Bird population declines and species turnover are changing the acoustic properties of spring soundscapes.

Natural sounds, and bird song in particular, play a key role in building and maintaining our connection with nature, but widespread declines in bird populations mean that the acoustic properties of natural soundscapes may be changing. Using data-driven reconstructions of soundscapes in lieu of historical recordings, here we quantify changes in soundscape characteristics at more than 200,000 sites across North America and Europe. We integrate citizen science bird monitoring data with recordings of individual species to reveal a pervasive loss of acoustic diversity and intensity of soundscapes across both continents over the past 25 years, driven by changes in species richness and abundance. These results suggest that one of the fundamental pathways through which humans engage with nature is in chronic decline, with potentially widespread implications for human health and well-being.

Prediction of pre-eclampsia in twin pregnancy by maternal factors and biomarkers at 11-13 weeks' gestation: data from EVENTS trial.

OBJECTIVES: First, to validate a previously developed model for screening for pre-eclampsia (PE) by maternal characteristics and medical history in twin pregnancies; second, to compare the distributions of mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI), serum placental growth factor (PlGF) and serum pregnancy-associated plasma protein-A (PAPP-A) in twin pregnancies that delivered with PE to those in singleton pregnancies and to develop new models based on these results; and, third, to examine the predictive performance of these models in screening for PE with delivery at < 32 and < 37 weeks' gestation. METHODS: Two datasets of prospective non-intervention multicenter screening studies for PE in twin pregnancies at 11 + 0 to 13 + 6 weeks' gestation were used. The first dataset was from the EVENTS (Early vaginal progesterone for the preVention of spontaneous prEterm birth iN TwinS) trial and the second was from a previously reported study that examined the distributions of biomarkers in twin pregnancies. Maternal demographic characteristics and medical history from the EVENTS-trial dataset were used to assess the validity of risks from our previously developed model. The combined data from the first and second datasets were used to compare the distributional properties of log10 multiples of the median (MoM) values of UtA-PI, MAP, PlGF and PAPP-A in twin pregnancies that delivered with PE to those in singleton pregnancies and develop new models based on these results. The competing-risks model was used to estimate the individual patient-specific risks of delivery with PE at < 32 and < 37 weeks' gestation. Screening performance was measured by detection rates (DR) and areas under the receiver-operating-characteristics curve. RESULTS: The EVENTS-trial dataset comprised 1798 pregnancies, including 168 (9.3%) that developed PE. In the validation of the prior model based on maternal characteristics and medical history, calibration plots demonstrated very good agreement between the predicted risks and the observed incidence of PE (calibration slope and intercept for PE < 32 weeks were 0.827 and 0.009, respectively, and for PE < 37 weeks they were 0.942 and -0.207, respectively). In the combined data, there were 3938 pregnancies, including 339 (8.6%) that developed PE and 253 (6.4%) that delivered with PE at < 37 weeks' gestation. In twin pregnancies that delivered with PE, MAP, UtA-PI and PlGF were, at earlier gestational ages, more discriminative than in singleton pregnancies and at later gestational ages they were less so. For PAPP-A, there was little difference between PE and unaffected pregnancies. The best performance of screening for PE was achieved by a combination of maternal factors, MAP, UtA-PI and PlGF. In screening by maternal factors alone, the DR, at a 10% false-positive rate, was 30.6% for delivery with PE at < 32 weeks' gestation and this increased to 86.4% when screening by the combined test; the respective values for PE < 37 weeks were 24.9% and 41.1%. CONCLUSIONS: In the assessment of risk for PE in twin pregnancy, we can use the same prior model based on maternal characteristics and medical history as reported previously, but in the calculation of posterior risks it is necessary to use the new distributions of log10 MoM values of UtA-PI, MAP and PlGF according to gestational age at delivery with PE. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

Historical analysis of epizootiological situation of rabies on the territory of the Slovak Republic.

Currently, Slovakia is a rabies-free country, but the epizootiological situation of rabies was not always favorable. The main reservoir species of rabies virus in the first half of the last century was the domestic dog. Since 1906, hundreds of cases were reported, of which approximately 90% were infected dogs. The disease had a typical urban character. Since 1929, the number of rabid domestic animals decreased due to the implementation of dog vaccination campaigns in particular parts of Slovakia. From the second half of 1950s, red foxes (Vulpes vulpes) have become an important reservoir of the RABV. In this time period urban rabies in Slovakia changed into sylvatic form. One effective method of prevention and control of wildlife rabies is an oral rabies vaccination of red foxes. It is carried out in Slovakia since 1993. A detailed development of the rabies epizootiological situation on the territory of the Slovak Republic until the application of oral antirabies immunisation of foxes and the current situation after its performance is the main object of this review. Keywords: rabies; Lyssavirus; red fox; incidence; oral vaccination.

