Search

Combining machine learning (ML) with physical models can significantly impact retrieval algorithms designed to invert geophysical parameters from remote sensing data. Such hybrid models integrate physical knowledge with domain expertise through a joint architecture, potentially enhancing performance by increasing the efficiency and flexibility of the physical model as well as the generalization and interpretability of the ML predictions. This work introduces a hybrid model for estimating forest height using single-baseline, single-polarization TanDEM-X interferometric coherence measurements. In this model, the vertical reflectivity profile is derived as a function of input features, including topographic and acquisition geometry descriptors, using a multilayer perceptron network. This profile is then used to invert forest height by leveraging the established physical relationship connecting the vertical reflectivity profile to forest height. The developed model is applied and validated on several TanDEM-X acquisitions over tropical sites with different acquisition geometries, and its performance is assessed against reference data derived from airborne LiDAR measurements.

The plant design process involves numerous engineering disciplines that generate and process various types of information. To guarantee an effective data and information exchange diverse technologies are available for a successful collaboration among the engineering disciplines. This paper aims to establish an evaluation methodology for selecting data exchange technologies for the plant design process. For this purpose, several surveys with experts from the plant design process are conducted and lead to a four step guide. The first two steps include the elicitation of relevant generalistic and project-individual requirements for the specific use case. The third step involves prioritizing all collected requirements with project-specific experts, which finally results in a predictable decision metric. The developed methodology is applied and validated by the use case of the research project DIAMOND (Digital Plant Modeling with Neutral Data Formats). For this, the Web-API is selected as the most suitable data exchange technology.

Digital transformations (DT) as part of currently implemented Industry 4.0 projects represent a key role in the competitiveness of manufacturing companies. However, the boundary conditions of a large company must be distinguished from those of a small and medium sized enterprise (SME). This means that an SME has a smaller specialist staff, tighter budgets and less market power available to implement DT projects internally and considering the prevailing conditions. This paper presents a methodology for handling a digitalization project in an SME. Due to its generality, this can be adapted to further use cases. The methodology was developed together with ATA Anlagentechnik (ATA), an SME in special purpose machinery sector. Focused on the internal process of technical sales, the method was used to optimize order data management. This was done through analysis and initial implementations in the areas of object recognition and the creation of efficient user interfaces in order to subject sales sub-processes such as the collection of customer input data to the creation of offers to a digital transformation. Once put into operation and supplemented by further internal or external processes, ATA moves towards complete digital data continuity, which represents an uninterrupted and consistent chain of business processes using digital data and tools. The paper outlines future steps to further refine what has been achieved using the presented DT method.

We present a novel silicon photomultiplier (SiPM) device integrated with high-speed two-transistor amplifier circuits on a single chip using standard 0.35- $\mu \text{m}$ complementary metal—oxide semiconductor (CMOS) technology. These amplifiers are configured as current followers to reduce the output capacitance and improve the amplitude and slew rate of the output signal. The efficiency of this solution is approximately proportional to the size of the SiPM. Measurement results show that the single-photon timing resolution (SPTR) can be enhanced for the segmented SiPM with integrated amplifiers compared with a conventional analog CMOS SiPM that is designed with the same architecture but without an integrated amplifier. The proposed $1\times1$ mm 2 SiPM, featuring integrated circuitry, achieves an SPTR of 117 ±6 ps. In contrast, the conventional analog CMOS SiPM exhibits an SPTR of 221 ±6 ps using the slow output and 155 ±6 ps using the fast output. In addition to timing resolution, we characterize the CMOS SiPM device in terms of dark count rate (DCR), correlated delayed noise (CDN), gain, crosstalk (CT), and PDE. The device exhibits a high gain of $1.16\times10\,\,^{\mathrm{ 6}}$ and low CT of 2.5%, but has a DCR of 2.8 Mhz/mm 2. The PDE, excluding CT and CDN, is 10.9% ± 0.3%.

