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Natural killer (NK) cell kill infected, transformed and stressed cells when an activating NK cell receptor is triggered1. Most NK cells and some innate lymphoid cells express the activating receptor NKp46, encoded by NCR1, the most evolutionarily ancient NK cell receptor2,3. Blockage of NKp46 inhibits NK killing of many cancer targets4. Although a few infectious NKp46 ligands have been identified, the endogenous NKp46 cell surface ligand is unknown. Here we show that NKp46 recognizes externalized calreticulin (ecto-CRT), which translocates from the endoplasmic reticulum (ER) to the cell membrane during ER stress. ER stress and ecto-CRT are hallmarks of chemotherapy-induced immunogenic cell death5,6, flavivirus infection and senescence. NKp46 recognition of the P domain of ecto-CRT triggers NK cell signalling and NKp46 caps with ecto-CRT in NK immune synapses. NKp46-mediated killing is inhibited by knockout or knockdown of CALR, the gene encoding CRT, or CRT antibodies, and is enhanced by ectopic expression of glycosylphosphatidylinositol-anchored CRT. NCR1)-deficient human (and Nrc1-deficient mouse) NK cells are impaired in the killing of ZIKV-infected, ER-stressed and senescent cells and ecto-CRT-expressing cancer cells. Importantly, NKp46 recognition of ecto-CRT controls mouse B16 melanoma and RAS-driven lung cancers and enhances tumour-infiltrating NK cell degranulation and cytokine secretion. Thus, NKp46 recognition of ecto-CRT as a danger-associated molecular pattern eliminates ER-stressed cells.
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Calreticulina , Estresse do Retículo Endoplasmático , Células Matadoras Naturais , Receptor 1 Desencadeador da Citotoxicidade Natural , Animais , Humanos , Camundongos , Alarminas/metabolismo , Calreticulina/imunologia , Calreticulina/metabolismo , Membrana Celular/metabolismo , Retículo Endoplasmático/metabolismo , Imunidade Inata , Sinapses Imunológicas , Células Matadoras Naturais/metabolismo , Neoplasias Pulmonares/metabolismo , Melanoma Experimental/metabolismo , Receptor 1 Desencadeador da Citotoxicidade Natural/metabolismo , Zika virus/fisiologiaRESUMO
We perform a systematic study on the modulation of electroosmotic flow (EOF), tuning the selectivity using electrolyte ions and hydrodynamic dispersion of the solute band across the soft nanochannel. The supporting walls of the channel are considered to be hydrophobic and bear non-zero surface charge. For such a channel, the inner side of the supporting rigid walls of the channel are coated with a soft polyelectrolyte layer (PEL). The inhomogeneous distribution of monomers and accompanying volume charge within the PEL is modelled via soft-step function. The dielectric permittivity of the PEL and electrolyte solution are in general different, which in turn leads to the ion partitioning effect. The impact of ion steric effects due to finite sized ions is further accounted through the modified ion activity coefficient. To model the EOF modulation considering the combined impact of the ion steric and ion partitioning effects as well as inhomogeneous distribution of monomers across the PEL, we adopt the modified Poisson-Boltzmann equation as the governing equation for electrostatic potential. The Debye-Bueche model is adopted to study the flow field across the PEL and the Stokes equation governs the EOF outside the PEL. In order to study the impact of the modulated EOF field on the dispersion of uncharged solution, we adopt three different models, i.e., a general 2D convective-diffusion model as well as cross-sectional averaged dispersion models due to Gill and late-time Taylor and Aris. Going beyond the widely employed Debye-Hückel approximation and uniform distribution of the monomer as well as accompanying volume charge, we find the results for the electric double layer (EDL) potential, EOF field and averaged throughput, by tuning the ion selectivity, etc., which is sufficient to analyze the transport of ionized liquid across the channel. The numerical results are supplemented with analytical results for the EDL potential as well as the EOF field under various limiting situations. Besides, we have further shown the impact of the modulated EOF field on the solute dispersion process. We have presented results that highlight the impact of parameters related to EOF field modulation, on solute dispersion governed by a convective-diffusive process, as well as obtaining the results for an effective dispersion coefficient. The dispersion models under the modulated EOF field adopted in the present study can thus be applied to study the dispersion process in engineered microdevices.
