RESUMO
We report modeling that demonstrates the reduction of transmission loss and broadening of the bandwidth of a conventional hollow-core photonic bandgap fiber (PBF). Numerical investigation reveals that transmission loss of the high-order TE01 mode is lower than that of the fundamental HE11 mode in fibers with thick cladding walls. By comparing dispersion curves of PBFs with different core-wall thicknesses, we show that the TE01 mode has weaker coupling strength to a surface mode than the HE11 mode. This result opens the way for a wider transmission band and lower transmission loss in PBFs that are subject to the detrimental effects of surface modes.
RESUMO
A novel technique is proposed for measuring the longitudinal fiber parameters of multi-core fiber (MCF). The mode field diameter (MFD)of a fiber link composed of MCF is successfully estimated with a modified optical time domain reflectometer (OTDR). The measurement accuracy of the MFD distribution is revealed by simulation as a function of the mode coupling coefficient. It is also shown that the relative-index difference and chromatic dispersion of MCF can be estimated with the present technique.
Assuntos
Dispositivos Ópticos , Fibras Ópticas , Fenômenos ÓpticosAssuntos
Descoberta de Drogas , Piperazinas/farmacologia , Canais de Cátion TRPV/antagonistas & inibidores , Administração Oral , Animais , Relação Dose-Resposta a Droga , Feminino , Células HEK293 , Humanos , Estrutura Molecular , Piperazinas/administração & dosagem , Piperazinas/química , Ratos , Ratos Endogâmicos Lew , Relação Estrutura-Atividade , Canais de Cátion TRPV/metabolismoRESUMO
The aim of the present study was to examine the effect of the somatic cell count (SCC) in milk on reproductive performance, such as pregnancy status in the prepartum period and ovarian function in the postpartum period, in dairy cows. Blood samples were collected every week from one month prepartum to parturition in order to measure the concentrations of 13,14-dihydro-15-keto-PGF2α (PGFM), estrone sulfate (E1S) and progesterone. Milk samples were collected three times per week in both the prepartum (for one month before the dry period) and postpartum periods (for 3 months immediately after parturition) to measure the SCC. Progesterone was also determined in the whole milk of postpartum cows to define the day of the first ovulation. In the prepartum period, the maximum SCC negatively correlated with the pregnancy period (r = -0.77), but not the calf birth weight. Positive and negative correlations were observed between the average SCC and PGFM or progesterone concentrations in plasma, respectively (r = 0.84 or -0.92, respectively), at 39 weeks of pregnancy. In the postpartum period, a correlation was observed between the day of the first ovulation and both the average and maximum SCC (r = -0.74 and -0.75, respectively), whereas days open was not related to the SCC. These results suggest that a high SCC in the prepartum period may advance parturition by increasing PGF2α and decreasing progesterone and that the first ovulation in the postpartum period was affected by a high SCC.
Assuntos
Bovinos/fisiologia , Leite/citologia , Reprodução/fisiologia , Animais , Contagem de Células , Dinoprosta/análogos & derivados , Dinoprosta/sangue , Estrona/análogos & derivados , Estrona/sangue , Feminino , Leite/química , Ovário/fisiologia , Período Pós-Parto , Gravidez , Prenhez/fisiologia , Progesterona/análise , Progesterona/sangueRESUMO
The first total synthesis of (+)-tanzawaic acid B, a natural polyketide bearing a pentadienoic ester and octalin moiety, has been accomplished. The synthetic improvement from previous synthetic conditions facilitated our gram-scale synthesis of the chiral octalin that possesses seven stereogenic centers and that is the core skeleton of almost all of the tanzawaic acid family.
RESUMO
[This corrects the article DOI: 10.1021/acsomega.3c03634.].
