We propose that degradation of the asymmetrically produced viral

We propose that degradation of the asymmetrically produced viral positive-strand RNAs associated with abundant virus accumulation contributes to

the positive-strand bias of viral small RNAs.”
“The mental-rotation task is a well known research paradigm to examine cognitive processes of mental imaging and mental manipulation (Shepard & Metzler, 1971). So far, research has been focused on stimulus orientation which indicates the necessary amount of mental rotation. But little attention has been paid to stimulus parity, specifically if and how identical and mirror-reversed stimuli are processed differently. We wanted to fill this gap by combining performance, eye-tracking, LCZ696 and neurofunctional measures using pairwise presented three-dimensional www.selleckchem.com/products/dinaciclib-sch727965.html Shepard-Metzler stimuli in a self-paced event-related fMRI design. Based on our results we tried to reason at which stage of the mental-rotation process the treatment of mirrored and identical stimuli begins to diverge.

As a common finding, response times for tasks with mirrored stimuli were longer compared to tasks with identical stimuli reflecting their higher cognitive demand. Moreover, we observed smaller saccade amplitudes for mirrored than for identical stimuli suggesting a smaller functional field of view during stimulus perception. The eye-movement results were complemented

by our neurofunctional findings. Here, the processing of mirrored stimuli led to less activation in parts of the early visual cortex that respond to the visual periphery than the processing of identical figures. This activation difference remained after eye-movement-associated activations had been excluded. We explain our findings by stimulus-parity-induced differences in saliency maps built up to enhance perception. Acyl CoA dehydrogenase Thus, the treatment of mirrored and identical stimuli begins to diverge very early in the mental-rotation process

and is associated with differences in visual processing. (C) 2012 Elsevier Ltd. All rights reserved.”
“The somatic recombination of lymphocyte antigen receptor loci is integral to lymphocyte differentiation and adaptive immunity. Here we review the relation of this highly choreographed process with the zinc finger protein CTCF and with cohesin, a protein complex best known for its essential functions in post-replicative DNA repair and chromosome segregation during the cell cycle. At lymphocyte antigen receptor loci, CTCF and cohesin shape long-range interactions and contribute to V(D)J recombination by facilitating lineage- and developmental-stage-specific transcription and accessibility.”
“Hepatitis B is the most common and serious liver disease, especially in developing countries. Although HBV pathogenesis has been extensively investigated, the proteomic alteration of hepatocytes during HBV chronic infection is still unclear.

Changes in expression of proteins related to tubulointerstitial f

Changes in expression of proteins related to tubulointerstitial function, podocyte structure, and mitochondrial apoptosis are implicated in the mechanism of DN and their reversal by TETA. These findings are consistent with the hypothesis that this new experimental therapy may be useful for treatment of DN.”
“BACKGROUND: The epidemiology of traumatic brain injury (TBI) is often studied through the use of International Classification of Disease, ninth revision, clinical modification (ICD-9-CM), diagnosis codes from the Centers for Disease Control and Prevention TBI Surveillance System.

Recent studies suggest that these codes may underestimate the burden of TBI because of inaccuracies

and low sensitivity.

OBJECTIVE: To determine the sensitivity and specificity NSC23766 mouse of ICD-9-CM codes in a severe TBI population.

METHODS: We retrospectively reviewed medical records of all hospital admissions including computed tomography of the head at a single center to identify severe blunt TBI patients, their injuries, and the neurosurgical procedures performed. We calculated sensitivity and specificity by comparing ICD-9-CM diagnosis and procedure codes assigned by hospital coders with medical records, the gold standard.

RESULTS: In 2008, there were 148 qualifying admissions. These codes were 89% sensitive for the presence of any severe TBI. However, one-fifth of these cases were identified only with SDHB a code defining a nonspecific head injury. Next, we studied types of TBI by categories defined by the Centers for PD0332991 solubility dmso Disease Control and Prevention (morbidity groups) and by ICD-9-CM codes for types of injury (any skull fracture, intracranial contusion, intracranial hemorrhage, concussion/loss of consciousness) and found widely varying sensitivity and specificity for both. In general, these codes had higher specificity than sensitivity. Both sensitivity and specificity were > 80% for only

2 categories: any skull fracture and intracranial hemorrhage. In contrast, we found high sensitivity and specificity for neurosurgical procedures (97% and 94%).

