Conclusion:  The discriminate ability of the m-JIS score is substantially better than those of other staging Regorafenib ic50 systems and has better prognostic predictive power in patients with

grade I accumulation of lipiodol after first chemoembolization. “
“Presenting Author: YONG WOO AHN Additional Authors: BYUNG CHUL YOON, EUN YOUNG DOO, KI DEOK YOO, KANG NYEONG LEE, DAE WON JUN, HANG LAK LEE, OH YOUNG LEE, HO SOON CHOI, JOON SOO HAHM Corresponding Author: YONG WOO AHN Affiliations: Hanyang University Medical Center, Hanyang University Medical Center, Hanyang University Medical Center, Hanyang University Medical Center, Hanyang University Medical Center, Hanyang Tamoxifen in vitro University Medical Center, Hanyang University Medical Center, Hanyang University Medical Center, Hanyang University Medical Center Objective: An association between obesity and unfavorable outcomes for various types of malignancy has been established. However, the relationship between fat distribution and lymph node metastasis has not been well studied.

The aim of our study is to determine the impact of visceral obesity on lymph node metastasis and overall survival in colon cancer. Methods: This study reviewed medical records for consecutive patients who underwent radical resection for colon cancer between 2003 and 2008. Metastatic lymph node ratio (MLR) was defined as the number of involved nodes by tumor divided to the total number of resected lymph nodes. Visceral obesity was determined by measuring abdominal fat volume distribution via CT scan and then calculating the percentage of visceral fat (VF%)

to total fat area. Results: 278 Silibinin patients were divided into two groups: VFs (VF% ≤ 29, n = 81) and VFv (VF% > 29, n = 197). The baseline characteristics showed some differences between two groups with respect to body mass index, total cholesterol and the proportion of MLR. In the multivariate analysis, MLR significantly decreased with the higher VF% (OR = 0.406, 95% CI = 0.206–0.801, P = 0.009). In addition, MLR was significantly associated with HbA1c, differentiation, lymphovascular invasion and perineural invasion. There was significant difference in overall survival between patients with VF% ≤ 29 and those with VF% > 29 (P = 0.009). Conclusion: A higher ratio of visceral fat was associated with a decreased ratio of metastatic lymph nodes and increased overall survival. Key Word(s): 1. visceral obestiy; 2. lymph node metastasis; 3.

5A,B,D). Although immunoblotting analysis did not show changes in CYP2E1 protein levels in WT mice upon starvation, immunohistochemical (IHC) staining revealed a significant increase in CYP2E1 expression in WT mice; however, starvation-induced up-regulation of CYP2E1 was markedly greater in CD1d−/− mice. CYP2E1 activity was higher in CD1d−/− mice than WT mice after 16-hour starvation (Fig. 5C). To confirm that increased susceptibility of CD1d−/− mice was the result of starvation-induced up-regulation of CYP2E1, we treated naïve nonstarved female WT and CD1d−/− mice with APAP (700 mg/kg). The results showed no

R428 difference in serum ALT levels between WT and CD1d−/− mice (Supporting Fig. 1). CYP2E1 regulation occurs at both transcriptional and post-translational levels.18, 19 To explore the mechanism of increased CYP2E1 protein expression in CD1d−/− mice after starvation, we examined hepatic Cyp2e1 messenger RNA (mRNA) levels. Real-time polymerase chain reaction (PCR) analysis of

naïve and starved WT and CD1d−/− mice demonstrated that starvation did not up-regulate Cyp2e1 mRNA and that mRNA levels were similar between WT and CD1d−/− mice (Fig. 6A). Furthermore, proteasome peptidase activities, measured by CT-L and T-L activity analyses, were selleck screening library similar between WT and CD1d−/− mice after starvation (Fig. 6B,C), suggesting that differential proteasomal degradation cannot explain the increased expression level in CD1d−/− mice. Post-translational stabilization

