Electrochemical synthesis of new electroactive polymers from dithienylene-vinylene derivatives

peer reviewedHighly conjugated thiophene derivatives, based on thienylene-vinylene and thieneylene-vinylene-phenylene units, have been synthesized in order to examine: (i) the effect of such regular conjugated monomer structures on the polymerization; (ii) the optical and electrochemical properties of the corresponding conjugated polymers. The all-trans monomers have been prepared by a Wittig reaction and the polymers have then been synthesized electrochemically. The polymers are electrochromic and can be reversibly doped both oxidatively and reductively. Their electrochemical behavior and optical properties have been analysed on the basis of quantum-chemical calculations

Transform-domain analysis of packet delay in network nodes with QoS-aware scheduling

In order to differentiate the perceived QoS between traffic classes in heterogeneous packet networks, equipment discriminates incoming packets based on their class, particularly in the way queued packets are scheduled for further transmission. We review a common stochastic modelling framework in which scheduling mechanisms can be evaluated, especially with regard to the resulting per-class delay distribution. For this, a discrete-time single-server queue is considered with two classes of packet arrivals, either delay-sensitive (1) or delay-tolerant (2). The steady-state analysis relies on the use of well-chosen supplementary variables and is mainly done in the transform domain. Secondly, we propose and analyse a new type of scheduling mechanism that allows precise control over the amount of delay differentiation between the classes. The idea is to introduce N reserved places in the queue, intended for future arrivals of class 1

Phase 2 Study of Anti-Human Cytomegalovirus Monoclonal Antibodies for Prophylaxis in Hematopoietic Cell Transplantation.

Human cytomegalovirus (HCMV) can cause significant disease in immunocompromised patients, and treatment options are limited by toxicities. CSJ148 is a combination of two anti-HCMV human monoclonal antibodies (LJP538 and LJP539) that bind to and inhibit the functions of viral HCMV glycoprotein B (gB) and the pentameric complex, consisting of glycoproteins gH, gL, UL128, UL130, and UL131. In this phase 2, randomized, placebo-controlled trial, we evaluated the safety and efficacy of CSJ148 for prophylaxis of HCMV in patients undergoing allogeneic hematopoietic stem cell transplantation. As would be expected in the study population, all the patients (100%) reported at least one treatment-emergent adverse event. There were 22 deaths during this study, and over 80% of the patients receiving placebo or CSJ148 developed at least one adverse event of grade 3 or higher severity. No subject who received antibody developed a hypersensitivity- or infusion-related reaction. CSJ148-treated patients showed trends toward decreased viral load, shorter median duration of preemptive therapy, and fewer courses of preemptive therapy. However, the estimated probability that CSJ148 decreases the need for preemptive therapy compared to placebo was 69%, with a risk ratio of 0.89 and a 90% credible interval of 0.61 to 1.31. The primary efficacy endpoint was therefore not met, indicating that CSJ148 did not prevent clinically significant HCMV reactivation in recipients of allogeneic hematopoietic cell transplants. (This study has been registered at ClinicalTrials.gov under identifier NCT02268526 and at EudraCT under number 2017-002047-15.)

Effect of feed restriction timing on live performance, breast myopathy occurrence, and muscle fiber degeneration in 2 broiler chicken genetic lines

During recent years, research on meat quality in poultry has aimed to evaluate the presence and consequences of breast myopathies as well as the factors which can affect their occurrence by modifying the growth rate. A total of 900 broiler chickens were reared until slaughter (48 D) to evaluate the effect of 2 genetic lines (A vs. B) and feeding plans (ad libitum [AL], early restricted [ER], from 13 to 23 D of age, and late restricted [LR], from 27 to 37 D of age; restriction rate: 80%) on performance, meat quality, and breast muscle myopathies. Calsequestrin and vascular endothelial growth factor (VEGF) expressions, and muscle fiber degeneration (MFD) were recorded at 22, 36, and 48 D. Chickens in the AL treatment had greater final live (P < 0.01) and carcass weights and proportion of pectoralis major muscle (P = 0.04) compared to chickens in the LR treatment, whereas chickens in the ER treatment had intermediate final live (3,454 g) and carcass weights, and proportion of pectoralis major muscle (25.6%). Chickens of line A were heavier than chickens of line B (P < 0.001), and had a greater feed conversion rate. Chickens of line A also had a greater dressing out percentage (P < 0.001), but a lower proportion of pectoralis major muscle (P = 0.04), as well as a greater meat pH (P < 0.001), meat cooking losses (P < 0.01), and shear force of the pectoralis major muscle (P = 0.03). Calsequestrin and VEGF mRNA were significantly lower in ER and LR chickens compared to AL chickens after feed restriction and during refeeding (P < 0.05). MFD scores increased with chicken age (P < 0.001) and differed between genetic lines (P < 0.001). Neither feeding plan nor genetic line affected the occurrence of white striping or wooden breast condition

An EORTC Phase II study of caspofungin as first-line therapy of invasive aspergillosis in haematological patients

