Improving the Accuracy and Efficiency of Abnormal Cervical Squamous Cell Detection With Cytologist-in-the-Loop Artificial Intelligence.

Population-based cervical cytology screening techniques are demanding and laborious and have relatively poor diagnostic accuracy. In this study, we present a cytologist-in-the-loop artificial intelligence (CITL-AI) system to improve the accuracy and efficiency of abnormal cervical squamous cell detection in cervical cancer screening. The artificial intelligence (AI) system was developed using 8000 digitalized whole slide images, including 5713 negative and 2287 positive cases. External validation was performed using an independent, multicenter, real-world data set of 3514 women, who were screened for cervical cancer between 2021 and 2022. Each slide was assessed using the AI system, which generated risk scores. These scores were then used to optimize the triaging of true negative cases. The remaining slides were interpreted by cytologists who had varying degrees of experience and were categorized as either junior or senior specialists. Stand-alone AI had a sensitivity of 89.4% and a specificity of 66.4%. These data points were used to establish the lowest AI-based risk score (ie, 0.35) to optimize the triage configuration. A total of 1319 slides were triaged without missing any abnormal squamous cases. This also reduced the cytology workload by 37.5%. Reader analysis found CITL-AI had superior sensitivity and specificity compared with junior cytologists (81.6% vs 53.1% and 78.9% vs 66.2%, respectively; both with P < .001). For senior cytologists, CITL-AI specificity increased slightly from 89.9% to 91.5% (P = .029); however, sensitivity did not significantly increase (P = .450). Therefore, CITL-AI could reduce cytologists' workload by more than one-third while simultaneously improving diagnostic accuracy, especially compared with less experienced cytologists. This approach could improve the accuracy and efficiency of abnormal cervical squamous cell detection in cervical cancer screening programs worldwide.

Assessing artificial intelligence enabled liquid-based cytology for triaging HPV-positive women: a population-based cross-sectional study.

INTRODUCTION: Cytology-based triaging is commonly used to manage the care of women with positive human papillomavirus (HPV) results, but it suffers from subjectivity and a lack of sensitivity and reproducibility. The diagnostic performance of an artificial intelligence-enabled liquid-based cytology (AI-LBC) triage approach remains unclear. Here, we compared the clinical performance of AI-LBC, human cytologists and HPV16/18 genotyping at triaging HPV-positive women. MATERIAL AND METHODS: HPV-positive women were triaged using AI-LBC, human cytologists and HPV16/18 genotyping. Histologically confirmed cervical intraepithelial neoplasia grade 2/3 or higher (CIN2+/CIN3+) were accepted as thresholds for clinical performance assessments. RESULTS: Of the 3514 women included, 13.9% (n = 489) were HPV-positive. The sensitivity of AI-LBC was comparable to that of cytologists (86.49% vs 83.78%, P = 0.744) but substantially higher than HPV16/18 typing at detecting CIN2+ (86.49% vs 54.05%, P = 0.002). While the specificity of AI-LBC was significantly lower than HPV16/18 typing (51.33% vs 87.17%, P < 0.001), it was significantly higher than cytologists at detecting CIN2+ (51.33% vs 40.93%, P < 0.001). AI-LBC reduced referrals to colposcopy by approximately 10%, compared with cytologists (51.53% vs 60.94%, P = 0.003). Similar patterns were also observed for CIN3+. CONCLUSIONS: AI-LBC has equivalent sensitivity and higher specificity compared with cytologists, with more efficient colposcopy referrals for HPV-positive women. AI-LBC could be particularly useful in regions where experienced cytologists are few in number. Further investigations are needed to determine triaging performance through prospective designs.

An Accurate and Robust Method for Absolute Pose Estimation with UAV Using RANSAC.

