bluuebunny/crossref_metadata_2025_split huggingface dataset:
New biochemical insights into the dynamics of water molecules at the GMP or IMP binding site of human GMPR enzyme: A molecular dynamics study
Authors: Bairagya Hridoy R. , Tasneem Alvea , Rai Gyan Prakash , Reyaz Saima 
Published: August 2021

AbstractHuman GMP reductase (hGMPR) enzyme is involved in a cellular metabolic pathway, converting GMP into IMP, and also it is an important target for anti‐leukemic agents. Present computational investigations explain dynamical behavior of water molecules during the conformational transition process from GMP to IMP using molecular dynamics simulations. Residues at substrate‐binding site of cancerous protein (PDB Id. 2C6Q) are mostly more dynamic in nature than the normal protein (PDB Id. 2BLE). Nineteen conserved water molecules are identified at the GMP/IMP binding site and are classified as (i) conserved stable dynamic and (ii) infrequent dynamic. Water molecules W11, W14, and W16 are classified as conserved stable dynamic due to their immobile character, whereas remaining water molecules (W1, W2, W3, W4, W5, W7, W8, W9, W10, W12, W13, W15, W17, W18, and W19) are infrequent with dynamic nature. Entrance or displacement of these infrequent water molecules at GMP/IMP sites may occur due to forward and backward movement of reference residues involving ligands. Four water molecules of hGMPR‐I and nine water molecules of hGMPR‐II are observed in repetitive transitions from GMP to IMP pathway, which indicates discrimination between two isoforms of hGMPRs. Water molecules in cancerous protein are more dynamic and unstable compared to normal protein. These water molecules execute rare dynamical events at GMP binding site and could assist in detailed understanding of conformational transitions that influence the hGMPR's biological functionality. The present study should be of interest to the experimental community engaged in leukemia research and drug discovery for CML cancer.
FKT is Not Universal — A Planar Holant Dichotomy
for Symmetric Constraints
Authors: Cai Jin-Yi , Fu Zhiguo , Guo Heng , Williams Tyson 
Published: August 2021

AbstractWe prove a complexity classification for Holant problems defined by an arbitrary set of complex-valued symmetric constraint functions on Boolean variables. This is to specifically answer the question: Is the Fisher-Kasteleyn-Temperley (FKT) algorithm under a holographic transformation (Valiant, SIAM J. Comput. 37(5), 1565–1594 2008) a universal strategy to obtain polynomial-time algorithms for problems over planar graphs that are intractable on general graphs? There are problems that are #P-hard on general graphs but polynomial-time solvable on planar graphs. For spin systems (Kowalczyk 2010) and counting constraint satisfaction problems (#CSP) (Guo and Williams, J. Comput. Syst. Sci. 107, 1–27 2020), a recurring theme has emerged that a holographic reduction to FKT precisely captures these problems. Surprisingly, for Holant, we discover new planar tractable problems that are not expressible by a holographic reduction to FKT. In particular, a straightforward formulation of a dichotomy for planar Holant problems along the above recurring theme is false. A dichotomy theorem for #CSPd, which denotes #CSP where every variable appears a multiple of d times, has been an important tool in previous work. However the proof for the #CSPd dichotomy violates planarity, and it does not generalize to the planar case easily. In fact, due to our newly discovered tractable problems, the putative form of a planar #CSPd dichotomy is false when d ≥ 5. Nevertheless, we prove a dichotomy for planar #CSP2. In this case, the putative form of the dichotomy is true. (This is presented in Part II of the paper.) We manage to prove the planar Holant dichotomy relying only on this planar #CSP2 dichotomy, without resorting to a more general planar #CSPd dichotomy for d ≥ 3. A special case of the new polynomial-time computable problems is counting perfect matchings (#PM) over k-uniform hypergraphs when the incidence graph is planar and k ≥ 5. The same problem is #P-hard when k = 3 or k = 4, which is also a consequence of our dichotomy. When k = 2, it becomes #PM over planar graphs and is tractable again. More generally, over hypergraphs with specified hyperedge sizes and the same planarity assumption, #PM is polynomial-time computable if the greatest common divisor (gcd) of all hyperedge sizes is at least 5. It is worth noting that it is the gcd, and not a bound on hyperedge sizes, that is the criterion for tractability.
To Scan or Not to Scan: Development of a Clinical Decision Support Tool to Determine if Imaging Would Aid in the Diagnosis of Appendicitis
Authors: Gunasingha Rathnayaka M. K. D. , Grey Scott F. , Munoz Beau , Schobel Seth , Lee Joseph , Erwin Casey , Irons Thomas , McMillan Elizabeth , Unselt Desiree , Elster Eric , Bradley Matthew 
Published: August 2021

