Miracle-dz/UniFAR-FTUs huggingface dataset:
Coating film thickness of pharmaceutical pellets measured by near infrared spectroscopy

Coated pellets typically used for filling pharmaceutical capsules and pressing tablets are increasingly replacing powder especially because of the better compression and flow characteristics and superior drug release rate management. However, the highly complex multivariable coating process needs to be well-controlled in order to ensure high product yield and prevent failures in the coating process resulting in discarded batches and potentially significant loss of revenue. This requires reliable in-process measurement of the coating film thickness. Near infrared (NIR) spectroscopy was found to be the most suitable tool for studying the properties of pellets. However, the existing methods are based on complex calibration requiring reference data on the coating film thickness of several production or even custom batches which are typically assessed by a microscope. Such approach is highly time consuming and impractical. Therefore, we propose an alternative method for analysis of NIR spectra, which produces useful results even without calibration. The proposed method also requires no prior knowledge on the coating process or previous batches of uncoated or coated pellets. The method was tested on samples taken from the coating process of two different batches of pharmaceutical pellets. The correlation coefficient between the average coating film thickness estimated from the NIR spectra and the average coating film thickness measured by the reference method was 0.99, which can be considered an excellent result. Therefore, the method was found feasible for laboratory or in-process approximation of the average coating film thickness of pharmaceutical pellets.
Use of hippocampal and amygdalar volumes on magnetic resonance imaging to predict dementia in cognitively intact elderly people.

CONTEXT The recent focus on the development of preventive interventions for Alzheimer disease has fueled the search for biomarkers of presymptomatic disease. Patients with Alzheimer disease and mild cognitive impairment have marked atrophy of the hippocampus and amygdala compared with healthy elderly people. Whether atrophy of these structures is also present in persons without cognitive impairment who later develop dementia is unknown. OBJECTIVE To assess whether volumetric assessment of the hippocampus and amygdala using magnetic resonance imaging (MRI) predicts dementia in elderly people without cognitive impairment. DESIGN Longitudinal cohort study. SETTING A general community in the Netherlands. PARTICIPANTS Five hundred eleven persons, aged 60 to 90 years, free of dementia at baseline were followed up during 3043 person-years (mean per person, 6.0 years). We performed volumetric assessment of the hippocampus and amygdala, obtained information about daily memory problems, and performed extensive neuropsychological testing in all study participants. MAIN OUTCOME MEASURE Dementia, as assessed by repeated neuropsychological screening and monitoring of medical records. RESULTS Thirty-five persons developed dementia (26 with Alzheimer disease). Hippocampal and amygdalar volumes were strongly associated with the risk of dementia; the age-, sex-, and education-adjusted hazard ratio per 1-SD decrease in volume was 3.0 (95% confidence interval, 2.0-4.6) for the hippocampus and 2.1 (95% confidence interval, 1.5-2.9) for the amygdala. The hazard ratios associated with atrophy were similar in persons without memory complaints or low cognitive function at baseline. Compared with those remaining free of dementia, baseline brain volumes were 17% smaller in persons who received a clinical diagnosis of dementia within 2 to 3 years after MRI and still 5% smaller in those whose conditions were diagnosed 6 years after MRI. CONCLUSION Atrophy of the hippocampus and amygdala on MRI in cognitively intact elderly people predicts dementia during a 6-year follow-up.
Squalene and squalane emulsions as adjuvants.

