Chimeric carrier proteins for targeted delivery of tumor antigens to professional antigen presenting cells

Tumor-specific T lymphocytes can be regarded as a highly effective mechanism for tumor rejection. A substantial number of T-cell defined tumor antigens including mutated oncoproteins and differentiation antigens have been identified. However, while most spontaneous tumors appear to be antigenic, few are immunogenic. Activation of tumor-specific cytotoxic T cells (CTL) requires presentation of tumor antigens by professional antigen presenting cells (APCs) via MHC I molecules. Due to their crucial role in T-cell activation, APCs are being exploited for active cancer immunotherapy. Present experimental strategies include the incubation of dendritic cells with synthetic, tumor specific peptides to achieve uptake of tumor antigens and presentation in the context of MHC molecules. Alternatively, gene therapeutic approaches are aimed at the endogenous expression of tumor antigens in APCs upon transfer of suitable vector constructs. Our strategy for the presentation of tumor antigens by APCs is based on the intracellular delivery of tumor antigens as part of a fusion protein specifically targeted to APC cell surface receptors. We have constructed prototype molecules that contain a soluble fragment of CTLA-4 for cell binding via interaction with B7 molecules, genetically fused to a protein fragment derived from the tumor-associated antigen ErbB2. To improve uptake and direct the antigenic determinant preferentially to the MHC class I pathway, in one of these protein vaccines also the translocation domain of the bacterial Pseudomonas exotoxin A has been included. In the parental toxin this protein domain facilitates escape from the endosomal compartment to the cytosol upon receptor mediated endocytosis. Here we have investigated the in vitro cell binding activity of such reagents and their antitumoral activity in immunocompetent murine model systems. Specific binding to B7 molecules and uptake of bacterially expressed protein vaccines could be demonstrated. Ex vivo restimulation with an ErbB2-derived peptide of splenocytes from Balb/c mice injected with the fusion proteins resulted in enhanced IFN-gamma production by T cells. Protective and therapeutic effects of ErbB2 protein vaccines were also investigated. Vaccinated animals were protected against subsequent challenge with syngeneic ErbB2 expressing tumor cells. Likewise, s.c. injection of ErbB2 protein vaccines in the vicinity of established tumors resulted in tumor rejection and long lasting protection indicating that immunological memory was induced. Our results suggest that chimeric proteins combining a tumor antigen and specific recognition of APCs in a single molecule are suitable for targeted delivery of antigens to professional APCs and might become valuable tools for cancer immunotherapy

Methods for sampling geographically mobile female traders in an East African market setting.

BACKGROUND:The role of migration in the spread of HIV in sub-Saharan Africa is well-documented. Yet migration and HIV research have often focused on HIV risks to male migrants and their partners, or migrants overall, often failing to measure the risks to women via their direct involvement in migration. Inconsistent measures of mobility, gender biases in those measures, and limited data sources for sex-specific population-based estimates of mobility have contributed to a paucity of research on the HIV prevention and care needs of migrant and highly mobile women. This study addresses an urgent need for novel methods for developing probability-based, systematic samples of highly mobile women, focusing on a population of female traders operating out of one of the largest open air markets in East Africa. Our method involves three stages: 1.) identification and mapping of all market stall locations using Global Positioning System (GPS) coordinates; 2.) using female market vendor stall GPS coordinates to build the sampling frame using replicates; and 3.) using maps and GPS data for recruitment of study participants. RESULTS:The location of 6,390 vendor stalls were mapped using GPS. Of these, 4,064 stalls occupied by women (63.6%) were used to draw four replicates of 128 stalls each, and a fifth replicate of 15 pre-selected random alternates for a total of 527 stalls assigned to one of five replicates. Staff visited 323 stalls from the first three replicates and from these successfully recruited 306 female vendors into the study for a participation rate of 94.7%. Mobilization strategies and involving traders association representatives in participant recruitment were critical to the study's success. CONCLUSION:The study's high participation rate suggests that this geospatial sampling method holds promise for development of probability-based samples in other settings that serve as transport hubs for highly mobile populations

Medial clavicular epiphysiolysis in children: the so-called sterno-clavicular dislocation

We retrospectively reviewed six pediatric cases of medial clavicular injury, i.e., epiphyseal separation (Salter/Harris type I or II injury), diagnosed between 1993 and 1997. The clavicular metaphysis was displaced posteriorly in three cases and anteriorly in three. On conventional radiographic views the diagnosis was initially missed in two of three retrosternal dislocations. A special X-ray projection (described by Heinig) or computed tomography (CT) permitted correct diagnosis. Anterior dislocations were immediately and correctly diagnosed. Closed reduction successfully treated retrosternal displacement in two of the three patients. The third patient needed open reduction and internal fixation. Open reduction and internal fixation had to be performed in all three patients with anterior displacement. Follow-up assessment showed perfect functional results in all cases. Direct visualization during open reduction, which was necessary in four of six cases, yielded clear evidence that the so-called sternoclavicular dislocation in children and young adults is, in fact, a fracture of the medial growth plate with posterior or anterior displacement of the metaphysi

Analisis Koordinasi dan Setting Over Current Relay (Ocr) pada Pemakaian Daya Sendiri Pltu SMS Energy Menggunakan Software Etap 12.6.0

Penelitian ini bertujuan untuk mengetahui besaran settingan OCR Motor Pump, Grading Time OCR Motor Pump, koordinasi OCR Motor Pump dan OCR auxiliary pada PLTU SMS Energi di kawasan industri Bolok.  Penelitian diawali dengan mengumpulkan data kelistrikan PLTU SMS Energy berupa data sekunder. Data-data tersebut digunakan  untuk membuat single line diagram, simulasi dan analisis menggunakan  ETAP 12.6.0. Hasil Penelitian mendapatkan Settingan OCR dengan parameter nilai arus hubung singkat sebagai berikut. Setting Rele Bus 1 FCP dengan Ip = 3 A dan TMS = 0,1 s,  Setting Rele Bus Auxiliary I dengan Ip = 2 A dan TMS = 0,21 s, Setting Rele Bus OutGoing 1 dengan Ip = 0,6666 A dan TMS = 0,30 s dan Setting Rele Bus G1 dengan Ip = 1 A dan TMS = 0,45 s. TMS OCR pada motor Pump disetting lebih cepat karena letak OCR paling hilir dengan ganguan hubung singkat lebih kecil. Dari koordinasi kurva didapatkan Grading Time yang sudah sesuai dengan standar IEEE 242-yakni 0.2 – 0.4 detik.  Kata Kunci: Over Current Relay, Koordinasi OCR, Grading time, Settingan OCR, ETAP 12.6.

Absorption of Ultrashort Laser Pulses in Strongly Overdense Targets

We report on the first absorption experiments of sub-10 fs high-contrast Ti:Sa laser pulses incident on solid targets. The very good contrast of the laser pulse assures the formation of a very small pre-plasma and the pulse interacts with the matter close to solid density. Experimental results indicate that p-polarized laser pulses are absorbed up to 80 percent at 80 degrees incidence angle. The simulation results of PSC PIC code clearly confirm the observations and show that the collisionless absorption works efficiently in steep density profiles