Biomedicine

Enhanced stability of polyacrylate-coated magnetite nanoparticles in biorelevant media

by Szekeres Márta

Published in 'Colloids and Surfaces B'

Magnetite nanoparticles (MNPs) were prepared by alkaline hydrolysis of Fe(II) and Fe(III) chlorides. Adsorption of... more Magnetite nanoparticles (MNPs) were prepared by alkaline hydrolysis of Fe(II) and Fe(III) chlorides. Adsorption of polyacrylic acid (PAA) on MNPs was measured at pH=6.5±0.3 and I=0.01 M (NaCl) to find the optimal PAA amount for MNP stabilization under physiological conditions. We detected an H-bond formation between magnetite surface groups and PAA by ATR-FTIR measurements, but bonds of metal ion-carboxylate complexes, generally cited in literature, were not identified at the given pH and ionic strength. The dependence of the electrokinetic potential and the aggregation state on the amount of added PAA at various pHs was measured by electrophoretic mobility and dynamic light-scattering methods. The electrokinetic potential of the naked MNPs was low at near physiological pH, but PAA adsorption overcharged the particles. Highly negatively charged, well-stabilized carboxylated MNPs formed via adsorption of PAA in an amount of approximately ten times of that necessary to compensate the original positive charge of the magnetite. Coagulation kinetics experiments revealed gradual enhancement of salt tolerance at physiological pH from ~ 0.001 M at no added PAA up to ~0.5 M at 1.12 mmol/g PAA. The PAA-coated MNPs exert no substantial effect on the proliferation of malignant (HeLa) or non-cancerous fibroblast cells (MRC-5) as determined by means of MTT assays.

HIV Interventions: Beyond the flesh/information distinction (Review essay)

by Mizanur Rahaman

(2012) 21 Science as Culture (forthcoming)

Morbidity in the Marshes: Using Spatial Epidemiology to Investigate Skeletal Evidence for Malaria in Anglo-Saxon England (AD410-1050).

by Gaynor Western

Gowland, R.L. & Western, A.G. 2012. American Journal of Physical Anthropology 147(2): 301-311.

Efficient CRM197-mediated drug targeting to monocytes

by Nicolas Legrand

G.J. Schenk et al.; Journal of Controlled Release (2012)

Efficient delivery of drugs to specific cellular reservoirs is of particular importance for therapeutics that are not... more Efficient delivery of drugs to specific cellular reservoirs is of particular importance for therapeutics that are not able to pass cellular barriers and that may have unwanted side effects in off-target tissues. Heparin-binding epidermal growth factor (HB-EGF) is expressed on leukocytes and may be targeted for specific drug delivery using cross-reacting material (CRM)197, a non-toxic variant of diphtheria toxin and exogenous substrate for HB-EGF. We used fluorescently labeled CRM197 and CRM197-coated liposomes to investigate their potential use for drug delivery to leukocytes. We demonstrate that CRM197-guided systems are efficiently taken up by human leukocytes in vitro. CRM197 was also found to specifically target leukocytes in vivo in mice with components of the human immune system (HIS mice) and hamsters. Monocytes represent the most prominent subset of leukocytes that showed highly specific CRM197-mediated uptake. We therefore propose the application of CRM197 as a novel targeting approach in diseases that require the selective treatment of monocytes.

Stem cell factor consistently improves thymopoiesis after experimental transplantation of murine or human hematopoietic cells in immunodeficient mice

by Nicolas Legrand

E.J. Wils et al.; The Journal of Immunology (2011)

