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PubMed2001

Optimised uncertainty at minimum overall cost to achieve fitness-for-purpose in food analysis.

An optimised uncertainty (OU) methodology is described, that balances the uncertainty of measurements on food against the cost of the measurements and the other expenditure that may arise as a consequence of the possible misclassification of the food. Measurement uncertainty from the sources of primary sampling and chemical analysis is estimated using an existing technique, which is based on the taking of duplicated samples and duplicated analyses. The input information required for the OU method is the actual costs of sampling and analysis, and the expected costs that could arise from either the 'false positive' or 'false negative' classification of batches of food. A loss function is then constructed that calculates the 'expectation of loss' which will arise for a given uncertainty of measurement. This function has a minimum value of cost at an optimal value of uncertainty, which can be estimated numerically. Application of this OU method to a case study on the determination of aflatoxin levels in pistachio nuts has demonstrated this minimum value. Below the optimum value of uncertainty, the costs increased due to higher measurement costs. Above the optimum value, the costs increased due to increasing probability of expenditure on consequences such as unnecessary rejection of the batch, potential litigation or loss of corporate reputation because of undetected contamination. A second stage of the OU method optimises the division of the expenditure on the measurement between that on sampling and that on analysis. The technique is demonstrated as a useful new approach for judging the fitness-for-purpose of chemical measurements in the food industry. Several areas for further development of the technique are identified. By matching the expenditure on the measurement against that caused by the misclassification of the food, the OU method has the potential to reduce overall expenditure whilst ensuring an appropriate reliability of measurement.

Aflatoxins↗

PubMed2002

Changes in the overall extent of protein glycosylation by Chinese hamster ovary cells over the course of batch culture.

Glycosylation of recombinant proteins can change during the culture of animal cells. Since lipid-linked oligosaccharides (LLOs) are the carbohydrate donors in N-linked glycosylation, their availability is postulated to influence the extent of glycosylation. To test this hypothesis, relative LLO and glycosylation levels in Chinese hamster ovary (CHO) cells were monitored over the course of batch culture for corresponding changes. Radiolabelling studies reveal that throughout the length of culture, intracellular LLO levels remained within a 2-fold range and overall CHO protein glycosylation varied by less than 30%. The implications of these results and hypotheses to explain the findings are discussed.

Animals↗

PubMed2004

Overall volumetric oxygen transfer coefficient in an aerated bench-top stirred fermenter in aqueous dispersions of sodium alginate.

The dynamic gassing-out method was used to assess the effect of stirrer speed, air flow rate and alginate concentration on the overall volumetric oxygen mass transfer coefficient (K(L)a) in a bench-top stirred fermenter equipped with two Rushton-type turbines. As the alginate concentration in the medium was increased from 0 to 2% (w/v), the liquid film time constant (tau(F)) increased from approx. 30 to 300% of the electrode time constant (tau(E)), clearly showing that the liquid-probe diffusion film affected the oxygen-electrode response. By accounting for delayed probe response, liquid film time constant and gas residence time, the corrected values of K(L)a were empirically correlated with the above independent variables as converted into gassed power input and aeration number per unit liquid volume and the effective liquid/water shear viscosity ratio. Despite an average error of 19%, such a correlation might be useful to adjust the oxygen transfer in bench-top stirred reactors during viscous aerobic fermentations.

Alginates↗

PubMed1973

Kinetic studies of the acylation of pig muscle D-glyceraldehyde 3-phosphate dehydrogenase by 1,3-diphosphoglycerate and of proton uptake and release in the overall enzyme mechanism.

In the presence of NAD(+) the acylation by 1,3-diphosphoglycerate of the four active sites of pig muscle d-glyceraldehyde 3-phosphate dehydrogenase can be monitored at 365nm by the disappearance of the absorption band present in the binary complex of NAD(+) and the enzyme. A non-specific salt effect decreased the acylation rate 25-fold when the ionic strength was increased from 0.10 to 1.0. This caused acylation to be the rate-limiting process in the enzyme-catalysed reductive dephosphorylation of 1,3-diphosphoglycerate at high ionic strength at pH8. The salt effect permitted investigation of the acylation over a wide range of conditions. Variation of pH from 5.4 to 8.6 produced at most a two-fold change in the acylation rate. One proton was taken up per site acylated at pH8.0. By using a chromophoric H(+) indicator the rate of proton uptake could be monitored during the acylation and was also almost invariant in the pH range 5.5-8.5. Transient kinetic studies of the overall enzyme-catalysed reaction indicated that acylation was the process involving proton uptake at pH8.0. The enzyme mechanism is discussed in the light of these results.

