Search

Exosome-based liquid biopsies highlight potential utility in diagnosis and determining the prognosis of patients with cancer and other diseases. However, the existing techniques are severely limited for practical applications due to the complications of high cost, low sensitivity, tedious procedures, and large sample consumption. Herein, we report a microstructured optical fiber sensor for fast, sensitive, and accurate quantification of exosomes in blood samples of breast cancer patients. Numerical simulations are applied to demonstrate that hollow-core microstructured antiresonant fibers (HARFs) can stringently confine light in the fiber core, ensuring strong light-matter interaction and thus maximumly amplifying the signal. Taking this advantage, a AuNPs-dsDNA assembly containing gold nanoparticles, a recognizing DNA aptamer, and a fluorescent reporter DNA sequence is fabricated followed by immobilization on the fiber wall to form a AuNPs-dsDNA-HARF sensor. Cancer-derived exosomes can be recognized and captured in the fiber channel and generate dose-dependent fluorescent signals for quantification. The microfiber sensor demonstrates enhanced sensitivity and specificity, enabling the detection of single digits of exosome particles at the nanoliter sample level. In addition, by tracking exosome phenotypic changes, the proposed fiber sensor can facilitate precise drug treatment monitoring. This work provides a robust platform for exosome-based biopsy for cancer diagnosis and prediction of therapeutic outcomes.

Xiao-Chai-Hu-Tang (XCHT), a representative of previous edition of Formulas of Traditional Chinese Medicine and harmonizing formulas, has multiple pharmacological functions. However, a variety of side effects could be caused by misuse or abuse, ignoring the theory of diagnosis and treatment based on the combination of syndrome and disease differentiation. Therefore, we conducted a retrospective study to evaluate the efficacy of XCHT, depending upon the individual patient’s condition. Among 98 patients treated with XCHT, most of the patients of syndromes could be cured after about two course. The therapeutic effect rate of prescribed XCHT in our 98 cases of treatment is 91.84% (90/98). In addition, the high frequently syndromes are consistent with Shanhanlun. With multiple years of experience, we believe that: patient feel pain and tenderness under the right costal arch is one of the symptoms of patients who fit for the treatment with XCHT.

Background Micronodular thymic tumors with lymphoid stroma include micronodular thymoma with lymphoid stroma (MNT) and micronodular thymic carcinoma with lymphoid hyperplasia (MNC), whose micromorphological features are lymphoid stromal hyperplasia and nodular arrangement of tumor epithelial cells. This type of tumor is rare; therefore, the corresponding clinical guidelines, histopathological diagnostic criteria, prognostic factors, and therapeutic regimens have not been established. Case summary This study covers a novel presentation of MNC in a patient and summarizes the clinicopathological characteristics of this type of tumor by using pooled-analysis methods. Morphologically, this tumor type is a series of benign to malignant pedigrees. We establish the following criteria for the classification of micronodular thymic tumors with lymphoid stroma: (1) Tumor cells with moderate-to-severe dysplasia; (2) Tumor cell mitotic figures > 2/10 high-power fields; (3) Appearance of neoplastic necrosis; (4) No terminal deoxynucleotidyl transferase-positive immature T lymphocytes within the tumor; (5) Tumor cells with a Ki-67 index ≥ 10%; and (6) Tumor cells express CD5. Cases that fall into the borders of two categories in terms of morphology are attributed to atypical MNT. It is proposed that the diagnosis of MNT should be established on the diagnostic criteria mentioned above. Conclusion Our diagnostic algorithm can effectively distinguish malignant tumors from benign tumors and provides a potent basis for predicting a prognosis, which offers a practical reference for oncologists and pathologists.

