219 research outputs found
T cell receptor sequence clustering and antigen specificity
There has been increasing interest in the role of T cells and their involvement in cancer, autoimmune and infectious diseases. However, the nature of T cell receptor (TCR) epitope recognition at a repertoire level is not yet fully understood. Due to technological advances a plethora of TCR sequences from a variety of disease and treatment settings has become readily available. Current efforts in TCR specificity analysis focus on identifying characteristics in immune repertoires which can explain or predict disease outcome or progression, or can be used to monitor the efficacy of disease therapy. In this context, clustering of TCRs by sequence to reflect biological similarity, and especially to reflect antigen specificity have become of paramount importance. We review the main TCR sequence clustering methods and the different similarity measures they use, and discuss their performance and possible improvement. We aim to provide guidance for non-specialists who wish to use TCR repertoire sequencing for disease tracking, patient stratification or therapy prediction, and to provide a starting point for those aiming to develop novel techniques for TCR annotation through clustering
Effects of several types of biomass fuels on the yield, nanostructure and reactivity of soot from fast pyrolysis at high temperatures
peer-reviewedThis study presents the effect of biomass origin on the yield, nanostructure and reactivity of soot. Soot
was produced from wood and herbaceous biomass pyrolysis at high heating rates and at temperatures
of 1250 and 1400° C in a drop tube furnace. The structure of solid residues was characterized by electron
microscopy techniques, X-ray diffraction and N2 adsorption. The reactivity of soot was investigated by
thermogravimetric analysis. Results showed that soot generated at 1400° C was more reactive than soot
generated at 1250° C for all biomass types. Pinewood, beechwood and wheat straw soot demonstrated
differences in alkali content, particle size and nanostructure. Potassium was incorporated in the soot
matrix and significantly influenced soot reactivity. Pinewood soot particles produced at 1250° C had a
broader particle size range (27.2–263 nm) compared to beechwood soot (33.2–102 nm) and wheat straw
soot (11.5–165.3 nm), and contained mainly multi-core structures
SO<sub>2 </sub>Oxidation Across Marine V<sub>2</sub>O<sub>5</sub>-WO<sub>3</sub>-TiO<sub>2</sub> SCR Catalysts: a Study at Elevated Pressure for Preturbine SCR Configuration
One week's treatment with the long-acting glucagon-like peptide 1 derivate liraglutide (NN2211) markedly improves 24-h glycemia and α- and β-cell function and reduces endogenous glucose release in patients with type 2 diabetes
Glukagonopodobny peptyd 1 (GLP-1, glucagon-like peptide 1) może być bardzo
skuteczny w leczeniu cukrzycy typu 2. Autorzy badali wpływ krótkiego (1 tydzień)
stosowania pochodnej GLP-1, liraglutydu (NN2211), na 24-godzinny profil glikemii
i stężenia krążących wolnych kwasów tłuszczowych, wydzielanie hormonów przez komórki
wysp trzustkowych oraz na opróżnianie żołądka podczas posiłków (z użyciem acetaminofenu).
Ponadto, oceniali endogenne uwalnianie glukozy na czczo oraz glukoneogenezę (odpowiednio
wlew 3-3H-glukozy i wypicie 2H2O), a następnie zbadali funkcję komórek wysp trzustkowych,
stosując homeostatyczny model oceny oraz 1. i 2. fazę wydzielania insuliny z użyciem
klamry hiperglikemicznej (stężenie glukozy w osoczu wynosiło ok. 16 mmol/l). Na
szczycie hiperglikemii wykonano test stymulacji argininą. W badaniu przeprowadzonym
jako podwójnie ślepa próba w układzie naprzemiennym z grupą kontrolną placebo
wzięło udział 13 chorych na cukrzycę typu 2. Liraglutyd podawano podskórnie raz
na dobę (6 µg/kg). Stosowanie leku spowodowało istotne zmniejszenie 24-godzinnego
pola pod krzywą dla glukozy (p = 0,01) i glukagonu (p = 0,04), natomiast pole
pod krzywą dla krążących wolnych kwasów tłuszczowych nie uległo zmianie. Dobowe
wydzielanie insuliny oceniane na podstawie dekonwolucji stężeń C-peptydu w osoczu
nie zmieniło się, co wskazuje na jego względny wzrost. Liraglutyd w zastosowanej
dawce nie wpłynął na opróżnianie żołądka. Uwalnianie endogennej glukozy na czczo
zmniejszyło się (p = 0,04) na skutek zahamowania glikogenolizy (p = 0,01), natomiast
nasilenie glukoneogenezy nie uległo zmianie. Pierwsza faza wydzielania insuliny
oraz reakcja na argininę w warunkach hiperglikemii wyraźnie się nasiliły (p <
0,001), a współczynnik proinsulina/insulina się zmniejszył (p = 0,001). Wskaźnik
podatności (disposition index) (maksymalne stężenie insuliny po dożylnym podaniu
bolusa glukozy pomnożone przez insulinowrażliwość obliczoną za pomocą modelu homeostatycznego)
niemal podwoił się w czasie leczenia liraglutydem (p < 0,01). W okresie stosowania
leku zaobserwowano również zmniejszone wydzielanie glukagonu, zarówno pod wpływem
samej hiperglikemii, jak i po podaniu argininy (p < 0,01; p = 0,01). Stosowanie
liraglutydu raz na dobę przez 1 tydzień u chorych na cukrzycę typu 2 poprawia
24-godzinną kontrolę glikemii (również po posiłkach i w nocy). Lek ten działa
na zasadzie kilku różnych mechanizmów, między innymi poprawia czynność komórek
wysp trzustkowych. W badaniu zwrócono uwagę na GLP-1 i jego pochodne jako nowe
i obiecujące leki w terapii cukrzycy typu 2.Glucagon-like peptide 1 (GLP-1) is potentially a very
attractive agent for treating type 2 diabetes. We
explored the effect of short-term (1 week) treatment
with a GLP-1 derivative, liraglutide (NN2211), on 24-h
