236 results on '"Hartmann, David"'
Search Results
202. Statement of Editorial Policy.
- Author
-
Hartmann, David J. and Van Valey, Thomas L.
- Subjects
APPLIED sociology ,SOCIOLOGY - Abstract
Presents an introduction to the January 1, 1998 issue of "Journal of Applied Sociology."
- Published
- 1998
203. Modeling customer-focused engineering program alignment by means of group consensus and analytical hierarchy process analysis
- Author
-
Hartmann, David Herbert
- Published
- 2004
204. A state-wide assessment: marital stability and client outcomes
- Author
-
Hartmann, David J., Sullivan, William P., and Wolk, James L.
- Published
- 1991
- Full Text
- View/download PDF
205. Successful second allogeneic stem cell transplantation in a patient with T-lymphoblastic leukemia (T-ALL) relapsed as myeloid sarcoma.
- Author
-
Matern, Svenja, Schmidt, Eva, Hartmann, David, Schliemann, Christoph, Groth, Christoph, Lenz, Georg, Hartmann, Wolfgang, Klapper, Wolfram, Berdel, Wolfgang, and Stelljes, Matthias
- Subjects
- *
LYMPHOBLASTIC leukemia , *COMBINATION drug therapy , *LYMPHADENITIS , *CYTARABINE ,MEDIASTINAL tumors - Abstract
The article presents a case study of 32-year-old male with T-cell acute lymphoblastic leukemia (T-ALL) and was treated with polychemotherapy. Patient presented seven years later with mediastinal tumor and lymphadenopathy. No remission was achieved after intensive salvage therapies with cytarabine/daunorubicin, cytarabine/mitoxantrone, and nelarabine/ifosfamide.
- Published
- 2017
- Full Text
- View/download PDF
206. The Managerial Nature of Case Management.
- Author
-
Wolk, James L., Sullivan, William P., and Hartmann, David J.
- Subjects
- *
SOCIAL services , *EXECUTIVES , *MANAGEMENT , *ORGANIZATIONAL sociology , *MANAGEMENT science , *COMMUNICATION in social work - Abstract
The article discusses how case managers in social work engage in the practice of management. The article presents factors which contribute to the increased attention to case management. The case manager is compared with managers in general, the properties of case managers are delineated, the complexities of managerial work are outlined, and the importance of improved case management is discussed. Circumstances unique to case management, such as large caseloads, varied expectations on the substance of case management, and organizational barriers, are discussed. Nevertheless, the fundamental objective of this article is to provide case managers with a different way of looking at the nature of their work. Much of the development of case management thinking has focused on its networking aspect. Specifically, definitions of case management speak to the linkages between clients to be served and the service delivery system. The literature in organization theory has reached consensus on the concept of management and the task of managers. The role of a case manager includes interpersonal roles. Every manager must perform some duties that are ceremonial in nature. Chief executive officers attend grand openings of distributors or introduce a speaker at a banquet.
- Published
- 1994
207. HIGH-TECH LEADERSHIP.
- Author
-
Hartmann, David H.
- Subjects
- *
LEADERSHIP , *TECHNOLOGICAL innovations , *INDUSTRIAL management , *PERSONNEL management , *SOCIAL networks , *BUSINESS enterprises , *INTERNET - Abstract
The article focuses on a character of an effective leadership in a high technology contemporary business. It mentions that knowing what currently motivates the employees to act toward attainment of goals is one factor to be an effective business leader. It also notes to consider those firms that proactively creating presence and acting in social Web sites and virtual communities.
- Published
- 2008
208. Predictions in engineering management.
- Author
-
Hartmann, David H.
- Subjects
- *
TECHNOLOGICAL innovations , *SOCIAL responsibility of business , *ORGANIZATIONAL learning , *INDUSTRIAL engineers , *MEMBERSHIP in associations, institutions, etc. , *ENGINEERS' associations , *COLLEGE teachers - Abstract
The article discusses the impact of future technological trends to industrial engineering and how managers must adapt to such trends, according to members of the U.S. Society for Engineering and Management Systems (SEMS). Professor emeritus at Ohio State University, George L. Smith, states that future innovation trend requires industrial engineers to practice in a global environment by attending to the entrepreneurs in the developing world as well as promoting corporate social responsibilities. Meanwhile, David H. Hartman, assistant professor at the University of Central Oklahoma, writes that the emergence of electronic network interfaces (Web 2.0) may help managers explore more rapid and economical ways to adapt to different sourcing opportunities.
- Published
- 2008
209. Synthesis and biological evaluation of novel myrtucommulones and structural analogues that target mPGES-1 and 5-lipoxygenase.
- Author
-
Wiechmann, Katja, Müller, Hans, Huch, Volker, Hartmann, David, Werz, Oliver, and Jauch, Johann
- Subjects
- *
CANCER cells , *LIPOXYGENASES , *OXYGENASES , *ARACHIDONATE 12-lipoxygenase , *ARACHIDONATE 15-lipoxygenase - Abstract
The natural acylphloroglucinol myrtucommulone A ( 1 ) inhibits microsomal prostaglandin E 2 synthase (mPGES)-1 and 5-lipoxygenase (5-LO), and induces apoptosis of cancer cells. Starting from 1 as lead, 28 analogues were synthesized following a straightforward modular strategy with high yielding convergent steps. Major structural variations concerned (I) replacement of the syncarpic acid moieties by dimedone or indandione, (II) cyclization of the syncarpic acid with the acylphloroglucinol core, and (III) substitution of the methine bridges and the acyl residue with isopropyl, isobutyl, n -pentyl or phenyl groups, each. The potency for mPGES-1 inhibition was improved by 12.5-fold for 43 (2-(1-(3-hexanoyl-2,4,6-trihydroxy-5-(1-(3-hydroxy-1-oxo-1H-inden-2-yl)-2-methylpropyl)phenyl)-2-methylpropyl)-3-hydroxy-1H-inden-1-one) with IC 50 = 0.08 μM, and 5-LO inhibition was improved 33-fold by 47 (2-((3-hexanoyl-2,4,6-trihydroxy-5-((3-hydroxy-1-oxo-1H-inden-2-yl) (phenyl)methyl)phenyl) (phenyl)methyl)-3-hydroxy-1H-inden-1-one) with IC 50 = 0.46 μM. SAR studies revealed divergent structural determinants for induction of cell death and mPGES-1/5-LO inhibition, revealing 43 and 47 as non-cytotoxic mPGES-1 and 5-LO inhibitors that warrant further preclinical assessment as anti-inflammatory drugs. [ABSTRACT FROM AUTHOR]
