Miracle-dz/UniFAR-FTUs huggingface dataset:
On achieving high accuracy and reliability in the calculation of relative protein–ligand binding affinities

We apply a free energy perturbation simulation method, free energy perturbation/replica exchange with solute tempering, to two modifications of protein–ligand complexes that lead to significant conformational changes, the first in the protein and the second in the ligand. The approach is shown to facilitate sampling in these challenging cases where high free energy barriers separate the initial and final conformations and leads to superior convergence of the free energy as demonstrated both by consistency of the results (independence from the starting conformation) and agreement with experimental binding affinity data. The second case, consisting of two neutral thrombin ligands that are taken from a recent medicinal chemistry program for this interesting pharmaceutical target, is of particular significance in that it demonstrates that good results can be obtained for large, complex ligands, as opposed to relatively simple model systems. To achieve quantitative agreement with experiment in the thrombin case, a next generation force field, Optimized Potentials for Liquid Simulations 2.0, is required, which provides superior charges and torsional parameters as compared to earlier alternatives.
The Relationship of Coronary Sinus Dilation with Pulmonary Artery Pressure in Pediatric Patients

Background: Increased right atrial pressure due to pulmonary hypertension may impair venous drainage with resultant coronary sinus dilatation. The aim of this study was to search for correlations between coronary sinus diameter and estimated pulmonary artery pressure in children. Methods: In a prospective study, 100 children who were referred consecutively for transthoracic echocardiography were included in this study. Ratios of coronary sinus diameter to weight, body surface area and aortic annulus were calculated for in each patient. Correlation between coronary sinus diameter and estimated pulmonary artery pressure was studied by person correlation. A tricuspid regurgitation peak gradient more than 36 mmHg or pulmonary regurgitation peak gradient more than 25 mmHg were considered as pulmonary hypertension. Results: Sixty-eight of our participants had no pulmonary hypertension and 32 did. Mean age was 7.6 years in the patients without pulmonary hypertension and 8.0 years in the patients with pulmonary hypertension (P=0.11). Mean coronary sinus diameter to aortic annulus diameter ratio was 0.49 ± 0.13 in the patient with pulmonary hypertension versus 0.38 ± 0.12 in the patient without pulmonary hypertension (P<0.001). The coronary sinus diameter to body surface area ratio was 1.3 ± 0.59 versus 0.7 ± 0.28 (P<0.001), and coronary sinus diameter to weight ratio was 0.06 ± 0.03 versus 0.02 ± 0.01 (P<0.001). Conclusion: coronary sinus dilation was documented in pediatric patients with pulmonary hypertension. The ratios of coronary sinus diameter to aortic annulus diameter, body surface area and weight correlated significantly with pulmonary hypertension.
The Primitive Thylakoid-Less Cyanobacterium Gloeobacter Is a Common Rock-Dwelling Organism

Cyanobacteria are an ancient group of photosynthetic prokaryotes, which are significant in biogeochemical cycles. The most primitive among living cyanobacteria, Gloeobacter violaceus, shows a unique ancestral cell organization with a complete absence of inner membranes (thylakoids) and an uncommon structure of the photosynthetic apparatus. Numerous phylogenetic papers proved its basal position among all of the organisms and organelles capable of plant-like photosynthesis (i.e., cyanobacteria, chloroplasts of algae and plants). Hence, G. violaceus has become one of the key species in evolutionary study of photosynthetic life. It also numbers among the most widely used organisms in experimental photosynthesis research. Except for a few related culture isolates, there has been little data on the actual biology of Gloeobacter, being relegated to an “evolutionary curiosity” with an enigmatic identity. Here we show that members of the genus Gloeobacter probably are common rock-dwelling cyanobacteria. On the basis of morphological, ultrastructural, pigment, and phylogenetic comparisons of available Gloeobacter strains, as well as on the basis of three new independent isolates and historical type specimen, we have produced strong evidence as to the close relationship of Gloeobacter to a long known rock-dwelling cyanobacterial morphospecies Aphanothece caldariorum. Our results bring new clues to solving the 40 year old puzzle of the true biological identity of Gloeobacter violaceus, a model organism with a high value in several biological disciplines. A probable broader distribution of Gloeobacter in common wet-rock habitats worldwide is suggested by our data, and its ecological meaning is discussed taking into consideration the background of cyanobacterial evolution. We provide observations of previously unknown genetic variability and phenotypic plasticity, which we expect to be utilized by experimental and evolutionary researchers worldwide.
Accelerating low bit-width convolutional neural networks with embedded FPGA

