However, cell line infections do not currently mimic ex vivo neut

However, cell line infections do not currently mimic ex vivo neutrophil p53 inhibitor infection characteristics. To understand these discrepancies, we compared infection of cell lines to ex vivo human neutrophils and differentiated hematopoietic stem cells with regard to infection capacity, oxidative burst, host defense gene expression,

and differentiation. Using established methods, marked ex vivo neutrophil infection heterogeneity was observed at 24-48h necessitating cell sorting to obtain homogeneously infected cells at levels observed in vivo. Moreover, gene expression of infected cell lines differed markedly from the prior standard of unsorted infected neutrophils. Differentiated HL-60 cells sustained similar infection levels to neutrophils in vivo and closely mimicked functional and transcriptional changes of sorted infected neutrophils. Thus, care must be exercised using ex vivo neutrophils for A.phagocytophilum infection studies because a major determinant of transcriptional Selleckchem EX 527 and functional changes among all cells was the intracellular bacteria quantity. Furthermore, comparisons of ex vivo neutrophils and the surrogate

HL-60 cell model allowed the determination that specific cellular functions and transcriptional programs are targeted by the bacterium without significantly modifying differentiation.”
“Individuals with low socioeconomic position have high rates of depression; however, it is not clear whether this reflects higher incidence or longer persistence of disorder. Past research focused on high-risk samples, and risk factors of long-term depression in the population are less well known. Our aim was to test the hypothesis that socioeconomic position predicts depression trajectory over 13 years of follow-up in a community sample. We studied 12 650 individuals participating in the French GAZEL study. Depression was assessed by the Center for Epidemiological Studies-Depression scale in 1996, 1999, 2002, 2005 and 2008. These five assessments served to estimate longitudinal depression trajectories (no depression, decreasing depression, intermediate/increasing depression, persistent depression).

Socioeconomic position was measured by occupational grade. Covariates included year of birth, marital status, Luminespib supplier tobacco smoking, alcohol consumption, body mass index, negative life events and preexisting psychological and non-psychological health problems. Data were analyzed using multinomial regression, separately in men and women. Overall, participants in intermediate and low occupational grades were significantly more likely than those in high grades to have an unfavorable depression trajectory and to experience persistent depression (age-adjusted ORs: respectively 1.40, 95% confidence interval (CI) 1.16-1.70 and 2.65, 95% CI 2.04-3.45 in men, 2.48, 95% CI 1.36-4.54 and 4.53, 95% CI 2.38-8.63 in women). In multivariate models, the socioeconomic gradient in long-term depression decreased by 21-59% in men and women.


“The virus surface protein neuraminidase (NA) is a main su


“The virus surface protein neuraminidase (NA) is a main subtype-specific antigen in influenza type A viruses. this website Neuraminidase functions as an enzyme to break the bonds between hemagglutinin (HA) and sialic acid to release newly formed viruses from infected cells. In this study, NA genes from the H3N2 subtype virus were sequenced and NA proteins were screened for B-cell epitopes and assessed based on immunoinformatics. Based on this information, three peptides ES8, RR9, and WK7 (covering amino

acid residues 221-228, 292-300, and 383-389, respectively) of the NA protein were selected and synthesized artificially. These peptides were used to immunize New Zealand rabbits subcutaneously to raise antisera. Results showed that these three peptides were capable of eliciting antibodies against H3N2 viruses in a specific and sensitive manner, detected in vitro by enzyme-linked immunosorbent assay. Furthermore, hemadsorption anti-releasing effects occurred in three antisera mixtures at a dilution of 1:40. Alignment using database software showed that amino acid residues in these three epitope peptides were substituted at specific sites in all the NAs sequenced in this study. We suggest that these NA epitope peptides might be used in conjunction with HA proteins as vaccine SBI-0206965 inhibitor antigens.”
“The FT-IR (4000-450 cm(-1))

and FT-Raman spectra (3500-100 cm(-1)) of benzophenone 2,4-dicarboxylic acid (2,4-BDA) have been recorded