Acylation↗

PubMed1995

Demonstration by pulsed neutron scattering that the arrangement of the Fab and Fc fragments in the overall structures of bovine IgG1 and IgG2 in solution is similar.

The bovine IgG1 and IgG2 isotypes exhibit large differences in effector functions. To examine the structural basis for this, the 12-domain structures of IgG1 and IgG2 were investigated by pulsed neutron scattering using a recently developed camera LOQ. This method reports on the average relative disposition in solution of the Fab and Fc fragments in IgG. The radii of gyration (RG) were found to be similar at 5.64 and 5.71 nm for IgG1 and IgG2 respectively in 100% 2H2O buffers. The two cross-sectional radii of gyration (RXS) were also similar at 2.38-2.41 and 0.98-1.02 nm. Similar values were obtained for porcine IgG. Both bovine IgG1 and IgG2 possess similar overall solution structures, despite sequence differences at the hinge region at the centre of their structures. An automated computer survey of possible IgG structures was developed, in which coordinates for the two Fab fragments were displaced in a two-dimensional plane relative to those of the Fc fragment in 0.25 nm steps. The scattering curves calculated from these structures were found to be sensitive to relative displacements of the three fragments, but not on their rotational orientation about their longest axes. Good agreement with the solution scattering data was obtained with a planar IgG model in which the C-terminus of the CH1 domain of Fab was 3.6 nm from the N-terminus of Fc in both IgG1 and IgG2, with a precision of 0.7 nm. Energy refinement showed that this spatial separation is compatible with the hinge sequences of bovine IgG1 and IgG2. The results show that multidomain protein structures can be modelled using LOQ data, and that a long hinge sequence does not necessarily reflect a large distance between Fab and Fc. The steric accessibility of Fc sites for interactions with cell-surface Fc receptors and C1q of complement is shown to be generally similar for IgG1 and IgG2, and the difference in effector function between IgG1 and IgG2 is probably based on deletions in the IgG2 hinge sequence.

Amino Acid Sequence↗

PubMed2003

Protective and determining factors for the overall lipid peroxidation in ultraviolet A1-irradiated fibroblasts: in vitro and in vivo investigations.

BACKGROUND: Lipid peroxidation (LPO) is one major effector mechanism by which ultraviolet (UV) A contributes to photoageing and the promotion of skin cancer. It is a fingerprint of photo-oxidative stress within the skin, and is initiated by several pathways, with different reactive oxygen species (ROS) and iron ions being involved. OBJECTIVES: To elucidate factors involved in UVA1-induced LPO in human dermal fibroblasts and mouse dermis, and the role of antioxidant enzymes in protecting cells against LPO. METHODS: Using a highly sensitive high-performance liquid chromatography procedure, we measured malondialdehyde (MDA), a specific metabolic tracer molecule for LPO, to determine the overall LPO produced by a given UVA1 dose in vitro and in vivo. By using the iron chelator desferrioxamine (DFO), the hydroxyl radical scavenger dimethylsulphoxide (DMSO) and fibroblasts that specifically overexpress single antioxidant enzymes, we further indirectly assessed the protective effect of manganese superoxide dismutase (MnSOD), catalase and phospholipid hydroperoxide glutathione peroxidase (PHGPx) as well as the relative importance of different ROS and the role of transitional iron for the total amount of LPO induced by a distinct UVA dose. RESULTS: UVA1 irradiation resulted in a time- and dose-dependent increase in MDA levels in vitro, and the in vitro results were shown to have in vivo relevance. Fibroblasts incubated with DFO or DMSO produced lower levels of MDA than controls, as did fibroblasts overexpressing MnSOD, catalase or PHGPx. CONCLUSIONS: The cellular iron pool and hydroxyl radicals were the most important determining factors for the total amount of MDA produced after a given UVA1 dose, and PHGPx overexpression had the greatest protective effect against LPO.

Animals↗

PubMed1997

Moderate hyperthyroidism reduces liver amino nitrogen conversion, muscle nitrogen contents and overall nitrogen balance in rats.