In this paper, we proposed an accurate and robust method for absolute pose estimation with UAV (unmanned aerial vehicle) using RANSAC (random sample consensus). Because the artificial 3D control points with high accuracy are time-consuming and the small point set may lead low measuring accuracy, we designed a customized UAV to efficiently obtain mass 3D points. A light source was mounted on the UAV and used as a 3D point. The position of the 3D point was given by RTK (real-time kinematic) mounted on the UAV, and the position of the corresponding 2D point was given by feature extraction. The 2D-3D point correspondences exhibited some outliers because of the failure of feature extraction, the error of RTK, and wrong matches. Hence, RANSAC was used to remove the outliers and obtain the coarse pose. Then, we proposed a method to refine the coarse pose, whose procedure was formulated as the optimization of a cost function about the reprojection error based on the error transferring model and gradient descent to refine it. Before that, normalization was given for all the valid 2D-3D point correspondences to improve the estimation accuracy. In addition, we manufactured a prototype of a UAV with RTK and light source to obtain mass 2D-3D point correspondences for real images. Lastly, we provided a thorough test using synthetic data and real images, compared with several state-of-the-art perspective-n-point solvers. Experimental results showed that, even with a high outlier ratio, our proposed method had better performance in terms of numerical stability, noise sensitivity, and computational speed.

A New Method for Absolute Pose Estimation with Unknown Focal Length and Radial Distortion.

Estimating the absolute pose of a camera is one of the key steps for computer vision. In some cases, especially when using a wide-angle or zoom lens, the focal length and radial distortion also need to be considered. Therefore, in this paper, an efficient and robust method for a single solution is proposed to estimate the absolute pose for a camera with unknown focal length and radial distortion, using three 2D-3D point correspondences and known camera position. The problem is decomposed into two sub-problems, which makes the estimation simpler and more efficient. The first sub-problem is to estimate the focal length and radial distortion. An important geometric characteristic of radial distortion, that the orientation of the 2D image point with respect to the center of distortion (i.e., principal point in this paper) under radial distortion is unchanged, is used to solve this sub-problem. The focal length and up to four-order radial distortion can be determined with this geometric characteristic, and it can be applied to multiple distortion models. The values with no radial distortion are used as the initial values, which are close to the global optimal solutions. Then, the sub-problem can be efficiently and accurately solved with the initial values. The second sub-problem is to determine the absolute pose with geometric linear constraints. After estimating the focal length and radial distortion, the undistorted image can be obtained, and then the absolute pose can be efficiently determined from the point correspondences and known camera position using the undistorted image. Experimental results indicate this method's accuracy and numerical stability for pose estimation with unknown focal length and radial distortion in synthetic data and real images.

[Material basis and molecular mechanism of Angelicae Sinensis Radix in activating blood:based on computer-aided drug design].

Angelicae Sinensis Radix excels in activating blood, but the scientific mechanism has not been systematically analyzed, thus limiting the development of the medicinal. This study employed the computer-aided drug design methods, such as structural similarity-based target reverse prediction, complex network analysis, molecular docking, binding free energy calculation, cluster analysis, and ADMET(absorption, distribution, metabolism, excretion, toxicity) calculation, and enzyme activity assay in vitro, to explore the components and mechanism of Angelicae Sinensis Radix in activating blood. Target reverse prediction and complex network analysis yielded 40 potential anticoagulant targets of the medicinal. Gene Ontology(GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis indicated that the targets mainly acted on the complement and coagulation cascade signaling pathway to exert the anticoagulant function. Among them, the key enzymes thrombin(THR) and coagulation factor Xa(FXa) in coagulation cascade and thrombosis were the drug targets for thromboembolic diseases. At the same time, molecular docking and cluster analysis showed that the medicinal had high selectivity for FXa. According to binding free energy score, 8 potential active components were selected for enzyme activity assay in vitro. The results demonstrated that 8 components inhibited THR and FXa, and the inhibition was stronger on FXa than on THR. The pharmacophore model of 8 active compounds was constructed, which suggested that the components had the common pharmacophore AAHH. The ADMET calculation result indicated that they had good pharmacokinetic properties and were safe. Based on target reverse prediction, complex network analysis, molecular docking and binding free energy calculation, anticoagulant activity in vitro, spatial binding conformation of molecules and targets, pharmacophore model construction, and ADMET calculation, this study preliminarily clarified the material basis and molecular mechanism of Angelicae Sinensis Radix in activating blood from the perspective of big data, and calculated the pharmacology and toxicology parameters of the active components. Our study, for the first time, revealed that the medicinal had obvious selectivity and pertinence for different coagulation proteins, reflecting the unique effect of different Chinese medicinals and the biological basis. Therefore, this study can provide clues for precision application of Angelicae Sinensis Radix and the development of the blood-activating components with modern technology.