Microfluidized squalene or squalane emulsions are efficient adjuvants, eliciting both humoral and cellular immune responses. Microfluidization stabilizes the emulsions and allows sterilization by terminal filtration. The emulsions are stable for years at ambient temperature and can be frozen. Antigens are added after emulsification so that conformational epitopes are not lost by denaturation and to facilitate manufacture. A Pluronic block copolymer can be added to the squalane or squalene emulsion. Soluble antigens administered in such emulsions generate cytotoxic T lymphocytes able to lyse target cells expressing the antigen in a genetically restricted fashion. Optionally a relatively nontoxic analog of muramyl dipeptide (MDP) or another immunomodulator can be added; however, the dose of MDP must be restricted to avoid systemic side effects in humans. Squalene or squalane emulsions without copolymers or MDP have very little toxicity and elicit potent antibody responses to several antigens in nonhuman primates. They could be used to improve a wide range of vaccines. Squalene or squalane emulsions have been administered in human cancer vaccines, with mild side effects and evidence of efficacy, in terms of both immune responses and antitumor activity.
On-Chip Open Microfluidic Devices for Chemotaxis Studies

Abstract Microfluidic devices can provide unique control over both the chemoattractant gradient and the migration environment of the cells. Our work incorporates laser-machined micro and nanofluidic channels into bulk fused silica and cover slip-sized silica wafers. We have designed “open” chemotaxis devices that produce passive chemoattractant gradients without an external micropipette system. Since the migration area is unobstructed, cells can be easily loaded and strategically placed into the devices with a standard micropipette. The reusable monolithic glass devices have integral ports that can generate multiple gradients in a single experiment. We also used cover slip microfluidics for chemotaxis assays. Passive gradients elicited from these cover slips could be readily adapted for high throughput chemotaxis assays. We have also demonstrated for the first time that cells can be recruited into cover slip ports eliciting passive chemoattractant gradients. This proves, in principle, that intravital cover slip configurations could deliver controlled amounts of drugs, chemicals, or pathogens as well as recruit cells for proteomic or histological analysis in living animals while under microscopic observation. Intravital cover slip fluidics will create a new paradigm for in vivo observation of biological processes.
Dependence between high sea-level and high river discharge increases flood hazard in global deltas and estuaries

When river and coastal floods coincide, their impacts are often worse than when they occur in isolation; such floods are examples of ‘compound events’. To better understand the impacts of these compound events, we require an improved understanding of the dependence between coastal and river flooding on a global scale. Therefore, in this letter, we: provide the first assessment and mapping of the dependence between observed high sea-levels and high river discharge for deltas and estuaries around the globe; and demonstrate how this dependence may influence the joint probability of floods exceeding both the design discharge and design sea-level. The research was carried out by analysing the statistical dependence between observed sea-levels (and skew surge) from the GESLA-2 dataset, and river discharge using gauged data from the Global Runoff Data Centre, for 187 combinations of stations across the globe. Dependence was assessed using Kendall’s rank correlation coefficient (τ) and copula models. We find significant dependence for skew surge conditional on annual maximum discharge at 22% of the stations studied, and for discharge conditional on annual maximum skew surge at 36% of the stations studied. Allowing a time-lag between the two variables up to 5 days, we find significant dependence for skew surge conditional on annual maximum discharge at 56% of stations, and for discharge conditional on annual maximum skew surge at 54% of stations. Using copula models, we show that the joint exceedance probability of events in which both the design discharge and design sea-level are exceeded can be several magnitudes higher when the dependence is considered, compared to when independence is assumed. We discuss several implications, showing that flood risk assessments in these regions should correctly account for these joint exceedance probabilities.
Application of Two‐Way Hierarchical Cluster Analysis for the Identification of Similarities between the Individual Lipid Fractions of Lucilia sericata

