1,976 research outputs found
YES: Women Do Have an Aptitude for Programming!
The ratio of women involved in computing has been historically moderate, and has receded at an alarming pace over the past decade, contributing to the critical labor shortage in the computing field. This paper investigates whether females lack aptitude for computer programming, or conversely whether they possess an aptitude for the discipline and could thus provide critical services within this high paying occupation if they chose to do so. Results demonstrate that females and males possess substantially the same level of aptitude for computer programming, and that for both groups a substantial portion of applicants from non-computing backgrounds demonstrated reasonable levels of progamming aptitude
Perforin gene transfer into hematopoietic stem cells improves immune dysregulation in murine models of perforin deficiency
Defects in perforin lead to the failure of T and NK cell cytotoxicity, hypercytokinemia, and the immune dysregulatory condition known as familial hemophagocytic lymphohistiocytosis (FHL). The only curative treatment is allogeneic hematopoietic stem cell transplantation which carries substantial risks. We used lentiviral vectors (LV) expressing the human perforin gene, under the transcriptional control of the ubiquitous phosphoglycerate kinase promoter or a lineage-specific perforin promoter, to correct the defect in different murine models. Following LV-mediated gene transfer into progenitor cells from perforin-deficient mice, we observed perforin expression in mature T and NK cells, and there was no evidence of progenitor cell toxicity when transplanted into irradiated recipients. The resulting perforin-reconstituted NK cells showed partial recovery of cytotoxicity, and we observed full recovery of cytotoxicity in polyclonal CD8 + T cells. Furthermore, reconstituted T cells with defined antigen specificity displayed normal cytotoxic function against peptide-loaded targets. Reconstituted CD8 + lymphoblasts had reduced interferon-Îł secretion following stimulation in vitro, suggesting restoration of normal immune regulation. Finally, upon viral challenge, mice with >30% engraftment of gene-modified cells exhibited reduction of cytokine hypersecretion and cytopenias. This study demonstrates the potential of hematopoietic stem cell gene therapy as a curative treatment for perforin-deficient FHL
Why Are Students Not Majoring in Information Systems?
The purpose of this study was to examine some of the factors that influence and impact business students when they select their major and, more particularly, to examine why students are not majoring in information systems. Students in an entry level business class responded that they were more knowledgeable about careers in management, marketing, accounting, and finance than they were about careers in information systems. These business students indicated that they are looking for majors that will be interesting, provide them with job security initially and over their careers, and pay them well. The most important information sources used by these students in their major selection decision were information on college/department websites, brochures about the major, and information on the Internet. When asked why they were not majoring in information systems, the top two reasons given were not what I wanted to do and subject not of interest
Pre-clinical Development of a Lentiviral Vector Expressing the Anti-sickling \u3b2AS3 Globin for Gene Therapy for Sickle Cell Disease
Sickle cell disease (SCD) is caused by a mutation (E6V) in the hemoglobin (Hb) \u3b2-chain that induces polymerization of Hb tetramers, red blood cell deformation, ischemia, anemia, and multiple organ damage. Gene therapy is a potential alternative to human leukocyte antigen (HLA)-matched allogeneic hematopoietic stem cell transplantation, available to a minority of patients. We developed a lentiviral vector expressing a \u3b2-globin carrying three anti-sickling mutations (T87Q, G16D, and E22A) inhibiting axial and lateral contacts in the HbS polymer, under the control of the \u3b2-globin promoter and a reduced version of the \u3b2-globin locus-control region. The vector (GLOBE-AS3) transduced 60%\u201380% of mobilized CD34+ hematopoietic stem-progenitor cells (HSPCs) and drove \u3b2AS3-globin expression at potentially therapeutic levels in erythrocytes differentiated from transduced HSPCs from SCD patients. Transduced HSPCs were transplanted in NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ (NSG)-immunodeficient mice to analyze biodistribution, chimerism, and transduction efficiency in bone marrow (BM), spleen, thymus, and peripheral blood 12\u201314 weeks after transplantation. Vector integration site analysis, performed in pre-transplant HSPCs and post-transplant BM cells from individual mice, showed a normal lentiviral integration pattern and no evidence of clonal dominance. An in vitro immortalization (IVIM) assay showed the low genotoxic potential of GLOBE-AS3. This study enables a phase I/II clinical trial aimed at correcting the SCD phenotype in juvenile patients by transplantation of autologous hematopoietic stem cells (HSC) transduced by GLOBE-AS3
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Genetic reporter analysis reveals an expandable reservoir of OCT4+ cells in adult skin
