Interprofessional Near-Peer Mentoring Teams Enhance Cancer Research Training: Sustainable Approaches for Biomedical Workforce Development of Historically Underrepresented Students.

A cancer research training program explored different approaches for staffing their in-person and virtual programs for high school students. The inclusion of undergraduate near-peer mentors had a universal benefit when implemented across in-person and virtual training programs of one- and ten-week durations. Benefits are described for four stakeholder groups: the high school trainees, program staff, scientist partners, and peer mentors themselves. Peer mentors described that their involvement enhanced their own professional development and, for some, drove a new interest in cancer research. Scientist partners described that peer mentors helped translate their work in the virtual environment for high school students. High school trainees reported their sessions with peer mentors to be one of their favorite parts of the program. Interprofessional peer mentors were highly relatable to students and modeled communication and paths in biomedical research. Staff reported that peer mentors supported student engagement during community shadowing sessions, allowing staff to focus on developing the shadowing experiences with partners. The benefit of including peer mentors was substantial from all viewpoints explored. Their intensive inclusion in cancer research training programs supports sustainability and capacity building in biomedical workforce development.

Knight Scholars Program: A Tiered Three-Year Mentored Training Program for Urban and Rural High School High School Students Increases Interest and Self-Efficacy in Interprofessional Cancer Research.

Cancer research training programs build our future biomedical workforce. Training is often centered for students residing close to research institutions, making access more challenging for rural students. A cancer research training program was developed for high school students residing in five geographical regions across Oregon. Training was tiered in duration and intensity across the three years, including a one-week Introduction program and subsequent 10-week summer research training programs (Immersion and Intensive). A total of 60 students participated in in-person and/or virtual training, with Immersion students receiving mentored shadowing experiences in clinical care, public health, and outreach in their home communities. Laboratory rotations at a research-intensive institution enabled students to sample research environments before selecting an area of interest for Intensive training the following summer. Aligning with Self-Determination Theory, the Knight Scholars Program aims to build competence, relatedness, and autonomy of its trainees in biomedical sciences. The program exposed students to a wide range of interprofessional careers and collaborative teams, enabling scholars to envision themselves in various paths. Results show strong gains in interest and research self-efficacy for both Introduction and Immersion scholars, with findings highlighting the importance of representation within mentoring and training efforts.

Investigating recurrent neural networks for OCT A-scan based tissue analysis.

OBJECTIVES: Optical Coherence Tomography (OCT) has been proposed as a high resolution image modality to guide transbronchial biopsies. In this study we address the question, whether individual A-scans obtained in needle direction can contribute to the identification of pulmonary nodules. METHODS: OCT A-scans from freshly resected human lung tissue specimen were recorded through a customized needle with an embedded optical fiber. Bidirectional Long Short Term Memory networks (BLSTMs) were trained on randomly distributed training and test sets of the acquired A-scans. Patient specific training and different pre-processing steps were evaluated. RESULTS: Classification rates from 67.5% up to 76% were archived for different training scenarios. Sensitivity and specificity were highest for a patient specific training with 0.87 and 0.85. Low pass filtering decreased the accuracy from 73.2% on a reference distribution to 62.2% for higher cutoff frequencies and to 56% for lower cutoff frequencies. CONCLUSION: The results indicate that a grey value based classification is feasible and may provide additional information for diagnosis and navigation. Furthermore, the experiments show patient specific signal properties and indicate that the lower and upper parts of the frequency spectrum contribute to the classification.

Genomics of ADME gene expression: mapping expression quantitative trait loci relevant for absorption, distribution, metabolism and excretion of drugs in human liver.