Deficient thymopoiesis is a pivotal determinant of impaired immune competence following hematopoietic stem cell... more Deficient thymopoiesis is a pivotal determinant of impaired immune competence following hematopoietic stem cell transplantation (HSCT). Stem cell factor (SCF) is essentially involved in early thymopoiesis. We evaluated whether SCF administration would improve recovery of thymopoiesis following HSCT in immunodeficient mice receiving: 1) bone marrow (BM) transplantation of congenic mice; or 2) human fetal liver HSCT in the human immune system mouse model. Following murine BM transplantation, SCF significantly enhanced thymopoiesis and peripheral T cell recovery in lymph nodes and spleen. SCF did not affect BM lymphoid progenitor recovery and/or expansion. Median thymic cellularity increased from 0.9 in PBS- to 266 × 10(4)/thymus in SCF-treated mice (p = 0.05). Following human HSCT in human immune system mice, higher thymic cellularity was observed in SCF-treated mice. Double-negative and early double-positive thymocyte subsets increased, but especially late double-positive, CD4 single-positive, and CD8 single-positive thymocyte subsets were significantly enhanced (p < 0.05). These results show that exogenous supply of SCF may significantly improve murine and human posttransplant thymopoiesis, for which the effect is probably exerted by directly promoting T cell development intrathymically rather than by enhanced entry of prethymically expanded lymphoid progenitors.

Autonomous and extrinsic regulation of thymopoiesis in human immune system (HIS) mice

by Nicolas Legrand

N.D. Huntington et al.; European Journal of Immunology (2011)

Human Immune System (HIS) mice represent a novel biotechnology platform to dissect human haematopoiesis and immune... more Human Immune System (HIS) mice represent a novel biotechnology platform to dissect human haematopoiesis and immune responses. However, the limited human T-cell development that is observed in HIS mice restricts its utility for these applications. Here, we address whether reduced thymopoiesis in HIS mice reflects an autonomous defect in T-cell precursors and/or a defect in the murine thymic niche. Human thymocyte precursors seed the mouse thymus and their reciprocal interactions with murine thymic epithelial cells (TECs) led to both T-cell and TEC maturation. The human thymocyte subsets observed in HIS mice demonstrated survival, proliferative and phenotypic characteristics of their normal human counterparts, suggesting that the intrinsic developmental program of human thymocytes unfolds normally in this xenograft setting. We observed that exogenous administration of human IL-15/IL-15Rα agonistic complexes induced the survival, proliferation and absolute numbers of immature human thymocyte subsets, without any obvious effect on cell-surface phenotype or TCR Vβ usage amongst the newly selected mature single-positive (SP) thymocytes. Finally, when IL-15 was administered early after stem cell transplantation, we noted accelerated thymopoiesis resulting in the more rapid appearance of peripheral naïve T cells. Our results highlight the functional capacity of murine thymic stroma cells in promoting human thymopoiesis in HIS mice but suggest that the "cross-talk" between murine thymic stroma and human haematopoietic precursors may be suboptimal. As IL-15 immunotherapy promotes early thymopoiesis, this novel approach could be used to reduce the period of T-cell immunodeficiency in the post-transplant clinical setting.

AF1q/MLLT11 regulates the emergence of human prothymocytes through cooperative interaction with the Notch signaling pathway

by Nicolas Legrand

A. Parcelier et al.; Blood (2011)

The mechanisms regulating the emergence of BM prothymocytes remain poorly characterized. Genome-wide transcriptome... more The mechanisms regulating the emergence of BM prothymocytes remain poorly characterized. Genome-wide transcriptome analyses looking for genes expressed in human prothymocytes led to the identification of AF1q/MLLT11 as a candidate gene conceivably involved in this process. Analysis of AF1q protein subcellular localization and intracellular trafficking showed that despite pronounced karyophily, it was subjected to constitutive nuclear export followed by ubiquitin-mediated degradation in the centrosomal area. Using in vitro assays based on either forced expression or shRNA-mediated silencing of AF1q, we provide evidence that the protein promotes T- over B-cell differentiation in multipotent hematopoietic progenitors. At the molecular level, AF1q confers to multipotent progenitors an increased susceptibility to Delta-like/Notch-mediated signaling. Consistent with these findings, enforced AF1q expression in humanized mice fosters the emergence of BM CD34(+)CD7(+) prothymocytes, enhances subsequent thymus colonization, and accelerates intrathymic T-cell development. In contrast, AF1q silencing provokes a global shift of BM lymphopoiesis toward the B-cell lineage, hinders prothymocyte development, inhibits thymus colonization, and leads to intrathymic accumulation of B cells. Our results indicate that AF1q cooperates with the Notch signaling pathway to foster the emergence of BM prothymocytes and drive subsequent intrathymic specification toward the T-cell lineage.

