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Photosynthetic production of carbohydrates in phytoplanktons is measured comparing daytime and nighttime levels. The monosaccharide constituents of water-extractable and residual carbohydrates were analyzed using coupled gas chromatography/mass spectrometry and radioactive tracing of isotopic carbon. Daytime production of monosaccharides for both fractions was higher than nighttime levels. Glucose, which is the main monosaccharide component for both carbohydrate fractions, showed significantly decreased production during nighttime.

The differences in daytime and nightime production of fatty acids and amino acids in phytoplanktons was evaluated. In 24-hour time-series experiments, the production rates were analyzed by coupled gas chromatography/mass spectrometry and radioactive tracing of isotopic carbon. The fatty acid composition of the photosynthetic products was found to be maximum between 9:00 and 12:00 hours. There was no definite pattern observed for amino acids. The production rates for both fatty acids and amino acids were lower than those observed for water-extractable carbohydrates and was attibuted to nitogen deficiency in phytoplanktons.

Fibroblast growth factor (FGF) activity has been implicated in a number of developmental processes in the early vertebrate embryo, including mesoderm formation and neural patterning. A primary interest of our laboratory is the elucidation of the signaling cascades triggered by FGF receptor activation during early development of the frog, Xenopus laevis. We report here the characterization of SNT-1, a scaffolding protein previously implicated in FGF-mediated neurite outgrowth in PC12 cells. Xenopus snt-1 is widely expressed during early development. Ventral ectodermal expression of SNT-1 produces tadpoles with multiple tails, while dorsal ectodermal expression results in tadpoles that lack eyes and other anterior structures. SNT-1 induces ventrolateral mesoderm in animal caps; this activity is completely blocked by coexpression of a dominant-inhibitory Ras construct, suggesting that SNT-1 functions as a component of the signaling pathway activated by FGF. SNT-1 directly interacts with Laloo, a Src-related kinase shown previously to function downstream of the FGF receptor. Biochemical and functional assays were used to determine the regions of interaction between SNT-1 and Laloo.

A thermoelastic model for calculating the high-pressure and high-temperature properties of isotropic solids is presented by extending the formalism by Thomsen and combining the resulting one with the Vinet model for static lattice and the Debye model for lattice vibration. Applying it to polycrystalline corundum, we have shown that the calculated values of entropy and heat capacity at constant pressure are in agreement with literature values to 2325 K at zero pressure and that the calculated values of thermal expansivity agree reasonably with experimental data to 1100 K at zero pressure. The model reproduces experimental data of sound velocities v p and v s of compressional and shear waves to 1825 K at zero pressure and those to 62 GPa at room temperature, and it reproduces also experimental shock-wave equation of state to 150 GPa. The velocity correlation (∂ln v s/∂ln v p) S was found to have weak pressure and temperature dependences and the results under lower mantle conditions are compared with those of magnesian and calcium silicate perovskites and magnesiowüstite, and the PREM values of the Earth's lower mantle. [ABSTRACT FROM AUTHOR]

Immunotherapy has greatly improved the outcomes of patients with metastatic melanoma. However, it has also led to new patterns of response and progression, creating an unmet need for better biomarkers to identify patients likely to achieve a lasting clinical benefit or experience immune-related adverse events. In this study, we performed a focused literature survey covering the application of artificial intelligence (AI; in the form of radiomics, machine learning, and deep learning) to patients diagnosed with melanoma and treated with immunotherapy, reviewing 12 studies relevant to the topic published up to early 2022. The most commonly investigated imaging modality was CT imaging in isolation ( n = 9, 75.0%), while patient cohorts were most frequently recruited retrospectively and from single institutions ( n = 7, 58.3%). Most studies concerned the development of AI tools to assist in prognostication ( n = 5, 41.7%) or the prediction of treatment response ( n = 6, 50.0%). Validation methods were disparate, with two studies (16.7%) performing no validation and equal numbers using cross-validation ( n = 3, 25%), a validation set ( n = 3, 25%), or a test set ( n = 3, 25%). Only one study used both validation and test sets ( n = 1, 8.3%). Overall, promising results have been observed for the application of AI to immunotherapy-treated melanoma. Further improvement and eventual integration into clinical practice may be achieved through the implementation of rigorous validation using heterogeneous, prospective patient cohorts.

