bluuebunny/crossref_metadata_2025_split huggingface dataset:
Posteromedial Corner Release with the Knee in Figure‐of‐Four Position vs Conventional Position for Varus Knee Arthroplasty
Authors: Ji Quan‐bo , Li Jun‐cheng , Zheng Qing‐yuan , Geng Zong‐jie , Ni Ming , Sun Jing‐yang , Wang Yan , Zhang Guo‐qiang 
Published: June 2021

ObjectiveTo introduce posteromedial corner release with the knee in the figure‐of‐four position versus the conventional position for varus knee arthroplasty.MethodsThis is a retrospective study. From March 2015 to September 2019, a series of 123 patients (139 knees) with varus knee were randomly and blindly allocated to experimental group (60 patients; 68 knees) and control group (57 patients; 65 knees). Patients in experimental group underwent posteromedial corner release with the knee in the figure‐of‐four position; and patients in control group with the knee in the conventional position. If soft tissue balance was not completely achieved or the medial gap was still tight, an additional loosening technique were used to achieve symmetric medial and lateral space in both groups. Time for soft tissue balancing was defined as the time from the start of the spacer test to the end of the balance test. Length of release was defined as the distance from the osteotomy surface of the tibial plateau to the farthest structures released. The rating system of Hospital for Special Surgery (HSS) knee score was used to evaluate the clinical results. Quantitative variables were described as mean and standard deviation, and compared by one‐way analysis of variance.ResultsThe mean age of experimental group and control group was 70.2 ± 8.7 years and 68.7 ± 6.2 years, respectively (P > 0.05). Preoperatively, the mean HSS score of the groups was 38.2 ± 11.3 and 39.1 ± 10.7, respectively (P > 0.05). The mean varus knee angle was 19.7° ± 9.3° and 19.3° ± 10.7°, respectively (P > 0.05). The mean time for soft tissue balancing was 8.4 ± 3.3 min and 11.3 ± 6.9 min in experimental and control group, respectively (P < 0.05). The mean length of releasing posteromedial corner structures was 35.5 ± 13.4 mm and 27.3 ± 9.7 mm in experimental and control group, respectively (P < 0.05). Additional special loosening techniques were performed in eight knees in experimental group and seven knees in control group. The HSS scores 5 years after surgery were 95.1 ± 16.9 and 94.8 ± 17.2 respectively (P > 0.05). No complications were found during the follow‐up time, and the clinical symptoms were observed to be significantly improved in the patients.ConclusionThe posteromedial corner can be released more extensively and thoroughly when the knee is placed in the figure‐of‐four position during varus knee arthroplasty.
The parental magma composition, crustal contamination process, and metallogenesis of the Shitoukengde Ni‐Cu sulfide deposit in the Eastern Kunlun Orogenic Belt, NW China
Authors: Li Liang , Zhang Dexin , Tan Shucheng , Sun Fengyue , Wang Chao , Zhao Tuofei , Li Shijin , Yang Yanqian 
Published: June 2021