There are conflicting data on the effect of thyroid hormones on nitrogen metabolism. We determined the basal blood amino nitrogen (amino-N) concentrations, the urea nitrogen (urea-N) synthesis rate and the maximum hepatic capacity of urea nitrogen synthesis during saturating infusion of alanine, in moderately acutely (24 h) and chronically (7 days) hyperthyroid rats and compared this with changes in organ nitrogen contents in muscles and kidney, nitrogen excretion and nitrogen balance. Forty-three rats were made acutely hyperthyroid through administration of 5 microg 100 g(-1) triiodothyronine twice daily (T3: 2.2 +/- 0.7 vs. 0.87 +/- 0.04 nmol L(-1), P < 0.01). Fifty-one rats were made chronically hyperthyroid through administration of 12.5 microg 100 g(-1) thyroxine twice daily (T3: 2.63 +/- 0.18 vs. 0.87 +/- 0.04 nmol L(-1), P < 0.01). Weight gain was halved in this group. Both acute and chronic hyperthyroidism increased basal blood amino-N concentration in both groups by 16% (4.5 +/- 0.15 vs. 3.9 +/- 0.13 mmol L(-1) and 4.7 +/- 0.12 vs. 3.9 +/- 0.13 mmol L(-1), respectively, P < 0.01), and decreased basal urea-N synthesis rate in both groups by 30% [2.7 +/- 0.3 vs. 4.1 +/- 0.3 micromol (min x 100 g)(-1) and 3.1 +/- 0.3 vs. 4.1 +/- 0.3 micromol (min x 100g)(-1), respectively, P < 0.01]. The capacity of urea-N synthesis during saturation fell in both groups by 35% compared with controls [6.5 +/- 0.4 vs. 9.3 +/- 0.5 micromol (min x 100 g)(-1) and 5.7 +/- 0.5 vs. 9.3 +/- 0.6 micromol (min x 100g)(-1), respectively, P < 0.01]. Nitrogen contents in the muscles, soleus and extensor digitorum longus, of chronically hyperthyroid rats decreased by 22% and 11%, respectively, whereas kidney N-content increased by 12% (P < 0.05). N-balance and urinary urea-N excretion fell by 30%, whereas faeces-N excretion increased by 80% in hyperthyroid rats. Overall liver function assessed by galactose elimination capacity did not differ among groups. Both acute and chronic moderate hyperthyroidism increase blood amino-N and decrease basal and maximum rate of urea formation. Furthermore, chronic hyperthyroidism reduces N-contents of muscles, urinary urea-N excretion and N-balance. Thyroid hormones thus mobilize muscle-N, whereas amino-N in the liver is spared from irretrievable conversion into urea.

Amino Acids↗

PubMed1995

Comparison of the overall quality of life in 50 long-term survivors of autologous and allogeneic bone marrow transplantation.

Fifty long-term survivors of bone marrow transplant (mean post-transplant time = 42.4 months) participated in a study examining their psychosocial adjustment and quality of life. Differences between patients who received an autologous marrow transplant and those who received an allogeneic marrow transplant were identified. Patients with an autologous transplant had mainly psychological difficulties in their post-transplant adaptation, whereas patients with allogeneic transplant developed more physical problems. Overall, their psychosocial adjustment was similar and comparable with other medical groups of patients. A quarter of both groups had failed to return to work/education and up to 9.5% had difficulty in carrying out daily tasks. Twenty per cent of the patients with autologous transplant had clinical signs of anxiety and 10% clinical signs of depression, whereas there was an incidence of 10% of patients with allogeneic transplant with anxiety, but no cases with clinical depression. Family relationships were found to be more integrated and lower in conflict compared with normal families. Quality of life has been described as good to excellent in most of the patients. Multiple regression analysis showed that physical symptomatology, vocational adjustment and depression are predictors of the degree of the patients' quality of life.

Activities of Daily Living↗

PubMed2001

cDNA cloning of the chicken branched-chain alpha-keto acid dehydrogenase complex. Chicken-specific residues of the acyltransferase affect the overall activity and the interaction with the dehydrogenase.

