Death Penalty; Cruel and Unusual Punishment; Individualized Sentencing Determination; Lockett v. Ohio; Bell v. Ohio

“In Bell v. Ohio and Lockett v. Ohio the United States Supreme Court found the sentencing provisions of the Ohio capital punishment statute to be incompatible with the eighth and fourteenth amendments which prohibit cruel and unusual punishment. These two opinions represent the most recent attempt by the Supreme Court to explain what elements must be included in a constitutionally valid capital punishment statute.

A Study of the Relationship Between Teacher Characteristics and Student Performance in High School Geometry

The purpose of this thesis is to investigate whether teacher characteristics, such as years of experience, degree level, degree type, certification type, race, or gender, impact student performance in high school geometry. Research has shown that each student’s mathematical understanding and problem solving ability is primarily shaped by the teaching experiences they encounter in school (Mewborn, 2007). It is hypothesized that there are teacher characteristics that are associated with student growth, which is defined as the numerical score increase from pre-assessment to post-assessment. Teacher characteristic and student assessment data were collected from geometry teachers in a suburban western New York State school district; the data was then analyzed using statistics software to identify any statistically significant relationships between teacher characteristics and student growth means. Through empirical testing, it was found that a geometry teacher’s years of experience, degree level, certification type, and gender all have an impact on student performance in high school geometry

Evidence of porcine and human endothelium activation by cancer-associated carbohydrates expressed on glycoproteins and tumour cells

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65560/1/jphysiol.2003.054783.pd

Absence of system xc⁻ on immune cells invading the central nervous system alleviates experimental autoimmune encephalitis

Background: Multiple sclerosis (MS) is an autoimmune demyelinating disease that affects the central nervous system (CNS), leading to neurodegeneration and chronic disability. Accumulating evidence points to a key role for neuroinflammation, oxidative stress, and excitotoxicity in this degenerative process. System x(c)- or the cystine/glutamate antiporter could tie these pathological mechanisms together: its activity is enhanced by reactive oxygen species and inflammatory stimuli, and its enhancement might lead to the release of toxic amounts of glutamate, thereby triggering excitotoxicity and neurodegeneration. Methods: Semi-quantitative Western blotting served to study protein expression of xCT, the specific subunit of system x(c)-, as well as of regulators of xCT transcription, in the normal appearing white matter (NAWM) of MS patients and in the CNS and spleen of mice exposed to experimental autoimmune encephalomyelitis (EAE), an accepted mouse model of MS. We next compared the clinical course of the EAE disease, the extent of demyelination, the infiltration of immune cells and microglial activation in xCT-knockout (xCT(-/-)) mice and irradiated mice reconstituted in xCT(-/-) bone marrow (BM), to their proper wild type (xCT(+/+)) controls. Results: xCT protein expression levels were upregulated in the NAWM of MS patients and in the brain, spinal cord, and spleen of EAE mice. The pathways involved in this upregulation in NAWM of MS patients remain unresolved. Compared to xCT(+/+) mice, xCT(-/-) mice were equally susceptible to EAE, whereas mice transplanted with xCT(-/-) BM, and as such only exhibiting loss of xCT in their immune cells, were less susceptible to EAE. In none of the above-described conditions, demyelination, microglial activation, or infiltration of immune cells were affected. Conclusions: Our findings demonstrate enhancement of xCT protein expression in MS pathology and suggest that system x(c)- on immune cells invading the CNS participates to EAE. Since a total loss of system x(c)- had no net beneficial effects, these results have important implications for targeting system x(c)- for treatment of MS

Integrin alpha V beta 3 targeted dendrimer‐rapamycin conjugate reduces fibroblast‐mediated prostate tumor progression and metastasis

Therapeutic strategies targeting both cancer cells and associated cells in the tumor microenvironment offer significant promise in cancer therapy. We previously reported that generation 5 (G5) dendrimers conjugated with cyclic‐RGD peptides target cells expressing integrin alpha V beta 3. In this study, we report a novel dendrimer conjugate modified to deliver the mammalian target of rapamycin (mTOR) inhibitor, rapamycin. In vitro analyses demonstrated that this drug conjugate, G5‐FI‐RGD‐rapamycin, binds to prostate cancer (PCa) cells and fibroblasts to inhibit mTOR signaling and VEGF expression. In addition, G5‐FI‐RGD‐rapamycin inhibits mTOR signaling in cancer cells more efficiently under proinflammatory conditions compared to free rapamycin. In vivo studies established that G5‐FI‐RGD‐rapamycin significantly inhibits fibroblast‐mediated PCa progression and metastasis. Thus, our results suggest the potential of new rapamycin‐conjugated multifunctional nanoparticles for PCa therapy.Here, we synthesized and characterized a novel dendrimer conjugate, G5‐FI‐RGD‐rapamycin. Multifunctional G5‐FI‐RGD‐rapamycin binds to PCa and fibroblasts via alpha V beta 3 integrin and significantly inhibits mTOR signaling and VEGF expression. These in vitro data were confirmed by in vivo data that G5‐FI‐RGD‐rapamycin inhibits fibroblast‐mediated PCa progression and metastasis.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146470/1/jcb26727.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146470/2/jcb26727_am.pd