- Published
- 2015
- Full Text
- View/download PDF
210. Space charge region effects in bidirectional illuminated P3HT:PCBM bulk heterojunction photodetectors.
- Author
-
Büchele, Patric, Morana, Mauro, Bagnis, Diego, Tedde, Sandro Francesco, Hartmann, David, Fischer, René, and Schmidt, Oliver
- Subjects
- *
SPACE charge , *LIGHTING , *POLYTHIOPHENES , *BUTYRIC acid , *HETEROJUNCTIONS , *PHOTODETECTORS , *ORGANIC semiconductors - Abstract
Organic semiconductors are widely investigated for their application in photovoltaics and photodetectors. We show that the efficiency of these devices is strongly influenced by the position of the space charge region, due to unintentional doping, and wavelength-dependent absorption properties in bulk heterojunctions. Spray-coated P3HT:PCBM bulk heterojunction photodiodes with thicknesses up to 4.2 μm and semitransparent top contact enable the characterization of exciton generation and separation in both irradiation directions. A large difference in external quantum efficiency (EQE) is observed for top and bottom illuminated configurations and is explained by a bias dependent arrangement of the space charge region at the two contact electrodes. Numerical drift–diffusion simulations allow to get insight into first order mechanisms behind the spectral features of EQE data in highly-doped organic photodiodes. [ABSTRACT FROM AUTHOR]
- Published
- 2015
- Full Text
- View/download PDF
211. A new Bacillus megaterium whole-cell catalyst for the hydroxylation of the pentacyclic triterpene 11-keto-β-boswellic acid (KBA) based on a recombinant cytochrome P450 system.
- Author
-
Bleif, Sabrina, Hannemann, Frank, Zapp, Josef, Hartmann, David, Jauch, Johann, and Bernhardt, Rita
- Subjects
- *
BACILLUS megaterium , *HYDROXYLATION , *CHEMICAL reactions , *CYTOCHROME P-450 , *CATALYSTS , *CATALYSIS - Abstract
The use of cytochromes P450 for the regio- and stereoselective hydroxylation of non-activated carbon atoms in biotechnological applications reflects an efficient and cost-effective alternative in comparison to classical organic chemistry. The prokaryotic cytochrome P450 CYP106A2 from Bacillus megaterium ATCC 13368 hydroxylates a variety of 3-oxo-Δ steroids and recently it was identified to carry out a one-step regioselective allylic hydroxylation of the diterpene abietic acid. The anti-inflammatory pentacyclic triterpene 11-Keto-β-boswellic acid (KBA) was found to be a further substrate of CYP106A2, being the first report of a pentacyclic triterpene conversion by a prokaryotic P450. The reaction products were analyzed by HPLC and the corresponding kinetic parameters were investigated. Structure determination of the main product by NMR revealed a 15α-hydroxylation of this substrate. In order to overcome the inability of a recombinant P450 whole-cell system in E. coli for the uptake of acids with terpene structure, we developed for the first time an expression system for cytochromes P450 in B. megaterium (strains MS941 and ATCC 13368). Interestingly, CYP106A2 was only successfully expressed in the plasmid-less B. megaterium strain MS941 but not in ATCC13368. This recombinant system, with the co-expressed heterologous redox chain of the P450, bovine adrenodoxin reductase (AdR), and bovine adrenodoxin (Adx), was applied for the whole-cell conversion of KBA. The formation of 15α-hydroxy-KBA was increased 15-fold in comparison with the naturally CYP106A2-expressing B. megaterium strain ATCC 13368. [ABSTRACT FROM AUTHOR]
- Published
- 2012
- Full Text
- View/download PDF
212. Pyridobenzodiazepines: A novel class of orally active, vasopressin V2 receptor selective agonists
- Author
-
Failli, Amedeo A., Shumsky, Jay S., Steffan, Robert J., Caggiano, Thomas J., Williams, David K., Trybulski, Eugene J., Ning, Xiaoping, Lock, Yeungwai, Tanikella, Tarak, Hartmann, David, Chan, Peter S., and Park, C.H.
- Subjects
- *
VASOPRESSIN , *ENURESIS , *CHEMICAL agonists , *MOLECULAR weights - Abstract
Abstract: Our efforts in seeking low molecular weight agonists of the antidiuretic peptide hormone arginine vasopressin (AVP) have led to the identification of the clinical candidate WAY-151932 (VNA-932). Further exploration of the structural requirements for agonist activity has provided another class of potent, orally active, non-peptidic vasopressin V2 receptor selective agonists exemplified by the 5,11-dihydro-pyrido[2,3-b][1,5]benzodiazepine as a candidate for further development. [Copyright &y& Elsevier]
- Published
- 2006
- Full Text
- View/download PDF
213. Cathepsins L of Diplostomum pseudospathaceum cercariae
- Author
-
Perháčová, Terézia, Mikeš, Libor, and Hartmann, David
- Subjects
trematode ,cathepsin L ,motolice ,Diplostomum ,penetration ,proteáza ,cercaria ,cerkárie ,peptidáza ,penetrace ,peptidase ,protease - Abstract
This study is focused on cercarial cysteine peptidases of the trematode Diplostomum pseudospathaceum. It follows previous research which confirmed the presence of a 24kDa cysteine peptidase in cercariae biochemically and by mass spectrometry. It was postulated, that the function of this peptidase is histolytic, when cercariae penetrate the tissues. During an attempt to purify this peptidase and characterize its peptidolytic activity, it was found out that the cercarial homogenate containsmore different peptidases varying in their pI. Tests of peptidolytic activity and inhibition have shown that these peptidases are cathepsin L-like. They are active over a broad spectrum of pH with optima of activities in weakly acidicor neutral pH. Using degenerate primers based on conserved motifs of cysteine pepridases, partial sequences of three genes for cathepsin L of D. pseudospataceum (DpCL1, 2 a 3) were obtained. Then the complete sequences of DpCL2 and 3 genes and partial sequence (without 5'end) of DpCL1 were obtained by RACE PCR. To confirm function of these peptidases we tried to immunolocalize them. We assumed that they are localized in penetration glands. Preliminary results suggested that some of the cathepsins could be also localized in the gut of cercariae. For more detailed biochemical...