If pulse pressure, one of the mechanical stresses, is a risk factor for atherosclerotic cardiovascular disease, then atherosclerosis should be progressive in aortic regurgitation which is a representative disease with increased pulse pressure. This cross-sectional study included 1,149 patients. We examined the influence of aortic regurgitation on maximum intima-media thickness or brachial-ankle pulse wave velocity. The degree of aortic regurgitation was classified into 4 grades by color Doppler examination. There were 177 patients with aortic regurgitation. Pulse pressure was significantly higher in patients with aortic regurgitation than in those without it. On multiple regression analysis, aortic regurgitation was not found to be a significant independent variable for maximum intima-media thickness [standard partial regression coefficient: aortic regurgitation = grade 1, 0.011, P = 0.7635; aortic regurgitation ≥ grade 2, -0.034, P = 0.3289] and brachial-ankle pulse wave velocity [standard partial regression coefficient: aortic regurgitation = grade1, -0.043, P = 0.1197; aortic regurgitation ≥ grade2, 0.002, P = 0.9358] after adjusting for age, sex, body mass index, presence or absence of cardiovascular disease, antihypertensive treatment, diabetes, dyslipidemia, and smoking. These results found no causal association between aortic regurgitation and atherosclerosis, and were a contradiction to the opinion that pulse pressure was a risk factor of atherosclerosis.

Amyloidosis is a well-known but uncommon disease, and the physician must maintain a high index of suspicion in order to make a timely diagnosis. The expected survival of patients with cardiac amyloidosis is generally poor. In particular, survival has been reported to be 4-12 months for patients with amyloid light-chain amyloidosis with congestive heart failure. We herein report a rare case of cardiac amyloidosis in which the patient presented with cardiac hypertrophy after a 20-year history of dilated cardiomyopathy and heart failure.

Background: Although fever is a common accompanying feature of acute aortic dissection, few reports have been published concerning the duration and character of this fever., Methods and Results: The mean duration of fever was calculated for a total of 57 patients with acute aortic dissection, who were then divided into 2 groups: those with duration of fever shorter than the mean (Group A) and those with duration of fever equal to or longer than the mean (Group B). The reduction in false lumen size and hematological parameters were compared between groups. The mean duration of fever was 15.9+/-11 days. The false lumen reduction ratio was significantly higher in Group A (18.3+/-5.0%) than in Group B (2.0+/-5.3%). There was a significant negative correlation between the false lumen reduction ratio and duration of fever. Hematological parameters did not differ significantly between the 2 groups except for fibrin degradation product, although the white blood cell count and platelet counts and C-reactive protein concentration tended to be higher in Group B., Conclusions: Checking for fever is important in assessing the status of individual cases of acute aortic dissection.

Members of the Src family of non-receptor tyrosine kinases play a critical role in mesoderm formation in the frog, Xenopus laevis, acting as required mediators downstream of the fibroblast growth factor receptor. At least four members of this gene family, Src, Fyn, Yes, and Laloo, are expressed during early embryonic development. Ectopic expression of Laloo and Fyn, but not Src, induce mesoderm in ectodermal explants, indicating that these factors are non-redundant during early vertebrate development. Here we investigate the basis for the differential activity of the Src and Laloo kinases during mesoderm formation. We demonstrate that although both Src and Laloo physically interact with the substrate protein SNT-1/FRS2alpha only Laloo phosphorylates SNT-1, an event previously shown to be required for the activity of the latter and for mesoderm induction in vivo. We show that Src is enzymatically capable of stimulating mesoderm formation, as an activated Src construct both phosphorylates SNT-1 and induces mesoderm in explant cultures. However, a chimeric Laloo construct containing a Src C-terminal tail is inactive, suggesting that the early embryo contains a specific Laloo-activating, or Src-inactivating, factor. Finally, through further chimeric analysis, we provide evidence to suggest that differences in Laloo and Src activity are also mediated by the SH2, SH3, and kinase domains of these molecules.