Revised competing-risks model in screening for pre-eclampsia in twin pregnancy by maternal characteristics and medical history.

BACKGROUND: We have proposed previously that the competing-risks model for prediction of pre-eclampsia (PE) based on maternal characteristics and medical history (prior model), developed in singleton pregnancies, can be extended to risk assessment for twins; in dichorionic (DC) and monochorionic (MC) twin pregnancies with the same characteristics as in singleton pregnancies, the distribution of gestational age at delivery with PE was shifted to the left by 8 and 10 weeks, respectively. However, in a subsequent validation study, we found that, in both the training and validation datasets, the observed incidence of PE was lower than the predicted one and such overestimation of risk was particularly marked for early PE. OBJECTIVES: First, to develop a new extension of the competing-risks prior model in screening for PE by maternal demographic characteristics and medical history in twin pregnancies in a training dataset. Second, to examine the predictive performance of this model in screening for PE with delivery < 34 weeks (early PE), < 37 weeks (preterm PE) and at any gestational age (all PE) in twins in a validation dataset. Third, to demonstrate the application of screening in a mixed population of singleton and twin pregnancies. METHODS: The data for this study were obtained from two prospective non-intervention multicenter screening studies for PE in twin pregnancies at 11 + 0 to 13 + 6 weeks' gestation. The training and validation datasets consisted of 2219 and 2999 women, respectively. We used the training dataset to fit a model in which the effect of twins on shifting the distribution of gestational age at delivery with PE in singletons to the left should not be the same for all gestational ages but the shift should depend on the singleton prior mean; the effect increases with increasing prior mean. We examined the predictive performance of the model in the training and validation datasets using the area under the receiver-operating characteristics curve (AUC) and calibration plots. Data on 16 747 singleton pregnancies obtained from the Screening ProgRamme for prE-Eclampsia (SPREE) study were included to examine the performance of screening in a mixed population of singleton and twin pregnancies. RESULTS: Calibration plots and calibration intercept and slope demonstrate superior predictive performance of the new model in the validation dataset. Although the AUC for twin pregnancies is lower than in singleton pregnancies, performance of screening in a mixed population of singleton and twin pregnancies is superior to that in singletons (AUC of 0.790 in a mixed population comprising 2% twins and 98% singletons compared to 0.775 in singletons). For the risk cut-offs likely to be used in practice, all twin pregnancies screen positive using maternal characteristics and medical history. CONCLUSIONS: A new competing-risks model in screening for PE by maternal risk factors in twin pregnancy has been developed and, using this model, the predicted risks for early PE, preterm PE and all PE are in relatively good agreement with the observed incidence of the disease. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Validation of competing-risks model in screening for pre-eclampsia in twin pregnancy by maternal factors.

OBJECTIVE: To examine the predictive performance of the competing-risks model in screening for pre-eclampsia (PE) by maternal demographic characteristics and medical history in twin pregnancy, in a training dataset used for development of the model and a validation dataset. METHODS: The data for this study were derived from two prospective non-intervention multicenter screening studies for PE in twin pregnancies at 11 + 0 to 13 + 6 weeks' gestation. The first study of 2219 women, which was reported previously, was used to develop the competing-risks model for prediction of PE and is therefore considered to be the training set. The validation study comprised 2999 women. Patient-specific risks of delivery with PE at < 34 (early), < 37 (preterm) and < 41 + 3 (all) weeks' gestation were calculated using the competing-risks model and the performance of screening for PE in the training and validation datasets was assessed. We examined the predictive performance of the model by, first, its ability to discriminate between the PE and no-PE groups using the area under the receiver-operating characteristics curve (AUC) and, second, calibration, which assesses agreement between the predicted risk and observed incidence of PE. RESULTS: The incidence of early PE, preterm PE and all PE in the training and validation datasets was similar (1.8% vs 1.4%, 5.6% vs 5.6% and 7.7% vs 7.2%, respectively) and this was substantially higher than in our previous studies in singleton pregnancies. The training and validation datasets had similar AUCs for early PE (0.670 (95% CI, 0.593-0.747) vs 0.677 (95% CI, 0.594-0.760)), preterm PE (0.666 (95% CI, (0.617-0.715) vs 0.652 (95% CI, 0.609-0.694)) and all PE (0.656 (95% CI, 0.615-0.697) vs 0.644 (95% CI, 0.606-0.682)). Calibration plots of the predictive performance of the competing-risks model demonstrated that, in both the training and validation datasets, the observed incidence of PE was lower than the predicted one and such overestimation of risk was particularly marked for early PE. CONCLUSIONS: Discrimination and calibration of the competing-risks model for PE in a validation dataset are consistent with those in the training dataset. However, the model needs to be adjusted to correct the observed overestimation of risk for early PE. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Competing-risks model in screening for pre-eclampsia in twin pregnancy by maternal characteristics and medical history.

