bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ice wedge polygon stability on steep slopes in West Greenland related to temperature and moisture dynamics of the active layer
Authors: Schwarzkopf Katharina , Seitz Steffen , Fritz Michael , Scholten Thomas , Kühn Peter 
Published: March 2023

AbstractIce wedge polygons on steep slopes have generally been described as being covered by periglacial sediments and, typically, the active layer on slopes becomes mobile during thaw periods, which can lead to solifluction. In West Greenland close to the ice margin, however, the active layer and ice wedge polygons are stable despite their occurrence on steep slopes with inclinations of ≥30°. We conducted a soil survey (including sampling for soil analyses and radiocarbon dating) in the Umimmalissuaq valley and installed a field station ~4 km east of the current ice margin to monitor soil temperature and water tension at depths of 10, 20 and 35 cm of the active layer on a steep, north‐facing slope in the middle of an ice wedge polygon from 2009 to 2015. Thawing and freezing periods lasted between 2 and 3 months and the active layer was usually completely frozen from November to April. We observed simultaneous and complete water saturation at all three depths of the active layer in one summer for 1 day. The amount of water in the active layer apparently was not enough to trigger solifluction during the summer thaw, even at slope inclinations above 30°. In addition, the dense shrub tundra absorbs most of the water during periods between thawing and freezing, which further stabilizes the slope. This process, together with the dry and continental climate caused by katabatic winds combined with no or limited frost heave, plays a crucial role in determining the stability of these slopes and can explain the presence of large‐scale stable ice wedge polygon networks in organic matter‐rich permafrost, which is about 5,000 years old. This study underlines the importance of soil hydrodynamics and local climate regime for landscape stability and differing intensities of solifluction processes in areas with strong geomorphological gradients and rising air temperatures.
Rational design of mini protein mimicking uricase: Encapsulation in ZIF‐8 for uric acid detection
Authors: Abdul Aziz Siti Fatimah Nur , Rahim Arilla Sri Masayu Abd , Normi Yahaya M. , Alang Ahmad Shahrul Ainliah , Salleh Abu Bakar 
Published: March 2023

AbstractFive mini proteins mimicking uricase comprising 20, 40, 60, 80, and 100 amino acids were designed based on the conserved active site residues within the same dimer, using the crystal structure of tetrameric uricase from Arthrobacter globiformis (PDB ID: 2yzb) as a template. Based on molecular docking analysis, the smallest mini protein, mp20, shared similar residues to that of native uricase that formed hydrogen bonds with uric acid and was chosen for further studies. Although purified recombinant mp20 did not exhibit uricase activity, it showed specific binding towards uric acid and evinced excellent thermotolerance and structural stability at temperatures ranging from 10°C to 100°C, emulating its natural origin. To explore the potential of mp20 as a bioreceptor in uric acid sensing, mp20 was encapsulated within zeolitic imidazolate framework‐8 (mp20@ZIF‐8) followed by the modification on rGO‐screen printed electrode (rGO/SPCE) to maintain the structural stability. An irreversible anodic peak and increased semicircular arcs of the Nyquist plot with an increase of the analyte concentrations were observed by utilizing cyclic voltammetry and electrochemical impedance spectroscopy (EIS), suggesting the detection of uric acid occurred, which is based on substrate–mp20 interaction.
Domain shuffling of a highly mutable ligand‐binding fold drives adhesin generation across the bacterial kingdom
Authors: Barringer Rob , Parnell Alice E. , Lafita Aleix , Monzon Vivian , Back Catherine R. , Madej Mariusz , Potempa Jan , Nobbs Angela H. , Burston Steven G. , Bateman Alex , Race Paul R. 
Published: March 2023

