Miracle-dz/UniFAR-FTUs huggingface dataset:
Mucus hypersecretion in asthma: intracellular signalling pathways as targets for pharmacotherapy

Purpose of reviewAirway mucus hypersecretion is a pathophysiological feature of asthma and, in many patients, contributes to morbidity and mortality. Although current pharmacotherapy is effective in patients with stable disease, severe asthma is poorly treated, and there is no specific treatment for the hypersecretion. Consequently, identification of potential targets for pharmacotherapy of hypersecretion in asthma is warranted. This review identifies intracellular signalling pathways as rational targets for treatment of excessive airway mucus production. Recent findingsThe inflammatory mediators and the associated intracellular signalling pathways underlying development of goblet cell hyperplasia, an index of mucus hypersecretion, are becoming ever clearer, and include T-helper type 2 (Th2) cytokines, in particular interleukin (IL)-9 and IL-13, as well as IL-1β, tumour necrosis factor (TNF)-α and cyclooxygenase (COX)-2. IL-9 may act predominantly via calcium-activated chloride channels (CLCAs), IL-13 via STAT-6 and FOXA2, TNF-α via nuclear factor (NF)-κB, and IL-1β via COX-2. Epidermal growth factor receptor (EGF-R) and FOXA2 appear to be convergent pathways for a number of mediator signals, with EGF-R up-regulated in the airways of asthmatic patients. SummaryAlthough many potential intracellular signalling pathways have been identified as possible targets for pharmacotherapy of airway mucus hypersecretion in asthma, the EGF-R and Th2 cytokine pathways offer the greatest potential for inhibition of excessive mucus production.
On the Relationship Between Change Coupling and Software Defects

Change coupling is the implicit relationship between two or more software artifacts that have been observed to frequently change together during the evolution of a software system. Researchers have studied this dependency and have observed that it points to design issues such as architectural decay. It is still unknown whether change coupling correlates with a tangible effect of design issues, i.e., software defects.In this paper we analyze the relationship between change coupling and software defects on three large software systems. We investigate whether change coupling correlates with defects, and if the performance of bug prediction models based on software metrics can be improved with change coupling information.
The Fast Cauchy Transform and Faster Robust Linear Regression

@ are a coreset for the problem, consisting of sampled and rescaled rows of A and b; and s is independent of n and polynomial in d. Our results improve on the best previous algorithms when n G d, for all p e [1, ∞) except p = 2; in particular, they improve the O(nd1.376+) running time of Sohler and Woodruff (STOC, 2011) for p = 1, that uses asymptotically fast matrix multiplication, and the O(nd5 log n) time of Dasgupta et al. (SICOMP, 2009) for general p, that uses ellipsoidal rounding. We also provide a suite of improved results for finding well-conditioned bases via ellipsoidal rounding, illustrating tradeoffs between running time and conditioning quality, including a one-pass conditioning algorithm for general ep problems. To complement this theory, we provide a detailed empirical evaluation of implementations of our algorithms for p = 1, comparing them with several related algorithms. Among other things, our empirical results clearly show that, in the asymptotic regime, the theory is a very good guide to the practical performance of these algorithms. Our algorithms use our faster constructions of well-conditioned bases for ep spaces and, for p = 1, a fast subspace embedding of independent interest that we call the Fast Cauchy Transform: a matrix Π:
Discrete-time switched systems, set-theoretic analysis and quasi-quadratic Lyapunov functions

The article establishes a constructive link between two approaches for analyzing the stability of discrete-time switched linear systems with arbitrary switching. The first approach is based on quasi-quadratic Lyapunov functions while the second one concerns a set-theoretic analysis of switched systems. An LMIs based procedure for deriving quasi-quadratic Lyapunov functions from the set-theoretic analysis is obtained. The approach may be used for constructing positively invariant sets for cases of switched discrete-time linear systems that are not quadratically stable.
A NOTE ON A-CONTRACTIONS AND COMMON FIXED POINTS

This article represents an appreciable generalization of the recent results of M. Akram et al which extended several results of B. Ahmad and F. U. Rehman, N. Shioji et al and Z. Chuanyi to the A-contractions. 2000 Mathematics Subject Classification: 47H10, 54H25.
Detecting infection and inflammation with technetium-99m-labeled Stealth liposomes.