in the condensed state. Density functional theory calculation with B3LYP/6-31G(d,p) basis set have been used to determine ground state molecular geometries (bond lengths Selleckchem VX-770 and bond angles), harmonic vibrational frequencies, infrared intensities, Raman activities and bonding features of the title compounds. The assignments of the vibrational spectra have been carried out with the help of normal co-ordinate analysis (NCA) following the scaled quantum mechanical force field (SQMFF) methodology. The first order hyperpolarizability (beta 0) and related properties (beta, alpha 0 and Delta alpha) of 2,4-BDA is calculated using HF/6-31G(d,p) method on the finite-field approach. The stability of molecule has been analyzed by using NBO analysis. The calculated first hyperpolarizability shows that the molecule is an attractive molecule for future applications in non-linear optics. The calculated HOMO and LUMO energies show that charge transfer occurs within these molecules. Mulliken population analysis on atomic charges is also calculated. Because of vibrational analyses, the thermodynamic properties of the title compound at different temperatures have been calculated. Finally, the UV-vis spectra and electronic absorption properties were explained and illustrated from the frontier molecular orbitals. (C) 2011 Elsevier B.V. All rights reserved.

6 mm (4 5-6); C = 5 5 mm (range 4 5-6) (p > 0 05) The UFML wa

6 mm (4.5-6); C = 5.5 mm (range 4.5-6) (p > 0.05). The UFML was: P = 189.7 N (114-336); C = 229.9 N (143-365) (p = 0.029).

Tendon tensioning with 80 N for 10 min produced 3% average elongation. These could be beneficial check details in ACLR since tendon tensioning decreases elongation of the graft after fixation. Regardless, tendon tensioning is not innocuous since it diminishes their resistance when continuously stressed until complete failure occurs. (C) 2009 Elsevier B.V. All rights reserved.”
“[Purpose] The present study was intended to examine the effect of excessive use of smartphones on the carpal tunnel and median nerve in the wrist. [Subjects and Methods] A questionnaire was used

to determine the degree of addiction to smartphones in 125 normal adults who used smartphones; then, ultrasonography of the median nerve, Phalen’s tests, and reverse Phalen’s tests were conducted on the subjects. [Results] Based on the results of the AS1842856 in vivo experiment, the thickness of the median nerve did not change in relation to duration of smartphone use per day, duration of continuous smartphone use, periods of the use of smartphones, or the degree of addiction; however, statistically significant shortening of time to wrist tingling was identified in the Phalen’s tests and reverse Phalen’s tests conducted to examine clinical symptoms. [Conclusion] In conclusion, excessive use of smartphones may act PF-03084014 mouse as a cause to trigger carpal tunnel syndrome

due to pressure on the carpal tunnel in the wrist joint; thus, precautions are necessary when using smartphones.”
“Cryopreservation is a key technology in biology and clinical practice. This paper presents a digital microfluidic device that automates sample preparation for mammalian embryo vitrification. Individual micro droplets manipulated on the microfluidic device were used as micro-vessels to transport a single mouse embryo through a complete vitrification procedure. Advantages of this approach, compared to manual operation and channel-based microfluidic vitrification, include automated operation, cryoprotectant concentration gradient generation, and feasibility of loading and retrieval of embryos.”
“HuR, an RNA binding protein, binds to adenine- and uridine-rich elements (ARE) in the 3′-untranslated region (UTR): of target mRNAs, regulating their stability and translation. HuR is highly abundant in many types of cancer, and it promotes tumorigenesis by interacting with cancer associated mRNAs, which encode proteins that are implicated:in different tumor processes including cell proliferation, :Cell survival, angiogenesis, invasion, and metastasis. Drugs that disrupt the stabilizing effect of HuR upon mRNA targets could have dramatic effects on inhibiting cancer growth and persistence.

The fundamental building units of the title structure are isolate

The fundamental building units of the title structure are isolated PO4 tetrahedra, AlO6 octahedra and P2O7 groups, which are further interlocked by corner-sharing O atoms, forming a three-dimensional framework structure. The Na+ atoms are located within the cavities of the framework, showing coordination numbers of 4, 6 and 7.”
“Objective:

