Nosocomial pneumonia: Search for an empiric and effective antibiotic regimen in high burden tertiary care centre.

PubMed

Gupta, Nitin; Soneja, Manish; Ray, Yogiraj; Sahu, Monalisa; Vinod, Kutty Sharada; Kapil, Arti; Biswas, Ashutosh; Wig, Naveet; Sood, Rita

2018-05-13

The clinical practice guidelines on nosocomial pneumonia recommends an empirical regimen that would work in 95% of the patients based on the local antibiogram. The aim of the study was development of an antibiogram for guiding empiric therapy in settings with high prevalence of multi-drug resistant organisms. A retrospective review of electronic health records (e-hospital portal) was done to analyze all respiratory isolates from patients admitted in medical wards and intensive care unit between May 2016 and May 2017. The samples included brocho-alveolar lavage (BAL), mini broncho-alveolar lavage (mini-BAL) and endotracheal aspirate. The sensitivity pattern (combined and individual) of all bacterial isolates were analysed for commonly used antibiotics and their combinations. Out of the 269 isolates, the most common organisms were Pseudomonas aeruginosa (125, 46%), Acinetobacter baumanni (74, 27%) and Klebsiella pneumoniae (50, 19%). Cefoperazone-sulbactam (43%) had the best sensitivity pattern overall. Cefoperazone-sulbactam plus amikacin (56%) was the combination with the best combined sensitivity overall. There is a high prevalence of resistance in the commonly implicated organisms to the available antibiotics. There is an urgent need for implementation of effective anti-microbial stewardship programmes and development of newer antimicrobials.

Ultra-sensitive magnetic microscopy with an optically pumped magnetometer

DOE PAGES

Kim, Young Jin; Savukov, Igor Mykhaylovich

2016-04-22

Optically pumped magnetometers (OPMs) based on lasers and alkali-metal vapor cells are currently the most sensitive non-cryogenic magnetic field sensors. Many applications in neuroscience and other fields require high-resolution, high-sensitivity magnetic microscopic measurements. In order to meet this demand we combined a cm-size spin-exchange relaxation-free (SERF) OPM and flux guides (FGs) to realize an ultra-sensitive FG-OPM magnetic microscope. The FGs serve to transmit the target magnetic flux to the OPM thus improving both the resolution and sensitivity to small magnetic objects. We investigated the performance of the FG-OPM device using experimental and numerical methods, and demonstrated that an optimized devicemore » can achieve a unique combination of high resolution (80 μm) and high sensitivity (8.1 pT/). Additionally, we also performed numerical calculations of the magnetic field distribution in the FGs to estimate the magnetic noise originating from the domain fluctuations in the material of the FGs. We anticipate many applications of the FG-OPM device such as the detection of micro-biological magnetic fields; the detection of magnetic nano-particles; and non-destructive testing. From our theoretical estimate, an FG-OPM could detect the magnetic field of a single neuron, which would be an important milestone in neuroscience.« less

Ultra-sensitive Magnetic Microscopy with an Optically Pumped Magnetometer

NASA Astrophysics Data System (ADS)

Kim, Young Jin; Savukov, Igor

2016-04-01

Optically pumped magnetometers (OPMs) based on lasers and alkali-metal vapor cells are currently the most sensitive non-cryogenic magnetic field sensors. Many applications in neuroscience and other fields require high-resolution, high-sensitivity magnetic microscopic measurements. In order to meet this demand we combined a cm-size spin-exchange relaxation-free (SERF) OPM and flux guides (FGs) to realize an ultra-sensitive FG-OPM magnetic microscope. The FGs serve to transmit the target magnetic flux to the OPM thus improving both the resolution and sensitivity to small magnetic objects. We investigated the performance of the FG-OPM device using experimental and numerical methods, and demonstrated that an optimized device can achieve a unique combination of high resolution (80 μm) and high sensitivity (8.1 pT/). In addition, we also performed numerical calculations of the magnetic field distribution in the FGs to estimate the magnetic noise originating from the domain fluctuations in the material of the FGs. We anticipate many applications of the FG-OPM device such as the detection of micro-biological magnetic fields; the detection of magnetic nano-particles; and non-destructive testing. From our theoretical estimate, an FG-OPM could detect the magnetic field of a single neuron, which would be an important milestone in neuroscience.

Ultra-sensitive magnetic microscopy with an optically pumped magnetometer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, Young Jin; Savukov, Igor Mykhaylovich

Optically pumped magnetometers (OPMs) based on lasers and alkali-metal vapor cells are currently the most sensitive non-cryogenic magnetic field sensors. Many applications in neuroscience and other fields require high-resolution, high-sensitivity magnetic microscopic measurements. In order to meet this demand we combined a cm-size spin-exchange relaxation-free (SERF) OPM and flux guides (FGs) to realize an ultra-sensitive FG-OPM magnetic microscope. The FGs serve to transmit the target magnetic flux to the OPM thus improving both the resolution and sensitivity to small magnetic objects. We investigated the performance of the FG-OPM device using experimental and numerical methods, and demonstrated that an optimized devicemore » can achieve a unique combination of high resolution (80 μm) and high sensitivity (8.1 pT/). Additionally, we also performed numerical calculations of the magnetic field distribution in the FGs to estimate the magnetic noise originating from the domain fluctuations in the material of the FGs. We anticipate many applications of the FG-OPM device such as the detection of micro-biological magnetic fields; the detection of magnetic nano-particles; and non-destructive testing. From our theoretical estimate, an FG-OPM could detect the magnetic field of a single neuron, which would be an important milestone in neuroscience.« less

Highly sensitive MicroRNA 146a detection using a gold nanoparticle-based CTG repeat probing system and isothermal amplification.

PubMed

Le, Binh Huy; Seo, Young Jun

2018-01-25

We have developed a gold nanoparticle (AuNP)-based CTG repeat probing system displaying high quenching capability and combined it with isothermal amplification for the detection of miRNA 146a. This method of using a AuNP-based CTG repeat probing system with isothermal amplification allowed the highly sensitive (14 aM) and selective detection of miRNA 146a. A AuNP-based CTG repeat probing system having a hairpin structure and a dT F fluorophore exhibited highly efficient quenching because the CTG repeat-based stable hairpin structure imposed a close distance between the AuNP and the dT F residue. A small amount of miRNA 146a induced multiple copies of the CAG repeat sequence during rolling circle amplification; the AuNP-based CTG repeat probing system then bound to the complementary multiple-copy CAG repeat sequence, thereby inducing a structural change from a hairpin to a linear structure with amplified fluorescence. This AuNP-based CTG probing system combined with isothermal amplification could also discriminate target miRNA 146a from one- and two-base-mismatched miRNAs (ORN 1 and ORN 2, respectively). This simple AuNP-based CTG probing system, combined with isothermal amplification to induce a highly sensitive change in fluorescence, allows the detection of miRNA 146a with high sensitivity (14 aM) and selectivity. Copyright © 2017 Elsevier B.V. All rights reserved.

A fluorescence high throughput screening method for the detection of reactive electrophiles as potential skin sensitizers

USDA-ARS?s Scientific Manuscript database

Skin sensitization is an important toxicological end-point in the risk assessment of chemical allergens. Because of the complexity of the biological mechanisms associated with skin sensitization integrated approaches combining different chemical, biological and in silico methods are recommended to r...

Ultra-long high-sensitivity Φ-OTDR for high spatial resolution intrusion detection of pipelines.

PubMed

Peng, Fei; Wu, Han; Jia, Xin-Hong; Rao, Yun-Jiang; Wang, Zi-Nan; Peng, Zheng-Pu

2014-06-02

An ultra-long phase-sensitive optical time domain reflectometry (Φ-OTDR) that can achieve high-sensitivity intrusion detection over 131.5km fiber with high spatial resolution of 8m is presented, which is the longest Φ-OTDR reported to date, to the best of our knowledge. It is found that the combination of distributed Raman amplification with heterodyne detection can extend the sensing distance and enhances the sensitivity substantially, leading to the realization of ultra-long Φ-OTDR with high sensitivity and spatial resolution. Furthermore, the feasibility of applying such an ultra-long Φ-OTDR to pipeline security monitoring is demonstrated and the features of intrusion signal can be extracted with improved SNR by using the wavelet detrending/denoising method proposed.

Pleural effusion biomarkers and computed tomography findings in diagnosing malignant pleural mesothelioma: A retrospective study in a single center.

PubMed

Otoshi, Takehiro; Kataoka, Yuki; Ikegaki, Shunkichi; Saito, Emiko; Matsumoto, Hirotaka; Kaku, Sawako; Shimada, Masatoshi; Hirabayashi, Masataka

2017-01-01

In this study, we aimed to examine the clinical value of the pleural effusion (PE) biomarkers, soluble mesothelin-related peptide (SMRP), cytokeratin 19 fragment (CYFRA 21-1) and carcinoembryonic antigen (CEA), and the utility of combining chest computed tomography (CT) findings with these biomarkers, in diagnosing malignant pleural mesothelioma (MPM). We conducted a retrospective cohort study in a single center. Consecutive patients with undiagnosed pleural effusions who underwent PE analysis between September 2014 and August 2016 were reviewed. This study included 240 patients (32 with MPM and 208 non-MPM). SMRP and the CYFRA 21-1/CEA ratio had a sensitivity and specificity for diagnosing MPM of 56.3% and 86.5%, and 87.5% and 74.0%, respectively. Using receiver operating characteristics (ROC) curve analysis of the ability of these markers to distinguish MPM from all other PE causes, the area under the ROC curve (AUC) for SMRP and the CYFRA 21-1/CEA ratio was 0.804 and 0.874, respectively. The sensitivity and specificity of SMRP combined with the CYFRA 21-1/CEA ratio were 93.8% and 64.9%, respectively. The sensitivity of the combination of SMRP, the CYFRA 21-1/CEA ratio, and the presence of Leung's criteria (a chest CT finding that is suggestive of malignant pleural disease) was 93.8%. In conclusion, the combined PE biomarkers had a high sensitivity for diagnosing MPM, although the addition of chest CT findings did not improve the sensitivity of SMRP combined with the CYFRA 21-1/CEA ratio. Combination of these biomarkers helped to rule out MPM effectively among patients at high risk of suffering MPM and would be valuable especially for old frail patients who have difficulty in undergoing invasive procedures such as thoracoscopy.

Sensitivity of Amoxicillin-Resistant Helicobacter pylori to Other Penicillins

PubMed Central

Dore, Maria P.; Graham, David Y.; Sepulveda, Antonia R.; Realdi, Giuseppe; Osato, Michael S.

1999-01-01

The sensitivities to penicillins and to a penicillin and β-lactamase inhibitor combination agent were determined for Helicobacter pylori strains that were sensitive, moderately resistant, or highly resistant to amoxicillin. All strains were resistant to nafcillin and oxacillin. Moderately resistant strains showed an intermediate zone of inhibition to ticarcillin, mezlocillin, piperacillin, and amoxicillin-clavulanic acid. High-level resistance was associated with the smallest zone size for all penicillins tested. PMID:10390249

Probing TeV scale top-philic resonances with boosted top-tagging at the high luminosity LHC

DOE PAGES

Kim, Jeong Han; Kong, Kyoungchul; Lee, Seung J.; ...

2016-08-24

Here, we investigate the discovery potential of singly produced top-philic resonances at the high luminosity (HL) LHC in the four-top final state. Our analysis spans over the fully-hadronic, semi-leptonic, and same-sign dilepton channels where we present concrete search strategies adequate to a boosted kinematic regime and high jet-multiplicity environments. We utilize the Template Overlap Method (TOM) with newly developed template observables for tagging boosted top quarks, a large-radius jet variablemore » $$M_J$$ and customized b-tagging tactics for background discrimination. Our results show that the same-sign dilepton channel gives the best sensitivity among the considered channels, with an improvement of significance up to 10%-20% when combined with boosted-top tagging. Both the fully-hadronic and semi-leptonic channels yield comparable discovery potential and contribute to further enhancements in the sensitivity by combining all channels. Finally, we show the sensitivity of a top-philic resonance at the LHC and HL-LHC by showing the $$2\\sigma$$ exclusion limit and $$5\\sigma$$ discovery reach, including a combination of all three channels.« less

Multiplex detection of microRNAs by combining molecular beacon probes with T7 exonuclease-assisted cyclic amplification reaction.

PubMed

Liu, Yacui; Zhang, Jiangyan; Tian, Jingxiao; Fan, Xiaofei; Geng, Hao; Cheng, Yongqiang

2017-01-01

A simple, highly sensitive, and specific assay was developed for the homogeneous and multiplex detection of microRNAs (miRNAs) by combining molecular beacon (MB) probes and T7 exonuclease-assisted cyclic amplification. An MB probe with five base pairs in the stem region without special modification can effectively prevent the digestion by T7 exonuclease. Only in the presence of target miRNA is the MB probe hybridized with the target miRNA, and then digested by T7 exonuclease in the 5' to 3' direction. At the same time, the target miRNA is released and subsequently initiates the nuclease-assisted cyclic digestion process, generating enhanced fluorescence signal significantly. The results show that the combination of T7 exonuclease-assisted cyclic amplification reaction and MB probe possesses higher sensitivity for miRNA detection. Moreover, multiplex detection of miRNAs was successfully achieved by designing two MB probes labeled with FAM and Cy3, respectively. As a result, the method opens a new pathway for the sensitive and multiplex detection of miRNAs as well as clinical diagnosis. Graphical Abstract A simple, highly sensitive, and specific assay was developed for the detection of microRNAs by combining molecular beacon probes with T7 exonuclease-assisted cyclic amplification reaction.

A highly sensitive and specific combined clinical and sonographic score to diagnose appendicitis.

PubMed

Reddy, Swathi B; Kelleher, Michael; Bokhari, S A Jamal; Davis, Kimberly A; Schuster, Kevin M

2017-10-01

Computed tomography (CT) scanning reduces the negative appendectomy rate however it exposes the patient to ionizing radiation. Ultrasound (US) does not carry this risk but may be nondiagnostic. We hypothesized that a clinical-US scoring system would improve diagnostic accuracy. We conducted a retrospective review of all patients (age, >15 years) who presented through the emergency department with suspected appendicitis and underwent initial US. A US score was developed using odds ratios for appendicitis given appendiceal diameter, compressibility, hyperemia, free fluid, and focal or diffuse tenderness. The US score was then combined with the Alvarado score. Final diagnosis of appendicitis was assigned by pathology reports. Three hundred patients who underwent US as initial imaging were identified. Thirty-two patients with evident nonappendiceal pathology on US were excluded. In 114 (38%), the appendix was not visualized and partially visualized in 36 (12%). Fifty-seven (21.3%) had an appendectomy with 1 (1.7%) negative. Six nonvisualized appendicies underwent appendectomy, with no negative cases. Sensitivity and specificity for the sonographic score were 86% and 90%, respectively, at a score of 1.5. The combined score demonstrated 98% sensitivity and 82% specificity at 6.5, and 95% sensitivity, and 87% specificity at a score of 7.5. Sensitivity and specificity were confirmed by bootstrap resampling for validation. Area under receiver operating characteristic (ROC) curves for our new US score were similar to the ROC curve for the Alvarado score (91.9 and 91.1, p = 0.8). The combined US and Alvarado score yielded an area under the ROC curve of 97.1, significantly better than either score alone (p = 0.017 and p < 0.001, respectively). Our scoring system based entirely on US findings was highly sensitive and specific for appendicitis, and it significantly improved when combined with the Alvarado score. After prospective evaluation, the combined US-Alvarado score might replace the need for computed tomography imaging in a majority of patients. Diagnostic Test, Level III.

Single High-Sensitivity Cardiac Troponin I to Rule Out Acute Myocardial Infarction.

PubMed

Sandoval, Yader; Smith, Stephen W; Love, Sara A; Sexter, Anne; Schulz, Karen; Apple, Fred S

2017-09-01

This study examined the performance of single high-sensitivity cardiac troponin I (hs-cTnI) measurement strategies to rule out acute myocardial infarction. This was a prospective, observational study of consecutive patients presenting to the emergency department (n = 1631) in whom cTnI measurements were obtained using an investigational hs-cTnI assay. The goals of the study were to determine 1) negative predictive value (NPV) and sensitivity for the diagnosis of acute myocardial infarction, type 1 myocardial infarction, and type 2 myocardial infarction; and 2) safety outcome of acute myocardial infarction or cardiac death at 30 days using hs-cTnI less than the limit of detection (LoD) (<1.9 ng/L) or the High-STEACS threshold (<5 ng/L) alone and in combination with normal electrocardiogram (ECG). Acute myocardial infarction occurred in 170 patients (10.4%), including 68 (4.2%) type 1 myocardial infarction and 102 (6.3%) type 2 myocardial infarction. For hs-cTnI

Brief assessment of food insecurity accurately identifies high-risk US adults.

PubMed

Gundersen, Craig; Engelhard, Emily E; Crumbaugh, Amy S; Seligman, Hilary K

2017-06-01

To facilitate the introduction of food insecurity screening into clinical settings, we examined the test performance of two-item screening questions for food insecurity against the US Department of Agriculture's Core Food Security Module. We examined sensitivity, specificity and accuracy of various two-item combinations of questions assessing food insecurity in the general population and high-risk population subgroups. 2013 Current Population Survey December Supplement, a population-based US survey. All survey participants from the general population and high-risk subgroups. The test characteristics of multiple two-item combinations of questions assessing food insecurity had adequate sensitivity (>97 %) and specificity (>70 %) for widespread adoption as clinical screening measures. We recommend two specific items for clinical screening programmes based on their widespread current use and high sensitivity for detecting food insecurity. These items query how often the household 'worried whether food would run out before we got money to buy more' and how often 'the food that we bought just didn't last and we didn't have money to get more'. The recommended items have sensitivity across high-risk population subgroups of ≥97 % and a specificity of ≥74 % for food insecurity.

Behavioral Control and Reward Sensitivity in Adolescents' Risk Taking Behavior: A Longitudinal TRAILS Study.

PubMed

Peeters, Margot; Oldehinkel, Tineke; Vollebergh, Wilma

2017-01-01

Neurodevelopmental theories of risk behavior hypothesize that low behavioral control in combination with high reward sensitivity explains adolescents' risk behavior. However, empirical studies examining this hypothesis while including actual risk taking behavior in adolescence are lacking. In this study we tested whether the imbalance between behavioral control and reward sensitivity underlies risk taking behavior in adolescence, using a nationally representative longitudinal sample of 715 adolescents, of which 66% revealed an increased risk for mental health problems. To assess behavioral control at age 11 we used both self-report (effortful control) as well as behavioral measures of cognitive control (i.e., working memory and response inhibition). Reward sensitivity was assessed with the Bangor Gambling Task. The main finding of this study was that effortful control at age 11 was the best predictor of risk taking behavior (alcohol and cannabis use) at age 16, particularly among adolescents who were more reward sensitive. Risk taking behavior in adolescents might be explained by relatively weak behavioral control functioning combined with high sensitivity for reward.

Hantavirus pulmonary syndrome clinical findings: evaluating a surveillance case definition.

PubMed

Knust, Barbara; Macneil, Adam; Rollin, Pierre E

2012-05-01

Clinical cases of hantavirus pulmonary syndrome (HPS) can be challenging to differentiate from other acute respiratory diseases, which can lead to delays in diagnosis, treatment, and disease reporting. Rapid onset of severe disease occurs, at times before diagnostic test results are available. This study's objective was to examine the clinical characteristics of patients that would indicate HPS to aid in detection and reporting. Test results of blood samples from U.S. patients suspected of having HPS submitted to the Centers for Disease Control and Prevention from 1998-2010 were reviewed. Patient information collected by case report forms was compared between HPS-confirmed and test-negative patients. Diagnostic sensitivity, specificity, predictive values, and likelihood ratios were calculated for individual clinical findings and combinations of variables. Of 567 patients included, 36% were HPS-confirmed. Thrombocytopenia, chest x-rays with suggestive signs, and receiving supplemental oxygenation were highly sensitive (>95%), while elevated hematocrit was highly specific (83%) in detecting HPS. Combinations that maximized sensitivity required the presence of thrombocytopenia. Using a national sample of suspect patients, we found that thrombocytopenia was a highly sensitive indicator of HPS and should be included in surveillance definitions for suspected HPS. Using a sensitive suspect case definition to identify potential HPS patients that are confirmed by highly specific diagnostic testing will ensure accurate reporting of this disease.

Interactional Effects of Instructional Quality and Teacher Judgement Accuracy on Achievement.

ERIC Educational Resources Information Center

Helmke, Andreas; Schrader, Friedrich-Wilhelm

1987-01-01

Analysis of predictions of 32 teachers regarding 690 fifth-graders' scores on a mathematics achievement test found that the combination of high judgement accuracy with varied instructional techniques was particularly favorable to students in contrast to a combination of high diagnostic sensitivity with a low frequency of cues or individual…

Spectral sensitization of nanocrystalline solar cells

DOEpatents

Spitler, Mark T.; Ehret, Anne; Stuhl, Louis S.

2002-01-01

This invention relates to dye sensitized polycrystalline photoelectrochemical solar cells for use in energy transduction from light to electricity. It concerns the utility of highly absorbing organic chromophores as sensitizers in such cells and the degree to which they may be utilized alone and in combination to produce an efficient photoelectrochemical cell, e.g., a regenerative solar cell.

Comparison between esophagography and chest computed tomography for evaluation of leaks after esophagectomy and gastric pull-through.

PubMed

Lantos, Joshua E; Levine, Marc S; Rubesin, Stephen E; Lau, Charles T; Torigian, Drew A

2013-03-01

To assess the diagnostic performance of esophagography and chest computed tomography (CT) for detecting leaks after esophagectomy and gastric pull-through. Our database revealed 29 patients who had undergone esophagography and chest CT after esophagectomy. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for postoperative leaks were determined for esophagography and CT, separately and combined, on the basis of a retrospective image review. Patients were also stratified for esophagograms with water-soluble contrast alone versus water-soluble contrast and high-density barium and for CT with and without oral contrast. Our findings were retrospectively compared with those reported at initial image interpretation. Clinically relevant leaks were present in 14 (48%) of 29 patients after esophagectomy. Esophagography had a sensitivity of 79%, specificity of 73%, PPV of 73%, and NPV of 79% for detecting leaks, whereas CT had a sensitivity of 86%, specificity of 33%, PPV of 55%, and NPV of 71% and esophagography and CT combined had a sensitivity of 100%, specificity of 27%, PPV of 56%, and NPV of 100%. The sensitivity of esophagography increased with high-density barium, whereas the sensitivity of CT was the same with and without oral contrast agent. Finally, esophagography and CT were seen to have a higher sensitivity and lower specificity on retrospective review compared with the results reported at initial image interpretation. Esophagography had a slightly lower sensitivity and substantially higher specificity compared with CT for detecting leaks after esophagectomy, whereas esophagography and CT combined had a sensitivity of 100% for detecting leaks. Therefore, postoperative leaks can be excluded with confidence after esophagectomy when both tests are negative.

Novel fluorescent probe for highly sensitive bioassay using sequential enzyme-linked immunosorbent assay-capillary isoelectric focusing (ELISA-cIEF).

PubMed

Henares, Terence G; Uenoyama, Yuta; Nogawa, Yuto; Ikegami, Ken; Citterio, Daniel; Suzuki, Koji; Funano, Shun-ichi; Sueyoshi, Kenji; Endo, Tatsuro; Hisamoto, Hideaki

2013-06-07

This paper presents a novel rhodamine diphosphate molecule that allows highly sensitive detection of proteins by employing sequential enzyme-linked immunosorbent assay and capillary isoelectric focusing (ELISA-cIEF). Seven-fold improvement in the immunoassay sensitivity and a 1-2 order of magnitude lower detection limit has been demonstrated by taking advantage of the combination of the enzyme-based signal amplification of ELISA and the concentration of enzyme reaction products by cIEF.

Combining isothermal rolling circle amplification and electrochemiluminescence for highly sensitive point mutation detection

NASA Astrophysics Data System (ADS)

Su, Qiang; Zhou, Xiaoming

2008-12-01

Many pathogenic and genetic diseases are associated with changes in the sequence of particular genes. We describe here a rapid and highly efficient assay for the detection of point mutation. This method is a combination of isothermal rolling circle amplification (RCA) and high sensitive electrochemluminescence (ECL) detection. In the design, a circular template generated by ligation upon the recognition of a point mutation on DNA targets was amplified isothermally by the Phi29 polymerase using a biotinylated primer. The elongation products were hybridized with tris (bipyridine) ruthenium (TBR)-tagged probes and detected in a magnetic bead based ECL platform, indicating the mutation occurrence. P53 was chosen as a model for the identification of this method. The method allowed sensitive determination of the P53 mutation from wild-type and mutant samples. The main advantage of RCA-ECL is that it can be performed under isothermal conditions and avoids the generation of false-positive results. Furthermore, ECL provides a faster, more sensitive, and economical option to currently available electrophoresis-based methods.

Epi-Fluorescence Microscopy

PubMed Central

Webb, Donna J.; Brown, Claire M.

2012-01-01

Epi-fluorescence microscopy is available in most life sciences research laboratories, and when optimized can be a central laboratory tool. In this chapter, the epi-fluorescence light path is introduced and the various components are discussed in detail. Recommendations are made for incident lamp light sources, excitation and emission filters, dichroic mirrors, objective lenses, and charge-coupled device (CCD) cameras in order to obtain the most sensitive epi-fluorescence microscope. The even illumination of metal-halide lamps combined with new “hard” coated filters and mirrors, a high resolution monochrome CCD camera, and a high NA objective lens are all recommended for high resolution and high sensitivity fluorescence imaging. Recommendations are also made for multicolor imaging with the use of monochrome cameras, motorized filter turrets, individual filter cubes, and corresponding dyes that are the best choice for sensitive, high resolution multicolor imaging. Images should be collected using Nyquist sampling and should be corrected for background intensity contributions and nonuniform illumination across the field of view. Photostable fluorescent probes and proteins that absorb a lot of light (i.e., high extinction co-efficients) and generate a lot of fluorescence signal (i.e., high quantum yields) are optimal. A neuronal immune-fluorescence labeling protocol is also presented. Finally, in order to maximize the utility of sensitive wide-field microscopes and generate the highest resolution images with high signal-to-noise, advice for combining wide-field epi-fluorescence imaging with restorative image deconvolution is presented. PMID:23026996

Detection of high-risk mucosal human papillomavirus DNA in human specimens by a novel and sensitive multiplex PCR method combined with DNA microarray.

PubMed

Gheit, Tarik; Tommasino, Massimo

2011-01-01

Epidemiological and functional studies have clearly demonstrated that certain types of human papillomavirus (HPV) from the genus alpha of the HPV phylogenetic tree, referred to as high-risk (HR) types, are the etiological cause of cervical cancer. Several methods for HPV detection and typing have been developed, and their importance in clinical and epidemiological studies has been well demonstrated. However, comparative studies have shown that several assays have different sensitivities for the detection of specific HPV types, particularly in the case of multiple infections. In this chapter, we describe a novel one-shot method for the detection and typing of 19 mucosal HR HPV types (types 16, 18, 26, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66, 68, 70, 73, and 82). The assay combines the advantages of the multiplex PCR methods, i.e., high sensitivity and the possibility to perform multiple amplifications in a single reaction, with an array primer extension (APEX) assay. The latter method offers the benefits of Sanger dideoxy sequencing with the high-throughput potential of the microarray. Initial studies have revealed that the assay is very sensitive in detecting multiple HPV infections.

Highly sensitive protein detection by biospecific AFM-based fishing with pulsed electrical stimulation.

PubMed

Pleshakova, Tatyana O; Malsagova, Kristina A; Kaysheva, Anna L; Kopylov, Arthur T; Tatur, Vadim Yu; Ziborov, Vadim S; Kanashenko, Sergey L; Galiullin, Rafael A; Ivanov, Yuri D

2017-08-01

We report here the highly sensitive detection of protein in solution at concentrations from 10 -15 to 10 -18 m using the combination of atomic force microscopy (AFM) and mass spectrometry. Biospecific detection of biotinylated bovine serum albumin was carried out by fishing out the protein onto the surface of AFM chips with immobilized avidin, which determined the specificity of the analysis. Electrical stimulation was applied to enhance the fishing efficiency. A high sensitivity of detection was achieved by application of nanosecond electric pulses to highly oriented pyrolytic graphite placed under the AFM chip. A peristaltic pump-based flow system, which is widely used in routine bioanalytical assays, was employed throughout the analysis. These results hold promise for the development of highly sensitive protein detection methods using nanosensor devices.

Excitatory, inhibitory and facilitatory frequency response areas in the inferior colliculus of hearing impaired mice.

PubMed

Felix, Richard A; Portfors, Christine V

2007-06-01

Individuals with age-related hearing loss often have difficulty understanding complex sounds such as basic speech. The C57BL/6 mouse suffers from progressive sensorineural hearing loss and thus is an effective tool for dissecting the neural mechanisms underlying changes in complex sound processing observed in humans. Neural mechanisms important for processing complex sounds include multiple tuning and combination sensitivity, and these responses are common in the inferior colliculus (IC) of normal hearing mice. We examined neural responses in the IC of C57Bl/6 mice to single and combinations of tones to examine the extent of spectral integration in the IC after age-related high frequency hearing loss. Ten percent of the neurons were tuned to multiple frequency bands and an additional 10% displayed non-linear facilitation to the combination of two different tones (combination sensitivity). No combination-sensitive inhibition was observed. By comparing these findings to spectral integration properties in the IC of normal hearing CBA/CaJ mice, we suggest that high frequency hearing loss affects some of the neural mechanisms in the IC that underlie the processing of complex sounds. The loss of spectral integration properties in the IC during aging likely impairs the central auditory system's ability to process complex sounds such as speech.

Image stacking approach to increase sensitivity of fluorescence detection using a low cost complementary metal-oxide-semiconductor (CMOS) webcam.

PubMed

Balsam, Joshua; Bruck, Hugh Alan; Kostov, Yordan; Rasooly, Avraham

2012-01-01

Optical technologies are important for biological analysis. Current biomedical optical analyses rely on high-cost, high-sensitivity optical detectors such as photomultipliers, avalanched photodiodes or cooled CCD cameras. In contrast, Webcams, mobile phones and other popular consumer electronics use lower-sensitivity, lower-cost optical components such as photodiodes or CMOS sensors. In order for consumer electronics devices, such as webcams, to be useful for biomedical analysis, they must have increased sensitivity. We combined two strategies to increase the sensitivity of CMOS-based fluorescence detector. We captured hundreds of low sensitivity images using a Webcam in video mode, instead of a single image typically used in cooled CCD devices.We then used a computational approach consisting of an image stacking algorithm to remove the noise by combining all of the images into a single image. While video mode is widely used for dynamic scene imaging (e.g. movies or time-lapse photography), it is not used to capture a single static image, which removes noise and increases sensitivity by more than thirty fold. The portable, battery-operated Webcam-based fluorometer system developed here consists of five modules: (1) a low cost CMOS Webcam to monitor light emission, (2) a plate to perform assays, (3) filters and multi-wavelength LED illuminator for fluorophore excitation, (4) a portable computer to acquire and analyze images, and (5) image stacking software for image enhancement. The samples consisted of various concentrations of fluorescein, ranging from 30 μM to 1000 μM, in a 36-well miniature plate. In the single frame mode, the fluorometer's limit-of-detection (LOD) for fluorescein is ∼1000 μM, which is relatively insensitive. However, when used in video mode combined with image stacking enhancement, the LOD is dramatically reduced to 30 μM, sensitivity which is similar to that of state-of-the-art ELISA plate photomultiplier-based readers. Numerous medical diagnostics assays rely on optical and fluorescence readers. Our novel combination of detection technologies, which is new to biodetection may enable the development of new low cost optical detectors based on an inexpensive Webcam (<$10). It has the potential to form the basis for high sensitivity, low cost medical diagnostics in resource-poor settings.

Image stacking approach to increase sensitivity of fluorescence detection using a low cost complementary metal-oxide-semiconductor (CMOS) webcam

PubMed Central

Balsam, Joshua; Bruck, Hugh Alan; Kostov, Yordan; Rasooly, Avraham

2013-01-01

Optical technologies are important for biological analysis. Current biomedical optical analyses rely on high-cost, high-sensitivity optical detectors such as photomultipliers, avalanched photodiodes or cooled CCD cameras. In contrast, Webcams, mobile phones and other popular consumer electronics use lower-sensitivity, lower-cost optical components such as photodiodes or CMOS sensors. In order for consumer electronics devices, such as webcams, to be useful for biomedical analysis, they must have increased sensitivity. We combined two strategies to increase the sensitivity of CMOS-based fluorescence detector. We captured hundreds of low sensitivity images using a Webcam in video mode, instead of a single image typically used in cooled CCD devices.We then used a computational approach consisting of an image stacking algorithm to remove the noise by combining all of the images into a single image. While video mode is widely used for dynamic scene imaging (e.g. movies or time-lapse photography), it is not used to capture a single static image, which removes noise and increases sensitivity by more than thirty fold. The portable, battery-operated Webcam-based fluorometer system developed here consists of five modules: (1) a low cost CMOS Webcam to monitor light emission, (2) a plate to perform assays, (3) filters and multi-wavelength LED illuminator for fluorophore excitation, (4) a portable computer to acquire and analyze images, and (5) image stacking software for image enhancement. The samples consisted of various concentrations of fluorescein, ranging from 30 μM to 1000 μM, in a 36-well miniature plate. In the single frame mode, the fluorometer's limit-of-detection (LOD) for fluorescein is ∼1000 μM, which is relatively insensitive. However, when used in video mode combined with image stacking enhancement, the LOD is dramatically reduced to 30 μM, sensitivity which is similar to that of state-of-the-art ELISA plate photomultiplier-based readers. Numerous medical diagnostics assays rely on optical and fluorescence readers. Our novel combination of detection technologies, which is new to biodetection may enable the development of new low cost optical detectors based on an inexpensive Webcam (<$10). It has the potential to form the basis for high sensitivity, low cost medical diagnostics in resource-poor settings. PMID:23990697

Probabilistic hazard assessment for skin sensitization potency by dose–response modeling using feature elimination instead of quantitative structure–activity relationships

PubMed Central

McKim, James M.; Hartung, Thomas; Kleensang, Andre; Sá-Rocha, Vanessa

2016-01-01

Supervised learning methods promise to improve integrated testing strategies (ITS), but must be adjusted to handle high dimensionality and dose–response data. ITS approaches are currently fueled by the increasing mechanistic understanding of adverse outcome pathways (AOP) and the development of tests reflecting these mechanisms. Simple approaches to combine skin sensitization data sets, such as weight of evidence, fail due to problems in information redundancy and high dimension-ality. The problem is further amplified when potency information (dose/response) of hazards would be estimated. Skin sensitization currently serves as the foster child for AOP and ITS development, as legislative pressures combined with a very good mechanistic understanding of contact dermatitis have led to test development and relatively large high-quality data sets. We curated such a data set and combined a recursive variable selection algorithm to evaluate the information available through in silico, in chemico and in vitro assays. Chemical similarity alone could not cluster chemicals’ potency, and in vitro models consistently ranked high in recursive feature elimination. This allows reducing the number of tests included in an ITS. Next, we analyzed with a hidden Markov model that takes advantage of an intrinsic inter-relationship among the local lymph node assay classes, i.e. the monotonous connection between local lymph node assay and dose. The dose-informed random forest/hidden Markov model was superior to the dose-naive random forest model on all data sets. Although balanced accuracy improvement may seem small, this obscures the actual improvement in misclassifications as the dose-informed hidden Markov model strongly reduced "false-negatives" (i.e. extreme sensitizers as non-sensitizer) on all data sets. PMID:26046447

Development of new resist materials for 193-nm dry and immersion lithography

NASA Astrophysics Data System (ADS)

Sasaki, Takashi; Shirota, Naoko; Takebe, Yoko; Yokokoji, Osamu

2006-03-01

We earlier developed new monocyclic fluoropolymers (FUGU) for F II resist materials. But, it is necessary for FUGU to improve of their characteristics, especially the dry-etching resistance, in order to apply for ArF lithography at fine design rules. We have tried to combine FUGUs with Adamntyl methacrylates based conventional ArF resist polymer. In this paper, we have investigated the role of cyclic fluorinated unit, FUGU, in 193 nm resist polymers by analyzing the dissolution behavior. We found that FGEAM showed high sensitivity and good dissolution contrast, compared with acrylate based conventional samples at low PEB temperature (100 °C). And this difference of sensitivity was clearly found when weak acidity PAGs were used. From the dissolution behaviors of FGEAM, FUGU unit can work to improve the resist sensitivity in acrylate based ArF resist polymers. And we also found that FGEAM showed long acid diffusion length on PEB process, compared with Conventional samples. These result show that FUGU unit has a unique characteristics of the sensitivity with 193nm exposure and the acid diffusion behavior. We also investigated a new series of fluorinated copolymers for 193-nm lithography, combination of FUGU monomer and acrylate units which are used in conventional ArF resist. Six ter-polymers of FUGU, combination of FUGU monomers and EAdMA, GBLMA and HAdMA were prepared. We found that FUGU ter-polymers had a good dry etching resistance keeping high transparency at 193nm. And FUGU ter-polymers showed high sensitivity toward 193nm exposure. FUGU ter-polymers also had a high hydrophobic properties compared conventional type ArF resist polymers. So we also expect FUGU ter-polymers to be useful for ArF dry and immersion lithography.

Probabilistic hazard assessment for skin sensitization potency by dose-response modeling using feature elimination instead of quantitative structure-activity relationships.

PubMed

Luechtefeld, Thomas; Maertens, Alexandra; McKim, James M; Hartung, Thomas; Kleensang, Andre; Sá-Rocha, Vanessa

2015-11-01

Supervised learning methods promise to improve integrated testing strategies (ITS), but must be adjusted to handle high dimensionality and dose-response data. ITS approaches are currently fueled by the increasing mechanistic understanding of adverse outcome pathways (AOP) and the development of tests reflecting these mechanisms. Simple approaches to combine skin sensitization data sets, such as weight of evidence, fail due to problems in information redundancy and high dimensionality. The problem is further amplified when potency information (dose/response) of hazards would be estimated. Skin sensitization currently serves as the foster child for AOP and ITS development, as legislative pressures combined with a very good mechanistic understanding of contact dermatitis have led to test development and relatively large high-quality data sets. We curated such a data set and combined a recursive variable selection algorithm to evaluate the information available through in silico, in chemico and in vitro assays. Chemical similarity alone could not cluster chemicals' potency, and in vitro models consistently ranked high in recursive feature elimination. This allows reducing the number of tests included in an ITS. Next, we analyzed with a hidden Markov model that takes advantage of an intrinsic inter-relationship among the local lymph node assay classes, i.e. the monotonous connection between local lymph node assay and dose. The dose-informed random forest/hidden Markov model was superior to the dose-naive random forest model on all data sets. Although balanced accuracy improvement may seem small, this obscures the actual improvement in misclassifications as the dose-informed hidden Markov model strongly reduced " false-negatives" (i.e. extreme sensitizers as non-sensitizer) on all data sets. Copyright © 2015 John Wiley & Sons, Ltd.

Highly sensitive evanescent wave combination tapered fiber optic fluorosensor for protein detection

NASA Astrophysics Data System (ADS)

Nardone, Vincent; Kapoor, Rakesh

2008-02-01

In this paper we are reporting the development of a highly sensitive evanescent wave combination tapered fiber optic fluorosensor. We have demonstrated detection of 5 pM Bovine Serum Albumin (BSA) protein using these fiber optic sensors. The sensor can be easily adopted for detection of other proteins. Six identical probes were prepared and affinity pure Goat anti-BSA antibodies were immobilized on the probe surface. We could detect signal from all the probes kept in 5 pM to 1 nM BSA solution while no signal was detected from the probes kept in 20 nM labeled ESA solution.

Quality of life in patients with nonalcoholic fatty liver disease in combination with essential hypertension considering taste sensitivity to sodium chloride.

PubMed

Mashura, Hanna Y; Hanych, Taras M; Rishko, Alexander A

2016-01-01

Nonalcoholic fatty liver disease and hypertensive disease - is the most common combination of abnormalities that occur in people suffering from metabolic syndrome. Their combination not only causes concurrent damage of the liver and the heart, caused by common pathogenic beginning, and also mutually complicate the disease course of each other. The leading role in the development of nonalcoholic fatty liver disease belongs to abdominal obesity and insulin resistance, and is seen as a manifestation of liver disease in metabolic syndrome. Genetic predisposition, lifestyle, improper nutrition, including excessive use of sodium chloride, lead to excessive formation of visceral adipose tissue with development of abdominal obesity, which is a likely criterion of insulin resistance. The long course of nonalcoholic fatty liver disease in combination with essential hypertension in excessive consumption of sodium chloride may negatively affect their quality of life. The aim of the study is to find out the features of quality of life in patients with nonalcoholic fatty liver disease in combination with hypertensive disease with different taste sensitivity to sodium chloride. We have investigated the quality of life of 65 patients with nonalcoholic fatty liver disease in combination with hypertensive disease II stage with different taste sensitivity to sodium chloride. Salt taste sensitivity threshold to sodium chloride is determined by the method of R. Henkin. Assessment of quality of life was performed using the Ukrainian version of the questionnaire Medical Outcomes Study Short Form 36 (MO S SF-36). Was revealed that in patients with nonalcoholic fatty liver disease in combination with hypertensive disease II stage with high salt taste sensitivity threshold observed the decline in the quality of life that manifests as a decline in physical condition (especially of the physical functioning, physical role functioning and general health perceptions) and mental health (especially social functioning). Also the increased salt intake and salt appetite in patients with high salt taste sensitivity threshold were noted (p <0,05). Reducing the use of sodium chloride can be a preventive measure easier than a decrease in body weight, and one that will reduce the body weight, especially in people with nonalcoholic fatty liver disease in combination with hypertensive disease, can reduce the risk of complications and improve quality of life in patients.

High sensitive and direct fluorescence detection of single viral DNA sequences by integration of double strand probes onto microgels particles.

PubMed

Aliberti, A; Cusano, A M; Battista, E; Causa, F; Netti, P A

2016-02-21

A novel class of probes for fluorescence detection was developed and combined to microgel particles for a high sensitive fluorescence detection of nucleic acids. A double strand probe with an optimized fluorescent-quencher couple was designed for the detection of different lengths of nucleic acids (39 nt and 100 nt). Such probe proved efficient in target detection in different contests and specific even in presence of serum proteins. The conjugation of double strand probes onto polymeric microgels allows for a sensitive detection of DNA sequences from HIV, HCV and SARS corona viruses with a LOD of 1.4 fM, 3.7 fM and 1.4 fM, respectively, and with a dynamic range of 10(-9)-10(-15) M. Such combination enhances the sensitivity of the detection of almost five orders of magnitude when compared to the only probe. The proposed platform based on the integration of innovative double strand probe into microgels particles represents an attractive alternative to conventional sensitive DNA detection technologies that rely on amplifications methods.

A novel lab-on-chip platform with integrated solid phase PCR and Supercritical Angle Fluorescence (SAF) microlens array for highly sensitive and multiplexed pathogen detection.

PubMed

Hung, Tran Quang; Chin, Wai Hoe; Sun, Yi; Wolff, Anders; Bang, Dang Duong

2017-04-15

Solid-phase PCR (SP-PCR) has become increasingly popular for molecular diagnosis and there have been a few attempts to incorporate SP-PCR into lab-on-a-chip (LOC) devices. However, their applicability for on-line diagnosis is hindered by the lack of sensitive and portable on-chip optical detection technology. In this paper, we addressed this challenge by combining the SP-PCR with super critical angle fluorescence (SAF) microlens array embedded in a microchip. We fabricated miniaturized SAF microlens array as part of a microfluidic chamber in thermoplastic material and performed multiplexed SP-PCR directly on top of the SAF microlens array. Attribute to the high fluorescence collection efficiency of the SAF microlens array, the SP-PCR assay on the LOC platform demonstrated a high sensitivity of 1.6 copies/µL, comparable to off-chip detection using conventional laser scanner. The combination of SP-PCR and SAF microlens array allows for on-chip highly sensitive and multiplexed pathogen detection with low-cost and compact optical components. The LOC platform would be widely used as a high-throughput biosensor to analyze food, clinical and environmental samples. Copyright © 2016 Elsevier B.V. All rights reserved.

Flexible Packaging by Film-Assisted Molding for Microintegration of Inertia Sensors

PubMed Central

Hera, Daniel; Berndt, Armin; Günther, Thomas; Schmiel, Stephan; Harendt, Christine; Zimmermann, André

2017-01-01

Packaging represents an important part in the microintegration of sensors based on microelectromechanical system (MEMS). Besides miniaturization and integration density, functionality and reliability in combination with flexibility in packaging design at moderate costs and consequently high-mix, low-volume production are the main requirements for future solutions in packaging. This study investigates possibilities employing printed circuit board (PCB-)based assemblies to provide high flexibility for circuit designs together with film-assisted transfer molding (FAM) to package sensors. The feasibility of FAM in combination with PCB and MEMS as a packaging technology for highly sensitive inertia sensors is being demonstrated. The results prove the technology to be a viable method for damage-free packaging of stress- and pressure-sensitive MEMS. PMID:28653992

The urine dipstick test useful to rule out infections. A meta-analysis of the accuracy

PubMed Central

Devillé, Walter LJM; Yzermans, Joris C; van Duijn, Nico P; Bezemer, P Dick; van der Windt, Daniëlle AWM; Bouter, Lex M

2004-01-01

Background Many studies have evaluated the accuracy of dipstick tests as rapid detectors of bacteriuria and urinary tract infections (UTI). The lack of an adequate explanation for the heterogeneity of the dipstick accuracy stimulates an ongoing debate. The objective of the present meta-analysis was to summarise the available evidence on the diagnostic accuracy of the urine dipstick test, taking into account various pre-defined potential sources of heterogeneity. Methods Literature from 1990 through 1999 was searched in Medline and Embase, and by reference tracking. Selected publications should be concerned with the diagnosis of bacteriuria or urinary tract infections, investigate the use of dipstick tests for nitrites and/or leukocyte esterase, and present empirical data. A checklist was used to assess methodological quality. Results 70 publications were included. Accuracy of nitrites was high in pregnant women (Diagnostic Odds Ratio = 165) and elderly people (DOR = 108). Positive predictive values were ≥80% in elderly and in family medicine. Accuracy of leukocyte-esterase was high in studies in urology patients (DOR = 276). Sensitivities were highest in family medicine (86%). Negative predictive values were high in both tests in all patient groups and settings, except for in family medicine. The combination of both test results showed an important increase in sensitivity. Accuracy was high in studies in urology patients (DOR = 52), in children (DOR = 46), and if clinical information was present (DOR = 28). Sensitivity was highest in studies carried out in family medicine (90%). Predictive values of combinations of positive test results were low in all other situations. Conclusions Overall, this review demonstrates that the urine dipstick test alone seems to be useful in all populations to exclude the presence of infection if the results of both nitrites and leukocyte-esterase are negative. Sensitivities of the combination of both tests vary between 68 and 88% in different patient groups, but positive test results have to be confirmed. Although the combination of positive test results is very sensitive in family practice, the usefulness of the dipstick test alone to rule in infection remains doubtful, even with high pre-test probabilities. PMID:15175113

Pleural effusion biomarkers and computed tomography findings in diagnosing malignant pleural mesothelioma: A retrospective study in a single center

PubMed Central

Kataoka, Yuki; Ikegaki, Shunkichi; Saito, Emiko; Matsumoto, Hirotaka; Kaku, Sawako; Shimada, Masatoshi; Hirabayashi, Masataka

2017-01-01

In this study, we aimed to examine the clinical value of the pleural effusion (PE) biomarkers, soluble mesothelin-related peptide (SMRP), cytokeratin 19 fragment (CYFRA 21–1) and carcinoembryonic antigen (CEA), and the utility of combining chest computed tomography (CT) findings with these biomarkers, in diagnosing malignant pleural mesothelioma (MPM). We conducted a retrospective cohort study in a single center. Consecutive patients with undiagnosed pleural effusions who underwent PE analysis between September 2014 and August 2016 were reviewed. This study included 240 patients (32 with MPM and 208 non-MPM). SMRP and the CYFRA 21-1/CEA ratio had a sensitivity and specificity for diagnosing MPM of 56.3% and 86.5%, and 87.5% and 74.0%, respectively. Using receiver operating characteristics (ROC) curve analysis of the ability of these markers to distinguish MPM from all other PE causes, the area under the ROC curve (AUC) for SMRP and the CYFRA 21-1/CEA ratio was 0.804 and 0.874, respectively. The sensitivity and specificity of SMRP combined with the CYFRA 21-1/CEA ratio were 93.8% and 64.9%, respectively. The sensitivity of the combination of SMRP, the CYFRA 21-1/CEA ratio, and the presence of Leung’s criteria (a chest CT finding that is suggestive of malignant pleural disease) was 93.8%. In conclusion, the combined PE biomarkers had a high sensitivity for diagnosing MPM, although the addition of chest CT findings did not improve the sensitivity of SMRP combined with the CYFRA 21-1/CEA ratio. Combination of these biomarkers helped to rule out MPM effectively among patients at high risk of suffering MPM and would be valuable especially for old frail patients who have difficulty in undergoing invasive procedures such as thoracoscopy. PMID:28968445

Pyocin-sensitivity testing as a method of typing Pseudomonas aeruginosa: use of "phage-free" preparations of pyocin.

PubMed

Rampling, A; Whitby, J L; Wildy, P

1975-11-01

A method for pyocin-sensitivity typing by means of "phage-free" preparations of pyocin is described. The method was tested on 227 isolates of P. aeruginosa, collected from 34 different foci of infection in hospitals in the British Isles and the results were compared with those for combined serological and phage typing of all strains and pyocin production of 105 of the isolates. It is concluded that pyocin-sensitivity typing is a simple and reliable method giving a high degree of discrimination, comparable to that of combined serological and phage typing, and it is suitable for use in routine hospital laboratories.

Testing for developmental neurotoxicity using a battery of in vitro assays for key cellular events in neurodevelopment.

PubMed

Harrill, Joshua A; Freudenrich, Theresa; Wallace, Kathleen; Ball, Kenneth; Shafer, Timothy J; Mundy, William R

2018-04-05

Medium- to high-throughput in vitro assays that recapitulate the critical processes of nervous system development have been proposed as a means to facilitate rapid testing and identification of chemicals which may affect brain development. In vivo neurodevelopment is a complex progression of distinct cellular processes. Therefore, batteries of in vitro assays that model and quantify effects on a variety of neurodevelopmental processes have the potential to identify chemicals which may affect brain development at different developmental stages. In the present study, the results of concentration-response screening of 67 reference chemicals in a battery of high content imaging and microplate reader-based assays that evaluate neural progenitor cell proliferation, neural proginitor cell apoptosis, neurite initiation/outgrowth, neurite maturation and synaptogenesis are summarized and compared. The assay battery had a high degree of combined sensitivity (87%) for categorizing chemicals known to affect neurodevelopment as active and a moderate degree of combined specificity (71%) for categorizing chemicals not associated with affects on neurodevelopment as inactive. The combined sensitivity of the assay battery was higher compared to any individual assay while the combined specificity of the assay battery was lower compared to any individual assay. When selectivity of effects for a neurodevelopmental endpoint as compared to general cytotoxicity was taken into account, the combined sensitivity of the assay battery decreased (68%) while the combined specificity increased (93%). The identity and potency of chemicals identified as active varied across the assay battery, underscoring the need for use of a combination of diverse in vitro models to comprehensively screen chemicals and identify those which potentially affect neurodevelopment. Overall, these data indicate that a battery of assays which address many different processes in nervous system development may be used to identify potential developmental neurotoxicants and to distinguish specific from generalized cytotoxic effects with a high degree of success. Published by Elsevier Inc.

Designing Metallic and Insulating Nanocrystal Heterostructures to Fabricate Highly Sensitive and Solution Processed Strain Gauges for Wearable Sensors.

PubMed

Lee, Woo Seok; Lee, Seung-Wook; Joh, Hyungmok; Seong, Mingi; Kim, Haneun; Kang, Min Su; Cho, Ki-Hyun; Sung, Yun-Mo; Oh, Soong Ju

2017-12-01

All-solution processed, high-performance wearable strain sensors are demonstrated using heterostructure nanocrystal (NC) solids. By incorporating insulating artificial atoms of CdSe quantum dot NCs into metallic artificial atoms of Au NC thin film matrix, metal-insulator heterostructures are designed. This hybrid structure results in a shift close to the percolation threshold, modifying the charge transport mechanism and enhancing sensitivity in accordance with the site percolation theory. The number of electrical pathways is also manipulated by creating nanocracks to further increase its sensitivity, inspired from the bond percolation theory. The combination of the two strategies achieves gauge factor up to 5045, the highest sensitivity recorded among NC-based strain gauges. These strain sensors show high reliability, durability, frequency stability, and negligible hysteresis. The fundamental charge transport behavior of these NC solids is investigated and the combined site and bond percolation theory is developed to illuminate the origin of their enhanced sensitivity. Finally, all NC-based and solution-processed strain gauge sensor arrays are fabricated, which effectively measure the motion of each finger joint, the pulse of heart rate, and the movement of vocal cords of human. This work provides a pathway for designing low-cost and high-performance electronic skin or wearable devices. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Sensitivity of the High Altitude Water Cherenkov Experiment to observe Gamma-Ray Bursts

NASA Astrophysics Data System (ADS)

González, M. M.

Ground based telescopes have marginally observed very high energy emission (>100GeV) from gamma-ray bursts(GRB). For instance, Milagrito observed GRB970417a with a significance of 3.7 sigmas over the background. Milagro have not yet observed TeV emission from a GRB with its triggered and untriggered searches or GeV emission with a triggered search using its scalers. These results suggest the need of new observatories with higher sensitivity to transient sources. The HAWC (High Altitute Water Cherenkov) observatory is proposed as a combination of the Milagro tecnology with a very high altitude (>4000m over see level) site. The expected HAWC sensitivity for GRBs is at least >10 times the Milagro sensitivity. In this work HAWC sensitivity for GRBs is discussed for different detector configurations such as altitude, distance between PMTs, depth under water of PMTs, number of PMTs required for a trigger, etc.

absorption sensor for sensitive temperature and species measurements in high-temperature gases

NASA Astrophysics Data System (ADS)

Spearrin, R. M.; Ren, W.; Jeffries, J. B.; Hanson, R. K.

2014-09-01

A continuous-wave laser absorption diagnostic, based on the infrared CO2 bands near 4.2 and 2.7 μm, was developed for sensitive temperature and concentration measurements in high-temperature gas systems using fixed-wavelength methods. Transitions in the respective R-branches of both the fundamental υ 3 band (~2,350 cm-1) and combination υ 1 + υ 3 band (~3,610 cm-1) were chosen based on absorption line-strength, spectral isolation, and temperature sensitivity. The R(76) line near 2,390.52 cm-1 was selected for sensitive CO2 concentration measurements, and a detection limit of <5 ppm was achieved in shock tube kinetics experiments (~1,300 K). A cross-band, two-line thermometry technique was also established utilizing the R(96) line near 2,395.14 cm-1, paired with the R(28) line near 3,633.08 cm-1. This combination yields high temperature sensitivity (ΔE" = 3,305 cm-1) and expanded range compared with previous intra-band CO2 sensors. Thermometry performance was validated in a shock tube over a range of temperatures (600-1,800 K) important for combustion. Measured temperature accuracy was demonstrated to be better than 1 % over the entire range of conditions, with a standard error of ~0.5 % and µs temporal resolution.

Combined high vacuum/high frequency fatigue tester

NASA Technical Reports Server (NTRS)

Honeycutt, C. R.; Martin, T. F.

1971-01-01

Apparatus permits application of significantly greater number of cycles or equivalent number of cycles in shorter time than conventional fatigue test machines. Environment eliminates problems associated with high temperature oxidation and with sensitivity of refractory alloy behavior to atmospheric contamination.

Instrumentation in molecular imaging.

PubMed

Wells, R Glenn

2016-12-01

In vivo molecular imaging is a challenging task and no single type of imaging system provides an ideal solution. Nuclear medicine techniques like SPECT and PET provide excellent sensitivity but have poor spatial resolution. Optical imaging has excellent sensitivity and spatial resolution, but light photons interact strongly with tissues and so only small animals and targets near the surface can be accurately visualized. CT and MRI have exquisite spatial resolution, but greatly reduced sensitivity. To overcome the limitations of individual modalities, molecular imaging systems often combine individual cameras together, for example, merging nuclear medicine cameras with CT or MRI to allow the visualization of molecular processes with both high sensitivity and high spatial resolution.

Curvature measurement with photonic crystal fiber based Mach-Zehnder interferometer

NASA Astrophysics Data System (ADS)

Deng, Ming; Tang, Chang-Ping; Zhu, Tao; Rao, Yun-Jiang

2011-05-01

A PCF-based MZI with regular and high-contrast fringe pattern is fabricated by splicing a section of PCF in between two SMFs with a commercial available fusion splicer. Its resonant wavelength is sensitive to external bending with a sensitivity of 3.046nm/m but independent on temperature. To that end, we also propose another kind of bending sensor with higher sensitivity of 5.129nm/m. This device is constructed by combining an LPG and an MZI with zero offset at the second splice. It is anticipated that the high sensitive structures will find applications in robot arms and artificial limbs.

Combining Monte Carlo methods with coherent wave optics for the simulation of phase-sensitive X-ray imaging

PubMed Central

Peter, Silvia; Modregger, Peter; Fix, Michael K.; Volken, Werner; Frei, Daniel; Manser, Peter; Stampanoni, Marco

2014-01-01

Phase-sensitive X-ray imaging shows a high sensitivity towards electron density variations, making it well suited for imaging of soft tissue matter. However, there are still open questions about the details of the image formation process. Here, a framework for numerical simulations of phase-sensitive X-ray imaging is presented, which takes both particle- and wave-like properties of X-rays into consideration. A split approach is presented where we combine a Monte Carlo method (MC) based sample part with a wave optics simulation based propagation part, leading to a framework that takes both particle- and wave-like properties into account. The framework can be adapted to different phase-sensitive imaging methods and has been validated through comparisons with experiments for grating interferometry and propagation-based imaging. The validation of the framework shows that the combination of wave optics and MC has been successfully implemented and yields good agreement between measurements and simulations. This demonstrates that the physical processes relevant for developing a deeper understanding of scattering in the context of phase-sensitive imaging are modelled in a sufficiently accurate manner. The framework can be used for the simulation of phase-sensitive X-ray imaging, for instance for the simulation of grating interferometry or propagation-based imaging. PMID:24763652

Streamlining the Evaluation of Low Back Pain in Children

PubMed Central

Auerbach, Joshua D.; Ahn, Jaimo; Zgonis, Miltiadis H.; Reddy, Sudheer C.; Ecker, Malcolm L.

2008-01-01

The workup of low back pain in children often results in overimaging so as not to miss organic back pain. The primary goal of this study was to identify which combination of imaging modalities provides the most sensitive and specific screening protocol for children with low back pain. Medical records from 100 consecutive patients between 2 and 18 years of age presenting with low back pain, without night pain or constitutional symptoms, were evaluated. A hyperextension test combined with a radiograph showed a negative predictive value of 0.81 and sensitivity of 0.90. The addition of a bone scan was highly effective in achieving good negative predictive value and sensitivity. Bone scans had perfect negative predictive value and sensitivity when symptom duration was less than 6 weeks. We identified a set of factors that is highly predictive for distinguishing organic back pain from mechanical back pain. Painless hyperextension combined with negative anteroposterior, lateral, and oblique lumbar radiographs and magnetic resonance images predicts mechanical back pain. For patients with nonneurologic back pain of less than 6 weeks duration, bone scan is the most useful screening test because it is accurate, accessible, inexpensive, and unlikely to require sedation. Level of Evidence: Level III, diagnostic study. See the Guidelines for Authors for a complete description of levels of evidence. PMID:18553213

Analytical Glycobiology at High Sensitivity: Current Approaches and Directions

PubMed Central

Novotny, Milos V.; Alley, William R.; Mann, Benjamin F.

2013-01-01

This review summarizes the analytical advances made during the last several years in the structural and quantitative determinations of glycoproteins in complex biological mixtures. The main analytical techniques used in the fields of glycomics and glycoproteomics involve different modes of mass spectrometry and their combinations with capillary separation methods such as microcolumn liquid chromatography and capillary electrophoresis. The needs for high-sensitivity measurements have been emphasized in the oligosaccharide profiling used in the field of biomarker discovery through MALDI mass spectrometry. High-sensitivity profiling of both glycans and glycopeptides from biological fluids and tissue extracts has been aided significantly through lectin preconcentration and the uses of affinity chromatography. PMID:22945852

Dasatinib is preclinically active against Src-overexpressing human transitional cell carcinoma of the urothelium with activated Src signaling.

PubMed

Levitt, Jonathan M; Yamashita, Hideyuki; Jian, Weiguo; Lerner, Seth P; Sonpavde, Guru

2010-05-01

Dasatinib is an orally administered multitargeted kinase inhibitor that targets Src family tyrosine kinases, Abl, c-Kit, and PDGFR. A preclinical study was conducted to evaluate dasatinib alone or combined with cisplatin for human transitional cell carcinoma (TCC). Expression of Src in a human TCC tissue microarray was evaluated by immunohistochemistry. The activity of dasatinib and/or cisplatin was evaluated in six human TCC cell lines. Western blot was done to assess Src and phosphorylated-Src (p-Src) expression. The activity of dasatinib alone and in combination with cisplatin was determined in murine subcutaneous xenografts. Sixty-two percent to 75% of human TCC expressed Src. Dasatinib displayed significant antiproliferative activity at nanomolar concentrations against two human TCC cell lines (RT4 and Hu456) that exhibited high Src and p-Src expression and were cisplatin-resistant. RT4 cells were the most sensitive and displayed the highest level of Src pathway activation (p-Src/Src ratio). Dasatinib downregulated p-Src in either sensitive or resistant cells. TCC cells that were sensitive to cisplatin (5637 and TCC-SUP) were highly resistant to dasatinib and exhibited low Src expression. Dasatinib showed antitumor activity in RT4 murine xenografts, and the combination of dasatinib and cisplatin was significantly more active than placebo. Combination dasatinib plus cisplatin significantly inhibited proliferation and promoted apoptosis in vivo. In conclusion, dasatinib displayed significant preclinical antitumor activity against Src-overexpressing human TCC with active Src signaling and was highly active in combination with cisplatin in vivo. Further clinical development might be warranted in selected human subjects.

Multidimensional NMR approaches towards highly resolved, sensitive and high-throughput quantitative metabolomics.

PubMed

Marchand, Jérémy; Martineau, Estelle; Guitton, Yann; Dervilly-Pinel, Gaud; Giraudeau, Patrick

2017-02-01

Multi-dimensional NMR is an appealing approach for dealing with the challenging complexity of biological samples in metabolomics. This article describes how spectroscopists have recently challenged their imagination in order to make 2D NMR a powerful tool for quantitative metabolomics, based on innovative pulse sequences combined with meticulous analytical chemistry approaches. Clever time-saving strategies have also been explored to make 2D NMR a high-throughput tool for metabolomics, relying on alternative data acquisition schemes such as ultrafast NMR. Currently, much work is aimed at drastically boosting the NMR sensitivity thanks to hyperpolarisation techniques, which have been used in combination with fast acquisition methods and could greatly expand the application potential of NMR metabolomics. Copyright © 2016 Elsevier Ltd. All rights reserved.

Screening markers for chronic atrophic gastritis in Chiapas, Mexico.

PubMed

Ley, C; Mohar, A; Guarner, J; Herrera-Goepfert, R; Figueroa, L S; Halperin, D; Parsonnet, J

2001-02-01

Intestinal-type gastric adenocarcinomas usually are preceded by chronic atrophic gastritis. Studies of gastric cancer prevention often rely on identification of this condition. In a clinical trial, we sought to determine the best serological screening method for chronic atrophic gastritis and compared our findings to the published literature. Test characteristics of potential screening tests (antibodies to Helicobacter pyloni or CagA, elevated gastrin, low pepsinogen, increased age) alone or in combination were examined among consecutive subjects enrolled in a study of H. pylori and preneoplastic gastric lesions in Chiapas, Mexico; 70% had chronic atrophic gastritis. English-language articles concerning screening for chronic atrophic gastritis were also reviewed. Sensitivity for chronic atrophic gastritis was highest for antibodies to H. pylori (92%) or CagA, or gastrin levels >25 ng/l (both 83%). Specificity, however, was low for these tests (18, 41, and 22%, respectively). Pepsinogen levels were highly specific but insensitive markers of chronic atrophic gastritis (for pepsinogen I <25 microg/l, sensitivity was 6% and specificity was 100%; for pepsinogen I:pepsinogen II ratio <2.5, sensitivity was 14% and specificity was 96%). Combinations of markers did not improve test characteristics. Screening test characteristics from the literature varied widely and did not consistently identify a good screening strategy. In this study, CagA antibodies alone had the best combination of test characteristics for chronic atrophic gastritis screening. However, no screening test was both highly sensitive and highly specific for chronic atrophic gastritis.

Evaluation of phenotypic detection methods for metallo-β-lactamases (MBLs) in clinical isolates of Pseudomonas aeruginosa.

PubMed

Peter, S; Lacher, A; Marschal, M; Hölzl, F; Buhl, M; Autenrieth, I; Kaase, M; Willmann, M

2014-07-01

Metallo-beta-lactamase (MBL) production in Pseudomonas aeruginosa is a growing issue across the globe. Fast and reliable diagnostic tools are needed for appropriate implementation of infection control measures. In this study we evaluated the performance of three commercial combined disk tests, two EDTA based in-house combined disk tests and the Carba NP test in comparison to molecular detection of MBL genes on 133 meropenem non-susceptible non-duplicate P. aeruginosa clinical isolates. The meropenem/DPA based commercial KPC + MBL-confirm ID kit (Rosco Diagnostica, Denmark) and the MASTDISCS™ ID carbapenemase (Enterobacteriaceae) detection disc set (MAST Diagnostics, UK) showed sensitivities of 31.1 % and 28.8 % and specificities of 69.3 % and 79.6 %, respectively. The total MBL confirm kit (Rosco Diagnostica, Denmark) contains imipenem/DPA and imipenem/EDTA combination disks. Evaluation of the single disk combinations revealed 84.4 % sensitivity and 81.8 % specificity for the imipenem/DPA assay and 86.7 % sensitivity and 51.1 % specificity for the imipenem/EDTA test. Applying both tests simultaneously resulted in a slightly higher sensitivity of 88.9 % but a lower specificity of 48.9 % when compared to the single tests alone. The Carba NP test showed 93.3 % sensitivity and 96.6 % specificity. All phenotypic combined disk tests lacked either sensitivity or specificity for the detection of MBL in P. aeruginosa. The Carba NP test showed excellent test properties, but suffers from drawbacks in handling and high costs. The optimal diagnostic approach needs to be chosen depending on the epidemiological situation, laboratory resources and availability of molecular confirmation tests.

Genetic Variation and Combining Ability Analysis of Bruising Sensitivity in Agaricus bisporus

PubMed Central

Gao, Wei; Baars, Johan J. P.; Dolstra, Oene; Visser, Richard G. F.; Sonnenberg, Anton S. M.

2013-01-01

Advanced button mushroom cultivars that are less sensitive to mechanical bruising are required by the mushroom industry, where automated harvesting still cannot be used for the fresh mushroom market. The genetic variation in bruising sensitivity (BS) of Agaricus bisporus was studied through an incomplete set of diallel crosses to get insight in the heritability of BS and the combining ability of the parental lines used and, in this way, to estimate their breeding value. To this end nineteen homokaryotic lines recovered from wild strains and cultivars were inter-crossed in a diallel scheme. Fifty-one successful hybrids were grown under controlled conditions, and the BS of these hybrids was assessed. BS was shown to be a trait with a very high heritability. The results also showed that brown hybrids were generally less sensitive to bruising than white hybrids. The diallel scheme allowed to estimate the general combining ability (GCA) for each homokaryotic parental line and to estimate the specific combining ability (SCA) of each hybrid. The line with the lowest GCA is seen as the most attractive donor for improving resistance to bruising. The line gave rise to hybrids sensitive to bruising having the highest GCA value. The highest negative SCA possibly indicates heterosis effects for resistance to bruising. This study provides a foundation for estimating breeding value of parental lines to further study the genetic factors underlying bruising sensitivity and other quality-related traits, and to select potential parental lines for further heterosis breeding. The approach of studying combining ability in a diallel scheme was used for the first time in button mushroom breeding. PMID:24116171

Atomic magnetometer-based ultra-sensitive magnetic microscopy

NASA Astrophysics Data System (ADS)

Kim, Young Jin; Savukov, Igor

2016-03-01

An atomic magnetometer (AM) based on lasers and alkali-metal vapor cells is currently the most sensitive non-cryogenic magnetic-field sensor. Many applications in neuroscience and other fields require high resolution, high sensitivity magnetic microscopic measurements. In order to meet this need we combined a cm-size spin-exchange relaxation-free AM with a flux guide (FG) to produce an ultra-sensitive FG-AM magnetic microscope. The FG serves to transmit the target magnetic flux to the AM thus enhancing both the sensitivity and resolution for tiny magnetic objects. In this talk, we will describe a prototype FG-AM device and present experimental and numerical tests of its sensitivity and resolution. We also demonstrate that an optimized FG-AM achieves high resolution and high sensitivity sufficient to detect a magnetic field of a single neuron in a few seconds, which would be an important milestone in neuroscience. We anticipate that this unique device can be applied to the detection of a single neuron, the detection of magnetic nano-particles, which in turn are very important for detection of target molecules in national security and medical diagnostics, and non-destructive testing.

Multiplexed Simultaneous High Sensitivity Sensors with High-Order Mode Based on the Integration of Photonic Crystal 1 × 3 Beam Splitter and Three Different Single-Slot PCNCs.

PubMed

Zhou, Jian; Huang, Lijun; Fu, Zhongyuan; Sun, Fujun; Tian, Huiping

2016-07-07

We simulated an efficient method for the sensor array of high-sensitivity single-slot photonic crystal nanobeam cavities (PCNCs) on a silicon platform. With the combination of a well-designed photonic crystal waveguide (PhCW) filter and an elaborate single-slot PCNC, a specific high-order resonant mode was filtered for sensing. A 1 × 3 beam splitter carefully established was implemented to split channels and integrate three sensors to realize microarrays. By applying the three-dimensional finite-difference-time-domain (3D-FDTD) method, the sensitivities calculated were S₁ = 492 nm/RIU, S₂ = 244 nm/RIU, and S₃ = 552 nm/RIU, respectively. To the best of our knowledge, this is the first multiplexing design in which each sensor cite features such a high sensitivity simultaneously.

Multiplexed Simultaneous High Sensitivity Sensors with High-Order Mode Based on the Integration of Photonic Crystal 1 × 3 Beam Splitter and Three Different Single-Slot PCNCs

PubMed Central

Zhou, Jian; Huang, Lijun; Fu, Zhongyuan; Sun, Fujun; Tian, Huiping

2016-01-01

We simulated an efficient method for the sensor array of high-sensitivity single-slot photonic crystal nanobeam cavities (PCNCs) on a silicon platform. With the combination of a well-designed photonic crystal waveguide (PhCW) filter and an elaborate single-slot PCNC, a specific high-order resonant mode was filtered for sensing. A 1 × 3 beam splitter carefully established was implemented to split channels and integrate three sensors to realize microarrays. By applying the three-dimensional finite-difference-time-domain (3D-FDTD) method, the sensitivities calculated were S1 = 492 nm/RIU, S2 = 244 nm/RIU, and S3 = 552 nm/RIU, respectively. To the best of our knowledge, this is the first multiplexing design in which each sensor cite features such a high sensitivity simultaneously. PMID:27399712

Aberrant DNA methylation of tumor-related genes in oral rinse: a noninvasive method for detection of oral squamous cell carcinoma.

PubMed

Nagata, Satoshi; Hamada, Tomofumi; Yamada, Norishige; Yokoyama, Seiya; Kitamoto, Sho; Kanmura, Yuji; Nomura, Masahiro; Kamikawa, Yoshiaki; Yonezawa, Suguru; Sugihara, Kazumasa

2012-09-01

The early detection of oral squamous cell carcinoma (OSCC) is important, and a screening test with high sensitivity and specificity is urgently needed. Therefore, in this study, the authors investigated the methylation status of tumor-related genes with the objective of establishing a noninvasive method for the detection of OSCC. Oral rinse samples were obtained from 34 patients with OSCC and from 24 healthy individuals (controls). The methylation status of 13 genes was determined by using methylation-specific polymerase chain reaction analysis and was quantified using a microchip electrophoresis system. Promoter methylation in each participant was screened by receiver operating characteristic analysis, and the utility of each gene's methylation status, alone and in combination with other genes, was evaluated as a tool for oral cancer detection. Eight of the 13 genes had significantly higher levels of DNA methylation in samples from patients with OSCC than in controls. The genes E-cadherin (ECAD), transmembrane protein with epidermal growth factor-like and 2 follistatin-like domains 2 (TMEFF2), retinoic acid receptor beta (RARβ), and O-6 methylguanine DNA methyltransferase (MGMT) had high sensitivity (>75%) and specificity for the detection of oral cancer. OSCC was detected with 100% sensitivity and 87.5% specificity using a combination of ECAD, TMEFF2, RARβ, and MGMT and with 97.1% sensitivity and 91.7% specificity using a combination of ECAD, TMEFF2, and MGMT. The aberrant methylation of a combination of marker genes present in oral rinse samples was used to detect OSCC with >90% sensitivity and specificity. The detection of methylated marker genes from oral rinse samples has great potential for the noninvasive detection of OSCC. Copyright © 2012 American Cancer Society.

Development of a highly sensitive immunochromatographic detection kit for H5 influenza virus hemagglutinin using silver amplification.

PubMed

Wada, Atsuhiko; Sakoda, Yoshihiro; Oyamada, Takayoshi; Kida, Hiroshi

2011-12-01

H5N1, a highly pathogenic avian influenza virus (HPAIV), has become a serious epizootic threat to the poultry population in Asia. In addition, significant numbers of human cases of HPAIV infection have been reported to date. To prevent the spread of HPAIV among humans and to allow for timely medical intervention, a rapid and high sensitive method is needed to detect and subtype the causative HPAIVs. In the present study, a silver amplification technique used in photographic development was combined with immunochromatography technologies and a highly sensitive and rapid diagnostic test to detect the hemagglutinin of H5 influenza viruses was developed. The sensitivity of the test kit was increased 500 times by silver amplification. The sensitivity of the method was more than 10 times higher than those of conventional rapid influenza diagnostic tests, which detect viral nucleoproteins. The diagnostic system developed in the present study can therefore provide rapid and highly sensitive results and will be useful for diagnosis of H5 HPAIV infection in humans and animals. Copyright © 2011 Elsevier B.V. All rights reserved.

A perceptual space of local image statistics.

PubMed

Victor, Jonathan D; Thengone, Daniel J; Rizvi, Syed M; Conte, Mary M

2015-12-01

Local image statistics are important for visual analysis of textures, surfaces, and form. There are many kinds of local statistics, including those that capture luminance distributions, spatial contrast, oriented segments, and corners. While sensitivity to each of these kinds of statistics have been well-studied, much less is known about visual processing when multiple kinds of statistics are relevant, in large part because the dimensionality of the problem is high and different kinds of statistics interact. To approach this problem, we focused on binary images on a square lattice - a reduced set of stimuli which nevertheless taps many kinds of local statistics. In this 10-parameter space, we determined psychophysical thresholds to each kind of statistic (16 observers) and all of their pairwise combinations (4 observers). Sensitivities and isodiscrimination contours were consistent across observers. Isodiscrimination contours were elliptical, implying a quadratic interaction rule, which in turn determined ellipsoidal isodiscrimination surfaces in the full 10-dimensional space, and made predictions for sensitivities to complex combinations of statistics. These predictions, including the prediction of a combination of statistics that was metameric to random, were verified experimentally. Finally, check size had only a mild effect on sensitivities over the range from 2.8 to 14min, but sensitivities to second- and higher-order statistics was substantially lower at 1.4min. In sum, local image statistics form a perceptual space that is highly stereotyped across observers, in which different kinds of statistics interact according to simple rules. Copyright © 2015 Elsevier Ltd. All rights reserved.

A perceptual space of local image statistics

PubMed Central

Victor, Jonathan D.; Thengone, Daniel J.; Rizvi, Syed M.; Conte, Mary M.

2015-01-01

Local image statistics are important for visual analysis of textures, surfaces, and form. There are many kinds of local statistics, including those that capture luminance distributions, spatial contrast, oriented segments, and corners. While sensitivity to each of these kinds of statistics have been well-studied, much less is known about visual processing when multiple kinds of statistics are relevant, in large part because the dimensionality of the problem is high and different kinds of statistics interact. To approach this problem, we focused on binary images on a square lattice – a reduced set of stimuli which nevertheless taps many kinds of local statistics. In this 10-parameter space, we determined psychophysical thresholds to each kind of statistic (16 observers) and all of their pairwise combinations (4 observers). Sensitivities and isodiscrimination contours were consistent across observers. Isodiscrimination contours were elliptical, implying a quadratic interaction rule, which in turn determined ellipsoidal isodiscrimination surfaces in the full 10-dimensional space, and made predictions for sensitivities to complex combinations of statistics. These predictions, including the prediction of a combination of statistics that was metameric to random, were verified experimentally. Finally, check size had only a mild effect on sensitivities over the range from 2.8 to 14 min, but sensitivities to second- and higher-order statistics was substantially lower at 1.4 min. In sum, local image statistics forms a perceptual space that is highly stereotyped across observers, in which different kinds of statistics interact according to simple rules. PMID:26130606

Re-scan confocal microscopy: scanning twice for better resolution.

PubMed

De Luca, Giulia M R; Breedijk, Ronald M P; Brandt, Rick A J; Zeelenberg, Christiaan H C; de Jong, Babette E; Timmermans, Wendy; Azar, Leila Nahidi; Hoebe, Ron A; Stallinga, Sjoerd; Manders, Erik M M

2013-01-01

We present a new super-resolution technique, Re-scan Confocal Microscopy (RCM), based on standard confocal microscopy extended with an optical (re-scanning) unit that projects the image directly on a CCD-camera. This new microscope has improved lateral resolution and strongly improved sensitivity while maintaining the sectioning capability of a standard confocal microscope. This simple technology is typically useful for biological applications where the combination high-resolution and high-sensitivity is required.

Combined use of late phase dimercapto-succinic acid renal scintigraphy and ultrasound as first line screening after urinary tract infection in children.

PubMed

Quirino, Isabel G; Silva, Jose Maria P; Diniz, Jose S; Lima, Eleonora M; Rocha, Ana Cristina S; Simões e Silva, Ana Cristina; Oliveira, Eduardo A

2011-01-01

The aim of this study was to evaluate the diagnostic accuracy of dimercapto-succinic acid renal scintigraphy and renal ultrasound in identifying high grade vesicoureteral reflux in children after a first episode of urinary tract infection. A total of 533 children following a first urinary tract infection were included in the analysis. Patients were assessed by 3 diagnostic imaging studies, renal ultrasound, dimercapto-succinic acid scan and voiding cystourethrography. The main event of interest was the presence of high grade (III to V) vesicoureteral reflux. The combined and separate diagnostic accuracy of screening methods was assessed by calculation of diagnostic OR, sensitivity, specificity, positive predictive value, negative predictive value and likelihood ratio. A total of 246 patients had reflux, of whom 144 (27%) had high grade (III to V) disease. Sensitivity, negative predictive value and diagnostic OR of ultrasound for high grade reflux were 83.3%, 90.8% and 7.9, respectively. Dimercapto-succinic acid scan had the same sensitivity as ultrasound but a higher negative predictive value (91.7%) and diagnostic OR (10.9). If both tests were analyzed in parallel by using the OR rule, ie a negative diagnosis was established only when both test results were normal, sensitivity increased to 97%, negative predictive value to 97% and diagnostic OR to 25.3. Only 9 children (6.3%) with dilating reflux had an absence of alterations in both tests. Our findings support the idea that ultrasound and dimercapto-succinic acid scan used in combination are reliable predictors of dilating vesicoureteral reflux. Copyright © 2011 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

In-line FINCH super resolution digital holographic fluorescence microscopy using a high efficiency transmission liquid crystal GRIN lens.

PubMed

Brooker, Gary; Siegel, Nisan; Rosen, Joseph; Hashimoto, Nobuyuki; Kurihara, Makoto; Tanabe, Ayano

2013-12-15

We report a new optical arrangement that creates high-efficiency, high-quality Fresnel incoherent correlation holography (FINCH) holograms using polarization sensitive transmission liquid crystal gradient index (TLCGRIN) diffractive lenses. In contrast, current universal practice in the field employs a reflective spatial light modulator (SLM) to separate sample and reference beams. Polarization sensitive TLCGRIN lenses enable a straight optical path, have >90% transmission efficiency, are not pixilated, and are free of many limitations of reflective SLM devices. For each sample point, two spherical beams created by a glass lens in combination with a polarization sensitive TLCGRIN lens interfere and create a hologram and resultant super resolution image.

High-resolution high-sensitivity elemental imaging by secondary ion mass spectrometry: from traditional 2D and 3D imaging to correlative microscopy

NASA Astrophysics Data System (ADS)

Wirtz, T.; Philipp, P.; Audinot, J.-N.; Dowsett, D.; Eswara, S.

2015-10-01

Secondary ion mass spectrometry (SIMS) constitutes an extremely sensitive technique for imaging surfaces in 2D and 3D. Apart from its excellent sensitivity and high lateral resolution (50 nm on state-of-the-art SIMS instruments), advantages of SIMS include high dynamic range and the ability to differentiate between isotopes. This paper first reviews the underlying principles of SIMS as well as the performance and applications of 2D and 3D SIMS elemental imaging. The prospects for further improving the capabilities of SIMS imaging are discussed. The lateral resolution in SIMS imaging when using the microprobe mode is limited by (i) the ion probe size, which is dependent on the brightness of the primary ion source, the quality of the optics of the primary ion column and the electric fields in the near sample region used to extract secondary ions; (ii) the sensitivity of the analysis as a reasonable secondary ion signal, which must be detected from very tiny voxel sizes and thus from a very limited number of sputtered atoms; and (iii) the physical dimensions of the collision cascade determining the origin of the sputtered ions with respect to the impact site of the incident primary ion probe. One interesting prospect is the use of SIMS-based correlative microscopy. In this approach SIMS is combined with various high-resolution microscopy techniques, so that elemental/chemical information at the highest sensitivity can be obtained with SIMS, while excellent spatial resolution is provided by overlaying the SIMS images with high-resolution images obtained by these microscopy techniques. Examples of this approach are given by presenting in situ combinations of SIMS with transmission electron microscopy (TEM), helium ion microscopy (HIM) and scanning probe microscopy (SPM).

High-sensitivity ESCA instrument

DOE Office of Scientific and Technical Information (OSTI.GOV)

Davies, R.D.; Herglotz, H.K.; Lee, J.D.