Members of the fibroblast growth factor (FGF) ligand family play a critical role in mesoderm formation in the frog Xenopus laevis. While many components of the signaling cascade triggered by FGF receptor activation have been identified, links between these intracellular factors and the receptor itself have been difficult to establish. We report here the characterization of Xenopus SNT-1 (FRS2alpha), a scaffolding protein previously identified as a mediator of FGF activity in other biological contexts. SNT-1 is widely expressed during early Xenopus development, consistent with a role for this protein in mesoderm formation. Ectopic SNT-1 induces mesoderm in Xenopus ectodermal explants, synergizes with low levels of FGF, and is blocked by inhibition of Ras activity, suggesting that SNT-1 functions to transmit signals from the FGF receptor during mesoderm formation. Furthermore, dominant-inhibitory SNT-1 mutants inhibit mesoderm induction by FGF, suggesting that SNT-1 is required for this process. Expression of dominant-negative SNT-1 in intact embryos blocks mesoderm formation and dramatically disrupts trunk and tail development, indicating a requirement for SNT-1, or a related factor inhibited by the mutant construct, during axis formation in vivo. Finally, we demonstrate that SNT-1 physically associates with the Src-like kinase Laloo, and that SNT-1 activity is required for mesoderm induction by Laloo, suggesting that SNT-1 and Laloo function as components of a signaling complex during mesoderm formation in the vertebrate.

Models employing gradients of diffusible morphogens are often invoked to explain regional specification in the early embryo. In these models, a concentration gradient of a secreted factor generates distinct cell fates, based on the differential response of cells to local concentrations of this morphogen. In recent years, there has been a great deal of focus on the factors involved in the dorsoventral patterning of the vertebrate mesoderm and ectoderm. Dorsoventral specification during amphibian gastrulation is regulated by the antagonistic actions of the Bone Morphogenetic Proteins (BMPs) and a number of dorsally expressed inhibitors, including the secreted factor, Chordin. In a recent paper, Blitz and colleagues explore the possibility that Chordin acts as a long-range factor in the amphibian gastrula embryo, to establish a functional gradient of BMP activity.

To examine whether protein kinase C (PKC) activation is essential for the induction of cardiac myocyte hypertrophy caused by alpha1-adrenergic stimulation, we investigated the hypertrophic effect of phenylephrine in PKC down-regulated and non-treated cultured cardiac myocytes obtained from neonatal Sprague-Dawley rat ventricles. The treatment with 10 nmol/L 12-tetra decanoylphorbol-13-acetate (TPA) for more than 2 hours decreased PKC activity by approximately 80% without marked hypertrophy. Phenylephrine increased [14C] phenylalanine (Phe) incorporation in both TPA non-treated and treated cells, 1.54- and 1.71-fold as large as control, respectively. The cell surface area also enlarged in both groups, 1.67- and 1.74-fold, respectively. Thus, phenylephrine induced the similar grade hypertrophy in cultured cardiac myocytes even when PKC was down-regulated. These results suggest that conventional PKC activation may not be essential for mediating myocyte hypertrophy by alpha1-adrenergic stimulation.