To evaluate the safety and feasibility of single-segment lumbar microdiscectomy without drainage.The clinical data of 135 patients with single-segment lumbar disc herniation treated by microdiscectomy surgery from January 2018 to August 2019 were retrospectively analyzed. There were 95 males and 40 females, aged from 18 to 40 years old, with a mean of (28.3±5.4) years. They were divided into drainage group (78 cases) and non-drainage group (57 cases) according to whether the drainage tube was placed during operation. The general conditions of patients were recorded such as age, gender, operation segment, body mass index(BMI), symptom duration, follow-up time, operation time, intraoperative blood loss, out-of-bed time, hospital stay, postoperative drainage removal time and drainage volume of drainage group, postoperative body temperature. VAS of incisional pain in supine resting state on the 1 and 3 days after operation, the VAS of low back pain and lower extremity radiating pain during ground exercise before operation, 3 days, 1 month and 3 months after operation were compared. Oswestry Disability Index (ODI) was collected before operation, 1 month and 3 months after operation. The ratio of complications was calculated such as symptomatic incision hematoma, poor incision healing, incision infection, exacerbation and progressive aggravation of neurological dysfunction, and unplanned secondary surgery.There were no significant differences in age, gender, operation segment, BMI, symptom duration, follow-up time, operation time, intraoperative blood loss, and postoperative body temperature between two groups. The average hospital stay and out-of-bed time in non-drainage group were shorter than in drainage group(Single-segment lumbar microdiscectomy without drainage can shorten the average hospital stay and promote early exercise out of bed, and reduce the trauma and stress reaction of drainage. No drainage may be an option for patients with enhanced recovery after lumbar microdiscectomy.

Objective To explore the value of elastography strain ratio(SR)combined with breast ultrasound imaging reporting and data system(BI-RADS-US)in the differential diagnosis of breast nodules.Methods A total of 471 breast nodules(from 471 patients)were reclassified by SR combined with BI-RADS-US.With the pathology results as gold standard,the area under the receiver operating characteristic(ROC)curve(AUC)was employed to evaluate the diagnostic performance,and the sensitivity,specificity,and accuracy were compared between the combined method and BI-RADS-US.Results Among the 471 breast nodules,180 nodules were benign and 291 were malignant.The AUC of the combined method was statistically significantly higher than that of BI-RADS-US(0.798 vs. 0.730;Z= 2.583, P= 0.010).SR,BI-RADS-US,and the combined method for diagnosing breast nodules had the sensitivity of 86.6%,99.0%,and 96.6%,the specificity of 67.2%,47.2%,and 63.3%,and the accuracy of 79.2%,79.2%,and 83.9%,respectively.The combined method increased the specificity from 47.2%(BI-RADS-US)to 63.3%(χ

Single cell analysis is crucial for elucidating cellular diversity and heterogeneity as well as for medical diagnostics operating at the ultimate detection limit. Although superbly sensitive biosensors have been developed using the strongly enhanced evanescent fields provided by optical microcavities, real-time quantification of intracellular molecules remains challenging due to the extreme low quantity and limitations of the current techniques. Here, we introduce an active-mode optical microcavity sensing stage with enhanced sensitivity that operates via Förster resonant energy transferring (FRET) mechanism. The mutual effects of optical microcavity and FRET greatly enhances the sensing performance by four orders of magnitude compared to pure Whispering gallery mode (WGM) microcavity sensing system. We demonstrate distinct sensing mechanism of FRET-WGM from pure WGM. Predicted lasing wavelengths of both donor and acceptor by theoretical calculations are in perfect agreement with the experimental data. The proposed sensor enables quantitative molecular analysis at single cell resolution, and real-time monitoring of intracellular molecules over extended periods while maintaining the cell viability. By achieving high sensitivity at single cell level, our approach provides a path toward FRET-enhanced real-time quantitative analysis of intracellular molecules.

By analyzing the shortcomings of Manhattan distance and Euclidean distance algorithm commonly applied in A* algorithm, this paper is to theoretically solve the traditional A* algorithm with problems, imprecise search results and long response time when being applied in path planning process, as well as improving and obtaining the complex diagonal distance with the heuristic function distance to simulate the path planning. Meanwhile, it proposes the eight-neighbor search optimization with the path planning simulation of the improved A* algorithm. The simulated results indicate that the improved A* algorithm can achieve the ideal effect of reducing and improving the search rate to finally locate the optimal path with precise search results and prompt response.

