Evaluation of Phage Display Discovered Peptides as Ligands for Prostate-Specific Membrane Antigen (PSMA)

The aim of this study was to identify potential ligands of PSMA suitable for further development as novel PSMA-targeted peptides using phage display technology. The human PSMA protein was immobilized as a target followed by incubation with a 15-mer phage display random peptide library. After one round of prescreening and two rounds of screening, high-stringency screening at the third round of panning was performed to identify the highest affinity binders. Phages which had a specific binding activity to PSMA in human prostate cancer cells were isolated and the DNA corresponding to the 15-mers were sequenced to provide three consensus sequences: GDHSPFT, SHFSVGS and EVPRLSLLAVFL as well as other sequences that did not display consensus. Two of the peptide sequences deduced from DNA sequencing of binding phages, SHSFSVGSGDHSPFT and GRFLTGGTGRLLRIS were labeled with 5-carboxyfluorescein and shown to bind and co-internalize with PSMA on human prostate cancer cells by fluorescence microscopy. The high stringency requirements yielded peptides with affinities KD∼1 μM or greater which are suitable starting points for affinity maturation. While these values were less than anticipated, the high stringency did yield peptide sequences that apparently bound to different surfaces on PSMA. These peptide sequences could be the basis for further development of peptides for prostate cancer tumor imaging and therapy. © 2013 Shen et al

Conductivity and quasinormal modes in holographic theories

We show that in field theories with a holographic dual the retarded Green's function of a conserved current can be represented as a convergent sum over the quasinormal modes. We find that the zero-frequency conductivity is related to the sum over quasinormal modes and their high-frequency asymptotics via a sum rule. We derive the asymptotics of the quasinormal mode frequencies and their residues using the phase-integral (WKB) approach and provide analytic insight into the existing numerical observations concerning the asymptotic behavior of the spectral densities.Comment: 24 pages, 3 figure

Quality of antimalarial drugs and antibiotics in Papua New Guinea: A survey of the health facility supply chain

Background: Poor-quality life-saving medicines are a major public health threat, particularly in settings with a weak regulatory environment. Insufficient amounts of active pharmaceutical ingredients (API) endanger patient safety and may contribute to the development of drug resistance. In the case of malaria, concerns relate to implications for the efficacy of artemisinin-based combination therapies (ACT). In Papua New Guinea (PNG), Plasmodium falciparum and P. vivax are both endemic and health facilities are the main source of treatment. ACT has been introduced as first-line treatment but other drugs, such as primaquine for the treatment of P. vivax hypnozoites, are widely available. This study investigated the quality of antimalarial drugs and selected antibiotics at all levels of the health facility supply chain in PNG.Methods and Findings: Medicines were obtained from randomly sampled health facilities and selected warehouses and hospitals across PNG and analysed for API content using validated high performance liquid chromatography (HPLC). Of 360 tablet/capsule samples from 60 providers, 9.7% (95% CI 6.9, 13.3) contained less, and 0.6% more, API than pharmacopoeial reference ranges, including 29/37 (78.4%) primaquine, 3/70 (4.3%) amodiaquine, and one sample each of quinine, artemether, sulphadoxine-pyrimethamine and amoxicillin. According to the package label, 86.5% of poor-quality samples originated from India. Poor-quality medicines were found in 48.3% of providers at all levels of the supply chain. Drug quality was unrelated to storage conditions.Conclusions: This study documents the presence of poor-quality medicines, particularly primaquine, throughout PNG. Primaquine is the only available transmission-blocking antimalarial, likely to become important to prevent the spread of artemisinin-resistant P. falciparum and eliminating P. vivax hypnozoites. The availability of poor-quality medicines reflects the lack of adequate quality control and regulatory mechanisms. Measures to stop the availability of poor-quality medicines should include limiting procurement to WHO prequalified products and implementing routine quality testing

Determinants of career aspirations of medical students in southern China

<p>Abstract</p> <p>Background</p> <p>With recent changes in both the Chinese medical system and compensation of medical doctors, the career aspirations of Chinese medical students have become more diverse. Shantou University Medical College has conducted evaluations and instituted programs to enhance student preparedness to enter a variety of medical careers.</p> <p>Methods</p> <p>A survey was conducted with 85 students to evaluate medical career aspirations and their association with family background, personal skills, English language proficiency, and interest in biomedical research, which were considered as possible factors affecting their career interest.</p> <p>Results</p> <p>Chinese students aspire to traditional as well as nontraditional medical careers. A significant minority of students are now interested in nontraditional careers such as medical teaching or research. However, poor proficiency in the English language and lack of computer skills may limit their academic and career opportunities.</p> <p>Conclusion</p> <p>Career aspirations have changed among medical undergraduates. Although many wish to pursue a traditional clinical doctor career, many are interested in research and teaching careers. Factors such as family background, personal characteristics, school mentoring, and extracurricular support may play a role.</p

