Assessment of Methylprednisolone Purging Efficacy on Daudi Burkitt Lymphoma Cells from Normal Bone Marrow

Studies on normal bone marrow and Daudi Burkitt lymphoma cells were performed to determine the efficacy of selective, in vitro chemopurging with methylprednisolone (MP). We found that MP reduces the numher of lymphoma cells without significant damage to bone marrow cells. This information is important because we need to improve the existing in vitro purging regimens used to cleanse autologous marrows of metastatic disease before transplantation into cancer patients who have received high-dose chemotherapy. Normal human bone marrow (NBM) and Daudi lymphoma cells were trealed in parallel with various purging regimens. NBM death was evaluated using soft-agar culture, while Daudi cell death was evaluated using one-week liquid culture. A protocol of 2.0 mg/mL of MP for four hours demonstrated optimal selectivity. When treatment was followed by cryopreservation, a 1.7 log purge of Daudi cells was increased to 2.3 logs while preserving 36% of committed NBM precursors. We repeated these experiments on a simulated contaminated marrow to model closely the mixture of normal and malignant cells found in advanced, metastatic disease. We evaluated this mixed system by flow cytometric immunoanalysis using the two-color CD10/CD20 markers to detect residual, viable Daudi cells. Our initial results were reproducible in this mixed-cell system, further supporting the evidence for effective in vitro purging of bone marrow using MP

Efficient trimming for strongly connected components calculation

Strongly Connected Components (SCCs) are useful for many applications, such as community detection and personalized recommendation. Determining the SCCs of a graph, however, can be very expensive, and parallelization is not an easy way out: the paral-lelization itself is challenging, and its performance impact varies non-trivially with the input graph structure. This variability is due to trivial components, i.e., SCCs consisting of a single vertex, which lead to significant workload imbalance. Trimming is an effective method to remove trivial components, but is inefficient when used on graphs with few trivial components. In this work, we propose FB-AI-Trim, a parallel SCC algorithm with selective trimming. Our algorithm decides dynamically, at runtime, based on the input graph how to trim the graph. To this end, we train a neural network to predict, using topological graph information, whether trimming is beneficial for performance. We evaluate FB-AI-Trim using 173 unseen graphs, and compare it against four different static trimming models. Our results demonstrate that, over the set of graphs, FB-AI-Trim is the fastest algorithm. Furthermore, FB-AI-Trim is, in 80% of the cases, less than 10% slower than the best performing model on a single graph. Finally, FB-AI-Trim shows significant performance degradation in less than 3% of the graphs.</p

Blood-borne origin of neointimal smooth muscle cells in transplant arteriosclerosis

Transplant arteriosclerosis (TA) is a major complication after solid organ transplantation. TA is characterized by persistent perivascular inflammation and concentric intimal thickening consisting of α-actin-positive vascular smooth muscle (VSM) cells. The current view on TA is that donor-derived medial VSM cells of affected arteries migrate and proliferate into the subendothelial space, resulting in luminal narrowing. Following this concept, the VSM cells present in the arteriosclerotic lesions are of donor origin. In this study, the authors analyzed the origin (donor vs recipient) of endothelium (EC) and neointimal α-actin-positive VSM cells in 2 different experimental transplant models. Aortic and cardiac allografting was performed in the PVG (RT-1c) to AO (RT-1u) rat strain combination. Aorta recipients were not immunosuppressed, whereas cardiac allograft recipients were intrathymically immune modulated to prevent acute rejection. Transplants were performed from female donor to male recipient rats. The α-actin-positive VSM cells present in arteriosclerotic lesions, in aortic as well as cardiac allografts, were of recipient, rather than donor, origin. Following aortic allografts, the ECs are completely replaced by host-derived ECs, whereas in cardiac allografts the ECs are still of donor origin.</p

MyoD-positive myoblasts are present in mature fetal organs lacking skeletal muscle

The epiblast of the chick embryo gives rise to the ectoderm, mesoderm, and endoderm during gastrulation. Previous studies revealed that MyoD-positive cells were present throughout the epiblast, suggesting that skeletal muscle precursors would become incorporated into all three germ layers. The focus of the present study was to examine a variety of organs from the chicken fetus for the presence of myogenic cells. RT-PCR and in situ hybridizations demonstrated that MyoD-positive cells were present in the brain, lung, intestine, kidney, spleen, heart, and liver. When these organs were dissociated and placed in culture, a subpopulation of cells differentiated into skeletal muscle. The G8 antibody was used to label those cells that expressed MyoD in vivo and to follow their fate in vitro. Most, if not all, of the muscle that formed in culture arose from cells that expressed MyoD and G8 in vivo. Practically all of the G8-positive cells from the intestine differentiated after purification by FACS®. This population of ectopically located cells appears to be distinct from multipotential stem cells and myofibroblasts. They closely resemble quiescent, stably programmed skeletal myoblasts with the capacity to differentiate when placed in a permissive environment

Hidden sector effects on double higgs production near threshold at the LHC

In this letter we study a novel effect of a hidden sector coupling to the standard model Higgs boson: an enhancement of the Higgs pair production cross section near threshold due to bound state effects. After summing the ladder contributions of the hidden sector to the effective $ggHH$ coupling, we find the amplitude for gluon-gluon scattering via a Higgs loop. We relate this amplitude to the double Higgs production cross section via the optical theorem. We find that enhancements of the order of 100 for the partonic cross section near the threshold region can be obtained for a hidden sector strongly coupled to the Higgs boson. The corresponding cross section at the LHC can be as large as a factor of 10 times the SM result for extreme values of the coupling. The detection of such an effect could in principle lead to important information about the hidden sector.Comment: 7 pages, 2 figures. Matches published versio