UNLABELLED The performance of 99mTc Stealth liposomes was investigated in various rat models. METHODS Preformed polyethyleneglycol-containing liposomes with encapsulated reduced glutathione, were radiolabeled using the lipophilic 99mTc-HMPAO. The labeled liposomes were intravenously administered to rats with focal S. aureus or E. coli infection, or turpentine-induced inflammation. For comparison, Tc-99m-nanocolloid- and 99mTc-labeled nonspecific IgG were tested. In rats with Pneumocystis carinii pneumonia (PCP), Tc-99m-liposomes were directly compared to In-111 labeled nonspecific IgG. RESULTS Technetium-99m-liposomes accumulated in the infectious and inflammatory muscle foci over 24 hr (0.59% injected dose per gram tissue (%ID/g) for S. aureus; 1.18 %ID/g for turpentine). Abscess-to-muscle ratios increased to values as high as 24.0, 41.7 and 44.5 for the respective models at 24 hr postinjection. Technetium-99m-liposomes visualized the foci as early as 1 hr postinjection. Technetium-99m-IgG visualized S. aureus infection, but abscess-to-muscle ratios and abscess uptake at the later time points were significantly lower. Technetium-99m-nanocolloid failed to visualize any of the muscle foci. In PCP however, 99mTc-liposomes did not show preferential localization in the infection. The control agent 111In-IgG showed a significant, two-fold increase in lung uptake. CONCLUSION Technetium-99m-Stealth liposomes preferentially accumulated in abscesses, leading to very high target-to-nontarget ratios. This property appears to be related to a process based on uptake of long-circulating particles. In a specific type of infection, i.c. PCP, 99mTc-liposomes did not accumulate in diseased lung tissue, thus mimicking the in vivo behavior of labeled leukocytes.
IDENTIFICATION OF ASPERGILLUS SPECIES USING MORPHOLOGICAL CHARACTERISTICS

Objectives: Although molecular methods continue to improve and become more rapidly available, microscopy and culture remain commonly used and essential tools for identification of Aspergillus spp. In this study we emphasize on morphological methods including; macroscopic and microscopic characteristics for identification of Aspergillus species isolated from environmental and clinical specimens. Methodology: We used four differential media: czapek dox agar (CZ), czapek yeast agar (CYA), malt extract agar (MEA), and czapek yeast 20% sucrose agar. Morphological features of colonies on above culture media as well as microscopically characteristics for the major strains were studied and then compared with those of standard Aspergillus strains. Our major subjects were Iranian Aspergillus strains isolated from clinical and environmental specimens. Standard Aspergillus strains for study development included; A. fumigatus, (JCM 10253), A. flavus (JCM 2061), A. niger (JCM 10254), A. nidulans (JCM 02728), A. tereus (JCM 10227). Morphological features of Aspergillus cultures were studied, the major and remarkable macroscopic features in species identification were the colony diameter, color (conidia and reverse), exudates and colony texture. Microscopic characteristics for the identification were conidial heads, stipes, color and length vesicles shape and seriation, metula covering, conidia size, shape and roughness also colony features including diameter after 7 days, color of conidia, mycelia, exudates and reverse, colony texture and shape. Finally we compared the morphological characteristics of tested Aspergillus isolates with those of the standard species Results: Aspergillus isolates were identified in the level of species using the differential culture media. A total of 205 Aspergillus isolates studied included: 153(75%) environmental Aspergilli and 52 (25%) clinical isolates. Within 11 Aspergillus species identified, A.flavus (55%), A.niger (31.7%) and A. fumigatus (8.7%) were the most common Aspergillus isolates from all of the specimens. Conclusion: In our view morphological method using the differential media is the most reliable and sensitive assay to identify more medically important Aspergillus species.
Learning to Extract Signature and Reply Lines from Email

We describe methods for automatically identifying signature blocks and reply lines in plain-text email messages. This analysis has many potential applications, such as preprocessing email for text-to-speech systems; anonymization of email corpora; improving automatic content-based mail classifiers; and email threading. Our method is based on applying machine learning methods to a sequential representation of an email message, in which each email is represented as a sequence of lines, and each line is represented as a set of features. We compare several state-of-the-art sequential and non-sequential machine learning algorithms on different feature sets, and present experimental results showing that the presence of a signature block in a message can be detected with accuracy higher than 97%; that signature block lines can be identified with accuracy higher than 99%; and that signature block and reply lines can be simultaneously identified with accuracy of higher than 98%.
Ambient Air Pollution and Lipoprotein-Associated Phospholipase A2 in Survivors of Myocardial Infarction

