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Diagnosis of Lynch syndrome (LS) may be complex. Knowledge of mutation spectrum and founder mutations in specific populations facilitates the diagnostic process. Aim of the study is to describe genetic features of LS in the Israeli population and report novel and founder mutations. Patients were studied at high-risk clinics. Diagnostics followed a multi-step process, including tumor testing, gene analysis and testing for founder mutations. LS was defined by positive mutation testing. We diagnosed LS in 242 subjects from 113 families coming from different ethnicities. We identified 54 different mutations; 13 of them are novel. Sixty-seven (59%) families had mutations in MSH2, 20 (18%) in MSH6, 19 (17%) in MLH1 and 7 (6%) in PMS2; 27% of the MSH2 mutations were large deletions. Seven founder mutations were detected in 61/113 (54%) families. Constitutional mismatch repair deficiency ( CMMR-D) was identified in five families. Gene distribution in the Israeli population is unique, with relatively high incidence of mutations in MSH2 and MSH6. The mutation spectrum is wide; however, 54% of cases are caused by one of seven founder mutations. CMMR-D occurs in the context of founder mutations and consanguinity. These features should guide the diagnostic process, risk estimation, and genetic counseling. [ABSTRACT FROM AUTHOR]

Background:PSA doubling time (PSADT) is an attractive intermediate end point for assessing novel therapies in biochemically recurrent prostate cancer (BRPC). This study explores whether PSADT calculations are influenced by frequency/duration of PSA measurements, and whether statistical variability leads investigators to find false significant results.Methods:In retrospective analyses of two BRPC cohorts: Johns Hopkins Hospital (JHH) patients who deferred therapy and placebo patients on a randomized clinical trial (RCT), we calculated changes in PSADT from early measurements to later measurements using subsets of available PSAs for patients with 6 and 9 PSAs. We simulated hypothetical single-arm trials using randomly selected, 50-patient subsets and simulated two-arm RCTs.Results:JHH cohort (n=205) had median follow-up 58 months, median age 61 years and median Gleason 7. PSA variability changed with duration of PSA measurement as median within-patient PSADT increases for men with >6 PSAs ranged from 1.0 to 1.4 months by PSA subset while increases for men with 9 PSAs ranged from 3.9 to 4.1 months. Frequency of measurement did not change PSA variability as PSADT increase was unchanged when odd values were used instead of all values. Approximately 30% of JHH men experienced >200% increases in PSADT. Up to 62% of 50-patient single-arm simulations detected a significant PSADT change, whereas simulated RCTs did not. Results were supported in the RCT placebo cohort; 46% of patients experienced PSADT increases >200%.Conclusions:These data suggest that calculated PSADT in BRPC may naturally increase over time in the absence of therapy and may be influenced by duration of PSA follow-up. As a result, single-arm trials could show false significant increases despite the lack of active treatment of these patients. Placebo-controlled RCTs including clinical end points are recommended to screen novel agents in men with BRPC to mitigate bias because of natural PSADT variability. [ABSTRACT FROM AUTHOR]

Great strides have been made in the understanding of bound states of the bottom quark, b, and its antiquark, b, since the discovery of the first T resonances in 1977. These bound states, known as bottomonium, have a rich spectrum whose masses and transition amplitudes shed valuable light on the strong interactions. We review some recent developments in bottomonium physics, including the discovery of the spin-singlet states nk(1S,2S) and hb(lP, 2P), the first D-wave states, one or more candidates for spin-triplet Xbj(3P) excitations, and above-threshold states with strong transitions to states below threshold. We also present information about transitions, production, and signatures of new physics. [ABSTRACT FROM AUTHOR]

Angular distributions of differential cross sections from the latest CLAS data sets,6 for the reaction γ + p→K+ + Λ have been analyzed using associated Legendre polynomials. This analysis is based upon theoretical calculations in Ref. 1 where all sixteen observables in kaon photoproduction can be classified into four Legendre classes. Each observable can be described by an expansion of associated Legendre polynomial functions. One of the questions to be addressed is how many associated Legendre polynomials are required to describe the data. In this preliminary analysis, we used data models with different numbers of associated Legendre polynomials. We then compared these models by calculating posterior probabilities of the models. We found that the CLAS data set needs no more than four associated Legendre polynomials to describe the differential cross section data. In addition, we also show the extracted coefficients of the best model. [ABSTRACT FROM AUTHOR]

