GPU-enabled real-time optical frequency comb spectroscopy and a photonic readout.

We describe a GPU-enabled approach for real-time optical frequency comb spectroscopy in which data is recorded, Fourier transformed, normalized, and fit at data rates up to 2.2 GB/s. As an initial demonstration we have applied this approach to rapidly interrogate the motion of an optomechanical accelerometer through the use of an electro-optic frequency comb. We note that this approach is readily amenable to both self-heterodyne and dual-comb spectrometers for molecular spectroscopy as well as a photonic readout where the approach's agility, speed, and simplicity are expected to enable future improvements and applications.

Single-modulator, direct frequency comb spectroscopy via serrodyne modulation.

Traditional electro-optic frequency comb spectrometers rely upon the use of an acousto-optic modulator (AOM) to provide a differential frequency shift between probe and local oscillator (LO) legs of the interferometer. Here we show that these modulators can be replaced by an electro-optic phase modulator (EOM) which is driven by a sawtooth waveform to induce serrodyne modulation. This approach enables direct frequency comb spectroscopy to be performed with a single dual-drive Mach-Zehnder modulator (DD-MZM), allowing for lower differential phase noise. Further, this method allows for simpler production of integrated photonic comb spectrometers on the chip scale.

Removal of Rb(6(2)P) by H(2), CH(4), and C(2)H(6).

The saturated hydrocarbons methane and ethane are often used as collisional energy transfer agents in diode-pumped alkali vapor lasers (DPALs). Problems are encountered because the hydrocarbons eventually react with the optically pumped alkali atoms, resulting in the contamination of the gas lasing medium and damage of the gas cell windows. The reactions require excitation of the more highly excited states of the alkali atoms, which can be generated in DPAL systems by energy pooling processes. Knowledge of the production and loss rates for the higher excited states is needed for a quantitative understanding of the photochemistry. In the present study, we have used experimental and theoretical techniques to characterize the removal of Rb(6P2) by hydrogen, methane, and ethane.

Antibody targeting of anaplastic lymphoma kinase induces cytotoxicity of human neuroblastoma.

Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase aberrantly expressed in neuroblastoma, a devastating pediatric cancer of the sympathetic nervous system. Germline and somatically acquired ALK aberrations induce increased autophosphorylation, constitutive ALK activation and increased downstream signaling. Thus, ALK is a tractable therapeutic target in neuroblastoma, likely to be susceptible to both small-molecule tyrosine kinase inhibitors and therapeutic antibodies-as has been shown for other receptor tyrosine kinases in malignancies such as breast and lung cancer. Small-molecule inhibitors of ALK are currently being studied in the clinic, but common ALK mutations in neuroblastoma appear to show de novo insensitivity, arguing that complementary therapeutic approaches must be developed. We therefore hypothesized that antibody targeting of ALK may be a relevant strategy for the majority of neuroblastoma patients likely to have ALK-positive tumors. We show here that an antagonistic ALK antibody inhibits cell growth and induces in vitro antibody-dependent cellular cytotoxicity of human neuroblastoma-derived cell lines. Cytotoxicity was induced in cell lines harboring either wild type or mutated forms of ALK. Treatment of neuroblastoma cells with the dual Met/ALK inhibitor crizotinib sensitized cells to antibody-induced growth inhibition by promoting cell surface accumulation of ALK and thus increasing the accessibility of antigen for antibody binding. These data support the concept of ALK-targeted immunotherapy as a highly promising therapeutic strategy for neuroblastomas with mutated or wild-type ALK.

Hyperparathyroidism and psychosis: possible prelude to murder.

The authors present a case of a middle aged attorney who suffered from hyperparathyroidism and a psychotic disorder. It is possible that the hyperparathyroidism may have precipitated an acute psychotic delusional rage leading to an attempted mass murder. They discuss the relationship between hyperparathyroidism and neuropsychiatric symptoms in consideration of available research.

Anxiety, self-control and shooting performance.