mediated by substrate binding is another possible mechanism accounting for the increased protein expression of CYP2E1.20 BOH represents a main ketone body produced in the liver, which is freely converted into acetoacetate and broken down into acetone, two molecules reported to stabilize CYP2E1 Flavopiridol (Alvocidib) post-translationally.18, 21 Our data demonstrated that naïve WT and CD1d−/− mice exhibited similar levels of BOH in serum. Starvation of mice increased BOH levels in WT and CD1d−/− mice. A significantly greater elevation of BOH levels was observed in CD1d−/− mice, compared to WT mice (Fig. 6D). To determine whether increased susceptibility of CD1d−/− mice to AILI was the result of NKT cell depletion, but not an unexpected effect of CD1d deletion, we examined another strain of NKT cell-deficient mice (i.e., Jα18−/− mice). Female WT and Jα18−/− mice were injected with APAP (350 mg/kg). A marked increase in serum ALT levels was observed in Jα18−/− mice, compared to WT mice, at 8, 24, and 48 hours post-APAP challenge (Fig. 7A). Similar to female mice, male Jα18−/− mice developed a greater degree of injury, compared to WT mice (Fig. 7B). Significantly higher APAP protein adducts and a significant decrease in MMP were observed in Jα18−/− mice after 1-hour APAP challenge, compared to WT mice (Fig. 7 C,D). A trending decrease in membrane potential was observed after starvation in Jα18−/−, compared to WT mice (data not shown).

[3] Thereafter, many studies have been performed to reveal the contribution of innate immunity to the pathology of PBC,[4-7] whereas the site of excess IgM production remained unknown. The IgM memory B cells are generated in the spleen. Namely, the naive B cells that are generated in bone marrow first enter the spleen through blood flow and subsequently enter the white pulp through the periarteriolar lymphoid sheath (PALS). They are stimulated by antigen presentation and co-stimulation by the dendritic cells and the T cells in lymph follicles of the white pulp, exhibit somatic hypermutation, and then differentiate into BMS-777607 datasheet the switched memory B cells that express IgG on the

cell surface and IgM memory B cells that actively produce high-affinity IgM.[8, 9] Circulating innate immune factors stimulate IgM memory B cells to proliferate.[10] For instance, pneumococcal capsular polysaccharide stimulates the proliferation of IgM B cells and increases IgM production in the

spleen.[11] Surgical removal of the spleen causes reduction in the number of the circulating IgM-producing B cells, and could cause overwhelming post-splenectomy infection.[11] Thus, we hypothesized that circulating pathogen-associated molecular patterns (PAMP) stimulate IgM memory B cells to proliferate in the spleen in PBC and produce excess IgM, and conducted the present immunohistochemical study. FORMALIN-FIXED during SPLENIC tissue samples were collected at the time of the autopsy from PBC patients with hepatic failure. click here All the participants,

including family members of deceased patients, provided written informed consent in full compliance with institutional regulations. Mean blood IgM level of eight PBC cases (six women and two men, mean age of 74.5 years old, and four cases of stage III and four cases of stage IV according to Scheuer’s classification) was 284.6 ± 87.9 mg/dL. All the patients were positive for antimitochondrial autoantibody and administrated 600 mg/day ursodeoxycholic acid. In positive controls, splenic tissue samples were obtained at the time of the surgery to remove gastric cancer. Splenic tissues from eight autopsy cases of chronic hepatitis C virus (HCV) infection with hepatic failure (six women and two men, mean age of 75.8 years old) were used as controls. Additionally, 10 liver biopsy samples from PBC were used as extrasplenic controls. Paraffin-embedded 4-μm splenic and liver tissue sections were stained with mouse monoclonal antihuman IgM antibody (DAKO, Glostrup, Denmark) and mouse monoclonal antihuman CD21 antibody (Nichirei, Tokyo, Japan) for identification of the follicular dendritic cell (FDC) network in lymph follicles, and goat polyclonal anti-CXCL13 antibody (R&D Systems, Minneapolis, MN, USA) as a chemokine related to B-cell homing and differentiation.

PK samples for boceprevir determination were obtained predose and at selected intervals until 24 hours postdose. After the final PK sample was obtained on day 2, subjects received another single dose of boceprevir (800 mg) together with a single dose of tacrolimus (0.5 mg). PK samples for boceprevir buy BVD-523 (in the presence of tacrolimus) were collected predose and then at selected intervals until the morning of day 3 (equivalent to 24 hours postdose). On day 3, after the last PK sample had been obtained, safety assessments were performed, and subjects were then discharged. All subjects returned to the clinic for final safety assessments on day 10. Concentrations of cyclosporine and tacrolimus in collected human

blood samples were determined using high-performance liquid chromatography (HPLC) and HPLC–tandem mass spectrometry, respectively, at PharmaNet Canada (Quebec, Quebec, Canada). The lower limit of quantification (LLOQ) for the cyclosporine assay was