Expression quantitative trait loci (eQTL) analysis is a powerful approach toward identifying genetic loci associated with quantitative changes in gene expression. We applied genome-wide association analysis to a data set of >300 000 single-nucleotide polymorphisms and >48 000 mRNA expression phenotypes obtained by Illumina microarray profiling of 149 human surgical liver samples obtained from Caucasian donors with detailed medical documentation. Of 1226 significant associations, only 200 were validated when comparing with a previously published similar study. Potential explanations for low replication rate include differences in microarray platforms, statistical modeling, covariates considered and origin and collection procedures of tissues. Focused analysis revealed a subset of 95 associations related to absorption, distribution, metabolism and excretion of drugs. Of these, 21 were true replications and 74 were newly discovered associations in enzymes, transporters, transcriptional regulators and other genes. This study extends our knowledge about the genetics of inter-individual variability of gene expression with particular emphasis on pharmacogenomics.

Activation of the mitogen-activated protein kinase (MAPK) signalling pathway in the liver of mice is related to plasma glucose levels after acute exercise.

AIMS/HYPOTHESIS: We aimed to identify, in the liver of mice, signal transduction pathways that show a pronounced regulation by acute exercise. We also aimed to elucidate the role of metabolic stress in this response. METHODS: C57Bl6 mice performed a 60 min run on a treadmill under non-exhaustive conditions. Hepatic RNA and protein lysates were prepared immediately after running and used for whole-genome-expression analysis, quantitative real-time PCR and immunoblotting. A subset of mice recovered for 3 h after the treadmill run. A further group of mice performed the treadmill run after having received a vitamin C- and vitamin E-enriched diet over 4 weeks. RESULTS: The highest number of genes differentially regulated by exercise in the liver was found in the mitogen-activated protein kinase (MAPK) signalling pathway, with a pronounced and transient upregulation of the transcription factors encoded by c-Fos (also known as Fos), c-Jun (also known as Jun), FosB (also known as Fosb) and JunB (also known as Junb) and phosphorylation of hepatic MAPK. Acute exercise also activated the p53 signalling pathway. A major role for oxidative stress is unlikely since the antioxidant-enriched diet did not prevent the activation of the MAPK pathway. In contrast, lower plasma glucose levels after running were related to enhanced levels of MAPK signalling proteins, similar to the upregulation of Igfbp1 and Pgc-1alpha (also known as Ppargc1a). In the working muscle the activation of the MAPK pathway was weak and not related to plasma glucose concentrations. CONCLUSIONS/INTERPRETATION: Metabolic stress evidenced as low plasma glucose levels appears to be an important determinant for the activation of the MAPK signalling pathway and the transcriptional response of the liver to acute exercise.

JCell--a Java-based framework for inferring regulatory networks from time series data.

MOTIVATION: JCell is a Java-based application for reconstructing gene regulatory networks from experimental data. The framework provides several algorithms to identify genetic and metabolic dependencies based on experimental data conjoint with mathematical models to describe and simulate regulatory systems. Owing to the modular structure, researchers can easily implement new methods. JCell is a pure Java application with additional scripting capabilities and thus widely usable, e.g. on parallel or cluster computers. AVAILABILITY: The software is freely available for download at http://www-ra.informatik.uni-tuebingen.de/software/JCell.

ParSeq: searching motifs with structural and biochemical properties.

SUMMARY: Searches for variable motifs such as protein-binding sites or promoter regions are more complex than the search for casual motifs. For example, in amino acid sequences comparing motifs alone mostly proves to be insufficient to detect regions that represent proteins with a special function, because the function depends on biochemical properties of individual amino acids (such as polarity or hydrophobicity). Pure string matching programs are not able to find these motifs; hence, we developed ParSeq, a program that combines the search for motifs with certain structural properties, the verification of biochemical properties, an approximate search mechanism and a stepwise creation of the motif description by allowing to search on previously obtained results. AVAILABILITY: http://www-pr.informatik.uni-tuebingen.de/parseq

Gene expression patterns of epithelial cells modulated by pathogenicity factors of Yersinia enterocolitica.

