Over 100 mW stable low-noise single-frequency ring-cavity fiber laser based on a saturable absorber of Bi/Er/Yb co-doped silica fiber

Two kinds of Yb-doped fibers were fabricated, namely, Yb: YAG crystal-derived silica fibers (YCDSFs) with a gain coefficient of 6.0 dB/cm, and Bi/Er/Yb co-doped silica fibers having a Yb concentration of 0.1310^26 ion/m^3. Based on these fibers, a ring-cavity single-frequency fiber laser (SFFL) has been constructed, in which the YCDSF was used as a gain medium and the Bi/Er/Yb co-doped fiber acted as a saturable absorber. It has been demonstrated that the SFFL had an over 100 mW output at 1030 nm, slope-efficiency of up to 18.3%, and an optical signal-to-noise ratio of over 63 dB. The fluctuation of the output power of the laser was less than 0.65% of 103.5 mW within 10 hrs and no mode-hopping was observed for 5 hrs. The SFFL had a linewidth <7.5 kHz at the maximum output power, and the measured relative intensity noise was lower than 142 dB/Hz at a frequency above 1.0 MHz. The results indicate that the ring-cavity SFFL built could be used as a laser source for applications in a high-power fiber laser, and high-precision optical fiber sensing and detection

Long-term outcomes of infantile spasms in children treated with ketogenic diet therapy in combination with anti-seizure medications in a resource-limited region

ObjectiveDespite numerous guidelines, the overall outcome of infantile spasms is poor, with only a small number of patients being able to attend school. The purpose of this study was to investigate long-term outcomes. Patients had poor access to the recommended first-line anti-seizure medications (ASMs), such as hormones (corticotropin or prednisolone/prednisone) and vigabatrin, and their alternative treatment was other ASMs and a ketogenic diet.MethodsPatients suffering from infantile spasms who had at least 2 years of medical records in the electronic medical record system between January 2014 and August 2022 were included in this study. Patient information was retrospectively reviewed. All patients had received ketogenic diet therapy (mainly classical ketogenic diet therapy). The ketogenic diet therapy was combined with ASMs not used as first-line therapies. The primary endpoint outcome measure was the number of patients with seizure freedom. The secondary measures included the duration of ketogenic diet therapy, choice of ASMs, and patient development at the last visit.ResultsA total of 177 patients with infantile spasms were included, and 152 (86%) of them had seizure freedom. The median duration from the first to the last hospital visit was 53.27 months, and the number of visits was 47.00. The median age at the initial hospital visit was 8.00 months, and the median age at initiation of the ketogenic diet was 17.73 months. At the last visit, the proportions of patients with neurodevelopmental delay, developmental epileptic encephalopathy, drug-resistant epilepsy, and generalized seizures increased significantly. The frequently used ASMs were topiramate, valproic acid, levetiracetam, nitrazepam, and vitamin B6 injection, while the recommended first-line drugs corticotropin and vigabatrin were rarely selected. The study duration of 9.5 years was divided into three periods but the prescription of ASMs did not change significantly between these periods.ConclusionsAlthough the seizure freedom rate was high with ketogenic diet therapy combined with non-standard ASMs, the patients had a significant neurodevelopmental delay at the last visit, which was, however, similar to that of standard treatment. To improve the outcomes of infantile spasms, multicenter clinical trials of the ketogenic diet as a first-line treatment in combination with non-standard ASMs are needed

HPV prevalence and genotype distribution in 2,306 patients with cervical squamous cell carcinoma in central and eastern China

BackgroundTo explore the positivity rate and genotype distribution of human papillomavirus (HPV) in cervical squamous cell carcinoma (CSCC) tissues in central and eastern China and to provide theoretical basis for cervical cancer screening and prophylactic HPV vaccine development in China.MethodsDNA was extracted from paraffin-embedded tissues of CSCC samples and exfoliated cervical cells of cervical cancer screening populations. 23 HPV genotypes were detected by combining polymerase chain reaction (PCR) and reverse dot hybridized gene chip detection technology in 2,306 CSCC tissues and 10,245 cervical cancer screening populations. The genotype distribution of HPV infection was analyzed.ResultsThe overall infection rate of HPVs in 2,306 CSCC patients was 92.71%. The frequency of single-type HPV infection and multiple-type HPV infection were 86.48% and 13.51%, respectively. The most common HPV genotypes detected in Chinese CSCC tissues were HPV-16, HPV-18, HPV-31, HPV-33, HPV-45, HPV-52, HPV-58, and HPV-59. The overall positivity rate of these eight high-risk HPV (HR-HPV) genotypes in HPV-positive CSCC was as high as 96.91%. Of which the positivity rate of seven HR-HPV genotypes related to nine-valent HPV vaccines in HPV-positive CSCC was 95.09%. Meanwhile, the overall infection rates of HR-HPV and low-risk HPV (LR-HPV) in female aged 35–64 years who underwent cervical cancer screening were 13.16% and 1.32%, respectively. The high-frequency HR-HPV genotypes in cervical cancer screening women were HPV-52, HPV-58, HPV-16, HPV-53, HPV-68, HPV-39, HPV-51, and HPV-56, with positivity rates of 2.25%, 1.60%, 1.31%, 1.22%, 0.93%, 0.92%, 0.78%, and 0.74%, respectively.ConclusionAmong women screened for cervical cancer in China, detecting the 8 high-frequency HR-HPV genotypes can reduce technical difficulty and reagent costs, while also improving the efficiency and effectiveness of cervical cancer screening. HPV genotyping assists gynecologists in assessing the risk of HR-HPV-positive cervical intraepithelial neoplasia and guiding them in implementing appropriate interventions. Furthermore, HPV genotyping is helpful for doctors to follow up HR-HPV-positive women and to evaluate the protective effect of HPV vaccine

