“The aim of our study was to detect the expression of Ku80


“The aim of our study was to detect the expression of Ku80 in primary central nervous system lymphoma and to evaluate the relationship between Ku80 expression level and clinical outcomes. Thirty-eight

patients with primary central nervous system lymphoma (PCNSL) were included in this retrospective study. The expression of Ku80 in tumor samples was determined by immunohistochemistry. One thousand neoplastic cells per specimen were counted. The BEZ235 expression levels were compared with the clinical data and statistically analyzed. The results of this study show that the expression of Ku80 can be found in the majority of PCNSLs. The mean expression level of Ku80 in 38 PCNSL is 64.1 +/- 24.5. A significant difference in Ku80 expression could be found between the age < 65 years group and age

>= 65 years group (P = 0.006). Kaplan-Meier analysis revealed that patients who showed a high Ku80 expression had a significantly shorter median survival time (MST) than patients who had low Ku80 expression LCL161 (P = 0.036). Patients’ age, tumor location, and treatment protocol were significantly related to prognosis in PCNSL (P < 0.05). The expression of Ku80 was observed in the majority of PCNSLs. Ku80 was a predictive factor for survival in this study. In addition to Ku80, other clinical variables including age, tumor location and Proteasome inhibitor therapeutic protocol are correlated significantly with overall survival.”
“Background Clothing is considered the second skin of the human body. The aim of this study was to determine 4 clothing-wearer interaction on skin physiology under mild cold conditions.\n\nMethods Skin physiological parameters, subjective sensory response, stress level, and physical properties of clothing fabric from two longitude parallel-designed wear trials were studied. The wear trials involved four kinds of pajamas made from cotton or polyester material that had hydrophilic or hydrophobic treatment, conducted for

three weeks under mild cold conditions. Statistical tools, factor analysis, hierarchical linear regression, and logistic regression were applied to analyze the strong predictors of skin physiological parameters, stress level, and sensory response.\n\nResults A framework was established to illustrate clothing-wearer interactions with clothing fabric properties, skin physiology, stress level, and sensory response under mild cold conditions.\n\nDiscussion Fabric has various effects on the human body under mild cold conditions. A fabric’s properties influence skin physiology, sensation, and psychological response.”
“Invasive species can increase the susceptibility of ecosystems to disease by acting as reservoir hosts for pathogens.

The level of nursing experience was not significantly correlated

The level of nursing experience was not significantly correlated with all-cause peritonitis risk.\n\nConclusions: The experience in general medicine of nurses might help to lower the risk of gram-positive peritonitis

among PD patients. These data are the first to indicate that nursing experience in areas other than PD practice can be vital in the training of PD patients.”
“Alcohol dependence is common among patients attending acute hospitals. It can be the major reason for attendance or a significant cofactor. Assessment of these patients in the acute setting can be challenging owing to the multidisciplinary approach required. Doctors in acute hospitals are often inexperienced in managing dependence, a mental health problem. They might focus Selleck STI571 on the physical harms or the withdrawal, a consequence of the dependence. For this reason, assessment of dependence and prevention and management of acute alcohol withdrawal RG7420 are often suboptimal. There is little existing guidance on how to 123 manage this patient population, especially in non-specialist settings. With recently published National Institute for Health and Clinical Excellence (NICE) guidance on the management of dependence and withdrawal, now is the perfect time to produce concise guidelines in the hope that a more succinct suite of guidance can reach

a larger audience.”
“In the past 50 years the incidence of multiple pregnancies has increased dramatically due almost exclusively to two factors: delayed childbearing and assisted reproductive techniques. In this paper we analyze the variations in the incidence of multiple gestations in Andalusia, one of the biggest administrative regions in Spain, over the last decade. Assisted reproduction techniques are very often evaluated only in terms of implantation and pregnancy rates per cycle, ignoring everything related to complications of multiple births, prematurity or economic overload. The rate of twins in Andalusia has increased

from 10.9 per thousand in 2000 to 16.2 per thousand in 2009. The rate of triplet births has also increased in recent years. After a decline in 2003, motivated by promulgation of the first Stattic Human Assisted Reproduction Law, there was an increase after a second law came into effect in 2006. Health care spending attributable to the excess of multiple pregnancies reported in the decade 20002010 may have been much higher than (sic)25 million.”
“Immune cells and structures of Annelida represent a complex subject that was studied for over 120 years. An overwhelming mountain of data have been accumulated during these studies, most of them being the subject of many excellent reviews and books. In the this paper we focused on a brief survay of old studies and some reflection on the findings during recent years.