CONCLUSION: ICD-9-CM codes were sensitive for the presence of any severe TBI, but further classification of specific types of TBI was limited by variable sensitivity/specificity. Use of these codes should be supplemented by other methodology.”
“Worldwide amphibian population declines have been ascribed to global warming, increasing pollution levels, and other factors directly related to human activities. These factors may additionally be favoring the emergence of novel pathogens. In this report, we have determined the complete genome sequence of the emerging common midwife toad ranavirus (CMTV), which has caused fatal disease in several amphibian species across Europe.

In dual task and passive viewing, this N1 latency-shift was aboli

In dual task and passive viewing, this N1 latency-shift was abolished. Comparisons of “”low-attention”" (dual task or passive viewing) with “”high-attention”" conditions (single task or active viewing) revealed that attention only shortened N1 peak-latency

when the target was preceded by stimulus sequences with spatial and temporal regularity. P1 this website latency was unaffected by manipulation of top-down attention factors. Attentional factors are likely to modulate influences of spatiotemporal context through re-afferent projections at later stages of visual processing in regions of extrastriate cortex associated with the generators of the N1 waveform. (C) 2011 IBRO. Published by Elsevier Ltd. All rights reserved.”
“Objective: Repeat percutaneous endoluminal interventions for femoropopliteal occlusive disease are common, but the outcomes are poorly understood. We sought to determine the results of second-time femoropopliteal percutaneous transluminal angioplasty/stenting (SPTAS) and identify factors associated with success or failure of a continued

endoluminal revascularization strategy.

Methods: A retrospective review of patients undergoing multiple percutaneous endoluminal lower extremity interventions at a single institution 4-Hydroxytamoxifen mw from 2002 and 2009 identified 70 SPTAS in 70 limbs. Patient comorbidities, anatomic severity of disease, and procedural characteristics were analyzed with respect to outcomes with descriptive statistics, Kaplan-Meier curves, and Cox proportional hazards modeling. Patency rates were determined from the time of SPTAS.

Results: Patients included 37 men (63%) and 22 women (27%) at a mean age of 70 10 years. Indications for SPTAS included claudication in 54 limbs (77%) and critical limb ischemia (CLI) in 16 (23%). Median time from the initial endoluminal intervention to SPTAS was 330 days. Lesion Trans Atlantic Inter Society Consensus II (TASCII) classification was A in 18 (25.7%), B in 18 (25.7%), C in 25 (35.7%), and D in 9 (12.9%). Technical success was achieved in secondly 68 (97%) with low

rates of intraprocedural (10%) and postprocedural (4%) complications as well as initial clinical improvement in 61 (87%) patients. Over a median follow-up of 22.9 months following SPTAS, 2-year primary patency, secondary patency, limb salvage (in patients with CLI), and survival were 33% +/- 7%, 63% +/- 7%, 87% +/- 9%, and 88% +/- 5%, respectively. Cox proportional hazard modeling showed that SPTAS within 180 days of the initial endovascular intervention was the only significant predictor of failure of primary patency (hazard ratio, 2.65; 95% confidence interval, 1.4-5.2) and secondary patency (hazard ratio, 3.1; 95% confidence interval, 1.4-7.1) of SPTAS.

Conclusions: Second-time femoropopliteal angioplasty/stenting has excellent technical success but limited midterm primary and secondary patency.

The method is versatile for the routine analysis of in-gel trypti

The method is versatile for the routine analysis of in-gel tryptic digests thereby allowing for an improved protein sequence coverage. Furthermore, reliable protein identification can be achieved without the need of desalting sample preparation. We demonstrate the performance and the robustness of our method using commercially available reference proteins and automated MS and MS/MS analyses of in-gel digests from lung tissue lysate proteins separated by 2-DE.”
“Response

inhibition refers to the suppression of inappropriate or irrelevant responses. It has a central role in executive functions, and has been linked to a wide spectrum of prevalent neuropsychiatric disorders. Increasing evidence Tucidinostat mouse from neuropharmacological studies has suggested that gene variants in the norepinephrine RG7112 mouse neurotransmission system make specific contributions to response inhibition. This study genotyped five tag single-nucleotide polymorphisms covering the whole alpha-2B-adrenergic receptor (ADRA2B) gene and investigated their associations with response

