Optimization Studies of the Important Drug Lead Kahalalide F which Acts on a Novel Cancer Target RPS25

Kahalalide F (KF, 1) is the largest and most biologically active cyclic peptide of the naturally occurring kahalalide family of depsipeptides. Previous evaluations of the compound have shown significant in vitro and in vivo activity against various forms of cancer. KF has been investigated in phase I clinical trials and is being evaluated in phase II clinical studies. The objective of this experiment was to prepare analogues of KF through semisynthetic modification of the parent compound to optimize activity against a slate of pathogens, as well as cancerous cells. Data revealed that KF and analogues were not active against malaria, leishmania, or bacteria. However, the series was active against various strains of fungi, including Fusarium, a genus known for causing opportunistic infections in plants, as well as humans. KF and analogues were also evaluated for in vitro activity against 60 human cancer cell lines. Analogue 5 exhibited greater activity than 1 against several cell lines, including leukemia, colon, ovarian, renal, and prostate cell lines. Through the evaluations of antiprotozoal, antibacterial, and antifungal activity, as well as the activity against a slate of human cancer cell lines, it was revealed that semisynthetic modification of the parent compound has an affect on activity. Further studies involving semisynthetic modification of KF could lead to vast improvements in current drug therapies

Dynamic Constitutive Equation For A Syntactic Foam Under Multi-Axial Stress State

Eco-Core is a fire resistant structural core material that was developed at North Carolina A&T State University in 2003. During the last 10 years, mechanical, fracture and fatigue properties as well as resistance to sea water were established for Eco-Core. A design methodology for Eco-Core in sandwich structures was provided. The objective of this research was to develop a dynamic constitutive equation for Eco-Core in a multi-axial stress state that is valid for both static and dynamic loadings, and then demonstrate the model to be used in a commercial code to solve real life problems. A special tri-axial loading and strain measurement test fixture was developed and used in static and dynamic tests. The material was tested at strain rates ranged from 3 10 /s to 3500/s. Analysis of the results showed that the net-deviatoric stress is independent of lateral stress. Based on the test results and a multi-variable regression analysis, a two part constitutive equation was developed. The first part was for the linear response and the second part was for the non-linear response that covers translation, crushing and densification of micro bubbles in the Eco-Core. The equation was validated by independent experiments and simulation by LS-DYNA. The dynamic energy absorption capability for Eco-Core was found to be superior compared to commercial materials such as PVC foam, Rohacell foam and Balsa wood

Genes and Cardiovascular Disease : Where do we go from here?

N

Speculating on architecture : morality, the new real estate, and the bourgeois apartment industry in late nineteenth-century France

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Architecture, 2011.Cataloged from PDF version of thesis.Includes bibliographical references (p. 216-232).The topic of architecture as a commodity-something that can be possessed and traded-has been largely ignored within the discipline of architectural history, or even written off altogether as an inevitable consequence of modem capitalism. But the history of the commodification of architecture is by no means as simple as it may seem. It has its roots in Haussmann's Paris, and the speculative property market of the 1860s, where we see, for the first time, a complex intermingling of new mortgage structures and residential typologies, the use of standardization, and the proliferation of discourses concerning apartment decoration. The project also treats reactions expressed by architects, aesthetic theorists, and religious and political figures over the course of the Third Republic against speculation practices and their architectural effects. The changes brought by property's increased circulation-the very idea of apartments designed for unknown future occupants-were compounded by the perception of a real estate market held in the grips of commodity culture. The possibility that anyone could own property was unsettling for some political and religious authorities; perhaps even more so was the sense of an assault on the way in which property had traditionally stood as a representation of individuality. Speculative architecture brought about a separation of the subject (the particular owner of an apartment) from its object (the apartment unit now rendered ubiquitous). The powerful critique of modem capitalism and the ostensive ill effects on private life that emerged from all of this was bound up in liberal and Catholic ideologies, as I argue in my dissertation. I look at a set of figures from vastly different professions who, perforce, collectively developed and implemented rules governing finances, architecture, decoration, and, ultimately, human conduct. These include developers like the Saint-Simonien Emile Pdreire, whose experimental Credit Mobilier sponsored standard models for residential architecture, democratized credit, and underwrote the design and construction of thousands of new apartments. These also include taste-makers like Charles Blanc, director of the Academie des beaux-arts, whose works included decoration manuals. And finally, these include politicians such as Frederic Le Play, the Catholic modernist and proto-sociologist who insisted on the connection between private property and morality, and Jules Simon, the conservative republican who linked the security of the family to that of the nation state. The reactionary moralization of design, to be detected in Catholic dogma, metaphysical philosophy, and the republican politics of the time, stands as one of the great unacknowledged precedents for the proselytizing ideology of architectural modernism at the dawn of the twentieth century.by Deborah Grace Kully.Ph.D