- Published
- 2015
214. One health approach to study human health risks associated with Dermanyssus gallinae mites.
- Author
-
Banović P, Foucault-Simonin A, Papić L, Savić S, Potkonjak A, Jurišić A, Radenković M, Mijatović D, Simin V, Bogdan I, Zając Z, Kulisz J, Woźniak A, Hartmann D, Perner J, Wu-Chuang A, Mateos-Hernandez L, Moutailler S, and Cabezas-Cruz A
- Abstract
Despite the significant health risks associated with Dermanyssus gallinae infestations in humans, they are often overlooked. This study investigated a household case of D. gallinae infestation and explored the resulting clinical manifestations and risk of infection in family members. Microfluidic PCR was employed for high-throughput screening of pathogens in collected mites and blood samples from both chickens and family members. Morphological and molecular examinations confirmed the identity of the mites as D. gallinae sensu stricto (s.s.), with evidence indicating recent blood feeding. Results indicated that the mites exclusively harbored various pathogens, including Bartonella spp., Ehrlichia spp., Apicomplexa, and Theileria spp. Blood samples from family members and poultry tested negative for these pathogens, suggesting a potential reservoir role for D. gallinae . The study further identified haplotypes of D. gallinae , classifying them into D. gallinae s.s., cosmopolitan haplogroup A. Serological analysis revealed elevated IgE seroreactivity against mite proteins in the family member with bite lesions. Antibodies against Bartonella spp. were detected in this individual, indicating exposure to the pathogen. In summary, this study sheds light on the clinical manifestations, pathogen detection, and genetic characterization of D. gallinae infestations, underscoring the necessity of adopting comprehensive approaches to manage such infestations effectively., Competing Interests: The authors declare that they do not have any conflicts of interests associated with the research presented here., (© 2024 The Author(s).)
- Published
- 2024
- Full Text
- View/download PDF
215. The fasciola cinereum of the hippocampal tail as an interventional target in epilepsy.
- Author
-
Jamiolkowski RM, Nguyen QA, Farrell JS, McGinn RJ, Hartmann DA, Nirschl JJ, Sanchez MI, Buch VP, and Soltesz I
- Subjects
- Animals, Humans, Mice, Epilepsy pathology, Male, Optogenetics, Female, Seizures, Epilepsy, Temporal Lobe physiopathology, Epilepsy, Temporal Lobe pathology, Adult, Hippocampus pathology, Neurons pathology
- Abstract
Targeted tissue ablation involving the anterior hippocampus is the standard of care for patients with drug-resistant mesial temporal lobe epilepsy. However, a substantial proportion continues to suffer from seizures even after surgery. We identified the fasciola cinereum (FC) neurons of the posterior hippocampal tail as an important seizure node in both mice and humans with epilepsy. Genetically defined FC neurons were highly active during spontaneous seizures in epileptic mice, and closed-loop optogenetic inhibition of these neurons potently reduced seizure duration. Furthermore, we specifically targeted and found the prominent involvement of FC during seizures in a cohort of six patients with epilepsy. In particular, targeted lesioning of the FC in a patient reduced the seizure burden present after ablation of anterior mesial temporal structures. Thus, the FC may be a promising interventional target in epilepsy., (© 2024. The Author(s).)
- Published
- 2024
- Full Text
- View/download PDF
216. Variation of bacterial community assembly over developmental stages and midgut of Dermanyssus gallinae.
- Author
-
Wu-Chuang A, Hartmann D, Maitre A, Mateos-Hernández L, Frantová H, Urbanová V, Obregon D, Cabezas-Cruz A, and Perner J
- Subjects
- Animals, Female, Chickens parasitology, Life Cycle Stages, Bacteria genetics, Poultry Diseases parasitology, Poultry Diseases prevention & control, Mites microbiology, Mite Infestations parasitology, Mite Infestations prevention & control
- Abstract
Bacterial microbiota play an important role in the fitness of arthropods, but the bacterial microflora in the parasitic mite Dermanyssus gallinae is only partially explored; there are gaps in our understanding of the microbiota localization and in our knowledge of microbial community assembly. In this work, we have visualized, quantified the abundance, and determined the diversity of bacterial occupancy, not only across developmental stages of D. gallinae, but also in the midgut of micro-dissected female D. gallinae mites. We explored community assembly and the presence of keystone taxa, as well as predicted metabolic functions in the microbiome of the mite. The diversity of the microbiota and the complexity of co-occurrence networks decreased with the progression of the life cycle. However, several bacterial taxa were present in all samples examined, indicating a core symbiotic consortium of bacteria. The relatively higher bacterial abundance in adult females, specifically in their midguts, implicates a function linked to the biology of D. gallinae mites. If such an association proves to be important, the bacterial microflora qualifies itself as an acaricidal or vaccine target against this troublesome pest., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
