These results suggest that there are may be significant behavioral consequences of antidepressant use during late pregnancy on offspring maternal attachment and social behavior, with implications for increased

risk of autism spectrum disorders. (c) 2014 Wiley Periodicals, Inc. Dev Psychobiol 57: 141-152, 2015.”
“Increasing evidence indicates that soluble aggregates of amyloid beta protein (A beta) are neurotoxic. However, difficulty in isolating IPI-145 chemical structure these unstable, dynamic species impedes studies of AP and other aggregating peptides and proteins. In this study, hydrogen-deuterium exchange (HX) detected by mass spectrometry (MS) was used to measure A beta(1-40) aggregate distributions without purification or modification that might alter the aggregate structure or distribution. Different peaks in the mass spectra

were assigned to monomer, low molecular weight oligomer, intermediate, and fibril based on HX labeling behavior and complementary assays. After I h labeling, the intermediates incorporated approximately ten more deuterons relative to fibrils, indicating a more solvent exposed structure of such intermediates. HX-MS also showed that the click here intermediate species dissociated much more slowly to monomer than did the very low molecular weight oligomers that were formed at very early times in A beta aggregation. Atomic force microscopy (AFM) measurements revealed the intermediates were roughly spherical with relatively homogenous diameters of 30-50 nm. Quantitative analysis of the HX mass spectra showed that the amount of intermediate species was correlated

with A beta toxicity patterns reported in a previous study under the same conditions. This study also demonstrates the potential of the HX-MS approach to characterizing complex, multi-component oligomer distributions of aggregating peptides and proteins.”
“The aerobic respiratory chain of the thermohalophilic bacterium Rhodothermus marinus, a nonphotosynthetic organism from the Pfizer Licensed Compound Library in vitro Bacteroidetes/Chlorobi group, contains a high-potential iron-sulfur protein (HiPIP) that transfers electrons from a bc (1) analog complex to a caa (3) oxygen reductase. Here, we describe the crystal structure of the reduced form of R. marinus HiPIP, solved by the single-wavelength anomalous diffraction method, based on the anomalous scattering of the iron atoms from the [4Fe-4S](3+/2+) cluster and refined to 1.0 resolution. This is the first structure of a HiPIP isolated from a nonphotosynthetic bacterium involved in an aerobic respiratory chain. The structure shows a similar environment around the cluster as the other HiPIPs from phototrophic bacteria, but reveals several features distinct from those of the other HiPIPs of phototrophic bacteria, such as a different fold of the N-terminal region of the polypeptide due to a disulfide bridge and a ten-residue-long insertion.”
“An integrated miniature multi-modal microscope (4M device) for microendoscopy was built and tested.

Adult male Sprague-Dawley rats were subject to CLP or sham operation and, after 12 h, CA3 underwent injurious mechanical ventilation (tidal volume 30 ml/kg, positive end-expiratory pressure 0 cmH(2)O) for either 0, 60, or 120 min. Biochemical and physiological measurements, as well as computed tomography, were used to assess injury at 0, 60, and 120 min of ventilation. Before ventilation, CLP rats had higher levels of alveolar neutrophils

and interleukin-1 beta. After 60 min of ventilation, CLP rats had worse injury as evidenced by increased alveolar inflammation, permeability, respiratory static compliance, edema, oxygenation, and computed tomography. By 120 min, CLP and sham rats had comparable levels of lung injury as assessed by many, but not all, of these metrics. CLP rats had an accelerated and worse loss of end-expiratory lung volume relative to sham, and consistently higher levels of alveolar interleukin-1 beta. Loss of aeration and progression of edema was more pronounced in dependent lung regions. We conclude

that CLP initiated pulmonary inflammation in rats, and accelerated the development of subsequent VILI.”
“The aim of the present paper was to compare different methods for detecting methicillin resistance in Staphylococcus aureus. selleck compound Among the isolates analyzed, 52 belonged to MRSA international lineages commonly detected in the American continent and 14 to sporadic MRSA clones. Both 30 mu g-cefoxitin disk and PBP2a had 100% sensibility/specificity when the low-level heterogeneous isolates were tested and, thus, are highly recommended.”
“Background: The diagnosis of primary ciliary dyskinesia (PCD) requires the analysis of ciliary

