To identify structural elements regulating this function, we introduced reactive cysteines into the alpha 7 ligand-binding domain allowing us to bind sulfhydryl-reactive (SH) agonist analogs or control reagents onto specific positions in the ligand binding domain. We identified four alpha 7 mutants (S36C, L38C, W55C, and L119C) in which the tethering of the SH reagents blocked further acetylcholine-evoked activation of the receptor. However, SCH727965 inhibitor after selective

reaction with SH agonist analogs, the type II allosteric modulator N-(5-chloro-2,4-dimethoxyphenyl)-N ‘-(5-methyl-3-isoxazolyl-3-isoxazolyl)-urea (PNU-120596) could reactivate L119C and W55C mutants and receptors with a reduced or modified C-loop. Modified S36C and L38C mutants were insensitive to reactivation by PNU-120596, whether they were reacted with agonist analogs or alternative SH reagents. Molecular modeling showed that in the W55C and L119C mutants, the ammonium pharmacophore of the agonist analog methanethiosulfonate-ethyltrimethylammonium would be in a similar but nonidentical position underneath

the C-loop. The orientation assumed by the ligand tethered to 119C was approximately 3-fold more sensitive to PNU-120596 than the alternative pose at 55C. Our results support the hypothesis that a single ligand can bind within the receptor in different ways and, depending on the specific binding pose, may variously find more promote activation or desensitization, or, alternatively, function as a competitive antagonist. This insight may provide

a new approach for drug development.”
“BACKGROUND\n\nBlack patients in the United States undergoing angiography for suspected coronary artery disease (CAD) have consistently been found to have less disease than whites. As the effects of hypertension are greater in blacks than whites, and hypertensive heart disease may mimic CAD and lead to catheterization, we examined the association between race and hypertension as an explanation for the disparities in angiographic CAD.\n\nMETHODS\n\nUsing an academic hospital’s institutional database, we studied patients undergoing first-time elective angiography from 2001 to 2008. Using multivariable logistic regression with data on patient demographics, CAD risk factors, and coronary stenoses, we compared rates of angiographic disease for blacks and whites, creating Z-IETD-FMK order models separately for patients with and without hypertension. We then tested the significance of an interaction term between race and hypertension on angiographic findings.\n\nRESULTS\n\nWe identified 1,203 black and 2,538 white patients who underwent initial elective angiography. Black patients were less likely to have a significant stenotic lesion (>= 50% stenosis in the left main artery or >= 70% stenosis elsewhere) than whites (adjusted risk ratio 0.65; 95% confidence interval (Cl) 0.55-0.75). Among patients with hypertension this difference was exaggerated (adjusted risk ratio 0.60; 95% Cl 0.51-0.71).

\n\nResults: The four leading symptoms were fatigue (96%), fever (86%), cough (81%), and dyspnea (79%). No significant differences in symptom prevalence were found between different sexes, ages, performance statuses, ward locations, or Flavopiridol in vivo underlying diseases, except for fewer episodes of

dizziness, more frequent episodes of cough in patients older than 80 years, and more episodes of jaundice in ward service subjects. Only the presence of abdominal distension differed significantly between surviving and deceased patients (22.9% vs. 40.3%; p = 0.004). After the start of palliative care, patients’ DNR consent increased (105/115 before, 114/115 after). Patients’ recognition of the diagnosis and prognosis increased from 13 to 64, respectively, with a simultaneous increase in family members’ recognition (66 before, 114 after).\n\nConclusion: Hospice care with good symptom control is warranted for patients

with late-stage nonmalignant disease who need appropriate end-of-life care. Medical personnel need education in the importance of palliative care and the identification of patients who could AZD1208 manufacturer benefit from it. In addition, patients should be informed of its availability. Copyright (C) 2012, Elsevier Taiwan LLC & Formosan Medical Association. All rights reserved.”
“Approximately 20-30% of patients with gastro-oesophageal reflux symptoms report inadequate symptom relief while on PPI therapy Persisting acid or non-acid reflux can be demonstrated in 40-50% of them suggesting that there is room for anti-reflux therapy in these patients New anti-reflux compounds