We present, for the first time, the cytological features of lymphoepithelioma-like carcinoma (LELC) of the breast in preoperative fine-needle aspiration (FNA) and touch imprints from secondary deposits in the sentinel lymph node (SLN). Study Design: We report a case of a 53-year-old woman who was diagnosed with breast carcinoma on preoperative FNA and was subjected to SLN biopsy, partial mastectomy and axillary lymph node dissection. The final diagnosis was LELC of the breast. Cytological and histological features were analyzed. Results: The smears GW3965 from preoperative FNA contained cohesive clusters and isolated tumour cells in a haemorrhagic background Z-IETD-FMK clinical trial with scattered lymphocytes. Some of the clusters were infiltrated by the inflammatory cells. The cells had large, pleomorphic nuclei and scanty, ill-defined cytoplasm. The intraoperative touch imprints from the SLN were highly cellular, comprising abundant scattered lymphoid cells, among which were tight clusters of indistinct cells, about 3 times larger than the lymphocyte

population. Conclusion: In our case, LELC shares many cytological features with LELC described in other organs. Immunostains with epithelial markers play an important role in establishing the epithelial nature of the neoplastic cells. LELC should be borne in mind in the evaluation of breast lesions with prominent lymphoid cell infiltration. Its cytological features, as presented, could contribute to its preoperative evaluation on cytological grounds. Copyright (C) 2012 S. Karger AG, Basel”
“Neuroscientific concepts of language mostly focus on distributed networks, comprising various

cortical areas that operate distinct linguistic processes. The role of subcortical structures in these networks is largely hypothetical, whereas their relevance in motor processing is certain. In this context, considerable evidence could be obtained from Deep Brain Stimulation (DBS), a therapy check details for different movement disorders. In DBS, the functional state of basal ganglia and thalamic nuclei is modulated by electrical impulses via electrodes implanted therein. Of note, these structures have been suggested to support speech and language functions. Indeed, DBS influences linguistic capacities and thus provides completely new insights into relations between biolinguistic functions and subcortical neuroanatomy. In this review important findings in this field shall be surveyed with respect to current models of language and speech. (C) 2011 Elsevier Ltd. All rights reserved.

Overall, these results indicate that accelerated disturbance regi

Overall, these results indicate that accelerated disturbance regimes have the potential to magnify the effects of warming temperature on vegetation. Consequently, understanding the relative effects of temperature and disturbance on Arctic plant communities is critical to predicting feedbacks between northern ecosystems and global climate change.”
“Kidney transplantation represents one of the medical achievements of the 20th century. However, its continued success is limited by the increasing shortage of donor grafts. As a result, more kidney grafts from marginal donors are being considered for transplantation, with concomitantly

more initial graft injury and limited organ and patient survival. This has led to Selleck Epigenetic inhibitor an increased need for interventions aiming

MS-275 to optimize and preserve graft quality. Interventions within the donor may protect against ischemia/reperfusion injury, and therefore, donor pre-treatment is a promising strategy to increase graft function and survival. During the last decade, diverse donor pre-treatment interventions have been explored in animal studies. Moreover, the first human trials concerning donor pre-treatment in kidney transplantation have provided encouraging results. Unfortunately, it remains difficult to determine how and where to intervene in the multifactorial and complex processes that affect the donor kidney. Moreover, ethical matters play a critical role in donor

interventions, and pre-treatment should principally not have any potentially unfavorable effects on other organs to be transplanted or on the living donor. This review provides an overview of promising therapeutical strategies for donor pre-treatment in kidney transplantation and discusses the clinical trials that have been conducted thus far.”
“Timely reaction to perturbation is important see more in activities of daily living. Modulation of reaction time to and early recovery from perturbation via vibrotactile noise was investigated. It was hypothesized that subthreshold vibrotactile noise applied to the upper extremity can accelerate a person’s reaction to and recovery from handle perturbation. This intervention was developed based on previous studies in which the earliest cue available for people to detect handle perturbation was somatosensation detecting changes in pressure on the hand whose sensitivity can improve with subthreshold vibrotactile noise. To induce a handle perturbation, a sudden upward load was applied to the handle that subjects were lightly grasping. Eighteen healthy subjects were instructed to stop the handle from moving up when they detected the perturbation. The muscle reaction time and handle stabilization time with and without vibrotactile noise were determined.