55 rifle shooters were administered state-trait anxiety and self-control questionnaires. Shooting performance was recorded on 7 competitive occasions. Analysis indicated shooting performance is dependent more on anxiety state than on anxiety trait and self-control. Highly skilled shooters were less anxious and performed better across all competitions than moderately skilled shooters but did not differ on self-control and anxiety trait. The assumption that increased anxiety negatively affects performance through the mediation of self-control should be further studied.

[Accumulation of DNA structural damages in human lymphocytes during aging]. / Narastanie povrezhdenii struktury DNK v limfotsitakh liudei pri starenii.

Elastoviscosometric parameters of DNA from normal subjects of different age and patients with Down syndrome were assessed. Characteristics of DNA isolated from lymphocytes trisomic for chromosome 21 were studied to compare normal and pathological rates of ageing. Increased elastoviscosity was observed in normal subjects above 60. Similar changes in this parameter were noted in aberrant lymphocytes isolated from patients above 10. The established dependence of elastoviscosity on ethidium bromide concentration led to the assumption that an increase in hydrodynamic DNA volume in human leukocytes during ageing was due to accumulation of spontaneous irreparable DNA lesions.

[Escherichia coli K-12 mutants with increased resistance to ionizing radiation. V. The effect of mutations on spontaneous and radiation mutagenesis]. / Mutanty Escherchia coli K-12 s povyshennoi ustoichivost'iu k ioniziruiushchei radiatsii. Soobshchenie V. Vliianie mutatsii na spontannyi i radiatsionnyi mutagenez.

The frequencies of spontaneous mutations (reversions his-4----His+ and forward mutations to rifampicin-, nalidixic acid- or valine-resistance) in radiation-resistant mutants Gamr444 and Gamr445 are much lower than in the wild-type strain AB1157. His+ revertants and rifampicin-resistant mutants Rifr are induced by low doses of gamma-rays more efficiently than in the wild-type. Low doses of UV light only enhanced mutagenic activity in Gamr strains for induction of His+ reversions but not for Rifr mutations. For the wild-type strain the frequencies of His+ and Rifr mutations increase proportionally to the square of dose both of UV light and gamma-rays. For the most radioresistant Gamr444 mutant the frequencies of UV- and gamma-rays-induced Rifr mutations and of gamma-rays-induced reversions increase linearly with the dose. Possible reasons for these anomalies of radiation-induced mutagenesis in Gamr mutants are discussed.

[Temperature-induced radioresistance of Escherichia coli cells]. / Termoindutsirovannaia radiorezistentnost' kletok Escherichia coli.

A marked increase in radioresistance of E. coli cells, of the wild-type repair genotype, was observed when they were exposed to gamma-radiation at 40-45 degrees C. The effect of the thermoinduced radioresistance did not depend on the growth medium and the pre-incubation temperature but disappeared completely after treatment of cells by chloramphenicol or CaCl2 or after modification of cell membranes by exogenous cholesterol. This phenomenon was not observed with UV-irradiation. It is suggested that the thermoinduced radioresistance is connected with the activation of the membrane-associated repair complex.

[Genetic determination and mechanism of realization of temperature-induced radioresistance]. / Geneticheskaia determinirovannost' i mekhanizm realizatsii termoindutsirovannoi radiorezistentnosti.

A study was made of the influence of the repair genotype of E. coli cells on the realization of the effect of enhanced radioresistance during gamma-irradiation at elevated temperatures (40-45 degrees C). The effect of the thermoinduced radioresistance (TIR) was diminished significantly but not abolished completely in mutant cells selectively deficient in excision or recombination repair systems (po1A1, recB21C22sbcB15, recF143 mutants). However mutations which exclude the recA gene product (recA13, recA13B21C22 or lexA3 mutants) inhibited TIR completely. The introduction of recA+ gene into recA- or lexA- mutants almost normalized TIR. On the basis of the data obtained the authors discuss the role of recA protein in activation of the membrane-associated repair complex whose efficiency depends on the temperature of gamma-irradiation.