Irinotecan, a chemotherapeutic agent against various solid tumors, is a prodrug requiring activation to SN-38. Irinotecan’s complex pharmacokinetics potentially allow for many genetic sources of variability. We explored relationships between pharmacokinetic pathways and polymorphisms in genes associated with irinotecan’s metabolism and transport. We fitted a seven-compartment pharmacokinetic model with enterohepatic recirculation (EHR) to concentrations of irinotecan and metabolites SN-38, SN-38 glucuronide (SN-38G), and aminopentanoic acid (APC). Principal component analysis (PCA) of patient-specific parameter estimates produced measures interpretable along pathways. Nine principal components provided good characterization of the overall variation. Polymorphisms in genes UGT1A1, UGT1A7, and UGT1A9 had strong associations with a component corresponding to the irinotecan-to-SN-38 pathway and SN-38 recirculation and to a component relating to SN-38-to-SN-38G conversion and elimination of SN-38G. The component characterizing irinotecan’s compartments was associated with HNF1α and ABCC2 polymorphisms. The exploratory analysis with PCA in this pharmacogenetic analysis was able to identify known associations and may have allowed identification of previously uncharacterized functional polymorphisms.Clinical Pharmacology & Therapeutics (2008); 84, 3, 393–402 doi:10.1038/clpt.2008.63 [ABSTRACT FROM AUTHOR]

The Glasgow photon tagging spectrometer at Mainz has been upgraded so that it can be used with the 1500MeV electron beam now available from the Mainz microtron MAMI-C. The changes made and the resulting properties of the spectrometer are discussed. [ABSTRACT FROM AUTHOR]

Background: Since the adoption of a universal hepatitis B immunisation strategy, the reported incidence of acute hepatitis B has declined dramatically worldwide including in Israel. However, new cases of acute hepatitis B still occur. The aim of this study was to describe the incidence of acute hepatitis B in a referral area, routes of transmission, and outcome. Methods: The charts of all new hepatitis B patients, who visited the clinic in the years 2002 and 2003 (January 2002 to December 2003), were reviewed. The main criteria for a diagnosis of acute hepatitis B were transient increase of alanine transaminase activity, and hepatitis B surface antigen seroconversion. Results: Twenty nine men and seven women were diagnosed with acute hepatitis B infection during the study period. Two patients were previously vaccinated with hepatitis B vaccine. One case of hepatitis D coinfection was reported. The incidence of acute hepatitis B in the referral area was estimated as 2.25 per 100 000 adult population. Mean age was 36 years (17–75). Twenty one patients (18 men and 3 women) acquired the virus through unprotected sexual contact, and seven patients through latrogenic exposure. Thirty three patients underwent spontaneous seroconversion while three patients became chronic carriers. Conclusions: Despite a universal immunisation policy, frequent cases of acute hepatitis B in Israel are still seen. High risk heterosexual activity and iatrogenic exposure seem to be the commonest routes of transmission. Further recommendations regarding vaccination policy are discussed. [ABSTRACT FROM AUTHOR]

Abstract: Background: Experience with larnivudine treatment of immunocompetent patients with acute hepatitis B is limited. Aim of study: To evaluate the safety and efficacy of larnivudine for the treatment of acute severe hepatitis B virus (HBV) infection in immunocompetent adults. Patients and Methods: Fifteen patients (10 men, 5 women, mean age 34.3 ± 7.3 years) with severe acute HBV infection were treated with larnivudine 100 mg daily for 3-6 months, starting 3-12 weeks after onset of infection. Prior to treatment, 5 patients had grade 1-4 encephalopathy; all patients had severe coagulopathy (mean INR was 4.5 ± 6.4), and all patients had evidence of severe hepatocyte lysis (mean alanine arninotransferase 3738 ± 1659 U/L, and mean total serum bilirubin 18 ± 6.8 mg/dl). All patients had evidence of highly replicative HBV (mean HBV DNA 13.5 × 106 ± 11 × 106 copies/ml). Results: Thirteen patients (86.6%) responded to treatment Encephalopathy disappeared within 3 days of treatment and coagulopathy improved within 1 week. Serum HBV DNA was undetectable (by polymerase chain reaction) within 4 weeks, and serum liver enzyme levels normalized within 8 weeks. Two patients in whom larnivudine therapy was delayed developed fulminant hepatitis and underwent urgent liver transplantation. (One died of vascular complications I month later). The 11 patients who were serum HBeAg-positive before treatment seroconverted, and HBeAb developed within 12 weeks in 9 of them; HBsAg was undetectable in all 11 tested patients, and protective titer of HBsAb developed within 12-16 weeks in 9 of them. Therapy was well tolerated in all cases. Conclusions: These data indicate that larnivudine induces a prompt clinical, biochemical, serological and virological response in immunocompetent patients with de novo HBV infection. Larnivudine may prevent the progression of severe acute disease to fulminant or chronic hepatitis and should be considered for use in selected patients. A large randomized controlled, double-blind prospective study is needed. [ABSTRACT FROM AUTHOR]

