A comparative study of an Yb-doped fiber gain-managed nonlinear amplifier seeded by femtosecond fiber lasers

In this work, we show that the nonlinear evolution of femtosecond seed pulses with different parameters (temporal and spectral shapes, repetition rate, pulse energy) in an Yb-fiber amplifier leads to gain-managed nonlinear amplification, enabling robust generation of high-peak-power and nearly transform-limited pulses after external compression. We demonstrate a compressed pulse duration of 33 fs with an energy of 80.5 nJ and a peak power of 2.29 MW for a source with a repetition rate of 30 MHz. For a second seed source with a repetition rate of 125 MHz, we obtained a pulse duration of 51 fs with an energy of 22.8 nJ and a peak power of 420 kW. Numerical simulations incorporating rate equations and nonlinear propagation in the amplifier provide evolutions that agree well with the experimental results. The discrepancies in the amplifier’s absorption edge appearing at low repetition rates and higher pump powers are attributed to the temperature dependence of the amplifier’s gain cross-sections. Here, we experimentally verify this attribution and thus underline the importance of accounting for the fiber core temperature for precise modelling of the short-wavelength spectral edge of the output pulses in nonlinear Yb-fiber amplifiers. We also measure, for the first time, the relative intensity noise of an amplifier operating in the gain-managed nonlinear regime. The measurements reveal a significant contribution of the amplification process to the overall output noise of the system.

RAP: A Novel Approach to the Rapid and Highly Sensitive Detection of Respiratory Viruses

Recombinase aided amplification (RAA) is an emerging isothermal amplification method used for detecting various pathogens. However, RAA requires a complex and long probe to ensure high sensitivity during fluorescence assay. TaqMan probe used for quantitative PCR (qPCR) is simple and universal. Herein, we developed a new approach for detecting nucleic acids of pathogens, known as RAP (Recombinase aided PCR). The method combines RAA and qPCR to ensure a rapid and highly sensitive detection using a conventional qPCR device. RAP is a two-stage amplification process performed in a single tube within 1 hour. The method involves an RAA reaction for 10 min at 39°C (first stage) followed by 15 cycles of qPCR (second stage). Using human adenovirus 3 (HADV3) and human adenovirus 7 (HADV7) plasmids, the sensitivities of RAP assays for detecting HADV3 and HADV7 were 6 and 17 copies per reaction, respectively. The limit of RAP detection was at least 16-fold lower than the corresponding qPCR, and no-cross reaction with other respiratory viruses was observed. The results of RAP analysis revealed 100% consistency with qPCR assay. This study shows that RAP assay is a rapid, specific, and highly sensitive detection method with a potential for clinical and laboratory application.

ABOUT THE APPLICATION OF THE ANALYTICAL AMPLIFICATION METHOD IN THE THERAPY OF A PATIENT WITH BORDERLINE MENTAL DISORDER BASED ON THE FAIRY TALE «GO THERE — I DON'T KNOW WHERE, BRING THAT — I DON'T KNOW WHAT»