Objectives Caspofungin was evaluated as first-line monotherapy of invasive aspergillosis (IA) in patients with haematological malignancies and undergoing autologous transplants. Methods Adults with proven or probable IA, defined strictly according to EORTC-MSG criteria, were eligible. Those with possible IA were enrolled, but were not evaluable for efficacy unless upgraded to proven/probable disease within 7 days of registration based on investigations performed within 48 h after enrolment. Caspofungin dosage was 70 mg (day 1) followed by 50 mg/day. The primary endpoint was the proportion of patients with complete or partial response at the end of caspofungin therapy in the modified intention to treat (MITT) group; secondary endpoints were response and survival at day 84 and safety. Results In the MITT group (n = 61), 75% of patients had cancer not in remission (relapsing or refractory), 85% were neutropenic at enrolment and 49% had a Karnofsky score of ≤50. At end of treatment, 1 and 19 patients had complete and partial response, respectively [success rate 33% (20/61)], 9 (15%) achieved stabilization and 31 (51%) had disease progression. One patient was not evaluable. The 6 and 12 week survival rates were 66% (40/61) and 53% (32/60), respectively. Baseline characteristics associated with survival at day 84 were an underlying disease in remission (not relapsing or refractory) and Karnofsky score. Recovery from neutropenia at the end of treatment was also significantly associated with survival. No serious drug-related adverse events or discontinuations due to drug-related adverse events were observed. Conclusions Caspofungin provided an observed response rate compatible with the null hypothesis of a true response rate of ≤35%. Underlying disease-related factors had a major impact on result

TREM1 regulates antifungal immune responses in invasive pulmonary aspergillosis.

Pattern recognition receptors (PRRs) are responsible for Aspergillus fumigatus recognition by innate immunity and its subsequent immune signaling. The triggering receptor expressed on myeloid cells 1 (TREM1) is a recently characterized pro-inflammatory receptor constitutively expressed on the surface of neutrophils and macrophages. A soluble form (sTREM1) of this protein that can be detected in human body fluids has been identified. Here we investigated the role of TREM1 during invasive pulmonary aspergillosis (IPA). IPA patients displayed significantly higher levels of sTREM1 in bronchoalveolar lavages when compared to control patients. Functional analysis in TREM1 showed that the levels of sTREM1 and TREM1 pathway-related cytokines were influenced by single nucleotide polymorphisms in TREM1. In addition, we confirmed a role of TREM1 on antifungal host defense against A. fumigatus in a murine model of IPA. TREM1 deficiency increased susceptibility to infection in the immunosuppressed murine host. Deletion of TREM1 showed delayed innate and adaptive immune responses and impaired pro-inflammatory cytokine responses. The absence of TREM1 in primary macrophages attenuated the TLR signaling by altering the expression of both receptor and effector proteins that are critical to the response against A. fumigatus. In this study, and for the first time, we demonstrate the key role for the TREM1 receptor pathway during IPA.This work was supported by the Fundação para a Ciência e a Tecnologia [PTDC/SAU-SER/29635/2017]; Fundação para a Ciência e a Tecnologia [UIDB/50026/2020 and UIDP/50026/2020]; Fundação para a Ciência e a Tecnologia [PTDC/MED-GEN/28778/2017]; H2020 Excellent Science [NORTE-01-0145-FEDER-000013 and NORTE-01-0145-FEDER-000023)]; Instituto de Salud Carlos III [RD16/CIII/0004/0003]; Instituto de Salud Carlos III [PI18CIII/00045]; Instituto de Salud Carlos III [MPY 1277/15]; Ministerio de Ciencia, Innovación y Universidades [RTI2018-099114-B-I00]; Associação Viver a Ciência (PT) [SFRH/BD/136814/2018]; “la Caixa” Foundation [ID 100010434].S

Fusion of EML1 to ABL1 in T-cell acute lymphoblastic leukemia with cryptic t(9;14)(q34;q32)

The BCR-ABL1 fusion kinase is frequently associated with chronic myeloid leukemia and B-cell acute lymphoblastic leukemia but is rare in T-cell acute lymphoblastic leukemia (T-ALL). We recently identified NUP214-ABL1 as a variant ABL1 fusion gene in 6% of T-ALL patients. Here we describe the identification of another ABL1 fusion, EML1-ABL1, in a T-ALL patient with a cryptic t(9;14)(q34;q32) associated with deletion of CDKN2A (p16) and expression of TLX1 (HOX11). Echinoderm microtubule-associated protein-like 1-Abelson 1 (EML1-ABL1) is a constitutively phosphorylated tyrosine kinase that transforms Ba/F3 cells to growth factor-independent growth through activation of survival and proliferation pathways, including extracellular signal-related kinase 1/2 (Erk1/2), signal transducers and activators of transcription 5 (Stat5), and Lyn kinase. Deletion of the coiled-coil domain of EML1 abrogated the transforming properties of the fusion kinase. EML1-ABL1 and breakpoint cluster region (BCR)-ABL1 were equally sensitive to the tyrosine kinase inhibitor imatinib. These data further demonstrate the involvement of ABL1 fusions in the pathogenesis of T-ALL and identify EML1-ABL1 as a novel therapeutic target of imatinib