A recoil detector will be installed surrounding the internal gas target of the HERMES experiment at DESY. The recoil detector will improve the selection of exclusive events by a direct measurement of the momentum and track direction of the recoiling particle. The innermost layer of this recoil detector is a new silicon strip detector (SSD). Since Monte Carlo simulations predict proton momenta as low as 100 MeV/c, the SSD will be placed inside the HERA vacuum. A new setup of the electronics enables a dynamic range from below 4 fC at a signal-to-noise ratio of 6.8 up to 270 fC. In this paper, the assembly of the first module and the final setup within the HERMES experiment will be presented. Results from charge-injection tests of a prototype module are given. [ABSTRACT FROM AUTHOR]

Differential cross-sections for quasi-free π0 photoproduction from the proton and neutron bound in the deuteron have been measured for Eγ 200-400 MeV at θγlab = 136.2° using the Glasgow photon tagger at MAMI, the Mainz 48 cm ø × 64 cm NaI(Tl) photon detector and the Göttingen SENECA recoil detector. For the proton measurements made with both liquid-deuterium and liquid-hydrogen targets allow direct comparison of "free" π0 photoproduction cross-sections as extracted from the bound-proton data with experimental free cross-sections which are found to be in reasonable agreement below 320 MeV. At higher energies the "free" cross-sections extracted from quasi-free data are significantly smaller than the experimental free cross-sections and theoretical predictions based on multipole analysis. For the first time, "free" neutron cross-section have been extracted in the Δ-region. They are also in agreement with the predictions from multipole analysis up to 320 MeV and significantly smaller at higher photon energies. [ABSTRACT FROM AUTHOR]

Background/Aims: Despite its being considered a primary mitogen for hepatocytes, triiodothyronine (T3) has no effect on the proliferation of hepatocytes in vitro , and in our studies, induces significant in vivo hepatocyte proliferation only during liver injury. We hypothesized that T3 may affect hepatocytes proliferation indirectly, by inducing other cells in the liver to secrete hepatic mitogens. Methods: In vivo studies: Lipopolysaccharide, T3 and a combination of the two were injected into rats, and hepatocyte proliferation was determined by PCNA staining and mitotic index. In vitro studies: a rat hepatic stellate cell line (HSC-6T) was cultured with T3, IL-6 and a combination of the two, and we assessed the effect of these cytokine/hormone combinations on the cell proliferation and on secretion of IL-6 and HGF, measured by ELISA. Expression of thyroid hormone receptors was assessed by RT-PCR. Results: In vivo: T3, together with lipopolysaccharide, enhances PCNA staining and the mitotic index of hepatocytes in the treated rats. In vitro: the hepatic stellate cell line expresses thyroid hormone receptor α1, but not β1. Proliferation of stellate cells is not affected by T3, with or without IL-6. T3 has no effect on secreted levels of IL-6 in the stellate cell line. Hepatic stellate cells cultured with T3 and IL-6 show significantly increased amounts of secreted HGF after 48 h in culture. Conclusion: T3 may induce hepatocyte proliferation in vivo during injury by turning on expression of HGF in stellate cells and acting together with IL-6. [ABSTRACT FROM AUTHOR]