В данной статье описан фрагмент психотерапевтической работы в парадигме юнгианского анализа с использованием метода амплификации с пациентом, имеющим пограничное расстройство психики. Амплификация — инструмент аналитической работы, введенный в практику К.Г. Юнгом, позволяющий исследовать и интерпретировать явные и скрытые психодинамические процессы через символический язык. По сути процесс амплификации — осмысление индивидуальной психической жизни индивида посредством использования коллективного опыта знаний: мифов, легенд, сказок и т.п. Современная психология, считал Юнг, так или иначе, имеет дело с продуктами бессознательной фантазии - мифологическими и сказочными мотивами, наиболее объективно отражающими динамику психической жизни. «Пользуясь методом мифологической амплификации, мы выбираем те или иные аналогии потому, что их смысловое ядро идентично содержанию исследуемых процессов или в каком-то отношении походит на него. Принимая в качестве данности, что все, когда-либо выраженное человеком в словесной или образной форме, обладает абсолютной психической реальностью, мы можем утверждать, что любая аналогия помогает уточнить, объяснить и подтвердить наше толкование мотивов бессознательных процессов» [4]. В случае с данным пациентом универсально подошла русская народная сказка «Пойди туда — не знаю куда, принеси то — не знаю что» [22]. Опираясь на исследования признанных авторов психоанализа и аналитической психологии, амплификацию этой сказки можно рассматривать как абрис мужского пути индивидуации, «синтетического процесса», описанного К.Г.Юнгом [12]. «Возможной целью, здоровым предназначением ассимилирующих процессов является путь индивидуации, подразумевающий самоосуществление, становление человека самим собой. Индивидуация от лат. in-dividuus означает «неделимый», «неразделенный», «неразведенный», «нерасщепленный» [19]. Индивидуация предполагает достижение психически нового интегрированного состояния, установление устойчивой связи между эго (осознаваемый идентифицированный образ «Я») и архетипом Самости (сложный центр психической жизни, соединяющий бессознательные и сознательные знания человека о себе самом и трансформирующий личность,). Амплификация данной сказки позволяет исследовать внутрипсихическое взаимодействие архетипической пары — маскулинного начала в сознательном поле мужчины и женского в его бессознательном — на разных этапах развития. Подобное взаимодействие отражает реальные отношения с противоположным полом, отзеркаливая внутреннюю/внешнюю мужскую/женскую часть личности. Также данная амплификация дает возможность предположить, что является основным фактором, «запускающим» процесс индивидуации у мужчин. This article describes a fragment of psychotherapeutic work in the paradigm of Jungian analysis using the amplification method with a patient with borderline mental disorder. Amplification is a tool of analytical work introduced into practice by C.G. Jung, which allows to investigate and interpret explicit and hidden psychodynamic processes through symbolic language. In essence, the amplification process is the comprehension of an individual's individual mental life through the use of collective experience of knowledge: myths, legends, fairy tales, etc. «In myths and fairy tales, as in dreams, the soul tells its own story, and the interaction of archetypes is revealed in its natural frame: "creation, re-creation, eternal spirit eternal entertainment»[13]. In the case of this patient, the Russian folk tale «Go there — I don't know where, bring that — I don't know what» was universally suitable [22]. Based on the research of recognized authors of psychoanalysis and analytical psychology, the amplification of this fairy tale can be considered as an outline of the male path of individuation, a «synthetic process» described by C.G. Jung[12]. «A possible goal, a healthy purpose of assimilating processes is the path of individuation, implying self-fulfillment, becoming a person himself. Individuation from Lat. in-dividuus means «indivisible», «undivided» [19]. Individuation presupposes the achievement of a psychically new integrated state, the establishment of a stable connection between the ego (a conscious identified image of the «I») and the archetype of the Self (a complex center of mental life that connects the unconscious and conscious knowledge of a person about himself and transforms the personality). The amplification of this fairy tale allows us to explore the intrapsychic interaction of the archetypal pair — the masculine principle in the conscious field of a man and the female in his unconscious — at different stages of development. Such interaction reflects a real relationship with the opposite sex, mirroring the inner/outer male/female part of the personality. Also, this amplification makes it possible to assume that it is the main factor «triggering» the process of individuation in men.

Carbon nanodot–based electrogenerated chemiluminescence biosensor for miRNA-21 detection

A simple carbon nanodot–based electrogenerated chemiluminescence biosensor is described for sensitive and selective detection of microRNA-21 (miRNA-21), a biomarker of several pathologies including cardiovascular diseases (CVDs). The photoluminescent carbon nanodots (CNDs) were obtained using a new synthesis method, simply by treating tiger nut milk in a microwave reactor. The synthesis is environmentally friendly, simple, and efficient. The optical properties and morphological characteristics of the CNDs were exhaustively investigated, confirming that they have oxygen and nitrogen functional groups on their surfaces and exhibit excitation-dependent fluorescence emission, as well as photostability. They act as co-reactant agents in the anodic electrochemiluminescence (ECL) of [Ru(bpy)3]2+, producing different signals for the probe (single-stranded DNA) and the hybridized target (double-stranded DNA). These results paved the way for the development of a sensitive ECL biosensor for the detection of miRNA-21. This was developed by immobilization of a thiolated oligonucleotide, fully complementary to the miRNA-21 sequence, on the disposable gold electrode. The target miRNA-21 was hybridized with the probe on the electrode surface, and the hybridization was detected by the enhancement of the [Ru(bpy)3]2+/DNA ECL signal using CNDs. The biosensor shows a linear response to miRNA-21 concentration up to 100.0 pM with a detection limit of 0.721 fM. The method does not require complex labeling steps, and has a rapid response. It was successfully used to detect miRNA-21 directly in serum samples from heart failure patients without previous RNA extraction neither amplification process. Graphical abstract

Using Cy5-dUTP labelling of RPA-amplicons with downstream microarray analysis for the detection of antibiotic resistance genes