function and ultrastructure. Diagnosis can be complicated by secondary effects on cilia such as damage during sampling, local inflammation or recent infection. To differentiate primary from secondary abnormalities, re-analysis of cilia following Selleckchem Z VAD FMK culture and re-differentiation of epithelial cells at an air-liquid interface (ALI) aids the diagnosis of PCD. However changes in ciliary beat pattern of cilia following epithelial cell culture has previously been described, which has brought the robustness of this method into question. This is the first systematic study to evaluate ALI culture as an aid to diagnosis of PCD in the light of these concerns.\n\nMethods: We retrospectively studied changes associated with ALI-culture in 158 subjects referred for diagnostic testing at two PCD centres. Ciliated nasal epithelium (PCD n = 54; non-PCD n = 111) was analysed by high-speed digital video microscopy and transmission electron microscopy before and after culture.

67 with ASIR (40%) and 4.97 with ASIR (80%).

Those in non-HR mode were 3.27 with ASIR (40%) and 3.90 with ASIR (80%). The mean artefact scores in HR mode were 3.13 with ASIR (40%) and 3.63 with ASIR (80%), but those in non-HR mode were 2.87 with ASIR (40%) and 2.53 with ASIR (80%). The mean scores of the other parameters were greater than 3, whereas those in HR mode were higher than those in non-HR mode. There were significant differences between ASIR (40%) and ASIR (80%) AZD4547 datasheet in overall image quality (p < 0.01). Contrast medium in the injection syringe was scanned to analyse image quality; ASIR did not suppress the severe artefacts of contrast medium.\n\nConclusion: In general, MPR image quality with ASIR (80%) was superior to that with ASIR (40%). However, there was an increased incidence

of artefacts by ASIR when CT images were obtained in non-HR mode.”
“Therapy-related ALL (t-ALL) is a rare secondary leukemia that develops after chemotherapy and/or radiotherapy for primary malignancies. Chromosomal 11q23 abnormalities are the most common karyotypic alterations Vactosertib mw in t-ALL. The t(11;19)(q23;p13) aberration is extremely rare and has not been confirmed at the molecular genetic level. Here, we report a case oft-ALL with t(11;19)(q23;p13.3) and MLL-MLLT1 (alias ENL) gene rearrangement confirmed by cytogenetic analysis, multiplex reverse transcription-PCR (multiplex RT-PCR), and DNA sequencing in a patient who had undergone treatment for breast cancer. A 40-yr-old woman developed acute leukemia 15 months after undergoing 6 cycles of adjuvant chemotherapy (doxorubicin 60 mg/m(2) and cyclophosphamide 600 mg/m(2)), radiation therapy (dose, 5,900 cGy), and anticancer endocrine therapy with tamoxifen. The complete blood cell counts and bone marrow examination showed increased blasts and the blasts showed B lineage immunophenotype (positive for CD19, CD34, and cytoplasmic CD79a). Cytogenetic BLZ945 analysis revealed the karyotype 47,XX,+X,t(11;19)(q23;p13.3)[4]/46,XX[16]. FISH analyses, multiplex RT-PCR, and DNA sequencing confirmed

the MLL-MLLT1 gene rearrangement. The patient underwent induction chemotherapy with fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (Hyper-CVAD) and achieved complete remission. Subsequently, she underwent consolidation chemotherapy, but died of brain ischemia in the pons and the region of the middle cerebral artery. To our knowledge, this is the first case report of t-ALL with t(11;19)(q23;p13.3) and the MLL-MLLT1 gene rearrangement.”
“OUTCOME OF THE CRITICAL PATIENT ACCORDING TO THE SEX AND THE AGE\n\nObjective. To determine if gender and age are associated with differences in mortality in patients requiring critical care.\n\nDesign. Retrospective analysis of prospectively collected data over 6 consecutive years.\n\nSetting. Polyvalent intensive care unit (ICU) of a tertiary hospital in the Canary Islands.\n\nPatients.