InP DFB lasers are flip-chip bonded to 300 mm Si photonic wafers using a pick-and-place tool with an advanced vision system, realizing high-precision and high-throughput passive assembly. By careful co-design of the InP-Si Photonics electrical, optical and mechanical interface, as well as dedicated alignment fiducials, sub-300 nm post-bonding alignment precision is realized in a 25 s cycle time. Optical coupling losses of −1.5±−0.5 dB are achieved at 1550 nm wavelength after epoxy underfill, with up to 40 mW of optical power coupled to the SiN waveguides on the Si photonics wafer. The bonding interface adds less than 10% to the series resistance of the laser diodes and post-bonding thermal resistance is measured to be 76 K/W (or 27 K.mm/W), mostly dominated by heat spreading resistance in the InP lasers as suggested by in-depth thermal modeling. Although the assembled lasers suffer from significant, unintentional optical backreflection from the fiber grating couplers used for optical characterization, laser linewidths well below 1 MHz have been measured under specific drive conditions, as supported by a detailed laser noise analysis. Finally, we demonstrate the ability of bonded laser assemblies to pass early reliability tests.

Datasets play a key role in developing superior building detection approaches. However, most of the previous work focuses on accurate building masks and scale expansion, while the categories are always missing, which hinders the further analysis of urban development and cultures. Therefore, we propose a benchmark for building detection and fine-grained classification from very high-resolution (VHR) satellite imagery. An extensive annotation is performed for about 0.5 million building instances with 12 fine-grained roof types and individual polygons. The annotation of building functions of two cities in the previous version (UBCv1) (Huang et al., 2022) is also integrated. To ensure the building variety, it consists of VHR optical images of 20 unique cities worldwide with various landforms and styles of architecture. Its variety and fine-grained categories pose great challenges and meanwhile provide a foundation for the building extraction and fine-grained classification on a global scale. Besides, 17 cities are provided with finely aligned synthetic aperture radar (SAR) images, which can be used for the development and evaluation of approaches optionally based on optical, SAR, or multimodal images. Significantly, the proposed benchmark is used as the base of the 2023 IEEE GRSS Data Fusion Contest (Persello et al., 2023). The dataset and codes of the baseline methods are available at: https://github.com/AICyberTeam/UBC-dataset/tree/UBCv2.

Digital X-ray radiogrammetry (DXR) is a computer-assisted technique used to quantify cortical bone density of the metacarpals. The influence of metacarpal bone rotation and type of cast material on bone mineral density (BMD) measurements using the DXR technique was tested. The bone mineral density of the hand was measured by DXR, and rotation error (DXR–RE) as coefficients of variation were calculated, to verify reliability and reproducibility of this radiogeometric technique to assess in particular minor disease-related changes in the metacarpal bone mass. The reproducibility of the DXR measurements was also investigated using different cast materials (mull, elastic, and plastic). There were no significant changes in absolute values of DXR–BMD observed between 0 to $$19^\circ $$ 19∘ angulation. The relative DXR–RE ranged between 0 % (degree 1) and 0.70 % (degrees 15 and 19) for DXR–BMD. Regarding the different cast materials, DXR–BMD revealed a coefficient of variation with 0.41 % (mull cast) and 0.21 % (elastic cast). For the plastic cast, the DXR technique was not able to perform an analysis of DXR–BMD. The study revealed no significant influence of metacarpal rotation on the measurements of metacarpal bone mineral density as estimated by DXR. DXR measurements are not optimal when cast material is used. DXR can accurately quantify periarticular cortical bone mass. This is significant especially for rheumatoid arthritis and related conditions where X-ray imaging of arthritic hands with varying degrees of deformity is performed.