Background: Increasing evidence suggests a proatherogenic role for lipoprotein-associated phospholipase A2 (Lp-PLA2). A meta-analysis of published cohorts has shown that Lp-PLA2 is an independent predictor of coronary heart disease events and stroke. Objective: In this study, we investigated whether the association between air pollution and cardiovascular disease might be partly explained by increased Lp-PLA2 mass in response to exposure. Methods: A prospective longitudinal study of 200 patients who had had a myocardial infarction was performed in Augsburg, Germany. Up to six repeated clinical examinations were scheduled every 4–6 weeks between May 2003 and March 2004. Supplementary to the multicenter AIRGENE protocol, we assessed repeated plasma Lp-PLA2 concentrations. Air pollution data from a fixed monitoring site representing urban background concentrations were collected. We measured hourly means of particle mass [particulate matter (PM) < 10 µm (PM10) and PM < 2.5 µm (PM2.5) in aerodynamic diameter] and particle number concentrations (PNCs), as well as the gaseous air pollutants carbon monoxide (CO), sulfur dioxide (SO2), ozone (O3), nitric oxide (NO), and nitrogen dioxide (NO2). Data were analyzed using mixed models with random patient effects. Results: Lp-PLA2 showed a positive association with PM10, PM2.5, and PNCs, as well as with CO, NO2, NO, and SO2 4–5 days before blood withdrawal (lag 4–5). A positive association with O3 was much more immediate (lag 0). However, inverse associations with some pollutants were evident at shorter time lags. Conclusion: These preliminary findings should be replicated in other study populations because they suggest that the accumulation of acute and subacute effects or the chronic exposure to ambient particulate and gaseous air pollution may result in the promotion of atherosclerosis, mediated, at least in part, by increased levels of Lp-PLA2.
Apomorphine can sustain the long-duration response to l-DOPA in fluctuating PD

Article abstract The authors investigated the ability of daytime infusions of apomorphine, a D-1 and D-2 dopamine agonist, to sustain the long-duration response (LDR) in seven subjects with fluctuating PD in whom l-DOPA was discontinued for 3 days. Apomorphine maintained the LDR to the extent that it kept the subjects “on” during the day. This observation suggests that the LDR can be a postsynaptic effect, independent of dopamine storage.
Low Dose, Low Cost Estradiol Pellets Can Support MCF-7 Tumour Growth in Nude Mice without Bladder Symptoms

MCF-7 cells are a slow growing estrogen receptor (ER) positive human breast cancer cell line that is commonly used to model estrogen responsive breast cancer cell growth in-vitro and tumour growth in-vivo. These tumours require estrogen supplementation, and in-vivo doses of between 0.72mg and 2mg estradiol pellets are commonly implanted in the dorsal flank of ovariectomised, immunocompromised mice. We wanted to grow MCF-7 tumours in immunocompromised mice without the need to be ovariectomised. When we treated immunocompromised mice with 0.72mg pellets to induce MCF7 tumour growth, the mice developed urosepsis. We have now shown that lower doses of estradiol pellets, 0.3mg and 0.5mg, induce elevated serum estrogen levels and maintain tumour growth, without causing urosepsis. Supplementation for only one week did not support sustained MCF7 tumour growth. In conclusion, 0.3mg and 0.5mg silastic pellets can be used to stimulate ER+ breast cancer growth in ovary-intact, immune compromised mice.
Experience Rating, Work Injuries and Benefit Costs : Some New Evidence

In 1986, British Columbia’s Workers’ Compensation Board introduced an experience rating program that provided a modest financial incentive for employers to reduce the costs of claims. Using a comprehensive panel data set, we find that claims frequency for health care only and short-term disability claims was reduced following the introduction of experience rating. The introduction of the program did not affect costs for most claim types, except for health care only claims.
Progranulin expression in brain tissue and cerebrospinal fluid levels in multiple sclerosis

