CHARACTERIZATION OF HIGH MOBILITY GROUP AND HISTONE H1 PROTEIN LEVELS AND SYNTHESIS DURING SPERMATOGENESIS IN THE RAT

In order to propose a role for internucleosomal high mobility group proteins (HMGs), and HI histone variants study of their levels and synthesis in a system of development and differentiation--rat spermatogenesis--was undertaken. HMG1, 2, 14, and 17 were isolated from rat testes and found to be very similar to calf thymus HMGs. Testis levels of HMGs, relative to DNA, were equivalent to other rat tissues for HMG1 (13 ug/mg DNA), HMG14 (2 ug/mg DNA), and HMG17 (5 ug/mg DNA). HMG2 levels were different among rat tissues, with three groups observed: (1) nonproliferating tissues (1-5 ug/mg DNA); (2) proliferating tissues (8-13 ug/mg DNA); and (3) the testis (32 ug/mg DNA). Other species (toad, opposum, mouse, dog, and monkey) showed the same testis-specific increase of HMG2. Populations of purified testis cell types were separated by centrifugal elutriation and density gradient centrifugation from adult and immature rat testes. Pachytene spermatocytes and early spermatids (56 and 47 ug/mg DNA, respectively) caused the testis-specific increase of HMG2 levels. Cell types preceding pachytenes (types A and B spermatogonia, mixtures of spermatogonia and early primary spermatocytes, and early pachytenes contained HMG2 levels similar to proliferating tissues (12 ug/mg DNA). Late spermatids did not contain HMGs. Somatic Sertoli and Leydig cells (2 ug/mg DNA) exhibited HMG2 levels similar to nonproliferating tissues. HMGs synthesized in spermatogonia and spermatocytes had similar specific activities, but early spermatids did not synthesize HMGs. Germ cells also contained an HMG2 species (on acid-urea gels) not found in somatic tissues. Other investigators have shown that HMGs may be associated with transcriptional or replicative processes. Thus, it is proposed that HMG2 plays a role in modulatable gene expression, while HMG1 is associated with housekeeping functions.^ HI histone variants were also studied throughout spermatogenesis. The minor somatic variant, HIa, is the predominant variant in spermatogonia and early primary spermatocytes. In early pachytenes, the testis-specific variant, HIt, is first synthesized and appears, largely replacing somatic variants HIbcd and e by late pachytene stage. Early spermatids contain the same HI composition as pachytenes, but do not synthesize HI histones. HI('0) is present in low amounts in all germ cells. These results suggest that expression of HI variants is developmentally controlled.^

Corporate Tax Avoidance and High Powered Incentives

This paper analyzes the links between corporate tax avoidance, the growth of highpowered incentives for managers, and the structure of corporate governance. We develop and test a simple model that highlights the role of complementarities between tax sheltering and managerial diversion in determining how high-powered incentives influence tax sheltering decisions. The model generates the testable hypothesis that firm governance characteristics determine how incentive compensation changes sheltering decisions. In order to test the model, we construct an empirical measure of corporate tax avoidance - the component of the book-tax gap not attributable to accounting accruals - and investigate the link between this measure of tax avoidance and incentive compensation. We find that, for the full sample of firms, increases in incentive compensation tend to reduce the level of tax sheltering, suggesting a complementary relationship between diversion and sheltering. As predicted by the model, the relationship between incentive compensation and tax sheltering is a function of a firm.s corporate governance. Our results may help explain the growing cross-sectional variation among firms in their levels of tax avoidance, the .undersheltering puzzle,. and why large book-tax gaps are associated with subsequent negative abnormal returns.

Prevalence of symptoms of neurotoxicity and potential occupational pesticide and solvent exposures among high school students in Starr County, Texas: A pilot study