In this report we describe Cy5-dUTP labelling of recombinase-polymerase-amplification (RPA) products directly during the amplification process for the first time. Nucleic acid amplification techniques, especially polymerase-chain-reaction as well as various isothermal amplification methods such as RPA, becomes a promising tool in the detection of pathogens and target specific genes. Actually, RPA even provides more advantages. This isothermal method got popular in point of care diagnostics because of its speed and sensitivity but requires pre-labelled primer or probes for a following detection of the amplicons. To overcome this disadvantages, we performed an labelling of RPA-amplicons with Cy5-dUTP without the need of pre-labelled primers. The amplification results of various multiple antibiotic resistance genes indicating great potential as a flexible and promising tool with high specific and sensitive detection capabilities of the target genes. After the determination of an appropriate rate of 1% Cy5-dUTP and 99% unlabelled dTTP we were able to detect the blaCTX-M15 gene in less than 1.6E−03 ng genomic DNA corresponding to approximately 200 cfu of Escherichia coli cells in only 40 min amplification time.

Genomic and transcriptomic analyses reveal a tandem amplification unit of 11 genes and mutations in mismatch repair genes in methotrexate-resistant HT-29 cells

DHFR gene amplification is commonly present in methotrexate (MTX)-resistant colon cancer cells and acute lymphoblastic leukemia. In this study, we proposed an integrative framework to characterize the amplified region by using a combination of single-molecule real-time sequencing, next-generation optical mapping, and chromosome conformation capture (Hi-C). We identified an amplification unit spanning 11 genes, from the DHFR gene to the ATP6AP1L gene position, with high adjusted interaction frequencies on chromosome 5 (~2.2 Mbp) and a twenty-fold tandemly amplified region, and novel inversions at the start and end positions of the amplified region as well as frameshift insertions in most of the MSH and MLH genes were detected. These mutations might stimulate chromosomal breakage and cause the dysregulation of mismatch repair. Characterizing the tandem gene-amplified unit may be critical for identifying the mechanisms that trigger genomic rearrangements. These findings may provide new insight into the mechanisms underlying the amplification process and the evolution of drug resistance.

Measuring Distortion-Product Otoacoustic Emission With a Single Loudspeaker in the Ear: Stimulus Design and Signal Processing Techniques

The distortion-product otoacoustic emission (DPOAE) is a backward propagating wave generated inside the cochlea during the wave amplification process. The DPOAE signal can be detected rapidly under relatively noisy conditions. In recent years, the earphone industry demonstrated interest in adopting DPOAE as an add-on feature to make their product “intelligent” of inner-ear status. However, a technical challenge remains to be tackled—the loudspeaker in an earphone generates its own cubic distortion at the same frequency as DPOAE. Unfortunately, the intensity of loudspeaker distortion is typically comparable to that of the DPOAE, if not higher. In this research, we propose two strategies, namely compensation and cancellation, to enable DPOAE measurement with a single loudspeaker. The compensation strategy exploits the part of the growth function of the loudspeaker distortion which is almost linear, and thus suppresses the distortion it generates while retaining a larger portion of DPOAE in the residual signal. The cancellation strategy utilizes a one-dimensional Volterra filter to remove the cubic distortion from the loudspeaker. Testing on normal-hearing ears shows that the compensation strategy improved the DPOAE-to-interference ratio by approximately 7 dB, resulting in a cross-correlation of 0.62 between the residual DPOAE level and the true DPOAE level. Meanwhile, the cancellation strategy directly recovered both the magnitude and the phase of DPOAE, reducing the magnitude estimation error from 15.5 dB to 3.9 dB in the mean-square sense. These pilot results suggest that the cancellation strategy may be suitable for further testing with more subjects.

Pre-Degassed Microfluidic Chamber-Based Digital PCR Device for Meat Authentication Applications

Droplet digital polymerase chain reaction (ddPCR) suffers from the need for specific equipment and skilled personnel; thus, we here present a chamber-based digital PCR microfluidic device that is compatible with fluorescence image read-out systems and removes bubbles by a pre-degassed microfluidic device that consists of a pilot channel and micro chamber arrays. Digitalized PCR reagents are introduced into micro chambers, and thermocycles are taken to perform a DNA amplification process. Then, fluorescence images of a micro chamber array are read out and analyzed to obtain the total number of positive chambers. Thereby, the copy numbers of target DNA are calculated for quantitative detections. As a validation, this device is evaluated by the application of meat authentication. We performed dPCR tests using DNA templates extracted from a pure mutton DNA template with different dilutions. Then, the dPCR chip was used to identify the meat authentication using mutton–chicken mixtures with different mass ratios, showing its performance in real biotechnical applications.