Miracle-dz/UniFAR-FTUs huggingface dataset:
Flow Separation in Rectangular Over-expanded Supersonic Nozzles

*This paper presents experimental results on shock structure, flow separation, and mixing enhancement of ambient dry air in rectangular over-expanded supersonic nozzles. A total of 44 symmetrical or asymmetrical nozzles with three different aspect ratios, namely 2.78, 3.57, and 5.00 varying in expansion ratio between 1.00 and 2.10 and varying in nozzle exit angles between 0 and 4.8 degrees, were investigated. Most results presented in this study pertain to nozzles with an aspect ratio of 5.00. Diagnostic tools utilized in this research included primarily Schlieren photography to capture the instantaneous flow structure in the nozzle and the jet plume as well as nozzle reservoir pressure measurements. The study indicates that mixing enhancement in the plume of a jet can be correlated to the shock structure in the nozzle. The shock structure is determined by the nozzle geometry and flow conditions. Nozzles with the most promising mixing enhancement characteristics were symmetrical and had half-nozzle exit angles of at least 2.6 degrees while operated at nozzle pressure ratios between 1.4 and 2.5, depending on the aspect ratio. In all cases with severe plume instability, the Mach stem with asymmetric incident and reflective shocks, needed to be placed at an area greater or equal to 1.2 times the sonic area.
Stability of Verapamil Hydrochloride in SyrSpend SF Compared to Sorbitol Containing Syrup and Suspending Vehicles

Verapamil hydrochloride is widely prescribed to treat multiple cardiovascular diseases. There are a number of generic manufacturers of verapamil tablets and injectables. The need for other administration options for patients who cannot take tablets has led compounding pharmacies to seek other alternatives, namely, oral solutions and suspensions. The stability of these compounded verapamil oral liquid preparations is a concern to anyone making them. The objective of this study was to determine the stability of verapamil hydrochloride in SyrSpend SF in comparison to stability of verapamil hydrochloride in ora-Sweet SF:ora-Plus (1:1). The two samples were compounded in 50-ml batches and stored in amber 60-ml plastic prescription bottles at united States Pharmacopeia refrigerated conditions. Five replicates at each pre-defined time point were assayed by a stability-indicating high performance liquid chromatographic method with an end date of 60 days. No degradation peaks were seen in the chromatograms for either preparation at any time point and the recovery of verapamil hydrochloride was within 90% to 110% of the initial concentration for all replicates. Verapamil hydrochloride is stable in amber plastic prescription bottles for 60 days when refrigerated for both SyrSpend SF
One-Dimensional Nanocomposites Based on Polypyrrole-Carbon Nanotubes and Their Thermoelectric Performance

Conducting polymers have attracted significant attention due to their easy fabrication, morphology modification, and their electrical properties. Amongst them, polypyrrole (PPy) has attractive thermoelectric (TE) properties. Engineering of this polymer in one-dimensional (1D) nanostructured form is found to enhance its TE performance. This was achieved in the present work by using multi-walled carbon nanotubes (MWCNTs) as a core template to direct the self-assembly of PPy and also to further enhance its TE performance. The growth of PPy on the sidewalls of MWCNTs was performed in an acidic medium based oxidative in situ polymerization. Various concentrations of MWCNTs within the range 1.1–14.6 wt. % were used to form the MWCNTs/PPy nanocomposites in 1D core-shell structures. The morphology and microstructure results of the produced nanocomposite samples showed that this MWCNTs were successfully coated by thick and thin layers of PPy. At low concentrations of MWCNTs, thick layers of PPy are formed. While at high concentrations thin layers are coated. The formed 1D nanocomposites have enhanced TE performance, particularly those containing higher contents of MWCNTs. The power factor and figure of merit values for the formed 1D nanocomposites recorded around 0.77 µV/mK2 and 1 × 10−3 at room temperature (RT), respectively. This enhancement was attributed to the perfect coating and good interaction between PPy and MWCNT through π–π stacking between the polymer chains and these nanotubes. These results might be useful for developing future TE materials and devices.
Novel Biopolymer Structures Synthesized by Dendronization of 6‐Deoxy‐6‐aminopropargyl cellulose