Background: Progranulin (PGRN) is a fundamental neurotrophic factor, and is also involved in inflammation and wound repair. PGRN may have pro- or anti-inflammatory properties, depending upon proteolysis of the anti-inflammatory parent PGRN protein and the generation of pro-inflammatory granulin peptides. Objectives: Our objectives were as follows: (1) to evaluate the presence and distribution of PGRN in multiple sclerosis (MS) brain tissue, correlating it with demyelination and inflammation; (2) to evaluate cerebrospinal fluid (CSF) PGRN concentrations in patients with MS and controls, in relationship to the clinical features of the disease. Methods: Our study involved the following: (1) neuropathological study of PGRN on post-mortem tissue of 19 MS and six control brains; (2) evaluation of PGRN CSF concentration in 40 MS patients, 15 non-inflammatory controls and five inflammatory controls (viral encephalitis). Results: In active demyelinating lesions, PGRN was expressed on macrophages/microglia. In the normal-appearing white matter (NAWM), expression of PGRN was observed on activated microglia. PGRN was expressed by neurons and microglia in cortical lesions and in normal-appearing cortex. No expression of PGRN was observed in controls, except on neurons. PGRN CSF concentrations were significantly higher in patients with relapsing–remitting MS during relapses and in progressive MS patients, compared with relapsing–remitting MS patients during remissions and with non-inflammatory controls. Conclusions: PGRN is strongly expressed in MS brains, by macrophages/microglia in active lesions, and by activated microglia in the NAWM; PGRN CSF concentrations in MS are correspondingly increased in conditions of enhanced macrophage/microglia activation, such as during relapses and in progressive MS.
Effects of roughage source and concentration on intake and performance by finishing heifers.

Three experiments were conducted to evaluate the effects of roughage source and concentration on intake and performance by finishing heifers. In Exp. 1, 12 medium-framed beef heifers (average BW = 389 kg) were used in three simultaneous 4 x 4 Latin square intake trials to evaluate the effects of dietary NDF supply from alfalfa hay, sudan hay, wheat straw, or cottonseed hulls fed in each Latin square at 5, 10, or 15% of dietary DM. Within each roughage concentration, roughage NDF accounted for the majority of variation in NEg intake/kg of BW0.75 among the roughage sources. Averaged across roughage concentrations, NEg intake/kg of BW0.75 tended to be greater (P < 0.10) when heifers were fed cottonseed hulls, sudan hay, or wheat straw than when they were fed alfalfa. In Exp. 2, six medium-framed beef heifers (average BW = 273 kg) were used in a 3 x 3 Latin square design to determine whether diets containing 10% (DM basis) alfalfa, cottonseed hulls, or sudan silage differed in eating rate. Average DM eating rates did not differ (P > 0.10) among roughage sources, which we interpreted to suggest that 90% concentrate diets containing alfalfa, cottonseed hulls, and sudan silage do not differ in the amount of chewing required during eating. In Exp. 3, 105 medium-framed beef heifers (average BW = 275 kg) were used in a 140-d finishing trial to evaluate three methods of dietary roughage exchange. Alfalfa at 12.5% of the dietary DM (ALF12.5) was used as a standard, and cottonseed hulls and sudan silage were each fed at three different levels: exchanged with ALF12.5 on an equal percentage DM basis, an equal NDF basis, or an equal NDF basis, where only NDF from particles larger than 2.36 mm (retained NDF) were considered to contribute to the NDF. No differences (P > 0.10) in ADG, DMI, gain:feed ratio, or NEg intake/kg of BW0.75 were detected between alfalfa and cottonseed hulls exchanged on an equal NDF basis. For sudan silage, exchanging with ALF12.5 on an equal retained NDF basis resulted in no differences (P > 0.10) in ADG, DMI, or NEg intake/kg of BW0.75. These data provide a preliminary indication that depending on the roughage sources evaluated, roughage NDF content and(or) roughage NDF from particles larger than 2.36 mm might provide a useful index of roughage value in high-concentrate finishing diets.
Robustness of polarization-mode-dispersion compensation in the presence of polarization-dependent loss

The robustness of polarization-mode dispersion (PMD) compensation utilizing radio-frequency feedback in the presence of polarization-dependent loss (PDL) is investigated using a closed-loop dynamic model. Simulations using mean PMD of 30% of the bit period show that mean PDL of up to 2 dB increases the Q-penalty after PMD compensation by less than 0.1 dB. We find that the compensator can become trapped in secondary optima at high PDL, incurring significant additional penalty.
Anti-HIV Drug Development Through Computational Methods

