Gold(I)-Catalyzed Functionalization of Pyrrole Derivatives: Stereoselective Synthesis of 7,8-Disubstituted 7,8-Dihydroindolizin-6(5)-ones.

A gold-catalyzed cycloisomerization/nucleophilic addition/C-O rearrangement was developed starting from readily available pyrrole precursors. This efficient synthesis of 7,8-dihydroindolizin-6(5)-ones (with the creation of new C-C and C-O bonds) allows access to key intermediates for the synthesis of natural and biologically active molecules. The functionalization process was independently optimized for both carbon and oxygen nucleophiles, and the versatility of this methodology was established by the synthesis of 36 different pyrrole derivatives (yields up to 90%).

Use of Limonene Epoxides and Derivatives as Promising Monomers for Biobased Polymers.

(R)-Limonene, a renewable terpene, and its epoxidized derivatives, i. e. limonene epoxides, have prompted growing attention over the last decade as building blocks for the synthesis of biobased monomers and polymers.

[Requirements for academic production of CAR-T cells in accordance with Good Pharmaceutical Practice (GMP). Guidelines from the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC)].

The extraordinary and unexpected success of cellular immunotherapy using genetically engineered T-cells to express a chimeric antigen receptor (CAR) targeting CD19, in the treatment of refractory or relapsing B-hematological malignancies, has provided a real therapeutic hope. Indeed, remission rates reach more than 80 % in patients at a stage, without any other possibilities of treatment, notably in the child's acute lymphoblastic leukemia. These results, initially resulting from academic research, led to Food and Drug accreditation for market access of two innovative autologous therapy drugs, Kimryah® and Yescarta®.

A comparison of two protocols for optimal red blood cell depletion using Sepax-2 device for ABO-major incompatible transplantation in adults.

Purpose Of The Study: In ABO-incompatible bone marrow transplantation, an efficient depletion of red blood cells (RBC) within the graft is mandatory to avoid adverse events in transplanted patients. Using non therapeutic products, we evaluated the substitution of the standard density gradient-based separation (DGBS) over Ficoll-Paque with the use of an automated procedure intended for buffy coat only (SmartRedux software) introducing modifications within the settings to achieve a drastic reduction of the initial volume of the product. Both methods were conducted on the Sepax-2 device.

Quality Control of a Functionalized Polymer Catalyst by Energy Dispersive X-ray Spectrometry (EDX or EDS).

Energy dispersive X-ray spectrometry (EDX or EDS) is a technique often implemented on scanning electron microscopes and a regularly used method for qualitative characterization of solid catalysts. This Technical Note reports a method for the determination of the metal content in a sulfonated polyether ether ketone in the form of an indium(III) salt. The possibility of quantitative determination of the sulfur/indium ratio by EDX was assessed by calibration with two indium salts (sulfide and sulfate) readily available in good purity.

Quantitative Ligand Affinity Scales for Metal Triflate Salts: Application to Isomer Differentiation.

Owing to the importance of metal triflates in catalysis, the affinity of the cationic center for a selection of organic ligands was explored for In and Zn triflates. The organic Lewis bases include a variety of carbonyls (amides, unsaturated ketones, a lactone) and cyclic 1,2-diols. The relative affinity of the ligands for the cationic center in triflates was quantitatively determined on the basis of relative ion concentrations determined by electrospray-ionization mass spectrometry.

Application of cooperative iron/copper catalysis to a palladium-free borylation of aryl bromides with pinacolborane.

A new cooperative copper/iron catalysis for the borylation of various aryl bromides with pinacolborane, at -10 °C, is reported. Use of the toxic, precious metal Pd is avoided. The mechanism of the protodebromination side reaction is discussed.

A quantitative approach of the interaction between metal triflates and organic ligands using electrospray mass spectrometry.

The interaction between two Lewis "superacid" catalysts Zn(OTf)(2) and In(OTf)(3) and series of amide and phosphate ligands is quantitatively characterized by electrospray ionization mass spectrometry (ESI-MS). A specific feature of the ESI-MS spectra of the mixture of metal triflates and Lewis bases is the formation of ionic adducts resulting from the displacement of one triflate anion by two neutral ligands. A ligand competition model is developed, which describes the relative intensities of the ionic adducts as a function of relative ligand concentrations.

Biomimetic cationic polyannulation reaction catalyzed by Bi(OTf)3: cyclization of 1,6-dienes, 1,6,10-trienes, and aryl polyenes.