Propargyl cellulose with regioselective functionalization pattern was synthesized by nucleophilic displacement reaction of 6-O-toluenesulfonyl ester of cellulose (degree of substitution, DS 0.58) with propargyl amine. The novel 6-deoxy-6-aminopropargyl cellulose provides an excellent starting material for the selective dendronization of cellulose at position 6 via the copper-catalyzed Huisgen reaction yielding 6-deoxy-6-amino-(4-methyl-[1,2,3-triazolo]-1-propyl-polyamido amine) cellulose derivatives of first- (DS 0.33) and second (DS 0.25) generation, which are soluble in polar aprotic solvents. The novel biopolymer derivatives were characterized by elemental analysis, FT-IR spectroscopy, and one- and two dimensional NMR spectroscopy, showing no side reactions (cross-linking) or impurities and no conversion at the secondary positions.
S. mansoni SmKI-1 Kunitz-domain: Leucine point mutation at P1 site generates enhanced neutrophil elastase inhibitory activity

The Schistosoma mansoni SmKI-1 protein is composed of two domains: a Kunitz-type serine protease inhibitor motif (KD) and a C-terminus domain with no similarity outside the genera. Our previous work has demonstrated that KD plays an essential role in neutrophil elastase (NE) binding blockage, in neutrophil influx and as a potential anti-inflammatory molecule. In order to enhance NE blocking capacity, we analyzed the KD sequence from a structure-function point of view and designed specific point mutations in order to enhance NE affinity. We substituted the P1 site residue at the reactive site for a leucine (termed RL-KD), given its central role for KD’s inhibition to NE. We have also substituted a glutamic acid that strongly interacts with the P1 residue for an alanine, to help KD to be buried on NE S1 site (termed EA-KD). KD and the mutant proteins were evaluated in silico by molecular docking to human NE, expressed in Escherichia coli and tested towards its NE inhibitory activity. Both mutated proteins presented enhanced NE inhibitory activity in vitro and RL-KD presented the best performance. We further tested RL-KD in vivo in an experimental model of monosodium urate (MSU)-induced acute arthritis. RL-KD showed reduced numbers of total cells and neutrophils in the mouse knee cavity when compared to KD. Nevertheless, both RL-KD and KD reduced mice hypernociception in a similar fashion. In summary, our results demonstrated that both mutated proteins showed enhanced NE inhibitory activity in vitro. However, RL-KD had a prominent effect in diminishing inflammatory parameters in vivo.
Improved Bioavailability and High Photostability of Methotrexate by Spray-Dried Surface-Attached Solid Dispersion with an Aqueous Medium

Low aqueous solubility and poor bioavailability are major concerns in the development of oral solid-dosage drug forms. In this study, we fabricated surface-attached solid dispersion (SASD) to enhance the solubility, bioavailability, and photostability of methotrexate (MTX), a highly lipophilic and photo-unstable drug. Several MTX-loaded SASD formulations were developed for spray-drying using water as the solvent, and were investigated for their aqueous solubility and dissolution kinetics. An optimized ternary SASD formulation composed of MTX/ sodium carboxymethyl cellulose (Na-CMC)/sodium lauryl sulfate (SLS) at 3/0.5/0.5 (w/w) had 31.78-fold and 1.88-fold higher solubility and dissolution, respectively, than MTX powder. For SASD, the in vivo pharmacokinetic parameters AUC and Cmax were 2.90- and 3.41-fold higher, respectively, than for the MTX powder. Solid-state characterizations by differential scanning calorimetry and X-ray diffraction revealed that MTX exists in its crystalline state within the spray-dried SASD. The MTX-loaded SASD formulation showed few physical changes with photostability testing. Overall, the results indicate that the spray-dried MTX-loaded SASD formulation without organic solvents enhances the solubility and oral bioavailability of MTX without a significant deterioration of its photochemical stability.
Full-Spectrum Targeted Mutagenesis in Plant and Animal Cells

