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1.
Nature ; 612(7939): 252-258, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36385531

RESUMO

Integrated femtosecond pulse and frequency comb sources are critical components for a wide range of applications, including optical atomic clocks1, microwave photonics2, spectroscopy3, optical wave synthesis4, frequency conversion5, communications6, lidar7, optical computing8 and astronomy9. The leading approaches for on-chip pulse generation rely on mode-locking inside microresonators with either third-order nonlinearity10 or with semiconductor gain11,12. These approaches, however, are limited in noise performance, wavelength and repetition rate tunability 10,13. Alternatively, subpicosecond pulses can be synthesized without mode-locking, by modulating a continuous-wave single-frequency laser using electro-optic modulators1,14-17. Here we demonstrate a chip-scale femtosecond pulse source implemented on an integrated lithium niobate photonic platform18, using cascaded low-loss electro-optic amplitude and phase modulators and chirped Bragg grating, forming a time-lens system19. The device is driven by a continuous-wave distributed feedback laser chip and controlled by a single continuous-wave microwave source without the need for any stabilization or locking. We measure femtosecond pulse trains (520-femtosecond duration) with a 30-gigahertz repetition rate, flat-top optical spectra with a 10-decibel optical bandwidth of 12.6 nanometres, individual comb-line powers above 0.1 milliwatts, and pulse energies of 0.54 picojoules. Our results represent a tunable, robust and low-cost integrated pulsed light source with continuous-wave-to-pulse conversion efficiencies an order of magnitude higher than those achieved with previous integrated sources. Our pulse generator may find applications in fields such as ultrafast optical measurement19,20 or networks of distributed quantum computers21,22.


Assuntos
Óxidos , Semicondutores , Olho , Micro-Ondas
2.
Opt Lett ; 49(12): 3504-3507, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38875656

RESUMO

Stable pulse and flat-top frequency comb generation are an indispensable component of many photonic applications, from ranging to communications. Lithium niobate on insulator is an excellent electro-optic (EO) platform, exhibiting high modulation efficiency and low optical loss, making it a fitting candidate for pulse generation through electro-optic modulation of continuous-wave (CW) light, a commonly utilized method for generating ultrashort pulses. Here, we demonstrate an on-chip electro-optic comb generation module on thin-film lithium niobate (TFLN) consisting of a Mach-Zehnder interferometer (MZI) amplitude modulator (AM) and a cascaded phase modulator (PM) system driven by a single-electrode drive. We show that when operated in the correct regime, the lithium niobate chips can generate frequency combs with excellent spectral power flatness. In addition, we optically package one of the pulse generator chips via photonic wire bonding. The pulses generated by the photonic-wire-bonded device are compressed to 840 fs pulse duration using an optical fiber and show extremely stable operation.

3.
Dis Esophagus ; 2024 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-38679488

RESUMO

Eosinophilic esophagitis (EoE) and gastroesophageal reflux disease (GERD) share many histopathological features; therefore, markers for differentiation are of diagnostic interest and may add to the understanding of the underlying mechanisms. The nitrergic system is upregulated in GERD and probably also in EoE. Esophageal biopsies of patients with EoE (n = 20), GERD (n = 20), and healthy volunteers (HVs) (n = 15) were exposed to antibodies against inducible nitric oxide synthase (iNOS), nitrotyrosine, eosinophilic peroxidase, eotaxin-3, and galectin-3. The stained object glasses were randomized, digitized, and blindly analyzed regarding the expression of DAB (3,3'-diaminobenzidine) by a protocol developed in QuPath software. A statistically significant overexpression of iNOS was observed in patients with any of the two inflammatory diseases compared with that in HVs. Eotaxin-3 could differentiate HVs versus inflammatory states. Gastroesophageal reflux patients displayed the highest levels of nitrotyrosine. Neither iNOS nor nitrotyrosine alone were able to differentiate between the two diseases. For that purpose, eosinophil peroxidase was a better candidate, as the mean levels increased stepwise from HVs via GERD to EoE. iNOS and nitrotyrosine are significantly overexpressed in patients with EoE and GERD compared with healthy controls, but only eosinophil peroxidase could differentiate the two types of esophagitis. The implications of the finding of the highest levels of nitrotyrosine among gastroesophageal reflux patients are discussed.