Differential cross-sections for quasi-free Compton scattering from the proton and neutron bound in the deuteron have been measured using the Glasgow/Mainz photon tagging spectrometer at the Mainz MAMI accelerator together with the Mainz [48]cm ; SPMOslash; × [64]cm NaI(Tl) photon detector and the Göttingen SENECA recoil detector. The data cover photon energies ranging from [200]MeV to [400]MeV at θLABγ = 136.2°. Liquid deuterium and hydrogen targets allowed direct comparison of free and quasi-free scattering from the proton. The neutron detection efficiency of the SENECA detector was measured via the reaction p(γ,π+ n). The “free” proton Compton scattering cross-sections extracted from the bound proton data are in reasonable agreement with those for the free proton which gives confidence in the method to extract the differential cross-section for free scattering from quasi-free data. Differential cross-sections on the free neutron have been extracted and the difference of the electromagnetic polarizabilities of the neutron has been determined to be αn - βn = 9.8±3.6(stat)+2.1-1.1(syst)±2.2(model) in units of[10-4] fm3. In combination with the polarizability sum αn + βn = 15.2±0.5 deduced from photoabsorption data, the neutron electric and magnetic polarizabilities, αn = 12.5±1.8(stat)+1.1-0.6(syst)±1.1(model) and βn = 2.7±1.8(stat)+0.6-1.1(syst)±1.1(model) are obtained. The backward spin polarizability of the neutron was determined to be γ(n)π = (58.6±4.0)×10-4 fm4. [ABSTRACT FROM AUTHOR]

We prospectively evaluated whether delivering a thermal dose of ≥10 cumulative equivalent minutes at 43°C to >90% of the tumour sites monitored (CEM43° T[sub 90]) would produce a pathologic complete response (pCR) in ≥ 75% of high-grade soft tissue sarcomas treated pre-operatively with thermoradiotherapy. The impact of thermal dose on local failure (LF), distant metastasis (DM), and toxicity was also assessed. Thirty-five patients ≥ 18 years old with grade 2 or 3 soft tissue sarcomas accessible for invasive thermometry were enrolled on the protocol. All patients received megavoltage external beam radiotherapy (RT) in daily fractions of 1.8-2.0Gy, five times a week, to a median total dose of 50Gy and an initial hyperthermia treatment (HT) of 1h duration utilizing the BSD 2000 with Sigma 60 or MAPA applicators at frequencies of 60-140MHz. Further HT was given for patients with CEM43° T[sub 90] > 0.5 after initial HT ('heatable' patients), twice a week to a maximum of 10 HT or CEM43° T[sub 90] > 100. Of the 35 patients entered, 30 had heatable tumours, one of which was inevaluable for pCR or LF as the patient died of DM prior to surgery, leaving 29 evaluable patients. Of these 29 patients, 15 (52%) had a pCR (95% CI: 37-73%), significantly less than the projected rate of ≥75% (p = 0.02). Of the 25 heatable tumours that achieved CEM43° T[sub 90] ≥10, 14 (56% ) had a pCR (95% CI: 39-78%) significantly less than the projected rate (p = 0.06). Three of the 29 patients (10% ) with heatable tumours had a LF, versus 1/5 unheatable tumours (p = 0.48). Fourteen of the 30 patients (47%) with heatable tumours developed DM, versus 2/5 unheatable tumours (p = 1.00). Ten of the 30 patients (33%) with heatable tumours developed treatment-induced toxicity. Thus, no correlation of thermal dose with histologic response was observed. Prospective control of CEM43° T[sub 90] failed to achieve the projected pCR rate following pre-operative thermoradiotherapy for high-grade soft tissue sarcomas, despite excellent local control. Possible explanations for this outcome are discussed. [ABSTRACT FROM AUTHOR]

Carbogen (95% O[SUB2] and 5% CO[SUB2]) has been used in preference to 100% oxygen (O[SUB2]) as a radiosensitizer, because it is believed that CO[SUB2] blocks O[SUB2]-induced vasoconstriction. However, recent work suggests that both normal and tumour arterioles of dorsal flap window chambers exhibit the opposite: no vasoconstriction vs constriction for O[SUB2] vs carbogen breathing respectively. We hypothesized that CO[SUB2] content might cause vasoconstriction and investigated the effects of three O[SUB2]-CO[SUB2] breathing mixtures on tumour arteriolar diameter (TAD) and blood flow (TBF). Fischer 344 rats with R3230Ac tumours transplanted into window chambers breathed either 1%, 5%, or 10% CO[SUB2] + O[SUB2]. Intravital microscopy and laser Doppler flowmetry were used to measure TAD and TBF respectively. Animals breathing 1% CO[SUB2] had increased mean arterial pressure (MAP), no change in heart rate (HR), transient reduction in TAD and no change in TBF. Rats breathing 5% CO[SUB2] (carbogen) had transiently increased MAP, decreased HR, reduced TAD and a sustained 25% TBF decrease. Animals exposed to 10% CO[SUB2] experienced a transient decrease in MAP, no HR change, reduced TAD and a 30-40% transient TBF decrease. The effects on MAP, HR, TAD and TBF were not CO[SUB2] dose-dependent, suggesting that complex physiologic mechanisms are involved. Nevertheless, when ≥ 5% CO[SUB2] was breathed, there was clear vasoconstriction and TBF reduction in this model. This suggests that the effects of hypercarbic gases on TBF are site-dependent and that use of carbogen as a radiosensitizer may be counterproductive in certain situations. [ABSTRACT FROM AUTHOR]

