Miracle-dz/UniFAR-FTUs huggingface dataset:
Enhancement of macrosphelide-induced apoptosis by mild hyperthermia

Hyperthermia is a useful adjunct in cancer therapy as it can increase the effectiveness and decrease the toxicity of currently available cancer treatments such as chemotherapy and radiation. In the present study, we investigated whether 41°C hyperthermia (mild HT) for 20 min can enhance macrosphelide (MS5)-induced apoptosis in human lymphoma U937 cells. Our results revealed that, compared with MS5 (5 µM) and mild HT alone, the combined treatment exhibited significant enhancement in apoptosis at 6 h, which was evaluated by observing morphological changes and DNA fragmentation. Marked increase in the reactive oxygen species (ROS) generation was observed immediately after the combined treatment. Significant increase in Fas externalization, caspase-8 and caspase-3 activation, and loss of mitochondrial membrane potential (MMP) was found after the combined treatment compared with MS5 and mild HT alone. Moreover, this combination can also alter the expression of apoptosis-related proteins as evident by the cleavage of Bid and down-regulation of Bcl-2 while no change in the expression of Bax was observed. Furthermore, an immediate rise in the intracellular calcium ion ([Ca2+]i) concentration was observed after the combined treatment, which continuously increased in a time-dependent manner. In addition, mild HT treatment alone also increases [Ca2+]i concentration without inducing apoptosis. Our data indicate that early increase in ROS generation is mainly responsible for the enhancement of apoptosis after the combined treatment.
Low levels of exhaled nitric oxide are associated with impaired lung function in cystic fibrosis

Fraction of exhaled nitric oxide (FENO) is often reduced in cystic fibrosis (CF). FENO at different expiratory flows can provide an indication of the site of nitric oxide production. The aim of this study was to examine whether NO parameters are related to overall (FEV1) or peripheral (lung clearance index, LCI, measured by multiple breath SF6 washout) airway function and systemic inflammation in CF. Secondary aim was to compare alveolar NO and bronchial NO flux calculated by two different mathematical models, a linear and a nonlinear method. Thirty‐five healthy and 45 CF children were recruited. FENO at 50 ml/sec (FENO50) and bronchial NO flux were lower in CF than controls, 9.5 (2.7–38.8) (median (range)) versus 12.4 (5.2–40.1) ppb, P = 0.029, and 391 (97–1772) versus 578 (123–1993) (pl/sec), P = 0.036, respectively. No difference in alveolar NO was shown. The nonlinear method resulted in lower alveolar NO and higher bronchial flux, than the linear method, but the result was closely correlated in both groups. LCI was higher in CF than controls, 8.4 (6.5–12.9) versus 5.9 (5.1–7.8), P < 0.001. FENO50 was negatively correlated with LCI (r = −0.43; P = 0.003) and positively correlated with FEV1 (r = 0.42, P = 0.004) in CF. Alveolar NO correlated negatively with inflammatory markers: orosomucoid (r = −0.42, P = 0.005), platelets (r = −0.50, P < 0.001) and white blood cell count (r = −0.48, P = 0.001). In conclusion, FENO50 and bronchial NO flux are reduced in young CF subjects and low FENO50 is associated with overall and small airway obstruction. NO parameters derived from the different models were closely related but the values differed slightly. Pediatr Pulmonol. 2010; 45:241–248. © 2010 Wiley‐Liss, Inc.
A Framework for Attack-Resilient Industrial Control Systems: Attack Detection and Controller Reconfiguration

Most existing industrial control systems (ICSs), such as building energy management systems (EMSs), were installed when potential security threats were only physical. With advances in connectivity, ICSs are now, typically, connected to communications networks and, as a result, can be accessed remotely. This extends the attack surface to include the potential for sophisticated cyber attacks, which can adversely impact ICS operation, resulting in service interruption, equipment damage, safety concerns, and associated financial implications. In this work, a novel cyber–physical security framework for ICSs is proposed, which incorporates an analytics tool for attack detection and executes a reliable estimation-based attack-resilient control policy, whenever an attack is detected. The proposed framework is adaptable to already implemented ICS and the stability and optimal performance of the controlled system under attack has been proved. The performance of the proposed framework is evaluated using a reduced order model of a real EMS site and simulated attacks.
First Report of Performance of the Versant CT/GC DNA 1.0 Assay (kPCR) for Detection of Chlamydia trachomatis and Neisseria gonorrhoeae