Clinico-pathological profile of sinonasal masses: an experience in national ear care center Kaduna, Nigeria

<p>Abstract</p> <p>Background</p> <p>The presence of a mass in the nose and paranasal sinuses may seem to be a simple problem; however it raises many questions about the differential diagnosis. The aim of this study is to evaluate the clinico-pathological profile of sinonasal masses in our environment</p> <p>This is a retrospective analytical review of all the patients with sinonasal masses that presented to the national ear care center, Kaduna over a six year (2003-2008) period. Their biodata, clinical profile and histological diagnoses were analyzed.</p> <p>Findings</p> <p>A total of 76 patients were analyzed, age range 5 to 64 yrs with a mean age of 33.3 yr median and modal age of 35.00 (SD = 13.1 ± 1.5). Majority of the patients were in the age groups 21-50 yrs. There were 34 male and 42 female with M: F ratio of 1:1.2. The main presenting symptoms are nasal blockage 97.4% and rhinorrhea 94.7%. It was bilateral in 34 (44.7%), left side in 24(31.6%) and right side in 18(23.7%) patients. The commonest clinical diagnoses were simple nasal polyp 47(61.8%) and antrochoanal polyp 10(13.2%). About 59 (77.6%) were benign, 2 (2.6%) were malignant and 15 (19.7%) were lost to follow up. The commonest histological diagnosis is simple inflammatory nasal polyp in 28 (36.8%) patients and the least was nasal capillary hemangioma 2 (2.6%). About 55(72.4%) patients had surgical treatment.</p> <p>Conclusions</p> <p>Nasal obstruction and rhinorrhea are the commonest symptoms of presentation, simple inflammatory nasal polyp is still the commonest histological pattern seen in our environment, and surgery is still the best modality of treatment for benign tumor thus the need for advocacy for early recognition and referral to the ENT surgeon.</p

Optimal Timing of Insecticide Fogging to Minimize Dengue Cases: Modeling Dengue Transmission among Various Seasonalities and Transmission Intensities

Dengue virus infection is a serious infectious disease transmitted by Aedes mosquitoes in the tropics and sub-tropics. Disease control often involves the use of insecticide fogging against mosquito vectors. However, the effectiveness of this method for reducing dengue cases, in addition to appropriate application procedures, is still debated. The previous mathematical simulation study reported that insecticide fogging reduces dengue cases most effectively when applied soon after the epidemic peak; however, the model did not take into account seasonality and population immunity, which strongly affect the epidemic pattern of dengue infection. Considering these important factors, we used a mathematical simulation model to explore the most effective time for insecticide fogging and to evaluate its impact on reducing dengue cases. Simulations were conducted with various lengths of the wet season and population immunity levels. We found that insecticide fogging substantially reduces dengue cases if conducted at an appropriate time. In contrast to the previously suggested application time during the peak of disease prevalence, the optimal timing is relatively early: between the beginning of the dengue season and the prevalence peak

Slab melting as a barrier to deep carbon subduction

Interactions between crustal and mantle reservoirs dominate the surface inventory of volatile elements over geological time, moderating atmospheric composition and maintaining a lifesupporting planet1. While volcanoes expel volatile components into surface reservoirs, subduction of oceanic crust is responsible for replenishment of mantle reservoirs2,3. Many natural, ‘superdeep’ diamonds originating in the deep upper mantle and transition zone host mineral inclusions, indicating an affinity to subducted oceanic crust4–7. Here we show that the majority of slab geotherms will intersect a deep depression along the melting curve of carbonated oceanic crust at depths of approximately 300 to 700 kilometres, creating a barrier to direct carbonate recycling into the deep mantle. Low-degree partial melts are alkaline carbonatites that are highly reactive with reduced ambient mantle, producing diamond. Many inclusions in superdeep diamonds are best explained by carbonate melt–peridotite reaction. A deep carbon barrier may dominate the recycling of carbon in the mantle and contribute to chemical and isotopic heterogeneity of the mantle reservoir