Numerous harmful occupational exposures affect working teens in the United States. Teens working in agriculture and other heavy-labor industries may be at risk for occupational exposures to pesticides and solvents. The neurotoxicity of pesticides and solvents at high doses is well-known; however, the long term effects of these substances at low doses on occupationally exposed adolescents have not been well-studied. To address this research gap, a secondary analysis of cross-sectional data was completed in order to estimate the prevalence of self-reported symptoms of neurotoxicity among a cohort of high school students from Starr County, Texas, a rural area along the Texas-Mexico border. Multivariable linear regression was used to estimate the association between work status (i.e., no work, farm work, and non-farm work) and symptoms of neurotoxicity, while controlling for age, gender, Spanish speaking preference, inhalant use, tobacco use, and alcohol use. The sample included 1,208 students. Of these, the majority (85.84%) did not report having worked during the prior nine months compared to 4.80% who did only farm work, 6.21% who did only non-farm work, and 3.15% who did both types of work. On average, students reported 3.26 symptoms with a range from 0-16. The most commonly endorsed items across work status were those related to memory impairment. Adolescents employed in non-farm work jobs reported more neurotoxicity symptoms than those who reported that they did not work (Mean 4.31; SD 3.97). In the adjusted multivariable regression model, adolescents reporting non-farm work status reported an average of 0.77 more neurotoxicity symptoms on the Q16 than those who did not work (P = 0.031). The confounding variables included in the final model were all found to be factors significantly associated with report of neurotoxicity symptoms. Future research should examine the relationship between these variables and self-report of symptoms of neurotoxicity.^

Modeling Techniques for the High-Resolution Interpretation of Cryo-Electron Microscopy Reconstructions