inhibition in a relatively large healthy Chinese sample (N = 421). The results revealed significant genetic effects of the ADRA2B conserved haplotype polymorphisms on response inhibition as measured by stop-signal reaction time (SSRT) (F(2, 418) = 5.938, p = 0.003). Individuals with the AAGG/AAGG genotype (n = 89; mean SSRT = 170.2 ms) had significantly shorter SSRTs than did those with either the CCAC/AAGG genotype (n = 216; mean SSRT = 182.4 ms; uncorrected p = 0.03; corrected p = 0.09)

or the CCAC/CCAC genotype (n = 116; mean SSRT = 195.8 ms; corrected p<0.002, Cohen’s d = 0.51). This finding provides the first evidence from association research in support of a critical role of the norepinephrine neurotransmission system in response inhibition. A better understanding of the genetic basis of response inhibition would allow us to develop more effective diagnosis, treatment, and prevention of deficient Ceramide glucosyltransferase or underdeveloped response inhibition as well as its related prevalent neuropsychiatric disorders. Neuropsychopharmacology (2012) 37, 1115-1121; doi:10.1038/npp.2011.266; published online 4 January 2012″
“Plant-derived polyphenols such as curcumin hold promise as a therapeutic agent in the treatment of chronic liver diseases. However, its development is plagued by poor aqueous solubility resulting in poor bioavailability. To circumvent the suboptimal bioavailability of free curcumin, we have developed a polymeric nanoparticle formulation of curcumin (NanoCurct (TM)) that overcomes this major pitfall of the free compound. In this study, we show that NanoCurct (TM) results in sustained intrahepatic curcumin levels that can be found in both hepatocytes and non-parenchymal cells. NanoCurct (TM) markedly inhibits carbon tetrachloride-induced liver injury, production of pro-inflammatory cytokines and fibrosis.

Male offspring exposed to diuron at 750 ppm displayed reduced bod

Male offspring exposed to diuron at 750 ppm displayed reduced body weight at PND 10, 21, 42, and 90 compared to controls. At PND 90, diuron treatment did not induce significant change in daily sperm production, sperm morphology

and motility, and testosterone levels selleck chemical compared to controls. In conclusion, diuron at 750 ppm induced male offspring toxicity but these alterations were not permanent, as evidenced by absence of reproductive-system alterations in adult Sprague Dawley rats.”
“Intracranial carotid artery atherosclerotic disease is an independent predictor for recurrent stroke. However, its quantitative assessment is not routinely performed in clinical practice. In this diagnostic study, we present and evaluate a novel semi-automatic application to quantitatively measure intracranial internal carotid artery (ICA) degree of stenosis and calcium volume in CT angiography (CTA) images.

In this retrospective study involving CTA images of 88

consecutive patients, intracranial ICA stenosis was quantitatively measured by two independent observers. Stenoses were categorized with cutoff values of 30% and 50%. The calcification in the intracranial ICA was qualitatively categorized as absent, www.selleckchem.com/products/Trichostatin-A.html mild, moderate, or severe and quantitatively measured using the semi-automatic application. Linear weighted kappa values were calculated to assess the interobserver agreement of the stenosis and calcium categorization. The find more average and the standard deviation of the quantitative calcium volume were calculated for the calcium categories.

For the stenosis measurements, the CTA images of 162 arteries yielded an interobserver correlation of 0.78

(P < 0.001). Kappa values of the categorized stenosis measurements were moderate: 0.45 and 0.58 for cutoff values of 30% and 50%, respectively. The kappa value for the calcium categorization was 0.62, with a good agreement between the qualitative and quantitative calcium assessment.

Quantitative degree of stenosis measurement of the intracranial ICA on CTA is feasible with a good interobserver agreement ICA. Qualitative calcium categorization agrees well with quantitative measurements.”
“Accumulating evidence shows that T cells penetrate the central nervous system (CNS) parenchyma in several autoimmune, infectious, and degenerative neurological diseases. The structural and functional consequences for CNS neurons of their encounter with activated T cells have been investigated in several experimental systems, including ex vivo co-cultures, electrophysiology, and in vivo imaging. Here, we review the modalities of neuron/T cell interactions.