2 ng/mL; the linear calibration range was 2-1,002 ng/mL. The LLOQ for the tacrolimus assay was 50.52 pg/mL; the linear calibration range was 50.52 to 50,520 pg/mL. Concentrations of boceprevir and its metabolites in collected human plasma samples were determined using HPLC–tandem mass spectrometry at PPD (Middleton, AZD2281 WI). Concentrations of boceprevir were determined as the sum of concentrations of two enantiomers of boceprevir: SCH 534128 and SCH 534129. Concentrations of SCH 629144, an inactive metabolite of boceprevir, were obtained as the sum of concentrations of four analytes: SCH 783004, SCH 783005, SCH 783006, and SCH 783007. The Dolichyl-phosphate-mannose-protein mannosyltransferase overall LLOQ for boceprevir was 4.80 ng/mL, and the overall LLOQ for SCH 629144 was 2.50 ng/mL. Standard PK variables were assessed, including area under the concentration-time curve from time 0 to the time of the last measurable sample (AUClast); area under the concentration-time curve from time 0 to infinity after single dosing (AUCinf);

maximum observed plasma (or blood) concentration (Cmax); time to maximum observed plasma (or blood) concentration (Tmax); terminal phase half-life (t1/2); and apparent total body clearance (CL/F). Safety variables including vital signs, electrocardiograms, adverse events (AEs), hematology, and blood chemistries also were monitored regularly. Assessment of safety and tolerability included all subjects who received at least one dose of boceprevir, and PK analyses were based on the per-protocol population, which included all protocol-compliant subjects. PK parameters were summarized by treatment using descriptive statistics and graphics. The log-transformed AUC and Cmax values were analyzed using mixed effect modeling extracting the effect due to treatment as fixed effect, and subject as random effect. Geometric mean ratios (GMRs) and associated 90% confidence intervals (CIs) were calculated using the following predefined limits to define clinically meaningful drug-drug interactions.

1% (1/92) 90.2% (83/92) 8.7% (8/92)   Well nourished 1.6% (1/61) 24.6% (15/61) 73.8% (45/61) Presenting Author: AMIT BERY Additional Authors: DINESH GUPTA, RAJOO CHHINA, CANDY SODHI

Corresponding Author: AMIT BERY Affiliations: Dayanand Medical College, Dayanand Medical College, Christian Medical College Objective: To assess the nutritional profile of patients with compensated alcoholic liver disease (ALD) cirrhosis in tertiary care center in Northern India. Methods: Nutritional profile in hundred patients of compensated ALD-cirrhosis was studied for its relationship to amount and duration of alcohol intake. Anthropometric, clinical signs of nutritional deficiencies, dietary assessment (by 24 hour dietary recall method), hematological and biochemical parameters were used for nutritional assessment. H 89 order Results: Clinical signs of nutritional deficiencies were found in all subjects. The mean value of body mass index (bmi), triceps fold thickness (TFT) and midarm circumference (MAC) were found to be decreased as compared to normal subjects. Vitamins b12 and serum folate levels were decreased in 16% and 52% cases respectively. Serum magnesium,

serum phosphorus and serum zinc levels were also lower than that found in normal population (in 48%, 40% and 40% cases respectively). Total calorie intake was found to be significantly decreased in these subjects. Nutritional deficiencies were more pronounced in patients with increased amount and duration of alcohol. Conclusion: thus, nutritional

deficiencies are present even in compensated ald-cirrhotics and correlate with amount and duration of alcohol intake. Key Word(s): 1. alcoholic liver disease; 2. cirrhosis; 3. nutritional profile Presenting Author: AMIT BERY Additional Authors: SHAVETA BATTA, VANDANA MIDHA Corresponding Author: AMIT BERY Affiliations: Dayanand Medical College, Dayanand Medical Methocarbamol College Objective: To assess the health and nutritional status and dietary compliance to gluten free diet in celiac disease patients in tertiary care center in northern India. Methods: a follow up study was conducted on randomly selected hundred recently diagnosed adult (18-30 years) patients with celiac disease. An interview schedule/questionnaire was drafted to obtain information on various aspects such as availability of gluten free food products, facility to cook separate meals, gastrointestinal symptoms, anthropometric measurements, biochemical analysis, histopathological reports and dietary intake of subjects. Results: the mean age of presentation was 24.6 years. Out of 100 biopsy proven cases 65 were females and 35 were males. Most of the respondents (70%) were aware about the gluten free products. Ninety six percent of the patients were able to cook their meals separately. Majority of the patients presented with anemia (80%) and diarrhea (70%). Good improvement in hemoglobin levels and weight of adults was seen after 3 months of follow up on gluten free diet.