The composition of the cuticular and internal lipids of larvae and pupae of Lucilia sericata was studied using chromatographic techniques. The lipids from both stages of L. sericata had similar free fatty acid (FFA) profiles and also contained alcohols and cholesterol. The range of the number of C‐atoms detected for these classes of compounds was to some extent similar in larvae and pupae, but the relative amounts of each class differed between stages. Saturated as well as unsaturated FFAs with even and odd numbered C‐atom chains were present in both cuticular and internal lipids. The alcohol fractions of L. sericata were represented by free, straight‐chain primary alcohols containing an even number of C‐atoms. The lipid composition of male and female L. sericata adults and the hydrocarbon composition of all stages of L. sericata had previously been analyzed. To have a full overview of the lipid composition and to identify similarities or dissimilarities between the individual lipid fractions in this insect species, two‐way hierarchical cluster analysis (HCA) was performed using also the data from these previous publications. The content of FFA 18 : 1 (n‐9) was noticed to be very high in the cuticular fractions of larvae and pupae as well as in all internal fractions (male, female, larvae, and pupae) and low in the cuticular fractions of male and female imago. The contents of FFAs 16 : 0 and 16 : 1 (n‐9), cholesterol, and the n‐alkanes n‐C31, n‐C29, n‐C27, n‐C25, and n‐C23 varied between particular fractions, whereas the amounts of other compounds were similar in all fractions.
Operational SER Calculations on the SAC-C Orbit Using the Multi-Scales Single Event Phenomena Predictive Platform (MUSCA ${\rm SEP}^{3}$)

In this paper, the Multi-Scales Single Event Phenomena Predictive Platform (MUSCA SEP3) is presented. This platform is dedicated to predicting SEE cross sections or rates and evaluated thanks to on-board operational results on memories from the ICARE experiment (SAC-C mission). It allows for investigating the single and multiple events thus, MUSCA SEP3 helps at estimating sensitivity trend for nano-metric technology and more particularly investigating the emerging effect related to the direct proton ionization. It is a critical problematic which concerns both the space and atmospheric environments.
A Systematic Review of the Literature on the Outcomes of Treatment for Recurrent and Persistent Carpal Tunnel Syndrome

Background: Recurrent and persistent carpal tunnel syndrome is an uncommon but potentially difficult surgical dilemma. Many surgical treatment options have been described in the literature without comparative data on outcome. Methods: A systematic review on recurrent carpal tunnel syndrome was performed for all articles from 1946 to 2012 in MEDLINE, EMBASE, CENTRAL, and hand-searched reference lists from all identified articles. Twenty-three articles were screened and identified from the time period 1972 to 2012, representing two general treatment groups: decompression with flap interposition and repeated open decompression. A meta-analysis was then performed, generating forest and funnel plots of the data. Results: In total, 294 patients from 14 studies in the flap arm of the meta-analysis had a weighted success rate of 86 percent (95 percent CI, 0.75 to 0.96), and 364 patients from nine studies in the nonflap arm had a weighted 75 percent success rate (95 percent CI, 0.66 to 0.84). Heterogeneity was statistically analyzed and revealed low heterogeneity with the I2 statistic. Forest plots were created and analyzed between subgroups, and chi-square analysis revealed a highly statistically significant difference (p = 0.001). The odds ratio of success in the nonflap group was 0.50 (95 percent CI, 0.33 to 0.75). Conclusions: Decompression with the use of vascularized flap coverage appears to have a higher success rate over simple repeated decompression. The relevance of these data is pertinent to all hand surgeons, as they could have an impact on treatment guidelines for this relatively uncommon but problematic condition, but further prospective study is needed. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.
Reconstruction of the shape of conductivity spectra using differential multi-frequency magnetic induction tomography