The most common diagnoses were arterionephrosclerosis, HIV-associ

The most common diagnoses were arterionephrosclerosis, HIV-associated nephropathy and glomerulonephritis. Other diagnoses included pyelonephritis,

interstitial nephritis, diabetic nephropathy, fungal infection and amyloidosis. Excluding 2 instances of acute tubular necrosis, slightly over one-third of the cases would have been predicted using current diagnostic criteria for chronic kidney disease. Based on see more semi-quantitative analysis of stored specimens, pre-mortem microalbuminuria testing could have identified an additional 12 cases. Future studies are needed to evaluate the cost-effectiveness of more sensitive methods for defining chronic kidney disease, in order to identify HIV-infected patients with early kidney disease who may benefit from antiretroviral therapy and other interventions known to delay disease progression and prevent complications.”
“The collecting duct of the kidney is composed of two morphologically and physiologically distinct cell types, principal and intercalated cells. To better understand intercalated cell function we generated a transgenic mouse expressing Cre recombinase under the control of a cell type-specific promoter. We used 7 kb of the ATP6V1B1 5′ untranslated region (B1 promoter), a gene found in the intercalated cells AZD4547 purchase of the kidney and the male reproductive tract. We first crossed these B1-Cre transgenic mice with the ROSA26-loxP-stop-loxP-yellow

fluorescent protein reporter mice to assess the specificity Bleomycin purchase of Cre expression. Immunohistochemistry and confocal fluorescence microscopy showed that Cre is selectively active in all intercalated cells (type A, type B, and non-A/B cells) within the collecting duct and

most cells of the connecting segment. About half of the principal cells of the connecting segment also expressed Cre, a pattern also seen in B1-driven enhanced green fluorescent protein transgenic mice. Cre was found to be active in the male reproductive tract and at a low level in limited non-ATP6V1B1 expressing tissues. The B1-Cre transgenic mice are healthy, breed normally, produce regular sized litters, and transmit the transgene in Mendelian fashion. This new cell-specific Cre expressing mouse should prove useful for the study of intercalated cell physiology and development.”
“Injection drug use accounts for approximately one-third of human immunodeficiency virus (HIV) infections in the United States. HIV-associated proteins have been shown to interact with various drugs of abuse to incite concerted neurotoxicity. One common area for their interaction is the nerve terminal, including dopamine transporter (DAT) systems. However, results regarding DAT function and regulation in HIV-infection, regardless of drug use, are mixed. Thus, the present experiments were designed to explicitly control Tat and cocaine administration in an in vivo rat model in order to reconcile differences that exist in the literature to date.

Multivariate analysis showed that the size of the primary tumor a

Multivariate analysis showed that the size of the primary tumor and the presence of vascular emboli were independent factors selleck chemicals of worse outcome.

Conclusions: Lobectomy with arterial sleeve resection has acceptable mortality and no specific complications. Late results in terms of survival are satisfactory.”
“OBJECTIVE AND IMPORTANCE: Our patient’s symptomatology, history, physical examination, diagnosis, management, and functional outcome 1 year after surgical repair is presented and discussed in light of the current literature on lipofibrohamartomas.

CLINICAL PRESENTATION: A 3-year-old boy presented

to the Louisiana State University Nerve Clinic for evaluation and management because he was experiencing progressive symptoms of left hand swelling, dysesthesia, and impaired motor function. Physical examination demonstrated median nerve distribution motor impairment. Electromyographic/nerve conduction

velocity studies also showed severely reduced conduction and amplitude of the median nerve response, and the magnetic Givinostat concentration resonance imaging findings were highly suggestive of lipofibrohamartoma. Hence, the presumed diagnosis was lipofibrohamartoma on the basis of imaging characteristics, location, and patient’s age.

INTERVENTION: The patient was brought to the operating room with the objectives of carpal tunnel release and biopsy. However, routine intraoperative nerve action potential recordings showed no or very poor responses, consistent with significant loss of median nerve function. On the basis of the intraoperative nerve action potentials, we opted to resect the tumor back to healthy median nerve fascicles and Ergoloid to perform graft repairs. Surgery proceeded uneventfully, without any complications. Pathology confirmed the diagnosis of lipofibrohamartoma.