AbstractBackgroundAppendicitis is one of the most common surgically treated diseases in the world. CT scans are often over‐utilized and ordered before a surgeon has evaluated the patient. Our aim was to develop a tool using machine learning (ML) algorithms that would help determine if there would be benefit in obtaining a CT scan prior to surgeon consultation.MethodsRetrospective chart review of 100 randomly selected cases who underwent appendectomy and 100 randomly selected controls was completed. Variables included components of the patient's history, laboratory values, CT readings, and pathology. Pathology was used as the gold standard for appendicitis diagnosis. All variables were then used to build the ML algorithms. Random Forest (RF), Support Vector Machine (SVM), and Bayesian Network Classifiers (BNC) models with and without CT scan results were trained and compared to CT scan results alone and the Alvarado score using area under the Receiver Operator Curve (ROC), sensitivity, and specificity measures as well as calibration indices from 500 bootstrapped samples.ResultsAmong the cases that underwent appendectomy, 88% had pathology‐confirmed appendicitis. All the ML algorithms had better sensitivity, specificity, and ROC than the Alvarado score. SVM with and without CT had the best indices and could predict if imaging would aid in appendicitis diagnosis.ConclusionThis study demonstrated that SVM with and without CT results can be used for selective imaging in the diagnosis of appendicitis. This study serves as the initial step and proof‐of‐concept to externally validate these results with larger and more diverse patient population.
A phase 1, open-label, drug–drug interaction study of rucaparib with rosuvastatin and oral contraceptives in patients with advanced solid tumors
Authors: Liao Mingxiang , Jeziorski Krzysztof G. , Tomaszewska-Kiecana Monika , Láng István , Jasiówka Marek , Skarbová Viera , Centkowski Piotr , Ramlau Rodryg , Górnaś Maria , Lee John , Edwards Sarah , Habeck Jenn , Nash Eileen , Grechko Nikolay , Xiao Jim J. 
Published: August 2021

Abstract
Purpose
This study aimed at evaluating the effect of rucaparib on the pharmacokinetics of rosuvastatin and oral contraceptives in patients with advanced solid tumors and the safety of rucaparib with and without coadministration of rosuvastatin or oral contraceptives.

Methods
Patients received single doses of oral rosuvastatin 20 mg (Arm A) or oral contraceptives ethinylestradiol 30 µg + levonorgestrel 150 µg (Arm B) on days 1 and 19 and continuous doses of rucaparib 600 mg BID from day 5 to 23. Serial blood samples were collected with and without rucaparib for pharmacokinetic analysis.

Results
Thirty-six patients (n = 18 each arm) were enrolled and received at least 1 dose of study drug. In the drug–drug interaction analysis (n = 15 each arm), the geometric mean ratio (GMR) of maximum concentration (Cmax) with and without rucaparib was 1.29 for rosuvastatin, 1.09 for ethinylestradiol, and 1.19 for levonorgestrel. GMR of area under the concentration–time curve from time zero to last quantifiable measurement (AUC0–last) was 1.34 for rosuvastatin, 1.43 for ethinylestradiol, and 1.56 for levonorgestrel. There was no increase in frequency of treatment-emergent adverse events (TEAEs) when rucaparib was given with either of the probe drugs. In both arms, most TEAEs were mild in severity and considered unrelated to study treatment.