Cross-Species Databases

by Sabina Leonelli

Published in Social Studies of Science, April 2012.

Design and Evaluation of Three Pair Primers for Exon 1 Amplification of Hyaluroglucosaminidase-1 Gene

by Arli Parikesit

Co-authored with Usman Sumo Friend Tambunan and Sylvia Sugito

Abstract: Problem statement: Hyaluronidase is an enzyme which catalyze hydrolysis of Hyaluronan (HA). Hyaluronan is... more Abstract: Problem statement: Hyaluronidase is an enzyme which catalyze hydrolysis of Hyaluronan (HA). Hyaluronan is important in cell migration during embryonic development, cellular proliferation and differentiation and has a structural role in connective tissues. Hyaluronidase deficiency is correlated with mucopolysaccharidosis IX. In human, hyaluronidase is encoded by HYAL1 gene. The mutation study of HYAL1 gene was carried out by many researchers, but until now, mutation study of HYAL1 still in progress and limited due to the lack of primer used in amplification of
selected DNA sequence of HYAL1 gene and maximum length limitation imposed by DNA sequencer. Approach: The search for three pairs of primers for human exon 1 segmented amplification of HYAL1 gene was conducted and evaluated. The first step was to acquire HYAL1 gene sequence and then had it aligned with human chromosome 3 genomic contig sequence. Exon 1 of HYAL1 gene was found to be located at nt 201-1711 of the acquired human chromosome 3 genomic contig. Online Primer3 program was used to design three pairs of primers. The selected pairs of primer had been subjected to BLASTn operation for selectivity examination while onlineNetPrimer operation
was carried out for examination of secondary structures. Results: The search for primers to amplify three different fragments of exon 1 of HYAL1 gene yielded three selected pairs of primers, namely forward primer 5’- GACCCCCTACAAAAGCTCA-3’ (20 bp) and reverse primer 5’- AAGTCTCCGATTCCCCCACT-3’ (20 bp) for amplifying nt 1-551 of HYAL1 gene, forward primer 5’- GTCCTGTGGGAGATGGCAGA-3’ (21 bp) and reverse primer 5’- CGGTAAATGTCCTTGGTGTCC-3’ (21 bp) for amplifying nt 355-1053 of HYAL1 gene and forward primer 5’-GCCATACCTGCTCCTGACTT-3’ (20 bp) and reverse primer 5’- ACAAGGTGGGCAGGTTACAG-3’ (20 bp) for amplifying nt 956-1511 of HYAL1 gene. When using these primers, nt 1-46 of amplified product of the first pair of primers and nt 555-584 of amplified product of the third pair of primers must not be considered because those are not part of exon 1 of HYAL1 gene. The results from both operations and trial to real samples using these primers
indicated that all three pairs of primer were satisfactory for use. Conclusion/Recommendations: The three pairs of primers could be used to amplify specified segments of HYAL1 gene.

Proposed Design of a low-cost mhealth System

by Rajat Kumar

Rajat Kumar and Arvind Rehalia ,Published in International Journal of Modelling and Optimization, IACSIT Press, Singapore.

This paper proposes a model for low cost design of mhealth solutions. The model presented here is based on RF... more This paper proposes a model for low cost design of mhealth solutions. The model presented here is based on RF transmitter and receiver, microcontroller and cellular network integration and uses F-BUS protocol for transmitting and receiving data using a NOKIA 3310 handset. The proposed design aims at eliminating the need of smart-phone dependent costly mhealth solutions. Also, the current paper presents the essential comparative data and statistics to support the concerned proposed design.