4.
Clin Exp Immunol ; 212(2): 147-155, 2023 04 25.
Artigo em Inglês | MEDLINE | ID: mdl-36808213

RESUMO

Eosinophilic esophagitis is a T-cell-driven allergic condition hallmarked by eosinophil infiltration of the esophagus. Eosinophils exposed to proliferating T cells release galectin-10 and have T-cell suppressive function in vitro. The aims of this study were to evaluate if eosinophils co-localize with T cells and release galectin-10 in the esophagus of patients with eosinophilic esophagitis. Esophageal biopsies from 20 patients with eosinophilic esophagitis were stained for major basic protein, galectin-10, CD4, CD8, CD16, and CD81 and analyzed by immunofluorescence confocal microscopy before and after topical corticosteroid treatment. CD4+ T-cell numbers decreased in the esophageal mucosa of responders to treatment but not in the non-responders. Suppressive (CD16+) eosinophils were present in the esophageal mucosa of patients with active disease and decreased after successful treatment. Unexpectedly, eosinophils and T cells were not in direct contact with each other. Instead, the esophageal eosinophils released large amounts of galectin-10-containing extracellular vesicles and featured cytoplasmic projections that contained galectin-10, both of which disappeared from the esophagus of the responders but remained in the non-responders. To conclude, the presence of CD16+ eosinophils together with the massive release of galectin-10-containing extracellular vesicles in the esophageal mucosa might indicate that eosinophils exert T-cell suppression in eosinophilic esophagitis.


Assuntos
Esofagite Eosinofílica , Humanos , Esofagite Eosinofílica/metabolismo , Esofagite Eosinofílica/patologia , Mucosa Esofágica/metabolismo , Mucosa Esofágica/patologia , Eosinófilos/metabolismo , Galectinas
5.
Opt Express ; 29(13): 19222-19239, 2021 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-34266036

RESUMO

A photonic integrated circuit (PIC) comprised of an 11 cm long multimode speckle waveguide, a 1 × 32 splitter, and a linear grating coupler array is fabricated and utilized to receive 2 GHz of radio-frequency (RF) signal bandwidth from 2.5 to 4.5 GHz using compressive sensing (CS). Incoming RF signals are modulated onto chirped optical pulses which are input to the multimode waveguide. The multimode waveguide produces the random projections needed for CS via optical speckle. The time-varying phase and amplitude of two test RF signals between 2.5 and 4.5 GHz are successfully recovered using the standard penalized l1-norm method. The PIC reduces the speckle mixer footprint compared with the previously demonstrated fiber system. Two new PIC structures, the "waveguide bus trombone flare" and the "matched 90 degree bus bend" are developed to support precise analog signal routing. The use of a passive PIC serves as an initial critical step towards the miniaturization of a compressive sensing RF receiver.

6.
Scand J Gastroenterol ; 56(6): 629-634, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33831327

RESUMO

OBJECTIVES: Topical corticosteroids are considered a cornerstone in the treatment of patients with eosinophilic esophagitis. The aim of this study was to evaluate the benefit of using mometasone furoate spray versus placebo on dysphagia and health-related quality of life in these patients. MATERIAL AND METHODS: Consecutive, newly diagnosed adult patients with eosinophilic esophagitis were randomized and treated with either 200 micrograms of orally administered topical mometasone furoate or placebo 4 times daily for 8 weeks. Symptoms and quality of life were evaluated using questionnaires including the Watson Dysphagia Scale, the European Organization for Research and Treatment of Cancer Quality of Life-Oesophageal Module 18 and the Short Form-36 before and after treatment. RESULTS: In the intention-to-treat analysis (n = 36) the Watson Dysphagia Scale score after mometasone treatment was reduced by 6.5 (median, p < .01) compared with 0 (median, ns) in the placebo group. The benefit of mometasone over placebo was significant (p < .05). In the per-protocol analysis (n = 33) the Watson Dysphagia Scale score was reduced by 5 (median, p = .01) after mometasone treatment compared with 0 (median, ns) in the placebo group. The advantage of mometasone over the placebo was significant (p < .05). The benefit of using mometasoneas evaluated by the two quality of life questionnaires was, however, insignificant. CONCLUSIONS: Our finding suggests that in adult patients with eosinophilic esophagitis, topical mometasone furoate exerts a beneficial effect compared with placebo regarding the main symptom, i.e., dysphagia. A corresponding benefit could not be verified regarding the various quality of life measurements. CLINICAL TRIAL REGISTRATION: Mometasone-furoate for Treatment of Eosinophilic Esophagitis - a Randomized Placebo Controlled Study ClinicalTrials.gov Identifier (NCT02113267).