- Published
- 2023
- Full Text
- View/download PDF
217. Blood-feeding adaptations and virome assessment of the poultry red mite Dermanyssus gallinae guided by RNA-seq.
- Author
-
Ribeiro JM, Hartmann D, Bartošová-Sojková P, Debat H, Moos M, Šimek P, Fara J, Palus M, Kučera M, Hajdušek O, Sojka D, Kopáček P, and Perner J
- Subjects
- Animals, Poultry, RNA-Seq, Virome, Chickens, Mite Infestations veterinary, Mite Infestations parasitology, Poultry Diseases, Mites genetics
- Abstract
Dermanyssus gallinae is a blood-feeding mite that parasitises wild birds and farmed poultry. Its remarkably swift processing of blood, together with the capacity to blood-feed during most developmental stages, makes this mite a highly debilitating pest. To identify specific adaptations to digestion of a haemoglobin-rich diet, we constructed and compared transcriptomes from starved and blood-fed stages of the parasite and identified midgut-enriched transcripts. We noted that midgut transcripts encoding cysteine proteases were upregulated with a blood meal. Mapping the full proteolytic apparatus, we noted a reduction in the suite of cysteine proteases, missing homologues for Cathepsin B and C. We have further identified and phylogenetically analysed three distinct transcripts encoding vitellogenins that facilitate the reproductive capacity of the mites. We also fully mapped transcripts for haem biosynthesis and the ferritin-based system of iron storage and inter-tissue trafficking. Additionally, we identified transcripts encoding proteins implicated in immune signalling (Toll and IMD pathways) and activity (defensins and thioester-containing proteins), RNAi, and ion channelling (with targets for commercial acaricides such as Fluralaner, Fipronil, and Ivermectin). Viral sequences were filtered from the Illumina reads and we described, in part, the RNA-virome of D. gallinae with identification of a novel virus, Red mite quaranjavirus 1., (© 2023. The Author(s).)
- Published
- 2023
- Full Text
- View/download PDF
218. Seizure forecasting using machine learning models trained by seizure diaries.
- Author
-
Gleichgerrcht E, Dumitru M, Hartmann DA, Munsell BC, Kuzniecky R, Bonilha L, and Sameni R
- Subjects
- Humans, Bayes Theorem, Seizures diagnosis, Machine Learning, Electroencephalography, Quality of Life, Epilepsy
- Abstract
Objectives. People with refractory epilepsy are overwhelmed by the uncertainty of their next seizures. Accurate prediction of future seizures could greatly improve the quality of life for these patients. New evidence suggests that seizure occurrences can have cyclical patterns for some patients. Even though these cyclicalities are not intuitive, they can be identified by machine learning (ML), to identify patients with predictable vs unpredictable seizure patterns. Approach. Self-reported seizure logs of 153 patients from the Human Epilepsy Project with more than three reported seizures (totaling 8337 seizures) were used to obtain inter-seizure interval time-series for training and evaluation of the forecasting models. Two classes of prediction methods were studied: (1) statistical approaches using Bayesian fusion of population-wise and individual-wise seizure patterns; and (2) ML-based algorithms including least squares, least absolute shrinkage and selection operator, support vector machine (SVM) regression, and long short-term memory regression. Leave-one-person-out cross-validation was used for training and evaluation, by training on seizure diaries of all except one subject and testing on the left-out subject. Main results. The leading forecasting models were the SVM regression and a statistical model that combined the median of population-wise seizure time-intervals with a test subject's prior seizure intervals. SVM was able to forecast 50%, 70%, 81%, 84%, and 87% of seizures of unseen subjects within 0, 1, 2, 3 to 4 d of mean absolute forecasting error, respectively. The subject-wise performances show that patients with more frequent seizures were generally better predicted. Significance. ML models can leverage non-random patterns within self-reported seizure diaries to forecast future seizures. While diary-based seizure forecasting alone is only one of many aspects of clinical care of patients with epilepsy, studying the level of predictability across seizures and patients paves the path towards a better understanding of predictable vs unpredictable seizures on individualized and population-wise bases., (© 2022 Institute of Physics and Engineering in Medicine.)
- Published
- 2022
- Full Text
- View/download PDF
219. 3D optogenetic control of arteriole diameter in vivo.
- Author
-
O'Herron PJ, Hartmann DA, Xie K, Kara P, and Shih AY
- Subjects
- Animals, Arterioles, Hemodynamics, Mice, Opsins, Neocortex, Optogenetics methods
- Abstract
Modulation of brain arteriole diameter is critical for maintaining cerebral blood pressure and controlling regional hyperemia during neural activity. However, studies of hemodynamic function in health and disease have lacked a method to control arteriole diameter independently with high spatiotemporal resolution. Here, we describe an all-optical approach to manipulate and monitor brain arteriole contractility in mice in three dimensions using combined in vivo two-photon optogenetics and imaging. The expression of the red-shifted excitatory opsin, ReaChR, in vascular smooth muscle cells enabled rapid and repeated vasoconstriction controlled by brief light pulses. Two-photon activation of ReaChR using a spatial light modulator produced highly localized constrictions when targeted to individual arterioles within the neocortex. We demonstrate the utility of this method for examining arteriole contractile dynamics and creating transient focal blood flow reductions. Additionally, we show that optogenetic constriction can be used to reshape vasodilatory responses to sensory stimulation, providing a valuable tool to dissociate blood flow changes from neural activity., Competing Interests: PO, DH, KX, PK, AS No competing interests declared, (© 2022, O', O'Herron et al.)