An Efficient Closed Form Solution to the Absolute Orientation Problem for Camera with Unknown Focal Length.

In this paper we propose an efficient closed form solution to the absolute orientation problem for cameras with an unknown focal length, from two 2D-3D point correspondences and the camera position. The problem can be decomposed into two simple sub-problems and can be solved with angle constraints. A polynomial equation of one variable is solved to determine the focal length, and then a geometric approach is used to determine the absolute orientation. The geometric derivations are easy to understand and significantly improve performance. Rewriting the camera model with the known camera position leads to a simpler and more efficient closed form solution, and this gives a single solution, without the multi-solution phenomena of perspective-three-point (P3P) solvers. Experimental results demonstrated that our proposed method has a better performance in terms of numerical stability, noise sensitivity, and computational speed, with synthetic data and real images.

AMG 580: a novel small molecule phosphodiesterase 10A (PDE10A) positron emission tomography tracer.

Phosphodiesterase 10A (PDE10A) inhibitors have therapeutic potential for the treatment of psychiatric and neurologic disorders, such as schizophrenia and Huntington's disease. One of the key requirements for successful central nervous system drug development is to demonstrate target coverage of therapeutic candidates in brain for lead optimization in the drug discovery phase and for assisting dose selection in clinical development. Therefore, we identified AMG 580 [1-(4-(3-(4-(1H-benzo[d]imidazole-2-carbonyl)phenoxy)pyrazin-2-yl)piperidin-1-yl)-2-fluoropropan-1-one], a novel, selective small-molecule antagonist with subnanomolar affinity for rat, primate, and human PDE10A. We showed that AMG 580 is suitable as a tracer for lead optimization to determine target coverage by novel PDE10A inhibitors using triple-stage quadrupole liquid chromatography-tandem mass spectrometry technology. [(3)H]AMG 580 bound with high affinity in a specific and saturable manner to both striatal homogenates and brain slices from rats, baboons, and human in vitro. Moreover, [(18)F]AMG 580 demonstrated prominent uptake by positron emission tomography in rats, suggesting that radiolabeled AMG 580 may be suitable for further development as a noninvasive radiotracer for target coverage measurements in clinical studies. These results indicate that AMG 580 is a potential imaging biomarker for mapping PDE10A distribution and ensuring target coverage by therapeutic PDE10A inhibitors in clinical studies.

All-Organic PTFE Coated PVDF Composite Film Exhibiting Low Conduction Loss and High Breakdown Strength for Energy Storage Applications.

Plastic film capacitors are widely used in pulse and energy storage applications because of their high breakdown strength, high power density, long lifetime, and excellent self-healing properties. Nowadays, the energy storage density of commercial biaxially oriented polypropylene (BOPP) is limited by its low dielectric constant (~2.2). Poly(vinylidene fluoride) (PVDF) exhibits a relatively high dielectric constant and breakdown strength, making it a candidate material for electrostatic capacitors. However, PVDF presents significant losses, generating a lot of waste heat. In this paper, under the guidance of the leakage mechanism, a high-insulation polytetrafluoroethylene (PTFE) coating is sprayed on the surface of a PVDF film. The potential barrier at the electrode-dielectric interface is raised by simply spraying PTFE and reducing the leakage current, and then the energy storage density is increased. After introducing the PTFE insulation coating, the high-field leakage current in the PVDF film shows an order of magnitude reduction. Moreover, the composite film presents a 30.8% improvement in breakdown strength, and a 70% enhancement in energy storage density is simultaneously achieved. The all-organic structure design provides a new idea for the application of PVDF in electrostatic capacitors.

Deep learning-based single-shot autofocus method for digital microscopy.

Digital pathology is being transformed by artificial intelligence (AI)-based pathological diagnosis. One major challenge for correct AI diagnoses is to ensure the focus quality of captured images. Here, we propose a deep learning-based single-shot autofocus method for microscopy. We use a modified MobileNetV3, a lightweight network, to predict the defocus distance with a single-shot microscopy image acquired at an arbitrary image plane without secondary camera or additional optics. The defocus prediction takes only 9 ms with a focusing error of only ∼1/15 depth of field. We also provide implementation examples for the augmented reality microscope and the whole slide imaging (WSI) system. Our proposed technique can perform real-time and accurate autofocus which will not only support pathologists in their daily work, but also provide potential applications in the life sciences, material research, and industrial automatic detection.

