Sessile rotifer species possessing idiosyncratic temperatures (T bigger than T +1.5 SD) exhibited a trend toward a record of cosmopolitanism. Important idiosyncratic hydrophytes included Ceratophyllum, Chara, and Utricularia.

Two of the three periphytic, rotifer datasets exhibited nestedness (T = 19.2 degrees, 39.9 degrees), but each was supported by only one of the four null models. The periphytic microcrustaceans did not show nestedness, while the insects did (T = 15.5 degrees; supported by four null models). The three other metrics varied considerably among the periphytic datasets, showing no discernable pattern.”
“Objective: To measure TH-302 purchase selleck kinase inhibitor the length and diameter of the

main bronchus using the three-dimensional reconstruction images from the spiral chest computerized tomography scans in Asian adult patients, and to evaluate the relationship between the height of patients and the length and diameter of main bronchi. Design: Prospective observational study. Setting: Academic, tertiary care hospital. Participants: Two hundred Asian adults undergoing a chest spiral computerized tomography scan. Intervention: No intervention. Measurements and Main Results: The authors measured the anteroposterior and transverse diameters of the mid-portion of the right main bronchus and 2 cm below the carina of the left main bronchus. In addition, the length of both main bronchi was also measured. The length of the left main bronchus was about 3-4 U0126 times greater than its right counterpart. The main bronchus of women was oval-shape, with a large

anteroposterior diameter, but the main bronchus of men was round-shape. There was no significant correlation between the measurements of main bronchi and the height of patients. Conclusions: The results showed that there is no direct relationship between the length and diameter of main bronchi and the height of patients. The height is not the criterion for choosing DLT size. Therefore, the authors proposed that 3-D images be used to determine the size of the main bronchi. The diameter of main bronchus using the 3-D images can be used to determine the optimal size of the DLT in a clinical setting, although further studies are needed. (C) 2014 Elsevier Inc. All rights reserved.”
“Introduction: Idiopathic Pulmonary Fibrosis (IPF) is a progressive, incurable fibrotic interstitial lung disease with a prognosis worse than many cancers. Its pathogenesis is poorly understood. Activated platelets can release pro-fibrotic mediators that have the potential to contribute to lung fibrosis. We determine platelet reactivity in subjects with IPF compared to age-matched controls.

Potential plasmodial targets are reported here. Methods: To study the mechanism of action of cepharanthine, a combined approach using phenotypic and transcriptomic techniques was undertaken. Results: Cepharanthine blocked

P. falciparum development in ring stage. On a culture of synchronized ring stage, the comparisons of expression profiles showed that the samples treated with 5 mu M of cepharanthine (IC90) were significantly closer to the initial controls than to the final ones. After a two-way ANOVA (p-value smaller than 0.05) on the microarray results, ARO 002 1,141 probes among 9,722 presented a significant differential expression. A gene ontology analysis showed that the Maurer’s clefts seem particularly down-regulated by cepharanthine. The analysis of metabolic pathways

showed an impact on cell-cell interactions (cytoadherence and rosetting), GSI-IX Proteases inhibitor glycolysis and isoprenoid pathways. Organellar functions, more particularly constituted by apicoplast and mitochondrion, are targeted too. Conclusion: The blockage at the ring stage by cepharanthine is described for the first time. Transcriptomic approach confirmed that cepharanthine might have a potential innovative antiplasmodial mechanism of action. Thus, cepharanthine might play an ongoing role in the progress on anti-malarial drug discovery efforts.”
“AimsActivation of vascular GPER has been linked to vasodepressor effects in animals. However, the significance of GPER regulation on chronic blood pressure control in humans buy GM6001 is unknown. MethodsTo examine this question we determined the functional significance of expression of a common missense single nucleotide variant of GPER, P16L in vascular smooth muscle cells, and its association