- Published
- 2022
- Full Text
- View/download PDF
220. Fast whole-slide cartography in colon cancer histology using superpixels and CNN classification.
- Author
-
Wilm F, Benz M, Bruns V, Baghdadlian S, Dexl J, Hartmann D, Kuritcyn P, Weidenfeller M, Wittenberg T, Merkel S, Hartmann A, Eckstein M, and Geppert CI
- Abstract
Purpose: Automatic outlining of different tissue types in digitized histological specimen provides a basis for follow-up analyses and can potentially guide subsequent medical decisions. The immense size of whole-slide-images (WSIs), however, poses a challenge in terms of computation time. In this regard, the analysis of nonoverlapping patches outperforms pixelwise segmentation approaches but still leaves room for optimization. Furthermore, the division into patches, regardless of the biological structures they contain, is a drawback due to the loss of local dependencies. Approach: We propose to subdivide the WSI into coherent regions prior to classification by grouping visually similar adjacent pixels into superpixels. Afterward, only a random subset of patches per superpixel is classified and patch labels are combined into a superpixel label. We propose a metric for identifying superpixels with an uncertain classification and evaluate two medical applications, namely tumor area and invasive margin estimation and tumor composition analysis. Results: The algorithm has been developed on 159 hand-annotated WSIs of colon resections and its performance is compared with an analysis without prior segmentation. The algorithm shows an average speed-up of 41% and an increase in accuracy from 93.8% to 95.7%. By assigning a rejection label to uncertain superpixels, we further increase the accuracy by 0.4%. While tumor area estimation shows high concordance to the annotated area, the analysis of tumor composition highlights limitations of our approach. Conclusion: By combining superpixel segmentation and patch classification, we designed a fast and accurate framework for whole-slide cartography that is AI-model agnostic and provides the basis for various medical endpoints., (© 2022 The Authors.)
- Published
- 2022
- Full Text
- View/download PDF
221. Pericyte Control of Blood Flow Across Microvascular Zones in the Central Nervous System.
- Author
-
Hartmann DA, Coelho-Santos V, and Shih AY
- Subjects
- Arterioles physiology, Central Nervous System, Cerebrovascular Circulation physiology, Humans, Capillaries, Pericytes
- Abstract
The vast majority of the brain's vascular length is composed of capillaries, where our understanding of blood flow control remains incomplete. This review synthesizes current knowledge on the control of blood flow across microvascular zones by addressing issues with nomenclature and drawing on new developments from in vivo optical imaging and single-cell transcriptomics. Recent studies have highlighted important distinctions in mural cell morphology, gene expression, and contractile dynamics, which can explain observed differences in response to vasoactive mediators between arteriole, transitional, and capillary zones. Smooth muscle cells of arterioles and ensheathing pericytes of the arteriole-capillary transitional zone control large-scale, rapid changes in blood flow. In contrast, capillary pericytes downstream of the transitional zone act on slower and smaller scales and are involved in establishing resting capillary tone and flow heterogeneity. Many unresolved issues remain, including the vasoactive mediators that activate the different pericyte types in vivo, the role of pericyte-endothelial communication in conducting signals from capillaries to arterioles, and how neurological disease affects these mechanisms.
- Published
- 2022
- Full Text
- View/download PDF
222. Clinical Problem Solving: An Older Woman With Weakness from Head to Toe.
- Author
-
Hartmann DA, Bock M, Douglas V, Gerdts J, Ramani B, and Shah M
- Abstract
A 67-year-old woman was admitted to our hospital for progressive weakness, dysphagia, muscle pain, and weight loss. Here we detail the clinical problem solving involved in diagnosing and treating her immune-mediated necrotizing myopathy caused by anti-HMGCoA reductase autoantibodies. Interestingly, this diagnosis coincided with discovery of a gastrointestinal stromal tumor (GIST) and positivity for anti-nuclear matrix protein (anti-NXP2), another myositis specific autoantibody., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2021.)
- Published
- 2022
- Full Text
- View/download PDF
223. Studying the Evolution of Neural Activation Patterns During Training of Feed-Forward ReLU Networks.
- Author
-
Hartmann D, Franzen D, and Brodehl S
- Abstract
The ability of deep neural networks to form powerful emergent representations of complex statistical patterns in data is as remarkable as imperfectly understood. For deep ReLU networks, these are encoded in the mixed discrete-continuous structure of linear weight matrices and non-linear binary activations. Our article develops a new technique for instrumenting such networks to efficiently record activation statistics, such as information content (entropy) and similarity of patterns, in real-world training runs. We then study the evolution of activation patterns during training for networks of different architecture using different training and initialization strategies. As a result, we see characteristic- and general-related as well as architecture-related behavioral patterns: in particular, most architectures form bottom-up structure, with the exception of highly tuned state-of-the-art architectures and methods (PyramidNet and FixUp), where layers appear to converge more simultaneously. We also observe intermediate dips in entropy in conventional CNNs that are not visible in residual networks. A reference implementation is provided under a free license., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Hartmann, Franzen and Brodehl.)
- Published
- 2021
- Full Text
- View/download PDF
224. Brain capillary pericytes exert a substantial but slow influence on blood flow.
- Author
-
Hartmann DA, Berthiaume AA, Grant RI, Harrill SA, Koski T, Tieu T, McDowell KP, Faino AV, Kelly AL, and Shih AY
- Subjects
- Animals, Mice, Brain blood supply, Capillaries physiology, Cerebrovascular Circulation physiology, Hemodynamics physiology, Pericytes physiology
- Abstract
The majority of the brain's vasculature is composed of intricate capillary networks lined by capillary pericytes. However, it remains unclear whether capillary pericytes influence blood flow. Using two-photon microscopy to observe and manipulate brain capillary pericytes in vivo, we find that their optogenetic stimulation decreases lumen diameter and blood flow, but with slower kinetics than similar stimulation of mural cells on upstream pial and precapillary arterioles. This slow vasoconstriction was inhibited by the clinically used vasodilator fasudil, a Rho-kinase inhibitor that blocks contractile machinery. Capillary pericytes were also slower to constrict back to baseline following hypercapnia-induced dilation, and slower to dilate towards baseline following optogenetically induced vasoconstriction. Optical ablation of single capillary pericytes led to sustained local dilation and a doubling of blood cell flux selectively in capillaries lacking pericyte contact. These data indicate that capillary pericytes contribute to basal blood flow resistance and slow modulation of blood flow throughout the brain.