“In cementless total hip arthroplasty, osteoporosis


“In cementless total hip arthroplasty, osteoporosis NCT-501 in vitro may jeopardize the achievement of immediate stability and lead to migration of anatomically shaped femoral stems. Poor quality of proximal cancellous bone per se may also affect the rate of osseointegration. In a selected group of female total hip arthroplasty patients (mean age 64 years) with unremarkable medical history, intertrochanteric cancellous bone biopsy was taken from the site of

stem implantation. Local bone quality, determined by structural mu CT imaging and destructive compression testing of the biopsy tissue, was used as the predictor of three-dimensional stem migration determined by radiostereometric analysis (RSA) up to 24 months. The patients exhibited major differences in mechanical properties of the intertrochanteric cancellous bone, which were closely related Barasertib to the structural parameters calculated from mu CT data. Unexpectedly, the major differences observed in the quality of trochanteric cancellous bone had

only minor reflections in the RSA migration of the femoral stems. In statistical analysis, the mu CT-based bone mineral density quartile (low, middle, high) was the only significant predictor for stem translation at 24 months (p = 0.022) but only a small portion (R(2)=0.16) of the difference in translation could be explained by changes in bone mineral density quartile. None of the other parameters investigated predicted stem migration in translation or rotation. In conclusion, poor quality of

intertrochanteric cancellous bone seems to contribute to the risk of implant migration less than expected. Probably also the importance of surgical preservation of intertrochanteric cancellous bone has been over-emphasized for osseointegration of cementless stem. (C) 2010 Elsevier Ltd. All rights reserved.”
“Bingeing on sugar may activate neural pathways in a manner similar to taking drugs of abuse, resulting in related signs of dependence. The present experiments test whether rats that have been bingeing on sucrose and then fasted demonstrate signs of opiate-like withdrawal. Rats were maintained on 12-h deprivation followed by 12-h access to a 10% sucrose solution and chow for 28 days, then fasted for 36 h. These animals spent less 3-Methyladenine datasheet time on the exposed arm of an elevated plus-maze compared with a similarly deprived ad libitum chow group, suggesting anxiety. Microdialysis revealed a concomitant increase in extracellular acetylcholine and decrease in dopamine release in the nucleus accumbens shell. These results did not appear to be due to hypoglycemia. The 3 findings suggest that a diet of bingeing on sucrose and chow followed by fasting creates a state that involves anxiety and altered accumbens dopamine and acetylcholine balance. This is similar to the effects of naloxone, suggesting opiate-like withdrawal. This may be a factor in some eating disorders. (C) 2008 Elsevier Inc. All rights reserved.

9% Polypectomy rates ranged between 22 6% and 26 2% for screenin

9%. Polypectomy rates ranged between 22.6% and 26.2% for screening colonoscopy, and between 27.1% and 30.8% for nonscreening colonoscopy. Adjusted ORs for indication ranged between 0.74 and 0.94.\n\nDISCUSSION: Although the proportion of colonoscopies identified as screening varied considerably among the indications, the estimated polypectomy rates were similar.\n\nCONCLUSION: The findings suggest that the way screening is defined does not greatly affect the estimates of polypectomy rate.”
“Vesicular trafficking plays a key role in tuning

the activity of Notch signaling. Here, we describe a novel and conserved Rab geranylgeranyltransferase (RabGGT)-alpha-like subunit that is required for Notch signaling-mediated lateral inhibition and cell fate determination of external sensory organs. This protein is encoded by tempura, and its loss affects the secretion of Scabrous and Delta, two proteins required for proper Notch signaling. VX-680 We show that Tempura forms a heretofore uncharacterized RabGGT complex that geranylgeranylates Rab1 and Rab11. This geranylgeranylation is