The physical properties of metal-organic chemical vapor deposition (MOCVD) and atomic layer deposition (ALD) deposited HfZrO4 films have been analyzed in detail by atom probe tomography, X-ray photoelectron spectroscopy, Rutherford backscattering spectrometry, transmission electron microscopy, atomic force microscopy, variable angle spectroscopic ellipsometry as well as temperature dependent grazing incidence X-ray diffraction. In addition we extend our recently presented electrical 32nm device results with MOCVD and ALD deposited HfZrO4 gate dielectrics by further evaluating 32 nm high performance logic devices on silicon on insulator (SOI) substrates with respect to interface trap charge densities Dit and time dependent dielectric breakdown (TDDB) reliability. All investigated parameters revealed a comparable behavior between ALD and MOCVD and therefore MOCVD is demonstrated to be a promising alternative to ALD in high volume manufacturing in this work.

The powerful inhibitory activity of podophyllotoxin (a natural product) on cell growth led to the development of clinically useful anticancer agents such as etoposide, teniposide, and etopophos. Although, these podophyllotoxin derivatives show good clinical effects against various cancers, its use often results in various undesired side effects, drug resistance, and cytotoxicity towards the normal cells. In order to overcome these limitations, it is essential to search new podophyllotoxin analogues with improved anticancer activity and fewer side effects to gain the maximum benefits for the cancer patients. With this purpose, the cytotoxicity data of two series of podophyllotoxin derivatives against four different cancer cell lines was used to develop 4 QSAR models. Hydrophobic property of the molecules was found one of the most important determining factors for their activity. The developed QSAR models showed a good correlative and predictive abilities having r2 0.960 to 0.836 and q2 0.911 to 0.705. On the basis of QSAR 1, two compounds (10-10 and 10-11) are suggested as potential synthetic targets. Statistical diagnostics and internal validation (cross validation and Y-randomization) tests have validated all the QSAR models. These QSAR models could be useful in the rational design of potential drug molecules with an enhanced inhibitory potency.

Cardiac disease is a major contributor to disease-related death in Churg-Strauss syndrome (CSS). We conducted the current study to determine the prevalence and clinical impact of cardiac involvement in CSS patients. We performed a multicenter, cross-sectional analysis of patients diagnosed with CSS. Cardiac workup included electrocardiography, echocardiography, cardiac magnetic resonance imaging (MRI), and endomyocardial biopsy.

The microtubule-stabilizing taxanes such as paclitaxel and docetaxel are the two most important anticancer drugs currently used in clinics for the treatment of various types of cancers. However, the major common drawbacks of these two drugs are drug resistance, neurotoxicity, substrate for drug transporter P-gp, cross-resistance with other chemotherapeutic agents, low oral bioavailability, and no penetration in the blood−brain barrier (BBB). These limitations have led to the search for new taxane derivatives with improved biological activity. In the present paper, we discuss the quantitative structure−activity relationship (QSAR) studies on a series of C2-modified 10-deacetyl-7-propionyl cephalomannines (IV) with respect to their binding affinities toward β-tubulin and cytotoxic activities against both drug-sensitive and drug-resistant tumor cells, in which resistance is mediated through either P-gp overexpression or β-tubulin mutation mechanisms, by the formulation of five QSARs. Hydrophobicity and molar refractivity of the substituents (πXand MRX) are found to be the most important determinants for the activity. Parabolic correlations in terms of MRX(eqs 2 and 4) are encouraging examples in which the optimum values of MRXare well-defined. We believe that these two QSAR models may prove to be adequate predictive models that can help to provide guidance in design and synthesis, and subsequently yield very specific cephalomannine derivatives (IV) that may have high biological activities. On the basis of these two QSAR models, 10 cephalomannine analogues (IV-21to IV-30) are suggested as potential synthetic targets. Internal (cross-validation (q2), quality factor (Q), Fischer statistics (F), and Y-randomization) and external validation tests have validated all the QSAR models.