- Published
- 2021
- Full Text
- View/download PDF
225. Managing the tempo of the emergency department as an off-service intern.
- Author
-
Hartmann DA
- Published
- 2021
- Full Text
- View/download PDF
226. VasoMetrics: unbiased spatiotemporal analysis of microvascular diameter in multi-photon imaging applications.
- Author
-
McDowell KP, Berthiaume AA, Tieu T, Hartmann DA, and Shih AY
- Abstract
Background: Multi-photon imaging of the cerebrovasculature provides rich data on the dynamics of cortical arterioles, capillaries, and venules. Vascular diameter is the major determinant of blood flow resistance, and is the most commonly quantified metric in studies of the cerebrovasculature. However, there is a lack of accessible and easy-to-use methods to quantify vascular diameter in imaging data., Methods: We created VasoMetrics, a macro written in ImageJ/Fiji for spatiotemporal analysis of microvascular diameter. The key feature of VasoMetrics is rapid analysis of many evenly spaced cross-sectional lines along the vessel of interest, permitting the extraction of numerous diameter measurements from individual vessels. Here we demonstrated the utility of VasoMetrics by analyzing in vivo multi-photon imaging stacks and movies collected from lightly sedated mice, as well as data from optical coherence tomography angiography (OCTA) of human retina., Results: Compared to the standard approach, which is to measure cross-sectional diameters at arbitrary points along a vessel, VasoMetrics accurately reported spatiotemporal features of vessel diameter, reduced measurement bias and time spent analyzing data, and improved the reproducibility of diameter measurements between users. VasoMetrics revealed the dynamics in pial arteriole diameters during vasomotion at rest, as well as changes in capillary diameter before and after pericyte ablation. Retinal arteriole diameter was quantified from a human retinal angiogram, providing proof-of-principle that VasoMetrics can be applied to contrast-enhanced clinical imaging of microvasculature., Conclusions: VasoMetrics is a robust macro for spatiotemporal analysis of microvascular diameter in imaging applications., Competing Interests: Conflicts of Interest: The authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/qims-20-920). The special issue “Advanced Optical Imaging in Biomedicine” was commissioned by the editorial office without any funding or sponsorship. The authors have no other conflicts of interest to declare., (2021 Quantitative Imaging in Medicine and Surgery. All rights reserved.)
- Published
- 2021
- Full Text
- View/download PDF
227. Organizational hierarchy and structural diversity of microvascular pericytes in adult mouse cortex.
- Author
-
Grant RI, Hartmann DA, Underly RG, Berthiaume AA, Bhat NR, and Shih AY
- Subjects
- Actins analysis, Animals, Arterioles anatomy & histology, Capillaries anatomy & histology, Cerebral Cortex anatomy & histology, Cerebral Cortex blood supply, Cerebral Cortex diagnostic imaging, Mice, Microscopy, Confocal methods, Microvessels diagnostic imaging, Brain blood supply, Cerebral Cortex cytology, Microvessels cytology, Myocytes, Smooth Muscle cytology, Pericytes cytology
- Abstract
Smooth muscle cells and pericytes, together called mural cells, coordinate many distinct vascular functions. Canonically, smooth muscle cells are ring-shaped and cover arterioles with circumferential processes, whereas pericytes extend thin processes that run longitudinally along capillaries. In between these canonical mural cell types are cells with features of both smooth muscle cells and pericytes. Recent studies suggest that these transitional cells are critical for controlling blood flow to the capillary bed during health and disease, but there remains confusion on how to identify them and where they are located in the brain microvasculature. To address this issue, we measured the morphology, vascular territory, and α-smooth muscle actin content of structurally diverse mural cells in adult mouse cortex. We first imaged intact 3D vascular networks to establish the locations of major gradations in mural cell appearance as arterioles branched into capillaries. We then imaged individual mural cells occupying the regions within these gradations. This revealed two transitional cells that were often similar in appearance, but with sharply contrasting levels of α-smooth muscle actin. Our findings highlight the diversity of mural cell morphologies in brain microvasculature, and provide guidance for identification and categorization of mural cell types.
- Published
- 2019
- Full Text
- View/download PDF
228. Heuristic Patterns of Ethical Decision Making.
- Author
-
Hartmann DJ and McLaughlin O
- Subjects
- Affect, Humans, Intuition, Thinking, Decision Making ethics, Ethics, Research, Heuristics, Research
- Abstract
This article describes the context of ethical decision making in research and suggests that direct attention to the ways in which decisions are actually made in such environments is needed. A decision-making model based on the literature on heuristic processing is proposed and is followed by a review of the method, data, and results of the authors' research on this model. The implications of the research are developed, and a research agenda is outlined. Key findings were that competent actors do indeed process ethics problems heuristically and in ways that interweave intuitive, affective, and more rational phases. This processing does not typically follow a simple progressive pattern but evidences a sort of trial-and-error processing that is consistent with the logic of heuristic processing more generally. Finally, while diverse, participant-level processing attempts appear to follow patterns which are associated with the experience and training of the actors.
