Miracle-dz/UniFAR-FTUs huggingface dataset:
Boundary properties of penalty functions for constrained minimization

This monograph is concerned with a number of penalty-function techniques for solving a constrained-minimization or nonlinear-programming problem. These techniques are designed to take into account the constraints of a minimization problem or, since almost none of the problems arising in practice have interior minima, to approach the boundary of the constraint set in a specifically controlled manner. The monograph starts therefore with a classification of penalty functions according to their behaviour in the neighbourhood of that boundary. Appropriate convexity and differentiability conditions are imposed on the problem under consideration. Furthermore, certain uniqueness conditions involving the Jacobian matrix of the Kuhn-Tucker relations are satisfied by assumption. This implies that the problem has a unique minimum x with a unique vector -;;; of associated Lagrangian multipliers. Under these conditions the minimizing trajectory generated by a mixed penalty-function technique can be expanded in a Taylor series about (X,Ü). This provides, as an important numerical application, a basis for extrapolation towards (X,ü). The series expansion is always one in terros of the cantrolling parameter independently of the behaviour of the mixed penalty function at the boundary of the constraint set. Next, there is the intriguing question of whether some penalty functions are easier or harder to minimize than other ones. Accordingly, the condition number of the principal Hessian matrix of a penalty function is studied. It comes out that the condition number varies with the inverse of the controlling parameter, independently of the behaviour of the mixed penalty function at the boundary of the constraint set. The parametrie penalty-function techniques just named can be modified into methods which do not explicitly operate with a cantrolling parameter. They may be considered as penalty-function techniques adjusting the cantrolling parameter automatically. It is established how the ra te of convergence of these methods depends on the vector u of Lagrangjan multipliers associated with x, on the boundary properties of a penalty function, on a weight factor p attached to the objective function and on a relaxation factor(! The metbod of eentres is a remarkable exception: its rate of convergence depends on the number of active constraints at x, and on p and IJ· The computational advantages and disadvantages of the penalty-function techniques treated in the monograph are discussed. There is an appendix presenting an ALGOL 60 procedure for constrained minimization via a mixed parametrie first-order penalty function.
The In ﬂ uence of Glycemic Index on Cognitive Functioning: A Systematic Review of the Evidence 1

The impact of the rate of carbohydrate absorption, as measured by the carbohydrate ’ s glycemic index (GI) on cognitive performance, is not clear. The aim of this review was to systematically assess the relevant research studies. A systematic review of English-language articles using Medline, Cochrane Central Register of Controlled Trials, EMBASE, PsycINFO, and PsycARTICLES (up to July 2012) using the search terms “ glyc(a)emic index ” or “ glycaemic load ” combined with “ cognitive function ” or “ cognition ” or “ memory ” was carried out. Inclusion and exclusion criteria were prespecified. Eligibility of the identified studies was assessed independently by the 2 reviewers. Independent extraction of data was carried out by the 2 authors using predefined data fields. The primary outcome measure was the effect on cognitive function (CF) after the consumption of meals varying in GI. Eleven eligible studies were identified. The age range of the participants varied from 6 to 82 y old. Overall, the findings were inconsistent, with some studies showing benefits toward either the high-GI or the low-GI meal, others not finding any differences between the 2 meals, and other studies showing a positive or negative effect on performance on only some cognitive domain or domains after consumption of 1 of the 2 meals. A number of methodologic and confounding factors were identified that could explain these inconsistencies. These include the study design, the selected sample (size, age, blood glucose regulation), the timing of testing, the cognitive domain being examined, the number and type of cognitive tests used, the meals provided (composition, size), the timing of blood samples collected, as well as the possibility of bias because participants and investigators were not blinded to randomization. A low-GI meal may favor CF in adults, but the findings at present are inconclusive. On the basis of this review, it is suggested that future studies address the identified methodologic issues and some recommendations are proposed to this effect. Adv. Nutr. 5: 119 – 130, 2014.
Expression of granulocyte-macrophage colony-stimulating factor is regulated by Fli-1 transcription factor, a potential drug target