RESUMO
We demonstrate 7-core fiber transmission of 10 x 96-Gb/s PDM-16QAM signals over 1000-km using distributed Raman amplification (DRA). DRA gain of 9-12 dB and equivalent noise figure of less than 1 dB are achieved in all cores. We also prove the feasibility of high power multi-core fiber transmission with per fiber power of 6.5 W.
Assuntos
Amplificadores Eletrônicos , Lasers , Fibras Ópticas , Desenho de Equipamento , Análise de Falha de Equipamento , Estudos de ViabilidadeRESUMO
Optimization starting with our lead compound 1 (IC(50)=4.9 nM) led to the identification of pyrrolidinyl phenylurea derivatives. Further modification toward improvement of the bioavailability provided (R)-1-(1-((6-fluoronaphthalen-2-yl)methyl)pyrrolidin-3-yl)-3-(2-(2-hydroxyethoxy)phenyl)urea 32 (IC(50)=1.7 nM), a potent and orally active CCR3 antagonist.
Assuntos
Compostos de Fenilureia/química , Pirrolidinas/química , Receptores CCR3/antagonistas & inibidores , Administração Oral , Animais , Disponibilidade Biológica , Meia-Vida , Macaca fascicularis , Compostos de Fenilureia/síntese química , Compostos de Fenilureia/farmacocinética , Pirrolidinas/síntese química , Pirrolidinas/farmacocinética , Receptores CCR3/metabolismoRESUMO
The synthesis and structure-activity relationships of ureas as CCR3 antagonists are described. Optimization starting with lead compound 2 (IC(50)=190 nM) derived from initial screening hit compound 1 (IC(50)=600 nM) led to the identification of (S)-N-((1R,3S,5S)-8-((6-fluoronaphthalen-2-yl)methyl)-8-azabicyclo[3.2.1]octan-3-yl)-N-(2-nitrophenyl)pyrrolidine-1,2-dicarboxamide 27 (IC(50)=4.9 nM) as a potent CCR3 antagonist.
Assuntos
Receptores CCR3/antagonistas & inibidores , Ureia/análogos & derivados , Avaliação Pré-Clínica de Medicamentos , Humanos , Naftalenos/síntese química , Naftalenos/química , Naftalenos/metabolismo , Prolina/química , Ligação Proteica , Pirrolidinas/síntese química , Pirrolidinas/química , Pirrolidinas/metabolismo , Receptores CCR3/metabolismo , Relação Estrutura-Atividade , Ureia/síntese química , Ureia/metabolismoRESUMO
Farm managers' decision to cull dairy cows is based on the cows' milk production, history of disorder(s), and reproductive performance, each of which affects dairy cows' lifetime (herd life and productive lifespan). We investigated the relationships among the incidence of clinical mastitis (CM), the reproductive performance, and the culling rate. We also assessed the effects of these relationships on the lifetimes of dairy cows, using the records made before and after the introduction of an automatic milking system (AMS) at Hiroshima University Farm. Milk yield, CM incidence density, and culling rate of dairy cows increased after the AMS introduction. The CM incidence was associated with an elongation of the calving interval in cows with the same parity. CM in the 1st parity might have caused the reductions of the cows' lifetime and their parity at culling. A higher age at first calving (AFC) was associated with an increase in culling rate but did not lead to a significant decrease in lifetime. Investigations of the factors mediating CM in the 1st parity or AFC with CM incidence or culling rate in the later stages might contribute to the control of lifetime of dairy cows.
Assuntos
Indústria de Laticínios , Mastite , Animais , Bovinos , Fazendas , Feminino , Incidência , Lactação , Mastite/veterinária , Gravidez , UniversidadesRESUMO
Our laboratory has identified several acrylamide derivatives with potent CCR3 inhibitory activity. In the present study, we evaluated the in vitro metabolic stability (CL(int); mL/min/kg) of these compounds in human liver microsomes (HLMs), and assessed the relationship between their structures and CL(int) values. Among the compounds identified, N-{(3R)-1-[(6-fluoro-2-naphthyl)methyl]pyrrolidin-3-yl}-2-[1-(2-hydroxybenzoyl)piperidin-4-ylidene]acetamide (30j) was found to be a potent inhibitor (IC(50)=8.4nM) with a high metabolic stability against HLMs.