AbstractBacterial fibrillar adhesins are specialized extracellular polypeptides that promote the attachment of bacteria to the surfaces of other cells or materials. Adhesin‐mediated interactions are critical for the establishment and persistence of stable bacterial populations within diverse environmental niches and are important determinants of virulence. The fibronectin (Fn)‐binding fibrillar adhesin CshA, and its paralogue CshB, play important roles in host colonization by the oral commensal and opportunistic pathogen Streptococcus gordonii. As paralogues are often catalysts for functional diversification, we have probed the early stages of structural and functional divergence in Csh proteins by determining the X‐ray crystal structure of the CshB adhesive domain NR2 and characterizing its Fn‐binding properties in vitro. Despite sharing a common fold, CshB_NR2 displays an ~1.7‐fold reduction in Fn‐binding affinity relative to CshA_NR2. This correlates with reduced electrostatic charge in the Fn‐binding cleft. Complementary bioinformatic studies reveal that homologues of CshA/B_NR2 domains are widely distributed in both Gram‐positive and Gram‐negative bacteria, where they are found housed within functionally cryptic multi‐domain polypeptides. Our findings are consistent with the classification of Csh adhesins and their relatives as members of the recently defined polymer adhesin domain (PAD) family of bacterial proteins.
Automated solid‐phase synthesis of metabolically stabilized triazolo‐peptidomimetics
Authors: Guarrochena Xabier , Kaudela Barbara , Mindt Thomas L. 
Published: March 2023

The use of 1,4‐disubstituted 1,2,3‐triazoles as trans‐amide bond surrogates has become an important tool for the synthesis of metabolically stabilized peptidomimetics. These heterocyclic bioisosters are generally incorporated into the peptide backbone by applying a diazo‐transfer reaction followed by CuAAC (click chemistry) with an α‐amino alkyne. Even though the manual synthesis of backbone‐modified triazolo‐peptidomimetics has been reported by us and others, no procedure has yet been described for an automated synthesis using peptide synthesizers. In order to efficiently adapt these reactions to an automated setup, different conditions were explored, putting special emphasis on the required long‐term stability of both the diazo‐transfer reagent and the Cu(I) catalyst in solution. ISA·HCl is the reagent of choice to accomplish the diazo‐transfer reaction; however, it was found instable in DMF, the most commonly used solvent for SPPS. Thus, an aqueous solution of ISA·HCl was used to prevent its degradation over time, and the composition in the final diazo‐transfer reaction was adjusted to preserve suitable swelling conditions of the resins applied. The CuAAC reaction was performed without difficulties using [Cu (CH3CN)4]PF6 as a catalyst and TBTA as a stabilizer to prevent oxidation to Cu(II). The optimized automated two‐step procedure was applied to the synthesis of structurally diverse triazolo‐peptidomimetics to demonstrate the versatility of the developed methodology. Under the optimized conditions, five triazolo‐peptidomimetics (8–5 amino acid residues) were synthesized efficiently using two different resins. Analysis of the crude products by HPLC‐MS revealed moderate to good purities of the desired triazolo‐peptidomimetics (70–85%). The synthesis time ranged between 9 and 12.5 h.
Pulmonary hypertension in patients with multiple myeloma: A comprehensive review
Authors: Maddipati Veeranna , Sankhyan Pratyaksha , Goswami Durga P. , Mahajan Akhilesh 
Published: March 2023

AbstractMultiple myeloma (MM) is a common hematological malignancy resulting from clonal proliferation of plasma cells and is defined by criteria set forth by the international myeloma working group. Pulmonary hypertension (PH) is defined by an elevated mean pulmonary artery pressure >20 mmHg measured during right heart catheterization. Echocardiography‐diagnosed PH is relatively common in patients with MM and has been associated with increased mortality, morbidity, and poor stem cell transplant outcomes. PH in patients with MM (PH‐MM) is usually multifactorial in origin. MM disease‐specific factors, host comorbidities, and treatment‐related adverse effects are the key factors for the development of PH‐MM. Pragmatically, patients with PH‐MM can be grouped into either (i) PH in patients with a new diagnosis of MM or (ii) PH that develops or worsens along the way of MM treatment. In the latter group, drug‐induced PH, venous thromboembolism, pulmonary veno occlusive disease, and cardiotoxicity should be considered as possible causes. PH‐MM should be evaluated and managed in a multidisciplinary setting. Select individuals with PH‐MM could be considered for pulmonary vasodilators at PH‐specialized centers.
Why does the upward surface turbulent heat flux resulting from sea ice loss over the Barents and Kara Seas last only for a few days?
Authors: Jiang Zhina , Feldstein Steven B. , Lee Sukyoung 
Published: March 2023

