Effects of relative arrangement of discrete surface charges and solvent granularity on the effective potential of mean force (EPMF) are studied. Main conclusions are summarized as follows: (i) With ...consideration of the solvent granularity the EPMF always becomes more attractive, and one like charge attraction always appears even if the counter-ion is univalent. Moreover, with transition from asymmetrical to symmetrical surface charge distributions of similar surface charge compactness, attraction strength of the EPMF always rises; with increase of the counter-ion valence the EPMF attraction strength rises unless the surface charge configuration is asymmetrical and less compact and the counter-ion high-valence. (ii) Whether the surface charge distribution is asymmetrical or symmetrical, the EPMF tends to become more attractive in the compactness charge configuration than in the non-compactness charge configuration. (iii) The correlation between the EPMF attraction strength and bulk mole concentration can be positive or negative depending on the counter-ion valence, compactness of surface charge distribution, and average surface charge strength. Highly taking value of each of the three quantities helps in inducing one negative correlation and vice versa. (iv) Co-ion size has almost no influence on the EPMF, increasing or decreasing the counter-ion size inhibits or enhances the solvent granularity effect.
The present study is performed on the way and mechanism by which ion size changes curves of differential electrical capacitance (C d) vs surface charge strength |σ| and energy storage density E vs ...applied voltage U of an electrical double layer (EDL) formed inside a cylindrical pore electrode. Several valuable findings are made. (i) The C d–|σ| curve generally rises as a result of solvent granularity, which combined with simultaneous higher ion (whether counter- or co-ion) size and higher electrolyte bulk concentration, causing obvious overall morphology change of the curve. (ii) Smaller counterion always raises greatly both C d and E, whereas the co-ion size only has a very weak influence on C d over a range of |σ| around zero, and has almost no influence on E. (iii) One higher counterion electrical valence helps in raising both C d and E, but the electrolyte bulk concentration has no obvious influence on both C d and E in the presence of a higher valence counterion. (iv) The change rate of E with σ exhibits an inflection point at an appropriately large value of |σ| if the counterion valence is not too high (for example, bivalence), and simultaneously the counterion diameter increases. The above findings and relevant mechanisms can be explained reasonably by the changes of ions local distributions in the EDL and their adsorption capacities.
Scarcity of annotated images hampers the building of automated solution for reliable COVID-19 diagnosis and evaluation from CT. To alleviate the burden of data annotation, we herein present a ...label-free approach for segmenting COVID-19 lesions in CT via voxel-level anomaly modeling that mines out the relevant knowledge from normal CT lung scans. Our modeling is inspired by the observation that the parts of tracheae and vessels, which lay in the high-intensity range where lesions belong to, exhibit strong patterns. To facilitate the learning of such patterns at a voxel level, we synthesize 'lesions' using a set of simple operations and insert the synthesized 'lesions' into normal CT lung scans to form training pairs, from which we learn a normalcy-recognizing network (NormNet) that recognizes normal tissues and separate them from possible COVID-19 lesions. Our experiments on three different public datasets validate the effectiveness of NormNet, which conspicuously outperforms a variety of unsupervised anomaly detection (UAD) methods.
1. P-glycoprotein (P-gp/MDR1), one of the most clinically important transmembrane transporters in humans, is encoded by the ABCB1/MDR1 gene. Recent insights into the structural features of P-gp/MDR1 ...enable a re-evaluation of the biochemical evidence on the binding and transport of drugs by P-gp/MDR1.
2. P-gp/MDR1 is found in various human tissues in addition to being expressed in tumours cells. It is located on the apical surface of intestinal epithelial cells, bile canaliculi, renal tubular cells, and placenta and the luminal surface of capillary endothelial cells in the brain and testes.
3. P-gp/MDR1 confers a multi-drug resistance (MDR) phenotype to cancer cells that have developed resistance to chemotherapy drugs. P-gp/MDR1 activity is also of great clinical importance in non-cancer-related drug therapy due to its wide-ranging effects on the absorption and excretion of a variety of drugs.
4. P-gp/MDR1 excretes xenobiotics such as cytotoxic compounds into the gastrointestinal tract, bile and urine. It also participates in the function of the blood-brain barrier.
5. One of the most interesting characteristics of P-gp/MDR1 is that its many substrates vary greatly in their structure and functionality, ranging from small molecules such as organic cations, carbohydrates, amino acids and some antibiotics to macromolecules such as polysaccharides and proteins.
6. Quite a number of single nucleotide polymorphisms have been found for the MDR1 gene. These single nucleotide polymorphisms are associated with altered oral bioavailability of P-gp/MDR1 substrates, drug resistance, and a susceptibility to some human diseases.
7. Altered P-gp/MDR1 activity due to induction and/or inhibition can cause drug-drug interactions with altered drug pharmacokinetics and response.
8. Further studies are warranted to explore the physiological function and pharmacological role of P-gp/MDR1.
•A novel loss function for multi-organ segmentation.•Handling both input and output class imbalance.•Smoothing dice (or similar discrete) loss function(s).•Preventing potential gradient ...vanishing/exploding problem caused by Dice or similar loss functions.•First deep network for PET multi-organ segmentation.•Tested on various data-sets: MRI, PET, and CT.