Essential biological processes are governed by organized, dynamic interactions between multiple biomolecular systems. Complexes are thus formed to enable the biological function and get dissembled as the process is completed. Examples of such processes include the translation of the messenger RNA into protein by the ribosome, the folding of proteins by chaperonins or the entry of viruses in host cells. Understanding these fundamental processes by characterizing the molecular mechanisms that enable then, would allow the (better) design of therapies and drugs. Such molecular mechanisms may be revealed trough the structural elucidation of the biomolecular assemblies at the core of these processes. Various experimental techniques may be applied to investigate the molecular architecture of biomolecular assemblies. High-resolution techniques, such as X-ray crystallography, may solve the atomic structure of the system, but are typically constrained to biomolecules of reduced flexibility and dimensions. In particular, X-ray crystallography requires the sample to form a three dimensional (3D) crystal lattice which is technically di‑cult, if not impossible, to obtain, especially for large, dynamic systems. Often these techniques solve the structure of the different constituent components within the assembly, but encounter difficulties when investigating the entire system. On the other hand, imaging techniques, such as cryo-electron microscopy (cryo-EM), are able to depict large systems in near-native environment, without requiring the formation of crystals. The structures solved by cryo-EM cover a wide range of resolutions, from very low level of detail where only the overall shape of the system is visible, to high-resolution that approach, but not yet reach, atomic level of detail. In this dissertation, several modeling methods are introduced to either integrate cryo-EM datasets with structural data from X-ray crystallography, or to directly interpret the cryo-EM reconstruction. Such computational techniques were developed with the goal of creating an atomic model for the cryo-EM data. The low-resolution reconstructions lack the level of detail to permit a direct atomic interpretation, i.e. one cannot reliably locate the atoms or amino-acid residues within the structure obtained by cryo-EM. Thereby one needs to consider additional information, for example, structural data from other sources such as X-ray crystallography, in order to enable such a high-resolution interpretation. Modeling techniques are thus developed to integrate the structural data from the different biophysical sources, examples including the work described in the manuscript I and II of this dissertation. At intermediate and high-resolution, cryo-EM reconstructions depict consistent 3D folds such as tubular features which in general correspond to alpha-helices. Such features can be annotated and later on used to build the atomic model of the system, see manuscript III as alternative. Three manuscripts are presented as part of the PhD dissertation, each introducing a computational technique that facilitates the interpretation of cryo-EM reconstructions. The first manuscript is an application paper that describes a heuristics to generate the atomic model for the protein envelope of the Rift Valley fever virus. The second manuscript introduces the evolutionary tabu search strategies to enable the integration of multiple component atomic structures with the cryo-EM map of their assembly. Finally, the third manuscript develops further the latter technique and apply it to annotate consistent 3D patterns in intermediate-resolution cryo-EM reconstructions. The first manuscript, titled An assembly model for Rift Valley fever virus, was submitted for publication in the Journal of Molecular Biology. The cryo-EM structure of the Rift Valley fever virus was previously solved at 27Å-resolution by Dr. Freiberg and collaborators. Such reconstruction shows the overall shape of the virus envelope, yet the reduced level of detail prevents the direct atomic interpretation. High-resolution structures are not yet available for the entire virus nor for the two different component glycoproteins that form its envelope. However, homology models may be generated for these glycoproteins based on similar structures that are available at atomic resolutions. The manuscript presents the steps required to identify an atomic model of the entire virus envelope, based on the low-resolution cryo-EM map of the envelope and the homology models of the two glycoproteins. Starting with the results of the exhaustive search to place the two glycoproteins, the model is built iterative by running multiple multi-body refinements to hierarchically generate models for the different regions of the envelope. The generated atomic model is supported by prior knowledge regarding virus biology and contains valuable information about the molecular architecture of the system. It provides the basis for further investigations seeking to reveal different processes in which the virus is involved such as assembly or fusion. The second manuscript was recently published in the of Journal of Structural Biology (doi:10.1016/j.jsb.2009.12.028) under the title Evolutionary tabu search strategies for the simultaneous registration of multiple atomic structures in cryo-EM reconstructions. This manuscript introduces the evolutionary tabu search strategies applied to enable a multi-body registration. This technique is a hybrid approach that combines a genetic algorithm with a tabu search strategy to promote the proper exploration of the high-dimensional search space. Similar to the Rift Valley fever virus, it is common that the structure of a large multi-component assembly is available at low-resolution from cryo-EM, while high-resolution structures are solved for the different components but lack for the entire system. Evolutionary tabu search strategies enable the building of an atomic model for the entire system by considering simultaneously the different components. Such registration indirectly introduces spatial constrains as all components need to be placed within the assembly, enabling the proper docked in the low-resolution map of the entire assembly. Along with the method description, the manuscript covers the validation, presenting the benefit of the technique in both synthetic and experimental test cases. Such approach successfully docked multiple components up to resolutions of 40Å. The third manuscript is entitled Evolutionary Bidirectional Expansion for the Annotation of Alpha Helices in Electron Cryo-Microscopy Reconstructions and was submitted for publication in the Journal of Structural Biology. The modeling approach described in this manuscript applies the evolutionary tabu search strategies in combination with the bidirectional expansion to annotate secondary structure elements in intermediate resolution cryo-EM reconstructions. In particular, secondary structure elements such as alpha helices show consistent patterns in cryo-EM data, and are visible as rod-like patterns of high density. The evolutionary tabu search strategy is applied to identify the placement of the different alpha helices, while the bidirectional expansion characterizes their length and curvature. The manuscript presents the validation of the approach at resolutions ranging between 6 and 14Å, a level of detail where alpha helices are visible. Up to resolution of 12 Å, the method measures sensitivities between 70-100% as estimated in experimental test cases, i.e. 70-100% of the alpha-helices were correctly predicted in an automatic manner in the experimental data. The three manuscripts presented in this PhD dissertation cover different computation methods for the integration and interpretation of cryo-EM reconstructions. The methods were developed in the molecular modeling software Sculptor (http://sculptor.biomachina.org) and are available for the scientific community interested in the multi-resolution modeling of cryo-EM data. The work spans a wide range of resolution covering multi-body refinement and registration at low-resolution along with annotation of consistent patterns at high-resolution. Such methods are essential for the modeling of cryo-EM data, and may be applied in other fields where similar spatial problems are encountered, such as medical imaging.

Vocational guidance in people with special educational needs as the result of visual impairment during the transition stage from high school to advanced education

This work proposes to seek for the factors related to the choices that people with special educational needs make as the result of the visual impairment, during the transition stage from high school to advanced education. Therefore, we have taken into consideration that Vocational Guidance and the transition towards adulthood get specific characteristics in case of visually impaired young people, particularly in what's related to continue with advanced education. The focus of this work is to be able to clarify the existence of factors that make this transition stage easier or harder, through the observation of visually impaired and blind people who complete high school. This matter has aroused interest and concern about the strategies to follow to ensure the successful entrance and remaining in the selected advanced education. However, if we don?t know the factors involved in the described fact, it's difficult to design an appropriate intervention strategy. Then, in order to take acknowledge about the specific issues of visually impaired young people who complete high school, we chose a special school for this disability and some students who will join this project

Vocational guidance in people with special educational needs as the result of visual impairment during the transition stage from high school to advanced education