OBJECTIVE: To compare normative data of joint space distances (JSD) with the JSD of patients with rheumatoid arthritis (RA) as measured by computer-aided joint space analysis (CAJSA) at the metacarpophalangeal (MCP) articulations, and to differentiate age- and sex-related alterations from the disease-related joint space narrowing. METHODS: In total, 256 healthy subjects and 248 patients with verified RA (following revised ACR criteria) underwent computerized semiautomated measurements of JSD (CAJSA, version 1.3.6) at the MCP articulation (JSD-MCP) based on digital radiographs. The Z-score, a comparative parameter that differentiates joint space alterations caused by RA-related cartilage destruction from age- and sex-related changes, was calculated. RESULTS: Our data showed a relationship between measured joint space widths (MCP total and MCP thumb to little finger) and age for healthy subjects and also the RA group. The RA group revealed an age-related joint space narrowing that was surpassed by the RA-related narrowing of joint space widths classified by Sharp joint space narrowing score and resulting in smaller Z-scores for RA patients. CONCLUSION: The CAJSA technique seems to distinguish age-related JSD changes in healthy volunteers from RA-induced alterations. In addition the Z-score was also able to differentiate RA-dependent narrowing of JSD. Calculation of the Z-scores based on sex- and age-specific reference data may facilitate earlier identification of patients with RA, allowing initiation of a more optimal, individually adapted therapeutic strategy.

AbstractAt the university, each institute or chair can be seen as a small independent enterprise in respect of education and research. For this reason, the efficiency of management as well as the improvement of education and research within this unit is more and more at a premium. The students need a good working environment and the opportunity to gain and share information in order to carry out successful research and course work. This paper shows how education at a university semiconductor laboratory can be improved by using a content management system to build a knowledge management system. The structuring and implementation will be shown as well as students’ rating of it. The results support the conclusion that the knowledge base is a great step forward for improving education and research in a complex environment.

At the university, each institute or chair can be seen as a small independent enterprise in respect of education and research. For this reason, the efficiency of management as well as the improvement of education and research within this unit is more and more at a premium. The students need a good working environment and the opportunity to gain and share information in order to carry out successful research and course work. This paper shows how education at a university semiconductor laboratory can be improved by using a content management system to build a knowledge management system. The structuring and implementation will be shown as well as students’ rating of it. The results support the conclusion that the knowledge base is a great step forward for improving education and research in a complex environment.

A semiconductor laser emitting at 972 nm is stabilised with respect to a vibrationally and thermally compensated reference Fabry--Perot resonator with the vertical axis. The supporting points lie in the horizontal symmetry plane of the resonator, the influence of vibrations in the vertical direction being substantially suppressed in this case. This configuration provides a low sensitivity of the laser emission frequency to vertical accelerations of the reference resonator. To reduce the influence of temperature fluctuations, the resonator is made of an ULE (ultra-low-expansion) glass and is kept at temperature at which the expansion coefficient of this glass is close to zero. The laser linewidth is smaller than 0.5 Hz and the frequency drift is [?]0.1 Hz s-1. The minimum of the Allan deviation achieved for 3 s is 2x10-15. The laser was used to record the spectra of the 1S--2S transition in atomic hydrogen.

Chiral nonracemic thiomorpholines have been synthesized in four to six steps from limonene or achiral alkenes using α‐methylbenzylamine to control absolute stereochemistry. These aminosulfides have been used to generate sulfur ylides, which have been applied in the asymmetric epoxidation of aldehydes as easily recoverable catalysts. Excellent yields (up to 98 %), enantioselectivities (up to 97:3 e.r.), and diastereoselectivities (≥98:2 trans/cis) were achieved in these epoxidations and the sulfides were easily recovered in high yield (up to 97 %) by simple acid/base extraction.

Bacterial agents or products more likely to be used as biological weapons of mass destruction are Bacillus anthracis, Francisella tularensis, Yersinia pestis, and the neurotoxin of Clostridium botulinum. Anthrax is an acute infectious disease with a high mortality rate caused by Bacillus anthracis, reinforcing the need for better adjunctive therapy and prevention strategies. In this paper, we developed 7 QSAR models on penicillin-based inhibitors of the class A and B β-lactamases from B. anthracisand inhibitors of anthrax lethal factor to understand the chemical−biological interactions. Hydrophobic and steric factors are found to be the most important determinants of the activity. Internal (cross-validation ( q2), quality factor ( Q), Fischer statistics ( F), and Y-randomization) and external validation tests have validated all the QSAR models.