The aims of the present study were to investigate the distribution of human papillomavirus (HPV) genotypes in cervical lesions, and the association between different HPV genotypes and cervical lesions. Between January 2013 and June 2014, the HPV type determinations of nucleic acid by use of fluorescence polymerase chain reaction (PCR) method of 15,192 outpatients in China-Japan Friendship Hospital were performed and the infection status was analyzed. The results showed that: i) 2,366 Cases were HPV positive and 12,826 cases were HPV negative, the overall infection rate was 15.57% (2,366/15,192), in which a single genotype of HPV infection rate was 11.63% (1,767/15,192), and multiple genotypes of HPV infection rate was 3.94% (599/15,192); ii) HPV16, HPV52 and HPV58 infections were the most common HPV genotypes, the infection rates were 3.95% (600/15,192), 2.86% (435/15,192) and 2.67% (406/15,192), respectively; and iii) According to the gold standard of histopathological analysis via hematoxylin-eosin staining, HPV16, HPV52 and HPV58 accounted for 58.80% (154/267) of all CIN2 or above squamous epithelial lesions. Furthermore, three cases with pathological changes of the cervical severe glandular epithelium were all HPV18 infection. The difference was statistically significant (χ2=60.74, P

Hollow core anti-resonant fiber (HARF) has found a handful applications in optical communications, nonlinear optics and high power delivery. The intrinsic property of the fiber also renders it an ideal candidate for biosensing, which has not been explored intensively. Herein, we demonstrate an optical fiber sensing platform, taking advantages of the state-of-the-art HARF technology and superior physicochemical properties of 2D material black phosphorus, for ultra-sensitive detection of bisphenol A (BPA) in blood and environmental samples. The specially designed HARF can not only achieve broadband transmission of light, but also confine light in the low refractive-index liquid core, ensuring maximum overlap of light and liquid core. Modification of the inner surface of HARF with 2D black phosphorus nanoflakes functionalized with fluorescently labeled BPA-specific aptamer provides a smart sensing interface enabling highly selective detection of BPA via measuring the fluorescence. The limit of detection is 1.69pM, which is more than two orders of magnitude enhancement compared to the conventional plate assay. The proposed assay is not interfered with the BPA analogues BPB and BPS. The long optical path with tight optical confinement greatly enhances the analyte-light interaction and improves the sensitivity of the sensing platform. The proposed sensing platform can be further developed for versatile applications.

In order to research the changes of concrete properties in freeze-thaw environment, five concrete samples with water-cement ratio respectively equal to 0.60, 0.65, 0.70, 0.75 and 0.80 were tested in freeze-thaw environment according to GB/T50082-2009 concrete rapid freeze-thaw cycles test method. Five samples were carried out 0, 25, 50, 75, 100 times faster freeze-thaw cycles test. With the increasing number of freeze-thaw cycles, the concrete relative dynamic modulus of elasticity loss rises, the compressive strength drops, and the carbonation depth increases. The greater the water-cement ratio of concrete specimens with freeze-thaw cycles, the greater the degree of damage increases.

Based on sparse representations, the problem of two-dimensional (2-D) direction of arrival (DOA) estimation is addressed in this paper. A novel sparse 2-D DOA estimation method, called Dimension Reduction Sparse Reconstruction (DRSR), is proposed with pairing by Spatial Spectrum Reconstruction of Sub-Dictionary (SSRSD). By utilizing the angle decoupling method, which transforms a 2-D estimation into two independent one-dimensional (1-D) estimations, the high computational complexity induced by a large 2-D redundant dictionary is greatly reduced. Furthermore, a new angle matching scheme, SSRSD, which is less sensitive to the sparse reconstruction error with higher pair-matching probability, is introduced. The proposed method can be applied to any type of orthogonal array without requirement of a large number of snapshots and a priori knowledge of the number of signals. The theoretical analyses and simulation results show that the DRSR-SSRSD method performs well for coherent signals, which performance approaches Cramer–Rao bound (CRB), even under a single snapshot and low signal-to-noise ratio (SNR) condition.

Product competition is depended on the each process success of product designing which contains complicated designing. A good many scholars promotes some design method. But each method applies to one problem in a certain phase of product innovation designing, and contains insufficiency. Therefore the only solution is to integrate all the variety of methods. HOQ (House OF Quality) is a good method which establishes the relationship between user and designer. But it can’t solve conflict between technology parameters. TRIZ ((Russian Abbreviation:Teorijz Rezhenija Izobretatel skich Zadach is very powerful method to solve the contradictions and obtains innovation. And TRIZ can only gives principle solutions. The paper integrates to use the above methods to design successfully force sensor of testing apparatus for micro-friction. Test shows its dependability and precision of designing project is very high. So reliability and feasibility of integrated technology of HOQ/TRIZ is very strong.