AbstractThis study explores the reason why strong upward anomalous surface turbulent heat fluxes (STHFs) over the Barents and Kara Seas (BKS) occur for a period of only a few days after wind‐driven sea ice loss, even though anomalously low sea ice persists for more than one month. Composite analysis with ERA5 reanalysis data reveals that the sea ice decline coincides with the poleward advection of warm, moist air on the eastern flank of a synoptic‐scale surface low. This results in the anomalous surface air temperature (SAT) exceeding the anomalous skin temperature (SKT) and a downward anomalous STHF. As the surface low propagates eastward, the wind direction changes, resulting in the advection of cold, dry air, the anomalous SKT exceeding the anomalous SAT and a brief period with a strong upward anomalous STHF. This period of strong upward anomalous STHF is cut short, as the surface low propagates southeastward out of the BKS. The eastward propagation of the surface low is crucial, as it allows for northward driving of sea ice to be followed by cold advection and a strong upward anomalous STHF. These results indicate that when wind‐driven sea ice motion exposes the ocean to the atmosphere, except for a brief episode, the reduction of sea ice does not coincide with an increase in a strong upward anomalous STHF.
Predictability of passive scalar dispersion in atmospheric surface layers with urban‐like roughness: A large‐eddy simulations study
Authors: Lu Yanle , Monache Luca Delle , Weil Jeffrey , Ngan Keith , Li Qi 
Published: March 2023

AbstractThe predictability of passive scalar dispersion is of both theoretical interest and practical importance, for example for high‐resolution numerical weather prediction and air quality modeling. However, the implications for the numerical modeling of urban areas remain relatively unexplored. Using obstacle‐resolving large‐eddy simulations (LES), we conducted twin experiments, with and without a velocity perturbation, to investigate how the presence of urban roughness affects error growth in streamwise velocity (u) and passive scalar (θ) fields, as well as the differences between error evolutions in u and θ fields. The predictability limit is characterized using the signal‐to‐noise ratio (SNR) as a continuous metric to indicate when error reaches saturation. The presence of urban roughness decreases of the passive scalar by around 20% compared to cases without them. The error statistics of θ indicate that urban roughness‐induced flow structures and different scalar source locations affect the scalar dispersion and relative fluctuations, which subsequently dictate the evolution of the SNR. Analysis of the passive scalar error energy (ϵθ2) budget indicates that the contributions from advective transport by the velocity and velocity error dominate. The error energy spectra of both u and θ exhibit a −5/3 slope in flat‐wall cases, but not in the presence of urban roughness, thereby highlighting the deviation from the assumption of locally isotropic turbulence. This study reveals that urban roughness can decrease the predictability of the passive scalar and destroy the similarity between the error statistics of the velocity and the passive scalar.
FMECA of CNC machine tool design stage based on CBWM and DEA
Authors: Yu Lijuan , Zhang Tianyu , Tian Hailong , Yang Zhaojun , Liu Ang , Zhang Fuyao 
Published: March 2023

AbstractIn view of the problems that FMECA in the design stage of CNC machine tools does not take into account the complexity of the designed functional structure, does not compare the weight of risk factors, and is not easy to distinguish the harm degree of failure mode, CBWM, and DEA are applied to the study of FMECA in the design stage of CNC machine tools. Based on the complexity of functional structure in machine tool design, score the factors of each potential failure mode, form a decision unit, re‐formulate the scoring table, and subdivide the severity into machine tool hazard (M), personal hazard (P), environmental hazard (E), and buyer satisfaction (B). The factors influencing risk factors were defined as the probability of failure mode (O), machine tool hazard (M), personal hazard (P), environmental hazard (E), and buyer satisfaction (B). On the basis of the scoring of each factor, the functional structure complexity (C) is taken as the input index, and the risk factor is taken as the output index. The CBWM method is applied to determine the weight of each risk factor, and DEA method is used to calculate the efficiency of each decision making unit. Finally, a new method for calculating risk priority number RPN is proposed by integrating the score value of factors, weight value of factors, and efficiency value of fault mode, and the hazard degree of fault mode is ranked according to the risk priority coefficient. Taking a machining center spindle system as an example, the proposed method is applied to analyze the fault mode and its influence, and the effectiveness of the proposed method is verified.
CRISPR/Cas9 Screen in Gastric Cancer Patient‐Derived Organoids Reveals KDM1A‐NDRG1 Axis as a Targetable Vulnerability
Authors: Mircetic Jovan , Camgöz Aylin , Abohawya Moustafa , Ding Li , Dietzel Julia , Tobar Sebastián García , Paszkowski‐Rogacz Maciej , Seidlitz Therese , Schmäche Tim , Mehnert Marie‐Christin , Sidorova Olga , Weitz Jürgen , Buchholz Frank , Stange Daniel E. 
Published: March 2023