Directed evolution is a powerful approach for protein engineering and functional studies. However, directed evolution outputs from bacterial and yeast systems do not always translate to higher organisms. In situ directed evolution in plant and animal cells has previously been limited by an inability to introduce targeted DNA sequence diversity. New hypermutation tools have emerged that can generate targeted mutations in plant and animal cells, by recruiting mutagenic proteins to defined DNA loci. Progress in this field, such as the development of CRISPR-derived hypermutators, now allows for all DNA nucleotides within user-defined regions to be altered through the recruitment of error-prone DNA polymerases or highly active DNA deaminases. The further engineering of these mutagenesis systems will potentially allow for all transition and transversion substitutions to be generated within user-defined genomic windows. Such targeted full-spectrum mutagenesis tools would provide a powerful platform for evolving antibodies, enzymes, structural proteins and RNAs with specific desired properties in relevant cellular contexts. These tools are expected to benefit many aspects of biological research and, ultimately, clinical applications.
SoilFlex‐LLWR: linking a soil compaction model with the least limiting water range concept

Soil compaction impacts growing conditions for plants: it increases the mechanical resistance to root growth and modifies the soil pore system and consequently the supply of water and oxygen to the roots. The least limiting water range (LLWR) defines a range of soil water contents within which root growth is minimally limited with regard to water supply, aeration and penetration resistance. The LLWR is a function of soil bulk density (BD), and hence directly affected by soil compaction. In this paper, we present a new model, ‘SoilFlex‐LLWR’, which combines a soil compaction model with the LLWR concept. We simulated the changes in LLWR due to wheeling with a self‐propelled forage harvester on a Swiss clay loam soil (Gleyic Cambisol) using the new SoilFlex‐LLWR model, and compared measurements of the LLWR components as a function of BD with model estimations. SoilFlex‐LLWR allows for predictions of changes in LLWR due to compaction caused by agricultural field traffic and therefore provides a quantitative link between impact of soil loading and soil physical conditions for root growth.
Recurrence risk factors in stage IA grade 1 endometrial cancer

Objectives Patients with early-stage endometrial cancers (EC) with disease recurrences have worse survival outcomes. The purpose of this study was to identify clinical and pathologic factors that predict for all recurrences in stage IA grade 1 (IAG1) EC. Methods Records from patients diagnosed with EC were retrospectively reviewed. Baseline characteristics of 222 patients with IAG1 EC who underwent surgical resection were analyzed. Cox proportional hazard analysis was used to identify univariate and multivariate risk factors that predict for recurrence. Results Seventeen (7.65%) patients had recurrences. The 3-year cumulative incidence of recurrence were significantly higher for patients with time from biopsy to surgery ≥6 months (54% vs. 8%, p=0.003), simple hysterectomy with ovarian preservation vs. total hysterectomy and bilateral salpingo-oophorectomy (31% vs. 9%, p=0.032), any myometrial invasion vs. no invasion (18% vs. 2%, p=0.004), and tumor size ≥2 cm (15% vs. 2%, p=0.021). On, multivariate analysis, any myometrial invasion, increasing time from biopsy to surgery, and larger tumor size were independent predictors of any recurrence. Patients with recurrences had worse outcomes than those without (5-year overall survival [OS]=60%; 95% confidence interval [CI]=16%–86% vs. 5-year OS=95%; 95% CI=87%–99%, respectively, p=0.003). Conclusion Time from biopsy to surgery, larger tumors, and myometrial invasion are the most important predictors of recurrence. Though the recurrence rates are generally low in IAG1 EC, the survival rate for the patients with recurrences was worse than those without. Identification of additional recurrence risk factors can help select patients who may benefit from adjuvant treatment.
AQP1-Driven Migration Is Independent of Other Known Adverse Factors but Requires a Hypoxic Undifferentiated Cell Profile in Neuroblastoma