Codon 215 Mutations in Human Immunodeficiency Virus—Infected Pregnant Women

In 1994, the Pediatric AIDS Clinical Trials Group (PACTG) Protocol 076 demonstrated a two-thirds reduction of perinatal human immunodeficiency virus (HIV) type 1 transmission with zidovudine chemoprophylaxis. However, zidovudine alone does not fully suppress HIV replication, and chemoprophylaxis with zidovudine alone might select for zidovudine-resistant viral variants, decreasing the efficacy of zidovudine prophylaxis and affecting future responses to combined antiretroviral regimens. Sixty-two HIV-infected pregnant women consecutively enrolled in the ongoing Swiss HIV and Pregnancy Study were prospectively evaluated for the presence or development of zidovudine resistance by analysis of codon 215 of the reverse transcriptase gene. Six women (9.6%) harbored a codon T215Y/F mutation, which is associated with high-level resistance to zidovudine. Postnatal evaluation was completed in all children of mothers harboring the mutation. None was HIV-infected. The observed prevalence of codon 215 mutations of 9.6% raises important concerns regarding the future use of the PACTG 076 regime

A gender synchronized family planning intervention for married couples in rural India: study protocol for the CHARM2 cluster randomized controlled trial evaluation.

BackgroundPrior research from India demonstrates a need for family planning counseling that engages both women and men, offers complete family planning method mix, and focuses on gender equity and reduces marital sexual violence (MSV) to promote modern contraceptive use. Effectiveness of the three-session (two male-only sessions and one couple session) Counseling Husbands to Achieve Reproductive Health and Marital Equity (CHARM) intervention, which used male health providers to engage and counsel husbands on gender equity and family planning (GE + FP), was demonstrated by increased pill and condom use and a reduction in MSV. However, the intervention had limited reach to women and was therefore unable to expand access to highly effective long acting reversible contraceptives such as the intrauterine device (IUD). We developed a second iteration of the intervention, CHARM2, which retains the three sessions from the original CHARM but adds female provider- delivered counseling to women and offers a broader array of contraceptives including IUDs. This protocol describes the evaluation of CHARM2 in rural Maharashtra.MethodsA two-arm cluster randomized controlled trial will evaluate CHARM2, a gender synchronized GE + FP intervention. Eligible married couples (n = 1200) will be enrolled across 20 clusters in rural Maharashtra, India. Health providers will be gender-matched to deliver two GE + FP sessions to the married couples in parallel, and then a final session will be delivered to the couple together. We will conduct surveys on demographics as well as GE and FP indicators at baseline, 9-month, and 18-month follow-ups with both men and women, and pregnancy tests at each time point from women. In-depth interviews will be conducted with a subsample of couples (n = 50) and providers (n = 20). We will conduct several implementation and monitoring activities for purposes of assuring fidelity to intervention design and quality of implementation, including recruitment and tracking logs, provider evaluation forms, session observation forms, and participant satisfaction surveys.DiscussionWe will complete the recruitment of participants and collection of baseline data by July 2019. Findings from this work will offer important insight for the expansion of the national family planning program and improving quality of care for India and family planning interventions globally.Trial registrationClinicalTrial.gov, NCT03514914

Antiretroviral Therapy Initiation Before, During, or After Pregnancy in HIV-1-Infected Women: Maternal Virologic, Immunologic, and Clinical Response

Pregnancy has been associated with a decreased risk of HIV disease progression in the highly active antiretroviral therapy (HAART) era. The effect of timing of HAART initiation relative to pregnancy on maternal virologic, immunologic and clinical outcomes has not been assessed.We conducted a retrospective cohort study from 1997–2005 among 112 pregnant HIV-infected women who started HAART before (N = 12), during (N = 70) or after pregnancy (N = 30).0.01). There were no statistical differences in rates of HIV disease progression between groups.HAART initiation during pregnancy was associated with better immunologic and virologic responses than initiation after pregnancy