PI 3-kinase delta enhances axonal PIP3 to support axon regeneration in the adult CNS

Peripheral nervous system (PNS) neurons support axon regeneration into adulthood, whereas central nervous system (CNS) neurons lose regenerative ability after development. To better understand this decline whilst aiming to improve regeneration, we focused on phosphoinositide 3-kinase (PI3K) and its product phosphatidylinositol(3,4,5)-trisphosphate (PIP3). We demonstrate that adult PNS neurons utilise two catalytic subunits of PI3K for axon regeneration: p110α and p110δ. However in the CNS, axonal PIP3 decreases with development at the time when axon transport declines and regenerative competence is lost. Overexpressing p110α in CNS neurons had no effect, however expression of p110δ restored axonal PIP3 and increased regenerative axon transport. p110δ expression enhanced CNS regeneration in both rat and human neurons and in transgenic mice, functioning in the same way as the hyperactivating H1047R mutation of p110α. Furthermore, viral delivery of p110δ promoted robust regeneration after optic nerve injury. These findings establish a deficit of axonal PIP3 as a key reason for intrinsic regeneration failure and demonstrate that native p110δ facilitates axon regeneration by functioning in a hyperactive fashion

Understanding (and tackling) need satisfier escalation

Contemporary consumption patterns, embedded in profit-maximizing economic systems, are driving a worsening socio-ecological crisis, in particular through the escalating production and consumption of goods with high material and/or energy intensity. Establishing minimum and maximum standards of consumption (or “consumption corridors”) has been suggested as a way to address this crisis. Consumption corridors provide the normative basis for sustainable consumption, that is, enough consumption for individuals to satisfy needs, but not too much to collectively surpass environmental limits. Current consumption patterns (especially in the global North) do not yet fall within consumption corridors, and standards are not fixed over time. Consumption is socially constructed and can escalate due to socio-economic, technological, or infrastructural influences. In this article, we propose a framework to understand such escalating trends. This approach can be used as a tool for comprehending how consumption evolves over time, as well as for identifying the most effective leverage points to intervene and prevent escalation from happening in the first place. We build on theories of human-need satisfaction and combine these conceptual understandings with insights from research on socio-technical provisioning systems, sociological approaches to consumption, and perspectives on infrastructure lock-in. We illustrate our framework by systemically considering escalation for a specific technological product – the private car

A Logic Test Chip for Optimal Test and Diagnosis

<p>The benefits of the continued progress in integrated circuit manufacturing have been numerous, most notably in the explosion of computing power in devices ranging from cell phones to cars. Key to this success has been strategies to identify, manage, and mitigate yield loss. One such strategy is the use of test structures to identify sources of yield loss early in the development of a new manufacturing process. However, the aggressive scaling of feature dimensions, the integration of new materials, and the increase in structural complexity in modern technologies has challenged the capabilities of conventional test structures. To help address these challenges, a new logic test chip, called the Carnegie Mellon Logic Characterization Vehicle (CM-LCV), has been developed. The CM-LCV utilizes a two- dimensional array of functional unit blocks (FUBs) that each implement an innovative functionality. Properties including fault coverage, logical and physical design features, and fault distinguishability are shown to be composable within the FUB array; that is, they exist regardless of the size and composition of the FUB array. A synthesis ow that leverages this composability to adapt the FUB array to a wide range of test chip design requirements is presented. The connection between the innovative FUB functionality and orthogonal Latin squares is identified and used to analyze the universe of possible FUB functions. Two additional variants to the FUB array are also developed: heterogenous FUB arrays utilize multiple FUB functions to improve the synthesis ow performance, while pipelined FUB arrays incorporate sequential circuit elements (e.g., ip- ops and latches) that are absent from the original combinational FUB array. In addition to the design of the CM-LCV, methods for testing it are presented. Techniques to create minimal sets of test patterns that exhaustively exercise each FUB within the FUB array are developed. Additional constraints are described for the heterogenous and pipelined FUB arrays that allow these techniques to be applied for both variant FUB arrays. Furthermore, a simple built-in self test (BIST) scheme is described and applied to a reference design, resulting in a 88.0% reduction in the number of test cycles required without loss in fault coverage. A hierarchical FUB array diagnosis methodology (HFAD) is also presented for the CM- LCV that leverages its unique properties to improve performance for multiple defects. Experiments demonstrate that this HFAD methodology is capable of perfect accuracy in 93.1% of simulations with two injected faults, an improvement on the state-of-the-art commercial diagnosis. Additionally, silicon fail data was collected from a CM-LCV manufactured using a 14nm process by an industry partner. A comparison of the diagnosis results for the 1,375 fail logs examined shows that the HFAD methodology discovers additional defects during multiple defect diagnosis that the commercial tool misses for 40 of the diagnosed fail logs. Examination of these cases shows that the additional defects found by the HFAD methodology can result in improved diagnosis confidence and more precise descriptions of the defect behavior(s). The contributions of this dissertation can thus be summarized as the description of the design, test, and diagnosis of a new logic test chip for use in yield learning during process development. This CM-LCV can be adapted to meet a wide range of test chip requirements, can be efficiently and rigorously tested, and exhibits properties that can be used to improve diagnosis outcomes. All of these claims are validated through both simulated experiments and silicon data.</p