Assuntos
Acetamidas/síntese química , Acrilamidas/química , Antialérgicos/síntese química , Naftalenos/síntese química , Receptores CCR3/antagonistas & inibidores , Acetamidas/química , Acetamidas/farmacologia , Acrilamidas/síntese química , Acrilamidas/farmacocinética , Animais , Antialérgicos/química , Antialérgicos/farmacocinética , Haplorrinos , Humanos , Camundongos , Microssomos Hepáticos/metabolismo , Naftalenos/química , Naftalenos/farmacologia , Piperidinas/síntese química , Piperidinas/química , Piperidinas/farmacologia , Isoformas de Proteínas/antagonistas & inibidores , Isoformas de Proteínas/metabolismo , Receptores CCR3/metabolismo , TermodinâmicaRESUMO
A novel class of potent CCR3 receptor antagonists were designed and synthesized starting from N-{1-[(6-fluoro-2-naphthyl)methyl]piperidin-4-yl}benzamide (1),which was found by subjecting our chemical library to high throughput screening (HTS). The CCR3 inhibitory activity of the synthesized compounds against eotaxin-induced Ca(2+) influx was evaluated using CCR3-expressing preB cells. Systematic chemical modifications of 1 revealed that the 6-fluoro-2-naphthylmethyl moiety was essential for CCR3 inhibitory activity in this new series of CCR3 antagonists. Further structural modifications of the benzamide and piperidine moieties of 1 led to the identification of exo-N-{8-[(6-fluoro-2-naphthyl)methyl]-8-azabicyclo[3.2.1]oct-3- yl}biphenyl-2-carboxamide [corrected] (31) as a potent CCR3 antagonist with an IC(50) value of 0.020 microM.
Assuntos
Benzamidas/farmacologia , Receptores CCR3/antagonistas & inibidores , Benzamidas/síntese química , Cálcio/metabolismo , Quimiocina CCL11 , Humanos , Concentração Inibidora 50 , Células Precursoras de Linfócitos B , Bibliotecas de Moléculas Pequenas , Relação Estrutura-AtividadeRESUMO
From a series of 4'-[(trifluoromethyl)pyrazol-1-yl]carboxanilides derived from 4-methyl-4'-[3,5-bis(trifluoromethyl)-1H-pyrazol-1-yl]-1,2,3-thiadiazole-5-carboxanilide, one inhibited thapsigargin-induced Ca2+ influx in Jurkat T cells (IC(50)=77 nM) and exhibited high selectivity for the CRAC channel over the VOC channel (index: >130). Another acted as an inhibitor for both T lymphocyte activation-induced diseases and ovalbumin-induced airway eosinophilia in rats (ED(50)=1.3 mg/kg) p.o.