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals &lt;1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

T Zell Antwort gegen mutmassliche Antigene und verminderte Zytokinproduktion durch Infiliximab bei Patienten mit ankylosierender Spondylitis

0\. Title and Contents 0 1\. Introduction 1 2 Aims 17 3 Materials and Methods 19 4 Results 41 5 Discussion 63 6 Summary 75 7 References 77 8 Abbreviations 95 9 Curriculum vitae 97 10 Acknowledgement 98The pathogenesis of two important inflammatory rheumatic diseases, RA and AS, is not clear. In both diseases an immune response against an unknown putative antigen could play a crucial role. T cell responses to antigens derived from bacteria such as klebsiella or to autoantigens derived from the cartilage such as proteoglycan have been tested, but no convincing evidence for their involvement in the pathogenesis has been obtained so far. In this study, I applied the more sensitive and more specific technique of antigen-specific cytometry to investigate the T cell response to h-hsp60 and y-19kd as well as various cartilage-derived autoantigens. Taking IFNg-secretion of CD4+ T cell as primary outcome parameter, I set out to quantify the antigen specific T cell response in peripheral blood and synovial fluid of patients with AS or RA, and controls to answer the questions which antigen-specific T cells are detectable in AS patients and compare this to RA patients and controls. The results indicate that a similar T cell response to h-hsp60 and y-19kd is present in patients with AS and RA compared to healthy controls, which suggests that these two antigens are not primarily involved in the pathogenesis of AS and RA. For cartilage-derived autoantigens, on the basis of the relative frequency of IFNg+ cells among CD4+ T cells, the results showed that the G1 domain of the proteoglycan aggrecan is recognized by almost two thirds of patients with AS (61.7%) and half of the investigated patients with RA (54.5%). In contrast, normal healthy individuals showed a reactivity only in a few cases (10%). No T cell responses to HC gp39 and collagen II was observed in AS-patients in the present study. Importantly, the response of synovial fluid CD4+ T cells to the G1-domain was shown to be significantly higher compared to PB. Further analysis indicated that two T cell epitopes of G1 domain were identified to be immunodominant in AS: AA residues 292 to 309 and 252 to 269. These data suggest that the G1 domain of aggrecan could be a target of the immune response in AS. A further aim of this study was to assess the possible effect of anti-TNFa treatment on the capacity of T cells and macrophages to produce cytokines. Treatment of active ankylosing spondylitis with the monclonal anti-TNFa antibody infliximab is clinically highly effective. The precise mechanism of action, however, is not known. I investigated the cytokine response in 20 active AS patients during infliximab therapy. The results indicated that infliximab could downregulate the T cell (but not macrophage) production of the proinflammatory cytokines IFNg and TNFa at week 6 and 12, but no effect on IL4- and IL10-production was seen. This downregulation of the proinflammatory cytokines is probably a relevant mechanism for the clinical efficacy.Die Pathogenese bei zwei wichtigen rheumatisch-entzündlichen Erkrankungen, der ankylosierenden Spondylitis (AS) und der rheumatoiden Arthritis (RA), ist bislang nicht klar. Bei beiden Erkrankungen könnte ein bislang nur postuliertes, unbekanntes Antigen eine entscheidende Rolle spielen. T Zell Antworten gegen Antigene von Bakterien, z.B von Klebsiella oder gegen. Autoantigene aus Knorpelgewebe, wie z.B. vom Proteoglycan, wurden früber bereits untersucht. Bisherige Untersuchungen haben aber keine überzeugende Evidenz für die Beteiligung von Proteoglycan-Autoantigen bei der Pathogenese erbracht. In meiner promotionsarbeit wandte ich daher die sensitivere und spezifischere Technik der Antigen-spezifischen