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Dynamic electrophoresis is the foundation for electroacoustical measurements, in which the electroacoustical signals may be used to analyze the size and electrostatic charge of colloidal entities by means of the results for dynamic electrophoretic mobility. Thus, the electrophoresis under an alternating electric field is the key foundation for electroacoustic theory. In this article, we develop a tractable analytical theory for the dynamic electrophoresis of hydrophobic and dielectric fluid droplets possessing uniform surface charge density. The tiny fluid droplets possess charged mobile surfaces and have found widespread applications in our day-to-day life. For dielectric fluid droplets (e.g., oil-water emulsions), the tangential electric stress at the interface is nonzero, which significantly affects its electrohydrodynamics under an oscillatory electric field, which has, however, a negligible impact on the electrophoretic motion of conducting droplets (e.g., mercury droplets). Besides, the micro/nanoscale fluid droplets often show hydrophobicity when they are immersed in an aqueous medium, and the impact of the electric field on hydrophobic surfaces remains a research frontier in the chemical discipline. Whereas a number of approximate expressions for electrophoretic mobility have been derived for the conducting droplet, none of them are applicable to such generic hydrophobic fluid droplets with dielectric permittivity that is significantly lower than or comparable to that of an aqueous medium. In this work, within the Debye-Hückel electrostatic framework, we elaborate an original analytical expression of dynamic electrophoretic mobility for this generic dielectric fluid droplet with a hydrophobic surface considering that the droplet retains its spherical shape during its oscillatory motion. We further derived a set of simplified expressions for dynamic electrophoretic mobility deduced under several limiting cases. The results are further illustrated, indicating the impact of pertinent parameters.
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Adsorption techniques are widely applied to detect underlying masked alloantibodies in warm autoimmune hemolytic anemia (WAIHA). We established various adsorption techniques with an aim to detect alloimmunization in WAIHA This study conducted over a period of nine years included 298 patients of WAIHA. Complete immunohematological evaluation was performed on these 298 samples following departmental protocols. Clinical and laboratory details of patients were obtained from patient files. Various adsorption methods were performed and statistically evaluated in the study. Out of 479 cases of autoimmune hemolytic anemia, WAIHA comprised of 62.2 % (N = 298). A total of 139 (46.6 %) serum samples revealed autoantibodies. Adsorption study was performed in 101 (72.7 %) indicated samples and 24 (23.8 %) of these showed 26 alloantibodies. Among the patients subjected to adsorption study hemolytic marker were significantly deranged in the alloimmunization group (p < 0.01). Polyethylene glycol (PEG) adsorption was the quickest (52.2-54.6 min) of all adsorption techniques with minimum (1.3-1.5) numbers of adsorptions needing for complete removal of serum antibodies. The LISS-papain (LP) technique was found to be more sensitive and specific compared to the other two techniques. The agreement between PEG adsorption and LP adsorption was found to be 'perfect' (96.4 %) with a Cohen's kappa (k) value of 0.9. We conclude that identification of alloantibody specificities underlying a warm autoantibody is critical for a safe and effective transfusion. All WAIHA patients with history of blood transfusion, pregnancy or both should be subjected to adsorption study. Selection of a suitable adsorption technique depends on multiple important factors.