Spectral characteristics of laser systems used for precision two-photon spectroscopy of the 1s--2s transition in the hydrogen atom are analysed. The spectral properties of radiation from a 972-nm external-cavity semiconductor laser stabilised by external monolithic cavities of different configurations are considered in detail. The classical cavity scheme with a horizontal axis and a new scheme with a vertical axis, which is weakly sensitive to vibrations, are considered. The emission spectrum of a stabilised laser exhibits a narrow central peak and a pedestal caused by the residual phase noise. The semiconductor laser stabilised with respect to the vertical-axis cavity emits the line of width less than 0.45 Hz, which contains [?]99% of the total output power. The transformation of the emission spectrum upon frequency doubling in nonlinear crystals is investigated. The laser system developed in the study provides the narrowing of the recorded 1s--2s transition line in the hydrogen atom down to 2 kHz at 121 nm.

For years, the microtubule-stabilizing agents paclitaxel and docetaxel (progenitors of the family of taxanes) have been the most successful anticancer drugs currently used in clinics. However, both drugs are associated with notorious side effects, drug resistance, and cross resistance with other chemotherapeutic agents. These limitations have led to the search for new drugs with improved biological activity. In the present paper, we discuss the interaction of taxanes with the tubulin/microtubule system by the formulation of 6 QSARs. Hydrophobicity of the substituents (π) is found to be one of the most important determinants of the activity followed by steric parameters. Parabolic correlations (eqs and ) with B5 and π are the most encouraging examples, where the optimum values of these parameters are well defined. We believe that these two QSARs may prove to be adequate predictive models that can help to provide guidance in design/synthesis and subsequently yield very specific compounds ( IVand VIII) that may have high biological activities. On the basis of these two QSARs 3 and 7, 18 compounds ( IV-12− IV-22and VIII-16− VIII-22) are suggested as potential synthetic targets. Cross-validation, quality factor ( Q), Fischer statistics ( F), and Y-randomization tests have validated all the QSAR models.

No Abstract

No Abstract

The interest in the application of structure−activity relationships has steadily increased in recent decades. In the present paper, we have discussed the cytotoxicity of various sets of organic compounds against ovarian cancer cells by the formulation of a total number of 11 QSARs. Hydrophobicity is found to be one of the most important determinants of activity followed by steric parameters. Parabolic correlation with hydrophobicity is an encouraging example, where the optimal hydrophobicity is well-defined. We believe that this may be the predictive model to narrow the synthetic challenges in order to yield very specific OVCAR-3 inhibitors. On the basis of this model, we can predict three compounds that may be the next synthetic target. Cross-validation and Y-randomization tests were used to validate all the QSAR models.

Al2O3 films 1 to 20 nm thick were deposited as alternative high-κ gate dielectric on hydrogen-terminated silicon by Atomic Layer Deposition (ALD) and characterized by Synchrotron X-ray Photoelectron Spec-troscopy (SXPS), Fourier Transform Infrared (FTIR) absorption spectroscopy and admittance measure-ments. The SXPS results indicate that about 60% of the original Si–H surface bonds are preserved at the Al2O3/Si interface and this is confirmed by monitoring the Si–H stretching modes by FTIR spectroscopy in the Attenuated Total Reflection (ATR) mode both before and after ALD of Al2O3. The remaining 40% of Si–H bonds are replaced by Si–O bonds as verified by SXPS. In addition, a fraction of a monolayer of SiO2 forms on top of the Al2O3 dielectric during deposition. The presence of OH-groups at a level of 3% of the total oxygen content was detected throughout the Al2O3 layer through a chemically shifted O 1s component in SXPS. Admittance measurements give a dielectric constant of 9.12, but a relatively high density of interface traps between 1011 and 1012 cm–2 eV–1. (© 2006 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)