- Published
- 2018
- Full Text
- View/download PDF
229. Validation of Babesia proteasome as a drug target.
- Author
-
Jalovecka M, Hartmann D, Miyamoto Y, Eckmann L, Hajdusek O, O'Donoghue AJ, and Sojka D
- Subjects
- Animals, Babesia genetics, Babesia growth & development, Babesia microti genetics, Babesia microti growth & development, Babesiosis drug therapy, Boronic Acids pharmacology, Cell Line, Disease Models, Animal, Female, Macrophages drug effects, Macrophages parasitology, Mice, Oligopeptides pharmacology, Proteasome Endopeptidase Complex drug effects, Proteasome Inhibitors administration & dosage, Proteasome Inhibitors adverse effects, Proteome genetics, Babesia drug effects, Babesia microti drug effects, Drug Delivery Systems, Proteasome Inhibitors pharmacology, Proteasome Inhibitors therapeutic use, Proteome drug effects
- Abstract
Babesiosis is a tick-transmitted zoonosis caused by apicomplexan parasites of the genus Babesia. Treatment of this emerging malaria-related disease has relied on antimalarial drugs and antibiotics. The proteasome of Plasmodium, the causative agent of malaria, has recently been validated as a target for anti-malarial drug development and therefore, in this study, we investigated the effect of epoxyketone (carfilzomib, ONX-0914 and epoxomicin) and boronic acid (bortezomib and ixazomib) proteasome inhibitors on the growth and survival of Babesia. Testing the compounds against Babesia divergens ex vivo revealed suppressive effects on parasite growth with activity that was higher than the cytotoxic effects on a non-transformed mouse macrophage cell line. Furthermore, we showed that the most-effective compound, carfilzomib, significantly reduces parasite multiplication in a Babesia microti infected mouse model without noticeable adverse effects. In addition, treatment with carfilzomib lead to an ex vivo and in vivo decrease in proteasome activity and accumulation of polyubiquitinated proteins compared to untreated control. Overall, our results demonstrate that the Babesia proteasome is a valid target for drug development and warrants the design of potent and selective B. divergens proteasome inhibitors for the treatment of babesiosis., (Copyright © 2018. Published by Elsevier Ltd.)
- Published
- 2018
- Full Text
- View/download PDF
230. Rodent Models of Cerebral Microinfarct and Microhemorrhage.
- Author
-
Shih AY, Hyacinth HI, Hartmann DA, and van Veluw SJ
- Subjects
- Animals, Humans, Rodentia, Cerebral Hemorrhage pathology, Cerebral Hemorrhage physiopathology, Cerebral Hemorrhage therapy, Cerebral Infarction pathology, Cerebral Infarction physiopathology, Cerebral Infarction therapy, Disease Models, Animal
- Published
- 2018
- Full Text
- View/download PDF
231. Multiple legumain isoenzymes in ticks.
- Author
-
Hartmann D, Šíma R, Konvičková J, Perner J, Kopáček P, and Sojka D
- Subjects
- Amino Acid Sequence, Animals, Arachnid Vectors enzymology, Arthropod Proteins classification, Arthropod Proteins genetics, Base Sequence, Cloning, Molecular, Cysteine Endopeptidases classification, Cysteine Endopeptidases genetics, Female, Gene Expression Regulation, Enzymologic, Isoenzymes, Male, Models, Molecular, Protein Conformation, Rabbits, Recombinant Proteins immunology, Tick Infestations prevention & control, Arthropod Proteins metabolism, Cysteine Endopeptidases metabolism, Ixodes enzymology, Tick Infestations veterinary, Vaccines immunology
- Abstract
By searching nucleotide databases for the North American Lyme disease vector, Ixodes scapularis, we have complemented the previously characterized European Ixodes ricinus legumain IrAE1 with a full set of nine analogous genes (isae1-9). Six of these were PCR confirmed as genes present in all tick genomes tested. The absolute mRNA copy number examined by quantitative (q)PCR enabled expression profiling and an absolute comparison of mRNA levels for individual I. scapularis (Is)AEs in tick tissues. Four IsAEs (1, 2, 4, 9) were expressed solely in the gut and thus are proposed to be involved in host blood digestion. Expression qPCR profiling over developmental stages confirmed IsAE1, the direct analogue of previously characterized I. ricinus IrAE1, as the principle legumain transcript in partially engorged females, and demonstrated its strong regulation by on-host feeding in larvae, nymphs and females. In contrast, IsAE2 was the predominant gut legumain in unfed nymphs, unfed females and males. In-silico, IsAE1 and IsAE2 protein three-dimensional structural models displayed minimal differences in overall proenzyme structures, even in comparison with recently resolved crystal structures of mammalian prolegumain. Three functional studies were performed in I. ricinus with IsAE1/IsAE2 analogues: double IrAE1/IrAE2 RNA interference silencing, feeding of ticks on IrAE1+IrAE2 immunized hosts and in vitro membrane tick feeding on blood containing a legumain-specific inhibitor. The latter experiment led to reduced weights of fully engorged ticks and limited oviposition, and indicated the potential of legumain inhibitors for novel anti-tick interventions., (Copyright © 2017 Australian Society for Parasitology. Published by Elsevier Ltd. All rights reserved.)
- Published
- 2018
- Full Text
- View/download PDF
232. Functional deficits induced by cortical microinfarcts.
- Author
-
Summers PM, Hartmann DA, Hui ES, Nie X, Deardorff RL, McKinnon ET, Helpern JA, Jensen JH, and Shih AY
- Subjects
- Animals, Cerebral Cortex diagnostic imaging, Cerebral Infarction diagnostic imaging, Cerebrovascular Circulation, Cognition Disorders diagnostic imaging, Immunohistochemistry, Intracranial Thrombosis complications, Intracranial Thrombosis diagnostic imaging, Intracranial Thrombosis psychology, Magnetic Resonance Imaging, Mice, Mice, Inbred C57BL, Neurons pathology, Physical Stimulation, Proto-Oncogene Proteins c-fos biosynthesis, Synapses pathology, Vibrissae, Cerebral Infarction psychology, Cognition Disorders etiology, Cognition Disorders psychology
- Abstract
Clinical studies have revealed a strong link between increased burden of cerebral microinfarcts and risk for cognitive impairment. Since the sum of tissue damage incurred by microinfarcts is a miniscule percentage of total brain volume, we hypothesized that microinfarcts disrupt brain function beyond the injury site visible to histological or radiological examination. We tested this idea using a mouse model of microinfarcts, where single penetrating vessels that supply mouse cortex were occluded by targeted photothrombosis. We found that in vivo structural and diffusion MRI reliably reported the acute microinfarct core, based on spatial co-registrations with post-mortem stains of neuronal viability. Consistent with our hypothesis, c-Fos assays for neuronal activity and in vivo imaging of single vessel hemodynamics both reported functional deficits in viable peri-lesional tissues beyond the microinfarct core. We estimated that the volume of tissue with functional deficit in cortex was at least 12-fold greater than the volume of the microinfarct core. Impaired hemodynamic responses in peri-lesional tissues persisted at least 14 days, and were attributed to lasting deficits in neuronal circuitry or neurovascular coupling. These data show how individually miniscule microinfarcts could contribute to broader brain dysfunction during vascular cognitive impairment and dementia.