The transcription factor Oct4 (Pou5f1) is a critical regulator of pluripotency in embryonic and induced pluripotent stem cells. Therefore, Oct4 expression might identify somatic stem cell populations with inherent multipotent potential or a propensity for facilitated reprogramming. However, analysis of Oct4 expression is confounded by Oct4 pseudogenes or non-pluripotency-related isoforms. Systematic analysis of a transgenic Oct4-EGFP reporter mouse identified testis and skin as two principle sources of Oct4+ cells in postnatal mice. While the prevalence of GFP+ cells in testis rapidly declined with age, the skin-resident GFP+ population expanded in a cyclical fashion. These cells were identified as epidermal stem cells dwelling in the stem cell niche of the hair follicle, which endogenously expressed all principle reprogramming factors at low levels. Interestingly, skin wounding or non-traumatic hair removal robustly expanded the GFP+ epidermal cell pool not only locally, but also in uninjured skin areas, demonstrating the existence of a systemic response. Thus, the epithelial stem cell niche of the hair follicle harbors an expandable pool of Oct4+ stem cells, which might be useful for therapeutic cell transfer or facilitated reprogramming. Electronic supplementary material The online version of this article (doi: 10.1186/2045-9769-3-9) contains supplementary material, which is available to authorized users
Neutrons from multiplicity-selected Au-Au collisions at 150, 250, 400, and 650 AMeV
We measured neutron triple-differential cross sections from
multiplicity-selected Au-Au collisions at 150, 250, 400, and 650 \AMeV. The
reaction plane for each collision was estimated from the summed transverse
velocity vector of the charged fragments emitted in the collision. We examined
the azimuthal distribution of the triple-differential cross sections as a
function of the polar angle and the neutron rapidity. We extracted the average
in--plane transverse momentum and the normalized
observable , where is the neutron
transverse momentum, as a function of the neutron center-of-mass rapidity, and
we examined the dependence of these observables on beam energy. These
collective flow observables for neutrons, which are consistent with those of
protons plus bound nucleons from the Plastic Ball Group, agree with the
Boltzmann--Uehling--Uhlenbeck (BUU) calculations with a momentum--dependent
interaction. Also, we calculated the polar-angle-integrated maximum azimuthal
anisotropy ratio R from the value of .Comment: 20 LaTeX pages. 11 figures to be faxed on request, send email to
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Biosafety Studies of a Clinically Applicable Lentiviral Vector for the Gene Therapy of Artemis-SCID
Genetic deficiency of the nuclease DCLRE1C/Artemis causes radiosensitive severe combined immunodeficiency (RS-SCID) with lack of peripheral T and B cells and increased sensitivity to ionizing radiations. Gene therapy based on transplanting autologous gene-modified hematopoietic stem cells could significantly improve the health of patients with RS-SCID by correcting their immune system. A lentiviral vector expressing physiological levels of human ARTEMIS mRNA from an EF1a promoter without post-transcriptional regulation was developed as a safe clinically applicable candidate for RS-SCID gene therapy. The vector was purified in GMP-comparable conditions and was not toxic in vitro or in vivo. Long-term engraftment of vector-transduced hematopoietic cells was achieved in irradiated Artemis-deficient mice following primary and secondary transplantation (6 months each). Vector-treated mice displayed T and B lymphopoiesis and polyclonal T cells, had structured lymphoid tissues, and produced immunoglobulins. Benign signs of inflammation were noted following secondary transplants, likely a feature of the model. There was no evidence of transgene toxicity and no induction of hematopoietic malignancy. In vitro, the vector had low genotoxic potential on murine hematopoietic progenitor cells using an immortalization assay. Altogether, these preclinical data show safety and efficacy, and support further development of the vector for the gene therapy of RS-SCID
Maximum Azimuthal Anisotropy of Neutrons from Nb-Nb Collisions at 400 AMeV and the Nuclear Equation of State
We measured the first azimuthal distributions of triple--differential cross
sections of neutrons emitted in heavy-ion collisions, and compared their
maximum azimuthal anisotropy ratios with Boltzmann--Uehling--Uhlenbeck (BUU)
calculations with a momentum-dependent interaction. The BUU calculations agree
with the triple- and double-differential cross sections for positive rapidity
neutrons emitted at polar angles from 7 to 27 degrees; however, the maximum
azimuthal anisotropy ratio for these free neutrons is insensitive to the size
of the nuclear incompressibility modulus K characterizing the nuclear matter
equation of state.Comment: Typeset using ReVTeX, with 3 ps figs., uuencoded and appende
Neutrons from multiplicity-selected La-La and Nb-Nb collisions at 400A MeV and La-La collisions at 250A MeV
Triple-differential cross sections for neutrons from high-multiplicity La-La
collisions at 250 and 400 MeV per nucleon and Nb-Nb collisions at 400 MeV per
nucleon were measured at several polar angles as a function of the azimuthal
angle with respect to the reaction plane of the collision. The reaction plane
was determined by a transverse-velocity method with the capability of
identifying charged-particles with Z=1, Z=2, and Z > 2. The flow of neutrons
was extracted from the slope at mid-rapidity of the curve of the average
in-plane momentum vs the center-of-mass rapidity. The squeeze-out of the
participant neutrons was observed in a direction normal to the reaction plane
in the normalized momentum coordinates in the center-of-mass system.
Experimental results of the neutron squeeze-out were compared with BUU
calculations. The polar-angle dependence of the maximum azimuthal anisotropy
ratio was found to be insensitive to the mass of the colliding
nuclei and the beam energy. Comparison of the observed polar-angle dependence
of the maximum azimuthal anisotropy ratio with BUU calculations for
free neutrons revealed that is insensitive also to the
incompressibility modulus in the nuclear equation of state.Comment: ReVTeX, 16 pages, 17 figures. To be published in Physical Review
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