This work proposes to seek for the factors related to the choices that people with special educational needs make as the result of the visual impairment, during the transition stage from high school to advanced education. Therefore, we have taken into consideration that Vocational Guidance and the transition towards adulthood get specific characteristics in case of visually impaired young people, particularly in what's related to continue with advanced education. The focus of this work is to be able to clarify the existence of factors that make this transition stage easier or harder, through the observation of visually impaired and blind people who complete high school. This matter has aroused interest and concern about the strategies to follow to ensure the successful entrance and remaining in the selected advanced education. However, if we don?t know the factors involved in the described fact, it's difficult to design an appropriate intervention strategy. Then, in order to take acknowledge about the specific issues of visually impaired young people who complete high school, we chose a special school for this disability and some students who will join this project

Vocational guidance in people with special educational needs as the result of visual impairment during the transition stage from high school to advanced education

This work proposes to seek for the factors related to the choices that people with special educational needs make as the result of the visual impairment, during the transition stage from high school to advanced education. Therefore, we have taken into consideration that Vocational Guidance and the transition towards adulthood get specific characteristics in case of visually impaired young people, particularly in what's related to continue with advanced education. The focus of this work is to be able to clarify the existence of factors that make this transition stage easier or harder, through the observation of visually impaired and blind people who complete high school. This matter has aroused interest and concern about the strategies to follow to ensure the successful entrance and remaining in the selected advanced education. However, if we don?t know the factors involved in the described fact, it's difficult to design an appropriate intervention strategy. Then, in order to take acknowledge about the specific issues of visually impaired young people who complete high school, we chose a special school for this disability and some students who will join this project

High resolution color reflectance and hematite and goethite record of ODP Hole 184-1143A in the South China Sea

Precipitation has a larger variability than temperature in tropical monsoon regions, thus it is an important climate variable. However, reconstructions of long-term rainfall histories are scarce because of the lack of reliable proxies. Here we document that iron oxide minerals, specifically the ratio of hematite to goethite (Hm/Gt), is a reasonable precipitation proxy. Using diffuse reflectance spectrophotometry, we measured samples from Ocean Drilling Program (ODP) 1143 drilling site (9°21.72'N, 113°17.11'E, 2777 m water depth) for hematite and goethite, whose formation processes are favored by opposing climate conditions. In order to determine the content of hematite and goethite we produced a set of calibration samples by removing the iron oxides to generate the natural matrix to which hematite and goethite in known percentages were added. From these calibration samples we developed a transfer function for determining hematite and goethite concentration from a sample's spectral reflectance. Applying this method to ODP 1143 sediments (top 34 m of a 510 m core with sampling interval of 10 cm) we were able to reconstruct a continuous precipitation history for SE Asia of the past 600 kyr using the Hm/Gt ratio as a proxy of the precipitation variability of Asian monsoon. The reliability of this Hm/Gt proxy is corroborated by its consistency with the stalagmite delta18O data from South China. Comparing long-term Hm/Gt records with the surface temperature gradient of equatorial Pacific Ocean, we found that monsoon precipitation and El Niño are correlated for the last 600 kyr. The development of El Niño-like conditions decreased SE Asia precipitation, whereas precipitation increases in response to La Niña intensification

(Table A1) Species list of the high Antarctic Weddell Sea food web

Human-induced habitat destruction, overexploitation, introduction of alien species and climate change are causing species to go extinct at unprecedented rates, from local to global scales. There are growing concerns that these kinds of disturbances alter important functions of ecosystems. Our current understanding is that key parameters of a community (e.g. its functional diversity, species composition, and presence/absence of vulnerable species) reflect an ecological network's ability to resist or rebound from change in response to pressures and disturbances, such as species loss. If the food web structure is relatively simple, we can analyse the roles of different species interactions in determining how environmental impacts translate into species loss. However, when ecosystems harbour species-rich communities, as is the case in most natural systems, then the complex network of ecological interactions makes it a far more challenging task to perceive how species' functional roles influence the consequences of species loss. One approach to deal with such complexity is to focus on the functional traits of species in order to identify their respective roles: for instance, large species seem to be more susceptible to extinction than smaller species. Here, we introduce and analyse the marine food web from the high Antarctic Weddell Sea Shelf to illustrate the role of species traits in relation to network robustness of this complex food web. Our approach was threefold: firstly, we applied a new classification system to all species, grouping them by traits other than body size; secondly, we tested the relationship between body size and food web parameters within and across these groups and finally, we calculated food web robustness. We addressed questions regarding (i) patterns of species functional/trophic roles, (ii) relationships between species functional roles and body size and (iii) the role of species body size in terms of network robustness. Our results show that when analyzing relationships between trophic structure, body size and network structure, the diversity of predatory species types needs to be considered in future studies.

