This communication demonstrates the homogeneous hydrogenation of CO2 to CH3OH via cascade catalysis. Three different homogeneous catalysts, (PMe3)4Ru(Cl)(OAc), Sc(OTf)3, and (PNN)Ru(CO)(H), operate ...in sequence to promote this transformation.
In situ Raman spectroscopy and cyclic voltammetry were used to investigate the mechanism of sulfur reduction in lithium–sulfur battery slurry cathodes with 1 M lithium bis(trifluoromethane ...sulfonyl)imide (LiTFSI) and tetraethylene glycol dimethyl ether (TEGDME)/1,3-dioxolane (DIOX) (1/1, v/v). Raman spectroscopy shows that long-chain polysulfides (S8 2–) were formed via S8 ring opening in the first reduction process at ∼2.4 V vs Li/Li+ and short-chain polysulfides such as S4 2–, S4 –, S3 •–, and S2O4 2– were observed with continued discharge at ∼2.3 V vs Li/Li+ in the second reduction process. Elemental sulfur can be reformed in the end of the charge process. Rate constants obtained for the appearance and disappearance polysulfide species shows that short-chain polysulfides are directly formed from S8 decomposition. The rate constants for S8 reappearance and polysulfide disappearance on charge were likewise similar. The formation of polysulfide mixtures at partial discharge was found to be quite stable. The CS2 additive was found to inhibit the sulfur reduction mechanism allowing the formation of long-chain polysulfides during discharge only and stabilizing the S8 2– product.
This paper reports the hydrogenation of carbon dioxide to formate catalyzed by the Ru pincer complex Ru(PNN)CO(H) (PNN = ...6-(di-tert-butylphosphinomethylene)-2-(N,N-diethylaminomethyl)-1,6-dihydropyridine). Stoichiometric studies are presented that support the feasibility of the individual steps in a proposed catalytic cycle for this transformation. The influence of base and solvent on catalyst performance is explored. Overall, under optimized conditions (using diglyme as the solvent and potassium carbonate as the base) up to 23,000 turnovers of formate and a turnover frequency of up to 2,200 h–1 can be achieved.
Selinexor, a drug that inhibits nuclear export of tumor suppressor proteins, was tested in a phase 2 trial involving patients with myeloma whose disease had progressed despite treatment with ...proteasome inhibitors, immunomodulatory agents, alkylating agents, and monoclonal antibodies. A partial response or better was observed in 26% of patients, and the median overall survival was 8.6 months.
This communication describes the activation of CO2 at the Ru pincer complex (PNN)Ru(H)(CO) (PNN = 6-(di-tert-butylphosphinomethylene)-2-(N,N-diethylaminomethyl)-1,6-dihydropyridine). The reaction ...proceeds to completion within minutes at room temperature to form a C–C bond between the pincer ligand and the electrophilic carbon atom of CO2. The characterization of both the kinetic and thermodynamic products of CO2 activation and the reversibility of this C–C bond formation are discussed.
Background
Intestinal failure–associated liver disease (IFALD) occurs in ≤85% of neonates receiving prolonged parenteral nutrition. Strategies for treatment of IFALD include alternative lipid ...therapies, such as Smoflipid (Fresenius Kabi). In this study, we reviewed our institutional Smoflipid use, including predictors of patient response and safety concerns.
Methods
This is a retrospective chart review of all pediatric patients who received Smoflipid therapy over a 2‐year period at Riley Hospital for Children. Forty‐two patients (89%) had cholestasis at the start of Smoflipid therapy and were included in group analysis. We compared patients based on response to Smoflipid therapy, identifying associations and predictors of patient response. We also documented patient safety concerns, including essential fatty acid deficiency (EFAD), rapid infusion, and compatibility/access issues.
Results
Sixteen patients (38%) with cholestasis had resolution with Smoflipid. Those patients with resolution were older at initiation (58 vs 33.5 days; P = .010), treated with Smoflipid for longer (85.5 vs 41 days; P = .001), and had lower direct bilirubin at the start of Smoflipid therapy (3.7 vs 5.2 mg/dL; P = .035). We identified multiple safety concerns, including EFAD (54%), rapid infusion (17%), and missed doses (51%). No patient characteristics were found to correlate with Smofllpid therapy and diagnosis of EFAD.