Branched-chain alpha-keto acid dehydrogenase complex is a macromolecule comprising three catalytic components: a dehydrogenase (E1) with alpha(2)beta(2) structure, an acyltransferase (E2) and a dihydrolipoamide dehydrogenase (E3). In the mammalian complex, the E2 component with 24 identical subunits forms a structural core, to which multiple copies of E1 and E3 bind noncovalently. We isolated cDNA clones encoding E1 alpha, E1 beta and E2 subunits from a chicken-liver cDNA library and performed nucleotide sequencing. Amino-acid sequences deduced from the nucleotide sequences revealed that chicken E1 alpha and E1 beta chains had substantially homologous sequences with the corresponding mammalian polypeptides, except for the N-terminus. Chicken E2 conserved three functional domains, a lipoyl-bearing domain, an E1/E3 binding domain and an inner-core domain, but contrasted strongly with mammalian E2 in respect of containing 11 additional residues in two interdomain linkers: nine sequential residues in one linker and two residues in the other. Replacement of many residues was also observed in the chicken linkers. When E2 activity for catalyzing the overall reaction was measured by activity reconstitution in combination with E1 and E3, chicken E2 was markedly less effective than mammalian E2. The capability of chicken E2 for binding E1 was also reduced when determined by the binding assay using sucrose density gradient centrifugation. Chicken E1 was functionally as well as structurally indistinguishable from mammalian E1. Thus the reduced catalytic activity of chicken E2 must arise from its reduced E1-binding capacity, which results from the characteristic structure of interdomain linkers in chicken E2.

3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)↗

PubMed1999

The milan overall dementia assessment and the mini-mental state examination compared: an epidemiological investigation of dementia.

We assessed the validity of two screening tests [the Mini-Mental State Examination (MMSE) and the Milan Overall Dementia Assessment or (MODA)] in a population study on the prevalence of Alzheimer's disease, carried out in a small town in the north of Italy. A random sample of 1000 subjects aged 60 years or over entered the study. Subjects who scored below the cut-off points on MODA or on MMSE, or both, were further investigated with neuropsychological, laboratory and instrumental tests to ascertain a final diagnosis, which was considered as the gold standard. Our findings show that MODA has a higher sensitivity than MMSE in detecting subjects affected by dementing illnesses, while MMSE shows a higher specificity. MODA seems to be preferable to MMSE as a screening test for studies where a very high sensitivity is required.

Aged↗

PubMed1999

Assessing linkage disequilibrium in a complex genetic system. I. Overall deviation from random association.

Linkage disequilibrium is an important tool both at the end stages of positional cloning studies to map genes of particular interest and in reconstruction of population histories. With advances in molecular biology, complex genetic systems involving multiple highly polymorphic markers are becoming more commonly used to study linkage disequilibrium. These systems contain much more genetic information than simple two marker systems. In this article, we introduce a measure to summarize the overall deviation from random association and propose a permutation-based estimate for this measure. The performance of the proposed estimation procedure is studied through simulations. The methods proposed in this paper are then applied to population data at the dopamine D2 receptor locus (DRD2) and at the homeobox B (HOXB) gene cluster.

Alleles↗

PubMed2000

The Estrogen Receptor Paradox in Breast Cancer: Association of High Receptor Concentrations with Reduced Overall Survival.

Occasional reports have suggested an unfavorable effect of high estrogen receptor (ER) concentrations in primary breast cancer. In a population-based study we identified a subgroup explicitly exhibiting this seemingly paradoxical effect. ER concentrations were prospectively measured in a single laboratory by multipoint DCC assay. The relative risk of death in relation to the concentration of the interval-scaled variables ER and PgR was continually estimated by serial Cox regression analyses. Thus we circumvented loss of information due to primary categorization and avoided assumptions about relations between factor and risk. Based on 2,735 consecutively accrued primary breast cancer cases (median follow-up 56 months) we identified node-negative patients up to 60 years of age as the relevant subpopulation. High (>/=300 fmol/mg protein) ER concentrations exhibited an even more unfavorable impact (p < 0.03) on overall survival than ER concentrations of less than 10 fmol/mg protein. The well-known association of age and ER concentration was definitely excluded as an underlying biological cause for the increased risk. Differences in the distribution of other prognostic factors (HER-2/neu, Ki-67, DNA ploidy) were also excluded. As we observed a preponderance of pT2 tumors in the high ER group, we repeated the analysis, selectively focusing on pT2 tumors in the relevant subgroup, but the effect remained unchanged. In contrast, node-positive patients adjusted for age significantly (p = 0.02) profited from high ER concentrations as compared to the ER-negative group. As the phenomenon did not occur in node-positive patients, receptor defects in the high-ER group seem unlikely. To the contrary, we suspect that ER overexpressing cells are hypersensitive even to low levels of estrogens. Once they have sneaked past local barriers prior to primary surgery, they may cause early death in the absence of appropriate adjuvant endocrine therapy.