aim at decreasing the occurrence of transient lower oesophageal sphincter relaxations (TLOSRs) which represent the main mechanism of all types of reflux The most promising classes of compounds are GABA(B) agonists and mGluR5 antagonists which have been shown to reduce both reflux episodes and symptoms and are currently under evaluation in phase II and III clinical trials Compounds that target TLOSR activity represent a promising new therapeutic option for patients who suffer from GORD symptoms These drugs will probably be developed as add-on therapy in combination with PPIs provided the tolerability and safety issues are resolved (C) 2010 Elsevier Ltd All rights reserved”
“In case of Zenker’s diverticulum, treatment is indicated as soon PF-02341066 solubility dmso as the diagnosis is established. Therapy should aim at the elimination of dysphagia and the symptoms of food retention and should reliably prevent recurrence. Currently, three different therapeutic approaches are applied: the classical option is open transcervical myotomy and diverticulectomy/diverticulopexy and alternatively stapled diverticulostomy with a linear stapler or flexible endoscopic diverticulostomy is propagated. As compared to the surgical (open) approach, rigid or flexible endotherapy is less invasive. However, endotherapy is not always feasible for all types of Zenker’s diverticulum and the recurrence rate is high.

Blood samples were obtained in the first hour of presentation for measurement of BNP levels from all patients. Detailed transthoracic

two-dimensional, Doppler and tissue Doppler echocardiographic studies were then performed within 24 hours of presentation. Statistical analyses were performed using Student’s t-test for independent samples, Mann Whitney U test and Pearson or Spearman correlation tests.\n\nResults: Plasma BNP levels were found to be significantly correlated with left ventricular end-systolic and end-diastolic diameter, left atrial diameter and the degree of mitral insufficiency HIF-1 activation (r=0.46, p=0.007; r=0.39, p=0.02; r=0.32, p=0.065; r=0.50, p=0.014, respectively). A significant inverse correlation was observed between plasma BNP levels and left ventricular ejection fraction (r=-0.5, p=0.003). When the patients were grouped according to their BNP levels, the mean ejection fraction of the group with BNP levels below median (578 pg/l) was 60.65 +/- 13.84%, whereas the mean ejection fraction of the group with BNP levels of 578 pg/l or above (BNP 2) was 49.41 +/-

15.26% (p=0.027). Out of parameters reflecting left ventricular diastolic functions, only transmitral Epeak/Apeak ratio was found to be significantly associated with BNP levels (r=0.4, p=0.05). Tissue Doppler study revealed significant correlations between BNP levels and right ventricular selleck compound basal and midsystolic velocities (r=-0.507, p=0.008; r=-0.562, p=0.005, respectively) while none of the left ventricular tissue velocities displayed significant correlation with BNP values.\n\nConclusion: Plasma BNP levels are found to be significantly associated with conventional echocardiographic parameters reflecting left ventricular systolic and diastolic functions and tissue Doppler velocities reflecting right ventricular functions. Our findings are in agreement with the notion that plasma BNP levels are beneficial in the differential diagnosis of patients admitted to emergency service with acute

dyspnea. (Anadolu Kardiyol Berg 2010; 10: 143-9)”
“A novel controllable hybrid-anode AlGaN/GaN Napabucasin nmr field-effect rectifier (HA-FER) with low operation voltage (LOV) is proposed. Its mechanism can be explained by the field-controlled energy band model. This model reveals that the electric field in the AlGaN layer alters the energy band to result in a variation of the two-dimensional electron gas (2DEG) at AlGaN/GaN interface; the field can be changed by the thickness.. of the AlGaN layer and the applied bias. As the.. reduces below the critical thickness, the 2DEG vanishes and then the channel is pinched off. Therefore, the threshold voltage of HA-FER can be designed as low as 0V leading to LOV (<1V). The analytical characteristic of the HA-FER is calculated and validated by the simulated results.