AbstractShitoukengde is an important magmatic Ni–Cu sulfide deposit in the Eastern Kunlun Orogenic Belt (EKOB). It comprises several mafic–ultramafic complexes and contains different kinds of mafic–ultramafic rocks. Lherzolite and olivine websterite are the most significant Ni–Cu‐hosted rocks. The No. I complex hosts six Ni–Cu ore bodies, and the depth of the intrusion has great exploration potential. Therefore, geochronology, geochemistry, and mineral chemistry of the Shitoukengde deposit were studied to constrain its mineralization time, parental magma composition, and crustal contamination process. Zircon U–Pb dating of olivine websterite shows the magmatic origin (Th/U = 0.40–1.05) and an age of 418.1 ± 8.7 Ma (MSWD = 0.01), which is coeval with the Xiarihamu, Akechukesai, and other Cu–Ni deposits in the EKOB. Geochemically, the mafic–ultramafic rocks are characterized by low SiO2, TiO2, and Na2O + K2O and high MgO (9.49–36.02%), with Mg# values of 80–87. They are relatively enriched in LREE and LILEs (e.g., K, Rb, and Th), with weakly positive Eu anomalies (δEu = 0.83–2.26), but depleted in HFSEs (e. g., Ta, Nb, Zr, and Ti). Based on the electron microprobe analyses, all of the olivines are chrysolite (Fo = 81–86), and the pyroxenes are dominated by clinoenstatite (En = 80–84) and augite (En = 49–55) in the mafic–ultramafic rocks. Therefore, the composition of parental magma is estimated to be picritic basaltic magma with SiO2 and MgO concentrations of 54.47 and 13.95%, respectively. The zircon εHf(t) values of olivine websterite vary from −0.8 to 4.6, with a TDM1 of 0.84–1.06 Ga, indicating that the parental magma was derived from relatively high degree partial melting (about 13.4%) of a depleted mantle source and experienced significant crustal contamination (about 12–16%). We propose that crustal assimilation, rather than fractional crystallization, played a key role in triggering the sulfide saturation of the Shitoukengde deposit, and the metallogenesis of “deep liquation–pulsing injection” is the key mechanism underlying its formation. The parental magma, before intruding, underwent liquation and partial crystallization at depth, partitioning into barren, ore‐bearing, and ore‐rich magma and ore pulp, and was then injected multiple times, resulting in the formation of the Shitoukengde Ni–Cu deposit.
Cramér‐von Mises tests for change points
Authors: Erlemann Rasmus , Lockhart Richard , Yao Rihan 
Published: June 2021

AbstractWe study two nonparametric tests of the hypothesis that a sequence of independent observations is identically distributed against the alternative that at a single change point the distribution changes. The tests are based on the Cramér–von Mises two‐sample test computed at every possible change point. One test uses the largest such test statistic over all possible change points; the other averages over all possible change points. Large sample theory for the average statistic is shown to provide useful p‐values much more quickly than bootstrapping, particularly in long sequences. Power is analyzed for contiguous alternatives. The average statistic is shown to have limiting power larger than its level for such alternative sequences. Evidence is presented that this is not true for the maximal statistic. Asymptotic methods and bootstrapping are used for constructing the test distribution. Performance of the tests is checked with a Monte Carlo power study for various alternative distributions.
Depression and its associated factors among people with multidrug‐resistant tuberculosis in Myanmar
Authors: Theingi Phyo , Kamiya Yasuhiko , Myat Moe Myat , Cho San Cho , Cox Sharon E. 
Published: June 2021

AbstractBackgroundDepression is an important potential comorbidity in persons with tuberculosis (TB), yet data in many settings are scarce.ObjectiveTo estimate the prevalence and risk factors of depression in persons with multidrug‐resistant tuberculosis (MDR‐TB) in Myanmar.MethodsA cross‐sectional survey among MDR‐TB participants at Aung San MDR‐TB treatment centre in Yangon during routine clinic follow‐up visits. Patients Health Questionnaire‐9 (PHQ‐9) in the local language was used to screen for depression and structured questionnaires conducted. Univariable and multivariable logistic regression models were performed to identify associations.ResultsThree‐hundred and twenty‐nine participants were enrolled between 19th December 2019 and 31st January 2020; 33% (111/329) in the intensive treatment phase. The prevalence of depressive symptoms (PHQ‐9 ≥ 10) was (34/329) 10.33%. Multivariable analysis indicated financial hardship as a result of MDR‐TB symptoms/treatment (aOR = 2.63, 95%CI: 1.12–6.67), suffering ≥1 respiratory symptoms (aOR = 6.72, 95%CI: 2.41–18.76), high education level (aOR = 4.26, 95%CI: 1.70–10.70), reported diabetes (aOR = 3.05, 95%CI: 1.16–7.99) as associated with depressive symptoms, with weak evidence of an association in females (aOR = 2.09, 95%CI: 0.94–4.65).ConclusionDepressive symptoms are more common in those with comorbidities/TB symptoms. Further research is required to determine the effects of interventions to support persons with depressive symptoms identified using simple, standardised validated tools like PHQ‐9.
Turbulence in Small Air Jets at Exit Velocities Up to 705 Feet per Second
Authors: Lassiter L. W. 
Published: June 2021