Assuntos
Anilidas/farmacologia , Bloqueadores dos Canais de Cálcio/farmacologia , Canais de Cálcio/efeitos dos fármacos , Cálcio/metabolismo , Pirazóis/farmacologia , Anilidas/síntese química , Anilidas/química , Animais , Bloqueadores dos Canais de Cálcio/síntese química , Bloqueadores dos Canais de Cálcio/química , Sinalização do Cálcio/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Feminino , Humanos , Hipersensibilidade/tratamento farmacológico , Interleucina-2/metabolismo , Células Jurkat , Ativação Linfocitária/efeitos dos fármacos , Masculino , Camundongos , Eosinofilia Pulmonar/induzido quimicamente , Eosinofilia Pulmonar/tratamento farmacológico , Pirazóis/síntese química , Pirazóis/química , Ratos , Ratos Endogâmicos BN , Relação Estrutura-Atividade , Linfócitos T/efeitos dos fármacos , Linfócitos T/metabolismo , Tapsigargina/farmacologiaRESUMO
In our previous study on discovering novel types of CCR3 antagonists, we found a fluoronaphthalene derivative (1) that exhibited potent CCR3 inhibitory activity with an IC(50) value of 20 nM. However, compound 1 also inhibited human cytochrome P450 2D6 (CYP2D6) with an IC(50) value of 400 nM. In order to reduce its CYP2D6 inhibitory activity, we performed further systematic structural modifications on 1. In particular, we focused on reducing the number of lipophilic moieties in the biphenyl part of 1, using ClogD(7.4) values as the reference index of lipophilicity. This research led to the identification of N-{(3-exo)-8-[(6-fluoro-2-naphthyl)methyl]-8-azabicyclo[3.2.1]oct-3-yl}-3-(piperidin-1-ylcarbonyl)isonicotinamide 1-oxide (30) which showed comparable CCR3 inhibitory activity (IC(50)=23 nM) with much reduced CYP2D6 inhibitory activity (IC(50)=29,000 nM) compared with 1.
Assuntos
Inibidores do Citocromo P-450 CYP2D6 , Desenho de Fármacos , Hidrocarbonetos Fluorados/farmacologia , Naftalenos/farmacologia , Receptores CCR3/antagonistas & inibidores , Cálcio/química , Cálcio/metabolismo , Citoplasma/química , Citoplasma/metabolismo , Humanos , Hidrocarbonetos Fluorados/síntese química , Concentração Inibidora 50 , Naftalenos/síntese química , Receptores CCR3/metabolismo , Relação Estrutura-AtividadeRESUMO
Mastitis is the most prevalent disease in dairy cattle worldwide and not only causes huge economic losses in the dairy industry but also threatens public health. To evaluate the therapeutic potential of melatonin in mastitis, we examined the ability of melatonin to protect bovine mammary epithelial cells (bMECs) from the harmful effects of lipopolysaccharide (LPS). We found that melatonin inhibited the LPS-binding protein-CD14-TLR4 signaling pathway in bMECs, which had opposing effects on pro-inflammatory and anti-inflammatory mediators. Melatonin decreased LPS-induced expression of pro-inflammatory cytokines, chemokines, and positive acute-phase proteins (APPs), including tumor necrosis factor-α, interleukin (IL)-1ß, IL-6, granulocyte-monocyte colony-stimulating factor, chemokine CC motif ligand (CCL)2, CCL5, serum amyloid A, haptoglobin, C-reactive protein, ceruloplasmin, and α-1 antitrypsin, and increased expression of the anti-inflammatory cytokine IL-1Ra and the negative APP fibrinogen. In addition, melatonin increased dityrosine levels but suppressed nitrite levels by upregulating the expression of Nrf2 and heme oxygenase-1 in the Nrf2 antioxidant defense pathway. Finally, melatonin administration increased the viability of LPS-stimulated bMECs. These results suggest that melatonin protects bMECs from LPS-induced inflammatory and oxidant stress damage and provide evidence that melatonin might have therapeutic utility in mastitis.