required for their proper subcellular BVD-523 datasheet localization. A partial dysfunction of Rab1 affects Scabrous and Delta in the secretory pathway. In addition, a partial loss Rab11 affects trafficking of Delta. In summary, Tempura functions as a new geranylgeranyltransferase that regulates the subcellular localization of Rab1 and Rab11, which in turn regulate trafficking of Scabrous and Delta, thereby affecting Notch signaling.”
“Aimed to evaluate the progression of the disease and oxidative damage in goats with anemia and respiratory disease by application of parenteral iron. Six goats, adults, with anemia and respiratory disease (coughing, sneezing and nasal discharge) were studied. The control group was composed of six adults goats, healthy. The goats of both groups after undergoing clinical evaluation received similar dose (0.5g)

of ferric hydroxide in complex dextran intramuscularly. Blood samples collected in EDTA before the application of iron and 48 hours were taken for determination of concentration of thiobarbituric acid reactive substances (TBARS). In patients goats before the application of iron TBARS values were equivalent to the measured values in the control group before and after applying the iron (p bigger than 0.05). The values measured in patients goats LGX818 purchase were significantly higher (p smaller than 0.001) in the group of animals even after the application of iron and controls before and after application. The application of iron worsened the clinical condition of the animals with respiratory disease, evidencing a condition of toxicity reflected by oxidative 432 stress. Therefore, one should not recommend to supplementation in goats with respiratory diseases.”
“Preserved human amniotic membrane either air dried or glycerol preserved has been used effectively to treat superficial and partial thickness wounds without leaving any obvious hypertrophic scar.

epuraeae, Urodinychidae: Uroobovella pulchella (Berlese, 1904), a

epuraeae, Urodinychidae: Uroobovella pulchella (Berlese, 1904), and Macrochelidae: Glyptholaspis americana (Berlese, 1888) were recorded for the first time in the Iberian Peninsula.”
“Although cowpox virus (CPXV) infections in a variety of dead-end hosts have been investigated in Germany for more than 50 years, data on species and geographical distribution of CPXV in reservoir hosts are sparse. Here we present the first comprehensive study of 825 rodents that have been collected in Bavaria, Southern

Germany. In summary, AZD8186 six different rodent species (Apodemus flavicollis, Myodes glareolus, Microtus arvalis, Apodemus sylvaticus, Microtus agrestis, and Arvicola amphibius) were trapped at three main 123 trapping sites and investigated using a serum neutralization test (SNT). Prevalence of orthopox virus (OPV)-neutralizing antibodies was (with exception of one trapping site) highest in bank voles, ranging from 24.5% to 42.4%; often with SNT titers >=

96. Two up to 25% of yellow-necked mice were OPV sero-positive, but wood mice only at one site with 5.5%. Up to 7.7% of common voles were found to be OPV seroreactive, while M. agrestis and A. amphibius only sporadically showed seroreactivity. Further analyses of a subset of 450 bank voles and yellow-necked mice trapped at one site over a 18-month period revealed that male yellow-necked mice and female gravid yellow-necked mice had significantly more OPV-neutralizing Tamatinib Fosdium antibodies. Mean body weight and OPV-seroreactivity were significantly negatively associated in male A. flavicollis. This was not due to shorter body length or smaller body mass index, but previously OPV-infected male A. flavicollis had dramatically reduced mean kidney WZB117 weights. Seroreactivity in female bank voles was positively related to lung weights. We also found that both male yellow-necked mice and male bank voles with positive SNT titers had higher infestation rates with ectoparasites.

We here show for the first time that A. flavicollis beside M. glareolus is a hypothetic host for CPXV, and that there are big geographical and spatial variations concerning the seroprevalence in rodent populations in South Germany.”
“In light of the increasing interest in the development of functional food, several researches have focused on the production of food grade emulsifiers of nutritional interest, especially enriched in the eicosapentaenoic (EPA) and docosahexaenoic acids (DHA). The aim of this paper is to make a review of the production of monoacylglycerols (MAG) and diacylglycerols (DAG) obtained from different feedstock, mainly fish oil. A section of this paper is dedicated to the raw materials used as feedstock for these emulsifiers production. The health benefits of these partial acylglycerols are outlined.