with blood pressure in humans. Further, to validate the importance of carrying GPER P16L in the development of hypertension we assessed allele frequency in a cohort of hard-to-treat hypertensive patients referred to a tertiary care clinic. ResultsExpression of the GPER P16L variant (V) vs. wild type (WT) in rat aortic vascular smooth muscle cells, was associated with a significant decrease in G1 (1m, a GPER agonist)-mediated ERK phosphorylation (slope of the function of G1-stimulated ERK phosphorylation: GPER content WT: 16.2, 95% CI 9.9, 22.6; V: 5.0, 95% CI 1.0, 9.0; P smaller than 0.005) and apoptosis (slope of the function of G1-stimulated apoptosis: GPER content: WT: 4.4, 95% CI: 3.4, 5.4; V: 2.5, 95% CI 1.6, 2.3 P smaller than 0.005). Normotensive female subjects, but not male subjects, carrying this hypofunctional variant (allele frequency 22%) have increased blood pressure [mean arterial pressure: P16/P16: 80 1mmHg (n = 204) vs.P16L carriers: 82 +/- 1mmHg (n = 127), 95% CI for difference: 0.6, 4.0mmHg, P smaller than 0.05], [systolic blood pressure: P16/P16: 105 +/- 1mmHg vs. P16L carriers: 108 +/- 1mmHg, 95% CI for difference:1.0, 5.1mmHg, P smaller than 0.05], [diastolic blood pressure: P16/P16: 66 +/- 0.5mmHg vs.

Here we present

direct structural evidence from cryo-electron tomography data that thread-like micelles with a uniform diameter of 6.5 Belinostat nm are organized into loops of different sizes at a surfactin concentration of >15 mol%. (C) 2010 Elsevier B.V. All rights reserved.”
“Orexin-A (OXA) regulates food intake and energy homeostasis. It increases insulin secretion in vivo and in vitro, although controversial effects of OXA on plasma glucagon are reported. We characterized the effects of OXA on glucagon secretion and identify intracellular target molecules in glucagon-producing cells. Glucagon secretion from in situ perfused rat pancreas, isolated rat pancreatic islets, and clonal pancreatic A-cells (InR1-G9) were measured by RIA. The expression of orexin receptor 1 (OXR1) was detected by Western blot and immunofluorescence. The effects of OXA on cAMP, adenylate-cyclase-kinase (AKT), phosphoinositide-dependent kinase (PDK)-1, forkhead box O-1 (Foxo1), and cAMP response element-binding

protein were measured by ELISA and Western blot. Intracellular calcium (Ca-i(2+)) concentration was detected by fura-2and glucagon expression by real-time PCR. Foxo1 was silenced in InR1-G9 cells by transfecting cells with short interfering RNA. OXR1 was expressed on pancreatic A and InR1-G9 cells. OXA reduced glucagon secretion from perfused rat pancreas, isolated rat pancreatic islets, and InR1-G9 cells. OXA inhibited proglucagon selleck inhibitor gene expression via the phosphatidylinositol LY2606368 3-kinase-dependent pathway. OXA decreased cAMP and Ca-i(2+) concentration and increased AKT, PDK-1, and Foxo1 phosphorylation. Silencing of Foxo1 caused a reversal of the inhibitory effect of OXA on proglucagon gene expression. Our study provides the first in vitro evidence for the interaction

of OXA with pancreatic A cells. OXA inhibits glucagon secretion and reduces intracellular cAMP and Ca-i(2+) concentration. OXA increases AKT/PDK-1 phosphorylation and inhibits proglucagon expression via phosphatidylinositol 3-kinase- and Foxo-1-dependent pathways. As a physiological inhibitor of glucagon secretion, OXA may have a therapeutic potential to reduce hyperglucagonemia in type 2 diabetes.”
“The British Bangladeshi community is one of the youngest and fastest growing ethnic minority groups in the UK. Many report poor socio-economic and health profiles with the existence of substantial health inequalities, particularly in relation to type 2 diabetes. Although there is compelling evidence for the effectiveness of lifestyle interventions in the prevention of type 2 diabetes, there is little understanding of how best to tailor treatments to the needs of minority ethnic groups. Little is known about nutrition related lifestyle choices in the Bangladeshi community or the factors influencing such decisions.