- Published
- 2017
- Full Text
- View/download PDF
233. Coding Ethical Decision-Making in Research.
- Author
-
Hartmann DJ, Van Valey T, and Fuqua W
- Subjects
- Models, Theoretical, Decision Making ethics, Ethics, Research
- Abstract
This paper presents methods and challenges attendant on the use of protocol analysis to develop a model of heuristic processing applied to research ethics. Participants are exposed to ethically complex scenarios and asked to verbalize their thoughts as they formulate a requested decision. The model identifies functional parts of the decision-making task: interpretation, retrieval, judgment and editing and seeks to reliably code participant verbalizations to those tasks as well as to a set of cognitive tools generally useful in such work. Important difficulties in the reliability and external validity of measurement are evaluated and a small set of illustrative data is used in support of that discussion. Results indicate that both intuitive emotional but also more deliberative cognition is present which is consistent with work in related literatures in expertise and in neuropsychology. Finally, the theoretical and practical potential of the approach is elaborated, particularly through links to a framing in Aristotelian ethics.
- Published
- 2017
- Full Text
- View/download PDF
234. Parasite Cathepsin D-Like Peptidases and Their Relevance as Therapeutic Targets.
- Author
-
Sojka D, Hartmann D, Bartošová-Sojková P, and Dvořák J
- Subjects
- Animals, Antiparasitic Agents pharmacology, Enzyme Inhibitors pharmacology, Parasitic Diseases enzymology, Protein Transport genetics, Antiparasitic Agents therapeutic use, Drug Delivery Systems, Parasites enzymology, Parasitic Diseases drug therapy, Peptide Hydrolases metabolism
- Abstract
Inhibition of aspartic cathepsin D-like peptidases (APDs) has been often discussed as an antiparasite intervention strategy. APDs have been considered as virulence factors of Trypanosoma cruzi and Leishmania spp., and have been demonstrated to have important roles in protein trafficking mechanisms of apicomplexan parasites. APDs also initiate blood digestion as components of multienzyme proteolytic complexes in malaria, platyhelminths, nematodes, and ticks. Increasing DNA and RNA sequencing data indicate that parasites express multiple APD isoenzymes of various functions that can now be specifically evaluated using new functional-genomic and biochemical tools, from which we can further assess the potential of APDs as targets for novel effective intervention strategies against parasitic diseases that still pose an alarming threat to mankind., (Copyright © 2016 Elsevier Ltd. All rights reserved.)
- Published
- 2016
- Full Text
- View/download PDF
235. IrFC - An Ixodes ricinus injury-responsive molecule related to Limulus Factor C.
- Author
-
Urbanová V, Hartmann D, Grunclová L, Šíma R, Flemming T, Hajdušek O, and Kopáček P
- Subjects
- Animals, Arthropod Proteins biosynthesis, Borrelia immunology, Candida albicans immunology, Complement System Proteins physiology, Enzyme Precursors biosynthesis, Escherichia coli immunology, Female, Gene Expression, Immunity, Innate, Ixodes enzymology, Ixodes immunology, Ixodes microbiology, Male, Micrococcus luteus immunology, Molecular Sequence Data, Phagocytosis, RNA, Messenger biosynthesis, RNA, Messenger genetics, Serine Endopeptidases biosynthesis, Up-Regulation immunology, Arthropod Proteins genetics, Enzyme Precursors genetics, Ixodes genetics, Serine Endopeptidases genetics
- Abstract
Limulus Clotting Factor C is a multi-domain serine protease that triggers horseshoe crab hemolymph clotting in the presence of trace amounts of bacterial lipopolysaccharides. Here we describe and functionally characterize an homologous molecule, designated as IrFC, from the hard tick Ixodes ricinus. Tick Factor C consists of an N-terminal cysteine-rich domain, four complement control protein (sushi) modules, an LCCL domain, a truncated C-lectin domain and a C-terminal trypsin-type domain. Developmental expression profiling by quantitative real-time PCR revealed that the irfc mRNA is expressed in all stages including eggs. In tissues dissected from adult I. ricinus females, the irfc mRNA is present mainly in tick hemocytes and accordingly, indirect immunofluorescence microscopy localized IrFC intracellularly, in tick hemocytes. Irfc mRNA levels were markedly increased upon injection of sterile saline, or different microbes, demonstrating that the irfc gene transcription occurs in response to injury. This indicates a possible role of IrFC in hemolymph clotting and/or wound healing, although these defense mechanisms have not been yet definitely demonstrated in ticks. RNAi silencing of irfc expression resulted in a significant reduction in phagocytic activity of tick hemocytes against the Gram-negative bacteria Chryseobacterium indologenes and Escherichia coli, but not against the yeast, Candida albicans. This result suggests that IrFC plays a role in the tick primordial complement system and as such possibly mediates transmission of tick-borne pathogens., (Copyright © 2014 Elsevier Ltd. All rights reserved.)
- Published
- 2014
- Full Text
- View/download PDF
236. Total synthesis of myrtucommulone A.
- Author
-
Müller H, Paul M, Hartmann D, Huch V, Blaesius D, Koeberle A, Werz O, and Jauch J
- Subjects
- Anti-Inflammatory Agents chemistry, Anti-Inflammatory Agents pharmacology, Apoptosis, Crystallography, X-Ray, Molecular Conformation, Myrtus chemistry, Phloroglucinol chemical synthesis, Phloroglucinol chemistry, Phloroglucinol pharmacology, Anti-Inflammatory Agents chemical synthesis, Phloroglucinol analogs & derivatives
- Published
- 2010
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.