CONCLUSION: At 18 months postoperatively, the patient had excellent left hand function. On the basis of our experience with this patient, we believe that intraoperative

nerve action potentials and the availability of usable proximal and distal nerve fascicles (which may be discernible on diagnostic imaging) are key factors in deciding whether a liprofibrohamartoma needs to be repaired or decompressed/biopsied. As illustrated by our case, we believe that resection and graft repair may be the best treatment option for some of these patients, and perhaps more so for pediatric patients.”
“Objective: Recently, interindividual differences in lymphatic vessel density among patients with cancer have become a focus of interest for surgeons as a significant prognostic factor. Little morphometric information is available about esophageal lymphatics in the absence of esophageal pathologic changes. We used D2-40 immunohistochemical examination to clarify the normal configuration of the esophageal intramural lymphatics and to evaluate morphometrically preexisting mucosal vessels.

Results We show that many of these assumptions can now be seen t

Results. We show that many of these assumptions can now be seen to be false and that the model of genetic heterogeneity is consistent with observed familial recurrence risks, endophenotype studies and other population-wide parameters.

Conclusions. We argue for a more biologically consilient mixed model that involves interactions between ISRIB cell line disease-causing and disease-modifying variants in each individual. We consider the implications of this model for moving SZ research beyond statistical associations to pathogenic mechanisms.”
“A mixed culture capable of dechlorinating perchloroethylene (PCE) to ethene was analyzed under non steady and pseudo-steady state conditions. Dehalococcoides mccartyi,

considered to be the primary dechlorinating bacterium able to completely degrade chlorinated hydrocarbons to Nec-1s research buy non toxic ethene, could be detected by CAtalyzed Reporter Deposition Fluorescence In Situ Hybridization (CARD-FISH)

since the beginning of culture operation but highlighted by conventional FISH only during active PCE dechlorination to ethene and vinyl chloride (VC). Data generated from FISH and CARD-FISH analyses were compared to those generated from applying PCR-based techniques directed at defining cell abundances (Real Time PCR, qPCR) and assessing cell activities (Reverse Transcription qPCR, RT-qPCR) of Dehalococcoides strains involved in the PCE reductive dechlorination (RD) process. qPCR targeting reductive dehalogenase genes coding for enzymes involved in the individual steps of the RD process, showed that Dehalococcoides strains carrying the tceA gene dominated the community. This observation was consistent with PCE conversion products detected under pseudo-steady state (ethene and VC production), since this tceA gene is known to be associated to strains capable of reducing chlorinated solvents beyond 1,2-cis-dichloroethene (cis-DCE). In line with the FISH data, Dehalococcoides learn more 16S rRNA and tceA genes were expressed only during pseudo-steady state conditions when PCE was converted completely to the final metabolic product ethene. Furthermore, Dehalococcoides cell abundances estimated by CARD-FISH

correlated positively with their 16SrRNA gene copy numbers quantified by qPCR. This is consistent with the ability of both these methods to estimate total Dehalococcoides cell numbers including those with low metabolic activities. Thus, this study shows that application potential of FISH analysis to quantify rapidly and efficiently only active dechlorinators in complex communities.”
“Background. Psychiatric conditions in which symptoms arise involuntarily (‘diseases’) might be assumed to be more heritable than those in which choices are essential (behavioral disorders). We sought to determine whether psychiatric ‘diseases’ (Alzheimer’s disease, schizophrenia, and mood and anxiety disorders) are more heritable than behavioral disorders (substance use disorders and anorexia nervosa).

Method.

We report what is, to our knowledge, a unique case of a calcified

We report what is, to our knowledge, a unique case of a calcified extra-axial cerebellopontine angle (CPA) cavernoma involving the lower CNs.

CLINICAL

PRESENTATION: Saracatinib cost A 48-year-old man was admitted to our department with a 5-month history of gait instability and loss in tone of voice, A clinical examination documented gait disturbances and hoarseness but was otherwise unremarkable. Neuroradiological studies revealed a calcified mass in the lower third of the CPA cistern that was angiographically occult. it was associated with 3 additional lesions with a radiological appearance suggestive of multiple cavernomas.

INTERVENTION: The patient underwent a retrosigmoid approach, and the calcified mass, tightly adherent to the lower CNs, was gently removed. The histopathological examination was consistent with a cavernoma. Adriamycin in vivo The postoperative course was characterized by a further lowering in the patient’s tone of voice. At the 3-month follow-up examination, the patient showed significant improvement.