CONCLUSIONS: Expression of activated LXR alpha blocks proliferation of human colorectal cancer cells and slows the growth of xenograft tumors in mice. It also reduces

intestinal tumor formation after administration of chemical carcinogens, and in Apc(min/+) mice. LXR agonists therefore might be developed as therapeutic treatments for colorectal cancer.”
“Aims Although several factors contribute to wound healing, bacterial infections and the presence of biofilm can significantly affect healing. Despite that this clearly indicates that therapies should address biofilm in wounds, only few wound care products have been evaluated for their antibiofilm effect. For this reason, find more we developed a rapid quantification approach to investigate

the efficacy of wound care products on wounds infected with Staphylococcus spp. Methods and Results An in vitro chronic wound infection model was used in which a fluorescent Staph.aureus strain was used to allow the rapid quantification of the bacterial burden after treatment. A good correlation was observed between the fluorescence signal and the bacterial counts. When evaluated in HDAC inhibitor review this model, several commonly used wound dressings and wound care products inhibited biofilm formation resulting in a decrease between one and seven log CFU per biofilm compared with biofilm formed in the absence of products. In contrast, most dressings only moderately affected mature biofilms. Conclusion Our model allowed the rapid quantification of the bacterial burden after treatment. However, the efficacy of treatment varied between the different types of

dressings and/or wound care products. Significance and Impact of the Study Our model can be used to compare the efficacy of wound care products to inhibit biofilm formation and/or eradicate mature biofilms. In addition, the results indicate that treatment of infected wounds should be started as soon as possible and that novel products with more potent antibiofilm activity are needed.”
“Duez H, Staels B. Rev-erb-alpha: an integrator of circadian rhythms and metabolism. J Appl Physiol 107: 1972-1980, 2009. First published August 20, 2009; doi:10.1152/japplphysiol.00570.2009.-The endogenous circadian clock ensures daily NVP-BSK805 molecular weight rhythms in diverse behavioral and physiological processes, including locomotor activity and sleep/wake cycles, but also food intake patterns. Circadian rhythms are generated by an internal clock system, which synchronizes these daily variations to the day/night alternance. In addition, circadian oscillations may be reset by the time of food availability in peripheral metabolic organs. Circadian rhythms are seen in many metabolic pathways (glucose and lipid metabolism, etc.) and endocrine secretions (insulin, etc.). As a consequence, misalignment of the internal timing system vs.

Methods Eighty-four social drinkers took part in two studies that followed a counterbalanced repeated measure design. Fifteen men and 33 women were tested the morning (09:00, 11:00 or 13:00?h) following normal/usual alcohol consumption and the morning after no alcohol consumption; the order of testing was counterbalanced. In a second study, 36 participants (18 men and 18 women) were

tested after receiving alcohol to attain a blood alcohol concentration of 0.08%, and after no alcohol administration, the order of testing was counterbalanced. In both studies, participants completed LDN-193189 ic50 a task battery of memory, reaction time and attention tasks. Results Alcohol had no effect on the free recall task and the spatial attention task. Alcohol consumption, either acute or the next day, significantly affected reaction time, divided attention, selective attention and Stroop interference. The impairments during intoxication and hangover were of comparable magnitude. Performance on tasks of delayed recognition and irregular interstimulus reaction time was worse during hangover when compared with intoxication. Conclusion It is evident that awareness selleck kinase inhibitor needs to be raised

that performance the morning after alcohol consumption is at the same level if not worse than when participants are at the legal limit for driving (0.08% blood alcohol concentration). Copyright (c) 2012 John PCI-34051 inhibitor Wiley & Sons, Ltd.”
“Traditionally, medical therapy for epilepsy has aimed to suppress seizure activity, but has been unable to alter the progression of the underlying disease. Recent advances in our understanding of mechanisms of epileptogenesis open the door for the development of new therapies which prevent the pathogenic changes in the brain that predispose to spontaneous seizures. In particular, the mammalian target of rapamycin (mTOR) signaling pathway has recently

garnered interest as an important regulator of cellular changes involved in epileptogenesis, and mTOR inhibitors have generated excitement as potential antiepileptogenic agents. mTOR hyperactivation occurs in tuberous sclerosis complex (TSC), a common genetic cause of epilepsy, as a result of genetic mutations in upstream regulatory molecules. mTOR inhibition prevents epilepsy and brain pathology in animal models of TSC. mTOR dysregulation has also been demonstrated in a variety of other genetic and acquired epilepsies, including brain tumors, focal cortical dysplasias, and animal models of brain injury due to status epilepticus or trauma. Indeed, mTOR inhibitors appear to possess antiepileptogenic properties in animal models of acquired epilepsy as well. Thus, mTOR dysregulation may represent a final common pathway in epilepsies of various causes.