Conclusion
Rucaparib 600 mg BID weakly increased the plasma exposure to rosuvastatin or oral contraceptives. Rucaparib safety profile when coadministered with rosuvastatin or oral contraceptives was consistent with that of rucaparib monotherapy. Dose adjustments of rosuvastatin and oral contraceptives are not necessary when coadministered with rucaparib.
ClinicalTrials.gov NCT03954366; Date of registration May 17, 2019.
The understudied links of the retromer complex to age-related pathways
Authors: Wilson Kenneth A. 
Published: August 2021

AbstractNeuronal aging is associated with numerous diseases resulting in memory impairment and functional decline. A common hallmark of these disorders is the accumulation of intracellular and extracellular protein aggregates. The retromer complex plays a central role in sorting proteins by marking them for reuse rather than degradation. Retromer dysfunction has been shown to induce protein aggregates and neurodegeneration, suggesting that it may be important for age-related neuronal decline and disease progression. Despite this, little is known about how aging influences retromer stability and the proteins with which it interacts. Detailed insights into age-dependent changes in retromer structure and function could provide valuable information towards treating and preventing many age-related neurodegenerative disorders. Here, we visit age-related pathways which interact with retromer function that ought to be further explored to determine its role in age-related neurodegeneration.
Process–Structure–Property Relationship in FeCoNiAlxMnx Complex Concentrated Alloys Processed by Additive Manufacturing
Authors: Poulia A. , Azar A. S. , Schrade M. , Graff J. S. , Bazioti C. , Gunnæs A. E. , Carvalho P. A. , Diplas S. 
Published: August 2021

AbstractFourteen alloys of the FeCoNiAlxMnx system were processed by laser metal deposition (LMD). The feedstock was a weighted and proportional blend of the containing elemental powders, targeting the nominal alloy compositions. Prior to processing, the composition and particle characteristics of the feedstock were assessed. The microstructural features and crystal structures of all LMD processed materials were characterized with scanning electron microscopy/energy dispersive spectroscopy and x-ray diffraction, in both as-received and heat-treated conditions. Selected samples were investigated via scanning transmission electron microscopy and electron backscattered diffraction for further structural understanding. Hardness tests, under various indentation loads and dwelling times, were performed to assess the mechanical properties of the processed samples. The results showed a rise in hardness as Al and Mn contents increase. The variation of hardness with composition follows a reverse sigma-type curve, reflecting the microstructural evolution and grain size variations in the alloys. Based on the hardness data, we suggest a trained and validated predictive model, which can be used in alloy design for future developments.
Logging evaluation on mechanical-damage characteristics of the vicinity of the wellbore in tight reservoirs
Authors: Ma Tianshou , Gui Junchuan , Chen Ping 
Published: August 2021

AbstractThe rock mechanical behavior and damage characteristic is of great importance for in situ stress evaluation, wellbore stability analysis and hydraulic fracturing design. The velocities of elastic waves are usually reduced in the presence of rock damage, it may be used for determining the progressive damage of the rock. Therefore, this paper aims to investigate the damage characteristics of transversely isotropic tight sand formation, the rock mechanical and damage parameters in the vicinity of the wellbore were calculated using acoustic logging data. The results indicated that the Poisson's ratio and damage parameters decrease with increasing in radial distance, while the elastic modulus and Thomsen’s coefficients increase. At the same radial position, the vertical elastic modulus is smaller than that of the horizontal, the degree of anisotropy for P-wave is greater than that of S-wave, and the horizontal damage parameter is greater than that of the vertical, which indicated that the micro-cracks near the wellbore mainly occur in the horizontal direction. The changes in mechanical parameters, Thomsen’s coefficients and damage parameters rapidly changed in the range of 1.0–1.8 times of borehole radius. The variations of Thomsen’s coefficients and damage parameters in mudstone are obviously greater than that of sandstone, which may be due to the induced damage between rocks and drilling fluid of mudstone is much higher than sandstone.
Electron beam welding of rectangular copper wires applied in electrical drives
Authors: Tóth Tamás , Hensel Jonas , Thiemer Sven , Sieber Philipp , Dilger Klaus 
Published: August 2021

AbstractThe so-called hairpin winding technology, which is specially tailored to electrical traction components, deploys rectangular plug-in copper wires in the stator. The fusion welding of the adjacent wire ends is associated with challenges due to the high thermal conductivity as well as the porosity formation of the copper. During this study, the electron beam (EB) welding of electrolytic tough pitch (ETP) and oxygen-free electronic grade (OFE) copper connectors was investigated. Subsequently, the specimens underwent X-ray computed tomography (CT) and metallographic examinations to characterize the joints. It was discovered that the residual oxygen content of the base material is responsible for the pore formation. With only a very low level of oxygen content in the copper, a porosity- and spatter-free welding can be reproducibly realized using the robust EB welding technology, especially for copper materials. By optimizing the parameters accordingly, joints exhibiting a low level of porosity were achieved even in the case of the alloy containing a high amount of residual oxygen. Beyond this, detailed analyses in terms of pore distribution were carried out and a good correlation between technological parameters and welding results was determined.
Asymptotic properties of distance-weighted discrimination and its bias correction for high-dimension, low-sample-size data
Authors: Egashira Kento , Yata Kazuyoshi , Aoshima Makoto 
Published: August 2021

