EXPRESSION OF A FUNCTIONAL CHIMERIC lg-MHC CLASS II PROTEIN

composed of the a- and ß-chains of the MHC class I1 I-E molecule fused to antibody V regions derived from anti-human CD4 mAb MT310. Expression vectors were constructed containing the functional, rearranged gene segments coding for the V region domains of the antibody H and L chains in place of the first domains of the complete structural genes of the I-E a- and ß-chains, respectively. Celltsr ansfected with both hybrid genes expressed a stable protein product on the cell surface. The chimeric molecule exhibited the idiotype of the antibody MT310 as shown by binding to the anti-idiotypic mAb 20-46. A protein of the anticipated molecular mass was immunoprecipitated witha nti-mouse IgG antiserum. Furthermore, human soluble CD4 did bind to thetr ansfected cell line, demonstrating that the chimeric protein possessed the binding capacity of the original mAb. Thus, the hybrid molecule retained: 1) the properties of a MHC class I1 protein with regardt o correct chain assembly and transport to the cell surface: as well as 2) the Ag binding capacity of the antibody genes used. Thgee neration of hybrid MHC class I1 molecules with highly specific, non-MHC-restricted bindingc apacities will be useful for studying MHC class 11-mediated effector functions such as selection of the T cell repertoire in thymus of transgenic mice

Corporate Governance, Opaque Bank Activities, and Risk/Return Efficiency: Pre- and Post-Crisis Evidence from Turkey

Does better corporate governance unambiguously improve the risk/return efficiency of banks? Or does either a re-orientation of banks' revenue mix towards more opaque products, an economic downturn, or tighter supervision create off-setting or reinforcing effects? The authors relate bank efficiency to shortfalls from a stochastic risk/return frontier. They analyze how internal governance mechanisms (CEO duality, board experience, political connections, and education profile) and external governance mechanisms (discipline exerted by shareholders, depositors, or skilled employees) determine efficiency in a sample of Turkish banks. The 2000 financial crisis was a wakeup call for bank efficiency and corporate governance. As a result, better corporate governance mechanisms have been able to improve risk/return efficiency when the economic, regulatory, and supervisory environments are more stable and bank products are more complex.corporate governance;bank risk;noninterest income;crisis;frontier

Microwave Sinterator Freeform Additive Construction System (MS-FACS)

The harmful properties of lunar dust, such as small size, glass composition, abnormal surface area, and coatings of imbedded nanophase iron, lead to a unique coupling of the dust with microwave radiation. This coupling can be exploited for rapid sintering of lunar soil for use as a construction material that can be formed to take on an infinite number of shapes and sizes. This work describes a system concept for building structures on the lunar surface using lunar regolith (soil). This system uses the ATHLETE (All-Terrain Hex- Limbed Extra-Terrestrial Explorer) mobility system as a positioning system with a microwave print head (similar to that of a smaller-scale 3D printer). A processing system delivers the lunar regolith to the microwave print head, where the microwave print head/chamber lays down a layer of melted regolith. An arm on the ATHLETE system positions the layer depending on the desired structure

The use of an e-learning constructivist solution in workplace learning

We wished to investigate whether an e-learning approach which uses constructivist principles can be successfully applied to train employees in a highly specialised skill thought to require expert individuals and extensive prolonged training. The approach involved the development of an e-learning package which included simulations and interactivity, then experimental testing in a case study workplace environment with the collection of both quantitative and qualitative data to assess the effectiveness of the package. Our study shows that this e-learning strategy improved the skills of the inexperienced operator significantly. We therefore propose that such programmes could be used as a work based training aid and used as a model system for the training of employees in complex skilled tasks in the workplace. This research demonstrates that the e-learning can be applied outside the traditional learning environment to train unskilled employees to undertake complex practical tasks which traditionally would involve prohibitively expensive instruction. This work also illustrates that simulations and interactivity are powerful tools in the design of successful e-learning packages in preparing learners for real world practical situations. Finally this study shows that workplace learners can be better served by elearning environments rather than conventional training as they allow asynchronous learning and private study which are valued by employees who have other demands on their time and are more comfortable receiving tuition privately Relevance to industry: E-learning using constructivist principles, and incorporating simulations and interactivity can be used successfully in the training of highly specialised and skilled tasks required in the modern workplace

MR-guided adaptive stereotactic body radiotherapy (SBRT) of primary tumor for pain control in metastatic pancreatic ductal adenocarcinoma (mPDAC): an open randomized, multicentric, parallel group clinical trial (MASPAC)

