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The extracellular signal-regulated kinases (ERK1 and 2) are widely-expressed and they modulate proliferation, survival, differentiation, and protein synthesis in multiple cell lineages. Altered ERK1/2 signaling is found in several genetic diseases with skeletal phenotypes, including Noonan syndrome, Neurofibromatosis type 1, and Cardio-facio-cutaneous syndrome, suggesting that MEK-ERK signals regulate human skeletal development. Here, we examine the consequence of Erk1 and Erk2 disruption in multiple functions of osteoclasts, specialized macrophage/monocyte lineage-derived cells that resorb bone. We demonstrate that Erk1 positively regulates osteoclast development and bone resorptive activity, as genetic disruption of Erk1 reduced osteoclast progenitor cell numbers, compromised pit formation, and diminished M-CSF-mediated adhesion and migration. Moreover, WT mice reconstituted long-term with Erk1(-/-) bone marrow mononuclear cells (BMMNCs) demonstrated increased bone mineral density as compared to recipients transplanted with WT and Erk2(-/-) BMMNCs, implicating marrow autonomous, Erk1-dependent osteoclast function. These data demonstrate Erk1 plays an important role in osteoclast functions while providing rationale for the development of Erk1-specific inhibitors for experimental investigation and/or therapeutic modulation of aberrant osteoclast function.

Despite the high prevalence and significant morbidity of spinal anomalies in neurofibromatosis type 1 (NF1), the pathogenesis of these defects remains largely unknown. Here, we present two murine models: Nf1flox/-;PeriCre and Nf1flox/-;Col.2.3Cre mice, which recapitulate spinal deformities seen in the human disease. Dynamic histomorphometry and microtomographic studies show recalcitrant bone remodeling and distorted bone microarchitecture within the vertebral spine of Nf1flox/-;PeriCre and Nf1flox/-;Col2.3Cre mice, with analogous histological features present in a human patient with dystrophic scoliosis. Intriguingly, 36-60% of Nf1flox/-;PeriCre and Nf1flox/-;Col2.3Cre mice exhibit segmental vertebral fusion anomalies with boney obliteration of the intervertebral disc (IVD). While analogous findings have not yet been reported in the NF1 patient population, we herein present two case reports of IVD defects and interarticular vertebral fusion in patients with NF1. Collectively, these data provide novel insights regarding the pathophysiology of dystrophic spinal anomalies in NF1, and provide impetus for future radiographic analyses of larger patient cohorts to determine whether IVD and vertebral fusion defects may have been previously overlooked or underreported in the NF1 patient population.

Skeletal abnormalities including osteoporosis and osteopenia occur frequently in both pediatric and adult neurofibromatosis type 1 (NF1) patients. NF1 (Nf1) haploinsufficient osteoclasts and osteoclast progenitors derived from both NF1 patients and Nf1(+/-) mice exhibit increased differentiation, migration, and bone resorptive capacity in vitro, mediated by hyperactivation of p21(Ras) in response to limiting concentrations of macrophage-colony stimulating factor (M-CSF). Here, we show that M-CSF binding to its receptor, c-Fms, results in increased c-Fms activation in Nf1(+/) (-) osteoclast progenitors, mediating multiple gain-in-functions through the downstream effectors Erk1/2 and p90RSK. PLX3397, a potent and selective c-Fms inhibitor, attenuated M-CSF mediated Nf1(+/-) osteoclast migration by 50%, adhesion by 70%, and pit formation by 60%. In vivo, we administered PLX3397 to Nf1(+/-) osteoporotic mice induced by ovariectomy (OVX) and evaluated changes in bone mass and skeletal architecture. We found that PLX3397 prevented bone loss in Nf1(+/-)-OVX mice by reducing osteoclast differentiation and bone resorptive activity in vivo. Collectively, these results implicate the M-CSF/c-Fms signaling axis as a critical pathway underlying the aberrant functioning of Nf1 haploinsufficient osteoclasts and may provide a potential therapeutic target for treating NF1 associated osteoporosis and osteopenia.

Anisakid larvae are regarded as an important hazard in marine products, and demand is growing for on-line nondestructive analytical techniques for effective monitoring of these parasites. A UV fluorescent imaging was developed for detection of the third-stage anisakid larvae in marine fishes, and different processing methods were investigated and optimized based on principal component and gray value analyses. Using cod fillets as samples, the efficiency of the developed technique was evaluated, and the overall detection ratio was greater than 80 % . These results indicate a promising application of UV fluorescent imaging as an effective and nondestructive technique for identification of anisakid larvae in fishery products.