AbstractWhile distance-weighted discrimination (DWD) was proposed to improve the support vector machine in high-dimensional settings, it is known that the DWD is quite sensitive to the imbalanced ratio of sample sizes. In this paper, we study asymptotic properties of the DWD in high-dimension, low-sample-size (HDLSS) settings. We show that the DWD includes a huge bias caused by a heterogeneity of covariance matrices as well as sample imbalance. We propose a bias-corrected DWD (BC-DWD) and show that the BC-DWD can enjoy consistency properties about misclassification rates. We also consider the weighted DWD (WDWD) and propose an optimal choice of weights in the WDWD. Finally, we discuss performances of the BC-DWD and the WDWD with the optimal weights in numerical simulations and actual data analyses.
Repeated and Systematic Intimate Partner Violence in Rural Areas in Sweden
Authors: Strand Susanne J. M. , Selenius Heidi , Petersson Joakim , Storey Jennifer E. 
Published: August 2021

AbstractViolence against women lacks geographical boundaries, although research demonstrates higher rates of such violence in rural areas compared to urban areas. The repeated and systematic intimate partner violence (IPV) is especially problematic in isolated areas. This study aims to investigate how repeated and systematic IPV, was handled by the criminal justice system in rural areas in Sweden and how risk and victim vulnerability factors were related to recidivism in this longitudinal prospective study. The sample consisted of alleged perpetrators of repeated and systematic IPV who had been either reported, charged, or convicted of repeated and systematic IPV defined according to the Swedish Law Gross Violation of a Woman’s Integrity targeting such violence, in two rural Swedish police districts during 2011–2014 (N = 258). Results demonstrated that 30% of IPV perpetrators were charged with the Gross violation offense and 5% were charged for other IPV-related offenses. The conviction for the Gross violation offense was 11% and 24% for other IPV-related offenses. 56% were not charged or convicted of any IPV-related offenses. Perpetrators convicted of the Gross Violation offense were more likely to receive longer prison sentences than perpetrators convicted of other IPV-related offenses. Victim cooperation in the police investigation increased the likelihood for prosecution with 7.3 times and for a conviction with 6.1 times. In terms of recidivism 24% engaged in IPV towards the same victim and another 27% recidivated into general criminality. Recidivists had higher summary risk ratings and more individual risk factors than non-recidivists, such as general criminality, employment problems and mental health problems, and victim vulnerability factors including personal problems. To reduce re-victimization, risk and vulnerability factors and supporting victims to cooperate in the police investigation should be considered when forming risk management strategies to protect victims of repeated and systematic IPV in such rural areas.
Aircraft descent performance based on flight data
Authors: Hall C.A. , Burnell S.R. , Deshpande A.P. 
Published: August 2021

AbstractThere are significant variations in the fuel consumption of aircraft during the descent phase of a flight. This paper uses aircraft flight data measurements to develop an improved understanding of these variations. A model of the aircraft engines is developed that is matched to flight data and shown to reproduce the time history of engine parameters. This model is used to determine the overall engine efficiency at each point during a descent. This enables an energy breakdown to be completed, in terms of mechanical energy from fuel, gravitational potential energy and kinetic energy. During descent, the aircraft engines operate at low overall pressure ratios corresponding to low fuel flow rates and low overall efficiencies. On average, the engine overall efficiency during descent is one-third of cruise efficiency. The airframe aerodynamic performance is deteriorated during descent with an average lift-to-drag ratio that is 87% of the average value at cruise. There are also large variations in air-track efficiency, and for the flights analysed the great circle descent distance was found to be 85% of the average descent air distance. To minimise fuel burn, flights should cruise as far as possible before starting descent and follow a trajectory with the shortest possible air distance. The descent air speed should be set to maximise the aircraft lift-to-drag ratio. Such descents could save up to 0.5% of the total aircraft mass in fuel.
Educating for diversity, equity, and inclusion: A review of commonly used educational approaches
Authors: Corsino Leonor , Fuller Anthony T. 
Published: August 2021