S2). The morphology of the differentiated cells also shared many characteristics with primary hepatocytes, including a large cytoplasmic-to-nuclear ratio, numerous vacuoles and vesicles, and prominent nucleoli. Several cells

were found to be binucleated (Fig. 2E, panel c, and Supporting Fig. 3); moreover, the differentiated cells formed sheets reminiscent of an epithelial layer and were capable of actively localizing dichlorofluorescein diacetate to their plasma membranes (Fig. 2E panel f, arrow). We further examined the extent of differentiation using gene array analyses, which were performed on MEK inhibitor undifferentiated H9 ES cells and cells subjected to the complete 20-day differentiation protocol in three independent

experiments. Genome-wide expression profiling studies by others23 have identified a cluster of 175 genes whose expression is restricted to normal human liver compared with 35 other tissues examined. A subset of 40 of these genes have successfully been used to identify hepatic character in other studies,23 and so we believe that expression of these 40 genes provides an accurate transcriptional fingerprint of a differentiated hepatic phenotype. As expected, this cluster of genes is not expressed in undifferentiated huES cells (Fig. 2F and Supporting Table S2); however, expression of nearly the entire gene set is robustly increased after completion of the differentiation selleckchem C59 wnt protocol. Based on our analyses shown in Fig. 2, we conclude that the we have in hand a protocol that can efficiently and reproducibly generate hepatocyte-like

cells from huES cells under well-defined culture conditions. If hepatocytes could be generated from human induced pluripotent stem cells (hiPS) cells with efficiencies that resembled those achieved using huES cells, the procedure would provide a reliable tool for the study and treatment of human hepatic disease as well as potentially provide human hepatocytes for toxicological studies and pharmaceutical screens. However, the effect of somatic cell nuclear reprogramming on hepatocyte differentiation from iPS cells is unknown. We therefore generated human iPS cells (hiPS) from foreskin fibroblasts by transduction with lentiviruses that independently expressed POU domain class 5 transcription factor 1 (OCT3/4) SRY-box containing gene 2, (SOX2), NANOG homeobox (NANOG), and Lin-28 homolog (LN28) as described by Yu et al.5 A detailed characterization of these iPS cells is shown in Supporting Fig. S4. We next determined the ability of iPS.C2a cells to form hepatocyte-like cells. Human iPS cells were subjected to the same protocol used to induce formation of hepatocytes from huES cells, and the same analyses were performed.

This criterion means that malingering cannot be ruled out unless it can be reasonably demonstrated that positive

B and/or C criteria are ‘fully’ accounted for by psychological or neurological disturbance and are not at all motivated by any identifiable external incentives. Using this system, all diagnoses of malingering require the presence of external incentive (Criterion A) plus Criterion B and/or C evidence as noted below. For purposes of this study, only B1, B2, and C5 were used for malingering group classifications as these criteria consist of indicators specifically designed to measure response validity (Ord, Greve, & Bianchini,

2007). The most powerful Criterion B evidence is documentation of a negative Selleckchem Talazoparib response bias on the basis of performance on a ‘forced-choice’ SVT (e.g., Portland Digit Recognition Test or Test of Memory Malingering; see Bianchini et al., 2001 for review). Performance Doxorubicin mouse on a forced-choice measure can indicate either ‘definite’ response bias (B1: obtained score is significantly below chance at α < 0.05, two-tailed) or ‘probable’ response bias (B2: obtained score on a well-validated measure of response bias is in a range consistent with exaggeration or feigning). Other response bias tests and indices from standard clinical measures can also meet B2. Criterion B2 could be met on the basis of a positive finding on either the Portland Digit Recognition Test (PDRT; Binder, 1993) or Test of Memory Malingering (TOMM; Tombaugh, 1996), or by a positive finding on well-validated clinical indicators. Clinical indicators