For the operation situation of the series-type electrostatic fabric filter precipitator, the deflectors in the inlet of the precipitator whose angle and spacing were changed to improve the air distribution characteristic and collection efficiency were assembled. The three-dimensional structural model of the series-type electrostatic fabric filter precipitator was built and meshed, then carried on the number simulation of air distribution characteristic with FLUENT. The simulation results show that when the deflector spacing is 0.7m and the incremental height is 0.15m the air distribution is more uniform. The numerical simulation result is reasonable and can be used as the reference to optimize the designing of electrostatic fabric filter precipitator.

Special reason and common reason bring on the process disturbance. Statistical process control (SPC) is commonly used to monitor the process disturbance which arises from assignable reason. Engineering process control (EPC) compensates the deviation of output for common reason based on the feedback adjustment principle. Therefore, integrated SPC/EPC approach has better performance than that merely using SPC or EPC. However, in practice, it is very hard to search the appropriate method to apply for integration of SPC/EPC. The main reason is that EPC’s compensation has depressed probability which assignable reason is monitored by control chart. In this paper, a joint-monitoring method is designed to account for the above problems through detecting process output as well as monitoring process input. An example is given to prove that joint-monitoring can detect the process disturbance more quickly and more accurately.

Former studies and application of vermifiltration process to organic wastewater treatment has given an affirmative effect for the pollutant removal in wastewater. It could be used for the disperse wastewater treatment, especially for rural living sewage. We developed a new multilayer vermifiltration system in this study, expecting to enhance this ability for the disposal of rural living sewage. The result showed that all the COD, BOD5 and SS values in outflow after vermifiltration could meet GB18918-2002. The removal rates of COD，BOD5 and SS were above 75%, 85% and 90% respectively. The N and P could be partly removed. These preliminary results give a positive prospective for the application of multilayer vermifiltration in rural sewage treatment in the future.

Metallothionein (MT) is one kind of proteins induced in organism under the stress of heavy metal. It plays a great pole in detoxification and tolerance of heavy metal. In this study, according to the rich conservative sequence in MT, we designed corresponding primer, then cloned MT mRNA gene induced by As in earthworm E. andrei and got its nucleotide sequence. The results proved the presence of MT in Eisenia andrei, and showed that roxarsone could induce the expression of arsenic MT gene.

One kind of multi-void three-dimensional microstructure models based on homogenization method is constructed. Based on multi-void microstructure, the mathematical models for the topological structural optimization which takes maximizing the total potential energy as the objective function is constructed, then the Kuhn-Tucker optimality condition of the update method about the designs variable based on the porous microstructure can be gotten when optimization iterates. Finally, in explaining the employed algorithm an example is provided.

The research of crack-tip field in damage materials is a very complex problem. The core question is how to give the damage constitutive equation and determine the crack tip singularity order of magnitude of the physical quantities. Taking into account the damage process is a process which the energy (strain) accumulates, and the initial damage threshold value existence, on the Lemaitre’s research foundation, the brittle material damage constitutive equation that has the initial damage quantity and the power order relationship with strain is given. Under the assumption that stress (strain) is finite, the construction of III mode crack tip damage fields is studied and the solution of crack-tip stress (strain) asymptotic field is given. Finally, the relationship of the initial crack tip damage zone and full damage zone Scale and material parameters are discusses. These works provide theoretical basis for the material engineering design and the appraisal structure reliability.

Ab initio calculations of the two title reactions have been made to compare reactivities of OCS and CS2 toward a nucleophile, NH 2 - . MP2/6-311++G(d, p) geometry optimizations on the singlet potential energy surface have demonstrated that respective channels start from key intermediates and have revealed that multistep paths give the most favorable products: (1) NH 2 - + OCS → H2NS− + CO; (2) NH 2 - + OCS → HS− + HNCO; (3) NH 2 - + OCS → NCS− + H2O; (4) NH 2 - + OCS → NCO− + H2S; (5) NH 2 - + CS2 → NCS− + H2S; (6) NH 2 - + CS2 → HS− + HNCS. Furthermore, to get more reliable energetic data, single-point calculations are carried out at CCSD/6-311++G(d, p) level. The calculated result is consistent with the measured large rate constant in experiment. A comparison of reaction mechanisms is offered between NH 2 - + OCS and NH 2 - + CS2.