[Mutagenic action of alkylating agents on prophage lambda]. / Mutagennoe deistvie alkiliruiushchikh agentov na profag liambda.

The lethal and mutagenic effects of 7 alkylating agents: N-nitroso-N-methylurea (NMU), N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), methyl methanesulfonate (MMS), ethyl methanesulfonate (EMS), nitrogen mustard (HN2), mitomycin C (MC), bifunctional acridine mustard (AM)--and of cyanate (KNCO) on heat inducible lambda cI857 prophage were studied. After treatment of lysogenic cells with mutagens, prophage was heat-induced either immediately or after 90 min incubation in nutrient broth and c mutants forming clear plaques at 32 degrees C were scored. NMU (0.02 M) when immediately induced with heat, induces c mutants very efficiently (maximal yield 10%) not only in the wild-type cells but also in repair-deficient mutants recA13, lexA102, uvrA6 umuC36, recF143, xthA9, polA1, uvrD3 and uvrD502. These data show that NMU-induced mutations are fixed as replication errors due to mispairing modified bases. After delayed heat induction, the prophage survival enhances and the frequency of c mutations declines considerably in host cells of all repair genotypes tested. Carbamoylation is not involved in the mutagenic action of NMU, because KNCO (0.02 M) has a very slight lethal effect and does not induce mutations. MNNG (100 micrograms/ml) and EMS (0.1 M) also induce mutations by replicative mechanism, because maximal yield of c mutations does not depend on RecA+ and is about 15 and 2%, respectively. MMS is a mutagen of the repair type, since its mutagenic action is suppressed by recA mutation of the host. NH2 only inactivates prophage, but does not induce mutations. MC (50 micrograms/ml) and AM (150 micrograms/ml) induce mutations rather inefficiently (the maximal yield 0.1 and 0.3%, respectively) both in recA+ and recA- hosts. The mutagenic action of these agents is probably due to intercalation.

[Escherichia coli K-12 mutants with enhanced resistance to ionizing radiation. IV. Recombination characteristics of Gamr mutants]. / Mutanty Escherichia coli K-12 s povyshennoi ustoichivost'iu k ioniziruiushchei radiatsii. Soobshchenie IV. Osobennosti rekombinatsii u mutantov Gamr.

In the radiation-resistant Gamr444 mutant the inheritance frequency of long F' episomes ORF1 (purE+ tsx+ procC+ lac+) and F'14 (ilv+--argE+) is lower, and the frequencies of chromosome mobilization and integrative suppression of temperature-sensitive dnaA46 mutation by the sex factor F are much higher than those in the wild-type strain AB1157 and another radiation-resistant mutant Gamr445. In this respect, the mutant Gamr444 is very similar to the recRC sbcB mutant (RecF-pathway of recombination).

[Escherichia coli K-12 mutants with enhanced resistance to ionizing radiation. III. The effect of rec and lexA mutations on radioresistance]. / Mutanty Escherichia coli K-12 s povyshennoi ustoichivost'iu k ioniziruiushchei radiatsii. Soobshchenie III. Vliianie mutatsii rec i lexA na radiorezistentnost'.

Lethal action of gamma-rays on derivatives of the wild-type strain AB1157 and of two radiation-resistant mutants (Gamr444 and Gamr445) containing additional mutations dnaA46, recB21, recF143, recA56, recA430, lexA3, lexA102 or lexA3 recAo98, was studied. When the mean number of genomes per cell was reduced by means of pre-incubation at 43 degrees C, radioresistance of the strains AB1157 dnaA46 and Gamr445 dnaA46 was not changed, and that of the strain Gamr444 dnaA46 was reduced to the level of the Gamr445 dnaA46 strain. Introduction of additional mutations recB21, recA56 or lexA3 (lexA102) into the genome of the strains Gamr444 or Gamr445 made them as radiosensitive as the corresponding variants of AB1157. Additional mutations recF143 or recA430 (lexB30) significantly decreased the radioresistance of Gamr444 and Gamr445 mutants, although did not level them to corresponding derivatives of AB1157. Operator-constitutive mutation recAo98 enhanced radioresistance of all lexA3 derivatives tested but not to the level of the corresponding lexA+ strains. The role of recombinational repair and the inducible SOS system in enhanced radioresistance of Gamr mutants is discussed. The data of post-irradiation DNA degradation in various derivatives of the strains AB1157 and Gamr suggest that Gamr mutants have a constitutive inhibitor of degradation which does coincide with RecA protein.