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Anemia Hemolítica Autoimune , Feminino , Gravidez , Humanos , Adsorção , Isoanticorpos , Eritrócitos , Autoanticorpos , PolietilenoglicóisRESUMO
BACKGROUND: The persistently high rates of maternal mortality and morbidity among historically marginalised social groups, such as adolescent Scheduled Castes (SCs) and Scheduled Tribes (STs) in India, can be attributed, in part, to the low utilisation of full antenatal healthcare services. Despite efforts by the Indian government, full antenatal care (ANC) usage remains low among this population. To address this issue, it is crucial to determine the factors that influence the utilisation of ANC services among adolescent SC/ST mothers. However, to date, no national-level comprehensive study in India has specifically examined this issue for this population. Our study aims to address this research gap and contribute to the understanding of how to improve the utilisation of ANC services among adolescent SC/ST mothers in India. DATA AND METHODS: Data from the fourth round of the National Family Health Survey 2015-16 (NFHS-4) was used. The outcome variable was full antenatal care (ANC). A pregnant mother was considered to have 'full ANC' only when she had at least four ANC visits, at least two tetanus toxoid (TT) injections, and consumed 100 or more iron-folic acid (IFA) tablets/syrup during her pregnancy. Bivariate analysis was used to examine the disparity in the coverage of full ANC. In addition, binary logistic regression was used to understand the net effect of predictor variables on the coverage of full ANC. RESULTS: The utilisation of full antenatal care (ANC) among adolescent SC/ST mothers was inadequate, with only 18% receiving full ANC. Although 83% of Indian adolescent SC/ST mothers received two or more TT injections, the utilisation of the other two vital components of full ANC was low, with only 46% making four or more ANC visits and 28% consuming the recommended number of IFA tablets or equivalent amount of IFA syrup. There were statistically significant differences in the utilisation of full ANC based on the background characteristics of the participants. The statistical analysis showed that there was a significant association between the receipt of full ANC and factors such as religion (OR = 0.143, CI = 0.044-0.459), household wealth (OR = 5.505, CI = 1.804-16.800), interaction with frontline health workers (OR = 1.821, CI = 1.241-2.670), and region of residence in the Southern region (OR = 3.575, CI = 1.917-6.664). CONCLUSION: In conclusion, the study highlights the low utilisation of full antenatal care services among Indian adolescent SC/ST mothers, with only a minority receiving the recommended number of ANC visits and consuming the required amount of IFA tablets/syrup. Addressing social determinants of health and recognising the role of frontline workers can be crucial in improving full ANC coverage among this vulnerable population. Furthermore, targeted interventions tailored to the unique needs of different subgroups of adolescent SC/ST mothers are necessary to achieve optimal maternal and child health outcomes.
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Mães Adolescentes , Cuidado Pré-Natal , Criança , Adolescente , Gravidez , Feminino , Humanos , Classe Social , Ácido Fólico , Fatores Socioeconômicos , Ferro , Toxoide Tetânico , Índia/epidemiologiaRESUMO
Short Birth Interval (SBI) is one of the main causes of adverse maternal and child health outcomes. A 33-month birth-to-birth interval between two successive live births should be followed to minimize the risk of adverse maternal and child health. This study aimed to examine the prevalence of SBI and the associated factors in rural India. Information on 98,522 rural mothers from the fourth round of National Family Health Survey data was analyzed. Bivariate statistics, logistic regression, Moran's I, and Cluster and Outlier Analysis have been used to assess the prevalence and spatial pattern of SBI in rural India. Results revealed that about half of the mothers in rural India had experienced SBI. Rural Indian mothers whose child was not alive (OR = 1.76, 95% CI = 1.63-1.90), were not using any contraceptive methods (OR = 1.42, 95 % CI = 1.37-1.48) and not breastfeeding (OR = 2.73, 95% CI = 2.50-2.97) were more likely to experience SBI. On the other hand, rural mothers from the middle, richer and richest wealth quintiles (OR = 0.91, 95% CI = 0.86-0.97; OR = 0.84, 95% CI = 0.80-0.92; OR = 0.60, 95% CI = 0.55-0.66) and of age over 30 years (OR = 0.38., 95% CI = 0.36-0.39) were less likely to experience SBI. Analysis of spatial patterns revealed clear east-west differences in the prevalence of SBI. There was strong clustering of high values of SBI in most districts across the central, northern, western, and southern regions. The study suggests the need to introduce appropriate interventions and programs focused on reducing the prevalence of SBI in rural India.