These intersect, forming a three-dimensional pore network in which the water molecules coordinated HSP990 to the Ni atoms and the K+ ions required to charge balance the framework reside. The K+ ions lie in a highly distorted environment surrounded by ten O atoms, six of which are closer than 3.1 angstrom. The coordinated water molecules are

within hydrogen-bonding distance to O atoms of bridging Ga-O-P groups.”
“Background: Pulmonary rehabilitation has been shown to be effective for improving quality of life and function in patients with chronic obstructive pulmonary disease (COPD) but has not been studied extensively in homebound patients. Furthermore, little is known about the effectiveness of specific types of home-based interventions.\n\nPurpose: The purpose of this study was to examine the effectiveness of in-home rehabilitation programs for individuals with COPD considered homebound according to Medicare definition and to compare outcomes of 2 different rehabilitation interventions.\n\nMethods: Patients were randomly assigned to 2 home-based interventions including aerobic conditioning (group A) or functional strength training (group PLK inhibitor B), which were conducted over 8 weeks. In addition, all patients received COPD self-management

education. Outcome measures were collected after completion of the Z-DEVD-FMK mw intervention and after 16 weeks and included the Chronic Respiratory Questionnaire (CRQ), Geriatric Depression Scale, and 2-minute walk test.\n\nResults: Of 41 patients enrolled, 24 completed the 8-week intervention. On average, all CRQ quality-of-life domains improved in both groups, with the largest improvements in the CRQ-dyspnea domain.

Overall, at 16 weeks, 80% of group A and 71% of group B patients had clinically significant improvements in the CRQ-dyspnea domain. Furthermore, depression scores improved in both groups. Only group A had a clinically significant improvement in walking distance.\n\nConclusion: The results of this pilot study suggest that both forms of home-based rehabilitation may improve disease-specific quality of life in homebound patients with COPD.”
“Objective: Placenta accreta is a general term describes abnormal adherent placenta to the uterine wall. When the chorionic villi invade the myometrium, the term placenta increta is appropriate. Nowadays, it is one of the increasing causes of rnaterno-fetal morbidities and mortality. The aim of this research was to evaluate density of decidual natural killer cells (dNK, CD56+(bright)) in decidua basalis in patients with placenta accreta.

Removal of ROS inhibited all parthenolide-associated events, such as cell death, AMPK activation, autophagy induction, and cell cycle arrest.

Blockade of autophagy relieved cell cycle arrest, whereas inhibition of AMPK activity significantly repressed the induction of both autophagy and cell cycle arrest. These observations clearly showed that parthenolide-driven ROS activated AMPK-autophagy pathway. Furthermore, inhibition of either AMPK or autophagy significantly potentiated parthenolide-induced apoptosis. Therefore, our results show that parthenolide activates both apoptosis pathway and AMPK-autophagy survival pathway through the generation of ROS, and that suppression of AMPK or autophagy can potentially enhance the anti-cancer effect of parthenolide on breast cancer cells. (C) 2014 Wiley JPH203 in vivo Periodicals, Inc.”
“Megachile rotundata (F.) (Hymenoptera: Megachilidae)

is the primary pollinator of alfalfa in the northwestern United States and western Canada and provides Belnacasan purchase pollination services for onion, carrot, hybrid canola, various legumes, and other specialty crops. M. rotundata females are gregarious, nest in cavities either naturally occurring or in artificial nesting blocks, where they construct a linear series of brood cells. Because of the physical layout of the nest, the age of the larvae within the nest and the microenvironment the individual larvae experience will vary. These interacting factors along with other maternal inputs affect the resulting phenotypes of the nest mates. To further our understanding of in-nest physiology, gender and developmental rates were examined in relationship to cell position within the nest. Eighty-two percent of the females were located within the first three cells, those furthest from

the nest entrance. For those individuals developing in cells located in the deepest half of the nest, the sex of the previous bee had a significant effect on the female decision of the gender of the selleck chemical following nest mate. Removing the prepupae from the nest and rearing them under identical conditions demonstrated that position within the nest during larval development had a significant effect on the postdiapause developmental rates, with males whose larval development occurred deeper in the nest developing more slowly than those toward the entrance. No positional effect on postdiapause developmental rates was noted for the females. The cell position effect on male postdiapause developmental rate demonstrates that postdiapause development is not a rigid physiological mechanism uniform in all individuals, but is a dynamic plastic process shaped by past environmental conditions.”
“How communication systems emerge is a topic of relevance to several academic disciplines.