Neuroblastoma is a biologically very heterogeneous tumor with its clinical manifestation ranging from spontaneous regression to highly aggressive metastatic disease. Several adverse factors have been linked to oncogenesis, tumor progression and metastases of neuroblastoma including NMYC amplification, the neural adhesion molecule NCAM, as well as CXCR4 as a promoter of metastases. In this study, we investigate to what extent the expression of AQP1 in neuroblastoma correlates with changing cellular factors such as the hypoxic status, differentiation, expression of known adverse factors such as NMYC and NCAM, and CXCR4-related metastatic spread. Our results show that while AQP1 expression leads to an increased migratory behavior of neuroblastoma cells under hypoxic conditions, we find that hypoxia is associated with a reduction of NMYC in the same cells. A similar effect can be observed when using the tetracycline driven mechanism of SH-EP/Tet cells. When NMYC is not expressed, the expression of AQP1 is increased together with an increased expression of HIF-1α and HIF-2α. We furthermore show that when growing cells in different cell densities, they express AQP1, HIF-1α, HIF-2α, NMYC and NCAM to different degrees. AQP1 expression correlates with a hypoxic profile of these cells with increased HIF-1α and HIF-2α expression, as well as with NMYC and NCAM expression in two out of three neuroblastoma cell lines. When investigating cell properties of the cells that actually migrate, we find that the increased APQ1 expression in the migrated cells correlates with an increased NMYC and NCAM expression again in two out of three cell lines. Expression of the tumor cell homing marker CXCR4 varies between different tumor areas and between cell lines. While some migrated tumor cells highly express CXCR4, cells of other origin do not. In the initial phase of migration, we determined a dominant role of AQP1 expression of migrating cells in the scratch assay.
Void-free direct bonding of InP to Si: Advantages of low H-content and ozone activation

Oxide-mediated direct bonding of InP to silicon has been investigated using a variety of oxidation and oxide-activation techniques to achieve void-free bonding without resorting to complex outgassing schemes. Void formation is shown to be related to the H content of the SiO2 layer. Transmission Fourier transformed infrared spectroscopy measurements corroborate this hypothesis. Finally, the use of ozone instead of oxygen plasma activation is also revealed to be beneficial for void-free bonding.
Specific Dimensions of Depression Have Different Associations With Cognitive Decline in Older Adults With Type 2 Diabetes

OBJECTIVE Depression is highly frequent in older adults with type 2 diabetes and is associated with cognitive impairment, yet little is known about how various depression dimensions differentially affect cognition. We investigated longitudinal associations of specific depression dimensions with cognitive decline. RESEARCH DESIGN AND METHODS Participants (N = 1,002) were from the Israel Diabetes and Cognitive Decline study, were ≥65 years of age, had type 2 diabetes, and were not experiencing dementia at baseline. Participants underwent a comprehensive neuropsychological battery at baseline and every 18 months thereafter, including domains of episodic memory, attention/working memory, semantic categorization/language, and executive function, and Z-scores of each domain were averaged and further normalized to calculate global cognition. Depression items from the 15-item Geriatric Depression Scale were measured at each visit and subcategorized into five dimensions: dysphoric mood, withdrawal-apathy-vigor (entitled apathy), anxiety, hopelessness, and memory complaint. Random coefficients models examined the association of depression dimensions with baseline and longitudinal cognitive functioning, adjusting for sociodemographics and baseline characteristics, including cardiovascular risk factors, physical activity, and use of diabetes medications. RESULTS In the fully adjusted model at baseline, all dimensions of depression, except for anxiety, were associated with some aspect of cognition (P values from 0.01 to <0.001). Longitudinally, greater apathy scores were associated with faster decline in executive function (P = 0.004), a result that withstood adjustment for multiple comparisons. Associations of other depression dimensions with cognitive decline were not significant (P > 0.01). CONCLUSIONS Apathy was associated with a faster cognitive decline in executive function. These findings highlight the heterogeneity of depression as a clinical construct rather than as a single entity and point to apathy as a specific risk factor for cognitive decline among older adults with type 2 diabetes.
Protocol for the development of the Wales Multimorbidity e-Cohort (WMC): data sources and methods to construct a population-based research platform to investigate multimorbidity