1973-01-01

A new electron spectroscopy for chemical analysis (ESCA) instrument has been developed to provide high sensitivity and efficient operation for laboratory analysis of composition and chemical bonding in very thin surface layers of solid samples. High sensitivity is achieved by means of the high-intensity, efficient x-ray source described by Davies and Herglotz at the 1968 Denver X-Ray Conference, in combination with the new electron energy analyzer described by Lee at the 1972 Pittsburgh Conference on Analytical Chemistry and Applied Spectroscopy. A sample chamber designed to provide for rapid introduction and replacement of samples has adequate facilities for various sample treatmentsmore » and conditiouing followed immediately by ESCA analysis of the sample. Examples of application are presented, demonstrating the sensitivity and resolution achievable with this instrument. Its usefulness in trace surface analysis is shown and some chemical shifts'' measured by the instrument are compared with those obtained by x-ray spectroscopy. (auth)« less

Ultra-sensitive magnetic microscopy with an atomic magnetometer and flux guides

NASA Astrophysics Data System (ADS)

Kim, Young Jin; Savukov, Igor

Many applications in neuroscience, biomedical research, and material science require high-sensitivity, high-resolution magnetometry. In order to meet this need we recently combined a cm-size spin-exchange relaxation-free Atomic Magnetometer (AM) with a flux guide (FG) to produce ultra-sensitive FG-AM magnetic microscopy. The FG serves to transmit the target magnetic flux to the AM thus enhancing both the sensitivity and resolution to tiny magnetic objects. In this talk, we will describe existing and next generation FG-AM devices and present experimental and numerical tests of its sensitivity and resolution. We demonstrate that an optimized FG-AM has sufficient resolution and sensitivity for the detection of a small number of neurons, which would be an important milestone in neuroscience. In addition, as a demonstration of one possible application of the FG-AM device, we conducted high-resolution magnetic imaging of micron-size magnetic particles. We will show that the device can produce clear microscopic magnetic image of 10 μm-size magnetic particles.

Ultrasonic-assisted extraction and dispersive liquid-liquid microextraction combined with gas chromatography-mass spectrometry as an efficient and sensitive method for determining of acrylamide in potato chips samples.

PubMed

Zokaei, Maryam; Abedi, Abdol-Samad; Kamankesh, Marzieh; Shojaee-Aliababadi, Saeedeh; Mohammadi, Abdorreza

2017-11-01

In this research, for the first time, we successfully developed ultrasonic-assisted extraction and dispersive liquid-liquid microextraction combined with gas chromatography-mass spectrometry as a new, fast and highly sensitive method for determining of acrylamide in potato chips samples. Xanthydrol was used as a derivatization reagent and parameters affecting in the derivatization and microextraction steps were studied and optimized. Under optimum conditions, the calibration curves showed high levels of linearity (R 2 >0.9993) for acrylamide in the range of 2-500ngmL -1 . The relative standard deviation (RSD) for the seven analyses was 6.8%. The limit of detection (LOD) and limit of quantification (LOQ) were 0.6ngg -1 and 2ngg -1 , respectively. The UAE-DLLME-GC-MS method demonstrated high sensitivity, good linearity, recovery, and enrichment factor. The performance of the new proposed method was evaluated for the determination of acrylamide in various types of chips samples and satisfactory results were obtained. Copyright © 2017 Elsevier Ltd. All rights reserved.

[Sensitivity of clinical Proteus strains to antibiotics and their combinations].

PubMed

Sheina, E P; Arutcheva, A A

1978-05-01

In 1976 isolation of Proteus from wounds of patients with various purulent processes amounted to 14.5 per cent. Serotypes 0-10, 0-3 and H-3 predominated among the isolates. Sensitivity of 35 clinical strains of Proteus to 10 antibiotics, furagin and nevigramone was studied by the method of serial dilutions in liquid media. All the isolates were highly resistant to the antibiotics except gentamicin, furagin and nevigramone, the MIC of which for most of the strains was 3.12, 1.6-3.12 and 6.25-12.5 gamma/ml, respectively. The effect of 14 combinations of chemotherapeutics was also studied. The combinations of gentamicin with carbenicillin, gentamicin with ampicillin and monomycin with ampicillin proved to be most effective against the Proteus strains tested. The following combinations may be of practical value: monomycin + carbenicillin, kanamycin + ampicillin, kanamycin + carbenicillin, ampicillin + furagin, gentamicin + nevigramone. The combinations of carbenicillin with furagin and gentamicin with furagin were also rational.

Increasing access to kidney transplantation for sensitized recipient through three-way kidney paired donation with desensitization: The first Indian report

PubMed Central

Kute, Vivek B; Patel, Himanshu V; Shah, Pankaj R; Modi, Pranjal R; Shah, Veena R; Rizvi, Sayyed J; Pal, Bipin C; Modi, Manisha P; Shah, Priya S; Varyani, Umesh T; Wakhare, Pavan S; Shinde, Saiprasad G; Ghodela, Viajay A; Patel, Minaxi H; Trivedi, Varsha B; Trivedi, Hargovind L

2016-01-01

The combination of kidney paired donation (KPD) with desensitization represents a promising method of increasing the rate of living donor kidney transplantation (LDKT) in immunologically challenging patients. Patients who are difficult to match and desensitize due to strong donor specific antibody are may be transplanted by a combination of desensitization and KPD protocol with more immunologically favorable donor. We present our experience of combination of desensitization protocol with three-way KPD which contributed to successful LDKT in highly sensitized end stage renal disease patient. All recipients were discharged with normal and stable allograft function at 24 mo follow up. We believe that this is first report from India where three-way KPD exchange was performed with the combination of KPD and desensitization. The combination of desensitization protocol with KPD improves access and outcomes of LDKT. PMID:27803919

Highly Sensitive Flexible Pressure Sensors Based on Printed Organic Transistors with Centro-Apically Self-Organized Organic Semiconductor Microstructures.

PubMed

Yeo, So Young; Park, Sangsik; Yi, Yeon Jin; Kim, Do Hwan; Lim, Jung Ah

2017-12-13

A highly sensitive pressure sensor based on printed organic transistors with three-dimensionally self-organized organic semiconductor microstructures (3D OSCs) was demonstrated. A unique organic transistor with semiconductor channels positioned at the highest summit of printed cylindrical microstructures was achieved simply by printing an organic semiconductor and polymer blend on the plastic substrate without the use of additional etching or replication processes. A combination of the printed organic semiconductor microstructure and an elastomeric top-gate dielectric resulted in a highly sensitive organic field-effect transistor (FET) pressure sensor with a high pressure sensitivity of 1.07 kPa -1 and a rapid response time of <20 ms with a high reliability over 1000 cycles. The flexibility and high performance of the 3D OSC FET pressure sensor were exploited in the successful application of our sensors to real-time monitoring of the radial artery pulse, which is useful for healthcare monitoring, and to touch sensing in the e-skin of a realistic prosthetic hand.

Method and apparatus for distributed intrusion protection system for ultra high bandwidth networks

DOEpatents

Goranson, Craig A.; Burnette, John R.; Greitzer, Frank L.; McMillan, Bryan H.

2013-10-15

A method for providing security to a network having a data stream with a plurality of portions of data, each having differing levels of sensitivity. The data stream is interrogated to determine the presence of predetermined characteristics associated with at least one of the portions of data within the data stream. At least one of the portions of data is then characterized, based upon the portion of data exhibiting a predetermined combination of characteristics, wherein the predetermined combination of characteristics is related to the sensitivity of the portion of data. The portions of the data stream are then distributed into a plurality of different channels, each of the channels associated with different level of sensitivity.

Re-scan confocal microscopy: scanning twice for better resolution

PubMed Central

De Luca, Giulia M.R.; Breedijk, Ronald M.P.; Brandt, Rick A.J.; Zeelenberg, Christiaan H.C.; de Jong, Babette E.; Timmermans, Wendy; Azar, Leila Nahidi; Hoebe, Ron A.; Stallinga, Sjoerd; Manders, Erik M.M.

2013-01-01

We present a new super-resolution technique, Re-scan Confocal Microscopy (RCM), based on standard confocal microscopy extended with an optical (re-scanning) unit that projects the image directly on a CCD-camera. This new microscope has improved lateral resolution and strongly improved sensitivity while maintaining the sectioning capability of a standard confocal microscope. This simple technology is typically useful for biological applications where the combination high-resolution and high-sensitivity is required. PMID:24298422

Sensitive Quantification of Cannabinoids in Milk by Alkaline Saponification-Solid Phase Extraction Combined with Isotope Dilution UPLC-MS/MS.

PubMed

Wei, Binnian; McGuffey, James E; Blount, Benjamin C; Wang, Lanqing

2016-01-01

Maternal exposure to marijuana during the lactation period-either active or passive-has prompted concerns about transmission of cannabinoids to breastfed infants and possible subsequent adverse health consequences. Assessing these health risks requires a sensitive analytical approach that is able to quantitatively measure trace-level cannabinoids in breast milk. Here, we describe a saponification-solid phase extraction approach combined with ultra-high-pressure liquid chromatography-tandem mass spectrometry for simultaneously quantifying Δ9-tetrahydrocannabinol (THC), cannabidiol (CBD), and cannabinol (CBN) in breast milk. We demonstrate for the first time that constraints on sensitivity can be overcome by utilizing alkaline saponification of the milk samples. After extensively optimizing the saponification procedure, the validated method exhibited limits of detections of 13, 4, and 66 pg/mL for THC, CBN, and CBD, respectively. Notably, the sensitivity achieved was significantly improved, for instance, the limits of detection for THC is at least 100-fold more sensitive compared to that previously reported in the literature. This is essential for monitoring cannabinoids in breast milk resulting from passive or nonrecent active maternal exposure. Furthermore, we simultaneously acquired multiple reaction monitoring transitions for 12 C- and 13 C-analyte isotopes. This combined analysis largely facilitated data acquisition by reducing the repetitive analysis rate for samples exceeding the linear limits of 12 C-analytes. In addition to high sensitivity and broad quantitation range, this method delivers excellent accuracy (relative error within ±10%), precision (relative standard deviation <10%), and efficient analysis. In future studies, we expect this method to play a critical role in assessing infant exposure to cannabinoids through breastfeeding.

Optimal CINAHL search strategies for identifying therapy studies and review articles.

PubMed

Wong, Sharon S L; Wilczynski, Nancy L; Haynes, R Brian

2006-01-01

To design optimal search strategies for locating sound therapy studies and review articles in CiNAHL in the year 2000. An analytic survey was conducted, comparing hand searches of 75 journals with retrievals from CINAHL for 5,020 candidate search terms and 17,900 combinations for therapy and 5,977 combinations for review articles. All articles were rated with purpose and quality indicators. Candidate search strategies were used in CINAHL, and the retrievals were compared with results of the hand searches. The proposed search strategies were treated as "diagnostic tests" for sound studies and the manual review of the literature was treated as the "gold standard." Operating characteristics of the search strategies were calculated. Of the 1,383 articles about treatment, 506 (36.6%) met basic criteria for scientific merit and 127 (17.9%) of the 711 articles classified as a review met the criteria for systematic reviews. For locating sound treatment studies, a three-term strategy maximized sensitivity at 99.4% but with compromised specificity at 58.3%, and a two-term strategy maximized specificity at 98.5% but with compromised sensitivity at 52.0%. For detecting systematic reviews, a three-term strategy maximized sensitivity at 91.3% while keeping specificity high at 95.4%, and a single-term strategy maximized specificity at 99.6% but with compromised sensitivity at 42.5%. Three-term search strategies optimizing sensitivity and specificity achieved these values over 91% for detecting sound treatment studies and over 76% for detecting systematic reviews. Search strategies combining indexing terms and text words can achieve high sensitivity and specificity for retrieving sound treatment studies and review articles in CINAHL.

A combination of immunohistochemistry and molecular approaches improves highly sensitive detection of BRAF mutations in papillary thyroid cancer.

PubMed

Martinuzzi, Claudia; Pastorino, Lorenza; Andreotti, Virginia; Garuti, Anna; Minuto, Michele; Fiocca, Roberto; Bianchi-Scarrà, Giovanna; Ghiorzo, Paola; Grillo, Federica; Mastracci, Luca

2016-09-01

The optimal method for BRAF mutation detection remains to be determined despite advances in molecular detection techniques. The aim of this study was to compare, against classical Sanger sequencing, the diagnostic performance of two of the most recently developed, highly sensitive methods: BRAF V600E immunohistochemistry (IHC) and peptide nucleic-acid (PNA)-clamp qPCR. BRAF exon 15 mutations were searched in formalin-fixed paraffin-embedded tissues from 86 papillary thyroid carcinoma using the three methods. The limits of detection of Sanger sequencing in borderline or discordant cases were quantified by next generation sequencing. BRAF mutations were found in 74.4 % of cases by PNA, in 71 % of cases by IHC, and in 64 % of cases by Sanger sequencing. Complete concordance for the three methods was observed in 80 % of samples. Better concordance was observed with the combination of two methods, particularly PNA and IHC (59/64) (92 %), while the combination of PNA and Sanger was concordant in 55 cases (86 %). Sensitivity of the three methods was 99 % for PNA, 94.2 % for IHC, and 89.5 % for Sanger. Our data show that IHC could be used as a cost-effective, first-line method for BRAF V600E detection in daily practice, followed by PNA analysis in negative or uninterpretable cases, as the most efficient method. PNA-clamp quantitative PCR is highly sensitive and complementary to IHC as it also recognizes other mutations besides V600E and it is suitable for diagnostic purposes.

Photonic crystal nanofiber air-mode cavity with high Q-factor and high sensitivity for refractive index sensing

NASA Astrophysics Data System (ADS)

Ma, Xiaoxue; Chen, Xin; Nie, Hongrui; Yang, Daquan

2018-01-01

Recently, due to its superior characteristics and simple manufacture, such as small size, low loss, high sensitivity and convenience to couple, the optical fiber sensor has become one of the most promising sensors. In order to achieve the most effective realization of light propagation by changing the structure of sensors, FOM(S •Q/λres) ,which is determined by two significant variables Q-factor and sensitivity, as a trade-off parameter should be optimized to a high value. In typical sensors, a high Q can be achieved by confining the optical field in the high refractive index dielectric region to make an interaction between analytes and evanescent field of the resonant mode. However, the ignored sensitivity is relatively low with a high Q achieved, which means that the resonant wavelength shift changes non-obviously when the refractive index increases. Meanwhile, the sensitivity also leads to a less desirable FOM. Therefore, a gradient structure, which can enhance the performance of sensors by achieving high Q and high sensitivity, has been developed by Kim et al. later. Here, by introducing parabolic-tapered structure, the light field localized overlaps strongly and sufficiently with analytes. And based on a one-dimensional photonic-crystal nanofiber air-mode cavity, a creative optical fiber sensor is proposed by combining good stability and transmission characteristics of fiber and strengths of tapered structure, realizing excellent FOM {4.7 x 105 with high Q-factors (Q{106) and high sensitivities (<700 nm/RIU).

Cluster secondary ion mass spectrometry microscope mode mass spectrometry imaging.

PubMed

Kiss, András; Smith, Donald F; Jungmann, Julia H; Heeren, Ron M A

2013-12-30

Microscope mode imaging for secondary ion mass spectrometry is a technique with the promise of simultaneous high spatial resolution and high-speed imaging of biomolecules from complex surfaces. Technological developments such as new position-sensitive detectors, in combination with polyatomic primary ion sources, are required to exploit the full potential of microscope mode mass spectrometry imaging, i.e. to efficiently push the limits of ultra-high spatial resolution, sample throughput and sensitivity. In this work, a C60 primary source was combined with a commercial mass microscope for microscope mode secondary ion mass spectrometry imaging. The detector setup is a pixelated detector from the Medipix/Timepix family with high-voltage post-acceleration capabilities. The system's mass spectral and imaging performance is tested with various benchmark samples and thin tissue sections. The high secondary ion yield (with respect to 'traditional' monatomic primary ion sources) of the C60 primary ion source and the increased sensitivity of the high voltage detector setup improve microscope mode secondary ion mass spectrometry imaging. The analysis time and the signal-to-noise ratio are improved compared with other microscope mode imaging systems, all at high spatial resolution. We have demonstrated the unique capabilities of a C60 ion microscope with a Timepix detector for high spatial resolution microscope mode secondary ion mass spectrometry imaging. Copyright © 2013 John Wiley & Sons, Ltd.

An approach to measure parameter sensitivity in watershed ...

EPA Pesticide Factsheets

Hydrologic responses vary spatially and temporally according to watershed characteristics. In this study, the hydrologic models that we developed earlier for the Little Miami River (LMR) and Las Vegas Wash (LVW) watersheds were used for detail sensitivity analyses. To compare the relative sensitivities of the hydrologic parameters of these two models, we used Normalized Root Mean Square Error (NRMSE). By combining the NRMSE index with the flow duration curve analysis, we derived an approach to measure parameter sensitivities under different flow regimes. Results show that the parameters related to groundwater are highly sensitive in the LMR watershed, whereas the LVW watershed is primarily sensitive to near surface and impervious parameters. The high and medium flows are more impacted by most of the parameters. Low flow regime was highly sensitive to groundwater related parameters. Moreover, our approach is found to be useful in facilitating model development and calibration. This journal article describes hydrological modeling of climate change and land use changes on stream hydrology, and elucidates the importance of hydrological model construction in generating valid modeling results.

Fiber optical sensors for aircraft applications

NASA Astrophysics Data System (ADS)

Pechstedt, Ralf D.

2014-09-01

In this paper selected fiber optical point sensors that are of potential interest for deployment in aircraft are discussed. The operating principles together with recent measurement results are described. Examples include a high-temperature combined pressure and temperature sensor for engine health, hydraulics and landing gear monitoring, an ultra-high sensitive pressure sensor for oil, pneumatic and fluid aero systems applications and a combined acceleration and temperature sensor for condition monitoring of rotating components.

In vitro activity of flomoxef and cefazolin in combination with vancomycin.

PubMed

Simon, C; Simon, M

1991-01-01

207 clinical isolates from strains of patients from the University Children's Hospital of Kiel were investigated for their in vitro activity with the agar dilution method against flomoxef and cefazolin (alone and partially in combination with vancomycin). Staphylococci were also tested with other cephalosporins (cefoxitin, cefamandole, cefotaxime, cefotetan and latamoxef). Flomoxef and cefazolin always acted more vigorously on staphylococci than the other cephalosporins. Resistance of Staphylococcus aureus strains against flomoxef and cefazolin did not occur but was found in 15 and 5 of 98 Staphylococcus epidermidis strains, respectively. Enterococcus faecalis strains were always resistant against both drugs; Streptococcus faecium strains were only moderately sensitive. Combined testing of flomoxef or cefazolin with vancomycin showed synergism in almost all staphylococcal strains. Synergism was stronger when S. epidermidis strains were only weakly sensitive to or resistant against flomoxef and cefazolin in comparison to highly sensitive strains. Flomoxef (or cefazolin) acted synergistically in combination with vancomycin on E. faecalis and S. faecium with the exception of two strains of E. faecalis which showed an additive effect of both drugs.

Development of a highly sensitive three-dimensional gel electrophoresis method for characterization of monoclonal protein heterogeneity.

PubMed

Nakano, Keiichi; Tamura, Shogo; Otuka, Kohei; Niizeki, Noriyasu; Shigemura, Masahiko; Shimizu, Chikara; Matsuno, Kazuhiko; Kobayashi, Seiichi; Moriyama, Takanori

2013-07-15

Three-dimensional gel electrophoresis (3-DE), which combines agarose gel electrophoresis and isoelectric focusing/SDS-PAGE, was developed to characterize monoclonal proteins (M-proteins). However, the original 3-DE method has not been optimized and its specificity has not been demonstrated. The main goal of this study was to optimize the 3-DE procedure and then compare it with 2-DE. We developed a highly sensitive 3-DE method in which M-proteins are extracted from a first-dimension agarose gel, by diffusing into 150 mM NaCl, and the recovery of M-proteins was 90.6%. To validate the utility of the highly sensitive 3-DE, we compared it with the original 3-DE method. We found that highly sensitive 3-DE provided for greater M-protein recovery and was more effective in terms of detecting spots on SDS-PAGE gels than the original 3-DE. Moreover, highly sensitive 3-DE separates residual normal IgG from M-proteins, which could not be done by 2-DE. Applying the highly sensitive 3-DE to clinical samples, we found that the characteristics of M-proteins vary tremendously between individuals. We believe that our highly sensitive 3-DE method described here will prove useful in further studies of the heterogeneity of M-proteins. Copyright © 2013 Elsevier Inc. All rights reserved.

Comparison of solid-phase bioassays and ecoscores to evaluate the toxicity of contaminated soils.

PubMed

Lors, Christine; Ponge, Jean-François; Martínez Aldaya, Maite; Damidot, Denis

2010-08-01

Five bioassays (inhibition of lettuce germination and growth, earthworm mortality, inhibition of springtail population growth, avoidance by springtails) were compared, using four coke factory soils contaminated by PAHs and trace elements, before and after biotreatment. For each bioassay, several endpoints were combined in an 'ecoscore', a measure of test sensitivity. Ecoscores pooled over all tested bioassays revealed that most organisms were highly sensitive to the concentration of 3-ring PAHs. When four soils were combined, behavioural tests using the springtail Folsomia candida showed higher ecoscores, i.e. they were most sensitive to soil contamination. However, despite overall higher sensitivity of behavioural tests, which could be used for cheap and rapid assessment of soil toxicity, especially at low levels of contamination, some test endpoints were more sensitive than others, and this may differ from a soil to another, pointing to the need for a battery of bioassays when more itemized results are expected. Copyright 2010 Elsevier Ltd. All rights reserved.

Increased thermal pain sensitivity in animals exposed to chronic high dose Vicodin but not pure hydrocodone.

PubMed

O'Connell, Thomas F; Carpenter, Patrick S; Caballero, Nadia; Putnam, Andrew J; Steere, Joshua T; Matz, Gregory J; Foecking, Eileen M

2014-01-01

Vicodin, the combination drug of acetaminophen and the opioid hydrocodone, is one of the most prescribed drugs on the market today. Opioids have demonstrated the ability to paradoxically cause increased pain sensitivity to users in a phenomena called opioid-induced hyperalgesia (OIH). While selected opioids have been shown to produce OIH symptoms in an animal model, hydrocodone and the combination drug Vicodin have yet to be studied. The purpose of this study was to explore the effect of exposure to chronic high dose Vicodin or its components on the sensitivity to both thermal and mechanical pain. Animals were randomly divided into 4 groups, Vicodin, acetaminophen, hydrocodone, or vehicle control, and administered the drug daily for 120 days. Rats were subsequently tested for thermal and mechanical sensitivity. The rats in the Vicodin group displayed a significant decrease in withdrawal time to thermal pain. The rats receiving acetaminophen, hydrocodone, and vehicle showed no statistically significant hypersensitivity in thermal testing. None of the groups demonstrated statistically significant hypersensitivity to mechanical testing. The data suggests Vicodin produces signs of OIH in a rodent model. However, increased pain sensitivity was only noted in the thermal pathway and the hypersensitivity was only seen with the opioid combination drug, not the opioid alone. The results of this study both support the results of previous rodent opioid studies while generating further questions about the specific properties of Vicodin that contribute to pain hypersensitivity. The growing use of Vicodin to treat chronic pain necessitates further research looking into this paradoxical pain response.

Deep-UV-sensitive high-frame-rate backside-illuminated CCD camera developments

NASA Astrophysics Data System (ADS)

Dawson, Robin M.; Andreas, Robert; Andrews, James T.; Bhaskaran, Mahalingham; Farkas, Robert; Furst, David; Gershstein, Sergey; Grygon, Mark S.; Levine, Peter A.; Meray, Grazyna M.; O'Neal, Michael; Perna, Steve N.; Proefrock, Donald; Reale, Michael; Soydan, Ramazan; Sudol, Thomas M.; Swain, Pradyumna K.; Tower, John R.; Zanzucchi, Pete

2002-04-01

New applications for ultra-violet imaging are emerging in the fields of drug discovery and industrial inspection. High throughput is critical for these applications where millions of drug combinations are analyzed in secondary screenings or high rate inspection of small feature sizes over large areas is required. Sarnoff demonstrated in1990 a back illuminated, 1024 X 1024, 18 um pixel, split-frame-transfer device running at > 150 frames per second with high sensitivity in the visible spectrum. Sarnoff designed, fabricated and delivered cameras based on these CCDs and is now extending this technology to devices with higher pixel counts and higher frame rates through CCD architectural enhancements. The high sensitivities obtained in the visible spectrum are being pushed into the deep UV to support these new medical and industrial inspection applications. Sarnoff has achieved measured quantum efficiencies > 55% at 193 nm, rising to 65% at 300 nm, and remaining almost constant out to 750 nm. Optimization of the sensitivity is being pursued to tailor the quantum efficiency for particular wavelengths. Characteristics of these high frame rate CCDs and cameras will be described and results will be presented demonstrating high UV sensitivity down to 150 nm.

Nonlinear processing of a multicomponent communication signal by combination-sensitive neurons in the anuran inferior colliculus.

PubMed

Lee, Norman; Schrode, Katrina M; Bee, Mark A

2017-09-01

Diverse animals communicate using multicomponent signals. How a receiver's central nervous system integrates multiple signal components remains largely unknown. We investigated how female green treefrogs (Hyla cinerea) integrate the multiple spectral components present in male advertisement calls. Typical calls have a bimodal spectrum consisting of formant-like low-frequency (~0.9 kHz) and high-frequency (~2.7 kHz) components that are transduced by different sensory organs in the inner ear. In behavioral experiments, only bimodal calls reliably elicited phonotaxis in no-choice tests, and they were selectively chosen over unimodal calls in two-alternative choice tests. Single neurons in the inferior colliculus of awake, passively listening subjects were classified as combination-insensitive units (27.9%) or combination-sensitive units (72.1%) based on patterns of relative responses to the same bimodal and unimodal calls. Combination-insensitive units responded similarly to the bimodal call and one or both unimodal calls. In contrast, combination-sensitive units exhibited both linear responses (i.e., linear summation) and, more commonly, nonlinear responses (e.g., facilitation, compressive summation, or suppression) to the spectral combination in the bimodal call. These results are consistent with the hypothesis that nonlinearities play potentially critical roles in spectral integration and in the neural processing of multicomponent communication signals.

The reduced local lymph node assay: the impact of group size.

PubMed

Ryan, Cindy A; Chaney, Joel G; Kern, Petra S; Patlewicz, Grace Y; Basketter, David A; Betts, Catherine J; Dearman, Rebecca J; Kimber, Ian; Gerberick, G Frank

2008-05-01

The local lymph node assay (LLNA) is a skin sensitization test that provides animal welfare benefits. To reduce animal usage further, a modified version (rLLNA) was proposed. Conducting the rLLNA as a screening test with a single high dose group and vehicle control differentiated accurately between skin sensitizers and non-sensitizers. This study examined whether a reduction in animal number/group is feasible. Historical data were utilized to examine the impact of conducting the rLLNA with two mice/group. To assess the effect on the stimulation index (SI) 41 datasets with individual animal data derived using five mice/group were analysed. SIs were calculated on all possible combinations of two control and two high dose group disintegrations per minute (dpm) values. For 25 of 33 sensitizer datasets, > 96% of possible dpm combinations resulted in a calculated SI > 3. The lowest percentages of positive SIs were observed with weak allergens when, in the standard LLNA, the mean SIs would have been nearer to the threshold value of 3. The results indicate that moderate, strong and extreme allergens are more likely than weak allergens to be identified as sensitizers when group sizes of two mice are used within the rLLNA. It is concluded that a rLLNA with two mice/group would display decreased sensitivity and is inappropriate for use in hazard identification. Copyright (c) 2007 John Wiley & Sons, Ltd.

Sensitivity of Hyperdense Basilar Artery Sign on Non-Enhanced Computed Tomography.

PubMed

Ernst, Marielle; Romero, Javier M; Buhk, Jan-Hendrik; Cheng, Bastian; Herrmann, Jochen; Fiehler, Jens; Groth, Michael

2015-01-01

The hyperdense basilar artery sign (HBAS) is an indicator of vessel occlusion on non contrast-enhanced computer tomography (NECT) in acute stroke patients. Since basilar artery occlusion (BAO) is associated with a high mortality and morbidity, its early detection is of great clinical value. We sought to analyze the influence of density measurement as well as a normalized ratio of Hounsfield unit/hematocrit (HU/Hct) ratio on the detection of BAO on NECT in patients with suspected BAO. 102 patients with clinically suspected BAO were examined with NECT followed immediately by Multidetector computed tomography Angiography. Two observers independently analyzed the images regarding the presence or absence of HBAS on NECT and performed HU measurements in the basilar artery. Receiver operating characteristic curve analysis was performed to determine the optimal density threshold for BAO using attenuation measurements or HU/Hct ratio. Sensitivity of visual detection of the HBAS on NECT was relatively low 81% (95%-CI, 54-95%) while specificity was high 91% (95%-CI, 82-96%). The highest sensitivity was achieved by the combination of visual assessment and additional quantitative attenuation measurements applying a cut-off value of 46.5 HU with 94% sensitivity and 81% specificity for BAO. A HU/Hct ratio >1.32 revealed sensitivity of 88% (95%-CI, 60-98%) and specificity of 84% (95%-CI, 74-90%). In patients with clinically suspected acute BAO the combination of visual assessment and additional attenuation measurement with a cut-off value of 46.5 HU is a reliable approach with high sensitivity in the detection of BAO on NECT.

Temporal diagnostic analysis of the SWAT model to detect dominant periods of poor model performance

NASA Astrophysics Data System (ADS)

Guse, Björn; Reusser, Dominik E.; Fohrer, Nicola

2013-04-01

Hydrological models generally include thresholds and non-linearities, such as snow-rain-temperature thresholds, non-linear reservoirs, infiltration thresholds and the like. When relating observed variables to modelling results, formal methods often calculate performance metrics over long periods, reporting model performance with only few numbers. Such approaches are not well suited to compare dominating processes between reality and model and to better understand when thresholds and non-linearities are driving model results. We present a combination of two temporally resolved model diagnostic tools to answer when a model is performing (not so) well and what the dominant processes are during these periods. We look at the temporal dynamics of parameter sensitivities and model performance to answer this question. For this, the eco-hydrological SWAT model is applied in the Treene lowland catchment in Northern Germany. As a first step, temporal dynamics of parameter sensitivities are analyzed using the Fourier Amplitude Sensitivity test (FAST). The sensitivities of the eight model parameters investigated show strong temporal variations. High sensitivities were detected for two groundwater (GW_DELAY, ALPHA_BF) and one evaporation parameters (ESCO) most of the time. The periods of high parameter sensitivity can be related to different phases of the hydrograph with dominances of the groundwater parameters in the recession phases and of ESCO in baseflow and resaturation periods. Surface runoff parameters show high parameter sensitivities in phases of a precipitation event in combination with high soil water contents. The dominant parameters give indication for the controlling processes during a given period for the hydrological catchment. The second step included the temporal analysis of model performance. For each time step, model performance was characterized with a "finger print" consisting of a large set of performance measures. These finger prints were clustered into four reoccurring patterns of typical model performance, which can be related to different phases of the hydrograph. Overall, the baseflow cluster has the lowest performance. By combining the periods with poor model performance with the dominant model components during these phases, the groundwater module was detected as the model part with the highest potential for model improvements. The detection of dominant processes in periods of poor model performance enhances the understanding of the SWAT model. Based on this, concepts how to improve the SWAT model structure for the application in German lowland catchment are derived.

The electrophotonic silicon biosensor

NASA Astrophysics Data System (ADS)

Juan-Colás, José; Parkin, Alison; Dunn, Katherine E.; Scullion, Mark G.; Krauss, Thomas F.; Johnson, Steven D.

2016-09-01

The emergence of personalized and stratified medicine requires label-free, low-cost diagnostic technology capable of monitoring multiple disease biomarkers in parallel. Silicon photonic biosensors combine high-sensitivity analysis with scalable, low-cost manufacturing, but they tend to measure only a single biomarker and provide no information about their (bio)chemical activity. Here we introduce an electrochemical silicon photonic sensor capable of highly sensitive and multiparameter profiling of biomarkers. Our electrophotonic technology consists of microring resonators optimally n-doped to support high Q resonances alongside electrochemical processes in situ. The inclusion of electrochemical control enables site-selective immobilization of different biomolecules on individual microrings within a sensor array. The combination of photonic and electrochemical characterization also provides additional quantitative information and unique insight into chemical reactivity that is unavailable with photonic detection alone. By exploiting both the photonic and the electrical properties of silicon, the sensor opens new modalities for sensing on the microscale.

The sensitivity and specificity of the neurological examination in polyneuropathy patients with clinical and electrophysiological correlations.

PubMed

Abraham, Alon; Alabdali, Majed; Alsulaiman, Abdulla; Albulaihe, Hana; Breiner, Ari; Katzberg, Hans D; Aljaafari, Danah; Lovblom, Leif E; Bril, Vera

2017-01-01

Polyneuropathy is one of the most prevalent neurologic disorders. Although several studies explored the role of the neurological examination in polyneuropathy, they were mostly restricted to specific subgroups of patients and have not correlated examination findings with symptoms and electrophysiological results. To explore the sensitivity and specificity of different neurological examination components in patients with diverse etiologies for polyneuropathy, find the most sensitive combination of examination components for polyneuropathy detection, and correlate examination findings with symptoms and electrophysiological results. Patients with polyneuropathy attending the neuromuscular clinic from 01/2013 to 09/2015 were evaluated. Inclusion criteria included symptomatic polyneuropathy, which was confirmed by electrophysiological studies. 47 subjects with no symptoms or electrophysiological findings suggestive for polyneuropathy, served as controls. The total cohort included 312 polyneuropathy patients, with a mean age of 60±14 years. Abnormal examination was found in 95%, most commonly sensory findings (86%). The most common abnormal examination components were impaired ankle reflexes (74%), vibration (73%), and pinprick (72%) sensation. Combining ankle reflex examination with vibration or pinprick perception had the highest sensitivity, of 88%. The specificities of individual examination component were generally high, excluding ankle reflexes (62%), and vibration perception (77%). Abnormal examination findings were correlated with symptomatic weakness and worse electrophysiological parameters. The neurological examination is a valid, sensitive and specific tool for diagnosing polyneuropathy, and findings correlate with polyneuropathy severity. Ankle reflex examination combined with either vibration or pinprick sensory testing is the most sensitive combination for diagnosing polyneuropathy, and should be considered minimal essential components of the physical examination in patients with suspected polyneuropathy.

Combining two serological assays optimises sensitivity and specificity for the identification of Streptococcus equi subsp. equi exposure.

PubMed

Robinson, Carl; Steward, Karen F; Potts, Nicola; Barker, Colin; Hammond, Toni-ann; Pierce, Karen; Gunnarsson, Eggert; Svansson, Vilhjálmur; Slater, Josh; Newton, J Richard; Waller, Andrew S

2013-08-01

The detection of anti-Streptococcus equi antibodies in the blood serum of horses can assist with the identification of apparently healthy persistently infected carriers and the prevention of strangles outbreaks. The aim of the current study was to use genome sequencing data to develop an indirect enzyme linked immunosorbent assay (iELISA) that targets two S. equi-specific protein fragments. The sensitivity and specificity of the antigen A and antigen C iELISAs were compared to an SeM-based iELISA marketed by IDvet - diagnostic Vétérinaire (IDvet). Individually, each assay compromised specificity in order to achieve sufficient sensitivity (SeM iELISA had a sensitivity of 89.9%, but a specificity of only 77.0%) or sensitivity to achieve high specificity. However, combining the results of the antigen A and antigen C iELISAs permitted optimisation of both sensitivity (93.3%) and specificity (99.3%), providing a robust assay for the identification of horses exposed to S. equi. Copyright © 2013 Elsevier Ltd. All rights reserved.

High mass resolution time of flight mass spectrometer for measuring products in heterogeneous catalysis in highly sensitive microreactors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Andersen, T.; Jensen, R.; Christensen, M. K.

2012-07-15

We demonstrate a combined microreactor and time of flight system for testing and characterization of heterogeneous catalysts with high resolution mass spectrometry and high sensitivity. Catalyst testing is performed in silicon-based microreactors which have high sensitivity and fast thermal response. Gas analysis is performed with a time of flight mass spectrometer with a modified nude Bayard-Alpert ionization gauge as gas ionization source. The mass resolution of the time of flight mass spectrometer using the ion gauge as ionization source is estimated to m/{Delta}m > 2500. The system design is superior to conventional batch and flow reactors with accompanying product detectionmore » by quadrupole mass spectrometry or gas chromatography not only due to the high sensitivity, fast temperature response, high mass resolution, and fast acquisition time of mass spectra but it also allows wide mass range (0-5000 amu in the current configuration). As a demonstration of the system performance we present data from ammonia oxidation on a Pt thin film showing resolved spectra of OH and NH{sub 3}.« less

High mass resolution time of flight mass spectrometer for measuring products in heterogeneous catalysis in highly sensitive microreactors

NASA Astrophysics Data System (ADS)

Andersen, T.; Jensen, R.; Christensen, M. K.; Pedersen, T.; Hansen, O.; Chorkendorff, I.

2012-07-01

We demonstrate a combined microreactor and time of flight system for testing and characterization of heterogeneous catalysts with high resolution mass spectrometry and high sensitivity. Catalyst testing is performed in silicon-based microreactors which have high sensitivity and fast thermal response. Gas analysis is performed with a time of flight mass spectrometer with a modified nude Bayard-Alpert ionization gauge as gas ionization source. The mass resolution of the time of flight mass spectrometer using the ion gauge as ionization source is estimated to m/Δm > 2500. The system design is superior to conventional batch and flow reactors with accompanying product detection by quadrupole mass spectrometry or gas chromatography not only due to the high sensitivity, fast temperature response, high mass resolution, and fast acquisition time of mass spectra but it also allows wide mass range (0-5000 amu in the current configuration). As a demonstration of the system performance we present data from ammonia oxidation on a Pt thin film showing resolved spectra of OH and NH3.

High mass resolution time of flight mass spectrometer for measuring products in heterogeneous catalysis in highly sensitive microreactors.

PubMed

Andersen, T; Jensen, R; Christensen, M K; Pedersen, T; Hansen, O; Chorkendorff, I

2012-07-01

We demonstrate a combined microreactor and time of flight system for testing and characterization of heterogeneous catalysts with high resolution mass spectrometry and high sensitivity. Catalyst testing is performed in silicon-based microreactors which have high sensitivity and fast thermal response. Gas analysis is performed with a time of flight mass spectrometer with a modified nude Bayard-Alpert ionization gauge as gas ionization source. The mass resolution of the time of flight mass spectrometer using the ion gauge as ionization source is estimated to m/Δm > 2500. The system design is superior to conventional batch and flow reactors with accompanying product detection by quadrupole mass spectrometry or gas chromatography not only due to the high sensitivity, fast temperature response, high mass resolution, and fast acquisition time of mass spectra but it also allows wide mass range (0-5000 amu in the current configuration). As a demonstration of the system performance we present data from ammonia oxidation on a Pt thin film showing resolved spectra of OH and NH(3).

A highly sensitive single-tube nested PCR assay for the detection of Pineapple mealybug wilt associated virus-2 (PMWaV-2)

USDA-ARS?s Scientific Manuscript database

An assay was developed for the detection of Pineapple mealybug wilt associated virus-2 (PMWaV-2), an important factor in the etiology of mealybug wilt of pineapple. The assay combines reverse transcription of RNA isolated from pineapple with a specific and very sensitive, single, closed-tube nested ...

A simple and rapid DNA extraction method for Chlamydia trachomatis detection from urogenital swabs.

PubMed

Butzler, Matthew A; Reed, Jennifer L; McFall, Sally M

2017-11-01

A highly sensitive and specific Chlamydia trachomatis (CT) diagnostic test was developed by combining filtration isolation of nucleic acid (FINA) extraction with quantitative polymerase chain reaction including an internal control to identify test inhibition. A pilot study of 40 clinical specimens yielded 100% sensitivity and specificity. Copyright © 2017 Elsevier Inc. All rights reserved.

High Sensitivity Gas Detection Using a Macroscopic Three-Dimensional Graphene Foam Network

PubMed Central

Yavari, Fazel; Chen, Zongping; Thomas, Abhay V.; Ren, Wencai; Cheng, Hui-Ming; Koratkar, Nikhil

2011-01-01

Nanostructures are known to be exquisitely sensitive to the chemical environment and offer ultra-high sensitivity for gas-sensing. However, the fabrication and operation of devices that use individual nanostructures for sensing is complex, expensive and suffers from poor reliability due to contamination and large variability from sample-to-sample. By contrast, conventional solid-state and conducting-polymer sensors offer excellent reliability but suffer from reduced sensitivity at room-temperature. Here we report a macro graphene foam-like three-dimensional network which combines the best of both worlds. The walls of the foam are comprised of few-layer graphene sheets resulting in high sensitivity; we demonstrate parts-per-million level detection of NH3 and NO2 in air at room-temperature. Further, the foam is a mechanically robust and flexible macro-scale network that is easy to contact (without Lithography) and can rival the durability and affordability of traditional sensors. Moreover, Joule-heating expels chemisorbed molecules from the foam's surface leading to fully-reversible and low-power operation. PMID:22355681

Combined ultrasound-guided cutting-needle biopsy and standard pleural biopsy for diagnosis of malignant pleural effusions.

PubMed

Wang, Jinlin; Zhou, Xinghua; Xie, Xiaohong; Tang, Qing; Shen, Panxiao; Zeng, Yunxiang

2016-11-17

The most efficient approach to diagnose malignant pleural effusions (MPEs) is still controversial and uncertain. This study aimed to evaluate the utility of a combined approach using ultrasound (US)-guided cutting-needle biopsy (CNB) and standard pleural biopsy (SPB) for diagnosing MPE. Pleural effusions were collected from 172 patients for biochemical and microbiological analyses. US-guided CNB and SPB were performed in the same operation sequentially to obtain specimens for histological analysis. US-guided CNB and SPB procedures provided adequate material for histological analysis in 90.7 and 93.0% of cases, respectively, while a combination of the 2 techniques was in 96.5% of cases. The sensitivity, specificity, positive-predictive value (PPV), negative-predictive value (NPV) and diagnostic accuracy of US-guided CNB versus SPB were: 51.2 vs 63.4%, 100 vs 100%, 100 vs 100%, 64.9 vs 72.2% and 74.4 vs 81.3%, respectively. When CNB was combined with SPB, the corresponding values were 88.6, 100, 100, 88.6 and 93.9%, respectively. Whereas sensitivity, NPV and diagnostic accuracy were not significantly different between CNB and SPB, the combination of CNB and SPB significantly improved the sensitivity, NPV and diagnostic accuracy versus each technique alone (p < 0.05). Significant pain (eight patients), moderate haemoptysis (two patients) and chest wall haematomas (two patients) were observed following CNB, while syncope (four patients) and a slight pneumothorax (four patients) were observed following SPB. Use of a combination of US-guided CNB and SPB afforded a high sensitivity to diagnose MPEs, it is a convenient and safe approach.

Integration of multiple cues allows threat-sensitive anti-intraguild predator responses in predatory mites

PubMed Central

Walzer, Andreas; Schausberger, Peter

2013-01-01

Intraguild (IG) prey is commonly confronted with multiple IG predator species. However, the IG predation (IGP) risk for prey is not only dependent on the predator species, but also on inherent (intraspecific) characteristics of a given IG predator such as its life-stage, sex or gravidity and the associated prey needs. Thus, IG prey should have evolved the ability to integrate multiple IG predator cues, which should allow both inter- and intraspecific threat-sensitive anti-predator responses. Using a guild of plant-inhabiting predatory mites sharing spider mites as prey, we evaluated the effects of single and combined cues (eggs and/or chemical traces left by a predator female on the substrate) of the low risk IG predator Neoseiulus californicus and the high risk IG predator Amblyseius andersoni on time, distance and path shape parameters of the larval IG prey Phytoseiulus persimilis. IG prey discriminated between traces of the low and high risk IG predator, with and without additional presence of their eggs, indicating interspecific threat-sensitivity. The behavioural changes were manifest in distance moved, activity and path shape of IG prey. The cue combination of traces and eggs of the IG predators conveyed other information than each cue alone, allowing intraspecific threat-sensitive responses by IG prey apparent in changed velocities and distances moved. We argue that graded responses to single and combined IG predator cues are adaptive due to minimization of acceptance errors in IG prey decision making. PMID:23750040

Highly sensitive on-site detection of drugs adulterated in botanical dietary supplements using thin layer chromatography combined with dynamic surface enhanced Raman spectroscopy.

PubMed

Fang, Fang; Qi, Yunpeng; Lu, Feng; Yang, Liangbao

2016-01-01

The phenomenon of botanical dietary supplements (BDS) doped with illegal adulterants has become a serious problem all over the world, which could cause great threat to human's health. Therefore, it is of great value to identify BDS. Herein, we put forward a highly sensitive method for on-site detection of antitussive and antiasthmatic drugs adulterated in BDS using thin layer chromatography (TLC) combined with dynamic surface enhanced Raman spectroscopy (DSERS). Adulterants in BDS were separated on a TLC plate and located under UV illumination. Then DSERS detection was performed using a portable Raman spectrometer with 50% glycerol silver colloid serving as DSERS active substrate. Here, the effects of different solvents on detection efficacy were evaluated using phenformin hydrochloride (PHE) as a probe. It was shown that 50% glycerol resulted in higher SERS enhancement and relatively higher stability. Moreover, practical application of this novel TLC-DSERS method was demonstrated with rapid analysis of real BDS samples and one sample adulterated with benproperine phosphate (BEN) was found. Furthermore, the obtained result was verified by ultra performance liquid chromatography-quadrupole time of flight mass spectrometry (UPLC-QTOF/MS). The sensitivity of the TLC-DSERS technique is 1-2 orders of magnitude higher than that of TLC-SERS technique. The results turned out that this combined method would have good prospects for on-site and sensitive detection of adulterated BDS. Copyright © 2015 Elsevier B.V. All rights reserved.

Highly sensitive, self-powered and wearable electronic skin based on pressure-sensitive nanofiber woven fabric sensor.

PubMed

Zhou, Yuman; He, Jianxin; Wang, Hongbo; Qi, Kun; Nan, Nan; You, Xiaolu; Shao, Weili; Wang, Lidan; Ding, Bin; Cui, Shizhong

2017-10-11

The wearable electronic skin with high sensitivity and self-power has shown increasing prospects for applications such as human health monitoring, robotic skin, and intelligent electronic products. In this work, we introduced and demonstrated a design of highly sensitive, self-powered, and wearable electronic skin based on a pressure-sensitive nanofiber woven fabric sensor fabricated by weaving PVDF electrospun yarns of nanofibers coated with PEDOT. Particularly, the nanofiber woven fabric sensor with multi-leveled hierarchical structure, which significantly induced the change in contact area under ultra-low load, showed combined superiority of high sensitivity (18.376 kPa -1 , at ~100 Pa), wide pressure range (0.002-10 kPa), fast response time (15 ms) and better durability (7500 cycles). More importantly, an open-circuit voltage signal of the PPNWF pressure sensor was obtained through applying periodic pressure of 10 kPa, and the output open-circuit voltage exhibited a distinct switching behavior to the applied pressure, indicating the wearable nanofiber woven fabric sensor could be self-powered under an applied pressure. Furthermore, we demonstrated the potential application of this wearable nanofiber woven fabric sensor in electronic skin for health monitoring, human motion detection, and muscle tremor detection.

Combining parasite lactate dehydrogenase-based and histidine-rich protein 2-based rapid tests to improve specificity for diagnosis of malaria Due to Plasmodium knowlesi and other Plasmodium species in Sabah, Malaysia.

PubMed

Grigg, Matthew J; William, Timothy; Barber, Bridget E; Parameswaran, Uma; Bird, Elspeth; Piera, Kim; Aziz, Ammar; Dhanaraj, Prabakaran; Yeo, Tsin W; Anstey, Nicholas M

2014-06-01

Plasmodium knowlesi causes severe and fatal malaria in Malaysia. Microscopic misdiagnosis is common and may delay appropriate treatment. P. knowlesi can cross-react with "species-specific" parasite lactate dehydrogenase (pLDH) monoclonal antibodies used in rapid diagnostic tests (RDTs) to detect P. falciparum and P. vivax. At one tertiary-care hospital and two district hospitals in Sabah, we prospectively evaluated two combination RDTs for malaria diagnosis by using both a pan-Plasmodium-pLDH (pan-pLDH)/P. falciparum-specific-pLDH (Pf-pLDH) RDT (OptiMAL-IT) and a non-P. falciparum VOM-pLDH/Pf-HRP2 RDT (CareStart). Differential cross-reactivity among these combinations was hypothesized to differentiate P. knowlesi from other Plasmodium monoinfections. Among 323 patients with PCR-confirmed P. knowlesi (n = 193), P. falciparum (n = 93), and P. vivax (n = 37) monoinfections, the VOM-pLDH individual component had the highest sensitivity for nonsevere (35%; 95% confidence interval [CI], 27 to 43%) and severe (92%; CI, 81 to 100%) P. knowlesi malaria. CareStart demonstrated a P. knowlesi sensitivity of 42% (CI, 34 to 49%) and specificity of 74% (CI, 65 to 82%), a P. vivax sensitivity of 83% (CI, 66 to 93%) and specificity of 71% (CI, 65 to 76%), and a P. falciparum sensitivity of 97% (CI, 90 to 99%) and specificity of 99% (CI, 97 to 100%). OptiMAL-IT demonstrated a P. knowlesi sensitivity of 32% (CI, 25 to 39%) and specificity of 21% (CI, 15 to 29%), a P. vivax sensitivity of 60% (CI, 42 to 75%) and specificity of 97% (CI, 94 to 99%), and a P. falciparum sensitivity of 82% (CI, 72 to 89%) and specificity of 39% (CI, 33 to 46%). The combination of CareStart plus OptiMAL-IT for P. knowlesi using predefined criteria gave a sensitivity of 25% (CI, 19 to 32%) and specificity of 97% (CI, 92 to 99%). Combining two RDT combinations was highly specific for P. knowlesi malaria diagnosis; however, sensitivity was poor. The specificity of pLDH RDTs was decreased for P. vivax and P. falciparum because of P. knowlesi cross-reactivity and cautions against their use alone in areas where P. knowlesi malaria is endemic. Sensitive P. knowlesi-specific RDTs and/or alternative molecular diagnostic tools are needed in areas where P. knowlesi malaria is endemic. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Combining Parasite Lactate Dehydrogenase-Based and Histidine-Rich Protein 2-Based Rapid Tests To Improve Specificity for Diagnosis of Malaria Due to Plasmodium knowlesi and Other Plasmodium Species in Sabah, Malaysia

PubMed Central

William, Timothy; Barber, Bridget E.; Parameswaran, Uma; Bird, Elspeth; Piera, Kim; Aziz, Ammar; Dhanaraj, Prabakaran; Yeo, Tsin W.; Anstey, Nicholas M.

2014-01-01

Plasmodium knowlesi causes severe and fatal malaria in Malaysia. Microscopic misdiagnosis is common and may delay appropriate treatment. P. knowlesi can cross-react with “species-specific” parasite lactate dehydrogenase (pLDH) monoclonal antibodies used in rapid diagnostic tests (RDTs) to detect P. falciparum and P. vivax. At one tertiary-care hospital and two district hospitals in Sabah, we prospectively evaluated two combination RDTs for malaria diagnosis by using both a pan-Plasmodium-pLDH (pan-pLDH)/P. falciparum-specific-pLDH (Pf-pLDH) RDT (OptiMAL-IT) and a non-P. falciparum VOM-pLDH/Pf-HRP2 RDT (CareStart). Differential cross-reactivity among these combinations was hypothesized to differentiate P. knowlesi from other Plasmodium monoinfections. Among 323 patients with PCR-confirmed P. knowlesi (n = 193), P. falciparum (n = 93), and P. vivax (n = 37) monoinfections, the VOM-pLDH individual component had the highest sensitivity for nonsevere (35%; 95% confidence interval [CI], 27 to 43%) and severe (92%; CI, 81 to 100%) P. knowlesi malaria. CareStart demonstrated a P. knowlesi sensitivity of 42% (CI, 34 to 49%) and specificity of 74% (CI, 65 to 82%), a P. vivax sensitivity of 83% (CI, 66 to 93%) and specificity of 71% (CI, 65 to 76%), and a P. falciparum sensitivity of 97% (CI, 90 to 99%) and specificity of 99% (CI, 97 to 100%). OptiMAL-IT demonstrated a P. knowlesi sensitivity of 32% (CI, 25 to 39%) and specificity of 21% (CI, 15 to 29%), a P. vivax sensitivity of 60% (CI, 42 to 75%) and specificity of 97% (CI, 94 to 99%), and a P. falciparum sensitivity of 82% (CI, 72 to 89%) and specificity of 39% (CI, 33 to 46%). The combination of CareStart plus OptiMAL-IT for P. knowlesi using predefined criteria gave a sensitivity of 25% (CI, 19 to 32%) and specificity of 97% (CI, 92 to 99%). Combining two RDT combinations was highly specific for P. knowlesi malaria diagnosis; however, sensitivity was poor. The specificity of pLDH RDTs was decreased for P. vivax and P. falciparum because of P. knowlesi cross-reactivity and cautions against their use alone in areas where P. knowlesi malaria is endemic. Sensitive P. knowlesi-specific RDTs and/or alternative molecular diagnostic tools are needed in areas where P. knowlesi malaria is endemic. PMID:24696029

Sensitivity and resolution in frequency comb spectroscopy of buffer gas cooled polyatomic molecules

NASA Astrophysics Data System (ADS)

Changala, P. Bryan; Spaun, Ben; Patterson, David; Doyle, John M.; Ye, Jun

2016-12-01

We discuss the use of cavity-enhanced direct frequency comb spectroscopy in the mid-infrared region with buffer gas cooling of polyatomic molecules for high-precision rovibrational absorption spectroscopy. A frequency comb coupled to an optical enhancement cavity allows us to collect high-resolution, broad-bandwidth infrared spectra of translationally and rotationally cold (10-20 K) gas-phase molecules with high absorption sensitivity and fast acquisition times. The design and performance of the combined apparatus are discussed in detail. Recorded rovibrational spectra in the CH stretching region of several organic molecules, including vinyl bromide (CH_2CHBr), adamantane (C_{10}H_{16}), and diamantane (C_{14}H_{20}) demonstrate the resolution and sensitivity of this technique, as well as the intrinsic challenges faced in extending the frontier of high-resolution spectroscopy to large complex molecules.

High Sensitivity Combined with Extended Structural Coverage of Labile Compounds via Nanoelectrospray Ionization at Subambient Pressures

DOE PAGES

Cox, Jonathan T.; Kronewitter, Scott R.; Shukla, Anil K.; ...

2014-09-15

Subambient pressure ionization with nanoelectrospray (SPIN) has proven to be effective in producing ions with high efficiency and transmitting them to low pressures for high sensitivity mass spectrometry (MS) analysis. Here we present evidence that not only does the SPIN source improve MS sensitivity but also allows for gentler ionization conditions. The gentleness of a conventional heated capillary electrospray ionization (ESI) source and the SPIN source was compared by the liquid chromatography mass spectrometry (LC-MS) analysis of colominic acid. Colominic acid is a mixture of sialic acid polymers of different lengths containing labile glycosidic linkages between monomer units necessitating amore » gentle ion source. By coupling the SPIN source with high resolution mass spectrometry and using advanced data processing tools, we demonstrate much extended coverage of sialic acid polymer chains as compared to using the conventional ESI source. Additionally we show that SPIN-LC-MS is effective in elucidating polymer features with high efficiency and high sensitivity previously unattainable by the conventional ESI-LC-MS methods.« less

Design Optimization and Fabrication of a Novel Structural SOI Piezoresistive Pressure Sensor with High Accuracy

PubMed Central

Li, Chuang; Cordovilla, Francisco; Jagdheesh, R.

2018-01-01

This paper presents a novel structural piezoresistive pressure sensor with four-grooved membrane combined with rood beam to measure low pressure. In this investigation, the design, optimization, fabrication, and measurements of the sensor are involved. By analyzing the stress distribution and deflection of sensitive elements using finite element method, a novel structure featuring high concentrated stress profile (HCSP) and locally stiffened membrane (LSM) is built. Curve fittings of the mechanical stress and deflection based on FEM simulation results are performed to establish the relationship between mechanical performance and structure dimension. A combination of FEM and curve fitting method is carried out to determine the structural dimensions. The optimized sensor chip is fabricated on a SOI wafer by traditional MEMS bulk-micromachining and anodic bonding technology. When the applied pressure is 1 psi, the sensor achieves a sensitivity of 30.9 mV/V/psi, a pressure nonlinearity of 0.21% FSS and an accuracy of 0.30%, and thereby the contradiction between sensitivity and linearity is alleviated. In terms of size, accuracy and high temperature characteristic, the proposed sensor is a proper choice for measuring pressure of less than 1 psi. PMID:29393916

[Value of desmopressin stimulation test and high dose dexamethasone suppression testin the etiologic diagnosis of ACTH dependent Cushing's syndrome].

PubMed

Zhang, Weiwei; Yu, Yerong; Tan, Huiwen; Wang, Chun; Li, Jianwei; An, Zhenmei; Liu, Yuping

2016-03-22

To investigate the value of desmopressin (DDAVP) stimulation test and high dose dexamethasone suppression test (HDDST) in establishing the cause of ACTH dependent Cushing's syndrome. The clinical data of patients with ACTH dependent Cushing's syndrome at West China Hospital from January 1, 2010 to September 30, 2015 was analyzed. The sensitivity and specificity of DDAVP stimulation test, HDDST, and the diagnostic accordance rate when the two tests were combined, were evaluated based on the diagnostic gold standard. A total of 85 patients with Cushing's disease and 10 patients with ectopic ACTH syndrome were included. The sensitivity and specificity of DDAVP stimulation test were 87% and 5/5, respectively, whereas those of HDDST were 79% and 8/10, respectively. The standard high dose dexamethasone suppression test showed a higher sensitivity than overnight 8 mg dexamethasone suppression test. When the two tests had consistent results, the diagnostic accordance rate was 100%. DDAVP stimulation test and HDDST are both efficient modalities for the diagnosis of Cushing's Disease and ectopic ACTH syndrome. The accuracy of diagnosis can be further improved by combining the two tests.

Highly-sensitive and large-dynamic diffuse optical tomography system for breast tumor detection

NASA Astrophysics Data System (ADS)

Du, Wenwen; Zhang, Limin; Yin, Guoyan; Zhang, Yanqi; Zhao, Huijuan; Gao, Feng

2018-02-01

Diffuse optical tomography (DOT) as a new functional imaging has important clinical applications in many aspects such as benign and malignant breast tumor detection, tumor staging and so on. For quantitative detection of breast tumor, a three-wavelength continuous-wave DOT prototype system combined the ultra-high sensitivity of the photon-counting detection and the measurement parallelism of the lock-in technique was developed to provide high temporal resolution, high sensitivity, large dynamic detection range and signal-to-noise ratio. Additionally, a CT-analogous scanning mode was proposed to cost-effectively increase the detection data. To evaluate the feasibility of the system, a series of assessments were conducted. The results demonstrate that the system can obtain high linearity, stability and negligible inter-wavelength crosstalk. The preliminary phantom experiments show the absorption coefficient is able to be successfully reconstructed, indicating that the system is one of the ideal platforms for optical breast tumor detection.

High sensitive formaldehyde graphene gas sensor modified by atomic layer deposition zinc oxide films

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mu, Haichuan; Zhang, Zhiqiang; Wang, Keke

2014-07-21

Zinc oxide (ZnO) thin films with various thicknesses were fabricated by Atomic Layer Deposition on Chemical Vapor Deposition grown graphene films and their response to formaldehyde has been investigated. It was found that 0.5 nm ZnO films modified graphene sensors showed high response to formaldehyde with the resistance change up to 52% at the concentration of 9 parts-per-million (ppm) at room temperature. Meanwhile, the detection limit could reach 180 parts-per-billion (ppb) and fast response of 36 s was also obtained. The high sensitivity could be attributed to the combining effect from the highly reactive, top mounted ZnO thin films, and high conductivemore » graphene base network. The dependence of ZnO films surface morphology and its sensitivity on the ZnO films thickness was also investigated.« less

CMOS Amperometric ADC With High Sensitivity, Dynamic Range and Power Efficiency for Air Quality Monitoring.

PubMed

Li, Haitao; Boling, C Sam; Mason, Andrew J

2016-08-01

Airborne pollutants are a leading cause of illness and mortality globally. Electrochemical gas sensors show great promise for personal air quality monitoring to address this worldwide health crisis. However, implementing miniaturized arrays of such sensors demands high performance instrumentation circuits that simultaneously meet challenging power, area, sensitivity, noise and dynamic range goals. This paper presents a new multi-channel CMOS amperometric ADC featuring pixel-level architecture for gas sensor arrays. The circuit combines digital modulation of input currents and an incremental Σ∆ ADC to achieve wide dynamic range and high sensitivity with very high power efficiency and compact size. Fabricated in 0.5 [Formula: see text] CMOS, the circuit was measured to have 164 dB cross-scale dynamic range, 100 fA sensitivity while consuming only 241 [Formula: see text] and 0.157 [Formula: see text] active area per channel. Electrochemical experiments with liquid and gas targets demonstrate the circuit's real-time response to a wide range of analyte concentrations.

Highly Stretchable and Transparent Thermistor Based on Self-Healing Double Network Hydrogel.

PubMed

Wu, Jin; Han, Songjia; Yang, Tengzhou; Li, Zhong; Wu, Zixuan; Gui, Xuchun; Tao, Kai; Miao, Jianmin; Norford, Leslie K; Liu, Chuan; Huo, Fengwei

2018-06-06

An ultrastretchable thermistor that combines intrinsic stretchability, thermal sensitivity, transparency, and self-healing capability is fabricated. It is found the polyacrylamide/carrageenan double network (DN) hydrogel is highly sensitive to temperature and therefore can be exploited as a novel channel material for a thermistor. This thermistor can be stretched from 0 to 330% strain with the sensitivity as high as 2.6%/°C at extreme 200% strain. Noticeably, the mechanical, electrical, and thermal sensing properties of the DN hydrogel can be self-healed, analogous to the self-healing capability of human skin. The large mechanical deformations, such as flexion and twist with large angles, do not affect the thermal sensitivity. Good flexibility enables the thermistor to be attached on nonplanar curvilinear surfaces for practical temperature detection. Remarkably, the thermal sensitivity can be improved by introducing mechanical strain, making the sensitivity programmable. This thermistor with tunable sensitivity is advantageous over traditional rigid thermistors that lack flexibility in adjusting their sensitivity. In addition to superior sensitivity and stretchability compared with traditional thermistors, this DN hydrogel-based thermistor provides additional advantages of good transparency and self-healing ability, enabling it to be potentially integrated in soft robots to grasp real world information for guiding their actions.

A split recognition mode combined with cascade signal amplification strategy for highly specific, sensitive detection of microRNA.

PubMed

Wang, Rui; Wang, Lei; Zhao, Haiyan; Jiang, Wei

2016-12-15

MicroRNAs (miRNAs) are vital for many biological processes and have been regarded as cancer biomarkers. Specific and sensitive detection of miRNAs is essential for cancer diagnosis and therapy. Herein, a split recognition mode combined with cascade signal amplification strategy is developed for highly specific and sensitive detection of miRNA. The split recognition mode possesses two specific recognition processes, which are based on toehold-mediated strand displacement reaction (TSDR) and direct hybridization reaction. Two recognition probes, hairpin probe (HP) with overhanging toehold domain and assistant probe (AP), are specially designed. Firstly, the toehold domain of HP and AP recognize part of miRNA simultaneously, accompanied with TSDR to unfold the HP and form the stable DNA Y-shaped junction structure (YJS). Then, the AP in YJS can further act as primer to initiate strand displacement amplification, releasing numerous trigger sequences. Finally, the trigger sequences hybridize with padlock DNA to initiate circular rolling circle amplification and generate enhanced fluorescence responses. In this strategy, the dual recognition effect of split recognition mode guarantees the excellent selectivity to discriminate let-7b from high-homology sequences. Furthermore, the high amplification efficiency of cascade signal amplification guarantees a high sensitivity with the detection limit of 3.2 pM and the concentration of let-7b in total RNA sample extracted from Hela cells is determined. These results indicate our strategy will be a promising miRNA detection strategy in clinical diagnosis and disease treatment. Copyright © 2016 Elsevier B.V. All rights reserved.

Reliability of high- and low-field magnetic resonance imaging systems for detection of cartilage and bone lesions in the equine cadaver fetlock.

PubMed

Smith, M A; Dyson, S J; Murray, R C

2012-11-01

To determine the reliability of 2 magnetic resonance imaging (MRI) systems for detection of cartilage and bone lesions of the equine fetlock. To test the hypotheses that lesions in cartilage, subchondral and trabecular bone of the equine fetlock verified using histopathology can be detected on high- and low-field MR images with a low incidence of false positive or negative results; that low-field images are less reliable than high-field images for detection of cartilage lesions; and that combining results of interpretation from different pulse sequences increases detection of cartilage lesions. High- and low-field MRI was performed on 19 limbs from horses identified with fetlock lameness prior to euthanasia. Grading systems were used to score cartilage, subchondral and trabecular bone on MR images and histopathology. Sensitivity and specificity were calculated for images. High-field T2*-weighted gradient echo (T2*W-GRE) and low-field T2-weighted fast spin echo (T2W-FSE) images had high sensitivity but low specificity for detection of cartilage lesions. All pulse sequences had high sensitivity and low-moderate specificity for detection of subchondral bone lesions and moderate sensitivity and moderate-high specificity for detection of trabecular bone lesions (histopathology as gold standard). For detection of lesions of trabecular bone low-field T2*W-GRE images had higher sensitivity and specificity than T2W-FSE images. There is high likelihood of false positive results using high- or low-field MRI for detection of cartilage lesions and moderate-high likelihood of false positive results for detection of subchondral bone lesions compared with histopathology. Combining results of interpretation from different pulse sequences did not increase detection of cartilage lesions. MRI interpretation of trabecular bone was more reliable than cartilage or subchondral bone in both MR systems. Independent interpretation of a variety of pulse sequences may maximise detection of cartilage and bone lesions in the fetlock. Clinicians should be aware of potential false positive and negative results. © 2012 EVJ Ltd.

Cost-effectiveness of WHO-Recommended Algorithms for TB Case Finding at Ethiopian HIV Clinics.

PubMed

Adelman, Max W; McFarland, Deborah A; Tsegaye, Mulugeta; Aseffa, Abraham; Kempker, Russell R; Blumberg, Henry M

2018-01-01

The World Health Organization (WHO) recommends active tuberculosis (TB) case finding and a rapid molecular diagnostic test (Xpert MTB/RIF) to detect TB among people living with HIV (PLHIV) in high-burden settings. Information on the cost-effectiveness of these recommended strategies is crucial for their implementation. We conducted a model-based cost-effectiveness analysis comparing 2 algorithms for TB screening and diagnosis at Ethiopian HIV clinics: (1) WHO-recommended symptom screen combined with Xpert for PLHIV with a positive symptom screen and (2) current recommended practice algorithm (CRPA; based on symptom screening, smear microscopy, and clinical TB diagnosis). Our primary outcome was US$ per disability-adjusted life-year (DALY) averted. Secondary outcomes were additional true-positive diagnoses, and false-negative and false-positive diagnoses averted. Compared with CRPA, combining a WHO-recommended symptom screen with Xpert was highly cost-effective (incremental cost of $5 per DALY averted). Among a cohort of 15 000 PLHIV with a TB prevalence of 6% (900 TB cases), this algorithm detected 8 more true-positive cases than CRPA, and averted 2045 false-positive and 8 false-negative diagnoses compared with CRPA. The WHO-recommended algorithm was marginally costlier ($240 000) than CRPA ($239 000). In sensitivity analysis, the symptom screen/Xpert algorithm was dominated at low Xpert sensitivity (66%). In this model-based analysis, combining a WHO-recommended symptom screen with Xpert for TB diagnosis among PLHIV was highly cost-effective ($5 per DALY averted) and more sensitive than CRPA in a high-burden, resource-limited setting.

Sensitivity of plankton indices to lake trophic conditions.

PubMed

Ochocka, A; Pasztaleniec, A

2016-11-01

Herein, we report the response of indices based on phytoplankton and zooplankton and their combination to different nutrient concentrations in lakes. The study was carried out in ten lakes in northeastern Poland. Integrated samples were collected from the epilimnion during the summer of 2012-2013. Secchi disk visibility (SD), total phosphorus (TP), total nitrogen (TN), and chlorophyll a were used as proxies for eutrophication. We calculated 16 plankton indices: two phytoplankton indices, six crustacean indices, five rotiferan indices, two zooplankton diversity indices, and one combined phytoplankton and zooplankton index. Among them, nine indices with the strongest correlations with TP were selected: percentage share of Crustacean species indicative of high trophy in the indicative group's numbers (IHT CRU ), percentage share of Rotifera species indicative of high trophy in the indicative group's numbers IHT ROT , Crustacean ratio of biomass to numbers B/N CRU , phytoplankton trophic index (TI TP+TN ), Margalef's index, percentage share of cyclopoid biomass in total biomass of Crustacea (CB), Rotifera numbers (N ROT ), biomass of Cyclopoida (B CY ), and ratio of the cyclopoid biomass to the biomass of Cladocera (CY/CL). The sensitivity of the normalized values of these indices to proxies of eutrophication was tested. IHT CRU , IHT ROT , and B/N CRU were the most sensitive and gave the strongest responses at lower TP concentrations (<35 μg/L). The phytoplankton trophic index, TI TP+TN , together with the zooplankton-based Margalef's index and CB were very sensitive in both low (<35 μg/L) and high (>60 μg/L) TP conditions. On the other hand, N ROT , B CY , and CY/CL were slightly sensitive at low TP concentrations while their reaction was notable at high TP concentrations. A similar pattern of response was observed for TN concentration and SD visibility.

Combining presentation high-sensitivity cardiac troponin I and glucose measurements to rule-out an acute myocardial infarction in patients presenting to emergency department with chest pain.

PubMed

Greenslade, J H; Kavsak, P; Parsonage, W; Shortt, C; Than, M; Pickering, J W; Aldous, S; Cullen, L

2015-03-01

The use of high sensitivity troponin (hs-Tn) may enable early rule out of acute myocardial infarction (AMI) for patients presenting to the emergency department (ED) with chest pain. This study evaluated two approaches to the early rule out of AMI; a combination of a presentation hs-Tn <4ng/L and normal glucose at presentation (dual testing) and a presentation hs-Tn troponin below the limit of detection (LoD). We utilised prospectively collected data on adult patients presenting with suspected ACS in two EDs in Australia and New Zealand. Blood samples were taken on presentation and tested for glucose and high sensitivity troponin I. The primary endpoint was index AMI and the secondary endpoint was 30-day acute coronary syndrome (ACS). Sensitivity, specificity, positive and negative predictive values were used to assess the diagnostic accuracy of the dual testing and LoD approaches. Of the 1412 participants, 182 (12.9%) had index AMI. The LoD and the dual testing approach were 100% sensitive for index AMI. The specificity of the dual testing approach (25.2%) was slightly higher than that of the LoD (20.4%). Sensitivity for ACS was similar for the two approaches (96.5% for dual testing and 98.1% for the LoD). The dual testing and LoD approach identified all patients with index AMI and could be used to reduce the proportion of patients requiring lengthy assessment and inpatient admission. Further investigation is still required to rule out unstable angina pectoris in patients identified as low risk. Copyright © 2014 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Sensitivity of Hyperdense Basilar Artery Sign on Non-Enhanced Computed Tomography

PubMed Central

Ernst, Marielle; Romero, Javier M.; Buhk, Jan-Hendrik; Cheng, Bastian; Herrmann, Jochen; Fiehler, Jens; Groth, Michael

2015-01-01

Purpose The hyperdense basilar artery sign (HBAS) is an indicator of vessel occlusion on non contrast-enhanced computer tomography (NECT) in acute stroke patients. Since basilar artery occlusion (BAO) is associated with a high mortality and morbidity, its early detection is of great clinical value. We sought to analyze the influence of density measurement as well as a normalized ratio of Hounsfield unit/hematocrit (HU/Hct) ratio on the detection of BAO on NECT in patients with suspected BAO. Materials and Methods 102 patients with clinically suspected BAO were examined with NECT followed immediately by Multidetector computed tomography Angiography. Two observers independently analyzed the images regarding the presence or absence of HBAS on NECT and performed HU measurements in the basilar artery. Receiver operating characteristic curve analysis was performed to determine the optimal density threshold for BAO using attenuation measurements or HU/Hct ratio. Results Sensitivity of visual detection of the HBAS on NECT was relatively low 81% (95%-CI, 54–95%) while specificity was high 91% (95%-CI, 82–96%). The highest sensitivity was achieved by the combination of visual assessment and additional quantitative attenuation measurements applying a cut-off value of 46.5 HU with 94% sensitivity and 81% specificity for BAO. A HU/Hct ratio >1.32 revealed sensitivity of 88% (95%-CI, 60–98%) and specificity of 84% (95%-CI, 74–90%). Conclusion In patients with clinically suspected acute BAO the combination of visual assessment and additional attenuation measurement with a cut-off value of 46.5 HU is a reliable approach with high sensitivity in the detection of BAO on NECT. PMID:26479718

Bulk and integrated acousto-optic spectrometers for radio astronomy

NASA Technical Reports Server (NTRS)

Chin, G.; Buhl, D.; Florez, J. M.

1981-01-01

The development of sensitive heterodyne receivers (front end) in the centimeter and millimeter range, and the construction of sensitive RF spectrometers (back end) enable the spectral lines of interstellar molecules to be detected and identified. A technique was developed which combines acoustic bending of a collimated coherent light beam by a Bragg cell followed by detection by a sensitive array of photodetectors (thus forming an RF acousto-optic spectrometer (AOS). An AOS has wide bandwidth, large number of channels, and high resolution, and is compact, lightweight, and energy efficient. The thrust of receiver development is towards high frequency heterodyne systems, particularly in the millimeter, submillimeter, far infrared, and 10 micron spectral ranges.

Suprathreshold Contrast Sensitivity Vision Test Chart

DTIC Science & Technology

1991-07-14

with data collected on patients having amblyopia , glaucoma and macular degeneration showed that the SCTS may be effectively used as an initial...dramatically in certain cases of abnormal vision, such as amblyopia (Ginsburg, 1978, 1981; Hess, Bradley and Piotrowski, 1983; Loshin and Levi, 1983). The...combination of frequencies. Amblyopia results in marked losses of contrast sensitivity particularly at high spatial frequencies, but may also result in

Ozone and haze pollution weakens net primary productivity in China

NASA Astrophysics Data System (ADS)

Yue, Xu; Unger, Nadine; Harper, Kandice; Xia, Xiangao; Liao, Hong; Zhu, Tong; Xiao, Jingfeng; Feng, Zhaozhong; Li, Jing

2017-05-01

Atmospheric pollutants have both beneficial and detrimental effects on carbon uptake by land ecosystems. Surface ozone (O3) damages leaf photosynthesis by oxidizing plant cells, while aerosols promote carbon uptake by increasing diffuse radiation and exert additional influences through concomitant perturbations to meteorology and hydrology. China is currently the world's largest emitter of both carbon dioxide and short-lived air pollutants. The land ecosystems of China are estimated to provide a carbon sink, but it remains unclear whether air pollution acts to inhibit or promote carbon uptake. Here, we employ Earth system modeling and multiple measurement datasets to assess the separate and combined effects of anthropogenic O3 and aerosol pollution on net primary productivity (NPP) in China. In the present day, O3 reduces annual NPP by 0.6 Pg C (14 %) with a range from 0.4 Pg C (low O3 sensitivity) to 0.8 Pg C (high O3 sensitivity). In contrast, aerosol direct effects increase NPP by 0.2 Pg C (5 %) through the combination of diffuse radiation fertilization, reduced canopy temperatures, and reduced evaporation leading to higher soil moisture. Consequently, the net effects of O3 and aerosols decrease NPP by 0.4 Pg C (9 %) with a range from 0.2 Pg C (low O3 sensitivity) to 0.6 Pg C (high O3 sensitivity). However, precipitation inhibition from combined aerosol direct and indirect effects reduces annual NPP by 0.2 Pg C (4 %), leading to a net air pollution suppression of 0.8 Pg C (16 %) with a range from 0.6 Pg C (low O3 sensitivity) to 1.0 Pg C (high O3 sensitivity). Our results reveal strong dampening effects of air pollution on the land carbon uptake in China today. Following the current legislation emission scenario, this suppression will be further increased by the year 2030, mainly due to a continuing increase in surface O3. However, the maximum technically feasible reduction scenario could drastically relieve the current level of NPP damage by 70 % in 2030, offering protection of this critical ecosystem service and the mitigation of long-term global warming.

Receiver operating characteristic analysis of prediction for gastric cancer development using serum pepsinogen and Helicobacter pylori antibody tests.

PubMed

Hamashima, Chisato; Sasazuki, Shizuka; Inoue, Manami; Tsugane, Shoichiro

2017-03-09

Chronic Helicobacter pylori infection plays a central role in the development of gastric cancer as shown by biological and epidemiological studies. The H. pylori antibody and serum pepsinogen (PG) tests have been anticipated to predict gastric cancer development. We determined the predictive sensitivity and specificity of gastric cancer development using these tests. Receiver operating characteristic analysis was performed, and areas under the curve were estimated. The predictive sensitivity and specificity of gastric cancer development were compared among single tests and combined methods using serum pepsinogen and H. pylori antibody tests. From a large-scale population-based cohort of over 100,000 subjects followed between 1990 and 2004, 497 gastric cancer subjects and 497 matched healthy controls were chosen. The predictive sensitivity and specificity were low in all single tests and combination methods. The highest predictive sensitivity and specificity were obtained for the serum PG I/II ratio. The optimal PG I/II cut-off values were 2.5 and 3.0. At a PG I/II cut-off value of 3.0, the sensitivity was 86.9% and the specificity was 39.8%. Even if three biomarkers were combined, the sensitivity was 97.2% and the specificity was 21.1% when the cut-off values were 3.0 for PG I/II, 70 ng/mL for PG I, and 10.0 U/mL for H. pylori antibody. The predictive accuracy of gastric cancer development was low with the serum pepsinogen and H. pylori antibody tests even if these tests were combined. To adopt these biomarkers for gastric cancer screening, a high specificity is required. When these tests are adopted for gastric cancer screening, they should be carefully interpreted with a clear understanding of their limitations.

The sensitivity and specificity of the neurological examination in polyneuropathy patients with clinical and electrophysiological correlations

PubMed Central

Alabdali, Majed; Alsulaiman, Abdulla; Albulaihe, Hana; Breiner, Ari; Katzberg, Hans D.; Aljaafari, Danah; Lovblom, Leif E.; Bril, Vera

2017-01-01

Introduction Polyneuropathy is one of the most prevalent neurologic disorders. Although several studies explored the role of the neurological examination in polyneuropathy, they were mostly restricted to specific subgroups of patients and have not correlated examination findings with symptoms and electrophysiological results. Objectives To explore the sensitivity and specificity of different neurological examination components in patients with diverse etiologies for polyneuropathy, find the most sensitive combination of examination components for polyneuropathy detection, and correlate examination findings with symptoms and electrophysiological results. Methods Patients with polyneuropathy attending the neuromuscular clinic from 01/2013 to 09/2015 were evaluated. Inclusion criteria included symptomatic polyneuropathy, which was confirmed by electrophysiological studies. 47 subjects with no symptoms or electrophysiological findings suggestive for polyneuropathy, served as controls. Results The total cohort included 312 polyneuropathy patients, with a mean age of 60±14 years. Abnormal examination was found in 95%, most commonly sensory findings (86%). The most common abnormal examination components were impaired ankle reflexes (74%), vibration (73%), and pinprick (72%) sensation. Combining ankle reflex examination with vibration or pinprick perception had the highest sensitivity, of 88%. The specificities of individual examination component were generally high, excluding ankle reflexes (62%), and vibration perception (77%). Abnormal examination findings were correlated with symptomatic weakness and worse electrophysiological parameters. Conclusion The neurological examination is a valid, sensitive and specific tool for diagnosing polyneuropathy, and findings correlate with polyneuropathy severity. Ankle reflex examination combined with either vibration or pinprick sensory testing is the most sensitive combination for diagnosing polyneuropathy, and should be considered minimal essential components of the physical examination in patients with suspected polyneuropathy. PMID:28249029

Portal radiation monitor

DOEpatents

Kruse, Lyle W.

1985-01-01

A portal radiation monitor combines 0.1% FAR with high sensitivity to special nuclear material. The monitor utilizes pulse shape discrimination, dynamic compression of the photomultiplier output and scintillators sized to maintain efficiency over the entire portal area.

Portal radiation monitor

DOEpatents

Kruse, L.W.

1982-03-23

A portal radiation monitor combines .1% FAR with high sensitivity to special nuclear material. The monitor utilizes pulse shape discrimination, dynamic compression of the photomultiplier output and scintillators sized to maintain efficiency over the entire portal area.

Synthesis of quantum dots

DOEpatents

McDaniel, Hunter

2017-10-17

Common approaches to synthesizing alloyed quantum dots employ high-cost, air-sensitive phosphine complexes as the selenium precursor. Disclosed quantum dot synthesis embodiments avoid these hazardous and air-sensitive selenium precursors. Certain embodiments utilize a combination comprising a thiol and an amine that together reduce and complex the elemental selenium to form a highly reactive selenium precursor at room temperature. The same combination of thiol and amine acts as the reaction solvent, stabilizing ligand, and sulfur source in the synthesis of quantum dot cores. A non-injection approach may also be used. The optical properties of the quantum dots synthesized by this new approach can be finely tuned for a variety of applications by controlling size and/or composition of size and composition. Further, using the same approach, a shell can be grown around a quantum dot core that improves stability, luminescence efficiency, and may reduce toxicity.

Combination of the non-invasive tests for the diagnosis of endometriosis.

