Miracle-dz/UniFAR-FTUs huggingface dataset:
Clarifying the influence of core amino acid hydrophobicity, secondary structure propensity, and molecular volume on amyloid-β 16-22 self-assembly.

The self-assembly of amyloid peptides is influenced by hydrophobicity, charge, secondary structure propensity, and sterics. Previous experiments have shown that increasing hydrophobicity at the aromatic positions of the amyloid-β 16-22 fragment (Aβ(16-22)) without introducing steric restraints greatly increases the rate of self-assembly and thermodynamically stabilizes the resulting fibrils [Senguen et al., Mol. BioSyst. , 2011, DOI: 10.1039/c0mb00080a]. Conversely, when increasing side chain hydrophobicity coincides with an increase in side chain volume, the increase in the rate of self-assembly is offset by a thermodynamic destabilization of the resulting amyloid fibrils when direct cross-strand side chain interactions occur. These findings indicate that steric effects also influence the self-assembly of amyloidogenic peptides. Herein, the aromatic Phe residues at positions 19, 20, and 19,20 of Aβ(16-22) have been systematically replaced by Val, Leu, Ile, or hexafluoroleucine (Hfl) and amyloid formation has been characterized. The Val variants, despite the high β-sheet propensity of Val, were thermodynamically destabilized (ΔΔG = +0.1-0.4 kcal mol(-1)) relative to the wild-type with the double mutant failing to self-assemble at the concentrations studied. Conversely, the Leu and Ile variants formed fibrils at enhanced rates relative to wild-type and exhibited similar, or in some cases enhanced thermodynamic stabilities relative to the wild-type (ΔΔG = 0-0.6 kcal mol(-1)). The more hydrophobic Hfl variants were greatly stabilized (ΔΔG = -0.3-2.1 kcal mol(-1)) relative to the wild-type. These data indicate that hydrophobicity and steric effects both influence peptide self-assembly processes, including nucleation and fibrillization rates and the thermodynamic stability of the resulting fibrils.
Elevated Oxygen Fraction Reduces Cilial Abundance in Explanted Human Bronchial Tissue

The effect of hyperoxia on ciliary abundance in cultured explants of adult human bronchus was investigated. Bronchus samples were removed during surgery from patients receiving pneumonectomy or lobectomy for malignancy. Part or all of each of these samples was used for measurement of cilial abundance by scanning electron microscopy (SEM); in many cases the remainder was subdivided and cultured at 37°C in DMEM medium, maintaining an air interface at the ciliated surface of each segment. Cultured segments were exposed to normoxia or hyperoxia (95% O2), and a segment was removed every other day for quantification of cilial abundance by SEM. There was a significant inverse relationship between smoking history and abundance (p = .017; ANOVA); mean values for nonsmokers, ex-smokers, and smokers were 98.2% (n = 6), 97.0% (n = 17), and 84.02% (n = 9), respectively. There was some loss of cilia on explant segments cultured under normoxia, but the rate of loss from segments cultured under hyperoxia was significantly greater (W test, p = .00011); rate constants (means ± SE) for cilial loss of 0.0208 ± 0.0044 day−1 and 0.0880 ± 0.0179 day−1 were found for explant segments exposed to 21 and 95% O2, respectively (n = 20).
Identifying cancer origin using circulating tumor cells