Simultaneous segmentation of multiple organs from different medical imaging modalities is a crucial task as it can be utilized for computer-aided diagnosis, computer-assisted surgery, and therapy planning. Thanks to the recent advances in deep learning, several deep neural networks for medical image segmentation have been introduced successfully for this purpose. In this paper, we focus on learning a deep multi-organ segmentation network that labels voxels. In particular, we examine the critical choice of a loss function in order to handle the notorious imbalance problem that plagues both the input and output of a learning model. The input imbalance refers to the class-imbalance in the input training samples (i.e., small foreground objects embedded in an abundance of background voxels, as well as organs of varying sizes). The output imbalance refers to the imbalance between the false positives and false negatives of the inference model. In order to tackle both types of imbalance during training and inference, we introduce a new curriculum learning based loss function. Specifically, we leverage Dice similarity coefficient to deter model parameters from being held at bad local minima and at the same time gradually learn better model parameters by penalizing for false positives/negatives using a cross entropy term. We evaluated the proposed loss function on three datasets: whole body positron emission tomography (PET) scans with 5 target organs, magnetic resonance imaging (MRI) prostate scans, and ultrasound echocardigraphy images with a single target organ i.e., left ventricular. We show that a simple network architecture with the proposed integrative loss function can outperform state-of-the-art methods and results of the competing methods can be improved when our proposed loss is used.
The three central phenomena of cuprate (copper oxide) superconductors are linked by a common doping level p*-at which the enigmatic pseudogap phase ends and the resistivity exhibits an anomalous ...linear dependence on temperature, and around which the superconducting phase forms a dome-shaped area in the phase diagram
. However, the fundamental nature of p* remains unclear, in particular regarding whether it marks a true quantum phase transition. Here we measure the specific heat C of the cuprates Eu-LSCO and Nd-LSCO at low temperature in magnetic fields large enough to suppress superconductivity, over a wide doping range
that includes p*. As a function of doping, we find that C
/T is strongly peaked at p* (where C
is the electronic contribution to C) and exhibits a log(1/T) dependence as temperature T tends to zero. These are the classic thermodynamic signatures of a quantum critical point
, as observed in heavy-fermion
and iron-based
superconductors at the point where their antiferromagnetic phase comes to an end. We conclude that the pseudogap phase of cuprates ends at a quantum critical point, the associated fluctuations of which are probably involved in d-wave pairing and the anomalous scattering of charge carriers.
There is evidence that Trigonella foenum-graecum L. (fenugreek), a traditional Chinese herb, and its components are beneficial in the prevention and treatment of diabetes and central nervous system ...disease. The pharmacological activities of trigonelline, a major alkaloid component of fenugreek, have been more thoroughly evaluated than fenugreek's other components, especially with regard to diabetes and central nervous system disease. Trigonelline has hypoglycemic, hypolipidemic, neuroprotective, antimigraine, sedative, memory-improving, antibacterial, antiviral, and anti-tumor activities, and it has been shown to reduce diabetic auditory neuropathy and platelet aggregation. It acts by affecting β cell regeneration, insulin secretion, activities of enzymes related to glucose metabolism, reactive oxygen species, axonal extension, and neuron excitability. However, further study of trigonelline's pharmacological activities and exact mechanism is warranted, along with application of this knowledge to its clinical usage. This review aims to give readers a survey of the pharmacological effects of trigonelline, especially in diabetes, diabetic complications and central nervous system disease. In addition, because of its pharmacological value and low toxicity, the reported adverse effects of trigonelline in experimental animal models and humans are briefly reviewed, and the pharmacokinetics of trigonelline are also discussed.
China was certified malaria-free by the WHO on June, 2021. Nevertheless, there are thousands of overseas imported malaria cases annually in China, and there are deaths of imported malaria cases ...reported every year in the country. In addition, there are secondary cases of imported malaria, and malaria vectors remain in regions where malaria were formerly endemic, resulting in a high risk of local transmission of imported malaria in eliminated regions in China. This article analyzes the risk of malaria control and the challenges of malaria surveillance and response during the post-elimination stage in China, and proposes some suggestions for future priorities.
The nature of the pseudogap phase of cuprates remains a major puzzle1,2. One of its signatures is a large negative thermal Hall conductivity3, whose origin is as yet unknown. This is observed even in ...the undoped Mott insulator La2CuO4, in which the charge carriers are localized and therefore cannot be responsible. Here, we show that the thermal Hall conductivity of La2CuO4 is roughly isotropic; that is, for heat transport parallel and normal to the CuO2 planes, it is nearly the same. This shows that the Hall response must come from phonons, as they are the only heat carriers that are able to move with the same ease both normal and parallel to the planes4. For doping levels higher than the critical doping level at which the pseudogap phase ends, both La1.6−xNd0.4SrxCuO4 and La1.8−xEu0.2SrxCuO4 show no thermal Hall signal for a heat current normal to the planes, which establishes that phonons have zero Hall response outside the pseudogap phase. Inside the pseudogap phase, the phonons must become chiral to generate the Hall response, but the mechanism by which this happens remains to be identified. It must be intrinsic (from a coupling of phonons to their electronic environment) rather than extrinsic (from structural defects or impurities), as these are the same on both sides of critical doping.Thermal transport measurements show that there is a thermal Hall effect in the out-of-plane direction in two cuprates in the pseudogap regime. This indicates that phonons are carrying the heat and that they have a handedness of unknown origin.
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