Assuntos
Transtornos de Deglutição , Esofagite Eosinofílica , Pregnadienodiois , Adulto , Transtornos de Deglutição/tratamento farmacológico , Transtornos de Deglutição/etiologia , Método Duplo-Cego , Esofagite Eosinofílica/complicações , Esofagite Eosinofílica/tratamento farmacológico , Humanos , Furoato de Mometasona , Qualidade de Vida , Resultado do Tratamento
7.
Dig Dis Sci ; 66(5): 1556-1564, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-32495256

RESUMO

BACKGROUND: Noninvasive methods to assess treatment response in eosinophilic esophagitis are needed. AIMS: Our aim was to determine whether a blood-based biomarker panel centered on immune parameters could identify histologic response to treatment in eosinophilic esophagitis patients. METHODS: A pilot study involving adult patients with active eosinophilic esophagitis recruited at two Ear, Nose, Throat clinics in Sweden was designed. The patients (n = 20) donated blood and esophageal biopsies and filled in three questionnaires before and after a 2-month course of topical corticosteroids. Blood samples were analyzed for absolute levels of granulocytes and T cells and the fractions of eosinophils expressing 10 different surface markers by flow cytometry. All data were analyzed by multivariate methods of pattern recognition. RESULTS: Multivariate modeling revealed that a combination of 13 immune parameters and 10 patient-reported outcome scores were required to create a model capable of separating responders (n = 15) from non-responders (n = 5). Questions regarding symptoms of esophageal dysfunction and capacity to eat certain foods from two of the questionnaires were discriminatory in the multivariate model, as were absolute counts of T cells, eosinophils, and eosinophil expression of activation markers and cell adhesion molecules. CONCLUSIONS: A combination of blood-based immune parameters and directed questions may prove helpful to monitor response to treatment, perhaps reducing the need for repeat endoscopies in eosinophilic esophagitis patients in the future.


Assuntos
Corticosteroides/administração & dosagem , Moléculas de Adesão Celular/sangue , Esofagite Eosinofílica/tratamento farmacológico , Eosinófilos/efeitos dos fármacos , Citometria de Fluxo , Medidas de Resultados Relatados pelo Paciente , Linfócitos T/efeitos dos fármacos , Administração Tópica , Adolescente , Adulto , Idoso , Biomarcadores/sangue , Esofagite Eosinofílica/sangue , Esofagite Eosinofílica/diagnóstico , Esofagite Eosinofílica/imunologia , Eosinófilos/imunologia , Eosinófilos/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Valor Preditivo dos Testes , Suécia , Linfócitos T/imunologia , Linfócitos T/metabolismo , Resultado do Tratamento , Adulto Jovem
8.
Opt Express ; 25(2): 681-695, 2017 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-28157957

RESUMO

An integrated heterodyne optical phase-locked loop was designed and demonstrated with an indium phosphide based photonic integrated circuit and commercial off-the-shelf electronic components. As an input reference, a stable microresonator-based optical frequency comb with a 50-dB span of 25 nm (~3 THz) around 1550 nm, having a spacing of ~26 GHz, was used. A widely-tunable on-chip sampled-grating distributed-Bragg-reflector laser is offset locked across multiple comb lines. An arbitrary frequency synthesis between the comb lines is demonstrated by tuning the RF offset source, and better than 100Hz tuning resolution with ± 5 Hz accuracy is obtained. Frequency switching of the on-chip laser to a point more than two dozen comb lines away (~5.6 nm) and simultaneous locking to the corresponding nearest comb line is also achieved in a time ~200 ns. A low residual phase noise of the optical phase-locking system is successfully achieved, as experimentally verified by the value of -80 dBc/Hz at an offset of as low as 200 Hz.