In this condition, they also exhibit an increase in the expression of osteogenic markers (runx-2, alkaline phosphatase) and extracellular calcium deposition, whereas the expression of receptors (VEGFR-1 and -2) for vascular endothelial growth factors (VEGF) and related VEGF binding

proteins was similar to that found in undifferentiated DPSC. Exposure of DPSC growing under undifferentiating or osteogenic conditions to VEGF-A(165) peptide (10-40 ng/ml) for 8 days dose- and time-dependently increased the number of proliferating cells without inducing differentiation towards endothelial lineage, as evaluated by the lack of expression of specific markers (CD31, CD34, CD144). Additionally, exposure of DPSC cultured in osteogenic medium to VEGF-A(165) for a similar period enhanced cell differentiation Cyclopamine nmr towards osteoblasts as evaluated after 14 and 21 days by Alizarin Red S staining and alkaline phosphatase activity quantification. These findings may have clinical implications possibly facilitating tissue repair and remodeling.”
“Functional magnetic resonance imaging (fMRI) has become the leading modality for studying the working

brain. Being based on measuring the haemodynamic changes after enhanced mass neuronal activity the spatiotemporal resolution of the method is somewhat limited. Alternative MR-based methods for detection of brain activity have been proposed and investigated

and studies have reported functional imaging based on diffusion weighted (DW) MRI. The basis for such DW fMRI is believed to be the sensitivity of diffusion GSK2879552 cell line weighted MRI to changes in tissue micro-structure. However, it remains unclear whether signal changes observed Prexasertib with these methods reflect cell swelling related to neural activation, residual vascular effects, or a combination of both. Here we present evidence of a detectable, activity-related change in the diffusion weighted MR-signal from the cellular level in live hippocampal slices in the absence of vasculature. Slices are exposed to substances which evoke or inhibit neural activity and the effects are evaluated and compared. The results are also compared to earlier DW fMRI studies in humans. (C) 2009 Elsevier Inc. All rights reserved.”
“Background: Mobile phone technologies for health promotion and disease prevention have evolved rapidly, but few studies have tested the efficacy of mobile health in full-fledged programs. Text4baby is an example of mobile health based on behavioral theory, and it delivers text messages to traditionally underserved pregnant women and new mothers to change their health, health care beliefs, practices, and behaviors in order to improve clinical outcomes. The purpose of this pilot evaluation study is to assess the efficacy of this text messaging campaign.

\n\nConclusion: [111-In] pentetreotide SPECT/CT imaging at

24 hours identifies pathologic disease sites and distinguishes physiologic activity equally well compared to traditional strategies using 2 imaging days. Routine use of SPECT/CT will allow single time-point imaging without loss of diagnostic accuracy, enhancing patient convenience, and clinical throughput.”
“Background: Percutaneous nephrolithotomy (PCNL) can be performed in the prone or in the supine position. Comparisons between the two techniques in obese patients are rare in the current literature.\n\nMethods: The records of obese patients (body mass index >30) who underwent PCNL in the prone or complete supine positions were reviewed. All patients had a noncontrast CT before and after the procedure. Stones were graded according to the Guy stone

score and complications according to the Clavien buy PR-171 grading. The stone-free rates, operative time, surgical complications, and hospital stay were analyzed.\n\nResults: A total of 56 PCNL were performed in 42 patients. Twenty-four PCNL were performed in the prone and 32 in the total supine position. Stone-free rate on the first postoperative day was 50% in the prone and 46.9% in the supine GDC-0941 datasheet position (P = 1.0). Final stone-free rates were 83.3% and 78.1%, respectively (P = 0.74). Mean operative time was 164.6 minutes in the prone and 120.3 minutes in the supine position (P = 0.0017), and hospital stay was 4.38 and 2.68 days (P = 0.014), respectively. The transfusion rate was 20.8% in the prone and zero in the supine position patients (P = 0.01).

Excluding Guy IV stones, transfusion rate was 8.3% in the prone position (P = 0.1). Significant surgical complications rate was 12.5% in the prone and 3.1% in the supine position (P = 0.302).\n\nConclusion: PCNL performed in the prone or in the complete supine position in obese patients presents similar outcomes. The supine decubitus position has the advantages of a significantly shorter operative time and hospital this website stay.”
“Objective: To assess the efficacy of upper airway surgical intervention in patients with Prader-Willi syndrome (PWS). Due to reports of sudden death in children undergoing treatment with growth hormone for PWS, detection of sleep-disordered breathing by polysomnography (PSG) has been recommended.\n\nDesign: Retrospective study.\n\nSetting: Multidisciplinary PWS Center at a tertiary care children’s hospital.\n\nPatients: Thirteen pediatric patients with PWS who underwent adenotonsillectomy (T&A) with pre-PSG and post-PSG.\n\nMain Outcome Measures: Comparison of PSG results before and after T&A.\n\nResults: Six of our patients were girls (46%); 8 had genetic characteristics consistent with deletion (61%), and the remaining 5 had genetic characteristics consistent with uniparental disomy (39%). The median age at T&A was 3 years (age range, 6 months to 11 years), and the median age at start of growth hormone treatment was 8.5 months (range, 2 months to 6 years).