ABSTRACT We evaluated the analytical, work flow, and clinical performance of the Versant CT/GC DNA 1.0 assay (Versant CT/GC assay, where “CT” represents Chlamydia trachomatis and “GC” represents Neisseria gonorrhoeae). The assay simultaneously detects Chlamydia trachomatis and Neisseria gonorrhoeae in swab and first-catch urine (FCU) specimens. The limit of detection (LoD) was determined to be 342 copies/ml for C. trachomatis and 137 copies/ml for GC. The Versant CT/GC assay detected 15 C. trachomatis serovars and 46 GC strains. The Versant CT/GC assay demonstrated no cross-reactivity with 136 potentially cross-reacting organisms. Clinical concordance of the Versant CT/GC assay to the Aptima Combo 2 (AC2) assay from Gen-Probe was demonstrated using 1,129 patient specimens, including 589 urine and 540 swab specimens. Discrepant specimens were subjected to DNA sequencing to identify the presence of amplified targets and to identify false-positive and false-negative results. Overall percent agreement was greater than 98%. Positive and negative percent agreements for detection of C. trachomatis were 94.4% and 99.1%, respectively, in urine specimens and 95.8% and 99.8%, respectively, in swab specimens. Positive percent agreement for the detection of N. gonorrhoeae was 100% in both urine and swab specimens, and negative percent agreements were 99.6% and 99% in urine and swab specimens, respectively. In conclusion, the performance of the Versant CT/GC assay was comparable to that of the AC2 assay. The Versant CT/GC assay can be recommended for the detection of C. trachomatis and N. gonorrhoeae in swab and urine specimens of symptomatic and asymptomatic individuals.
Investigational beta-2 adrenergic agonists for the treatment of chronic obstructive pulmonary disease

ABSTRACT Introduction: Long-acting bronchodilators are pivotal in the therapeutic management of COPD patients with moderate-to-severe airflow obstruction. New ultra-long-acting β2-agnoists (ultra-LABAs) have been developed, some of which have been licensed for use as monotherapy and/or in combination with other bronchodilators or inhaled corticosteroids, for use in COPD patients with persistent symptoms and worsening airflow limitation. These new agents are faster in onset and have a prolonged duration of action, with a similar safety profile to the traditional twice-daily bronchodilators which may have an impact on patient concordance. Areas covered: A number of these ultra-LABAs are still under development and bi-functional hybrid molecules containing regions functioning as β2-agonists, and as muscarinic agonists (MABAs) has been developed. This review summarizes these (excluding the licensed ultra-LABAs) with attention on phase II studies data available to-date on their pharmacological profiles, clinical efficacy and safety, and future perspectives. Expert opinion: Despite all the new agents’ available, the challenges that persist include any differences in efficacy and safety between the various possible LAMA/LABA combinations, relative advantages of MABAs over fixed-dose LAMA/LABAs, and the impact of these new molecules in terms of long term safety, especially in certain populations in co-morbidities frequently associated with COPD.
Effects of tissue age, presence of neurones and endothelin‐3 on the ability of enteric neurone precursors to colonize recipient gut: implications for cell‐based therapies

Background Most enteric neurones arise from neural crest cells that originate in the post‐otic hindbrain, and migrate into and along the developing gastrointestinal tract. There is currently great interest in the possibility of cell therapy to replace diseased or absent enteric neurones in patients with enteric neuropathies, such as Hirschsprung’s disease. However, it is unclear whether neural crest stem/progenitor cells will be able to colonize colon (i) in which the mesenchyme has differentiated into distinct layers, (ii) that already contains enteric neurones or (iii) that lacks a gene expressed by the gut mesenchyme, such as endothelin‐3 (Et‐3).
Evaluating the Performance of Kalman-Filter-Based EEG Source Localization

