Preclinical activity and determinants of response of the GPRC5DxCD3 bispecific antibody talquetamab in multiple myeloma.

Cell surface expression levels of GPRC5D, an orphan G protein-coupled receptor, are significantly higher on multiple myeloma (MM) cells, compared with normal plasma cells or other immune cells, which renders it a promising target for immunotherapeutic strategies. The novel GPRC5D-targeting T-cell redirecting bispecific antibody, talquetamab, effectively kills GPRC5D+ MM cell lines in the presence of T cells from both healthy donors or heavily pretreated MM patients. In addition, talquetamab has potent anti-MM activity in bone marrow (BM) samples from 45 patients, including those with high-risk cytogenetic aberrations. There was no difference in talquetamab-mediated killing of MM cells from newly diagnosed, daratumumab-naïve relapsed/refractory (median of 3 prior therapies), and daratumumab-refractory (median of 6 prior therapies) MM patients. Tumor cell lysis was accompanied by T-cell activation and degranulation, as well as production of pro-inflammatory cytokines. High levels of GPRC5D and high effector:target ratio were associated with improved talquetamab-mediated lysis of MM cells, whereas an increased proportion of T cells expressing PD-1 or HLA-DR, and elevated regulatory T-cell (Treg) counts were associated with suboptimal killing. In cell line experiments, addition of Tregs to effector cells decreased MM cell lysis. Direct contact with bone marrow stromal cells also impaired the efficacy of talquetamab. Combination therapy with daratumumab or pomalidomide enhanced talquetamab-mediated lysis of primary MM cells in an additive fashion. In conclusion, we show that the GPRC5D-targeting T-cell redirecting bispecific antibody talquetamab is a promising novel antimyeloma agent. These results provide the preclinical rationale for ongoing studies with talquetamab in relapsed/refractory MM

DATABASE OF RECIPROCATING INTERNAL COMBUSTION ENGINES SELECTED MANUFACTURERS

During research works concerning piston internal-combustion engines specifications of these objects are often needed. This data is usually dispersed and reaching to some is hampered or impossible. Therefore, an electronic database was drawn up about the most important ship producer’s piston internal-combustion engines for needs of exploitation investigations in the destination of gathering the necessary information. This paper presents a database of global marine diesel engines. For example, engines of the following companies were described: Akasaka Diesel, CAT, Cummins, Fiat, Hyundai, MTU, Niigata Power Systems, Pielstick, Scania, Volvo Penta etc. Information was obtained from various sources, so as websites of producers, advertising catalogues, or books and magazines about subject matter associated with marine diesel engines. This information was collected and written with the help of the program Microsoft Office. Gathered data was divided in engines of the main drive and emergency, containing details about producers, types and parameters of 2-stroke engines and four-stroke. The base enables supplementing and the alteration of entered data. Produced engines are usually operated by several dozen years after producing on swimming objects. Produced internal combustion engines are usually operated by several dozen years after producing on floating objects, and producers are merging or are stopping existing

Database of reciprocating internal combustion engines selected manufacturers

During research works concerning piston internal-combustion engines specifications of these objects are often needed. This data is usually dispersed and reaching to some is hampered or impossible. Therefore, an electronic database was drawn up about the most important ship producer’s piston internal-combustion engines for needs of exploitation investigations in the destination of gathering the necessary information. This paper presents a database of global marine diesel engines. For example, engines of the following companies were described: Akasaka Diesel, CAT, Cummins, Fiat, Hyundai, MTU, Niigata Power Systems, Pielstick, Scania, Volvo Penta etc. Information was obtained from various sources, so as websites of producers, advertising catalogues, or books and magazines about subject matter associated with marine diesel engines. This information was collected and written with the help of the program Microsoft Office. Gathered data was divided in engines of the main drive and emergency, containing details about producers, types and parameters of 2-stroke engines and four-stroke. The base enables supplementing and the alteration of entered data. Produced engines are usually operated by several dozen years after producing on swimming objects. Produced internal combustion engines are usually operated by several dozen years after producing on floating objects, and producers are merging or are stopping existing

A database of piston marine diesel engines produced in H. Cegielski Poznań S. A. and ZUT Zgoda