Magnetic induction tomography (MIT) of biological tissue is used for the reconstruction of the complex conductivity distribution κ inside the object under investigation. It is based on the perturbation of an alternating magnetic field caused by the object and can be used in all applications of electrical impedance tomography (EIT) such as functional lung monitoring and assessment of tissue fluids. In contrast to EIT, MIT does not require electrodes and magnetic fields can also penetrate non-conducting barriers such as the skull. As in EIT, the reconstruction of absolute conductivity values is very difficult because of the method's sensitivity to numerical errors and noise. To overcome this problem, image reconstruction in EIT is often done differentially. Analogously, this concept has been adopted for MIT. Two different methods for differential imaging are applicable. The first one is state-differential, for example when the conductivity change between inspiration and expiration in the lung regions is being detected. The second one is frequency-differential, which is of high interest in motionless organs like the brain, where a state-differential method cannot be applied. An equation for frequency-differential MIT was derived taking into consideration the frequency dependence of the sensitivity matrix. This formula is valid if we can assume that only small conductivity changes occur. In this way, the non-linear inverse problem of MIT can be approximated by a linear one (depending only on the frequency), similar to in EIT. Keeping this limitation in mind, the conductivity changes between one or more reference frequencies and several measurement frequencies were reconstructed, yielding normalized conductivity spectra. Due to the differential character of the method, these spectra do not provide absolute conductivities but preserve the shape of the spectrum. The validity of the method was tested with artificial data generated with a spherical perturbation within a conducting cylinder as well as for real measurement data. The measurement data were obtained from a potato immersed in saline. The resulting spectra were compared with reference measurements and the preservation of the shape of the spectra was analyzed.
SURGICAL RESECTION PLUS ADJUVANT RADIOTHERAPY IS SUPERIOR TO SURGERY OR RADIOTHERAPY ALONE IN THE PREVENTION OF NEUROLOGICAL DECLINE IN A RAT METASTATIC SPINAL TUMOR MODEL

OBJECTIVEThe optimal management of spinal column metastatic disease is controversial. Furthermore, the literature lacks an accurate animal model to study the efficacy of surgical treatment options for spinal column metastases. We compared the efficacy of surgery, radiotherapy, or surgery plus adjuvant radiotherapy in a rat model of metastatic epidural spinal cord compression. METHODSThirty-two Fischer 344 rats underwent a transabdominal approach for implantation of a CRL-1666 breast adenocarcinoma cell line within the vertebral body of L6. Animals were randomly assigned to receive one of four treatments (n = 8 per group) 7 days after tumor implantation: 1) control: no treatment; 2) external beam radiation therapy (XRT) (total 20 Gy in 400-cGy daily fractions); 3) surgery: L6 vertebral corpectomy, tumor resection, and polymethyl methacrylate reconstruction; and 4) surgery + XRT: corpectomy and tumor resection followed by XRT (total 20 Gy in 400-cGy daily fractions) 72 hours after surgery. Hind-limb function was tested daily after treatment using the Basso-Beattie-Bresnahan (BBB) scale (range, 1–21). RESULTSAll animals (n = 32) demonstrated normal hind-limb function (BBB score, 21) on posttreatment Day 1. The XRT, surgery, and surgery + XRT groups all experienced a delay in onset of paresis versus the control group. Compared to the XRT group, the surgery group demonstrated greater median BBB scores on Days 3 (21 versus 20, P = 0.02) through 9 (12 versus 8, P = 0.002) after treatment. Compared with the surgery group, the surgery + XRT group demonstrated even greater median BBB scores on Days 6 (21 versus 19, P = 0.0008) through 11 (16 versus 8, P = 0.0001) after treatment. Median time to loss of ambulation (BBB ≤ 7) was greatest in the surgery + XRT group (15 d) when compared with the surgery (12 d, P = 0.001), XRT (9 d, P = 0.001), or control groups (7 d, P = 0.0005). CONCLUSIONIn a rat model of metastatic epidural spinal cord compression, decompressive surgery followed by radiotherapy yielded the greatest efficacy in the prevention of neurological decline when compared with surgery or radiotherapy alone. Radiotherapy alone attenuated neurological decline but was the least efficacious treatment in this model. These results support this animal model as an effective platform to investigate novel interventions for metastatic spine tumors.
International Evidence on Economic Policy Uncertainty and Asymmetric Adjustment of Audit Pricing: Big 4 Versus Non‐Big 4 Auditors