used in this study included the Millis formula from the California Verbal Learning Test (Millis, Putnam, Adams, & Ricker, selleck chemical 1995); and the Suhr formula (Suhr & Boyer, 1999) and Unique responses (Greve et al., 2002) from the Wisconsin Card Sorting Test (WCST; Heaton, Chelune, Talley, Kay, & Curtiss, 1993). Criterion C5 includes evidence of exaggeration or fabrication of psychological symptoms on self-report measures with well-validated validity scales (e.g., Minnesota Multiaxial Personality Inventory – II [MMPI-2]; Butcher, Dahlstrom, Graham, Tellegren, & Kaemmer, 1989). See Table 2 for the specific cut-offs related to these indicators. In the context of external incentive, a B1 finding is sufficient for a diagnosis of ‘Definite MND’. A diagnosis of ‘Probable MND’ can be made with two types of Criterion B evidence or one type of Criterion B evidence and one or more types of Criterion C evidence. Criterion C evidence is not sufficient for a diagnosis in the absence of Criterion B evidence.

Despite being predictions of a point estimate, these maps provide some insight into the third dimension of habitat use in marine animals. The capacity to predict this aspect of vertical habitat use may help avoid

conflict between animal habitat and coastal or offshore developments. “
“We examined melon-headed whales that mass-stranded live in two events in Japan: (1) 171 animals at Tanegashima Island in 2001 and (2) 85 animals at Hasaki in 2002. We report here the results of life history traits and group composition of these strandings, and compare them to another mass stranding with 135 individuals at Aoshima in 1982. In the Hasaki event, most stranded animals, including those released were sexed and measured. The proportion of live males released was much higher than that of females, and this website larger animals, Trametinib especially females, were more likely to have died. Females were estimated to attain sexual maturity at around 7 yr and give birth every 3–4 yr. The sex ratio was significantly different between the Hasaki and Aoshima events. Among dead specimens, females of various age classes were included in all strandings, while age distribution of males varied considerably among strandings. This suggests females show group fidelity while males move between groups.

Asymptotic body length of females from Hasaki was significantly smaller than that from Tanegashima, suggesting that more than one population of melon-headed whales exist off Japan. “
“A total of 56 vaquitas (Phocoena sinus) were examined to evaluate their sexual dimorphism and isometric and/or allometric growth in 35 external characteristics. Absolute and relative (to total length) measurements and growth rates

were compared between sexually immature and mature females and males. T-tests and analysis of variance (ANOVA) and covariance (ANCOVA) were used to evaluate sexual dimorphism. Sexual dimorphism in the vaquita was detected in the total length, selleck chemicals llc head region (from blowhole to tip of upper jaw), anterior section of the body (from dorsal fin to tip of upper jaw), dorsal fin and the genital and anal regions. Fluke width is relatively larger in mature males than immature males, but in females this relative metric does not change during their development. In addition, males present a higher dorsal fin. These somatic changes are probably related to the swimming capacity (speed, agility, maneuvering) during the breeding season and/or foraging activities. A linear model of growth was used to determine possible proportional changes with respect to total body length through the development of 33 external characteristics. The anterior region of the body and the flippers were relatively larger in immature individuals than in mature ones. “
“Total estimated abundance of Hawaiian monk seals was just 1,161 individuals in 2008 and this number is decreasing.

Despite being predictions of a point estimate, these maps provide some insight into the third dimension of habitat use in marine animals. The capacity to predict this aspect of vertical habitat use may help avoid

conflict between animal habitat and coastal or offshore developments. “
“We examined melon-headed whales that mass-stranded live in two events in Japan: (1) 171 animals at Tanegashima Island in 2001 and (2) 85 animals at Hasaki in 2002. We report here the results of life history traits and group composition of these strandings, and compare them to another mass stranding with 135 individuals at Aoshima in 1982. In the Hasaki event, most stranded animals, including those released were sexed and measured. The proportion of live males released was much higher than that of females, and INK 128 mouse larger animals, Selleck GW-572016 especially females, were more likely to have died. Females were estimated to attain sexual maturity at around 7 yr and give birth every 3–4 yr. The sex ratio was significantly different between the Hasaki and Aoshima events. Among dead specimens, females of various age classes were included in all strandings, while age distribution of males varied considerably among strandings. This suggests females show group fidelity while males move between groups.