Background: One underlying cause of unexplained recurrent abortions (RA) may be a maternal immunological malfunction preventing the mother from developing immune responses that are required for maternofetal tolerance. Although published results are conflicting, several authors have reported successful treatment by immunization of the prospective mother with paternal leukocytes. We report our 15-year experience with immunotherapy for prevention of recurrent abortions and our first results with immunotherapy in case of unsuccessful in vitro fertilization (IVF) program. Patients and Methods: Between 1990 and 2004, 202 women with RA and 47 patients with unsuccessful IVF treatment were immunized intradermally with 3-5 × 107 paternal lymphocytes separated from 50 ml whole blood. Results: In the analysis of all treated women with RA, the overall success rate (live births in all patients treated) was 75% (132/177). In the analysis of pregnant women only, the success rate was 87% (132/152). Out of the 47 patients with unsuccessful IVF treatment, 34% (16/47) got pregnant, with a successful delivery of a baby in 75% (12/16). Except for transitory inflammatory reactions at the injection site, we did not register any adverse reactions related to the immunotherapy. Conclusion: Immunotherapy with paternal lymphocytes is a therapeutic option for patients with recurrent miscarriages. Also in patients with unsuccessful IVF program, the rate of successful pregnancy could be increased by active immunotherapy.

HeLa cells were named for Henrietta Lacks, who died in 1952 from an infection of a special type of cancer. Margaret Gey, her physician, started working with these cancer cells that are still used for medical research. In the present review, an attempt has been made to collect the data for the effects of different chemicals on HeLa cells and to discuss them by the formulation of a total number of 22 QSAR.

The aim of our work was to evaluate digital x-ray radiogrammetry (DXR) for the quantification of disease-related periarticular demineralization and computerized analysis of joint space distances (JSDA) for the measurement of joint space narrowing as a new diagnostic method for the early detection of joint-associated alterations and for monitoring disease progression in patients with rheumatoid arthritis (RA).

The aldol‐Tishchenko reaction of ketone aldols as enol equivalents has been developed as an efficient strategy to furnish differentiated 1,3‐anti‐diol monoesters in one step. The thermodynamically unstable ketone aldols undergo a facile retro‐aldolization to yield a presumed zirconium enolate in situ, which then undergoes the aldol‐Tishchenko reaction in typically high yields and with complete 1,3‐antidiastereocontrol. Evaluation of a broad range of metal alkoxides as catalysts and optimization of the reaction protocol led to a modified zirconium alkoxide catalyst with attenuated Lewis acidity and dichloromethane as solvent, which resulted in suppression of the undesired acyl migration to a large extent. Various ketone aldols have been prepared and subjected to the general process, giving rise to a broad range of differently substituted 1,3‐anti‐diol monoesters, which may be hydrolyzed to the corresponding 1,3‐anti‐diols.

ObjectiveTo evaluate the reproducibility of imaging and analysis for bone mineral density (BMD) determination using digital computer-assisted X-ray radiogrammetry (DXR; Pronosco X-posure, version V.2, Sectra Pronosco, Denmark); to verify potential factors that influence BMD extrapolation such as tube voltage, film-focus distance (FFD), film quality and brand (Kodak T-MAT-Plus, Konika SRH, Agfa Scopix), imaging technology (conventional, digital), imaging system (Kodak, Agfa) and exposure level (mAs); and to clarify whether DXR analysis based on printouts of digital images is comparable to analysis of conventional images.Design and patientsThe hand of a cadaver was X-rayed using varied parameters: 4–8 mAs, 40–52 kV, 90–130 cm FFD. Radiographs under standardised conditions were performed 10 times using a conventional machine (Philips Super 80 CP) and the printouts of a digital system (Digital Diagnost Philips Optimus) for the analysis of reproducibility. One image was scanned and analysed 10 times additionally for imaging reproducibility.ResultsReliability error of the system for the imaging process using conventional radiographs-rays was 0.49% (standard conditions: 6 mAs, 40 kV, 1 m FFD), using printouts of digital images was 2.89% (4 mAs, 42 kV, 1 m FFD) and regarding the analysis process was 0.22%. BMD calculation is not affected by alterations in FFD (precision error 1.21%), mAs (0.83%) or film quality/brand (0.38%), but differs significantly depending on tube voltage (2.70%). The system was not able to analyse conventional images with tube voltages of 49/52 kV.ConclusionDXR technology is stable with most of the tested parameters. Normative data should exclusively be used for calculations using similar tube voltage or correction factors. All other parameters had no significant influence on the BMD calculation. Reproducibility is high. For technical reasons it is not recommended to use the printouts of digital images for BMD determination.