Methods: A nationally representative sample of 952 Asian American adults extracted from the Wave BMS-777607 2 National Epidemiologic Survey of Alcohol and Related Conditions data was used. Multiple logistic and linear regression models were fitted, some of which were stratified by nativity. Results: Controlling for financial stress, discrimination and demographic variables, a hypothesized, positive relationship between ethnic drinking cultures and alcohol outcomes held for most drinking outcomes. A hypothesis on the moderating effect of integration into ethnic cultures indicated by ethnic language use was supported for US-born Asian

Americans. Conclusion: Ethnic drinking cultures may significantly influence alcohol use by Asian Americans.

The influence of ethnic drinking cultures may be conditioned by the degree of integration into the ethnic cultures. To inform alcohol interventions for reducing harmful and hazardous alcohol use among immigrants, future research needs to explore the cultural and social processes occurring in immigrant communities that might significantly influence drinking.”
“Three new eriococcid species from Italy are described and illustrated, namely Greenisca oreophila sp. n. off Poaceae, and Ovaticoccus exoticus sp. n. and O. agavacearum sp. n., off Agavaceae. Their morphological relationships are discussed and keys to Greenisca and Ovaticoccus species are provided, together with a key to the Eriococcidae genera so far known in Europe. A check-list of Italian Eriococcids is added.”
“Background: buy AZD1208 Cymbopogon citratus (Poaceae) a tropical perennial herb plant that is widely cultivated to be eaten either fresh with food or dried in tea or soft drink has been reported to possess a number of medicinal and aromatic properties. This study aimed at evaluating the protective effects of C. citratus aqueous extract against Angiogenesis inhibitor liver injury induced by hydrogen

peroxide (H2O2), in male rats.\n\nMaterials and Methods: Twenty-five rats were randomly divided into five different groups of five animals in each group; (1) Control. (2) Received H2O2 (0.5%) with drinking water. (3), and (4) received H2O2 and C. citratus (100 mg.kg(-1) b wt), vitamin C (250 mg.kg(-1) b wt) respectively. (5), was given C. citratus alone. The treatments were administered for 30 days. Blood samples were collected and serum was used for biochemical assay including liver enzymes activities, total protein, total bilirubin and malonaldehyde, glutathione in serum and liver homogenates. Liver was excised and routinely processed for histological examinations.\n\nResults: C. citratus attenuated liver damage due to H2O2 administration as indicated by the significant reduction (p<0.

Thirty-six tumors from 33 patients (mean age: 60.4, range: 26 to 88; 17 men and 16 women) were studied. Three patients had bilateral tumors and 1 patient had von Hippel-Lindau disease. Follow-up was available in 60% (20/33) of the patients for a mean of 27.4 (range 1 to 85) months. No patient had evidence of the disease after surgery except for the patient with von Hippel-Lindau disease, who was alive with stable disease in the contralateral kidney. All 36 tumors were small (mean size 2.4 cm; range 0.9 to 4.5 cm) and low stage (pT1). The majority was cystic and had prominent fibrous capsule and stroma. The tumors were composed of variable amount of cysts, papillae,

tubules, acini, and solid nests. The most characteristic histologic features were branching tubules and acini and anastomosing clear cell ribbons

with low-grade nuclei. All tumors were strongly positive for Ricolinostat purchase CK7 and variably positive for CA9, but largely negative for CD10, and negative for alpha-methylacyl-CoA racemase and TFE-3. All but 1 tumor had no gains of AG-120 molecular weight chromosomes 7 and 17 and deletion of 3p. Only 1 tumor had low copy number gains of chromosomes 7 and 17. VHL gene mutation and promoter methylation were negative in 2 tumors analyzed. We show that these tumors, which we term as “clear cell tubulopapillary renal cell carcinoma,” constitute a unique subtype in the spectrum of renal epithelial neoplasia based on their characteristic morphologic and immunohistochemical features.”
“Adult lymphoblastic lymphoma (LBL) is