\n\nMethods and Results: Rats were 5-Fluoracil injected with NaHS (an H2S donor, 2-200 mu mol.kg(-1).day(-1), i.p.) or saline for 3 weeks. MBP was measured with a tail-cuff method. C erebral arterioles were isolated and cannulated

in an organ bath system, and vessel diameters were measured with an image-shearing device. Changes in diameter in response to stepwise increases in intravascular pressure (20-120 mmHg) were investigated under no-flow conditions. After the treatments, plasma H2S increased and MBP decreased significantly. NaHS reduced the myogenic response in a dose-dependent manner. This effect was markedly attenuated by glibenclamide, a K-ATP channel blocker. Blockade of nitric oxide (NO) production with NG-nitro-L-arginine methyl ester (L-NAME, a NO synthase inhibitor) enhanced,

whereas removal of the endothelium abolished the inhibitory role of NaHS on the myogenic response.\n\nConclusions: For the first time it has been demonstrated that H2S decreases the myogenic response of cerebral arterioles in vivo, and this effect is selleck chemical endothelium-dependent and partially mediated by K-ATP channels. (Circ J 2012; 76: 1012 1019)”
“BACKGROUND & AIMS: Liver X receptors (LXRs) are transcriptional regulators of cholesterol metabolism, controlling cholesterol flow into cells, catabolism, and efflux. Cholesterol controls cell proliferation; disruptions in cholesterol metabolism have been associated with the development of colon cancer. We investigated whether expression of activated LXR protects against intestinal tumorigenesis in mice. METHODS: We analyzed the development of colon cancer in mice that express a constitutive active form of LXR alpha only in the intestinal epithelium, under the control of villin promoter (iVP16LXR alpha). These mice were crossed with adenomatous polyposis coli (Apc)(min/+) mice,

or given azoxymethane followed by dextran sodium sulfate, to assess intestinal tumor formation. We also assessed proliferation and apoptosis of a human Selleckchem Proteasome inhibitor colorectal cancer cell line (HT29) transfected with an adenoviral vector that expressed Ad VP16hLXR alpha, compared with cells expressing AdVP16 (control), and their ability to form xenograft tumors in mice. HT29 cells also were incubated with the LXR ligand GW3965. RESULTS: In human colorectal cancer cells, ligand-induced activation of LXR or transfection with Ad VP16hLXR alpha blocked the G1 phase, increased caspase-dependent apoptosis, and slowed growth of xenograft tumors in mice. iVP16LXR alpha mice formed fewer, smaller tumors than VP16 (control) mice after administration of azoxymethane and dextran sodium sulfate. APC(min/+)/iVP16LXR alpha mice also developed fewer, smaller intestinal tumors than APC(min/+)/iVP16 mice.

Studies of TSH and FT4 levels over a period of 3 years indicated that the TRIAC effect is dose dependent.\n\nConclusions: TRIAC was effective and safe in ameliorating the effects of hyperthyroidism

and ADHD symptoms in a child with known genetic RTH. Further, it was demonstrated that TRIAC has a short half-life and functions dose dependently.”
“Spinal angiolipomas are benign uncommon neoplasm composed of mature lipocytes admixed with abnormal blood vessels. They account for only 0.04-1.2% of all spinal tumors. We report two cases of lumbar extradural angiolipoma and review previously reported cases. We found 118 cases of spinal epidural angiolipoma (70 females and 48 males; age range 1.5-85 years, mean 44.03) spanning from 1890 to 2006. Prior to diagnosis 40.6% of the patients had weakness of the lower limbs. The interval Selleck PLX4032 between the initial symptoms and tumor diagnosis ranged from 1 day to 17 years (mean 20.2 months). Except

for four cases diagnosed at autopsy, 109 patients underwent surgery and gross-total resection was performed in 79 cases (72.4%). Spinal angiolipomas are tumors containing angiomatous and lipomatous tissue, predominantly located in the mid-thoracic region. All angiolipomas show iso- or hyperintensity on T1-weighted images and hyperintensity on T2-weighted images and most lesions enhance with gadolinium administration. The RG-7388 treatment for spinal extradural angiolipomas is total surgical resection and no adjuvant therapy should be administered.”
“Background: Originally described as osteochondromatous Fedratinib nmr lesions arising from the tarsal bones, osteochondromas arising from the epiphysis or carpal/tarsal bones are less common than those arising from the metaphysis. Histologically, all osteochondromas are indistinguishable regardless