Friend leukemia virus integration 1 (Fli-1) is an ETS transcription factor and a critical regulator of inflammatory mediators, including MCP-1, CCL5, IL-6, G-CSF, CXCL2, and caspase-1. GM-CSF is a regulator of granulocyte and macrophage lineage differentiation and a key player in the pathogenesis of inflammatory/autoimmune diseases. In this study, we demonstrated that Fli-1 regulates the expression of GM-CSF in both T cells and endothelial cells. The expression of GM-CSF was significantly reduced in T cells and endothelial cells when Fli-1 was reduced. We found that Fli-1 binds directly to the GM-CSF promoter using chromatin immunoprecipitation (ChIP) assay. Transient transfection assays indicated that Fli-1 drives transcription from the GM-CSF promoter in a dose-dependent manner and mutation of the Fli-1 DNA binding domain resulted in a significant loss of transcriptional activation. Mutation of a known phosphorylation site within the Fli-1 protein led to a significant increase in GM-CSF promoter activation. Thus, direct binding to the promoter and phosphorylation are two important mechanisms behind Fli-1 driven activation of the GM-CSF with another transcription factor Sp1. Finally, we demonstrated that a low dose of a chemotherapeutic drug, camptothecin, inhibited expression of Fli-1 and reduced GM-CSF production in human T cells. These results demonstrate novel mechanisms for regulating the expression of GM-CSF and suggest that Fli-1 is a critical druggable regulator of inflammation and immunity. expression of several inflammatory mediators, including monocyte chemotactic protein 1 (MCP-1), chemokine ligand 5 (CCL5), interleukin 6 (IL-6), granulocyte colony-stimulating factor (G-CSF), chemokine ligand 2 (CXCL2), and IL-17A (26–32). Given the role of Fli-1 in autoimmune diseases (20, 33, 34) and that Ets transcription factors have been shown to modulate GM-CSF production in T cells (13, 17), the role of Fli-1 in promoting GM-CSF expression was investigated in this study. We report here that Fli-1 regulation of GM-CSF expression in T cells and endothelial cells by partial binding to the promoter, with phosphorylation of Fli-1, impacting its activation of the regulation of GM-CSF expression.
RNA polymerase alpha subunit recognizes the DNA shape of the Upstream Promoter element

We demonstrate here that the alpha subunit C-terminal domain of E. coli RNA polymerase ( α CTD) recognizes the upstream promoter (UP) DNA element via its characteristic minor groove shape and electrostatic potential. In two compositionally distinct crystallized assemblies, a pair of α CTD subunits bind in tandem to the UP element consensus A-tract of six base pairs in length (A 6 -tract), each with their arginine 265 guanidinium group inserted into the minor groove. The A 6 tract minor groove is significantly narrowed in these crystal structures, as well as in computationally predicted structures of free and bound DNA duplexes derived by Monte Carlo and molecular dynamics simulations, respectively. The negative electrostatic potential of free A 6 -tract DNA is substantially enhanced compared to generic DNA. Shortening the A-tract by one base-pair is shown to “knock out” binding of the second α CTD through widening of the minor groove. Furthermore, in computationally derived structures with arginine 265 mutated to alanine in either α CTD, either with or without the “knock-out” DNA mutation, contact with the DNA is perturbed, highlighting the importance of arginine 265 in achieving α CTD–DNA binding. These results demonstrate that the importance of DNA shape in sequence-dependent recognition of DNA by RNA polymerase is comparable to certain transcription factors.
The Impact of Parkinson ’ s Disease on Breath Pauses and Their Relationship to Speech Impairment: A Longitudinal Study