(C) 2013 Elsevier Ltd All rights reserved “
“P>1 Endocr

(C) 2013 Elsevier Ltd. All rights reserved.”
“P>1. Endocrine disrupting chemicals (EDCs) are chemicals that interfere with proper hormonal functioning in exposed animals. They enter the natural environment through multiple sources, and many non-target wildlife species are exposed to them via several modes. Exposure causes altered hormone levels, importantly gonadal hormones, resulting in changed reproductive characteristics.\n\n2. Vertebrate male mating signals convey important mate quality information to females. These signals are dependent on androgens for their

production and maintenance. Female responses to signals depend on oestrogens. Disrupting these pathways jeopardizes signal production and reception, which has implications find protocol for mating system ecology.\n\n3. Besides affecting various aspects of the vertebrate physiology, EDCs can impair hormonal functioning by binding to or blocking hormone receptors,

or by altering production and function of hormones or hormone receptors.\n\n4. We consider the ecological implications of multi-generational signal disruption by EDCs. Altered signals can influence population dynamics and sex ratios; local extinctions are possible. Community-level dynamics may be affected via interspecific dependence on signals or population fluctuations.\n\n5. We then address the evolutionary effects of EDC-altered male mating signals in vertebrates and discuss how females may respond to altered signals over AR-13324 inhibitor CH5183284 mouse evolutionary time. Trans-generational reduction in signal reliability can lead to reduced preference and eventual loss of the signal trait and to the evolution of new traits as signals of mate quality. Genetic 432 divergence between endocrine disrupted and undisrupted populations may result, perhaps giving rise to speciation.\n\n6. Finally, we recommend areas of research to further explore some of the issues addressed in this review. We suggest field surveys to document

existing alterations in mating systems and genetic divergence in endocrine disrupted populations. Long-term mesocosm studies and mathematical models would be useful to predict the fate of mating signals and female responses as a result of prolonged endocrine disruption. EDCs have been the focus of ecotoxicology for some time now, and we feel that this analysis should now enter the realm of evolutionary biology to determine the subtle, yet far-reaching effects on exposed non-target wildlife.”
“Spatial and temporal dissection of the genomic changes occurring during the evolution of human non-small cell lung cancer (NSCLC) may help elucidate the basis for its dismal prognosis. We sequenced 25 spatially distinct regions from seven operable NSCLCs and found evidence of branched evolution, with driver mutations arising before and after subclonal diversification.

In this context, this paper presents an empirical time-dimension

In this context, this paper presents an empirical time-dimension model of spectrum use that is appropriate for DSA/CR S63845 datasheet studies. Concretely, a two-state discrete-time Markov chain with novel deterministic and stochastic duty cycle models is proposed as an adequate mean to accurately describe spectrum occupancy in the time domain. The validity and accuracy of the proposed modeling approach is evaluated and corroborated with extensive empirical data from a multiband spectrum measurement campaign. The obtained results demonstrate

that the proposed approach is able to accurately capture and reproduce the relevant statistical properties of spectrum use observed in real-world channels of various radio technologies. The importance of accurately modeling spectrum use in the design and evaluation of novel DSA/CR techniques is highlighted with a practical case study.”
“Background: The role of diagnostic catheter cerebral angiography has been recently thought to have diminished with the increasing use of noninvasive modalities such as computed tomography angiography and magnetic resonance angiography. Because it is invasive and costly, we sought to elucidate

the clinical utility of catheter angiography by evaluating the indications, incidence of new selleck chemicals llc and clinically meaningful findings, and its utility 4 compared with noninvasive studies. Methods: We performed an observational cross-sectional study of consecutive patients undergoing diagnostic cerebral angiography at an urban tertiary care center. We prospectively recorded procedural indications, the findings of previously performed noninvasive GM6001 manufacturer studies, the actual angiogram findings, and whether these were new. We defined a new finding as any novel and clinically meaningful piece of anatomic brain vascular information. Results: Of the 200 consecutive studies over 8 months, 55% were for purely diagnostic purposes, whereas the

remaining were for surveillance. The most common indications were subarachnoid hemorrhage, ischemic stroke, intracerebral hemorrhage, cerebral aneurysm, and arteriovenous malformation. New findings were detected in 43% of purely diagnostic angiograms and 32% of surveillance studies. We found false-negative rates of 9.9% and false-positive rates of 11.7%. In 23.4% of cases, more precise anatomic information was found that was subjectively deemed clinically meaningful. Conclusions: Our snapshot of 200 consecutive catheter cerebral angiograms shows that it is used for both primary diagnosis and surveillance in a wide variety of indications. Despite recent imaging trends, diagnostic catheter angiography provides clinically meaningful diagnostic information in enough cases to warrant continued use.”
“Antigen-85A (Ag85A) is one of the major proteins secreted by Mycobacterium tuberculosis. Many studies on animal models have shown that vaccination with the recombinant Ag85A-DNA or Ag85A protein induces powerful immune response.