Assuntos
Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Células Epiteliais/efeitos dos fármacos , Lipopolissacarídeos/farmacologia , Melatonina/farmacologia , Proteínas de Fase Aguda/metabolismo , Animais , Proteína C-Reativa/metabolismo , Proteínas de Transporte/metabolismo , Bovinos , Doenças dos Bovinos/tratamento farmacológico , Doenças dos Bovinos/metabolismo , Fatores Estimuladores de Colônias/metabolismo , Células Epiteliais/metabolismo , Feminino , Heme Oxigenase-1/metabolismo , Proteína Antagonista do Receptor de Interleucina 1/metabolismo , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Receptores de Lipopolissacarídeos/metabolismo , Glândulas Mamárias Animais , Mastite/tratamento farmacológico , Mastite/metabolismo , Glicoproteínas de Membrana/metabolismo , Transdução de Sinais/efeitos dos fármacos , Receptor 4 Toll-Like/metabolismo , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Glucose and fructose selection patters of rats were analyzed for 28 d by a 2-choice selection in either Zn-adequate or Zn-deficient status. In this paper, we describe the following serial studies: (1) For the first 24 h, rats fed a Zn-deficient diet preferred a fructose-diet compared with a glucose-diet. On and after the third day, rats fed both Zn-adequate and Zn-deficient diets preferred the glucose-diet. (2) Throughout the experimental period, many of the rats fed a Zn-adequate and Zn-deficient diet continuously selected one diet. (3) Some of the rats fed a Zn-adequate and Zn-deficient diet suddenly changed preference for the glucose-diet or the fructose-diet. (4) The sum of daily glucose- and fructose-diet intake in rats fed a Zn-deficient diet showed a characteristic variation with the cyclic period of 3.9 +/- 0.4 d.
Assuntos
Carboidratos da Dieta , Preferências Alimentares/fisiologia , Frutose/administração & dosagem , Glucose/administração & dosagem , Zinco/deficiência , Animais , Dieta , Ingestão de Alimentos , Masculino , Ratos , Ratos Wistar , Aumento de Peso , Zinco/administração & dosagemRESUMO
The incidence of different types of luteal activity postpartum and their effect on reproductive performance were studied in 21 postpartum dairy cows. Progesterone concentrations in defatted milk collected 3 times a week were determined by EIA. Reproductive tract examination was undertaken every other week postpartum. Body weight and body condition score (BCS) were measured before and after calving and the average 100-day milk yield was calculated. Nine (42.9%) cows had normal ovarian activity (first luteal activity < or = 50 days postpartum followed by regular cycles), 5 (23.8%) had prolonged luteal phase (PLP; ovarian cycle with luteal activity > or = 20 days pre-service) and in 7 (33.3%) cows the first luteal activity was shown later than 50 days postpartum (DOV). When compared with normal cows, both PLP and DOV had longer interval to first insemination (63.1 +/- 22.0 days versus 77.6 +/- 21.6 and 93.0 +/- 22.3 days, P<0.05 and P<0.01, respectively), lower first insemination conception rate (88.9% versus 0.0% and 57.1%, P<0.01 and P<0.05, respectively) and greater BCS loss (0.81 +/- 0.2 versus 1.05 +/- 0.21 and 1.04 +/- 0.10, respectively, P<0.01). Cows with PLP showed longer interval to uterine involution than normal and DOV groups (54.0 +/- 8.3 days versus 42.4 +/- 5.5 and 43.3 +/- 8.3 days, respectively, P<0.01) and higher 100-day milk yield (38.8 +/- 2.7 kg versus 33.6 +/- 4.7 and 29.9 +/- 6.1 kg, respectively, P<0.01). In conclusion, more than half of the cows had abnormal luteal activity postpartum, which adversely affected reproductive performance.