9.
Eur Arch Otorhinolaryngol ; 272(12): 3833-9, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26153377

RESUMO

Eosinophilic esophagitis (EoE) is a chronic immune/antigen-mediated disease, with dysphagia as the main symptom. The aim of this study was to survey symptoms and health-related quality of life in adult patients with EoE at least 1 year after diagnosis and a 2-month course of topical corticosteroids. Forty-seven consecutive patients [79 % males, mean age 49 years (range 18-90 years)] were evaluated using three different questionnaires at three different occasions: the Watson Dysphagia Scale (WDS), the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Oesophageal Module 18 (EORTC QLQ-OES18) and the Short Form-36 (SF-36). The median time from diagnosis to the long-term follow-up was 23 months (range 12-34 months). The WDS scores and the EORTC QLQ-OES18 Dysphagia and Eating scale scores were improved after 2 months of treatment (p = 0.00007, p = 0.01, p = 0.004, respectively), as were the long-term follow-up scores (p = 0.01, p = 0.03, p = 0.005, respectively), relative to the scores at diagnosis. In addition, the EORTC QLQ-OES18 Choking scores were improved after the steroid course (p = 0.003) but not after the long-term follow-up. No significant differences were detected with respect to the SF-36 scores. In summary, EoE seems to be associated with a substantial burden of symptoms that improve significantly after treatment. A partial remission persists more than 1 year after diagnosis and the discontinuation of medication. The WDS and the EORTC QLQ-OES18 appear to be sensitive instruments appropriate for surveillance in these patients.


Assuntos
Transtornos de Deglutição/etiologia , Esofagite Eosinofílica/complicações , Esofagite Eosinofílica/psicologia , Qualidade de Vida , Adolescente , Adulto , Idoso , Transtornos de Deglutição/psicologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários , Adulto Jovem
10.
Rhinology ; 53(1): 25-8, 2015 03.
Artigo em Inglês | MEDLINE | ID: mdl-25756074

RESUMO

BACKGROUND: Nasal polyps is a common disease but little is known about its` pathogenesis. Our hypothesis was that there are genetic factors involved in the development of this disease. The aim of this study was to examine close relatives of patients with nasal polyps and comparing them with a general population with regard to prevalence of polyps. METHODOLOGY: Patients with nasal polyps who attended the clinic were recruited to the study and were asked whether they had any close adult relatives (siblings, parents or children). We intended to recruit two relatives per patient, one of each gender, for nasal endoscopy. The prevalence of nasal polyps in these relatives was compared with the prevalence of nasal polyps in a general population. RESULTS: During a 4-year period, 368 patients and 410 relatives were recruited to the study. Although we were unable to recruit two close relatives for every patient, we were able to calculate nasal polyp prevalence within families as being 19.2%. Compared with the prevalence of nasal polyps among individuals in a general Swedish population from the same geographical area, the relative risk for polyps among relatives was almost five times higher. CONCLUSION: This study strongly indicates that heredity is a factor of importance for development of nasal polyps.


Assuntos
Pólipos Nasais/genética , Adulto , Idoso , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Pólipos Nasais/epidemiologia , Prevalência , Suécia/epidemiologia
11.
Opt Express ; 22(1): 102-9, 2014 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-24514971

RESUMO

We propose a super-channel flexible wavelength division multiplexing (WDM) receiver architecture. The receiver, which requires no optical filtering, only a pair (I and Q phases) of coherent optical detectors, and an electrical receiver system, can simultaneously recover multiple wavelength-multiplexed channels using cascaded optical and electrical down-conversion. The receiver data capacity increases in proportion to the number of electrical sub-carrier channels. The proposed receiver concept has been described using a six-channel WDM receiver, and a two-channel ( ± 25 GHz) receiver IC, which is a key block of the WDM receiver, has been successfully demonstrated with two and three 2.5 Gb/s binary-phase-shift-key (BPSK) modulated channels.

12.
Transpl Int ; 27(5): 482-92, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24533727

RESUMO

Acute cellular rejection (ACR) the first year after heart transplantation (HT) and its impact on survival was investigated. All 215 HT patients at our centre 1988-2010, including 219 HTs and 2990 first-year endomyocardial biopsies (EMBs), were studied. 'Routine' EMBs obtained 1, 2, 3, 4, 6, 8, 10, 12, 16, 20, 24, 32, 40 and 52 weeks after HT, and 'additional clinically indicated' (ACI) EMBs, were graded according to the 1990-ISHLT-WF. The frequency and severity of first-year ACRs was low, with 6.5% of routine EMBs and 14.1% of ACI EMBs showing ACR ≥ grade 2. Proportionally more (P < 0.05) first-year ACRs ≥ grade 2 were found among EMBs in HTs performed during 1988-1999 (9.6%) than 2000-2010 (5.5%), EMBs performed during 16-52 weeks (8.8%) than 1-12 weeks (6.3%) after HT, EMBs in HTs with paediatric (11.3%) than adult (7.1%) donors, and EMBs in sex-mismatched (10.4%) than sex-matched (6.3%) HTs. Five- and ten-year survival was furthermore lower (P < 0.05) among HTs with ≥ 1 compared with 0 first-year ACRs ≥ grade 3A/3B (82% vs. 92% and 69% vs. 82%, respectively). Ten-year survival was 74% compared with 53% in the ISHLT registry. In conclusion, our results indicate that first-year ACRs ≥ grade 3A/3B affect long-term survival. We believe frequent first-year EMBs may allow early ACR detection and continuous immunosuppressive adjustments, preventing low-grade ACRs from progressing to ACRs ≥ grade 3A/3B, thereby improving survival.