Conclusion
In our patient population, Smoflipid therapy led to cholestasis resolution in patients with lower direct bilirubin or less‐severe IFALD. Use of Smoflipid is also associated with significant safety concerns, and its use should be coupled with close monitoring in pediatric patients, particularly in neonates.
Systematic investigation of reactivation-induced memory updating began in the 1960s, and a wave of research in this area followed the seminal articulation of “reconsolidation” theory in the early ...2000s. Myriad studies indicate that memory reactivation can cause previously consolidated memories to become labile and sensitive to weakening, strengthening, or other forms of modification. However, from its nascent period to the present, the field has been beset by inconsistencies in researchers’ abilities to replicate seemingly established effects. Here we review these many studies, synthesizing the human and nonhuman animal literature, and suggest that these failures-to-replicate reflect a highly complex and delicately balanced memory modification system, the substrates of which must be finely tuned to enable adaptive memory updating while limiting maladaptive, inaccurate modifications. A systematic approach to the entire body of evidence, integrating positive and null findings, will yield a comprehensive understanding of the complex and dynamic nature of long-term memory storage and the potential for harnessing modification processes to treat mental disorders driven by pervasive maladaptive memories.
•We discuss evidence for reactivation-induced memory updating in humans and animals.•Decades of research indicate that memory reactivation can promote updating.•Replication failures raise valid questions about the nature of this phenomenon.•Conditions for inducing memory destabilization require clarification.•Specificity of destabilization triggers might explain discrepant results.
Successful adoptive T cell therapy (ACT) requires the ability to activate tumor-specific T cells with the ability to traffic to the tumor site and effectively kill their target as well as persist ...over time. We hypothesized that ACT using marrow-infiltrating lymphocytes (MILs) in multiple myeloma (MM) could impart greater antitumor immunity in that they were obtained from the tumor microenvironment. We describe the results from the first clinical trial using MILs in MM. Twenty-five patients with either newly diagnosed or relapsed disease had their MILs harvested, activated and expanded, and subsequently infused on the third day after myeloablative therapy. Cells were obtained and adequately expanded in all patients with anti-CD3/CD28 beads plus interleukin-2, and a median of 9.5 × 10(8) MILs were infused. Factors indicative of response to MIL ACT included (i) the presence of measurable myeloma-specific activity of the ex vivo expanded product, (ii) low endogenous bone marrow T cell interferon-γ production at baseline, (iii) a CD8(+) central memory phenotype at baseline, and (iv) the generation and persistence of myeloma-specific immunity in the bone marrow at 1 year after ACT. Achieving at least a 90% reduction in disease burden significantly increased the progression-free survival (25.1 months versus 11.8 months; P = 0.01). This study demonstrates the feasibility and efficacy of MILs as a form of ACT with applicability across many hematologic malignancies and possibly solid tumors infiltrating the bone marrow.
This communication describes the reversible reaction of a ruthenium pincer complex with a variety of carbonyl compounds. Both NMR spectroscopic and X-ray crystallographic characterization of isomeric ...carbonyl adducts are reported, and the equilibrium constants for carbonyl binding have been determined.
The cancer stem cell hypothesis suggests that malignant growth depends on a subset of tumor cells with stem cell-like properties of self-renewal. Because hedgehog (Hh) signaling regulates progenitor ...cell fate in normal development and homeostasis, aberrant pathway activation might be involved in the maintenance of such a population in cancer. Indeed, mutational activation of the Hh pathway is associated with medulloblastoma and basal cell carcinoma; pathway activity is also critical for growth of other tumors lacking such mutations, although the mechanism of pathway activation is poorly understood. Here we study the role and mechanism of Hh pathway activation in multiple myeloma (MM), a malignancy with a well defined stem cell compartment. In this model, rare malignant progenitors capable of clonal expansion resemble B cells, whereas the much larger tumor cell population manifests a differentiated plasma cell phenotype that pathologically defines the disease. We show that the subset of MM cells that manifests Hh pathway activity is markedly concentrated within the tumor stem cell compartment. The Hh ligand promotes expansion of MM stem cells without differentiation, whereas the Hh pathway blockade, while having little or no effect on malignant plasma cell growth, markedly inhibits clonal expansion accompanied by terminal differentiation of purified MM stem cells. These data reveal that Hh pathway activation is heterogeneous across the spectrum of MM tumor stem cells and their more differentiated progeny. The potential existence of similar relationships in other adult cancers may have important biologic and clinical implications for the study of aberrant Hh signaling.
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