Electroencephalographic (EEG) source localization is an important tool for noninvasive study of brain dynamics, due to its ability to probe neural activity more directly, with better temporal resolution than other imaging modalities. One promising technique for solving the EEG inverse problem is Kalman filtering, because it provides a natural framework for incorporating dynamic EEG generation models in source localization. Here, a recently developed inverse solution is introduced, which uses spatiotemporal Kalman filtering tuned through likelihood maximization. Standard diagnostic tests for objectively evaluating Kalman filter performance are then described and applied to inverse solutions for simulated and clinical EEG data. These tests, employed for the first time in Kalman-filter-based source localization, check the statistical properties of the innovation and validate the use of likelihood maximization for filter tuning. However, this analysis also reveals that the filter's existing space- and time-invariant process model, which contains a single fixed-frequency resonance, is unable to completely model the complex spatiotemporal dynamics of EEG data. This finding indicates that the algorithm could be improved by allowing the process model parameters to vary in space.
Swine as an In Vivo Model for Electrophysiologic Evaluation of Cardiac Pacing Parameters

Pre‐clinical studies of cardiac pacemakers and new electrodes, materials, and designs are for the most part conducted in dogs. Dogs, however, have electrophysiological differences which may preclude accurate translation to clinical trials. The purpose of this study was to develop normal electrophysiological parameters for an animal whose cardiovascular system more closely resembles that of man than any nonprimate animal. The threshold (voltage and current) strength‐duration curves of the pig showed the same inverse relationship between the pulse duration and threshold requirements as other species. At 0.5 ms the atrium had 3.5–5.5 times greater energy requirements, over twice the current (2.04 mA vs 0.72 mA) and twice the voltage (0.75 mV vs 0.32 mV) requirements when compared to the ventricles. The pig's S‐A nodal P‐wave was superior in amplitude (7.80 ± 1.80 mV vs 4.28 ± 2.27 mV) and the slew rate was faster (1.30 ± 0.56 mV/ms vs 0.44 ± 0.50 mV/ms) compared to that of the atrial appendage. The pig's left ventricular myocardial R‐wave had significantly greater amplitude (19.00 ± 6.44 mVvs 10.70 ± 4.34 mV) and faster slew rate (1.60 ± 0.62 mV/ms vs 0.90 ± 0.30 mV/ms) compared to the right ventricular endocardial R‐wave. The electrophysiological parameters of the pig were more similar to those of man than the dog; therefore, the pig is a useful animal model for electrophysiological studies and the testing of pacemaker equipment.
Buprenorphine–naloxone buccal soluble film for the treatment of opioid dependence: current update

Introduction: Opioid dependence is a severe medical disorder with a high psychiatric and somatic comorbidity and mortality rate. The opioid agonist methadone, mixed agonist-antagonist buprenorphine and the combination of buprenorphine with the opioid antagonist naloxone are the first-line maintenance treatments for opioid dependence. Risk of diversion and accidental intoxications, especially in children, are of great concern. To lower these risks, a novel buprenorphine–naloxone film has been developed and introduced in the USA and Australia. Areas covered: This review evaluates the available preclinical and clinical data on the novel buprenorphine–naloxone film for treatment of opioid dependence. Literature was identified through a comprehensive PubMed search. Data sources also included official FDA information and material made public by the manufacturer. Expert opinion: Few preclinical and clinical data on safety and efficacy have been published. The pharmacological differences between the novel film and the conventional buprenorphine/naloxone are small. In an experimental study, the new formulation suppressed symptoms of opioid withdrawal. The spectrum of adverse events seems to be similar to that of the conventional sublingual tablet. Recent data show that patients prefer the novel film over the conventional sublingual tablet. Emerging surveillance data indicate a lower risk of accidental poisoning in children compared with the conventional formulation. Further clinical and preclinical data are needed to explore additional possible advantages of the new formulation.
The history and historical treatments of deep vein thrombosis