Assuntos
Rejeição de Enxerto/etiologia , Transplante de Coração/efeitos adversos , Doença Aguda , Adulto , Idoso , Biópsia , Causas de Morte , Feminino , Transplante de Coração/mortalidade , Humanos , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Miocárdio/patologia , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo
13.
Genes Chromosomes Cancer ; 52(11): 1088-96, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24019021

RESUMO

Characterization of molecules within important oncogenetic pathways may have future implications for development of therapies and biomarkers in lung cancer. One such target is the tyrosine kinase receptor KIT (c-KIT). We evaluated alterations and expression of KIT and its ligand, KITLG (also known as SCF), in 72 clinical lung tumor specimens of different histologies. Gene copy number, mRNA expression levels, and protein expression were assayed using array-based comparative genomic hybridization, real-time quantitative reverse transcription PCR and immunohistochemistry, respectively. For validation, we investigated copy number alterations and mRNA expression in external microarray data sets of 1,600 and 555 primary lung tumors, respectively. Positivity for KIT staining was most common in large cell neuroendocrine carcinoma (LCNEC) which also showed the highest KIT mRNA expression levels whereas expression was lowest in squamous cell carcinoma (SqCC). KIT mRNA expression levels were higher in KIT immunopositive samples, but expression was not affected by KIT copy numbers. Copy number gains of KIT were significantly more frequent in SqCC compared with adenocarcinoma in our own series and in the 1,600-sample data set. Immunopositivity for both KIT and KITLG in the same tumor was rare except in LCNEC. Our results highlight an increased KIT mRNA expression and frequent KIT immunopositivity in LCNEC but point out a poor correlation between KIT copy numbers and expression in SqCC, perhaps reflecting the existence of a protective mechanism against KIT alterations in this subgroup.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Neoplasias Pulmonares/genética , Proteínas Proto-Oncogênicas c-kit/genética , Fator de Células-Tronco/genética , Transcrição Gênica , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/patologia , Hibridização Genômica Comparativa , Variações do Número de Cópias de DNA , Feminino , Humanos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Proteínas Proto-Oncogênicas c-kit/biossíntese , RNA Mensageiro/biossíntese , Fator de Células-Tronco/biossíntese , Análise de Sobrevida
14.
Head Neck ; 46(4): 760-771, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38192119

RESUMO

BACKGROUND: Head and neck cancer (HNC) patients have a high risk of developing malnutrition. This randomized study aimed to compare the effect of weekly cisplatin or cetuximab combined with radiotherapy on weight loss at 3 months after treatment was started. Secondary outcomes were the prevalence of malnutrition using the Global Leadership Initiative on Malnutrition (GLIM) criteria, feeding tube dependence and health related quality of life from a nutritional perspective. METHODS: Patients from the ARTSCAN III study with advanced HNC were assessed for weight, body composition, enteral tube dependence and selected quality-of-life scores (EORTC QLQ-C30 and QLQ-H&N35) at diagnosis and 6 weeks 3, 6 and 12 months after treatment initiation. RESULTS: Of the 80 patients, 38 and 42 were randomized to receive cetuximab and cisplatin treatment, respectively. There was no significant difference in weight loss at 3 months between the two study groups. However, the cetuximab group had significantly less weight loss, fewer enteral feeding tubes and better physical functioning at the end of treatment but more pain-related problems 3 months after treatment initiation. No differences between the groups were found at 6 and 12 months. The prevalence of malnutrition was not significantly different at any time point. CONCLUSION: The hypothesized benefit of concomitant treatment with cetuximab over cisplatin regarding the prevalence of malnutrition was not supported by this study.