CONCLUSION: CPA cavernomas are an extremely rare entity. Symptoms are generally related to CN compression, and subarachnoid hemorrhage is a very rare occurrence. The clinical and radiological appearance may mimic that of other CPA tumors (meningiomas, schwannomas). In spite of the benign nature and the very low risk of hemorrhage, we believe, with support from the literature, that surgical treatment is mandatory to prevent significant

neurological deficits owing to the chronic CN compression.”
“PVS-RIPO is it recombinant oncolytic poliovirus

designed for clinical application to target CD155 expressing malignant gliomas and other Clomifene malignant diseases. PVS-RIPO does not replicate in healthy neurons and is therefore non-pathogenic in rodent and non-human primate models of poliomyelitis. A tetrazolium salt dye-based cellular assay was developed and qualified to define the cytotoxicity of virus preparations on susceptible cells and to explore the target cell specificity of PVS-RIPO. In this assay, PVS-RIPO inhibited proliferation of U87-MG astrocytoma cells in a dose-dependent manner. However, HEK293 cells were much less susceptible to cell killing by PVS-RIPO. In contrast, the Sabin type 1 live attenuated poliovirus vaccine strain (PV(1)S) was cytotoxic to both HEK293 and U87-MG cells. The correlation between expression of CD155 and cytotoxicity was also explored using six different cell lines. There was little or no expression of CD155 and PVS-RIPO-induced cytotoxicity in Jurkat and Daudi cells. HEK293 was the only cell line tested that showed CD155 expression and resistance to PVS-RIPO cytotoxicity. The results indicate that differential cytotoxicity measured by the colorimetric assay can be used to evaluate the cytotoxicity and cell-type specificity of recombinant strains of poliovirus and to demonstrate lot to lot consistency during the manufacture of viruses intended for clinical use.

The following tests were performed on the MSCs: the

downf

The following tests were performed on the MSCs: the

downflow test, intake velocity test, high-efficiency particulate air filter leak test and the airflow smoke pattern test. These performance tests were carried out Selleckchem Gemcitabine in accordance with the standard procedures. Only 23% of Class II A1 (8), A2 (19) and unknown MSCs (4) passed these performance tests. The main reasons for the failure of MSCs were inappropriate intake velocity (65%), leakage in the HEPA filter sealing (50%), unbalanced airflow smoke pattern in the cabinets (39%) and inappropriate downflow (27%).

Conclusions: This study showed that routine checks of MSCs are important to detect and strengthen the weak spots that frequently develop, as observed during the evaluation of the MSCs of various institutions.

Significance and Impact of the Study: Routine evaluation and maintenance of MSCs are critical for TPCA-1 optimizing performance.”
“The posterior parietal cortex, including the medial superior parietal lobule (mSPL), becomes transiently more active during acts of cognitive

control in a wide range of domains, including shifts of spatial and nonspatial visual attention, shifts between working memory representations, and shifts between categorization rules. Furthermore, spatial patterns of activity within mSPL, identified using multivoxel pattern analysis (MVPA), reliably distinguish between different acts of control. Here we describe a novel multivoxel pattern-based analysis that uses fluctuations in cognitive state over time to reveal inter-regional functional connectivity.

First, we used MVPA to model patterns of activity in mSPL associated with shifting or maintaining spatial attention. We then computed a multivoxel pattern time course (MVPTC) that reflects, moment-by-moment, the degree to which the pattern of activity in mSPL more closely matches an attention-shift pattern or a sustained-attention pattern. We then entered the MVPTC as a regressor in a univariate (i.e., voxelwise) general linear model (GLM) to identify voxels whose BOLD activity covaried with the MVPTC. This analysis revealed several regions, including the striatum Tau-protein kinase of the basal ganglia and bilateral middle frontal gyrus, whose activity was significantly correlated with the MVPTC in mSPL For comparison, we also conducted a conventional functional connectivity analysis, entering the mean BOLD time course in mSPL as a regressor in a univariate GLM. The latter analysis revealed correlations in extensive regions of the frontal lobes but not in any subcortical area. The MVPTC analysis provides greater sensitivity (e.g., revealing the striatal-mSPL connectivity) and greater specificity (i.e., revealing more-focal clusters) than a conventional functional connectivity analysis. We discuss the broad applicability of MVPTC analysis to a variety of neuroimaging contexts. Published by Elsevier Ltd.