Although highly active antiretroviral therapy (HAART) is effective in controlling the progression of AIDS, the emergence of drug-resistant strains increases the difficulty of successful treatment of patients with HIV infection. Increasing numbers of patients are facing the dilemma that comes with the running out of drug combinations for HAART. Computational methods play a key role in anti-HIV drug development. A substantial number of studies have been performed in anti-HIV drug development using various computational methods, such as virtual screening, QSAR, molecular docking, and homology modeling, etc. In this review, we summarize recent advances in the application of computational methods to anti-HIV drug development for five key targets as follows: reverse transcriptase, protease, integrase, CCR5, and CXCR4. We hope that this review will stimulate researchers from multiple disciplines to consider computational methods in the anti-HIV drug development process.
Sustained Loss of a Neoplastic Phenotype by Brief Inactivation of MYC

Pharmacological inactivation of oncogenes is being investigated as a possible therapeutic strategy for cancer. One potential drawback is that cessation of such therapy may allow reactivation of the oncogene and tumor regrowth. We used a conditional transgenic mouse model forMYC-induced tumorigenesis to demonstrate that brief inactivation of MYC results in the sustained regression of tumors and the differentiation of osteogenic sarcoma cells into mature osteocytes. Subsequent reactivation of MYC did not restore the cells' malignant properties but instead induced apoptosis. Thus, brief MYC inactivation appears to cause epigenetic changes in tumor cells that render them insensitive to MYC-induced tumorigenesis. These results raise the possibility that transient inactivation of MYC may be an effective therapy for certain cancers.
SOSYAL BİLGİLER ADAY ÖĞRETMENLERİNİN SINIF İÇİ ÖĞRETİM YETERLİKLERİ

Bu calisma, egitim fakultelerinde ogrenim goren ogretmen adaylarinin sinif ici ogretim yeterliklerini ne duzeyde kazanabildiklerini belirlemek amaciyla yapilmistir. Arastirma tarama modelinde yurutulmustur. Aday ogretmenlerin sinif ici ogretim yeterlikleri betimlenmeye calisilmistir. Arastirmanin verileri, arastirmaci tarafindan gelistirilen gozlem formu ile toplanmistir. Gozlem faaliyeti, Sosyal Bilgiler Ogretmenligi Programi son sinif ogrencileri tarafindan yapilmistir. Veriler uzerinde baslica, aritmetik ortalama, korelasyon testi, anova testi ve Scheffe testi uygulanmistir. Arastirma sonunda, aday ogretmenlerin sinif ici ogretim becerilerinde belirli yetersizliklerinin oldugu belirlenmistir. Ayrica, belirlenen arastirma alt boyutlari arasinda anlamli ve pozitif iliskilerin bulundugu gorulmustur. Ek olarak, sinif duzeyi yukseldikce ogretim becerilerini gosterme yeterliklerinin de iyilestigi belirlenmistir. Bu sonuclara gore oneriler sunulmustur. Anahtar Sozcukler: Sosyal bilgiler, aday ogretmen, ogretim becerileri, sinif.
Potassium and fatigue: the pros and cons.

A general finding is that muscle activity leads to potassium fluxes across the muscle membrane as well as to muscle fatigue, defined as a reduction in the force-generating capacity of the muscle. However, much controversy exists regarding the causal role of potassium in fatigue development. The experimental model used is decisive in this context, e.g. whether we study intact in vivo organs in situ with voluntary contractions and reflex feedback for cardiorespiratory regulation, or whether we study in vitro isolated muscles or cells-or even skinned fibres. In the latter models, clear evidence has been presented that Ca2+ is the variable significant for force development and that K+ may be ignored. However, in the in situ situation the limiting link in the chain leading to muscle contraction may be one preventing the Ca2+ release from taking place. The sites are the triads, T-tubules, and the surface membrane. The function of the latter two regarding action potential amplitude and propagation depends on [K+] gradients. Again, conflicting results exist regarding the electrophysiological changes and [K+] in fatigue. The activity pattern must then be taken into consideration. During high-intensity (high-frequency) activity the increased interstitial [K+] has been demonstrated to relate to fatigue, while in low-intensity fatiguing protocols, the T-tubule may be the limiting site. This fits with the concept of interstitial [K+] playing an essential role as a regulatory feedback mechanism, e.g. adjusting muscle blood flow to the metabolic load during muscle activity.