Abstract
Turbulence intensity, scale, and spectrum measurements were made on model jets of 1 in. and 2-in. diam at various mean velocities. The indications are that only in the fully developed flow is turbulence intensity invariant with mean velocity; intensity in the core, in the turbulent annulus, and in the transition region decreases in varying degrees with mean velocity increase. Longitudinal and radial scales of turbulence were found to increase in the annulus in proportion to about the square root of axial distance, and longitudinal scale is about 65 per cent greater than radial scale. Both radial and longitudinal scales seem to be essentially constant with mean velocity. Turbulence spectra were found to consist of a sharply peaked band of frequencies in the core, degenerating to a slightly peaked broad band at points in the mixing regions.
The Mobility of Levers Having Uniformly Distributed Mass
Authors: Creech M. D. 
Published: June 2021

Abstract
This paper shows how the mobility of a uniform rigid lever of mass M with m arbitrary mobilities connected along its length can be analyzed. The mass of the lever is divided into n equal mobilities connected to a rigid weightless lever together with the m other mobilities. It is shown that the infinite-series expansion representing this case is convergent to a finite value.
Response of Nonlinearly Supported Spherical Boundaries to Shock Waves
Authors: Baron M. L. 
Published: June 2021

Abstract
An integral transform technique is used to solve a boundary-value problem in which the partial differential equation is linear but the associated boundary condition is nonlinear. A spherical cavity in an infinite acoustic medium has an elastically supported boundary such that the pressure-displacement relation on the boundary is nonlinear. The response of the boundary to a plane shock wave which progresses across the cavity and envelops it is obtained by solving two auxiliary boundary-value problems with linear boundary conditions. Using influence coefficients obtained from these solutions, a nonlinear integral equation for the response of the actual boundary is obtained. The integral equation is solved numerically for a set of parameters, and curves for the pressure-time and displacement-time responses of the boundary are presented.
Thermal Drift of Floated Gyroscopes
Authors: Goodman L. E. , Robinson A. R. 
Published: June 2021

Abstract
When a floated gyroscope is subjected to a temperature distribution which is not symmetrical about a plane parallel to the gravitational force, convection currents tend to rotate the gimbal. The rebalance torque and the free drift rate due to thermal effects are first determined for the case of an exactly centered gimbal. It is then shown that moderate gimbal eccentricity has little influence on thermal drift, and, in fact, reduces thermal rebalance torque.
The Forced Lateral Oscillations of Trailers
Authors: Slibar A. , Paslay P. R. 
Published: June 2021

Abstract
This paper gives the mechanical response of a simplified model of a trailer when its tow point moves along a certain prescribed path. The type of path considered here is described by a constant forward velocity on which is superimposed a low-velocity-amplitude, sidewise, periodic motion. In this investigation analytical expressions proposed by Huber (3) were used for the forces and moments on the tires. The equations of motion are studied for small slip angles. The analysis leads to a prediction of the natural frequency of the trailer and shows that the damping of the system due to slip of the tires is inversely proportional to the forward velocity of the trailer.
Stress Concentrations in a Strip Under Tension and Containing Two Pairs of Semicircular Notches Placed on the Edges Symmetrically
Authors: Atsumi A. 
Published: June 2021

Abstract
Distributions of stresses in an infinite strip of finite breadth under tension and containing two pairs of equal semicircular notches placed symmetrically on the edges are studied theoretically. The state of decreasing of stress concentration is studied and compared with those corrected by M. Isida or newly determined by the author in their calculations as the reliable results of Ling’s problem of an infinite strip of finite breadth under tension and containing two semicircular notches placed symmetrically on the edges.
Blood Biomarker Landscape in Patients with High-risk Nonmetastatic Castration-Resistant Prostate Cancer Treated with Apalutamide and Androgen-Deprivation Therapy as They Progress to Metastatic Disease
Authors: Smith Matthew R. , Thomas Shibu , Gormley Michael , Chowdhury Simon , Olmos David , Oudard Stéphane , Feng Felix Y. , Rajpurohit Yashoda , Urtishak Karen , Ricci Deborah S. , Rooney Brendan , Lopez-Gitlitz Angela , Yu Margaret , Wyatt Alexander W. , Li Mark , Attard Gerhardt , Small Eric J. 
Published: June 2021

Abstract

Purpose:
In the placebo-controlled SPARTAN study, apalutamide added to androgen-deprivation therapy (ADT) improved metastasis-free survival, second progression-free survival (PFS2), and overall survival (OS) in patients with nonmetastatic castration-resistant prostate cancer (nmCRPC). Mechanisms of resistance to apalutamide in nmCRPC require evaluation.