A method for the separation of structure functions in ( e, e′ p) experiments is proposed, which is an extension of the traditional Rosenbluth-type techniques of [1,2]. In our approach, we use a very flexible Ansatz to describe the structure functions within an extended kinematical region G and determine its free parameters with a x minimization. The procedure is tested by pseudo data (C( e, e′p)B) in the quasi-free region. [ABSTRACT FROM AUTHOR]

Background: Chemotherapy-induced myelosuppression often limits escalation of cancer chemotherapy doses. Cyclophosphamide, an alkylating agent, is an ideal candidate for dose escalation: A log-linear relationship between cell kill and dose has been demonstrated, and the drug spares hematopoietic stem cells. In addition, studies suggest that granulocyte-macrophage colony-stimulating factor (GM-CSF) can enhance the ability to achieve optimal dose intensity as well as ameliorating chemotherapy-induced myelosuppression.Purpose: The purpose of this study was to determine the maximum tolerated dose and the toxic effects of cyclophosphamide administered every 2 weeks with GM-CSF support.Methods: For this trial by the Cancer and Leukemia Group B (CALGB), cohorts of patients were treated with cyclophosphamide as a 1-hour intravenous infusion every 14 days; GM-CSF was given subcutaneously on days 3-10. Four dose levels of cyclophosphamide (1.5, 3.0, 4.5, and 6.0 g/m2) and three dose levels of GM-CSF (2.5, 5.0, and 10.0 micrograms/kg per day) were evaluated. There was no dose escalation in individual patients. Fifty-one patients with solid tumors who had CALGB performance status 0 or 1 and minimal prior radiotherapy were eligible for analysis. Drug clearance and area under the curve for plasma drug concentration x time (AUC) were estimated at completion of the infusion and at 4 and 24 hours after the start of the infusion.Results: Ninety-five courses of therapy were analyzed. Treatment with cyclophosphamide at 3.0 g/m2 or more resulted in neutropenia (absolute neutrophil counts < 100/microL) in all cycles of therapy. At those doses, blood cell count recovery adequate for re-treatment occurred in 67%-85% of cycles (median, 16 days). Doses of 6.0 g/m2 were associated with the greatest degree of myelosuppression and frequent hospitalization (88% of cycles); requirements for blood transfusion prohibited further dose escalation. Nonhematologic toxic effects were tolerable, with two episodes of reversible cardiotoxicity and four episodes of hemorrhagic cystitis that precluded further therapy. Degree of myelosuppression was not correlated with cyclophosphamide AUC or clearance.Conclusions: The recommended phase II dose of cyclophosphamide is 4.5 g/m2 administered every 2 weeks with GM-CSF given at 5.0 micrograms/kg per day of GM-CSF. Our results suggest that, with GM-CSF support, high cumulative doses of cyclophosphamide can be given to achieve optimal dose intensity, with reproducible blood cell count recovery and without the need for autologous bone marrow transplantation.Implications: Phase II studies of this intensive regimen in malignant diseases sensitive to alkylating agents are currently being done in CALGB. [ABSTRACT FROM AUTHOR]

The pharmacokinetics of cytarabine (ara-C) were determined in 265 patients with acute myeloid leukemia (AML) receiving ara-C (200 mg/m2 per day for 7 days as a continuous infusion) and daunorubicin during induction therapy. The mean (standard deviation) ara-C concentration at steady-state (Css) and systemic clearance (Cl) were 0.30 (0.13) microM and 134 (71) l/h per m2 respectively. Males had a significantly faster ara-C Cl (139 vs 131 l/h per m2, P = 0.025) than females. Significant correlations were noted between ara-C Cl and the pretreatment, peripheral white blood cell count (P = 0.005) and pretreatment blast count (P = 0.020). No significant differences in ara-C Css or Cl were noted in patients achieving complete remission compared with those failing therapy (P = 0.315, P = 0.344, respectively). No significant correlations were observed between ara-C pharmacokinetic parameters and several indices of patient toxicity. Our findings indicate that variability in ara-C disposition in plasma at this dosage level does not correlate with remission status or toxicity in patients with AML receiving initial induction therapy with ara-C and daunorubicin. [ABSTRACT FROM AUTHOR]