PubMed

Nisenblat, Vicki; Prentice, Lucy; Bossuyt, Patrick M M; Farquhar, Cindy; Hull, M Louise; Johnson, Neil

2016-07-13

About 10% of women of reproductive age suffer from endometriosis, a costly chronic disease causing pelvic pain and subfertility. Laparoscopy is the gold standard diagnostic test for endometriosis, but is expensive and carries surgical risks. Currently, there are no non-invasive tests available in clinical practice to accurately diagnose endometriosis. This review assessed the diagnostic accuracy of combinations of different non-invasive testing modalities for endometriosis and provided a summary of all the reviews in the non-invasive tests for endometriosis series. To estimate the diagnostic accuracy of any combination of non-invasive tests for the diagnosis of pelvic endometriosis (peritoneal and/or ovarian or deep infiltrating) compared to surgical diagnosis as a reference standard. The combined tests were evaluated as replacement tests for diagnostic surgery and triage tests to assist decision-making to undertake diagnostic surgery for endometriosis. We did not restrict the searches to particular study designs, language or publication dates. We searched CENTRAL to July 2015, MEDLINE and EMBASE to May 2015, as well as the following databases to April 2015: CINAHL, PsycINFO, Web of Science, LILACS, OAIster, TRIP, ClinicalTrials.gov, DARE and PubMed. We considered published, peer-reviewed, randomised controlled or cross-sectional studies of any size, including prospectively collected samples from any population of women of reproductive age suspected of having one or more of the following target conditions: ovarian, peritoneal or deep infiltrating endometriosis (DIE). We included studies comparing the diagnostic test accuracy of a combination of several testing modalities with the findings of surgical visualisation of endometriotic lesions. Three review authors independently collected and performed a quality assessment of the data from each study by using the QUADAS-2 tool. For each test, the data were classified as positive or negative for the surgical detection of endometriosis and sensitivity and specificity estimates were calculated. The bivariate model was planned to obtain pooled estimates of sensitivity and specificity whenever sufficient data were available. The predetermined criteria for a clinically useful test to replace diagnostic surgery were a sensitivity of 0.94 and a specificity of 0.79 to detect endometriosis. We set the criteria for triage tests at a sensitivity of 0.95 and above and a specificity of 0.50 and above, which 'rules out' the diagnosis with high accuracy if there is a negative test result (SnOUT test), or a sensitivity of 0.50 and above and a specificity of 0.95 and above, which 'rules in' the diagnosis with high accuracy if there is a positive result (SpIN test). Eleven eligible studies included 1339 participants. All the studies were of poor methodological quality. Seven studies evaluated pelvic endometriosis, one study considered DIE and/or ovarian endometrioma, two studies differentiated endometrioma from other ovarian cysts and one study addressed mapping DIE at specific anatomical sites. Fifteen different diagnostic combinations were assessed, including blood, urinary or endometrial biomarkers, transvaginal ultrasound (TVUS) and clinical history or examination. We did not pool estimates of sensitivity and specificity, as each study analysed independent combinations of the non-invasive tests.Tests that met the criteria for a replacement test were: a combination of serum IL-6 (cut-off >15.4 pg/ml) and endometrial PGP 9.5 for pelvic endometriosis (sensitivity 1.00 (95% confidence interval (CI) 0.91 to 1.00), specificity 0.93 (95% CI, 0.80, 0.98) and the combination of vaginal examination and transvaginal ultrasound (TVUS) for rectal endometriosis (sensitivity 0.96 (95% CI 0.86 to 0.99), specificity 0.98 (95% CI 0.94 to 1.00)). Tests that met the criteria for SpIN triage tests for pelvic endometriosis were: 1. a multiplication of urine vitamin-D-binding protein (VDBP) and serum CA-125 (cut-off >2755) (sensitivity 0.74 (95% CI 0.60 to 0.84), specificity 0.97 (95% CI 0.86 to 1.00)) and 2. a combination of history (length of menses), serum CA-125 (cut-off >35 U/ml) and endometrial leukocytes (sensitivity 0.61 (95% CI 0.54 to 0.69), specificity 0.95 (95% CI 0.91 to 0.98)). For endometrioma, the following combinations qualified as SpIN test: 1. TVUS and either serum CA-125 (cut-off ≥25 U/ml) or CA 19.9 (cut-off ≥12 U/ml) (sensitivity 0.79 (95% CI 0.64 to 0.91), specificity 0.97 (95% CI 0.91 to 1.00)); 2. TVUS and serum CA 19.9 (cut-off ≥12 U/ml) (sensitivity 0.54 (95% CI 0.37 to 0.70), specificity 0.97 (95% CI 0.91 to 1.0)); 3-4. TVUS and serum CA-125 (cut-off ≥20 U/ml or cut-off ≥25 U/ml) (sensitivity 0.69 (95% CI 0.49 to 0.85), specificity 0.96 (95% CI 0.88 to 0.99)); 5. TVUS and serum CA-125 (cut-off ≥35 U/ml) (sensitivity 0.52 (95% CI 0.33 to 0.71), specificity 0.97 (95% CI 0.90 to 1.00)). A combination of vaginal examination and TVUS reached the threshold for a SpIN test for obliterated pouch of Douglas (sensitivity 0.87 (95% CI 0.69 to 0.96), specificity 0.98 (95% CI 0.95 to 1.00)), vaginal wall endometriosis (sensitivity 0.82 (95% CI 0.60 to 0.95), specificity 0.99 (95% CI 0.97 to 1.0)) and rectovaginal septum endometriosis (sensitivity 0.88 (95% CI 0.47 to 1.00), specificity 0.99 (95% CI 0.96 to 1.00)).All the tests were evaluated in individual studies and displayed wide CIs. Due to the heterogeneity and high risk of bias of the included studies, the clinical utility of the studied combination diagnostic tests for endometriosis remains unclear. None of the biomarkers evaluated in this review could be evaluated in a meaningful way and there was insufficient or poor-quality evidence. Laparoscopy remains the gold standard for the diagnosis of endometriosis and using any non-invasive tests should only be undertaken in a research setting.

Misalignment sensitivity in an intra-cavity coherently combined crossed-Porro resonator configuration

NASA Astrophysics Data System (ADS)

Alperovich, Z.; Buchinsky, O.; Greenstein, S.; Ishaaya, A. A.

2017-08-01

We investigate the misalignment sensitivity in a crossed-Porro resonator configuration when coherently combining two pulsed multimode Nd:YAG laser channels. To the best of our knowledge, this is the first reported study of this configuration. The configuration is based on a passive intra-cavity interferometric combiner that promotes self-phase locking and coherent combining. Detailed misalignment sensitivity measurements are presented, examining both translation and angular deviations of the end prisms and combiner, and are compared to the results for standard flat end-mirror configurations. The results show that the most sensitive parameter in the crossed-Porro resonator configuration is the angular tuning of the intra-cavity interferometric combiner, which is ~±54 µrad. In comparison, with the flat end mirror configuration, the most sensitive parameter in the resonator is the angular tuning of the output coupler, which is ~±11 µrad. Thus, with the crossed-Porro configuration, we obtain significantly reduced sensitivity. This ability to reduce the misalignment sensitivity in coherently combined solid-state configurations may be beneficial in paving their way into practical use in a variety of demanding applications.

Increasing sensitivity and angle-of-view of mid-wave infrared detectors by integration with dielectric microspheres

DOE Office of Scientific and Technical Information (OSTI.GOV)

Allen, Kenneth W., E-mail: kenneth.allen@gtri.gatech.edu; Astratov, Vasily N., E-mail: astratov@uncc.edu; Air Force Research Laboratory, Sensors Directorate, Wright Patterson AFB, Ohio 45433

2016-06-13

We observed up to 100 times enhancement of sensitivity of mid-wave infrared photodetectors in the 2–5 μm range by using photonic jets produced by sapphire, polystyrene, and soda-lime glass microspheres with diameters in the 90–300 μm range. By finite-difference time-domain (FDTD) method for modeling, we gain insight into the role of the microspheres refractive index, size, and alignment with respect to the detector mesa. A combination of enhanced sensitivity with angle-of-view (AOV) up to 20° is demonstrated for individual photodetectors. It is proposed that integration with microspheres can be scaled up for large focal plane arrays, which should provide maximal light collectionmore » efficiencies with wide AOVs, a combination of properties highly attractive for imaging applications.« less

Evaluation of peanut cultivars, wild species, and experimental lines for drought and heat tolerance

USDA-ARS?s Scientific Manuscript database

Peanut (Arachis hypogea) is an important crop grown worldwide for its nutritional value and economic significance. Although the demand for peanuts remains high, increasing drought episodes, combined with high temperatures, threaten the supply. Peanut plants are most sensitive to drought and heat str...

Frequency organization and responses to complex sounds in the medial geniculate body of the mustached bat.

PubMed

Wenstrup, J J

1999-11-01

The auditory cortex of the mustached bat (Pteronotus parnellii) displays some of the most highly developed physiological and organizational features described in mammalian auditory cortex. This study examines response properties and organization in the medial geniculate body (MGB) that may contribute to these features of auditory cortex. About 25% of 427 auditory responses had simple frequency tuning with single excitatory tuning curves. The remainder displayed more complex frequency tuning using two-tone or noise stimuli. Most of these were combination-sensitive, responsive to combinations of different frequency bands within sonar or social vocalizations. They included FM-FM neurons, responsive to different harmonic elements of the frequency modulated (FM) sweep in the sonar signal, and H1-CF neurons, responsive to combinations of the bat's first sonar harmonic (H1) and a higher harmonic of the constant frequency (CF) sonar signal. Most combination-sensitive neurons (86%) showed facilitatory interactions. Neurons tuned to frequencies outside the biosonar range also displayed combination-sensitive responses, perhaps related to analyses of social vocalizations. Complex spectral responses were distributed throughout dorsal and ventral divisions of the MGB, forming a major feature of this bat's analysis of complex sounds. The auditory sector of the thalamic reticular nucleus also was dominated by complex spectral responses to sounds. The ventral division was organized tonotopically, based on best frequencies of singly tuned neurons and higher best frequencies of combination-sensitive neurons. Best frequencies were lowest ventrolaterally, increasing dorsally and then ventromedially. However, representations of frequencies associated with higher harmonics of the FM sonar signal were reduced greatly. Frequency organization in the dorsal division was not tonotopic; within the middle one-third of MGB, combination-sensitive responses to second and third harmonic CF sonar signals (60-63 and 90-94 kHz) occurred in adjacent regions. In the rostral one-third, combination-sensitive responses to second, third, and fourth harmonic FM frequency bands predominated. These FM-FM neurons, thought to be selective for delay between an emitted pulse and echo, showed some organization of delay selectivity. The organization of frequency sensitivity in the MGB suggests a major rewiring of the output of the central nucleus of the inferior colliculus, by which collicular neurons tuned to the bat's FM sonar signals mostly project to the dorsal, not the ventral, division. Because physiological differences between collicular and MGB neurons are minor, a major role of the tecto-thalamic projection in the mustached bat may be the reorganization of responses to provide for cortical representations of sonar target features.

Proteomic differential display analysis for TS-1-resistant and -sensitive pancreatic cancer cells using two-dimensional gel electrophoresis and mass spectrometry.

PubMed

Yoshida, Kanako; Kuramitsu, Yasuhiro; Murakami, Kohei; Ryozawa, Shomei; Taba, Kumiko; Kaino, Seiji; Zhang, Xiulian; Sakaida, Isao; Nakamura, Kazuyuki

2011-06-01

TS-1 is an oral anticancer agent containing two biochemical modulators for 5-fluorouracil (5-FU) and tegafur (FT), a metabolically activated prodrug of 5-FU. TS-1 has been recognized as an effective anticancer drug using standard therapies for patients with advanced pancreatic cancer along with gemcitabine. However, a high level of inherent and acquired tumor resistance to TS-1 induces difficulty in the treatment. To identify proteins linked to the TS-1-resistance of pancreatic cancer, we profiled protein expression levels in samples of TS-1-resistant and -sensitive pancreatic cancer cell lines by using two-dimensional gel electrophoresis (2-DE) and liquid chromatography-tandem mass spectrometry (LC-MS/MS). The cytotoxicity of a 5-FU/5-chloro-2,4-dihydroxypyridine (CDHP) combination towards pancreatic cancer cell lines was evaluated by MTS assay. Panc-1, BxPC-3, MiaPaCa-2 and PK59 showed high sensitivity to the 5-FU/CDHP combination (TS-1-sensitive), whereas PK45p and KLM-1 were much less sensitive (TS-1-resistant). Proteomic analysis showed that eleven spots, including T-complex protein 1 subunit beta, ribonuclease inhibitor, elongation factor 1-delta, peroxiredoxin-2 and superoxide dismutase (Cu-Zn), appeared to be down-regulated, and 29 spots, including hypoxia up-regulated protein 1, lamin-A/C, endoplasmin, fascin and annexin A1, appeared to be up-regulated in TS-1-resistant cells compared with -sensitive cells. These results suggest that the identified proteins showing different expression between TS-1-sensitive and -resistant pancreatic cancer cells possibly relate to TS-1-sensitivity. These findings could be useful to overcome the TS-1-resistance of pancreatic cancer cells.

Combined use of high-sensitivity C-reactive protein and apolipoprotein B/apolipoprotein A-1 ratio prior to elective coronary angiography and oral glucose tolerance tests.

PubMed

Wen, Zhu-zhi; Geng, Deng-feng; Luo, Jin-gang; Wang, Jing-feng

2011-11-01

The study aimed to investigate the predictive value of the combination of high-sensitivity C-reactive protein (hs-CRP) and apolipoprotein B (apoB)/apoA-1 ratio for the outcomes of coronary angiography (CAG), echocardiography and oral glucose tolerance tests (OGTTs). Hs-CRP, apoB, apoA-1, and the profiles of CAG, echocardiography and OGTTs as well as traditional risk factors were measured in 1757 cardiology patients. Hs-CRP or apoB/apoA-1 ratio was significantly correlated with the presence and severity of angiographic profiles, the levels of left ventricular (LV) ejection fraction, LV mass and LV mass index, and the presence of abnormal glucose metabolism. The combination of hs-CRP and apoB/apoA-1 ratio had greater correlation with abnormal glucose metabolism than its individual components in patients with normal fasting glucose, and was an independent predictor for coronary artery disease. The combination of hs-CRP and apoB/apoA-1 ratio may be a strong predictor for coronary artery disease and abnormal glucose metabolism. Copyright © 2011 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Cold-Adapted Viral Attenuation (CAVA): Highly Temperature Sensitive Polioviruses as Novel Vaccine Strains for a Next Generation Inactivated Poliovirus Vaccine

PubMed Central

Sanders, Barbara P.; de los Rios Oakes, Isabel; van Hoek, Vladimir; Bockstal, Viki; Kamphuis, Tobias; Uil, Taco G.; Song, Yutong; Cooper, Gillian; Crawt, Laura E.; Martín, Javier; Zahn, Roland; Lewis, John; Wimmer, Eckard; Custers, Jerome H. H. V.; Schuitemaker, Hanneke; Cello, Jeronimo; Edo-Matas, Diana

2016-01-01

The poliovirus vaccine field is moving towards novel vaccination strategies. Withdrawal of the Oral Poliovirus Vaccine and implementation of the conventional Inactivated Poliovirus Vaccine (cIPV) is imminent. Moreover, replacement of the virulent poliovirus strains currently used for cIPV with attenuated strains is preferred. We generated Cold-Adapted Viral Attenuation (CAVA) poliovirus strains by serial passage at low temperature and subsequent genetic engineering, which contain the capsid sequences of cIPV strains combined with a set of mutations identified during cold-adaptation. These viruses displayed a highly temperature sensitive phenotype with no signs of productive infection at 37°C as visualized by electron microscopy. Furthermore, decreases in infectious titers, viral RNA, and protein levels were measured during infection at 37°C, suggesting a block in the viral replication cycle at RNA replication, protein translation, or earlier. However, at 30°C, they could be propagated to high titers (9.4–9.9 Log10TCID50/ml) on the PER.C6 cell culture platform. We identified 14 mutations in the IRES and non-structural regions, which in combination induced the temperature sensitive phenotype, also when transferred to the genomes of other wild-type and attenuated polioviruses. The temperature sensitivity translated to complete absence of neurovirulence in CD155 transgenic mice. Attenuation was also confirmed after extended in vitro passage at small scale using conditions (MOI, cell density, temperature) anticipated for vaccine production. The inability of CAVA strains to replicate at 37°C makes reversion to a neurovirulent phenotype in vivo highly unlikely, therefore, these strains can be considered safe for the manufacture of IPV. The CAVA strains were immunogenic in the Wistar rat potency model for cIPV, inducing high neutralizing antibody titers in a dose-dependent manner in response to D-antigen doses used for cIPV. In combination with the highly productive PER.C6 cell culture platform, the stably attenuated CAVA strains may serve as an attractive low-cost and (bio)safe option for the production of a novel next generation IPV. PMID:27032093

Cold-Adapted Viral Attenuation (CAVA): Highly Temperature Sensitive Polioviruses as Novel Vaccine Strains for a Next Generation Inactivated Poliovirus Vaccine.

PubMed

Sanders, Barbara P; de Los Rios Oakes, Isabel; van Hoek, Vladimir; Bockstal, Viki; Kamphuis, Tobias; Uil, Taco G; Song, Yutong; Cooper, Gillian; Crawt, Laura E; Martín, Javier; Zahn, Roland; Lewis, John; Wimmer, Eckard; Custers, Jerome H H V; Schuitemaker, Hanneke; Cello, Jeronimo; Edo-Matas, Diana

2016-03-01

The poliovirus vaccine field is moving towards novel vaccination strategies. Withdrawal of the Oral Poliovirus Vaccine and implementation of the conventional Inactivated Poliovirus Vaccine (cIPV) is imminent. Moreover, replacement of the virulent poliovirus strains currently used for cIPV with attenuated strains is preferred. We generated Cold-Adapted Viral Attenuation (CAVA) poliovirus strains by serial passage at low temperature and subsequent genetic engineering, which contain the capsid sequences of cIPV strains combined with a set of mutations identified during cold-adaptation. These viruses displayed a highly temperature sensitive phenotype with no signs of productive infection at 37°C as visualized by electron microscopy. Furthermore, decreases in infectious titers, viral RNA, and protein levels were measured during infection at 37°C, suggesting a block in the viral replication cycle at RNA replication, protein translation, or earlier. However, at 30°C, they could be propagated to high titers (9.4-9.9 Log10TCID50/ml) on the PER.C6 cell culture platform. We identified 14 mutations in the IRES and non-structural regions, which in combination induced the temperature sensitive phenotype, also when transferred to the genomes of other wild-type and attenuated polioviruses. The temperature sensitivity translated to complete absence of neurovirulence in CD155 transgenic mice. Attenuation was also confirmed after extended in vitro passage at small scale using conditions (MOI, cell density, temperature) anticipated for vaccine production. The inability of CAVA strains to replicate at 37°C makes reversion to a neurovirulent phenotype in vivo highly unlikely, therefore, these strains can be considered safe for the manufacture of IPV. The CAVA strains were immunogenic in the Wistar rat potency model for cIPV, inducing high neutralizing antibody titers in a dose-dependent manner in response to D-antigen doses used for cIPV. In combination with the highly productive PER.C6 cell culture platform, the stably attenuated CAVA strains may serve as an attractive low-cost and (bio)safe option for the production of a novel next generation IPV.

Social stress reactivity alters reward and punishment learning

PubMed Central

Frank, Michael J.; Allen, John J. B.

2011-01-01

To examine how stress affects cognitive functioning, individual differences in trait vulnerability (punishment sensitivity) and state reactivity (negative affect) to social evaluative threat were examined during concurrent reinforcement learning. Lower trait-level punishment sensitivity predicted better reward learning and poorer punishment learning; the opposite pattern was found in more punishment sensitive individuals. Increasing state-level negative affect was directly related to punishment learning accuracy in highly punishment sensitive individuals, but these measures were inversely related in less sensitive individuals. Combined electrophysiological measurement, performance accuracy and computational estimations of learning parameters suggest that trait and state vulnerability to stress alter cortico-striatal functioning during reinforcement learning, possibly mediated via medio-frontal cortical systems. PMID:20453038

Social stress reactivity alters reward and punishment learning.

PubMed

Cavanagh, James F; Frank, Michael J; Allen, John J B

2011-06-01

To examine how stress affects cognitive functioning, individual differences in trait vulnerability (punishment sensitivity) and state reactivity (negative affect) to social evaluative threat were examined during concurrent reinforcement learning. Lower trait-level punishment sensitivity predicted better reward learning and poorer punishment learning; the opposite pattern was found in more punishment sensitive individuals. Increasing state-level negative affect was directly related to punishment learning accuracy in highly punishment sensitive individuals, but these measures were inversely related in less sensitive individuals. Combined electrophysiological measurement, performance accuracy and computational estimations of learning parameters suggest that trait and state vulnerability to stress alter cortico-striatal functioning during reinforcement learning, possibly mediated via medio-frontal cortical systems.

Design of organic dyes and cobalt polypyridine redox mediators for high-efficiency dye-sensitized solar cells.

PubMed

Feldt, Sandra M; Gibson, Elizabeth A; Gabrielsson, Erik; Sun, Licheng; Boschloo, Gerrit; Hagfeldt, Anders

2010-11-24

Dye-sensitized solar cells (DSCs) with cobalt-based mediators with efficiencies surpassing the record for DSCs with iodide-free electrolytes were developed by selecting a suitable combination of a cobalt polypyridine complex and an organic sensitizer. The effect of the steric properties of two triphenylamine-based organic sensitizers and a series of cobalt polypyridine redox mediators on the overall device performance in DSCs as well as on transport and recombination processes in these devices was compared. The recombination and mass-transport limitations that, previously, have been found to limit the performance of these mediators were avoided by matching the properties of the dye and the cobalt redox mediator. Organic dyes with higher extinction coefficients than the standard ruthenium sensitizers were employed in DSCs in combination with outer-sphere redox mediators, enabling thinner TiO(2) films to be used. Recombination was reduced further by introducing insulating butoxyl chains on the dye rather than on the cobalt redox mediator, enabling redox couples with higher diffusion coefficients and more suitable redox potential to be used, simultaneously improving the photocurrent and photovoltage of the device. Optimization of DSCs sensitized with a triphenylamine-based organic dye in combination with tris(2,2'-bipyridyl)cobalt(II/III) yielded solar cells with overall conversion efficiencies of 6.7% and open-circuit potentials of more than 0.9 V under 1000 W m(-2) AM1.5 G illumination. Excellent performance was also found under low light intensity indoor conditions.

Is it useful to combine sputum cytology and low-dose spiral computed tomography for early detection of lung cancer in formerly asbestos-exposed power industry workers?

PubMed Central

2014-01-01

Background Low-dose spiral computed tomography (LDSCT) in comparison to conventional chest X-ray proved to be a highly sensitive method of diagnosing early stage lung cancer. However, centrally located early stage lung tumours remain a diagnostic challenge. We determined the practicability and efficacy of early detection of lung cancer when combining LDSCT and sputum cytology. Methods Of a cohort of 4446 formerly asbestos exposed power industry workers, we examined a subgroup of 187 (4.2%) high risk participants for lung cancer at least once with both LDSCT and sputum cytology. After the examination period the participants were followed-up for more than three years. Results The examinations resulted in the diagnosis of lung cancer in 12 participants (6.4%). Six were in clinical stage I. We found 10 non-small cell lung carcinomas and one small cell lung carcinoma. Sputum specimens showed suspicious pathological findings in seven cases and in 11 cases the results of LDSCT indicated malignancies. The overall sensitivity and specificity of sputum cytology was 58.0% and 98% with positive (PPV) and negative (NPV) predictive values of 70% and 97%. For LDSCT we calculated the sensitivity and specificity of 92% and 97%. The PPV and NPV were 65% and 99% respectively. Conclusions Our results confirmed that in surveillance programmes a combination of sputum cytology and LDSCT is well feasible and accepted by the participants. Sputum examination alone is not effective enough for the detection of lung cancer, especially at early stage. Even in well- defined risk groups highly exposed to asbestos, we cannot recommend the use of combined LDSCT and sputum cytology examinations as long as no survival benefit has been proved for the combination of both methods. For ensuring low rates of false-positive and false-negative results, programme planners must closely cooperate with experienced medical practitioners and pathologists in a well-functioning interdisciplinary network. PMID:24739456

Integrated digital error suppression for improved detection of circulating tumor DNA

PubMed Central

Kurtz, David M.; Chabon, Jacob J.; Scherer, Florian; Stehr, Henning; Liu, Chih Long; Bratman, Scott V.; Say, Carmen; Zhou, Li; Carter, Justin N.; West, Robert B.; Sledge, George W.; Shrager, Joseph B.; Loo, Billy W.; Neal, Joel W.; Wakelee, Heather A.; Diehn, Maximilian; Alizadeh, Ash A.

2016-01-01

High-throughput sequencing of circulating tumor DNA (ctDNA) promises to facilitate personalized cancer therapy. However, low quantities of cell-free DNA (cfDNA) in the blood and sequencing artifacts currently limit analytical sensitivity. To overcome these limitations, we introduce an approach for integrated digital error suppression (iDES). Our method combines in silico elimination of highly stereotypical background artifacts with a molecular barcoding strategy for the efficient recovery of cfDNA molecules. Individually, these two methods each improve the sensitivity of cancer personalized profiling by deep sequencing (CAPP-Seq) by ~3 fold, and synergize when combined to yield ~15-fold improvements. As a result, iDES-enhanced CAPP-Seq facilitates noninvasive variant detection across hundreds of kilobases. Applied to clinical non-small cell lung cancer (NSCLC) samples, our method enabled biopsy-free profiling of EGFR kinase domain mutations with 92% sensitivity and 96% specificity and detection of ctDNA down to 4 in 105 cfDNA molecules. We anticipate that iDES will aid the noninvasive genotyping and detection of ctDNA in research and clinical settings. PMID:27018799

Visual sensitivity for luminance and chromatic stimuli during the execution of smooth pursuit and saccadic eye movements.

PubMed

Braun, Doris I; Schütz, Alexander C; Gegenfurtner, Karl R

2017-07-01

Visual sensitivity is dynamically modulated by eye movements. During saccadic eye movements, sensitivity is reduced selectively for low-spatial frequency luminance stimuli and largely unaffected for high-spatial frequency luminance and chromatic stimuli (Nature 371 (1994), 511-513). During smooth pursuit eye movements, sensitivity for low-spatial frequency luminance stimuli is moderately reduced while sensitivity for chromatic and high-spatial frequency luminance stimuli is even increased (Nature Neuroscience, 11 (2008), 1211-1216). Since these effects are at least partly of different polarity, we investigated the combined effects of saccades and smooth pursuit on visual sensitivity. For the time course of chromatic sensitivity, we found that detection rates increased slightly around pursuit onset. During saccades to static and moving targets, detection rates dropped briefly before the saccade and reached a minimum at saccade onset. This reduction of chromatic sensitivity was present whenever a saccade was executed and it was not modified by subsequent pursuit. We also measured contrast sensitivity for flashed high- and low-spatial frequency luminance and chromatic stimuli during saccades and pursuit. During saccades, the reduction of contrast sensitivity was strongest for low-spatial frequency luminance stimuli (about 90%). However, a significant reduction was also present for chromatic stimuli (about 58%). Chromatic sensitivity was increased during smooth pursuit (about 12%). These results suggest that the modulation of visual sensitivity during saccades and smooth pursuit is more complex than previously assumed. Copyright © 2017 Elsevier Ltd. All rights reserved.

Three-dimensional conformal graphene microstructure for flexible and highly sensitive electronic skin

NASA Astrophysics Data System (ADS)

Yang, Jun; Ran, Qincui; Wei, Dapeng; Sun, Tai; Yu, Leyong; Song, Xuefen; Pu, Lichun; Shi, Haofei; Du, Chunlei

2017-03-01

We demonstrate a highly stretchable electronic skin (E-skin) based on the facile combination of microstructured graphene nanowalls (GNWs) and a polydimethylsiloxane (PDMS) substrate. The microstructure of the GNWs was endowed by conformally growing them on the unpolished silicon wafer without the aid of nanofabrication technology. Then a stamping transfer method was used to replicate the micropattern of the unpolished silicon wafer. Due to the large contact interface between the 3D graphene network and the PDMS, this type of E-skin worked under a stretching ratio of nearly 100%, and showed excellent mechanical strength and high sensitivity, with a change in relative resistance of up to 6500% and a gauge factor of 65.9 at 99.64% strain. Furthermore, the E-skin exhibited an obvious highly sensitive response to joint movement, eye movement and sound vibration, demonstrating broad potential applications in healthcare, body monitoring and wearable devices.

Flexible, highly sensitive pressure sensor with a wide range based on graphene-silk network structure

NASA Astrophysics Data System (ADS)

Liu, Ying; Tao, Lu-Qi; Wang, Dan-Yang; Zhang, Tian-Yu; Yang, Yi; Ren, Tian-Ling

2017-03-01

In this paper, a flexible, simple-preparation, and low-cost graphene-silk pressure sensor based on soft silk substrate through thermal reduction was demonstrated. Taking silk as the support body, the device had formed a three-dimensional structure with ordered multi-layer structure. Through a simple and low-cost process technology, graphene-silk pressure sensor can achieve the sensitivity value of 0.4 kPa - 1 , and the measurement range can be as high as 140 kPa. Besides, pressure sensor can have a good combination with knitted clothing and textile product. The signal had good reproducibility in response to different pressures. Furthermore, graphene-silk pressure sensor can not only detect pressure higher than 100 kPa, but also can measure weak body signals. The characteristics of high-sensitivity, good repeatability, flexibility, and comfort for skin provide the high possibility to fit on various wearable electronics.

Skin inspired fractal strain sensors using a copper nanowire and graphite microflake hybrid conductive network.

PubMed

Jason, Naveen N; Wang, Stephen J; Bhanushali, Sushrut; Cheng, Wenlong

2016-09-22

This work demonstrates a facile "paint-on" approach to fabricate highly stretchable and highly sensitive strain sensors by combining one-dimensional copper nanowire networks with two-dimensional graphite microflakes. This paint-on approach allows for the fabrication of electronic skin (e-skin) patches which can directly replicate with high fidelity the human skin surface they are on, regardless of the topological complexity. This leads to high accuracy for detecting biometric signals for applications in personalised wearable sensors. The copper nanowires contribute to high stretchability and the graphite flakes offer high sensitivity, and their hybrid coating offers the advantages of both. To understand the topological effects on the sensing performance, we utilized fractal shaped elastomeric substrates and systematically compared their stretchability and sensitivity. We could achieve a high stretchability of up to 600% and a maximum gauge factor of 3000. Our simple yet efficient paint-on approach enabled facile fine-tuning of sensitivity/stretchability simply by adjusting ratios of 1D vs. 2D materials in the hybrid coating, and the topological structural designs. This capability leads to a wide range of biomedical sensors demonstrated here, including pulse sensors, prosthetic hands, and a wireless ankle motion sensor.

Sinoporphyrin sodium triggered sono-photodynamic effects on breast cancer both in vitro and in vivo.

PubMed

Liu, Yichen; Wang, Pan; Liu, Quanhong; Wang, Xiaobing

2016-07-01

Sono-photodynamic therapy (SPDT) is a promising anti-cancer strategy. Briefly, SPDT combines ultrasound and light to activate sensitizers that produce mechanical, sonochemical and photochemical activities. Sinoporphyrin sodium (DVDMS) is a newly identified sensitizer that shows great potential in both sonodynamic therapy (SDT) and photodynamic therapy (PDT). In this study, we primarily evaluated the combined effects of SDT and PDT by using DVDMS on breast cancer both in vitro and in vivo. In vitro, DVDMS-SPDT elicits much serious cytotoxicity compared with either SDT or PDT alone by MTT and colony formation assays. 2',7'-Dichlorodihydrofluo-rescein-diacetate (DCFH-DA) and dihydroethidium (DHE) staining revealed that intracellular reactive oxygen species (ROS) were significantly increased in groups given combined therapy. Terephthalic acid (TA) method and FD500-uptake assay reflected that cavitational effects and cell membrane permeability changes after ultrasound irradiation were also involved in the enhancement of combination therapy. In vivo, DVDMS-SPDT markedly inhibits the tumor volume and tumor weight growth. Hematoxylin-eosin staining and immunohistochemistry analysis show DVDMS-SPDT greatly suppressed tumor proliferation. Further, DVDMS-SPDT significantly inhibits tumor lung metastasis in the highly metastatic 4T1 mouse xenograft model, which is consistent well with the in vitro findings evaluated by transwell assay. Moreover, DVDMS-SPDT did not produces obvious effect on body weight and major organs in 4T1 xenograft model. The results suggest that by combination SDT and PDT, the sensitizer DVDMS would produce much better therapeutic effects, and DVDMS-SPDT may be a potential strategy against highly metastatic breast cancer. Copyright © 2016 Elsevier B.V. All rights reserved.

Fines classification based on sensitivity to pore-fluid chemistry

USGS Publications Warehouse

Jang, Junbong; Santamarina, J. Carlos

2016-01-01

The 75-μm particle size is used to discriminate between fine and coarse grains. Further analysis of fine grains is typically based on the plasticity chart. Whereas pore-fluid-chemistry-dependent soil response is a salient and distinguishing characteristic of fine grains, pore-fluid chemistry is not addressed in current classification systems. Liquid limits obtained with electrically contrasting pore fluids (deionized water, 2-M NaCl brine, and kerosene) are combined to define the soil “electrical sensitivity.” Liquid limit and electrical sensitivity can be effectively used to classify fine grains according to their fluid-soil response into no-, low-, intermediate-, or high-plasticity fine grains of low, intermediate, or high electrical sensitivity. The proposed methodology benefits from the accumulated experience with liquid limit in the field and addresses the needs of a broader range of geotechnical engineering problems.

Highly Sensitive H2S Sensor Based on the Metal-Catalyzed SnO2 Nanocolumns Fabricated by Glancing Angle Deposition

PubMed Central

Yoo, Kwang Soo; Han, Soo Deok; Moon, Hi Gyu; Yoon, Seok-Jin; Kang, Chong-Yun

2015-01-01

As highly sensitive H2S gas sensors, Au- and Ag-catalyzed SnO2 thin films with morphology-controlled nanostructures were fabricated by using e-beam evaporation in combination with the glancing angle deposition (GAD) technique. After annealing at 500 °C for 40 h, the sensors showed a polycrystalline phase with a porous, tilted columnar nanostructure. The gas sensitivities (S = Rgas/Rair) of Au and Ag-catalyzed SnO2 sensors fabricated by the GAD process were 0.009 and 0.015, respectively, under 5 ppm H2S at 300 °C, and the 90% response time was approximately 5 s. These sensors showed excellent sensitivities compared with the SnO2 thin film sensors that were deposited normally (glancing angle = 0°, S = 0.48). PMID:26134105

Sensitivity study for a remotely piloted microwave-powered sailplane used as a high-altitude observation

NASA Technical Reports Server (NTRS)

Turriziani, R. V.

1979-01-01

The sensitivity of several performance characteristics of a proposed design for a microwave-powered, remotely piloted, high-altitude sailplane to changes in independently varied design parameters was investigated. Results were expressed as variations from baseline values of range, final climb altitude and onboard storage of radiated energy. Calculated range decreased with increases in either gross weight or parasite drag coefficient; it also decreased with decreases in lift coefficient, propeller efficiency, or microwave beam density. The sensitivity trends for range and final climb altitude were very similar. The sensitivity trends for stored energy were reversed from those for range, except for decreasing microwave beam density. Some study results for single parameter variations were combined to estimate the effect of the simultaneous variation of several parameters: for two parameters, this appeared to give reasonably accurate results.

Nucleic acid detection system and method for detecting influenza

DOEpatents

Cai, Hong; Song, Jian

2015-03-17

The invention provides a rapid, sensitive and specific nucleic acid detection system which utilizes isothermal nucleic acid amplification in combination with a lateral flow chromatographic device, or DNA dipstick, for DNA-hybridization detection. The system of the invention requires no complex instrumentation or electronic hardware, and provides a low cost nucleic acid detection system suitable for highly sensitive pathogen detection. Hybridization to single-stranded DNA amplification products using the system of the invention provides a sensitive and specific means by which assays can be multiplexed for the detection of multiple target sequences.

Sensitometric properties of Agfa Dentus OrthoLux, Agfa Dentus ST8G, and Kodak Ektavision panoramic radiographic film.

PubMed

Wakoh, M; Nishikawa, K; Kobayashi, N; Farman, A G; Kuroyanagi, K

2001-02-01

The purpose of this study was to compare the sensitometric properties of and visualization of anatomical structures with Agfa OrthoLux green-sensitive panoramic radiographic film, Agfa ST8G green sensitive panoramic radiographic film, and Kodak Ektavision green-sensitive panoramic radiographic film used in combination with an Agfa Ortho Regular 400 imaging screen, Kodak Ektavision imaging screen, and Kodak Lanex Regular imaging screen. The density response and resolution of panoramic radiographic film/intensifying screen combinations was evaluated by means of Hunter and Driffield curves, modulation transfer functions, and noise-equivalent number of quanta. Image clarity of selected anatomical structures was rated independently by 6 oral and maxillofacial radiologists. The ISO speed for the Agfa OrthoLux panoramic radiographic film combinations was the fastest, and the ISO speed for the Kodak Ektavision green-sensitive panoramic radiographic film combinations was the slowest. The average gradient for the Agfa ST8G systems was relatively steep in comparison with those for the other film/screen combinations. The modulation transfer functions for the Kodak Ektavision film were higher than those for the other films, irrespective of the screen combination used, and those for Agfa OrthoLux film were slightly higher than those for Agfa ST8G film. The noise-equivalent number of quanta for the Agfa ST8G film/screen combinations was lower than those for the other film/screen combinations. The noise-equivalent number of quanta for the Kodak Ektavision film/screen combinations was well within the high-frequency range, whereas Agfa OrthoLux combined with either the Kodak Ektavision imaging screen or the Kodak Lanex Regular imaging screen produced a noise-equivalent number of quanta similar to those of the Kodak Ektavision film/screen combinations in the low-frequency range. Agfa OrthoLux was perceived to provide clearer images of the selected anatomical details than Agfa ST8G, and the Agfa OrthoLux/Agfa Ortho Regular 400 combination was not significantly different from the Kodak Ektavision/Kodak Lanex Regular combination in terms of perceived image quality. Agfa OrthoLux is an improvement over Agfa ST8G in film speed, spatial resolution, granularity, and perceived diagnostic image quality. The Agfa OrthoLux/Agfa Ortho Regular 400 combination did not exceed the Kodak Ektavision film/Kodak Ektavision imaging screen combination in resolution, granularity, or perceived image quality.

Blinded Validation of Breath Biomarkers of Lung Cancer, a Potential Ancillary to Chest CT Screening

PubMed Central

Phillips, Michael; Bauer, Thomas L.; Cataneo, Renee N.; Lebauer, Cassie; Mundada, Mayur; Pass, Harvey I.; Ramakrishna, Naren; Rom, William N.; Vallières, Eric

2015-01-01

Background Breath volatile organic compounds (VOCs) have been reported as biomarkers of lung cancer, but it is not known if biomarkers identified in one group can identify disease in a separate independent cohort. Also, it is not known if combining breath biomarkers with chest CT has the potential to improve the sensitivity and specificity of lung cancer screening. Methods Model-building phase (unblinded): Breath VOCs were analyzed with gas chromatography mass spectrometry in 82 asymptomatic smokers having screening chest CT, 84 symptomatic high-risk subjects with a tissue diagnosis, 100 without a tissue diagnosis, and 35 healthy subjects. Multiple Monte Carlo simulations identified breath VOC mass ions with greater than random diagnostic accuracy for lung cancer, and these were combined in a multivariate predictive algorithm. Model-testing phase (blinded validation): We analyzed breath VOCs in an independent cohort of similar subjects (n = 70, 51, 75 and 19 respectively). The algorithm predicted discriminant function (DF) values in blinded replicate breath VOC samples analyzed independently at two laboratories (A and B). Outcome modeling: We modeled the expected effects of combining breath biomarkers with chest CT on the sensitivity and specificity of lung cancer screening. Results Unblinded model-building phase. The algorithm identified lung cancer with sensitivity 74.0%, specificity 70.7% and C-statistic 0.78. Blinded model-testing phase: The algorithm identified lung cancer at Laboratory A with sensitivity 68.0%, specificity 68.4%, C-statistic 0.71; and at Laboratory B with sensitivity 70.1%, specificity 68.0%, C-statistic 0.70, with linear correlation between replicates (r = 0.88). In a projected outcome model, breath biomarkers increased the sensitivity, specificity, and positive and negative predictive values of chest CT for lung cancer when the tests were combined in series or parallel. Conclusions Breath VOC mass ion biomarkers identified lung cancer in a separate independent cohort, in a blinded replicated study. Combining breath biomarkers with chest CT could potentially improve the sensitivity and specificity of lung cancer screening. Trial Registration ClinicalTrials.gov NCT00639067 PMID:26698306

Multimodal imaging system for dental caries detection

NASA Astrophysics Data System (ADS)

Liang, Rongguang; Wong, Victor; Marcus, Michael; Burns, Peter; McLaughlin, Paul

2007-02-01

Dental caries is a disease in which minerals of the tooth are dissolved by surrounding bacterial plaques. A caries process present for some time may result in a caries lesion. However, if it is detected early enough, the dentist and dental professionals can implement measures to reverse and control caries. Several optical, nonionized methods have been investigated and used to detect dental caries in early stages. However, there is not a method that can singly detect the caries process with both high sensitivity and high specificity. In this paper, we present a multimodal imaging system that combines visible reflectance, fluorescence, and Optical Coherence Tomography (OCT) imaging. This imaging system is designed to obtain one or more two-dimensional images of the tooth (reflectance and fluorescence images) and a three-dimensional OCT image providing depth and size information of the caries. The combination of two- and three-dimensional images of the tooth has the potential for highly sensitive and specific detection of dental caries.

Impact of two rounds of mass treatment with diethylcarbamazine plus albendazole on Wuchereria bancrofti infection and the sensitivity of immunochromatographic test in Malindi, Kenya.

PubMed

Njenga, S M; Wamae, C N; Njomo, D W; Mwandawiro, C S; Molyneux, D H

2008-10-01

Annual single-dose mass treatment of endemic populations with a combination of either diethylcarbamazine (DEC) or ivermectin plus albendazole is recommended as the mainstay of lymphatic filariasis elimination programmes. We evaluated the impact of two rounds of annual mass drug administration (MDA) of DEC and albendazole on bancroftian filariasis in a pilot elimination programme in an endemic area of Kenya. Overall prevalence of microfilaraemia decreased by 65.4%, whereas community microfilarial load decreased by 84% after the two MDAs. The prevalence of parasite antigenaemia determined by immunochromatographic test (ICT) declined significantly by 43.5% after the two MDAs. We also studied the effect of mass treatment on the sensitivity of the ICT. Although the sensitivity of the test before treatment was high (89.9%; kappa=0.909) sensitivity was lower after two MDAs (59.3%; kappa=0.644). The finding raises concern about the reliability of the ICT in long-term monitoring of infection and for establishing programmatic endpoints. The results of the present study indicate a relatively high effectiveness of MDA using a DEC/albendazole combination against Wuchereria bancrofti infection and, therefore, it may be a useful strategy to eliminate lymphatic filariasis in onchocerciasis-free areas.

Low-resistivity photon-transparent window attached to photo-sensitive silicon detector

DOEpatents

Holland, Stephen Edward

2000-02-15

The invention comprises a combination of a low resistivity, or electrically conducting, silicon layer that is transparent to long or short wavelength photons and is attached to the backside of a photon-sensitive layer of silicon, such as a silicon wafer or chip. The window is applied to photon sensitive silicon devices such as photodiodes, charge-coupled devices, active pixel sensors, low-energy x-ray sensors and other radiation detectors. The silicon window is applied to the back side of a photosensitive silicon wafer or chip so that photons can illuminate the device from the backside without interference from the circuit printed on the frontside. A voltage sufficient to fully deplete the high-resistivity photosensitive silicon volume of charge carriers is applied between the low-resistivity back window and the front, patterned, side of the device. This allows photon-induced charge created at the backside to reach the front side of the device and to be processed by any circuitry attached to the front side. Using the inventive combination, the photon sensitive silicon layer does not need to be thinned beyond standard fabrication methods in order to achieve full charge-depletion in the silicon volume. In one embodiment, the inventive backside window is applied to high resistivity silicon to allow backside illumination while maintaining charge isolation in CCD pixels.

A highly sensitive protocol for microscopy of alkyne lipids and fluorescently tagged or immunostained proteins[S

PubMed Central

Gaebler, Anne; Penno, Anke; Kuerschner, Lars; Thiele, Christoph

2016-01-01

The demand to study the cellular localization of specific lipids has led to recent advances in lipid probes and microscopy. Alkyne lipids bear a small, noninterfering tag and can be detected upon click reaction with an azide-coupled reporter. Fluorescent alkyne lipid imaging crucially depends on appropriate azide reporters and labeling protocols that allow for an efficient click reaction and therefore a sensitive detection. We synthesized several azide reporters with different spacer components and tested their suitability for alkyne lipid imaging in fixed cells. The implementation of a copper-chelating picolyl moiety into fluorescent or biotin-based azide reagents strongly increased the sensitivity of the imaging routine. We demonstrate the applicability and evaluate the performance of this approach using different lipid classes and experimental setups. As azide picolyl reporters allow for reduced copper catalyst concentrations, they also enable coimaging of alkyne lipids with multiple fluorescent proteins including enhanced green fluorescent protein. Alternatively, and as we also show, microscopy of alkyne lipids can be combined with protein detection by immunocytochemistry. In summary, we present a robust, sensitive, and highly versatile protocol for the labeling of alkyne lipids with azide-coupled reporters for fluorescence microscopy that can be combined with different protein detection and imaging techniques. PMID:27565170

A new concept of efficient therapeutic drug monitoring using the high-resolution continuum source absorption spectrometry and the surface enhanced Raman spectroscopy

NASA Astrophysics Data System (ADS)

Xing, Yanlong; Fuss, Harald; Lademann, Jürgen; Huang, Mao Dong; Becker-Ross, Helmut; Florek, Stefan; Patzelt, Alexa; Meinke, Martina C.; Jung, Sora; Esser, Norbert

2018-04-01

In this study, a new therapeutic drug monitoring approach has been tested based on the combination of CaF molecular absorption using high-resolution continuum source absorption spectrometry (HR-CSAS) and surface enhanced Raman spectroscopy (SERS). HR-CSAS with mini graphite tube was successfully tested for clinical therapeutic drug monitoring of the fluorine-containing drug capecitabine in sweat samples of cancer patients: It showed advantageous features of high selectivity (no interference from Cl), high sensitivity (characteristic mass of 0.1 ng at CaF 583.069 nm), low sample consumption (down to 30 nL) and fast measurement (no sample pretreatment and less than 1 min of responding time) in tracing the fluorine signal out of capecitabine. However, this technique has the disadvantage of the total loss of the drug's structure information after burning the sample at very high temperature. Therefore, a new concept of combining HR-CSAS with a non-destructive spectroscopic method (SERS) was proposed for the sensitive sensing and specific identification of capecitabine. We tested and succeed in obtaining the molecular characteristics of the metabolite of capecitabine (named 5-fluorouracil) by the non-destructive SERS technique. With the results shown in this work, it is demonstrated that the combined spectroscopic technique of HR-CSAS and SERS will be very useful in efficient therapeutic drug monitoring in the future.

Establishing a cost-effective national surveillance system for Bluetongue using scenario tree modelling.

PubMed

Hadorn, Daniela C; Racloz, Vanessa; Schwermer, Heinzpeter; Stärk, Katharina D C

2009-01-01

Vector-borne diseases pose a special challenge to veterinary authorities due to complex and time-consuming surveillance programs taking into account vector habitat. Using stochastic scenario tree modelling, each possible surveillance activity of a future surveillance system can be evaluated with regard to its sensitivity and the expected cost. The overall sensitivity of various potential surveillance systems, composed of different combinations of surveillance activities, is calculated and the proposed surveillance system is optimized with respect to the considered surveillance activities, the sensitivity and the cost. The objective of this project was to use stochastic scenario tree modelling in combination with a simple cost analysis in order to develop the national surveillance system for Bluetongue in Switzerland. This surveillance system was established due to the emerging outbreak of Bluetongue virus serotype 8 (BTV-8) in Northern Europe in 2006. Based on the modelling results, it was decided to implement an improved passive clinical surveillance in cattle and sheep through campaigns in order to increase disease awareness alongside a targeted bulk milk testing strategy in 200 dairy cattle herds located in high-risk areas. The estimated median probability of detection of cases (i.e. sensitivity) of the surveillance system in this combined approach was 96.4%. The evaluation of the prospective national surveillance system predicted that passive clinical surveillance in cattle would provide the highest probability to detect BTV-8 infected animals, followed by passive clinical surveillance in sheep and bulk milk testing of 200 dairy cattle farms in high-risk areas. This approach is also applicable in other countries and to other epidemic diseases.

The accuracy of confrontation visual field test in comparison with automated perimetry.

PubMed Central

Johnson, L. N.; Baloh, F. G.

1991-01-01

The accuracy of confrontation visual field testing was determined for 512 visual fields using automated static perimetry as the reference standard. The sensitivity of confrontation testing excluding patchy defects was 40% for detecting anterior visual field defects, 68.3% for posterior defects, and 50% for both anterior and posterior visual field defects combined. The sensitivity within each group varied depending on the type of visual field defect encountered. Confrontation testing had a high sensitivity (75% to 100%) for detecting altitudinal visual loss, central/centrocecal scotoma, and homonymous hemianopsia. Confrontation testing was fairly insensitive (20% to 50% sensitivity) for detecting arcuate scotoma and bitemporal hemianopsia. The specificity of confrontation testing was high at 93.4%. The high positive predictive value (72.6%) and negative predictive value (75.7%) would indicate that visual field defects identified during confrontation testing are often true visual field defects. However, the many limitations of confrontation testing should be remembered, particularly its low sensitivity for detecting visual field loss associated with parasellar tumors, glaucoma, and compressive optic neuropathies. PMID:1800764

The Science and Design of the AGIS Observatory

NASA Astrophysics Data System (ADS)

Schroedter, Martin

2010-02-01

The AGIS observatory is a next-generation array of imaging atmospheric Cherenkov telescopes (IACTs) for gamma-ray astronomy between 100 GeV and 100 TeV. The AGIS observatory is the next logical step in high energy gamma-ray astronomy, offering improved angular resolution and sensitivity compared to FERMI, and overlapping the high energy end of FERMI's sensitivity band. The baseline AGIS observatory will employ an array of 36 Schwarzschild-Couder IACTs in combination with a highly pixelated (0.05^o diameter) camera. The instrument is designed to provide millicrab sensitivity over a wide (8^o diameter) field of view, allowing both deep studies of faint point sources as well as efficient mapping of the Galactic plane and extended sources. I will describe science drivers behind the AGIS observatory and the design and status of the project. )

The Science and Design of the AGIS Observatory

NASA Astrophysics Data System (ADS)

Falcone, Abraham; Aliu, E.; Arlen, T.; Benbow, W.; Buckley, J.; Bugaev, S.; Byrum, K.; Ciupik, L.; Coppi, P.; Digel, S.; Drake, G.; Finley, J.; Fortson, L.; Franco, J.; Funk, S.; Guarino, V.; Gyuk, G.; Hanna, D.; Hiriart, D.; Humensky, B.; Holder, J.; Kaaret, P.; Karlsson, N.; Kieda, D.; Konopelko, A.; Krawczynski, H.; Krennrich, F.; LeBohec, S.; Maier, G.; Mukherjee, R.; Ong, R.; Otte, N.; Pareschi, G.; Pohl, M.; Quinn, J.; Ramsey, B.; Romani, R.; Rovero, A. C.; Schroedter, M.; Sinnis, C.; Slane, P.; Smith, A.; Swordy, S.; Tajima, H.; Vassiliev, V.; Wagner, R.; Wakely, S. P.; Weekes, T. C.; Weinstein, A.; Williams, D.

2010-01-01

The AGIS observatory is a next-generation array of imaging atmospheric Cherenkov telescopes (IACTs) for gamma-ray astronomy between 100GeV and 100 TeV. The AGIS observatory is the next logical step in high energy gamma-ray astronomy, offering improved angular resolution and sensitivity compared to FERMI, and overlapping the high energy end of FERMI's sensitivity band. The baseline AGIS observatory will employ an array of 36 Schwarzschild-Couder IACTs in combination with a highly pixelated (0.05 degree/pixel) camera. The instrument is designed to provide millicrab sensitivity over a wide (8 degree diameter) field of view, allowing both deep studies of faint point sources as well as efficient mapping of the Galactic plane and extended sources. This presentation will include a description of science drivers behind the AGIS observatory and the design and status of the project.

A high sensitivity ultralow temperature RF conductance and noise measurement setup.

PubMed

Parmentier, F D; Mahé, A; Denis, A; Berroir, J-M; Glattli, D C; Plaçais, B; Fève, G

2011-01-01

We report on the realization of a high sensitivity RF noise measurement scheme to study small current fluctuations of mesoscopic systems at milli-Kelvin temperatures. The setup relies on the combination of an interferometric amplification scheme and a quarter-wave impedance transformer, allowing the measurement of noise power spectral densities with gigahertz bandwidth up to five orders of magnitude below the amplifier noise floor. We simultaneously measure the high frequency conductance of the sample by derivating a portion of the signal to a microwave homodyne detection. We describe the principle of the setup, as well as its implementation and calibration. Finally, we show that our setup allows to fully characterize a subnanosecond on-demand single electron source. More generally, its sensitivity and bandwidth make it suitable for applications manipulating single charges at GHz frequencies.

Microelectromechanical systems for experimental physics and optical telecommunications

NASA Astrophysics Data System (ADS)

Aksyuk, Vladimir Anatolyevich

1999-12-01

Micro-Electro-Mechanical Systems (MEMS) are an emerging technology, which, when applied to the field of physical sensors, offers not only an obvious advantage of being small and cheap, but more importantly, provides some unique experimental opportunities. These are based on the way physical properties scale with decreasing size. This thesis discusses these basic principles and corresponding advantages and limitations of MEMS technology and presents several experiments in which micromachines are used to do physical measurements that could not be done before. Three types of micromechanical magnetometers are demonstrated. When compared to the state of the art traditional techniques they show greater sensitivity, faster response and can be applied over a wider range of experimental conditions. The high-Q micromechanical torsional oscillator magnetometer is used to observe mesoscopic vortex physics, including single flux lines penetrating into a type-II superconductor just above the first critical field. The Faraday balance ``Trampoline'' magnetometer combines high sensitivity, high bandwidth and can be operated in a wide temperature range. It is used in both high pulsed magnetic fields to record deHaas-vanAlphen oscillations and in DC magnetic fields for magnetization measurements at temperatures down to 100mK. The high sensitivity DC torque magnetometer offers yet higher sensitivity and can be used for a variety of magnetization measurements. Several other MEMS devices for physics and telecommunications applications are presented, including a micromachined near field scanning optical microscope, MEMS fiberoptic switches and large-area large-angle scanners. They provide examples of complex functionality that can be achieved with micromechanics by combining sensors with inherently low-power electrostatic actuators. The optically powered optical power limiter demonstrates the possibility of operating MEMS with optical rather than electrical power.

Age estimation using cortical surface pattern combining thickness with curvatures

PubMed Central

Wang, Jieqiong; Li, Wenjing; Miao, Wen; Dai, Dai; Hua, Jing; He, Huiguang

2014-01-01

Brain development and healthy aging have been proved to follow a specific pattern, which, in turn, can be applied to help doctors diagnose mental diseases. In this paper, we design a cortical surface pattern (CSP) combining the cortical thickness with curvatures, which constructs an accurate human age estimation model with relevance vector regression. We test our model with two public databases. One is the IXI database (360 healthy subjects aging from 20 to 82 years old were selected), and the other is the INDI database (303 subjects aging from 7 to 22 years old were selected). The results show that our model can achieve as small as 4.57 years deviation in the IXI database and 1.38 years deviation in the INDI database. Furthermore, we employ this surface pattern to age groups classification, and get a remarkably high accuracy (97.77%) and a significantly high sensitivity/specificity (97.30%/98.10%). These results suggest that our designed CSP combining thickness with curvatures is stable and sensitive to brain development, and it is much more powerful than voxel-based morphometry used in previous methods for age estimation. PMID:24395657

Design of a Multi-Pinhole Collimator for I-123 DaTscan Imaging on Dual-Headed SPECT Systems in Combination with a Fan-Beam Collimator.

PubMed

King, Michael A; Mukherjee, Joyeeta M; Könik, Arda; Zubal, I George; Dey, Joyoni; Licho, Robert

2016-02-01

For the 2011 FDA approved Parkinson's Disease (PD) SPECT imaging agent I-123 labeled DaTscan, the volume of interest (VOI) is the interior portion of the brain. However imaging of the occipital lobe is also required with PD for calculation of the striatal binding ratio (SBR), a parameter of significance in early diagnosis, differentiation of PD from other disorders with similar clinical presentations, and monitoring progression. Thus we propose the usage of a combination of a multi-pinhole (MPH) collimator on one head of the SPECT system and a fan-beam on the other. The MPH would be designed to provide high resolution and sensitivity for imaging of the interior portion of the brain. The fan-beam collimator would provide lower resolution but complete sampling of the brain addressing data sufficiency and allowing a volume-of-interest to be defined over the occipital lobe for calculation of SBR's. Herein we focus on the design of the MPH component of the combined system. Combined reconstruction will be addressed in a subsequent publication. An analysis of 46 clinical DaTscan studies was performed to provide information to define the VOI, and design of a MPH collimator to image this VOI. The system spatial resolution for the MPH was set to 4.7 mm, which is comparable to that of clinical PET systems, and significantly smaller than that of fan-beam collimators employed in SPECT. With this set, we compared system sensitivities for three aperture array designs, and selected the 3 × 3 array due to it being the highest of the three. The combined sensitivity of the apertures for it was similar to that of an ultra-high resolution fan-beam (LEUHRF) collimator, but smaller than that of a high-resolution fan-beam collimator (LEHRF). On the basis of these results we propose the further exploration of this design through simulations, and the development of combined MPH and fan-beam reconstruction.

High Sensitivity Detection of CdSe/ZnS Quantum Dot-Labeled DNA Based on N-type Porous Silicon Microcavities

PubMed Central

Lv, Changwu; Jia, Zhenhong; Lv, Jie; Zhang, Hongyan; Li, Yanyu

2017-01-01

N-type macroporous silicon microcavity structures were prepared using electrochemical etching in an HF solution in the absence of light and oxidants. The CdSe/ZnS water-soluble quantum dot-labeled DNA target molecules were detected by monitoring the microcavity reflectance spectrum, which was characterized by the reflectance spectrum defect state position shift resulting from changes to the structures’ refractive index. Quantum dots with a high refractive index and DNA coupling can improve the detection sensitivity by amplifying the optical response signals of the target DNA. The experimental results show that DNA combined with a quantum dot can improve the sensitivity of DNA detection by more than five times. PMID:28045442

High Sensitivity Detection of CdSe/ZnS Quantum Dot-Labeled DNA Based on N-type Porous Silicon Microcavities.

PubMed

Lv, Changwu; Jia, Zhenhong; Lv, Jie; Zhang, Hongyan; Li, Yanyu

2017-01-01

N-type macroporous silicon microcavity structures were prepared using electrochemical etching in an HF solution in the absence of light and oxidants. The CdSe/ZnS water-soluble quantum dot-labeled DNA target molecules were detected by monitoring the microcavity reflectance spectrum, which was characterized by the reflectance spectrum defect state position shift resulting from changes to the structures' refractive index. Quantum dots with a high refractive index and DNA coupling can improve the detection sensitivity by amplifying the optical response signals of the target DNA. The experimental results show that DNA combined with a quantum dot can improve the sensitivity of DNA detection by more than five times.

Highly Sensitive Measurements of 222Rn Diffusion and Emanation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zuzel, Grzegorz

Highly sensitive techniques for determination of the 222Rn emanation from solids and diffusion through different membranes are presented. 222Rn and its daughters are measured via the alpha decays in special proportional counters at the absolute sensitivity of {approx}30 {mu}Bq. Radon diffusion can be measured at the level of {approx}10-13 cm2/s. Several samples were examined, e.g. stainless steel, teflon, various gaskets (emanation and diffusion measurements) and tanks. A combination of measurements of the 222Rn diffusion and emanation of thin nylon foils (used in the Borexino experiment) allowed the determination of 226Ra in the materials of interest at the level of {approx}10-12more » g/g 238U-equivalent.« less

Time and position sensitive single photon detector for scintillator read-out

NASA Astrophysics Data System (ADS)

Schössler, S.; Bromberger, B.; Brandis, M.; Schmidt, L. Ph H.; Tittelmeier, K.; Czasch, A.; Dangendorf, V.; Jagutzki, O.

2012-02-01

We have developed a photon counting detector system for combined neutron and γ radiography which can determine position, time and intensity of a secondary photon flash created by a high-energy particle or photon within a scintillator screen. The system is based on a micro-channel plate photomultiplier concept utilizing image charge coupling to a position- and time-sensitive read-out anode placed outside the vacuum tube in air, aided by a standard photomultiplier and very fast pulse-height analyzing electronics. Due to the low dead time of all system components it can cope with the high throughput demands of a proposed combined fast neutron and dual discrete energy γ radiography method (FNDDER). We show tests with different types of delay-line read-out anodes and present a novel pulse-height-to-time converter circuit with its potential to discriminate γ energies for the projected FNDDER devices for an automated cargo container inspection system (ACCIS).

Assessing fitness-for-duty and predicting performance with cognitive neurophysiological measures

NASA Astrophysics Data System (ADS)

Smith, Michael E.; Gevins, Alan

2005-05-01

Progress is described in developing a novel test of neurocognitive status for fitness-for-duty testing. The Sustained Attention & Memory (SAM) test combines neurophysiologic (EEG) measures of brain activation with performance measures during a psychometric test of sustained attention and working memory, and then gauges changes in neurocognitive status relative to an individual"s normative baseline. In studies of the effects of common psychoactive substances that can affect job performance, including sedating antihistamines, caffeine, alcohol, marijuana, and prescription medications, test sensitivity was greater for the combined neurophysiological and performance measures than for task performance measures by themselves. The neurocognitive effects of overnight sleep deprivation were quite evident, and such effects predicted subsequent performance impairment on a flight simulator task. Sensitivity to diurnal circadian variations was also demonstrated. With further refinement and independent validation, the SAM Test may prove useful for assessing readiness-to-perform in high-asset personnel working in demanding, high risk situations.

New Perspectives on the Diagnosis of Allergy to Anisakis spp.

PubMed

Moneo, Ignacio; Carballeda-Sangiao, Noelia; González-Muñoz, Miguel

2017-05-01

To compare the prevalence of sensitization in different countries based on specific IgE values and to evaluate the use of isolated native or recombinant allergens for diagnosis. Isolated allergens help in the diagnosis of truly sensitized patients avoiding false positives due to cross-reactions. Their use is therefore highly recommended, especially when used as a combination of several relevant allergens. The use of purified allergens allows an accurate diagnosis and this has led to three important findings: (1) in addition to the digestive route of sensitization, occupational and non-digestive exposure seems to be clinically relevant. (2) The parasite appears as an important agent for chronic urticaria. And (3) in endemic countries, the amount of highly sensitized subjects in the general population could be as high as 7%. Adequate information to asymptomatic patients on fish consumption habits would avoid new contacts with parasite allergens and decrease their specific IgE levels and consequently the appearance of acute or chronic episodes induced by the parasite.

GRIDSS: sensitive and specific genomic rearrangement detection using positional de Bruijn graph assembly

PubMed Central

Do, Hongdo; Molania, Ramyar

2017-01-01

The identification of genomic rearrangements with high sensitivity and specificity using massively parallel sequencing remains a major challenge, particularly in precision medicine and cancer research. Here, we describe a new method for detecting rearrangements, GRIDSS (Genome Rearrangement IDentification Software Suite). GRIDSS is a multithreaded structural variant (SV) caller that performs efficient genome-wide break-end assembly prior to variant calling using a novel positional de Bruijn graph-based assembler. By combining assembly, split read, and read pair evidence using a probabilistic scoring, GRIDSS achieves high sensitivity and specificity on simulated, cell line, and patient tumor data, recently winning SV subchallenge #5 of the ICGC-TCGA DREAM8.5 Somatic Mutation Calling Challenge. On human cell line data, GRIDSS halves the false discovery rate compared to other recent methods while matching or exceeding their sensitivity. GRIDSS identifies nontemplate sequence insertions, microhomologies, and large imperfect homologies, estimates a quality score for each breakpoint, stratifies calls into high or low confidence, and supports multisample analysis. PMID:29097403

Effect of homogenization and pasteurization on the structure and thermal stability of whey protein in milk

USDA-ARS?s Scientific Manuscript database

The effect of homogenization alone or in combination with high temperature, short time (HTST) pasteurization or UHT processing on the whey fraction of milk was investigated using highly sensitive spectroscopic techniques. In pilot plant trials, 1-L quantities of whole milk were homogenized in a two-...

Aptamer-mediated 'turn-off/turn-on' nanozyme activity of gold nanoparticles for kanamycin detection.

PubMed

Sharma, Tarun Kumar; Ramanathan, Rajesh; Weerathunge, Pabudi; Mohammadtaheri, Mahsa; Daima, Hemant Kumar; Shukla, Ravi; Bansal, Vipul

2014-12-28

A new ultrafast and highly sensitive 'turn-off/turn-on' biosensing approach that combines the intrinsic peroxidase-like activity of gold nanoparticles (GNPs) with the high affinity and specificity of a ssDNA aptamer is presented for the efficient detection of a model small molecule kanamycin.

Polycarbonates: a long-term highly sensitive radon monitor

NASA Astrophysics Data System (ADS)

Pressyanov, D.; Buysse, J.; Poffijn, A.; Meesen, G.; Van Deynse, A.

2000-06-01

An approach for long-term (either retrospective or prospective) 222Rn measurements is proposed that is based on the combination of the high radon absorption ability of some polycarbonates with their alpha track-etch properties. The detection limit is projected to be <10 Bq m -3 for an exposure time of 20 yr.

Highly sensitive protein detection by combination of atomic force microscopy fishing with charge generation and mass spectrometry analysis.

PubMed

Ivanov, Yuri D; Pleshakova, Tatyana; Malsagova, Krystina; Kozlov, Andrey; Kaysheva, Anna; Kopylov, Arthur; Izotov, Alexander; Andreeva, Elena; Kanashenko, Sergey; Usanov, Sergey; Archakov, Alexander

2014-10-01

An approach combining atomic force microscopy (AFM) fishing and mass spectrometry (MS) analysis to detect proteins at ultra-low concentrations is proposed. Fishing out protein molecules onto a highly oriented pyrolytic graphite surface coated with polytetrafluoroethylene film was carried out with and without application of an external electric field. After that they were visualized by AFM and identified by MS. It was found that injection of solution leads to charge generation in the solution, and an electric potential within the measuring cell is induced. It was demonstrated that without an external electric field in the rapid injection input of diluted protein solution the fishing is efficient, as opposed to slow fluid input. The high sensitivity of this method was demonstrated by detection of human serum albumin and human cytochrome b5 in 10(-17) -10(-18) m water solutions. It was shown that an external negative voltage applied to highly oriented pyrolytic graphite hinders the protein fishing. The efficiency of fishing with an external positive voltage was similar to that obtained without applying any voltage. © 2014 FEBS.

Clinical utility of circulating matrix metalloproteinase-7 (MMP-7), CC chemokine ligand 18 (CCL18) and CC chemokine ligand 11 (CCL11) as markers for diagnosis of epithelial ovarian cancer.

PubMed

Zohny, Samir F; Fayed, Salah T

2010-12-01

Ovarian cancer remains a highly lethal disease. The aim of the present study was to evaluate the usefulness of measuring serum matrix metalloproteinase-7 (MMP-7), CC chemokine ligand 18 (CCL18) and CC chemokine ligand 11 (CCL11) in comparison with serum cancer antigen 125 (CA 125) for diagnosis of epithelial ovarian cancer (EOC). This study included 51 patients with EOC, 27 patients with benign ovarian lesions and 29 healthy volunteers. Serum CA 125 was determined by microparticle enzyme immunoassay, while serum MMP-7, CCL18 and CCL11 were measured using enzyme-linked immunosorbent assay. The sensitivity and specificity were 86.3% and 92.9% for CA 125, 80.4% and 87.5% for MMP-7, 84.3% and 91.1% for CCL18 and, 68.6% and 62.5% for CCL11. Combination of CA 125, MMP-7, CCL18 and CCL11 gave a promising sensitivity of 100%, but specificity was decreased to 60.7%. The combined use of serum CA 125, MMP-7, CCL18 and CCL11 effectively detected early stages EOC with high sensitivity of 94.4%. Our data indicate that serum MMP-7, CCL18 and CCL11, in combination with CA 125 could be useful in diagnosis of EOC.

Testing for new physics: neutrinos and the primordial power spectrum

DOE Office of Scientific and Technical Information (OSTI.GOV)

Canac, Nicolas; Abazajian, Kevork N.; Aslanyan, Grigor

2016-09-01

We test the sensitivity of neutrino parameter constraints from combinations of CMB and LSS data sets to the assumed form of the primordial power spectrum (PPS) using Bayesian model selection. Significantly, none of the tested combinations, including recent high-precision local measurements of H{sub 0} and cluster abundances, indicate a signal for massive neutrinos or extra relativistic degrees of freedom. For PPS models with a large, but fixed number of degrees of freedom, neutrino parameter constraints do not change significantly if the location of any features in the PPS are allowed to vary, although neutrino constraints are more sensitive to PPSmore » features if they are known a priori to exist at fixed intervals in log k . Although there is no support for a non-standard neutrino sector from constraints on both neutrino mass and relativistic energy density, we see surprisingly strong evidence for features in the PPS when it is constrained with data from Planck 2015, SZ cluster counts, and recent high-precision local measurements of H{sub 0}. Conversely combining Planck with matter power spectrum and BAO measurements yields a much weaker constraint. Given that this result is sensitive to the choice of data this tension between SZ cluster counts, Planck and H{sub 0} measurements is likely an indication of unmodeled systematic bias that mimics PPS features, rather than new physics in the PPS or neutrino sector.« less

High-sensitivity microfluidic calorimeters for biological and chemical applications.

PubMed

Lee, Wonhee; Fon, Warren; Axelrod, Blake W; Roukes, Michael L

2009-09-08

High-sensitivity microfluidic calorimeters raise the prospect of achieving high-throughput biochemical measurements with minimal sample consumption. However, it has been challenging to realize microchip-based calorimeters possessing both high sensitivity and precise sample-manipulation capabilities. Here, we report chip-based microfluidic calorimeters capable of characterizing the heat of reaction of 3.5-nL samples with 4.2-nW resolution. Our approach, based on a combination of hard- and soft-polymer microfluidics, provides both exceptional thermal response and the physical strength necessary to construct high-sensitivity calorimeters that can be scaled to automated, highly multiplexed array architectures. Polydimethylsiloxane microfluidic valves and pumps are interfaced to parylene channels and reaction chambers to automate the injection of analyte at 1 nL and below. We attained excellent thermal resolution via on-chip vacuum encapsulation, which provides unprecedented thermal isolation of the minute microfluidic reaction chambers. We demonstrate performance of these calorimeters by resolving measurements of the heat of reaction of urea hydrolysis and the enthalpy of mixing of water with methanol. The device structure can be adapted easily to enable a wide variety of other standard calorimeter operations; one example, a flow calorimeter, is described.

OPTIMA: sensitive and accurate whole-genome alignment of error-prone genomic maps by combinatorial indexing and technology-agnostic statistical analysis.

PubMed

Verzotto, Davide; M Teo, Audrey S; Hillmer, Axel M; Nagarajan, Niranjan

2016-01-01

Resolution of complex repeat structures and rearrangements in the assembly and analysis of large eukaryotic genomes is often aided by a combination of high-throughput sequencing and genome-mapping technologies (for example, optical restriction mapping). In particular, mapping technologies can generate sparse maps of large DNA fragments (150 kilo base pairs (kbp) to 2 Mbp) and thus provide a unique source of information for disambiguating complex rearrangements in cancer genomes. Despite their utility, combining high-throughput sequencing and mapping technologies has been challenging because of the lack of efficient and sensitive map-alignment algorithms for robustly aligning error-prone maps to sequences. We introduce a novel seed-and-extend glocal (short for global-local) alignment method, OPTIMA (and a sliding-window extension for overlap alignment, OPTIMA-Overlap), which is the first to create indexes for continuous-valued mapping data while accounting for mapping errors. We also present a novel statistical model, agnostic with respect to technology-dependent error rates, for conservatively evaluating the significance of alignments without relying on expensive permutation-based tests. We show that OPTIMA and OPTIMA-Overlap outperform other state-of-the-art approaches (1.6-2 times more sensitive) and are more efficient (170-200 %) and precise in their alignments (nearly 99 % precision). These advantages are independent of the quality of the data, suggesting that our indexing approach and statistical evaluation are robust, provide improved sensitivity and guarantee high precision.

Oxidative responsiveness to multiple stressors in the key Antarctic species, Adamussium colbecki: Interactions between temperature, acidification and cadmium exposure.

PubMed

Benedetti, Maura; Lanzoni, Ilaria; Nardi, Alessandro; d'Errico, Giuseppe; Di Carlo, Marta; Fattorini, Daniele; Nigro, Marco; Regoli, Francesco

2016-10-01

High-latitude marine ecosystems are ranked to be among the most sensitive regions to climate change since highly stenothermal and specially adapted organisms might be seriously affected by global warming and ocean acidification. The present investigation was aimed to provide new insights on the sensitivity to such environmental stressors in the key Antarctic species, Adamussium colbecki, focussing also on their synergistic effects with cadmium exposure, naturally abundant in this area for upwelling phenomena. Scallops were exposed for 2 weeks to various combinations of Cd (0 and 40 μgL-1), pH (8.05 and 7.60) and temperature (-1 and +1 °C). Beside Cd bioaccumulation, a wide panel of early warning biomarkers were analysed in digestive glands and gills including levels of metallothioneins, individual antioxidants and total oxyradical scavenging capacity, onset of oxidative cell damage like lipid peroxidation, lysosomal stability, DNA integrity and peroxisomal proliferation. Results indicated reciprocal interactions between multiple stressors and their elaboration by a quantitative hazard model based on the relevance and magnitude of effects, highlighted a different sensitivity of analysed tissues. Due to cellular adaptations to high basal Cd content, digestive gland appeared more tolerant toward other prooxidant stressors, but sensitive to variations of the metal. On the other hand, gills were more affected by various combinations of stressors occurring at higher temperature. Copyright © 2016 Elsevier Ltd. All rights reserved.

Sensitivity and specificity enhanced enzyme-linked immunosorbent assay by rational hapten modification and heterogeneous antibody/coating antigen combinations for the detection of melamine in milk, milk powder and feed samples.

PubMed

Cao, Biyun; Yang, Hong; Song, Juan; Chang, Huafang; Li, Shuqun; Deng, Anping

2013-11-15

The adulteration of food products with melamine has led to an urgent requirement for sensitive, specific, rapid and reliable quantitative/screening methods. To enhance the sensitivity and specificity of the enzyme-linked immunosorbent assay (ELISA) for the detection of melamine in milk, milk powder and feed samples, rational hapten modification and heterogeneous antibody/coating antigen combinations were adopted. Three melamine derivatives with different length of carboxylic spacer at the end were synthesized and linked to carrier proteins for the production of immunogens and coating antigens. Monoclonal antibody against melamine was produced by hybridoma technology. Under optimal experimental conditions, the standard curves of the ELISAs for melamine were constructed in range of 0.1-100 ng mL(-1). The sensitivity was 10-300 times enhanced compared to those in the published literatures. The cross-reactivity values of the ELISAs also demonstrated the assays exhibited high specificity. Five samples were spiked with melamine at different concentrations and detected by the ELISA. The recovery rates of 72.8-123.0% and intra-assay coefficients of variation of 0.8-18.9% (n=3) were obtained. The ELISA for milk sample was confirmed by high-performance liquid chromatography with a high correlation coefficient of 0.9902 (n=6). The proposed ELISA was proven to be a feasible quantitative/screening method for melamine analysis. Copyright © 2013 Elsevier B.V. All rights reserved.

Incremental value of copeptin to highly sensitive cardiac Troponin I for rapid rule-out of myocardial infarction.

PubMed

Wildi, Karin; Zellweger, Christa; Twerenbold, Raphael; Jaeger, Cedric; Reichlin, Tobias; Haaf, Philip; Faoro, Jonathan; Giménez, Maria Rubini; Fischer, Andreas; Nelles, Berit; Druey, Sophie; Krivoshei, Lian; Hillinger, Petra; Puelacher, Christian; Herrmann, Thomas; Campodarve, Isabel; Rentsch, Katharina; Steuer, Stephan; Osswald, Stefan; Mueller, Christian

2015-01-01

The incremental value of copeptin, a novel marker of endogenous stress, for rapid rule-out of non-ST-elevation myocardial infarction (NSTEMI) is unclear when sensitive or even high-sensitivity cardiac troponin cTn (hs-cTn) assays are used. In an international multicenter study we evaluated 1929 consecutive patients with symptoms suggestive of acute myocardial infarction (AMI). Measurements of copeptin, three sensitive and three hs-cTn assays were performed at presentation in a blinded fashion. The final diagnosis was adjudicated by two independent cardiologists using all clinical information including coronary angiography and levels of hs-cTnT. The incremental value in the diagnosis of NSTEMI was quantified using four outcome measures: area under the receiver-operating characteristic curve (AUC), integrated discrimination improvement (IDI), sensitivity and negative predictive value (NPV). Early presenters (< 4h since chest pain onset) were a pre-defined subgroup. NSTEMI was the adjudicated final diagnosis in 358 (18.6%) patients. As compared to the use of cTn alone, copeptin significantly increased AUC for two (33%) and IDI (between 0.010 and 0.041 (all p < 0.01)), sensitivity and NPV for all six cTn assays (100%); NPV to 96-99% when the 99 th percentile of the respective cTnI assay was combined with a copeptin level of 9 pmol/l (all p < 0.01). The incremental value in early presenters was similar to that of the overall cohort. When used for rapid rule-out of NSTEM in combination with sensitive or hs-cTnI assays, copeptin provides a numerically small, but statistically and likely also clinically significant incremental value. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

The Danish test battery for auditory processing disorder evaluated with patient and control data.

PubMed

Raben Pedersen, Ellen

2018-06-10

This study evaluates the Danish test battery for auditory processing disorder (APD). The battery consists of four behavioural tests, two speech and two non-speech stimuli tests. The evaluation includes determination of: (1) new cut-off values (pass-fail criteria), (2) the sensitivity and the specificity of the entire test battery and (3) the failure rate of different test combinations. For each test in the battery, cut-off values were determined using the weighted Youden index. Applying the newly derived cut-off values, the distribution of failing specific test combinations was determined. A group of 112 children diagnosed with APD (57 boys, 55 girls, aged 6-16 years) and a control group containing 158 children without auditory problems (75 boys, 83 girls, aged 6-16 years). Cut-off values for different weights of the sensitivity and the specificity have been determined. Using the criterion that at least two tests have to be failed for APD to be suspected, the sensitivity and the specificity of the entire test battery were 95.3% and 91.6%, respectively. Some test combinations were found to have higher failure rates than others. Due to the high sensitivity and specificity the test battery has good predictive value in APD assessment.

Kidney paired exchange and desensitization: Strategies to transplant the difficult to match kidney patients with living donors.

PubMed

Pham, Thomas A; Lee, Jacqueline I; Melcher, Marc L

2017-01-01

With organs in short supply, only a limited number of kidney transplants can be performed a year. Live donor donation accounts for 1/3rd of all kidney transplants performed in the United States. Unfortunately, not every donor recipient pair is feasible because of Human leukocyte antigen (HLA) sensitization and ABO incompatibility. To overcome these barriers to transplant, strategies such as kidney paired donation (KPD) and desensitization have been developed. KPD is the exchange of donors between at least two incompatible donor-recipient pairs such that they are now compatible. Desensitization is the removal of circulating donor specific antibodies to prevent graft rejection. Regardless of the treatment strategy, highly sensitized patients whose calculated panel reactive antibody (cPRA) is ≥95% remain difficult to transplant with match rates as low as 15% in KPD pools. Desensitization has proved to be difficult in those with high antibody titers. A novel approach is the combination of both KPD and desensitization to facilitate compatible and successful transplantation. A highly sensitized patient can be paired with a better immunological match in the KPD pool and subsequently desensitized to a lesser degree. This article reviews the current progress in KPD and desensitization and their use as a combined therapy. Copyright © 2017 Elsevier Inc. All rights reserved.

Transparent, Flexible, Conformal Capacitive Pressure Sensors with Nanoparticles.

PubMed

Kim, Hyeohn; Kim, Gwangmook; Kim, Taehoon; Lee, Sangwoo; Kang, Donyoung; Hwang, Min-Soo; Chae, Youngcheol; Kang, Shinill; Lee, Hyungsuk; Park, Hong-Gyu; Shim, Wooyoung

2018-02-01

The fundamental challenge in designing transparent pressure sensors is the ideal combination of high optical transparency and high pressure sensitivity. Satisfying these competing demands is commonly achieved by a compromise between the transparency and usage of a patterned dielectric surface, which increases pressure sensitivity, but decreases transparency. Herein, a design strategy for fabricating high-transparency and high-sensitivity capacitive pressure sensors is proposed, which relies on the multiple states of nanoparticle dispersity resulting in enhanced surface roughness and light transmittance. We utilize two nanoparticle dispersion states on a surface: (i) homogeneous dispersion, where each nanoparticle (≈500 nm) with a size comparable to the visible light wavelength has low light scattering; and (ii) heterogeneous dispersion, where aggregated nanoparticles form a micrometer-sized feature, increasing pressure sensitivity. This approach is experimentally verified using a nanoparticle-dispersed polymer composite, which has high pressure sensitivity (1.0 kPa -1 ), and demonstrates excellent transparency (>95%). We demonstrate that the integration of nanoparticle-dispersed capacitor elements into an array readily yields a real-time pressure monitoring application and a fully functional touch device capable of acting as a pressure sensor-based input device, thereby opening up new avenues to establish processing techniques that are effective on the nanoscale yet applicable to macroscopic processing. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Differential Acclimation of Enzymatic Antioxidant Metabolism and Photosystem II Photochemistry in Tall Fescue under Drought and Heat and the Combined Stresses

PubMed Central

Bi, Aoyue; Fan, Jibiao; Hu, Zhengrong; Wang, Guangyang; Amombo, Erick; Fu, Jinmin; Hu, Tao

2016-01-01

Quality inferiority in cool-season turfgrass due to drought, heat, and a combination of both stresses is predicted to be more prevalent in the future. Understanding the various response to heat and drought stress will assist in the selection and breeding of tolerant grass varieties. The objective of this study was to investigate the behavior of antioxidant metabolism and photosystem II (PSII) photochemistry in two tall fescue genotypes (PI 234881 and PI 578718) with various thermotolerance capacities. Wide variations were found between heat-tolerant PI 578718 and heat-sensitive PI 234881 for leaf relative water content, malondialdehyde and electrolyte leakage under drought, high-temperature or a combination of both stresses. The sensitivity of PI 234881 exposed to combined stresses was associated with lower superoxide dismutase activity and higher H2O2 accumulation than that in PI 578718. Various antioxidant enzymes displayed positive correlation with chlorophyll content, but negative with membrane injury index at most of the stages in both tall fescue genotypes. The JIP-test analysis in PI 578718 indicated a significant improvement in ABS/RC, TR0/RC, RE0/RC, RE0/ABS values as compared to the control regime, which indicated that PI 578718 had a high potential to protect the PSII system under drought and high temperature stress. And the PS II photochemistry in PI 234881 was damaged significantly compared with PI578718. Moreover, quantitative RT-PCR revealed that heat and drought stresses deduced the gene expression of psbB and psbC, but induced the expression of psbA. These findings to some extent confirmed that the various adaptations of physiological traits may contribute to breeding in cold-season turfgrass in response to drought, high-temperature, and a combination of both stresses. PMID:27148288

Antihypertensive and anti-inflammatory actions of combined azilsartan and chlorthalidone in Dahl salt-sensitive rats on a high-fat, high-salt diet.