BACKGROUND Pain symptoms in the upper abdomen and back are prevalent in 80% of patients with metastatic pancreatic ductal adenocarcinoma (mPDAC), where the current standard treatment is a systemic therapy consisting of at least doublet-chemotherapy for fit patients. Palliative low-dose radiotherapy is a well-established local treatment option but there is some evidence for a better and longer pain response after a dose-intensified radiotherapy of the primary pancreatic cancer (pPCa). Stereotactic body radiation therapy (SBRT) can deliver high radiation doses in few fractions, therefore reducing chemotherapy-free intervals. However, prospective data on pain control after SBRT of pPCa is very limited. Therefore, we aim to investigate the impact of SBRT on pain control in patients with mPDAC in a prospective trial. METHODS This is a prospective, double-arm, randomized controlled, international multicenter study testing the added benefit of MR-guided adaptive SBRT of the pPca embedded between standard of care-chemotherapy (SoC-CT) cycles for pain control and prevention of pain in patients with mPDAC. 92 patients with histologically proven mPDAC and at least stable disease after initial 8 weeks of SoC-CT will be eligible for the trial and 1:1 randomized in 3 centers in Germany and Switzerland to either experimental arm A, receiving MR-guided SBRT of the pPCa with 5 × 6.6 Gy at 80% isodose with continuation of SoC-CT thereafter, or control arm B, continuing SoC-CT without SBRT. Daily MR-guided plan adaptation intents to achieve good target coverage, while simultaneously minimizing dose to organs at risk. Patients will be followed up for minimum 6 and maximum of 18 months. The primary endpoint of the study is the "mean cumulative pain index" rated every 4 weeks until death or end of study using numeric rating scale. DISCUSSION An adequate long-term control of pain symptoms in patients with mPDAC is an unmet clinical need. Despite improvements in systemic treatment, local complications due to pPCa remain a clinical challenge. We hypothesize that patients with mPDAC will benefit from a local treatment of the pPCa by MR-guided SBRT in terms of a durable pain control with a simultaneously favorable safe toxicity profile translating into an improvement of quality-of-life. TRIAL REGISTRATION German Registry for Clinical Trials (DRKS): DRKS00025801. Meanwhile the study is also registered at ClinicalTrials.gov with the Identifier: NCT05114213

MR-guided adaptive stereotactic body radiotherapy (SBRT) of primary tumor for pain control in metastatic pancreatic ductal adenocarcinoma (mPDAC): an open randomized, multicentric, parallel group clinical trial (MASPAC)

BACKGROUND: Pain symptoms in the upper abdomen and back are prevalent in 80% of patients with metastatic pancreatic ductal adenocarcinoma (mPDAC), where the current standard treatment is a systemic therapy consisting of at least doublet-chemotherapy for fit patients. Palliative low-dose radiotherapy is a well-established local treatment option but there is some evidence for a better and longer pain response after a dose-intensified radiotherapy of the primary pancreatic cancer (pPCa). Stereotactic body radiation therapy (SBRT) can deliver high radiation doses in few fractions, therefore reducing chemotherapy-free intervals. However, prospective data on pain control after SBRT of pPCa is very limited. Therefore, we aim to investigate the impact of SBRT on pain control in patients with mPDAC in a prospective trial. METHODS: This is a prospective, double-arm, randomized controlled, international multicenter study testing the added benefit of MR-guided adaptive SBRT of the pPca embedded between standard of care-chemotherapy (SoC-CT) cycles for pain control and prevention of pain in patients with mPDAC. 92 patients with histologically proven mPDAC and at least stable disease after initial 8 weeks of SoC-CT will be eligible for the trial and 1:1 randomized in 3 centers in Germany and Switzerland to either experimental arm A, receiving MR-guided SBRT of the pPCa with 5 × 6.6 Gy at 80% isodose with continuation of SoC-CT thereafter, or control arm B, continuing SoC-CT without SBRT. Daily MR-guided plan adaptation intents to achieve good target coverage, while simultaneously minimizing dose to organs at risk. Patients will be followed up for minimum 6 and maximum of 18 months. The primary endpoint of the study is the “mean cumulative pain index” rated every 4 weeks until death or end of study using numeric rating scale. DISCUSSION: An adequate long-term control of pain symptoms in patients with mPDAC is an unmet clinical need. Despite improvements in systemic treatment, local complications due to pPCa remain a clinical challenge. We hypothesize that patients with mPDAC will benefit from a local treatment of the pPCa by MR-guided SBRT in terms of a durable pain control with a simultaneously favorable safe toxicity profile translating into an improvement of quality-of-life. TRIAL REGISTRATION: German Registry for Clinical Trials (DRKS): DRKS00025801. Meanwhile the study is also registered at ClinicalTrials.gov with the Identifier: NCT05114213