an aggressive form of non-Hodgkin lymphoma occurring in predominantly adolescent and young adult men. Lymphoblastic lymphoma is rare, accounting for 1% to 2% of all non-Hodgkin lymphomas and is of T-cell phenotype in 90% of cases. Lymphoblastic lymphoma is morphologically indistinct from acute lymphoblastic leukemia (ALL). Both express their lineage-specific markers as well as terminal deoxynucleotidyl transferase. The differences are often made on clinical grounds. Lymphoblastic lymphoma is characterized by a predominantly nodal distribution of disease, often with a large mediastinal mass. Patients with less than 25% bone marrow involvement have typically been categorized as LBL rather than ALL, although this has not been applied consistently in the literature. Gene expression studies have identified differences in gene expression, Selleckchem GSK1838705A with LBL expressing higher levels of genes associated with cytoskeleton, adhesion, angiogenesis, and chemotaxis than ALL. Although LBL and ALL can be distinct clinically, chemotherapy strategies are often very similar. Acute lymphoblastic leukemia regimens, which incorporate intensive multidrug induction, consolidation, delayed intensification, and maintenance, have been shown to be superior to standard lymphoma regimens. As central nervous system (CNS) relapse is common, CNS prophylaxis with high-dose chemotherapy and intrathecal therapy is also standard.

“
“Polymorphonuclear neutrophils (PMN) are the most abundant circulating leukocytes. They represent a first line of innate immunity against a large panel of microbial pathogens, pending development of specific immune responses. The role of PMN in human immunodeficiency virus type 1 (HIV-1) disease has mainly been investigated from the point of view of the increased susceptibility of HIV-1-infected patients to bacterial and fungal infections. However, it is now clear that the relationship

between PMN and HIV-1 is far more complex. This review examines both the beneficial and the detrimental effects of PMN during HIV infection. (C) 2013 S. Karger AG, Basel”
“Objective: To describe the CA3 investigation and learn more management

of patients admitted to hospitals in China with suspected acute coronary syndromes (ACS) and to identify potential areas for improvement in practice.\n\nDesign: A multicentre prospective survey of socio-demographic characteristics, medical history, clinical features, in-hospital investigations, treatment practices and major events among patients with suspected ACS.\n\nSetting: Large urban public hospitals.\n\nPatients: Consecutive patients admitted to in-patient facilities with a diagnosis of suspected acute myocardial infarction (MI) or unstable angina pectoris.\n\nMain outcome measures: Myocardial infarction/reinfarction, heart failure, death.\n\nResults: Between September 2004 and May 2005, data were collected prospectively from 2973 patients admitted to 51 hospitals in 18 provinces of China. selleck chemical An initial diagnosis of ST elevation MI, non-ST elevation MI and unstable angina was made in 43%, 11% and 46% of patients, respectively. Diagnosis was inconsistent with objective measures in up to 20% of cases. At both tertiary and non-tertiary centres, there was little evidence that clinical risk stratification was used to determine the intensity of investigation and management. The mortality rate during hospitalisation was 5% overall and similar in tertiary and non-tertiary centres, but reported in-hospital

re-infarction rates (8%) and heart failure rates (16%) were substantially higher at non-tertiary centres.\n\nConclusion: This study has identified a number of areas in the management of ACS patients, including diagnosis and risk stratification, which deviate from current guidelines. These findings will help inform the introduction of widely used quality improvement initiatives such as clinical pathways.”
“Driving is a complex task and is susceptible to inattention and distraction. Moreover, alcohol has a detrimental effect on driving performance, possibly due to alcohol-induced attention deficits. The aim of the present study was to assess the effects of alcohol on simulated driving performance and attention orienting and allocation, as assessed by event-related potentials (ERPs).

In this study, direct enantiomeric resolution of metalaxyl and its main degradation product metalaxyl acid,

often co-occurring in the environment, was carried out in normal-phase high-performance liquid chromatography with a Chiralcel OJ-H column. (R)-Metalaxyl acid and (S)-metalaxyl, which were almost parallel bonding to the chiral stationary phase, tended to separate, started to overlap, coeluted, and separated again with subtle changes of the mobile phase consisting of n-hexane, 2-propanol, acetic acid, and trace water. Their competition above hampered an acceptable direct separation in fresh mobile phases. Aged mobile phases with a storage period of 3-5 days, however, significantly improved their separation, in which trace water from moisture air diffusion was found to play VS-6063 cost a major role. Trace water differentially affected peak width and retention times and then induced enhanced peak separation, confirmed by deliberate addition of water to fresh mobile phases. Furthermore, none of the studied factors, involving temperature, concomitant analytes, and trace water, could cause changes of the configuration of the chiral stationary phase. Simultaneous