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Intervalo entre Nascimentos , Mães , Feminino , Humanos , Adulto , Estudos Transversais , Aleitamento Materno , Índia/epidemiologia , Fatores SocioeconômicosRESUMO
BACKGROUND: Exclusive use of hygienic methods (sanitary napkins, locally prepared napkins, tampons, and menstrual cups) to prevent the visibility of bloodstains during menstruation is still considerably low among adolescent women in rural India. However, no prior research has explored the prevalence and determinants of exclusive hygienic methods among rural Indian adolescent women. To address this gap, this study examines the factors affecting adolescent women's exclusive use of hygienic methods in rural India. Additionally, this study explores state- and district-level geographical disparities in the exclusive use of hygienic methods among adolescent women in rural India. METHODS: Information on 95,551 adolescent women from rural India from the latest round of National Family Health Survey (NFHS-5) was analyzed. Bivariate statistics and multilevel logistic regression analysis were used to assess the Individual- and community-level factors associated with exclusive use of hygienic methods among adolescent women in rural India. Choropleth maps were used to discern the geographical disparities in the exclusive use of hygienic methods. RESULTS: In rural India, only 42% of adolescent women exclusively used hygienic methods, with substantial geographic disparities at the state and district levels. At the state level, the exclusive use of hygienic methods varied from 23% in Uttar Pradesh to 85% in Tamil Nadu. Even greater variation was observed at the district level. There was a clear north-south divide in the exclusive use of hygienic methods among adolescent women in rural India. The results of multilevel logistic regression indicated a considerable amount of variation in the exclusive use of hygienic methods at community level which further reduced when controlled for individual and community-level factors. Rural Indian adolescent women with higher education (AOR:3.20, 95% CI: 2.81-3.64), from general category (AOR: 1.14, 95% CI: 1.07-1.21), with medium mass media exposure (AOR: 1.43, 95% CI: 1.35-1.51), and from richest wealth quintile (AOR: 3.98, 95% CI: 3.69-4.30) were more likely to use hygienic methods exclusively. CONCLUSION: Wide differential across biodemographic and socioeconomic groups, and substantial geographic disparities at state- and district-level in the exclusive use of hygienic methods suggests a need to adopt context-specific interventions for adolescent women in rural India. Distribution of subsidized or free menstrual hygiene methods to disadvantaged adolescent women, and in the low-prevalence districts may increase the level of exclusive use of hygienic methods remarkably.
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Higiene , Menstruação , Adolescente , Feminino , Humanos , Estudos Transversais , Índia/epidemiologia , Produtos de Higiene MenstrualRESUMO
BaBiO3(BBO) is known to be a valence-skipping perovskite, which avoids the metallic state through charge disproportionation (CD), the mechanism of which is still unresolved. A novel mechanism for CD is presented here in the covalent limit using a molecular orbital (MO) picture under two scenarios: (case i) Bi 6sp-O 2p and (case ii) Bi 6p-O 2p hybridizations that favor 5+ and 3+ states, respectively. The proposed model is further validated by using a combinatorial approach of X-ray spectroscopic experiments and first-principle calculations. The bulk X-ray photoemission spectrum reveals that, at room temperature, the CD is dynamic in nature, whereas, at 200 K, it approaches a quasi-static limit. Under compressive strain, the octahedral breathing mode is damped and drives the system to a quasi-static limit even at room temperature, giving rise to asymmetric CD.
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Análise EspectralRESUMO
A crucial contribution to the heterogeneity of the conformational landscape of a protein comes from the way an intermediate relates to another intermediate state in its journey from the unfolded to folded or misfolded form. Unfortunately, it is extremely hard to decode this relatedness in a quantifiable manner. Here, we developed an application of statistical cluster analyses to explore the conformational heterogeneity of a metalloenzyme, human cytosolic copper-zinc superoxide dismutase (SOD1), using the inputs from infrared spectroscopy. This study provides a quantifiable picture of how conformational information at one particular site (for example, the copper-binding pocket) is related to the information at the second site (for example, the zinc-binding pocket), and how this relatedness is transferred to the global conformational information of the protein. The distance outputs were used to quantitatively generate a network capturing the folding sub-stages of SOD1.
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Cobre/química , Agregados Proteicos/genética , Superóxido Dismutase-1/química , Zinco/química , Sítios de Ligação , Clonagem Molecular , Análise por Conglomerados , Cobre/metabolismo , Escherichia coli/genética , Escherichia coli/metabolismo , Expressão Gênica , Vetores Genéticos/química , Vetores Genéticos/metabolismo , Humanos , Modelos Moleculares , Mutagênese Sítio-Dirigida , Ligação Proteica , Conformação Proteica em alfa-Hélice , Conformação Proteica em Folha beta , Dobramento de Proteína , Domínios e Motivos de Interação entre Proteínas , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Espectroscopia de Infravermelho com Transformada de Fourier , Superóxido Dismutase-1/genética , Superóxido Dismutase-1/metabolismo , Zinco/metabolismoRESUMO
BACKGROUND: Malignant diseases have become a threat for health care system. A panoply of biological processes is involved as the cause of these diseases. In order to unveil the mechanistic details of these diseased states, we analyzed protein families relevant to these diseases. RESULTS: Our present study pivots around four apparently unrelated cancer types among which two are commonly occurring viz. Prostate Cancer, Breast Cancer and two relatively less frequent viz. Acute Lymphoblastic Leukemia and Lymphoma. Eight protein families were found to have implications for these cancer types. Our results strikingly reveal that some of the proteins with implications in the cancerous cellular states were showing the structural organization disparate from the signature of the family it constitutes. The sequences were further mapped onto respective structures and compared with the entropic profile. The structures reveal that entropic scores were able to reveal the inherent structural bias of these proteins with quantitative precision, otherwise unseen from other analysis. Subsequently, the betweenness centrality scoring of each residue from the structure network models was resorted to explore the changes in dependencies on residue owing to structural disorder. CONCLUSION: These observations help to obtain the mechanistic changes resulting from the structural orchestration of protein structures. Finally, the hydropathy indexes were obtained to validate the sequence space observations using Shannon entropy and in-turn establishing the compatibility.