Asymptotic body length of females from Hasaki was significantly smaller than that from Tanegashima, suggesting that more than one population of melon-headed whales exist off Japan. “
“A total of 56 vaquitas (Phocoena sinus) were examined to evaluate their sexual dimorphism and isometric and/or allometric growth in 35 external characteristics. Absolute and relative (to total length) measurements and growth rates

were compared between sexually immature and mature females and males. T-tests and analysis of variance (ANOVA) and covariance (ANCOVA) were used to evaluate sexual dimorphism. Sexual dimorphism in the vaquita was detected in the total length, click here head region (from blowhole to tip of upper jaw), anterior section of the body (from dorsal fin to tip of upper jaw), dorsal fin and the genital and anal regions. Fluke width is relatively larger in mature males than immature males, but in females this relative metric does not change during their development. In addition, males present a higher dorsal fin. These somatic changes are probably related to the swimming capacity (speed, agility, maneuvering) during the breeding season and/or foraging activities. A linear model of growth was used to determine possible proportional changes with respect to total body length through the development of 33 external characteristics. The anterior region of the body and the flippers were relatively larger in immature individuals than in mature ones. “
“Total estimated abundance of Hawaiian monk seals was just 1,161 individuals in 2008 and this number is decreasing.

We therefore assessed glucose homeostasis. Oral glucose tolerance tests revealed that Slco1b2−/− mice exhibited a significantly reduced ability to lower glucose levels associated with a significant delay in glucose removal (Fig. 2A). Moreover, knockout animals showed a trend for increased glucose levels (glucose level ± SD: wild-type, 117.41 ± 1.35 [n = 15]; Slco1b2−/−, 131.60 ± 1.46 [n = 15]; adjusted P = 0.056), that was not related to changes in insulin levels after 3 hours of fasting (insulin level ± SD: wild-type, 0.72 ± 0.08 [n = 5]; Slco1b2−/−, 0.62 ± 0.09 [n = 5]; adjusted P = 0.441). Subsequently, the hepatic uptake of [3H]-D-glucose was determined 3 minutes after

DNA Damage inhibitor intravenous administration, revealing significantly reduced glucose accumulation in livers of Slco1b2−/− compared with wild-type animals, yet no differences were observed in plasma levels (Fig. 2B). To test whether gluconeogenesis is affected, we measured glucose levels after pyruvate challenge. Whereas wild-type mice responded with significantly increased blood glucose levels 15 minutes after intraperitoneal pyruvate injection, knockout animals did not (Fig. 2C). Hepatic glucose catabolism appeared

similarly disturbed, as shown by a preiodic acid–Schiff staining of livers revealing significant higher glycogen accumulation in hepatocytes of knockout animals, which was confirmed by way of calorimetric

selleck Opaganib analysis (Fig. 2D,E). Examination of the hepatic expression of known TR target genes further supported the reduced hepatic TH activity, showing significant down-regulation of Dio1 and phosphoenolpyruvate carboxykinase (Pepck) (Fig. 3A,B). In addition, determining the TH status comparing wild-type and knockout mice revealed significantly reduced levels of free thyroxine (fT4) in livers associated with significantly elevated plasma levels translating into lower liver/plasma ratios of the latter (Fig. 4A). However, no significant alterations in free triiodothyronine (fT3) levels were detected (Fig. 4A). Similarly, no difference was seen for the pituitary thyroid stimulating hormone (TSH [μg/mL]) comparing wild-type (0.12 ± 0.01) and Slco1b2−/− (0.17 ± 0.09) mice. The interaction of mouse Oatp1b2 with TH was determined performing in vitro experiments using Oatp1b2-overexpressing cells. In accordance with our assumption, THs significantly inhibited the Oatp1b2-mediated uptake of the known substrate E1S. E1S uptake (180.16 ± 14.64% of vector control) was significantly reduced by concomitant exposure with 100 nM T4 (151.99 ± 5.60%), 100 nM T3 (112.46 ± 15.52%), or 100 nM rT3 (96.64 ± 16.30%) (adjusted P = 0.0007). To test whether THs are indeed substrates for mouse Oatp1b2, we used a cell-based reporter gene assay whose luciferase signal was driven by the TR-sensitive DIO1 promoter.