C/EBPa was able to significantly reverse the inhibitory activity of E4BP4 on SREBP-1 a promoter. These results demonstrated that HBx activates SREBP-la activity at the transcription level through a complex mechanism involving two bZIP transcription factors C/EBP and E4BP4 with C/EBP being the dominant positive factor. Finally, we showed that knocking down SREBP-1 abolishes HBV enhancer II/core promoter activation by HBx. (C) 2013 Elsevier Inc. All rights reserved.”
“Background: Tacrolimus causes post-transplant diabetes mellitus, Bafilomycin A1 datasheet however the pathogenetic mechanisms

remain controversial. In this study we probed into the mechanisms of tacrolimus-induced diabetes mellitus in rats. Methods: Glucose levels were determined on whole blood samples using a glucose oxidase method. Levels of serum insulin and C-peptide

were measured with ELISA. Histological damage CAL-101 of ultra-structure and apoptosis of beta cells of the pancreas were assayed with electric microscope and tunnel methods respectively.-Ultra-structure were assayed with electric microscope and apoptosis of beta cells of the pancreas were assayed with tunel methods. Immunohistochemistry was utilized to detect the sum of insulin receptors of hepatic cells. Results: Compared to control group, insulin and C peptide levels in serum decreased in rats of diabetes mellitus models induced with FK506(P < 0.05). Compared to the control group, the sum of apoptosis body in pancreatic islets increased in rats of diabetes mellitus models induced with FK506 (P < 0.05). Compared to the control group, electron microscopy showed cytoplasm swelling and vacuolization, and marked decrease or absence of dense-core secretory granules in beta cells in rats

with diabetes mellitus induced with FK506.Compared to the control group, expression of insulin receptor of hepatic cell decreased in rats of diabetes mellitus models induced with FK506 (P < 0.05). Conclusion: Pathogenetic mechanisms of rats of diabetes mellitus models induced with FK506 including reduction of secretion Ferroptosis inhibitor of insulin in beta cells of pancreatic islets, damages of ultra-structure of beta cells of pancreatic islets, increasing of apoptosis of beta cells of pancreatic islets and decreasing of expression of insulin receptors in hepatic cells.</.”
“People with a psychiatric illness are at high risk for suicide; however, variation of the risk by patients’ sex and age and by specific diagnosis needs to be explored in a more detail. This large population study systematically assesses suicide incidence rate ratio (IRR) and population attributable risk (PAR) associated with various psychiatric disorders by comparing 21,169 suicides in Denmark over a 17-year period with sex-age-time-matched population controls.

This was a prospective study to compare the success of colonoscopy with minimal sedation using water immersion and conventional air insufflation.\n\nPatients and methods: A total of 229 patients were randomized to either water immersion or the standard air insertion technique. The primary outcome Staurosporine was success of minimal sedation colonoscopy, which was defined as reaching the cecum without additional sedation, exchange of the adult colonoscope or hands-on assistance for trainees. Patient comfort and satisfaction were also assessed.\n\nResults: Successful minimal-sedation colonoscopy was achieved in 51% of the water immersion group compared with 28% in the standard air

group (OR, 2.66; 95% CI 1.48-4.79; P = 0.0004). Attending physicians had 79% success with water immersion compared with 47% with air insufflation (OR, 4.19; 95% CI 1.5-12.17; P = 0.002), whereas trainees had 34% success with water compared with 16% using air (OR, 2.75; 95% CI 1.15-6.86; P = 0.01). Using the water method, endoscopists intubated the cecum faster and this was particularly notable for trainees (13.0 +/- 7.5

minutes with water vs. 20.5 +/- 13.9 minutes with air; P = 0.0001). Total procedure time was significantly shorter with water for both experienced and trainee endoscopists (P < 0.05). Patients reported less intraprocedural pain with water compared with air (4.1 +/- 2.7 vs. 5.3 +/- 2.7; P = 0.001), with a similar level of satisfaction. There Temsirolimus order was no difference in the neoplasm detection rates between the groups.\n\nConclusion: Colonoscopy insertion using water immersion increases the success rate of minimal sedation colonoscopy. Use of the technique leads to a decrease in discomfort, time to reach the cecum, and the amount of sedative and analgesic used, without compromising patient satisfaction.”
“There are to date no objective clinical laboratory blood tests for mood disorders. The current reliance on patient self-report of symptom severity and on the clinicians’ impression