Journal Article↗

PubMed2000

Overall 5-year survival rate and prognostic factors in patients with stage IB and IIA cervical cancer treated by radical hysterectomy and pelvic lymph node dissection.

The objective of this paper was to analyze the 5-year survival rate and prognostic factors for stage Ib and IIa cervical cancer treated by radical hysterectomy. A total of 366 patients with invasive cervical cancer treated by radical hysterectomy from June 1985 to June 1994 at Chonnam National University Hospital, Kwangju, Korea were retrospectively analyzed. Survival analysis was performed using the Kaplan-Meier estimator. Multivariate analysis was performed using the Cox proportional hazards regression model. The overall 5-year survival rate was 92% in stage Ib and 87% in stage IIa. Factors assessed for prognostic value included age, FIGO stage, cell type, tumor size, depth of invasion, lymphovascular space invasion (LVSI), and pelvic lymph node metastases (LNM). In the multivariate analysis, age, cell type, and lymph node metastases were independent predictors of survival. Lower survival was associated with age greater than 50 years, adenocarcinoma, and presence of lymph node metastases. The higher survival rates in patients with single lymph node involvement or lymph node metastases below the level of the common iliac nodes (85 and 84.6%, respectively) versus multiple or extrapelvic lymph node metastases (50 and 20%, respectively) were statistically significant (P < 0.01). In conclusion, patients who had lymph node metastases, adenocarcinoma, and were older than 50 years had a poorer survival rate. Such patients require more intense postoperative treatment and closer surveillance. Low-risk patients with a single lymph node metastasis below the level of the common iliac nodes may benefit from thorough lymphadenectomy without adjuvant therapy to prevent unpleasant complications.

Journal Article↗

PubMedDate not supplied

The CA125 regression rate to predict overall survival differ between paclitaxel-containing regimen and nonpaclitaxel regimen in patients with advanced ovarian cancer.

In this study, we compare the time to normalization of CA125 after cytoreductive surgery between a paclitaxel-containing regimen and a non-paclitaxel regimen. This study demonstrates that CA125 regression in a paclitaxel-containing regimen was slower than that in a non-paclitaxel regimen. When we determine the CA125 regression rate to predict overall survival in ovarian cancer, we should take into account the kind of chemotherapy regimen, especially the use of paclitaxel.

Adult↗

PubMed2003

Predictors of relapse and overall survival in Philadelphia chromosome-positive acute lymphoblastic leukemia after transplantation.

Allogeneic transplantation offers a potential cure for patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). We performed a retrospective analysis examining pretransplantation and posttransplantation prognostic factors in 90 patients with Ph+ ALL. The median age of the patients was 33 years, with slightly more than half of the patients (58%) in clinical remission at the time of transplantation. Overall, patients had a nonrelapse mortality rate of 30%, a relapse percentage of 34%, and an estimated 5-year disease-free survival rate of 30%. Pretransplantation risk factors for relapse included the expression of the p190 transcript (relative risk [RR] = 5.1; P =.037), evidence of morphologic disease at the time of transplantation (RR = 3.9; P <.001), and type of donor (RR = 2.5; P =.015), with patients receiving autologous or matched related transplants having the highest risk of relapse. The detection of minimal residual disease by reverse transcription polymerase chain reaction for bcr-abl transcripts was a significant posttransplantation risk factor for relapse (RR = 4.4; P =.001), with posttransplantation patients expressing the p190 transcript having the highest risk of relapse (RR = 8.7; P =.0001). In addition, patients with chronic extensive graft-versus-host disease showed a significantly lower risk of relapse (RR = 0.33; P =.038). Thus, these findings indicate that several pretransplantation and posttransplantation risk factors exist for patients with Ph+ ALL. Together, these factors can be used to improve our risk stratification of patients with Ph+ ALL who undergo transplantation, which will greatly enhance our ability to counsel these patients and potentially lead to the development of more specific treatment plans for them.