PubMed

Jin, Chunhua; O'Boyle, Sean; Kleven, Daniel T; Pollock, Jennifer S; Pollock, David M; White, John J

2014-08-01

Metabolic syndrome (MetS) and chronic kidney disease are global health issues. Metabolic syndrome induces hypertension and commonly results in renal damage. The optimal therapy for hypertension in MetS is unknown. Thiazide diuretics are first-line therapy; however, these drugs may have untoward effects. In the present study we investigated the effects of azilsartan (AZL), chlorthalidone (CLTD) and their combination on blood pressure and renal injury in a rodent model with features of MetS. Dahl salt-sensitive rats were fed high-fat (36% fat), high-salt (4% NaCl) diet. Groups were then treated with vehicle, AZL (3 mg/kg per day), CLTD (5 mg/kg per day) or AZL + CLTD. Mean arterial pressure was recorded continuously by telemetry. After 26 days, rats were killed humanely and their kidneys were harvested for histology. Both AZL and CLTD attenuated the rise in blood pressure compared with vehicle and the combination further reduced blood pressure compared with CLTD alone. All treatments reduced proteinuria and albuminuria. Nephrinuria was prevented only in groups treated with AZL. Nephrinuria was 57% lower and proteinuria was 47% lower with combination therapy compared with AZL alone. All treatments reduced the number of inflammatory cells in the kidney. In conclusion, in our model, AZL and CLTD lower blood pressure and exhibit renal protective effects. Treatment with AZL offers additional protection, as evidenced by lower nephrinuria and plasma monocyte chemoattractant protein-1 levels. Combination therapy afforded the greatest protective effects and may be the best choice for hypertensive therapy in MetS. © 2014 Wiley Publishing Asia Pty Ltd.

Identification of resistance of Plasmodium falciparum to artesunate-mefloquine combination in an area along the Thai-Myanmar border: integration of clinico-parasitological response, systemic drug exposure, and in vitro parasite sensitivity

PubMed Central

2013-01-01

Background A markedly high failure rate of three-day artesunate-mefloquine was observed in the area along the Thai-Myanmar border. Methods Identification of Plasmodium falciparum isolates with intrinsic resistance to each component of the artesunate-mefloquine combination was analysed with integrated information on clinico-parasitological response, together with systemic drug exposure (area under blood/plasma concentration-time curves (AUC)) of dihydroartemisinin and mefloquine, and in vitro sensitivity of P. falciparum in a total of 17 out of 29 P. falciparum isolates from patients with acute uncomplicated falciparum malaria. Analysis of the contribution of in vitro parasite sensitivity and systemic drug exposure and relationship with pfmdr1 copy number in the group with sensitive response was performed in 21 of 69 cases. Results Identification of resistance and/or reduced intrinsic parasitocidal activity of artesunate and/or mefloquine without pharmacokinetic or other host-related factors were confirmed in six cases: one with reduced sensitivity to artesunate alone, two with resistance to mefloquine alone, and three with reduced sensitivity to artesunate combined with resistance to mefloquine. Resistance and/or reduced intrinsic parasitocidal activity of mefloquine/artesunate, together with contribution of pharmacokinetic factor of mefloquine and/or artesunate were identified in seven cases: two with resistance to mefloquine alone, and five with resistance to mefloquine combined with reduced sensitivity to artesunate. Pharmacokinetic factor alone contributed to recrudescence in three cases, all of which had inadequate whole blood mefloquine levels (AUC0-7days). Other host-related factors contributed to recrudescence in one case. Amplification of pfmdr1 (increasing of pfmdr1 copy number) is a related molecular marker of artesunate-mefloquine resistance and seems to be a suitable molecular marker to predict occurrence of recrudescence. Conclusions Despite the evidence of a low level of a decline in sensitivity of P. falciparum isolates to artemisinins in areas along the Thai-Myanmar border, artemisinin-based combination therapy (ACT) would be expected to remain the key anti-malarial drug for treatment of multidrug resistance P. falciparum. Continued monitoring and active surveillance of clinical efficacy of ACT, including identification of true artemisinin resistant parasites, is required for appropriate implementation of malaria control policy in this area. PMID:23898808

Parental acceptance, postpartum depression, and maternal sensitivity: mediating and moderating processes.

PubMed

Crockenberg, Susan C; Leerkes, Esther M

2003-03-01

Mothers (n = 92), fathers (n = 84), and their infants (60% male) participated in a longitudinal study of postpartum depression and maternal sensitivity. Mothers completed questionnaire measures of remembered parental acceptance, depressive symptoms, and infant distress to novelty and limits. Mothers and partners reported on marital aggression and avoidance. Maternal sensitivity was observed in the laboratory at 6 months. Characteristics of mothers, partners, and infants combined to predict postpartum depression and maternal sensitivity. Remembered parental rejection predicted postpartum depressive symptoms with prenatal depression controlled; self-esteem mediated this effect. Paternal acceptance buffered against postpartum depression when infants were highly reactive and when partners were aggressive. Paternal acceptance reduced the impact of postpartum depression on maternal sensitivity; having an aggressive marital partner exacerbated the effect.

An enzymatic biosensor based on three-dimensional ZnO nanotetrapods spatial net modified AlGaAs/GaAs high electron mobility transistors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Song, Yu; Bioengineering Program, Lehigh University, Bethlehem, Pennsylvania 18015; Zhang, Xiaohui

2014-11-24

We designed and constructed three dimensional (3D) zinc oxide Nanotetrapods (T-ZnOs) modified AlGaAs/GaAs high electron mobility transistors (HEMTs) for enzymatic uric acid (UA) detection. The chemical vapor deposition synthesized T-ZnOs was distributed on the gate areas of HEMTs in order to immobilize uricase and improve the sensitivity of the HEMTs. Combining with the high efficiency of enzyme immobilization by T-ZnOs and high sensitivity from HEMT, the as-constructed uricase/T-ZnOs/HEMTs biosensor showed fast response towards UA at ∼1 s, wide linear range from 0.2 nM to 0.2 mM and the low detect limit at 0.2 nM. The results point out an avenue to design electronic devicemore » as miniaturized lab-on-chip device for high sensitive and specific in biomedical and clinical diagnosis applications.« less

Separation of density and viscosity influence on liquid-loaded surface acoustic wave devices

NASA Astrophysics Data System (ADS)

Herrmann, F.; Hahn, D.; Büttgenbach, S.

1999-05-01

Love-mode sensors are reported for separate measurement of liquid density and viscosity. They combine the general merits of Love-mode devices, e.g., ease of sensitivity adjustment and robustness, with a highly effective procedure of separate determination of liquid density and viscosity. A model is proposed to describe the frequency response of the devices to liquid loading. Moreover, design rules are given for further optimization and sensitivity enhancement.

Miniaturized Ion Mobility Spectrometer

NASA Technical Reports Server (NTRS)

Stimac, Robert M. (Inventor); Kaye, William J (Inventor)

2017-01-01

By utilizing the combination of a unique electronic ion injection control circuit in conjunction with a particularly designed drift cell construction, the instantly disclosed ion mobility spectrometer (IMS) achieves increased levels of sensitivity, while achieving significant reductions in size and weight. The instant IMS is of a much simpler and easy to manufacture design, rugged and hermetically sealed, capable of operation at high temperatures to at least 250 degrees Centigrade, and is uniquely sensitive, particularly to explosive chemicals.

Miniaturized Ion Mobility Spectrometer

NASA Technical Reports Server (NTRS)

Kaye, William J. (Inventor); Stimac, Robert M. (Inventor)

2015-01-01

By utilizing the combination of a unique electronic ion injection control circuit in conjunction with a particularly designed drift cell construction, the instantly disclosed ion mobility spectrometer achieves increased levels of sensitivity, while achieving significant reductions in size and weight. The instant IMS is of a much simpler and easy to manufacture design, rugged and hermetically sealed, capable of operation at high temperatures to at least 250.degree. C., and is uniquely sensitive, particularly to explosive chemicals.

Proteomic biomarkers apolipoprotein A1, truncated transthyretin and connective tissue activating protein III enhance the sensitivity of CA125 for detecting early stage epithelial ovarian cancer.

PubMed

Clarke, Charlotte H; Yip, Christine; Badgwell, Donna; Fung, Eric T; Coombes, Kevin R; Zhang, Zhen; Lu, Karen H; Bast, Robert C

2011-09-01

The low prevalence of ovarian cancer demands both high sensitivity (>75%) and specificity (99.6%) to achieve a positive predictive value of 10% for successful early detection. Utilizing a two stage strategy where serum marker(s) prompt the performance of transvaginal sonography (TVS) in a limited number (2%) of women could reduce the requisite specificity for serum markers to 98%. We have attempted to improve sensitivity by combining CA125 with proteomic markers. Sera from 41 patients with early stage (I/II) and 51 with late stage (III/IV) epithelial ovarian cancer, 40 with benign disease and 99 healthy individuals, were analyzed to measure 7 proteins [Apolipoprotein A1 (Apo-A1), truncated transthyretin (TT), transferrin, hepcidin, ß-2-microglobulin (ß2M), Connective Tissue Activating Protein III (CTAPIII), and Inter-alpha-trypsin inhibitor heavy chain 4 (ITIH4)]. Statistical models were fit by logistic regression, followed by optimization of factors retained in the models determined by optimizing the Akaike Information Criterion. A validation set included 136 stage I ovarian cancers, 140 benign pelvic masses and 174 healthy controls. In a training set analysis, the 3 most effective biomarkers (Apo-A1, TT and CTAPIII) exhibited 54% sensitivity at 98% specificity, CA125 alone produced 68% sensitivity and the combination increased sensitivity to 88%. In a validation set, the marker panel plus CA125 produced a sensitivity of 84% at 98% specificity (P=0.015, McNemar's test). Combining a panel of proteomic markers with CA125 could provide a first step in a sequential two-stage strategy with TVS for early detection of ovarian cancer. Copyright © 2011. Published by Elsevier Inc.

Proteomic Biomarkers Apolipoprotein A1, Truncated Transthyretin and Connective Tissue Activating Protein III Enhance the Sensitivity of CA125 for Detecting Early Stage Epithelial Ovarian Cancer

PubMed Central

Clarke, Charlotte H.; Yip, Christine; Badgwell, Donna; Fung, Eric T.; Coombes, Kevin R.; Zhang, Zhen; Lu, Karen H.; Bast, Robert C.

2011-01-01

Objective The low prevalence of ovarian cancer demands both high sensitivity (>75%) and specificity (99.6%) to achieve a positive predictive value of 10% for successful early detection. Utilizing a two stage strategy where serum marker(s) prompt the performance of transvaginal sonography (TVS) in a limited number (2%) of women could reduce the requisite specificity for serum markers to 98%. We have attempted to improve sensitivity by combining CA125 with proteomic markers. Methods Sera from 41 patients with early stage (I/II) and 51 with late stage (III/IV) epithelial ovarian cancer, 40 with benign disease and 99 healthy individuals, were analyzed to measure 7 proteins [Apolipoprotein A1 (Apo-A1), truncated transthyretin (TT), transferrin, hepcidin, ß-2-microglobulin (ß2M), Connective Tissue Activating Protein III (CTAPIII), and Inter-alpha-trypsin inhibitor heavy chain 4 (ITIH4)]. Statistical models were fit by logistic regression, followed by optimization of factors retained in the models determined by optimizing the Akaike Information Criterion. A validation set included 136 stage I ovarian cancers, 140 benign pelvic masses and 174 healthy controls. Results In a training set analysis, the 3 most effective biomarkers (Apo-A1, TT and CTAPIII) exhibited 54% sensitivity at 98% specificity, CA125 alone produced 68% sensitivity and the combination increased sensitivity to 88%. In a validation set, the marker panel plus CA125 produced a sensitivity of 84% at 98% specificity (P= 0.015, McNemar's test). Conclusion Combining a panel of proteomic markers with CA125 could provide a first step in a sequential two-stage strategy with TVS for early detection of ovarian cancer. PMID:21708402

High sensitive vectorial B-probe for low frequency plasma waves.

PubMed

Ullrich, Stefan; Grulke, Olaf; Klinger, Thomas; Rahbarnia, Kian

2013-11-01

A miniaturized multidimensional magnetic probe is developed for application in a low-temperature plasma environment. A very high sensitivity for low-frequency magnetic field fluctuations with constant phase run, a very good signal-to-noise ratio combined with an efficient electrostatic pickup rejection, renders the probe superior compared with any commercial solution. A two-step calibration allows for absolute measurement of amplitude and direction of magnetic field fluctuations. The excellent probe performance is demonstrated by measurements of the parallel current pattern of coherent electrostatic drift wave modes in the VINETA (versatile instrument for studies on nonlinearity, electromagnetism, turbulence, and applications) experiment.

Revisiting Short-Wave-Infrared (SWIR) Bands for Atmospheric Correction in Coastal Waters

NASA Technical Reports Server (NTRS)

Pahlevan, Nima; Roger, Jean-Claude; Ahmad, Ziauddin

2017-01-01

The shortwave infrared (SWIR) bands on the existing Earth Observing missions like MODIS have been designed to meet land and atmospheric science requirements. The future geostationary and polar-orbiting ocean color missions, however, require highly sensitive SWIR bands (greater than 1550nm) to allow for a precise removal of aerosol contributions. This will allow for reasonable retrievals of the remote sensing reflectance (R(sub rs)) using standard NASA atmospheric corrections over turbid coastal waters. Design, fabrication, and maintaining high-performance SWIR bands at very low signal levels bear significant costs on dedicated ocean color missions. This study aims at providing a full analysis of the utility of alternative SWIR bands within the 1600nm atmospheric window if the bands within the 2200nm window were to be excluded due to engineering/cost constraints. Following a series of sensitivity analyses for various spectral band configurations as a function of water vapor amount, we chose spectral bands centered at 1565 and 1675nm as suitable alternative bands within the 1600nm window for a future geostationary imager. The sensitivity of this band combination to different aerosol conditions, calibration uncertainties, and extreme water turbidity were studied and compared with that of all band combinations available on existing polar-orbiting missions. The combination of the alternative channels was shown to be as sensitive to test aerosol models as existing near-infrared (NIR) band combinations (e.g., 748 and 869nm) over clear open ocean waters. It was further demonstrated that while in extremely turbid waters the 1565/1675 band pair yields R(sub rs) retrievals as good as those derived from all other existing SWIR band pairs (greater than 1550nm), their total calibration uncertainties must be less than 1% to meet current science requirements for ocean color retrievals (i.e., delta R(sub rs) (443) less than 5%). We further show that the aerosol removal using the NIR and SWIR bands (available on the existing polar-orbiting missions) can be very sensitive to calibration uncertainties. This requires the need for monitoring the calibration of these bands to ensure consistent multi-mission ocean color products in coastal/inland waters.

Revisiting short-wave-infrared (SWIR) bands for atmospheric correction in coastal waters.

PubMed

Pahlevan, Nima; Roger, Jean-Claude; Ahmad, Ziauddin

2017-03-20

The shortwave infrared (SWIR) bands on the existing Earth Observing missions like MODIS have been designed to meet land and atmospheric science requirements. The future geostationary and polar-orbiting ocean color missions, however, require highly sensitive SWIR bands (> 1550nm) to allow for a precise removal of aerosol contributions. This will allow for reasonable retrievals of the remote sensing reflectance (R_rs) using standard NASA atmospheric corrections over turbid coastal waters. Design, fabrication, and maintaining high-performance SWIR bands at very low signal levels bear significant costs on dedicated ocean color missions. This study aims at providing a full analysis of the utility of alternative SWIR bands within the 1600nm atmospheric window if the bands within the 2200nm window were to be excluded due to engineering/cost constraints. Following a series of sensitivity analyses for various spectral band configurations as a function of water vapor amount, we chose spectral bands centered at 1565 and 1675nm as suitable alternative bands within the 1600nm window for a future geostationary imager. The sensitivity of this band combination to different aerosol conditions, calibration uncertainties, and extreme water turbidity were studied and compared with that of all band combinations available on existing polar-orbiting missions. The combination of the alternative channels was shown to be as sensitive to test aerosol models as existing near-infrared (NIR) band combinations (e.g., 748 and 869nm) over clear open ocean waters. It was further demonstrated that while in extremely turbid waters the 1565/1675 band pair yields R_rs retrievals as good as those derived from all other existing SWIR band pairs (> 1550nm), their total calibration uncertainties must be < 1% to meet current science requirements for ocean color retrievals (i.e., Δ R_rs (443) < 5%). We further show that the aerosol removal using the NIR and SWIR bands (available on the existing polar-orbiting missions) can be very sensitive to calibration uncertainties. This requires the need for monitoring the calibration of these bands to ensure consistent multi-mission ocean color products in coastal/inland waters.

In silico designing of power conversion efficient organic lead dyes for solar cells using todays innovative approaches to assure renewable energy for future

NASA Astrophysics Data System (ADS)

Kar, Supratik; Roy, Juganta K.; Leszczynski, Jerzy

2017-06-01

Advances in solar cell technology require designing of new organic dye sensitizers for dye-sensitized solar cells with high power conversion efficiency to circumvent the disadvantages of silicon-based solar cells. In silico studies including quantitative structure-property relationship analysis combined with quantum chemical analysis were employed to understand the primary electron transfer mechanism and photo-physical properties of 273 arylamine organic dyes from 11 diverse chemical families explicit to iodine electrolyte. The direct quantitative structure-property relationship models enable identification of the essential electronic and structural attributes necessary for quantifying the molecular prerequisites of 11 classes of arylamine organic dyes, responsible for high power conversion efficiency of dye-sensitized solar cells. Tetrahydroquinoline, N,N'-dialkylaniline and indoline have been least explored classes under arylamine organic dyes for dye-sensitized solar cells. Therefore, the identified properties from the corresponding quantitative structure-property relationship models of the mentioned classes were employed in designing of "lead dyes". Followed by, a series of electrochemical and photo-physical parameters were computed for designed dyes to check the required variables for electron flow of dye-sensitized solar cells. The combined computational techniques yielded seven promising lead dyes each for all three chemical classes considered. Significant (130, 183, and 46%) increment in predicted %power conversion efficiency was observed comparing with the existing dye with highest experimental %power conversion efficiency value for tetrahydroquinoline, N,N'-dialkylaniline and indoline, respectively maintaining required electrochemical parameters.

Experimental determination of release fields in cut railroad car wheels

DOT National Transportation Integrated Search

1999-02-01

A new approach to the measurement of residual stresses in railroad wheels is investigated using a saw cut method of releasing stresses in the structure. High-sensitivity moire interferometry combined with Michelson interferometry provides full-field ...

Combination Chemotherapy in Treating Young Patients With Newly Diagnosed High-Risk B Acute Lymphoblastic Leukemia and Ph-Like TKI Sensitive Mutations

ClinicalTrials.gov

2018-06-25

B Acute Lymphoblastic Leukemia; Central Nervous System Leukemia; Ph-Like Acute Lymphoblastic Leukemia; Testicular Leukemia; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Childhood Acute Lymphoblastic Leukemia

Electronic pictures from charged-coupled devices

NASA Technical Reports Server (NTRS)

Mccann, D. H.; Turly, A. P.; White, M.

1979-01-01

Imaging system uses charge-coupled devices (CCD's) to generate TV-like pictures with high resolution, sensitivity, and signal-to-noise ratio. It combines detectors for five spectral bands as well as processing and control circuitry all on single silicon chip.

High sensitivity plasmonic sensor using hybrid structure of graphene stripe combined with gold gap-ring

NASA Astrophysics Data System (ADS)

Du, Zhiyuan; Hu, Bin; Cyril, Planchon; Liu, Juan; Wang, Yongtian

2017-10-01

Local surface plasmonic resonance (LSPR) produced by metallic nano-structures is often sensitive to the refractive index of the surrounding media and can be applied for sensing. However, it often suffers from large line width caused by large plasmonic radiative damping, especially in the infrared (IR) frequencies, which reduces the sensitivity. Here we propose a hybrid structure consists of a graphene stripe and a gold gap-ring at short-IR frequencies (1-3 µm). Due to the low loss and high plasmonic confinement of graphene, LSPR line width of 6 nm is obtained. In addition, due to the strong coupling of the gold gap-ring with graphene stripe, the intensity of graphene LSPR is enhanced by 100 times. Simulation results show that the sensitivity of the sensor is ~1000 nm/RIU (refractive index unit) and the figure of merit (FoM) can reach up to 383.

[Primary cervical cancer screening].

PubMed

Vargas-Hernández, Víctor Manuel; Vargas-Aguilar, Víctor Manuel; Tovar-Rodríguez, José María

2015-01-01

Cervico-uterine cancer screening with cytology decrease incidence by more than 50%. The cause of this cancer is the human papilloma virus high risk, and requires a sensitive test to provide sufficient sensitivity and specificity for early detection and greater interval period when the results are negative. The test of the human papilloma virus high risk, is effective and safe because of its excellent sensitivity, negative predictive value and optimal reproducibility, especially when combined with liquid-based cytology or biomarkers with viral load, with higher sensitivity and specificity, by reducing false positives for the detection of cervical intraepithelial neoplasia grade 2 or greater injury, with excellent clinical benefits to cervical cancer screening and related infection of human papilloma virus diseases, is currently the best test for early detection infection of human papillomavirus and the risk of carcinogenesis. Copyright © 2015 Academia Mexicana de Cirugía A.C. Published by Masson Doyma México S.A. All rights reserved.

Conditions of excitation and sensitivity of diffractively-coupled surface lattice resonances over plasmonic nanoparticle arrays in ATR geometry

NASA Astrophysics Data System (ADS)

Danilov, Artem; Tselikov, Gleb; Wu, Fan; Kravets, Vasyl G.; Ozerov, Igor; Bedu, Frederic; Grigorenko, Alexander N.; Kabashin, Andrei V.

2018-02-01

We investigate conditions of excitation and properties of Plasmonic Surface Lattice Resonances (PSLR) over glass substrate-supported Au nanoparticle dimers ( 100-200 nm) arranged in a periodic metamaterial lattice, in Attenuated Total Reflection (ATR) optical excitation geometry, and assess their sensitivities to variations of refractive index (RI) of the adjacent sample dielectric medium. We show that spectral sensitivity of PSLR to RI variations is determined by the lattice periodicity ( 320 nm per RIU change in our case), while ultranarrow resonance lineshapes (down to a few nm full-widthat-half-maximum) provide very high figure-of-merit values evidencing the possibility of ultrasensitive biosensing measurements. Combining advantages of nanoscale architectures, including a strong concentration of electric field, the possibility of manipulation at the nanoscale etc, and high phase and spectral sensitivities, PSLRs promise a drastic advancement of current state-of-the-art plasmonic biosensing technology.

Blood free-circulating DNA testing by highly sensitive methylation assay to diagnose colorectal neoplasias.

PubMed

Suehiro, Yutaka; Hashimoto, Shinichi; Higaki, Shingo; Fujii, Ikuei; Suzuki, Chieko; Hoshida, Tomomi; Matsumoto, Toshihiko; Yamaoka, Yuko; Takami, Taro; Sakaida, Isao; Yamasaki, Takahiro

2018-03-30

Although methylated TWIST1 is a biomarker of colorectal neoplasia, its detection from serum samples is very difficult by conventional bisulfite-based methylation assays. Therefore, we have developed a new methylation assay that enables counting of even one copy of a methylated gene in a small DNA sample amount without DNA bisulfite treatment. We performed this study to evaluate the sensitivity and specificity of serum DNA testing by the new methylation assay in combination with and without the fecal immunochemical test for hemoglobin for the detection of colorectal neoplasia. This study comprised 113 patients with colorectal neoplasia and 25 control individuals. For the new methylation assay, DNA was treated in two stages with methylation-sensitive restriction enzymes, followed by measurement of copy numbers of hTERT and methylated TWIST1 by multiplex droplet digital PCR. The fecal immunochemical test had a sensitivity of 8.0% for non-advanced adenoma, 24.3% for advanced adenoma, and 44.4% for colorectal cancer, and a specificity of 88.0%. The new assay had a sensitivity of 36.0% for non-advanced adenoma, 30.0% for advanced adenoma, and 44.4% for colorectal cancer, and a specificity of 92.0%. Combination of the both tests increased the sensitivity to 40.0%, 45.7%, and 72.2% for the detection of non-advanced adenoma, advanced adenoma, and colorectal cancer, respectively, and resulted in a specificity of 84.0%. Combination of both tests may provide an alternative screening strategy for colorectal neoplasia including potentially precancerous lesions and colorectal cancer.

Highly Sensitive Liquid Core Temperature Sensor Based on Multimode Interference Effects

PubMed Central

Fuentes-Fuentes, Miguel A.; May-Arrioja, Daniel A.; Guzman-Sepulveda, José R.; Torres-Cisneros, Miguel; Sánchez-Mondragón, José J.

2015-01-01

A novel fiber optic temperature sensor based on a liquid-core multimode interference device is demonstrated. The advantage of such structure is that the thermo-optic coefficient (TOC) of the liquid is at least one order of magnitude larger than that of silica and this, combined with the fact that the TOC of silica and the liquid have opposite signs, provides a liquid-core multimode fiber (MMF) highly sensitive to temperature. Since the refractive index of the liquid can be easily modified, this allows us to control the modal properties of the liquid-core MMF at will and the sensor sensitivity can be easily tuned by selecting the refractive index of the liquid in the core of the device. The maximum sensitivity measured in our experiments is 20 nm/°C in the low-temperature regime up to 60 °C. To the best of our knowledge, to date, this is the largest sensitivity reported for fiber-based MMI temperature sensors. PMID:26512664

Antiviral Combination Approach as a Perspective to Combat Enterovirus Infections.

PubMed

Galabov, Angel S; Nikolova, Ivanka; Vassileva-Pencheva, Ralitsa; Stoyanova, Adelina

2015-01-01

Human enteroviruses distributed worldwide are causative agents of a broad spectrum of diseases with extremely high morbidity, including a series of severe illnesses of the central nervous system, heart, endocrine pancreas, skeleton muscles, etc., as well as the common cold contributing to the development of chronic respiratory diseases, including the chronic obstructive pulmonary disease. The above mentioned diseases along with the significantly high morbidity and mortality in children, as well as in the high-risk populations (immunodeficiencies, neonates) definitely formulate the chemotherapy as the main tool for the control of enterovirus infections. At present, clinically effective antivirals for use in the treatment of enteroviral infection do not exist, in spite of the large amount of work carried out in this field. The main reason for this is the development of drug resistance. We studied the process of development of resistance to the strongest inhibitors of enteroviruses, WIN compounds (VP1 protein hydrophobic pocket blockers), especially in the models in vivo, Coxsackievirus B (CV-B) infections in mice. We introduced the tracing of a panel of phenotypic markers (MIC50 value, plaque shape and size, stability at 50℃, pathogenicity in mice) for characterization of the drug-mutants (resistant and dependent) as a very important stage in the study of enterovirus inhibitors. Moreover, as a result of VP1 RNA sequence analysis performed on the model of disoxaril mutants of CVB1, we determined the molecular basis of the drug-resistance. The monotherapy courses were the only approach used till now. For the first time in the research for anti-enterovirus antivirals our team introduced the testing of combination effect of the selective inhibitors of enterovirus replication with different mode of action. This study resulted in the selection of a number of very effective in vitro double combinations with synergistic effect and a broad spectrum of sensitive enteroviruses. The most prospective attainment in our examinations in this field was the development of a novel scheme for the combined application of anti-enteroviral substances in coxsackievirus B1 neuroinfection in newborn mice. It consisted of a consecutive, alternating and non simultaneous administration of the substances in the combination. The triple combination - disoxaril- guanidine. HCl-oxoglaucine (DGO) showed a high effectiveness expressed in the marked reduction of the mortality rate in infected mice as compared both to the placebo group, and to the partner compounds used alone every day, and to the same combination applied simultaneously every day. The studies of the drug sensitivity of viral brain isolates from mice treated with DGO combination showed not only preserved, but even increased sensitivity to the drugs included in the combination. Obviously, the consecutive alternating administration of anti-enteroviral substances hinders the occurrence of drug-resistance in the course of the experimental enteroviral infections in mice.

Bragg projection ptychography on niobium phase domain

DOE PAGES

Burdet, Nicolas; Shi, Xiaowen; Huang, Xiaojing; ...

2016-08-10

Here, we demonstrate that the highly sensitive phase-contrast properties of Bragg coherent diffraction measurements combined with the translational diversity of ptychography can provide a Bragg “dark field” imaging method capable of revealing the finger print of domain structure in metallic thin films. Experimental diffraction data was taken from a epitaxially grown niobium metallic thin film on sapphire; and analyzed with the help of a careful combination of implemented refinement mechanisms.

Sensitivity of GBM cells to cAMP agonist-mediated apoptosis correlates with CD44 expression and agonist resistance with MAPK signaling.

PubMed

Daniel, Paul M; Filiz, Gulay; Mantamadiotis, Theo

2016-12-01

In some cell types, activation of the second messenger cAMP leads to increased expression of proapoptotic Bim and subsequent cell death. We demonstrate that suppression of the cAMP pathway is a common event across many cancers and that pharmacological activation of cAMP in glioblastoma (GBM) cells leads to enhanced BIM expression and apoptosis in specific GBM cell types. We identified the MAPK signaling axis as the determinant of cAMP agonist sensitivity in GBM cells, with high MAPK activity corresponding to cAMP resistance and low activity corresponding to sensitization to cAMP-induced apoptosis. Sensitive cells were efficiently killed by cAMP agonists alone, while targeting both the cAMP and MAPK pathways in resistant GBM cells resulted in efficient apoptosis. We also show that CD44 is differentially expressed in cAMP agonist-sensitive and -resistant cells. We thus propose that CD44 may be a useful biomarker for distinguishing tumors that may be sensitive to cAMP agonists alone or cAMP agonists in combination with other pathway inhibitors. This suggests that using existing chemotherapeutic compounds in combination with existing FDA-approved cAMP agonists may fast track trials toward improved therapies for difficult-to-treat cancers, such as GBM.

Probabilistic material strength degradation model for Inconel 718 components subjected to high temperature, high-cycle and low-cycle mechanical fatigue, creep and thermal fatigue effects

NASA Technical Reports Server (NTRS)

Bast, Callie C.; Boyce, Lola

1995-01-01

This report presents the results of both the fifth and sixth year effort of a research program conducted for NASA-LeRC by The University of Texas at San Antonio (UTSA). The research included on-going development of methodology for a probabilistic material strength degradation model. The probabilistic model, in the form of a postulated randomized multifactor equation, provides for quantification of uncertainty in the lifetime material strength of aerospace propulsion system components subjected to a number of diverse random effects. This model is embodied in the computer program entitled PROMISS, which can include up to eighteen different effects. Presently, the model includes five effects that typically reduce lifetime strength: high temperature, high-cycle mechanical fatigue, low-cycle mechanical fatigue, creep and thermal fatigue. Statistical analysis was conducted on experimental Inconel 718 data obtained from the open literature. This analysis provided regression parameters for use as the model's empirical material constants, thus calibrating the model specifically for Inconel 718. Model calibration was carried out for five variables, namely, high temperature, high-cycle and low-cycle mechanical fatigue, creep and thermal fatigue. Methodology to estimate standard deviations of these material constants for input into the probabilistic material strength model was developed. Using an updated version of PROMISS, entitled PROMISS93, a sensitivity study for the combined effects of high-cycle mechanical fatigue, creep and thermal fatigue was performed. Then using the current version of PROMISS, entitled PROMISS94, a second sensitivity study including the effect of low-cycle mechanical fatigue, as well as, the three previous effects was performed. Results, in the form of cumulative distribution functions, illustrated the sensitivity of lifetime strength to any current value of an effect. In addition, verification studies comparing a combination of high-cycle mechanical fatigue and high temperature effects by model to the combination by experiment were conducted. Thus, for Inconel 718, the basic model assumption of independence between effects was evaluated. Results from this limited verification study strongly supported this assumption.

Highly efficient monolithic dye-sensitized solar cells.

PubMed

Kwon, Jeong; Park, Nam-Gyu; Lee, Jun Young; Ko, Min Jae; Park, Jong Hyeok

2013-03-01

Monolithic dye-sensitized solar cells (M-DSSCs) provide an effective way to reduce the fabrication cost of general DSSCs since they do not require transparent conducting oxide substrates for the counter electrode. However, conventional monolithic devices have low efficiency because of the impediments resulting from counter electrode materials and spacer layers. Here, we demonstrate highly efficient M-DSSCs featuring a highly conductive polymer combined with macroporous polymer spacer layers. With M-DSSCs based on a PEDOT/polymer spacer layer, a power conversion efficiency of 7.73% was achieved, which is, to the best of our knowledge, the highest efficiency for M-DSSCs to date. Further, PEDOT/polymer spacer layers were applied to flexible DSSCs and their cell performance was investigated.

Multimodal instrument for high-sensitivity autofluorescence and spectral optical coherence tomography of the human eye fundus

PubMed Central

Komar, Katarzyna; Stremplewski, Patrycjusz; Motoczyńska, Marta; Szkulmowski, Maciej; Wojtkowski, Maciej

2013-01-01

In this paper we present a multimodal device for imaging fundus of human eye in vivo which combines functionality of autofluorescence by confocal SLO with Fourier domain OCT. Native fluorescence of human fundus was excited by modulated laser beam (λ = 473 nm, 20 MHz) and lock-in detection was applied resulting in improving sensitivity. The setup allows for acquisition of high resolution OCT and high contrast AF images using fluorescence excitation power of 50-65 μW without averaging consecutive images. Successful functioning of constructed device have been demonstrated for 8 healthy volunteers of different age ranging from 24 to 83 years old. PMID:24298426

Environmental management zoning for coal mining in mainland China based on ecological and resources conditions.

PubMed

Geng, Haiqing; Chen, Fan; Wang, Zhiyuan; Liu, Jie; Xu, Weihua

2017-05-01

The purpose of this research is to establish an environmental management zoning for coal mining industry which is served as a basis for making environmental management policies. Based on the specific impacts of coal mining and regional characteristics of environment and resources, the ecological impact, water resources impact, and arable land impact are chose as the zoning indexes to construct the index system. The ecological sensitivity is graded into three levels of low, medium, and high according to analytical hierarchy processes and gray fixed weight clustering analysis, and the water resources sensitivity is divided into five levels of lower, low, medium, high, and higher according to the weighted sum of sub-indexes, while only the arable land sensitive zone was extracted on the basis of the ratio of arable land to the county or city. By combining the ecological sensitivity zoning and the water resources sensitive zoning and then overlapping the arable-sensitive areas, the mainland China is classified into six types of environmental management zones for coal mining except to the forbidden exploitation areas.

Noise sensitivity: Symptoms, health status, illness behavior and co-occurring environmental sensitivities

DOE Office of Scientific and Technical Information (OSTI.GOV)

Baliatsas, Christos, E-mail: c.baliatsas@nivel.nl

Epidemiological evidence on the symptomatic profile, health status and illness behavior of people with subjective sensitivity to noise is still scarce. Also, it is unknown to what extent noise sensitivity co-occurs with other environmental sensitivities such as multi-chemical sensitivity and sensitivity to electromagnetic fields (EMF). A cross-sectional study performed in the Netherlands, combining self-administered questionnaires and electronic medical records of non-specific symptoms (NSS) registered by general practitioners (GP) allowed us to explore this further. The study sample consisted of 5806 participants, drawn from 21 general practices. Among participants, 722 (12.5%) responded “absolutely agree” to the statement “I am sensitive tomore » noise”, comprising the high noise-sensitive (HNS) group. Compared to the rest of the sample, people in the HNS group reported significantly higher scores on number and duration of self-reported NSS, increased psychological distress, decreased sleep quality and general health, more negative symptom perceptions and higher prevalence of healthcare contacts, GP-registered NSS and prescriptions for antidepressants and benzodiazepines. These results remained robust after adjustment for demographic, residential and lifestyle characteristics, objectively measured nocturnal noise exposure from road-traffic and GP-registered morbidity. Co-occurrence rates with other environmental sensitivities varied between 9% and 50%. Individuals with self-declared sensitivity to noise are characterized by high prevalence of multiple NSS, poorer health status and increased illness behavior independently of noise exposure levels. Findings support the notion that different types of environmental sensitivities partly overlap. - Highlights: • People with self-reported noise sensitivity experience multiple non-specific symptoms. • They also report comparatively poorer health and increased illness behavior. • Co-occurrence with other environmental sensitivities is moderate to high. • Road-traffic noise and GP-registered morbidity did not account for these results.« less

Highly antireflective AlGaN/GaN ultraviolet photodetectors using ZnO nanorod arrays on inverted pyramidal surfaces

NASA Astrophysics Data System (ADS)

So, Hongyun; Lim, Jongwoo; Suria, Ateeq J.; Senesky, Debbie G.

2017-07-01

Highly antireflective heterostructured aluminum gallium nitride (AlGaN)/GaN ultraviolet (UV) photodetectors were demonstrated using a combination of inverted pyramidal surfaces and zinc oxide nanorod arrays (i.e., antireflective surface modification) to enhance the optical sensitivity. The microfabricated hierarchical surfaces significantly reduced the average surface reflectance to less than 0.3% in the UV region and less than 1% in the visible light region, allowing near-perfect absorption of incident light regardless of the angle of incidence (5-80°). As a result, the photodetectors fabricated on highly antireflective AlGaN/GaN surfaces showed higher sensitivity and responsivity over a broad range of incidence angles compared to photodetectors on planar AlGaN/GaN surfaces, supporting the use of a hierarchically modified sensing surface for omnidirectional UV monitoring with higher sensitivity.

CRDS with a VECSEL for broad-band high sensitivity spectroscopy in the 2.3 μm window.

PubMed

Čermák, P; Chomet, B; Ferrieres, L; Vasilchenko, S; Mondelain, D; Kassi, S; Campargue, A; Denet, S; Lecocq, V; Myara, M; Cerutti, L; Garnache, A

2016-08-01

The integration of an industry ready packaged Sb-based Vertical-External-Cavity Surface-Emitting-Laser (VECSEL) into a Cavity Ring Down Spectrometer (CRDS) is presented. The instrument operates in the important 2.3 μm atmospheric transparency window and provides a high sensitivity (minimum detectable absorption of 9 × 10(-11) cm(-1)) over a wide spectra range. The VECSEL performances combine a large continuous tunability over 120 cm(-1) around 4300 cm(-1) together with a powerful (∼5 mW) TEM00 diffraction limited beam and linewidth at MHz level (for 1 ms of integration time). The achieved performances are illustrated by high sensitivity recordings of the very weak absorption spectrum of water vapor in the region. The developed method gives potential access to the 2-2.7 μm range for CRDS.

Higher sensitivity secondary ion mass spectrometry of biological molecules for high resolution, chemically specific imaging.

PubMed

McDonnell, Liam A; Heeren, Ron M A; de Lange, Robert P J; Fletcher, Ian W

2006-09-01

To expand the role of high spatial resolution secondary ion mass spectrometry (SIMS) in biological studies, numerous developments have been reported in recent years for enhancing the molecular ion yield of high mass molecules. These include both surface modification, including matrix-enhanced SIMS and metal-assisted SIMS, and polyatomic primary ions. Using rat brain tissue sections and a bismuth primary ion gun able to produce atomic and polyatomic primary ions, we report here how the sensitivity enhancements provided by these developments are additive. Combined surface modification and polyatomic primary ions provided approximately 15.8 times more signal than using atomic primary ions on the raw sample, whereas surface modification and polyatomic primary ions yield approximately 3.8 and approximately 8.4 times more signal. This higher sensitivity is used to generate chemically specific images of higher mass biomolecules using a single molecular ion peak.

CRDS with a VECSEL for broad-band high sensitivity spectroscopy in the 2.3 μm window

DOE Office of Scientific and Technical Information (OSTI.GOV)

Čermák, P., E-mail: cermak@fmph.uniba.sk; CNRS, LIPhy, UMR 5588, F-38000 Grenoble; Department of Experimental Physics, Faculty of Mathematics, Physics and Informatics, Comenius University, Mlynská Dolina, 842 48 Bratislava

2016-08-15

The integration of an industry ready packaged Sb-based Vertical-External-Cavity Surface-Emitting-Laser (VECSEL) into a Cavity Ring Down Spectrometer (CRDS) is presented. The instrument operates in the important 2.3 μm atmospheric transparency window and provides a high sensitivity (minimum detectable absorption of 9 × 10{sup −11} cm{sup −1}) over a wide spectra range. The VECSEL performances combine a large continuous tunability over 120 cm{sup −1} around 4300 cm{sup −1} together with a powerful (∼5 mW) TEM{sub 00} diffraction limited beam and linewidth at MHz level (for 1 ms of integration time). The achieved performances are illustrated by high sensitivity recordings of themore » very weak absorption spectrum of water vapor in the region. The developed method gives potential access to the 2-2.7 μm range for CRDS.« less

[Comparison of efficacy between the serum cortisol and 24 hour urine free cortisol in combined dexamethasone suppression test in the diagnosis of Cushing syndrome].

PubMed

Lu, L; Chen, J H; Zhu, H J; Song, A L; Li, M; Chen, S; Pan, H; Gong, F Y; Wang, R Z; Xing, B; Yao, Y; Feng, M; Lu, Z L

2016-07-19

To compare the sensitivity and specificity between the 24 hour urine free cortisol (24 h UFC) and serum cortisol in dexamethasone suppression test (DST) in the diagnosis of Cushing syndrome (CS). Combined low dose DST (LDDST) and high dose DST (HDDST) were carried out in 67 cases of CS with surgically confirmed cases in recent 3 years(from January 2011 to November 2015). The serum cortisol and 24 h UFC were collected simultaneously for each subject and the sensitivity and specificity of serum cortisol and 24 h UFC were compared. There were Cushing disease (CD) group (n=53), ectopic adrenocorticotropic hormone (ACTH) syndrome group (n=7) and ACTH-independent Cushing syndrome group (n=7) according to the etiology of hypercorticordism.There were no significant differences among 3 groups in gender and age.The sensitivity of serum cortisol of different cut off points(50, 110, 140 nmol/L and 50% of control)after LDDST was 97.01%, 86.57%, 83.58% and 70.15% respectively.Meanwhile, the sensitivity of cutoff point of 24 h UFC <32 nmol in combined LDDST was 92.54% in the diagnosis of Cushing syndrome.There was no significant differences in two groups between serum cortisol <110 nmol/L and 24 h UFC <32 nmol.However, the sensitivity of serum cortisol <50 nmol/L was significantly higher than 24 h UFC<32 nmol (P<0.05). Furthermore, in combined HDDST, if the suppression rate was ≥50%, the sensitivity of serum cortisol and 24 h UFC in differentiating the etiology of Cushing disease was 60.38% and 90.57%, and the specificity was 91.43% and 96.00% respectively.There were significant differences between serum cortisol and 24 h UFC in both of sensitivity and specificity (both P<0.05). In addition, if the suppression rate of 24 h UFC in HDDST was adjusted to 60.85% according to receiver operating characteristic (ROC) curve, it could have the best levels of sensitivity (92.6%) with the specificity of 85.7%. If the suppression rate of serum cortisol was adjusted to 61.53% in HDDST according to ROC curve, it could have the best sensitivity (64.8%) with the specificity of 78.6% accordingly. In combined LDDST, the serum cortisol <50 nmol/L had a higher sensitivity than the 24 h UFC<32 nmol when they were used as the criteria in determining the diagnosis of CS.In HDDST, the sensitivity and specificity of suppression rate of 24 h UFC ≥50% were better than serum cortisol to differentiate the etiology of CS.

Deposition and characterization of B4C/CeO2 multilayers at 6.x nm extreme ultraviolet wavelengths

NASA Astrophysics Data System (ADS)

Sertsu, M. G.; Giglia, A.; Brose, S.; Park, D.; Wang, Z. S.; Mayer, J.; Juschkin, L.; Nicolosi, P.

2016-03-01

New multilayers of boron carbide/cerium dioxide (B4C/CeO2) combination on silicon (Si) substrate are manufactured to represent reflective-optics candidates for future lithography at 6.x nm wavelength. This is one of only a few attempts to make multilayers of this kind. Combination of several innovative experiments enables detailed study of optical properties, structural properties, and interface profiles of the multilayers in order to open up a room for further optimization of the manufacturing process. The interface profile is visualized by high-angle annular dark-field imaging which provides highly sensitive contrast to atomic number. Synchrotron based at-wavelength extreme ultraviolet (EUV) reflectance measurements near the boron (B) absorption edge allow derivation of optical parameters with high sensitivity to local atom interactions. X-ray reflectivity measurements at Cu-Kalpha (8 keV ) determine the period of multilayers with high in-depth resolution. By combining these measurements and choosing robust nonlinear curve fitting algorithms, accuracy of the results has been significantly improved. It also enables a comprehensive characterization of multilayers. Interface diffusion is determined to be a major cause for the low reflectivity performance. Optical constants of B4C and CeO2 layers are derived in EUV wavelengths. Besides, optical properties and asymmetric thicknesses of inter-diffusion layers (interlayers) in EUV wavelengths near the boron edge are determined. Finally, ideal reflectivity of the B4C/CeO2 combination is calculated by using optical constants derived from the proposed measurements in order to evaluate the potentiality of the design.

Management of neonatal sepsis at Muhimbili National Hospital in Dar es Salaam: diagnostic accuracy of C-reactive protein and newborn scale of sepsis and antimicrobial resistance pattern of etiological bacteria.

PubMed

Mkony, Martha Franklin; Mizinduko, Mucho Michael; Massawe, Augustine; Matee, Mecky

2014-12-05

We determined the accuracy of Rubarth's newborn scale of sepsis and C- reactive protein in diagnosing neonatal sepsis and assessed antimicrobial susceptibility pattern of etiological bacteria. This cross sectional study was conducted at Muhimbili National Hospital in Dar es Salaam, Tanzania between July 2012 and March 2013. Neonates suspected to have sepsis underwent physical examination using Rubarth's newborn scale of sepsis (RNSOS). Blood was taken for culture and antimicrobial sensitivity testing, full blood picture and C - reactive protein (CRP) performed 12 hours apart. The efficacy of RNSOS and serial CRP was assessed by calculating sensitivity, specificity, negative and positive predictive values, receiver operating characteristics (ROC) analysis as well as likelihood ratios (LHR) with blood culture result used as a gold standard. Out of 208 blood samples, 19.2% had a positive blood culture. Single CRP had sensitivity and specificity of 87.5% and 70.9% respectively, while RNSOS had sensitivity of 65% and specificity of 79.7%. Serial CRP had sensitivity of 69.0% and specificity of 92.9%. Combination of CRP and RNSOS increased sensitivity to 95.6% and specificity of 56.4%. Combination of two CRP and RNSOS decreased sensitivity to 89.1% but increased specificity to 74%. ROC for CRP was 0.86; and for RNSOS was 0.81. For CRP the LHR for positive test was 3 while for negative test was 0.18, while for RNSOS the corresponding values were 3.24 and for negative test was 0.43. Isolated bacteria were Klebsiella spp 14 (35%), Escherichia coli 12 (22.5%), Coagulase negative staphlococci 9 (30%), Staphylococcus aureus 4 (10%), and Pseudomonas spp 1 (2.5%). The overall resistance to the WHO recommended first line antibiotics was 100%, 92% and 42% for cloxacillin, ampicillin and gentamicin, respectively. For the second line drugs resistance was 45%, 40%, and 7% for ceftriaxone, vancomycin and amikacin respectively. Single CRP in combination with RNSOS can be used for rapid identification of neonates with sepsis due to high sensitivity (95.6%) but cannot exclude those without sepsis due to low specificity (56.4%). Serial CRP done 12hrs apart can be used to exclude non-cases. This study demonstrated very high levels of resistance to the first-line antibiotics.

Screening for attention-deficit/hyperactivity disorder in borderline personality disorder.

PubMed

Weibel, Sébastien; Nicastro, Rosetta; Prada, Paco; Cole, Pierre; Rüfenacht, Eva; Pham, Eléonore; Dayer, Alexandre; Perroud, Nader

2018-01-15

A valid screening instrument is needed to detect attention-deficit/hyperactivity disorder (ADHD) in treatment-seeking borderline personality disorder (BPD) patients. We aimed to test the performance of the widely-used Adult ADHD Self-Report Scale v1.1 screener (ASRS-v1.1). 317 BPD subjects were systematically assessed for comorbid ADHD and completed the ASRS-v1.1. 79 BPD patients also completed the Wender Utah Rating Scale (WURS-25). The prevalence of adult ADHD was of 32.4%. The overall positive predictive value of the ASRS-v1.1 was of 38.5%, the negative predictive value 77.0%, the sensitivity 72.8%, and the specificity 43.9%. Combining WURS-25 and ASRS-v1.1 improved sensitivity to 81.8% and specificity to 59.6%. Cross-sectional study on treatment-seeking patients. We found a high prevalence of ADHD using structured interviews. The ASRS-v1.1 was not a sensitive screener for identifying possible ADHD cases in a BPD population, with a high number of false positives. When combined with the WURS-25, it offered improved screening. Copyright © 2017 Elsevier B.V. All rights reserved.

A rapid molecular diagnosis of cutaneous leishmaniasis by colorimetric malachite green-loop-mediated isothermal amplification (LAMP) combined with an FTA card as a direct sampling tool.

PubMed

Nzelu, Chukwunonso O; Cáceres, Abraham G; Guerrero-Quincho, Silvia; Tineo-Villafuerte, Edwin; Rodriquez-Delfin, Luis; Mimori, Tatsuyuki; Uezato, Hiroshi; Katakura, Ken; Gomez, Eduardo A; Guevara, Angel G; Hashiguchi, Yoshihisa; Kato, Hirotomo

2016-01-01

Leishmaniasis remains one of the world's most neglected diseases, and early detection of the infectious agent, especially in developing countries, will require a simple and rapid test. In this study, we established a quick, one-step, single-tube, highly sensitive loop-mediated isothermal amplification (LAMP) assay for rapid detection of Leishmania DNA from tissue materials spotted on an FTA card. An FTA-LAMP with pre-added malachite green was performed at 64°C for 60min using a heating block and/or water bath and DNA amplification was detected immediately after incubation. The LAMP assay had high detection sensitivity down to a level of 0.01 parasites per μl. The field- and clinic-applicability of the colorimetric FTA-LAMP assay was demonstrated with 122 clinical samples collected from patients suspected of having cutaneous leishmaniasis in Peru, from which 71 positives were detected. The LAMP assay in combination with an FTA card described here is rapid and sensitive, as well as simple to perform, and has great potential usefulness for diagnosis and surveillance of leishmaniasis in endemic areas. Copyright © 2015 Elsevier B.V. All rights reserved.

Graphene Oxide Based Nanocarrier Combined with a pH-Sensitive Tracer: A Vehicle for Concurrent pH Sensing and pH-Responsive Oligonucleotide Delivery.

PubMed

Hsieh, Chia-Jung; Chen, Yu-Cheng; Hsieh, Pei-Ying; Liu, Shi-Rong; Wu, Shu-Pao; Hsieh, You-Zung; Hsu, Hsin-Yun

2015-06-03

We chemically tuned the oxidation status of graphene oxide (GO) and constructed a GO-based nanoplatform combined with a pH-sensitive fluorescence tracer that is designed for both pH sensing and pH-responsive drug delivery. A series of GOs oxidized to distinct degrees were examined to optimize the adsorption of the model drug, poly dT30. We determined that highly oxidized GO was a superior drug-carrier candidate in vitro when compared to GOs oxidized to lesser degrees. In the cell experiment, the synthesized pH-sensitive rhodamine dye was first applied to monitor cellular pH; under acidic conditions, protonated rhodamine fluoresces at 588 nm (λex=561 nm). When the dT30-GO nanocarrier was introduced into cells, a rhodamine-triggered competition reaction occurred, and this led to the release of the oligonucleotides and the quenching of rhodamine fluorescence by GO. Our results indicate high drug loading (FAM-dT30/GO=25/50 μg/mL) and rapid cellular uptake (<0.5 h) of the nanocarrier which can potentially be used for targeted RNAi delivery to the acidic milieu of tumors.

Assessment of the presence of mucosal human papillomaviruses in malignant melanomas using combined fluorescent in situ hybridization and chemiluminescent immunohistochemistry.

PubMed

Ambretti, S; Venturoli, S; Mirasoli, M; La Placa, M; Bonvicini, F; Cricca, M; Zerbini, M; Roda, A; Musiani, M

2007-01-01

The vast majority of studies aimed at detecting human papillomavirus (HPV) DNA in skin cancer have used sensitive polymerase chain reaction (PCR) methods but the PCR technique, despite its high sensitivity, is not suitable to ascertain whether (i) the presence of HPV can be related only to few cells harbouring the virus, (ii) the presence of HPV is due to a tumour surface contamination and (iii) the presence of HPV is localized in cancer cells, rather than in normal keratinocytes present in the tumour biopsy. In a recent work we have found mucosal high-risk (HR) HPV genotypes in primary melanoma by PCR. To localize mucosal HR-HPV nucleic acids and tumoural melanocytic marker in the same sections of primary melanoma samples in order to understand the relationship between HPVs and melanoma cells. We have developed a very sensitive method that combines an enzyme-amplified fluorescent in situ hybridization (ISH) for the detection of HPV nucleic acids (types 16 and 18) with a chemiluminescent immunohistochemistry (IHC) method for the detection of the tumoural melanocytic marker HMB-45 sequentially in the same section. Digital images of fluorescent ISH and chemiluminescent IHC were separately recorded, assigned different colours and merged using specific software for image analysis. The combined fluorescent ISH and chemiluminescent IHC demonstrated a sharp colocalization (in the range 60-80%) of HPV nucleic acids and melanoma marker inside the same sections of melanoma biopsies, with a strong specificity and sensitivity. The strong colocalization of mucosal HR-HPV nucleic acids and HMB-45 melanocytic marker emphasized that viral nucleic acids were specifically present in melanoma cells and supported a possible active role of HPV in malignant melanoma.

Sensitivity of the weather research and forecasting model to parameterization schemes for regional climate of Nile River Basin

NASA Astrophysics Data System (ADS)

Tariku, Tebikachew Betru; Gan, Thian Yew

2018-06-01

Regional climate models (RCMs) have been used to simulate rainfall at relatively high spatial and temporal resolutions useful for sustainable water resources planning, design and management. In this study, the sensitivity of the RCM, weather research and forecasting (WRF), in modeling the regional climate of the Nile River Basin (NRB) was investigated using 31 combinations of different physical parameterization schemes which include cumulus (Cu), microphysics (MP), planetary boundary layer (PBL), land-surface model (LSM) and radiation (Ra) schemes. Using the European Centre for Medium-Range Weather Forecast (ECMWF) ERA-Interim reanalysis data as initial and lateral boundary conditions, WRF was configured to model the climate of NRB at a resolution of 36 km with 30 vertical levels. The 1999-2001 simulations using WRF were compared with satellite data combined with ground observation and the NCEP reanalysis data for 2 m surface air temperature (T2), rainfall, short- and longwave downward radiation at the surface (SWRAD, LWRAD). Overall, WRF simulated more accurate T2 and LWRAD (with correlation coefficients >0.8 and low root-mean-square error) than SWRAD and rainfall for the NRB. Further, the simulation of rainfall is more sensitive to PBL, Cu and MP schemes than other schemes of WRF. For example, WRF simulated less biased rainfall with Kain-Fritsch combined with MYJ than with YSU as the PBL scheme. The simulation of T2 is more sensitive to LSM and Ra than to Cu, PBL and MP schemes selected, SWRAD is more sensitive to MP and Ra than to Cu, LSM and PBL schemes, and LWRAD is more sensitive to LSM, Ra and PBL than Cu, and MP schemes. In summary, the following combination of schemes simulated the most representative regional climate of NRB: WSM3 microphysics, KF cumulus, MYJ PBL, RRTM longwave radiation and Dudhia shortwave radiation schemes, and Noah LSM. The above configuration of WRF coupled to the Noah LSM has also been shown to simulate representative regional climate of NRB over 1980-2001 which include a combination of wet and dry years of the NRB.

Sensitivity of the weather research and forecasting model to parameterization schemes for regional climate of Nile River Basin

NASA Astrophysics Data System (ADS)

Tariku, Tebikachew Betru; Gan, Thian Yew

2017-08-01

Regional climate models (RCMs) have been used to simulate rainfall at relatively high spatial and temporal resolutions useful for sustainable water resources planning, design and management. In this study, the sensitivity of the RCM, weather research and forecasting (WRF), in modeling the regional climate of the Nile River Basin (NRB) was investigated using 31 combinations of different physical parameterization schemes which include cumulus (Cu), microphysics (MP), planetary boundary layer (PBL), land-surface model (LSM) and radiation (Ra) schemes. Using the European Centre for Medium-Range Weather Forecast (ECMWF) ERA-Interim reanalysis data as initial and lateral boundary conditions, WRF was configured to model the climate of NRB at a resolution of 36 km with 30 vertical levels. The 1999-2001 simulations using WRF were compared with satellite data combined with ground observation and the NCEP reanalysis data for 2 m surface air temperature (T2), rainfall, short- and longwave downward radiation at the surface (SWRAD, LWRAD). Overall, WRF simulated more accurate T2 and LWRAD (with correlation coefficients >0.8 and low root-mean-square error) than SWRAD and rainfall for the NRB. Further, the simulation of rainfall is more sensitive to PBL, Cu and MP schemes than other schemes of WRF. For example, WRF simulated less biased rainfall with Kain-Fritsch combined with MYJ than with YSU as the PBL scheme. The simulation of T2 is more sensitive to LSM and Ra than to Cu, PBL and MP schemes selected, SWRAD is more sensitive to MP and Ra than to Cu, LSM and PBL schemes, and LWRAD is more sensitive to LSM, Ra and PBL than Cu, and MP schemes. In summary, the following combination of schemes simulated the most representative regional climate of NRB: WSM3 microphysics, KF cumulus, MYJ PBL, RRTM longwave radiation and Dudhia shortwave radiation schemes, and Noah LSM. The above configuration of WRF coupled to the Noah LSM has also been shown to simulate representative regional climate of NRB over 1980-2001 which include a combination of wet and dry years of the NRB.

Studentized continuous wavelet transform (t-CWT) in the analysis of individual ERPs: real and simulated EEG data

PubMed Central

Real, Ruben G. L.; Kotchoubey, Boris; Kübler, Andrea

2014-01-01

This study aimed at evaluating the performance of the Studentized Continuous Wavelet Transform (t-CWT) as a method for the extraction and assessment of event-related brain potentials (ERP) in data from a single subject. Sensitivity, specificity, positive (PPV) and negative predictive values (NPV) of the t-CWT were assessed and compared to a variety of competing procedures using simulated EEG data at six low signal-to-noise ratios. Results show that the t-CWT combines high sensitivity and specificity with favorable PPV and NPV. Applying the t-CWT to authentic EEG data obtained from 14 healthy participants confirmed its high sensitivity. The t-CWT may thus be well suited for the assessment of weak ERPs in single-subject settings. PMID:25309308

Studentized continuous wavelet transform (t-CWT) in the analysis of individual ERPs: real and simulated EEG data.

PubMed

Real, Ruben G L; Kotchoubey, Boris; Kübler, Andrea

2014-01-01

This study aimed at evaluating the performance of the Studentized Continuous Wavelet Transform (t-CWT) as a method for the extraction and assessment of event-related brain potentials (ERP) in data from a single subject. Sensitivity, specificity, positive (PPV) and negative predictive values (NPV) of the t-CWT were assessed and compared to a variety of competing procedures using simulated EEG data at six low signal-to-noise ratios. Results show that the t-CWT combines high sensitivity and specificity with favorable PPV and NPV. Applying the t-CWT to authentic EEG data obtained from 14 healthy participants confirmed its high sensitivity. The t-CWT may thus be well suited for the assessment of weak ERPs in single-subject settings.

Rational molecular engineering of cyclopentadithiophene-bridged D-A-π-A sensitizers combining high photovoltaic efficiency with rapid dye adsorption

PubMed Central

Chai, Qipeng; Li, Wenqin; Liu, Jingchuan; Geng, Zhiyuan; Tian, He; Zhu, Wei-hong

2015-01-01

Dye-sensitized solar cell (DSSC) is considered as a feasible route to the clean and renewable energy conversion technique. The commercial application requires further enhancements on photovoltaic efficiency and simplification on the device fabrication. For avoiding the unpreferable trade-off between photocurrent (JSC) and photovoltage (VOC), here we report the molecular engineering and comprehensive photovoltaic characterization of three cyclopentadithiophene-bridged D-A-π-A motif sensitizers with a change in donor group. We make a careful choice on the donor and conjugation bridge for synergistically increasing JSC and VOC. Comparing with the reference dye WS-2, the photovoltaic efficiency with the single component dye of WS-51 increases by 18%, among one of the rare examples in pure metal-free organic dyes exceeding 10% in combination with traditional iodine redox couples. Moreover, WS-51 exhibits several prominent merits on potentially scale-up industrial application: i) facile synthetic route to target molecule, ii) simple dipping procedure without requirement of co-sensitization, and iii) rapid dye adsorption capability. PMID:26066974

A new nanobiosensor for glucose with high sensitivity and selectivity in serum based on fluorescence resonance Energy transfer (FRET) between CdTe quantum dots and Au nanoparticles.

PubMed

Tang, Bo; Cao, Lihua; Xu, Kehua; Zhuo, Linhai; Ge, Jiechao; Li, Qingling; Yu, Lijuan

2008-01-01

A novel assembled nanobiosensor QDs-ConA-beta-CDs-AuNPs was designed for the direct determination of glucose in serum with high sensitivity and selectivity. The sensing approach is based on fluorescence resonance energy transfer (FRET) between CdTe quantum dots (QDs) as an energy donor and gold nanoparticles (AuNPs) as an energy acceptor. The specific combination of concanavalin A (ConA)-conjugated QDs and thiolated beta-cyclodextrins (beta-SH-CDs)-modified AuNPs assembles a hyperefficient FRET nanobiosensor. In the presence of glucose, the AuNPs-beta-CDs segment of the nanobiosensor is displaced by glucose which competes with beta-CDs on the binding sites of ConA, resulting in the fluorescence recovery of the quenched QDs. Experimental results show that the increase in fluorescence intensity is proportional to the concentration of glucose within the range of 0.10-50 muM under the optimized experimental conditions. In addition, the nanobiosensor has high sensitivity with a detection limit as low as 50 nM, and has excellent selectivity for glucose over other sugars and most biological species present in serum. The nanobiosensor was applied directly to determine glucose in normal adult human serum, and the recovery and precision of the method were satisfactory. The unique combination of high sensitivity and good selectivity of this biosensor indicates its potential for the clinical determination of glucose directly and simply in serum, and provides the possibility to detect low levels of glucose in single cells or bacterial cultures. Moreover, the designed nanobiosensor achieves direct detection in biological samples, suggesting the use of nanobiotechnology-based assembled sensors for direct analytical applications in vivo or in vitro.

Subclinical Atherosclerosis, Cardiac and Kidney Function, Heart Failure, and Dementia in the Very Elderly.

PubMed

Kuller, Lewis H; Lopez, Oscar L; Gottdiener, John S; Kitzman, Dalane W; Becker, James T; Chang, Yuefang; Newman, Anne B

2017-07-22

Heart failure (HF) and dementia are major causes of disability and death among older individuals. Risk factors and biomarkers of HF may be determinants of dementia in the elderly. We evaluated the relationship between biomarkers of cardiovascular disease and HF and risk of dementia and death. Three hypotheses were tested: (1) higher levels of high-sensitivity cardiac troponin T, N-terminal of prohormone brain natriuretic peptide, and cystatin C predict risk of death, cardiovascular disease, HF, and dementia; (2) higher levels of cardiovascular disease biomarkers are associated with increased risk of HF and then secondary increased risk of dementia; and (3) risk of dementia is lower among participants with a combination of lower coronary artery calcium, atherosclerosis, and lower high-sensitivity cardiac troponin T (myocardial injury). The Cardiovascular Health Study Cognition Study was a continuation of the Cardiovascular Health Study limited to the Pittsburgh, PA, center from 1998-1999 to 2014. In 1992-1994, 924 participants underwent magnetic resonance imaging of the brain. There were 199 deaths and 116 developed dementia before 1998-1999. Of the 609 participants eligible for the Pittsburgh Cardiovascular Health Study Cognition Study, 87.5% (n=532) were included in the study. There were 120 incident HF cases and 72% had dementia. In 80 of 87, dementia preceded HF. A combination of low coronary artery calcium score and low high-sensitivity cardiac troponin T was significantly associated with reduced risk of dementia and HF. Most participants with HF had dementia but with onset before HF. Lower high-sensitivity cardiac troponin T and coronary artery calcium was associated with low risk of dementia based on a small number of events. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00005133. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

High-field/high-pressure ESR

NASA Astrophysics Data System (ADS)

Sakurai, T.; Okubo, S.; Ohta, H.

2017-07-01

We present a historical review of high-pressure ESR systems with emphasis on our recent development of a high-pressure, high-field, multi-frequency ESR system. Until 2000, the X-band system was almost established using a resonator filled with dielectric materials or a combination of the anvil cell and dielectric resonators. Recent developments have shifted from that in the low-frequency region, such as X-band, to that in multi-frequency region. High-pressure, high-field, multi-frequency ESR systems are classified into two types. First are the systems that use a vector network analyzer or a quasi-optical bridge, which have high sensitivity but a limited frequency region; the second are like our system, which has a very broad frequency region covering the THz region, but lower sensitivity. We will demonstrate the usefulness of our high-pressure ESR system, in addition to its experimental limitations. We also discuss the recent progress of our system and future plans.

Low cost automated whole smear microscopy screening system for detection of acid fast bacilli.

PubMed

Law, Yan Nei; Jian, Hanbin; Lo, Norman W S; Ip, Margaret; Chan, Mia Mei Yuk; Kam, Kai Man; Wu, Xiaohua

2018-01-01

In countries with high tuberculosis (TB) burden, there is urgent need for rapid, large-scale screening to detect smear-positive patients. We developed a computer-aided whole smear screening system that focuses in real-time, captures images and provides diagnostic grading, for both bright-field and fluorescence microscopy for detection of acid-fast-bacilli (AFB) from respiratory specimens. To evaluate the performance of dual-mode screening system in AFB diagnostic algorithms on concentrated smears with auramine O (AO) staining, as well as direct smears with AO and Ziehl-Neelsen (ZN) staining, using mycobacterial culture results as gold standard. Adult patient sputum samples requesting for M. tuberculosis cultures were divided into three batches for staining: direct AO-stained, direct ZN-stained and concentrated smears AO-stained. All slides were graded by an experienced microscopist, in parallel with the automated whole smear screening system. Sensitivity and specificity of a TB diagnostic algorithm in using the screening system alone, and in combination with a microscopist, were evaluated. Of 488 direct AO-stained smears, 228 were culture positive. These yielded a sensitivity of 81.6% and specificity of 74.2%. Of 334 direct smears with ZN staining, 142 were culture positive, which gave a sensitivity of 70.4% and specificity of 76.6%. Of 505 concentrated smears with AO staining, 250 were culture positive, giving a sensitivity of 86.4% and specificity of 71.0%. To further improve performance, machine grading was confirmed by manual smear grading when the number of AFBs detected fell within an uncertainty range. These combined results gave significant improvement in specificity (AO-direct:85.4%; ZN-direct:85.4%; AO-concentrated:92.5%) and slight improvement in sensitivity while requiring only limited manual workload. Our system achieved high sensitivity without substantially compromising specificity when compared to culture results. Significant improvement in specificity was obtained when uncertain results were confirmed by manual smear grading. This approach had potential to substantially reduce workload of microscopists in high burden countries.

Reach-scale channel sensitivity to multiple human activities and natural events: Lower Santa Clara River, California, USA

NASA Astrophysics Data System (ADS)

Downs, Peter W.; Dusterhoff, Scott R.; Sears, William A.

2013-05-01

Understanding the cumulative impact of natural and human influences on the sensitivity of channel morphodynamics, a relative measure between the drivers for change and the magnitude of channel response, requires an approach that accommodates spatial and temporal variability in the suite of primary stressors. Multiple historical data sources were assembled to provide a reach-scale analysis of the lower Santa Clara River (LSCR) in Ventura County, California, USA. Sediment supply is naturally high due to tectonic activity, earthquake-generated landslides, wildfires, and high magnitude flow events during El Niño years. Somewhat typically for the region, the catchment has been subject to four reasonably distinct land use and resource management combinations since European-American settlement. When combined with analysis of channel morphological response (quantifiable since ca. 1930), reach-scale and temporal differences in channel sensitivity become apparent. Downstream reaches have incised on average 2.4 m and become narrower by almost 50% with changes focused in a period of highly sensitive response after about 1950 followed by forced insensitivity caused by structural flood embankments and a significant grade control structure. In contrast, the middle reaches have been responsive but are morphologically resilient, and the upstream reaches show a mildly sensitive aggradational trend. Superimposing the natural and human drivers for change reveals that large scale stressors (related to ranching and irrigation) have been replaced over time by a suite of stressors operating at multiple spatial scales. Lower reaches have been sensitive primarily to 'local' scale impacts (urban growth, flood control, and aggregate mining) whereas, upstream, catchment-scale influences still prevail (including flow regulation and climate-driven sediment supply factors). These factors illustrate the complexity inherent to cumulative impact assessment in fluvial systems, provide evidence for a distinct Anthropocene fluvial response, and underpin the enormity of the challenge faced in trying to sustainably manage and restore rivers.

A highly sensitive protocol for microscopy of alkyne lipids and fluorescently tagged or immunostained proteins.

PubMed

Gaebler, Anne; Penno, Anke; Kuerschner, Lars; Thiele, Christoph

2016-10-01

The demand to study the cellular localization of specific lipids has led to recent advances in lipid probes and microscopy. Alkyne lipids bear a small, noninterfering tag and can be detected upon click reaction with an azide-coupled reporter. Fluorescent alkyne lipid imaging crucially depends on appropriate azide reporters and labeling protocols that allow for an efficient click reaction and therefore a sensitive detection. We synthesized several azide reporters with different spacer components and tested their suitability for alkyne lipid imaging in fixed cells. The implementation of a copper-chelating picolyl moiety into fluorescent or biotin-based azide reagents strongly increased the sensitivity of the imaging routine. We demonstrate the applicability and evaluate the performance of this approach using different lipid classes and experimental setups. As azide picolyl reporters allow for reduced copper catalyst concentrations, they also enable coimaging of alkyne lipids with multiple fluorescent proteins including enhanced green fluorescent protein. Alternatively, and as we also show, microscopy of alkyne lipids can be combined with protein detection by immunocytochemistry. In summary, we present a robust, sensitive, and highly versatile protocol for the labeling of alkyne lipids with azide-coupled reporters for fluorescence microscopy that can be combined with different protein detection and imaging techniques. Copyright © 2016 by the American Society for Biochemistry and Molecular Biology, Inc.

A stereo-compound hybrid microscope for combined intracellular and optical recording of invertebrate neural network activity.

PubMed

Frost, William N; Wang, Jean; Brandon, Christopher J

2007-05-15

Optical recording studies of invertebrate neural networks with voltage-sensitive dyes seldom employ conventional intracellular electrodes. This may in part be due to the traditional reliance on compound microscopes for such work. While such microscopes have high light-gathering power, they do not provide depth of field, making working with sharp electrodes difficult. Here we describe a hybrid microscope design, with switchable compound and stereo objectives, that eases the use of conventional intracellular electrodes in optical recording experiments. We use it, in combination with a voltage-sensitive dye and photodiode array, to identify neurons participating in the swim motor program of the marine mollusk Tritonia. This microscope design should be applicable to optical recording studies in many preparations.

Chemically Designed Metallic/Insulating Hybrid Nanostructures with Silver Nanocrystals for Highly Sensitive Wearable Pressure Sensors.

PubMed

Kim, Haneun; Lee, Seung-Wook; Joh, Hyungmok; Seong, Mingi; Lee, Woo Seok; Kang, Min Su; Pyo, Jun Beom; Oh, Soong Ju

2018-01-10

With the increase in interest in wearable tactile pressure sensors for e-skin, researches to make nanostructures to achieve high sensitivity have been actively conducted. However, limitations such as complex fabrication processes using expensive equipment still exist. Herein, simple lithography-free techniques to develop pyramid-like metal/insulator hybrid nanostructures utilizing nanocrystals (NCs) are demonstrated. Ligand-exchanged and unexchanged silver NC thin films are used as metallic and insulating components, respectively. The interfaces of each NC layer are chemically engineered to create discontinuous insulating layers, i.e., spacers for improved sensitivity, and eventually to realize fully solution-processed pressure sensors. Device performance analysis with structural, chemical, and electronic characterization and conductive atomic force microscopy study reveals that hybrid nanostructure based pressure sensor shows an enhanced sensitivity of higher than 500 kPa -1 , reliability, and low power consumption with a wide range of pressure sensing. Nano-/micro-hierarchical structures are also designed by combining hybrid nanostructures with conventional microstructures, exhibiting further enhanced sensing range and achieving a record sensitivity of 2.72 × 10 4 kPa -1 . Finally, all-solution-processed pressure sensor arrays with high pixel density, capable of detecting delicate signals with high spatial selectivity much better than the human tactile threshold, are introduced.

Epidermis Microstructure Inspired Graphene Pressure Sensor with Random Distributed Spinosum for High Sensitivity and Large Linearity.

PubMed

Pang, Yu; Zhang, Kunning; Yang, Zhen; Jiang, Song; Ju, Zhenyi; Li, Yuxing; Wang, Xuefeng; Wang, Danyang; Jian, Muqiang; Zhang, Yingying; Liang, Renrong; Tian, He; Yang, Yi; Ren, Tian-Ling

2018-03-27

Recently, wearable pressure sensors have attracted tremendous attention because of their potential applications in monitoring physiological signals for human healthcare. Sensitivity and linearity are the two most essential parameters for pressure sensors. Although various designed micro/nanostructure morphologies have been introduced, the trade-off between sensitivity and linearity has not been well balanced. Human skin, which contains force receptors in a reticular layer, has a high sensitivity even for large external stimuli. Herein, inspired by the skin epidermis with high-performance force sensing, we have proposed a special surface morphology with spinosum microstructure of random distribution via the combination of an abrasive paper template and reduced graphene oxide. The sensitivity of the graphene pressure sensor with random distribution spinosum (RDS) microstructure is as high as 25.1 kPa -1 in a wide linearity range of 0-2.6 kPa. Our pressure sensor exhibits superior comprehensive properties compared with previous surface-modified pressure sensors. According to simulation and mechanism analyses, the spinosum microstructure and random distribution contribute to the high sensitivity and large linearity range, respectively. In addition, the pressure sensor shows promising potential in detecting human physiological signals, such as heartbeat, respiration, phonation, and human motions of a pushup, arm bending, and walking. The wearable pressure sensor array was further used to detect gait states of supination, neutral, and pronation. The RDS microstructure provides an alternative strategy to improve the performance of pressure sensors and extend their potential applications in monitoring human activities.

Flexible polymer transistors with high pressure sensitivity for application in electronic skin and health monitoring

NASA Astrophysics Data System (ADS)

Schwartz, Gregor; Tee, Benjamin C.-K.; Mei, Jianguo; Appleton, Anthony L.; Kim, Do Hwan; Wang, Huiliang; Bao, Zhenan

2013-05-01

Flexible pressure sensors are essential parts of an electronic skin to allow future biomedical prostheses and robots to naturally interact with humans and the environment. Mobile biomonitoring in long-term medical diagnostics is another attractive application for these sensors. Here we report the fabrication of flexible pressure-sensitive organic thin film transistors with a maximum sensitivity of 8.4 kPa-1, a fast response time of <10 ms, high stability over >15,000 cycles and a low power consumption of <1 mW. The combination of a microstructured polydimethylsiloxane dielectric and the high-mobility semiconducting polyisoindigobithiophene-siloxane in a monolithic transistor design enabled us to operate the devices in the subthreshold regime, where the capacitance change upon compression of the dielectric is strongly amplified. We demonstrate that our sensors can be used for non-invasive, high fidelity, continuous radial artery pulse wave monitoring, which may lead to the use of flexible pressure sensors in mobile health monitoring and remote diagnostics in cardiovascular medicine.

Flexible polymer transistors with high pressure sensitivity for application in electronic skin and health monitoring.

PubMed

Schwartz, Gregor; Tee, Benjamin C-K; Mei, Jianguo; Appleton, Anthony L; Kim, Do Hwan; Wang, Huiliang; Bao, Zhenan

2013-01-01

Flexible pressure sensors are essential parts of an electronic skin to allow future biomedical prostheses and robots to naturally interact with humans and the environment. Mobile biomonitoring in long-term medical diagnostics is another attractive application for these sensors. Here we report the fabrication of flexible pressure-sensitive organic thin film transistors with a maximum sensitivity of 8.4 kPa(-1), a fast response time of <10 ms, high stability over >15,000 cycles and a low power consumption of <1 mW. The combination of a microstructured polydimethylsiloxane dielectric and the high-mobility semiconducting polyisoindigobithiophene-siloxane in a monolithic transistor design enabled us to operate the devices in the subthreshold regime, where the capacitance change upon compression of the dielectric is strongly amplified. We demonstrate that our sensors can be used for non-invasive, high fidelity, continuous radial artery pulse wave monitoring, which may lead to the use of flexible pressure sensors in mobile health monitoring and remote diagnostics in cardiovascular medicine.

Enabling inspection solutions for future mask technologies through the development of massively parallel E-Beam inspection

NASA Astrophysics Data System (ADS)

Malloy, Matt; Thiel, Brad; Bunday, Benjamin D.; Wurm, Stefan; Jindal, Vibhu; Mukhtar, Maseeh; Quoi, Kathy; Kemen, Thomas; Zeidler, Dirk; Eberle, Anna Lena; Garbowski, Tomasz; Dellemann, Gregor; Peters, Jan Hendrik

2015-09-01

The new device architectures and materials being introduced for sub-10nm manufacturing, combined with the complexity of multiple patterning and the need for improved hotspot detection strategies, have pushed current wafer inspection technologies to their limits. In parallel, gaps in mask inspection capability are growing as new generations of mask technologies are developed to support these sub-10nm wafer manufacturing requirements. In particular, the challenges associated with nanoimprint and extreme ultraviolet (EUV) mask inspection require new strategies that enable fast inspection at high sensitivity. The tradeoffs between sensitivity and throughput for optical and e-beam inspection are well understood. Optical inspection offers the highest throughput and is the current workhorse of the industry for both wafer and mask inspection. E-beam inspection offers the highest sensitivity but has historically lacked the throughput required for widespread adoption in the manufacturing environment. It is unlikely that continued incremental improvements to either technology will meet tomorrow's requirements, and therefore a new inspection technology approach is required; one that combines the high-throughput performance of optical with the high-sensitivity capabilities of e-beam inspection. To support the industry in meeting these challenges SUNY Poly SEMATECH has evaluated disruptive technologies that can meet the requirements for high volume manufacturing (HVM), for both the wafer fab [1] and the mask shop. Highspeed massively parallel e-beam defect inspection has been identified as the leading candidate for addressing the key gaps limiting today's patterned defect inspection techniques. As of late 2014 SUNY Poly SEMATECH completed a review, system analysis, and proof of concept evaluation of multiple e-beam technologies for defect inspection. A champion approach has been identified based on a multibeam technology from Carl Zeiss. This paper includes a discussion on the need for high-speed e-beam inspection and then provides initial imaging results from EUV masks and wafers from 61 and 91 beam demonstration systems. Progress towards high resolution and consistent intentional defect arrays (IDA) is also shown.

Comparison of the Wake-up Test and Combined TES-MEP and CSEP Monitoring in Spinal Surgery.

PubMed

Chen, Bailing; Chen, Yuguang; Yang, Junlin; Xie, Denghui; Su, Haihua; Li, Fobao; Wan, Yong; Peng, Xinsheng; Zheng, Zhaomin

2015-11-01

A retrospective clinical analysis. The aim of this study was to compare the effectiveness of the wake-up test with that of combined monitoring of transcranial electrical stimulation motor evoked potentials (TES-MEP) and cortical somatosensory evoked potentials (CSEP) in spinal surgery. TES-MEP/CSEP combined monitoring is being increasingly recognized as the ideal approach to detect spinal neurophysiological compromise during spinal surgery; however, as a result the merit of the wake-up test is now in doubt. TES-MEP/CSEP combined monitoring was performed simultaneously in 426 patients who underwent spinal surgery at our department, and wake-up tests were conducted on 23 patients because of positive neurophysiological monitoring results with uncertain causes or persistent positive monitoring findings after all potential causes had been resolved. Preoperative and postoperative neurological examinations were performed as the gold standard to detect irreversible spinal function compromise. All data were collected to compare the efficiency of TES-MEP/CSEP combined monitoring with that of the wake-up test. Positive results of TES-MEP/CSEP combined monitoring were recorded in 64 cases. Among them, the positive monitoring findings agreed with the results of the neurological examination in 51 cases, and the monitoring results did not match that of neurological examination in 13 cases. No false-negative result was observed. The sensitivity of TES-MEP/CSEP monitoring was 100%, the specificity was 96.5%, and the Youden index was 0.965. Wake-up tests were conducted in 23 cases. In 8 patients the positive monitoring findings completely matched the postoperative neurological examination results. In contrast, in the other 15 cases with negative neurophysiological monitoring results, only 9 patients retained intact neurological function and 6 patients suffered compromised neurological function. The sensitivity of the wake-up test was 57.1%, the specificity was 100%, and the Youden index was 0.571. Combined TES-MEP and CSEP monitoring, with its high sensitivity and specificity, is an effective method for monitoring spinal function during surgery and should be the preferred choice. The wake-up test is a useful complementary method for monitoring because of its high specificity.

A Wireless Fiber Photometry System Based on a High-Precision CMOS Biosensor With Embedded Continuous-Time Modulation.

PubMed

Khiarak, Mehdi Noormohammadi; Martianova, Ekaterina; Bories, Cyril; Martel, Sylvain; Proulx, Christophe D; De Koninck, Yves; Gosselin, Benoit

2018-06-01

Fluorescence biophotometry measurements require wide dynamic range (DR) and high-sensitivity laboratory apparatus. Indeed, it is often very challenging to accurately resolve the small fluorescence variations in presence of noise and high-background tissue autofluorescence. There is a great need for smaller detectors combining high linearity, high sensitivity, and high-energy efficiency. This paper presents a new biophotometry sensor merging two individual building blocks, namely a low-noise sensing front-end and a order continuous-time modulator (CTSDM), into a single module for enabling high-sensitivity and high energy-efficiency photo-sensing. In particular, a differential CMOS photodetector associated with a differential capacitive transimpedance amplifier-based sensing front-end is merged with an incremental order 1-bit CTSDM to achieve a large DR, low hardware complexity, and high-energy efficiency. The sensor leverages a hardware sharing strategy to simplify the implementation and reduce power consumption. The proposed CMOS biosensor is integrated within a miniature wireless head mountable prototype for enabling biophotometry with a single implantable fiber in the brain of live mice. The proposed biophotometry sensor is implemented in a 0.18- CMOS technology, consuming from a 1.8- supply voltage, while achieving a peak dynamic range of over a 50- input bandwidth, a sensitivity of 24 mV/nW, and a minimum detectable current of 2.46- at a 20- sampling rate.