dynamics in glycemia and circulating free fatty acids,
islet cell hormone profiles, and gastric emptying
during meals using acetaminophen. Furthermore,
fasting endogenous glucose release and gluconeogenesis
(3-3Hglucose infusion and 2H2O ingestion, respectively)
were determined, and aspects of pancreatic
islet cell function were elucidated on the subsequent
day using homeostasis model assessment
and first- and second-phase insulin response during
a hyperglycemic clamp (plasma glucose ~16 mmol/l),
and, finally, on top of hyperglycemia, an arginine
stimulation test was performed. For accomplishing
this, 13 patients with type 2 diabetes were examined
in a double-blind, placebo-controlled crossover
design. Liraglutide (6 μg/kg) was administered subcutaneously
once daily. Liraglutide significantly reduced
the 24-h area under the curve for glucose
(P = 0.01) and glucagon (P = 0.04), whereas the area
under the curve for circulating free fatty acids was
unaltered. Twenty-four-hour insulin secretion rates
as assessed by deconvolution of serum C-peptide
concentrations were unchanged, indicating a relative
increase. Gastric emptying was not influenced at
the dose of liraglutide used. Fasting endogenous
glucose release was decreased (P = 0.04) as a result
of a reduced glycogenolysis (P = 0.01), whereas gluconeogenesis
was unaltered. First-phase insulin response
and the insulin response to an arginine stimulation
test with the presence of hyperglycemia
were markedly increased (P < 0.001), whereas the
proinsulin/insulin ratio fell (P = 0.001). The disposition
index (peak insulin concentration after intravenous
bolus of glucose multiplied by insulin sensitivity
as assessed by homeostasis model assessment)
almost doubled during liraglutide treatment (P < 0.01).
Both during hyperglycemia per se and after arginine
exposure, the glucagon responses were reduced
during liraglutide administration (P < 0.01 and
P = 0.01). Thus, 1 week’s treatment with a single
daily dose of the GLP-1 derivative liraglutide, operating
through several different mechanisms including
an ameliorated pancreatic islet cell function in individuals
with type 2 diabetes, improves glycemic control
throughout 24 h of daily living, i.e., prandial and
nocturnal periods. This study further emphasizes
GLP-1 and its derivatives as a promising novel concept
for treatment of type 2 diabetes
Reaction mechanism of dimethyl ether carbonylation to methyl acetate over mordenite: a combined DFT/experimental study
Dimethyl ether carbonylation to methyl acetate over mordenite was studied theoretically with density functional theory calculations and experimentally in a fixed bed flow reactor. A new reaction path to methyl acetate entirely in the 8 membered ring was discovered.</p
One-Year Treatment With Exenatide Improves β-Cell Function, Compared With Insulin Glargine, in Metformin-Treated Type 2 Diabetic Patients: A randomized, controlled trial
0.0001). beta-Cell function measures returned to pretreatment values in both groups after a 4-week off-drug period. A1C and body weight rose to pretreatment values 12 weeks after discontinuation of either exenatide or insulin glargine therapy. CONCLUSIONS: Exenatide significantly improves beta-cell function during 1 year of treatment compared with titrated insulin glargine. After cessation of both exenatide and insulin glargine therapy, beta-cell function and glycemic control returned to pretreatment values, suggesting that ongoing treatment is necessary to maintain the beneficial effects of either therap
Pharmacokinetic Properties of Liraglutide as Adjunct to Insulin in Subjects with Type 1 Diabetes Mellitus.
BACKGROUND: The pharmacokinetic properties of liraglutide, a glucagon-like peptide-1 receptor agonist approved for the treatment of type 2 diabetes mellitus (T2D), have been established in healthy individuals and subjects with T2D. Liraglutide has been under investigation as adjunct treatment to insulin in type 1 diabetes mellitus (T1D). This single-center, double-blind, placebo-controlled, crossover, clinical pharmacology trial is the first to analyze the pharmacokinetic properties of liraglutide as add-on to insulin in T1D. METHODS: Subjects (18-64 years; body mass index 20.0-28.0 kg/m(2); glycated hemoglobin ≤9.5 %) were randomized 1:1:1 to 0.6, 1.2, or 1.8 mg liraglutide/placebo. Each group underwent two 4-week treatment periods (liraglutide then placebo or placebo then liraglutide) separated by a 2- to 3-week washout. Both trial drugs were administered subcutaneously, once daily, as adjunct to insulin. A stepwise hypoglycemic clamp was performed at the end of each treatment period (data reported previously). Pharmacokinetic endpoints were derived from liraglutide concentration-time curves after the final dose and exposure was compared with data from previous trials in healthy volunteers and subjects with T2D. RESULTS: The pharmacokinetic properties of liraglutide in T1D were comparable with those observed in healthy volunteers and subjects with T2D. Area under the steady-state concentration-time curve (AUC) and maximum plasma concentration data were consistent with dose proportionality of liraglutide. Comparison of dose-normalized liraglutide AUC suggested that exposure in T1D, when administered with insulin, is comparable with that observed in T2D. CONCLUSIONS: Liraglutide, administered as adjunct to insulin in subjects with T1D, shows comparable pharmacokinetics to those in subjects with T2D. ClinicalTrials.gov Identifier: NCT01536665
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