AbstractDiversity, equity, and inclusion (DEI) are fundamentally important concepts for advancing clinical and translational science (CTS) education. CTS education spans a wide range of disciplines from cell biology to clinical and community/population research. This large scope both in terms of intellectual areas and target groups requires an understanding of existing educational approaches for DEI as we translate DEI from mere concepts into equitable actions within CTS education. In this review, we provide the readers with the most common DEI educational approaches, including cultural humility, bias training, and improving mentoring to diversify the workforce. DEI educational materials can achieve maximal success and long-term impact when implemented as institutional-wide interventions, and the materials are not seen as an isolated or independent curriculum. Approaches, strategies, and programs to achieve this are many. However, many questions remain unanswered about what the best approach, strategies, and programs are to be implemented in institutional-wide education that will be embedded in CTS education.
Davidson on Pure Intending: A Non-Reductionist Judgement-Dependent Account
Authors: Hossein Khani Ali 
Published: August 2021

AbstractI will argue that Davidson's account of pure intending can be construed as a first-person-based judgement-dependent account of intention. For Davidson, pure intending to do φ is to make an all-out judgement that φing is desirable. On this anti-reductionist account, intention is treated as an irreducible state of the subject. I will draw a comparison between this account and Wright's and I will show that Davidson's account can be viewed as a non-reductionist judgement-dependent account along the lines suggested by Wright. I then explain how this account can help deal with various perplexities in Davidson's later view of meaning and mental content.
Immune cell arrival kinetics to peritoneum and role during murine-experimental trichomoniasis
Authors: Rangel-Mata F. J. , Ávila-Muro E. E. , Reyes-Martínez J. E. , Olmos-Ortiz L. M. , Brunck M. E. , Arriaga-Pizano L. A. , Cuéllar-Mata P. 
Published: August 2021

AbstractTrichomonas vaginaliscauses trichomoniasis, an inflammatory process related to an increased rate of HIV transmission. In order to studyT. vaginalisinfection response in a microorganism-free environment, an infection model was established providing a host–parasite interaction system useful to study the interplay between immune cells and the parasite. Infected mice peritoneal cells were immunophenotyped at different times after infection using flow cytometry. Neutrophils and macrophages showed the most relevant increase from third to 12th day post-infection. A high number of B lymphocytes were present on 15th day post-infection, and an increase in memory T cells was observed on sixth day post-infection. The levels of NO increased at day 10 post-infection; no significant influence was observed onT. vaginalisclearance. Increased viability ofT. vaginaliswas observed when the NETs inhibitors, metformin and Cl−amidine, were administrated, highlighting the importance of this mechanism to control parasite infection (43 and 86%, respectively). This report presents a comprehensive cell count of the immune cells participating against trichomoniasis in anin vivointeraction system. These data highlight the relevance of innate mechanisms such as specific population changes of innate immune cells and their impact on theT. vaginalisviability.
Molecular and morphological characterisation of Diplostomum phoxini (Faust, 1918) with a revised classification and an updated nomenclature of the species-level lineages of Diplostomum (Digenea: Diplostomidae) sequenced worldwide
Authors: Schwelm Jessica , Georgieva Simona , Grabner Daniel , Kostadinova Aneta , Sures Bernd 
Published: August 2021

AbstractWe characterised morphologically and molecularly Diplostomum phoxini (Faust, 1918) based on cercarial isolates from the snail Ampullaceana balthica (L.) (Gastropoda: Lymnaeidae) and metacercariae from the Eurasian minnow, Phoxinus phoxinus (L.) (Cypriniformes: Leuciscidae), and provided molecular evidence for the identification of the snail intermediate host. Phylogenetic analyses based on the cytochrome c oxidase subunit 1 (cox1) gene depicted 44 molecularly characterised species and genetically distinct lineages of Diplostomum, and resulted in: (i) a re-identification/re-classification of 98 isolates plus D. baeri sampled in North America; (ii) re-definition of the composition of the D. baeri species complex which now includes nine molecularly characterised species/lineages; (iii) re-definition of the composition of the D. mergi species complex which now includes seven molecularly characterised species/lineages; and (iv) an updated nomenclature for the molecularly characterised species-level lineages of Diplostomum.