is deduced as the principle of increase of entropy in irreversible adiabatic processes that take one equilibrium state to another. The entropy constructed here is defined only for equilibrium states and no attempt is made to define it otherwise. Statistical mechanics does not enter these considerations. One of the main concepts that makes everything work is the comparison principle (which, in essence, states that given any two states of the same chemical composition at least one is adiabatically accessible from the other) and we show that it can be derived from some assumptions about the pressure and thermal equilibrium. Temperature is derived from entropy, but at the start not even the concept of `hotness' is assumed. Our formulation offers a certain clarity and rigor that goes beyond most textbook discussions of the second law.Comment: 93 pages, TeX, 8 eps figures. Updated, published version. A summary appears in Notices of the Amer. Math. Soc. 45 (1998) 571-581, math-ph/980500

Caprin-1, a novel Cyr61-interacting protein, promotes osteosarcoma tumor growth and lung metastasis in mice

Osteosarcoma (OS) is the most common primary bone malignancy in children and adolescents. More than 30% of patients develop lung metastasis, which is the leading cause of mortality. Recently, the extracellular matrix protein Cyr61 has been recognized as a malignancy promoting protein in OS mouse model with prognostic potential in human OS. In this study, we aimed at the identification of novel Cyr61-interacting proteins. Here we report that Cyr61 associates with Caprin-1, and confocal microscopy showed that stable ectopic expression of Caprin-1 leads to the formation of stress granules containing Caprin-1 and Cyr61, confers resistance to cisplatin-induced apoptosis, and resulted in constitutive phosphorylation of Akt and ERK1/2. Importantly, ectopic expression of Caprin-1 dramatically enhanced primary tumor growth, remarkably increased lung metastatic load in a SCID intratibial OS mouse model, and decreased significantly (p<0.0018) the survival of the mice. Although Caprin-1 expression, evaluated with a tissue microarray including samples from 59 OS patients, failed to be an independent predictor for the patients' outcome in this limited cohort of patients, increased Caprin-1 expression indicated a tendency to shortened overall survival, and more strikingly, Cyr61/Caprin-1 co-expression was associated with worse survival than that observed for patients with tumors expressing either Cyr61 or Caprin-1 alone or none of these proteins. The findings imply that Caprin-1 may have a metastasis promoting role in OS and show that through resistance to apoptosis and via the activation of Akt and ERK1/2 pathways, Caprin-1 is significantly involved in the development of OS metastasis

Scapuloperoneal syndrome type Kaeser and a wide phenotypic spectrum of adult-onset, dominant myopathies are associated with the desmin mutation R350P

In 1965, an adult-onset, autosomal dominant disorder with a peculiar scapuloperoneal distribution of weakness and atrophy was described in a large, multi-generation kindred and named ‘scapuloperoneal syndrome type Kaeser' (OMIM #181400). By genetic analysis of the original kindred, we discovered a heterozygous missense mutation of the desmin gene (R350P) cosegregating with the disorder. Moreover, we detected DES R350P in four unrelated German families allowing for genotype-phenotype correlations in a total of 15 patients carrying the same mutation. Large clinical variability was recognized, even within the same family, ranging from scapuloperoneal (n = 2, 12%), limb girdle (n = 10, 60%) and distal phenotypes (n = 3, 18%) with variable cardiac (n = 7, 41%) or respiratory involvement (n = 7, 41%). Facial weakness, dysphagia and gynaecomastia were frequent additional symptoms. Overall and within each family, affected men seemingly bear a higher risk of sudden, cardiac death as compared to affected women. Moreover, histological and immunohistochemical examination of muscle biopsy specimens revealed a wide spectrum of findings ranging from near normal or unspecific pathology to typical, myofibrillar changes with accumulation of desmin. This study reveals that the clinical and pathological variability generally observed in desminopathies may not be attributed to the nature of the DES mutation alone, but may be influenced by additional genetic and epigenetic factors such as gender. In addition, mutations of the desmin gene should be considered early in the diagnostic work-up of any adult-onset, dominant myopathy, even if specific myofibrillar pathology is absen