[Determination of the level of spontaneous damage in human and mammalian cell DNA]. / Opredelenie urovnia spontannykh povrezhdenii DNK kletok cheloveka i mlekopitaiushchikh.

A technique for registration of spontaneous DNA lesions in intact mammalian cells is proposed. Arabinosid cytosine and hydroxyurea were shown to inhibit the repair of gaps spontaneously formed and accumulated in DNA leading to the formation of double-strand DNA breaks and cell death. The rate of spontaneous lesions was different in cells from different animal species and different tissues. A considerable increase in the level of spontaneous lesions was noted with ageing. It is concluded that the level of spontaneous DNA lesions is one of the fundamental biologically important characteristics of a cell.

Induction by gamma irradiation of double-strand breaks of Escherichia coli chromosomes and their role in cell lethality.

Viscoelastometric measurements of DNA from gamma-irradiated bacteria were used to identify the induction of double-strand breaks ( DSBs ) in the chromosome of Escherichia coli. It is shown by means of inhibitors of repair endonucleases and different repair mutants that most DSBs in DNA of E. coli, gamma-irradiated in buffer, arise from enzymatic incision of primary gamma-damages; therefore, previous conclusions regarding DSB repair must be reconsidered. Based on these results, much of the reparable damage is single-strand breaks, and this damage can initiate formation of gaps and ultimately, when repair is insufficient, generation of enzymatically caused DSBs . After extensive repair, the first residual DSB in the E. coli chromosome is generated at approximately 160 Gray (Gy), which corresponds to the D37 dose. We propose that DSBs induced directly by gamma-irradiation are not repaired in wild-type strains. In a recently isolated gamma-resistant strain, E. coli Gamr444 , the dose required for observation of DSB after postirradiation incubation is 1,000 Gy, which corresponds to the D37 of the strain. The resistance is proposed to be due to an ability to repair genuine DSBs .

[Mutagenic action of O-methlhydroxylamide on transforming DNA]. / Mutagennoe deistvie O-metilgidroksilamina na transformiruiushchuiu DNK.

The mutagenic effect of O-methylhydroxylamine (OMHA) on transforming DNA of Bacillus subtilis was studied. In accordance with the earlier reported chemical and functional data, the mutagenic effect was observed at 4.5 and 6.0 pH. An increase in pH caused a decrease in the rate of mutagenesis, though the maximal level of mutagenesis was equal at both values of pH. The results obtained with recipients defective in the system of UV-repair revealed that both products of reaction of OMHA with the cytosine-base of DNA, N4-metoxycytidine and N4-metoxy-6-metoxyamino-5,6-dihydrocytidine, are effectively eliminated through the system of UV repair.

Postexcision transposition of the transposon Tn10 in Escherichia coli K12.

An experimental analysis of the fate of transposon Tn10 after excision from a proA::Tn10 site localized on the plasmid F' leads to the conclusions: 1. The precise excision is a progressive process. Its probability is estimated per time unit. 2. An excised Tn10 is always integrated into a different genetic locus. 2. An excised Tn10 is always integrated into a different genetic locus. 3. The kinetics of postexcision transposition are sometimes very slow. The excised transposon is inherited in one cell line in spite of cell multiplication. 4. The processes of excision and secondary insertion have no absolute requirement for the recA+ genotype but they are strongly enhanced in recA+ cells. 5. The kinetics of postexcision transposition are strongly dependent on the genetic site from which the transposon was excised. 6. The probability of postexcision transposition is fully determined by the probability of excision and depends on the genotype of the host and many other factors.