High Activity Mutants of Butyrylcholinesterase for Cocaine Hydrolysis

Butyrylcholinesterase (BChE) polypeptide variants of the presently-disclosed subject matter have enhanced catalytic efficiency for (−)-cocaine, as compared to wild-type BChE. Pharmaceutical compositions of the presently-disclosed subject matter include a BChE polypeptide variant having an enhanced catalytic efficiency for (−)-cocaine. A method of the presently-disclosed subject matter for treating a cocaine-induced condition includes administering to an individual an effective amount of a BChE polypeptide variant, as disclosed herein, to lower blood cocaine concentration

High Activity Mutants of Butyrylcholinesterase for Cocaine Hydrolysis

Butyrylcholinesterase (BChE) polypeptide variants of the presently-disclosed subject matter have enhanced catalytic efficiency for (−)-cocaine, as compared to wild-type BChE. Pharmaceutical compositions of the presently-disclosed subject matter include a BChE polypeptide variant having an enhanced catalytic efficiency for (−)-cocaine. A method of the presently-disclosed subject matter for treating a cocaine-induced condition includes administering to an individual an effective amount of a BChE polypeptide variant, as disclosed herein, to lower blood cocaine concentration

High Activity Mutants of Butyrylcholinesterase for Cocaine Hydrolysis

Butyrylcholinesterase (BChE) polypeptide variants of the presently-disclosed subject matter have enhanced catalytic efficiency for (−)-cocaine, as compared to wild-type BChE. Pharmaceutical compositions of the presently-disclosed subject matter include a BChE polypeptide variant having an enhanced catalytic efficiency for (−)-cocaine. A method of the presently-disclosed subject matter for treating a cocaine-induced condition includes administering to an individual an effective amount of a BChE polypeptide variant, as disclosed herein, to lower blood cocaine concentration

Cocaine Hydrolase-Fc Fusion Proteins for Cocaine and Methods for Utilizing the Same

The presently-disclosed subject matter includes isolated polypeptides that comprise a butyrylcholinestrase (BChE) polypeptide and a second polypeptide. The BChE polypeptide as well as the second polypeptide can be variants and/or fragments thereof. The presently-disclosed subject matter also includes a pharmaceutical composition that comprises the present isolated polypeptide and a suitable pharmaceutical carrier. Further still, methods are provided for treating cocaine-induced conditions, and comprise administering the isolated polypeptide and/or pharmaceutical compositions thereof to an individual

The fast light of CsI(Na) crystals

The responds of different common alkali halide crystals to alpha-rays and gamma-rays are tested in our research. It is found that only CsI(Na) crystals have significantly different waveforms between alpha and gamma scintillations, while others have not this phenomena. It is suggested that the fast light of CsI(Na) crystals arises from the recombination of free electrons with self-trapped holes of the host crystal CsI. Self-absorption limits the emission of fast light of CsI(Tl) and NaI(Tl) crystals.Comment: 5 pages, 11 figures Submit to Chinese Physics

Towards Better Query Classification with Multi-Expert Knowledge Condensation in JD Ads Search

Search query classification, as an effective way to understand user intents, is of great importance in real-world online ads systems. To ensure a lower latency, a shallow model (e.g. FastText) is widely used for efficient online inference. However, the representation ability of the FastText model is insufficient, resulting in poor classification performance, especially on some low-frequency queries and tailed categories. Using a deeper and more complex model (e.g. BERT) is an effective solution, but it will cause a higher online inference latency and more expensive computing costs. Thus, how to juggle both inference efficiency and classification performance is obviously of great practical importance. To overcome this challenge, in this paper, we propose knowledge condensation (KC), a simple yet effective knowledge distillation framework to boost the classification performance of the online FastText model under strict low latency constraints. Specifically, we propose to train an offline BERT model to retrieve more potentially relevant data. Benefiting from its powerful semantic representation, more relevant labels not exposed in the historical data will be added into the training set for better FastText model training. Moreover, a novel distribution-diverse multi-expert learning strategy is proposed to further improve the mining ability of relevant data. By training multiple BERT models from different data distributions, it can respectively perform better at high, middle, and low-frequency search queries. The model ensemble from multi-distribution makes its retrieval ability more powerful. We have deployed two versions of this framework in JD search, and both offline experiments and online A/B testing from multiple datasets have validated the effectiveness of the proposed approach

Idiopathic Ventricular Arrhythmias Originating From the Pulmonary Sinus Cusp Prevalence, Electrocardiographic/Electrophysiological Characteristics, and Catheter Ablation

AbstractBackgroundIdiopathic ventricular arrhythmias (VAs) originating from the pulmonary sinus cusp (PSC) have not been sufficiently clarified.ObjectivesThe goal of this study was to investigate the prevalence, electrocardiographic characteristics, mapping, and ablation of idiopathic VAs arising from the PSC.MethodsData were analyzed from 218 patients undergoing successful endocardial ablation of idiopathic VAs with a left bundle branch block morphology and inferior axis deviation.ResultsTwenty-four patients had VAs originating from the PSC. In the first 7 patients, initial ablation performed in the right ventricular outflow tract failed to abolish the clinical VAs but produced a small change in the QRS morphology in 3 patients. In all 24 patients, the earliest activation was eventually identified in the PSC, at which a sharp potential was observed preceding the QRS complex onset by 28.2 ± 2.9 ms. The successful ablation site was in the right cusp (RC) in 10 patients (42%), the left cusp (LC) in 8 (33%), and the anterior cusp (AC) in 6 (25%). Electrocardiographic analysis showed that RC-VAs had significantly larger R-wave amplitude in lead I and a smaller aVL/aVR ratio of Q-wave amplitude compared with AC-VAs and LC-VAs, respectively. The R-wave amplitude in inferior leads was smaller in VAs localized in the RC than in the LC but did not differ between VAs from the AC and LC.ConclusionsVAs arising from the PSC are not uncommon, and RC-VAs have unique electrocardiographic characteristics. These VAs can be successfully ablated within the PSC