Epithelial cells express genes whose products signal the presence of pathogenic microorganisms to the immune system. Pathogenicity factors of enteric bacteria modulate host cell gene expression. Using microarray technology we have profiled epithelial cell gene expression upon interaction with Yersinia enterocolitica. Yersinia enterocolitica wild-type and isogenic mutant strains were used to identify host genes modulated by invasin protein (Inv), which is involved in enteroinvasion, and Yersinia outer protein P (YopP) which inhibits innate immune responses. Among 22 283 probesets (14,239 unique genes), we found 193 probesets (165 genes) to be regulated by Yersinia infection. The majority of these genes were induced by Inv, whose recognition leads to expression of NF-kappa B-regulated factors such as cytokines and adhesion molecules. Yersinia virulence plasmid (pYV)-encoded factors counter regulated Inv-induced gene expression. Thus, YopP repressed Inv-induced NF-kappa B regulated genes at 2 h post infection whereas other pYV-encoded factors repressed host cell genes at 4 and 8 h post infection. Chromosomally encoded factors of Yersinia, other than Inv, induced expression of genes known to be induced by TGF-beta receptor signalling. These genes were also repressed by pYV-encoded factors. Only a few host genes were exclusively induced by pYV-encoded factors. We hypothesize that some of these genes may contribute to pYV-mediated silencing of host cells. In conclusion, the data demonstrates that epithelial cells express a limited number of genes upon interaction with enteric Yersinia. Both Inv and YopP appear to modulate gene expression in order to subvert epithelial cell functions involved in innate immunity.

[Bilateral kidney tumor. Therapy management and histopathological results with long-term follow-up of 66 patients]. / Der bilaterale Nierentumor. Therapiemanagement und histopathologische Ergebnisse mit Langzeitverlauf bei 66 Patienten.

Bilateral renal cell carcinoma is detected at an incidence rate of 1.6-6% of all renal tumors. The management, histopathological results and the long-term follow-up of 66 patients with bilateral renal cell carcinoma (29 synchronous, 37 asynchronous tumors) are presented in this issue. The incidence rate of bilateral renal cell carcinoma (RCC) at our hospital was 3.5%. Nephron-sparing surgery should be used first for the smaller and favourably located tumor when radical nephrectomy of the contralateral tumor is necessary. Thus, the patients can be spared dialysis. The histopathological results showed a significantly higher incidence rate of chromophil RCCs in cases of synchronous bilateral renal tumors (36%). The 5-year survival rate was 82%. Patients with asynchronous renal cell carcinomas were significantly younger than those with synchronous RCCs (median age: 60.2 years). The histopathological results were similar to unilateral renal cell carcinomas. Clear cell carcinoma was detected in 70% of cases. The 5-year survival rate was 61% and lower than that of synchronous tumors (82%). There was no significant difference because of the small number of cases. Current standardised techniques of nephron-sparing surgery achieve good survival rates, therefore making bilateral nephrectomy only necessary in very poor cases. In cases of chromophil renal cell carcinomas, the contralateral kidney should always be carefully examined, because these tumors were significantly more often detected to be bilateral. The risk of also developing a tumor in the contralateral kidney increases with decreasing age at first manifestation (< 55 years, 6%). Especially in those younger than 55 years, partial nephrectomy seems to be recommended for unilateral renal tumors in patients with a normal contralateral kidney (tumor size < 4 cm in diameter).

Bioelectronic noses: a status report. Part II.

The present state of the art to record or to mimic electronically the human senses of olfaction and taste is characterized. In this part II, strategies are outlined to utilize chemical and biological structures with their different complexities which serve as sensor elements in (bio-) electronic noses. Finally a survey is given on the computer-science aspects of odor recognition based on these elements.

Locating biologically active compounds in medium-sized heterogeneous datasets by topological autocorrelation vectors: dopamine and benzodiazepine agonists.

Electronic properties located on the atoms of a molecule such as partial atomic charges as well as electronegativity and polarizability values are encoded by an autocorrelation vector accounting for the constitution of a molecule. This encoding procedure is able to distinguish between compounds being dopamine agonists and those being benzodiazepine receptor agonists even after projection into a two-dimensional self-organizing network. The two types of compounds can still be distinguished if they are buried in a dataset of 8323 compounds of a chemical supplier catalog comprising a wide structural variety. The maps obtained by this sequence of events, calculation of empirical physicochemical effects, encoding in a topological autocorrelation vector, and projection by a self-organizing neural network, can thus be used for searching for structural similarity, and, in particular, for finding new lead structures with biological activity.