Collaborative Training With a More Experienced Partner: Remediating Low Pretraining Self-Efficacy in Complex Skill Acquisition

Objective: This study examined the effectiveness of collaborative training for individuals with low pretraining self-efficacy versus individuals with high pretraining selfefficacy regarding the acquisition of a complex skill that involved strong cognitive and psychomotor demands. Background: Despite support for collaborative learning from the educational literature and the similarities between collaborative learning and interventions designed to remediate low self-efficacy, no research has addressed how selfefficacy and collaborative learning interact in contexts concerning complex skills and human-machine interactions. Method: One hundred fifty-five young male adults trained either individually or collaboratively with a more experienced partner on a complex computer task that simulated the demands of a dynamic aviation environment. Participants also completed a task-specific measure of self-efficacy before, during, and after training. Results: Collaborative training enhanced skill acquisition significantly more for individuals with low pretraining self-efficacy than for individuals with high pretraining self-efficacy. However, collaborative training did not bring the skill acquisition levels of those persons with low pretraining self-efficacy to the levels found for persons with high pretraining self-efficacy. Moreover, tests of mediation suggested that collaborative training may have enhanced appropriate skill development strategies without actually raising self-efficacy. Conclusion: Although collaborative training can facilitate the skill acquisition process for trainees with low self-efficacy, future research is needed that examines how the negative effects of low pretraining self-efficacy on complex skill acquisition can be more fully remediated. Application: The differential effects of collaborative training as a function of self-efficacy highlight the importance of person analysis and tailoring training to meet differing trainee needs.Yeshttps://us.sagepub.com/en-us/nam/manuscript-submission-guideline

Identification of SOX2 as a novel glioma-associated antigen and potential target for T cell-based immunotherapy

Prognosis for patients suffering from malignant glioma has not substantially improved. Specific immunotherapy as a novel treatment concept critically depends on target antigens, which are highly overexpressed in the majority of gliomas, but the number of such antigens is still very limited. SOX2 was identified by screening an expression database for transcripts that are overexpressed in malignant glioma, but display minimal expression in normal tissues. Expression of SOX2 mRNA was further investigated in tumour and normal tissues by real-time PCR. Compared to cDNA from pooled normal brain, SOX2 was overexpressed in almost all (9 out of 10) malignant glioma samples, whereas expression in other, non-malignant tissues was almost negligible. SOX2 protein expression in glioma cell lines and tumour tissues was verified by Western blot and immunofluorescence. Immunohistochemistry demonstrated SOX2 protein expression in all malignant glioma tissues investigated ranging from 6 to 66% stained tumour cells. Human leucocyte antigen-A*0201-restricted SOX2-derived peptides were tested for the activation of glioma-reactive CD8+ cytotoxic T lymphocytes (CTLs). Specific CTLs were raised against the peptide TLMKKDKYTL and were capable of lysing glioma cells. The abundant and glioma-restricted overexpression of SOX2 and the generation of SOX2-specific and tumour-reactive CTLs may recommend this antigen as target for T-cell-based immunotherapy of glioma

Acellular Pertussis Booster in Adolescents Induces Th1 and Memory CD8+ T Cell Immune Response

In a number of countries, whole cell pertussis vaccines (wcP) were replaced by acellular vaccines (aP) due to an improved reactogenicity profile. Pertussis immunization leads to specific antibody production with the help of CD4+ T cells. In earlier studies in infants and young children, wcP vaccines selectively induced a Th1 dominated immune response, whereas aP vaccines led to a Th2 biased response. To obtain data on Th1 or Th2 dominance of the immune response in adolescents receiving an aP booster immunization after a wcP or aP primary immunization, we analyzed the concentration of Th1 (IL-2, TNF-α, INF-γ) and Th2 (IL-4, IL-5, IL-10) cytokines in supernatants of lymphocyte cultures specifically stimulated with pertussis antigens. We also investigated the presence of cytotoxic T cell responses against the facultative intracellular bacterium Bordetella pertussis by quantifying pertussis-specific CD8+ T cell activation following the aP booster immunization. Here we show that the adolescent aP booster vaccination predominantly leads to a Th1 immune response based on IFNgamma secretion upon stimulation with pertussis antigen, irrespective of a prior whole cell or acellular primary vaccination. The vaccination also induces an increase in peripheral CD8+CD69+ activated pertussis-specific memory T cells four weeks after vaccination. The Th1 bias of this immune response could play a role for the decreased local reactogenicity of this adolescent aP booster immunization when compared to the preceding childhood acellular pertussis booster. Pertussis-specific CD8+ memory T cells may contribute to protection against clinical pertussis