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Entropia , Evolução Molecular , Proteínas Intrinsicamente Desordenadas/química , Neoplasias/metabolismo , Animais , Humanos , Interações Hidrofóbicas e HidrofílicasRESUMO
In this Letter, experimental observation of dissipative rogue waves (DRWs) due to spectral filtering induced pulse instabilities in a mode-locked ytterbium (Yb) fiber laser has been presented. A semiconductor saturable absorber mirror was used to mode-lock the linear cavity laser and a chirped fiber Bragg grating (CFBG) was used for dispersion management, which also acted as a spectral filter and output coupler. Under stable conditions, the cavity delivered dispersion managed dissipative solitons of 447 fs duration and 0.69 nJ pulse energy at 10.19 MHz repetition rate with uniform intensity distribution over a long time span. As the spectral width increased with pump power, random intensity fluctuations were observed in the pulse train due to the filtering effect of the CFBG. Employing a dispersive Fourier transform by stretching the output pulse train in time allowed the existence of DRWs more than 4 times stronger than the significant wave height to be observed. Further increments of pump power led to a stable multi-pulsing state.
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A novel rhodamine-tryptamine conjugate-based fluorescent and chromogenic chemosensor (RTS) for detection of Hg2+ present in water was reported. After gradual addition of Hg2+ in aqueous methanol solution of RTS, a strong orange fluorescence and deep-pink coloration were observed. The probe showed high selectivity towards Hg2+ compared to other competitive metal ions. The 1:1 binding stoichiometry between RTS and Hg2+ was established by Job's plot analysis and mass spectroscopy. Initial studies showed that the synthesized probe RTS possessed fair non-toxicity and effectively passed through cell walls of model cell systems, viz., human neuroblastoma (SHSY5Y) cells and cervical cells (HeLa) to detect intercellular Hg2+ ions, signifying its utility in biological system. The limit of detection (LOD) was found to be 2.1 nM or 0.42 ppb by fluorescence titration. Additionally, the potential relevance of synthesized chemosensor for detecting Hg2+ ions in environmental water samples has been demonstrated. Graphical abstract á .
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Corantes Fluorescentes/química , Mercúrio/análise , Imagem Óptica/métodos , Rodaminas/química , Triptaminas/química , Linhagem Celular Tumoral , Monitoramento Ambiental/métodos , Humanos , Limite de Detecção , Microscopia Confocal/métodos , Espectrometria de Fluorescência/métodos , Poluentes Químicos da Água/análiseRESUMO
A diode-pumped, air-cooled, all-fiber, quasi-continuous-wave thulium laser at an operating wavelength of 1.94 µm has been designed to study the performance of the laser parameter on the rate of fragmentation and its dependence on stone composition, fragmented particle size, as well as the retropulsion effect. The optimized laser cavity with an active fiber core/cladding diameter of 10/130 µm under a counter-propagating pump provides a stable laser power of 30 W at a slope efficiency of 50% and wall plug efficiency of 17%. The rate of fragmentation along with the retropulsion effect has been studied with human calcium oxalate monohydrate (COM) urinary stones (N=36) of different composition by using the designed laser and 200-µm-core low OH silica delivery fiber. The thulium fiber laser setting of 2.7 J pulse energy at the pulse rate of 10 Hz, pulse width of 90 ms, and peak power of 30 W is successful in breaking human COM stones in a controlled manner at a fragmentation rate of 0.8±0.4 mg/s, with almost uniform fragments of particle size less than 1.6 mm. During the stone fragmentation, the stone displacement (retropulsion effect) is less than 15 mm, even for the fragmented stone mass of 15±5 mg.