enantiomeric separation of both compounds was achieved in aged or fresh mobile phases with adventitious or added water and gave satisfactory peak separation, all with Rs values of more than 1.20 in environmental samples.”
“We present Tariquidar molecular weight an uncommon and yet interesting congenital anomaly and discuss the difficulties with diagnosis and controversies in management. C1 arch deficiency is an important consideration in check details the differential diagnosis of neck pain in children.\n\nA 12-year-old girl presented initially

with a loud clicking emanating from the cervical spine during nappy changes in early childhood. Subsequent investigation by way of CT and MRI revealed her to have a deficient posterior arch of the C1 vertebra, and due to persistent and painful clicking she was placed into a cervical brace, which was worn for approximately 1 year. At age 12, her clicking had all but completely resolved but she continued to complain of minor neck pain. She is advised to avoid contact sports and her parents are instructed to observe any new worrying symptoms.\n\nNo definitive guidelines exist for the management of this congenital anomaly. Indications for surgical intervention prior to any neurological disturbance are unclear, and restricting a child from partaking in healthy activity may not be necessary. We discuss the anomaly and identified management strategies as reported in the literature so far.”
“Nano-particles with controllable particle size and shape are of great interest in biomedical applications (1). From the standpoint of drug carrier design with wide applicability to a variety of hydrophobic drugs, an effective strategy would be to prepare a simple copolymer having the property to form stable polymeric micelles which can entrap hydrophobic drugs in the core (2).

Although the molecular mechanisms that regulate NLK activity remain unclear, our recent research has presented

a new model for NLK activation. Here, we summarize the current understanding of the function and regulation of NLK and discuss the aspects of NLK regulation that remain to be resolved. (C) 2012 Elsevier Inc. All rights reserved.”
“The viability of iron(III/II) reduction as the initial step in the in vivo release of iron from its thermodynamically Selleckchem Nocodazole stable siderophore complex is explored.”
“Ataxia-telangiectasia mutated (ATM) kinase is a component of a signalling mechanism that determines the process of decision-making in response to DNA damage and involves the participation of multiple proteins. ATM is activated by DNA double-strand breaks (DSBs) through the Mre11-Rad50-Nbs1 (MRN) DNA repair complex, and orchestrates signalling cascades that initiate the DNA damage response. Cells lacking ATM are hypersensitive to insults, particularly genotoxic stress, induced through radiation or radiomimetic drugs. Here, we investigate the degree of ATM activation during time-dependent treatment with genotoxic agents and the effects of ATM on phospho-induction and localization of its downstream substrates. Additionally, we have demonstrated a new cell-cycle-independent mechanism of ATM gene regulation following ATM kinase inhibition with KU5593. Inhibition of ATM activity causes induction of ATM protein followed by oscillation and

this mechanism is governed at the transcriptional level. Furthermore, GSK690693 inhibitor this autoregulatory induction of ATM is also accompanied by a transient upregulation of p53, pATR and E2F1 levels. Since ATM inhibition is believed to sensitize cancer cells to genotoxic agents, this novel insight into the mechanism of ATM regulation might be useful for designing more see more precise strategies for modulation of ATM activity in cancer therapy.”
“Optimal decision

making requires that we integrate mnemonic information regarding previous decisions with value signals that entail likely rewards and punishments. The fact that memory and value signals appear to be coded by segregated brain regions, the hippocampus in the case of memory and sectors of prefrontal cortex in the case of value, raises the question as to how they are integrated during human decision making. Using magnetoencephalography to study healthy human participants, we show increased theta oscillations over frontal and temporal sensors during nonspatial decisions based on memories from previous trials. Using source reconstruction we found that the medial temporal lobe (MTL), in a location compatible with the anterior hippocampus, and the anterior cingulate cortex in the medial wall of the frontal lobe are the source of this increased theta power. Moreover, we observed a correlation between theta power in the MTL source and behavioral performance in decision making, supporting a role for MTL theta oscillations in decision-making performance.