is a rate-limiting www.selleckchem.com/products/p5091-p005091.html step in effective treatment and new drug development. We propose, and provide proof of principle for, an approach to help identify blood biomarkers for mood state. We measured whole-genome gene expression differences in blood samples from subjects with bipolar disorder that had low mood vs those that had high mood at the time of the blood draw, and separately, changes in gene expression in brain and blood of a mouse pharmacogenomic model. We then integrated our human blood gene expression data with animal model gene expression data, human genetic linkage/association data and human postmortem brain data, an approach called convergent functional genomics, as a Bayesian strategy for cross-validating and prioritizing findings. Topping our list of candidate blood biomarker genes we have five genes involved in myelination (Mbp, Edg2, Mag, Pmp22 and Ugt8), and six genes involved in growth factor signaling (Fgfr1, Fzd3, Erbb3, Igfbp4, Igfbp6 and Ptprm).

The buy Epoxomicin difference in the compared region between A(u) and A is mainly caused by four differential TE insertion and two deletion events between these genomes. The estimated divergence time of A genomes calculated on nucleotide substitution rate in both shared TEs and collinear genes further supports the closer evolutionary relationship of A to A(u) than to A(m). The structure conservation in the repetitive regions promoted us to develop repeat

junction markers based on the A(u) sequence for mapping the A genome in hexaploid wheat. Eighty percent of these repeat junction markers were successfully mapped to the corresponding region in hexaploid wheat, suggesting that T. urartu could serve as a useful resource for developing molecular markers for genetic and breeding studies

in hexaploid wheat.”
“Epidemiologic observations that have been made in the context of the current pandemic influenza virus include a stable virulence phenotype and a lack of propensity to reassort with seasonal strains. In an attempt to determine whether either of these observations could change in the future, we coinfected differentiated human airway cells with seasonal oseltamivir-resistant A/New Jersey/15/07 and pandemic A/Tennessee/1-560/09 (H1N1) viruses in three ratios (10: 90, 50: 50, and Dinaciclib research buy 90: 10) and examined the resulting progeny viruses after 10 sequential passages. When the pandemic virus was initially present at multiplicities of infection equal to or greater than those for the seasonal virus, only pandemic virus genotypes were detected. These adapted pandemic strains did, however, contain two nonsynonymous mutations

(hemagglutinin K154Q and polymerase acidic protein L295P) that conferred a more virulent phenotype, both in cell cultures and in ferrets, than their parental strains. The polymerase acidic protein mutation increased polymerase activity at 37 degrees C, and the hemagglutinin change affected binding of the virus to alpha 2,6-sialyl receptors. When the seasonal A/H1N1 virus was initially present in excess, the dominant progeny virus was a reassortant containing the hemagglutinin gene from the seasonal strain and the remaining genes from the pandemic virus. Our study demonstrates that the emergence of an A/H1N1 pandemic strain of higher virulence is Kinase Inhibitor Library ic50 possible and that, despite their lack of detection thus far in humans, viable seasonal/pandemic virus reassortants can be generated.\n\nIMPORTANCE This report supplies a key piece of information for investigating future evolution scenarios of pandemic A/H1N1 influenza in the human population. We report that the emergence of an A/H1N1 pandemic strain of higher virulence is possible and that, despite their lack of detection thus far in humans, viable seasonal/pandemic virus reassortants can be generated.”
“Weissella cibaria, Lactobacillus plantarum, Lactobacillus sp.

We determined BMS-777607 cell line plasma levels of vitamin K compound, bone-Gla-protein, matrix-Gla-protein, and routine biochemistry. Vertebral fractures (reduction in vertebral body height by >= 20%) and aortic and iliac calcifications were also investigated in a spine (D-5-L-4) radiograph. Three-year patient survival was analyzed. Important proportions of patients had deficiency of MK7 (35.4%), vitamin K1 (23.5%), and MK4 (14.5%). A total of 55.3% of patients had vertebral fractures, 80.6% had abdominal aorta calcification, and 56.1% had iliac calcification. Vitamin K1 deficiency was the strongest