MethodsInhibition of FXa by TFPI in plasma was determined by meas

MethodsInhibition of FXa by TFPI in plasma was determined by measuring thrombin generation triggered with FXa, the FX activator from Russell’s viper venom (RVV-X), FXIa, or FIXa. TF-independent anticoagulant activities of TFPI and its cofactor, proteinS, were quantified: (i) after 3 neutralization of TFPI and proteinS with anti-TFPI or anti-proteinS antibodies; and (ii) in TFPI-depleted or proteinS-depleted plasmas supplemented with varying amounts of TFPI or proteinS. ResultsBoth anti-TFPI and anti-proteinS antibodies

enhanced thrombin generation in plasma triggered with RVV-X, FXa, FIXa, or FXIa. Anti-TFPI and anti-proteinS antibodies decreased the lag time and increased the peak height of thrombin generation to the learn more same extent, indicating that inhibition of FXa by TFPI requires the presence of proteinS. TFPI and proteinS titrations in TFPI-depleted or proteinS-depleted plasma in which thrombin formation was initiated with triggers other than TF also revealed TF-independent anticoagulant activity of TFPI, which was completely dependent on the presence of proteinS. ConclusionDirect inhibition of FXa by TFPI contributes to the downregulation of coagulation.”
“Magnetic resonance imaging is increasingly used to assess neonatal hypoxic-ischemic

injury, and several scoring systems were developed to predict neurologic outcomes in these patients. We examined the magnetic resonance imaging studies of 33 neonates/infants who manifested acute perinatal hypoxicischemic https://www.selleckchem.com/products/gsk923295.html injuries. Using a seven-point susceptibility-weighted imaging categorical grading scale, each patient received a “prominence

of vein” score, which was dichotomized into a “normal” or “abnormal” group. Six-month outcomes were assessed using the Pediatric Cerebral Performance Category Scale. We then determined whether “prominence of vein” scores correlated with neurologic outcomes in patients with hypoxic-ischemic injuries, and compared these results with the Barkovich magnetic resonance imaging scoring system. Patients with “normal” “prominence of vein” scores demonstrated better outcomes (mean Pediatric Cerebral Performance Category Scale value = 2) than patients with “abnormal” “prominence of vein” scores (mean Pediatric Cerebral Performance Screening Library Category Scale value = 4). The dichotomized “prominence of vein” groups demonstrated correlations with the Barkovich magnetic resonance imaging scores of the proton density-weighted basal ganglia, watershed, and combined basal ganglia/watershed regions. The susceptibility-weighted imaging categorical grading scale may aid in predicting neurologic outcomes after hypoxic-ischemic injuries. (C) 2011 Elsevier Inc. All rights reserved.”
“Background: Accurate assessment of probiotics with targeted anti-Salmonella activity requires suitable models accounting for both, microbe-microbe and host-microbe interactions in gut environments.

A549 cell pretreatment with WRW4, an antagonist of the transmembr

A549 cell pretreatment with WRW4, an antagonist of the transmembrane formyl peptide receptor-like 1 protein attenuated LL-37′s ability to increase cell stiffness. The LL-37-mediated increase in cell stiffness was accompanied by a decrease in permeability and P. aeruginosa uptake by a confluent monolayer of polarized normal human bronchial epithelial cells. These results suggested that the antibacterial effect of LL-37 involves an LL-37-dependent increase in cell stiffness

that prevents epithelial invasion by bacteria. The find more Journal of Immunology, 2011, 187: 6402-6409.”
“Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by a gradual loss of motoneurons. The majority of ALS cases are associated with a sporadic form whose 432 etiology is unknown. Several pieces of evidence favor autoimmunity as a potential contributor to sporadic ALS pathology. To gain understanding concerning possible antigens interacting with IgGs from sporadic ALS patients (ALS-IgGs), we studied immunoreactivity against neuromuscular junction (NMJ), spinal cord and cerebellum of mice with and without the Ca(V)2.1 pore-forming subunit check details of the P/Q-type voltage-gated calcium (Ca(2+)) channel. ALS-IgGs showed a strong reactivity against