ABSTRACT Circulating tumor cells (CTCs) have become an established clinical evaluation biomarker. CTC count provides a good correlation with the prognosis of cancer patients, but has only been used with known cancer patients, and has been unable to predict the origin of the CTCs. This study demonstrates the analysis of CTCs for the identification of their primary cancer source. Twelve mL blood samples were equally dispensed on 6 CMx chips, microfluidic chips coated with an anti-EpCAM-conjugated supported lipid bilayer, for CTC capture and isolation. Captured CTCs were eluted to an immunofluorescence (IF) staining panel consisting of 6 groups of antibodies: anti-panCK, anti-CK18, anti-CK7, anti-TTF-1, anti-CK20/anti-CDX2, and anti-PSA/anti-PSMA. Cancer cell lines of lung (H1975), colorectal (DLD-1, HCT-116), and prostate (PC3, DU145, LNCaP) were selected to establish the sensitivity and specificity for distinguishing CTCs from lung, colorectal, and prostate cancer. Spiking experiments performed in 2mL of culture medium or whole blood proved the CMx platform can enumerate cancer cells of lung, colorectal, and prostate. The IF panel was tested on blood samples from lung cancer patients (n = 3), colorectal cancer patients (n = 5), prostate cancer patients (n = 5), and healthy individuals (n = 12). Peripheral blood samples found panCK+ and CK18+ CTCs in lung, colorectal, and prostate cancers. CTCs expressing CK7+ or TTF-1+, (CK20/ CDX2)+, or (PSA/ PSMA)+ corresponded to lung, colorectal, or prostate cancer, respectively. In conclusion, we have designed an immunofluorescence staining panel to identify CTCs in peripheral blood to correctly identify cancer cell origin.
Muscle Activation During Landing Before and After Fatigue in Individuals With or Without Chronic Ankle Instability.

CONTEXT Ankle instability is a common condition in physically active individuals. It often occurs during a jump landing or lateral motion, particularly when participants are fatigued. OBJECTIVE To compare muscle activation during a lateral hop prefatigue and postfatigue in individuals with or without chronic ankle instability (CAI). DESIGN Cross-sectional study. SETTING Sports medicine research laboratory. PATIENTS OR OTHER PARTICIPANTS A total of 32 physically active participants volunteered for the study. Sixteen participants with CAI (8 men, 8 women; age = 20.50 ± 2.00 years, height = 172.25 ± 10.87 cm, mass = 69.13 ± 13.31 kg) were matched with 16 control participants without CAI (8 men, 8 women; age = 22.00 ± 3.30 years, height = 170.50 ± 9.94 cm, mass = 69.63 ± 14.82 kg) by age, height, mass, sex, and affected side. INTERVENTION(S) Electromyography of the tibialis anterior, peroneus longus, gluteus medius, and gluteus maximus was measured before and after a functional fatigue protocol. MAIN OUTCOME MEASURE(S) Activation of 4 lower extremity muscles was measured 200 milliseconds before and after landing from a lateral hop. RESULTS We observed no interactions. The group main effects for the peroneus longus demonstrated higher muscle activation in the CAI group (52.89% ± 11.36%) than in the control group (41.12% ± 11.36%) just before landing the lateral hop (F1,30 = 8.58, P = .01), with a strong effect size (d = 1.01). The gluteus maximus also demonstrated higher muscle activation in the CAI group (45.55% ± 12.08%) than in the control group (36.81% ± 12.08%) just before landing the lateral hop (F1,30 = 4.19, P = .049), with a moderate effect size (d = 0.71). We observed a main effect for fatigue for the tibialis anterior, with postfatigue activation higher than prefatigue activation (F1,30 = 7.45, P = .01). No differences were present between groups for the gluteus medius. CONCLUSIONS Our results support the presence of a centralized feed-forward neuromuscular alteration in patients with CAI, not only in the ankle-joint muscles but also in the proximal hip muscles. These results may have implications for rehabilitation programs in these patients.
Understanding dendritic cell and T‐lymphocyte traffic through the analysis of chemokine receptor expression

The immune response requires a timely interaction among different cell types within distinct microenvironments. Our studies have focused on the regulation of chemokine receptors in dendritic cells (DC) and T lymphocytes. Chemokine receptors expressed by immature DC promote their migration to inflamed tissues, where antigens are captured and maturation is induced. Maturing DC upregulate CCR7, which drives their migration to the T-cell areas of the draining lymph nodes where antigen is presented to naïve T cells. DC produce a variety of chemokines that influence DC recruitment into inflamed tissues and DC-T-cell interaction in the lymph nodes. Chemokine receptors are differentially acquired by developing Th1 and Th2 cells and are differentially expressed on subsets of "central memory" and "effector memory" T cells. Furthermore, following antigenic stimulation, effector T cells can rapidly switch chemokine receptor expression, acquiring new migratory capacities. These studies provide insights into the mechanisms that control T-cell priming as well as memory and effector immune responses.
Frequent attenders in general practice: medical, psychological and social characteristics.