Latest advances in confocal microscopy of skin cancers toward guiding patient care: a Mohs surgeon's review and perspective (Conference Presentation)

NASA Astrophysics Data System (ADS)

Nehal, Kishwer S.; Rajadhyaksha, Milind

2016-02-01

Latest advances in confocal microscopy of skin cancers toward guiding patient care: a Mohs surgeon's review and perspective About 350 publications worldwide have reported the ability of reflectance confocal microscopy (RCM) imaging to detect melanocytic skin lesions in vivo with specificity of 84-88% and sensitivity of 71-92%, and non-melanocytic skin lesions with specificity of 85-97% and sensitivity 100-92%. Lentigo maligna melanoma can be detected with sensitivity of 93% and specificity 82%. While the sensitivity is comparable to that of dermoscopy, the specificity is 2X superior, especially for lightly- and non-pigmented lesions. Dermoscopy combined with RCM imaging is proving to be both highly sensitive and highly specific. Recent studies have reported that the ratio of equivocal (i.e., would have been biopsied) lesions to detected melanomas dropped by ~2X when guided by dermoscopy and RCM imaging, compared to that with dermoscopy alone. Dermoscopy combined with RCM imaging is now being implemented to guide noninvasive diagnosis (to rule out malignancy and biopsy) and to also guide treatment, with promising initial impact: thus far, about 3,000 patients have been saved from biopsies of benign lesions. These are currently under follow-up monitoring. With fluorescence confocal microscopy (FCM) mosaicing, residual basal cell carcinomas can be detected in Mohs surgically excised fresh tissue ex vivo, with sensitivity of 94-97% and specificity 89-94%. FCM mosaicing is now being implemented for guiding Mohs surgery. To date, about 600 Mohs procedures have been performed, guided with mosaicing, and with pathology being performed in parallel to confirm the final outcome. These latest advances demonstrate the promising ability of RCM and FCM to guide patient care.

Diagnostic markers for the detection of ovarian cancer in BRCA1 mutation carriers

PubMed Central

Weingartshofer, Sigrid; Rappaport-Fürhauser, Christine; Zeilinger, Robert; Pils, Dietmar; Muhr, Daniela; Braicu, Elena I.; Kastner, Marie-Therese; Tan, Yen Y.; Semmler, Lorenz; Sehouli, Jalid; Singer, Christian F.

2017-01-01

Background Screening for ovarian cancer (OC) in women at high risk consists of a combination of carbohydrate antigen 125 (CA125) and transvaginal ultrasound, despite their low sensitivity and specificity. This could be improved by the combination of several biomarkers, which has been shown in average risk patients but has not been investigated until now in female BRCA mutation carriers. Methods Using a multiplex, bead-based, immunoassay system, we analyzed the concentrations of leptin, prolactin, osteopontin, insulin-like growth factor II, macrophage inhibitory factor, CA125 and human epididymis antigen 4 in 26 healthy wild type women, 26 healthy BRCA1 mutation carriers, 28 wildtype OC patients and 26 OC patients with BRCA1 mutation. Results Using the ROC analysis, we found a high overall sensitivity of 94.3% in differentiating healthy controls from OC patients with comparable results in the wildtype subgroup (sensitivity 92.8%, AUC = 0.988; p = 5.2e-14) as well as in BRCA1 mutation carriers (sensitivity 95.2%, AUC = 0.978; p = 1.7e-15) at an overall specificity of 92.3%. The used algorithm also allowed to identify healthy BRCA1 mutation carriers when compared to healthy wildtype women (sensitivity 88.4%, specificity 80.7%, AUC = 0.895; p = 6e-08), while this was less pronounced in patients with OC (sensitivity 66.7%, specificity 67.8%, AUC = 0.724; p = 0.00065). Conclusion We have developed an algorithm, which can differentiate between healthy women and OC patients and have for the first time shown, that such an algorithm can also be used in BRCA mutation carriers. To clarify a suggested benefit to the existing early detection program, large prospective trials with mainly early stage OC cases are warranted. PMID:29244844

Development of a Fluorescent Based Immunosensor for the Serodiagnosis of Canine Leishmaniasis Combining Immunomagnetic Separation and Flow Cytometry

PubMed Central

Sousa, Susana; Cardoso, Luís; Reed, Steven G.; Reis, Alexandre B.; Martins-Filho, Olindo A.; Silvestre, Ricardo; Cordeiro da Silva, Anabela

2013-01-01

Background An accurate diagnosis is essential for the control of infectious diseases. In the search for effective and efficient tests, biosensors have increasingly been exploited for the development of new and highly sensitive diagnostic methods. Here, we describe a new fluorescent based immunosensor comprising magnetic polymer microspheres coated with recombinant antigens to improve the detection of specific antibodies generated during an infectious disease. As a challenging model, we used canine leishmaniasis due to the unsatisfactory sensitivity associated with the detection of infection in asymptomatic animals where the levels of pathogen-specific antibodies are scarce. Methodology Ni-NTA magnetic microspheres with 1,7 µm and 8,07 µm were coated with the Leishmania recombinant proteins LicTXNPx and rK39, respectively. A mixture of equal proportions of both recombinant protein-coated microspheres was used to recognize and specifically bind anti-rK39 and anti-LicTNXPx antibodies present in serum samples of infected dogs. The microspheres were recovered by magnetic separation and the percentage of fluorescent positive microspheres was quantified by flow cytometry. Principal Findings A clinical evaluation carried out with 129 dog serum samples using the antigen combination demonstrated a sensitivity of 98,8% with a specificity of 94,4%. rK39 antigen alone demonstrated a higher sensitivity for symptomatic dogs (96,9%), while LicTXNPx antigen showed a higher sensitivity for asymptomatic (94,4%). Conclusions Overall, our results demonstrated the potential of a magnetic microsphere associated flow cytometry methodology as a viable tool for highly sensitive laboratorial serodiagnosis of both clinical and subclinical forms of canine leishmaniasis. PMID:23991232

Diagnostic Accuracy of Combinations of Tumor Markers for Malignant Pleural Effusion: An Updated Meta-Analysis.

PubMed

Yang, Yuan; Liu, Ya-Lan; Shi, Huan-Zhong

2017-01-01

The role of combinations of tumor markers such as carcinoembryonic antigen (CEA), carbohydrate antigens (CA) 125, 15-3, and 19-9, and CYFRA 21-1 (a fragment of cytokeratin 19) in diagnosing malignant pleural effusion (MPE) has not been clearly established. This meta-analysis was performed to establish the overall diagnostic accuracies of combinations of these pleural fluid tumor markers for MPE. The PubMed, Ovid, Embase, Web of Science, and Cochrane bibliographic databases were searched. Sensitivity, specificity, and other measures of the accuracy of combinations of pleural CEA, CA 125, CA 15-3, CA 19-9, and CYFRA 21-1 in the diagnosis of MPE were pooled after a systematic review of English-language studies. Twenty studies met the inclusion criteria. For pleural fluid tumor marker combinations including more than 3 studies, the summary estimates of the sensitivity/specificity for diagnosing MPE were as follows: CEA + CA 125, 0.65/0.98; CEA + CA 15-3, 0.64/0.98; CEA + CA 19-9, 0.58/0.98; CEA + CYFRA 21-1, 0.82/0.92; and CA 15-3 + CYFRA 21-1, 0.88/0.94. In patients with undiagnosed pleural effusion, the combinations of positive pleural CEA + CA 15-3 and CEA + CA 19-9 are highly suspicious for pleural malignancy, but the sensitivity of these tests is poor. Therefore, their routine role in the diagnostic algorithm of these patients is questionable, and management decisions should depend on positive cytological or biopsy results from the pleura. © 2017 S. Karger AG, Basel.

Molecular Imprinting Technology in Quartz Crystal Microbalance (QCM) Sensors.

PubMed

Emir Diltemiz, Sibel; Keçili, Rüstem; Ersöz, Arzu; Say, Rıdvan

2017-02-24

Molecularly imprinted polymers (MIPs) as artificial antibodies have received considerable scientific attention in the past years in the field of (bio)sensors since they have unique features that distinguish them from natural antibodies such as robustness, multiple binding sites, low cost, facile preparation and high stability under extreme operation conditions (higher pH and temperature values, etc.). On the other hand, the Quartz Crystal Microbalance (QCM) is an analytical tool based on the measurement of small mass changes on the sensor surface. QCM sensors are practical and convenient monitoring tools because of their specificity, sensitivity, high accuracy, stability and reproducibility. QCM devices are highly suitable for converting the recognition process achieved using MIP-based memories into a sensor signal. Therefore, the combination of a QCM and MIPs as synthetic receptors enhances the sensitivity through MIP process-based multiplexed binding sites using size, 3D-shape and chemical function having molecular memories of the prepared sensor system toward the target compound to be detected. This review aims to highlight and summarize the recent progress and studies in the field of (bio)sensor systems based on QCMs combined with molecular imprinting technology.

Whispering Gallery Mode Optomechanical Resonator

NASA Technical Reports Server (NTRS)

Aveline, David C.; Strekalov, Dmitry V.; Yu, Nan; Yee, Karl Y.

2012-01-01

Great progress has been made in both micromechanical resonators and micro-optical resonators over the past decade, and a new field has recently emerged combining these mechanical and optical systems. In such optomechanical systems, the two resonators are strongly coupled with one influencing the other, and their interaction can yield detectable optical signals that are highly sensitive to the mechanical motion. A particularly high-Q optical system is the whispering gallery mode (WGM) resonator, which has many applications ranging from stable oscillators to inertial sensor devices. There is, however, limited coupling between the optical mode and the resonator s external environment. In order to overcome this limitation, a novel type of optomechanical sensor has been developed, offering great potential for measurements of displacement, acceleration, and mass sensitivity. The proposed hybrid device combines the advantages of all-solid optical WGM resonators with high-quality micro-machined cantilevers. For direct access to the WGM inside the resonator, the idea is to radially cut precise gaps into the perimeter, fabricating a mechanical resonator within the WGM. Also, a strategy to reduce losses has been developed with optimized design of the cantilever geometry and positions of gap surfaces.

Competitive amplification of differentially melting amplicons (CADMA) enables sensitive and direct detection of all mutation types by high-resolution melting analysis.

PubMed

Kristensen, Lasse S; Andersen, Gitte B; Hager, Henrik; Hansen, Lise Lotte

2012-01-01

Sensitive and specific mutation detection is of particular importance in cancer diagnostics, prognostics, and individualized patient treatment. However, the majority of molecular methodologies that have been developed with the aim of increasing the sensitivity of mutation testing have drawbacks in terms of specificity, convenience, or costs. Here, we have established a new method, Competitive Amplification of Differentially Melting Amplicons (CADMA), which allows very sensitive and specific detection of all mutation types. The principle of the method is to amplify wild-type and mutated sequences simultaneously using a three-primer system. A mutation-specific primer is designed to introduce melting temperature decreasing mutations in the resulting mutated amplicon, while a second overlapping primer is designed to amplify both wild-type and mutated sequences. When combined with a third common primer very sensitive mutation detection becomes possible, when using high-resolution melting (HRM) as detection platform. The introduction of melting temperature decreasing mutations in the mutated amplicon also allows for further mutation enrichment by fast coamplification at lower denaturation temperature PCR (COLD-PCR). For proof-of-concept, we have designed CADMA assays for clinically relevant BRAF, EGFR, KRAS, and PIK3CA mutations, which are sensitive to, between 0.025% and 0.25%, mutated alleles in a wild-type background. In conclusion, CADMA enables highly sensitive and specific mutation detection by HRM analysis. © 2011 Wiley Periodicals, Inc.

Combined Effects of Gamma Radiation and High Dietary Iron on Peripheral Leukocyte Distribution and Function

NASA Technical Reports Server (NTRS)

Crucian, Brian E.; Morgan, Jennifer L. L.; Quiriarte, Heather A.; Sams, Clarence F.; Smith, Scott M.; Zwart, Sara R.

2012-01-01

Both radiation and increased iron stores can independently increase oxidative damage, resulting in protein, lipid and DNA oxidation. Oxidative stress increases the risk of many health problems including cancer, cataracts, and heart disease. This study, a subset of a larger interdisciplinary investigation of the combined effect of iron overload on sensitivity to radiation injury, monitored immune parameters in the peripheral blood of rats subjected to gamma radiation, high dietary iron or both. Specific immune measures consisted of: (1) peripheral leukocyte distribution, (2) plasma cytokine levels and (3) cytokine production profiles following whole blood mitogenic stimulation

Can we improve clinical prediction of at-risk older drivers?

PubMed Central

Bowers, Alex R.; Anastasio, R. Julius; Sheldon, Sarah S.; O’Connor, Margaret G.; Hollis, Ann M.; Howe, Piers D.; Horowitz, Todd S.

2013-01-01

Objectives To conduct a pilot study to evaluate the predictive value of the Montreal Cognitive Assessment test (MoCA) and a brief test of multiple object tracking (MOT) relative to other tests of cognition and attention in identifying at-risk older drivers, and to determine which combination of tests provided the best overall prediction. Methods Forty-seven currently-licensed drivers (58 to 95 years), primarily from a clinical driving evaluation program, participated. Their performance was measured on: (1) a screening test battery, comprising MoCA, MOT, MiniMental State Examination (MMSE), Trail-Making Test, visual acuity, contrast sensitivity, and Useful Field of View (UFOV); and (2) a standardized road test. Results Eighteen participants were rated at-risk on the road test. UFOV subtest 2 was the best single predictor with an area under the curve (AUC) of .84. Neither MoCA nor MOT was a better predictor of the at-risk outcome than either MMSE or UFOV, respectively. The best four-test combination (MMSE, UFOV subtest 2, visual acuity and contrast sensitivity) was able to identify at-risk drivers with 95% specificity and 80% sensitivity (.91 AUC). Conclusions Although the best four-test combination was much better than a single test in identifying at-risk drivers, there is still much work to do in this field to establish test batteries that have both high sensitivity and specificity. PMID:23954688

Vorinostat and metformin sensitize EGFR-TKI resistant NSCLC cells via BIM-dependent apoptosis induction.

PubMed

Chen, Hengyi; Wang, Yubo; Lin, Caiyu; Lu, Conghua; Han, Rui; Jiao, Lin; Li, Li; He, Yong

2017-11-07

There is a close relationship between low expression of BIM and resistance to epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI). Vorinostat is a pan-histone deacetylase inhibitor (HDACi) that augments BIM expression in various types of tumor cells, however, this effect is attenuated by the high expression of anti-apoptotic proteins in EGFR-TKI resistant non-small cell lung cancer (NSCLC) cells. Vorinostat in combination with metformin - a compound that can inhibit anti-apoptotic proteins expression, might cooperate to activate apoptotic signaling and overcome EGFR-TKI resistance. This study aimed to investigate the cooperative effect and evaluate possible molecular mechanisms. The results showed that vorinostat combined with gefitinib augmented BIM expression and increased the sensitivity of EGFR-TKI resistant NSCLC cells to gefitinib, adding metformin simultaneously could obviously inhibit the expression of anti-apoptotic proteins, and further increased expression levels of BIM and BAX, and as a result, further improved the sensitivity of gefitinib both on the NSCLC cells with intrinsic and acquired resistance to EGFR-TKI. In addition, autophagy induced by gefitinib and vorinostat could be significantly suppressed by metformin, which might also contribute to enhance apoptosis and improve sensitivity of gefitinib. These results suggested that the combination of vorinostat and metformin might represent a novel strategy to overcome EGFR-TKI resistance associated with BIM-dependent apoptosis in larger heterogeneous populations.

Convective and microphysics parameterization impact on simulating heavy rainfall in Semarang (case study on February 12th, 2015)

NASA Astrophysics Data System (ADS)

Faridatussafura, Nurzaka; Wandala, Agie

2018-05-01

The meteorological model WRF-ARW version 3.8.1 is used for simulating the heavy rainfall in Semarang that occurred on February 12th, 2015. Two different convective schemes and two different microphysics scheme in a nested configuration were chosen. The sensitivity of those schemes in capturing the extreme weather event has been tested. GFS data were used for the initial and boundary condition. Verification on the twenty-four hours accumulated rainfall using GSMaPsatellite data shows that Kain-Fritsch convective scheme and Lin microphysics scheme is the best combination scheme among the others. The combination also gives the highest success ratio value in placing high intensity rainfall area. Based on the ROC diagram, KF-Lin shows the best performance in detecting high intensity rainfall. However, the combination still has high bias value.

Fusion Molecules of Heat Shock Protein HSPX with Other Antigens of Mycobacterium tuberculosis Show High Potential in Serodiagnosis of Tuberculosis.

PubMed

Khalid, Ruqyya; Afzal, Madeeha; Khurshid, Sana; Paracha, Rehan Zafar; Khan, Imran H; Akhtar, Muhammad Waheed

Variable individual response against the antigens of Mycobacterium tuberculosis necessitates detection of multiple antibodies for enhancing reliability of serodiagnosis of tuberculosis. Fusion molecules consisting of two or more antigens showing high sensitivity would be helpful in achieving this objective. Antigens of M. tuberculosis HSPX and PE35 were expressed in a soluble form whereas tnPstS1 and FbpC1 were expressed as inclusion bodies at 37°C. Heat shock protein HSPX when attached to the N-termini of the antigens PE35, tnPstS1 and FbpC1, all the fusion molecules were expressed at high levels in E. coli in a soluble form. ELISA analysis of the plasma samples of TB patients against HSPX-tnPstS1 showed 57.7% sensitivity which is nearly the same as the expected combined value obtained after deducting the number of plasma samples (32) containing the antibodies against both the individual antigens. Likewise, the 54.4% sensitivity of HSPX-PE35 was nearly the same as that expected from the combined values of the contributing antigens. Structural analysis of all the fusion molecules by CD spectroscopy showed that α-helical and β-sheet contents were found close to those obtained through molecular modeling. Molecular modeling studies of HSPX-tnPstS1 and HSPX-PE35 support the analytical results as most of the epitopes of the contributing antigens were found to be available for binding to the corresponding antibodies. Using these fusion molecules in combination with other antigenic molecules should reduce the number of antigenic proteins required for a more reliable and economical serodiagnosis of tuberculosis. Also, HSPX seems to have potential application in soluble expression of heterologous proteins in E. coli.

Discrimination of soft tissues using laser-induced breakdown spectroscopy in combination with k nearest neighbors (kNN) and support vector machine (SVM) classifiers

NASA Astrophysics Data System (ADS)

Li, Xiaohui; Yang, Sibo; Fan, Rongwei; Yu, Xin; Chen, Deying

2018-06-01

In this paper, discrimination of soft tissues using laser-induced breakdown spectroscopy (LIBS) in combination with multivariate statistical methods is presented. Fresh pork fat, skin, ham, loin and tenderloin muscle tissues are manually cut into slices and ablated using a 1064 nm pulsed Nd:YAG laser. Discrimination analyses between fat, skin and muscle tissues, and further between highly similar ham, loin and tenderloin muscle tissues, are performed based on the LIBS spectra in combination with multivariate statistical methods, including principal component analysis (PCA), k nearest neighbors (kNN) classification, and support vector machine (SVM) classification. Performances of the discrimination models, including accuracy, sensitivity and specificity, are evaluated using 10-fold cross validation. The classification models are optimized to achieve best discrimination performances. The fat, skin and muscle tissues can be definitely discriminated using both kNN and SVM classifiers, with accuracy of over 99.83%, sensitivity of over 0.995 and specificity of over 0.998. The highly similar ham, loin and tenderloin muscle tissues can also be discriminated with acceptable performances. The best performances are achieved with SVM classifier using Gaussian kernel function, with accuracy of 76.84%, sensitivity of over 0.742 and specificity of over 0.869. The results show that the LIBS technique assisted with multivariate statistical methods could be a powerful tool for online discrimination of soft tissues, even for tissues of high similarity, such as muscles from different parts of the animal body. This technique could be used for discrimination of tissues suffering minor clinical changes, thus may advance the diagnosis of early lesions and abnormalities.

Evaluation of gastro-oesophageal reflux disease in wheezy infants using 24-h oesophageal combined impedance and pH monitoring.

PubMed

Abdallah, Ahmed; El-Desoky, Tarek; Fathi, Khalid; Fawzi Elkashef, Wagdi; Zaki, Ahmed

2017-06-01

Gastro-oesophageal reflux disease (GERD) is incriminated as a cause of non-asthmatic infantile wheeze. To date, no diagnostic test is considered standard for GERD-related airway reflux diagnosis. Oesophageal combined multiple channel intraluminal impedance and pH (MII-pH) monitoring is proposed to be a sensitive tool for evaluation of all GERD including infantile wheeze. We aimed to determine the GERD prevalence amongst wheezy infants in the first year of life using combined MII-pH versus pH monitoring alone and evaluate the sensitivity and specificity of objective MII-pH monitoring parameters in GERD-associated infantile wheeze diagnosis compared to those of lipid-laden macrophage index (LLMI). Thirty-eight wheezy infants below 1year of age were evaluated for GERD using oesophageal combined MII-pH monitoring and LLMI. Totally, 60.5% of cases had abnormal MII-pH; only 7.9% of them had abnormal pH monitoring. LLMI was significantly higher in wheezy infants with abnormal MII-pH than infants with normal MII-pH monitoring (112±88 versus 70±48; P=0.036). The current definitions of abnormal MII-pH study, reflux index≥10% and distal reflux episodes≥100, had low sensitivity (23%) but high specificity (100% and 96%, respectively) in GERD-related aspiration diagnosis defined by LLMI≥100. Using ROC curves, bolus contact time≥2.4% and proximal reflux episodes≥46 had 61% and 54% sensitivity and 64% and 76% specificity, respectively, in GERD-related aspiration diagnosis. Combined MII-pH is superior to pH monitoring in reflux-associated infantile wheeze diagnosis. Objective data including proximal reflux episodes and bolus contact time should be combined with the current parameters used in reflux-associated infantile wheeze diagnosis. Copyright © 2017 Pan-Arab Association of Gastroenterology. Published by Elsevier B.V. All rights reserved.

Convenient, Sensitive and High-Throughput Method for Screening Botanic Origin

NASA Astrophysics Data System (ADS)

Yuan, Yuan; Jiang, Chao; Liu, Libing; Yu, Shulin; Cui, Zhanhu; Chen, Min; Lin, Shufang; Wang, Shu; Huang, Luqi

2014-06-01

In this work, a rapid (within 4-5 h), sensitive and visible new method for assessing botanic origin is developed by combining loop-mediated isothermal amplification with cationic conjugated polymers. The two Chinese medicinal materials (Jin-Yin-Hua and Shan-Yin-Hua) with similar morphology and chemical composition were clearly distinguished by gene SNP genotyping assays. The identification of plant species in Patented Chinese drugs containing Lonicera buds is successfully performed using this detection system. The method is also robust enough to be used in high-throughput screening. This new method is very helpful to identify herbal materials, and is beneficial for detecting safety and quality of botanic products.

Methionine Deprivation Induces a Targetable Vulnerability in Triple-negative Breast Cancer Cells by Enhancing TRAIL Receptor-2 Expression

PubMed Central

Strekalova, Elena; Malin, Dmitry; Good, David M.; Cryns, Vincent L.

2015-01-01

Purpose Many neoplasms are vulnerable to methionine deficiency by mechanisms that are poorly understood. Because gene profiling studies have revealed that methionine depletion increases TNF-related apoptosis-inducing ligand receptor-2 (TRAIL-R2) mRNA, we postulated that methionine stress sensitizes breast cancer cells to proapoptotic TRAIL-R2 agonists. Experimental Design Human triple (ER/PR/HER2)-negative breast carcinoma cell lines were cultured in control or methionine-free media. The effects of methionine depletion on TRAIL receptor expression and sensitivity to chemotherapy or a humanized agonistic TRAIL-R2 monoclonal antibody (lexatumumab) were determined. The melanoma-associated antigen MAGED2 was silenced to delineate its functional role in sensitizing TNBC cells to methionine stress. An orthotopic TNBC model was utilized to evaluate the effects of dietary methionine deficiency, lexatumumab or the combination. Results Methionine depletion sensitized TNBC cells to lexatumumab-induced caspase activation and apoptosis by increasing TRAIL-R2 mRNA and cell surface expression. MCF-10A cells transformed by oncogenic H-Ras, but not untransformed cells, and matrix-detached TNBC cells were highly sensitive to the combination of lexatumumab and methionine depletion. Proteomics analyses revealed that MAGED2, which has been reported to reduce TRAIL-R2 expression, was suppressed by methionine stress. Silencing MAGED2 recapitulated features of methionine deprivation, including enhanced mRNA and cell surface expression of TRAIL receptors and increased sensitivity to TRAIL receptor agonists. Dietary methionine deprivation enhanced the antitumor effects of lexatumumab in an orthotopic metastatic TNBC model. Conclusion Methionine depletion exposes a targetable defect in TNBC cells by increasing TRAIL-R2 expression. Our findings provide the foundation for a clinical trial combining dietary methionine restriction and TRAIL-R2 agonists. PMID:25724522

Facile and sensitive determination of N-nitrosamines in food samples by high-performance liquid chromatography via combining fluorescent labeling with dispersive liquid-liquid microextraction.

PubMed

Lu, Shuaimin; Wu, Di; Li, Guoliang; Lv, Zhengxian; Gong, Peiwei; Xia, Lian; Sun, Zhiwei; Chen, Guang; Chen, Xuefeng; You, Jinmao; Wu, Yongning

2017-11-01

The intake of N-nitrosamines (NAs) from foodstuffs is considered to be an important influence factor for several cancers. But the rapid and sensitive screening of NAs remains a challenge in the field of food safety. Inspired by that, a sensitive and rapid method was demonstrated for determination of five NAs (Nitrosopyrrolidine, Nitrosodimethylamine, Nitrosodiethylamine, Nitrosodipropylamine and Nitrosodibutylamine) using dispersive liquid-liquid microextraction (DLLME) followed by high-performance liquid chromatography with fluorescence detection (HPLC-FLD). The NAs were firstly denitrosated and labeled by 2-(11H-benzo[a]carbazol-11-yl) ethyl carbonochloridate (BCEC-Cl) and finally enriched by DLLME. Furthermore, the main DLLME conditions were optimized systematically. Under the optimal conditions, satisfactory limits of detection (LODs) were obtained with a range of 0.01-0.07ngg -1 , which were significantly lower than the reported methods. The developed method showed many merits including rapidity, simplicity, high sensitivity and excellent selectivity, which shows a broad prospect in food safety analysis. Copyright © 2017 Elsevier Ltd. All rights reserved.

Investigation of optimal use of computer-aided detection systems: the role of the "machine" in decision making process.

PubMed

Paquerault, Sophie; Hardy, Paul T; Wersto, Nancy; Chen, John; Smith, Robert C

2010-09-01

The aim of this study was to explore different computerized models (the "machine") as a means to achieve optimal use of computer-aided detection (CAD) systems and to investigate whether these models can play a primary role in clinical decision making and possibly replace a clinician's subjective decision for combining his or her own assessment with that provided by a CAD system. Data previously collected from a fully crossed, multiple-reader, multiple-case observer study with and without CAD by seven observers asked to identify simulated small masses on two separate sets of 100 mammographic images (low-contrast and high-contrast sets; ie, low-contrast and high-contrast simulated masses added to random locations on normal mammograms) were used. This allowed testing two relative sensitivities between the observers and CAD. Seven models that combined detection assessments from CAD standalone, unaided read, and CAD-aided read (second read and concurrent read) were developed using the leave-one-out technique for training and testing. These models were personalized for each observer. Detection performance accuracies were analyzed using the area under a portion of the free-response receiver-operating characteristic curve (AUFC), sensitivity, and number of false-positives per image. For the low-contrast set, the use of computerized models resulted in significantly higher AUFCs compared to the unaided read mode for all readers, whereas the increased AUFCs between CAD-aided (second and concurrent reads; ie, decisions made by the readers) and unaided read modes were statistically significant for a majority, but not all, of the readers (four and five of the seven readers, respectively). For the high-contrast set, there were no significant trends in the AUFCs whether or not a model was used to combine the original reading modes. Similar results were observed when using sensitivity as the figure of merit. However, the average number of false-positives per image resulting from the computerized models remained the same as that obtained from the unaided read modes. Individual computerized models (the machine) that combine image assessments from CAD standalone, unaided read, and CAD-aided read can increase detection performance compared to the reading done by the observer. However, relative sensitivity (ie, the difference in sensitivity between CAD standalone and unaided read) was a critical factor that determined incremental improvement in decision making, whether made by the observer or using computerized models. Published by Elsevier Inc.

Boundary Layer Remote Sensing with Combined Active and Passive Techniques: GPS Radio Occultation and High-Resolution Stereo Imaging (WindCam) Small Satellite Concept

NASA Technical Reports Server (NTRS)

Mannucci, A.J.; Wu, D.L.; Teixeira, J.; Ao, C.O.; Xie, F.; Diner, D.J.; Wood, R.; Turk, Joe

2012-01-01

Objective: significant progress in understanding low-cloud boundary layer processes. This is the Single largest uncertainty in climate projections. Radio occultation has unique features suited to boundary layer remote sensing (1) Cloud penetrating (2) Very high vertical resolution (approximately 50m-100m) (3) Sensitivity to thermodynamic variables

Ultrahigh resolution radiation imaging system using an optical fiber structure scintillator plate.

PubMed

Yamamoto, Seiichi; Kamada, Kei; Yoshikawa, Akira

2018-02-16

High resolution imaging of radiation is required for such radioisotope distribution measurements as alpha particle detection in nuclear facilities or high energy physics experiments. For this purpose, we developed an ultrahigh resolution radiation imaging system using an optical fiber structure scintillator plate. We used a ~1-μm diameter fiber structured GdAlO 3 :Ce (GAP) /α-Al 2 O 3 scintillator plate to reduce the light spread. The fiber structured scintillator plate was optically coupled to a tapered optical fiber plate to magnify the image and combined with a lens-based high sensitivity CCD camera. We observed the images of alpha particles with a spatial resolution of ~25 μm. For the beta particles, the images had various shapes, and the trajectories of the electrons were clearly observed in the images. For the gamma photons, the images also had various shapes, and the trajectories of the secondary electrons were observed in some of the images. These results show that combining an optical fiber structure scintillator plate with a tapered optical fiber plate and a high sensitivity CCD camera achieved ultrahigh resolution and is a promising method to observe the images of the interactions of radiation in a scintillator.

Recent advances on multidimensional liquid chromatography-mass spectrometry for proteomics: from qualitative to quantitative analysis--a review.

PubMed

Wu, Qi; Yuan, Huiming; Zhang, Lihua; Zhang, Yukui

2012-06-20

With the acceleration of proteome research, increasing attention has been paid to multidimensional liquid chromatography-mass spectrometry (MDLC-MS) due to its high peak capacity and separation efficiency. Recently, many efforts have been put to improve MDLC-based strategies including "top-down" and "bottom-up" to enable highly sensitive qualitative and quantitative analysis of proteins, as well as accelerate the whole analytical procedure. Integrated platforms with combination of sample pretreatment, multidimensional separations and identification were also developed to achieve high throughput and sensitive detection of proteomes, facilitating highly accurate and reproducible quantification. This review summarized the recent advances of such techniques and their applications in qualitative and quantitative analysis of proteomes. Copyright © 2012 Elsevier B.V. All rights reserved.

Mesoporous titania-vertical nanorod films with interfacial engineering for high performance dye-sensitized solar cells.

PubMed

Ahmed, Irfan; Fakharuddin, Azhar; Wali, Qamar; Bin Zainun, Ayib Rosdi; Ismail, Jamil; Jose, Rajan

2015-03-13

Working electrode (WE) fabrication offers significant challenges in terms of achieving high-efficiency dye-sensitized solar cells (DSCs). We have combined the beneficial effects of vertical nanorods grown on conducting glass substrate for charge transport and mesoporous particles for dye loading and have achieved a high photoconversion efficiency of (η) > 11% with an internal quantum efficiency of ∼93% in electrode films of thickness ∼7 ± 0.5 μm. Controlling the interface between the vertical nanorods and the mesoporous film is a crucial step in attaining high η. We identify three parameters, viz., large surface area of nanoparticles, increased light scattering of the nanorod-nanoparticle layer, and superior charge transport of nanorods, that simultaneously contribute to the improved photovoltaic performance of the WE developed.

Combined use of endometrial sample and magnetic resonance imaging in the preoperative risk-stratification of endometrial carcinomas.

PubMed

Luomaranta, Anna; Bützow, Ralf; Pauna, Arja-Riitta; Leminen, Arto; Loukovaara, Mikko

2015-01-01

To compare two treatment strategies in women undergoing surgery for endometrial carcinoma. Retrospective cohort study. Tertiary care center. 1166 patients. Uterine biopsy/curettage was obtained in 1140 women, of whom 229 also had pelvic magnetic resonance imaging (MRI). We compared two strategies: (i) routine pelvic lymphadenectomy and (ii) selective pelvic lymphadenectomy for women with high-risk carcinomas as determined from preoperative histology and MRI. High-risk carcinomas included grade 1-2 endometrioid carcinomas with ≥50% myometrial invasion, grade 3 endometrioid carcinomas, and nonendometrioid carcinomas. Others were considered low-risk carcinomas. Diagnostic indices, treatment algorithms. Of the women who underwent lymphadenectomy, positive pelvic nodes were found in 2.3% of low-risk carcinomas and 18.3% of high-risk carcinomas. The combination of preoperative histology and MRI detected high-risk carcinomas with a sensitivity of 85.7%, a specificity of 75.0%, a positive predictive value of 74.4%, and a negative predictive value of 86.1%. Area under curve was 0.804. In the routine lymphadenectomy algorithm, 54.1% of lymphadenectomies were performed for low-risk carcinomas. In the selective lymphadenectomy algorithm, 14.3% of women with high-risk carcinomas did not receive lymphadenectomy. Missed positive pelvic nodes were estimated to occur in 2.1% of patients in the selective strategy. Similarly, the estimated risk for isolated para-aortic metastasis was 2.1%, regardless of treatment strategy. The combination of preoperative histology and MRI is moderately sensitive and specific in detecting high-risk endometrial carcinomas. The clinical utility of the method is hampered by the relatively high proportion of high-risk cases that remain unrecognized preoperatively. © 2014 Nordic Federation of Societies of Obstetrics and Gynecology.

Immuno-magnetic beads-based extraction-capillary zone electrophoresis-deep UV laser-induced fluorescence analysis of erythropoietin.

PubMed

Wang, Heye; Dou, Peng; Lü, Chenchen; Liu, Zhen

2012-07-13

Erythropoietin (EPO) is an important glycoprotein hormone. Recombinant human EPO (rhEPO) is an important therapeutic drug and can be also used as doping reagent in sports. The analysis of EPO glycoforms in pharmaceutical and sports areas greatly challenges analytical scientists from several aspects, among which sensitive detection and effective and facile sample preparation are two essential issues. Herein, we investigated new possibilities for these two aspects. Deep UV laser-induced fluorescence detection (deep UV-LIF) was established to detect the intrinsic fluorescence of EPO while an immuno-magnetic beads-based extraction (IMBE) was developed to specifically extract EPO glycoforms. Combined with capillary zone electrophoresis (CZE), CZE-deep UV-LIF allows high resolution glycoform profiling with improved sensitivity. The detection sensitivity was improved by one order of magnitude as compared with UV absorbance detection. An additional advantage is that the original glycoform distribution can be completely preserved because no fluorescent labeling is needed. By combining IMBE with CZE-deep UV-LIF, the overall detection sensitivity was 1.5 × 10⁻⁸ mol/L, which was enhanced by two orders of magnitude relative to conventional CZE with UV absorbance detection. It is applicable to the analysis of pharmaceutical preparations of EPO, but the sensitivity is insufficient for the anti-doping analysis of EPO in blood and urine. IMBE can be straightforward and effective approach for sample preparation. However, antibodies with high specificity were the key for application to urine samples because some urinary proteins can severely interfere the immuno-extraction. Copyright © 2012 Elsevier B.V. All rights reserved.

Clock Drawing Test and the diagnosis of amnestic mild cognitive impairment: can more detailed scoring systems do the work?

PubMed

Rubínová, Eva; Nikolai, Tomáš; Marková, Hana; Siffelová, Kamila; Laczó, Jan; Hort, Jakub; Vyhnálek, Martin

2014-01-01

The Clock Drawing Test is a frequently used cognitive screening test with several scoring systems in elderly populations. We compare simple and complex scoring systems and evaluate the usefulness of the combination of the Clock Drawing Test with the Mini-Mental State Examination to detect patients with mild cognitive impairment. Patients with amnestic mild cognitive impairment (n = 48) and age- and education-matched controls (n = 48) underwent neuropsychological examinations, including the Clock Drawing Test and the Mini-Mental State Examination. Clock drawings were scored by three blinded raters using one simple (6-point scale) and two complex (17- and 18-point scales) systems. The sensitivity and specificity of these scoring systems used alone and in combination with the Mini-Mental State Examination were determined. Complex scoring systems, but not the simple scoring system, were significant predictors of the amnestic mild cognitive impairment diagnosis in logistic regression analysis. At equal levels of sensitivity (87.5%), the Mini-Mental State Examination showed higher specificity (31.3%, compared with 12.5% for the 17-point Clock Drawing Test scoring scale). The combination of Clock Drawing Test and Mini-Mental State Examination scores increased the area under the curve (0.72; p < .001) and increased specificity (43.8%), but did not increase sensitivity, which remained high (85.4%). A simple 6-point scoring system for the Clock Drawing Test did not differentiate between healthy elderly and patients with amnestic mild cognitive impairment in our sample. Complex scoring systems were slightly more efficient, yet still were characterized by high rates of false-positive results. We found psychometric improvement using combined scores from the Mini-Mental State Examination and the Clock Drawing Test when complex scoring systems were used. The results of this study support the benefit of using combined scores from simple methods.

Broadband pump-probe spectroscopy at 20-MHz modulation frequency.

PubMed

Preda, Fabrizio; Kumar, Vikas; Crisafi, Francesco; Figueroa Del Valle, Diana Gisell; Cerullo, Giulio; Polli, Dario

2016-07-01

We introduce an innovative high-sensitivity broadband pump-probe spectroscopy system, based on Fourier-transform detection, operating at 20-MHz modulation frequency. A common-mode interferometer employing birefringent wedges creates two phase-locked delayed replicas of the broadband probe pulse, interfering at a single photodetector. A single-channel lock-in amplifier demodulates the interferogram, whose Fourier transform provides the differential transmission spectrum. Our approach combines broad spectral coverage with high sensitivity, due to high-frequency modulation and detection. We demonstrate its performances by measuring two-dimensional differential transmission maps of a carbon nanotubes sample, simultaneously acquiring the signal over the entire 950-1350 nm range with 2.7·10^-6  rms noise over 1.5 s integration time.

Combined two-dimensional velocity and temperature measurements of natural convection using a high-speed camera and temperature-sensitive particles

NASA Astrophysics Data System (ADS)

Someya, Satoshi; Li, Yanrong; Ishii, Keiko; Okamoto, Koji

2011-01-01

This paper proposes a combined method for two-dimensional temperature and velocity measurements in liquid and gas flows using temperature-sensitive particles (TSPs), a pulsed ultraviolet laser, and a high-speed camera. TSPs respond to temperature changes in the flow and can also serve as tracers for the velocity field. The luminescence from the TSPs was recorded at 15,000 frames per second as sequential images for a lifetime-based temperature analysis. These images were also used for the particle image velocimetry calculations. The temperature field was estimated using several images, based on the lifetime method. The decay curves for various temperature conditions fit well to exponential functions, and from these the decay constants at each temperature were obtained. The proposed technique was applied to measure the temperature and velocity fields in natural convection driven by a Marangoni force and buoyancy in a rectangular tank. The accuracy of the temperature measurement of the proposed technique was ±0.35-0.40°C.

A comparative study of biomass integrated gasification combined cycle power systems: Performance analysis.

PubMed

Zang, Guiyan; Tejasvi, Sharma; Ratner, Albert; Lora, Electo Silva

2018-05-01

The Biomass Integrated Gasification Combined Cycle (BIGCC) power system is believed to potentially be a highly efficient way to utilize biomass to generate power. However, there is no comparative study of BIGCC systems that examines all the latest improvements for gasification agents, gas turbine combustion methods, and CO 2 Capture and Storage options. This study examines the impact of recent advancements on BIGCC performance through exergy analysis using Aspen Plus. Results show that the exergy efficiency of these systems is ranged from 22.3% to 37.1%. Furthermore, exergy analysis indicates that the gas turbine with external combustion has relatively high exergy efficiency, and Selexol CO 2 removal method has low exergy destruction. Moreover, the sensitivity analysis shows that the system exergy efficiency is more sensitive to the initial temperature and pressure ratio of the gas turbine, whereas has a relatively weak dependence on the initial temperature and initial pressure of the steam turbine. Copyright © 2018 Elsevier Ltd. All rights reserved.

Groundwater sensitivity mapping in Kentucky using GIS and digitally vectorized geologic quadrangles

NASA Astrophysics Data System (ADS)

Croskrey, Andrea; Groves, Chris

2008-05-01

Groundwater sensitivity (Ray and O’dell in Environ Geol 22:345 352, 1993a) refers to the inherent ease with which groundwater can be contaminated based on hydrogeologic characteristics. We have developed digital methods for identifying areas of varying groundwater sensitivity for a ten county area of south central Kentucky at a scale of 1:100,000. The study area includes extensive limestone karst sinkhole plains, with groundwater extremely sensitive to contamination. Digitally vectorized geologic quadrangles (DVGQs) were combined with elevation data to identify both hydrogeologic groundwater sensitivity regions and zones of “high risk runoff” where contaminants could be transported in runoff from less sensitive to higher sensitivity (particularly karst) areas. While future work will fine-tune these maps with additional layers of data (soils for example) as digital data have become available, using DVGQs allows a relatively rapid assessment of groundwater sensitivity for Kentucky at a more useful scale than previously available assessment methods, such as DRASTIC and DIVERSITY.

Urine albumin/creatinine ratio, high sensitivity C-reactive protein and N-terminal pro brain natriuretic peptide--three new cardiovascular risk markers--do they improve risk prediction and influence treatment?

PubMed

Olsen, Michael H; Sehestedt, Thomas; Lyngbaek, Stig; Hansen, Tine W; Rasmussen, Susanne; Wachtell, Kristian; Torp-Pedersen, Christian; Hildebrandt, Per R; Ibsen, Hans

2010-01-01

In order to prioritize limited health resources in a time of increasing demands optimal cardiovascular risk stratification is essential. We tested the additive prognostic value of 3 relatively new, but established cardiovascular risk markers: N-terminal pro brain natriuretic peptide (Nt-proBNP), related to hemodynamic cardiovascular risk factors, high sensitivity C-reactive protein (hsCRP), related to metabolic cardiovascular risk factors and urine albumin/creatinine ratio (UACR), related to hemodynamic as well as metabolic risk factors. In healthy subjects with a 10-year risk of cardiovascular death lower than 5% based on HeartScore and therefore not eligible for primary prevention, the actual 10-year risk of cardiovascular death exceeded 5% in a small subgroup of subjects with UACR higher than the 95-percentile of approximately 1.6 mg/mmol. Combined use of high UACR or high hsCRP identified a larger subgroup of 16% with high cardiovascular risk in which primary prevention may be advised despite low-moderate cardiovascular risk based on HeartScore. Furthermore, combined use of high UACR or high Nt-proBNP in subjects with known cardiovascular disease or diabetes identified a large subgroup of 48% with extremely high cardiovascular risk who should be referred for specialist care to optimize treatment.

Xpert MTB/RIF assay can be used on archived gastric aspirate and induced sputum samples for sensitive diagnosis of paediatric tuberculosis.

PubMed

Singh, Sarman; Singh, Amit; Prajapati, Suneel; Kabra, Sushil K; Lodha, Rakesh; Mukherjee, Aparna; Singh, Varinder; Hesseling, Anneke C; Grewal, Harleen M S

2015-09-29

Tuberculosis (TB) in children is neglected, mainly due to lack of sensitive diagnostic tools. Recently Xpert MTB/RIF assay has revolutionized the diagnostic field, but its usefulness in pediatric TB has not been reported from India and no report is available on its use on long term archived samples. We recruited 130 pediatric patients with probable intrathoracic tuberculosis and their gastric aspirate (GA) and induced sputum (IS) samples on 2 consecutive days were collected between January 2009 and December 2012. All samples (n = 520) were subjected to smear examination, BACTEC-MGIT culture and in-house multiplex PCR. An aliquot of each sample was stored at -80 °C and tested in Xpert MTB/RIF assay in 2013. Sample wise and patient wise detection rate of smear microscopy was 4.4 % and 10 %, while for BACTEC-MGIT culture this rate was 24.4 % and 46.9 %, respectively. Of the 130 day 1 GA samples, 31.5 % and 27.7 % day 2 GA samples were culture positive. Only 17.7 % GA samples were positive on both days. Of the 130 IS samples collected on day 1 and day 2, 15.4 % and 23.1 % samples were culture positive. A combination of GA and IS yielded best results. Combining both GA and IS, the overall sensitivity of Xpert MTB/RIF on smear and culture positive samples was 95.6 %. In smear negative and culture positive samples its sensitivity was 62.5 %. The duration of sample storage impacted the Xpert MTB/RIF test performance (p = 0.0001). In smear positive samples stored for 650-849 days, its sensitivity was 85.7 % and 77.1 % for IS and GA samples which dropped to 33.3 % and 50 %, respectively, if stored for more than 1050 days. Confirmatory diagnosis of tuberculosis particularly in children is a medical challenge. No laboratory or radiological test can reach to a satisfactory level of diagnostic sensitivity. However, in this study we found that combination of multiple samples and multiple diagnostic tests can give much better yield, though not optimum. In present study, combination of 2 gastric aspirates (GA) and 2 induced sputum (IS) samples collected on two consecutive days, and tested on three diagnostic methods yielded a significantly high detection rate. Despite long term storage, the overall sensitivity of Xpert MTB/RIF on smear and -culture positive samples remained very high. But after storing these samples under subfreezing conditions the sensitivity of Xpert MTB/RIF decreased significantly. This is expected because even if the sample is smear and culture positive, the count of surviving mycobacteria goes down, after several years this count can reach to a undetectable level. This report shows that smear and culture positive samples stored at subfreezing conditions for several years can be used in the Xpert MTB/RIF assay, while maintaining appreciable diagnostic test sensitivity and specificity.

Integrated Patient-Derived Models Delineate Individualized Therapeutic Vulnerabilities of Pancreatic Cancer.

PubMed

Witkiewicz, Agnieszka K; Balaji, Uthra; Eslinger, Cody; McMillan, Elizabeth; Conway, William; Posner, Bruce; Mills, Gordon B; O'Reilly, Eileen M; Knudsen, Erik S

2016-08-16

Pancreatic ductal adenocarcinoma (PDAC) harbors the worst prognosis of any common solid tumor, and multiple failed clinical trials indicate therapeutic recalcitrance. Here, we use exome sequencing of patient tumors and find multiple conserved genetic alterations. However, the majority of tumors exhibit no clearly defined therapeutic target. High-throughput drug screens using patient-derived cell lines found rare examples of sensitivity to monotherapy, with most models requiring combination therapy. Using PDX models, we confirmed the effectiveness and selectivity of the identified treatment responses. Out of more than 500 single and combination drug regimens tested, no single treatment was effective for the majority of PDAC tumors, and each case had unique sensitivity profiles that could not be predicted using genetic analyses. These data indicate a shortcoming of reliance on genetic analysis to predict efficacy of currently available agents against PDAC and suggest that sensitivity profiling of patient-derived models could inform personalized therapy design for PDAC. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

Rapid and Sensitive Enumeration of Viable Diluted Cells of Members of the Family Enterobacteriaceae in Freshwater and Drinking Water

PubMed Central

Baudart, Julia; Coallier, Josée; Laurent, Patrick; Prévost, Michèle

2002-01-01

Water quality assessment involves the specific, sensitive, and rapid detection of bacterial indicators and pathogens in water samples, including viable but nonculturable (VBNC) cells. This work evaluates the specificity and sensitivity of a new method which combines a fluorescent in situ hybridization (FISH) approach with a physiological assay (direct viable count [DVC]) for the direct enumeration, at the single-cell level, of highly diluted viable cells of members of the family Enterobacteriaceae in freshwater and drinking water after membrane filtration. The approach (DVC-FISH) uses a new direct detection device, the laser scanning cytometer (Scan RDI). Combining the DVC-FISH method on a membrane with Scan RDI detection makes it possible to detect as few as one targeted cell in approximately 108 nontargeted cells spread over the membrane. The ability of this new approach to detect and enumerate VBNC enterobacterial cells in freshwater and drinking water distribution systems was investigated and is discussed. PMID:12324357

Efficient estimators for likelihood ratio sensitivity indices of complex stochastic dynamics.

PubMed

Arampatzis, Georgios; Katsoulakis, Markos A; Rey-Bellet, Luc

2016-03-14

We demonstrate that centered likelihood ratio estimators for the sensitivity indices of complex stochastic dynamics are highly efficient with low, constant in time variance and consequently they are suitable for sensitivity analysis in long-time and steady-state regimes. These estimators rely on a new covariance formulation of the likelihood ratio that includes as a submatrix a Fisher information matrix for stochastic dynamics and can also be used for fast screening of insensitive parameters and parameter combinations. The proposed methods are applicable to broad classes of stochastic dynamics such as chemical reaction networks, Langevin-type equations and stochastic models in finance, including systems with a high dimensional parameter space and/or disparate decorrelation times between different observables. Furthermore, they are simple to implement as a standard observable in any existing simulation algorithm without additional modifications.

Direct Printing of Stretchable Elastomers for Highly Sensitive Capillary Pressure Sensors.

PubMed

Liu, Wenguang; Yan, Chaoyi

2018-03-28

We demonstrate the successful fabrication of highly sensitive capillary pressure sensors using an innovative 3D printing method. Unlike conventional capacitive pressure sensors where the capacitance changes were due to the pressure-induced interspace variations between the parallel plate electrodes, in our capillary sensors the capacitance was determined by the extrusion and extraction of liquid medium and consequent changes of dielectric constants. Significant pressure sensitivity advances up to 547.9 KPa -1 were achieved. Moreover, we suggest that our innovative capillary pressure sensors can adopt a wide range of liquid mediums, such as ethanol, deionized water, and their mixtures. The devices also showed stable performances upon repeated pressing cycles. The direct and versatile printing method combined with the significant performance advances are expected to find important applications in future stretchable and wearable electronics.

Efficient estimators for likelihood ratio sensitivity indices of complex stochastic dynamics

NASA Astrophysics Data System (ADS)

Arampatzis, Georgios; Katsoulakis, Markos A.; Rey-Bellet, Luc

2016-03-01

We demonstrate that centered likelihood ratio estimators for the sensitivity indices of complex stochastic dynamics are highly efficient with low, constant in time variance and consequently they are suitable for sensitivity analysis in long-time and steady-state regimes. These estimators rely on a new covariance formulation of the likelihood ratio that includes as a submatrix a Fisher information matrix for stochastic dynamics and can also be used for fast screening of insensitive parameters and parameter combinations. The proposed methods are applicable to broad classes of stochastic dynamics such as chemical reaction networks, Langevin-type equations and stochastic models in finance, including systems with a high dimensional parameter space and/or disparate decorrelation times between different observables. Furthermore, they are simple to implement as a standard observable in any existing simulation algorithm without additional modifications.

Efficient estimators for likelihood ratio sensitivity indices of complex stochastic dynamics

DOE Office of Scientific and Technical Information (OSTI.GOV)

Arampatzis, Georgios; Katsoulakis, Markos A.; Rey-Bellet, Luc

2016-03-14

We demonstrate that centered likelihood ratio estimators for the sensitivity indices of complex stochastic dynamics are highly efficient with low, constant in time variance and consequently they are suitable for sensitivity analysis in long-time and steady-state regimes. These estimators rely on a new covariance formulation of the likelihood ratio that includes as a submatrix a Fisher information matrix for stochastic dynamics and can also be used for fast screening of insensitive parameters and parameter combinations. The proposed methods are applicable to broad classes of stochastic dynamics such as chemical reaction networks, Langevin-type equations and stochastic models in finance, including systemsmore » with a high dimensional parameter space and/or disparate decorrelation times between different observables. Furthermore, they are simple to implement as a standard observable in any existing simulation algorithm without additional modifications.« less

APPLIED PHYSICS. Mid-infrared plasmonic biosensing with graphene.

PubMed

Rodrigo, Daniel; Limaj, Odeta; Janner, Davide; Etezadi, Dordaneh; García de Abajo, F Javier; Pruneri, Valerio; Altug, Hatice

2015-07-10

Infrared spectroscopy is the technique of choice for chemical identification of biomolecules through their vibrational fingerprints. However, infrared light interacts poorly with nanometric-size molecules. We exploit the unique electro-optical properties of graphene to demonstrate a high-sensitivity tunable plasmonic biosensor for chemically specific label-free detection of protein monolayers. The plasmon resonance of nanostructured graphene is dynamically tuned to selectively probe the protein at different frequencies and extract its complex refractive index. Additionally, the extreme spatial light confinement in graphene—up to two orders of magnitude higher than in metals—produces an unprecedentedly high overlap with nanometric biomolecules, enabling superior sensitivity in the detection of their refractive index and vibrational fingerprints. The combination of tunable spectral selectivity and enhanced sensitivity of graphene opens exciting prospects for biosensing. Copyright © 2015, American Association for the Advancement of Science.

Ab initio structure determination of nanocrystals of organic pharmaceutical compounds by electron diffraction at room temperature using a Timepix quantum area direct electron detector.

PubMed

van Genderen, E; Clabbers, M T B; Das, P P; Stewart, A; Nederlof, I; Barentsen, K C; Portillo, Q; Pannu, N S; Nicolopoulos, S; Gruene, T; Abrahams, J P

2016-03-01

Until recently, structure determination by transmission electron microscopy of beam-sensitive three-dimensional nanocrystals required electron diffraction tomography data collection at liquid-nitrogen temperature, in order to reduce radiation damage. Here it is shown that the novel Timepix detector combines a high dynamic range with a very high signal-to-noise ratio and single-electron sensitivity, enabling ab initio phasing of beam-sensitive organic compounds. Low-dose electron diffraction data (∼ 0.013 e(-) Å(-2) s(-1)) were collected at room temperature with the rotation method. It was ascertained that the data were of sufficient quality for structure solution using direct methods using software developed for X-ray crystallography (XDS, SHELX) and for electron crystallography (ADT3D/PETS, SIR2014).

Ultra-sensitive high performance liquid chromatography-laser-induced fluorescence based proteomics for clinical applications.

PubMed

Patil, Ajeetkumar; Bhat, Sujatha; Pai, Keerthilatha M; Rai, Lavanya; Kartha, V B; Chidangil, Santhosh

2015-09-08

An ultra-sensitive high performance liquid chromatography-laser induced fluorescence (HPLC-LIF) based technique has been developed by our group at Manipal, for screening, early detection, and staging for various cancers, using protein profiling of clinical samples like, body fluids, cellular specimens, and biopsy-tissue. More than 300 protein profiles of different clinical samples (serum, saliva, cellular samples and tissue homogenates) from volunteers (normal, and different pre-malignant/malignant conditions) were recorded using this set-up. The protein profiles were analyzed using principal component analysis (PCA) to achieve objective detection and classification of malignant, premalignant and healthy conditions with high sensitivity and specificity. The HPLC-LIF protein profiling combined with PCA, as a routine method for screening, diagnosis, and staging of cervical cancer and oral cancer, is discussed in this paper. In recent years, proteomics techniques have advanced tremendously in life sciences and medical sciences for the detection and identification of proteins in body fluids, tissue homogenates and cellular samples to understand biochemical mechanisms leading to different diseases. Some of the methods include techniques like high performance liquid chromatography, 2D-gel electrophoresis, MALDI-TOF-MS, SELDI-TOF-MS, CE-MS and LC-MS techniques. We have developed an ultra-sensitive high performance liquid chromatography-laser induced fluorescence (HPLC-LIF) based technique, for screening, early detection, and staging for various cancers, using protein profiling of clinical samples like, body fluids, cellular specimens, and biopsy-tissue. More than 300 protein profiles of different clinical samples (serum, saliva, cellular samples and tissue homogenates) from healthy and volunteers with different malignant conditions were recorded by using this set-up. The protein profile data were analyzed using principal component analysis (PCA) for objective classification and detection of malignant, premalignant and healthy conditions. The method is extremely sensitive to detect proteins with limit of detection of the order of femto-moles. The HPLC-LIF combined with PCA as a potential proteomic method for the diagnosis of oral cancer and cervical cancer has been discussed in this paper. This article is part of a Special Issue entitled: Proteomics in India. Copyright © 2015 Elsevier B.V. All rights reserved.

Sensory Processing Sensitivity: Factors of the Highly Sensitive Person Scale and Their relationships to Personality and Subjective Health Complaints.

PubMed

Listou Grimen, Hanne; Diseth, Åge

2016-12-01

The aim of the present study was to examine the factor structure of a Norwegian version of the Highly Sensitive Person Scale (HSPS) and to investigate how sensory processing sensitivity (SPS) is related to personality traits of neuroticism, extraversion, and openness and to subjective health complaints (SHC) in a sample of 167 undergraduate psychology students. The results showed that the variance in a shortened version of the HSPS was best described by three separate factors: ease of excitation (EOE), aesthetic sensitivity (AES), and low sensory threshold (LST). Furthermore, the result showed than an overall SPS factor (EOE, LST, and AES combined) was predicted positively by neuroticism and openness and negatively by extraversion. With respect to SHC, the results showed that EOE and LST were positively associated with psychological health complaints. However, the personality trait of neuroticism contributed more than the SPS factors as predictor of SHC. In conclusion, the present study supported a shortened version of the HSPS and its relation to personality factors and SHC. © The Author(s) 2016.

Vegetation sensitivity to global anthropogenic carbon dioxide emissions in a topographically complex region

USGS Publications Warehouse

Diffenbaugh, N.S.; Sloan, L.C.; Snyder, M.A.; Bell, J.L.; Kaplan, J.; Shafer, S.L.; Bartlein, P.J.

2003-01-01

Anthropogenic increases in atmospheric carbon dioxide (CO2) concentrations may affect vegetation distribution both directly through changes in photosynthesis and water-use efficiency, and indirectly through CO2-induced climate change. Using an equilibrium vegetation model (BIOME4) driven by a regional climate model (RegCM2.5), we tested the sensitivity of vegetation in the western United States, a topographically complex region, to the direct, indirect, and combined effects of doubled preindustrial atmospheric CO2 concentrations. Those sensitivities were quantified using the kappa statistic. Simulated vegetation in the western United States was sensitive to changes in atmospheric CO2 concentrations, with woody biome types replacing less woody types throughout the domain. The simulated vegetation was also sensitive to climatic effects, particularly at high elevations, due to both warming throughout the domain and decreased precipitation in key mountain regions such as the Sierra Nevada of California and the Cascade and Blue Mountains of Oregon. Significantly, when the direct effects of CO2 on vegetation were tested in combination with the indirect effects of CO2-induced climate change, new vegetation patterns were created that were not seen in either of the individual cases. This result indicates that climatic and nonclimatic effects must be considered in tandem when assessing the potential impacts of elevated CO2 levels.

The high throughput virtual slit enables compact, inexpensive Raman spectral imagers

NASA Astrophysics Data System (ADS)

Gooding, Edward; Deutsch, Erik R.; Huehnerhoff, Joseph; Hajian, Arsen R.

2018-02-01

Raman spectral imaging is increasingly becoming the tool of choice for field-based applications such as threat, narcotics and hazmat detection; air, soil and water quality monitoring; and material ID. Conventional fiber-coupled point source Raman spectrometers effectively interrogate a small sample area and identify bulk samples via spectral library matching. However, these devices are very slow at mapping over macroscopic areas. In addition, the spatial averaging performed by instruments that collect binned spectra, particularly when used in combination with orbital raster scanning, tends to dilute the spectra of trace particles in a mixture. Our design, employing free space line illumination combined with area imaging, reveals both the spectral and spatial content of heterogeneous mixtures. This approach is well suited to applications such as detecting explosives and narcotics trace particle detection in fingerprints. The patented High Throughput Virtual Slit1 is an innovative optical design that enables compact, inexpensive handheld Raman spectral imagers. HTVS-based instruments achieve significantly higher spectral resolution than can be obtained with conventional designs of the same size. Alternatively, they can be used to build instruments with comparable resolution to large spectrometers, but substantially smaller size, weight and unit cost, all while maintaining high sensitivity. When used in combination with laser line imaging, this design eliminates sample photobleaching and unwanted photochemistry while greatly enhancing mapping speed, all with high selectivity and sensitivity. We will present spectral image data and discuss applications that are made possible by low cost HTVS-enabled instruments.

A 3D Chemically Modified Graphene Hydrogel for Fast, Highly Sensitive, and Selective Gas Sensor.

PubMed

Wu, Jin; Tao, Kai; Guo, Yuanyuan; Li, Zhong; Wang, Xiaotian; Luo, Zhongzhen; Feng, Shuanglong; Du, Chunlei; Chen, Di; Miao, Jianmin; Norford, Leslie K

2017-03-01

Reduced graphene oxide (RGO) has proved to be a promising candidate in high-performance gas sensing in ambient conditions. However, trace detection of different kinds of gases with simultaneously high sensitivity and selectivity is challenging. Here, a chemiresistor-type sensor based on 3D sulfonated RGO hydrogel (S-RGOH) is reported, which can detect a variety of important gases with high sensitivity, boosted selectivity, fast response, and good reversibility. The NaHSO 3 functionalized RGOH displays remarkable 118.6 and 58.9 times higher responses to NO 2 and NH 3 , respectively, compared with its unmodified RGOH counterpart. In addition, the S-RGOH sensor is highly responsive to volatile organic compounds. More importantly, the characteristic patterns on the linearly fitted response-temperature curves are employed to distinguish various gases for the first time. The temperature of the sensor is elevated rapidly by an imbedded microheater with little power consumption. The 3D S-RGOH is characterized and the sensing mechanisms are proposed. This work gains new insights into boosting the sensitivity of detecting various gases by combining chemical modification and 3D structural engineering of RGO, and improving the selectivity of gas sensing by employing temperature dependent response characteristics of RGO for different gases.

High sensitivity, loop-mediated isothermal amplification combined with colorimetric gold-nanoparticle probes for visual detection of high risk human papillomavirus genotypes 16 and 18.

PubMed

Kumvongpin, Ratchanida; Jearanaikool, Patcharee; Wilailuckana, Chotechana; Sae-Ung, Nattaya; Prasongdee, Prinya; Daduang, Sakda; Wongsena, Metee; Boonsiri, Patcharee; Kiatpathomchai, Wansika; Swangvaree, Sukumarn Sanersak; Sandee, Alisa; Daduang, Jureerut

2016-08-01

High-risk human papillomavirus (HR-HPV) causes cervical cancer. HPV16 and HPV18 are the most prevalent strains of the virus reported in women worldwide. Loop-mediated isothermal amplification (LAMP) is an alternative method for DNA detection under isothermal conditions. However, it results in a turbid amplified product which is not easily detected by the naked eye. This study aimed to develop an improved technique by using gold nanoparticles (AuNPs) attached to a single-stranded DNA probe for the detection of HPV16 and HPV18. Detection of the LAMP product by AuNP color change was compared with detection by visual turbidity. The optimal conditions for this new LAMP-AuNP assay were an incubation time of 20min and a temperature of 65°C. After LAMP amplification was complete, its products were hybridized with the AuNP probe for 5min and then detected by the addition of magnesium salt. The color changed from red to blue as a result of aggregation of the AuNP probe under high ionic strength conditions produced by the addition of the salt. The sensitivity of the LAMP-AuNP assay was greater than the LAMP turbidity assay by up to 10-fold for both HPV genotypes. The LAMP-AuNP assay showed higher sensitivity and ease of visualization than did the LAMP turbidity for the detection of HPV16 and HPV18. Additionally, AuNP-HPV16 and AuNP-HPV18 probes were stable for over 1year. The combination of LAMP and the AuNP-probe colorimetric assay offers a simple, rapid and highly sensitive alternative diagnostic tool for the detection of HPV16 and HPV18 in district hospitals or field studies. Copyright © 2016 Elsevier B.V. All rights reserved.

A stereo-compound hybrid microscope for combined intracellular and optical recording of invertebrate neural network activity

PubMed Central

Frost, William N.; Wang, Jean; Brandon, Christopher J.

2007-01-01

Optical recording studies of invertebrate neural networks with voltage-sensitive dyes seldom employ conventional intracellular electrodes. This may in part be due to the traditional reliance on compound microscopes for such work. While such microscopes have high light-gathering power, they do not provide depth of field, making working with sharp electrodes difficult. Here we describe a hybrid microscope design, with switchable compound and stereo objectives, that eases the use of conventional intracellular electrodes in optical recording experiments. We use it, in combination with a voltage-sensitive dye and photodiode array, to identify neurons participating in the swim motor program of the marine mollusk Tritonia. This microscope design should be applicable to optical recording studies in many preparations. PMID:17306887

Development and Validation of a Protein Based Signature for the Detection of Ovarian Cancer

PubMed Central

Kim, Kyongjin; Visintin, Irene; Alvero, Ayesha B.; Mor, Gil

2009-01-01

In order to overcome the significant mortality associated with ovarian cancer, a highly sensitive and specific screening test is urgently needed. CA125 is used to monitor response to chemotherapy, detect recurrence and detect late stage ovarian cancer. However, CA-125 alone or in combination with ultrasonography has not been adequate for early detection of ovarian cancer. Here we discuss our recent report of a novel multiplex assay that uses a panel of six serum biomarkers:Leptin, Prolactin, Osteopontin, Insulin-Like Growth Factor II, Macrophage Inhibitory Factor and CA-125. The combination of these six proteins yielded 95.3 % sensitivity and 99.4% specificity. The application of this test in the clinical context and the most appropriate population which could benefit of the test is discussed. PMID:19389550

Visualization of Global Sensitivity Analysis Results Based on a Combination of Linearly Dependent and Independent Directions

NASA Technical Reports Server (NTRS)

Davies, Misty D.; Gundy-Burlet, Karen

2010-01-01

A useful technique for the validation and verification of complex flight systems is Monte Carlo Filtering -- a global sensitivity analysis that tries to find the inputs and ranges that are most likely to lead to a subset of the outputs. A thorough exploration of the parameter space for complex integrated systems may require thousands of experiments and hundreds of controlled and measured variables. Tools for analyzing this space often have limitations caused by the numerical problems associated with high dimensionality and caused by the assumption of independence of all of the dimensions. To combat both of these limitations, we propose a technique that uses a combination of the original variables with the derived variables obtained during a principal component analysis.

Simultaneous ultramicroanalysis of both 17-keto-and 17beta-hydroxy androgens in biological fluids.

PubMed

Ganjam, V K

1976-11-01

Sensitive methods for quantifying androgens were lacking. Therefore, a relatively simple procedure for separating steroids was combined with highly specific assay methods so that eight androgens could be measured with high accuracy, precision and sensitivity. Semi-automated separations on Sephadex LH-20 columns used heptane:methylene chloride:ethanol:water (50:50:1:0.12) and a flow rate of 17.0 min/ml. The six peaks eluted contained androstenedine; androsterone, epiandrosterone and dihydrotestosterone; testosterone and dehydroepiandrosterone; 3alpha-androstanediol; 3beta-androstanediol; and androstenediol. Androstenedione, dehydroepiandrosterone and androstenediol were quantified using specific antisera (sensitivity less than or equal to 75 pg). Testosterone and dihydrotestosterone were measured by competitive protein-binding assays using rabbit TeBG (sensitivity less than or equal to 150 pg). 3alpha- and 3beta-androstanediol were similarly assayed using human TeBG (sensitivity approximately 150 pg). Androsterone was reduced with NaBH4 and the resulting 3alpha-androstanediol was assayed using human TeBG (sensitivity approximately 200 pg). Inter- and intra-assay variations were less than 10% for radioimmunoassays and less than 16% for competitive protein-binding assays over the entire dose response curve.

Vectorial capacity and vector control: reconsidering sensitivity to parameters for malaria elimination

PubMed Central

Brady, Oliver J.; Godfray, H. Charles J.; Tatem, Andrew J.; Gething, Peter W.; Cohen, Justin M.; McKenzie, F. Ellis; Perkins, T. Alex; Reiner, Robert C.; Tusting, Lucy S.; Sinka, Marianne E.; Moyes, Catherine L.; Eckhoff, Philip A.; Scott, Thomas W.; Lindsay, Steven W.; Hay, Simon I.; Smith, David L.

2016-01-01

Background Major gains have been made in reducing malaria transmission in many parts of the world, principally by scaling-up coverage with long-lasting insecticidal nets and indoor residual spraying. Historically, choice of vector control intervention has been largely guided by a parameter sensitivity analysis of George Macdonald's theory of vectorial capacity that suggested prioritizing methods that kill adult mosquitoes. While this advice has been highly successful for transmission suppression, there is a need to revisit these arguments as policymakers in certain areas consider which combinations of interventions are required to eliminate malaria. Methods and Results Using analytical solutions to updated equations for vectorial capacity we build on previous work to show that, while adult killing methods can be highly effective under many circumstances, other vector control methods are frequently required to fill effective coverage gaps. These can arise due to pre-existing or developing mosquito physiological and behavioral refractoriness but also due to additive changes in the relative importance of different vector species for transmission. Furthermore, the optimal combination of interventions will depend on the operational constraints and costs associated with reaching high coverage levels with each intervention. Conclusions Reaching specific policy goals, such as elimination, in defined contexts requires increasingly non-generic advice from modelling. Our results emphasize the importance of measuring baseline epidemiology, intervention coverage, vector ecology and program operational constraints in predicting expected outcomes with different combinations of interventions. PMID:26822603

Troponin elevation in severe sepsis and septic shock: the role of left ventricular diastolic dysfunction and right ventricular dilatation*.

PubMed

Landesberg, Giora; Jaffe, Allan S; Gilon, Dan; Levin, Phillip D; Goodman, Sergey; Abu-Baih, Abed; Beeri, Ronen; Weissman, Charles; Sprung, Charles L; Landesberg, Amir

2014-04-01

Serum troponin concentrations predict mortality in almost every clinical setting they have been examined, including sepsis. However, the causes for troponin elevations in sepsis are poorly understood. We hypothesized that detailed investigation of myocardial dysfunction by echocardiography can provide insight into the possible causes of troponin elevation and its association with mortality in sepsis. Prospective, analytic cohort study. Tertiary academic institute. A cohort of ICU patients with severe sepsis or septic shock. Advanced echocardiography using global strain, strain-rate imaging and 3D left and right ventricular volume analyses in addition to the standard echocardiography, and concomitant high-sensitivity troponin-T measurement in patients with severe sepsis or septic shock. Two hundred twenty-five echocardiograms and concomitant high-sensitivity troponin-T measurements were performed in a cohort of 106 patients within the first days of severe sepsis or septic shock (2.1 ± 1.4 measurements/patient). Combining echocardiographic and clinical variables, left ventricular diastolic dysfunction defined as increased mitral E-to-strain-rate e'-wave ratio, right ventricular dilatation (increased right ventricular end-systolic volume index), high Acute Physiology and Chronic Health Evaluation-II score, and low glomerular filtration rate best correlated with elevated log-transformed concomitant high-sensitivity troponin-T concentrations (mixed linear model: t = 3.8, 3.3, 2.8, and -2.1 and p = 0.001, 0.0002, 0.006, and 0.007, respectively). Left ventricular systolic dysfunction determined by reduced strain-rate s'-wave or low ejection fraction did not significantly correlate with log(concomitant high-sensitivity troponin-T). Forty-one patients (39%) died in-hospital. Right ventricular end-systolic volume index and left ventricular strain-rate e'-wave predicted in-hospital mortality, independent of Acute Physiology and Chronic Health Evaluation-II score (logistic regression: Wald = 8.4, 6.6, and 9.8 and p = 0.004, 0.010, and 0.001, respectively). Concomitant high-sensitivity troponin-T predicted mortality in univariate analysis (Wald = 8.4; p = 0.004), but not when combined with right ventricular end-systolic volume index and strain-rate e'-wave in the multivariate analysis (Wald = 2.3, 4.6, and 6.2 and p = 0.13, 0.032, and 0.012, respectively). Left ventricular diastolic dysfunction and right ventricular dilatation are the echocardiographic variables correlating best with concomitant high-sensitivity troponin-T concentrations. Left ventricular diastolic and right ventricular systolic dysfunction seem to explain the association of troponin with mortality in severe sepsis and septic shock.

FDA Expands Abiraterone Approval for Prostate Cancer

Cancer.gov

The FDA has expanded the approval of abiraterone (Zytiga) to treat men with metastatic prostate cancer. The agency approved abiraterone, in combination with prednisone, for men whose cancer that is responsive to hormone-blocking treatments (also known as castration-sensitive) and is at high risk of progressing.

Apples to Apples: Equivalent-Reliability Power Systems Across Diverse Resource Mix Scenarios

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stephen, Gordon W; Frew, Bethany A; Sigler, Devon

Electricity market research is highly price sensitive, and prices are strongly influenced by balance of supply and demand. This work looks at how to combine capacity expansion models and reliability assessment tools to assess equivalent-reliability power systems across diverse resource mix scenarios.

77 FR 11137 - Government-Owned Inventions; Availability for Licensing

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-24

... nonspecific, and the diagnosis is frequently difficult and delayed. The inventors established a rapid ELISA assay to evaluate biomarker levels in serum. The ELISA assay tests a novel combination of two biomarkers...-invasive ELISA serum assay. Potential for high sensitivity. Cost effective. Development Stage: Pilot. Early...

7 CFR 623.2 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-01-01

... cropland that is highly erodible or environmentally sensitive. (f) Prior converted wetland—means wetland... from being planted to the commodity during the crop year. (b) Applicant—means a person who submits to... combination of counties in which the landowner's farm or ranch is located. (p) Participant—means a person(s...

7 CFR 623.2 - Definitions.

Code of Federal Regulations, 2012 CFR

2012-01-01

... cropland that is highly erodible or environmentally sensitive. (f) Prior converted wetland means wetland... from being planted to the commodity during the crop year. (b) Applicant means a person who submits to... combination of counties in which the landowner's farm or ranch is located. (p) Participant means a person(s...

7 CFR 623.2 - Definitions.

Code of Federal Regulations, 2013 CFR

2013-01-01

... cropland that is highly erodible or environmentally sensitive. (f) Prior converted wetland—means wetland... from being planted to the commodity during the crop year. (b) Applicant—means a person who submits to... combination of counties in which the landowner's farm or ranch is located. (p) Participant—means a person(s...

Profilometry of three-dimensional discontinuous solids by combining two-steps temporal phase unwrapping, co-phased profilometry and phase-shifting interferometry

NASA Astrophysics Data System (ADS)

Servin, Manuel; Padilla, Moises; Garnica, Guillermo; Gonzalez, Adonai

2016-12-01

In this work we review and combine two techniques that have been recently published for three-dimensional (3D) fringe projection profilometry and phase unwrapping, namely: co-phased profilometry and 2-steps temporal phase-unwrapping. By combining these two methods we get a more accurate, higher signal-to-noise 3D profilometer for discontinuous industrial objects. In single-camera single-projector (standard) profilometry, the camera and the projector must form an angle between them. The phase-sensitivity of the profilometer depends on this angle, so it cannot be avoided. This angle produces regions with self-occluding shadows and glare from the solid as viewed from the camera's perspective, making impossible the demodulation of the fringe-pattern there. In other words, the phase data is undefined at those shadow regions. As published recently, this limitation can be solved by using several co-phased fringe-projectors and a single camera. These co-phased projectors are positioned at different directions towards the object, and as a consequence most shadows are compensated. In addition to this, most industrial objects are highly discontinuous, which precludes the use of spatial phase-unwrappers. One way to avoid spatial unwrapping is to decrease the phase-sensitivity to a point where the demodulated phase is bounded to one lambda, so the need for phase-unwrapping disappears. By doing this, however, the recovered non-wrapped phase contains too much harmonic distortion and noise. Using our recently proposed two-step temporal phase-unwrapping technique, the high-sensitivity phase is unwrapped using the low-frequency one as initial gross estimation. This two-step unwrapping technique solves the 3D object discontinuities while keeping the accuracy of the high-frequency profilometry data. In scientific research, new art are derived as logical and consistent result of previous efforts in the same direction. Here we present a new 3D-profilometer combining these two recently published methods: co-phased profilometry and two-steps temporal phase-unwrapping. By doing this, we obtain a new and more powerful 3D profilometry technique which overcomes the two main limitations of previous fringe-projection profilometers namely: high phase-sensitivity digitalization of discontinuous objects and solid's self-generated shadow minimization. This new 3D profilometer is demonstrated by an experiment digitizing a discontinuous 3D industrial-solid where the advantages of this new profilometer with respect to previous art are clearly shown.

Toluidine blue aids in detection of dysplasia and carcinoma in suspicious oral lesions.

PubMed

Chainani-Wu, N; Madden, E; Cox, D; Sroussi, H; Epstein, J; Silverman, S

2015-10-01

Accurate clinical identification of 'higher-risk' oral premalignant lesions or 'higher-risk' areas within lesions is important. Assessment methods that predict their presence have great utility. A cross-sectional, observational study enrolled a consecutive sample of consenting patients diagnosed with oral leukoplakia, erythroleukoplakia, or erythroplakia. Medical history, visual oral examination, ViziLite(®) examination, toluidine blue staining (TBlue(®) ), and finally a biopsy were completed in a single clinic visit. Seventy-seven of 100 examined lesions in 43 patients were biopsied. Sensitivity, specificity, and positive and negative predictive values were computed for visual examination, ViziLite(®) , and TBlue(®) using biopsy results as the gold standard. The sensitivity of TBlue(®) in detecting high-risk lesions (carcinoma in situ or carcinoma) was 94 (71-100, P < 0.0003) and specificity 45 (32-58, P < 0.53), while for carcinoma, sensitivity was 100 (54-100, P < 0.032) and specificity 39 (28-52, P < 0.097). The results of ViziLite(®) testing either by itself or in combination with the information from toluidine blue testing revealed low sensitivity for the detection of high-risk lesions. Clinical examination of leukoplakia, erythroplakia, or erythroleukoplakia lesions combined with toluidine blue staining may aid in the identification of severe dysplasia (carcinoma in situ) or carcinoma. This may help in determining whether, when, and where (the site within a lesion) a biopsy should be taken. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Colorimetry and SERS dual-mode detection of telomerase activity: combining rapid screening with high sensitivity.

PubMed

Zong, Shenfei; Wang, Zhuyuan; Chen, Hui; Hu, Guohua; Liu, Min; Chen, Peng; Cui, Yiping

2014-01-01

As an important biomarker and therapeutic target, telomerase has attracted considerable attention concerning its detection and monitoring. Here, we present a colorimetry and surface enhanced Raman scattering (SERS) dual-mode telomerase activity detection method, which has several distinctive advantages. First, colorimetric functionality allows rapid preliminary discrimination of telomerase activity by the naked eye. Second, the employment of SERS technique results in greatly improved detection sensitivity. Third, the combination of colorimetry and SERS into one detection system can ensure highly efficacious and sensitive screening of numerous samples. Besides, the avoidance of polymerase chain reaction (PCR) procedures further guarantees fine reliability and simplicity. Generally, the presented method is realized by an "elongate and capture" procedure. To be specific, gold nanoparticles modified with Raman molecules and telomeric repeat complementary oligonucleotide are employed as the colorimetric-SERS bifunctional reporting nanotag, while magnetic nanoparticles functionalized with telomerase substrate oligonucleotide are used as the capturing substrate. Telomerase can synthesize and elongate telomeric repeats onto the capturing substrate. The elongated telomeric repeats subsequently facilitate capturing of the reporting nanotag via hybridization between telomeric repeat and its complementary strand. The captured nanotags can cause a significant difference in the color and SERS intensity of the magnetically separated sediments. Thus both the color and SERS can be used as indicators of the telomerase activity. With fast screening ability and outstanding sensitivity, we anticipate that this method would greatly promote practical application of telomerase-based early-stage cancer diagnosis.

Preservation of Metabolic Flexibility in Skeletal Muscle by a Combined Use of n-3 PUFA and Rosiglitazone in Dietary Obese Mice

PubMed Central

van Schothorst, Evert M.; Bunschoten, Annelies; Flachs, Pavel; Kus, Vladimir; Kuda, Ondrej; Bardova, Kristina; Janovska, Petra; Hensler, Michal; Rossmeisl, Martin; Wang-Sattler, Rui; Prehn, Cornelia; Adamski, Jerzy; Illig, Thomas; Keijer, Jaap; Kopecky, Jan

2012-01-01

Insulin resistance, the key defect in type 2 diabetes (T2D), is associated with a low capacity to adapt fuel oxidation to fuel availability, i.e., metabolic inflexibility. This, in turn, contributes to a further damage of insulin signaling. Effectiveness of T2D treatment depends in large part on the improvement of insulin sensitivity and metabolic adaptability of the muscle, the main site of whole-body glucose utilization. We have shown previously in mice fed an obesogenic high-fat diet that a combined use of n-3 long-chain polyunsaturated fatty acids (n-3 LC-PUFA) and thiazolidinediones (TZDs), anti-diabetic drugs, preserved metabolic health and synergistically improved muscle insulin sensitivity. We investigated here whether n-3 LC-PUFA could elicit additive beneficial effects on metabolic flexibility when combined with a TZD drug rosiglitazone. Adult male C57BL/6N mice were fed an obesogenic corn oil–based high-fat diet (cHF) for 8 weeks, or randomly assigned to various interventions: cHF with n-3 LC-PUFA concentrate replacing 15% of dietary lipids (cHF+F), cHF with 10 mg rosiglitazone/kg diet (cHF+ROSI), cHF+F+ROSI, or chow-fed. Indirect calorimetry demonstrated superior preservation of metabolic flexibility to carbohydrates in response to the combined intervention. Metabolomic and gene expression analyses in the muscle suggested distinct and complementary effects of the interventions, with n-3 LC-PUFA supporting complete oxidation of fatty acids in mitochondria and the combination with n-3 LC-PUFA and rosiglitazone augmenting insulin sensitivity by the modulation of branched-chain amino acid metabolism. These beneficial metabolic effects were associated with the activation of the switch between glycolytic and oxidative muscle fibers, especially in the cHF+F+ROSI mice. Our results further support the idea that the combined use of n-3 LC-PUFA and TZDs could improve the efficacy of the therapy of obese and diabetic patients. PMID:22952760

High-Resolution “Fleezers”: Dual-Trap Optical Tweezers Combined with Single-Molecule Fluorescence Detection

PubMed Central

Whitley, Kevin D.; Comstock, Matthew J.; Chemla, Yann R.