Patients and Methods:
In a subset of patients from SPARTAN, aberrations were assessed at baseline and end of study treatment (EOST) using targeted next-generation sequencing or qRT-PCR. Circulating-tumor DNA (ctDNA) levels were assessed qualitatively. Select aberrations in androgen receptor (AR) and other common PC-driving genes were detected and summarized by the treatment group; genomic aberrations were summarized in ctDNA-positive samples. Association between detection of aberrations in all patients and outcomes was assessed using Cox proportional-hazards models and multivariate analysis.

Results:
In 247 patients, the overall prevalence of ctDNA, AR aberrations, and TP53 inactivation increased from baseline (40.6%, 13.6%, and 22.2%) to EOST (57.1%, 25.4%, and 35.0%) and was comparable between treatment groups at EOST. In patients who received subsequent androgen signaling inhibition after study treatment, detectable biomarkers at EOST were significantly associated with poor outcomes: ctDNA with PFS2 or OS (HR, 2.01 or 2.17, respectively; P &lt; 0.0001 for both), any AR aberration with PFS2 (1.74; P = 0.024), and TP53 or BRCA2 inactivation with OS (2.06; P = 0.003; or 3.1; P &lt; 0.0001).

Conclusions:
Apalutamide plus ADT did not increase detectable AR/non-AR aberrations over ADT alone. Detectable ctDNA, AR aberrations, and TP53/BRCA2 inactivation at EOST were associated with poor outcomes in patients treated with first subsequent androgen signaling inhibitor.
Abstract A02: Probing amino acids residues chemical reactivity of KRAS 4b using N-hydroxysuccinimide esters
Authors: Chertov Oleg , Ye Xiaoying , Waybright Timothy , Stephen Andrew G. 
Published: June 2021

Abstract
RAS oncoproteins are frequently mutated in pancreatic, colon and lung cancers and play a causal role in human carcinogenesis. Although it is a potentially good target for anticancer drugs development, it has been challenging to specifically target different forms of RAS using small molecules because of absence of evident target binding sites. Chemical reactivity of protein functional groups depends on the environment of a particular residue and reagent accessibility due to protein structure. We wanted to explore chemical reactivity of KRAS 4b functional groups using chemical reagents to identify novel sites for covalent and noncovalent drug development. NHS esters have been used for years for chemical modification of proteins. They are believed to selectively react with primary amino groups. However, there are reports in the literature that other nucleophilic groups such as sulfhydryl group of Cys can react with N-hydroxysuccinimide esters. It is possible that other functional groups may also react. Sulfo-NHS-acetate, sulfo-NHS-biotin and NHS-biotin were used for modification of K, HRAS proteins in GDP and GppNHp-loaded forms. To follow the extent of protein modification, MALDI-TOF MS was used. Generally, the reaction was performed until almost no unmodified protein was left. After modification the protein was digested by Glu-C and peptides were analyzed by MALDI-TOF MS and ES-MS/MS. A “modification index” (ratio of intensities of modified and unmodified peptide forms in MALDI-TOF MS spectra) was calculated to enable relative quantitation for all modified peptides. The comparison of the modification indexes for peptides derived from NHS-biotin modified KRAS and HRAS in GDP or GppNHp form suggested that GppNHp-loaded protein in general allows higher degree of modification. This suggests that there are inducible and expandable binding sites for small organic molecules that could be exploited for design of covalent and noncovalent drug leads. Acknowledgments: Supported by NCI contract HHSN261200800001E.
Citation Format: Oleg Chertov, Xiaoying Ye, Timothy Waybright, Andrew G. Stephen. Probing amino acids residues chemical reactivity of KRAS 4b using N-hydroxysuccinimide esters [abstract]. In: Proceedings of the AACR Special Conference on Targeting RAS-Driven Cancers; 2018 Dec 9-12; San Diego, CA. Philadelphia (PA): AACR; Mol Cancer Res 2020;18(5_Suppl):Abstract nr A02.
Abstract A04: Biophysical and biochemical characterization of Src-phosphorylated KRas
Authors: Gebregiworgis Teklab , Marshall Christopher B. , Kano Yoshihito , Ohh Michael , Ikura Mitsuhiko 
Published: June 2021