Nonactivated trienes and aryltrienes were cyclized into polycyclic compounds in good to excellent yields under bismuth triflate catalysis in a biomimetic fashion. The reaction showed broad applicability and allowed for the formation of functionalized bicyclic to tetracyclic structures from simple precursors in one pot. For some specific substrates, the cyclization was followed by a methyl shift as encountered in terpenoid biosynthesis.

A new method for the determination of short-chain fatty acids from the aliphatic series in wines by headspace solid-phase microextraction-gas chromatography-ion trap mass spectrometry.

A new analytical method for the determination of nine short-chain fatty acids (acetic, propionic, isobutyric, butyric, isovaleric, 2-methylbutyric, hexanoic, octanoic and decanoic acids) in wines using the automated HS/SPME-GC-ITMS technique was developed and optimised. Five different SPME fibers were tested and the influence of different factors such as temperature and time of extraction, temperature and time of desorption, pH, strength ionic, tannins, anthocyans, SO(2), sugar and ethanol content were studied and optimised using model solutions. Some analytes showed matrix effect so a study of recoveries was performed.

Relative basicities toward metal triflates Lewis acids by electrospray mass spectrometry.

The relative Lewis basicity of a series of phosphoryl compounds toward cations M(n+)(OTf)(n-1) derived from triflate salts, M(OTf)(n), is ranked using electrospray mass spectrometry according to competitive adduct formation.

Mass spectrometric characterization of metal triflates and triflimides (Lewis superacid catalysts) by electrospray ionization and tandem mass spectrometry.

Trifluoromethylsulfonate (triflate) and bis(trifluoromethylsulfonyl)imide (triflimide) salts, well-known Lewis acid catalysts, present some difficulty in their characterization. By using nitromethane as the solvent, useful electrospray mass spectra in positive and negative ion mode were obtained for salts of metals in oxidation states +2 and +3. In positive mode, addition of a strong Lewis base (triphenylphosphine oxide, TPPO), capable of displacing a triflate (TfO(-)) or a triflimide (Tf(2)N(-)) anion, is necessary for obtaining useful spectra.

An opportunity for Mg-catalyzed Grignard-type reactions: direct coupling of benzylic halides with pinacolborane with 10 mol % of magnesium.

Mg in catalytic amounts as the only metal permits the reductive coupling between benzyl halides and pinacolborane. HBpin acts both as an electrophile and as a reducing agent to regenerate an organomagnesium species in situ. An hydride oxidation mechanism is proposed on the basis of DFT calculations.

Subsurface iron and arsenic removal for shallow tube well drinking water supply in rural Bangladesh.

Subsurface iron and arsenic removal has the potential to be a cost-effective technology to provide safe drinking water in rural decentralized applications, using existing shallow tube wells. A community-scale test facility in Bangladesh was constructed for injection of aerated water (∼1 m(3)) into an anoxic aquifer with elevated iron (0.27 mmolL(-1)) and arsenic (0.

Aluminium(III) trifluoromethanesulfonate as an efficient catalyst for the intramolecular hydroalkoxylation of unactivated olefins: experimental and theoretical approaches.

The Al(OTf)(3)-catalyzed cycloisomerization of unactivated unsaturated alcohols was studied from experimental and theoretical points of view. A series of cyclic ethers was obtained in excellent yields and regioselectivities. This catalyst system provides one of the most straightforward routes to cyclic ethers with Markovnikov-type regioselectivity under mild conditions.

CD34(+) immunoselected cells for poor graft function following allogeneic BMT.

Background: Poor graft function without signs of graft rejection following allogeneic BMT (allo-BMT) occurs in around 9% of patients. A high incidence of hazardous complications may be encountered, leading to life-threatening situations.

Methods: We describe three patients who underwent allo-BMT for acute leukemia in first complete remission and untreated myelodysplastic syndrome.

Detection of epithelial cells in hematopoietic organs of patients with breast cancer. Physiopathological significance and clinical consequences.

Breast cancer is the most frequent neoplastic disease in populations of developed countries. It will affect 1 of every 6 or 7 women during their lifetime. The disease eventually evolves to a metastatic stage, and currently appears to be not curable at that stage.

Ex vivo expansion of human hematopoietic progenitors and cells to support high-dose chemoradiation therapy: five years of clinical experience.