A group of frequent attenders at a general practice surgery have been studied by comparison with a group of age-and sex-matched controls. Frequent attenders are distinguished by a high predisposition to neurotic illness (as measured by the ;N' score of the Eysenck personality questionnaire) and a high prevalence of affective neurosis. Poor past physical health was commonly found among the frequent attenders and comprised for the most part the common chronic physical illnesses. Of the social characteristics studied only marital breakdown was found significantly more often in frequent attenders than controls.
Reynolds stress and eddy diffusivity of β-plane shear flows

The Reynolds stress induced by anisotropically forcing an unbounded Couette flow, with uniform shear γ, on a β-plane, is calculated in conjunction with the eddy diffusivity of a co-evolving passive tracer. The flow is damped by linear drag on a time scale μ. The stochastic forcing is white-noise in time and its spatial anisotropy is controlled by a parameter α, that characterizes whether eddies are elongated along the zonal direction (α < 0), along the meridional direction (α > 0) or are isotropic (α = 0). The Reynolds stress varies linearly with α and non-linearly and non-monotonically with γ; but the Reynolds stress is independent of β. For positive values of α, the Reynolds stress displays a “anti-frictional” effect (energy is transferred from the eddies to the mean flow) and a frictional effect for negative values of α. When γ/μ ≪ 1, these transfers can be identified as negative and positive eddy-viscosities, respectively. With γ = β = 0, the meridional tracer eddy diffusivity is v/(2μ), where v is the meridional eddy velocity. In general, non-zero β and γ suppress the eddy diffusivity below v/(2μ). When the shear is strong, the suppression due to γ varies as γ while the suppression due to β varies between β and β depending on whether the shear is strong or weak, respectively.
Added prognostic value of myocardial blood flow quantitation in rubidium-82 positron emission tomography imaging.

AIMS We studied the respective added value of the quantitative myocardial blood flow (MBF) and the myocardial flow reserve (MFR) as assessed with (82)Rb positron emission tomography (PET)/CT in predicting major adverse cardiovascular events (MACEs) in patients with suspected myocardial ischaemia. METHODS AND RESULTS Myocardial perfusion images were analysed semi-quantitatively (SDS, summed difference score) and quantitatively (MBF, MFR) in 351 patients. Follow-up was completed in 335 patients and annualized MACE (cardiac death, myocardial infarction, revascularization, or hospitalization for congestive heart failure or de novo stable angor) rates were analysed with the Kaplan-Meier method in 318 patients after excluding 17 patients with early revascularizations (<60 days). Independent predictors of MACEs were identified by multivariate analysis. During a median follow-up of 624 days (inter-quartile range 540-697), 35 MACEs occurred. An annualized MACE rate was higher in patients with ischaemia (SDS >2) (n = 105) than those without [14% (95% CI = 9.1-22%) vs. 4.5% (2.7-7.4%), P < 0.0001]. The lowest MFR tertile group (MFR <1.8) had the highest MACE rate [16% (11-25%) vs. 2.9% (1.2-7.0%) and 4.3% (2.1-9.0%), P < 0.0001]. Similarly, the lowest stress MBF tertile group (MBF <1.8 mL/min/g) had the highest MACE rate [14% (9.2-22%) vs. 7.3% (4.2-13%) and 1.8% (0.6-5.5%), P = 0.0005]. Quantitation with stress MBF or MFR had a significant independent prognostic power in addition to semi-quantitative findings. The largest added value was conferred by combining stress MBF to SDS. This holds true even for patients without ischaemia. CONCLUSION Perfusion findings in (82)Rb PET/CT are strong MACE outcome predictors. MBF quantification has an added value allowing further risk stratification in patients with normal and abnormal perfusion images.
Nonsurgical management of pancreaticopleural fistula.