By investigating the association between economic policy uncertainty and audit fees using data from eight countries, this study examines whether and how Big 4 auditors reinforce their advantages over nonâ€ Big 4 auditors through audit pricing. We find that both Big 4 and nonâ€ Big 4 auditors reduce their audit fees when economic policy uncertainty increases. However, while nonâ€ Big 4 auditors adjust audit pricing asymmetrically as economic policy uncertainty changes, i.e., the magnitude of decline in audit fees when economic policy uncertainty increases exceeds the magnitude of rise when economic policy uncertainty decreases, Big 4 auditors regulate their audit pricing in a symmetric manner. Further analyses reveal that: (1) the asymmetric pricing of nonâ€ Big 4 auditors mainly exists in countries where Big 4 auditors have dominant market share, (2) Big 4 auditors provide higherâ€ quality audits when economic policy uncertainty increases and (3) many firms in better financial condition turn to Big 4 auditors during uncertain years. Our findings suggest that the symmetric audit pricing helps Big 4 auditors maintain a favorable position in the audit market.
Sustainability Managed against Downside Risk and the Cost of Equity: Evidence in Korea

This study examines the relationship between sustainability managed against downside risk and the cost of equity in the Korean stock market during the 2000–2016 period. We employ downside co-skewness and downside beta as a measure of downside risk, to analyze the cross-sectional relationship between them and average portfolio stock returns. We have also carried out Fama–MacBeth regressions to find the required return for bearing downside risk. The results show that downside co-skewness can be used more effectively than downside beta to explain a cross-section of stock returns or cost of equity. The required premium for bearing downside risk, as measured by downside co-skewness, is approximately 19% per annum in the Korean stock market. This finding suggests that sustainable companies can raise their capital in the form of equity at 19% lower costs, and also implies that increasing sustainability can reduce the cost of capital.
Intersubunit Interaction between Transmembrane Helices of the Bacterial Aspartate Chemoreceptor Homodimer*

The transmembrane domain that connects the extracellular and intracellular domains of cell-surface receptors must play a critical role in signal transduction. Here, we report studies of the interaction between the transmembrane helices (TM1 and TM2) of theEscherichia coli aspartate chemoreceptor (Tar). Tar exists as a homodimer regardless of its state of ligand occupancy. A particular residue substitution in TM1 (A19K) abolishes the signaling ability of Tar. This signaling defect can be suppressed by single residue substitutions in TM2 (W192R, A198E, V201E, and V202L). We have found that these suppressors can be divided into two groups. A198E and V201E (class 1) almost completely suppress the defects caused by A19K, and this suppression occurs between two subunits of the Tar dimer. In contrast, W192R and V202L (class 2) fail to suppress some signaling defects, and their suppression does not occur between subunits. Because disulfide-crosslinking studies predict that residues 198 and 201 point toward residue 19 of the partner subunit, we propose that the class 1 suppressors form an intersubunit salt bridge with Lys-19. Indeed, A19K was suppressed by several additional aspartate or glutamate substitutions on the same face of TM2 occupied by residues 198 and 201. None of these intersubunit salt bridges perturb signaling function, suggesting that the mechanism of transmembrane signal propagation does not involve large displacements (such as extensive rotation) of the TM1 and TM2 helices relative to each other.
Modeling and optimization oriented to the micro-grid-EV joint system

With the increasingly serious energy scarcity and environment pollution, the wide application of the renewable energy and the popularization of the electric vehicle are considered as two effective ways to improve the energy and environment situation. However, the negative effect on the system stability could not be ignored for their intermittent, fluctuant and random characteristics. Aiming to study the operation of micro-grid with access of the renewable energy and EVs, the synthetically modeling method that includes agent-based modeling and system dynamics modeling is applied to built the micro-grid-EV joint system model. Considering the time difference of renewable energy generation, EV charging and the residential load demands, the cascade charging strategy is proposed for scheduling the EV charging behavior to maintain the stable operation of the micro-grid-EV joint system and extremely improve the utilization of the renewable energy. Finally, the comparative simulations are carried out in the same conditions with the other two strategies include charging after travel and charging at night, and the optimal performance of the proposed cascade charging strategy is verified by index evaluation of the renewable energy utilization rate, the energy supplement ability and the peak-to-average ratio.