2017-01-01

Recent advances in optical tweezers have greatly expanded their measurement capabilities. A new generation of hybrid instrument that combines nanomechanical manipulation with fluorescence detection—fluorescence optical tweezers, or “fleezers”—is providing a powerful approach to study complex macromolecular dynamics. Here, we describe a combined high-resolution optical trap/confocal fluorescence microscope that can simultaneously detect sub-nanometer displacements, sub-piconewton forces, and single-molecule fluorescence signals. The primary technical challenge to these hybrid instruments is how to combine both measurement modalities without sacrificing the sensitivity of either one. We present general design principles to overcome this challenge and provide detailed, step-by-step instructions to implement them in the construction and alignment of the instrument. Lastly, we present a set of protocols to perform a simple, proof-of-principle experiment that highlights the instrument capabilities. PMID:27844430

Fibroblast-induced switching to the mesenchymal-like phenotype and PI3K/mTOR signaling protects melanoma cells from BRAF inhibitors

PubMed Central

Seip, Kotryna; Nygaard, Vigdis; Haugen, Mads H.; Engesæter, Birgit Ø.; Mælandsmo, Gunhild M.; Prasmickaite, Lina

2016-01-01

The knowledge on how tumor-associated stroma influences efficacy of anti-cancer therapy just started to emerge. Here we show that lung fibroblasts reduce melanoma sensitivity to the BRAF inhibitor (BRAFi) vemurafenib only if the two cell types are in close proximity. In the presence of fibroblasts, the adjacent melanoma cells acquire de-differentiated mesenchymal-like phenotype. Upon treatment with BRAFi, such melanoma cells maintain high levels of phospho ribosomal protein S6 (pS6), i.e. active mTOR signaling, which is suppressed in the BRAFi sensitive cells without stromal contacts. Inhibitors of PI3K/mTOR in combination with BRAFi eradicate pS6high cell subpopulations and potentiate anti-cancer effects in melanoma protected by the fibroblasts. mTOR and BRAF co-inhibition also delayed the development of early-stage lung metastases in vivo. In conclusion, we demonstrate that upon influence from fibroblasts, melanoma cells undergo a phenotype switch to the mesenchymal state, which can support PI3K/mTOR signaling. The lost sensitivity to BRAFi in such cells can be overcome by co-targeting PI3K/mTOR. This knowledge could be explored for designing BRAFi combination therapies aiming to eliminate both stroma-protected and non-protected counterparts of metastases. PMID:26918352

Optical Microresonators for Sensing and Transduction: A Materials Perspective.

PubMed

Heylman, Kevin D; Knapper, Kassandra A; Horak, Erik H; Rea, Morgan T; Vanga, Sudheer K; Goldsmith, Randall H

2017-08-01

Optical microresonators confine light to a particular microscale trajectory, are exquisitely sensitive to their microenvironment, and offer convenient readout of their optical properties. Taken together, this is an immensely attractive combination that makes optical microresonators highly effective as sensors and transducers. Meanwhile, advances in material science, fabrication techniques, and photonic sensing strategies endow optical microresonators with new functionalities, unique transduction mechanisms, and in some cases, unparalleled sensitivities. In this progress report, the operating principles of these sensors are reviewed, and different methods of signal transduction are evaluated. Examples are shown of how choice of materials must be suited to the analyte, and how innovations in fabrication and sensing are coupled together in a mutually reinforcing cycle. A tremendously broad range of capabilities of microresonator sensors is described, from electric and magnetic field sensing to mechanical sensing, from single-molecule detection to imaging and spectroscopy, from operation at high vacuum to in live cells. Emerging sensing capabilities are highlighted and put into context in the field. Future directions are imagined, where the diverse capabilities laid out are combined and advances in scalability and integration are implemented, leading to the creation of a sensor unparalleled in sensitivity and information content. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Variation in sensitivity of large benthic Foraminifera to the combined effects of ocean warming and local impacts.

PubMed

Prazeres, Martina; Roberts, T Edward; Pandolfi, John M

2017-03-23

Large benthic foraminifera (LBF) are crucial marine calcifiers in coral reefs, and sensitive to environmental changes. Yet, many species successfully colonise a wide range of habitats including highly fluctuating environments. We tested the combined effects of ocean warming, local impacts and different light levels on populations of the common LBF Amphistegina lobifera collected along a cross-shelf gradient of temperature and nutrients fluctuations. We analysed survivorship, bleaching frequency, chlorophyll a content and fecundity. Elevated temperature and nitrate significantly reduced survivorship and fecundity of A. lobifera across populations studied. This pattern was exacerbated when combined with below optimum light levels. Inshore populations showed a consistent resistance to increased temperature and nitrate levels, but all populations studied were significantly affected by light reduction. These findings demonstrated the capacity of some populations of LBF to acclimate to local conditions; nonetheless improvements in local water quality can ultimately ameliorate effects of climate change in local LBF populations.

Lamotrigine blocks repeated high-dose methamphetamine-induced behavioral sensitization to dizocilpine (MK-801), but not methamphetamine in rats.

PubMed

Nakato, Yasuya; Abekawa, Tomohiro; Inoue, Takeshi; Ito, Koki; Koyama, Tsukasa

2011-10-24

We recently proposed a new psychostimulant animal model of the progressive pathophysiological changes of schizophrenia. Studies using that model produced a treatment strategy for preventing progression. Lamotrigine (LTG) blocks repeated high-dosage methamphetamine (METH)-induced initiation and expression of prepulse inhibition deficit and development of apoptosis in the medial prefrontal cortex (mPFC). Moreover, it inhibits METH-induced increases in extracellular glutamate levels in the mPFC (Nakato et al., 2011, Neurosci. Lett.). Abnormal behavior induced by METH or NMDA receptor antagonists is regarded as an animal model of schizophrenia. This study examined the effects of LTG on the development of behavioral sensitization to METH and cross-sensitization to dizocilpine (MK-801) by repeated administration of high-dose METH (2.5mg/kg, 10 times s.c.). Rats were injected repeatedly with LTG (30mg/kg) after 120min METH administration (2.5mg/kg). Repeated co-administration of LTG blocked the development of behavioral cross-sensitization to MK-801 (0.15mg/kg), but it did not prevent behavioral sensitization to METH (0.2mg/kg). The LTG-induced prevention of increased glutamate by high-dose METH might be related to the former finding. Combined results of our previous studies and this study suggest that LTG is useful to treat schizophrenia, especially at a critical point in its progression. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Multi-Drug Resistance Transporters and a Mechanism-Based Strategy for Assessing Risks of Pesticide Combinations to Honey Bees

PubMed Central

Guseman, Alex J.; Miller, Kaliah; Kunkle, Grace; Dively, Galen P.; Pettis, Jeffrey S.; Evans, Jay D.; vanEngelsdorp, Dennis; Hawthorne, David J.

2016-01-01

Annual losses of honey bee colonies remain high and pesticide exposure is one possible cause. Dangerous combinations of pesticides, plant-produced compounds and antibiotics added to hives may cause or contribute to losses, but it is very difficult to test the many combinations of those compounds that bees encounter. We propose a mechanism-based strategy for simplifying the assessment of combinations of compounds, focusing here on compounds that interact with xenobiotic handling ABC transporters. We evaluate the use of ivermectin as a model substrate for these transporters. Compounds that increase sensitivity of bees to ivermectin may be inhibiting key transporters. We show that several compounds commonly encountered by honey bees (fumagillin, Pristine, quercetin) significantly increased honey bee mortality due to ivermectin and significantly reduced the LC50 of ivermectin suggesting that they may interfere with transporter function. These inhibitors also significantly increased honey bees sensitivity to the neonicotinoid insecticide acetamiprid. This mechanism-based strategy may dramatically reduce the number of tests needed to assess the possibility of adverse combinations among pesticides. We also demonstrate an in vivo transporter assay that provides physical evidence of transporter inhibition by tracking the dynamics of a fluorescent substrate of these transporters (Rhodamine B) in bee tissues. Significantly more Rhodamine B remains in the head and hemolymph of bees pretreated with higher concentrations of the transporter inhibitor verapamil. Mechanism-based strategies for simplifying the assessment of adverse chemical interactions such as described here could improve our ability to identify those combinations that pose significantly greater risk to bees and perhaps improve the risk assessment protocols for honey bees and similar sensitive species. PMID:26840460

Multi-Drug Resistance Transporters and a Mechanism-Based Strategy for Assessing Risks of Pesticide Combinations to Honey Bees.

PubMed

Guseman, Alex J; Miller, Kaliah; Kunkle, Grace; Dively, Galen P; Pettis, Jeffrey S; Evans, Jay D; vanEngelsdorp, Dennis; Hawthorne, David J

2016-01-01

Annual losses of honey bee colonies remain high and pesticide exposure is one possible cause. Dangerous combinations of pesticides, plant-produced compounds and antibiotics added to hives may cause or contribute to losses, but it is very difficult to test the many combinations of those compounds that bees encounter. We propose a mechanism-based strategy for simplifying the assessment of combinations of compounds, focusing here on compounds that interact with xenobiotic handling ABC transporters. We evaluate the use of ivermectin as a model substrate for these transporters. Compounds that increase sensitivity of bees to ivermectin may be inhibiting key transporters. We show that several compounds commonly encountered by honey bees (fumagillin, Pristine, quercetin) significantly increased honey bee mortality due to ivermectin and significantly reduced the LC50 of ivermectin suggesting that they may interfere with transporter function. These inhibitors also significantly increased honey bees sensitivity to the neonicotinoid insecticide acetamiprid. This mechanism-based strategy may dramatically reduce the number of tests needed to assess the possibility of adverse combinations among pesticides. We also demonstrate an in vivo transporter assay that provides physical evidence of transporter inhibition by tracking the dynamics of a fluorescent substrate of these transporters (Rhodamine B) in bee tissues. Significantly more Rhodamine B remains in the head and hemolymph of bees pretreated with higher concentrations of the transporter inhibitor verapamil. Mechanism-based strategies for simplifying the assessment of adverse chemical interactions such as described here could improve our ability to identify those combinations that pose significantly greater risk to bees and perhaps improve the risk assessment protocols for honey bees and similar sensitive species.

Investigation of UV photocurable microcapsule inner crosslink extent

NASA Astrophysics Data System (ADS)

Li, Xiaowei; Meng, Shuangshuang; Lai, Weidong; Yu, Haiyang; Fu, Guangsheng

2008-11-01

UV photocuring technology has encountered increased applications in recent years, which finds a variety of applications on protective coating of the optical-fiber, ink and optical recording materials. Combined with techniques of photohardenable, microcapsule, heat-sensitive and interface-polymerization method, a novel photoheat sensitive recording material of non-silver salt is explored in this thesis. Microcapsules are particulate substance with a core and shell structure, where photopolymerizable composition, monofunctional/polyfunctional diluents, photopolymerization initiator, photosensitivity enhancing agent and dye precursor are encapsulated as the internal phase. In this paper introduced the characteristics and curing mechanism of photo-sensitive microcapsule materials. The photocuring process may be a complex-function with photopolymerizable compound and photopolymerization initiator. For the sake of high photocuring speed and degree, optimal photo-sensitive materials were selected. In order to match with the light source excitation wavelength and absorb more wider ultraviolet band, combined type of photo-polymerization initiators were employed. With the kinds and dosage of photopolymerization initiator changing, the photocuring speed and quality can be ameliorated. Through studying the UV-visible absorption spectrum and infra-red spectrum of the material , the optical response property of the inner compound can be obtained.

Maternal Dispositional Empathy and Electrodermal Reactivity: Interactive Contributions to Maternal Sensitivity with Toddler-Aged Children

PubMed Central

Emery, Helen T.; McElwain, Nancy L.; Groh, Ashley M.; Haydon, Katherine C.; Roisman, Glenn I.

2015-01-01

The present study investigated maternal dispositional empathy and skin conductance level (SCL) reactivity to infant emotional cues as joint predictors of maternal sensitivity. Sixty-four mother-toddler dyads (31 boys) were observed across a series of interaction tasks during a laboratory visit, and maternal sensitivity was coded from approximately 55 minutes of observation per family. In a second, mother-only laboratory visit, maternal SCL reactivity to infant cues was assessed using a cry-laugh audio paradigm. Mothers reported on their dispositional empathy via a questionnaire. As hypothesized, mothers with greater dispositional empathy exhibited more sensitive behavior at low, but not high, levels of SCL reactivity to infant cues. Analyses examining self-reported emotional reactivity to the cry-laugh audio paradigm yielded a similar finding: dispositional empathy was related to greater sensitivity when mothers reported low, but not high, negative emotional reactivity. Results provide support for Dix’s (1991) affective model of parenting that underscores the combined contribution of the parent’s empathic tendencies and his/her own emotional experience in response to child emotions. Specificity of the Empathy × Reactivity interaction is discussed with respect to the context in which reactivity was assessed (infant cry versus laugh) and the type of sensitivity examined (sensitivity to the child’s distress versus non-distress). PMID:24955589

Maternal dispositional empathy and electrodermal reactivity: Interactive contributions to maternal sensitivity with toddler-aged children.

PubMed

Emery, Helen T; McElwain, Nancy L; Groh, Ashley M; Haydon, Katherine C; Roisman, Glenn I

2014-08-01

The present study investigated maternal dispositional empathy and skin conductance level (SCL) reactivity to infant emotional cues as joint predictors of maternal sensitivity. Sixty-four mother-toddler dyads (31 boys) were observed across a series of interaction tasks during a laboratory visit, and maternal sensitivity was coded from approximately 55 minutes of observation per family. In a second, mother-only laboratory visit, maternal SCL reactivity to infant cues was assessed using a cry-laugh audio paradigm. Mothers reported on their dispositional empathy via a questionnaire. As hypothesized, mothers with greater dispositional empathy exhibited more sensitive behavior at low, but not high, levels of SCL reactivity to infant cues. Analyses examining self-reported emotional reactivity to the cry-laugh audio paradigm yielded a similar finding: Dispositional empathy was related to greater sensitivity when mothers reported low, but not high, negative emotional reactivity. Results provide support for Dix's (1991) affective model of parenting that underscores the combined contribution of the parent's empathic tendencies and his or her own emotional experience in response to child emotions. Specificity of the Empathy × Reactivity interaction is discussed with respect to the context in which reactivity was assessed (infant cry vs. laugh) and the type of sensitivity examined (sensitivity to the child's distress vs. nondistress).

A highly sensitive search strategy for clinical trials in Literatura Latino Americana e do Caribe em Ciências da Saúde (LILACS) was developed.

PubMed

Manríquez, Juan J

2008-04-01

Systematic reviews should include as many articles as possible. However, many systematic reviews use only databases with high English language content as sources of trials. Literatura Latino Americana e do Caribe em Ciências da Saúde (LILACS) is an underused source of trials, and there is not a validated strategy for searching clinical trials to be used in this database. The objective of this study was to develop a sensitive search strategy for clinical trials in LILACS. An analytical survey was performed. Several single and multiple-term search strategies were tested for their ability to retrieve clinical trials in LILACS. Sensitivity, specificity, and accuracy of each single and multiple-term strategy were calculated using the results of a hand-search of 44 Chilean journals as gold standard. After combining the most sensitive, specific, and accurate single and multiple-term search strategy, a strategy with a sensitivity of 97.75% (95% confidence interval [CI]=95.98-99.53) and a specificity of 61.85 (95% CI=61.19-62.51) was obtained. LILACS is a source of trials that could improve systematic reviews. A new highly sensitive search strategy for clinical trials in LILACS has been developed. It is hoped this search strategy will improve and increase the utilization of LILACS in future systematic reviews.

Detection of thermal-induced prompt fission neutrons of highly-enriched uranium: A position sensitive technique

NASA Astrophysics Data System (ADS)

Tartaglione, A.; Di Lorenzo, F.; Mayer, R. E.

2009-07-01

Cargo interrogation in search for special nuclear materials like highly-enriched uranium or 239Pu is a first priority issue of international borders security. In this work we present a thermal-pulsed neutron-based approach to a technique which combines the time-of-flight method and demonstrates a capability to detect small quantities of highly-enriched uranium shielded with high or low Z materials providing, in addition, a manner to know the approximate position of the searched material.

A microelectromechanical systems (MEMS) force-displacement transducer for sub-5 nm nanoindentation and adhesion measurements

NASA Astrophysics Data System (ADS)

Zhang, Youfeng; Oh, Yunje; Stauffer, Douglas; Polycarpou, Andreas A.

2018-04-01

We present a highly sensitive force-displacement transducer capable of performing ultra-shallow nanoindentation and adhesion measurements. The transducer utilizes electrostatic actuation and capacitive sensing combined with microelectromechanical fabrication technologies. Air indentation experiments report a root-mean-square (RMS) force resolution of 1.8 nN and an RMS displacement resolution of 0.019 nm. Nanoindentation experiments on a standard fused quartz sample report a practical RMS force resolution of 5 nN and an RMS displacement resolution of 0.05 nm at sub-10 nm indentation depths, indicating that the system has a very low system noise for indentation experiments. The high sensitivity and low noise enables the transducer to obtain high-resolution nanoindentation data at sub-5 nm contact depths. The sensitive force transducer is used to successfully perform nanoindentation measurements on a 14 nm thin film. Adhesion measurements were also performed, clearly capturing the pull-on and pull-off forces during approach and separation of two contacting surfaces.

Sensitizers in EUV chemically amplified resist: mechanism of sensitivity improvement

NASA Astrophysics Data System (ADS)

Vesters, Yannick; Jiang, Jing; Yamamoto, Hiroki; De Simone, Danilo; Kozawa, Takahiro; De Gendt, Stefan; Vandenberghe, Geert

2018-03-01

EUV lithography utilizes photons with 91.6 eV energy to ionize resists, generate secondary electrons, and enable electron driven reactions that produce acid in chemically amplified photoresist. Efficiently using the available photons is of key importance. Unlike DUV lithography, where photons are selectively utilized by photoactive compounds, photons at 13.5nm wavelength ionize almost all materials. Nevertheless, specific elements have a significantly higher atomic photon-absorption cross section at 91.6 eV. To increase photon absorption, sensitizer molecules, containing highly absorbing elements, can be added to photoresist formulations. These sensitizers have gained growing attention in recent years, showing significant sensitivity improvement. But there are few experimental evidences that the sensitivity improvement is due to the higher absorption only, as adding metals salts into the resist formulation can induce other mechanisms, like modification of the dissolution rate, potentially affecting patterning performance. In this work, we used different sensitizers in chemically amplified resist. We measured experimentally the absorption of EUV light, the acid yield, the dissolution rate and the patterning performance of the resists. Surprisingly, the absorption of EUV resist was decreased with addition of metal salt sensitizers. Nevertheless, the resist with sensitizer showed a higher acid yield. Sensitizer helps achieving higher PAG conversion to acid, notably due to an increase of the secondary electron generation. Patterning data confirm a significant sensitivity improvement, but at the cost of roughness degradation at high sensitizer loading. This can be explained by the chemical distribution of the sensitizer in the resist combined with a modification of the dissolution contrast, as observed by Dissolution Rate Monitor.

Genotypic tropism testing by massively parallel sequencing: qualitative and quantitative analysis.

PubMed

Däumer, Martin; Kaiser, Rolf; Klein, Rolf; Lengauer, Thomas; Thiele, Bernhard; Thielen, Alexander

2011-05-13

Inferring viral tropism from genotype is a fast and inexpensive alternative to phenotypic testing. While being highly predictive when performed on clonal samples, sensitivity of predicting CXCR4-using (X4) variants drops substantially in clinical isolates. This is mainly attributed to minor variants not detected by standard bulk-sequencing. Massively parallel sequencing (MPS) detects single clones thereby being much more sensitive. Using this technology we wanted to improve genotypic prediction of coreceptor usage. Plasma samples from 55 antiretroviral-treated patients tested for coreceptor usage with the Monogram Trofile Assay were sequenced with standard population-based approaches. Fourteen of these samples were selected for further analysis with MPS. Tropism was predicted from each sequence with geno2pheno[coreceptor]. Prediction based on bulk-sequencing yielded 59.1% sensitivity and 90.9% specificity compared to the trofile assay. With MPS, 7600 reads were generated on average per isolate. Minorities of sequences with high confidence in CXCR4-usage were found in all samples, irrespective of phenotype. When using the default false-positive-rate of geno2pheno[coreceptor] (10%), and defining a minority cutoff of 5%, the results were concordant in all but one isolate. The combination of MPS and coreceptor usage prediction results in a fast and accurate alternative to phenotypic assays. The detection of X4-viruses in all isolates suggests that coreceptor usage as well as fitness of minorities is important for therapy outcome. The high sensitivity of this technology in combination with a quantitative description of the viral population may allow implementing meaningful cutoffs for predicting response to CCR5-antagonists in the presence of X4-minorities.

Multi-Country Evaluation of the Sensitivity and Specificity of Two Commercially-Available NS1 ELISA Assays for Dengue Diagnosis

PubMed Central

Guzman, Maria G.; Jaenisch, Thomas; Gaczkowski, Roger; Ty Hang, Vo Thi; Sekaran, Shamala Devi; Kroeger, Axel; Vazquez, Susana; Ruiz, Didye; Martinez, Eric; Mercado, Juan C.; Balmaseda, Angel; Harris, Eva; Dimano, Efren; Leano, Prisca Susan A.; Yoksan, Sutee; Villegas, Elci; Benduzu, Herminia; Villalobos, Iris; Farrar, Jeremy; Simmons, Cameron P.

2010-01-01

Background Early diagnosis of dengue can assist patient triage and management and prevent unnecessary treatments and interventions. Commercially available assays that detect the dengue virus protein NS1 in the plasma/serum of patients offers the possibility of early and rapid diagnosis. Methodology/Principal Findings The sensitivity and specificity of the Pan-E Dengue Early ELISA and the Platelia™ Dengue NS1 Ag assays were compared against a reference diagnosis in 1385 patients in 6 countries in Asia and the Americas. Platelia was more sensitive (66%) than Pan-E (52%) in confirmed dengue cases. Sensitivity varied by geographic region, with both assays generally being more sensitive in patients from SE Asia than the Americas. Both kits were more sensitive for specimens collected within the first few days of illness onset relative to later time points. Pan-E and Platelia were both 100% specific in febrile patients without evidence of acute dengue. In patients with other confirmed diagnoses and healthy blood donors, Platelia was more specific (100%) than Pan-E (90%). For Platelia, when either the NS1 test or the IgM test on the acute sample was positive, the sensitivity versus the reference result was 82% in samples collected in the first four days of fever. NS1 sensitivity was not associated to disease severity (DF or DHF) in the Platelia test, whereas a trend for higher sensitivity in DHF cases was seen in the Pan-E test (however combined with lower overall sensitivity). Conclusions/Significance Collectively, this multi-country study suggests that the best performing NS1 assay (Platelia) had moderate sensitivity (median 64%, range 34–76%) and high specificity (100%) for the diagnosis of dengue. The poor sensitivity of the evaluated assays in some geographical regions suggests further assessments are needed. The combination of NS1 and IgM detection in samples collected in the first few days of fever increased the overall dengue diagnostic sensitivity. PMID:20824173

Predictive genetic testing for the identification of high-risk groups: a simulation study on the impact of predictive ability

PubMed Central

2011-01-01

Background Genetic risk models could potentially be useful in identifying high-risk groups for the prevention of complex diseases. We investigated the performance of this risk stratification strategy by examining epidemiological parameters that impact the predictive ability of risk models. Methods We assessed sensitivity, specificity, and positive and negative predictive value for all possible risk thresholds that can define high-risk groups and investigated how these measures depend on the frequency of disease in the population, the frequency of the high-risk group, and the discriminative accuracy of the risk model, as assessed by the area under the receiver-operating characteristic curve (AUC). In a simulation study, we modeled genetic risk scores of 50 genes with equal odds ratios and genotype frequencies, and varied the odds ratios and the disease frequency across scenarios. We also performed a simulation of age-related macular degeneration risk prediction based on published odds ratios and frequencies for six genetic risk variants. Results We show that when the frequency of the high-risk group was lower than the disease frequency, positive predictive value increased with the AUC but sensitivity remained low. When the frequency of the high-risk group was higher than the disease frequency, sensitivity was high but positive predictive value remained low. When both frequencies were equal, both positive predictive value and sensitivity increased with increasing AUC, but higher AUC was needed to maximize both measures. Conclusions The performance of risk stratification is strongly determined by the frequency of the high-risk group relative to the frequency of disease in the population. The identification of high-risk groups with appreciable combinations of sensitivity and positive predictive value requires higher AUC. PMID:21797996

High-Sensitivity C-Reactive Protein as a Predictor of Cardiovascular Events after ST-Elevation Myocardial Infarction

PubMed Central

Ribeiro, Daniel Rios Pinto; Ramos, Adriane Monserrat; Vieira, Pedro Lima; Menti, Eduardo; Bordin, Odemir Luiz; de Souza, Priscilla Azambuja Lopes; de Quadros, Alexandre Schaan; Portal, Vera Lúcia

2014-01-01

Background The association between high-sensitivity C-reactive protein and recurrent major adverse cardiovascular events (MACE) in patients with ST-elevation myocardial infarction who undergo primary percutaneous coronary intervention remains controversial. Objective To investigate the potential association between high-sensitivity C-reactive protein and an increased risk of MACE such as death, heart failure, reinfarction, and new revascularization in patients with ST-elevation myocardial infarction treated with primary percutaneous coronary intervention. Methods This prospective cohort study included 300 individuals aged >18 years who were diagnosed with ST-elevation myocardial infarction and underwent primary percutaneous coronary intervention at a tertiary health center. An instrument evaluating clinical variables and the Thrombolysis in Myocardial Infarction (TIMI) and Global Registry of Acute Coronary Events (GRACE) risk scores was used. High-sensitivity C-reactive protein was determined by nephelometry. The patients were followed-up during hospitalization and up to 30 days after infarction for the occurrence of MACE. Student's t, Mann-Whitney, chi-square, and logistic regression tests were used for statistical analyses. P values of ≤0.05 were considered statistically significant. Results The mean age was 59.76 years, and 69.3% of patients were male. No statistically significant association was observed between high-sensitivity C-reactive protein and recurrent MACE (p = 0.11). However, high-sensitivity C-reactive protein was independently associated with 30-day mortality when adjusted for TIMI [odds ratio (OR), 1.27; 95% confidence interval (CI), 1.07-1.51; p = 0.005] and GRACE (OR, 1.26; 95% CI, 1.06-1.49; p = 0.007) risk scores. Conclusion Although high-sensitivity C-reactive protein was not predictive of combined major cardiovascular events within 30 days after ST-elevation myocardial infarction in patients who underwent primary angioplasty and stent implantation, it was an independent predictor of 30-day mortality. PMID:25120085

The reliability and validity of using the urine dipstick test by patient self-assessment for urinary tract infection screening in spinal cord injury patients.

PubMed

Duanngai, Krit; Sirasaporn, Patpiya; Ngaosinchai, Siriwan Surapaitoon

2017-01-01

The aim of this is to evaluate the reliability of the urine dipstick test by patients' self-assessment for urinary tract infection (UTI) screening and to determine the validity of urine dipstick test. Rehabilitation Department, Srinagarind Hospital, Thailand. A diagnostic study. This study compared the urine dipstick test (index test) with the National Institute on Disability and Rehabilitation Research (NIDRR) criteria (gold standard test) in spinal cord injury (SCI) patients. The urine dipstick test informed positive and negative results. Besides the NIDRR criteria classified as UTI and no UTI. The interrater reliability was measured in the sense of Kappa whereas the validity of urine dipstick test was reported in terms of sensitivity, specificity, positive likelihood ratio (LR) (+LR), negative LR (-LR), positive predictive value (PPV), and negative predictive value (NPV). Out of the 56 participants, the kappa of urine dipstick test for leukocyte esterase, nitrite, and combined leukocyte esterase and nitrite were 0.09, 0.21, and 0.52, respectively. The nitrite urine dipstick test showed the highest sensitivity (90%). The combined leukocyte esterase and nitrite urine dipstick test gave the highest specificity (87%), PPV (60%), NPV (93%), and +LR (5.63). The interrater reliability of combined leukocyte esterase and nitrite urine dipstick test was moderate agreement. The combined leukocyte esterase and nitrite urine dipstick test showed high level of both sensitivity and specificity. The combined leukocyte esterase and nitrite urine dipstick test should be promoted for patients' self-assessment for UTI screening in SCI patients.

Fasting boosts sensitivity of human skin melanoma to cisplatin-induced cell death

DOE Office of Scientific and Technical Information (OSTI.GOV)

Antunes, Fernanda; Corazzari, Marco; National Institute for Infectious Diseases IRCCS “Lazzaro Spallanzani”

Melanoma is one of leading cause of tumor death worldwide. Anti-cancer strategy includes combination of different chemo-therapeutic agents as well as radiation; however these treatments have limited efficacy and induce significant toxic effects on healthy cells. One of most promising novel therapeutic approach to cancer therapy is the combination of anti-cancer drugs with calorie restriction. Here we investigated the effect Cisplatin (CDDP), one of the most potent chemotherapeutic agent used to treat tumors, in association with fasting in wild type and mutated BRAF{sup V600E} melanoma cell lines. Here we show that nutrient deprivation can consistently enhance the sensitivity of tumormore » cells to cell death induction by CDDP, also of those malignancies particularly resistant to any treatment, such as oncogenic BRAF melanomas. Mechanistic studies revealed that the combined therapy induced cell death is characterized by ROS accumulation and ATF4 in the absence of ER-stress. In addition, we show that autophagy is not involved in the enhanced sensitivity of melanoma cells to combined CDDP/EBSS-induced apoptosis. While, the exposure to 2-DG further enhanced the apoptotic rate observed in SK Mel 28 cells upon treatment with both CDDP and EBSS. - Highlights: • Calorie restriction associated to chemo-therapeutic drugs enhance cell death induction in many resistant malignancies • Cisplatin in association with starvation significantly increases cell death also in those high resistant melanoma cells bearing BRAF mutations • Combined treatment also including 2-DG results in similar cell death levels in both wild type and mutated BRAF cells.« less

Improved Pancreatic Adenocarcinoma Diagnosis in Jaundiced and Non-Jaundiced Pancreatic Adenocarcinoma Patients through the Combination of Routine Clinical Markers Associated to Pancreatic Adenocarcinoma Pathophysiology.

PubMed

Ferri, María José; Saez, Marc; Figueras, Joan; Fort, Esther; Sabat, Miriam; López-Ben, Santiago; de Llorens, Rafael; Aleixandre, Rosa Núria; Peracaula, Rosa

2016-01-01

There is still no reliable biomarker for the diagnosis of pancreatic adenocarcinoma. Carbohydrate antigen 19-9 (CA 19-9) is a tumor marker only recommended for pancreatic adenocarcinoma follow-up. One of the clinical problems lies in distinguishing between this cancer and other benign pancreatic diseases such as chronic pancreatitis. In this study we will assess the value of panels of serum molecules related to pancreatic cancer physiopathology to determine whether alone or in combination could help to discriminate between these two pathologies. CA 19-9, carcinoembryonic antigen (CEA), C-reactive protein, albumin, insulin growth factor-1 (IGF-1) and IGF binding protein-3 were measured using routine clinical analyzers in a cohort of 47 pancreatic adenocarcinoma, 20 chronic pancreatitis and 15 healthy controls. The combination of CA 19-9, IGF-1 and albumin resulted in a combined area under the curve (AUC) of 0.959 with 93.6% sensitivity and 95% specificity, much higher than CA 19-9 alone. An algorithm was defined to classify the patients as chronic pancreatitis or pancreatic cancer with the above specificity and sensitivity. In an independent validation group of 20 pancreatic adenocarcinoma and 13 chronic pancreatitis patients, the combination of the four molecules classified correctly all pancreatic adenocarcinoma and 12 out of 13 chronic pancreatitis patients. Although this panel of markers should be validated in larger cohorts, the high sensitivity and specificity values and the convenience to measure these parameters in clinical laboratories shows great promise for improving pancreatic adenocarcinoma diagnosis.

Usefulness of combining gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging and contrast-enhanced ultrasound for diagnosing the macroscopic classification of small hepatocellular carcinoma.

PubMed

Kobayashi, Tomoki; Aikata, Hiroshi; Hatooka, Masahiro; Morio, Kei; Morio, Reona; Kan, Hiromi; Fujino, Hatsue; Fukuhara, Takayuki; Masaki, Keiichi; Ohno, Atsushi; Naeshiro, Noriaki; Nakahara, Takashi; Honda, Yohji; Murakami, Eisuke; Kawaoka, Tomokazu; Tsuge, Masataka; Hiramatsu, Akira; Imamura, Michio; Kawakami, Yoshiiku; Hyogo, Hideyuki; Takahashi, Shoichi; Chayama, Kazuaki

2015-11-01

Non-simple nodules in hepatocellular carcinoma (HCC) correlate with poor prognosis. Therefore, we examined the diagnostic ability of gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging (EOB-MRI) and contrast-enhanced ultrasound (CEUS) for diagnosing the macroscopic classification of small HCCs. A total of 85 surgically resected nodules (≤30 mm) were analyzed. HCCs were pathologically classified as simple nodular (SN) and non-SN. By evaluating hepatobiliary phase (HBP) of EOB-MRI and Kupffer phase of CEUS, the diagnostic abilities of both modalities to correctly distinguish between SN and non-SN were compared. Forty-six nodules were diagnosed as SN and the remaining 39 nodules as non-SN. The area under the ROC curve (AUROCs, 95% confidence interval) for the diagnosis of non-SN were EOB-MRI, 0.786 (0.682-0.890): CEUS, 0.784 (0.679-0.889), in combination, 0.876 (0.792-0.959). The sensitivity, specificity, and accuracy were 64.1%, 95.7%, and 81.2% in EOB-MRI, 56.4%, 97.8%, and 78.8% in CEUS, and 84.6%, 95.7%, and 90.6% in combination, respectively. High diagnostic ability was obtained when diagnosed in both modalities combined. The sensitivity was especially statistically significant compared to CEUS. Combined diagnosis by EOB-MRI and CEUS can provide high-quality imaging assessment for determining non-SN in small HCCs. • Non-SN has a higher frequency of MVI and intrahepatic metastasis than SN. • Macroscopic classification is useful to choose the treatment strategy for small HCCs. • Diagnostic ability for macroscopic findings of EOB-MRI and CEUS were statistically equal. • The diagnosis of macroscopic findings by individual modality has limitations. • Combined diagnosis of EOB-MRI and CEUS provides high diagnostic ability.

Development of gamma-photon/Cerenkov-light hybrid system for simultaneous imaging of I-131 radionuclide

NASA Astrophysics Data System (ADS)

Yamamoto, Seiichi; Suzuki, Mayumi; Kato, Katsuhiko; Watabe, Tadashi; Ikeda, Hayato; Kanai, Yasukazu; Ogata, Yoshimune; Hatazawa, Jun

2016-09-01

Although iodine 131 (I-131) is used for radionuclide therapy, high resolution images are difficult to obtain with conventional gamma cameras because of the high energy of I-131 gamma photons (364 keV). Cerenkov-light imaging is a possible method for beta emitting radionuclides, and I-131 (606 MeV maximum beta energy) is a candidate to obtain high resolution images. We developed a high energy gamma camera system for I-131 radionuclide and combined it with a Cerenkov-light imaging system to form a gamma-photon/Cerenkov-light hybrid imaging system to compare the simultaneously measured images of these two modalities. The high energy gamma imaging detector used 0.85-mm×0.85-mm×10-mm thick GAGG scintillator pixels arranged in a 44×44 matrix with a 0.1-mm thick reflector and optical coupled to a Hamamatsu 2 in. square position sensitive photomultiplier tube (PSPMT: H12700 MOD). The gamma imaging detector was encased in a 2 cm thick tungsten shield, and a pinhole collimator was mounted on its top to form a gamma camera system. The Cerenkov-light imaging system was made of a high sensitivity cooled CCD camera. The Cerenkov-light imaging system was combined with the gamma camera using optical mirrors to image the same area of the subject. With this configuration, we simultaneously imaged the gamma photons and the Cerenkov-light from I-131 in the subjects. The spatial resolution and sensitivity of the gamma camera system for I-131 were respectively 3 mm FWHM and 10 cps/MBq for the high sensitivity collimator at 10 cm from the collimator surface. The spatial resolution of the Cerenkov-light imaging system was 0.64 mm FWHM at 10 cm from the system surface. Thyroid phantom and rat images were successfully obtained with the developed gamma-photon/Cerenkov-light hybrid imaging system, allowing direct comparison of these two modalities. Our developed gamma-photon/Cerenkov-light hybrid imaging system will be useful to evaluate the advantages and disadvantages of these two modalities.

Prediction of genotoxic potential of cosmetic ingredients by an in silico battery system consisting of a combination of an expert rule-based system and a statistics-based system.

PubMed

Aiba née Kaneko, Maki; Hirota, Morihiko; Kouzuki, Hirokazu; Mori, Masaaki

2015-02-01

Genotoxicity is the most commonly used endpoint to predict the carcinogenicity of chemicals. The International Conference on Harmonization (ICH) M7 Guideline on Assessment and Control of DNA Reactive (Mutagenic) Impurities in Pharmaceuticals to Limit Potential Carcinogenic Risk offers guidance on (quantitative) structure-activity relationship ((Q)SAR) methodologies that predict the outcome of bacterial mutagenicity assay for actual and potential impurities. We examined the effectiveness of the (Q)SAR approach with the combination of DEREK NEXUS as an expert rule-based system and ADMEWorks as a statistics-based system for the prediction of not only mutagenic potential in the Ames test, but also genotoxic potential in mutagenicity and clastogenicity tests, using a data set of 342 chemicals extracted from the literature. The prediction of mutagenic potential or genotoxic potential by DEREK NEXUS or ADMEWorks showed high values of sensitivity and concordance, while prediction by the combination of DEREK NEXUS and ADMEWorks (battery system) showed the highest values of sensitivity and concordance among the three methods, but the lowest value of specificity. The number of false negatives was reduced with the battery system. We also separately predicted the mutagenic potential and genotoxic potential of 41 cosmetic ingredients listed in the International Nomenclature of Cosmetic Ingredients (INCI) among the 342 chemicals. Although specificity was low with the battery system, sensitivity and concordance were high. These results suggest that the battery system consisting of DEREK NEXUS and ADMEWorks is useful for prediction of genotoxic potential of chemicals, including cosmetic ingredients.

Periprosthetic infection: where do we stand with regard to Gram stain?

PubMed

Ghanem, Elie; Ketonis, Constantinos; Restrepo, Camilo; Joshi, Ashish; Barrack, Robert; Parvizi, Javad

2009-02-01

One of the routinely used intraoperative tests for diagnosis of periprosthetic infection (PPI) is the Gram stain. It is not known if the result of this test can vary according to the type of joint affected or the number of specimen samples collected. We examined the role of this diagnostic test in a large cohort of patients from a single institution. A positive gram stain was defined as the visualization of bacterial cells or "many neutrophils" (> 5 per high-power field) in the smear. The sensitivity, specificity, and predictive values of each individual diagnostic arm of Gram stain were determined. Combinations were performed in series, which required both tests to be positive to confirm infection, and also in parallel, which necessitated both tests to be negative to rule out infection. The presence of organisms and "many" neutrophils on a Gram smear had high specificity (98-100%) and positive predictive value (89-100%) in both THA and TKA. The sensitivities (30-50%) and negative predictive values (70-79%) of the 2 tests were low for both joint types. When the 2 tests were combined in series, the specificity and positive predictive value were absolute (100%). The sensitivity and the negative predictive value improved for both THA and TKA (43-64% and 82%, respectively). Although the 2 diagnostic arms of Gram staining can be combined to achieve improved negative predictive value (82%), Gram stain continues to have little value in ruling out PPI. With the advances in the field of molecular biology, novel diagnostic modalities need to be designed that can replace these traditional and poor tests.

Crizotinib Synergizes with Chemotherapy in Preclinical Models of Neuroblastoma

PubMed Central

Krytska, Kateryna; Ryles, Hannah T.; Sano, Renata; Raman, Pichai; Infarinato, Nicole R.; Hansel, Theodore D.; Makena, Monish R.; Song, Michael M.; Reynolds, C. Patrick; Mossé, Yael P.

2015-01-01

Purpose The presence of an ALK aberration correlates with inferior survival for patients with high-risk neuroblastoma. The emergence of ALK inhibitors such as crizotinib has provided novel treatment opportunities. However, certain ALK mutations result in de novo crizotinib resistance, and a phase I trial of crizotinib showed a lack of response in patients harboring those ALK mutations. Thus, understanding mechanisms of resistance and defining circumvention strategies for the clinic is critical. Experimental Design The sensitivity of human neuroblastoma-derived cell lines, cell line-derived and patient-derived xenograft (PDX) models with varying ALK statuses to crizotinib combined with topotecan and cyclophosphamide (topo/cyclo) was examined. Cultured cells and xenografts were evaluated for effects of these drugs on proliferation, signaling, and cell death, and assessment of synergy. Results In neuroblastoma murine xenografts harboring the most common ALK mutations, including those mutations associated with resistance to crizotinib (but not in those with wild-type ALK), crizotinib combined with topo/cyclo enhanced tumor responses and mouse event-free-survival. Crizotinib + topo/cyclo showed synergistic cytotoxicity and higher caspase-dependent apoptosis than crizotinib or topo/cyclo alone in neuroblastoma cell lines with ALK aberrations (mutation or amplification). Conclusions Combining crizotinib with chemotherapeutic agents commonly used in treating newly diagnosed patients with high-risk neuroblastoma restores sensitivity in preclinical models harboring both sensitive ALK aberrations and de novo resistant ALK mutations. These data support clinical testing of crizotinib and conventional chemotherapy with the goal of integrating ALK inhibition into multi-agent therapy for ALK-aberrant neuroblastoma patients. PMID:26438783

Effect of Microstructure and Alloy Chemistry on Hydrogen Embrittlement of Precipitation-Hardened Ni-Based Alloys

NASA Astrophysics Data System (ADS)

Obasi, G. C.; Zhang, Z.; Sampath, D.; Morana, Roberto; Akid, R.; Preuss, M.

2018-04-01

The sensitivity to hydrogen embrittlement (HE) has been studied in respect of precipitation size distributions in two nickel-based superalloys: Alloy 718 (UNS N07718) and Alloy 945X (UNS N09946). Quantitative microstructure analysis was carried out by the combination of scanning and transmission electron microscopy and energy dispersive x-ray spectroscopy (EDS). While Alloy 718 is mainly strengthened by γ″, and therefore readily forms intergranular δ phase, Alloy 945X has been designed to avoid δ formation by reducing Nb levels providing high strength through a combination of γ' and γ″. Slow strain rate tensile tests were carried out for different microstructural conditions in air and after cathodic hydrogen (H) charging. HE sensitivity was determined based on loss of elongation due to the H uptake in comparison to elongation to failure in air. Results showed that both alloys exhibited an elevated sensitivity to HE. Fracture surfaces of the H precharged material showed quasi-cleavage and transgranular cracks in the H-affected region, while ductile failure was observed toward the center of the sample. The crack origins observed on the H precharged samples exhibited quasi-cleavage with slip traces at high magnification. The sensitivity is slightly reduced for Alloy 718, by coarsening γ″ and reducing the overall strength of the alloy. However, on further coarsening of γ″, which promotes continuous decoration of grain boundaries with δ phase, the embrittlement index rose again indicating a change of hydrogen embrittlement mechanism from hydrogen-enhanced local plasticity (HELP) to hydrogen-enhanced decohesion embrittlement (HEDE). In contrast, Alloy 945X displayed a strong correlation between strength, based on precipitation size and embrittlement index, due to the absence of any significant formation of δ phase for the investigated microstructures. For the given test parameters, Alloy 945X did not display any reduced sensitivity to HE compared with Alloy 718 when considering high-strength conditions despite the absence of intergranular δ phase.

Modular, Antibody-free Time-Resolved LRET Kinase Assay Enabled by Quantum Dots and Tb3+-sensitizing Peptides

NASA Astrophysics Data System (ADS)

Cui, Wei; Parker, Laurie L.

2016-07-01

Fluorescent drug screening assays are essential for tyrosine kinase inhibitor discovery. Here we demonstrate a flexible, antibody-free TR-LRET kinase assay strategy that is enabled by the combination of streptavidin-coated quantum dot (QD) acceptors and biotinylated, Tb3+ sensitizing peptide donors. By exploiting the spectral features of Tb3+ and QD, and the high binding affinity of the streptavidin-biotin interaction, we achieved multiplexed detection of kinase activity in a modular fashion without requiring additional covalent labeling of each peptide substrate. This strategy is compatible with high-throughput screening, and should be adaptable to the rapidly changing workflows and targets involved in kinase inhibitor discovery.

Stable Fe nanomagnets encapsulated inside vertically-aligned carbon nanotubes.

PubMed

Bondino, Federica; Magnano, Elena; Ciancio, Regina; Castellarin Cudia, Carla; Barla, Alessandro; Carlino, Elvio; Yakhou-Harris, Flora; Rupesinghe, Nalin; Cepek, Cinzia

2017-12-06

Well-defined sized (5-10 nm) metallic iron nanoparticles (NPs) with body-centered cubic structure encapsulated inside the tip of millimeter-long vertically aligned carbon nanotubes (VACNTs) of uniform length have been investigated with high-resolution transmission electron microscopy and soft X-ray spectroscopy techniques. Surface-sensitive and chemically-selective measurements have been used to evaluate the magnetic properties of the encapsulated NPs. The encapsulated Fe NPs display magnetic remanence up to room temperature, low coercivity, high chemical stability and no significant anisotropy. Our surface-sensitive measurements combined with the specific morphology of the studied VACNTs allow us to pinpoint the contribution of the surface oxidized or hydroxidized iron catalysts present at the VACNT-substrate interface.

Convenient, sensitive and high-throughput method for screening botanic origin.

PubMed

Yuan, Yuan; Jiang, Chao; Liu, Libing; Yu, Shulin; Cui, Zhanhu; Chen, Min; Lin, Shufang; Wang, Shu; Huang, Luqi

2014-06-23

In this work, a rapid (within 4-5 h), sensitive and visible new method for assessing botanic origin is developed by combining loop-mediated isothermal amplification with cationic conjugated polymers. The two Chinese medicinal materials (Jin-Yin-Hua and Shan-Yin-Hua) with similar morphology and chemical composition were clearly distinguished by gene SNP genotyping assays. The identification of plant species in Patented Chinese drugs containing Lonicera buds is successfully performed using this detection system. The method is also robust enough to be used in high-throughput screening. This new method is very helpful to identify herbal materials, and is beneficial for detecting safety and quality of botanic products.

Analysis of single quantum-dot mobility inside 1D nanochannel devices

NASA Astrophysics Data System (ADS)

Hoang, H. T.; Segers-Nolten, I. M.; Tas, N. R.; van Honschoten, J. W.; Subramaniam, V.; Elwenspoek, M. C.

2011-07-01

We visualized individual quantum dots using a combination of a confining nanochannel and an ultra-sensitive microscope system, equipped with a high numerical aperture lens and a highly sensitive camera. The diffusion coefficients of the confined quantum dots were determined from the experimentally recorded trajectories according to the classical diffusion theory for Brownian motion in two dimensions. The calculated diffusion coefficients were three times smaller than those in bulk solution. These observations confirm and extend the results of Eichmann et al (2008 Langmuir 24 714-21) to smaller particle diameters and more narrow confinement. A detailed analysis shows that the observed reduction in mobility cannot be explained by conventional hydrodynamic theory.

Biomagnetic separation of Salmonella Typhimurium with high affine and specific ligand peptides isolated by phage display technique

NASA Astrophysics Data System (ADS)

Steingroewer, Juliane; Bley, Thomas; Bergemann, Christian; Boschke, Elke

2007-04-01

Analyses of food-borne pathogens are of great importance in order to minimize the health risk for customers. Thus, very sensitive and rapid detection methods are required. Current conventional culture techniques are very time consuming. Modern immunoassays and biochemical analysis also require pre-enrichment steps resulting in a turnaround time of at least 24 h. Biomagnetic separation (BMS) is a promising more rapid method. In this study we describe the isolation of high affine and specific peptides from a phage-peptide library, which combined with BMS allows the detection of Salmonella spp. with a similar sensitivity as that of immunomagnetic separation using antibodies.

Ultrafast and nonlinear surface-enhanced Raman spectroscopy.

PubMed

Gruenke, Natalie L; Cardinal, M Fernanda; McAnally, Michael O; Frontiera, Renee R; Schatz, George C; Van Duyne, Richard P

2016-04-21

Ultrafast surface-enhanced Raman spectroscopy (SERS) has the potential to study molecular dynamics near plasmonic surfaces to better understand plasmon-mediated chemical reactions such as plasmonically-enhanced photocatalytic or photovoltaic processes. This review discusses the combination of ultrafast Raman spectroscopic techniques with plasmonic substrates for high temporal resolution, high sensitivity, and high spatial resolution vibrational spectroscopy. First, we introduce background information relevant to ultrafast SERS: the mechanisms of surface enhancement in Raman scattering, the characterization of plasmonic materials with ultrafast techniques, and early complementary techniques to study molecule-plasmon interactions. We then discuss recent advances in surface-enhanced Raman spectroscopies with ultrafast pulses with a focus on the study of molecule-plasmon coupling and molecular dynamics with high sensitivity. We also highlight the challenges faced by this field by the potential damage caused by concentrated, highly energetic pulsed fields in plasmonic hotspots, and finally the potential for future ultrafast SERS studies.

Targeted inhibition of histone H3K27 demethylation is effective in high-risk neuroblastoma.

PubMed

Lochmann, Timothy L; Powell, Krista M; Ham, Jungoh; Floros, Konstantinos V; Heisey, Daniel A R; Kurupi, Richard I J; Calbert, Marissa L; Ghotra, Maninderjit S; Greninger, Patricia; Dozmorov, Mikhail; Gowda, Madhu; Souers, Andrew J; Reynolds, C Patrick; Benes, Cyril H; Faber, Anthony C

2018-05-16

High-risk neuroblastoma is often distinguished by amplification of MYCN and loss of differentiation potential. We performed high-throughput drug screening of epigenetic-targeted therapies across a large and diverse tumor cell line panel and uncovered the hypersensitivity of neuroblastoma cells to GSK-J4, a small-molecule dual inhibitor of lysine 27 of histone 3 (H3K27) demethylases ubiquitously transcribed tetratricopeptide repeat, X chromosome (UTX), and histone demethylase Jumonji D3 (JMJD3). Mechanistically, GSK-J4 induced neuroblastoma differentiation and endoplasmic reticulum (ER) stress, with accompanying up-regulation of p53 up-regulated modulator of apoptosis (PUMA) and induction of cell death. Retinoic acid (RA)-resistant neuroblastoma cells were sensitive to GSK-J4. In addition, GSK-J4 was effective at blocking the growth of chemorefractory and patient-derived xenograft models of high-risk neuroblastoma in vivo. Furthermore, GSK-J4 and RA combination increased differentiation and ER stress over GSK-J4 effects and limited the growth of neuroblastomas resistant to either drug alone. In MYCN -amplified neuroblastoma, PUMA induction by GSK-J4 sensitized tumors to the B cell lymphoma 2 (BCL-2) inhibitor venetoclax, demonstrating that epigenetic-targeted therapies and BCL-2 homology domain 3 mimetics can be rationally combined to treat this high-risk subset of neuroblastoma. Therefore, H3K27 demethylation inhibition is a promising therapeutic target to treat high-risk neuroblastoma, and H3K27 demethylation can be part of rational combination therapies to induce robust antineuroblastoma activity. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

A strong and stretchable self-healing film with self-activated pressure sensitivity for potential artificial skin applications

PubMed Central

Hou, Chengyi; Huang, Tao; Wang, Hongzhi; Yu, Hao; Zhang, Qinghong; Li, Yaogang

2013-01-01

Artificial skin, which mimics the functions of natural skin, will be very important in the future for robots used by humans in daily life. However, combining skin's pressure sensitivity and mechanical self-healing properties in a man-made material remains a challenging task. Here, we show that graphene and polymers can be integrated into a thin film which mimics both the mechanical self-healing and pressure sensitivity behavior of natural skin without any external power supply. Its ultimate strain and tensile strength are even two and ten times larger than the corresponding values of human skin, respectively. It also demonstrates highly stable sensitivity to a very light touch (0.02 kPa), even in bending or stretching states. PMID:24190511

Environmental and Hydroclimatic Sensitivities of Greenhouse Gas (GHG) Fluxes from Coastal Wetlands

NASA Astrophysics Data System (ADS)

Abdul-Aziz, O. I.; Ishtiaq, K. S.

2016-12-01

We computed the reference environmental and hydroclimatic sensitivities of the greenhouse gas (GHG) fluxes (CO2 and CH4) from coastal salt marshes. Non-linear partial least squares regression models of CO2 (net uptake) and CH4 (net emissions) fluxes were developed with a bootstrap resampling approach using the photosynthetically active radiation (PAR), air and soil temperatures, water height, soil moisture, porewater salinity, and pH as predictors. Analytical sensitivity coefficients of different predictors were then analytically derived from the estimated models. The numerical sensitivities of the dominant drivers were determined by perturbing the variables individually and simultaneously to compute their individual and combined (respectively) effects on the GHG fluxes. Four tidal wetlands of Waquoit Bay, MA — incorporating a gradient in land-use, salinity and hydrology — were considered as the case study sites. The wetlands were dominated by native Spartina Alterniflora, and characterized by high salinity and frequent flooding. Results indicated a high sensitivity of CO2 fluxes to temperature and PAR, a moderate sensitivity to soil salinity and water height, and a weak sensitivity to pH and soil moisture. In contrast, the CH4 fluxes were more sensitive to temperature and salinity, compared to that of PAR, pH, and hydrologic variables. The estimated sensitivities and mechanistic insights can aid the management of coastal carbon under a changing climate and environment. The sensitivity coefficients also indicated the most dominant drivers of GHG fluxes for the development of a parsimonious predictive model.

A highly sensitive ethanol sensor based on mesoporous ZnO-SnO2 nanofibers.

PubMed

Song, Xiaofeng; Wang, Zhaojie; Liu, Yongben; Wang, Ce; Li, Lijuan

2009-02-18

A facile and versatile method for the large-scale synthesis of sensitive mesoporous ZnO-SnO(2) (m-Z-S) nanofibers through a combination of surfactant-directed assembly and an electrospinning approach is reported. The morphology and the structure were investigated by scanning electron microscopy (SEM), transmission electron microscopy (TEM), x-ray diffraction (XRD), and nitrogen adsorption-desorption isotherm analysis. The results showed that the diameters of fibers ranged from 100 to 150 nm with mixed structures of wurtzite (ZnO) and rutile (SnO(2)), and a mesoporous structure was observed in the m-Z-S nanofibers. The sensor performance of the prepared m-Z-S nanofibers was measured for ethanol. It is found that the mesoporous fiber film obtained exhibited excellent ethanol sensing properties, such as high sensitivity, quick response and recovery, good reproducibility, and linearity in the range 3-500 ppm.

High-sensitivity detection of triacetone triperoxide (TATP) and its precursor acetone

NASA Astrophysics Data System (ADS)

Dunayevskiy, Ilya; Tsekoun, Alexei; Prasanna, Manu; Go, Rowel; Patel, C. Kumar N.

2007-09-01

Triacetone triperoxide (C9H18O6, molecular mass of 222.24 g/mol) (TATP) is a powerful explosive that is easy to synthesize using commonly available household chemicals, acetone, and hydrogen peroxide 1 2. Because of the simplicity of its synthesis, TATP is often the explosive of choice for terrorists, including suicide bombers. For providing safety to the population, early detection of TATP and isolation of such individuals are essential. We report unambiguous, high-sensitivity detection of TATP and its precursor, acetone, using room-temperature quantum cascade laser photoacoustic spectroscopy (QCL-PAS). The available sensitivity is such that TATP, carried on a person (at a nominal body temperature of 37 °C), should be detectable at some distance. The combination of demonstrated detection of TATP and acetone should be ideal for screening at airports and other public places for providing increased public safety.

Imaging alpha particle detector

DOEpatents

Anderson, David F.

1985-01-01

A method and apparatus for detecting and imaging alpha particles sources is described. A conducting coated high voltage electrode (1) and a tungsten wire grid (2) constitute a diode configuration discharge generator for electrons dislodged from atoms or molecules located in between these electrodes when struck by alpha particles from a source (3) to be quantitatively or qualitatively analyzed. A thin polyester film window (4) allows the alpha particles to pass into the gas enclosure and the combination of the glass electrode, grid and window is light transparent such that the details of the source which is imaged with high resolution and sensitivity by the sparks produced can be observed visually as well. The source can be viewed directly, electronically counted or integrated over time using photographic methods. A significant increase in sensitivity over other alpha particle detectors is observed, and the device has very low sensitivity to gamma or beta emissions which might otherwise appear as noise on the alpha particle signal.

Imaging alpha particle detector

DOEpatents

Anderson, D.F.

1980-10-29

A method and apparatus for detecting and imaging alpha particles sources is described. A dielectric coated high voltage electrode and a tungsten wire grid constitute a diode configuration discharge generator for electrons dislodged from atoms or molecules located in between these electrodes when struck by alpha particles from a source to be quantitatively or qualitatively analyzed. A thin polyester film window allows the alpha particles to pass into the gas enclosure and the combination of the glass electrode, grid and window is light transparent such that the details of the source which is imaged with high resolution and sensitivity by the sparks produced can be observed visually as well. The source can be viewed directly, electronically counted or integrated over time using photographic methods. A significant increase in sensitivity over other alpha particle detectors is observed, and the device has very low sensitivity to gamma or beta emissions which might otherwise appear as noise on the alpha particle signal.

Sensitivity to musical structure in the human brain

PubMed Central

McDermott, Josh H.; Norman-Haignere, Sam; Kanwisher, Nancy

2012-01-01

Evidence from brain-damaged patients suggests that regions in the temporal lobes, distinct from those engaged in lower-level auditory analysis, process the pitch and rhythmic structure in music. In contrast, neuroimaging studies targeting the representation of music structure have primarily implicated regions in the inferior frontal cortices. Combining individual-subject fMRI analyses with a scrambling method that manipulated musical structure, we provide evidence of brain regions sensitive to musical structure bilaterally in the temporal lobes, thus reconciling the neuroimaging and patient findings. We further show that these regions are sensitive to the scrambling of both pitch and rhythmic structure but are insensitive to high-level linguistic structure. Our results suggest the existence of brain regions with representations of musical structure that are distinct from high-level linguistic representations and lower-level acoustic representations. These regions provide targets for future research investigating possible neural specialization for music or its associated mental processes. PMID:23019005

Ab initio structure determination of nanocrystals of organic pharmaceutical compounds by electron diffraction at room temperature using a Timepix quantum area direct electron detector

PubMed Central

van Genderen, E.; Clabbers, M. T. B.; Das, P. P.; Stewart, A.; Nederlof, I.; Barentsen, K. C.; Portillo, Q.; Pannu, N. S.; Nicolopoulos, S.; Gruene, T.; Abrahams, J. P.

2016-01-01

Until recently, structure determination by transmission electron microscopy of beam-sensitive three-dimensional nanocrystals required electron diffraction tomography data collection at liquid-nitrogen temperature, in order to reduce radiation damage. Here it is shown that the novel Timepix detector combines a high dynamic range with a very high signal-to-noise ratio and single-electron sensitivity, enabling ab initio phasing of beam-sensitive organic compounds. Low-dose electron diffraction data (∼0.013 e− Å−2 s−1) were collected at room temperature with the rotation method. It was ascertained that the data were of sufficient quality for structure solution using direct methods using software developed for X-ray crystallography (XDS, SHELX) and for electron crystallography (ADT3D/PETS, SIR2014). PMID:26919375

Ethacrynic acid and a derivative enhance apoptosis in arsenic trioxide-treated myeloid leukemia and lymphoma cells: the role of glutathione S-transferase P1-1

PubMed Central

Wang, Rui; Liu, Changda; Xia, Lijuan; Zhao, Guisen; Gabrilove, Janice; Waxman, Samuel; Jing, Yongkui

2012-01-01

Purpose Arsenic trioxide (ATO) as a single agent is used for treatment of acute promyelocytic leukemia (APL) with minimal toxicity but therapeutic effect of ATO in other types of malignancies has not been achieved. We tested whether a combination with ethacrynic acid (EA), a glutathione S-transferase P1-1 (GSTP1-1) inhibitor and a reactive oxygen species (ROS) inducer will extend the therapeutic effect of ATO beyond APL. Experimental Design The combined apoptotic effects of ATO plus EA were tested in non-APL leukemia and lymphoma cell lines. The role of ROS, GSTP1-1, glutathione, and Mcl-1 in apoptosis was determined. The selective response to this combination of cells with and without GSTP1-1 expression was compared. Results ATO/EA combination synergistically induced apoptosis in myeloid leukemia and lymphoma cells. This treatment produced high ROS levels, activated c-jun-NH2-terminal kinase and reduced Mcl-1 protein. This led to the decrease of mitochondrial transmembrane potential, release of cytochrome c and, subsequently, to activation of caspase 3 and 9. Induction of apoptosis in leukemia and lymphoma cells expressing GSTP1-1 required that high EA concentrations be combined with ATO. Silencing of GSTP1 in leukemia cells sensitized them to ATO/EA-induced apoptosis. In a sub-group of B-cell lymphoma which do not express GSTP1-1, lower concentrations of EA and its more potent derivative, ethacrynic acid butyl-ester, decreased intracellular glutathione levels and synergistically induced apoptosis when combined with ATO. Conclusion B-cell lymphoma cells lacking GSTP1-1 are more sensitive than myeloid leukemia cells to ATO/EA-induced apoptosis. PMID:23082001

Practical SQUID Instrument for Nondestructive Testing

NASA Technical Reports Server (NTRS)

Tralshawala, N.; Claycomb, J. R.; Miller, John H., Jr.

1997-01-01

We report on the development of a scanning eddy-current imaging system designed to detect deep subsurface flaws in conducting materials. A high transition temperature (high-T c) superconducting quantum interference device (SQUID) magnetometer is employed to provide the required sensitivity at low frequencies, while a combination of small cylindrical high-Tc superconducting and A-metal shields enable the instrument to be scanned in a magnetically noisy environment, rather than the object under test. The shields are arranged to prevent unwanted excitation and ambient noise fields from reaching the SQUID, and to enhance spatial resolution and minimize undesirable edge effects. Thus far, the instrument has successfully detected cracks and pits through 10 layers of aluminum, with a combined thickness of 5 cm at room temperature.

MACC1 mediates chemotherapy sensitivity of 5-FU and cisplatin via regulating MCT1 expression in gastric cancer.

PubMed

Wang, Chunlin; Wen, Zhaowei; Xie, Jianming; Zhao, Yang; Zhao, Liang; Zhang, Shuyi; Liu, Yajing; Xue, Yan; Shi, Min

2017-04-08

Chemotherapeutic insensitivity is a main obstacle for effective treatment of gastric cancer (GC), the underlying mechanism remains to be investigated. Metastasis-associated in colon cancer-1 (MACC1), a transcription factor highly expressed in GC, is found to be related to chemotherapy sensitivity. Monocarboxylate transporter 1 (MCT1), a plasma membrane protein co-transporting lactate and H + , mediates drug sensitivity by regulating lactate metabolism. Targeting MCT1 has recently been regarded as a promising way to treat cancers and MCT1 inhibitor has entered the clinical trial for GC treatment. However, the correlation of these two genes and their combined effects on chemotherapy sensitivity has not been clarified. In this study, we found that MACC1 and MCT1 were both highly expressed in GC and exhibited a positive correlation in clinical samples. Further, we demonstrated that MACC1 could mediate sensitivity of 5-FU and cisplatin in GC cells, and MACC1 mediated MCT1 regulation was closely related to this sensitivity. A MCT1 inhibitor AZD3965 recovered the sensitivity of 5-FU and cisplatin in GC cells which overexpressed MACC1. These results suggested that MACC1 could influence the chemotherapy sensitivity by regulating MCT1 expression, providing new ideas and strategy for GC treatment. Copyright © 2017 Elsevier Inc. All rights reserved.

Combination of STOP-Bang Score with Mallampati Score fails to improve specificity in the prediction of sleep-disordered breathing.

PubMed

Dette, Frank G; Graf, Juergen; Cassel, Werner; Lloyd-Jones, Carla; Boehm, Stefan; Zoremba, Martin; Schramm, Patrick; Pestel, Gunther; Thal, Serge C

2016-06-01

Sleep-disordered breathing (SDB) is closely associated with perioperative complications. STOP-Bang score was validated for preoperative screening of SDB. However, STOP-Bang Score lacks adequately high specificity. We aimed to improve it by combining it with the Mallampati Score. The study included 347 patients, in which we assessed both STOP-Bang and Mallampati scores. Overnight oxygen saturation was measured to calculate ODI4%. We calculated the sensitivity and specificity for AHI and ODI4% of both scores separately and in combination. We found that STOP-Bang Score ≥3 was present in 71%, ODI≥5/h (AHI ≥5/h) in 42.6% (39.3%) and ODI≥15/h (AHI ≥15/h) in 13.5% (17.8%). For ODI4%≥5/h (AHI ≥5/h) we observed in men a response rate for sensitivity and specificity of STOP-Bang of 94.5% and 17.1% (90.9% and 12.5%) and in women 66% and 51% (57.8% and 46.9%). For ODI4%≥15/h (AHI≥15/h) it was 92% and 12% (84.6% and 10.3%) and 93% and 49% (75% and 49.2%). For ODI4%≥5 (AHI≥5) sensitivity and specificity of Mallampati score were in men 38.4% and 78.6% (27.3% and 68.2%) and in women 25% and 82.7% (21.9% and 81.3%), for ODI≥15 (AHI ≥15/h) 38.5% and 71.8% (26.9% and 69.2%) and 33.3% and 81.4% (17.9% and 79.6%). In combination, for ODI4%≥15/h, we found sensitivity in men to be 92.3% and in women 93.3%, specificity 10.3% and 41.4%. STOP-Bang Score combined with Mallampati Score fails to increase specificity. Low specificity should be considered when using both scores for preoperative screening of SDB.

Application of DNA Aptamers and Quantum Dots to Lateral Flow Test Strips for Detection of Foodborne Pathogens with Improved Sensitivity versus Colloidal Gold

PubMed Central

Bruno, John G.

2014-01-01

Preliminary studies aimed at improving the sensitivity of foodborne pathogen detection via lateral flow (LF) test strips by use of high affinity DNA aptamers for capture and reporter functions when coupled to red-emitting quantum dots (Qdot 655) are reported. A variety of DNA aptamers developed against Escherichia coli, Listeria monocytogenes, and Salmonella enterica were paired in capture and reporter combinations to determine which yielded the strongest detection of their cognate bacteria using a colloidal gold screening system. Several promising sandwich combinations were identified for each of the three bacterial LF strip systems. The best E. coli aptamer-LF system was further studied and yielded a visible limit of detection (LOD) of ~3,000 E. coli 8739 and ~6,000 E. coli O157:H7 in buffer. These LODs were reduced to ~300–600 bacterial cells per test respectively by switching to a Qdot 655 aptamer-LF system. Novel aspects of these assays such as the use of high levels of detergents to avoid quantum dot agglutination and enhance migration in analytical membranes, identification of optimal analytical membrane types, UV-immobilization of capture aptamers, and novel dual biotin/digoxigenin-end labeled aptamer streptavidin-colloidal gold or -Qdot 655 conjugates plus anti-digoxigenin antibody control lines are also discussed. In general, this work provides proof-of-principle for highly sensitive aptamer-Qdot LF strip assays for rapid foodborne pathogen detection. PMID:25437803

Nano-LC/MALDI-MS using a column-integrated spotting probe for analysis of complex biomolecule samples.

PubMed

Hioki, Yusaku; Tanimura, Ritsuko; Iwamoto, Shinichi; Tanaka, Koichi

2014-03-04

Nanoflow liquid chromatography (nano-LC) is an essential technique for highly sensitive analysis of complex biological samples, and matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) is advantageous for rapid identification of proteins and in-depth analysis of post-translational modifications (PTMs). A combination of nano-LC and MALDI-MS (nano-LC/MALDI-MS) is useful for highly sensitive and detailed analysis in life sciences. However, the existing system does not fully utilize the advantages of each technique, especially in the interface of eluate transfer from nano-LC to a MALDI plate. To effectively combine nano-LC with MALDI-MS, we integrated a nano-LC column and a deposition probe for the first time (column probe) and incorporated it into a nano-LC/MALDI-MS system. Spotting nanoliter eluate droplets directly from the column onto the MALDI plate prevents postcolumn diffusion and preserves the chromatographic resolution. A DHB prespotted plate was prepared to suit the fabricated column probe to concentrate the droplets of nano-LC eluate. The performance of the advanced nano-LC/MALDI-MS system was substantiated by analyzing protein digests. When the system was coupled with multidimensional liquid chromatography (MDLC), trace amounts of glycopeptides that spiked into complex samples were successfully detected. Thus, a nano-LC/MALDI-MS direct-spotting system that eliminates postcolumn diffusion was constructed, and the efficacy of the system was demonstrated through highly sensitive analysis of the protein digests or spiked glycopeptides.

Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein.

PubMed

Ridker, Paul M; Danielson, Eleanor; Fonseca, Francisco A H; Genest, Jacques; Gotto, Antonio M; Kastelein, John J P; Koenig, Wolfgang; Libby, Peter; Lorenzatti, Alberto J; MacFadyen, Jean G; Nordestgaard, Børge G; Shepherd, James; Willerson, James T; Glynn, Robert J

2008-11-20

Increased levels of the inflammatory biomarker high-sensitivity C-reactive protein predict cardiovascular events. Since statins lower levels of high-sensitivity C-reactive protein as well as cholesterol, we hypothesized that people with elevated high-sensitivity C-reactive protein levels but without hyperlipidemia might benefit from statin treatment. We randomly assigned 17,802 apparently healthy men and women with low-density lipoprotein (LDL) cholesterol levels of less than 130 mg per deciliter (3.4 mmol per liter) and high-sensitivity C-reactive protein levels of 2.0 mg per liter or higher to rosuvastatin, 20 mg daily, or placebo and followed them for the occurrence of the combined primary end point of myocardial infarction, stroke, arterial revascularization, hospitalization for unstable angina, or death from cardiovascular causes. The trial was stopped after a median follow-up of 1.9 years (maximum, 5.0). Rosuvastatin reduced LDL cholesterol levels by 50% and high-sensitivity C-reactive protein levels by 37%. The rates of the primary end point were 0.77 and 1.36 per 100 person-years of follow-up in the rosuvastatin and placebo groups, respectively (hazard ratio for rosuvastatin, 0.56; 95% confidence interval [CI], 0.46 to 0.69; P<0.00001), with corresponding rates of 0.17 and 0.37 for myocardial infarction (hazard ratio, 0.46; 95% CI, 0.30 to 0.70; P=0.0002), 0.18 and 0.34 for stroke (hazard ratio, 0.52; 95% CI, 0.34 to 0.79; P=0.002), 0.41 and 0.77 for revascularization or unstable angina (hazard ratio, 0.53; 95% CI, 0.40 to 0.70; P<0.00001), 0.45 and 0.85 for the combined end point of myocardial infarction, stroke, or death from cardiovascular causes (hazard ratio, 0.53; 95% CI, 0.40 to 0.69; P<0.00001), and 1.00 and 1.25 for death from any cause (hazard ratio, 0.80; 95% CI, 0.67 to 0.97; P=0.02). Consistent effects were observed in all subgroups evaluated. The rosuvastatin group did not have a significant increase in myopathy or cancer but did have a higher incidence of physician-reported diabetes. In this trial of apparently healthy persons without hyperlipidemia but with elevated high-sensitivity C-reactive protein levels, rosuvastatin significantly reduced the incidence of major cardiovascular events. (ClinicalTrials.gov number, NCT00239681.) 2008 Massachusetts Medical Society

Rapid and sensitive detection of malachite green in aquaculture water by electrochemical preconcentration and surface-enhanced Raman scattering.

PubMed

Xu, Kai-Xuan; Guo, Mei-Hong; Huang, Yu-Ping; Li, Xiao-Dong; Sun, Jian-Jun

2018-04-01

A highly sensitive and rapid method of in-situ surface-enhanced Raman spectroscopy (SERS) combining with electrochemical preconcentration (EP) in detecting malachite green (MG) in aquaculture water was established. Ag nanoparticles (AgNPs) were synthesized and spread onto the surface of gold electrodes after centrifuging to produce SERS-active substrates. After optimizing the pH values, preconcentration potentials and times, in-situ EP-SERS detection was carried out. A sensitive and rapid analysis of the low-concentration MG was accomplished within 200s and the limit of detection was 2.4 × 10 -16 M. Copyright © 2017 Elsevier B.V. All rights reserved.

Trityl radicals in perfluorocarbon emulsions as stable, sensitive, and biocompatible oximetry probes.

PubMed

Dhimitruka, Ilirian; Alzarie, Yasmin Alsayed; Hemann, Craig; Samouilov, Alexandre; Zweier, Jay L

2016-12-01

EPR oximetry with the use of trityl radicals can enable sensitive O 2 measurement in biological cells and tissues. However, in vitro cellular and in vivo biological applications are limited by rapid trityl probe degradation or biological clearance and the need to enhance probe O 2 sensitivity. We synthesized novel perfluorocarbon (PFC) emulsions, ∼200nm droplet size, containing esterified perchlorinated triphenyl methyl (PTM) radicals dispersed in physiological aqueous buffers. These formulations exhibit excellent EPR signal stability, over 20-fold greater than free PTM probes, with high oxygen sensitivity ∼17mG/mmHg enabling pO 2 measurement in aqueous solutions or cell suspensions with sensitivity >0.5mmHg. Thus, PFC-PTM probes hold great promise to enable combined O 2 delivery and sensing as needed to restore or enhance tissue oxygenation in disease. Copyright © 2016 Elsevier Ltd. All rights reserved.

Exercise Training and Calorie Restriction Influence the Metabolic Parameters in Ovariectomized Female Rats

PubMed Central

Pósa, Anikó; Kupai, Krisztina; Szalai, Zita; Veszelka, Médea; Török, Szilvia; Varga, Csaba

2015-01-01

The estrogen deficiency after menopause leads to overweight or obesity, and physical exercise is one of the important modulators of this body weight gain. Female Wistar rats underwent ovariectomy surgery (OVX) or sham operation (SO). OVX and SO groups were randomized into new groups based on the voluntary physical activity (with or without running) and the type of diet for 12 weeks. Rats were fed standard chow (CTRL), high triglyceride diet (HT), or restricted diet (CR). The metabolic syndrome was assessed by measuring the body weight gain, the glucose sensitivity, and the levels of insulin, triglyceride, leptin, and aspartate aminotransferase transaminase (AST) and alanine aminotransferase (ALT). The exercise training combined with the CR resulted in improvements in the glucose tolerance and the insulin sensitivity. Plasma TG, AST, and ALT levels were significantly higher in OVX rats fed with HT but these high values were suppressed by exercise and CR. Compared to SO animals, estrogen deprivation with HT caused a significant increase in leptin level. Our data provide evidence that CR combined with voluntary physical exercise can be a very effective strategy to prevent the development of a metabolic syndrome induced by high calorie diet. PMID:25874022

Detection of cervical intraepithelial neoplasia by using optical coherence tomography in combination with microscopy

NASA Astrophysics Data System (ADS)

Gallwas, Julia; Jalilova, Aydan; Ladurner, Roland; Kolben, Theresa Maria; Kolben, Thomas; Ditsch, Nina; Homann, Christian; Lankenau, Eva; Dannecker, Christian

2017-01-01

Optical coherence tomography (OCT) is a noninvasive high-resolution imaging technique that permits the detection of cancerous and precancerous lesions of the uterine cervix. The purpose of this study was to evaluate a new system that integrates an OCT device into a microscope. OCT images were taken from loop electrosurgical excision procedure (LEEP) specimens under microscopic guidance. The images were blinded with respect to their origin within the microscopic image and analyzed independently by two investigators using initially defined criteria and later compared to the corresponding histology. Sensitivity and specificity were calculated with respect to the correct identification of high-grade squamous intraepithelial lesions (HSIL). The interinvestigator agreement was assessed by using Cohen's kappa statistics. About 160 OCT images were obtained from 20 LEEP specimens. Sixty randomly chosen images were used to define reproducible criteria for evaluation. The assessment of the remaining 100 images showed a sensitivity of 88% (second investigator 84%) and a specificity of 69% (65%) in detecting HSIL. Surgical microscopy-guided OCT appears to be a promising technique for immediate assessment of microanatomical changes. In the gynecological setting, the combination of OCT with a colposcope may improve the detection of high-grade squamous intraepithelial lesions.

Molecular Imprinting Technology in Quartz Crystal Microbalance (QCM) Sensors

PubMed Central

Emir Diltemiz, Sibel; Keçili, Rüstem; Ersöz, Arzu; Say, Rıdvan

2017-01-01

Molecularly imprinted polymers (MIPs) as artificial antibodies have received considerable scientific attention in the past years in the field of (bio)sensors since they have unique features that distinguish them from natural antibodies such as robustness, multiple binding sites, low cost, facile preparation and high stability under extreme operation conditions (higher pH and temperature values, etc.). On the other hand, the Quartz Crystal Microbalance (QCM) is an analytical tool based on the measurement of small mass changes on the sensor surface. QCM sensors are practical and convenient monitoring tools because of their specificity, sensitivity, high accuracy, stability and reproducibility. QCM devices are highly suitable for converting the recognition process achieved using MIP-based memories into a sensor signal. Therefore, the combination of a QCM and MIPs as synthetic receptors enhances the sensitivity through MIP process-based multiplexed binding sites using size, 3D-shape and chemical function having molecular memories of the prepared sensor system toward the target compound to be detected. This review aims to highlight and summarize the recent progress and studies in the field of (bio)sensor systems based on QCMs combined with molecular imprinting technology. PMID:28245588

Comparative study of CEA and CA19-9 in esophageal, gastric and colon cancers individually and in combination (ROC curve analysis).

PubMed

Bagaria, Bhawna; Sood, Sadhna; Sharma, Rameshwaram; Lalwani, Soniya

2013-09-01

To determine the clinical serum levels of carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9), individually and in combination, for the diagnosis of 50 healthy subjects and 150 cases of esophageal, gastric, and colon cancers. The sensitivities of the two markers were compared individually and in combination, with specificity set at 100%. Receiver operating characteristic (ROC) curves were plotted. Serum CEA levels were significantly higher in cancer patients than in the control group. The sensitivity of CEA was determined: in esophageal cancer, sensitivity=28%, negative predictive value (NPV)=61.72%, and AUC=0.742 
(SE=0.05), with a significance level of P<0.0001; in gastric cancer, sensitivity=30%, NPV=58.82%, and AUC=0.734 (SE=0.05), with a significance level of P<0.0001; in colon cancer, sensitivity=74%, NPV=79.36%, and AUC=0.856 
(SE=0.04), with a significance level of P<0.0001. The sensitivity of CA19-9 was also evaluated: in esophageal cancer, sensitivity=18%, NPV=54.94%, and AUC=0.573 (SE =0.05), with a significance level of P=0.2054. In gastric cancer, sensitivity=42%, NPV=63.29%, and AUC=0.679 (SE =0.05), with a significance level of P<0.0011. In colon cancer, sensitivity=26%, NPV=57.47%, and AUC=0.580 (SE =0.05), with a significance level of P=0.1670. The following were the sensitivities of CEA/CA19-9 combined: in esophageal cancer, sensitivity=42%, NPV=63.29%, SE=0.078 (95% CI: 0.0159-0.322); gastric cancer, sensitivity=58%, NPV=70.42%, SE=0.072 (95% CI: -0.0866-0.198); and colon cancer, sensitivity=72%, NPV=78.12%, SE=0.070 (95% CI: 0.137-0.415). CEA exhibited the highest sensitivity for colon cancer, and CA19-9 exhibited the highest sensitivity for gastric cancer. Combined analysis indicated an increase in diagnostic sensitivity in esophageal and gastric cancer compared with that in colon cancer.

Nano-porous electrode systems by colloidal lithography for sensitive electrochemical detection: fabrication technology and properties

NASA Astrophysics Data System (ADS)

Lohmüller, Theobald; Müller, Ulrich; Breisch, Stefanie; Nisch, Wilfried; Rudorf, Ralf; Schuhmann, Wolfgang; Neugebauer, Sebastian; Kaczor, Markus; Linke, Stephan; Lechner, Sebastian; Spatz, Joachim; Stelzle, Martin

2008-11-01

A porous metal-insulator-metal sensor system was developed with the ultimate goal of enhancing the sensitivity of electrochemical sensors by taking advantage of redox cycling of electro active molecules between closely spaced electrodes. The novel fabrication technology is based on thin film deposition in combination with colloidal self-assembly and reactive ion etching to create micro- or nanopores. This cost effective approach is advantageous compared to common interdigitated electrode arrays (IDA) since it does not require high definition lithography technology. Spin-coating and random particle deposition, combined with a new sublimation process are discussed as competing strategies to generate monolayers of colloidal spheres. Metal-insulator-metal layer systems with low leakage currents < 10 pA and an insulator thickness as low as 100 nm were obtained at high yield (typically > 90%). We also discuss possible causes of sensor failure with respect to critical fabrication processes. Short circuits which could occur during or as a result of the pore etching process were investigated in detail. Infrared microscopy in combination with focused ion beam etching/SEM were used to reveal a defect mechanism creating interconnects and increased leakage current between the top and bottom electrodes. Redox cycling provides for amplification factors of >100. A general applicability for electrochemical diagnostic assays is therefore anticipated.

Delta-doped hybrid advanced detector for low energy particle detection

NASA Technical Reports Server (NTRS)

Cunningham, Thomas J. (Inventor); Fossum, Eric R. (Inventor); Nikzad, Shouleh (Inventor); Pain, Bedabrata (Inventor); Soli, George A. (Inventor)

2000-01-01

A delta-doped hybrid advanced detector (HAD) is provided which combines at least four types of technologies to create a detector for energetic particles ranging in energy from hundreds of electron volts (eV) to beyond several million eV. The detector is sensitive to photons from visible light to X-rays. The detector is highly energy-sensitive from approximately 10 keV down to hundreds of eV. The detector operates with milliwatt power dissipation, and allows non-sequential readout of the array, enabling various advanced readout schemes.

Delta-doped hybrid advanced detector for low energy particle detection

NASA Technical Reports Server (NTRS)

Cunningham, Thomas J. (Inventor); Fossum, Eric R. (Inventor); Nikzad, Shouleh (Inventor); Pain, Bedabrata (Inventor); Soli, George A. (Inventor)

2002-01-01

A delta-doped hybrid advanced detector (HAD) is provided which combines at least four types of technologies to create a detector for energetic particles ranging in energy from hundreds of electron volts (eV) to beyond several million eV. The detector is sensitive to photons from visible light to X-rays. The detector is highly energy-sensitive from approximately 10 keV down to hundreds of eV. The detector operates with milliwatt power dissipation, and allows non-sequential readout of the array, enabling various advanced readout schemes.