CONTEXT Pancreaticopleural fistula is seen in acute and chronic pancreatitis or after traumatic or surgical disruption of the pancreatic duct. Surgery leads to healing in 80-90% of cases but carries a mortality of up to 10%. AIM Our aim was to assess the management of pancreaticopleural fistula on a specialist pancreatic Unit. METHODS Patients presenting with pancreaticopleural fistulae were identified from acute and chronic pancreatitis databases. Management and outcome were compared with previous studies identified in MEDLINE and EMBASE. RESULTS Four patients presented with dyspnoea from large unilateral pleural effusions. Three had a history of alcohol abuse and one of asymptomatic gallstones. All were treated with chest drainage, octreotide and endoscopic retrograde cholangiopancreatography plus/minus pancreatic stent. Two had a pancreatic stent in situ for 5 and 8.5 months respectively. In the third sphincterotomy was performed; in the fourth the pancreatic duct could not be cannulated. The fistula healed in all cases, with no recurrence after 12-30 months, and no deaths. There are 14 reports including 16 cases treated with endoscopic retrograde cholangiopancreatography plus/minus pancreatic stent in the literature, with no recurrence after follow up ranging 4-30 months and no deaths in these 16 cases. CONCLUSIONS A high index of suspicion is necessary to be aware of its presence. These data suggest that endoscopic management is preferable alternative to surgery for pancreaticopleural fistula.
Creditor Rights, Enforcement, and Debt Ownership Structure: Evidence from the Global Syndicated Loan Market

Abstract Using a sample of 495 project finance loan tranches (worth $151 billion) to borrowers in 61 different countries, we examine the relation between legal risk and debt ownership structure. The tranches exhibit high absolute levels of debt ownership concentration: the largest single bank holds 20.3% while the top five banks collectively hold 61.2% of a typical tranche. In countries with strong creditor rights and reliable legal enforcement, lenders create smaller and more concentrated syndicates to facilitate monitoring and low cost contracting. When lenders cannot rely on legal enforcement mechanisms to protect their claims, they create larger and more diffuse syndicates as a way to deter strategic default.
A dozen ways to prevent nickel-titanium rotary instrument fracture.

BACKGROUND and Overview. With the increased use of nickel-titanium (NiTi) rotary instruments for root canal preparation in endodontics, instrument fracture has become more prevalent. Extensive research has been conducted on the physical properties and mechanical characteristics of NiTi rotary instruments, as well as the factors that can contribute to instrument failure. NiTi rotary instruments are subjected to torque and are susceptible to cyclic fatigue, which are the main causes of instrument fracture. However, with an understanding of how these instruments function in preparing root canals and by applying ways to reduce torque-generated metal fatigue, clinicians can use the instruments safely in clinical practice. RESULTS The author presents 12 measures that clinicians can take to prevent NiTi rotary instrument fracture and discusses them in detail. CLINICAL IMPLICATIONS NiTi rotary instrument fracture complicates the progress, and compromises the prognosis of endodontic treatment. However, when clinicians take appropriate measures, rotary instrument fractures can be prevented.
Energy-efficient resource allocation in multiuser MIMO systems: A game-theoretic framework

This paper focuses on the cross-layer issue of resource allocation for energy efficiency in the uplink of a multiuser MIMO wireless communication system. Assuming that all of the transmitters and the uplink receiver are equipped with multiple antennas, the situation considered is that in which each terminal is allowed to vary its transmit power, beamforming vector, and uplink receiver in order to maximize its own utility, which is defined as the ratio of data throughput to transmit power; the case in which non-linear interference cancellation is used at the receiver is also investigated. Applying a game-theoretic formulation, several non-cooperative games for utility maximization are thus formulated, and their performance is compared in terms of achieved average utility, achieved average SINR and average transmit power at the Nash equilibrium. Numerical results show that the use of the proposed cross-layer resource allocation policies brings remarkable advantages to the network performance.
UvA-DARE ( Digital Academic Repository ) Locally finite reducts of Heyting algebras and canonical formulas