At present the study on the application of the topology optimum design in scraper conveyor is still under development. In this paper the topology optimization based on the homogenization method is applied to the design of the baffle on the scraper conveyer, which can provide a valuable conceptual design scheme for the selection of the baffle pattern. In conjunction with the homogenization theory and Finite Element Method (FEA), the mathematical models for designing the baffle by the minimizing mean compliance are developed in this paper. By applying the topology optimum design to the baffle, the topology optimization based on the homogenization method is proved to be reliable and practical at the conceptual design stage of baffle.

With the use of energy, the pollution is more and more serious. As the largest pollution family, coal-fired power plant must control the pollution strictly. It established model of a coal-fired power plant SCR system, and simulated the denitration under different boiler load conditions, to get the denitration efficiencies and the regular of the denitration efficiency under different boiler load conditions. It can provide recommendations for practicality run in coal-fired power plant SCR system.

The dehydrogenation reaction of [Pd(H)(OH)] + toward methane has been investigated theoretically. Both high- and low-spin states potential-energy surfaces for the reaction were built up by using density functional theory (DFT). As compared with the [PdH] + system, there is having many features in common. Our calculations indicate that the ground-states species have low electron spin and low s population in the metal-center for the transition states. After extensive sampling of the potential-energy surfaces (PESs), the finding shows that the σ-complex assisted metathesis (σ-CAM) process favor energetically low-spin singlet state in a spin-conserving manner.

At present the study on the application of the topology optimum design in scraper conveyor is still under development. In this paper the topology optimization based on the Solid Isotropic Material Penalization (SIMP) is applied to the design of the middle pan, which can provide a valuable conceptual design scheme for the selection of the middle pan pattern. In conjunction with the homogenization theory and Finite Element Method (FEA), the mathematical models for designing the middle pan by maximizing the rigidity are developed in this paper. By applying the topology optimum design to the middle pan, the topology optimization based on the SIMP method is proved to be reliable and practical at the conceptual design stage of middle pan.

Numerical simulation is used to study the combustion process，temperature distridution and NOx emission for a 10t/h chain boiler with and without flue gas recycle. And at the same time,it is constrasted that differences when flue gas is recycled to the primary wind inlet and to secondry wind inlet.The results show the temperature distridution decreased with flue gas recycle,so there is less NOx emission.And when flue gas is recycled to secondry wind inlet ,the NOx emission dropped mostly. The result offer a reference to design and operate a chain boiler.

In this paper, we prepared a novel cationic self-assembled micelle from poly(epsilon-caprolactone)-poly(ethyl glycol)-poly(epsilon-caprolactone) grafted polyethyleneimine (PCEC-g-PEI). The PCEC-g-PEI micelles, formed by self-assembly method, had mean particle size of ca. 82 nm and zeta potential of +22.5 mV at 37 degrees C, and could efficiently transfer pGFP into HEK293 cells in vitro. Meanwhile, as a model hydrophobic chemotherapeutic drug, honokiol was loaded into PCEC-g-PEI micelles by direct dissolution method assisted by ultrasonication. The honokiol loaded cationic PCEC-g-PEI micelles could effectively adsorb DNA onto its surface, while it could release honokiol in an extended period in vitro. This study demonstrated a novel DNA and hydrophobic chemotherapeutic drug co-delivery system.

Three-dimensional imaging in biological samples usually suffers from performance degradation caused by optical inhomogeneities. Here we proposed an approach to adaptive optics in fluorescence microscopy where the aberrations are measured by self-interference holographic recording and then corrected by a post-processing optimization procedure. In our approach, only one complex-value hologram is sufficient to measure and then correct the aberrations, which results in fast acquisition speed, lower exposure time, and the ability to image in three-dimensions without the need to scan the sample or any other element in the system. We show proof-of-principle experiments on a tissue phantom containing fluorescence particles. Furthermore, we present three-dimensional reconstructions of actin-labeled MCF7 breast cancer cells, showing improved resolution after the correction of aberrations. Both experiments demonstrate the validity of our method and show the great potential of non-scanning adaptive three-dimensional microscopy in imaging biological samples with improved resolution and signal-to-noise ratio.

The morphological differences of chitosan (CS) in the hydroxyapatite (HA)/CS nanocomposites were investigated in detailed, which were prepared via in situ hydrothermal precipitation. The results show that the obtained nanocomposites have excellent crystallinity and the crystal has excellent ordered structure, which is important to the composites performances in the biomedical application. Moreover, the CS arrangement and crystallinity in the composites greatly depend on the hydrothermal temperature and the pH value of precipitating agent. The temperature ranging from 373 to 413K and pH value of precipitating agent ranging from 12 to 14 were favorable to the crystallization and oriented growth of CS molecules in the composites. The CS crystals with better arrangement are assembled in the order of layer-by-layer in these composites.