NMJs of wild-type diaphragms. ALS-IgGs also increased muscle miniature end-plate potential frequency, suggesting a functional role for ALS-IgGs on synaptic signaling. In support, in mice lacking the Ca(V)2.1 subunit ALS-IgGs showed significantly reduced NMJ immunoreactivity and did not alter spontaneous acetylcholine release. This difference in reactivity was absent when comparing N-type Ca(2+) channel wild-type or null mice. These results are particularly relevant because motoneurons are known to be early pathogenic targets in ALS. Our findings add further evidence supporting autoimmunity as one of the possible mechanisms contributing to ALS pathology. They also suggest that serum autoantibodies in a subset of ALS patients would see more interact with NMJ proteins down-regulated when P/Q-type

channels are absent.”
“Recycling of poly(ethyleneterephthalate) waste was achieved through glycolysis using diethyleneglycol (DEG) and poly(ethyleneglycol) (PEG 400), which yielded different fractions that exhibited hydroxyl numbers of 174.41 and 54.86 mg of KOH/g, respectively, whereas GPC profiles revealed bimodality in both cases corresponding to Mn values equivalent to 534 and 1648. The products of glycolysis from both cases were individually incorporated as modifiers during the synthesis of urea-formaldehyde resins from both the basic as well as acidic stages, respectively. It was found that the free formaldehyde level was remarkably decreased for the modified resins while the gel time was slightly affected indicating some activation of the resins.

Effluents from continuous in vitro three-stage fermentation colon

Effluents from continuous in vitro three-stage fermentation colonic models of Salmonella Typhimurium infection inoculated with immobilized child microbiota and Salmonella were directly applied to confluent mucussecreting HT29-MTX cell layers. The effects of Salmonella, addition of two bacteriocinogenic strains, Bifidobacterium thermophilum RBL67 (thermophilicin B67) and Escherichia coli L1000 (microcin B17), and inulin were tested Prexasertib in vitro on Salmonella growth and interactions

with epithelial cell layers. Salmonella adhesion and invasion were investigated and epithelial integrity assessed by transepithelial electrical resistance (TER) measurements and confocal microscopy observation. Data from complex effluents were compared with pure Salmonella cultures.\n\nResults: Salmonella in effluents of all reactors of the colonic fermentation model stabilized at mean values of selleck chemicals llc 5.3 +/- 0.8 log(10) cfu/ml effluent. Invasion of cell-associated Salmonella was up to 50-fold lower in complex reactor samples compared to pure Salmonella cultures. It further depended on environmental factors, with 0.2 +/- 0.1% being measured with proximal, 0.6 +/- 0.2% with transverse and 1.3 +/- 0.7% with distal reactor effluents,

accompanied by a similar high decrease of TER across cell monolayers (minus 45%) and disruption of tight junctions. Subsequent addition of E. coli L1000 stimulated Salmonella growth (6.4 +/- 0.6 log(10) cfu/ml effluent of all 3 reactors) and further decreased TER, but led to 10-fold decreased invasion efficiency when tested with distal reactor samples. In contrast, presence of B. thermophilum RBL67 revealed a protective effect on epithelial learn more integrity compared to previous E. coli L1000 periods, as reflected by a significant mean increase of TER by 58% in all reactors. Inulin addition enhanced Salmonella

growth and invasion when tested with distal and proximal reactor samples, respectively, but induced a limited decrease of TER (minus 18%) in all reactors.\n\nConclusions: Our results highlight the benefits of combining suitable cellular and colonic fermentation models to assess strain-specific first-level host protection properties of probiotics during Salmonella infection, providing an efficient system biology tool for preclinical development of new antimicrobials.”
“Are microalgae a potential energy source for biofuel production? This paper presents the laboratory results from a Nannochloropsis sp. microalga biorefinery for the production of oil, high-value pigments, and biohydrogen (bioH(2)). The energy consumption and CO2 emissions involved in the whole process (microalgae cultivation, harvest, dewater, mill, extraction and leftover biomass fermentation) were evaluated. An economic evaluation was also performed. Oil was obtained by soxhlet (SE) and supercritical fluid extraction (SFE). The bioH(2) was produced by fermentation of the leftover biomass.