OBJECTIVE: A survival-time regression model for gestational age at delivery with pre-eclampsia (PE) in singleton pregnancy, using maternal demographic characteristics and medical history, was reported previously. The objective of this study was to extend this model to dichorionic (DC) and monochorionic (MC) twin pregnancy. METHODS: The study population included 1789 DC and 430 MC twin pregnancies and 93 297 singleton pregnancies. A survival-time model for gestational age at delivery with PE was developed from variables of maternal characteristics and medical history. The risk of PE with delivery < 37 weeks and < 42 weeks in twin pregnancies was determined and compared with that in singleton pregnancies. RESULTS: In singleton pregnancies comprising women of Caucasian racial origin, mean weight of 69 kg at 12 weeks' gestation, mean height of 164 cm, nulliparous, with spontaneous conception, no family history of PE and no history of diabetes mellitus, systemic lupus erythematosus or antiphospholipid syndrome, the mean of the Gaussian distribution of gestational age at delivery with PE was 55 weeks. In DC twins with PE, mean gestational age at delivery was shifted to the left by 8.2 (95% CI, 7.2-9.1) weeks and in MC twins it was shifted to the left by 10.0 (95% CI, 8.5-11.4) weeks. The risk of delivery with PE occurring at, or before, a specified gestational age is given by the area under the fitted distribution curve. For a reference population with the above characteristics, the estimated risk of PE < 37 weeks' gestation, assuming no other cause of delivery, was 0.6% for singletons, 9.0% for DC twins and 14.2% for MC twins; the respective values for PE < 42 weeks were 3.6%, 27.0% and 36.5%. CONCLUSIONS: A model based on maternal characteristics and medical history has been developed for estimation of patient-specific risks for PE in DC and MC twin pregnancy. Such estimation of the a-priori risk for PE is an essential first step in the use of Bayes' theorem to combine maternal factors with biomarkers for the continuing development of more effective methods of screening for the disease. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Competing-risks model in screening for pre-eclampsia in twin pregnancy according to maternal factors and biomarkers at 11-13 weeks' gestation.

OBJECTIVE: To develop a model for screening for pre-eclampsia (PE) in twin pregnancies based on maternal demographic characteristics and medical history and biomarkers at 11-13 weeks' gestation. METHODS: This was a screening study in twin pregnancies at 11-13 weeks' gestation. Bayes theorem was used to combine the a-priori risk from maternal factors with various combinations of uterine artery pulsatility index (UtA-PI), mean arterial pressure (MAP), serum pregnancy-associated plasma protein-A (PAPP-A) and placental growth factor (PlGF) multiples of the median (MoM) values. The performance of screening for PE requiring delivery at < 32, < 37 and < 42 weeks' gestation was estimated in 1100 twin pregnancies and 35 948 singleton pregnancies with complete data on UtA-PI, MAP, PlGF and PAPP-A. RESULTS: In twin pregnancies that developed PE, the values of MAP and UtA-PI were increased and the values of PlGF and PAPP-A were decreased. The distributions of log10 MoM values of biomarkers with gestational age at delivery were similar to those that were previously reported in singleton pregnancies and it was therefore assumed that the same model could be used for both singleton and twin pregnancies. The performance of screening for PE by maternal factors was improved by the addition of MAP, UtA-PI and PlGF; there was no further improvement with the addition of PAPP-A. In a mixed population of singleton and twin pregnancies, combined screening by maternal factors, MAP, UtA-PI and PlGF and risk cut-off of 1 in 75 for PE at < 37 weeks, the detection rate of PE at < 32, < 37 and < 42 weeks in singleton pregnancies was 91%, 77% and 57%, respectively, at a screen-positive rate (SPR) of 13%; the respective rates for twin pregnancies were 100%, 99% and 97%, at a SPR of 75%. CONCLUSION: First-trimester combined screening for PE in singleton pregnancies can be adapted for screening in twins, leading to detection of nearly all affected cases but at a high SPR. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Hidden high rate of pre-eclampsia in twin compared with singleton pregnancy.