Introduction Multimorbidity is widely recognised as the presence of two or more concurrent long-term conditions, yet remains a poorly understood global issue despite increasing in prevalence. We have created the Wales Multimorbidity e-Cohort (WMC) to provide an accessible research ready data asset to further the understanding of multimorbidity. Our objectives are to create a platform to support research which would help to understand prevalence, trajectories and determinants in multimorbidity, characterise clusters that lead to highest burden on individuals and healthcare services, and evaluate and provide new multimorbidity phenotypes and algorithms to the National Health Service and research communities to support prevention, healthcare planning and the management of individuals with multimorbidity. Methods and analysis The WMC has been created and derived from multisourced demographic, administrative and electronic health record data relating to the Welsh population in the Secure Anonymised Information Linkage (SAIL) Databank. The WMC consists of 2.9 million people alive and living in Wales on the 1 January 2000 with follow-up until 31 December 2019, Welsh residency break or death. Published comorbidity indices and phenotype code lists will be used to measure and conceptualise multimorbidity. Study outcomes will include: (1) a description of multimorbidity using published data phenotype algorithms/ontologies, (2) investigation of the associations between baseline demographic factors and multimorbidity, (3) identification of temporal trajectories of clusters of conditions and multimorbidity and (4) investigation of multimorbidity clusters with poor outcomes such as mortality and high healthcare service utilisation. Ethics and dissemination The SAIL Databank independent Information Governance Review Panel has approved this study (SAIL Project: 0911). Study findings will be presented to policy groups, public meetings, national and international conferences, and published in peer-reviewed journals.
Trimethylsilylcellulose/Polystyrene Blends as a Means To Construct Cellulose Domains on Cellulose

A method to prepare films of conspicuous domains of cellulose on a closed cellulose layer is introduced. These films can be used as model surfaces which are closer to the natural environment than most organic model surfaces that are usually coated directly on an inorganic substrate. The method is based on spin-coating a hydrophobic derivative of cellulose, trimethylsilylcellulose (TMSC), blended with polystyrene (PS) onto a silicon substrate. TMSC can be hydrolyzed to cellulose with acid hydrolysis, leaving domains of cellulose and PS embedded on a sublayer of cellulose. Selective dissolving of PS leaves a closed cellulose surface (sublayer) with eminent cellulose domains whose size depends on the original TMSC/PS ratio. The chemistry of the films was analyzed with X-ray photoelectron spectroscopy (XPS) and the morphology with atomic force microscopy (AFM). Scrutiny of the AFM data showed that the films are quantifiable and quantitatively reproducible.
Photodynamic Therapy for Benign Cutaneous Neurofibromas Using Aminolevulinic Acid Topical Application and 633 nm Red Light Illumination

Background: Neurofibromatosis type 1 (NF1) has no current effective treatments beyond surgery. Topical photodynamic therapy (PDT) has the potential to provide a less invasive treatment modality. Objective: Based on murine data, we hypothesized PDT could be used for the treatment of cutaneous neurofibromas (cNF). Methods and results: We conducted a phase I trial to examine absorption and conversion of topical aminolevulinic acid (ALA) in cNF and determine safety in a dose escalation study. ALA or control vehicle was applied to neurofibromas through microneedle-assisted delivery (n = 4) and excised specimens were examined 24 h later for protoporphyrin IX fluorescence. Fluorescence was detected in the tumors at 304 ± 94 U/μm2, while adjacent paralesional normal skin and vehicle-treated tumors showed no fluorescence (p < 0.0001). Subsequently, neurofibromas (n = 27) were treated with ALA and irradiated with 633 nm red light 18 h later, at escalating dosages of 50 and 100 mJ/cm2. Maximum tolerable dose was established at 100 mJ/cm2. Light microscopy study of tumors biopsied 48 h after PDT (ALA n = 14 and vehicle n = 4) showed mixed inflammatory infiltrate in the ALA, but not in the vehicle-treated tumors or perilesional normal skin. TUNEL evaluation showed 42.5 ± 19.9 apoptotic cells per visual field for ALA-treated and 1.1 ± 1.4 for vehicle-treated tumors (p = 0.002). Conclusions: In the first reported clinical trial of PDT for NF1, PDT targeted neurofibromas specifically, and may offer a normal tissue-sparing treatment modality in the future. This study is registered at Clintrials.gov (NCT01682811).