Cite: Rajat Kumar and Arvind Rehalia, "Proposed Design of a Low Cost mHealth System," International Journal of Modeling and Optimization vol. 2, no. 1, pp. 15-18, 2012.

Rajat Kumar is with the Bharati Vidyapeeth's College of Engineering, Guru Gobind Singh Indraprastha University , New Delhi , India (e-mail: rajatk489@gmail.com).

Arvind Rehalia is with the Bharati Vidyapeeth's College of Engineering, Guru Gobind Singh Indraprastha University, New Delhi, India (e-mail: rehaliaarvind@gmail.com).

For Gabe and Ari

by Rebecca Sachs Norris

In The Patient’s Voice: Experiences of Illness, Jeanine Young-Mason, ed., Philadelphia: F. A. Davis C., 1997.

The Paradox of Healing Pain

by Rebecca Sachs Norris

In Religion, 39(1), 22-33, 2009.

Pain may be seen as a problem to be healed or as a means for healing. The secular biomedical view of pain is that it... more Pain may be seen as a problem to be healed or as a means for healing. The secular biomedical view of pain is that it is to be avoided and alleviated; its only meaning is as a symptom of underlying disease. In contrast, there have been throughout history other views of suffering—as redemptive or as transformative, for example. This paper considers the disparity between these perspectives, examining the role of the emotions and the underlying neurobiological processes though which pain and suffering come to be experienced as meaningful, then analyzes interview material exploring how religion and religious beliefs help people cope with suffering or with pain. The experience of pain is subjective, enculturated experience; the meaning that pain or suffering holds within a given cultural context affects the experience of pain and suffering. In a context where pain and suffering are understood to be valuable, those experiences can be used for spiritual transformation and integrated within a meaningful identity. In contrast, in a context where pain and suffering are not understood to have value, that attitude can create more suffering, even in conditions meant to alleviate suffering, such as in biomedical situations.

Experiments in discourse analysis impact on information classification and retrieval algorithms

by Jorge Morato

Morato, J.; Llorens, J., Genova, G., Moreiro, J. A. Experiments in discourse analysis impact on information classification and retrieval algorithms. Information Processing & Management, vol 39 nº 6 November 2003: 825- 851

Researchers in indexing and retrieval systems have been advocating the inclusion of more contextual information to... more Researchers in indexing and retrieval systems have been advocating the inclusion of more contextual information to improve results. The proliferation of full-text databases and advances in computer storage capacity have made it possible to carry out text analysis by means of linguistic and extralinguistic knowledge. Since the mid 80s, research has tended to pay more attention to context, giving discourse analysis a more central role. The research presented in this paper aims to check whether discourse variables have an impact on modern information retrieval and classification algorithms. In order to evaluate this hypothesis, a functional framework for information analysis in an automated environment has been proposed, where the n-grams (filtering) and the k-means and Chen's classification algorithms have been tested against sub-collections of documents based on the following discourse variables: "Genre", "Register", "Domain terminology", and "Document structure". The results obtained with the algorithms for the different sub-collections were compared to the MeSH information structure. These demonstrate that n-grams does not appear to have a clear dependence on discourse variables, though the k-means classification algorithm does, but only on domain terminology and document structure, and finally Chen's algorithm has a clear dependence on all of the discourse variables. This information could be used to design better classification algorithms, where discourse variables should be taken into account. Other minor conclusions drawn from these results are also presented.