[The relationships between different surgical approaches for maxillary sinus augmentation and implant failure and complications: a retrospective cohort study].

PURPOSE: To investigate the 5-year survival and complication rates of implants placed in grafted sinuses with different surgical approaches and analyze the causes for failure. METHODS: This study retrospectively observed the prognosis of patients who underwent maxillary sinus augmentation by means of lateral window technique(LWT) or transalveolar osteotomy technique (TOT) and simultaneously installed implants performed, in Hefei Stomatological Hospital. The primary predictor variables were surgical approaches, including LWT and TOT. The primary outcome measurement was the 5-year implant survival rate, complication rates and failure causes. Potential confounders included diabetes, age at surgery, gender, smoking habit, oral hygiene, tooth position, length and diameter of implants and type of prosthesis. Chi-square test and logistic regression analysis were performed with SPSS 21.0 software package. RESULTS: Fifty-nine patients (31 males and 28 females), installed with 93 implants, with a mean age of (61.3±10.1) years old, were enrolled. Over (5±1.2) years of follow-up, five implants failed, with a total survival rate of 94.6%. In detail, there were 3 failed implants in the LWT group and 2 failed implants in the TOT group, for a survival rate of 85.7% and 97.2%, respectively. Chi-square test showed that smoking habit (P=0.010), oral hygiene(P=0.037) as well as operative approach(P=0.040) were significantly associated with the final survival rates, multivariate logistic regression analysis displayed that smoking habit (OR=0.030, 95%CI: 0.002-0.493, P=0.014) was still associated with the finial survival rates. Surgical approach(P=0.025) was markedly related to causes for the failed implants. Of which, three (100%) failed implants in the LWT group was due to poor osseointegration and implant mobility 3 months after sinus augmentation, and 2(100%) in the TOT group was because of persistent peri-implantitis and loss of the graft or alveolar bone 4 years after sinus augmentation. Smoking habit was also significantly relevant to complication rates(P=0.014), and the occurrence incidence of controllable peri-implantitis in patient having a smoking habit was relatively higher, accounting for 6.8%(6/88), compared with patients without smoking habit. Significant relationship between surgical approaches and implant complications was not observed(P=0.051). CONCLUSIONS: Different surgical approaches for maxillary sinus augmentation do not significantly correlate with implant survival rates and implant complications. However, surgical approach is markedly related to the causes of failed implants. Smoking will lead to a decreased implant survival rate and controllable peri-implantitis.

Cervical cytology screening facilitated by an artificial intelligence microscope: A preliminary study.

BACKGROUND: Cervical cytology screening is usually laborious with a heavy workload and poor diagnostic consistency. The authors have developed an artificial intelligence (AI) microscope that can provide onsite diagnostic assistance for cervical cytology screening in real time. METHODS: A total of 2167 cervical cytology slides were selected from a cohort of 10,601 cases from Shenzhen Maternity and Child Healthcare Hospital, and the training data set consisted of 42,073 abnormal cervical epithelial cells. The recognition results of an AI technique were presented in a microscope eyepiece by an augmented reality technique. Potentially abnormal cells were highlighted with binary classification results in a 10× field of view (FOV) and with multiclassification results according to the Bethesda system in 20× and 40× FOVs. In addition, 486 slides were selected for the reader study to evaluate the performance of the AI microscope. RESULTS: In the reader study, which compared manual reading with AI assistance, the sensitivities for the detection of low-grade squamous intraepithelial lesions and high-grade squamous intraepithelial lesions were significantly improved from 0.837 to 0.923 (P < .001) and from 0.830 to 0.917 (P < .01), respectively; the κ score for atypical squamous cells of undetermined significance (ASCUS) was improved from 0.581 to 0.637; the averaged pairwise κ of consistency for multiclassification was improved from 0.649 to 0.706; the averaged pairwise κ of consistency for binary classification was improved from 0.720 to 0.798; and the averaged pairwise κ of ASCUS was improved from 0.557 to 0.639. CONCLUSIONS: The results of this study show that an AI microscope can provide real-time assistance for cervical cytology screening and improve the efficiency and accuracy of cervical cytology diagnosis.