of the location from which they arise. Few case reports and case series exist describing these lesions in the upper limb.\n\nMethods: We review 7 cases of osteochondromas arising from epiphyses and ossicles in the upper limb treated at 3 institutions. Patients were followed for an average of 5.7 years. The average patient age at the presentation was 7.8 years.\n\nResults: We identified 25 lesions: 5 distal radial epiphyseal, 3 distal radial metaphyseal, 4 scaphoid, 4 lunate, 4 trapezial, 2 accessory ossicles adjacent to the trapezium, 2 trapezoid, and 1 metacarpal lesion. Three patients presented with pain, 5 with decreased motion, and 3 with angular deformity. In 1 case, the lesion presented as an incidental finding. Four patients underwent a total of 7 procedures: 2 open biopsies, 2 distal radial epiphyseal lesion excisions, 2 revisions, and 1 excision of all lesions with a scaphoid osteotomy.

VFA-SWIFT allowed reliable measurement of T-1 in the osteochondral specimens, including regions where FSE-based methods failed. The T(1)s measured by VFA-SWIFT were shifted toward shorter values in specimens. However, the measurements correlated significantly (highest correlation VFA-SWIFT versus FSE was r=0.966). SNR efficiency was generally highest for SWIFT, especially in the subchondral bone. ConclusionFeasibility of measuring T-1 relaxation time using VFA-SWIFT in osteochondral specimens and phantoms was demonstrated. A shift toward shorter T(1)s was observed for VFA-SWIFT in specimens, reflecting the higher sensitivity of SWIFT to short T-2* spins.

Magn Reson Med 74:175-184, 2015. (c) 2014 Wiley Periodicals, Inc.”
“Fluorescence microscopy has profoundly changed cell and molecular biology studies CH5183284 clinical trial by permitting tagged gene products to be followed as they function and interact. The ability of a fluorescent dye to absorb and emit light of different wavelengths allows it to generate startling contrast that, in the best cases, can permit single molecule detection and tracking. However, in many experimental settings, fluorescent probes fall short of their potential due to dye bleaching, dye signal saturation, and tissue autofluorescence. Here, we demonstrate that

second harmonic generating (SHG) nanoprobes can be used for in vivo imaging, circumventing many of the limitations of classical fluorescence SNX-5422 probes. Under intense illumination, such as at the focus of a laser-scanning microscope, these SHG nanocrystals convert two photons into one photon of half the wavelength; thus, when imaged by conventional two-photon microscopy, SHG nanoprobes appear to generate a signal with an inverse Stokes shift like a fluorescent dye, but with a narrower emission.

Unlike commonly AL3818 used fluorescent probes, SHG nanoprobes neither bleach nor blink, and the signal they generate does not saturate with increasing illumination intensity. The resulting contrast and detectability of SHG nanoprobes provide unique advantages for molecular imaging of living cells and tissues.”
“An efficient L-proline catalyzed one-pot synthesis of 3-amino-alkylated indoles has been developed via a three-component Mannich-type reaction viz. secondary amines, aldehyde and indoles under solvent-free conditions at room temperature. Several amino acids (acidic, basic and neutral) have been screened for the reaction but the best results were obtained with L-proline.”
“Background Inhalation incidents are an important cause of acute respiratory symptoms, but little is known about how these incidents affect chronic respiratory health.\n\nMethods We assessed reported inhalation incidents among 3,763 European Community Respiratory Health Survey (ECRHS) participants with and without cough, phlegm, asthma, wheezing, or bronchial hyperresponsiveness.

Reexpression of CRBP-1 LY2606368 nmr increased retinol sensitivity and reduced viability of ovarian cancer cells in vitro. Further studies are needed to explore new therapeutic strategies aimed at restoring CRBP-1-mediated intracellular retinol trafficking and the meaning of CRBP-1 expression in cancer patients’ screening for a more personalized and efficacy retinoid therapy.”
“Circulating endothelial cells (CECs) and circulating endothelial progenitors (CEPs) are currently being investigated in a variety of diseases as markers of vascular turnover or damage

and, also in the case of CEPs, vasculogenesis. CEPs appear to have a “catalytic” role in different steps of cancer progression and recurrence after therapy, and there are preclinical and clinical data suggesting that CEC enumeration might be useful to select and stratify patients who are candidates for anti-angiogenic treatments. In some types of cancer, CECs and CEPs might be one of the possible