High remission and low relapse with prolonged intensive DMARD therapy in rheumatoid arthritis (PRINT): A multicenter randomized clinical trial

Objectives: To determine whether prolonged intensive disease-modifying antirheumatic drug (DMARD) treatment (PRINT) leads to high remission and low relapse rates in patients with severe rheumatoid arthritis (RA). Methods: In this multicenter, randomized and parallel treatment trial, 346 patients with active RA (disease activity score (28 joints) [DAS28] (erythrocyte sedimentation rate [ESR]) > 5.1) were enrolled from 9 centers. In phase 1, patients received intensive treatment with methotrexate, leflunomide, and hydroxychloroquine, up to 36 weeks, until remission (DAS28 ≤ 2.6) or a low disease activity (2.6 < DAS28 ≤ 3.2) was achieved. In phase 2, patients achieving remission or low disease activity were followed up with randomization to 1 of 2 step-down protocols: leflunomide plus hydroxychloroquine combination or leflunomide monotherapy. The primary endpoints were good European League Against Rheumatism (EULAR) response (DAS28 (ESR) < 3.2 and a decrease of DAS28 by at least 1.2) during the intensive treatment and the disease state retention rate during step-down maintenance treatment. Predictors of a good EULAR response in the intensive treatment period and disease flare in the maintenance period were sought. Results: A good EULAR response was achieved in 18.7%, 36.9%, and 54.1% of patients at 12, 24, and 36 weeks, respectively. By 36 weeks, 75.4% of patients achieved good and moderate EULAR responses. Compared with those achieving low disease activity and a high health assessment questionnaire (HAQ > 0.5), patients achieving remission (DAS28 ≤ 2.6) and low HAQ (≤ 0.5) had a significantly higher retention rate when tapering the DMARDs treatment (P = 0.046 and P = 0.01, respectively). There was no advantage on tapering to combination rather than monotherapy. Conclusions: Remission was achieved in a proportion of patients with RA receiving prolonged intensive DMARD therapy. Low disease activity at the start of disease taper leads to less subsequent flares. Leflunomide is a good maintenance treatment as single treatment

Photoactive hourglass-type M{P4Mo6}2 networks for efficient removal of hexavalent chromium

The exploration of high-efficiency photocatalysts to drive the conversion of highly toxic heavy metal hexavalent chromium (Cr(VI)) in wastewater to low-toxic trivalent chromium (Cr(III)) is of great significance for purifying water that contains emerging contaminants. Herein, four hourglass-type phosphomolybdate-based hybrid networks—(H2bpe)2[M(H2O)3]2{M[P4Mo6O31H7]2}·8H2O (M = Mn for 1, Co for 2) and (Hbpe)(H2bpe)Na[M(H2O)3]2{M[P4Mo6O31H7]2}·9H2O (M = Mn for 3, Co for 4; {M[P4Mo6O31H7]2}8− (abbr. M{P4Mo6}2); bpe = 1,2-di(4-pyridyl)ethylene)—were hydrothermally synthesized as heterogeneous photocatalysts for Cr(VI) reduction. A structural analysis showed that the four hybrids 1–4 exhibited two-dimensional inorganic sheet-like structures with a 3,6-connected kgd topology built of hourglass phosphomolybdate clusters having different central metal ions, which further interacted with organic bpe cations via abundant hydrogen-bonding interactions to extend the structure to a three-dimensional (3D) supramolecular network. The four hybrids displayed excellent redox properties and wide visible-light absorption. When used as heterogeneous photocatalysts, hybrids 1–4 exhibited excellent photocatalytic activity for Cr(VI) reduction under 10 W white light irradiation, with reduction rates of 91% for 1, 74% for 2, 90% for 3, and 71% for 4, respectively, within 80 min. The Cr(VI) reduction reaction over hybrids 1–4 followed the pseudo first-order kinetics model with reaction rate constants k of 0.0237 min−1 for 1, 0.0143 min−1 for 2, 0.0221 min−1 for 3 and 0.0134 min−1 for 4, respectively. The Mn{P4Mo6}2-based hybrids 1 and 3 showed better photocatalytic performance than the Co{P4Mo6}2-based hybrids 2 and 4, along with excellent recycle stability. This mechanism study shows that the different central metals M in the M{P4Mo6}2 cluster have a considerable impact on photocatalytic performance due to their regulation effect on the electronic structure. This work provides evidence for the important role of the central metal in hourglass-type phosphomolybdate in the regulation of photocatalytic performance, and it brings inspiration for the design of highly efficient photocatalysts based on polyoxometalates