[Different concentration of lidocaine used for an exodontia of the impacted mandibular third molar].

PURPOSE: To investigate the anesthesia outcomes of 1% lidocaine with 1∶100 000 epinephrine (EPI) for inferior alveolar nerve, lingual nerve and buccal nerve block, compared with 2% lidocaine with 1∶100 000 EPI. METHODS: A study with a cross-over design, with each patient also serving as their own control, was implemented to estimate the clinical outcomes. Predictor variable was 1% lidocaine with 1∶100 000 EPI versus 2% lidocaine with 1∶100 000 EPI. Outcome variables were patients' responses to pain on injection, onset time of anesthetizing, efficacy of anesthesia, and the time to sensation return for the lower lip and tongue. Patients reported pain level at every experimental stage with a 10-point Numerical Rating Scale(NRS). Three weeks later, the patients were tested with the alternate drug combinations. The same outcomes were assessed. A verification of treatment difference was performed using SPSS 17.0 software package. RESULTS: Twenty-one patients were recruited and completed the study protocol. Sixty-two percent of the patients were women and 38% were men with a median age of 24 years [interquartile range (IQR), 20-30 yr]. Patients reported significantly lower pain scores with 1% lidocaine (1.09,95%CI，0.77-1.41) on injection, compared with 2% lidocaine (1.66, 95%CI, 1.33-1.99) (P=0.010). Patients undergoing 1% lidocaine with 1∶100 000 EPI (52-63 s) had a markedly quicker onset time of anesthetizing than those using 2% lidocaine with 1∶100 000 EPI (259-335 s, P=0.000). The efficacy of anesthesia between 2 groups was not significantly different (P=0.751). Among the patients with the pain values of 1~3, there were 9 patients(100%) perceiving slight pain when splitting teeth was performed in 1% lidocaine group, while 4 patients(57%) felt slight pain when elevating soft flaps was performed and 3 patients(43%) perceived mild pain when splitting teeth was performed in 2% lidocaine group (P=0.019). The time to sensation return for the lower lip and tongue was significantly different between the 2 drug formulations (P=0.000), with an extended period of average 61 min (52-69 min) in 2% lidocaine group. CONCLUSIONS: 1% lidocaine with EPI plays a similar role in clinical outcomes for inferior alveolar nerve, lingual nerve and buccal nerve block as 2% lidocaine with EPI, which produces lower pain on injection as well as a relatively short time to sensation return. The reasons for slight pain during surgical operation are a relative lower efficacy of anesthesia on the inferior alveolar nerve in 1% lidocaine group, and on the buccal nerve anesthesia in 2% lidocaine group.

Design and development of compact coaxial to coplanar waveguide directional coupler for HPM measurement.

A compact, high-directivity, weak-coupling directional coupler with coaxial-coplanar waveguide structure and diamond-shaped coupling slot was developed at L band for a high-power microwave measurement by both theoretical analysis and experiments. The relation between the dimension of the coupling slot and the characteristic parameters of the coupler was studied by the small-hole coupling theory and the infinitesimal method. According to the analysis results, the directivity could be better than 20 dB while the length of the slot is just less than a single λ because of the use of the diamond coupling slot. For demonstration, a 45-dB L band coaxial-coplanar waveguide directional coupler was designed and verified by test. The experiment results and the theoretical analysis are in good agreement, which indicates that in the range of 1-2 GHz, the coupling was approximately -45 dB and the directivity was better than 17 dB. The power-handling capacity was demonstrated to reach 2 MW with a length (150 mm) of less than λ and a cross section (46 mm × 55 mm) of less than one-twelfth of the BJ-14 waveguide directional coupler.

Research on calorimeter for high-power microwave measurements.