Cterminal EGFP-fused NELL2 showed a typical expression pattern of

Cterminal EGFP-fused NELL2 showed a typical expression pattern of secreted proteins, especially with respect to its localization in the endoplasmic reticulum, Golgi apparatus, and punctate structures. Vesicles containing NELL2 exhibited bidirectional movement in HiB5 cells. The majority of the vesicles (70.1%) moved in an anterograde direction with an average velocity of 0.454 mu m/s, whereas some vesicles (28.7%) showed retrograde movement with an average velocity of 0.302 mu m/s. The movement patterns of NELL2 vesicles were dependent

upon the presence of microtubules in HiB5 cells. Anterograde movement of NELL2 did not lead to a detectable accumulation of NELL2 in the peripheral region of the cell, indicating that it was secreted into the culture medium. We also showed that the N-terminal 29 amino acids of NELL2 were important for secretion of this protein. Taken together, these results strongly suggest that the N-terminal Navitoclax in vitro region of NELL2 determines both the pattern of its intracellular expression and transport of NELL2 vesicles by high-velocity movement. Therefore, NELL2 may affect the cellular activity of cells in a paracrine or autocrine manner.”
“Objectives: Data concerning the levels of metalloproteinase-2 (MMP-2) and MMP-9 in uremia and dialysis are conflicting and incomplete.\n\nDesign and

methods: We measured the serum MMP levels in patients with chronic kidney disease (CKD) and undergoing maintenance hemodialysis (HD), and we tried to identify factors that could affect their levels.\n\nResults: MMP-2 and the high sensitivity C-reactive protein (hsCRP) were inversely

correlated with hematological SHP099 datasheet parameters in the whole CKD group. CKD patients with stages 3 + 4 showed a significant increase in the MMP-9 levels compared to the other studied groups: this metalloproteinase was inversely correlated with learn more lymphocyte count, and positively correlated with the hsCRP. The MMP-2 levels were higher in pre and post HD patients compared to the control group and CKD stage 1 + 2. In contrast, there was no difference in the MMP-9 levels. Both MMP-2 and MMP-9 were associated with the leukocyte count in pre HD group.\n\nConclusions: This study suggests a connection between an inflammatory state, biochemical response and the MMP levels in uremic and dialysis patients. (C) 2011 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.”
“Methicillin-resistant Staphylococcus aureus (MRSA) has been a major cause of nosocomial infection in Irish hospitals for 4 decades, and replacement of predominant MRSA clones has occurred several times. An MRSA isolate recovered in 2006 as part of a larger study of sporadic MRSA exhibited a rare spa (t878) and multilocus sequence (ST779) type and was nontypeable by PCR- and DNA microarray-based staphylococcal cassette chromosome mec (SCCmec) element typing.

For greater

For greater CH5424802 in vitro accuracy when smear quality is poor, Plasmodium AutoCount, can be used in conjunction with Counting Aid.”
“Calcium-dependent protein kinases (CDPKs) play a vital regulatory role in abiotic stress responses in plants. We isolated the ZmCK1 gene encoding a CDPK from maize seedlings. The predicted ZmCK1 protein contains a typical Ser/Thr protein kinase domain and four EF-hand calcium-binding motifs in its N-terminal and C-terminal halves, respectively. The catalytic and regulatory domains were linked by a well-conserved junction domain. A ZmCK1::hGFP fusion protein was found to localize into the cytoplasma and nucleus upon introduction into Arabidopsis mesophyll protoplasts. ZmCK1 transcription was

highly activated by salt and cold, and moderately by drought and exogenous ABA in maize seedling. Isolation of the ZmCK1 promoter revealed some cis-acting elements responding to stresses. Overexpression of ZmCK1 improved drought, salt, and cold stress tolerance in transgenic Arabidopsis plants. Our results suggested that ZmCK1 produces a functional kinase that may play a regulatory role in abiotic stress response.”
“We characterize a mechanism of injury, injury pattern, and treatment algorithm for adductor pollicis myotendinous injuries in 2 professional baseball players.