Hydrate abundances at the high-flux Batumi seep area in the southeastern Black Sea

Submarine gas hydrates are a major global reservoir of the potent greenhouse gas methane. Since current assessments of worldwide hydrate-bound carbon vary by one order of magnitude, new technical efforts are required for improved and accurate hydrate quantifications. Here we present hydrate abundances determined for surface sediments at the high-flux Batumi seep area in the southeastern Black Sea at 840 m water depth using state-of-the art autoclave technology. Pressure sediment cores of up to 2.65 m in length were recovered with an autoclave piston corer backed by conventional gravity cores. Quantitative core degassing yielded volumetric gas/bulk sediment ratios of up to 20.3 proving hydrate presence. The cores represented late glacial to Holocene hemipelagic sediments with the shallowest hydrates found at 90 cmbsf. Calculated methane concentrations in the different cores surpassed methane equilibrium concentrations in the two lowermost lithological Black Sea units sampled. The results indicated hydrate fractions of 5.2% of pore volume in the sapropelic Unit 2 and mean values of 21% pore volume in the lacustrine Unit 3. We calculate that the studied area of ~ 0.5 km**2 currently contains about 11.3 kt of methane bound in shallow hydrates. Episodic detachment and rafting of such hydrates is suggested by a rugged seafloor topography along with variable thicknesses in lithologies. We propose that sealing by hydrate precipitation in coarse-grained deposits and gas accumulation beneath induces detachment of hydrate/sediment chunks. Floating hydrates will rapidly transport methane into shallower waters and potentially to the sea-atmosphere boundary. In contrast, persistent in situ dissociation of shallow hydrates appears unlikely in the near future as deep water warming by about 1.6 °C and/or decrease in hydrostatic pressure corresponding to a sea level drop of about 130 m would be required. Because hydrate detachment should be primarily controlled by internal factors in this area and in similar hydrated settings, it serves as source of methane in shallow waters and the atmosphere which is mainly decoupled from external forcing.

Paleoenvironmental changes in the western Mediterranean since the last glacial maximum: High resolution multiproxy record from the Algero-Balearic basin

The present study uses a multiproxy approach in order to further understand the evolution of climate responses in the western Mediterranean as of the Last Glacial Maximum. Sediments from ODP Site 975 in the Algero-Balearic basin have been analysed at high resolution, both geochemically andmineralogicallly. The resulting data have been used as proxies to establish a sedimentary regime, primary marine productivity, the preservation of the proxies and oxygen conditions. Fluctuations in detrital element concentrations were mainly the consequence of wet/arid oscillations. Productivity has been established using Ba excess, according to which marine productivity appears to have been greatest during cold events Heinrich 1 and Younger Dryas. The S1 time interval was not as marked by increases in productivity as was the eastern Mediterranean. In contrast, the S1 interval was first characterized by a decreasing trend and then by a fall in productivity after the 8.2 ky BP dry-cold event. Since then productivity has remained low. Here we report that there was an important redox event in this basin, probably a consequence of the major oceanographic circulation change occurring in the western Mediterranean at 7.7 ky BP. This circulation change led to reventilation as well as to diagenetic remobilization of redox-sensitive elements and organic matter oxidation. Comparisons between our paleoceanographic reconstruction for this basin and those regarding other Mediterranean basins support the hypothesis that across the Mediterranean there were different types of responses to climate forcing mechanism. The Algero-Balearic basin is likely to be a key area for further understanding of the relationships between the North Atlantic and the eastern Mediterranean basins.

