Synthesis of enantioenriched spirocyclic 2-arylpiperidines via kinetic resolution.

Kinetic resolution of N-Boc-spirocyclic 2-arylpiperidines with spiro substitution at C-4 was achieved with high enantiomeric ratios using the chiral base n-BuLi/sparteine. Cyclopropanation or metallaphotoredox catalysis were used to access the piperidines, which could be further functionalised without loss of enantiopurity, highlighting their use as potential 3D fragments for drug discovery.

Kinetic Resolution of 2-Aryldihydroquinolines Using Lithiation - Synthesis of Chiral 1,2- and 1,4-Dihydroquinolines.

Highly enantiomerically enriched dihydrohydroquinolines were prepared in two steps from quinoline. Addition of aryllithiums to quinoline with tert-butoxycarbonyl (Boc) protection gave N-Boc-2-aryl-1,2-dihydroquinolines. These were treated with n-butyllithium and electrophilic trapping occurred exclusively at C-4 of the dihydroquinoline, a result supported by DFT studies. Variable temperature NMR spectroscopy gave kinetic data for the barrier to rotation of the carbonyl group (ΔG≠ ≈49 kJ mol-1 , 195 K). Lithiation using the diamine sparteine allowed kinetic resolutions with high enantioselectivities (enantiomer ratio up to 99 : 1). The enantioenriched 1,2-dihydroquinolines could be converted to 1,4-dihydroquinolines with retention of stereochemistry. Further functionalisation led to trisubstituted products. Reduction provided enantioenriched tetrahydroquinolines, whereas acid-promoted removal of Boc led to quinolines, and this was applied to a synthesis of the antimalarial compound M5717.

Kinetic Resolution of 2-Aryl-4-methylenepiperidines toward Enantioenriched Functionalizable Piperidine Fragments.

The base n-BuLi with sparteine allows a kinetic resolution of N-Boc-2-aryl-4-methylenepiperidines. The 2,2-disubstituted products and recovered starting materials were isolated with high enantiomeric ratios. From VT-NMR spectroscopy and DFT studies, the rate of rotation of the N-Boc group is fast. Lithiation and trapping of the enantioenriched starting materials gave 2,2-disubstituted piperidines with retention of stereochemistry. Functionalization of the 4-methylene group led to a variety of 2,4-disubstituted piperidines without loss of enantiopurity that could be useful building blocks for drug discovery.

Ultrasonic Sound Guide System with Eyeglass Device for the Visually Impaired.

The ultrasonic sound guide system presents the audio broadcasting system based on the inaudible ultrasonic sound to assist the indoor and outdoor navigation of the visually impaired. The transmitters are placed at the point of interest to propagate the frequency modulated voice signal in ultrasonic sound range. The dual channel receiver device is carried by the visually impaired person in the form of eyeglasses to receive the ultrasonic sound for the voice signal via demodulation. Since the ultrasonic sound demonstrates the acoustic properties, the velocity, directivity, attenuation, and superposition of ultrasonic sound provide the acoustic clue to the user for localizing the multiple transmitter positions by binaural localization capability. The visually impaired hear the designated voice signal and follow the signal attributions to arrive at the specific location. Due to the low microphone gain from side addressing, the time delay between the receiver channels demonstrates the high variance and high bias in end directions. However, the perception experiment shows the further prediction accuracy in end directions as compared to the center direction outcomes. The overall evaluations show the precise directional prediction for narrow- and wide-angle situations. The ultrasonic sound guide system is a useful device to localize places in the near field without touching braille.

Asymmetric Synthesis of 2-Arylindolines and 2,2-Disubstituted Indolines by Kinetic Resolution.