Assuntos
Bovinos/fisiologia , Fertilização/fisiologia , Fase Luteal/fisiologia , Leite/química , Período Pós-Parto/fisiologia , Análise de Variância , Animais , Constituição Corporal , Peso Corporal , Feminino , Técnicas Imunoenzimáticas/veterinária , Progesterona/análise , Fatores de TempoRESUMO
The objective of this study was to investigate the types and incidence of luteal sub-function in lactating cows after artificial insemination (AI) and their relationship with pregnancy, and to clarify the relationship between luteal function and parity, body condition score (BCS), milk yield, and dietary intake. In 19 cows, milk samples were collected daily from AI to confirmation of pregnancy. Milk progesterone concentrations were determined by EIA. Based on peak progesterone concentration and the day of onset of luteal phase, 15 of 30 progesterone profiles (50%) were normal, with progesterone concentration reaching 1.0 ng/ml within 5 days after insemination and > or =2.0 ng/ml thereafter. In addition, 6 (20%) were insufficient, (progesterone concentration remained < 2.0 ng/ml), 5 (17%) were delayed (progesterone reached 1.0 ng/ml after 5 days), 2 (7%) were both delayed and insufficient, one (3%) was short (progesterone >1.0 ng/ml for only 7 days), and one (3%) remained basal. Cows with a normal profile had a higher (P < 0.05) pregnancy rate than those with an abnormal profile (87% versus 33%, respectively). The amount of progesterone secreted in milk after first AI, as indicated by progesterone area under curve (AUC), was negatively correlated with milk yield (r = -0.83, P < 0.01), dry matter intake (r = -0.81, P < 0.05), total digestible nutrients (r = -0.82, P< 0.05), and digestible crude protein (r = -0.79, P <0.05). Cows that produced more milk and consumed more dry matter had less progesterone during the luteal phase. In conclusion, abnormal luteal function was associated with reduced pregnancy rates and high milk production and increased dietary intake during breeding were associated with reduced progesterone concentrations.
Assuntos
Bovinos/fisiologia , Corpo Lúteo/fisiologia , Fertilização , Inseminação Artificial/veterinária , Lactação , Animais , Feminino , Gravidez , Taxa de Gravidez , Progesterona/sangueRESUMO
Atresia ani, a common genetic defect in animals, is often accompanied by urogenital defects in calves. This paper reports a case of atresia ani with diphallus and separate scrota in a calf. The calf was born with atresia ani; surgery (to open the anus) was performed 3 days after birth. No urogenital abnormalities were noticed until 4 months after birth. At that time, two separate scrota (each containing a testis) and a sac-like structure in the middle of two scrota, were visible. The gait was abnormal, with abduction of the hind limbs while walking. Additionally, the hind legs appeared wider than usual at the hip joints. Two weeks later, two peni (diphallia) was observed, each in a separate preputial sheath. The calf had a normal karyotype on cytogenetic examination. Plasma concentrations of testosterone at 5.5, 6, and 7 months of age were 3.5, 1.9, and 1.7 ng/ml, respectively. At necropsy (7 months of age), the prepuce was thick and the glans of the right penis was adhered to the prepuce. The left penis did not have a urethra or retractor penis muscles. The sac-like structure in the middle of the two scrota contained the urinary bladder and a loop of small intestine. The pubic bone had failed to fuse at the pelvic symphysis. In conclusion, this is the first reported case of atresia ani with diphallus, separate scrota, and pubic bone separation in a calf.
Assuntos
Anus Imperfurado/veterinária , Doenças dos Bovinos , Pênis/anormalidades , Escroto/anormalidades , Animais , Bovinos , Doenças dos Bovinos/sangue , Doenças dos Bovinos/patologia , Masculino , Pênis/patologia , Osso Púbico/anormalidades , Osso Púbico/patologia , Escroto/patologia , Testículo/anormalidades , Testículo/patologia , Testosterona/sangueRESUMO
Recent progress on time-division multiplexed (TDM) and wavelength-division multiplexed (WDM) soliton transmission is described, in which dispersion management plays an important role in increasing the power margin and the dispersion tolerance. The characteristics of the dispersion-managed soliton are compared with those of return to zero and nonreturn to zero pulses. With a small dispersion swing, the system can still be described as an average soliton using the nonlinear Schrodinger equation, while with a large dispersion swing, the solitonlike steady-state pulse becomes a chirped Gaussian pulse, in which the governing equation is closer to a linear Schrodinger equation with a parabolic potential well. We describe an in-line modulation scheme for up to 80 Gbit/s per channel and its two channel WDM transmission over 10 000 km. Finally, we describe 640 Gbit/s (40 Gbit/sx16 channels) WDM soliton transmission over 1000 km with a dispersion-managed single-mode fiber. (c) 2000 American Institute of Physics.