Die rheumatoide Arthritis ist eine sich systemisch manifestierende Erkrankung, die eine frühzeitige Affektion der peripheren Extremitätengelenke im Hand- bzw. Fußbereich aufweist. Ziel dieser Studie ist die Evaluierung eines neuen Knochendichtemessverfahrens, der Digitalen Radiogrammetrie (DXR), deren Ergebnisse im Vergleich zu etablierten Osteodensitometriemethoden, wie pQCT und DXA unter Berücksichtigung des Schweregrades der rheumatoiden Arthritis und einer systemischen Kortisongabe diskutiert werden. Die Untersuchungen wurden an insgesamt 153 Patienten mit einer nach den Kriterien des American College of Rheumatology verifizierten rheumatoiden Arthritis durchgeführt. Alle Patienten erhielten eine Knochenmineraldichtemessung mittels DXR unter Verwendung einer Röntgenaufnahme der nicht dominanten Hand zur Bestimmung der kortikalen Knochenmineraldichte (BMD) und des Metacarpal-Index (MCI). Mittels DXA wurden die BMD-Werte des proximalen Femur (i. e. total femur) sowie der Lendenwirbelsäule (i. e. LWK 1–4) bei 102 Patienten erhoben, wobei für diese Patientengruppe eine Klassifikation des Schweregrades der rheumatoiden Arthritis unter Verwendung des Ratingen Scores erfolgte. Initiale Messresultate der Gesamtknochenmineraldichte als auch ein kortikaler/subkortikaler bzw. trabekulärer Knochenmineraldichtewert des distalen Radius lagen für 51 Patienten mittels pQCT vor. Die DXA- als auch die pQCT-Kollektive wurden in Untergruppen mit bzw. ohne systemische Kortisongabe unterteilt. Alle Korrelationen zwischen der DXRBMD und den DXA-Werten (prox. Femur: R=0,61; LWS: R=0,44) als auch pQCT-Parametern (0,46

Near-infrared range fluorescence (NIRF) imaging is a potential tool to diagnose biologic processes in vivo. This applicability study sought to define whether imaging with fluorochrome Cy5.5 can identify arthritis in murine antigen-induced arthritis (AIA).

Polarizability is a property of molecules that has long been of interest to scientists from a variety of viewpoints. However, in the area of the QSAR of chemical−biological interactions, it has received little attention. Recently we have shown that one can use the simple summation of the valence electrons (H 1, C 4, O 6, etc.) in a molecule as a measure of its polarizability. We have found this parameter to correlate nerve toxicity of a wide variety of chemicals acting on nerves of frogs, rabbits, cockroaches, and humans.

The detection of arthritis by autofluorescence was investigated using an antigen-induced arthritis model.

An excellent example in the field of rational drug design is the discovery and development of more than a dozen drugs for the treatment of AIDS. The major targets for the development of new chemotherapeutic agents are Reverse Transcriptase and Protease, the enzymes encoded by HIV-1. The introduction of HIV-1 protease (HIV-1 PR) inhibitors, in particular, has drastically decreased the mortality and morbidity associated with AIDS. The inhibition of this enzyme results in production of immature and noninfectious virions. In the present review, a comparative quantitative structure activity relationship (QSAR) study of various peptidomimetic and non-peptidomimetic molecules investigated for their inhibitory activity has been reported. Among the various physicochemical properties studied, hydrophobicity, steric and electronic interactions are found to play important role in binding to the receptor.