The standard approaches to initial dose selection and dose escalation in phase I trials may be inappropriately conservative. These approaches mandate accrual of large numbers of patients, most of whom are treated at low and potentially ineffective doses. We compared the clinically determined maximum tolerable dose (MTD) with the starting dose of 45 drugs that had undergone phase I studies during the period 1977-1989. We also examined the number of dose-escalation steps required to achieve the MTD in relation to nonhematologic and hematologic dose-limiting toxicity. The median ratio of MTD to starting dose for all drugs was 20 (range, < 1-433) and the median number of dose levels studied to reach the MTD was 8 (range, 0-23). For drugs with nonhematologic dose-limiting toxicity, the median ratio of MTD to starting dose was 30 (range, 3-385) as compared with 12.8 (range, < 1-433) for those with hematologic dose-limiting toxicity (P = 0.023). The median number of dose-escalation steps required to reach the MTD was 9 (range, 2-18) for drugs with nonhematologic dose-limiting toxicity as compared with 5.5 (range, 0-23) for those with hematologic dose-limiting toxicity (P = 0.038). We also examined the response rate for 1,110 patients treated with 21 phase-I-study drugs for which response information was available. Responses were reported for 29 patients (2.6%). Among the 476 patients treated at the 3 highest dose steps, 17 responded (3.6%), which is double the response rate obtained at the lower doses (P = 0.08). It is suggested that although the usual methods for choosing starting doses and dose-escalation schemes for phase I studies are safe, they are overly conservative and delay opportunities for therapeutic benefit in phase I and subsequent phase II trials. [ABSTRACT FROM AUTHOR]

The angular correlations of protons evaporated from the compound nucleusCe exhibit strong anisotropies which are inconsistent with the emission from a spherical source. The data can be explained by an enhanced emission probability due to a lower Coulomb barrier perpendicular to the spin axis of strongly deformed nuclei. [ABSTRACT FROM AUTHOR]

The neutron-rich nucleiSi,Si,Si,P,P,S andS were investigated by studyingC andO - induced transfer reactions onS using a Q3 D magnetic spectrograph and a position sensitive focal plane gas detector. The previously unknown mass of the isotopeSi was determined. The accuracy of the mass excess values of the isotopesSi,Si,P andP has been improved. Excited states of the isotopesSi,Si,P,P andS were identified for the first time. In addition the γ-decay of excited states inS andS was studied with a Ge(Li) detector in coincidence with the Q3 D focal plane detector. Experimental values for the mass excesses are compared with published mass formulae. [ABSTRACT FROM AUTHOR]

The spectral sensitivity of the visual cells in the compound eye of the moth Deilephila elpenor was determined by electrophysiological mass recordings during exposure to monochromatic adapting light. Three types of receptors were identified. The receptors are maximally sensitive at about 350 nm (ultraviolet), 450 nm (violet), and 525 nm (green). The spectral sensitivity of the green receptors is identical to a nomogram for a rhodopsin with λ at 525 nm. The spectral sensitivity of the other two receptors rather well agrees with nomograms for corresponding rhodopsins. The recordings indicate that the green receptors occur in larger number than the other receptors. The ultra-violet and violet receptors probably occur in about equal number. The sensitivity after monochromatic adapting illumination varies with the wavelength of the adapting light, but is not proportional to the spectral sensitivity of the receptors. The sensitivity is proportional to the concentration of visual pigment at photoequilibrium. The equilibrium is determined by the absorbance coefficients of the visual pigment and its photoproduct at each wavelength. The concentration of the visual pigment, and thereby the sensitivity, is maximal at about 450 nm, and minimal at wavelengths exceeding about 570 nm. The light from a clear sky keeps the relative concentration of visual pigment in the green receptors, and the relative sensitivity, at about 0.62. The pigment concentration in the ultra-violet receptors is about 0.8 to 0.9, and that in the violet receptors probably about 0.6. At low ambient light intensities a chemical regeneration of the visual pigments may cause an increase in sensitivity. At higher intensities the concentrations of the visual pigments remain constant. Due to the constant pigment concentrations the input signals from the receptors to the central nervous system contain unequivocal information about variations in intensity and spectral distribution of the stimulating light. [ABSTRACT FROM AUTHOR]