Background-Oriented Schlieren for Large-Scale and High-Speed Aerodynamic Phenomena

NASA Technical Reports Server (NTRS)

Mizukaki, Toshiharu; Borg, Stephen; Danehy, Paul M.; Murman, Scott M.; Matsumura, Tomoharu; Wakabayashi, Kunihiko; Nakayama, Yoshio

2015-01-01

Visualization of the flow field around a generic re-entry capsule in subsonic flow and shock wave visualization with cylindrical explosives have been conducted to demonstrate sensitivity and applicability of background-oriented schlieren (BOS) for field experiments. The wind tunnel experiment suggests that BOS with a fine-pixel imaging device has a density change detection sensitivity on the order of 10(sup -5) in subsonic flow. In a laboratory setup, the structure of the shock waves generated by explosives have been successfully reconstructed by a computed tomography method combined with BOS.

Voltage-induced ferromagnetic resonance in magnetic tunnel junctions.

PubMed

Zhu, Jian; Katine, J A; Rowlands, Graham E; Chen, Yu-Jin; Duan, Zheng; Alzate, Juan G; Upadhyaya, Pramey; Langer, Juergen; Amiri, Pedram Khalili; Wang, Kang L; Krivorotov, Ilya N

2012-05-11

We demonstrate excitation of ferromagnetic resonance in CoFeB/MgO/CoFeB magnetic tunnel junctions (MTJs) by the combined action of voltage-controlled magnetic anisotropy (VCMA) and spin transfer torque (ST). Our measurements reveal that GHz-frequency VCMA torque and ST in low-resistance MTJs have similar magnitudes, and thus that both torques are equally important for understanding high-frequency voltage-driven magnetization dynamics in MTJs. As an example, we show that VCMA can increase the sensitivity of an MTJ-based microwave signal detector to the sensitivity level of semiconductor Schottky diodes.

Hybridization chain reaction amplification for highly sensitive fluorescence detection of DNA with dextran coated microarrays.

PubMed

Chao, Jie; Li, Zhenhua; Li, Jing; Peng, Hongzhen; Su, Shao; Li, Qian; Zhu, Changfeng; Zuo, Xiaolei; Song, Shiping; Wang, Lianhui; Wang, Lihua

2016-07-15

Microarrays of biomolecules hold great promise in the fields of genomics, proteomics, and clinical assays on account of their remarkably parallel and high-throughput assay capability. However, the fluorescence detection used in most conventional DNA microarrays is still limited by sensitivity. In this study, we have demonstrated a novel universal and highly sensitive platform for fluorescent detection of sequence specific DNA at the femtomolar level by combining dextran-coated microarrays with hybridization chain reaction (HCR) signal amplification. Three-dimensional dextran matrix was covalently coated on glass surface as the scaffold to immobilize DNA recognition probes to increase the surface binding capacity and accessibility. DNA nanowire tentacles were formed on the matrix surface for efficient signal amplification by capturing multiple fluorescent molecules in a highly ordered way. By quantifying microscopic fluorescent signals, the synergetic effects of dextran and HCR greatly improved sensitivity of DNA microarrays, with a detection limit of 10fM (1×10(5) molecules). This detection assay could recognize one-base mismatch with fluorescence signals dropped down to ~20%. This cost-effective microarray platform also worked well with samples in serum and thus shows great potential for clinical diagnosis. Copyright © 2016 Elsevier B.V. All rights reserved.

Sensitive high-throughput screening for the detection of reducing sugars.

PubMed

Mellitzer, Andrea; Glieder, Anton; Weis, Roland; Reisinger, Christoph; Flicker, Karlheinz

2012-01-01

The exploitation of renewable resources for the production of biofuels relies on efficient processes for the enzymatic hydrolysis of lignocellulosic materials. The development of enzymes and strains for these processes requires reliable and fast activity-based screening assays. Additionally, these assays are also required to operate on the microscale and on the high-throughput level. Herein, we report the development of a highly sensitive reducing-sugar assay in a 96-well microplate screening format. The assay is based on the formation of osazones from reducing sugars and para-hydroxybenzoic acid hydrazide. By using this sensitive assay, the enzyme loads and conversion times during lignocellulose hydrolysis can be reduced, thus allowing higher throughput. The assay is about five times more sensitive than the widely applied dinitrosalicylic acid based assay and can reliably detect reducing sugars down to 10 μM. The assay-specific variation over one microplate was determined for three different lignocellulolytic enzymes and ranges from 2 to 8%. Furthermore, the assay was combined with a microscale cultivation procedure for the activity-based screening of Pichia pastoris strains expressing functional Thermomyces lanuginosus xylanase A, Trichoderma reesei β-mannanase, or T. reesei cellobiohydrolase 2. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Sensitivity and specificity of radiographic methods for predicting insertion torque of dental implants.

PubMed

Cortes, Arthur Rodriguez Gonzalez; Eimar, Hazem; Barbosa, Jorge de Sá; Costa, Claudio; Arita, Emiko Saito; Tamimi, Faleh

2015-05-01

Subjective radiographic classifications of alveolar bone have been proposed and correlated with implant insertion torque (IT). The present diagnostic study aims to identify quantitative bone features influencing IT and to use these findings to develop an objective radiographic classification for predicting IT. Demographics, panoramic radiographs (taken at the beginning of dental treatment), and cone-beam computed tomographic scans (taken for implant surgical planning) of 25 patients receiving 31 implants were analyzed. Bone samples retrieved from implant sites were assessed with dual x-ray absorptiometry, microcomputed tomography, and histology. Odds ratio, sensitivity, and specificity of all variables to predict high peak IT were assessed. A ridge cortical thickness >0.75 mm and a normal appearance of the inferior mandibular cortex were the most sensitive variables for predicting high peak IT (87.5% and 75%, respectively). A classification based on the combination of both variables presented high sensitivity (90.9%) and specificity (100%) for predicting IT. Within the limitations of this study, the results suggest that it is possible to predict IT accurately based on radiographic findings of the patient. This could be useful in the treatment plan of immediate loading cases.

Application and Optimization of Stiffness Abruption Structures for Pressure Sensors with High Sensitivity and Anti-Overload Ability

PubMed Central

Xu, Tingzhong; Lu, Dejiang; Zhao, Libo; Jiang, Zhuangde; Wang, Hongyan; Guo, Xin; Li, Zhikang; Zhou, Xiangyang; Zhao, Yulong

2017-01-01

The influence of diaphragm bending stiffness distribution on the stress concentration characteristics of a pressure sensing chip had been analyzed and discussed systematically. According to the analysis, a novel peninsula-island-based diaphragm structure was presented and applied to two differenet diaphragm shapes as sensing chips for pressure sensors. By well-designed bending stiffness distribution of the diaphragm, the elastic potential energy induced by diaphragm deformation was concentrated above the gap position, which remarkably increased the sensitivity of the sensing chip. An optimization method and the distribution pattern of the peninsula-island based diaphragm structure were also discussed. Two kinds of sensing chips combined with the peninsula-island structures distributing along the side edge and diagonal directions of rectangular diaphragm were fabricated and analyzed. By bonding the sensing chips with anti-overload glass bases, these two sensing chips were demonstrated by testing to achieve not only high sensitivity, but also good anti-overload ability. The experimental results showed that the proposed structures had the potential to measure ultra-low absolute pressures with high sensitivity and good anti-overload ability in an atmospheric environment. PMID:28846599

Intracellular flow cytometry may be combined with good quality and high sensitivity RT-qPCR analysis.

PubMed

Sandstedt, Mikael; Jonsson, Marianne; Asp, Julia; Dellgren, Göran; Lindahl, Anders; Jeppsson, Anders; Sandstedt, Joakim

2015-12-01

Flow cytometry (FCM) has become a well-established method for analysis of both intracellular and cell-surface proteins, while quantitative RT-PCR (RT-qPCR) is used to determine gene expression with high sensitivity and specificity. Combining these two methods would be of great value. The effects of intracellular staining on RNA integrity and RT-qPCR sensitivity and quality have not, however, been fully examined. We, therefore, intended to assess these effects further. Cells from the human lung cancer cell line A549 were fixed, permeabilized and sorted by FCM. Sorted cells were analyzed using RT-qPCR. RNA integrity was determined by RNA quality indicator analysis. A549 cells were then mixed with cells of the mouse cardiomyocyte cell line HL-1. A549 cells were identified by the cell surface marker ABCG2, while HL-1 cells were identified by intracellular cTnT. Cells were sorted and analyzed by RT-qPCR. Finally, cell cultures from human atrial biopsies were used to evaluate the effects of fixation and permeabilization on RT-qPCR analysis of nonimmortalized cells stored prior to analysis by FCM. A large amount of RNA could be extracted even when cells had been fixed and permeabilized. Permeabilization resulted in increased RNA degradation and a moderate decrease in RT-qPCR sensitivity. Gene expression levels were also affected to a moderate extent. Sorted populations from the mixed A549 and HL-1 cell samples showed gene expression patterns that corresponded to FCM data. When samples were stored before FCM sorting, the RT-qPCR analysis could still be performed with high sensitivity and quality. In summary, our results show that intracellular FCM may be performed with only minor impairment of the RT-qPCR sensitivity and quality when analyzing sorted cells; however, these effects should be considered when comparing RT-qPCR data of not fixed samples with those of fixed and permeabilized samples. © 2015 International Society for Advancement of Cytometry.

Concurrent evaluation of visual, cytological and HPV testing as screening methods for the early detection of cervical neoplasia in Mumbai, India.

PubMed

Shastri, Surendra S; Dinshaw, Ketayun; Amin, Geetanjali; Goswami, Smriti; Patil, Sharmila; Chinoy, Roshini; Kane, S; Kelkar, Rohini; Muwonge, Richard; Mahé, Cédric; Ajit, Dulhan; Sankaranarayanan, R

2005-03-01

Naked eye visual inspection with acetic acid (VIA), magnified VIA (VIAM), visual inspection with Lugol's iodine (VILI), cytology and human papillomavirus (HPV) testing were evaluated as screening methods for the detection of high-grade squamous intraepithelial lesions (HSIL) of the uterine cervix in a cross-sectional study in Mumbai, India. Cytology, HPV testing, VIA, VIAM and VILI were carried out concurrently for 4039 women aged 30-65 years. All women were investigated with colposcopy and biopsies were taken from 939 women who had colposcopic abnormalities. The reference standard for final disease status was histology or negative colposcopy. The presence of HSIL was confirmed in 57 women (1.4%). The test characteristics for each method were calculated using standard formulae. The sensitivities of cytology, HPV testing, VIA, VIAM and VILI were 57.4%, 62.0%, 59.7%, 64.9%, and 75.4%, respectively (differences were not statistically significant). The specificities were 98.6%, 93.5%, 88.4%, 86.3%, and 84.3%, respectively. Adding a visual test to cytology or HPV testing in parallel combination resulted in a substantial increase in sensitivity, with a moderate decrease in specificity. The parallel combination of VILI and HPV testing resulted in a sensitivity of 92.0% and a specificity of 79.9%. As a single test, cytology had the best balance of sensitivity and specificity. Visual tests are promising in low-resource settings, such as India. The use of both VIA and VILI may be considered where good quality cytology or HPV testing are not feasible. The sensitivity of cytology and HPV testing increased significantly when combined with VIA or VILI.

Spectrotemporal Modulation Sensitivity as a Predictor of Speech Intelligibility for Hearing-Impaired Listeners

PubMed Central

Bernstein, Joshua G.W.; Mehraei, Golbarg; Shamma, Shihab; Gallun, Frederick J.; Theodoroff, Sarah M.; Leek, Marjorie R.

2014-01-01

Background A model that can accurately predict speech intelligibility for a given hearing-impaired (HI) listener would be an important tool for hearing-aid fitting or hearing-aid algorithm development. Existing speech-intelligibility models do not incorporate variability in suprathreshold deficits that are not well predicted by classical audiometric measures. One possible approach to the incorporation of such deficits is to base intelligibility predictions on sensitivity to simultaneously spectrally and temporally modulated signals. Purpose The likelihood of success of this approach was evaluated by comparing estimates of spectrotemporal modulation (STM) sensitivity to speech intelligibility and to psychoacoustic estimates of frequency selectivity and temporal fine-structure (TFS) sensitivity across a group of HI listeners. Research Design The minimum modulation depth required to detect STM applied to an 86 dB SPL four-octave noise carrier was measured for combinations of temporal modulation rate (4, 12, or 32 Hz) and spectral modulation density (0.5, 1, 2, or 4 cycles/octave). STM sensitivity estimates for individual HI listeners were compared to estimates of frequency selectivity (measured using the notched-noise method at 500, 1000measured using the notched-noise method at 500, 2000, and 4000 Hz), TFS processing ability (2 Hz frequency-modulation detection thresholds for 500, 10002 Hz frequency-modulation detection thresholds for 500, 2000, and 4000 Hz carriers) and sentence intelligibility in noise (at a 0 dB signal-to-noise ratio) that were measured for the same listeners in a separate study. Study Sample Eight normal-hearing (NH) listeners and 12 listeners with a diagnosis of bilateral sensorineural hearing loss participated. Data Collection and Analysis STM sensitivity was compared between NH and HI listener groups using a repeated-measures analysis of variance. A stepwise regression analysis compared STM sensitivity for individual HI listeners to audiometric thresholds, age, and measures of frequency selectivity and TFS processing ability. A second stepwise regression analysis compared speech intelligibility to STM sensitivity and the audiogram-based Speech Intelligibility Index. Results STM detection thresholds were elevated for the HI listeners, but only for low rates and high densities. STM sensitivity for individual HI listeners was well predicted by a combination of estimates of frequency selectivity at 4000 Hz and TFS sensitivity at 500 Hz but was unrelated to audiometric thresholds. STM sensitivity accounted for an additional 40% of the variance in speech intelligibility beyond the 40% accounted for by the audibility-based Speech Intelligibility Index. Conclusions Impaired STM sensitivity likely results from a combination of a reduced ability to resolve spectral peaks and a reduced ability to use TFS information to follow spectral-peak movements. Combining STM sensitivity estimates with audiometric threshold measures for individual HI listeners provided a more accurate prediction of speech intelligibility than audiometric measures alone. These results suggest a significant likelihood of success for an STM-based model of speech intelligibility for HI listeners. PMID:23636210

Capillary electrophoresis-high resolution sector field inductively coupled plasma mass spectrometry.

PubMed

Sonke, Jeroen E; Salters, Vincent J M

2007-08-03

The background and applications of high resolution sector field inductively coupled plasma mass spectrometry (HR-ICP-MS) as a detector for capillary (CE) and gel electrophoretic separations are reviewed. Notable progress has been made in the fields of bioinorganic and environmental (geo-) chemistry. Metallomics, the study of metal species interactions and functions in biological systems, puts substantial technical demands on speciation analysis. The combination of high species resolving power (CE) and high sensitivity-high mass resolving power (HR-ICP-MS) provides a solid base to meet such demands.

High signal-to-noise-ratio electro-optical terahertz imaging system based on an optical demodulating detector array.

PubMed

Spickermann, Gunnar; Friederich, Fabian; Roskos, Hartmut G; Bolívar, Peter Haring

2009-11-01

We present a 64x48 pixel 2D electro-optical terahertz (THz) imaging system using a photonic mixing device time-of-flight camera as an optical demodulating detector array. The combination of electro-optic detection with a time-of-flight camera increases sensitivity drastically, enabling the use of a nonamplified laser source for high-resolution real-time THz electro-optic imaging.

Combined Real-Time PCR and Pyrosequencing Strategy for Objective, Sensitive, Specific, and High-Throughput Identification of Reduced Susceptibility to Penicillins in Neisseria meningitidis▿

PubMed Central

Thulin, Sara; Olcén, Per; Fredlund, Hans; Unemo, Magnus

2008-01-01

A segment of penA in Neisseria meningitidis strains (n = 127), including two nucleotide sites closely associated to reduced susceptibility to penicillins, was amplified and pyrosequenced. All results were in concordance with Sanger sequencing, and a high correlation between alterations in the two Peni-specific sites and reduced susceptibility to penicillins was identified. PMID:18070955

Method and apparatus for real time imaging and monitoring of radiotherapy beams

DOEpatents

Majewski, Stanislaw [Yorktown, VA; Proffitt, James [Newport News, VA; Macey, Daniel J [Birmingham, AL; Weisenberger, Andrew G [Yorktown, VA

2011-11-01

A method and apparatus for real time imaging and monitoring of radiation therapy beams is designed to preferentially distinguish and image low energy radiation from high energy secondary radiation emitted from a target as the result of therapeutic beam deposition. A detector having low sensitivity to high energy photons combined with a collimator designed to dynamically image in the region of the therapeutic beam target is used.

An intelligent clinical decision support system for patient-specific predictions to improve cervical intraepithelial neoplasia detection.

PubMed

Bountris, Panagiotis; Haritou, Maria; Pouliakis, Abraham; Margari, Niki; Kyrgiou, Maria; Spathis, Aris; Pappas, Asimakis; Panayiotides, Ioannis; Paraskevaidis, Evangelos A; Karakitsos, Petros; Koutsouris, Dimitrios-Dionyssios

2014-01-01

Nowadays, there are molecular biology techniques providing information related to cervical cancer and its cause: the human Papillomavirus (HPV), including DNA microarrays identifying HPV subtypes, mRNA techniques such as nucleic acid based amplification or flow cytometry identifying E6/E7 oncogenes, and immunocytochemistry techniques such as overexpression of p16. Each one of these techniques has its own performance, limitations and advantages, thus a combinatorial approach via computational intelligence methods could exploit the benefits of each method and produce more accurate results. In this article we propose a clinical decision support system (CDSS), composed by artificial neural networks, intelligently combining the results of classic and ancillary techniques for diagnostic accuracy improvement. We evaluated this method on 740 cases with complete series of cytological assessment, molecular tests, and colposcopy examination. The CDSS demonstrated high sensitivity (89.4%), high specificity (97.1%), high positive predictive value (89.4%), and high negative predictive value (97.1%), for detecting cervical intraepithelial neoplasia grade 2 or worse (CIN2+). In comparison to the tests involved in this study and their combinations, the CDSS produced the most balanced results in terms of sensitivity, specificity, PPV, and NPV. The proposed system may reduce the referral rate for colposcopy and guide personalised management and therapeutic interventions.

An Intelligent Clinical Decision Support System for Patient-Specific Predictions to Improve Cervical Intraepithelial Neoplasia Detection

PubMed Central

Bountris, Panagiotis; Haritou, Maria; Pouliakis, Abraham; Margari, Niki; Kyrgiou, Maria; Spathis, Aris; Pappas, Asimakis; Panayiotides, Ioannis; Paraskevaidis, Evangelos A.; Karakitsos, Petros; Koutsouris, Dimitrios-Dionyssios

2014-01-01

Nowadays, there are molecular biology techniques providing information related to cervical cancer and its cause: the human Papillomavirus (HPV), including DNA microarrays identifying HPV subtypes, mRNA techniques such as nucleic acid based amplification or flow cytometry identifying E6/E7 oncogenes, and immunocytochemistry techniques such as overexpression of p16. Each one of these techniques has its own performance, limitations and advantages, thus a combinatorial approach via computational intelligence methods could exploit the benefits of each method and produce more accurate results. In this article we propose a clinical decision support system (CDSS), composed by artificial neural networks, intelligently combining the results of classic and ancillary techniques for diagnostic accuracy improvement. We evaluated this method on 740 cases with complete series of cytological assessment, molecular tests, and colposcopy examination. The CDSS demonstrated high sensitivity (89.4%), high specificity (97.1%), high positive predictive value (89.4%), and high negative predictive value (97.1%), for detecting cervical intraepithelial neoplasia grade 2 or worse (CIN2+). In comparison to the tests involved in this study and their combinations, the CDSS produced the most balanced results in terms of sensitivity, specificity, PPV, and NPV. The proposed system may reduce the referral rate for colposcopy and guide personalised management and therapeutic interventions. PMID:24812614

Rapid and specific detection of Salmonella in water samples using real-time PCR and High Resolution Melt (HRM) curve analysis.

PubMed

van Blerk, G N; Leibach, L; Mabunda, A; Chapman, A; Louw, D

2011-01-01

A real-time PCR assay combined with a pre-enrichment step for the specific and rapid detection of Salmonella in water samples is described. Following amplification of the invA gene target, High Resolution Melt (HRM) curve analysis was used to discriminate between products formed and to positively identify invA amplification. The real-time PCR assay was evaluated for specificity and sensitivity. The assay displayed 100% specificity for Salmonella and combined with a 16-18 h non-selective pre-enrichment step, the assay proved to be highly sensitive with a detection limit of 1.0 CFU/ml for surface water samples. The detection assay also demonstrated a high intra-run and inter-run repeatability with very little variation in invA amplicon melting temperature. When applied to water samples received routinely by the laboratory, the assay showed the presence of Salmonella in particularly surface water and treated effluent samples. Using the HRM based assay, the time required for Salmonella detection was drastically shortened to less than 24 h compared to several days when using standard culturing methods. This assay provides a useful tool for routine water quality monitoring as well as for quick screening during disease outbreaks.

Comparison of ELISA antigen preparations alone or in combination for serodiagnosing Helicobacter pylori infections.

PubMed Central

Hirschl, A M; Rathbone, B J; Wyatt, J I; Berger, J; Rotter, M L

1990-01-01

The immunoglobulin G antibody response to Helicobacter pylori was assessed in 78 patients with non-ulcer dyspepsia using five different antigen preparations. All patients were endoscoped and biopsied. The H pylori state was determined histologically on at least two endoscopic biopsy specimens using a modified Giemsa stain. The ultracentrifuged cell sonicate, acid glycine extract, and 120 kilodalton protein antigens were specific in diagnosing infection (95-98%), but had only moderate sensitivity (70-84%). By mixing either of the two complex antigens with the 120 kilodalton protein, the sensitivity of the test was increased to 97% without affecting the high specificity. The combination of ultracentrifuged sonicate or acid glycine extract with the 120 kilodalton protein therefore seems to be superior to the individual antigen preparations and is particularly suitable for the serodiagnosis of H pylori infection. PMID:2380396

Screening techniques to identify people at high risk for diabetic foot ulceration: a prospective multicenter trial.

PubMed

Pham, H; Armstrong, D G; Harvey, C; Harkless, L B; Giurini, J M; Veves, A

2000-05-01

Diabetic foot ulceration is a preventable long-term complication of diabetes. A multicenter prospective follow-up study was conducted to determine which risk factors in foot screening have a high association with the development of foot ulceration. A total of 248 patients from 3 large diabetic foot centers were enrolled in a prospective study. Neuropathy symptom score, neuropathy disability score (NDS), vibration perception threshold (VPT), Semmes-Weinstein monofilaments (SWFs), joint mobility, peak plantar foot pressures, and vascular status were evaluated in all patients at the beginning of the study. Patients were followed-up every 6 months for a mean period of 30 months (range 6-40), and all new foot ulcers were recorded. The sensitivity, specificity, and positive predictive value of each risk factor were evaluated. Foot ulcers developed in 95 feet (19%) or 73 patients (29%) during the study. Patients who developed foot ulcers were more frequently men, had diabetes for a longer duration, had nonpalpable pedal pulses, had reduced joint mobility, had a high NDS, had a high VPT, and had an inability to feel a 5.07 SWE NDS alone had the best sensitivity, whereas the combination of the NDS and the inability to feel a 5.07 SWF reached a sensitivity of 99%. On the other hand, the best specificity for a single factor was offered by foot pressures, and the best combination was that of NDS and foot pressures. Univariate logistical regression analysis yielded a statistically significant odds ratio (OR) for sex, race, duration of diabetes, palpable pulses, history of foot ulceration, high NDSs, high VPTs, high SWFs, and high foot pressures. In addition, 94 (99%) of the 95 ulcerated feet had a high NDS and/or SWF which resulted in the highest OR of 26.2 (95% CI 3.6-190). Furthermore, in multivariate logistical regression analysis, the only significant factors were high NDSs, VPTs, SWFs, and foot pressures. Clinical examination and a 5.07 SWF test are the two most sensitive tests in identifying patients at risk for foot ulceration, especially when the tests are used in conjunction with each other. VPT measurements are also helpful and can be used as an alternative. Finally, foot pressure measurements offer a substantially higher specificity and can be used as a postscreening test in conjunction with providing appropriate footwear.

Enhanced Detection of Chromosomal Abnormalities in Chronic Lymphocytic Leukemia by Conventional Cytogenetics Using CpG Oligonucleotide in Combination with Pokeweed Mitogen and Phorbol Myristate Acetate

PubMed Central

Muthusamy, Natarajan; Breidenbach, Heather; Andritsos, Leslie; Flynn, Joseph; Jones, Jeffrey; Ramanunni, Asha; Mo, Xiaokui; Jarjoura, David; Byrd, John C.; Heerema, Nyla A.

2011-01-01

Reproducible cytogenetic analysis in CLL has been limited by the inability to obtain reliable metaphase cells for analysis. CpG oligonucleotide and cytokine stimulation have been shown to improve metaphase analysis of CLL cytogenetic abnormalities, but is limited by variability in the cytokine receptor levels, stability and biological activity of the cytokine in culture conditions and high costs associated with these reagents. We report here use of a novel, stable CpG, GNKG168 along with pokeweed mitogen (PWM) and phorbol 12-myristate 13-acetate (PMA) for conventional cytogenetic assessment in CLL. We demonstrate that the combined use of GNKG168+PWM/PMA increased the sensitivity of detection of chromosomal abnormalities compared to PWM/PMA (n=207, odds ratio=2.2, p=0.0002) and GNKG168 (n=219, odds ratio=1.5, p=0.0452). Further, a significant increase in sensitivity to detect complexity ≥3 with GNKG168+PWM/PMA compared to GNKG168 alone (odds ratio 8.0, p=0.0022) or PWM/PMA alone (odds ratio 9.6, p=0.0007) was observed. The trend toward detection of higher complexity was significantly greater with GNKG168+PWM/PMA compared to GNKG168 alone (p=0.0412). The increased sensitivity was mainly attributed to the addition of PWM/PMA with GNKG168 because GNKG168 alone showed no difference in sensitivity for detection of complex abnormalities (p=0.17). Comparison of fluorescence in situ hybridization (FISH) results with karyotypic results showed a high degree of consistency, although some complex karyotypes were present in cases with no adverse FISH abnormality. These studies provide evidence for potential use of GNKG168 in combination with PWM and PMA in karyotypic analysis of CLL patient samples to better identify chromosomal abnormalities for risk stratification. PMID:21494579

Role of focused assessment with sonography for trauma as a screening tool for blunt abdominal trauma in young children after high energy trauma.

PubMed

Tummers, W; van Schuppen, J; Langeveld, H; Wilde, J; Banderker, E; van As, A

2016-06-01

The objective of the study was to review the utility of focused assessement with sonography for trauma (FAST) as a screening tool for blunt abdominal trauma (BAT) in children involved in high energy trauma (HET), and to determine whether a FAST could replace computed tomography (CT) in clinical decision-making regarding paediatric BAT. Children presented at the Trauma Unit of the Red Cross War Memorial Children's Hospital, Cape Town, after HET, and underwent both a physical examination and a FAST. The presence of free fluid in the abdomen and pelvis was assessed using a FAST. Sensitivity, specificity, and positive and negative predictive values (PPV and NPV) for identifying intraabdominal injury were calculated for the physical examination and the FAST, both individually and when combined. Seventy-five patients were included as per the criteria for HET as follows: pedestrian motor vehicle crashes (MVCs) ( n = 46), assault ( n = 14), fall from a height ( n = 9), MVC passenger ( n = 4) and other ( n = 2). The ages of the patients ranged from 3 months to 13 years. The sensitivity of the physical examination was 0.80, specificity 0.83, PPV 0.42 and NPV 0.96. The sensitivity of the FAST was 0.50, specificity 1.00, PPV 1.00 and NPV 0.93. Sensitivity increased to 0.90 when the physical examination was combined with the FAST. Nonoperative management was used in 73 patients. Two underwent an operation. A FAST should be performed in combination with a physical examination on every paediatric patient involved in HET to detect BAT. When both are negative, nonoperative management can be implemented without fear of missing a clinically significant injury. FAST is a safe, effective and easily accessible alternative to CT, which avoids ionising radiation and aids in clinical decision-making.

A survey on microorganisms and their sensitivity by E-test in ventilator-associated pneumonia at Toxicological-Intensive Care Unit of Loghman-Hakim Hospital.

PubMed

Talaie, Haleh; Sabeti, Shahram; Mahdavinejad, Arezou; Barari, Behjat; Kamalbeik, Sepideh

2010-12-01

Ventilator associated pneumonia (VAP) is the most common nosocomial infection at ICUs, with high mortality and morbidity. The diagnostic method for VAP is based on the combination of clinical, radiological, and microbiological criteria. Lower respiratory tract culture results are useful to confirm the etiology of VAP and adjusted antibiotics. Endotracheal aspiration (EA) is the simplest noninvasive technique for performing lower respiratory tract culture, with high sensitivity and moderately high specificity. The aim of this survey was to evaluate the quantitative cultures of endotracheal aspirates in VAP patients and the sensitivity patterns of microorganisms through E-test. Among 582 ICU admitted patients who were under mechanical ventilation for more than 48 hours, 72 suspected patients of VAP were prospectively evaluated during a 10 month period. Evaluation of our ICU standards by APACHE III scoring, and GCS were carried out on the first day of admission in all patients. Quantitative cultures of EA were performed on all 72 patients. Antibiotic resistance pattern of isolated pathogens was defined by E-test. VAP was confirmed in 46 out of 72 cases (50, 69.4% males and 22, 30.6% females - mean age was 33 +/- 12 years) through quantitative cultures of EA samples. The probable incidence of VAP was 7.9% (per ventilated patients > or = 48 hours). The mean APACHE III score was 31.28 +/- 16. GCS in most of the patients was between 8 and 12. Staphylococcus aureus was the most frequently isolated organism (58.7%), with high sensitivity to Amikacin, Ciprofloxacin, and Teicoplanin (>92%); Pseudomonas aeruginosa was the second most frequent organism (17.4 percent); Acinetobacter isolates were potentially drug resistant, and only Amikacin was effective. Tracheal aspirates in combination with clinical findings show important roles in the management of VAP and decrease inappropriate antimicrobial therapy. S. aureus is the main agent leading to VAP in the TICU of the Loghman Hakim Hospital.

Responses of aquatic insects to Cu and Zn in stream microcosms: understanding differences between single species tests and field responses.

PubMed

Clements, William H; Cadmus, Pete; Brinkman, Stephen F

2013-07-02

Field surveys of metal-contaminated streams suggest that some aquatic insects, particularly mayflies (Ephemeroptera) and stoneflies (Plecoptera), are highly sensitive to metals. However, results of single species toxicity tests indicate these organisms are quite tolerant, with LC50 values often several orders of magnitude greater than those obtained using standard test organisms (e.g., cladocerans and fathead minnows). Reconciling these differences is a critical research need, particularly since water quality criteria for metals are based primarily on results of single species toxicity tests. In this research we provide evidence based on community-level microcosm experiments to support the hypothesis that some aquatic insects are highly sensitive to metals. We present results of three experiments that quantified effects of Cu and Zn, alone and in combination, on stream insect communities. EC50 values, defined as the metal concentration that reduced abundance of aquatic insects by 50%, were several orders of magnitude lower than previously published values obtained from single species tests. We hypothesize that the short duration of laboratory toxicity tests and the failure to evaluate effects of metals on sensitive early life stages are the primary factors responsible for unrealistically high LC50 values in the literature. We also observed that Cu alone was significantly more toxic to aquatic insects than the combination of Cu and Zn, despite the fact that exposure concentrations represented theoretically similar toxicity levels. Our results suggest that water quality criteria for Zn were protective of most aquatic insects, whereas Cu was highly toxic to some species at concentrations near water quality criteria. Because of the functional significance of aquatic insects in stream ecosystems and their well-established importance as indicators of water quality, reconciling differences between field and laboratory responses and understanding the mechanisms responsible for variation in sensitivity among metals and metal mixtures is of critical importance.

Immune Profiles to Predict Response to Desensitization Therapy in Highly HLA-Sensitized Kidney Transplant Candidates

PubMed Central

Yabu, Julie M.; Siebert, Janet C.; Maecker, Holden T.

2016-01-01

Background Kidney transplantation is the most effective treatment for end-stage kidney disease. Sensitization, the formation of human leukocyte antigen (HLA) antibodies, remains a major barrier to successful kidney transplantation. Despite the implementation of desensitization strategies, many candidates fail to respond. Current progress is hindered by the lack of biomarkers to predict response and to guide therapy. Our objective was to determine whether differences in immune and gene profiles may help identify which candidates will respond to desensitization therapy. Methods and Findings Single-cell mass cytometry by time-of-flight (CyTOF) phenotyping, gene arrays, and phosphoepitope flow cytometry were performed in a study of 20 highly sensitized kidney transplant candidates undergoing desensitization therapy. Responders to desensitization therapy were defined as 5% or greater decrease in cumulative calculated panel reactive antibody (cPRA) levels, and non-responders had 0% decrease in cPRA. Using a decision tree analysis, we found that a combination of transitional B cell and regulatory T cell (Treg) frequencies at baseline before initiation of desensitization therapy could distinguish responders from non-responders. Using a support vector machine (SVM) and longitudinal data, TRAF3IP3 transcripts and HLA-DR-CD38+CD4+ T cells could also distinguish responders from non-responders. Combining all assays in a multivariate analysis and elastic net regression model with 72 analytes, we identified seven that were highly interrelated and eleven that predicted response to desensitization therapy. Conclusions Measuring baseline and longitudinal immune and gene profiles could provide a useful strategy to distinguish responders from non-responders to desensitization therapy. This study presents the integration of novel translational studies including CyTOF immunophenotyping in a multivariate analysis model that has potential applications to predict response to desensitization, select candidates, and personalize medicine to ultimately improve overall outcomes in highly sensitized kidney transplant candidates. PMID:27078882

Immune Profiles to Predict Response to Desensitization Therapy in Highly HLA-Sensitized Kidney Transplant Candidates.

PubMed

Yabu, Julie M; Siebert, Janet C; Maecker, Holden T

2016-01-01

Kidney transplantation is the most effective treatment for end-stage kidney disease. Sensitization, the formation of human leukocyte antigen (HLA) antibodies, remains a major barrier to successful kidney transplantation. Despite the implementation of desensitization strategies, many candidates fail to respond. Current progress is hindered by the lack of biomarkers to predict response and to guide therapy. Our objective was to determine whether differences in immune and gene profiles may help identify which candidates will respond to desensitization therapy. Single-cell mass cytometry by time-of-flight (CyTOF) phenotyping, gene arrays, and phosphoepitope flow cytometry were performed in a study of 20 highly sensitized kidney transplant candidates undergoing desensitization therapy. Responders to desensitization therapy were defined as 5% or greater decrease in cumulative calculated panel reactive antibody (cPRA) levels, and non-responders had 0% decrease in cPRA. Using a decision tree analysis, we found that a combination of transitional B cell and regulatory T cell (Treg) frequencies at baseline before initiation of desensitization therapy could distinguish responders from non-responders. Using a support vector machine (SVM) and longitudinal data, TRAF3IP3 transcripts and HLA-DR-CD38+CD4+ T cells could also distinguish responders from non-responders. Combining all assays in a multivariate analysis and elastic net regression model with 72 analytes, we identified seven that were highly interrelated and eleven that predicted response to desensitization therapy. Measuring baseline and longitudinal immune and gene profiles could provide a useful strategy to distinguish responders from non-responders to desensitization therapy. This study presents the integration of novel translational studies including CyTOF immunophenotyping in a multivariate analysis model that has potential applications to predict response to desensitization, select candidates, and personalize medicine to ultimately improve overall outcomes in highly sensitized kidney transplant candidates.

Incremental prognostic value of biomarkers beyond the GRACE (Global Registry of Acute Coronary Events) score and high-sensitivity cardiac troponin T in non-ST-elevation acute coronary syndrome.

PubMed

Widera, Christian; Pencina, Michael J; Bobadilla, Maria; Reimann, Ines; Guba-Quint, Anja; Marquardt, Ivonne; Bethmann, Kerstin; Korf-Klingebiel, Mortimer; Kempf, Tibor; Lichtinghagen, Ralf; Katus, Hugo A; Giannitsis, Evangelos; Wollert, Kai C

2013-10-01

Guidelines recommend the use of validated risk scores and a high-sensitivity cardiac troponin assay for risk assessment in non-ST-elevation acute coronary syndrome (NSTE-ACS). The incremental prognostic value of biomarkers in this context is unknown. We calculated the Global Registry of Acute Coronary Events (GRACE) score and measured the circulating concentrations of high-sensitivity cardiac troponin T (hs-cTnT) and 8 selected cardiac biomarkers on admission in 1146 patients with NSTE-ACS. We used an hs-cTnT threshold at the 99th percentile of a reference population to define increased cardiac marker in the score. The magnitude of the increase in model performance when individual biomarkers were added to GRACE was assessed by the change (Δ) in the area under the receiver-operating characteristic curve (AUC), integrated discrimination improvement (IDI), and category-free net reclassification improvement [NRI(>0)]. Seventy-eight patients reached the combined end point of 6-month all-cause mortality or nonfatal myocardial infarction. The GRACE score alone had an AUC of 0.749. All biomarkers were associated with the risk of the combined end point and offered statistically significant improvement in model performance when added to GRACE (likelihood ratio test P ≤ 0.015). Growth differentiation factor 15 [ΔAUC 0.039, IDI 0.049, NRI(>0) 0.554] and N-terminal pro-B-type natriuretic peptide [ΔAUC 0.024, IDI 0.027, NRI(>0) 0.438] emerged as the 2 most promising biomarkers. Improvements in model performance upon addition of a second biomarker were small in magnitude. Biomarkers can add prognostic information to the GRACE score even in the current era of high-sensitivity cardiac troponin assays. The incremental information offered by individual biomarkers varies considerably, however.

Combined venetoclax and alvocidib in acute myeloid leukemia.

PubMed

Bogenberger, James; Whatcott, Clifford; Hansen, Nanna; Delman, Devora; Shi, Chang-Xin; Kim, Wontak; Haws, Hillary; Soh, Katherine; Lee, Ye Sol; Peterson, Peter; Siddiqui-Jain, Adam; Weitman, Steven; Stewart, Keith; Bearss, David; Mesa, Ruben; Warner, Steven; Tibes, Raoul

2017-12-05

More effective treatment options for elderly acute myeloid leukemia (AML) patients are needed as only 25-50% of patients respond to standard-of-care therapies, response duration is typically short, and disease progression is inevitable even with some novel therapies and ongoing clinical trials. Anti-apoptotic BCL-2 family inhibitors, such as venetoclax, are promising therapies for AML. Nonetheless, resistance is emerging. We demonstrate that venetoclax combined with cyclin-dependent kinase (CDK) inhibitor alvocidib is potently synergistic in venetoclax-sensitive and -resistant AML models in vitro , ex vivo and in vivo . Alvocidib decreased MCL-1, and/or increased pro-apoptotic proteins such as BIM or NOXA, often synergistically with venetoclax. Over-expression of BCL-XL diminished synergy, while knock-down of BIM almost entirely abrogated synergy, demonstrating that the synergistic interaction between alvocidib and venetoclax is primarily dependent on intrinsic apoptosis. CDK9 inhibition predominantly mediated venetoclax sensitization, while CDK4/6 inhibition with palbociclib did not potentiate venetoclax activity. Combined, venetoclax and alvocidib modulate the balance of BCL-2 family proteins through complementary, yet variable mechanisms favoring apoptosis, highlighting this combination as a promising therapy for AML or high-risk MDS with the capacity to overcome intrinsic apoptosis mechanisms of resistance. These results support clinical testing of combined venetoclax and alvocidib for the treatment of AML and advanced MDS.

Combined venetoclax and alvocidib in acute myeloid leukemia

PubMed Central

Bogenberger, James; Whatcott, Clifford; Hansen, Nanna; Delman, Devora; Shi, Chang-Xin; Kim, Wontak; Haws, Hillary; Soh, Katherine; Lee, Ye Sol; Peterson, Peter; Siddiqui-Jain, Adam; Weitman, Steven; Stewart, Keith; Bearss, David; Mesa, Ruben; Warner, Steven; Tibes, Raoul

2017-01-01

More effective treatment options for elderly acute myeloid leukemia (AML) patients are needed as only 25–50% of patients respond to standard-of-care therapies, response duration is typically short, and disease progression is inevitable even with some novel therapies and ongoing clinical trials. Anti-apoptotic BCL-2 family inhibitors, such as venetoclax, are promising therapies for AML. Nonetheless, resistance is emerging. We demonstrate that venetoclax combined with cyclin-dependent kinase (CDK) inhibitor alvocidib is potently synergistic in venetoclax-sensitive and -resistant AML models in vitro, ex vivo and in vivo. Alvocidib decreased MCL-1, and/or increased pro-apoptotic proteins such as BIM or NOXA, often synergistically with venetoclax. Over-expression of BCL-XL diminished synergy, while knock-down of BIM almost entirely abrogated synergy, demonstrating that the synergistic interaction between alvocidib and venetoclax is primarily dependent on intrinsic apoptosis. CDK9 inhibition predominantly mediated venetoclax sensitization, while CDK4/6 inhibition with palbociclib did not potentiate venetoclax activity. Combined, venetoclax and alvocidib modulate the balance of BCL-2 family proteins through complementary, yet variable mechanisms favoring apoptosis, highlighting this combination as a promising therapy for AML or high-risk MDS with the capacity to overcome intrinsic apoptosis mechanisms of resistance. These results support clinical testing of combined venetoclax and alvocidib for the treatment of AML and advanced MDS. PMID:29291023

Probabilistic Material Strength Degradation Model for Inconel 718 Components Subjected to High Temperature, Mechanical Fatigue, Creep and Thermal Fatigue Effects

NASA Technical Reports Server (NTRS)

Bast, Callie Corinne Scheidt

1994-01-01

This thesis presents the on-going development of methodology for a probabilistic material strength degradation model. The probabilistic model, in the form of a postulated randomized multifactor equation, provides for quantification of uncertainty in the lifetime material strength of aerospace propulsion system components subjected to a number of diverse random effects. This model is embodied in the computer program entitled PROMISS, which can include up to eighteen different effects. Presently, the model includes four effects that typically reduce lifetime strength: high temperature, mechanical fatigue, creep, and thermal fatigue. Statistical analysis was conducted on experimental Inconel 718 data obtained from the open literature. This analysis provided regression parameters for use as the model's empirical material constants, thus calibrating the model specifically for Inconel 718. Model calibration was carried out for four variables, namely, high temperature, mechanical fatigue, creep, and thermal fatigue. Methodology to estimate standard deviations of these material constants for input into the probabilistic material strength model was developed. Using the current version of PROMISS, entitled PROMISS93, a sensitivity study for the combined effects of mechanical fatigue, creep, and thermal fatigue was performed. Results, in the form of cumulative distribution functions, illustrated the sensitivity of lifetime strength to any current value of an effect. In addition, verification studies comparing a combination of mechanical fatigue and high temperature effects by model to the combination by experiment were conducted. Thus, for Inconel 718, the basic model assumption of independence between effects was evaluated. Results from this limited verification study strongly supported this assumption.

Uncooled IR imager with 5-mK NEDT

NASA Astrophysics Data System (ADS)

Amantea, Robert; Knoedler, C. M.; Pantuso, Francis P.; Patel, Vipulkumar; Sauer, Donald J.; Tower, John R.

1997-08-01

The bi-material concept for room-temperature infrared imaging has the potential of reaching an NE(Delta) T approaching the theoretical limit because of its high responsivity and low noise. The approach, which is 100% compatible with silicon IC foundry processing, utilizes a novel combination of surface micromachining and conventional integrated circuits to produce a bimaterial thermally sensitive element that controls the position of a capacitive plate coupled to the input of a low noise MOS amplifier. This approach can achieve the high sensitivity, the low weight, and the low cost necessary for equipment such as helmet mounted IR viewers and IR rifle sights. The pixel design has the following benefits: (1) an order of magnitude improvement in NE(Delta) T due to extremely high sensitivity and low noise, (2) low cost due to 100% silicon IC compatibility, (3) high image quality and increased yield due to ability to do offset and sensitivity corrections on the imager, pixel-by-pixel; (4) no cryogenic cooler and no high vacuum processing; and (5) commercial applications such as law enforcement, home security, and transportation safety. Two designs are presented. One is a 50 micrometer pixel using silicon nitride as the thermal isolation element that can achieve 5 mK NE(Delta) T; the other is a 29 micrometer pixel using silicon carbide that provides much higher thermal isolation and can achieve 10 mK NE(Delta) T.

Preclinical rationale for combination of crizotinib with mitomycin C for the treatment of advanced colorectal cancer.

PubMed

Lev, Avital; Deihimi, Safoora; Shagisultanova, Elena; Xiu, Joanne; Lulla, Amriti R; Dicker, David T; El-Deiry, Wafik S

2017-09-02

Colorectal cancer (CRC) is a leading cause of cancer-related deaths in the United States. We analyzed 26 MSI-High and 558 non-MSI-High CRC tumors. BRCA2 mutations were highly enriched (50%) in MSI-High CRC. Immunohistochemistry showed that BRCA2-mutated MSI-High CRC had high c-MET (64%) expression compared with BRCA-WT (17%). We hypothesized a mechanistic link between BRCA2-deficiency and c-MET overexpression and synergistic interaction between drugs that treat BRCA-deficient tumors (mitomycin C (MMC) or PARP inhibitors) and c-MET inhibitors (crizotinib). We tested CRC cell lines for sensitivity to MMC plus crizotinib or other drug combinations including PARP-inhibitors. Combined treatment of tumor cells with crizotinib and MMC led to increased apoptosis as compared with each drug alone. Additionally, combination treatment with increasing concentrations of both drugs demonstrated a synergistic anti-cancer effect (CI = 0.006-0.74). However, we found no evidence for c-MET upregulation upon effective BRCA2 knockdown in tumor cells -/+DNA damage. Although we found no mechanistic link between BRCA2 deficiency and c-MET overexpression, c-MET is frequently overexpressed in CRC and BRCA2 is mutated especially in MSI-H CRC. The combination of crizotinib with MMC appeared synergistic regardless of MSI or BRCA2 status. Using an in-vivo CRC xenograft model we found reduced tumor growth with combined crizotinib and MMC therapy (p = 0.0088). Our preclinical results support clinical testing of the combination of MMC and crizotinib in advanced CRC. Targeting cell survival mediated by c-MET in combination with targeting DNA repair may be a reasonable strategy for therapy development in CRC or other cancers.

Fasciculations in nerve and muscle disorders - A prospective study of muscle ultrasound compared to electromyography.

PubMed

Johansson, M T; Ellegaard, H R; Tankisi, H; Fuglsang-Frederiksen, A; Qerama, E

2017-11-01

We examined the clinical utility of muscle ultrasound (MUS) in detecting fasciculations in patients with nerve and muscle disorders (NMD) and investigated the impact on diagnostic sensitivity when combining electromyography (EMG) and MUS. We included 58 consecutive patients suspected to have NMD and 38 healthy subjects (HS). Patients and HS underwent MUS in 14 skeletal and two bulbar muscles and the video recordings of the MUS were anonymised. Only patients underwent EMG. The follow-up diagnoses were: 15 Amyotrophic lateral sclerosis (ALS), 15 polyneuropathy, 14 patients had other diagnoses (disease-control group) and 14 patients had no pathological findings. MUS detected more muscles with fasciculations among ALS patients compared to all other groups. In ALS patients, the dominating pattern of fasciculations was continuous (45%). More proximal muscles showed fasciculations among ALS patients compared to all other patient groups. MUS was more sensitive than EMG in detecting fasciculations (58% vs. 48%). When combining the two methods, the sensitivity in detecting fasciculations increased to 65%. Fasciculations in nine muscles could predict the ALS diagnosis with high sensitivity and specificity. MUS is a sensitive tool in detecting fasciculations in patients with NMD and performs well compared to EMG in diagnosing ALS. MUS may add valuable information in the clinic, especially in diagnosing ALS. Copyright © 2017 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

[Predicating the sensibility of patients with multiple myeloma to glucocorticoid by cochaperone P23].

PubMed

Xue, Jun; Xie, Xiao-Jing; Cao, Peng

2012-02-01

This study was aimed to investigate the sensitive index for predicting the sensitivity of patients with multiple myeloma (MM) to glucocorticoid (GC). MM1.S, MM1.R cell lines and 10 MM patients sensitive or non-sensitive to GC were enrolled in this study. The expression of heat shock protein 90 (HSP90) and P23 in peripheral blood mononuclear cells (PBMNC) of MM patients was detected by Western blot, and its relation with GC resistance was explored. The results showed that there were no differences in HSP90, GR and IκB-α expressions among MM1.S, MM1.R, PBMNC of normal persons and MM patients, while there was apparent difference in P23; along with increasing of dexamethasone dose, the survival rate of MM1.S decreased, but that of MM1.R did not change so obviously. Among 7 cases with P23 low expression, combination treatment scheme with GC was effective in 6 cases (86%), uneffective in 1 cases (14%); while among 3 cases with P23 high expression, 1 cases (33%) showed effective to combination treatment with GC, 2 cases (67%) showed uneffective (P < 0.05). It is concluded that the P23 expression may predict the sensitivity of MM patients to GC and may be used as index for guiding clinical treatment.

[Screening interview for early detection of high-functioning autism spectrum disorders].

PubMed

Hoffmann, Wiebke; Heinzel-Gutenbrunner, Monika; Becker, Katja; Kamp-Becker, Inge

2015-05-01

Various different questionnaires are available for the screening of autism spectrum disorders (ASD). These screening instruments show high sensitivity and are able to identify a large number of individuals with ASD, but they lack the specificity to differentiate individuals with ASD from those children and adolescents with other complex neurobehavioural disorders (such as attention-deficit/hyperactivity disorder, emotional disorders, and others), especially for those without intellectual disabilities. The present study evaluates the data of 309 individuals (153 with high-functioning ASD, 156 with other psychiatric disorders, IQ > 70) to find out whether selected items of the ADI-R can be used for an economic and sensitive screening of high-functioning ASD. The results show that 8 items of the ADI-R can be used to discriminate high-functioning ASD and other psychiatric disorders. A cutoff of 5 led to a sensitivity of 0.93 and a cutoff of 6 to a specificity of 0.74. The combination of early onset, serious abnormalities in social contact with stereotyped or compulsive-ritualized behaviour or interests can be detected with few interview questions for screening of ASD. Nevertheless, a more detailed and specific assessment in an expert setting should follow the screening process.

Electron-rich triphenylamine-based sensors for picric acid detection.

PubMed

Chowdhury, Aniket; Mukherjee, Partha Sarathi

2015-04-17

This paper demonstrates the role of solvent in selectivity and sensitivity of a series of electron-rich compounds for the detection of trace amounts of picric acid. Two new electron-rich fluorescent esters (6, 7) containing a triphenylamine backbone as well as their analogous carboxylic acids (8, 9) have been synthesized and characterized. Fluorescent triphenylamine coupled with an ethynyl moiety constitutes π-electron-rich selective and sensitive probes for electron-deficient picric acid (PA). In solution, the high sensitivity of all the sensors toward PA can be attributed to a combined effect of the ground-state charge-transfer complex formation and resonance energy transfer between the sensor and analyte. The acids 8 and 9 also showed enhanced sensitivity for nitroaromatics in the solid state, and their enhanced sensitivity could be attributed to exciton migration due to close proximity of the neighboring acid molecules, as evident from the X-ray diffraction study. The compounds were found to be quite sensitive for the detection of trace amount of nitroaromatics in solution, solid, and contact mode.

Antibiotic combination efficacy (ACE) networks for a Pseudomonas aeruginosa model

PubMed Central

Barbosa, Camilo; Beardmore, Robert; Jansen, Gunther

2018-01-01

The spread of antibiotic resistance is always a consequence of evolutionary processes. The consideration of evolution is thus key to the development of sustainable therapy. Two main factors were recently proposed to enhance long-term effectiveness of drug combinations: evolved collateral sensitivities between the drugs in a pair and antagonistic drug interactions. We systematically assessed these factors by performing over 1,600 evolution experiments with the opportunistic nosocomial pathogen Pseudomonas aeruginosa in single- and multidrug environments. Based on the growth dynamics during these experiments, we reconstructed antibiotic combination efficacy (ACE) networks as a new tool for characterizing the ability of the tested drug combinations to constrain bacterial survival as well as drug resistance evolution across time. Subsequent statistical analysis of the influence of the factors on ACE network characteristics revealed that (i) synergistic drug interactions increased the likelihood of bacterial population extinction—irrespective of whether combinations were compared at the same level of inhibition or not—while (ii) the potential for evolved collateral sensitivities between 2 drugs accounted for a reduction in bacterial adaptation rates. In sum, our systematic experimental analysis allowed us to pinpoint 2 complementary determinants of combination efficacy and to identify specific drug pairs with high ACE scores. Our findings can guide attempts to further improve the sustainability of antibiotic therapy by simultaneously reducing pathogen load and resistance evolution. PMID:29708964

Combining the test of memory malingering trial 1 with behavioral responses improves the detection of effort test failure.

PubMed

Denning, John Henry

2014-01-01

Validity measures derived from the Test of Memory Malingering Trial 1 (TOMM1) and errors across the first 10 items of TOMM1 (TOMMe10) may be further enhanced by combining these scores with "embedded" behavioral responses while patients complete these measures. In a sample of nondemented veterans (n = 151), five possible behavioral responses observed during completion of the first 10 items of the TOMM were combined with TOMM1 and TOMMe10 to assess any increased sensitivity in predicting Medical Symptom Validity Test (MSVT) performance. Both TOMM1 and TOMMe10 alone were highly accurate overall in predicting MSVT performance (TOMM1 [area under the curve (AUC)] = .95, TOMMe10 [AUC] = .92). The combination of TOMM measures and behavioral responses did not increase overall accuracy rates; however, when specificity was held at approximately 90%, there was a slight increase in sensitivity (+7%) for both TOMM measures when combined with the number of "point and name" responses. Examples are provided demonstrating that at a given TOMM score (TOMM1 or TOMMe10), with an increase in "point and name" responses, there is an incremental increase in the probability of failing the MSVT. Exploring the utility of combining freestanding or embedded validity measures with behavioral features during test administration should be encouraged.

Protection against salt toxicity in Azolla pinnata-Anabaena azollae symbiotic association by using combined-N sources.

PubMed

Mishra, A K; Singh, Satya S

2006-09-01

Protection from salt stress was observed in the terms of yield (fresh and dry weight, chlorophyll and protein) and nitrogenase activity. Azollapinnata appeared highly sensitive to 40 mM external NaCl stress. Fronds of Azolla unable to grow beyond a concentration of 30 mM NaCl and accordingly death was recorded at 40 mM NaCl on the 6th day of incubation. Yield was inhibited by various levels of NaCl (0, 10, 20 and 30 mM). Addition of combined-N to the growth medium protected the association partially from salt toxicity. Among the N-sources (NO3-, NH4+ and urea) tried, urea mitigated the salt-induced toxicity most efficiently. Reduction in nitrogenase activity was observed when intact Azolla was grown in nutrient medium either supplemented with different levels of NaCl or combined nitrogen. Only NO3- (5 mM) protected the enzymatic activity from salt toxicity while other concentrations of ammonium, nitrate and urea slowed down the salt-induced inhibition of enzyme activity in Azolla-Anabaena association. These results suggested that an optimum protection from salt stress could be obtained by using a combination of combined nitrogen sources. The reason for this protection might be due to the availability of combined nitrogen to the association, nitrogen is only available through the biological nitrogen fixation which is the most sensitive to salt stress.

A novel compound which sensitizes BRAF wild-type melanoma cells to vemurafenib in a TRIM16-dependent manner.

PubMed

Sutton, Selina K; Carter, Daniel R; Kim, Patrick; Tan, Owen; Arndt, Greg M; Zhang, Xu Dong; Baell, Jonathan; Noll, Benjamin D; Wang, Shudong; Kumar, Naresh; McArthur, Grant A; Cheung, Belamy B; Marshall, Glenn M

2016-08-09

There is an urgent need for better therapeutic options for advanced melanoma patients, particularly those without the BRAFV600E/K mutation. In melanoma cells, loss of TRIM16 expression is a marker of cell migration and metastasis, while the BRAF inhibitor, vemurafenib, induces melanoma cell growth arrest in a TRIM16-dependent manner. Here we identify a novel small molecule compound which sensitized BRAF wild-type melanoma cells to vemurafenib. High throughput, cell-based, chemical library screening identified a compound (C012) which significantly reduced melanoma cell viability, with limited toxicity for normal human fibroblasts. When combined with the BRAFV600E/K inhibitor, vemurafenib, C012 synergistically increased vemurafenib potency in 5 BRAFWT and 4 out of 5 BRAFV600E human melanoma cell lines (Combination Index: CI < 1), and, dramatically reduced colony forming ability. In addition, this drug combination was significantly anti-tumorigenic in vivo in a melanoma xenograft mouse model. The combination of vemurafenib and C012 markedly increased expression of TRIM16 protein, and knockdown of TRIM16 significantly reduced the growth inhibitory effects of the vemurafenib and C012 combination. These findings suggest that the combination of C012 and vemurafenib may have therapeutic potential for the treatment of melanoma, and, that reactivation of TRIM16 may be an effective strategy for patients with this disease.

A novel compound which sensitizes BRAF wild-type melanoma cells to vemurafenib in a TRIM16-dependent manner

PubMed Central

Sutton, Selina K.; Carter, Daniel R.; Kim, Patrick; Tan, Owen; Arndt, Greg M.; Zhang, Xu Dong; Baell, Jonathan; Noll, Benjamin D.; Wang, Shudong; Kumar, Naresh; McArthur, Grant A.; Cheung, Belamy B.; Marshall, Glenn M.

2016-01-01

There is an urgent need for better therapeutic options for advanced melanoma patients, particularly those without the BRAFV600E/K mutation. In melanoma cells, loss of TRIM16 expression is a marker of cell migration and metastasis, while the BRAF inhibitor, vemurafenib, induces melanoma cell growth arrest in a TRIM16-dependent manner. Here we identify a novel small molecule compound which sensitized BRAF wild-type melanoma cells to vemurafenib. High throughput, cell-based, chemical library screening identified a compound (C012) which significantly reduced melanoma cell viability, with limited toxicity for normal human fibroblasts. When combined with the BRAFV600E/K inhibitor, vemurafenib, C012 synergistically increased vemurafenib potency in 5 BRAFWT and 4 out of 5 BRAFV600E human melanoma cell lines (Combination Index: CI < 1), and, dramatically reduced colony forming ability. In addition, this drug combination was significantly anti-tumorigenic in vivo in a melanoma xenograft mouse model. The combination of vemurafenib and C012 markedly increased expression of TRIM16 protein, and knockdown of TRIM16 significantly reduced the growth inhibitory effects of the vemurafenib and C012 combination. These findings suggest that the combination of C012 and vemurafenib may have therapeutic potential for the treatment of melanoma, and, that reactivation of TRIM16 may be an effective strategy for patients with this disease. PMID:27447557

LOX/GOX sensitivity of fluoroelastomers. [effect of formulation components and addition of fire retardants

NASA Technical Reports Server (NTRS)

Kirshen, N.; Mill, T.

1973-01-01

The effect of formulation components and the addition of fire retardants on the impact sensitivity of Viton B fluoroelastomer in liquid oxygen was studied with the objective of developing a procedure for reliably reducing this sensitivity. Component evaluation, carried out on more than 40 combinations of components and cure cycles, showed that almost all the standard formulation agents, including carbon, MgO, Diak-3, and PbO2, will sensitize the Viton stock either singly or in combinations, some combinations being much more sensitive than others. Cure and postcure treatments usually reduced the sensitivity of a given formulation, often dramatically, but no formulated Viton was as insensitive as the pure Viton B stock. Coating formulated Viton with a thin layer of pure Viton gave some indication of reduced sensitivity, but additional tests are needed. It is concluded that sensitivity in formulated Viton arises from a variety of sources, some physical and some chemical in origin. Elemental analyses for all the formulated Vitons are reported as are the results of a literature search on the subject of LOX impact sensitivity.

Enhanced sensitivity for optical loss measurement in planar thin-films (Conference Presentation)

NASA Astrophysics Data System (ADS)

Yuan, Hua-Kang

2016-09-01

An organic-inorganic hybrid material benefits from processing advantages of organics and high refractive indices of inorganics. We focus on a titanium oxide hydrate system combined with common bulk polymers. In particular, we target thin-film structures of a few microns in thickness. Traditional Beer-Lambert approaches for measuring optical losses can only provide an upper limit estimate. This sensitivity is highly limited when considering the low-losses required for mid-range optical applications, on the order of 0.1 cm-1. For intensity based measurements, improving the sensitivity requires an increase in the optical path length. Instead, a new sensitive technique suitable for simple planar thin films is required. A number of systems were modelled to measure optical losses in films of 1 micron thick. The presented techniques utilise evanescent waves and total internal reflection to increase optical path length through the material. It was found that a new way of using prism coupling provides the greatest improvement in sensitivity. In keeping the requirements on the material simple, this method for measuring loss is well suited to any future developments of new materials in thin-film structures.

Prognostic Validation of SKY92 and Its Combination With ISS in an Independent Cohort of Patients With Multiple Myeloma.

PubMed

van Beers, Erik H; van Vliet, Martin H; Kuiper, Rowan; de Best, Leonie; Anderson, Kenneth C; Chari, Ajai; Jagannath, Sundar; Jakubowiak, Andrzej; Kumar, Shaji K; Levy, Joan B; Auclair, Daniel; Lonial, Sagar; Reece, Donna; Richardson, Paul; Siegel, David S; Stewart, A Keith; Trudel, Suzanne; Vij, Ravi; Zimmerman, Todd M; Fonseca, Rafael

2017-09-01

High risk and low risk multiple myeloma patients follow a very different clinical course as reflected in their PFS and OS. To be clinically useful, methodologies used to identify high and low risk disease must be validated in representative independent clinical data and available so that patients can be managed appropriately. A recent analysis has indicated that SKY92 combined with the International Staging System (ISS) identifies patients with different risk disease with high sensitivity. Here we computed the performance of eight gene expression based classifiers SKY92, UAMS70, UAMS80, IFM15, Proliferation Index, Centrosome Index, Cancer Testis Antigen and HM19 as well as the combination of SKY92/ISS in an independent cohort of 91 newly diagnosed MM patients. The classifiers identified between 9%-21% of patients as high risk, with hazard ratios (HRs) between 1.9 and 8.2. Among the eight signatures, SKY92 identified the largest proportion of patients (21%) also with the highest HR (8.2). Our analysis also validated the combination SKY92/ISS for identification of three classes; low risk (42%), intermediate risk (37%) and high risk (21%). Between low risk and high risk classes the HR is >10. Copyright © 2017 Elsevier Inc. All rights reserved.

Impact of the integration of proton magnetic resonance imaging spectroscopy to PI-RADS 2 for prediction of high grade and high stage prostate cancer.

PubMed

Leapman, Michael S; Wang, Zhen J; Behr, Spencer C; Kurhanewicz, John; Zagoria, Ronald J; Carroll, Peter R; Westphalen, Antonio C

2017-01-01

To compare the predictions of dominant Gleason pattern ≥ 4 or non-organ confined disease with Prostate Imaging Reporting and Data System (PI-RADS v2) with or without proton magnetic resonance spectroscopic imaging ( 1 H-MRSI). Thirty-nine men underwent 3-tesla endorectal multiparametric MRI including 1 H-MRSI and prostatectomy. Two radiologists assigned PI-RADS v2 and 1 H-MRSI scores to index lesions. Statistical analyses used logistic regressions, receiver operating characteristic (ROC) curves, and 2x2 tables for diagnostic accuracies. The sensitivity and specificity of 1 H-MRSI and PI-RADS v2 for high-grade prostate cancer (PCa) were 85.7% (57.1%) and 92.9% (100%), and 56% (68.0%) and 24.0% (24.0%). The sensitivity and specificity of 1 H-MRSI and PI-RADS v2 for extra-prostatic extension (EPE) were 64.0% (40%) and 20.0% (48%), and 50.0% (57.1%) and 71.4% (64.3%). The area under the ROC curves (AUC) for prediction of high-grade prostate cancer were 0.65 and 0.61 for PI-RADS v2 and 0.72 and 0.70 when combined with 1 H-MRSI (readers 1 and 2, p = 0.04 and 0.21). For prediction of EPE the AUC were 0.54 and 0.60 for PI-RADS v2 and 0.55 and 0.61 when combined with 1 H-MRSI ( p > 0.05). 1 H-MRSI might improve the discrimination of high-grade prostate cancer when combined to PI-RADS v2, particularly for PI-RADS v2 score 4 lesions, but it does not affect the prediction of EPE.

Apertureless near-field/far-field CW two-photon microscope for biological and material imaging and spectroscopic applications.

PubMed

Nowak, Derek B; Lawrence, A J; Sánchez, Erik J

2010-12-10

We present the development of a versatile spectroscopic imaging tool to allow for imaging with single-molecule sensitivity and high spatial resolution. The microscope allows for near-field and subdiffraction-limited far-field imaging by integrating a shear-force microscope on top of a custom inverted microscope design. The instrument has the ability to image in ambient conditions with optical resolutions on the order of tens of nanometers in the near field. A single low-cost computer controls the microscope with a field programmable gate array data acquisition card. High spatial resolution imaging is achieved with an inexpensive CW multiphoton excitation source, using an apertureless probe and simplified optical pathways. The high-resolution, combined with high collection efficiency and single-molecule sensitive optical capabilities of the microscope, are demonstrated with a low-cost CW laser source as well as a mode-locked laser source.

Risk-based residential HLB/ACP survey for California, Texas and Arizona

USDA-ARS?s Scientific Manuscript database

The recent discoveries of HLB in the Los Angeles Basin and the Rio Grande Valley of Texas underscore the imminent danger of HLB spread in these two States and the urgent need for highly sensitive survey methods for early detection of new residential infections of HLB combined with rapid intervention...

Development of an immunomagnetic separation-polymerase chain reaction (IMS-PCR) assay specific for Enterocytozoon bieneusi in water samples.

PubMed

Sorel, N; Guillot, E; Thellier, M; Accoceberry, I; Datry, A; Mesnard-Rouiller, L; Miégeville, M

2003-01-01

Microsporidia have become widely recognized as important human pathogens. Among Microsporidia, Enterocytozoon bieneusi is responsible for severe gastrointestinal disease. To date, no current therapy has been proven effective. Their mode of transmission and environmental occurrence are poorly documented because of the lack of detection methods that are both species-specific and sensitive. In this study, we developed a sensitive and specific molecular method to detect E. bieneusi spores in water samples. The molecular assay combined immunomagnetic separation (IMS) and polymerase chain reaction (PCR) amplification to detect E. bieneusi spores. A comparison was made of IMS magnetic beads coated with two different monoclonal antibodies, one specific for the Encephalitozoon genus that cross-reacts with E. bieneusi and the other specific only for the E. bieneusi species itself. Immunotech beads coated with the antibody specific for E. bieneusi were found to be the most effective combination. The highly specific IMS-PCR assay developed in this study provides a rapid and sensitive means of screening water samples for the presence of E. bieneusi spores.

Investigation of subcellular localization and dynamics of membrane proteins in living bacteria by combining optical micromanipulation and high-resolution microscopy (Conference Presentation)

NASA Astrophysics Data System (ADS)

Barroso Peña, Álvaro; Nieves, Marcos; Teper, Konrad; Wedlich-Soldner, Roland; Denz, Cornelia

2016-09-01

The plasma membrane serves as protective interface between cells and their environment. It also constitutes a hub for selective nutrient uptake and signal transduction. Increasing evidence over the last years indicates that, similar to eukaryotic cells, lateral membrane organization plays an important role in the regulation of prokaryotic signaling pathways. However, the mechanisms underlying this phenomenon are still poorly understood. Spatiotemporal characterization of bacterial signal transduction demands very sensitive high-resolution microscopy techniques due to the low expression levels of most signaling proteins and the small size of bacterial cells. In addition, direct study of subcellular confinement and dynamics of bacterial signaling proteins during the different stages of the signal transduction also requires immobilization in order to avoid cell displacement caused by Brownian motion, local fluid flows and bacterial self-propulsion. In this work we present a novel approach based on the combination of high resolution imaging and optical manipulation that enables the investigation of the distribution and dynamics of proteins at the bacterial plasma membrane. For this purpose, we combine the versatility of holographic optical tweezers (HOT) with the sensitivity and resolution of total internal reflection fluorescence (TIRF) microscopy. Furthermore, we discuss the implementation of microfluidic devices in our integrated HOT+TIRF system for the control of growth conditions of bacterial cells. The capabilities of our workstation provides thus new valuable insights into the fundamental cellular and physical mechanisms underlying the regulation of bacterial signal transduction.

A combined strategy for screening a clustered mobile population returning from highly endemic areas for Plasmodium falciparum.

PubMed

Li, Mei; Li, Jun; Xia, Zhigui; Xiao, Ning; Jiang, Weikang; Wen, Yongkang

2017-04-30

Early and accurate diagnosis of imported malaria cases in clusters is crucial for protecting the health of patients and local populations, especially confirmed parasitic persons who are asymptomatic. A total of 226 gold miners who had stayed in highly endemic areas of Ghana for more than six months and returned in clusters were selected randomly. Blood samples from them were tested with microscopy, nest polymerase chain reaction, and rapid diagnostic test (RDT). The sensitivity, specificity, predictive values, agreement rate, and Youden's index of each of three diagnostic methods were calculated and compared with the defined gold standard. A quick and efficient way to respond to screening such a clustered mobile population was predicted and analyzed by evaluating two assumed results of combining microscopy and RDT with or without symptoms of illness. The rate of the carriers of malaria parasites in the populations of gold miners was 19.47%, including 39 P. falciparum. Among the three diagnostic methods, the microscopy method showed the highest specificity, while the RDT method showed the highest sensitivity but the lowest specificity in detecting P. falciparum. The assumed results of combining RDT and microscopy with symptoms showed the best results among all the test results in screening P. falciparum. It was too complex and difficult to catch all parasite carriers in a short period of time among populations with such a complicated situation as that in Shanglin County. A strategy of combing microscopy and RDT for diagnosis is highly recommended.

Vectorial capacity and vector control: reconsidering sensitivity to parameters for malaria elimination.

PubMed

Brady, Oliver J; Godfray, H Charles J; Tatem, Andrew J; Gething, Peter W; Cohen, Justin M; McKenzie, F Ellis; Perkins, T Alex; Reiner, Robert C; Tusting, Lucy S; Sinka, Marianne E; Moyes, Catherine L; Eckhoff, Philip A; Scott, Thomas W; Lindsay, Steven W; Hay, Simon I; Smith, David L

2016-02-01

Major gains have been made in reducing malaria transmission in many parts of the world, principally by scaling-up coverage with long-lasting insecticidal nets and indoor residual spraying. Historically, choice of vector control intervention has been largely guided by a parameter sensitivity analysis of George Macdonald's theory of vectorial capacity that suggested prioritizing methods that kill adult mosquitoes. While this advice has been highly successful for transmission suppression, there is a need to revisit these arguments as policymakers in certain areas consider which combinations of interventions are required to eliminate malaria. Using analytical solutions to updated equations for vectorial capacity we build on previous work to show that, while adult killing methods can be highly effective under many circumstances, other vector control methods are frequently required to fill effective coverage gaps. These can arise due to pre-existing or developing mosquito physiological and behavioral refractoriness but also due to additive changes in the relative importance of different vector species for transmission. Furthermore, the optimal combination of interventions will depend on the operational constraints and costs associated with reaching high coverage levels with each intervention. Reaching specific policy goals, such as elimination, in defined contexts requires increasingly non-generic advice from modelling. Our results emphasize the importance of measuring baseline epidemiology, intervention coverage, vector ecology and program operational constraints in predicting expected outcomes with different combinations of interventions. © The Author 2016. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.

Advanced Mass Spectrometric Methods for the Rapid and Quantitative Characterization of Proteomes

DOE PAGES

Smith, Richard D.

2002-01-01

Progress is reviewedmore » towards the development of a global strategy that aims to extend the sensitivity, dynamic range, comprehensiveness and throughput of proteomic measurements based upon the use of high performance separations and mass spectrometry. The approach uses high accuracy mass measurements from Fourier transform ion cyclotron resonance mass spectrometry (FTICR) to validate peptide ‘accurate mass tags’ (AMTs) produced by global protein enzymatic digestions for a specific organism, tissue or cell type from ‘potential mass tags’ tentatively identified using conventional tandem mass spectrometry (MS/MS). This provides the basis for subsequent measurements without the need for MS/ MS. High resolution capillary liquid chromatography separations combined with high sensitivity, and high resolution accurate FTICR measurements are shown to be capable of characterizing peptide mixtures of more than 10 5 components. The strategy has been initially demonstrated using the microorganisms Saccharomyces cerevisiae and Deinococcus radiodurans. Advantages of the approach include the high confidence of protein identification, its broad proteome coverage, high sensitivity, and the capability for stableisotope labeling methods for precise relative protein abundance measurements. Abbreviations : LC, liquid chromatography; FTICR, Fourier transform ion cyclotron resonance; AMT, accurate mass tag; PMT, potential mass tag; MMA, mass measurement accuracy; MS, mass spectrometry; MS/MS, tandem mass spectrometry; ppm, parts per million.« less

A CMOS-based large-area high-resolution imaging system for high-energy x-ray applications

NASA Astrophysics Data System (ADS)

Rodricks, Brian; Fowler, Boyd; Liu, Chiao; Lowes, John; Haeffner, Dean; Lienert, Ulrich; Almer, John

2008-08-01

CCDs have been the primary sensor in imaging systems for x-ray diffraction and imaging applications in recent years. CCDs have met the fundamental requirements of low noise, high-sensitivity, high dynamic range and spatial resolution necessary for these scientific applications. State-of-the-art CMOS image sensor (CIS) technology has experienced dramatic improvements recently and their performance is rivaling or surpassing that of most CCDs. The advancement of CIS technology is at an ever-accelerating pace and is driven by the multi-billion dollar consumer market. There are several advantages of CIS over traditional CCDs and other solid-state imaging devices; they include low power, high-speed operation, system-on-chip integration and lower manufacturing costs. The combination of superior imaging performance and system advantages makes CIS a good candidate for high-sensitivity imaging system development. This paper will describe a 1344 x 1212 CIS imaging system with a 19.5μm pitch optimized for x-ray scattering studies at high-energies. Fundamental metrics of linearity, dynamic range, spatial resolution, conversion gain, sensitivity are estimated. The Detective Quantum Efficiency (DQE) is also estimated. Representative x-ray diffraction images are presented. Diffraction images are compared against a CCD-based imaging system.

Methionine Deprivation Induces a Targetable Vulnerability in Triple-Negative Breast Cancer Cells by Enhancing TRAIL Receptor-2 Expression.

PubMed

Strekalova, Elena; Malin, Dmitry; Good, David M; Cryns, Vincent L

2015-06-15

Many neoplasms are vulnerable to methionine deficiency by mechanisms that are poorly understood. Because gene profiling studies have revealed that methionine depletion increases TNF-related apoptosis-inducing ligand receptor-2 (TRAIL-R2) mRNA, we postulated that methionine stress sensitizes breast cancer cells to proapoptotic TRAIL-R2 agonists. Human triple (ER/PR/HER2)-negative breast carcinoma cell lines were cultured in control or methionine-free media. The effects of methionine depletion on TRAIL receptor expression and sensitivity to chemotherapy or a humanized agonistic TRAIL-R2 monoclonal antibody (lexatumumab) were determined. The melanoma-associated antigen MAGED2 was silenced to delineate its functional role in sensitizing TNBC cells to methionine stress. An orthotopic TNBC model was utilized to evaluate the effects of dietary methionine deficiency, lexatumumab, or the combination. Methionine depletion sensitized TNBC cells to lexatumumab-induced caspase activation and apoptosis by increasing TRAIL-R2 mRNA and cell surface expression. MCF-10A cells transformed by oncogenic H-Ras, but not untransformed cells, and matrix-detached TNBC cells were highly sensitive to the combination of lexatumumab and methionine depletion. Proteomics analyses revealed that MAGED2, which has been reported to reduce TRAIL-R2 expression, was suppressed by methionine stress. Silencing MAGED2 recapitulated features of methionine deprivation, including enhanced mRNA and cell surface expression of TRAIL receptors and increased sensitivity to TRAIL receptor agonists. Dietary methionine deprivation enhanced the antitumor effects of lexatumumab in an orthotopic metastatic TNBC model. Methionine depletion exposes a targetable defect in TNBC cells by increasing TRAIL-R2 expression. Our findings provide the foundation for a clinical trial combining dietary methionine restriction and TRAIL-R2 agonists. Clin Cancer Res; 21(12); 2780-91. ©2015 AACR. ©2015 American Association for Cancer Research.

High performance gel imaging with a commercial single lens reflex camera

NASA Astrophysics Data System (ADS)

Slobodan, J.; Corbett, R.; Wye, N.; Schein, J. E.; Marra, M. A.; Coope, R. J. N.

2011-03-01

A high performance gel imaging system was constructed using a digital single lens reflex camera with epi-illumination to image 19 × 23 cm agarose gels with up to 10,000 DNA bands each. It was found to give equivalent performance to a laser scanner in this high throughput DNA fingerprinting application using the fluorophore SYBR Green®. The specificity and sensitivity of the imager and scanner were within 1% using the same band identification software. Low and high cost color filters were also compared and it was found that with care, good results could be obtained with inexpensive dyed acrylic filters in combination with more costly dielectric interference filters, but that very poor combinations were also possible. Methods for determining resolution, dynamic range, and optical efficiency for imagers are also proposed to facilitate comparison between systems.

High blood pressure and visual sensitivity

NASA Astrophysics Data System (ADS)

Eisner, Alvin; Samples, John R.

2003-09-01

The study had two main purposes: (1) to determine whether the foveal visual sensitivities of people treated for high blood pressure (vascular hypertension) differ from the sensitivities of people who have not been diagnosed with high blood pressure and (2) to understand how visual adaptation is related to standard measures of systemic cardiovascular function. Two groups of middle-aged subjects-hypertensive and normotensive-were examined with a series of test/background stimulus combinations. All subjects met rigorous inclusion criteria for excellent ocular health. Although the visual sensitivities of the two subject groups overlapped extensively, the age-related rate of sensitivity loss was, for some measures, greater for the hypertensive subjects, possibly because of adaptation differences between the two groups. Overall, the degree of steady-state sensitivity loss resulting from an increase of background illuminance (for 580-nm backgrounds) was slightly less for the hypertensive subjects. Among normotensive subjects, the ability of a bright (3.8-log-td), long-wavelength (640-nm) adapting background to selectively suppress the flicker response of long-wavelength-sensitive (LWS) cones was related inversely to the ratio of mean arterial blood pressure to heart rate. The degree of selective suppression was also related to heart rate alone, and there was evidence that short-term changes of cardiovascular response were important. The results suggest that (1) vascular hypertension, or possibly its treatment, subtly affects visual function even in the absence of eye disease and (2) changes in blood flow affect retinal light-adaptation processes involved in the selective suppression of the flicker response from LWS cones caused by bright, long-wavelength backgrounds.

Two Clock Transitions in Neutral Yb for the Highest Sensitivity to Variations of the Fine-Structure Constant.

PubMed

Safronova, Marianna S; Porsev, Sergey G; Sanner, Christian; Ye, Jun

2018-04-27

We propose a new frequency standard based on a 4f^{14}6s6p ^{3}P_{0}-4f^{13}6s^{2}5d (J=2) transition in neutral Yb. This transition has a potential for high stability and accuracy and the advantage of the highest sensitivity among atomic clocks to variation of the fine-structure constant α. We find its dimensionless α-variation enhancement factor to be K=-15, in comparison to the most sensitive current clock (Yb^{+}  E3, K=-6), and it is 18 times larger than in any neutral-atomic clocks (Hg, K=0.8). Combined with the unprecedented stability of an optical lattice clock for neutral atoms, this high sensitivity opens new perspectives for searches for ultralight dark matter and for tests of theories beyond the standard model of elementary particles. Moreover, together with the well-established ^{1}S_{0}-^{3}P_{0} transition, one will have two clock transitions operating in neutral Yb, whose interleaved interrogations may further reduce systematic uncertainties of such clock-comparison experiments.

Time-Resolved Fluorescent Immunochromatography of Aflatoxin B1 in Soybean Sauce: A Rapid and Sensitive Quantitative Analysis.

PubMed

Wang, Du; Zhang, Zhaowei; Li, Peiwu; Zhang, Qi; Zhang, Wen

2016-07-14

Rapid and quantitative sensing of aflatoxin B1 with high sensitivity and specificity has drawn increased attention of studies investigating soybean sauce. A sensitive and rapid quantitative immunochromatographic sensing method was developed for the detection of aflatoxin B1 based on time-resolved fluorescence. It combines the advantages of time-resolved fluorescent sensing and immunochromatography. The dynamic range of a competitive and portable immunoassay was 0.3-10.0 µg·kg(-1), with a limit of detection (LOD) of 0.1 µg·kg(-1) and recoveries of 87.2%-114.3%, within 10 min. The results showed good correlation (R² > 0.99) between time-resolved fluorescent immunochromatographic strip test and high performance liquid chromatography (HPLC). Soybean sauce samples analyzed using time-resolved fluorescent immunochromatographic strip test revealed that 64.2% of samples contained aflatoxin B1 at levels ranging from 0.31 to 12.5 µg·kg(-1). The strip test is a rapid, sensitive, quantitative, and cost-effective on-site screening technique in food safety analysis.

Two Clock Transitions in Neutral Yb for the Highest Sensitivity to Variations of the Fine-Structure Constant

NASA Astrophysics Data System (ADS)

Safronova, Marianna S.; Porsev, Sergey G.; Sanner, Christian; Ye, Jun

2018-04-01

We propose a new frequency standard based on a 4 f146 s 6 p P0 3 -4 f136 s25 d (J =2 ) transition in neutral Yb. This transition has a potential for high stability and accuracy and the advantage of the highest sensitivity among atomic clocks to variation of the fine-structure constant α . We find its dimensionless α -variation enhancement factor to be K =-15 , in comparison to the most sensitive current clock (Yb+ E 3 , K =-6 ), and it is 18 times larger than in any neutral-atomic clocks (Hg, K =0.8 ). Combined with the unprecedented stability of an optical lattice clock for neutral atoms, this high sensitivity opens new perspectives for searches for ultralight dark matter and for tests of theories beyond the standard model of elementary particles. Moreover, together with the well-established 1S0-3P0 transition, one will have two clock transitions operating in neutral Yb, whose interleaved interrogations may further reduce systematic uncertainties of such clock-comparison experiments.

Polystyrene Oxygen Optodes Doped with Ir(III) and Pd(II) meso-Tetrakis(pentafluorophenyl)porphyrin Using an LED-Based High-Sensitivity Phosphorimeter.