Kinetic resolution of 2-arylindolines (2,3-dihydroindoles) was achieved by treatment of their N-tert-butoxycarbonyl (Boc) derivatives with n-butyllithium and sparteine in toluene at -78 °C followed by electrophilic quench. The unreacted starting materials together with the 2,2-disubstituted products could be isolated with high enantiomer ratios. Variable temperature NMR spectroscopy showed that the rate of Boc rotation was fast (ΔG≠ ≈57 kJ/mol at 195 K). This was corroborated by DFT studies and by in situ ReactIR spectroscopy. The enantioenriched N-Boc-2-arylindolines were converted to 2,2-disubstituted products without significant loss in enantiopurity. Hence, either enantiomer of the 2,2-disubstituted products could be obtained with high selectivity from the same enantiomer of the chiral ligand sparteine (one from the kinetic resolution and the other from subsequent lithiation-trapping of the recovered starting material). Secondary amine products were prepared by removing the Boc group with acid to provide a way to access highly enantioenriched 2-aryl and 2,2-disubstituted indolines.

Endoscopic Ultrasound Guided Gastroenterostomy: What Is the Learning Curve?

INTRODUCTION: Endoscopic ultrasound guided gastroenterostomy (EUS-GE) is a minimally invasive option for gastric outlet obstruction. It requires skills in endoscopic ultrasound, fluoroscopy, and lumen-apposing metal stent deployment. The aim of this study was to determine the learning curve for EUS-GE. METHODS: Consecutive patients undergoing EUS-GE by a single operator were included from a prospective registry over 3 years. Demographics, procedure info, postprocedure follow-up data, and adverse events were collected. Nonlinear regression and cumulative sum analyses were conducted for the learning curve. Clinical success was defined as tolerating a diet postprocedure. RESULTS: Twenty-three patients were included (39% male, mean age 65.8 y). Technical success was achieved in 22 (96%) patients. Clinical success was achieved in 21/22 (95%) patients. Average follow-up time 10.8 months (9.1 SD). Five patients had minor postprocedure complications; 1 patient had a periprocedural esophageal tear treated with clips. Four patients required repeat intervention for stent revision or removal if no longer needed.Median procedure time was 88 minutes (range: 45 to 140 min). Cumulative sum chart shows 88-minute procedure time was achieved at the seventh procedure indicating efficiency. Even with bridging of a misdeployed lumen-apposing metal stent, the procedure duration further reduced with consequent procedures indicating continued improvement with experience (nonlinear regression P<0.0001). CONCLUSIONS: Endoscopists experienced in EUS-GE achieve a reduction in procedure time over successive cases, with efficiency reached at 88 minutes and a learning rate of 7 cases. Misdeployed stents that require bridging add to the procedure time even after competency is achieved but do not affect the overall learning curve trend.

Single-Channel Multiple-Receiver Sound Source Localization System with Homomorphic Deconvolution and Linear Regression.

The conventional sound source localization systems require the significant complexity because of multiple synchronized analog-to-digital conversion channels as well as the scalable algorithms. This paper proposes a single-channel sound localization system for transport with multiple receivers. The individual receivers are connected by the single analog microphone network which provides the superimposed signal over simple connectivity based on asynchronized analog circuit. The proposed system consists of two computational stages as homomorphic deconvolution and machine learning stage. A previous study has verified the performance of time-of-flight estimation by utilizing the non-parametric and parametric homomorphic deconvolution algorithms. This paper employs the linear regression with supervised learning for angle-of-arrival prediction. Among the circular configurations of receiver positions, the optimal location is selected for three-receiver structure based on the extensive simulations. The non-parametric method presents the consistent performance and Yule-Walker parametric algorithm indicates the least accuracy. The Steiglitz-McBride parametric algorithm delivers the best predictions with reduced model order as well as other parameter values. The experiments in the anechoic chamber demonstrate the accurate predictions in proper ensemble length and model order.

Gastrointestinal Bleeding in Patients With Coronavirus Disease 2019: A Matched Case-Control Study.