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BACKGROUND/AIMS: The conformation, folding and lipid binding properties of the intestinal fatty acid binding proteins (IFABP) have been extensively investigated. In contrast, the functional aspects of these proteins are not understood and matter of debates. In this study, we aim to address the deleterious effects of FA overload on cellular components, particularly mitochondria; and how IFABP helps in combating this stress by restoring the mitochondrial dynamics. METHODS: In the present study the functional aspect of IFABP under conditions of lipid stress was studied by a string of extensive in-cell studies; flow cytometry by fluorescence-activated cell sorting (FACS), confocal imaging, western blotting and quantitative real time PCR. We deployed ectopic expression of IFABP in rescuing cells under the condition of lipid stress. Again in order to unveil the mechanistic insights of functional traits, we arrayed extensive computational approaches by means of studying centrality calculations along with protein-protein association and ligand induced cluster dissociation. While addressing its functional importance, we used FCS and in-silico computational analyses, to show the structural distribution and the underlying mechanism of IFABP's action. RESULTS: Ectopic expression of IFABP in HeLa cells has been found to rescue mitochondrial morphological dynamics and restore membrane potential, partially preventing apoptotic damage induced by the increased FAs. These findings have been further validated in the functionally relevant intestinal Caco-2 cells, where the native expression of IFABP protects mitochondrial morphology from abrogation induced by FA overload. However, this native level expression is insufficient to protect against apoptotic cell death, which is rescued, at least partially in cells overexpressing IFABP. In addition, shRNA mediated IFABP knockdown in Caco-2 cells compromises mitochondrial dynamics and switches on intrinsic apoptotic pathways under FA-induced metabolic stress. CONCLUSION: To summarize, the present study implicates functional significance of IFABP in controlling ligand-induced damage in mitochondrial dynamics and apoptosis.
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Apoptose , Proteínas de Ligação a Ácido Graxo/metabolismo , Ácidos Graxos/metabolismo , Dinâmica Mitocondrial , Células CACO-2 , Células HeLa , Humanos , Mitocôndrias/metabolismo , Mitocôndrias/ultraestrutura , Modelos Moleculares , Estresse FisiológicoRESUMO
In this paper, we propose an all-normal-dispersion ytterbium-fiber laser with a novel ring cavity architecture having two nonlinear amplifying loop mirrors (NALM) as saturable absorbers, capable of delivering distinctly different pulses with adjustable features. By optimizing the loop lengths of the individual NALMs, the cavity can be operated to deliver Q-switched mode-locked (Q-ML) pulse bunches with adjustable repetition rates, mode-locked pulses in dissipative soliton resonance (DSR) regime or noise-like pulse (NLP) regime with tunable pulse width. The DSR pulses exhibit characteristic narrowband spectrum, while the NLPs exhibit large broadband spectrum. The operation regime of the laser can be controlled by adjusting the amplifier pump powers and the polarization controllers. To the best of the authors' knowledge, this is the first demonstration of a single mode-locked cavity where narrowband DSR pulses and broadband NLPs alongside Q-ML pulse bunches can be selectively generated by employing two NALMs.
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A gain-switched all-fiber thulium laser at 2 µm with high repetition rate has been demonstrated under a hybrid pumping scheme combined of a pulsed pump at 1.56 µm and CW pump at 793 nm. The in-band pulsed pump at 1.56 µm triggers the gain-switching pulses while the CW pump at 793 nm facilitates the energy storage. Therefore, the seed cavity delivers high energy pulses allowing the elimination of multistage amplification. Such hybrid pump configuration is effective for generating gain-switched pulses of high average power with better slope efficiency and pulse width of a few hundreds of a nanosecond. The optimized cavity under such hybrid pump configuration provides output power of 5.92 W from the gain-switched oscillator with slope efficiency of 60% and pulse width of 300 ns at a repetition rate of 344 kHz. Maximum pulse energy of 17.2 µJ and peak power of 53.9 W has been achieved at this repetition rate. Stable gain-switched pulses at reduced pump pulse energy have been achieved by the use of a CW pump at 793 nm. This novel pump configuration facilitates gain switch at higher repetition rates where enough pump pulse energy may not be available. The gain-switched laser also operates at 520 kHz and 1.3 MHz repetition rate by changing the 1.56 µm pulsed pump and cavity length.