AbstractViability CRISPR screens have proven indispensable in parsing genome function. However, their application in new, more physiologically relevant culturing systems like patient‐derived organoids (PDOs) has been much slower. To probe epigenetic contribution to gastric cancer (GC), the third leading cause of cancer‐related deaths worldwide, the first negative selection CRISPR screen in GC PDOs that faithfully preserve primary tumor characteristics is performed. Extensive quality control measurements showing feasibility of CRISPR screens in primary organoid culture are provided. The screen reveals the histone lysine demethylase‐1A (KDM1A) to constitute a GC vulnerability. Both genetic and pharmacological inhibition of KDM1A cause organoid growth retardation. Further, it is shown that most of KDM1A cancer‐supporting functions center on repression of N‐myc downstream regulates gene‐1 (NDRG1). De‐repression of NDRG1 by KDM1A inhibitors (KDM1Ai) causes inhibition of Wnt signaling and a strong G1 cell cycle arrest. Finally, by profiling 20 GC PDOs, it is shown that NDRG1 upregulation predicts KDM1Ai response with 100% sensitivity and 82% specificity in the tested cohort. Thus, this work pioneers the use of negative selection CRISPR screens in patient‐derived organoids, identifies a marker of KDM1Ai response, and accordingly a cohort of patients who may benefit from such therapy.
Long‐term treatment outcomes and risk factors for recurrence in feline corneal sequestrum: 72 cases (2009–2017)
Authors: Gómez Alberto Palella , Mazzucchelli Samuela , Smith Kinley , de Lacerda Rodrigo Pinheiro 
Published: March 2023

AbstractBackgroundThis study aimed to evaluate long‐term treatment outcomes in feline corneal sequestrum (FCS), compare the recurrence rates between different surgical techniques, identify possible recurrence risk factors and monitor the development of FCS in the contralateral eye.MethodsThe medical records of 72 cats (79 eyes) with FCS treated between 2009 and 2017 were retrospectively analysed.ResultsThe most commonly affected breeds were Persian, domestic shorthaired and Burmesecats. The mean age was 6.9 years. Sixty‐five cats (90%) were affected unilaterally. Sixty‐six eyes (83%) underwent surgery: keratectomy in 34 eyes (52%) and keratectomy followed by a graft procedure in 32 eyes (48%). Recurrence occurred in 13 out of 66 eyes (19%) at a median of 245 days after surgery. Skull conformation, location of the FCS, type of surgical procedure and concurrent ocular surgery did not significantly affect the recurrence rate. Eighteen cats (27%) developed FCS in the contralateral eye at a median of 635 days after surgery.LimitationsLimitations are related to the retrospective nature of the study, the use of telephone follow‐up for assessment of recurrence in some cats and the small number of cases.ConclusionsSurgical excision had a successful outcome in most cases. The type of surgical procedure and skull conformation did not affect the recurrence rate. One‐quarter of the cats developed FCS in the contralateral eye.
OLFML3, as a potential predictor of prognosis and therapeutic target for glioma, is closely related to immune cell infiltration
Authors: Qu Shanqiang , Huang Chengying , Zhu Taichen , Wang Kaicheng , Zhang Huayang , Wang Luyao , Xu Rongyang , Zheng Haojie , Yuan Xi , Liu Guangjie , Zhu Rongzhang , Qu Jiayi , Yi Guozhong , Qi Songtao 
Published: March 2023