Purpose: The purposes of this longitudinal study were to (a) examine the impact of Parkinson ’ s disease (PD) progression on breath pause patterns and speech and linguistic errors and (b) determine the extent to which breath pauses and speech and linguistic errors contribute to speech impairment. Method: Eight individuals with PD and eight age- and sex-matched control participants produced a reading passage on two occasions (Time 1 and Time 2) 3 years and 7 months apart on average. Two speech-language pathologists rated the severity of speech impairment for all participants at each time. Dependent variables included the location of each breath pause relative to syntax and punctuation as well as the number of disfluencies and mazes. Results: At Time 1, there were no significant differences between the groups regarding breath pause patterns. At Time 2, individuals with PD produced significantly fewer breath pauses at major syntactic boundaries and periods as well as significantly more breath pauses at locations with no punctuation than control participants. Individuals with PD produced a significantly greater number of disfluencies than control participants at both time points. There were no significant differences between the groups in the number of mazes produced at either time point. Together, the number of mazes and the percentage of breath pauses at locations with no punctuation explained 50% of the variance associated with the ratings of severity of speech impairment. Conclusion: These results highlight the importance of targeting both respiratory physiological and cognitive – linguistic systems in order to improve speech production in individuals with PD.
Developmental Trends of Performance Monitoring Measures in 7-to 25-year-olds: Unravelling the Complex Nature of Brain Measures (EEG) dipole modeling and functional magnetic resonance imaging

This study explores how trial-to-trial latency variability contributes to the developmental trends observed in ERN amplitude found in the incorrect trials of a performance monitoring task, the visual flanker task. An Adaptive Woody Filter was used to measure and correct for the trial-to-trial latency variability of the ERN in 240 participants aged 7–25 years. Using three measures of latency variability, the degree of trial-to-trial latency variability was shown to decrease as the age of the participants increased from 7 to 25 years. The success of the Adaptive Woody Filter technique to remove the trial-to-trial latency variability was demonstrated in a straightforward manner by the significant changes in the measures of fit and intra-individual variability obtained before and after applying the filter. After the latency variability effects were removed and adjusted averaged ERPs were obtained, a more subtle but significant nonlinear developmental trend was still found in the amplitude of the ERN component. of in the temporal consistency the average ERN amplitude in measures of phase variability for the underlying theta oscillations across trials. Their study did not include procedures for correcting the ERPs to remove the latency variability from the averaged ERPs and, then obtain a direct measure of the ERN amplitude after correction. Interestingly though, signal strength measured as the average spectral power of the theta band from 0 to 100 ms did not correlate with temporal consistency (i.e., phase coherence values) suggesting that power and phase coherence each may contribute independently to ERN amplitude. Thus, DuPuis, et al. only measured the phase coherence aspect of the ERN signal and did not accordingly adjust the signal strength or amplitude of the ERN typically measured from averaged ERPs. These findings suggest that further examination is still needed to determine how intra-individual variability in latency affects the developmental trend of the ERN amplitude from young children to adulthood.
Separation of (cid:1) -Opioid Receptor Desensitization and Internalization: Endogenous Receptors in Primary Neuronal Cultures

A close relationship between desensitization and internalization of (cid:1) -opioid receptors (MORs) has been proposed based on differential actions of series of agonists. The role that these two processes have in the development of tolerance and dependence to opioids has been a controversial subject that has been studied in a variety of model systems. Here, we examine desensitization and internalization of endogenous MORs simultaneously in primary cultures of locus ceruleus neurons using fluorescently tagged peptide agonists. With the use of two fluorescent opioid peptides, dermorphin-Bodipy Texas Red and dermorphin-Alexa594 (Derm-A594), desensitization was measured electrophysiologically and trafficking was followed by the accumulation of intracellular fluorescent puncta. Blocking endocytosis with concanavalin A eliminated the accumulation of fluorescent puncta but desensitization induced by Derm-A594 was unaffected. Likewise,aftertreatmentwithconcanavalinA,therewasnochangeineitherdesensitizationorrecoveryfromdesensitizationinducedby[Met] 5 enkephalin. The results demonstrate that desensitization and the recovery from desensitization are not dependent on receptor internalization and suggest that the activity of endogenous MORs in primary neurons can be modulated at the level of the plasma membrane. Im-ageJ(NationalInstitutesofHealth,Bethesda,MD),andAdobe(SanJose,CA)Photoshop6.0. Two-photon microscopy and intracellular recording . Simultaneous recording of membrane potential and imaging was done with an electrophysiological setup equipped with a custom-built two-photon microscope. Intracellular recordings of membrane potential were done with glass electrodes filled with KCl (300 m M ) having a resistance of 100–200 M (cid:1) . Experiments with a combination of intracellular recordings and imaging were all done at 35°C. Data collection was done with Power Lab (Chart version 4.1). Drugs were applied by perfusion. Images were acquired using Scan Image software (Pologruto et al., 2003). The Ti-sapphire laser was set at 810 nm. The emission filter sets were 510 nm for EGFP and 600 nm for Derm-A594. Cells were imaged with a z-series taken through the cell at 0.5 (cid:1) m intervals, averaging two frames per image. Data were processed off-line using Image J and Adobe Photoshop 6.0.
Comparison of clinical characteristics in patients with coronavirus disease and inﬂ uenza A in Guangzhou, China