Assuntos
Neoplasias de Cabeça e Pescoço , Desnutrição , Humanos , Cetuximab/efeitos adversos , Cisplatino/efeitos adversos , Qualidade de Vida , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/radioterapia , Desnutrição/epidemiologia , Desnutrição/etiologia , Redução de Peso
15.
Int J Cancer ; 132(9): 2020-31, 2013 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-23023297

RESUMO

Lung cancer is the worldwide leading cause of death from cancer and has been shown to be a heterogeneous disease at the genomic level. To delineate the genomic landscape of copy number alterations, amplifications, loss-of-heterozygosity (LOH), tumor ploidy and copy-neutral allelic imbalance in lung cancer, microarray-based genomic profiles from 2,141 tumors and cell lines including adenocarcinomas (AC, n = 1,206), squamous cell carcinomas (SqCC, n = 467), large cell carcinomas (n = 37) and small cell lung carcinomas (SCLC, n = 88) were assembled from different repositories. Copy number alteration differences between lung cancer histologies were confirmed in 285 unrelated tumors analyzed by BAC array comparative genomic hybridization. Tumor ploidy patterns were validated by DNA flow cytometry analysis of 129 unrelated cases. Eighty-nine recurrent copy number alterations (55 gains, 34 losses) were identified harboring genes with gene expression putatively driven by gene dosage through integration with gene expression data for 496 cases. Thirteen and 26 of identified regions discriminated AC/SqCC and AC/SqCC/SCLC, respectively, while 48 regions harbored recurrent (n > 15) high-level amplifications comprising established and putative oncogenes, differing in frequency and coamplification patterns between histologies. Lung cancer histologies displayed differences in patterns/frequency of copy number alterations, genomic architecture, LOH, copy-neutral allelic imbalance and tumor ploidy, with AC generally displaying less copy number alterations and allelic imbalance. Moreover, a strong association was demonstrated between different types of copy number alterations and allelic imbalances with tumor aneuploidy. In summary, these analyses provide a comprehensive overview of the landscape of genomic alterations in lung cancer, highlighting differences but also similarities between subgroups of the disease.


Assuntos
Desequilíbrio Alélico , Carcinoma Pulmonar de Células não Pequenas/genética , Variações do Número de Cópias de DNA , Neoplasias Pulmonares/genética , Carcinoma de Pequenas Células do Pulmão/genética , Adenocarcinoma/genética , Adenocarcinoma/patologia , Carcinoma Adenoescamoso/genética , Carcinoma Adenoescamoso/patologia , Carcinoma de Células Grandes/genética , Carcinoma de Células Grandes/patologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Estudos de Coortes , Hibridização Genômica Comparativa , Citometria de Fluxo , Perfilação da Expressão Gênica , Genoma Humano , Humanos , Perda de Heterozigosidade , Neoplasias Pulmonares/patologia , Estadiamento de Neoplasias , Análise de Sequência com Séries de Oligonucleotídeos , Ploidias , Prognóstico , Carcinoma de Pequenas Células do Pulmão/patologia
16.
Opt Express ; 21(25): 31092-7, 2013 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-24514683

RESUMO

We report on a study of polarization properties of asymmetric, multimode vertical-cavity surface-emitting lasers (VCSEL) subjected to electrical RF modulation. When subjected to RF modulation, complex frequency-dependent polarization properties, especially near the polarization switching point are revealed. We propose a scheme of rapidly switching the two RF frequencies modulating the VCSEL, in order to achieve fast polarization modulation in these VCSEL. Polarization modulation up to 300 MHz by modulating the RF frequency and up to 1.5 GHz with RF power modulation has been demonstrated; the fastest reported electrically controlled polarization modulation for multimode VCSELs.