The variety of Heyting algebras has two well-behaved locally finite reducts, the variety of bounded distributive lattices and the variety of implicative semilattices. The variety of bounded distributive lattices is generated by the→-free reducts of Heyting algebras while the variety of implicative semilattices by the ∨-free reducts. Each of these reducts gives rise to canonical formulas that generalize Jankov formulas and provide an axiomatization of all superintuitionistic logics (si-logics for short). The ∨-free reducts of Heyting algebras give rise to the (∧,→)-canonical formulas that were studied in [3]. Here we introduce the (∧,∨)-canonical formulas, which are obtained from the study of the →-free reducts of Heyting algebras. We prove that every si-logic is axiomatizable by (∧,∨)-canonical formulas. We also discuss the similarities and differences between these two kinds of canonical formulas. One of the main ingredients of these formulas is a designated subset D of pairs of elements of a finite subdirectly irreducible Heyting algebra A. When D = A, we show that the (∧,∨)canonical formula of A is equivalent to the Jankov formula of A. On the other hand, when D = ∅, the (∧,∨)-canonical formulas produce a new class of si-logics we term stable si-logics. We prove that there are continuum many stable si-logics and that all stable si-logics have the finite model property. We also compare stable si-logics to splitting and subframe si-logics.
Prediction Of Heart Disease Using Classification Algorithms

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RFa‐related peptides are algogenic: evidence in vitro and in vivo

RFamide (RFa)‐related peptides modulate pain processing in the mammalian CNS. The effects of these peptides are generally considered as ‘anti‐opioid’. They also decrease the rate of desensitization of acid‐sensing ionic channels (ASICs), putative nociceptors in dorsal root ganglia neurons [C. Askwith et al. (2000) Neuron, 26, 133–141]. We have tested the role of mollusc‐derived peptide, FMRFa (Phe‐Met‐Arg‐Phe‐amide) and its synthetic analogues in peripheral nociception. Here we demonstrate that RFa‐related peptides powerfully excite the majority of C‐fibres in the skin–nerve preparation of rat: 76% of 55 tested fibres with the conduction velocity below 2 m/s responded with long‐lasting discharges to the application of peptides (20 µm). When injected subcutaneously in vivo (mice), they initiate nociceptive behaviour. We confirm the data on humans [S. Ugawa et al. (2002) J. Clin. Invest. , 110, 1185–1190]: the activation of C‐fibres by acid is inhibited by channel blocker of ASICs, amiloride. However, there is no correlation in the sensitivity of C‐fibres to RFa peptides, protons and amiloride: 74% of tested RFa‐sensitive C‐fibres were insensitive to protons and in 67% of cases the response to peptides was insensitive to amiloride. Thus, powerful excitatory/algogenic action of RFa‐related peptides cannot be interpreted solely in terms of their interaction with ASICs. The peptides do not activate any conductance in the somatic membrane of dorsal root ganglion neurons of rats and probably affect still unidentified molecular target(s) responsible for nociceptive signalling.
Pancreas divisum: evaluation with secretin-enhanced magnetic resonance cholangiopancreatography.

BACKGROUND The clinical significance of pancreas divisum (PD) remains controversial. Secretin-enhanced magnetic resonance cholangiopancreatography (S-MRCP) is a noninvasive diagnostic procedure that relies on the dynamic response of the main pancreatic duct (MPD) to secretin stimulation. The aim of this study was to determine the frequency of PD and to analyze the dynamic changes of the MPD by using S-MRCP in patients referred for suspected pancreatic diseases before ERCP. METHODS MRCP was obtained before and at 30-second intervals over 10 minutes after secretin stimulation in consecutive patients with idiopathic acute pancreatitis (n = 67), persistent hydrolasemia (n = 42), recurrent abdominal pain thought to be of pancreatic origin (n = 48), severe chronic pancreatitis (n = 68), and in a control group (n = 54). RESULTS Thirty patients (10.8%) had a PD at S-MRCP. Secretin stimulation improved the detection of PD in 23% (7/30). The frequency of PD was not significantly different (p > 0.2) between these groups. The occurrence of an abnormal response at S-MRCP (persistent dilatation of the MPD) did not significantly differ in patients with or without PD (p > 0.4). CONCLUSION The frequency of PD did not differ between groups, and the dynamic changes of the MPD during S-MRCP were similar in patients with and without PD.