OBJECTIVES: To examine the gestational age at delivery in dichorionic (DC) and monochorionic (MC) twin pregnancies, with and without pre-eclampsia (PE), and to determine the relative risk of total and preterm PE compared with that in singleton pregnancies. METHODS: This was a screening study for PE in twin pregnancies undergoing first-trimester combined screening for aneuploidy and subsequently delivering two phenotypically normal live or stillborn babies at ≥ 24 weeks' gestation. The distribution of gestational age at delivery in DC and MC twins was determined and compared with that in singleton pregnancies from the same population. The relative risk for total and preterm PE in twins compared with singleton pregnancies was determined. Kaplan-Meier estimates of the cumulative incidence of PE in twin and singleton pregnancies, assuming no other cause for delivery, were determined and hazard ratios for twins relative to singletons were obtained from a Cox proportional hazards regression model. RESULTS: The incidence of PE in singletons was 2.3% (2162/93 297), in DC twin pregnancies was 8.1% (145/1789) and in MC twin pregnancies was 6.0% (26/430). Compared with singletons, the relative risk of total PE was 3.5 for DC twins and 2.6 for MC twins. Delivery < 37 weeks' gestation occurred in 5.5% of singletons, 46.5% of DC twins and 91.4% of MC twins. The incidence of preterm PE was 0.6%, 5.5% and 5.8% for singletons, DC twins and MC twins, respectively. Compared with singletons, the relative risk of preterm PE was 8.7 for DC twins and 9.1 for MC twins. In the Cox proportional hazards regression model, the hazard ratios for DC and MC twin pregnancies relative to singleton pregnancies were 14 and 23, respectively. CONCLUSIONS: The relative risk of preterm PE in DC and MC twins is similar and substantially higher than in singleton pregnancies. In ongoing twin pregnancies, the high relative risk of PE may merit a higher intensity of monitoring than is routine for singleton pregnancies. © 2017 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.

H2S preconditioning of human adipose tissue-derived stem cells increases their efficacy in an in vitro model of cell therapy for simulated ischemia.

AIMS: A major limitation of cell-based therapies for ischemia-reperfusion injury is the excessive loss of administered cells. We investigated whether H2S can improve the survival and efficacy of therapeutic cells in an in vitro model of cell-based therapy for simulated ischemia. MAIN METHODS: H9c2 rat cardiomyoblasts were exposed to oxygen-glucose deprivation and NaHS (3-30 µM) pretreated human adipose tissue derived stem cells (hASCs) were added after reoxygenization. Viability of both cell lines was assessed with flow cytometry after 24h. The effects of H2S on antioxidant defense, proliferation, AKT and ERK1/2 phosphorylation and mitochondrial activity were analyzed in hASCs. Proliferation was evaluated using propargylglycine, an inhibitor of endogenous H2S synthesis. KEY FINDINGS: NaHS pretreatment decreased the ratio of necrotic therapeutic cells by 41.8% in case of 3 µM NaHS and by 34.3% with 30 µM NaHS. The ratio of necrotic postischemic cardiomyocytes decreased by 35%, but only with the use of 3 µM NaHS. Antioxidant defense mechanisms and ERK-phosphorylation were enhanced after 3 µM NaHS treatment while AKT-phosphorylation was suppressed. NaHS dose-dependently increased the proliferation of hASCs while pretreatment with propargylglycine decreased it. SIGNIFICANCE: NaHS pretreatment can increase the survival of therapeutically used human adipose tissue-derived stem cells via increased antioxidant defense and improves the postischemic cardiac derived cells' survival as well. Proliferation of human adipose tissue-derived stem cells is enhanced by H2S. The underlying mechanisms involve enhanced ERK-phosphorylation and decreased AKT-phosphorylation. Pretreatment with NaHS may represent a simple pharmacological step that may enhance the efficacy of cell-based therapies.