Deep vein thrombosis (DVT) is a common disease. However, unlike that of varicose veins, which have been depicted since antiquity in art and literature, its description was more recent in the history of medicine. The first well‐documented case of DVT was reported during the Middle Ages: in 1271, Raoul developed a unilateral edema in the ankle, which then extended to the leg. The number of reported DVT cases steadily increased thereafter, particularly in pregnant and postpartum women. During the first half of the 20th century, well before the discovery of anticoagulants, many therapeutic approaches were used, and arose from the pathologic hypotheses that prevailed at their time. Despite the development of anticoagulants, and the fact that they were thought to dramatically decrease DVT mortality, numerous complementary treatments have also been developed during the last 50 years: they include vena cava clips and surgical thrombectomy, and are intended to decrease mortality or to prevent late complications. Most of these treatments have now been abandoned, or even forgotten. In this review, we recall also the discovery and the use of vitamin K antagonists and heparin, which have constituted the mainstay of treatment for decades. We also bring some perspective to historical aspects of this disease and its treatment, notably regarding elastic compression and early mobilization, but also abandoned and complementary treatments. In these times of change regarding DVT treatment, mainly marked by the arrival of new oral anticoagulants, efforts of physicians through the ages to treat this common disease provide a beautiful example of the history of knowledge.
Notice of RetractionResearch on CSI 300 index futures arbitrage

Stock index futures is a innovative product result from the combination of stock market futures and securities markets, and the arbitrage function of stock index futures is an important factor to promote market operation efficiency. This paper explains the operation of stock index futures arbitrage, introduces several common methods to build stock portfolio and calculates arbitrage-free interval of stock index futures based on the cost of carry model. Finally according to the actual situation of securities market, discusses CSI300 index futures arbitrage with the simulation of Harvest 300 Fund, which has a certain reference value for investors.
Simulation of TaOx-based complementary resistive switches by a physics-based memristive model

Highly predictive memristive models of resistive switches are required to simulate the behavior of anti-serially connected resistive switches, so called complementary resistive switches (CRSs). As an emerging non-volatile device suited for ultra-dense memory architectures, CRS cells offer great potential also as content addressable memories. Here, we introduce a circuit model for TaOx-based resistive switches which we implemented in VerilogA. This model is capable of predicting CRS behavior correctly.
Emerging Leadership at Operational Level: The Convergence of Self-and Social Construction of Leadership

Operational level workers constitute an active and energetic workforce from which leaders emerge in organizations. Existing theories support the view that leadership is constructed by self and others. However, the process through which leaders emerge at operational level exists as an unattended agenda in leadership research. Thus, the purpose of this study is to examine and theorize how leaders emerge in a convergent process of self and social construction of leadership among operational level workers. This study is based on a comprehensive literature review followed by a case study. With the support of theories on impression construction, leadership outcomes, self-fulfilling prophecy, implicit leadership, and leader prototypes, the study identifies the emerged leadership at operational level as a convergent process of self- and social-construction at the workplace. Deploying a case from a labor-intensive industry for empirical support, the study develops eight propositions for this theorization. It finds that leadership in a large group of operational level workers emerges in a process consisting of: impressive engagement and symbolized positive performance of emerging leaders, and follower narrations and collective embracing of emerged leadership by peer followers. This theorization offers a cluster of implications for human resource managers, leader trainers, organizational line managers, and theorists while providing insights into the processes of emerging leadership at operational level. It recognizes the social processes enacted among young workers who belong to new generations, and emphasizes the significance of theorizing leadership construction processes of emerging leaders, while identifying their implications for organizations in managing new generations.
Confirmation of ProMisE: A simple, genomics‐based clinical classifier for endometrial cancer

Classification of endometrial carcinomas (ECs) by morphologic features is irreproducible and imperfectly reflects tumor biology. The authors developed the Proactive Molecular Risk Classifier for Endometrial Cancer (ProMisE), a molecular classification system based on The Cancer Genome Atlas genomic subgroups, and sought to confirm both feasibility and prognostic ability in a new, large cohort of ECs.
APACHE II, POSSUM, and ASA scores and the risk of perioperative complications in patients with oral or oropharyngeal cancer.