The identification of cytokines-soluble or membrane-bound regulators of hematopoietic stem and progenitor cell survival, proliferation, and differentiation - and the definition of culture conditions that enable cell and progenitor expansion, has lead to the first clinical trials using cultured cells in addition to or in place of unmanipulated cells. The use of ex vivo expanded cells can improve several aspects of autologous and allogeneic hematopoietic cell and progenitor transplantation, such as reducing or abolishing the nadir that follows high-dose chemoradiation therapy regimens, or reducing the clinical risks associated with the use of small numbers of progenitors as in cord blood transplantation and in autologous transplantation for poor mobilizers. In addition, biological questions raised by ex vivo expansion are shared by scientists and clinicians interested in gene transfer into hematopoietic stem cells.

Detection of different Ikaros isoforms in human leukaemias using real-time quantitative polymerase chain reaction.

The Ikaros gene is an essential regulator in development and haematopoiesis. Dysregulated Ikaros gene expression participates in leukaemic processes, as evidenced in animal models, and by analyses of blast-cell populations from leukaemic patients. We used real-time quantitative polymerase chain reaction (PCR) to evaluate the relative abundance of several Ikaros transcript isoforms in a variety of leukaemic-cell samples.

The role of autologous hematopoietic progenitor and cell reinfusion for intensive chemotherapy in women with poor-prognosis breast cancer. Clinical studies with ex-vivo expanded cells produced with the Aastrom Replicell technology.

In recent years, we have initiated two clinical studies, to evaluate the usefulness of ex-vivo expanded cells in patients with breast cancer who receive sequential high-dose chemotherapy. Ex-vivo expanded cells were produced from autologous cryopreserved bone marrow nucleated cells, using a biomedical device. The Aastrom Replicell system cultures cells in animal serum-replete medium, with a combination of flt3-L, PIXY321 and Epo, for 12 days.

CD34+ cell enumeration in peripheral blood and apheresis samples, using two laboratory diagnostic kits or an institutional protocol.

In order to prepare the substitution of a commercially available diagnostic kit, ProCOUNT (Becton Dickinson) or Stem-Kit (Coulter Immunotech), for our institutional protocol, we compared the three techniques for the numeration of CD34+ progenitor cells in 50 peripheral blood and 51 apheresis samples, obtained from cancer patients or healthy donors. We show here that the three techniques yield results of the same order of magnitude. Although statistical analyses demonstrate significant differences between the three methods, these differences turned out to be clinically insignificant in most situations.

T-cell depletion of allogeneic bone marrow grafts: enrichment of mononuclear cells using the COBE Spectra cell processor, followed by immunoselection of CD34(+) cells.

Background: Enrichment in mononuclear cells (MNC) is a prerequisite for CD34(+) cell selection from BM allografts. However, centrifugation over a density gradient (Ficoll), does not comply with good manufacturing practice (GMP), because Ficoll is not a clinical grade reagent. We evaluated the COBE Spectra cell separator as an alternative and evaluated the recovery of MNC and CD34(+) cells.

Differential association of phosphatases with hematopoietic co-receptors bearing immunoreceptor tyrosine-based inhibition motifs.

A novel family of inhibitory co-receptors has been recently defined according to the presence in their intracytoplasmic domain of immunoreceptor tyrosine-based inhibition motifs (ITIM). In particular, this family includes a low-affinity receptor for IgG, Fc gammaRIIB, which is widely expressed on hematopoietic cells, as well as killer cell inhibitory receptors (KIR) for major histocompatibility complex (MHC) class I proteins, expressed on both T and natural killer (NK) lymphocytes. Fc gammaRIIB and KIR inhibitory function depends upon the tyrosine phosphorylation of their respective ITIM.

Transduction of cytotoxic signals in natural killer cells: a general model of fine tuning between activatory and inhibitory pathways in lymphocytes.

NK-cells are large granular lymphocytes, which are capable of exerting two major types of effector function, cell cytotoxicity and lymphokine secretion. NK-cells can exert cell cytotoxicity in one of two ways. First, NK-cells are able to recognize and to induce the lysis of antibody-coated target cells during antibody-dependent cell cytotoxicity (ADCC).

Hemostatic efficacy and safety of TachoComb in surgery. Ready to use and rapid hemostatic agent.

TachoComb is a new, ready-to-use hemostatic agent consisting of a collagen sheet coated on one side with human fibrinogen, bovine thrombin, and bovine aprotinin. The product was used in 125 surgical operations (vascular, hepatic, urological and ENT) in which secondary hemostasis was required. It was placed over the cut surface or over the edges of the wound.