hidden identities of cancer stem cells. The definition of CEC and CEP phenotype and the standardization of CEC and CEP enumeration strategies are highly desirable goals find more in order to exploit these cells as reliable biomarkers in oncology clinical trials. (C) 2009 Elsevier B.V. All rights reserved.”
“The use of antiretroviral therapy (ART) to treat HIV infection, by restoring CD4+ cell count and immune function, is associated with significant reductions in morbidity and mortality. Soon after ART initiation, there is a rapid phase of restoration of pathogen-specific immunity. In certain patients, this

results in inflammatory responses that may result in clinical deterioration known as ‘the immune reconstitution inflammatory syndrome’ (IRIS). IRIS may be targeted at viable infective antigens, dead or dying infective antigens, host antigens, tumour antigens and other antigens, giving rise OSI-906 solubility dmso to a heterogeneous range of clinical manifestations. The commonest forms of IRIS are associated with mycobacterial infections, fungi and herpes viruses. In most patients, ART should be continued and treatment for the associated condition optimized, and there is anecdotal evidence for the use of corticosteroids in patients who are severely affected. In this review, we discuss research relating to pathogenesis, the range of clinical manifestations, treatment options and prevention issues.”
“Purpose Genetic polymorphisms of organic cation transporter 2 (OCT2) have been recently described, but their genotype-phenotype relationship in humans is unknown. We performed this study to (i) characterize genetic variations of the OCT2 gene in the Chinese population and 00 investigate the potential functional significance of OCT2 polymorphisms using metformin (an OCT2 substrate) alone or in the presence of its transport inhibitor (cimetidine).

Morbidity and mortality rates are high for total exenteration and abdominosacral resection. After curative surgery, 5-year global survival from 30% to 40% is observed. Careful selection of patients with better preoperative status before resection SB273005 in vivo is needed to achieve more curative resections and increase long-term survivor rates. (C) 2013 Elsevier Masson SAS. All rights reserved.”
“The work presented here investigates the cross-linking of various nucleophilic amino acids with lignin under aqueous conditions, thus providing insight as to which amino acids might cross-link with lignin in planta. Lignin dehydrogenation polymer (DHP) was prepared in aqueous solutions that

contained tripeptides with the general structure XGG, where X represents an amino acid with a nucleophilic side chain. Fourier-transform infrared spectroscopy and energy dispersive X-ray spectroscopy showed that peptides containing cysteine and tyrosine were incorporated GS-7977 in vivo into the DHP to form DHPCGG and DHPYGG adducts, whereas peptides containing other nucleophilic amino acids were not incorporated. Scanning electron microscopy showed that the physical morphology

of DHP was altered by the presence of peptides in the aqueous solution, regardless of peptide incorporation into the DHP. Nuclear magnetic resonance (NMR) spectroscopy showed that cysteine-containing peptide cross-linked with lignin at the lignin ?-position, whereas in the case of the lignintyrosine adduct the exact cross-linking pathway could not be determined. This

is the first study to use NMR to confirm cross-linking between lignin and peptides under biomimetic conditions. The results of this study may indicate the potential for ligninprotein linkage formation in planta, particularly between lignin and cysteine- and/or tyrosine-rich proteins.”
“This study was undertaken to compare the phenotype of human articular chondrocytes (ACs) and bone marrow-derived mesenchymal stem cells (MSCs) after cell expansion by studying the spectrum of proteins secreted by cells into the culture medium. ACs and MSCs were expanded in monolayer cultures for some weeks, as done in standard cell transplantation procedures. Initially, the expression of cartilage signature genes was compared by real-time PCR. Selleckchem SRT1720 Metabolic labeling of proteins (SILAC) in combination with mass spectrometry (LC/MS-MS) was applied to investigate differences in released proteins. In addition, multiplex assays were carried out to quantify the amounts of several matrix metalloproteases (MMPs) and their natural inhibitors (TIMPs). Expanded chondrocytes showed a slightly higher expression of cartilage-specific genes than MSCs, whereas the overall spectra of released proteins were very similar for the two cell types. In qualitative terms MSCs seemed to secrete similar number of extracellular matrix proteins (43% vs.