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A dissipative soliton resonance (DSR) mode-locked Er:Yb fiber laser has been used to pump a thulium fiber laser to generate gain-switched pulses at high repetition rates. Here 412 ns long DSR pulses with a center wavelength of around 1.56 µm at a repetition rate of 410 kHz have been fed to a thulium fiber laser, resulting in generation of gain-switched pulses at 1.94 µm. The minimum pulse width achieved was 256 ns with an average power of 4.6 W at 66% slope efficiency. Gain-switched pulses at 520 kHz and 750 kHz were generated through changing the pump pulse repetition rate by modifying the DSR cavity. To the best of our knowledge, this is the first demonstration of a high repetition rate gain-switched thulium fiber laser pumped by a DSR mode-locked fiber laser. As DSR pulses can be generated with high seed average power and energy independent of the operating wavelength regime as well as mode-locking technique, the proposed method can be applied to generate gain-switched pulses at high repetition rates and various wavelengths without the need of any optical or electrical modulators.
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The sole existence of a t-bone-shaped naphthalimide derivative [2-(2-aminoethyl)-1H-benzo[de]isoquinoline-1,3(2H)dione] (NAP), which gives rise to a photoinduced electron transfer (PET) mechanism, has been established using a combination of experimental and theoretical studies. In parallel an in vitro-in cell PET mechanism has also been shown. To understand the photophysics of NAP, solvent studies have been carried out in different solvents. In addition, theoretical calculations have been conducted to explain the spectroscopic properties through optimized structures. A "turn off" PET mechanism has also been observed in the presence of specific metal ions, namely, Cr3+ , Fe3+ and Hg2+ among a series of metal ions. Theoretical studies reveal that NAP-Cr3+ , NAP-Fe3+ and NAP-Hg2+ have their HOMO energy states lying in between a HOMO-LUMO energy state of the t-bone-type NAP molecule. On the contrary, the HOMO state of the other metal ion-NAP conjugate (NAP-Mn+ ) does not lie in between the HOMO-LUMO energy gap of the t-bone-type NAP molecule. Coupled with in vitro studies, in cell investigations reveal an enhancement of fluorescence intensity of NAP upon cytosolic metal sensing. Furthermore, a very high cell viability of NAP treated cells as tested by MTT assay and a fast permeation of the said compound as revealed by flow cytometry suggest NAP to be a potential candidate in metal sensing and bioimaging applications.
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There has been widespread interest in studying early intermediate states and their roles in protein folding. The interest in intermediate states has been further emphasized in the recent literature because of their implications for protein aggregation. Unfortunately, direct kinetic characterization of intermediates has been difficult because of the limited time resolutions offered by the kinetic techniques and the heterogeneity of the folding and aggregation landscape. Even in equilibrium experiments, the characterization of intermediate states could be difficult because (a) their populations in equilibrium could be low and/or (b) they lack any specific biochemical or biophysical signatures for their identification. In this paper, we have used fluorescence correlation spectroscopy to study the nature of a low-pH intermediate state of the intestinal fatty acid binding protein, a small protein with predominantly ß-sheet structure. Our results have shown that the pH 3 intermediate diffuses faster than the folded protein and has strong helix forming propensity. These behaviors support Lim's hypothesis according to which even an entirely ß-sheet protein would form helical bundles at the early stage. Using dynamic light scattering and thioflavin T binding measurements, we have observed that the pH 3 intermediate is prone to aggregation. We believe that early helix formation is the result of a local effect, which originates from the interaction of the neighboring amino acids around the hydrophobic core residues. This early intermediate reorganizes subsequently, and this structural reorganization is initiated by the destabilizing interactions induced by the distant residues, unfavorable entropic costs, and steric constraints of the hydrophobic side chains. Mutational analyses show further that the increase in the hydrophobicity in the hydrophobic core region increases the population of the α-helical intermediate, enhancing the aggregation propensity of the protein, while an identical change, distant from the hydrophobic core, does not show any effect. This study re-emphasizes an overlap between the folding and aggregation landscape of a protein, where the fine-tuning between the local and global effects may be important for the protein to fold efficiently or to aggregate.