BACKGROUND: This study aims to compare the epidemiological, clinical and laboratory characteristics between patients with coronavirus disease (COVID-19) and influenza A (H1N1), and to develop a diﬀ erentiating model and a simple scoring system. METHODS: We retrospectively analyzed the data from patients with COVID-19 and H1N1. The logistic regression model based on clinical and laboratory characteristics was constructed to distinguish COVID-19 from H1N1. Scores were assigned to each of independent discrimination factors based on their odds ratios. The performance of the prediction model and scoring system was assessed. RESULTS: A total of 236 patients were recruited, including 20 COVID-19 patients and 216 H1N1 patients. Logistic regression revealed that age >34 years, temperature ≤37.5 °C, no sputum or myalgia, lymphocyte ratio ≥20% and creatine kinase-myocardial band isoenzyme (CK-MB) >9.7 U/L were independent diﬀ erentiating factors for COVID-19. The area under curves (AUCs) of the prediction model and scoring system in diﬀ erentiating COVID-19 from H1N1 were 0.988 and 0.962, respectively. CONCLUSIONS: There are certain differences in clinical and laboratory features between patients with COVID-19 and H1N1. The simple scoring system may be a useful tool for the early identiﬁ cation of COVID-19 patients from H1N1 patients. and kinase-myocardial band isoenzyme (CK-MB, was lower in COVID-19 patients than in H1N1 patients.
Modeling Regulation of Cardiac K ATP and L-type Ca 2 1 Currents by ATP, ADP, and Mg 2 1

Changes in cytosolic free Mg 2 1 and adenosine nucleotide phosphates affect cardiac excitability and contractility. To investigate how modulation by Mg 2 1 , ATP, and ADP of K ATP and L-type Ca 2 1 channels inﬂuences excitation-contraction coupling, we incorporated equations for intracellular ATP and MgADP regulation of the K ATP current and MgATP regulation of the L-type Ca 2 1 current in an ionic-metabolic model of the canine ventricular myocyte. The new model: 1), quantitatively reproduces a dose-response relationship for the effects of changes in ATP on K ATP current, 2), simulates effects of ADP in modulating ATP sensitivity of K ATP channel, 3), predicts activation of Ca 2 1 current during rapid increase in MgATP, and 4), demonstrates that decreased ATP/ADP ratio with normal total Mg 2 1 or increased free Mg 2 1 with normal ATP and ADP activate K ATP current, shorten action potential, and alter ionic currents and intracellular Ca 2 1 signals. The model predictions are in agreement with experimental data measured under normal and a variety of pathological conditions.
Treatment with ,-adrenoceptor blockers reduces plasma melatonin concentration

In treated hypertensive patients plasma melatonin levels were lower in subjects receiving ,B-adrenoceptor blockers than those treated with diuretics. Melatonin concentrations in middle-aged and young control subjects were similar to each other and to those of the diuretic-treated patients. The results suggest that treatment with P-adrenoceptor blockers causes a persistent reduction in plasma melatonin but it is unclear if this finding has clinical implications.
Augmented Lipocalin-2 Is Associated with Chronic Obstructive Pulmonary Disease and Counteracts Lung Adenocarcinoma Development