In this study, the cytotoxicities of a series of X-thiophenols vs rapidly growing mouse leukemia cells in vitro are determined. The resulting ID50 values are then used to formulate a quantitative structure−activity relationship, which is well-correlated by the Brown variation of the Hammett electronic parameter, σ-plus (σ⁺ ), such that Log 1/ID50 = −0.93 (±0.18) σ⁺ + 0.86 (±0.24) IH + 3.99 (±0.13). IH represents an indicator variable that calls attention to the unusual activity of halogens and pseudohalogens. In lieu of σ⁺, homolytic bond dissociation energies (BDE) are also used successfully to correlate the cellular cytotoxicities of thiophenols. The nature of substituent effects on cellular toxicity is examined, and they reveal that electron-releasing substituted thiophenols such as 4-amino thiophenol and the 4-alkoxy thiophenols are highly cytotoxic and effective at inhibiting cellular proliferation at physiological pH. On the other hand, electron-attracting substituted thiophenols such as the 4-cyano and 4-halogen analogues show a reduced ability to inhibit the cell growth of this cell line. Thus, there is a clear parallel between enhanced biological activity and electron releasing ability as measured by σ⁺ constants or BDE values. The susceptibility of the cellular interaction to electronic effects as delineated by the coefficient with the σ⁺ term (also called the Hammett ρ value) is high (−0.96), suggesting that substantial energetic assistance is provided by the substituents and that a weak initiating radical reactant such as superoxide radical may be involved. Previous cytotoxicity studies of a large diverse data set of X-phenols in this cell line and embryo cells have also revealed a more pronounced dependence on σ⁺ and ΔBDE. A comparison of reaction constants obtained from thiophenoxy radical formation reactions and phenoxy radical formation reactions in organic media suggests radical-mediated involvement in cell cytotoxicity. Such cells could be more vulnerable to the effects of reactive thiyl species on their metabolism and subsequent proliferation.

This report considers the importance of electronic effects in their role in the QSAR of chemical−biological interactions. The problem of accounting for polarizability effects in ligand−substrate interactions is discussed in terms of molecular polarizability (MR) and NVE (number of valence electrons) using additive values for valence electrons. The two approaches give essentially the same result in examples of frog nerve toxicity and examples of nerve toxicity with rabbits and cockroaches. The point is made that no matter how one approaches QSAR, electronic interactions must be considered if we are to begin to develop a science of chemical−biological interactions.

This report considers the importance of electronic effects in their role in the QSAR of chemical−biological interactions. The problem of accounting for polarizability effects in ligand−substrate interactions is discussed in terms of molecular polarizability (MR) and NVE (number of valence electrons) using additive values for valence electrons. The two approaches give essentially the same result in examples of frog nerve toxicity and examples of nerve toxicity with rabbits and cockroaches. The point is made that no matter how one approaches QSAR, electronic interactions must be considered if we are to begin to develop a science of chemical−biological interactions.

In this report we illustrate the importance of making an effort to ensure that all of the dependent variables in a QSAR are associated with one mechanism of action. If this cannot be established, it will not be possible to compare the QSAR with others acting on different biological systems. That is, such information cannot be used to develop a science of chemical−biological interactions. A study of the action of a large set of phenols acting on Tetrahymena pyriformismade by Cronin and Schultz is analyzed to illustrate the problem.

In this report we illustrate the importance of making an effort to ensure that all of the dependent variables in a QSAR are associated with one mechanism of action. If this cannot be established, it will not be possible to compare the QSAR with others acting on different biological systems. That is, such information cannot be used to develop a science of chemical−biological interactions. A study of the action of a large set of phenols acting on Tetrahymena pyriformis made by Cronin and Schultz is analyzed to illustrate the problem.