Background: The administration of calcium antagonists to patients with healed myocardial infarction is a controversial treatment. This study was conducted to elucidate the effect of short-acting nifedipine and diltiazem on cardiac events in patients with healed myocardial infarction., Methods and Results: A controlled clinical open trial of 1115 patients with healed myocardial infarction was carried out between 1986 and 1994. The patients included 595 who received no calcium antagonist, 341 who received short-acting nifedipine 30 mg/d, and 179 who received short-acting diltiazem 90 mg/d. The primary end points were cardiac events, which were defined as fatal or nonfatal recurrent myocardial infarction; death from congestive heart failure; sudden death; and hospitalization because of worsening angina, congestive heart failure, or premature ventricular contractions. Cardiac events occurred in 51 patients (8.6%) in the no-calcium-antagonist group and 54 (10.4%) in the calcium-antagonist group (odds ratio, 1.24; 95% CI, 0.83 to 1.85), demonstrating that the calcium antagonists did not reduce the incidence of cardiac events. Subgroup analysis revealed no beneficial effects of these drugs for reducing cardiac events in patients with such complications as hypertension or angina pectoris., Conclusions: This study showed that use of short-acting nifedipine and diltiazem in this postmyocardial infarction population was associated with a 24% higher cardiac event rate, but this strong adverse trend did not reach statistical significance.

We retrospectively analyzed the effect of beta-blocking agents on the incidence of cardiac events in elderly patients who had had myocardial infarction. A total of 1169 patients who had had a myocardial infarction (age, 60.2 +/- 11.4 years) were followed for a mean of 18.0 +/- 19.7 months and the incidence of cardiac events (fatal or nonfatal myocardial infarction, sudden cardiac death, and death due to congestive heart failure) was computed. There were 21 cardiac events in 653 patients who received beta-blocking agents (3.2%) and 39 events in 516 patients who did not receive beta-blocking agents (7.6%, p < 0.01). Among patients less than 50 years old, the incidences of cardiac events were 4.1% in those who received beta-blocking agents and 7.6% in those who did not; among those 50 to 59 years old the incidences were 3.0% and 7.5%, respectively; among those 60 to 69 years old they were 4.3% and 6.0%, respectively; and among those 70 years old or older they were 0.8% and 11.4%, respectively (p < 0.01). We found that beta-blocking agents prevented cardiac events both in elderly and in younger patients after myocardial infarction.

The efficacy of combining antiplatelet agents with low doses of aspirin to prevent cardiac events in patients with myocardial infarction was examined. A total of 1,083 patients with prior myocardial infarction were randomly divided into those who were (618) and were not (465) treated with antiplatelet agents, and observed for 12.5 +/- 18.5 months. Those treated with antiplatelet agents included 113 patients treated with aspirin (50 mg) plus dipyridamole (150 mg/day), 253 treated with aspirin (50 mg) plus ticlopidine (200 mg/day), and 252 treated with only 1 of the 3 antiplatelet agents. Cardiac events, including fatal or nonfatal recurrent myocardial infarction, death by congestive heart failure, and sudden death, occurred in 34 patients (7.3%) in the nontreatment group and in 19 patients (3.1%; p < 0.01) in the treatment group; odds ratio 0.40, 95% confidence interval 0.23-0.71. There were only 2 cardiac events (1.8%) in the aspirin + dipyridamole group (p < 0.05 vs nontreatment group: odds ratio 0.28: 0.08-1.03), and 5 such events (2.0%) in the aspirin + ticlopidine group (p < 0.01; odds ratio 0.28: 0.11-0.69). Subgroup analysis to exclude differences in the patients' background confirmed the efficacy of these antiplatelet agents. We conclude that combined treatment with low doses of aspirin plus either dipyridamole or ticlopidine is effective in preventing cardiac events in patients who have had prior myocardial infarction.