Zytometrie an, um die T Zell Antwort gegen h-hsp60 und y-19kD zu untersuchen, wie auch gegenüber unterschiedlichen, aus Knorpel stammenden Autoantigenen bei AS- und zum Teil auch bei RA-Patienten. Durch IFNg-Sekretion bei CD4+ T-Zellen als primären Parameter quantifizierte ich die Antigen-spezifische T Zell Antwort im peripheren Blut und in der Synovial-Flüssigkeit bei Patienten mit AS, RA und bei Kontroll-Individuen, um die Frage zu beantworten, welche Antigen- spezifischen T Zellen bei AS-Patienten im Vergleich zu RA-Patienten und Kontrollen auftreten. Die Ergebnisse zeigen, dass im Vergleich zu gesunden Kontrollen eine ähnliche T-Zell Antwort gegenüber h-hsp60 und y-19kD auch bei Patienten mit AS oder RA auftritt, was nahelegt, dass diese beiden Antigene nicht die Antigene sind, die primär eine Rolle in der Pathogenese der AS oder RA spielen. Für die Knorpel-Autoantigene zeigte sich, dass auf der Basis der relativen Frequenzhäufigkeit von IFNg+ produzierenden CD4+ T Zellen die G1-Domäne des Proteoglycan-Aggrecan bei mehr als zwei Dritteln der Patienten mit AS (61.7%) und bei der Hälfte der untersuchten Patienten mit RA (54.5%) erkannt wurde. Im Gegensatz dazu zeigten gesunde Probanden nur eine Reaktivität in einigen wenigen Fällen (10%). Keine T Zell Antwort wurde hingegen bei dieser Untersuchung bei AS-Patienten gegenüber gp39, einem humanen Knorpel-Protein und gegenüber Collagen II gefunden.Wichtig dagegen, die Immunantwort von CD4+ T Zellen aus der Synovial-Flüssigkeit gegenüber der G1-Domäne war signifikant höher als im Vergleich zu der von CD4+ T-Zellen aus peripherem Blut (PB). Weitere Analysen bestätigten, dass zwei T Zell Epitope aus der G1-Domäne bei AS-Patienten immundominant waren: die Aminosäuren-(AA)-Fragmente 292-309 und 252-269. Diese Befunde führen zu der Vermutung, dass die G1 Domäne des Aggrecan eine Zielstruktur für die Immunantwort bei AS-Patienten sein könnte. Ein weiteres Ziel dieser Untersuchung war es, den möglichen Effekt einer anti-TNFa Behandlung bei AS- Patienten hinsichtlich der Produktion von Zytokinen durch ihre T Zellen und Makrophagen zu bestimmen. Die Behandlung von aktiver ankylosierender Spondylitis mit dem monoklonalen anti-TNFa Antikörper Infliximab ist klinisch hoch effektiv. Der genaue Wirkmechanismus ist dagegen noch unbekannt. Ich untersuchte die Zytokin-Antwort bei 20 Patienten mit aktiver AS während ihrer Infliximab-Therapie. Die Ergebnisse zeigen, dass Infliximab bei T-Zellen (aber nicht bei Makrophagen) die Produktion der proinflammatorischen Zytokine IFNg und TNFa in der 6. und 12. Woche herunterregulieren konnte, hingegen kein Effekt auf die IL-4 und IL-10 Produktion zu sehen war. Die Herunterregulation der proinflammatorischen Zytokine stellt wahrscheinlich einen bedeutsamen Mechanismus für die Klinik dar

High Sensitivity Refractometer Based on TiO2-Coated Adiabatic Tapered Optical Fiber via ALD Technology

Atomic layer deposition (ALD) technology is introduced to fabricate a high sensitivity refractometer based on an adiabatic tapered optical fiber. Different thicknesses of titanium dioxide (TiO2) nanofilm were coated around the tapered fiber precisely and uniformly under different deposition cycles. Attributed to the higher refractive index of the TiO2 nanofilm compared to that of silica, an asymmetric Fabry–Perot (F-P) resonator could be constructed along the fiber taper. The central wavelength of the F-P resonator could be controlled by adjusting the thickness of the TiO2 nanofilm. Such a F-P resonator is sensitive to changes in the surrounding refractive index (SRI), which is utilized to realize a high sensitivity refractometer. The refractometer developed by depositing 50.9-nm-thickness TiO2 on the tapered fiber shows SRI sensitivity as high as 7096 nm/RIU in the SRI range of 1.3373–1.3500. Due to TiO2’s advantages of high refractive index, lack of toxicity, and good biocompatibility, this refractometer is expected to have wide applications in the biochemical sensing field