Based on measurement of the volume increment of polar liquid that is a result of heating by absorbed microwave energy, two types of calorimeters with coaxial capacitive probes for measurement of high-power microwave energy are designed in this paper. The first is an "inline" calorimeter, which is placed as an absorbing load at the end of the output waveguide, and the second is an "offline" calorimeter that is placed 20 cm away from the radiation horn of the high-power microwave generator. Ethanol and high density polyethylene are used as the absorbing and housing materials, respectively. Results from both simulations and a "cold test" on a 9.3 GHz klystron show that the "inline" calorimeter has a measurement range of more than 100 J and an energy absorption coefficient of 93%, while the experimental results on a 9.3 GHz relativistic backward-wave oscillator show that the device's power capacity is approximately 0.9 GW. The same experiments were also carried out for the "offline" calorimeter, and the results indicate that it can be used to eliminate the effects of the shock of the solenoid on the measurement curves and that the device has a higher power capacity of 2.5 GW. The results of the numerical simulations, the "cold tests," and the experiments show good agreement.

[The automatic iris map overlap technology in computer-aided iridiagnosis].

In the paper, iridology and computer-aided iridiagnosis technologies are briefly introduced and the extraction method of the collarette contour is then investigated. The iris map can be overlapped on the original iris image based on collarette contour extraction. The research on collarette contour extraction and iris map overlap is of great importance to computer-aided iridiagnosis technologies.

Automated movement correction for dynamic PET/CT images: evaluation with phantom and patient data.

Head movement during a dynamic brain PET/CT imaging results in mismatch between CT and dynamic PET images. It can cause artifacts in CT-based attenuation corrected PET images, thus affecting both the qualitative and quantitative aspects of the dynamic PET images and the derived parametric images. In this study, we developed an automated retrospective image-based movement correction (MC) procedure. The MC method first registered the CT image to each dynamic PET frames, then re-reconstructed the PET frames with CT-based attenuation correction, and finally re-aligned all the PET frames to the same position. We evaluated the MC method's performance on the Hoffman phantom and dynamic FDDNP and FDG PET/CT images of patients with neurodegenerative disease or with poor compliance. Dynamic FDDNP PET/CT images (65 min) were obtained from 12 patients and dynamic FDG PET/CT images (60 min) were obtained from 6 patients. Logan analysis with cerebellum as the reference region was used to generate regional distribution volume ratio (DVR) for FDDNP scan before and after MC. For FDG studies, the image derived input function was used to generate parametric image of FDG uptake constant (Ki) before and after MC. Phantom study showed high accuracy of registration between PET and CT and improved PET images after MC. In patient study, head movement was observed in all subjects, especially in late PET frames with an average displacement of 6.92 mm. The z-direction translation (average maximum = 5.32 mm) and x-axis rotation (average maximum = 5.19 degrees) occurred most frequently. Image artifacts were significantly diminished after MC. There were significant differences (P<0.05) in the FDDNP DVR and FDG Ki values in the parietal and temporal regions after MC. In conclusion, MC applied to dynamic brain FDDNP and FDG PET/CT scans could improve the qualitative and quantitative aspects of images of both tracers.

Factors affecting tumor (18) F-FDG uptake in longitudinal mouse PET studies.

BACKGROUND: Many biological factors of 2-[(18) F]fluoro-2-deoxy-d-glucose ((18) F-FDG) in blood can affect (18) F-FDG uptake in tumors. In this study, longitudinal (18) F-FDG positron emission tomography (PET) studies were performed on tumor-bearing mice to investigate the effect of blood glucose level and tumor size on (18) F-FDG uptake in tumors. METHODS: Six- to eight-week-old severe combined immunodeficiency mice were implanted with glioblastoma U87 (n = 8) or adenocarcinoma MDA-MB-231 (MDA) (n = 11) in the shoulder. When the tumor diameter was approximately 2.5 mm, a 60-min dynamic (18) F-FDG PET scan was performed weekly until the tumor diameter reached 10 mm. Regions of interests were defined in major organs and tumor. A plasma curve was derived based on a modeling method that utilizes the early heart time-activity curve and a late-time blood sample. The (18) F-FDG uptake constant K i was calculated using Patlak analysis on the tumors without an apparent necrotic center shown in the PET images. For each tumor type, the measured K i was corrected for partial volume (PV), and multivariate regression analysis was performed to examine the effects of blood glucose level ([Glc]) and tumor growth. Corrected Akaike's information criterion was used to determine the best model. RESULTS: The regression model that best fit the PV-corrected K i for U87 data was K i /RC = (1/[Glc]) × (0.27 ± 0.027) mL/min/mL (where [Glc] is in mmol/L), and for MDA, it was K i /RC = (0.04 ± 0.005) mL/min/mL, where K i /RC denotes the PV-corrected K i using an individual recovery coefficient (RC). The results indicated that (18) F-FDG K i /RC for U87 was inversely related to [Glc], while [Glc] had no effect on (18) F-FDG K i /RC of MDA. After the effects of PV and [Glc] were accounted for, the data did not support any increase of (18) F-FDG K i as the tumor (of either type) grew larger in size. CONCLUSIONS: The effect of [Glc] on the tumor (18) F-FDG K i was tumor-dependent. PV- and [Glc]-corrected (18) F-FDG K i did not show significant increase as the tumor of either type grew in size.