BIX 01294 purchase Similar to myotendinous eccentric injuries in other anatomical areas, the adductor pollicis sustains a sudden forceful eccentric load during a jammed swing, resulting in intramuscular strain or tendon rupture. Based on the reported injury mechanism, and magnetic resonance imaging features of these myotendinous injuries, the thumb of the top hand during a jammed 4EGI-1 molecular weight swing was suddenly and forcefully eccentrically abducted from a contracted and adducted position, resulting in injury patterns. (Copyright (C) 2013 by the American Society for Surgery of the Hand. All rights reserved.)”
“While transcatheter closure of mitral and aortic paravalvular leaks has been well-described,

there are no prior reports of such procedures for prosthetic tricuspid valves. We describe our experience with percutaneous closure of a tricuspid paravalvular leak in a 34-year-old patient with a history of tricuspid atresia. He had previously undergone repair with placement of a right atrium-to-right ventricle conduit and most recently, placement of a bio-prosthetic tricuspid valve. He subsequently developed significant tricuspid paravalvular leak with symptoms of severe right heart failure. His clinical status was improved following successful transcatheter closure of the defect. (c) 2013 Wiley Periodicals, Inc.”
“A rare amyloid precursor protein gene variant, A673T (rs63750847) was recently reported to protect against Alzheimer’s disease and age-related cognitive decline among Icelanders and the same rare variant was observed also in Finnish, Norwegian, and Swedish populations.

The current study compared outcomes between actual body weight an

The current study compared outcomes between actual body weight and ideal body weight dosing of daptomycin before and after this intervention. In the evaluable group, 69 patients received doses based on actual body weight and 48 patients received doses based on ideal body weight. Patients were treated for documented Enterococcus species, Staphylococcus aureus, or coagulase-negative Staphylococcus infections, including bloodstream, intraabdominal, skin and soft tissue, urinary, and bone. There was no statistically significant difference in clinical success

between the groups (88.9% for actual body weight compared to 89.1% for ideal body weight, P = 0.97). After we adjusted for gender, age, body mass index, concomitant 3-hydroxy-3-methylglutaryl-coenzyme selleck chemicals A reductase inhibitors, infection type, and organism type, clinical success rates remained similar between groups (adjusted odds ratio of 0.68 in favor of actual body weight, 95% confidence interval [CI] of 0.13 to 3.55). Microbiological outcomes, length of stay, mortality, and adverse effects were also similar between groups.

Further studies are warranted to confirm that ideal body weight dosing provides similar outcomes to actual body weight dosing for all click here patients and types of infections and organisms.”
“Background: Wild waterfowl are recognized as the natural reservoir for influenza A viruses. Two distinct lineages, the American

and Eurasian lineages, have been identified in wild birds. Gene flow between the two lineages is limited. The H9N2 virus has become prevalent in poultry throughout Eurasia, and mainly circulates in wild ducks and shorebirds in North America. Methods: In this study, 22 H9N2 avian influenza viruses were isolated Autophagy Compound Library concentration from wild waterfowl feces in East Dongting Lake Nature Reserve in November 2011 and March 2012. The phylogenetic, molecular, and antigenic characteristics of these viruses were analyzed based on analyses of the whole genome sequence of each isolate. Results: Phylogenetic analyses indicated that these H9N2 viruses were generated by reassortment events. The HA, NA, PA, and NS genes were derived from the American gene pool, and the other four genes were derived from the Eurasian gene pool. Antigenic analyses indicated that these viruses were significantly different from the Eurasian lineage viruses. Conclusions: This study presents the isolation of novel intercontinental recombinant H9N2 viruses from wild waterfowl in the East Dongting Lake wetland. The novel genotype H9N2 virus has not been detected in poultry in the region yet, and may be transmitted to naive birds in poultry farms. Therefore, our results highlight the need for ongoing surveillance of wild birds and poultry in this region.

We recommend the use of prophylactic nephropexy to prevent torsio

We recommend the use of prophylactic nephropexy to prevent torsion.”
“Sesuvium portulacastrum is a promising halophyte well adapted to salt and to drought. However, no information in the literature was available about its antioxidant capacity.

The objective of this study is to investigate the effects of water deficit applied alone or combined with salinity on some physiological parameters, proline and polyphenol accumulation, and antioxidant selleckchem and antiradical activities. Seedlings were cultivated under optimal or limiting water supply (respectively, 100% and 25% of field capacity, FC). The amount of the evapotranspirated water was replaced by a nutrient solution containing either 0 or 200 mM NaCl. Water deficit stress reduced plant growth together with a significant decline in leaf water content. Salinity mitigated the deleterious effects of water deficit stress on growth and led to an increase in net CO2 assimilation and stomatal conductance. In addition, salt supply under water deficit significantly increased leaf proline concentration and reduced lipid membrane peroxidation, assessed by leaf malondialdehyde concentration. Phenolic compound content increased significantly when plants were transferred from water deficit stress to 100% FC. However, plants