Germline mutations in the NF1 tumor suppressor gene cause neurofibromatosis type 1 (NF1), a complex genetic disorder with a high predisposition of numerous skeletal dysplasias including short stature, osteoporosis, kyphoscoliosis, and fracture non-union (pseudoarthrosis). We have developed murine models that phenocopy many of the skeletal dysplasias observed in NF1 patients, including reduced bone mass and fracture non-union. We also show that the development of these skeletal manifestations requires an Nf1 haploinsufficient background in addition to nullizygous loss of Nf1 in mesenchymal stem/progenitor cells (MSCs) and/or their progenies. This is replicated in two animal models of NF1, PeriCre(+);Nf1(flox/-) and Col2.3Cre(+);Nf1(flox/-) mice. Adoptive transfer experiments demonstrate a critical role of the Nf1+/- marrow microenvironment in the impaired fracture healing in both models and adoptive transfer of WT bone marrow cells improves fracture healing in these mice. To our knowledge, this is the first demonstration of a non-cell autonomous mechanism in non-malignant NF1 manifestations. Collectively, these data provide evidence of a combinatory effect between nullizygous loss of Nf1 in osteoblast progenitors and haploinsufficiency in hematopoietic cells in the development of non-malignant NF1 manifestations.

To achieve transformation, libraries must undertake a profound and rapid reconfiguration of space. The spatial literacy competencies of librarians are directly related to the construction and service level of library spaces. This paper clarifies the concept of spatial literacy and its constituent elements. Using the method of systematic literature review, the current status of research on librarians’ spatial literacy is analyzed from three aspects: spatial theory, spatial method, and spatial practice by focusing on the trajectory of library space-related literature.

The half-life of 95m Tc and the cross-sections of the 96 Ru ( n, x ) 95m Tc reaction induced by D–T neutrons were measured through the neutron activation technique in combination with off-line γ-ray spectrometry. The neutron beam was generated from the T ( d, n ) 4 He reaction using the K-400 neutron generator at the Chinese Academy of Engineering Physics (CAEP). Through exponential function fitting and a detailed discussion of the uncertainty evaluation, the measured half-life of 95m Tc was 61.88 ± 0.22 days, which uncertainty is reduced greatly compared with the currently recommended value. Based on the determination of the 95m Tc half-life, the cross-sections of 96 Ru ( n, x ) 95m Tc reaction at the 13.85 ± 0.2, 14.30 ± 0.2 and 14.72 ± 0.2 MeV neutron energies were measured relative to the 93 Nb ( n, 2n ) 92m Nb monitor reaction. Considering the correlations between different attributes, detailed uncertainty propagation was performed by the covariance analysis and the cross-sections were reported with their uncertainties and correlation matrix. Then, experimentally determined cross-sections were analyzed by comparing with the literature data available in the EXFOR database and theoretically calculated values using the TALYS-1.95 and EMPIRE-3.2.3 codes. The accuracy of current experimental results with the thorough uncertainties and covariance information is greatly improved, which is critical for verifying the reliability of the theoretical model and improving the quality of the nuclear database.

With the increasingly deeper application of multimedia and network technology in education, the proportion of web-based learning presents a trend of continuous growth in people's daily study, and the webbased learners tend to have learning fatigue during their learning process of distance education. Under the 4 learning states of normal study, fatigue and doubt, the eye opening degrees of web-based learner have certain difference. Through preprocessing of the color images of web-based learners' eye state, the 2-dimensional kernel function is selected to build 48 optimal filters and obtain 48 eigenvalues, and then, through HMM, training is conducted to identify the eye state and feature classification. The experiment results show that, this algorithm has very high identification ability of the web-based learning fatigue.

The signal obtained through measurement is inevitably with noise and interference. Traditional signal denoising method often takes the threshold way to process the wavelets or wavelet packets of noise signal for the purpose of denoising. Denoising by making use of slip threshold value of wavelet packets is proposed by this paper, to quantize the slip threshold value of wavelet packet decomposition coefficient, so as to obtain the reconstructed signal denoising. It is shown by the computer simulation results that the slip threshold value is with good practical value.

In order for the effective recognition of face in the videos of complex environments, this paper presents an algorithm of face tracking of robust. Basing on the rigid constraints, this algorithm generates the potential rectangular area of face tracking,generates the isosceles triangle for the front–view images, generates the right angled triangle for the side images, and reaches the effective rate as 98.18% of face recognition in different sizes, lightings, poses,expressions and even under different noises.