Phase I dose escalation and pharmacokinetic study of pluronic polymer-bound doxorubicin (SP1049C) in patients with advanced cancer

SP1049C is a novel anticancer agent containing doxorubicin and two nonionic pluronic block copolymers. In preclinical studies, SP1049C demonstrated increased efficacy compared to doxorubicin. The objectives of this first phase I study were to determine the toxicity profile, dose-limiting toxicity, maximum tolerated dose and pharmacokinetic profile of SP1049C, and to document any antitumour activity. The starting dose was 5 mg m−2 (doxorubicin content) as an intravenous infusion once every 3 weeks for up to six cycles. A total of 26 patients received 78 courses at seven dose levels. The dose-limiting toxicity was myelosuppression and DLT was reached at 90 mg m−2. The maximum tolerated dose was 70 mg m−2 and is recommended for future trials. The pharmacokinetic profile of SP1049C showed a slower clearance than has been reported for conventional doxorubicin. Evidence of antitumour activity was seen in some patients with advanced resistant solid tumours. Phase II trials with this agent are now warranted to further define its antitumour activity and safety profile

Molecular Mechanisms Governing IL-24 Gene Expression

Interleukin-24 (IL-24) belongs to the IL-10 family of cytokines and is well known for its tumor suppressor activity. This cytokine is released by both immune and nonimmune cells and acts on non-hematopoietic tissues such as skin, lung and reproductive tissues. Apart from its ubiquitous tumor suppressor function, IL-24 is also known to be involved in the immunopathology of autoimmune diseases like psoriasis and rheumatoid arthritis. Although the cellular sources and functions of IL-24 are being increasingly investigated, the molecular mechanisms of IL-24 gene expression at the levels of signal transduction, epigenetics and transcription factor binding are still unclear. Understanding the specific molecular events that regulate the production of IL-24 will help to answer the remaining questions that are important for the design of new strategies of immune intervention involving IL-24. Herein, we briefly review the signaling pathways and transcription factors that facilitate, induce, or repress production of this cytokine along with the cellular sources and functions of IL-24

O impacto da psoríase na autoimagem e sua influência no trabalho

Psoriasis is a skin disease that affects the body in a systemic way of affected by it, may also affect the joints. Its impact goes beyond the skin, causing psychosocial damage and occupational arising from prejudice and social stigma. This study aimed to evaluate the impact of psoriasis on self-image and their influence on the work of the individuals affected. It is a qualitative study of the case study type with 7 patients in the Reference Center, Support and Treatment of Carriers of Paraiba State of psoriasis, installed at the Dermatology Clinic of the University Hospital Lauro Wanderley - HULW/UFPB - João Pessoa / PB. Data were collected through semi-structured interview, categorized and treated according to the Content Analysis. The results showed interference in the self-image of participants, mainly caused by situations involving prejudice, but there were few significant influences to the work of the respondents, only difficulties of functional performance in cases of arthropathic psoriasis. They also suggest that it is important to comprehensive care by multidisciplinary team and social support for individuals with psoriasis for good promotion of quality of life and are necessary awareness actions to society in order to reduce situations of prejudice and stigma.A psoríase é uma doença dermatológica que afeta de maneira sistêmica o organismo dos acometidos por ela, podendo afetar também as articulações. Seu impacto vai além da pele, ocasionando prejuízos psicossociais e ocupacionais, decorrentes do preconceito e estigma social. O presente trabalho objetivou avaliar o impacto da psoríase na autoimagem e sua influência no trabalho dos indivíduos acometidos. É um estudo qualitativo do tipo estudo de caso com 7 pacientes do Centro de Referência, Apoio e Tratamento aos Portadores da Psoríase do Estado da Paraíba, instalado no ambulatório de dermatologia do Hospital Universitário Lauro Wanderley – HULW/UFPB – João Pessoa/PB. Os dados foram coletados por meio de entrevista semiestruturada, categorizados e tratados de acordo com a Análise de Conteúdo. Os resultados indicaram interferência na autoimagem dos participantes, causadas principalmente por situações que envolvem preconceito, porém houveram poucas influências significativas em relação ao trabalho dos entrevistados, apenas dificuldades de desempenho funcional nos casos de psoríase artropática. Também sugerem que é importante a assistência integral por equipe multiprofissional e o apoio social para os indivíduos com psoríase para a boa promoção da qualidade de vida, bem como são necessárias ações de conscientização para a sociedade, a fim de reduzir situações de preconceito e estigma