A parallel neural network simulator on the connection machine CM-5.

We here present a parallel implementation of artificial neural networks on the connection machine CM-5 and compare it with other parallel implementations on SIMD and MIMD architectures. This parallel implementation was developed with the goal of efficiently training large neural networks with huge training pattern sets for applications in molecular biology, in particular the prediction of coding regions in DNA sequences. The implementation uses training pattern parallelism and makes use of the parallel I/O facilities of the CM-5 and its efficient reduction operations available within the control network to achieve a high scalability. The parallel simulator obtains a maximum speed of 149.25 MCUPS for training feedforward networks with backpropagation on a 512 processor CM-5 system without using the CM-5 vector facility. The implementation poses no restriction on the type of network topology and works with different batch training algorithms like BP. Quickprop and Rprop.

Study on the inhibition of adenosine deaminase.

4(R)-(1-Hydroxyethyl)-5-methyl-1-beta-D-ribofuranosylimidazole (10), which contains only the asymmetric alcohol center of the diazepinol ring of the adenosine deaminase inhibitor coformycin (12), is a much less potent inhibitor of the enzyme but still binds to the enzyme about as tightly as the normal substrate.

Model for calcium binding to gamma-carboxyglutamic acid residues of proteins: crystal structure of calcium alpha-ethylmalonate.

The crystal structure of a Ca2+ salt of alpha-ethylmalonic acid was determined from three-dimensional X-ray diffraction data. The dicarboxylate anion represents the functional side chain of gamma-carboxyglutamic acid (Gla) residues, which are implicated as essential calcium-binding ligands in a variety of proteins. The alpha-ethylmalonate ion chelates the Ca2+ ion in a bidentate manner that involves an O atom from each of the two malonate carboxylate groups. This type of binding arises from the constrained arrangement of carboxylate ligands in the malonate group and may be of significance to the calcium-binding properties of Gla-containing sites in proteins. The Ca2+-malonate chelation forms a six-membered ring, which is stabilized by interactions that are consistent with the preferred stereochemistries of both calcium-carboxylate and metal-malonate complexes. No other interactions are observed between Ca2+ ions and alpha-ethylmalonate ions that depend upon the malonate juxtaposition of two carboxylate groups. The potential for this type of binding distinguishes Gla residues from the monocarboxylate residues, aspartate and glutamate, and confers a novel calcium-chelation ability upon Gla-containing sites in proteins.

[Ocular scanning modalities in dyslexic children (author's transl)]. / Modalités du balayage oculaire chez l'enfant dyslexique.

Voluntary and reflex ocular scanning has been investigated in 55 dyslexic children, aged from 8 to 14 years 3 months, by means of potentiometric electrooculography with multiple monocular electrodes. Results are expressed in terms of amplitude, frequency, shape of movements and ocular congruence. A comparison between the oculomotor behaviour of dyslexic and normal children with no reading problem shows the same types of ocular movements as observed in normal schoolchildren, but they differ in their distribution according to age. Moreover, the evolution of oblique movements, described in normal children and correlated with the degree of schooling, is not the same in dyslexic children, where it instead seems to follow particular patterns. Finally, in stereotyped ocular scanning simulating reading movements, the dyslexics are characterized by the absence of two important stages leading to ocular congruence: scanning with random alternate monocular predominance and scanning with selected alternate monocular predominance.

Combined surgical and orthodontic management of anterior open bite using corticotomy.

Two cases of dentoalveolar abnormality have been presented that were treated successfully in a relatively short time by using the combined efforts of the oral surgeon and orthodontist. Although corticotomy has limited applications, it has a place in the armamentarium of the orthognathic surgeon.

Cleidocranial dysostosis: a multidisciplinary approach to treatment.

To ensure eruption of the dentition in patients with cleidocranial dysostosis, close collatoration between the oral surgeon and the orthodontist is essential to determine the sequence of extraction, the teeth to be ligated, the preferred technique of ligation, and the approach for surgical exposure.