Effects of decreased specific glutathione reductase activity in a chromate-tolerant mutant of Schizosaccharomyces pombe.

A chromate-tolerant mutant chr1-663T bearing a stable one-gene mutation and its parental strain 6chr(+) were used to investigate the background of Cr(VI) tolerance in the fission yeast Schizosaccharomyces pombe. The mutant chr1-663T displayed a significantly decreased specific glutathione reductase (GR) activity coded by the pgr1 (+) gene compared with its parental strain. Transformants of the mutant chr1-663T with a nonintegrative pUR18N vector expressing the pgr1 (+) gene exhibited the same Cr(VI) sensitivity and specific GR activity as their parental strain, demonstrating the importance of the GR-NADPH system in Cr(VI) tolerance. Transformants, nevertheless, exhibited an increased intracellular peroxide concentration, a decreased Cr(VI)-reducing and HO*-producing ability, which suggested an unbalanced oxidoreduction state of cells and partial complementation of the GR function. No mutation was found in the sequences of the pgr1 (+) and the pap1 (+) (transcriptional regulatory gene of GR) genes of the Cr(VI)-tolerant mutant by sequence analysis.

The transcription factor Pap1/Caf3 plays a central role in the determination of caffeine resistance in Schizosaccharomyces pombe.

We previously identified four nuclear genes (caf1+-caf4+) in Schizosaccharomyces pombe, mutations in which confer resistance to caffeine and brefeldin A. caf1+, caf2+ and caf4+ were sequenced and found to be identical to the multidrug-resistance/stress-response genes hba1, crm1 and trr1, respectively. Here we show that caf3 is allelic to pap1, which encodes an AP-1-like transcription factor. The allele associated with caffeine resistance, caf3-89, contains a single-nucleotide exchange that results in a Leu-->Ser exchange in the NES (nuclear export signal) domain of the gene product. Due to this alteration, the modified protein can not be exported from the nucleus back into the cytoplasm, and thus accumulates in the nucleus. The activity of pap1/caf3 is shown to be necessary for manifestation of the caffeine resistance caused by mutations in the genes hba1/caf1 and crm1/caf2. We also cloned two genes that confer caffeine resistance when carried on a multicopy plasmid. One of them turned out to be a truncated allele of pad1/bfr2/sks1, which codes for a subunit of the 26 S proteosome. The putative product of the other gene, designated caf5, has a structure highly similar to that of MFS permeases. It contains two groups of six transmembrane spanning domains each, with the conserved motifs WRW, PET and GAIGGPVLGP in the fifth and sixth domains. These results are all consistent with our earlier hypothesis, which suggested that the caf genes are functionally interlinked in a complex detoxification mechanism. caf5 and pad1 may also encode parts of this mechanism.

Marker construction and cloning of a cut1-like sequence with ARS activity in the fission yeast Schizosaccharomyces japonicus.

The dimorphic fission yeast Schizosaccharomyces japonicus has proved to be an excellent experimental model for the investigation of the eukaryotic cell. Here we show that it has a haplontic life cycle, in which the diploid phase is confined to the zygote. To make it amenable to genetic and molecular analysis, we generated genetic markers and cloned a genomic sequence which acts as ars when integrated into a plasmid. Diploids suitable for testing complementation and recombination between markers can be formed by protoplast fusion. The complementation tests and the recombination frequencies determined in octads of spores identified 28 non-allelic groups (genes) of mutations of the auxotrophic and mycelium-negative mutants. Two groups of linked markers were also identified. The cloned fragment, which expresses ars activity, encodes a putative amino acid sequence highly similar to a conserved domain of proteins Cut1 (Schizosaccharomyces pombe), BimB (Aspergillus nidulans) and Esp1 (Saccharomyces cerevisiae).

Cloning of caf1+, caf2+ and caf4+ from Schizosaccharomyces pombe: their involvement in multidrug resistance, UV and pH sensitivity.

We previously identified four nuclear genes (caf1+ to caf4+) in Schizosaccharomyces pombe, mutations in which can confer caffeine resistance. Here we report the cloning and sequencing of caf1+, caf2+ and caf4+. All three genes are allelic to genes (hba1+, crm1+ and trr1+, respectively) involved in multidrug resistance mechanisms or in stress response systems. In agreement with this the caffeine-resistant mutants caf1(hba1)-21, caf2(crm1)-3 and caf4(trr1)-83 are also resistant to brefeldin. Disruption of caf1(hba1)+ and caf4(trr1)+ makes cells sensitive to high pH. The overlapping ranges of pleiotropic effects and the genetic interaction detected between caf1(hba1)+ and caf2(crm1)+ suggest that the three genes function in interlinked systems.