Adolescent↗

PubMed1998

Importance of heart failure as a cause of death. Changing contribution to overall mortality and coronary heart disease mortality in Scotland 1979-1992.

AIMS: As heart failure is a syndrome arising from another condition, such as coronary heart disease, it is rarely officially coded as the underlying cause of death regardless of the cause recorded by the physician at the time of certification. We sought to assess the true contribution of heart failure to overall mortality and coronary heart disease mortality and to examine how this contribution has changed over time. METHODS AND RESULTS: We carried out a retrospective analysis of all death certificates in Scotland between 1979 and 1992 for which heart failure was coded as the underlying or a contributory cause of death. From a total of 833622 deaths in Scotland between 1979 and 1992, heart failure was coded as the underlying cause in only 1.5% (13695), but as a contributory cause in a further 14.3% (126073). In 1979, 28.5% of male and 40.4% of female deaths attributed to coronary heart disease (coded as the underlying cause of death) also had a coding for heart failure. In 1992 these percentages had risen significantly to 34.1% and 44.8%, respectively (both P<0.001). Mortality rates for heart failure as the underlying or contributory cause of death, standardized by age and sex, fell significantly over the period studied in all ages and in both sexes: by 31% in men and 41% in women <65 years and 15.8% in men and 5.1% in women > or =65 years, respectively (P<0.01 for all changes). CONCLUSIONS: Death from heart failure is substantially underestimated by official statistics. Furthermore, one third or more of deaths currently attributed to coronary heart disease may be related to heart failure and this proportion appears to be increasing. While the absolute numbers of deaths caused by heart failure remains constant, this study is the first to show that standardized mortality rates are declining.

Age Distribution↗

PubMed2006

Long-term patient survival: strategies to improve overall health.

The use of potent immunosuppressant therapy has led to an increase in number of patients with successful long-term kidney transplants. These individuals come to kidney transplantation with varying levels of comorbidity associated with end-stage renal disease and are susceptible to immunologic and nonimmunologic comorbidities that arise late after transplantation, including cardiovascular disease, infection, malignancy, and bone disease, which negatively impact on patient and graft survival. In addition, nonadherence to immunosuppressant regimens increases with time after transplantation, which further augments the risk for late-term graft failure and mortality. Consistent and frequent follow-up of kidney transplant recipients beyond the first year permits early diagnosis and successful treatment of many posttransplantation comorbidities. Implementation of preventive practices and aggressive management of risk factors throughout the life of the transplant improves overall health and long-term outcomes. Establishment and maintenance of close relationships among transplant centers, physicians, patients, and their families improves patient adherence to medications and reduces the risk for morbidity and mortality.

Cardiovascular Diseases↗

PubMed2001

Sustained expression of naked plasmid DNA encoding hepatocyte growth factor in mice promotes liver and overall body growth.

To understand the physiological functions of exogenous hepatocyte growth factor (HGF) on normal adult animals, we delivered human HGF gene into mice by a hydrodynamics-based in vivo gene transfection approach using a naked plasmid vector. Systemic administration of naked plasmid containing HGF cDNA driven under cytomegalovirus promoter (pCMV-HGF) by rapid injection via the tail vein produced a remarkable level of human HGF protein in the circulation, beginning to appear at 4 hours and peaking at 12 hours following injection. Tissue distribution studies identified the liver as the organ with the highest level of transgene expression. Through weekly repeated injections of plasmid vector, we achieved sustained, long-term, high levels of exogenous HGF expression in mice for 8 weeks. Increases of more than 31% and 16% in liver and body weights were found, respectively, in the mice that received pCMV-HGF plasmid compared with that given the control vector for 8 weeks. Expression of exogenous HGF in vivo activated mitogen-activated protein kinases and induced proliferating cell nuclear antigen expression in normal adult liver and kidneys. These data suggest that systemic administration of naked plasmid vector is a convenient, safe, and highly efficient approach to introduce and maintain exogenous HGF gene expression in vivo in a controllable fashion. Our results also indicate that long-term expression of human HGF in mice markedly activates growth-related signal transduction events, promotes cell proliferation, and leads to liver and overall body growth in whole adult animals.

Animals↗