PubMed

Filho, Alexandre F De Moraes; Gewehr, Pedro M; Maia, Joaquim M; Jakubiak, Douglas R

2018-06-15

This paper presents a gaseous oxygen detection system based on time-resolved phosphorimetry (time-domain), which is used to investigate O2 optical transducers. The primary sensing elements were formed by incorporating iridium(III) and palladium(II) meso -tetrakis(pentafluorophenyl)porphyrin complexes (IrTFPP-CO-Cl and PdTFPP) in polystyrene (PS) solid matrices. Probe excitation was obtained using a violet light-emitting diode (LED) (low power), and the resulting phosphorescence was detected by a high-sensitivity compact photomultiplier tube. The detection system performance and the preparation of the transducers are presented along with their optical properties, phosphorescence lifetimes, calibration curves and photostability. The developed lifetime measuring system showed a good signal-to-noise ratio, and reliable results were obtained from the optodes, even when exposed to moderate levels of O2. The new IrTFPP-CO-Cl membranes exhibited room temperature phosphorescence and moderate sensitivity: <τ0>/<τ21%> ratio of ≈6. A typically high degree of dynamic phosphorescence quenching was observed for the traditional indicator PdTFPP: <τ0>/<τ21%> ratio of ≈36. Pulsed-source time-resolved phosphorimetry combined with a high-sensitivity photodetector can offer potential advantages such as: (i) major dynamic range, (ii) extended temporal resolution (Δτ/Δ[O2]) and (iii) high operational stability. IrTFPP-CO-Cl immobilized in polystyrene is a promising alternative for O2 detection, offering adequate photostability and potentially mid-range sensitivity over Pt(II) and Pd(II) metalloporphyrins.

Application of flowerlike MgO for highly sensitive determination of lead via matrix-assisted laser desorption/ionization mass spectrometry.

PubMed

Hou, Jian; Chen, Suming; Cao, Changyan; Liu, Huihui; Xiong, Caiqiao; Zhang, Ning; He, Qing; Song, Weiguo; Nie, Zongxiu

2016-08-01

Matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS) is a high-throughput method to achieve fast and accurate identification of lead (Pb) exposure, but is seldom used because of low ionization efficiency and insufficient sensitivity. Nanomaterials applied in MS are a promising technique to overcome the obstacles of MALDI. Flowerlike MgO nanostructures are applied for highly sensitive lead profiling in real samples. They can be used in two ways: (a) MgO is mixed with N-naphthylethylenediamine dihydrochloride (NEDC) as a novel matrix MgO/NEDC; (b) MgO is applied as an absorbent to enrich Pb ions in very dilute solution. The signal intensities of lead by MgO/NEDC were ten times higher than the NEDC matrix. It also shows superior anti-interference ability when analyzing 10 μmol/L Pb ions in the presence of organic substances or interfering metal ions. By applying MgO as adsorbent, the LOD of lead before enrichment is 1 nmol/L. Blood lead test can be achieved using this enrichment process. Besides, MgO can play the role of internal standard to achieve quantitative analysis. Flowerlike MgO nanostructures were applied for highly sensitive lead profiling in real samples. The method is helpful to prevent Pb contamination in a wide range. Further, the combination of MgO with MALDI MS could inspire more nanomaterials being applied in highly sensitive profiling of pollutants. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Multi-pinhole collimator design for small-object imaging with SiliSPECT: a high-resolution SPECT

NASA Astrophysics Data System (ADS)

Shokouhi, S.; Metzler, S. D.; Wilson, D. W.; Peterson, T. E.

2009-01-01

We have designed a multi-pinhole collimator for a dual-headed, stationary SPECT system that incorporates high-resolution silicon double-sided strip detectors. The compact camera design of our system enables imaging at source-collimator distances between 20 and 30 mm. Our analytical calculations show that using knife-edge pinholes with small-opening angles or cylindrically shaped pinholes in a focused, multi-pinhole configuration in combination with this camera geometry can generate narrow sensitivity profiles across the field of view that can be useful for imaging small objects at high sensitivity and resolution. The current prototype system uses two collimators each containing 127 cylindrically shaped pinholes that are focused toward a target volume. Our goal is imaging objects such as a mouse brain, which could find potential applications in molecular imaging.

Long range surface plasmon resonance with ultra-high penetration depth for self-referenced sensing and ultra-low detection limit using diverging beam approach

DOE Office of Scientific and Technical Information (OSTI.GOV)

Isaacs, Sivan, E-mail: sivan.isaacs@gmail.com; Abdulhalim, Ibrahim; NEW CREATE Programme, School of Materials Science and Engineering, 1 CREATE Way, Research Wing, #02-06/08, Singapore 138602

2015-05-11

Using an insulator-metal-insulator structure with dielectric having refractive index (RI) larger than the analyte, long range surface plasmon (SP) resonance exhibiting ultra-high penetration depth is demonstrated for sensing applications of large bioentities at wavelengths in the visible range. Based on the diverging beam approach in Kretschmann-Raether configuration, one of the SP resonances is shown to shift in response to changes in the analyte RI while the other is fixed; thus, it can be used as a built in reference. The combination of the high sensitivity, high penetration depth and self-reference using the diverging beam approach in which a dark linemore » is detected of the high sensitivity, high penetration depth, self-reference, and the diverging beam approach in which a dark line is detected using large number of camera pixels with a smart algorithm for sub-pixel resolution, a sensor with ultra-low detection limit is demonstrated suitable for large bioentities.« less

Human papillomavirus DNA testing as an adjunct to cytology in cervical screening programs.

PubMed

Lörincz, Attila T; Richart, Ralph M

2003-08-01

Our objective was to review current large studies of human papillomavirus (HPV) DNA testing as an adjunct to the Papanicolaou test for cervical cancer screening programs. We analyzed 10 large screening studies that used the Hybrid Capture 2 test and 3 studies that used the polymerase chain reaction test in a manner that enabled reliable estimates of accuracy for detecting or predicting high-grade cervical intraepithelial neoplasia (CIN). Most studies allowed comparison of HPV DNA and Papanicolaou testing and estimates of the performance of Papanicolaou and HPV DNA as combined tests. The studies were selected on the basis of a sufficient number of cases of high-grade CIN and cancer to provide meaningful statistical values. Investigators had to demonstrate the ability to generate reasonably reliable Hybrid Capture 2 or polymerase chain reaction data that were either minimally biased by nature of study design or that permitted analytical techniques for addressing issues of study bias to be applied. Studies had to provide data for the calculation of test sensitivity, specificity, predictive values, odds ratios, relative risks, confidence intervals, and other relevant measures. Final data were abstracted directly from published articles or estimated from descriptive statistics presented in the articles. In some studies, new analyses were performed from raw data supplied by the principal investigators. We concluded that HPV DNA testing was a more sensitive indicator for prevalent high-grade CIN than either conventional or liquid cytology. A combination of HPV DNA and Papanicolaou testing had almost 100% sensitivity and negative predictive value. The specificity of the combined tests was slightly lower than the specificity of the Papanicolaou test alone, but this decrease could potentially be offset by greater protection from neoplastic progression and cost savings available from extended screening intervals. One "double-negative" HPV DNA and Papanicolaou test indicated better prognostic assurance against risk of future CIN 3 than 3 subsequent negative conventional Papanicolaou tests and may safely allow 3-year screening intervals for such low-risk women.

Factorizing the motion sensitivity function into equivalent input noise and calculation efficiency.

PubMed

Allard, Rémy; Arleo, Angelo

2017-01-01

The photopic motion sensitivity function of the energy-based motion system is band-pass peaking around 8 Hz. Using an external noise paradigm to factorize the sensitivity into equivalent input noise and calculation efficiency, the present study investigated if the variation in photopic motion sensitivity as a function of the temporal frequency is due to a variation of equivalent input noise (e.g., early temporal filtering) or calculation efficiency (ability to select and integrate motion). For various temporal frequencies, contrast thresholds for a direction discrimination task were measured in presence and absence of noise. Up to 15 Hz, the sensitivity variation was mainly due to a variation of equivalent input noise and little variation in calculation efficiency was observed. The sensitivity fall-off at very high temporal frequencies (from 15 to 30 Hz) was due to a combination of a drop of calculation efficiency and a rise of equivalent input noise. A control experiment in which an artificial temporal integration was applied to the stimulus showed that an early temporal filter (generally assumed to affect equivalent input noise, not calculation efficiency) could impair both the calculation efficiency and equivalent input noise at very high temporal frequencies. We conclude that at the photopic luminance intensity tested, the variation of motion sensitivity as a function of the temporal frequency was mainly due to early temporal filtering, not to the ability to select and integrate motion. More specifically, we conclude that photopic motion sensitivity at high temporal frequencies is limited by internal noise occurring after the transduction process (i.e., neural noise), not by quantal noise resulting from the probabilistic absorption of photons by the photoreceptors as previously suggested.

Combining Diffusion Tensor Metrics and DSC Perfusion Imaging: Can It Improve the Diagnostic Accuracy in Differentiating Tumefactive Demyelination from High-Grade Glioma?

PubMed

Hiremath, S B; Muraleedharan, A; Kumar, S; Nagesh, C; Kesavadas, C; Abraham, M; Kapilamoorthy, T R; Thomas, B

2017-04-01

Tumefactive demyelinating lesions with atypical features can mimic high-grade gliomas on conventional imaging sequences. The aim of this study was to assess the role of conventional imaging, DTI metrics ( p:q tensor decomposition), and DSC perfusion in differentiating tumefactive demyelinating lesions and high-grade gliomas. Fourteen patients with tumefactive demyelinating lesions and 21 patients with high-grade gliomas underwent brain MR imaging with conventional, DTI, and DSC perfusion imaging. Imaging sequences were assessed for differentiation of the lesions. DTI metrics in the enhancing areas and perilesional hyperintensity were obtained by ROI analysis, and the relative CBV values in enhancing areas were calculated on DSC perfusion imaging. Conventional imaging sequences had a sensitivity of 80.9% and specificity of 57.1% in differentiating high-grade gliomas ( P = .049) from tumefactive demyelinating lesions. DTI metrics ( p : q tensor decomposition) and DSC perfusion demonstrated a statistically significant difference in the mean values of ADC, the isotropic component of the diffusion tensor, the anisotropic component of the diffusion tensor, the total magnitude of the diffusion tensor, and rCBV among enhancing portions in tumefactive demyelinating lesions and high-grade gliomas ( P ≤ .02), with the highest specificity for ADC, the anisotropic component of the diffusion tensor, and relative CBV (92.9%). Mean fractional anisotropy values showed no significant statistical difference between tumefactive demyelinating lesions and high-grade gliomas. The combination of DTI and DSC parameters improved the diagnostic accuracy (area under the curve = 0.901). Addition of a heterogeneous enhancement pattern to DTI and DSC parameters improved it further (area under the curve = 0.966). The sensitivity increased from 71.4% to 85.7% after the addition of the enhancement pattern. DTI and DSC perfusion add profoundly to conventional imaging in differentiating tumefactive demyelinating lesions and high-grade gliomas. The combination of DTI metrics and DSC perfusion markedly improved diagnostic accuracy. © 2017 by American Journal of Neuroradiology.

Combined sodium ion sensitivity in agonist binding and internalization of vasopressin V1b receptors.

PubMed

Koshimizu, Taka-Aki; Kashiwazaki, Aki; Taniguchi, Junichi

2016-05-03

Reducing Na(+) in the extracellular environment may lead to two beneficial effects for increasing agonist binding to cell surface G-protein coupled receptors (GPCRs): reduction of Na(+)-mediated binding block and reduce of receptor internalization. However, such combined effects have not been explored. We used Chinese Hamster Ovary cells expressing vasopressin V1b receptors as a model to explore Na(+) sensitivity in agonist binding and receptor internalization. Under basal conditions, a large fraction of V1b receptors is located intracellularly, and a small fraction is in the plasma membrane. Decreases in external Na(+) increased cell surface [(3)H]AVP binding and decreased receptor internalization. Substitution of Na(+) by Cs(+) or NH4(+) inhibited agonist binding. To suppress receptor internalization, the concentration of NaCl, but not of CsCl, had to be less than 50 mM, due to the high sensitivity of the internalization machinery to Na(+) over Cs(+). Iso-osmotic supplementation of glucose or NH4Cl maintained internalization of the V1b receptor, even in a low-NaCl environment. Moreover, iodide ions, which acted as a counter anion, inhibited V1b agonist binding. In summary, we found external ionic conditions that could increase the presence of high-affinity state receptors at the cell surface with minimum internalization during agonist stimulations.

Combined sodium ion sensitivity in agonist binding and internalization of vasopressin V1b receptors

PubMed Central

Koshimizu, Taka-aki; Kashiwazaki, Aki; Taniguchi, Junichi

2016-01-01

Reducing Na+ in the extracellular environment may lead to two beneficial effects for increasing agonist binding to cell surface G-protein coupled receptors (GPCRs): reduction of Na+-mediated binding block and reduce of receptor internalization. However, such combined effects have not been explored. We used Chinese Hamster Ovary cells expressing vasopressin V1b receptors as a model to explore Na+ sensitivity in agonist binding and receptor internalization. Under basal conditions, a large fraction of V1b receptors is located intracellularly, and a small fraction is in the plasma membrane. Decreases in external Na+ increased cell surface [3H]AVP binding and decreased receptor internalization. Substitution of Na+ by Cs+ or NH4+ inhibited agonist binding. To suppress receptor internalization, the concentration of NaCl, but not of CsCl, had to be less than 50 mM, due to the high sensitivity of the internalization machinery to Na+ over Cs+. Iso-osmotic supplementation of glucose or NH4Cl maintained internalization of the V1b receptor, even in a low-NaCl environment. Moreover, iodide ions, which acted as a counter anion, inhibited V1b agonist binding. In summary, we found external ionic conditions that could increase the presence of high-affinity state receptors at the cell surface with minimum internalization during agonist stimulations. PMID:27138239

Probabilistic Simulation of Combined Thermo-Mechanical Cyclic Fatigue in Composites

NASA Technical Reports Server (NTRS)

Chamis, Christos C.

2011-01-01

A methodology to compute probabilistically-combined thermo-mechanical fatigue life of polymer matrix laminated composites has been developed and is demonstrated. Matrix degradation effects caused by long-term environmental exposure and mechanical/thermal cyclic loads are accounted for in the simulation process. A unified time-temperature-stress-dependent multifactor-interaction relationship developed at NASA Glenn Research Center has been used to model the degradation/aging of material properties due to cyclic loads. The fast probability-integration method is used to compute probabilistic distribution of response. Sensitivities of fatigue life reliability to uncertainties in the primitive random variables (e.g., constituent properties, fiber volume ratio, void volume ratio, ply thickness, etc.) computed and their significance in the reliability-based design for maximum life is discussed. The effect of variation in the thermal cyclic loads on the fatigue reliability for a (0/+/-45/90)s graphite/epoxy laminate with a ply thickness of 0.127 mm, with respect to impending failure modes has been studied. The results show that, at low mechanical-cyclic loads and low thermal-cyclic amplitudes, fatigue life for 0.999 reliability is most sensitive to matrix compressive strength, matrix modulus, thermal expansion coefficient, and ply thickness. Whereas at high mechanical-cyclic loads and high thermal-cyclic amplitudes, fatigue life at 0.999 reliability is more sensitive to the shear strength of matrix, longitudinal fiber modulus, matrix modulus, and ply thickness.

DEFINING THE 'BLIND SPOT' OF HINODE EIS AND XRT TEMPERATURE MEASUREMENTS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Winebarger, Amy R.; Cirtain, Jonathan; Mulu-Moore, Fana

2012-02-20

Observing high-temperature, low emission measure plasma is key to unlocking the coronal heating problem. With current instrumentation, a combination of EUV spectral data from Hinode Extreme-ultraviolet Imaging Spectrometer (EIS; sensitive to temperatures up to 4 MK) and broadband filter data from Hinode X-ray Telescope (XRT; sensitive to higher temperatures) is typically used to diagnose the temperature structure of the observed plasma. In this Letter, we demonstrate that a 'blind spot' exists in temperature-emission measure space for combined Hinode EIS and XRT observations. For a typical active region core with significant emission at 3-4 MK, Hinode EIS and XRT are insensitivemore » to plasma with temperatures greater than {approx}6 MK and emission measures less than {approx}10{sup 27} cm{sup -5}. We then demonstrate that the temperature and emission measure limits of this blind spot depend upon the temperature distribution of the plasma along the line of sight by considering a hypothetical emission measure distribution sharply peaked at 1 MK. For this emission measure distribution, we find that EIS and XRT are insensitive to plasma with emission measures less than {approx}10{sup 26} cm{sup -5}. We suggest that a spatially and spectrally resolved 6-24 Angstrom-Sign spectrum would improve the sensitivity to these high-temperature, low emission measure plasma.« less

Probabilistic Simulation of Combined Thermo-Mechanical Cyclic Fatigue in Composites

NASA Technical Reports Server (NTRS)

Chamis, Christos C.

2010-01-01

A methodology to compute probabilistically-combined thermo-mechanical fatigue life of polymer matrix laminated composites has been developed and is demonstrated. Matrix degradation effects caused by long-term environmental exposure and mechanical/thermal cyclic loads are accounted for in the simulation process. A unified time-temperature-stress-dependent multifactor-interaction relationship developed at NASA Glenn Research Center has been used to model the degradation/aging of material properties due to cyclic loads. The fast probability-integration method is used to compute probabilistic distribution of response. Sensitivities of fatigue life reliability to uncertainties in the primitive random variables (e.g., constituent properties, fiber volume ratio, void volume ratio, ply thickness, etc.) computed and their significance in the reliability-based design for maximum life is discussed. The effect of variation in the thermal cyclic loads on the fatigue reliability for a (0/+/-45/90)s graphite/epoxy laminate with a ply thickness of 0.127 mm, with respect to impending failure modes has been studied. The results show that, at low mechanical-cyclic loads and low thermal-cyclic amplitudes, fatigue life for 0.999 reliability is most sensitive to matrix compressive strength, matrix modulus, thermal expansion coefficient, and ply thickness. Whereas at high mechanical-cyclic loads and high thermal-cyclic amplitudes, fatigue life at 0.999 reliability is more sensitive to the shear strength of matrix, longitudinal fiber modulus, matrix modulus, and ply thickness.

Raman spectroscopy and PCA-SVM as a non-invasive diagnostic tool to identify and classify qualitatively glycated hemoglobin levels in vivo.

PubMed

Villa-Manríquez, J F; Castro-Ramos, J; Gutiérrez-Delgado, F; Lopéz-Pacheco, M A; Villanueva-Luna, A E

2017-08-01

In this study we identify and classify high and low levels of glycated hemoglobin (HbA1c) in healthy volunteers (HV) and diabetic patients (DP). Overall, 86 subjects were evaluated. The Raman spectrum was measured in three anatomical regions of the body: index fingertip, right ear lobe, and forehead. The measurements were performed to compare the difference between the HV and DP (22 well controlled diabetic patients (WCDP) (HbA1c <6.5%), and 49 not controlled diabetic patients (NCDP) (HbA1c ≥6.5%)). Multivariable methods such as principal components analysis (PCA) combined with support vector machine (SVM) were used to develop effective diagnostic algorithms for classification among these groups. The forehead of HV versus WCDP showed the highest sensitivity (100%) and specificity (100%). Sensitivity (100%) and specificity (60%), were highest in the forehead of WCDP, versus NCDP. In HV versus NCDP, the fingertip had the highest sensitivity (100%) and specificity (80%). The efficacy of the diagnostic algorithm by receiver operating characteristic (ROC) curve was confirmed. Overall, our study demonstrated that the combination of Raman spectroscopy and PCA-SVM are feasible non-invasive diagnostic tool in diabetes to classify qualitatively high and low levels of HbA1c in vivo. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

High Throughput Measurement of Locomotor Sensitization to Volatilized Cocaine in Drosophila melanogaster.

PubMed

Filošević, Ana; Al-Samarai, Sabina; Andretić Waldowski, Rozi

2018-01-01

Drosophila melanogaster can be used to identify genes with novel functional roles in neuronal plasticity induced by repeated consumption of addictive drugs. Behavioral sensitization is a relatively simple behavioral output of plastic changes that occur in the brain after repeated exposures to drugs of abuse. The development of screening procedures for genes that control behavioral sensitization has stalled due to a lack of high-throughput behavioral tests that can be used in genetically tractable organism, such as Drosophila . We have developed a new behavioral test, FlyBong, which combines delivery of volatilized cocaine (vCOC) to individually housed flies with objective quantification of their locomotor activity. There are two main advantages of FlyBong: it is high-throughput and it allows for comparisons of locomotor activity of individual flies before and after single or multiple exposures. At the population level, exposure to vCOC leads to transient and concentration-dependent increase in locomotor activity, representing sensitivity to an acute dose. A second exposure leads to further increase in locomotion, representing locomotor sensitization. We validate FlyBong by showing that locomotor sensitization at either the population or individual level is absent in the mutants for circadian genes period (per) , Clock (Clk) , and cycle (cyc) . The locomotor sensitization that is present in timeless (tim) and pigment dispersing factor (pdf) mutant flies is in large part not cocaine specific, but derived from increased sensitivity to warm air. Circadian genes are not only integral part of the neural mechanism that is required for development of locomotor sensitization, but in addition, they modulate the intensity of locomotor sensitization as a function of the time of day. Motor-activating effects of cocaine are sexually dimorphic and require a functional dopaminergic transporter. FlyBong is a new and improved method for inducing and measuring locomotor sensitization to cocaine in individual Drosophila . Because of its high-throughput nature, FlyBong can be used in genetic screens or in selection experiments aimed at the unbiased identification of functional genes involved in acute or chronic effects of volatilized psychoactive substances.

High Throughput Measurement of Locomotor Sensitization to Volatilized Cocaine in Drosophila melanogaster

PubMed Central

Filošević, Ana; Al-samarai, Sabina; Andretić Waldowski, Rozi

2018-01-01

Drosophila melanogaster can be used to identify genes with novel functional roles in neuronal plasticity induced by repeated consumption of addictive drugs. Behavioral sensitization is a relatively simple behavioral output of plastic changes that occur in the brain after repeated exposures to drugs of abuse. The development of screening procedures for genes that control behavioral sensitization has stalled due to a lack of high-throughput behavioral tests that can be used in genetically tractable organism, such as Drosophila. We have developed a new behavioral test, FlyBong, which combines delivery of volatilized cocaine (vCOC) to individually housed flies with objective quantification of their locomotor activity. There are two main advantages of FlyBong: it is high-throughput and it allows for comparisons of locomotor activity of individual flies before and after single or multiple exposures. At the population level, exposure to vCOC leads to transient and concentration-dependent increase in locomotor activity, representing sensitivity to an acute dose. A second exposure leads to further increase in locomotion, representing locomotor sensitization. We validate FlyBong by showing that locomotor sensitization at either the population or individual level is absent in the mutants for circadian genes period (per), Clock (Clk), and cycle (cyc). The locomotor sensitization that is present in timeless (tim) and pigment dispersing factor (pdf) mutant flies is in large part not cocaine specific, but derived from increased sensitivity to warm air. Circadian genes are not only integral part of the neural mechanism that is required for development of locomotor sensitization, but in addition, they modulate the intensity of locomotor sensitization as a function of the time of day. Motor-activating effects of cocaine are sexually dimorphic and require a functional dopaminergic transporter. FlyBong is a new and improved method for inducing and measuring locomotor sensitization to cocaine in individual Drosophila. Because of its high-throughput nature, FlyBong can be used in genetic screens or in selection experiments aimed at the unbiased identification of functional genes involved in acute or chronic effects of volatilized psychoactive substances. PMID:29459820

Laser confocal feedback tomography and nano-step height measurement

PubMed Central

Tan, Yidong; Wang, Weiping; Xu, Chunxin; Zhang, Shulian

2013-01-01

A promising method for tomography and step height measurement is proposed, which combines the high sensitivity of the frequency-shifted feedback laser and the axial positioning ability of confocal microscopy. By demodulating the feedback-induced intensity modulation signals, the obtained amplitude and phase information are used to respectively determine the coarse and fine measurement of the samples. Imaging the micro devices and biological samples by the demodulated amplitude, this approach is proved to be able to achieve the cross-sectional image in highly scattered mediums. And then the successful height measurement of nano-step on a glass-substrate grating by combination of both amplitude and phase information indicates its axial high resolution (better than 2 nm) in a non-ambiguous range of about ten microns. PMID:24145717

Inductively Coupled Plasma Mass Spectrometry (ICP-MS) and its Application in Life Sciences

NASA Astrophysics Data System (ADS)

Xu, Gu-feng; Wang, Hong-mei

2001-08-01

Inductively-coupled plasma mass spectrometry (ICP-MS) has made much progress since its birth in the late 1990s. This paper will give a rather systematic overview on the use of this technique in new devices and technologies related to plasma source, sample-introducing device and detecting spectrometer etc. In this overview, an emphasis will be put on the evaluation of the ICP-MS technique in combination with a series of physical, chemical and biological techniques, such as laser ablation (LA), capillary electrophoresis (CE) and high performance liquid chromatograph (HPLC), along with their representative high accuracy and high sensitivity. Finally, comprehensive and fruitful applications of the ICP-MS and its combinative techniques in the detection of trace metallic elements and isotopes in complex biological and environmental samples will be revealed.

Aerosol-Cloud Interaction Determined by Both in Situ and Satellite Data Over a Northern High-Latitude Site

NASA Technical Reports Server (NTRS)

Lihavainen, H.; Kerminen, V.-M.; Remer, L. A.

2009-01-01

The first aerosol indirect effect over a clean, northern high-latitude site was investigated by determining the aerosol cloud interaction (ACI) using three different approaches; ground-based in situ measurements, combined ground-based in situ measurements 5 and satellite retrievals and using only satellite retrievals. The obtained values of ACI were highest for in situ ground-based data, clearly lower for combined ground-based and satellite data, and lowest for data relying solely on satellite retrievals. One of the key findings of this study was the high sensitivity of ACI to the definition of the aerosol burden. We showed that at least a part of the variability in ACI can be explained by 10 how different investigators have related dierent cloud properties to "aerosol burden".

Periprosthetic infection: where do we stand with regard to Gram stain?

PubMed Central

Ghanem, Elie; Ketonis, Constantinos; Restrepo, Camilo; Joshi, Ashish; Barrack, Robert

2009-01-01

Background and purpose One of the routinely used intraoperative tests for diagnosis of periprosthetic infection (PPI) is the Gram stain. It is not known if the result of this test can vary according to the type of joint affected or the number of specimen samples collected. We examined the role of this diagnostic test in a large cohort of patients from a single institution. Materials and methods A positive gram stain was defined as the visualization of bacterial cells or “many neutrophils” (> 5 per high-power field) in the smear. The sensitivity, specificity, and predictive values of each individual diagnostic arm of Gram stain were determined. Combinations were performed in series, which required both tests to be positive to confirm infection, and also in parallel, which necessitated both tests to be negative to rule out infection. Results The presence of organisms and “many” neutrophils on a Gram smear had high specificity (98–100%) and positive predictive value (89–100%) in both THA and TKA. The sensitivities (30–50%) and negative predictive values (70–79%) of the 2 tests were low for both joint types. When the 2 tests were combined in series, the specificity and positive predictive value were absolute (100%). The sensitivity and the negative predictive value improved for both THA and TKA (43–64% and 82%, respectively). Interpretation Although the 2 diagnostic arms of Gram staining can be combined to achieve improved negative predictive value (82%), Gram stain continues to have little value in ruling out PPI. With the advances in the field of molecular biology, novel diagnostic modalities need to be designed that can replace these traditional and poor tests. PMID:19297787

Combining magnetic nanoparticle with biotinylated nanobodies for rapid and sensitive detection of influenza H3N2

PubMed Central

2014-01-01

Our objective is to develop a rapid and sensitive assay based on magnetic beads to detect the concentration of influenza H3N2. The possibility of using variable domain heavy-chain antibodies (nanobody) as diagnostic tools for influenza H3N2 was investigated. A healthy camel was immunized with inactivated influenza H3N2. A nanobody library of 8 × 108 clones was constructed and phage displayed. After three successive biopanning steps, H3N2-specific nanobodies were successfully isolated, expressed in Escherichia coli, and purified. Sequence analysis of the nanobodies revealed that we possessed four classes of nanobodies against H3N2. Two nanobodies were further used to prepare our rapid diagnostic kit. Biotinylated nanobody was effectively immobilized onto the surface of streptavidin magnetic beads. The modified magnetic beads with nanobody capture specifically influenza H3N2 and can still be recognized by nanobodies conjugated to horseradish peroxidase (HRP) conjugates. Under optimized conditions, the present immunoassay exhibited a relatively high sensitive detection with a limit of 50 ng/mL. In conclusion, by combining magnetic beads with specific nanobodies, this assay provides a promising influenza detection assay to develop a potential rapid, sensitive, and low-cost diagnostic tool to screen for influenza infections. PMID:25328501

Combining magnetic nanoparticle with biotinylated nanobodies for rapid and sensitive detection of influenza H3N2

NASA Astrophysics Data System (ADS)

Zhu, Min; Hu, Yonghong; Li, Guirong; Ou, Weijun; Mao, Panyong; Xin, Shaojie; Wan, Yakun

2014-09-01

Our objective is to develop a rapid and sensitive assay based on magnetic beads to detect the concentration of influenza H3N2. The possibility of using variable domain heavy-chain antibodies (nanobody) as diagnostic tools for influenza H3N2 was investigated. A healthy camel was immunized with inactivated influenza H3N2. A nanobody library of 8 × 108 clones was constructed and phage displayed. After three successive biopanning steps, H3N2-specific nanobodies were successfully isolated, expressed in Escherichia coli, and purified. Sequence analysis of the nanobodies revealed that we possessed four classes of nanobodies against H3N2. Two nanobodies were further used to prepare our rapid diagnostic kit. Biotinylated nanobody was effectively immobilized onto the surface of streptavidin magnetic beads. The modified magnetic beads with nanobody capture specifically influenza H3N2 and can still be recognized by nanobodies conjugated to horseradish peroxidase (HRP) conjugates. Under optimized conditions, the present immunoassay exhibited a relatively high sensitive detection with a limit of 50 ng/mL. In conclusion, by combining magnetic beads with specific nanobodies, this assay provides a promising influenza detection assay to develop a potential rapid, sensitive, and low-cost diagnostic tool to screen for influenza infections.

Analytic and Clinical Performance of cobas HPV Testing in Anal Specimens from HIV-Positive Men Who Have Sex with Men

PubMed Central

Follansbee, Stephen; Borgonovo, Sylvia; Tokugawa, Diane; Sahasrabuddhe, Vikrant V.; Chen, Jie; Lorey, Thomas S.; Gage, Julia C.; Fetterman, Barbara; Boyle, Sean; Sadorra, Mark; Tang, Scott Dahai; Darragh, Teresa M.; Castle, Philip E.

2014-01-01

Anal human papillomavirus (HPV) infections are common, and the incidence of anal cancer is high in HIV-infected men who have sex with men (MSM). To evaluate the performance of HPV assays in anal samples, we compared the cobas HPV test (cobas) to the Roche Linear Array HPV genotyping assay (LA) and cytology in HIV-infected MSM. Cytology and cobas and LA HPV testing were conducted for 342 subjects. We calculated agreement between the HPV assays and the clinical performance of HPV testing and HPV genotyping alone and in combination with anal cytology. We observed high agreement between cobas and LA, with cobas more likely than LA to show positive results for HPV16, HPV18, and other carcinogenic types. Specimens testing positive in cobas but not in LA were more likely to be positive for other markers of HPV-related disease compared to those testing negative in both assays, suggesting that at least some of these were true positives for HPV. cobas and LA showed high sensitivities but low specificities for the detection of anal intraepithelial neoplasia grade 2/3 (AIN2/3) in this population (100% sensitivity and 26% specificity for cobas versus 98.4% sensitivity and 28.9% specificity for LA). A combination of anal cytology and HPV genotyping provided the highest accuracy for detecting anal precancer. A higher HPV load was associated with a higher risk of AIN2/3 with HPV16 (Ptrend < 0.001), HPV18 (Ptrend = 0.07), and other carcinogenic types (Ptrend < 0.001). We demonstrate that cobas can be used for HPV detection in anal cytology specimens. Additional tests are necessary to identify men at the highest risk of anal cancer among those infected with high-risk HPV. PMID:24899025

Metabolomic analysis of insulin resistance across different mouse strains and diets.

PubMed

Stöckli, Jacqueline; Fisher-Wellman, Kelsey H; Chaudhuri, Rima; Zeng, Xiao-Yi; Fazakerley, Daniel J; Meoli, Christopher C; Thomas, Kristen C; Hoffman, Nolan J; Mangiafico, Salvatore P; Xirouchaki, Chrysovalantou E; Yang, Chieh-Hsin; Ilkayeva, Olga; Wong, Kari; Cooney, Gregory J; Andrikopoulos, Sofianos; Muoio, Deborah M; James, David E

2017-11-24

Insulin resistance is a major risk factor for many diseases. However, its underlying mechanism remains unclear in part because it is triggered by a complex relationship between multiple factors, including genes and the environment. Here, we used metabolomics combined with computational methods to identify factors that classified insulin resistance across individual mice derived from three different mouse strains fed two different diets. Three inbred ILSXISS strains were fed high-fat or chow diets and subjected to metabolic phenotyping and metabolomics analysis of skeletal muscle. There was significant metabolic heterogeneity between strains, diets, and individual animals. Distinct metabolites were changed with insulin resistance, diet, and between strains. Computational analysis revealed 113 metabolites that were correlated with metabolic phenotypes. Using these 113 metabolites, combined with machine learning to segregate mice based on insulin sensitivity, we identified C22:1-CoA, C2-carnitine, and C16-ceramide as the best classifiers. Strikingly, when these three metabolites were combined into one signature, they classified mice based on insulin sensitivity more accurately than each metabolite on its own or other published metabolic signatures. Furthermore, C22:1-CoA was 2.3-fold higher in insulin-resistant mice and correlated significantly with insulin resistance. We have identified a metabolomic signature composed of three functionally unrelated metabolites that accurately predicts whole-body insulin sensitivity across three mouse strains. These data indicate the power of simultaneous analysis of individual, genetic, and environmental variance in mice for identifying novel factors that accurately predict metabolic phenotypes like whole-body insulin sensitivity. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Antibiotic-resistant bacteria show widespread collateral sensitivity to antimicrobial peptides.

PubMed

Lázár, Viktória; Martins, Ana; Spohn, Réka; Daruka, Lejla; Grézal, Gábor; Fekete, Gergely; Számel, Mónika; Jangir, Pramod K; Kintses, Bálint; Csörgő, Bálint; Nyerges, Ákos; Györkei, Ádám; Kincses, András; Dér, András; Walter, Fruzsina R; Deli, Mária A; Urbán, Edit; Hegedűs, Zsófia; Olajos, Gábor; Méhi, Orsolya; Bálint, Balázs; Nagy, István; Martinek, Tamás A; Papp, Balázs; Pál, Csaba

2018-06-01

Antimicrobial peptides are promising alternative antimicrobial agents. However, little is known about whether resistance to small-molecule antibiotics leads to cross-resistance (decreased sensitivity) or collateral sensitivity (increased sensitivity) to antimicrobial peptides. We systematically addressed this question by studying the susceptibilities of a comprehensive set of 60 antibiotic-resistant Escherichia coli strains towards 24 antimicrobial peptides. Strikingly, antibiotic-resistant bacteria show a high frequency of collateral sensitivity to antimicrobial peptides, whereas cross-resistance is relatively rare. We identify clinically relevant multidrug-resistance mutations that increase bacterial sensitivity to antimicrobial peptides. Collateral sensitivity in multidrug-resistant bacteria arises partly through regulatory changes shaping the lipopolysaccharide composition of the bacterial outer membrane. These advances allow the identification of antimicrobial peptide-antibiotic combinations that enhance antibiotic activity against multidrug-resistant bacteria and slow down de novo evolution of resistance. In particular, when co-administered as an adjuvant, the antimicrobial peptide glycine-leucine-amide caused up to 30-fold decrease in the antibiotic resistance level of resistant bacteria. Our work provides guidelines for the development of efficient peptide-based therapies of antibiotic-resistant infections.

Magnetic Penetration Effects in Small Superconducting Devices

NASA Technical Reports Server (NTRS)

Stevenson, T. R.; Adams, J. S.; Balvin, M. A.; Bandler, S. R.; Denis, K. L.; Hsieh, W.-T.; Kelly, D. P.; Nagler, P. C.; Porst, J.-P.; Sadleir, J. E.;

Co/Cu multilayers with reduced magnetoresistive hysteresis

NASA Astrophysics Data System (ADS)

Kubinski, D. J.; Holloway, H.

1997-01-01

Practical applications of Co/Cu multilayers (MLs) require copper thicknesses either ≈ 9 Å or ≈ 20 Å corresponding to the first or second antiferromagnetic maximum (AFM). The first AFM has much smaller magnetoresistive hysteresis than the second, but also has lower sensitivity. We discuss application of these MLs when low hysteresis is required. For the first AFM we may improve the sensitivity while retaining low hysteresis by increasing the cobalt thickness to 30-40 Å. At the second AFM we can reduce the magnetoresistive hysteresis by reducing the cobalt thickness to ˜ 3 Å. A particularly attractive combination of high sensitivity and low hysteresis is obtained at the second AFM by alternating such very thin Co layers with 15 Å thick Co layers.

Patient-derived solitary fibrous tumour xenografts predict high sensitivity to doxorubicin/dacarbazine combination confirmed in the clinic and highlight the potential effectiveness of trabectedin or eribulin against this tumour.

PubMed

Stacchiotti, S; Saponara, M; Frapolli, R; Tortoreto, M; Cominetti, D; Provenzano, S; Negri, T; Dagrada, G P; Gronchi, A; Colombo, C; Vincenzi, B; Badalamenti, G; Zuco, V; Renne, S L; Collini, P; Morosi, C; Dei Tos, A P; Bello, E; Pilotti, S; Casali, P G; D'Incalci, M; Zaffaroni, N

2017-05-01

Preclinical models that mimic pathological and molecular features of solitary fibrous tumour (SFT) represent an important tool to select effective regimes and novel compounds to be tested in the clinic. This study was aimed at developing two preclinical models of SFT, assessing their predictive value in the clinic and selecting potential novel effective treatments. Two dedifferentiated-SFT (D-SFT) models obtained from patients' biopsies were grown in immunodeficient mice. The antitumour activity on these models of doxorubicin, dacarbazine (DTIC), ifosfamide (monotherapy or combination), trabectedin and eribulin was tested. Twelve SFT patients were treated with doxorubicin and DTIC. Response by RECIST, progression-free survival and overall survival were retrospectively evaluated, distinguishing malignant-SFT (M-SFT) and D-SFT. Two D-SFT patient-derived xenografts (PDXs) that represent the first available preclinical in vivo models of SFT were developed and characterised. Doxorubicin/DTIC, DTIC/ifosfamide, doxorubicin/ifosfamide combinations consistently induced better antitumour activity than the single-agents. Particularly, doxorubicin/DTIC combination caused a max tumour volume inhibition >80% in both models. Doxorubicin/DTIC combo showed activity also in the case-series. Best RECIST responses were: 6 responses (M-SFT = 2 of 7, D-SFT = 4 of 5), 1 stable disease, 5 progressions, with a 6-month median progression-free survival (M-SFT = 6, D-SFT = 10 months). The PDXs were very sensitive to trabectedin and eribulin. Doxorubicin plus DTIC combination was effective in our two D-SFT mice models and appeared to be active also in the clinic, especially in high-grade D-SFT patients. Among additional drugs tested in the PDXs, trabectedin and eribulin were highly effective, providing a rational to test these drugs in D-SFT patients. Copyright © 2017 Elsevier Ltd. All rights reserved.

Atomic Structure and Properties of Extended Defects in Silicon

DOE Office of Scientific and Technical Information (OSTI.GOV)

Buczko, R.; Chisholm, M.F.; Kaplan, T.

1998-10-15

The Z-contrast technique represents a new approach to high-resolution electron microscopy allowing for the first time incoherent imaging of materials on the atomic scale. The key advantages of the technique, an intrinsically higher resolution limit and directly interpretable, compositionally sensitive imaging, allow a new level of insight into the atomic configurations of extended defects in silicon. This experimental technique has been combined with theoretical calculations (a combination of first principles, tight binding, and classical methods) to extend this level of insight by obtaining the energetic and electronic structure of the defects.

[Study on the TLC-SERS of sulfamethoxazole].

PubMed

Zhang, Jin-Zhi; Wang, Yuan; Chen, Xiang-Ming

2006-08-01

The spectra of sulfamethoxazole, the efficient ingredient of sulfanilamide-like medicine, were investigated by combining the TLC and FT-Raman spectroscopy using the surface enhanced Raman spectroscopy technique. The result indicatesthat the main vibrant characteristic spectral band can be obtained by TLC in a samples of just about 1 microg. The difference between the compound sulfamethoxazole and the corresponding spectra picture is analyzed. The analysis shows that the method of combining TLC and FT-Raman spectroscopy by the SERS is practical and advantageous in the highly sensitive measurement of the chemical ingredient in medicine.

The diagnostic accuracy of the rapid dipstick test to predict asymptomatic urinary tract infection of pregnancy.

PubMed

Eigbefoh, J O; Isabu, P; Okpere, E; Abebe, J

2008-07-01

Untreated urinary tract infection can have devastating maternal and neonatal effects. Thus, routine screening for bacteriuria is advocated. This study was designed to evaluate the diagnostic accuracy of the rapid dipstick test to predict urinary tract infection in pregnancy with the gold standard of urine microscopy, culture and sensitivity acting as the control. The urine dipstick test uses the leucocyte esterase, nitrite and test for protein singly and in combination. The result of the dipstick was compared with the gold standard, urine microscopy, culture and sensitivity using confidence interval for proportions. The reliability and validity of the urine dipstick was also evaluated. Overall, the urine dipstick test has a poor correlation with urine culture (p = 0.125, CI 95%). The same holds true for individual components of the dipstick test. The overall sensitivity of the urine dipstick test was poor at 2.3%. Individual sensitivity of the various components varied between 9.1% for leucocyte esterase and the nitrite test to 56.8% for leucocyte esterase alone. The other components of the dipstick test, the test of nitrite, test for protein and combination of the test (leucocyte esterase, nitrite and proteinuria) appear to decrease the sensitivity of the leucocyte esterase test alone. The ability of the urine dipstick test to correctly rule out urinary tract infection (specificity) was high. The positive predictive value for the dipstick test was high, with the leucocyte esterase test having the highest positive predictive value compared with the other components of the dipstick test. The negative predictive value (NPV) was expectedly highest for the leucocyte esterase test alone with values higher than the other components of the urine dipstick test singly and in various combinations. Compared with the other parameters of the urine dipstick test, singly and in combination, leucocyte esterase appears to be the most accurate (90.25%). The dipstick test has a limited use in screening for asymptomatic bacteriuria. The leucocyte esterase test component of the dipstick test appears to have the highest reliability and validity. The other parameters of the dipstick test decreases the reliability and validity of the leucocyte esterase test. A positive test merits empirical antibiotics, while a negative test is an indication for urine culture. The urine dipstick test if positive will also be useful in follow-up of patient after treatment of urinary tract infection. This is useful in poor resource setting especially in the third world where there is a dearth of trained personnel and equipment for urine culture.

Using gas chromatography with ion mobility spectrometry to resolve explosive compounds in the presence of interferents.

PubMed

Cook, Greg W; LaPuma, Peter T; Hook, Gary L; Eckenrode, Brian A

2010-11-01

Ion mobility spectrometry (IMS) is a valued field detection technology because of its speed and high sensitivity, but IMS cannot easily resolve analytes of interest within mixtures. Coupling gas chromatography (GC) to IMS adds a separation capability to resolve complex matrices. A GC-IONSCAN® operated in IMS and GC⁄ IMS modes was evaluated with combinations of five explosives and four interferents. In 100 explosive/interferent combinations, IMS yielded 21 false positives while GC⁄ IMS substantially reduced the occurrence of false positives to one. In addition, the results indicate that through redesign or modification of the preconcentrator there would be significant advantages to using GC⁄ IMS, such as enhancement of the linear dynamic range (LDR) in some situations. By balancing sensitivity with LDR, GC⁄ IMS could prove to be a very advantageous tool when addressing real world complex mixture situations.

Clinical potential of proteomics in the diagnosis of ovarian cancer.

PubMed

Ardekani, Ali M; Liotta, Lance A; Petricoin, Emanuel F

2002-07-01

The need for specific and sensitive markers of ovarian cancer is critical. Finding a sensitive and specific test for its detection has an important public health impact. Currently, there are no effective screening options available for patients with ovarian cancer. CA-125, the most widely used biomarker for ovarian cancer, does not have a high positive predictive value and it is only effective when used in combination with other diagnostic tests. However, pathologic changes taking place within the ovary may be reflected in biomarker patterns in the serum. Combination of mass spectra generated by new proteomic technologies, such as surface-enhanced laser desorption ionization time-of-flight (SELDI-TOF) and artificial-intelligence-based informatic algorithms, have been used to discover a small set of key protein values and discriminate normal from ovarian cancer patients. Serum proteomic pattern analysis might be applied ultimately in medical screening clinics, as a supplement to the diagnostic work-up and evaluation.

Multiplexed and portable nucleic acid detection platform with Cas13, Cas12a, and Csm6

PubMed Central

Gootenberg, Jonathan S.; Abudayyeh, Omar O.; Kellner, Max J.; Joung, Julia; Collins, James J.; Zhang, Feng

2018-01-01

Rapid detection of nucleic acids is integral for clinical diagnostics and biotechnological applications. We recently developed a platform termed SHERLOCK (Specific High Sensitivity Enzymatic Reporter UnLOCKing) that combines isothermal pre-amplification with Cas13 to detect single molecules of RNA or DNA. Through characterization of CRISPR enzymology and application development, we report here four advances integrated into SHERLOCKv2: 1) 4-channel single reaction multiplexing using orthogonal CRISPR enzymes; 2) quantitative measurement of input down to 2 aM; 3) 3.5-fold increase in signal sensitivity by combining Cas13 with Csm6, an auxilary CRISPR-associated enzyme; and 4) lateral flow read-out. SHERLOCKv2 can detect Dengue or Zika virus ssRNA as well as mutations in patient liquid biopsy samples via lateral flow, highlighting its potential as a multiplexable, portable, rapid, and quantitative detection platform of nucleic acids. PMID:29449508

18F-FDG-PET/CT Angiography for the Diagnosis of Infective Endocarditis.

PubMed

Roque, A; Pizzi, M N; Cuéllar-Calàbria, H; Aguadé-Bruix, S

2017-02-01

This article reviews the current imaging role of 18 F-fluordeoxyglucose positron emission computed tomography ( 18 F-FDG-PET/CT) combined with cardiac CT angiography (CTA) in infective endocarditis and discusses the strengths and limitations of this technique. The diagnosis of infective endocarditis affecting prosthetic valves and intracardiac devices is challenging because echocardiography and, therefore, the modified Duke criteria have well-recognized limitations in this clinical scenario. The high sensitivity of 18 F-FDG-PET/CT for the detection of infection associated with the accurate definition of structural damage by gated cardiac CTA in a combined technique (PET/CTA) has provided a significant increase in diagnostic sensitivity for the detection of IE. PET/CTA has proven to be a useful diagnostic tool in patients with suspected infective endocarditis. The additional information provided by this technique improves diagnostic performance in prosthetic valve endocarditis when it is used in combination with the Duke criteria. The findings obtained in PET/CTA studies have been included as a major criterion in the recently updated diagnostic algorithm in infective endocarditis guidelines.

Supersonic molecular beam-hyperthermal surface ionisation coupled with time-of-flight mass spectrometry applied to trace level detection of polynuclear aromatic hydrocarbons in drinking water for reduced sample preparation and analysis time.

PubMed

Davis, S C; Makarov, A A; Hughes, J D

1999-01-01

Analysis of sub-ppb levels of polynuclear aromatic hydrocarbons (PAHs) in drinking water by high performance liquid chromatography (HPLC) fluorescence detection typically requires large water samples and lengthy extraction procedures. The detection itself, although selective, does not give compound identity confirmation. Benchtop gas chromatography/mass spectrometry (GC/MS) systems operating in the more sensitive selected ion monitoring (SIM) acquisition mode discard spectral information and, when operating in scanning mode, are less sensitive and scan too slowly. The selectivity of hyperthermal surface ionisation (HSI), the high column flow rate capacity of the supersonic molecular beam (SMB) GC/MS interface, and the high acquisition rate of time-of-flight (TOF) mass analysis, are combined here to facilitate a rapid, specific and sensitive technique for the analysis of trace levels of PAHs in water. This work reports the advantages gained by using the GC/HSI-TOF system over the HPLC fluorescence method, and discusses in some detail the nature of the instrumentation used.

The power of liking: Highly sensitive aesthetic processing for guiding us through the world

PubMed Central

Faerber, Stella J.; Carbon, Claus-Christian

2012-01-01

Assessing liking is one of the most intriguing and influencing types of processing we experience day by day. We can decide almost instantaneously what we like and are highly consistent in our assessments, even across cultures. Still, the underlying mechanism is not well understood and often neglected by vision scientists. Several potential predictors for liking are discussed in the literature, among them very prominently typicality. Here, we analysed the impact of subtle changes of two perceptual dimensions (shape and colour saturation) of three-dimensional models of chairs on typicality and liking. To increase the validity of testing, we utilized a test-adaptation–retest design for extracting sensitivity data of both variables from a static (test only) as well as from a dynamic perspective (test–retest). We showed that typicality was only influenced by shape properties, whereas liking combined processing of shape plus saturation properties, indicating more complex and integrative processing. Processing the aesthetic value of objects, persons, or scenes is an essential and sophisticated mechanism, which seems to be highly sensitive to the slightest variations of perceptual input. PMID:23145310

NIFTE: The Near Infrared Faint-Object Telescope Experiment

NASA Technical Reports Server (NTRS)

Bock, James J.; Lange, Andrew E.; Matsumoto, T.; Eisenhardt, Peter B.; Hacking, Perry B.; Schember, Helene R.

1994-01-01

The high sensitivity of large format InSb arrays can be used to obtain deep images of the sky at 3-5 micrometers. In this spectral range cool or highly redshifted objects (e.g. brown dwarfs and protogalaxies) which are not visible at shorter wavelengths may be observed. Sensitivity at these wavelengths in ground-based observations is severly limited by the thermal flux from the telescope and from the earth's atmosphere. The Near Infrared Faint-Object Telescope Experiment (NIFTE), a 50 cm cooled rocket-borne telescope combined with large format, high performance InSb arrays, can reach a limiting flux less than 1 micro-Jy(1-sigma) over a large field-of-view in a single flight. In comparison, the Infrared Space Observatory (ISO) will require days of observation to reach a sensitivity more than one order of magnitude worse over a similar area of the sky. The deep 3-5 micrometer images obtained by the rocket-borne telescope will assist in determining the nature of faint red objects detected by ground-based telescopes at 2 micrometers, and by ISO at wavelengths longer than 5 micrometers.

Wide field and highly sensitive angiography based on optical coherence tomography with akinetic swept source.

PubMed

Xu, Jingjiang; Song, Shaozhen; Wei, Wei; Wang, Ruikang K

2017-01-01

Wide-field vascular visualization in bulk tissue that is of uneven surface is challenging due to the relatively short ranging distance and significant sensitivity fall-off for most current optical coherence tomography angiography (OCTA) systems. We report a long ranging and ultra-wide-field OCTA (UW-OCTA) system based on an akinetic swept laser. The narrow instantaneous linewidth of the swept source with its high phase stability, combined with high-speed detection in the system enable us to achieve long ranging (up to 46 mm) and almost negligible system sensitivity fall-off. To illustrate these advantages, we compare the basic system performances between conventional spectral domain OCTA and UW-OCTA systems and their functional imaging of microvascular networks in living tissues. In addition, we show that the UW-OCTA is capable of different depth-ranging of cerebral blood flow within entire brain in mice, and providing unprecedented blood perfusion map of human finger in vivo . We believe that the UW-OCTA system has promises to augment the existing clinical practice and explore new biomedical applications for OCT imaging.

Wide field and highly sensitive angiography based on optical coherence tomography with akinetic swept source

PubMed Central

Xu, Jingjiang; Song, Shaozhen; Wei, Wei; Wang, Ruikang K.

2016-01-01

Wide-field vascular visualization in bulk tissue that is of uneven surface is challenging due to the relatively short ranging distance and significant sensitivity fall-off for most current optical coherence tomography angiography (OCTA) systems. We report a long ranging and ultra-wide-field OCTA (UW-OCTA) system based on an akinetic swept laser. The narrow instantaneous linewidth of the swept source with its high phase stability, combined with high-speed detection in the system enable us to achieve long ranging (up to 46 mm) and almost negligible system sensitivity fall-off. To illustrate these advantages, we compare the basic system performances between conventional spectral domain OCTA and UW-OCTA systems and their functional imaging of microvascular networks in living tissues. In addition, we show that the UW-OCTA is capable of different depth-ranging of cerebral blood flow within entire brain in mice, and providing unprecedented blood perfusion map of human finger in vivo. We believe that the UW-OCTA system has promises to augment the existing clinical practice and explore new biomedical applications for OCT imaging. PMID:28101428

A highly sensitive and selective diagnostic assay based on virus nanoparticles

NASA Astrophysics Data System (ADS)

Park, Jin-Seung; Cho, Moon Kyu; Lee, Eun Jung; Ahn, Keum-Young; Lee, Kyung Eun; Jung, Jae Hun; Cho, Yunjung; Han, Sung-Sik; Kim, Young Keun; Lee, Jeewon

2009-04-01

Early detection of the protein marker troponin I in patients with a higher risk of acute myocardial infarction can reduce the risk of death from heart attacks. Most troponin assays are currently based on the conventional enzyme linked immunosorbent assay and have detection limits in the nano- and picomolar range. Here, we show that by combining viral nanoparticles, which are engineered to have dual affinity for troponin antibodies and nickel, with three-dimensional nanostructures including nickel nanohairs, we can detect troponin levels in human serum samples that are six to seven orders of magnitude lower than those detectable using conventional enzyme linked immunosorbent assays. The viral nanoparticle helps to orient the antibodies for maximum capture of the troponin markers. High densities of antibodies on the surfaces of the nanoparticles and nanohairs lead to greater binding of the troponin markers, which significantly enhances detection sensitivities. The nickel nanohairs are re-useable and can reproducibly differentiate healthy serum from unhealthy ones. We expect other viral nanoparticles to form similar highly sensitive diagnostic assays for a variety of other protein markers.

Fluorescence-based assay as a new screening tool for toxic chemicals

PubMed Central

Moczko, Ewa; Mirkes, Evgeny M.; Cáceres, César; Gorban, Alexander N.; Piletsky, Sergey

2016-01-01

Our study involves development of fluorescent cell-based diagnostic assay as a new approach in high-throughput screening method. This highly sensitive optical assay operates similarly to e-noses and e-tongues which combine semi-specific sensors and multivariate data analysis for monitoring biochemical processes. The optical assay consists of a mixture of environmental-sensitive fluorescent dyes and human skin cells that generate fluorescence spectra patterns distinctive for particular physico-chemical and physiological conditions. Using chemometric techniques the optical signal is processed providing qualitative information about analytical characteristics of the samples. This integrated approach has been successfully applied (with sensitivity of 93% and specificity of 97%) in assessing whether particular chemical agents are irritating or not for human skin. It has several advantages compared with traditional biochemical or biological assays and can impact the new way of high-throughput screening and understanding cell activity. It also can provide reliable and reproducible method for assessing a risk of exposing people to different harmful substances, identification active compounds in toxicity screening and safety assessment of drugs, cosmetic or their specific ingredients. PMID:27653274

Fluorescence-based assay as a new screening tool for toxic chemicals.

PubMed

Moczko, Ewa; Mirkes, Evgeny M; Cáceres, César; Gorban, Alexander N; Piletsky, Sergey

2016-09-22

Our study involves development of fluorescent cell-based diagnostic assay as a new approach in high-throughput screening method. This highly sensitive optical assay operates similarly to e-noses and e-tongues which combine semi-specific sensors and multivariate data analysis for monitoring biochemical processes. The optical assay consists of a mixture of environmental-sensitive fluorescent dyes and human skin cells that generate fluorescence spectra patterns distinctive for particular physico-chemical and physiological conditions. Using chemometric techniques the optical signal is processed providing qualitative information about analytical characteristics of the samples. This integrated approach has been successfully applied (with sensitivity of 93% and specificity of 97%) in assessing whether particular chemical agents are irritating or not for human skin. It has several advantages compared with traditional biochemical or biological assays and can impact the new way of high-throughput screening and understanding cell activity. It also can provide reliable and reproducible method for assessing a risk of exposing people to different harmful substances, identification active compounds in toxicity screening and safety assessment of drugs, cosmetic or their specific ingredients.

Fluorescence-based assay as a new screening tool for toxic chemicals

NASA Astrophysics Data System (ADS)

Moczko, Ewa; Mirkes, Evgeny M.; Cáceres, César; Gorban, Alexander N.; Piletsky, Sergey

2016-09-01

Our study involves development of fluorescent cell-based diagnostic assay as a new approach in high-throughput screening method. This highly sensitive optical assay operates similarly to e-noses and e-tongues which combine semi-specific sensors and multivariate data analysis for monitoring biochemical processes. The optical assay consists of a mixture of environmental-sensitive fluorescent dyes and human skin cells that generate fluorescence spectra patterns distinctive for particular physico-chemical and physiological conditions. Using chemometric techniques the optical signal is processed providing qualitative information about analytical characteristics of the samples. This integrated approach has been successfully applied (with sensitivity of 93% and specificity of 97%) in assessing whether particular chemical agents are irritating or not for human skin. It has several advantages compared with traditional biochemical or biological assays and can impact the new way of high-throughput screening and understanding cell activity. It also can provide reliable and reproducible method for assessing a risk of exposing people to different harmful substances, identification active compounds in toxicity screening and safety assessment of drugs, cosmetic or their specific ingredients.

Novel rolling circle amplification and DNA origami-based DNA belt-involved signal amplification assay for highly sensitive detection of prostate-specific antigen (PSA).

PubMed

Yan, Juan; Hu, Chongya; Wang, Ping; Liu, Rui; Zuo, Xiaolei; Liu, Xunwei; Song, Shiping; Fan, Chunhai; He, Dannong; Sun, Gang

2014-11-26

Prostate-specific antigen (PSA) is one of the most important biomarkers for the early diagnosis and prognosis of prostate cancer. Although many efforts have been made to achieve significant progress for the detection of PSA, challenges including relative low sensitivity, complicated operation, sophisticated instruments, and high cost remain unsolved. Here, we have developed a strategy combining rolling circle amplification (RCA)-based DNA belts and magnetic bead-based enzyme-linked immunosorbent assay (ELISA) for the highly sensitive and specific detection of PSA. At first, a 96-base circular DNA template was designed and prepared for the following RCA. Single stranded DNA (ssDNA) products from RCA were used as scaffold strand for DNA origami, which was hybridized with three staple strands of DNA. The resulting DNA belts were conjugated with multiple enzymes for signal amplification and then employed to magnetic bead based ELISA for PSA detection. Through our strategy, as low as 50 aM of PSA can be detected with excellent specificity.

High sensitivity and high resolution element 3D analysis by a combined SIMS–SPM instrument

PubMed Central

Wirtz, Tom

2015-01-01

Summary Using the recently developed SIMS–SPM prototype, secondary ion mass spectrometry (SIMS) data was combined with topographical data from the scanning probe microscopy (SPM) module for five test structures in order to obtain accurate chemical 3D maps: a polystyrene/polyvinylpyrrolidone (PS/PVP) polymer blend, a nickel-based super-alloy, a titanium carbonitride-based cermet, a reticle test structure and Mg(OH)2 nanoclusters incorporated inside a polymer matrix. The examples illustrate the potential of this combined approach to track and eliminate artefacts related to inhomogeneities of the sputter rates (caused by samples containing various materials, different phases or having a non-flat surface) and inhomogeneities of the secondary ion extraction efficiencies due to local field distortions (caused by topography with high aspect ratios). In this respect, this paper presents the measured relative sputter rates between PVP and PS as well as in between the different phases of the TiCN cermet. PMID:26171285

Integrated and isolated impact of high-performance work practices on employee health and well-being: A comparative study.

PubMed

Ogbonnaya, Chidiebere; Daniels, Kevin; Connolly, Sara; van Veldhoven, Marc

2017-01-01

We investigate the positive relationships between high-performance work practices (HPWP) and employee health and well-being and examine the conflicting assumption that high work intensification arising from HPWP might offset these positive relationships. We present new insights on whether the combined use (or integrated effects) of HPWP has greater explanatory power on employee health, well-being, and work intensification compared to their isolated or independent effects. We use data from the 2004 British Workplace Employment Relations Survey (22,451 employees nested within 1,733 workplaces) and the 2010 British National Health Service Staff survey (164,916 employees nested within 386 workplaces). The results show that HPWP have positive combined effects in both contexts, and work intensification has a mediating role in some of the linkages investigated. The results also indicate that the combined use of HPWP may be sensitive to particular organizational settings, and may operate in some sectors but not in others. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Towards the determination of sulfonamides in meat samples: A magnetic and mesoporous metal-organic framework as an efficient sorbent for magnetic solid phase extraction combined with high-performance liquid chromatography.

PubMed

Xia, Lian; Liu, Lijie; Lv, Xiaoxia; Qu, Fei; Li, Guoliang; You, Jinmao

2017-06-02

A magnetic, mesoporous core/shell structured Fe 3 O 4 @JUC-48 nanocomposite was synthesized and employed as a magnetic solid phase extraction (MSPE) sorbent for the determination of trace sulfonamides (SAs) in meat samples. The synthesized nanocomposite was characterized by X-ray diffraction, Fourier transform infrared spectra, transmission electron microscopy, scanning electron microscopy, Brunner-Emmet-Teller, and vibrating sample magnetometry; the Fe 3 O 4 @JUC-48 nanocomposite exhibited a distinctive morphology, large surface area, high magnetism, open adsorption sites, and high chemical stability. By combining the optimized MSPE conditions with high performance liquid chromatography diode array detection, an accurate and sensitive method for the determination of 5 SAs, including sulfadiazine (SDZ), sulfathiazole (STZ), sulfamerazine (SMR), sulfamethazine (SMZ), and sulfamethoxypyridazine (SMP), was developed. The method exhibited good linearity in the range of 3.97-1000ng/g with R ranging from 0.9991 to 0.9994, high sensitivity with LODs ranging from 1.73 to 5.23ng/g, adequate recoveries between 76.1 and 102.6% with low relative standard deviations ranging from 2.1 to 6.4%, and high precision with RSD<4.5%. The Fe 3 O 4 @JUC-48 magnetic nanocomposite is a promising sorbent for the rapid and efficient extraction of SAs from complex biological samples such as chicken, pork, and shrimp. Copyright © 2017 Elsevier B.V. All rights reserved.

Performance of syndromic management for the detection and treatment of genital Chlamydia trachomatis, Neisseria gonorrhoeae and Trichomonas vaginalis among women attending antenatal, well woman and sexual health clinics in Papua New Guinea: a cross-sectional study

PubMed Central

Vallely, Lisa M; Toliman, Pamela; Ryan, Claire; Rai, Glennis; Wapling, Johanna; Gabuzzi, Josephine; Allen, Joyce; Opa, Christine; Munnull, Gloria; Kaima, Petronia; Kombuk, Benny; Kumbia, Antonia; Kombati, Zure; Law, Greg; Kelly-Hanku, Angela; Wand, Handan; Siba, Peter M; Mola, Glen D L; Kaldor, John M

2017-01-01

Objective Papua New Guinea (PNG) has among the highest estimated prevalences of genital Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG) and Trichomonas vaginalis (TV) of any country in the Asia-Pacific region. Diagnosis and treatment of these infections have relied on the WHO-endorsed syndromic management strategy that uses clinical presentation without laboratory confirmation to make treatment decisions. We evaluated the performance of this strategy in clinical settings in PNG. Design Women attending antenatal (ANC), well woman (WWC) and sexual health (SHC) clinics in four provinces were invited to participate, completed a face-to-face interview and clinical examination, and provided genital specimens for laboratory testing. We estimated the performance characteristics of syndromic diagnoses against combined laboratory diagnoses. Results 1764 women were enrolled (ANC=765; WWC=614; SHC=385). The prevalences of CT, NG and TV were highest among women attending ANC and SHC. Among antenatal women, syndromic diagnosis of sexually transmitted infection had low sensitivity (9%–21%) and positive predictive value (PPV) (7%–37%), but high specificity (76%–89%) and moderate negative predictive value (NPV) (55%–86%) for the combined endpoint of laboratory-confirmed CT, NG or TV. Among women attending WWC and SHC, ‘vaginal discharge syndrome’ had moderate to high sensitivity (72%–78%) and NPV (62%–94%), but low specificity (26%–33%) and PPV (8%–38%). ‘Lower abdominal pain syndrome’ had low sensitivity (26%–41%) and PPV (8%–23%) but moderate specificity (66%–68%) and high NPV (74%–93%) among women attending WWC, and moderate-high sensitivity (67%–79%) and NPV (62%–86%) but low specificity (26%–28%) and PPV (14%–33%) among SHC attendees. Conclusion The performance of syndromic management for the detection and treatment of genital chlamydia, gonorrhoea and trichomonas was poor among women in different clinical settings in PNG. New diagnostic strategies are needed to control these infections and to prevent their adverse health outcomes in PNG and other high-burden countries. PMID:29288183

The Sensitivity and Specificity of Loop-Mediated Isothermal Amplification (LAMP) Assay for Tuberculosis Diagnosis in Adults with Chronic Cough in Malawi.

PubMed

Nliwasa, Marriott; MacPherson, Peter; Chisala, Palesa; Kamdolozi, Mercy; Khundi, McEwen; Kaswaswa, Kruger; Mwapasa, Mphatso; Msefula, Chisomo; Sohn, Hojoon; Flach, Clare; Corbett, Elizabeth L

2016-01-01

Current tuberculosis diagnostics lack sensitivity, and are expensive. Highly accurate, rapid and cheaper diagnostic tests are required for point of care use in low resource settings with high HIV prevalence. To investigate the sensitivity and specificity, and cost of loop-mediated isothermal amplification (LAMP) assay for tuberculosis diagnosis in adults with chronic cough compared to Xpert® MTB/RIF, fluorescence smear microscopy. Between October 2013 and March 2014, consecutive adults at a primary care clinic were screened for cough, offered HIV testing and assessed for tuberculosis using LAMP, Xpert® MTB/RIF and fluorescence smear microscopy. Sensitivity and specificity (with culture as reference standard), and costs were estimated. Of 273 adults recruited, 44.3% (121/273) were HIV-positive and 19.4% (53/273) had bacteriogically confirmed tuberculosis. The sensitivity of LAMP compared to culture was 65.0% (95% CI: 48.3% to 79.4%) with 100% (95% CI: 98.0% to 100%) specificity. The sensitivity of Xpert® MTB/RIF (77.5%, 95% CI: 61.5% to 89.2%) was similar to that of LAMP, p = 0.132. The sensitivity of concentrated fluorescence smear microscopy with routine double reading (87.5%, 95% CI: 73.2% to 95.8%) was higher than that of LAMP, p = 0.020. All three tests had high specificity. The lowest cost per test of LAMP was at batch size of 14 samples (US$ 9.98); this was lower than Xpert® MTB/RIF (US$ 13.38) but higher than fluorescence smear microscopy (US$ 0.65). The sensitivity of LAMP was similar to Xpert® MTB/RIF but lower than fluorescence smear microscopy; all three tests had high specificity. These findings support the Malawi policy that recommends a combination of fluorescence smear microscopy and Xpert® MTB/RIF prioritised for people living with HIV, already found to be smear-negative, or being considered for retreatment of tuberculosis.

The Sensitivity and Specificity of Loop-Mediated Isothermal Amplification (LAMP) Assay for Tuberculosis Diagnosis in Adults with Chronic Cough in Malawi

PubMed Central

Nliwasa, Marriott; MacPherson, Peter; Chisala, Palesa; Kamdolozi, Mercy; Khundi, McEwen; Kaswaswa, Kruger; Mwapasa, Mphatso; Msefula, Chisomo; Sohn, Hojoon; Flach, Clare; Corbett, Elizabeth L.

2016-01-01

Background Current tuberculosis diagnostics lack sensitivity, and are expensive. Highly accurate, rapid and cheaper diagnostic tests are required for point of care use in low resource settings with high HIV prevalence. Objective To investigate the sensitivity and specificity, and cost of loop-mediated isothermal amplification (LAMP) assay for tuberculosis diagnosis in adults with chronic cough compared to Xpert® MTB/RIF, fluorescence smear microscopy. Methods Between October 2013 and March 2014, consecutive adults at a primary care clinic were screened for cough, offered HIV testing and assessed for tuberculosis using LAMP, Xpert® MTB/RIF and fluorescence smear microscopy. Sensitivity and specificity (with culture as reference standard), and costs were estimated. Results Of 273 adults recruited, 44.3% (121/273) were HIV-positive and 19.4% (53/273) had bacteriogically confirmed tuberculosis. The sensitivity of LAMP compared to culture was 65.0% (95% CI: 48.3% to 79.4%) with 100% (95% CI: 98.0% to 100%) specificity. The sensitivity of Xpert® MTB/RIF (77.5%, 95% CI: 61.5% to 89.2%) was similar to that of LAMP, p = 0.132. The sensitivity of concentrated fluorescence smear microscopy with routine double reading (87.5%, 95% CI: 73.2% to 95.8%) was higher than that of LAMP, p = 0.020. All three tests had high specificity. The lowest cost per test of LAMP was at batch size of 14 samples (US$ 9.98); this was lower than Xpert® MTB/RIF (US$ 13.38) but higher than fluorescence smear microscopy (US$ 0.65). Conclusion The sensitivity of LAMP was similar to Xpert® MTB/RIF but lower than fluorescence smear microscopy; all three tests had high specificity. These findings support the Malawi policy that recommends a combination of fluorescence smear microscopy and Xpert® MTB/RIF prioritised for people living with HIV, already found to be smear-negative, or being considered for retreatment of tuberculosis. PMID:27171380

In-Vivo Imaging of Cell Migration Using Contrast Enhanced MRI and SVM Based Post-Processing.

PubMed

Weis, Christian; Hess, Andreas; Budinsky, Lubos; Fabry, Ben

2015-01-01

The migration of cells within a living organism can be observed with magnetic resonance imaging (MRI) in combination with iron oxide nanoparticles as an intracellular contrast agent. This method, however, suffers from low sensitivity and specificty. Here, we developed a quantitative non-invasive in-vivo cell localization method using contrast enhanced multiparametric MRI and support vector machines (SVM) based post-processing. Imaging phantoms consisting of agarose with compartments containing different concentrations of cancer cells labeled with iron oxide nanoparticles were used to train and evaluate the SVM for cell localization. From the magnitude and phase data acquired with a series of T2*-weighted gradient-echo scans at different echo-times, we extracted features that are characteristic for the presence of superparamagnetic nanoparticles, in particular hyper- and hypointensities, relaxation rates, short-range phase perturbations, and perturbation dynamics. High detection quality was achieved by SVM analysis of the multiparametric feature-space. The in-vivo applicability was validated in animal studies. The SVM detected the presence of iron oxide nanoparticles in the imaging phantoms with high specificity and sensitivity with a detection limit of 30 labeled cells per mm3, corresponding to 19 μM of iron oxide. As proof-of-concept, we applied the method to follow the migration of labeled cancer cells injected in rats. The combination of iron oxide labeled cells, multiparametric MRI and a SVM based post processing provides high spatial resolution, specificity, and sensitivity, and is therefore suitable for non-invasive in-vivo cell detection and cell migration studies over prolonged time periods.

Highly-sensitive microRNA detection based on bio-bar-code assay and catalytic hairpin assembly two-stage amplification.

PubMed

Tang, Songsong; Gu, Yuan; Lu, Huiting; Dong, Haifeng; Zhang, Kai; Dai, Wenhao; Meng, Xiangdan; Yang, Fan; Zhang, Xueji

2018-04-03

Herein, a highly-sensitive microRNA (miRNA) detection strategy was developed by combining bio-bar-code assay (BBA) with catalytic hairpin assembly (CHA). In the proposed system, two nanoprobes of magnetic nanoparticles functionalized with DNA probes (MNPs-DNA) and gold nanoparticles with numerous barcode DNA (AuNPs-DNA) were designed. In the presence of target miRNA, the MNP-DNA and AuNP-DNA hybridized with target miRNA to form a "sandwich" structure. After "sandwich" structures were separated from the solution by the magnetic field and dehybridized by high temperature, the barcode DNA sequences were released by dissolving AuNPs. The released barcode DNA sequences triggered the toehold strand displacement assembly of two hairpin probes, leading to recycle of barcode DNA sequences and producing numerous fluorescent CHA products for miRNA detection. Under the optimal experimental conditions, the proposed two-stage amplification system could sensitively detect target miRNA ranging from 10 pM to 10 aM with a limit of detection (LOD) down to 97.9 zM. It displayed good capability to discriminate single base and three bases mismatch due to the unique sandwich structure. Notably, it presented good feasibility for selective multiplexed detection of various combinations of synthetic miRNA sequences and miRNAs extracted from different cell lysates, which were in agreement with the traditional polymerase chain reaction analysis. The two-stage amplification strategy may be significant implication in the biological detection and clinical diagnosis. Copyright © 2017 Elsevier B.V. All rights reserved.

Inhibition of telomerase potentiates enzalutamide efficiency of androgen-sensitive human prostate cancer cells.

PubMed

Gecgel, Karaca Kaan; Muduroglu, Mustafa; Erdogan, Suat

2017-01-01

Androgen deprivation therapy (ADT) is one of the main strategies to treat prostate cancer (PCa) at various stages of its development. Androgen receptor (AR) antagonists such as enzalutamide are mainstay treatments for castration-sensitive prostate cancer. Though, a majority of patients initially respond to ADT, most will eventually progress to castrate-resistant, due to the development of different mutations on the AR. PCa cells express high telomerase activity, and there is a correlation between the total activity of telomerase and the Gleason score. Therefore, we hypothesized that the combination of enzalutamide plus a telomerase inhibitor could be more effective than enzalutamide alone in decreasing cell survival. In this study MTT test, RT-qPCR and imagebased cytometry were used to investigate cell viability, apoptosis and cell cycle progression of androgen-responsive human prostate cancer LNCaP cells. The cells were treated with 5 μM enzalutamide and 40 μM telomerase inhibitor BIBR 1532, or with their combinations for 72 hrs. Enzalutamide and BIBR 1532 alone inhibited cell proliferation in a dose-dependent manner. The combinations of the two agents could synergistically induce apoptotic and necrotic cell death. Either inhibition of telomerase by BIBR 1532 or AR blockages by enzalutamide decreased prostate-specific antigen (PSA) and the catalytic component of telomerase, hTERT, expression. These results suggest that telomerase inhibition therapy may contribute to the efficacy of enzalutamide in the androgen-sensitive PCa model.

Microchannel plate streak camera

DOEpatents

Wang, Ching L.

1989-01-01

An improved streak camera in which a microchannel plate electron multiplier is used in place of or in combination with the photocathode used in prior streak cameras. The improved streak camera is far more sensitive to photons (UV to gamma-rays) than the conventional x-ray streak camera which uses a photocathode. The improved streak camera offers gamma-ray detection with high temporal resolution. It also offers low-energy x-ray detection without attenuation inside the cathode. Using the microchannel plate in the improved camera has resulted in a time resolution of about 150 ps, and has provided a sensitivity sufficient for 1000 KeV x-rays.

Evaluation of first-draw whole blood, point-of-care cardiac markers in the context of the universal definition of myocardial infarction: a comparison of a multimarker panel to troponin alone and to testing in the central laboratory.

PubMed

Lee-Lewandrowski, Elizabeth; Januzzi, James L; Grisson, Ricky; Mohammed, Asim A; Lewandrowski, Grant; Lewandrowski, Kent

2011-04-01

Previous studies evaluating point-of-care testing (POCT) for cardiac biomarkers did not use current recommendations for troponin cutoff values or recognize the recent universal definition of acute myocardial infarction. Traditionally, achieving optimal sensitivity for the detection of myocardial injury on initial presentation required combining cardiac troponin and/or creatine kinase isoenzyme MB with an early marker, usually myoglobin. In recent years, the performance of central laboratory combining cardiac troponin assays has improved significantly, potentially obviating the need for a multimarker panel to achieve optimum sensitivity. To compare 2 commonly used POCT strategies to a fourth generation, central laboratory cardiac troponin T assay on first-draw specimens from patients being evaluated for acute myocardial infarction in the emergency department. The 2 strategies included a traditional POCT multimarker panel and a newer POCT method using cardiac troponin I alone. Blood specimens from 204 patients presenting to the emergency department with signs and/or symptoms of myocardial ischemia were measured on the 2 POCT systems and by a central laboratory method. The diagnosis for each patient was determined by retrospective chart review. The cardiac troponin T assasy alone was more sensitive for acute myocardial infarction than the multimarker POCT panel with equal or better specificity. When compared with a POCT troponin I, the cardiac troponin T was also more sensitive, but this difference was not significant. The POCT troponin I alone also had the same sensitivity as the multimarker panel. Testing for combining cardiac troponin alone using newer, commercially available, central laboratory or POCT assays performed with equal or greater sensitivity to acute myocardial infarction as the older, traditional, multimarker panel. In the near future, high-sensitivity, central laboratory troponins will be available for routine clinical use. As a result, the quality gap between central laboratories and older POCT methods will continue to widen, unless the performance of the POCT methods is improved.

The sensitivity and specificity of thermometry and plethysmography in the assessment of hand-arm vibration syndrome.

PubMed

Thompson, Aaron; House, Ron; Manno, Michael

2008-05-01

Finger plethysmography and thermometry are objective measures used to assess the vascular aspect of hand-arm vibration syndrome (HAVS). Research to date shows poor correlation between these tests and Stockholm Workshop Scale (SWS) vascular stage. Clinicians, researchers and compensation boards require objective means to diagnose and quantify HAVS. To define the specificity and sensitivity of thermometry and plethysmography using the SWS as the reference criterion. A secondary goal was to consider cut points for the tests optimizing sensitivity and specificity. A cross-sectional analysis was conducted on HAVS patients seen at an occupational medicine specialty clinic. Plethysmography and thermometry were analyzed using SWS vascular stage as the outcome variable. Logistic regression controlled for age, smoking and time since last vibration exposure and use of vasoactive medications. The sensitivity and specificity of the combined tests were calculated using varying cut points. A total of 139 patients consented to participate in the study. Plethysmography stage 1 or greater showed the highest sensitivity (sensitivity 94% and specificity 15%). Specificity was optimized combining plethysmography stage 3 and thermometry stage 3 (specificity 98% and sensitivity 23%). Maximal diagnostic accuracy was achieved by plethysmography alone setting the criteria for a positive test as being stage 1 or greater (70%). Neither plethysmography nor thermometry either alone or in combination demonstrated sufficient sensitivity and specificity to serve as an objective correlate for SWS vascular stage. All combinations of plethysmography and thermometry showed a lower specificity than sensitivity indicating that the SWS may be less sensitive in detecting vascular pathology than the objective tests.

Using solute and heat tracers for aquifer characterization in a strongly heterogeneous alluvial aquifer

NASA Astrophysics Data System (ADS)

Sarris, Theo S.; Close, Murray; Abraham, Phillip

2018-03-01

A test using Rhodamine WT and heat as tracers, conducted over a 78 day period in a strongly heterogeneous alluvial aquifer, was used to evaluate the utility of the combined observation dataset for aquifer characterization. A highly parameterized model was inverted, with concentration and temperature time-series as calibration targets. Groundwater heads recorded during the experiment were boundary dependent and were ignored during the inversion process. The inverted model produced a high resolution depiction of the hydraulic conductivity and porosity fields. Statistical properties of these fields are in very good agreement with estimates from previous studies at the site. Spatially distributed sensitivity analysis suggests that both solute and heat transport were most sensitive to the hydraulic conductivity and porosity fields and less sensitive to dispersivity and thermal distribution factor, with sensitivity to porosity greatly reducing outside the monitored area. The issues of model over-parameterization and non-uniqueness are addressed through identifiability analysis. Longitudinal dispersivity and thermal distribution factor are highly identifiable, however spatially distributed parameters are only identifiable near the injection point. Temperature related density effects became observable for both heat and solute, as the temperature anomaly increased above 12 degrees centigrade, and affected down gradient propagation. Finally we demonstrate that high frequency and spatially dense temperature data cannot inform a dual porosity model in the absence of frequent solute concentration measurements.

Detection and discrimination of colour, a comparison of physiological and psychophysical data

NASA Astrophysics Data System (ADS)

Valberg, A.; Lee, B. B.

1989-01-01

Whereas the physiological basis of colorimetry (colour matches) is well understood in terms of the trireceptor theory of colour vision, colour discrimination and scaling still lack a comparable foundation. We present here experimental data that demonstrate how sensitivity and responsiveness of different types of cone-opponent and non-opponent cells of the macaque monkey correlate with human threshold sensitivity on the one hand, and how they in combination can be used to construct a suprathreshold equidistant colour space. Psychophysical thresholds correlate well with the threshold envelope of the most sensitive cells when stimuli are projected upon a steady white background. Detection thresholds for stimuli of differing wavelength and purity (saturation) generally indicate a transition from a phasic non-opponent system to a tonic opponent system of on-centre cells as purity increases. Detection and chromatic discrimination thresholds coincide only for long and short wavelengths of high purity, whereas they differ for mid-spectral lights. Different cell types may thus support detection and discrimination with different stimuli. With chromatic scaling of surface colours on the other hand, when stimuli are darker than an adaptation field still other cell types are needed. We demonstrate that it is possible, from a combination of on- and off-opponent cells, to reconstruct a uniform colour space, using summed outputs of cells with the same cone combination and vector addition for cells with different combinations. Different hues are represented by opponent cells with inputs from different cone types, the hue percept being related to the ratio of the activities of these cell systems.

Nanocellulose-based biosensors: design, preparation, and activity of peptide-linked cotton cellulose nanocrystals having fluorimetric and colorimetric elastase detection sensitivity

USDA-ARS?s Scientific Manuscript database

Nanocrystalline cellulose is an amphiphilic, high surface area material that can be easily functionalized and is biocom-patible and eco-friendly. It has been used singularly and in combination with other nanomaterials to optimize biosensor design. The attachment of peptides and proteins to nanocryst...

Combining Excellence and Ethics: Implications for Moral Education for the Gifted

ERIC Educational Resources Information Center

Tirri, Kirsi

2011-01-01

In this article the current empirical research on morality and giftedness is reviewed with an emphasis on moral sensitivity. The component of moral judgment has been the most studied aspect in morality. Although high-ability students have been shown to be superior in moral judgment when compared to average-ability students, morality includes other…