Background: Nitrates dilate coronary arteries, ameliorate myocardial ischemia, minimize left ventricular remodeling, and reduce mortality in patients with acute myocardial infarction. However, the effects of long-term treatment with nitrates on cardiac events in patients with healed myocardial infarction are not known., Methods and Results: A total of 1,002 patients with healed myocardial infarction (789 male and 213 female) were randomly divided into 2 groups: treatment with nitrates or nontreatment. The mean observation period was 18.0 +/- 19.9 months. Primary end points were nonfatal and fatal recurrent myocardial infarction, death from congestive heart failure, and sudden death. Baseline characteristics of the 2 groups were also compared to determine any effects on outcome. Among the 621 cases treated with nitrates, 41 cases (6.6%) experienced cardiac events during the observation period, whereas only 12 of the 381 cases that were not treated with nitrates (3.1%) had cardiac events. This difference was statistically significant (p < 0.05; odds ratio 2.17; 95% confidence interval 1.13-4.19). There were no differences in the incidence of noncardiac death or being lost to follow-up between the 2 groups. Although the precise mechanism of this increase in the occurrence of cardiac events by long-term treatment with nitrates is not clear, nitrate tolerance with possible rebound and neurohormonal effects may be involved., Conclusion: Long-term treatment with nitrates increased cardiac events in patients with healed myocardial infarction.

1. In the present study, we examined the effect of a novel angiotensin II type I receptor antagonist, TCV-116, on carotid neointimal formation after balloon injury in SHR and WKY rats. 2. Oral administration of TCV-116 at a dose of 10 mg/kg per day reduced not only systolic blood pressure but also neointimal formation after carotid balloon injury. TCV-116 also suppressed cardiac hypertrophy. An angiotensin-converting enzyme inhibitor, lisinopril (20 mg/kg per day), had a similar effect to that of TCV-116. 3. In the WKY experiment, both TCV-116 and lisinopril suppressed neointimal formation as well as systolic blood pressure, but did not suppress cardiac hypertrophy. 4. Although SHR showed markedly enhanced neointimal formation after balloon injury compared with age-matched WKY rat, both TCV-116 and lisinopril showed similar suppressive effects on neointimal formation in both SHR and WKY rats. 5. These results confirm the important role of angiotensin II in neointimal formation following balloon injury. Further studies are needed to clarify the mechanism of the difference between SHR and WKY rats in the response of vascular smooth muscle cells.

The effects of beta-blocker treatment on hemodynamics were studied in relation to plasma atrial natriuretic peptide (ANP) levels in 17 outpatients with essential hypertension. Administration of propranolol for twelve weeks to untreated subjects resulted in a significant (P < 0.001) rise in plasma ANP levels (from 37.9 +/- 21.2 to 66.7 +/- 46.2 pg/mL, mean +/- SD). Systolic and diastolic blood pressures were significantly decreased (P < 0.05 and P < 0.01, respectively). Heart rate was also significantly decreased (P < 0.001). On the other hand, a significant reduction of cardiac index was detected (from 4.12 +/- 1.34 to 2.96 +/- 0.75 L/min/m2, P < 0.01) with chronic administration of propranolol, suggesting a reflection of decreased cardiac function. A significant negative correlation was observed between %changes in systolic blood pressure and %changes in plasma ANP (r = -0.594, P < 0.05). These results suggest that the increased plasma ANP levels may contribute to the antihypertensive effect with propranolol.

Arterial injury by a balloon catheter produces marked smooth muscle cell proliferation and the participation of angiotensin II in this response has been suggested. In this study, we examined the effect of a novel angiotensin II type I receptor antagonist, TCV-116, on neointimal formation after rat carotid artery balloon injury. Oral administration of TCV-116 at doses of 1, 5 or 10 mg/kg/day significantly reduced the cross-sectional intimal area by 30%, 46% and 54%, respectively, and reduced the ratio of the intimal to medial cross-sectional areas by 23%, 41% and 50%. An angiotensin-converting enzyme inhibitor, lisinopril, had an effect similar to that of TCV-116. The effect of both drugs was significantly correlated with the reduction of both blood pressure and cardiac hypertrophy. We conclude that TCV-116 can prevent neointimal formation after balloon injury as well as reducing blood pressure and preventing cardiac hypertrophy.