Caffeine-resistance in S. pombe: mutations in three novel caf genes increase caffeine tolerance and affect radiation sensitivity, fertility, and cell cycle.

Caffeine is a well known base analogue and is cytotoxic to both animal and yeast cells. There are two possible mechanisms by which yeast cells tolerate caffeine concentrations higher than normal, by mutation or by physiological adaptation. We have isolated novel caffeine-resistant mutants of S. pombe which define three distinct genes caf2, caf3 and caf4. These mutants achieved a level of caffeine resistance which is presumed to represent the upper limit attainable by mutation. The caf2-caf4 mutations, as well as the previously identified caf1 mutation, confer UV-sensitivity, caffeine-resistant UV repair, impaired fertility and sporulation, as well as a lengthened cell cycle. They are partially dominant for caffeine resistance and recessive for UV sensitivity. Some auxotrophic caf3-89 double mutants show drastically decreased caffeine resistance. The caf4 mutant is more resistant to gamma-radiation than wild-type cells and shows pH-sensitive growth. As each caf mutation can, individually, confer maximum caffeine resistance to the cells, all four genes are expected to operate in the same pathway. This pathway might also be responsible for the physiological adaptation since adaptation is lost in caf1-caf4 mutants.

[Diagnostic value of abdominal ultrasonography and endoscopic retrograde cholangiopancreatography in obstructive jaundice]. / A hasi ultrahangvizsgálat és az endoscopos retrograd cholangiopancreatographia diagnosztikus értéke elzáródásos sárgaságban.

The diagnostic value of ultrasonography (US) and endoscopic retrograde cholangio-pancreatography (ERCP) was compared, in 66 patients with bile duct obstruction, who underwent subsequent biliary surgery. The level of the blockage was diagnosed by US with a 80%, by ERCP with a 95.4% sensitivity, while the cause of the obstruction was determined with a 50% and a 89% sensitivity, respectively. Predictive value of these examinations is over 90%. Based on the clinical results and on the high diagnostic value of the above mentioned examinations, it is essential to fill up the bile ducts with direct contrast material.

Osmotolerant yeasts isolated from Tokaj wines.

Yeasts growing in "Tokaj Aszu" wine and in "Aszu essence" were isolated and characterised. They proved to be physiological races of Saccharomyces cerevisiae and showed high osmotolerance, which was an inherited feature rather than the result of adaptation. No correlations were found between the osmotolerance and the ethanol tolerance or the cell size and morphology. Yeasts in "Aszu essence" are usually undesirable contaminants that impair the quality of the essence. The isolate characterized in this work exhibited physiological parameters very similar to those of the "Tokaj Aszu" strain, which make it a potent competitor of other yeasts in Aszu fermentation. However, the high termo sensitivity of its cells offers a possibility to eliminate them selectively.

Caffeine tolerance in Schizosaccharomyces pombe: physiological adaptation and interaction with theophylline.

Caffeine at concentrations of 8 mM or higher inhibited cell propagation and killed a fraction of the population. Cell inactivation increased incrementally with increasing concentrations. The survivors developed tolerance by physiological adaptation that enabled them to propagate in the presence of the drug, but the tolerance could easily be lost if the cells grew in the absence of caffeine for a few generations. Theophylline was found to diminish the toxic effect of caffeine. Possible mechanisms for the observed cellular response and its implications for studies of the effects of these drugs in eukaryotes are discussed.

Design considerations of an infrared spectrometer based on difference-frequency generation in AgGaSe(2).

The availability of new nonlinear optical materials such as AgGaS(2) and AgGaSe(2) and improvements in compact, tunable, pulsed and continuous-wave (cw) solid-state pump lasers now make it possible to generate tunable, infrared narrow-band coherent radiation over a wide wavelength range (4-18 µm) by means of difference-frequency generation (DFG). This article describes the wavelength and outputpower characteristics of a tunable infrared source based on AgGaSe(2) and certain proven cw near-infrared pump sources for application to high-resolution spectroscopy.