Convolutional Neural Networks (CNNs) can achieve high classification accuracy while they require complex computation. Binarized Neural Networks (BNNs) with binarized weights and activations can simplify computation but suffer from obvious accuracy loss. In this paper, low bit-width CNNs, BNNs and standard CNNs are compared to show that low bit-width CNNs is better suited for embedded systems. An architecture based on the two-stage arithmetic unit (TSAU) as the basic processing element is proposed to process each layer iteratively for low bit-width CNN accelerators. Then the DoReFa-Net which is trained with weights and activations represented in 1 bit and 2 bits respectively is implemented on Zynq XC7Z020 FPGA with a 410.2 GOPS performance. The accelerator can meet the real-time requirement of embedded applications with a 106 FPS throughput and a 73.1% top-5 accuracy on the ImageNet dataset. The accelerator outperforms existing FPGA-based CNN accelerators in the tradeoff among accuracy, energy and resource efficiency.
A Study on the Packaging for Fast Boot-up Time in the Embedded Linux

This paper attempts to analyze the boot-up time of bootloader and Linux kernel, and to compare performance of several root file-systems for fast boot-up time in the embedded Linux. Therefore, it was implemented with time measurement module to analyze the boot-up time of bootloader and Linux kernel, and measured the time at each event point related to boot-up. As a result of analysis of six cases packaging, it has turned out the fact that the data checksum routine, decompressing the kernel and ramdisk image takes most of the boot-up time. Root file-system was packaged through analyzing such performance as boot-up time, memory usage, file-system size. This is based on raw-kernel image and a combination of CRAMFS and JFFS2, and it has small size of the root file-system, the boot-up time is decreased.
A Survey on Static Routing Wavelength Assignment Considering Physical Layer Impairments in Wavelength Divison Multiplexing Optical Networks

Imagine a world of people who are connected through networks either they are far or close to each other and they could communicate in just “planks time”(that is believed to be the possible shortest duration) by paying less and obtaining great speed to communicate, this is just what the researchers are trying to obtain these days. One of the major problems facing optical networks is Routing and Wavelength Assignment (RWA) of optical signals taking into consideration the impairments caused by the physical layer. A regular RWA which does not consider impairments is often used to solve the RWA of optical signals but this approach could be improved. Various researchers have tried to solve regular RWA under physical impairments in order to improve or replace it. This survey is about their research.
Wireless patch sensor for remote monitoring of heart rate, respiration, activity, and falls

Unobtrusive continuous monitoring of important vital signs and activity metrics has the potential to provide remote health monitoring, at-home screening, and rapid notification of critical events such as heart attacks, falls, or respiratory distress. This paper contains validation results of a wireless Bluetooth Low Energy (BLE) patch sensor consisting of two electrocardiography (ECG) electrodes, a microcontroller, a tri-axial accelerometer, and a BLE transceiver. The sensor measures heart rate, heart rate variability (HRV), respiratory rate, posture, steps, and falls and was evaluated on a total of 25 adult participants who performed breathing exercises, activities of daily living (ADLs), various stretches, stationary cycling, walking/running, and simulated falls. Compared to reference devices, the heart rate measurement had a mean absolute error (MAE) of less than 2 bpm, time-domain HRV measurements had an RMS error of less than 15 ms, respiratory rate had an MAE of 1.1 breaths per minute during metronome breathing, posture detection had an accuracy of over 95% in two of the three patch locations, steps were counted with an absolute error of less than 5%, and falls were detected with a sensitivity of 95.2% and specificity of 100%.
Scalable Image Retrieval by Sparse Product Quantization

Fast approximate nearest neighbor (ANN) search technique for high-dimensional feature indexing and retrieval is the crux of large-scale image retrieval. A recent promising technique is product quantization, which attempts to index high-dimensional image features by decomposing the feature space into a Cartesian product of low-dimensional subspaces and quantizing each of them separately. Despite the promising results reported, their quantization approach follows the typical hard assignment of traditional quantization methods, which may result in large quantization errors, and thus, inferior search performance. Unlike the existing approaches, in this paper, we propose a novel approach called sparse product quantization (SPQ) to encoding the high-dimensional feature vectors into sparse representation. We optimize the sparse representations of the feature vectors by minimizing their quantization errors, making the resulting representation is essentially close to the original data in practice. Experiments show that the proposed SPQ technique is not only able to compress data, but also an effective encoding technique. We obtain state-of-the-art results for ANN search on four public image datasets and the promising results of content-based image retrieval further validate the efficacy of our proposed method.
PhD Proposal : An Adaptive Sensor Network Architecture for Multi-scale Communication