BACKGROUND The indications for surgical treatment of patients with head and neck cancer can be limited by the risk of perioperative complications. Prediction of outcome is important in disease stratification and the subsequent decision-making process. OBJECTIVE To assess the value of the APACHE II (Acute Physiology and Chronic Health Evaluation II) score, POSSUM (Physiological and Operative Severity Score for the Enumeration of Mortality and Morbidity), and ASA (American Society of Anesthesiologists) classification in the prediction of complications in patients with oral or oropharyngeal cancer. METHODS Five hundred thirty patients with oral or oropharyngeal carcinomas who underwent surgical treatment were evaluated using ASA, POSSUM, and APACHE II scores. The outcome measure was morbidity within 30 days. Logistic regression and receiver operating characteristic curve analyses were used to estimate the predictive ability of the scoring systems. RESULTS The overall complication rate was 58.9%. Most of the patients had local complications. The mortality was 2.6%. The results showed that APACHE II (relative risk, 1.09; P =.001) and POSSUM (relative risk, 1.09; P<.001) equally predicted perioperative complications and were superior to the ASA system (relative risk, 0.98; P =.89) (area under the curve, 0.65 for APACHE II, 0.68 for POSSUM, and 0.56 for ASA). CONCLUSIONS The POSSUM and APACHE II scores were useful in predicting perioperative morbidity for patients with oral or oropharyngeal cancer, serving as objective methods to assist the surgeon in classifying patients into risk groups with different probabilities of perioperative complications. The poorer results achieved with the ASA classification are possibly because this system is primarily based on subjective clinical judgments.
Silencing-specific methylation and single nucleotide polymorphism of hMLH1 promoter in gastric carcinomas.

AIM To investigate CpG methylation and single nucleotide polymorphism (SNP) of a specific promoter region of hMLH1 in primary gastric carcinoma. METHODS Primary gastric carcinomas (n=80), their corresponding normal mucosal samples, and gastric mucosal biopsies from normal/gastritis control patients (n=54) were used. Hypermethylation at -253 nt and -251 nt in relation with the translational start site and SNP of a silencing specific region (-339 nt-46 nt) in the hMLH1 promoter were analyzed by Bst UI-combined bisulfite assay (COBRA), denaturing high performance liquid chromatogram (DHPLC), and sequencing. RESULTS (A) The specific methylation at -253 nt and -251 nt was observed in 2 of 60 primary gastric carcinomas, but neither in all of the corresponding mucosa nor in normal/gastritis samples, by Bst UI-COBRA and DHPLC. (B) The hMLH1 promoter was methylated homogeneously in the xenograft of the primary gastric carcinoma with the methylated and unmethylated hMLH1. (C) The pattern of SNP at -93 nt of the hMLH1 promoter in 54 Chinese patients with gastric carcinoma was the same as that in the control patients: 51 % was A/G heteroalleles, 34 % and 15 % were A/A and G/G homoalleles, respectively. CONCLUSION Biallelic inactivation of hMLH1 by epigenetic silencing existed in human primary gastric carcinoma homogeneously. Hypermethylation of hMLH1 may play a role in the early stage of development of a few gastric carcinomas. The SNP at -93 nt is not related to the susceptibility of gastric carcinomas.
Calcitonin gene‐related peptide regulates gene transcription in primary afferent neurons

Although primary afferent neurons express receptors for calcitonin gene‐related peptide (CGRP), understanding of the cellular effects of these receptors is limited. We determined that CGRP receptors regulate gene transcription in primary afferent neurons through a cyclic AMP (cAMP)‐dependent pathway. CGRP increased cAMP in neonatal dorsal root ganglion (DRG) neurons in a concentration‐dependent manner that was blocked by the receptor antagonist CGRP8‐37. The response to CGRP also occurred in adult DRG cells. In contrast, CGRP did not alter the concentration of free intracellular calcium in neonatal or adult DRG neurons. Immunohistochemical data showed that one downstream effect of the cAMP signaling pathway was phosphorylation of cAMP response element binding (CREB) protein, suggesting that CGRP regulates gene expression. This interpretation was supported by evidence that CGRP increased CRE‐dependent gene transcription in neurons transiently transfected with a CRE‐luciferase DNA reporter construct. The effect of CGRP on gene transcription was inhibited by H89, myristoylated‐protein kinase A inhibitor14−22‐amide and U0126, indicating that protein kinase A and mitogen‐activated protein kinase/extracellular receptor kinase kinase are enzymes that mediate effects of CGRP on gene transcription. Therefore, CGRP receptors may regulate expression of proteins by primary afferent neurons during development and in response to tissue‐damaging stimuli.