Bacteriophage Associated Silicon Particles: Design and Characterization of a Novel Theranostic Vector with Improved Payload Carrying Potential.

There has been extensive research on the use of nanovectors for cancer therapy. Targeted delivery of nanotherapeutics necessitates two important characteristics; the ability to accumulate at the disease locus after overcoming sequential biological barriers and the ability to carry a substantial therapeutic payload. Successful combination of the above two features is challenging, especially in solid porous materials where chemical conjugation of targeting entities on the particle surface will generally prevent successful loading of the therapeutic substance. In this study, we propose a novel strategy for decorating the surface of mesoporous silicon particles with targeting entities (bacteriophage) and gold nanoparticles (AuNP) while maintaining their payload carrying potential. The resulting Bacteriophage Associated Silicon Particles (BASP) demonstrates efficient encapsulation of macromolecules and therapeutic nanoparticles into the porous structures. In vitro targeting data show enhanced targeting efficiency with about four orders of magnitude lower concentration of bacteriophage. In vivo targeting data suggest that BASP maintain their integrity following intravenous administration in mice and display up to three fold higher accumulation in the tumor.

Calmodulin increases Ca-dependent inhibition of the Na,K-ATPase in human red blood cells.

Proteins in human red cell hemolysate were purified to determine which of them increase inhibition of the Na,K-ATPase in the presence of 2 microM free Ca. Samples purified 600,000-fold inhibited the Na,K-ATPase of human red cells in a Ca-dependent manner and stimulated the (Ca+Mg)-ATPase. These samples contained two proteins as analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE): calmodulin (18,000 Mr), which comprised most (greater than 90%) of the total protein, and an unidentified protein of approximately 13,000 Mr. Both proteins were a distinctive light yellow when stained with silver. Calmodulin from bovine testes also inhibited the Na,K-ATPase and stimulated the (Ca+Mg)-ATPase. This preparation also contained two proteins as analyzed by SDS-PAGE: calmodulin (95 to 99% of the total protein) and another protein of approximately 13,000 Mr (1 to 5% of the total protein). Both were light yellow when stained with silver. Since the amount of red cell protein was limited, the remainder of the study was carried out with the bovine testes preparation. Heating the testes preparation decreased, but did not abolish, inhibition of the Na,K-ATPase and reduced stimulation of the (Ca+Mg)-ATPase. When corrected for denatured calmodulin, both heated and unheated proteins increased inhibition of the Na,K-ATPase to the same extent. The Na,K-ATPase was inhibited at 2 microM free Ca in a dose-dependent manner over a range of 15 to 100 nM calmodulin. To establish if the inhibition was due to the calmodulin or the 13,000 Mr protein, both were electroeluted after SDS-PAGE. Electroeluted calmodulin stimulated the (Ca+Mg)-ATPase and increased Ca inhibition of the Na,K-ATPase. Electroeluted amounts of the smaller Mr protein slightly stimulated the (Ca+Mg)-ATPase, but had no effect on the Na,K-ATPase. This protein was digested with cyanogen bromide, partially sequenced, and thereby identified as a fragment of calmodulin. We conclude that intact calmodulin increases inhibition of the Na,K-ATPase at 2 microM free Ca. We suggest that calmodulin is part of a mechanism mediating the effects of physiological free Ca on the Na,K-ATPase.