Sistemas de recuperación de información adaptados al dominio biomédico

by Jorge Morato

Marrero, M, Sanchez-Cuadrado, S, Urbano, J, Morato, J, Moreiro, JA (2010) Sistemas de recuperación de información adaptados al dominio biomédico. El Profesional de la Información, 19 (3), p. 246-254

La terminología usada en biomedicina tiene rasgos léxicos que han requerido la elaboración de recursos terminológicos... more La terminología usada en biomedicina tiene rasgos léxicos que han requerido la elaboración de recursos terminológicos y sistemas de recuperación de información con funciones específicas.
Las principales características son las elevadas tasas de sinonimia y homonimia, debidas a fenómenos como la proliferación de siglas polisémicas y su interacción con el lenguaje común. Los sistemas de recuperación de información en el dominio biomédico utilizan técnicas orientadas al tratamiento de estas peculiaridades léxicas. Se revisan algunas de estas técnicas, como la aplicación de Procesamiento del Lenguaje Natural (BioNLP), la incorporación de recursos léxico-semánticos, y la aplicación de Reconocimiento de Entidades (BioNER). Se presentan los métodos de evaluación adoptados para comprobar la adecuación de estas técnicas en la recuperación de recursos biomédicos.

The terminology used in biomedicine has lexical characteristics that have required the elaboration of terminological resources and information retrieval systems with specific functionalities. The
main characteristics are the high rates of synonymy and homonymy, due to phenomena such as the proliferation
of polysemic acronyms and their interaction with common language. Information retrieval systems in the biomedical domain use techniques oriented to the treatment of these lexical peculiarities.
In this paper we review some of these techniques, such as the application of Natural Language Processing (BioNLP), the incorporation of lexical-semantic resources, and the application of Named Entity Recognition (BioNER). Finally, we present the evaluation methods adopted to assess the suitability of these techniques for retrieving biomedical resources.

Knowledge Management in Biomedical Libraries: A Semantic Web Approach

by Jorge Morato

Damaris Fuentes Lorenzo, Jorge Morato, Juan Miguel Gómez: Knowledge Management in Biomedical Libraries: A Semantic Web Approach. In: Information Systems Frontiers. Special issue: Knowledge Discovery and Management in Biomedical Information Systems. DOI: 10.1007/s10796-009-9159-y . Information Systems Frontiers, Vol. 11, No. 4. (1 September 2009), pp. 471-480.

In recent years, technological advances in high-throughput techniques and efficient data gathering methods, coupled... more In recent years, technological advances in high-throughput techniques and efficient data gathering methods, coupled with a world-wide effort in computational biology, have resulted in an enormous amount of life science data available in repositories devoted to biomedical literature. These repositories lack the ability to attain an effective and accurate search. Using semantic technologies as the key for interoperation enables searching and processing of biomedical literature in a more efficient way. However, emerging semantic applications take for granted specific knowledge that biomedical researchers may not have. This paper presents design principles for easy-to-use biomedical semantic applications by means of ontology-based annotations and faceted search. The proposed approach is backed with a usable prototype that shows the breakthroughs of adding these principles to a biomedical digital library where identifying and searching information are critical aspects for non-semantic Web experts.

Combinatorial development of biomaterials for clonal growth of human pluripotent stem cells

by Krishanu Saha

Both human embryonic stem cells and induced pluripotent stem cells can self-renew indefinitely in culture; however,... more Both human embryonic stem cells and induced pluripotent stem cells can self-renew indefinitely in culture; however, present methods to clonally grow them are inefficient and poorly defined for genetic manipulation and therapeutic purposes. Here we develop the first chemically defined, xeno-free, feeder-free synthetic substrates to support robust self-renewal of fully dissociated human embryonic stem and induced pluripotent stem cells. Material properties including wettability, surface topography, surface chemistry and indentation elastic modulus of all polymeric substrates were quantified using high-throughput methods to develop structure–function relationships between material properties and biological performance. These analyses show that optimal human embryonic stem cell substrates are generated from monomers with high acrylate content, have a moderate wettability and employ integrin αvβ3 and αvβ5 engagement with adsorbed vitronectin to promote colony formation. The structure–function methodology employed herein provides a general framework for the combinatorial development of synthetic substrates for stem cell culture.