INTRODUCTION: Although current literature has addressed gastrointestinal presentations including nausea, vomiting, diarrhea, abnormal liver chemistries, and hyperlipasemia as possible coronavirus disease 2019 (COVID-19) manifestations, the risk and type of gastrointestinal bleeding (GIB) in this population is not well characterized. METHODS: This is a matched case-control (1:2) study with 41 cases of GIB (31 upper and 10 lower) in patients with COVID-19 and 82 matched controls of patients with COVID-19 without GIB. The primary objective was to characterize bleeding etiologies, and our secondary aim was to discuss outcomes and therapeutic approaches. RESULTS: There was no difference in the presenting symptoms of the cases and controls, and no difference in severity of COVID-19 manifestations (P > 0.05) was observed. Ten (32%) patients with upper GIB underwent esophagogastroduodenoscopy and 5 (50%) patients with lower GIBs underwent flexible sigmoidoscopy or colonoscopy. The most common upper and lower GIB etiologies were gastric or duodenal ulcers (80%) and rectal ulcers related to rectal tubes (60%), respectively. Four of the esophagogastroduodenoscopies resulted in therapeutic interventions, and the 3 patients with rectal ulcers were referred to colorectal surgery for rectal packing. Successful hemostasis was achieved in all 7 cases that required interventions. Transfusion requirements between patients who underwent endoscopic therapy and those who were conservatively managed were not significantly different. Anticoagulation and rectal tube usage trended toward being a risk factor for GIB, although it did not reach statistical significance. DISCUSSION: In COVID-19 patients with GIB, compared with matched controls of COVID-19 patients without GIB, there seemed to be no difference in initial presenting symptoms. Of those with upper and lower GIB, the most common etiology was peptic ulcer disease and rectal ulcers from rectal tubes, respectively. Conservative management seems to be a reasonable initial approach in managing these complex cases, but larger studies are needed to guide management.

Parametric Estimations Based on Homomorphic Deconvolution for Time of Flight in Sound Source Localization System.

Vehicle-mounted sound source localization systems provide comprehensive information to improve driving conditions by monitoring the surroundings. The three-dimensional structure of vehicles hinders the omnidirectional sound localization system because of the long and uneven propagation. In the received signal, the flight times between microphones delivers the essential information to locate the sound source. This paper proposes a novel method to design a sound localization system based on the single analog microphone network. This article involves the flight time estimation for two microphones with non-parametric homomorphic deconvolution. The parametric methods are also suggested with Yule-walker, Prony, and Steiglitz-McBride algorithm to derive the coefficient values of the propagation model for flight time estimation. The non-parametric and Steiglitz-McBride method demonstrated significantly low bias and variance for 20 or higher ensemble average length. The Yule-walker and Prony algorithms showed gradually improved statistical performance for increased ensemble average length. Hence, the non-parametric and parametric homomorphic deconvolution well represent the flight time information. The derived non-parametric and parametric output with distinct length will serve as the featured information for a complete localization system based on machine learning or deep learning in future works.

Synthesis of pyrrolo[1,2-a]quinolines by formal 1,3-dipolar cycloaddition reactions of quinolinium salts.

Quinolinium salts, Q+-CH2-CO2Me Br- and Q+-CH2-CONMe2 Br- (where Q = quinoline), were prepared from quinolines. Deprotonation of these salts with triethylamine promoted the reaction of the resulting quinolinium ylides (formally azomethine ylides) with electron-poor alkenes by conjugate addition followed by cyclization or by [3 + 2] dipolar cycloaddition. The pyrroloquinoline products were formed as single regio- and stereoisomers. These could be converted to other derivatives by Suzuki-Miyaura coupling, reduction or oxidation reactions.

Monaural Sound Localization Based on Reflective Structure and Homomorphic Deconvolution.

The asymmetric structure around the receiver provides a particular time delay for the specific incoming propagation. This paper designs a monaural sound localization system based on the reflective structure around the microphone. The reflective plates are placed to present the direction-wise time delay, which is naturally processed by convolutional operation with a sound source. The received signal is separated for estimating the dominant time delay by using homomorphic deconvolution, which utilizes the real cepstrum and inverse cepstrum sequentially to derive the propagation response's autocorrelation. Once the localization system accurately estimates the information, the time delay model computes the corresponding reflection for localization. Because of the structure limitation, two stages of the localization process perform the estimation procedure as range and angle. The software toolchain from propagation physics and algorithm simulation realizes the optimal 3D-printed structure. The acoustic experiments in the anechoic chamber denote that 79.0% of the study range data from the isotropic signal is properly detected by the response value, and 87.5% of the specific direction data from the study range signal is properly estimated by the response time. The product of both rates shows the overall hit rate to be 69.1%.