subjected B-Raf mutation to water deficit stress combined to salt had high polyphenol content and the highest level of the antiradical activity in their stems. As a whole, cultivatingS. portulacastrum under water deficit stress combined with salinity might be an interesting approach to exploit antioxidant metabolites from this species for medicinal and industrial purposes. Recovery of most of the studied parameters was substantial following relief of stress. Drought stress alone or combined with salinity did not cause permanent alterations in S. portulacastrum plants, which conserve their growth potentialities, and which can be a useful species in re-vegetation programs in arid saline areas. (C) 2015 Elsevier GmbH. All rights reserved.”
“Bioactivity-guided fractionation for an EtOAc-soluble

fraction of methanolic extract of Arthraxon hispidus, Geneticin nmr using primary cell assay with bone marrow-derived mast cells (BMMC), led to an isolation of six new flavones and nine known compounds. The structures of the new compounds were established by one dimensional (1D)- and 2D-NMR spectroscopic data, as luteolin 8-C-beta-kerriopyranoside (1), luteolin 8-acetic acid methyl ester (2), 7-methyl-luteolin 8-C-beta-(6-deoxyxylo-3-uloside) (3), apigenin 8-C-alpha-fucopyranoside (4), apigenin 8-C-beta-fucopyranoside (5) and luteolin 8-C-beta-fucopyranoside (6). All the isolates were evaluated for inhibitory activities on interleukin-6 release in the primary cultures using BMMC. Of the tested compounds, compounds 2, 3 and 10 were found to inhibit interleukin-6 release.

That is a good thing if it is done correctly, but poorly designed

That is a good thing if it is done correctly, but poorly designed quality GDC-0994 purchase measures might actually interfere with patient care. It will be necessary for ASBrS to remain involved in the development of

relevant, true data-based measures of quality that have appropriate benchmarks and no unintended consequences. Importantly, the quality measures need to include all reasonable treatment options so that quality care is enhanced and not impeded.”
“This review provides an overview of emerging techniques, namely, photodynamic diagnosis (PDD), narrow band imaging (NBI), Raman spectroscopy, optical coherence tomography, virtual cystoscopy, and endoscopic microscopy for its use in the diagnosis and surveillance of bladder cancer. The technology, clinical evidence and future applications of these approaches are discussed with particular emphasis on PDD and NBI.

These approaches show promise to optimise cystoscopy and transurethral resection of bladder tumours.”
“Objectives of this study were to record, classify and describe cutaneous and ocular neoplasms of sheep and goats as well as their diagnosis after surgical excision, and to determine the link of tumor occurrence with breed, sex, age, fleece or coat color, and tumor location. Clinical cases (n = 104) of tumors (sheep = 89, goats = 15) were presented for surgical treatment. Sheep and goats with tumors were subjected to detailed study including breed, age, sex, and fleece or coat color of the animal, case history, gross and microscopic Staurosporine inhibitor appearance of the tumor, surgical treatment, and buy Sapitinib postoperative care. Five different types of tumors were diagnosed in sheep and goats namely; squamous cell carcinoma (SCC), malignant

melanoma, lipoma, fibroma, and fibrosarcoma. Mixed tumors in the form of SCC with melanoma were also recorded. Tumors were frequent in females and were observed in two sheep breeds (Awassi and Najdi) and in Ardi goats. Detailed gross and microscopic descriptions of neoplasms were cited. Predilection sites of neoplasia in sheep were on the ear(s), eye and eyelids, shoulder region, on the back, flank region, lateral to the umbilicus, lateral to the udder, on the udder, hind limbs, and on the inner aspect of the tail. Tumors in goats were present on the eye and eyelids, base of the horn, carpus, udder, anus, perineum, vulva, and both anus and vulva. In conclusion, SCC and malignant melanoma were prevalent neoplasms in sheep and goats, respectively. Ocular SCC was frequent in Najdi sheep that have white colored head; however, SCC was frequent in the flank and tail of Awassi sheep that have white colored trunk. Ovine and caprine neoplasms were prevalent in females and at ages of 4-6 years and 3-6 years, respectively. (C) 2012 Elsevier B.V. All rights reserved.”
“Background: recurrent falls are a major public health problem associated with high morbidity and mortality as well as increased dependence.