17.
Laryngoscope ; 133(9): 2211-2221, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-36695154

RESUMO

OBJECTIVES: Fatigue due to cancer is a challenging symptom that might be long-lasting after cancer treatment. The aim of this study was to follow the development of fatigue among head and neck cancer (HNC) patients prospectively and longitudinally and to analyze predictors for acute and chronic fatigue. METHODS: HNC patients treated with curative intent were included at diagnosis and completed the following questionnaires multiple times, up to 5 years after treatment: the EORTC QLQ-FA12 for fatigue, EORTC QLQ-C30, and HNC-specific EORTC QLQ-H&N35 together with an anxiety and depression questionnaire. Predictors of fatigue were evaluated at 3 months and 5 years after treatment. RESULTS: Of the 311 study participants, 74% responded at the 5-year follow-up. Physical fatigue was significantly worse 3 months after treatment, while emotional and cognitive fatigue were the worst at diagnosis and at 3 months. All fatigue domains were significantly better after 1 year, and the fatigue scores remained stable from 1 until 5 years after treatment. Three months after chemoradiotherapy, physical fatigue was more significant, but no long-term differences due to treatment modalities were found. Depression and anxiety were predictors for chronic emotional fatigue, and local HN pain and swallowing problems were predictors for chronic physical fatigue. Better global quality of life at diagnosis was associated with less physical and emotional fatigue. CONCLUSION: Fatigue was worst in the short term for HNC patients and improved after 1 year, and long-term fatigue remained stable up to 5 years after treatment. A few predictors for chronic fatigue were found. LEVEL OF EVIDENCE: 3 Laryngoscope, 133:2211-2221, 2023.


Assuntos
Sobreviventes de Câncer , Síndrome de Fadiga Crônica , Neoplasias de Cabeça e Pescoço , Humanos , Qualidade de Vida , Neoplasias de Cabeça e Pescoço/complicações , Neoplasias de Cabeça e Pescoço/terapia , Sobreviventes , Inquéritos e Questionários
18.
Int J Cancer ; 131(10): 2264-73, 2012 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-22392539

RESUMO

The complex interaction between cancer cells and the microenvironment plays an essential role in all stages of tumourigenesis. Despite the significance of this interplay, alterations in protein composition underlying tumour-stroma interactions are largely unknown. The aim of this study was to identify stromal proteins with clinical relevance in non-small cell lung cancer (NSCLC). A list encompassing 203 stromal candidate genes was compiled based on gene expression array data and available literature. The protein expression of these genes in human NSCLC was screened using the Human Protein Atlas. Twelve proteins were selected that showed a differential stromal staining pattern (BGN, CD99, DCN, EMILIN1, FBN1, PDGFRB, PDLIM5, POSTN, SPARC, TAGLN, TNC and VCAN). The corresponding antibodies were applied on tissue microarrays, including 190 NSCLC samples, and stromal staining was correlated with clinical parameters. Higher stromal expression of CD99 was associated with better prognosis in the univariate (p = 0.037) and multivariate (p = 0.039) analysis. The association was independent from the proportion of tumour stroma, the fraction of inflammatory cells and clinical and pathological parameters like stage, performance status and tumour histology. The prognostic impact of stromal CD99 protein expression was confirmed in an independent cohort of 240 NSCLC patients (p = 0.008). Furthermore, double-staining confocal fluorescence microscopy showed that CD99 was expressed in stromal lymphocytes as well as in cancer-associated fibroblasts. Based on a comprehensive screening strategy the membrane protein CD99 was identified as a novel stromal factor with clinical relevance. The results support the concept that stromal properties have an important impact on tumour progression.


Assuntos
Antígenos CD/metabolismo , Biomarcadores Tumorais , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Moléculas de Adesão Celular/metabolismo , Neoplasias Pulmonares/metabolismo , Células Estromais/metabolismo , Antígeno 12E7 , Antígenos CD/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Moléculas de Adesão Celular/genética , Progressão da Doença , Perfilação da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidade , Prognóstico , Transporte Proteico , Proteoma , Microambiente Tumoral
19.
Opt Express ; 20(26): B197-203, 2012 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-23262851

RESUMO

A highly integrated 40 Gbit/s coherent optical receiver is reported using a Costas loop as a homodyne optical phase locked loop (OPLL). A photonic IC, an electrical IC, and a hybrid loop filter are characterized, and the feedback loop system is fully analyzed to build a stable homodyne OPLL. All components are integrated on a single substrate within the compact size of 10 × 10mm(2), and a 1.1 GHz loop bandwidth and a 120 psloop delay are achieved. The binary phase-shift keying receiver exhibits error-free (BER<10(-12)) up to 35 Gbit/s and BER<10(-7) for 40 Gbit/s with no latency, and consumes less than 3 W power.

20.
Opt Express ; 20(26): B377-85, 2012 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-23262876

RESUMO

Compared to traditional optics, photonic integrated circuits have advantages in size, weight, performance, reliability, power consumption, and cost. The size and stability also enable them to realize unique functions in coherent optics. Optical phase-locked loop (OPLL) based transmitters and receivers are examples. With photonic integration, the loop bandwidth of the OPLL can increase by orders of magnitude, and stable OPLLs have been achieved with closed-loop bandwidths >1 GHz.

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