Objective: This study aims to explore the treatment method of myocardial ischemia-reperfusion injury. Methods: Myocardial Ischemia-reperfusion rabbit model was established in this study. They were divided into four groups: sham operation (S) group, IRI control (I/R) group and IRI with morphine (MF) group and sufentanil (SF). Myocardial infarct size was compared with HE staining method. TUNEL assay was used to detect cell apoptosis. Results: Myocardial infarct size of control group and morphine and sufetanil group was 36.0±3.6, 23.0±1.2 and 27.1±2.3, respectively. There were significant differences between them (P < 0.01). Apoptotic index of I/R, MF and SF groups was 26.9±2.2, 12.5±2.3, 15.8±2.0, with statistical significance (P < 0.05). The concentration of CK-MB in serum: there were no significant differences of CK-MB between each group at baseline. The concentration of CK-MB after reperfusion were higher than that of baseline, except for group S (P < 0.05); Compared with group S, after reperfusion, the CK-MB of other three groups were higher (P < 0.05); The concentration of CK-MB in group MF and SF were lower than group I/R (P < 0.05); In contrast to group MF, the concentration of CK-MB after reperfusion was higher in group SF (P < 0.05). Conclusion: Morphine and sufentanil can specifically protect the myocardial function.

A fast DOA estimation algorithm developed from MUSIC, which also benefits from the processing of the signals' polarization information, is presented. Besides performance enhancement in precision and resolution, the proposed algorithm can be exerted on various forms of polarization sensitive arrays, without specific requirement on the array's pattern. Depending on the continuity property of the space spectrum, a huge amount of computation incurred in the calculation of 4-D space spectrum is averted. Performance and computation complexity analysis of the proposed algorithm is discussed and the simulation results are presented. Compared with conventional MUSIC, it is indicated that the proposed algorithm has considerable advantage in aspects of precision and resolution, with a low computation complexity proportional to a conventional 2-D MUSIC.

The etiology of Keshan disease (KD), an endemic myocardiopathy in regions of China, is largely unknown. To show the protein changes in serum from KD patients versus controls and idiopathic dilated cardiomyopathy (IDCM) and to search specific biological markers for differential diagnosis for KD. Serum of 65 patients with KD was compared with 29 patients with IDCM, 62 controls from KD areas and 28 controls from non-KD areas by ClinProt/MALDI-ToF technique. The genetic algorithm, quick classifier algorithm and supervised neural network algorithm methods were used to screen marker proteins and establish diagnostic model. Thirty-four differential peaks were identified in KD patients compared with the healthy controls from non-KD areas. Thirty-eight differentially peaks were identified in KD patients and controls from KD areas; and sixty-seven differentially peaks were identified in patients with KD and patients with IDCM. We believe that marker protein peaks screened in KD patients, healthy controls and IDCM patients may provide clues for the differential diagnosis and treatment of KD.

We have isolated a family of insect-selective neurotoxins from the venom of the Australian funnel-web spider that appear to be good candidates for biopesticide engineering. These peptides, which we have named the Janus-faced atracotoxins (J-ACTXs), each contain 36 or 37 residues, with four disulfide bridges, and they show no homology to any sequences in the protein/DNA databases. The three-dimensional structure of one of these toxins reveals an extremely rare vicinal disulfide bridge that we demonstrate to be critical for insecticidal activity. We propose that J-ACTX comprises an ancestral protein fold that we refer to as the disulfide-directed beta-hairpin.

We have isolated and determined the amino acid sequence of a novel peptide component from the venom of the Australian funnel-web spider Hadronyche versuta. This 68-residue toxin, ACTX-Hvf17, does not function like classical neurotoxins in modulating ion channel function as evidenced by its lack of insecticidal activity and its inability to affect vertebrate smooth or skeletal muscle contractility. The peptide shows significant sequence homology with mamba intestinal toxin 1 (MIT1) and to a lesser extent with a variety of colipases. The strong structural homology between MIT1 and porcine colipase leads us to propose that ACTX-Hvf17 also adopts the MIT1/colipase three-dimensional fold. However, we show that ACTX-Hvf17 has no colipase activity and does not stimulate muscle contractility like MIT1. We also show that MIT1 and ACTX-Hvf17 display significant sequence homology with the C-terminal cysteine-rich domain of the Dickkopf-1 family of proteins that induce head formation in developing embryos, which leads us to propose that this domain of Dickkopf-1 also adopts the MIT1/colipase fold. (C) 1999 Elsevier Science Ltd. All rights reserved.