W czasie prac badawczych dotyczących tłokowych silników spalinowych często potrzebne są dane techniczne tych obiektów. Dane te są zwykle rozproszone i dotarcie do niektórych jest utrudnione lub niemożliwe. Opracowano, zatem elektroniczną bazę danych o najważniejszych producentach okrętowych tłokowych silnikach spalinowych dla potrzeb badań eksploatacyjnych w celu zgromadzenia niezbędnych informacji. W tej pracy przedstawiono bazę danych głównych polskich producentów okrętowych tłokowych silników spalinowych. Informacje zostały pozyskane z różnych źródeł, takich jak: strony internetowe producentów, katalogi reklamowe, książki i czasopisma o tematyce związanej z okrętowymi silnikami spalinowymi. Informacje te zostały zebrane i zapisane przy pomocy programu Microsoft Office. Zgromadzone dane podzielono na silniki napędu głównego i pomocnicze, zawierający dane o producentach, typach i parametrach silników dwusuwowych i czterosuwowych. Baza umożliwia uzupełnianie i modyfikację wprowadzonych danych. Wyprodukowane silniki eksploatowane są zwykle przez kilkadziesiąt lat po wytworzeniu na obiektach pływających.During research works concerning piston internal-combustion engines specifications of these objects are often needed. This data is usually dispersed and reaching to some is hampered or impossible. And so an electronic database was drawn up about the most important ship's producer’s piston internal-combustion engines for needs of exploitation investigations in the destination of gathering the necessary information. At this work a database of main Polish producers of marine diesel engines was presented. Information was obtained from various sources, so as: websites of producers, advertising catalogues, or books and magazines about subject matter associated with marine diesel engines. This information was collected and written with the help of the program Microsoft Office. Gathered data was divided in engines of the main drive and emergency, containing details about producers, types and parameters of 2-stroke engines and four-stroke. The base enables supplementing and the alteration of entered data. Produced engines are usually operated by several dozen years after producing on swimming objects

Supported Lipid Bilayers with Phosphatidylethanolamine as the Major Component

Phosphatidylethanolamine (PE) is notoriously difficult to incorporate into model membrane systems, such as fluid supported lipid bilayers (SLBs), at high concentrations because of its intrinsic negative curvature. Using fluorescence-based techniques, we demonstrate that having fewer sites of unsaturation in the lipid tails leads to high-quality SLBs because these lipids help to minimize the curvature. Moreover, shorter saturated chains can help maintain the membranes in the fluid phase. Using these two guidelines, we find that up to 70 mol % PE can be incorporated into SLBs at room temperature and up to 90 mol % PE can be incorporated at 37 °C. Curiously, conditions under which three-dimensional tubules project outward from the planar surface as well as conditions under which domain formation occurs can be found. We have employed these model membrane systems to explore the ability of Ni²⁺ to bind to PE. It was found that this transition metal ion binds 1000-fold tighter to PE than to phosphatidylcholine lipids. In the future, this platform could be exploited to monitor the binding of other transition metal ions or the binding of antimicrobial peptides. It could also be employed to explore the physical properties of PE-containing membranes, such as phase domain behavior and intermolecular hydrogen bonding

Clinical-pathological features and treatment modalities associated with recurrence in DCIS and micro-invasive carcinoma: Who to treat more and who to treat less

The primary aim in the management of DCIS is the prevention of recurrence and contralateral tumor. Risk factors for DCIS recurrence and appropriate treatments are still widely debated. Adjuvant therapies after surgical resection reduce recurrences and contralateral disease, but these treatments have significant financial costs, side effects and there is a group of low-risk patients who would not gain additional benefit. The aim of our analysis was to identify clinical-pathological features and treatment modalities associated with recurrence in DCIS and microinvasive carcinoma. In the Thomas Jefferson University Cancer Registry of Philadelphia, we identified 865 patients with DCIS or micro-invasive carcinoma treated between 2003 and 2013. Associations between recurrence and demographic factors (age at diagnosis, ethnicity), biological features (ER, PR and HER2) and treatment modalities (surgery, radiotherapy and endocrine treatment) were assessed. Our single institution register-based study showed that distribution of age at diagnosis and biological features did not significantly differ among ethnic groups. Younger women and micro-invasive carcinoma patients were more likely to undergo mastectomy, while African Americans were more likely to take endocrine therapy and undergo radiotherapy. In our sample only ER/PR negative DCIS were associated with significantly higher recurrence rate. Moreover, we reported a high rate of HER2 positive recurrences, suggesting that expression of this oncogene may represent a potential biomarker for DCIS at high risk of recurrence. To better define the molecular profile of the subgroup at worse prognosis might help to identify biomarkers predictive of recurrence or second tumors, identifying patients candidates for more appropriate treatments