Nurses and midwives in alternative health care: comparative processes of boundary re-configuration in Israel

by Sky Gross

in: Complementary and alternative medicine in nursing and midwifery: towards a critical social science edited by Jon Adams and Philip Tovey Publisher: London ; Routledge, 2008. co authored with Judith Shuval

This comparative study of nurses and midwives practicing CAM is an additional link in our on-going research concerning... more This comparative study of nurses and midwives practicing CAM is an additional link in our on-going research concerning the co-habitation of bio and alternative medicine in Israel. We have been interested  in negotiative processes of boundary crossing which take place when alternative practitioners work within the organizational context of bio medical institutions. 
The present paper expands the context of our research by focusing on two groups of allied health professionals who utilize CAM  practices. Like increasing numbers of physicians who practice CAM,  the nurses and midwives under study are trained and experienced in mainstream bio medicine and have at some point in their careers opted to study and practice a variety of CAM skills.  Their experiences in the processes of boundary crossing are analyzed in terms of 'boundary work' to include practices utilized in the work context. 

Structural Causes of Cultural Insensitivity in Anne Fadiman’s The Spirit Catches You and You Fall Down

by Eric Gallager

The first paper I wrote for my Peace Studies class with Professor Irene Oh in the fall semester of my junior year at GWU.

This paper argue that the failure of the doctors Neil and Peggy in Anne Fadiman's book The Spirit Catches You and You... more This paper argue that the failure of the doctors Neil and Peggy in Anne Fadiman's book The Spirit Catches You and You Fall Down to be more culturally sensitive to their Hmong patients was caused by structural issues in the American biomedical system. To prove this point, this paper will first present a background to Lia’s case, then discuss possibilities for assigning blame to Neil and Peggy, then show evidence for the structural issues in American biomedicine, before finally concluding.

2009. Failed recipients: extracting blood in a Papua New Guinean hospital

by Alice Street

Anthropologists studying voluntary-anonymous systems of blood donation have noted the ways in which they facilitate... more Anthropologists studying voluntary-anonymous systems of blood donation have noted the ways in which they facilitate imaginings of national relatedness and integration. This paper focuses on family replacement systems in Papua New Guinea, where blood donated by a patient's relative replaces the units taken from the bank, in order to examine what kinds of relational imaginings are possible when blood is transacted between people who know one another. Patients in Madang Hospital are led to believe that it is their responsibility to obtain blood donations from their relatives within a kinship obligation system. However, articulations of kinship exchange with a biomedical blood economy are not as straightforward as hospital workers suggest. Instead the hospital emerges as a crucial, but hidden, mediator in these transactions. Doctors conceal from patients the fact that blood group incompatibilities mean blood intended for a specific person may be redirected elsewhere. The obviation of this 'biomedical technology' thus enables the hospital to harness patients' 'relational technologies' of gift exchange to feed the institution's blood economy. In contrast to anthropologists' common focus on blood donation, here attention is drawn to the role of recipients in negotiating different regimes of extraction.

2011. Artefacts of Not-Knowing: The Medical Record, Diagnosis and the Production of Uncertainty in Papua New Guinean Biomedicine. Social Studies of Science Vol. 42.

by Alice Street

Anthropological and STS scholars of biomedical work have traditionally explored contexts where inconsistencies and... more Anthropological and STS scholars of biomedical work have traditionally explored contexts where inconsistencies and lacunas in diagnostic knowledge production are fundamentally problematic for medical practitioners and have consequently focused on the social and political processes by which such epistemic uncertainties are resolved. This article draws on ethnographic material from a Papua New Guinean hospital where diagnostic uncertainty is not rendered problematic and where the open-endedness of the diagnostic process gives rise to new forms of medical expertise and practice. The paper focuses on the medical record as an artefact of not-knowing that both documents and performs uncertainty as a valuable resource. It shows that medical records can operate as either technologies of 'opening' that multiply opportunities for pragmatic action within a hospital space or as technologies of 'closure' that move people and documents between spaces. Practices of not-knowing and knowing are therefore shown to be interdependent and interchangeable 'moments' of bureaucratic-biomedical work.