The omega-atracotoxins are a family of 36 to 37-residue peptide neurotoxins that block insect but not mammalian voltage-gated calcium channels. The high phylogenetic specificity of these toxins recommends them as lead compounds for targeting insects that have developed resistance to chemical pesticides. We have begun to examine structure-function relationships in the omega-atracotoxins in order to explore the molecular basis of their activity and phylogenetic specificity. By probing the venom of the Blue Mountains funnel-web spider, Hadronyche versuta, for insecticidal toxins with masses close to that of omega-atracotoxin-Hv1a (omega-ACTX-Hv1a), we have isolated and sequenced five additional omega-atracotoxins. Five of the six omega-atracotoxins isolated from the venom of H. versuta (omega-ACTX-Hv1a to -Hv1e) differ from one another by only 1-3 residues and have similar insecticidal potencies. In contrast, omega-ACTX-Hv1f differs from the other toxins by up to 10 residues and it has markedly reduced insecticidal potency, thus providing information on key functional residues. The new atracotoxin sequences have revealed that the three N-terminal residues are highly conserved. Despite the fact that these residues are structurally disordered in solution we show here, by a series of N-terminal truncations, that they contribute significantly to insecticidal potency. However, loss of activity does not correlate with deletion of highly conserved residues, which leads us to propose that the disposition of the N-terminal charge, rather than the chemical properties of the N-terminal residues themselves, may be critical for the activity of omega-atracotoxin on insect calcium channels.

Three defensin-like peptides (DLPs) were isolated from platypus venom and sequenced. One of these peptides, DLP-1, was synthesized chemically and its three-dimensional structure was determined using NMR spectroscopy. The main structural elements of this 42-residue peptide were an anti-parallel β-sheet comprising residues 15-18 and 37-40 and a small 310 helix spanning residues 10-12. The overall three-dimensional fold is similar to that of β-defensin-12, and similar to the sodium-channel neurotoxin ShI (Stichodactyla helianthusneurotoxin I). However, the side chains known to be functionally important in β-defensin-12 and ShI are not conserved in DLP-1, suggesting that it has a different biological function. Consistent with this contention, we showed that DLP-1 possesses no anti-microbial properties and has no observable activity on rat dorsal-root-ganglion sodium-channel currents.

Spider toxins that target potassium channels constitute a new class of pharmacological tools that can be used to probe the structure and function of these channels at the molecular level. The limited studies performed to date indicate that these peptide toxins may facilitate the analysis of K+ channels that have proved insensitive to peptide inhibitors isolated from other animal sources. Thus far, two classes of K+ channel-selective spider toxins have been isolated, sequenced, and pharmacologically characterised – the hanatoxins (HaTx) from Grammastola spatulata and heteropodatoxins (HpTx) from Heteropoda venatoria. The hanatoxins block Kv2.1 and Kv4.2 voltage-gated K+ channels. In Kv2.1 K+ channels this occurs as a consequence of a depolarising shift in the voltage dependence of activation and not by occlusion of the channel pore. These toxins show minimal sequence homology with other peptide inhibitors of K+ channels, but they do share some homology with other ion channel toxins from spiders, particularly with regard to the spacing between cysteine residues. We have recently isolated three K+ channel antagonists from the venom of the Australian funnel-web spider Hadronyche versuta; at least two of these toxins are likely to constitute a new class of spider toxins active on K+ channels as they are approximately twice as large as HaTx and HpTx.

We present a bidirectional reflection distribution function (BRDF) model for thermal coating surfaces based on a three-component reflection assumption, in which the specular reflection is given according to the microfacet theory and Snell's law, the multiple reflection is considered Nth cosine distributed, and the volume scattering is uniformly distributed in reflection angles according to the experimental results. This model describes the reflection characteristics of thermal coating surfaces more completely and reasonably. Simulation and measurement results of two thermal coating samples SR107 and S781 are given to validate that this three-component model significantly improves the modeling accuracy for thermal coating surfaces compared with the existing BRDF models.