Abstract
Tyrosine phosphorylation of several small GTPase proteins including Ras has been reported; however, investigations to understand the biologic role of tyrosine phosphorylated small GTPases have been limited. We will present the detailed characterization of the impact of tyrosyl phosphorylation of KRas on each stage of the GTPase cycle, and on the binding to the RBD of BRaf. Using NMR and MS analysis we demonstrate that a catalytic amount of Src (1 mole of Src into 250 moles of KRas) specifically phosphorylates KRas at two of the eight tyrosine residues (Y32 and Y64) in vitro. In HEK293 cells, ectopic expression of Src with KRas results in tyrosyl phosphorylation of the same sites in KRas. Tyrosyl phosphorylation of KRas perturbs the chemical shifts of residues in the two switch regions. Using our real-time NMR-based small GTPase assay, we illustrate that tyrosyl phosphorylation alters regulation of the KRas GTPase cycle by guanine exchange factor (SOScat) and GTPase activating protein (p120GAP), rendering KRas resistant to both activities. Furthermore, using an Octet BLI binding assay, we demonstrated that tyrosyl phosphorylation of KRas strongly impairs BRaf-RBD binding. In vitro, Src-phosphorylated KRas can be completely dephosphorylated by the phosphatase SHP2. In cells, we were able to detect endogenous tyrosyl phosphorylated Ras upon SHP2 CRISPR knockout. Together, our findings demonstrate that the GTPase cycle and effector binding affinity of KRas can be regulated by the balance of Src and SHP2 activities.
Citation Format: Teklab Gebregiworgis, Christopher B. Marshall, Yoshihito Kano, Michael Ohh, Mitsuhiko Ikura. Biophysical and biochemical characterization of Src-phosphorylated KRas [abstract]. In: Proceedings of the AACR Special Conference on Targeting RAS-Driven Cancers; 2018 Dec 9-12; San Diego, CA. Philadelphia (PA): AACR; Mol Cancer Res 2020;18(5_Suppl):Abstract nr A04.
Abstract A09: Cooperative membrane interaction between G-domain and HVR defines unique diffusion behavior of KRAS4b
Authors: Goswami Debanjan , Chen De , Columbus John , Turbyville Thomas 
Published: June 2021

Abstract
Rat sarcoma (RAS) family of proteins function as GTP/GDP-dependent control switch to regulate Raf-MAPK effector pathway for cell proliferation and are frequently mutated in human cancer. RAS is anchored to the inner leaflet of the plasma membrane (PM) via C-terminal lipid-tether(s) and hypothesized to concentrate in distinct locations in membrane nano-domains to control the activation step. However, very little is known about the molecular dynamics of RAS on PM and the precise mechanism of activation. Here we characterize the molecular mobility of RAS variants by single-molecule tracking (SMT) method and estimate underlying mobility states. KRAS4b exhibit confined mobility with three diffusive states, a unique characteristic compared to all the other RAS isoforms (KRAS4a, NRAS, and HRAS). Although the major difference across RAS isoforms lies within the C-terminus HVR (hypervariable region) and its post-translational lipid modifications, the additional confinement for KRAS4b is contributed by the G-domain (globular domain) of the protein. Simulation of KRAS4b on membrane revealed a detailed atomistic mechanism that corroborates with the experimental results. Importantly, the oncogenic mutant of KRAS4b shows an altered mode of diffusion, implicating a plausible attribution to/from enhanced effector interaction. This study uncovers a novel underlying principle of KRAS4b functionality on living cell membrane with a potential for innovation in therapeutic strategies against its oncogenic variant.
Citation Format: Debanjan Goswami, De Chen, John Columbus, Thomas Turbyville. Cooperative membrane interaction between G-domain and HVR defines unique diffusion behavior of KRAS4b [abstract]. In: Proceedings of the AACR Special Conference on Targeting RAS-Driven Cancers; 2018 Dec 9-12; San Diego, CA. Philadelphia (PA): AACR; Mol Cancer Res 2020;18(5_Suppl):Abstract nr A09.