predictor of vertebral fractures (odds ratio [OR], 2.94; 95% confidence interval [CI], 1.38-6.26). MK4 deficiency was a predictor of aortic calcification (OR, 2.82; 95% CI, 1.14-7.01), whereas MK5 deficiency actually protected against it (OR, 0.38; 95% CI, 0.15-0.95). MK7 deficiency was a predictor of iliac calcification (OR, 1.64; 95% CI, 1.03-2.60). The presence of vertebral fractures was also Nepicastat nmr a predictor of vascular calcifications (OR, 1.76; 95% CI, 1.00-3.08). Increased alkaline phosphatase and C reactive protein (CRP), age, and cerebrovascular events were predictors of mortality. Our study suggests that the vitamin K system may be important for preserving bone mass and avoiding vascular calcification in hemodialysis patients,

pointing out a possible role of vitamin K in bone and vascular health. Based on our results, we suggest that the general population should also be studied for vitamin K deficiency as a possible cause of both vertebral fractures and vascular calcification. (C) 2012 American Society for Bone and Mineral Research.”
“The chemical composition of 42 essential-oil samples isolated from the leaves of Xylopia quintasii harvested in three Ivoirian forests was investigated by GC-FID, including the determination

of retention indices (RIs), and by C-13-NMR analyses. CA4P price In total, 36 components accounting for 91.9-92.6% of the oil composition were identified. The content of the main components varied drastically from sample to sample: (E)-beta-caryophyllene (0.9-56.9%), (Z)-beta-ocimene (0.3-54.6%), beta-pinene (0.8-27.9%), alpha-pinene (0.1-22.8%), and furanoguaia-1,4-diene (0.0-17.6%). The 42 oil compositions were submitted to hierarchical cluster and principal components analysis, which allowed the distinction of three groups within the oil samples. The composition of the oils of the major group (22 samples) was dominated by (E)-beta-caryophyllene. The oils of the second group (12 samples) contained beta-pinene and alpha-pinene as the principal compounds, while the oils of the third group (8 samples) were dominated by (Z)-beta-ocimene, germacrene D, (E)-beta-ocimene, and furanoguaia-1,4-diene. The oil samples of Group I and II came from clay-soil forests, while the oil samples belonging to Group III were isolated from leaves harvested in a sandy-soil forest.

Chemical Leasing is an innovative business model that shows a great potential to become a global model for sustainable development within chemical management. This paper provides a review of the current standings of literature regarding the implementation of Chemical Leasing in the past decade. In doing so, the paper highlights the potential of this business model to serve as an approach for dematerializing production processes and managing the risks of chemicals at all levels. More in detail, it provides an outline of how Chemical Leasing has supported the alignment and implementation of the objectives of chemicals policy-makers and industry regarding

the production and use of chemicals and analyses to what extent Chemical Leasing contributes to the implementation

of a number of voluntary global initiatives, such as Cleaner Production, Sustainable Chemistry and Corporate Social Responsibility. This paper provides a systematic analysis of the gaps identified in literature AR-13324 regarding the implementation of Chemical Leasing business models. Based on this analysis, specific aspects in the field of Chemical Leasing are recommended to be further elaborated in order to increase the understanding and applicability of the business model.”
“Cats corticocerebellar units within the anterior vermis are affected by the vestibular input and show directionally tuned responses. The aim of the study was investigating whether a similar representation of labyrinth signals was present in the rat cerebellar vermis by recording units activity during tilt and wobble rotations. The analysis of the neuronal discharge during both clockwise

(CW) and Thiazovivin in vitro LY2090314 purchase counterclockwise (CCW) wobble allowed to determine the spatial (preferred direction) and temporal (response phase) response properties of the recorded neurons. Many units were affected by labyrinthine stimulation. “Bidirectional” units responded to both CVV and CCW stimuli. being characterized by a direction of maximal sensitivity (G a), the distribution of which covered all the sectors of the horizontal plane, with contralaterally pointing vectors more represented within the caudal part of the explored region. Differences in the amplitude of the CVV and CCW responses indicated that neurons received a convergence of vestibular signals endowed with different spatial and temporal properties, a process that is expected to link their response phase with the tilt direction. Population vector analysis showed that recorded neurons coded both the amplitude and direction of head tilt during different types of rotational stimuli. In conclusion, the present results show that the processing of vestibular signals with complex spatiotemporal properties represents a general function of the mammalian cerebellar vermis, allowing accurate monitoring of head rotational movements (of the head) in vertical planes. Finally, in rats, different cerebellar regions seem to receive specific vestibular inputs. (C) 2008 Elsevier Inc.