Rationale: Early pathogenesis of lung adenocarcinoma (LUAD) remains largely unknown. We found that, relative to wild-type littermates, the innate immunomodulator Lcn2 (lipocalin-2) was increased in normal airways from mice with knockout of the airway lineage gene Gprc5a ( Gprc5a 2 / 2 ) and that are prone to developing in ﬂ ammation and LUAD. Yet, the role of LCN2 in lung in ﬂ ammation and LUAD is poorly understood. Delineate the role of Lcn2 induction in LUAD pathogenesis. Methods: Normal airway brushings, uninvolved lung tissues, and tumors from Gprc5a 2 / 2 mice before and after tobacco carcinogen exposure were analyzed by RNA sequencing. LCN2 mRNA was analyzed in public and in-house data sets of LUAD, lung squamous cancer (LUSC), chronic obstructive pulmonary disease (COPD), and LUAD/LUSC with COPD. LCN2 protein was immunohistochemically analyzed in a tissue microarray of 510 tumors. Temporal lung tumor development, gene expression programs, and host immune responses were compared between Gprc5a 2 / 2 and Gprc5a 2 / 2 / Lcn2 2 / 2 littermates. Measurements and Main Results: Lcn2 was progressively elevated during LUAD development and positively correlated with proin ﬂ ammatory cytokines and in ﬂ ammation gene sets. LCN2 was distinctively elevated in human LUADs, but not in LUSCs, relative to normal lungs and was associated with COPD among smokers and patients with LUAD. Relative to Gprc5a 2 / 2 mice, Gprc5a 2 / 2 / Lcn2 2 / 2 littermates exhibited signi ﬁ cantly increased lung tumor development concomitant with reduced T-cell abundance (CD4 1 ) and richness, attenuated antitumor immune gene programs, and increased immune cell expression of protumor in ﬂ ammatory cytokines. COPD-associated LUAD and counteracts LUAD development in vivo by maintaining antitumor immunity. was strongly associated with COPD among both lung cancer – free smokers and patients with LUAD. Deletion of Lcn2 in Gprc5a 2 / 2 mice increased LUAD development as well as elevated protumor in ﬂ ammatory signaling and reduced antitumor immunity. Our ﬁ ndings suggest that elevated LCN2 is a molecular feature of COPD and antagonizes LUAD development. Some of the results of this study have been previously reported in the form of an abstract (14).
Return-to-Duty Toolkit: Assessments and Tasks for Determining Military Functional Performance Following Neurosensory Injury

Abstract : One of the most challenging decisions facing military health care providers is if and when a previously wounded warfighter is fit for return to duty (RTD). A variety of assessments is available to decision makers to assist in making informed and accurate determinations of RTD status. The purpose of this Toolkit is to be a reference guide and resource containing currently available assessments for use by healthcare providers who make RTD and fitness-for-[military] duty (FFD) decisions. Depending on the nature of the original injury, the Toolkit is intended to provide a tailorable selection of assessments from which to measure progress toward FFD and from which to make final RTD determinations. While many of the assessments are well known and well validated, others contained in this reference document possess various states of trial and validation. Some of the assessments included here are considered good clinical practice, while others should more appropriately be viewed as clinical options. The Toolkit includes several assessments that were recently developed and are based on military functional tasks.
Shared molecular genetic risk of alcohol dependence and PTSD

Alcohol use disorder (AUD) and posttraumatic stress disorder (PTSD) frequently co-occur, highlighting the importance of understanding the etiology of these comorbid conditions. While AUD and PTSD are moderately heritable with modest overlap in genetic risk as estimated from family studies, there has been a paucity of work using molecular genetic data to estimate shared genetic effects on these conditions. This study used large-scale genome-wide molecular data to examine shared genetic risk for PTSD and AUD, specifically alcohol dependence (AD), through cross-trait LD score regression (LDSC/LDSR). Summary statistics came from the Psychiatric Genomics Consortium (PGC) PTSD workgroup Freeze 2 (PGC2) European (EA) participants (N=174,659), and AD summary statistics in EA participants (N=38,686) came from the PGC Substance Use Disorders (SUD) workgroup. We performed LDSC to estimate genetic correlation between AD and PTSD using HapMap3 variants and LD scores from the 1000 Genomes project. A moderate, significant correlation was observed between AD and PTSD (r g =.35, p=.02), with sex differences identified through stratified analyses. Our results are the first to demonstrate evidence of a shared molecular genetic etiology for AD and PTSD. Further research is needed to better understand possible sex differences in shared heritability and extend these results to additional populations.