Sensor networks have emerged as a promising tool for monitoring (and possibly actuating) the physical world, utilizing self-organizing networks of battery-powered wireless sensors that can sense, process and communicate. These sensor networks can be rapidly deployed and at low cost, thereby enabling large-scale, on-demand monitoring and tracking over a wide area. The sensors can be deployed where it is difficult to monitor otherwise, such as natural or man-made crises like severe weather, wild-fires, earthquakes, volcanic activities, chemical, biological or nuclear agents, structural and habitat monitoring. Generally the model of sensor networks is: the sensors measure physical properties at different spatial and temporal positions, signal processing and data assimilation is performed in-network, queried results are communicated with one or more data sinks, and the sinks monitor, compute or actuate based on the data. I propose the design of an adaptive cross-layered Sensor Network Architecture for enabling multi-scale collaboration and communication. In sensor networks, energy and communication bandwidth are scarce resources, while applications exhibit a limited set of characteristics. Thus, there is both a need and an opportunity for adapting the network architecture to match the applications, in order to minimize the resource consumed and extend the life of the network. There are various requirements and limitations of sensor networks, which make their architecture and protocols both challenging and divergent from the needs of traditional internet architecture. Many applications, such as large-scale collaborative sensing, distributed signal processing, and distributed data assimilation require the sensor data to be available at multiple resolutions, or allow fidelity to be traded-off for energy efficiency. The architecture I propose enables scalability, localization and resolution-tuning, while simplifying application design by providing communication abstractions. Examples of a few applications of this multi-scale approach are as follows:
Patent Ductus Arteriosus and Brain Volume

BACKGROUND AND OBJECTIVES: A hemodynamically significant patent ductus arteriosus (PDA) can compromise perfusion and oxygenation of the preterm brain. Reports suggest that PDA is associated with increased mortality and morbidity. We hypothesize that long-standing low cerebral oxygenation due to PDA might affect brain volume at term equivalent age. METHODS: Observational study in 140 infants investigating the relationship between near-infrared spectroscopy–monitored cerebral oxygen saturation (rSco2) and MRI-assessed regional brain volume and maturation of the posterior limb of the internal capsule at term-equivalent age in 3 groups: those whose PDA closed with indomethacin, those who needed additional surgical closure, and matched controls. RESULTS: The surgery group had the lowest rSco2 values before closure (n = 35), 48% ± 9.7% (mean ± SD) as compared with the indomethacin (n = 35), 59% ± 10.4 (P < .001), and control groups (n = 70), 66% ± 6.9 (P < .001); the highest postnatal age before effective treatment; and the lowest volumes of most brain regions at term-equivalent age. Multiple linear regression analysis showed a significant effect of preductal closure rSco2 on cerebellar volume in this group. No differences were found in maturation of the posterior limb of the internal capsule. CONCLUSIONS: Long-standing suboptimal cerebral oxygenation due to a PDA may negatively influence brain growth, affecting neurodevelopmental outcome.
Helical Defects in MicroRNA Influence Protein Binding by TAR RNA Binding Protein

Background MicroRNAs (miRNAs) are critical post-transcriptional regulators of gene expression. Their precursors have a globally A-form helical geometry, which prevents most proteins from identifying their nucleotide sequence. This suggests the hypothesis that local structural features (e.g., bulges, internal loops) play a central role in specific double-stranded RNA (dsRNA) selection from cellular RNA pools by dsRNA binding domain (dsRBD) containing proteins. Furthermore, the processing enzymes in the miRNA maturation pathway require tandem-dsRBD cofactor proteins for optimal function, suggesting that dsRBDs play a key role in the molecular mechanism for precise positioning of the RNA within these multi-protein complexes. Here, we focus on the tandem-dsRBDs of TRBP, which have been shown to bind dsRNA tightly. Methodology/Principal Findings We present a combination of dsRNA binding assays demonstrating that TRBP binds dsRNA in an RNA-length dependent manner. Moreover, circular dichroism data shows that the number of dsRBD moieties bound to RNA at saturation is different for a tandem-dsRBD construct than for constructs with only one dsRBD per polypeptide, revealing another reason for the selective pressure to maintain multiple domains within a polypeptide chain. Finally, we show that helical defects in precursor miRNA alter the apparent dsRNA size, demonstrating that imperfections in RNA structure influence the strength of TRBP binding. Conclusion/Significance We conclude that TRBP is responsible for recognizing structural imperfections in miRNA precursors, in the sense that TRBP is unable to bind imperfections efficiently and thus is positioned around them. We propose that once positioned around structural defects, TRBP assists Dicer and the rest of the RNA-induced silencing complex (RISC) in providing efficient and homogenous conversion of substrate precursor miRNA into mature miRNA downstream.
Early Brain Vulnerability in Wolfram Syndrome