AbstractThe low response rate to immunosuppressant is mainly due to the lack of adequate knowledge about the tumor microenvironment (TME) and screening biomarkers for gliomas. We aimed to identify the promising immune biomarkers and new immune classification of glioma. In this study, multiple‐immune algorithms were used to calculate immune‐infiltration scores. Unsupervised and supervised machine learning methods were used to perform the classification. We observed that OLFML3 overexpression was indicated in gliomas and linked to poor prognosis. OLFML3 knockdown inhibited proliferation, invasion and increased the sensitivity of glioma cells to temozolomide. OLFML3 expression could also reflect the aberrant immune status. Based on the immune‐related signature, patients were divided into three immune subtypes via consensus clustering. Patients with C2 subtype presented poorer prognosis and shorter progression free survival than patients with other two subtypes. The TME patterns among subtypes were different. C2 and C3 subtypes are the immune‐inflamed and immune‐desert tumors, respectively. Additionally, compared with C3 subtype, patients with C1/C2 subtypes were more likely to respond to immunotherapy. The pRRophetic algorithm indicated patients with C1/C2 subtypes were more resistant to temozolomide, but sensitive to paclitaxel and cisplatin. To conclude, OLFML3 overexpression affects glioma cell proliferation, invasion, and TMZ sensitivity and has been proved to be an independent prognostic‐ and immune‐related biomarker. Additionally, the novel immune subtype's classification could provide the prognostic and predictive predictors for glioma patients and may guide physicians in selecting potential responders.
Influence of trans‐ferulic acid on the quality of ram semen upon cold preservation
Authors: Salimi Ali , Eslami Mohsen , Farrokhi‐Ardabili Farhad 
Published: March 2023

AbstractBackgroundDue to lower antioxidant capacity and higher amounts of polyunsaturated fatty acids, ram spermatozoa are very susceptible during cooling process.ObjectivesThe objective was to examine the effect of the trans‐ferulic acid (t‐FA) on the ram semen during liquid preservation.MethodsSemen samples were collected from the Qezel rams, pooled, and extended with the Tris‐based diluent. Pooled samples enriched with different amounts of the t‐FA (0, 2.5, 5, 10, and 25 mM) and preserved at 4°C for 72 h. Spermatozoa's kinematics, membrane functionality, and viability were assessed by CASA system, hypoosmotic swelling test, and eosin‐nigrosin staining, respectively. Moreover, biochemical parameters were measured at 0, 24, 48, and 72 h.ResultsResults showed that 5 and 10 mM t‐FA improved forward progressive motility (FPM) and curvilinear velocity compared to the other groups at 72 h (p < 0.05). Samples treated with 25 mM t‐FA showed the lowest total motility, FPM, and viability at 24, 48, and 72 h of storage (p < 0.05). Higher total antioxidant activity levels were observed in the 10 mM t‐FA‐treated group compared to the negative control at 72 h (p < 0.05). Treatment with 25 mM t‐FA increased malondialdehyde amounts and decreased superoxide dismutase activity compared to other groups at the final time assessment (p < 0.05). Nitrate‐nitrite and lipid hydroperoxides values were not affected by treatment.ConclusionsThe current study indicates the positive and negative influences of different concentrations of t‐FA on the ram semen upon cold storage.
Molecular study of feline dermatophytosis and Toll‐like receptor 2 and 4 gene expression in their lesions
Authors: Kasmaei Anahita , Salimi Alireza , Helan Javad Ashrafi , Asl Seyed Ali Shabestari , Katiraee Farzad 
Published: March 2023

AbstractBackgroundPattern recognition receptors (PRRs) as the recognition of pathogenic fungal structures induce the secretion of cytokines by immune systems. Toll‐like receptors (TLRs) 2 and 4 are the main PRRs that recognize fungal components.AimThe present study aimed to assess the presence of dermatophyte species in symptomatic cats in a region of Iran and to investigate the expression of TLR‐2 and 4 in cat lesions with dermatophytosis.MethodsA total of 105 cats suspected of dermatophytosis with skin lesions were examined. Samples were analysed by direct microscopy using potassium hydroxide (20%) and culture on Mycobiotic agar. Dermatophytes strains were confirmed by the polymerase chain reaction (PCR) amplification and then sequencing of the Internal Transcribed Spacer rDNA region. Also, for pathology and real‐time PCR studies, skin biopsies were taken by sterile single‐use biopsy punch from active ringworm lesions.ResultsDermatophytes were found in 41 felines. Based on the sequencing of all strains, Microsporum canis (80.48%, p < 0.05), Microsporum gypseum (17.07%) and Trichophyton mentagrophytes (2.43%) were the dermatophytes isolated from cultures. Cats under 1 year (78.04%) revealed a statistically significantly higher prevalence of infection (p < 0.05). Gene expression by real‐time PCR revealed the increased TLR‐2 and 4 mRNA levels in skin biopsies of cats with dermatophytosis.ConclusionsM. canis is the most prevalent dermatophyte species isolated from feline dermatophytosis lesions. Increased expression of TLR‐2 and TLR‐4 mRNAs in cat skin biopsies suggests that these receptors are involved in the immune response by recognizing dermatophytosis.