Desing and Validation of a Light Inference System to Support Embedded Context Reasoning

Embedded context management in resource-constrained devices (e.g. mobile phones, autonomous sensors or smart objects) imposes special requirements in terms of lightness for data modelling and reasoning. In this paper, we explore the state-of-the-art on data representation and reasoning tools for embedded mobile reasoning and propose a light inference system (LIS) aiming at simplifying embedded inference processes offering a set of functionalities to avoid redundancy in context management operations. The system is part of a service-oriented mobile software framework, conceived to facilitate the creation of context-aware applications—it decouples sensor data acquisition and context processing from the application logic. LIS, composed of several modules, encapsulates existing lightweight tools for ontology data management and rule-based reasoning, and it is ready to run on Java-enabled handheld devices. Data management and reasoning processes are designed to handle a general ontology that enables communication among framework components. Both the applications running on top of the framework and the framework components themselves can configure the rule and query sets in order to retrieve the information they need from LIS. In order to test LIS features in a real application scenario, an ‘Activity Monitor’ has been designed and implemented: a personal health-persuasive application that provides feedback on the user’s lifestyle, combining data from physical and virtual sensors. In this case of use, LIS is used to timely evaluate the user’s activity level, to decide on the convenience of triggering notifications and to determine the best interface or channel to deliver these context-aware alerts.d

Accident Management Actions In An Upper-Head Small-Break Loss-Of-Coolant Accident With High-Pressure Safety Injection Failed

Since the Three Mile Island accident, an important focus of pressurized water reactor (PWR) transient analyses has been a small-break loss-of-coolant accident (SBLOCA). In 2002, the discovery of thinning of the vessel head wall at the Davis Besse nuclear power plant reactor indicated the possibility of an SBLOCA in the upper head of the reactor vessel as a result of circumferential cracking of a control rod drive mechanism penetration nozzle - which has cast even greater importance on the study of SBLOCAs. Several experimental tests have been performed at the Large Scale Test Facility to simulate the behavior of a PWR during an upper-head SBLOCA. The last of these tests, Organisation for Economic Co-operation and Development Nuclear Energy Agency Rig of Safety Assessment (OECD/NEA ROSA) Test 6.1, was performed in 2005. This test was simulated with the TRACE 5.0 code, and good agreement with the experimental results was obtained. Additionally, a broad analysis of an upper-head SBLOCA with high-pressure safety injection failed in a Westinghouse PWR was performed taking into account different accident management actions and conditions in order to check their suitability. This issue has been analyzed also in the framework of the OECD/NEA ROSA project and the Code Applications and Maintenance Program (CAMP). The main conclusion is that the current emergency operating procedures for Westinghouse reactor design are adequate for these kinds of sequences, and they do not need to be modified.

Isotopic uncertainty assessment due to nuclear data uncertainties in high-burnup samples.

The accurate prediction of the spent nuclear fuel content is essential for its safe and optimized transportation, storage and management. This isotopic evolution can be predicted using powerful codes and methodologies throughout irradiation as well as cooling time periods. However, in order to have a realistic confidence level in the prediction of spent fuel isotopic content, it is desirable to determine how uncertainties affect isotopic prediction calculations by quantifying their associated uncertainties.

Optimization of a label-free biosensor vertically characterized based on a periodic lattice of high aspect ratio SU-8 nano-pillars with a simplified 2D theoretical model

We have recently demonstrated a biosensor based on a lattice of SU8 pillars on a 1 μm SiO2/Si wafer by measuring vertically reflectivity as a function of wavelength. The biodetection has been proven with the combination of Bovine Serum Albumin (BSA) protein and its antibody (antiBSA). A BSA layer is attached to the pillars; the biorecognition of antiBSA involves a shift in the reflectivity curve, related with the concentration of antiBSA. A detection limit in the order of 2 ng/ml is achieved for a rhombic lattice of pillars with a lattice parameter (a) of 800 nm, a height (h) of 420 nm and a diameter(d) of 200 nm. These results correlate with calculations using 3D-finite difference time domain method. A 2D simplified model is proposed, consisting of a multilayer model where the pillars are turned into a 420 nm layer with an effective refractive index obtained by using Beam Propagation Method (BPM) algorithm. Results provided by this model are in good correlation with experimental data, reaching a reduction in time from one day to 15 minutes, giving a fast but accurate tool to optimize the design and maximizing sensitivity, and allows analyzing the influence of different variables (diameter, height and lattice parameter). Sensitivity is obtained for a variety of configurations, reaching a limit of detection under 1 ng/ml. Optimum design is not only chosen because of its sensitivity but also its feasibility, both from fabrication (limited by aspect ratio and proximity of the pillars) and fluidic point of view. (© 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)