Wolfram Syndrome (WFS) is a rare autosomal recessive disease characterized by insulin-dependent diabetes mellitus, optic nerve atrophy, diabetes insipidus, deafness, and neurological dysfunction leading to death in mid-adulthood. WFS is caused by mutations in the WFS1 gene, which lead to endoplasmic reticulum (ER) stress-mediated cell death. Case studies have found widespread brain atrophy in late stage WFS. However, it is not known when in the disease course these brain abnormalities arise, and whether there is differential vulnerability across brain regions and tissue classes. To address this limitation, we quantified regional brain abnormalities across multiple imaging modalities in a cohort of young patients in relatively early stages of WFS. Children and young adults with WFS were evaluated with neurological, cognitive and structural magnetic resonance imaging measures. Compared to normative data, the WFS group had intact cognition, significant anxiety and depression, and gait abnormalities. Compared to healthy and type 1 diabetic control groups, the WFS group had smaller intracranial volume and preferentially affected gray matter volume and white matter microstructural integrity in the brainstem, cerebellum and optic radiations. Abnormalities were detected in even the youngest patients with mildest symptoms, and some measures did not follow the typical age-dependent developmental trajectory. These results establish that WFS is associated with smaller intracranial volume with specific abnormalities in the brainstem and cerebellum, even at the earliest stage of clinical symptoms. This pattern of abnormalities suggests that WFS has a pronounced impact on early brain development in addition to later neurodegenerative effects, representing a significant new insight into the WFS disease process. Longitudinal studies will be critical for confirming and expanding our understanding of the impact of ER stress dysregulation on brain development.
Anaesthesia and myotonia.

h� 1 for 15 min, then 4 mg kg � 1 h � 1 for another 10 min and finally 2 mg kg � 1 h � 1 [2] for the remainder of the operation. Atracurium 20 mg was also given. No other sedative or analgesic drugs were used. The patient underwent femoral embolectomy without any major problems. The propofol infusion was discontinued 55 min after induction. Within 3 min his respiratory efforts were adequate and the trachea was extubated. However, although respiration was satisfactory and the airway was well maintained, it was a further 65 min before verbal contact was made with the patient. The immediate postoperative period was uneventful but on day 7 he began to develop increasing weakness, including bulbar weakness, and he died on day 14. The second case was a 27-yr-old female with moderately severe myotonia dystrophica causing cataracts, marked muscle weakness, slurred speech and swallowing difficulties. However, she was mobile and had no respiratory or cardiovascular system involvement. She was admitted for laparoscopic cholecystectomy. The patient was premedicated with temazepam 10 mg, and heparin 5000 u. was administered s.c. After preoxygenation, fentanyl 100 g was given and the effect observed. Three 25-mg increments of propofol were given at 1-min intervals to assess the patient’s sensitivity to propofol. When it was evident that the patient was not sensitive, propofol 125 mg was given followed by atracurium 15 mg. Anaesthesia was maintained with 0.5–1.0 % isoflurane and nitrous oxide in oxygen. The operation and anaesthetic proceeded uneventfully with a further 100 mg of fentanyl and 10 mg of atracurium being required. Morphine 10 mg was administered at the end of operation. The patient made a rapid recovery and was fit to leave theatre recovery 35 min after the anaesthetic. The third case was female with moderate myotonia undergoing total abdominal hysterectomy. She had mild muscle weakness with no other problems (she had only been diagnosed because of family screening.) After premedication with temazepam 10 mg, anaesthesia was induced with alfentanil 2 mg followed by propofol 140 mg given slowly. Intubation was performed without formal paralysis and anaesthesia was maintained with a propofol infusion of 10 mg kg � 1 h � 1 followed by 8 mg kg � 1 h � 1 followed by
Issues around the Prescription of Half Tablets in Northern Switzerland: The Irrational Case of Quetiapine

Background. Prescription of fragmented tablets is useful for individualisation of dose but includes several drawbacks. Although without score lines, the antipsychotic drug quetiapine was in 2011 the most often prescribed 1/2 tablet in discharge prescriptions at the University Hospital in Basel (USB, 671 beds). We aimed at analysing the prescription patterns of split tablets in general and of quetiapine in particular in Switzerland. Methods. All orders of community pharmacies for unit-of-use soft pouch blisters placed at Medifilm AG, the leader company in Switzerland for repackaging into pouch blisters, were analysed. Results. Out of 4,784,999 tablets that were repacked in 2012 in unit-of-use pouch blisters, 8.5% were fragmented, mostly in half (87.6%), and were predominantly psycholeptics (pipamperone 15.8%). Prescription of half quetiapine appears to be a Basel specificity (highest rates of fragments and half quetiapine). Conclusions. Prescription of fragmented tablet is frequent. It represents a safety issue for the patient, and a pharmaceutical care issue for the pharmacist. In ambulatory care, the patient's cognitive and physical capacities must be clarified, suitability of the splitting of the tablet must be checked, appropriate aids must be offered, like a pill-splitting device in order to improve accuracy, and safe use of the drug must be ensured.