Multiple Experimental Sets Research Articles

On the impact of central Pacific warming events on Atlantic tropical storm activity

A recent study by Kim et al. (2009) claim that central Pacific warming (CPW) events in 1969, 1991, 1994, 2002 and 2004 are associated with a greater‐than‐average frequency of tropical storms and increasing landfall potential along the Gulf of Mexico coast and Central America. Based on an independent data analysis of tropical cyclone activity in the five CPW years, it is shown here that only 1969, 2002 and 2004 were characterized with significantly greater‐than‐average cyclone activity in the Gulf of Mexico and Caribbean Sea, whereas 1991 and 1994 were characterized with significantly lower‐than‐average activity. Coincidently, the Atlantic warm pool (AWP) was significantly larger than average during 1969 and 2004, and significantly smaller than average during 1991 and 1994. By performing multiple sets of ensemble model experiments using the NCAR atmospheric general circulation model, it is shown here that the increased tropical storm frequency in 1969 and 2004 can be readily explained by a large AWP and the associated vertical wind shear reduction and enhanced moist convective instability in the main development region for Atlantic hurricanes, without invoking a remote influence from the tropical Pacific. Therefore, we conclude that it is premature to associate CPW events to an increasing frequency of cyclone activity in the Gulf of Mexico and Caribbean Sea.

Remote electronic experiments using LabVIEW over controller area network

Remote laboratories are essential for many distance learning institutions in the area of engineering. There are useful experimental sets proposed by researchers in different scientific areas. The structure of remote laboratories is still under development. This paper presents an electronic laboratory controlled by a server operated with LabVIEW software. Controller area network (CAN) behind the server computer provides multiple experimental sets running simultaneously. This architecture allows controlling multiple modules over a network using only one server computer. Key words: Remote laboratory, engineering education, controller area network.

Mathematical psychology.

Mathematical psychology is a sub-field of psychology that started in the 1950s and has continued to grow as an important contributor to formal psychological theory, especially in the cognitive areas of psychology such as learning, memory, classification, choice response time, decision making, attention, and problem solving. In addition, there are several scientific sub-areas that were originated by mathematical psychologists such as the foundations of measurement, stochastic memory models, and psychologically motivated reformulations of expected utility theory. Mathematical psychology does not include all uses of mathematics and statistics in psychology, and indeed there is a long history of such uses especially in the areas of perception and psychometrics. What is most unique about mathematical psychology is its approach to theory construction. While accepting the behaviorist dictum that the data in psychology must be observable and replicable, mathematical models are specified in terms of unobservable formal constructs that can predict detailed aspects of data across multiple experimental and natural settings. By now almost all the substantive areas of cognitive and experimental psychology have formal mathematical models and theories, and many of these are due to researchers that identify with mathematical psychology. Copyright © 2010 John Wiley & Sons, Ltd. For further resources related to this article, please visit the WIREs website.

Quadratic system identification: A statistical framework for the paired-pulse paradigm

System Identification refers to the problem of identifying a model or description of a system based on a stretch of input and the corresponding output from the system. The paired-pulse paradigm or the conditioning test pulse paradigm is often used in neurophysiology experiments. In this work we provide a statistical framework for the conditioning test pulse paradigm which also serves as a system identification tool for quadratic or second order Volterra systems. A nonparametric spectral domain based methodology is proposed for the quadratic system identification. It is shown that by carrying out the analysis in the spectral domain one needs to perform only a single set of double pulse experiments as opposed to multiple sets of experiments in the time domain. Simulation studies are performed to assess the performance of the methodology and to study the conditions under which the methods are expected to perform well.

A novel meta-analysis method exploiting consistency of high-throughput experiments

Large-scale biological experiments provide snapshots into the huge number of processes running in parallel within the organism. These processes depend on a large number of (hidden) (epi)genetic, social, environmental and other factors that are out of experimentalists' control. This makes it extremely difficult to identify the dominant processes and the elements involved in them based on a single experiment. It is therefore desirable to use multiple sets of experiments targeting the same phenomena while differing in some experimental parameters (hidden or controllable). Although such datasets are becoming increasingly common, their analysis is complicated by the fact that the various biological elements could be influenced by different sets of factors. The central hypothesis of this article is that biologically related elements and processes are affected by changes in similar ways while unrelated ones are affected differently. Thus, the relations between related elements are more consistent across experiments. The method outlined here looks for groups of elements with robust intra-group relationships in the expectation that they are related. The major groups of elements may be identified in this way. The strengths of relationships per se are not valued, just their consistency. This represents a completely novel and unutilized source of information. In the analysis of time course microarray experiments, I found cell cycle- and ribosome-related genes to be the major groups. Despite not looking for these groups in particular, the identification of these genes rivals that of methods designed specifically for this purpose. A C++ implementation is available at http://www.rinst.org/ICS/ICS_Programs.tar.gz.

Rooting into the Soil, a Model for the Role of Sox4 in Leukemia

Development and progression of leukemia requires interaction of leukemia-initiating cells with their bone marrow niches. The niches serve as the nursery and shelter for the leukemic cells, which can result in drug resistance, disease recurrence, and minimal residual disease, the most important causes for the death of patients with leukemia. Therefore, obliteration of the interaction between the leukemic cells and their niches is of utmost importance in eradicating leukemic cells during therapy to cure the disease. However, little is currently known of the molecular mechanisms underlying the interaction of the two types of cells. Sox4, a SRY-related HMG-box containing transcription factor that is vital during development, plays an important role in leukemia. Published mouse studies demonstrated that increased expression of Sox4 was associated with leukemogenesis. We determined the expression levels of Sox4 by real-time RT-PCR in 100 human leukemic samples and found high levels of expression in B- and T-ALL, but not in AML, CML, CLL, Sezary syndrome, or T cell prolymphocytic leukemia. In accordance, 7 of the 8 ALL cell lines (the exception was 697) we tested showed high expression levels of Sox4, but AML cell lines, normal mature B cells, T cells, and bone marrow CD34+ cells had low levels of expression. Since the majority of clinical B-ALL cases correspond to the pre-B cell stage, we investigated the role of Sox4 in a pre-B cell line (Nalm6) by lentivirus-mediated RNAi. Remarkably, knockdown of Sox4 in Nalm6 cells caused 70% reduction in the formation of leukemic cell clusters under the monolayer of co-cultured M2-10B4 bone marrow stromal cells, a phenomenon known as pseudo-emperipolesis. Similar results were obtained with ex vivo cultured bone marrow cells from conditional Sox4 knockout mice that displayed B cell developmental arrest at the transition from pro-B to pre-B cell stage and an absence of pre-B cells. These findings suggested that Sox4 is required for the interaction of the developing B cells or leukemic cells with bone marrow stromal cells, a component of the bone marrow niche. Since CXCR4/SDF1-mediated “homing” is known to be required for pseudo-emperipolesis, we tested the effect of Sox4 on Nalm6 cell migration toward SDF1 gradient and found that Sox4 did not affect the migration, suggesting that Sox4 is not acting through “homing”. Instead, our data indicated that the role of Sox4 in the interaction of leukemic cells with stromal cells is most likely mediated by its ability in enhancing the adhesion of the leukemic cells because we found that lentivirus-medicated overexpression of Sox4 in the 697 B cell line caused the suspension cells to display a spindle and adhesive morphology. In addition, 21% of the putative Sox4 downstream genes that we identified by multiple sets of gene expression microarray experiments are known to be involved in cell adhesion. Moreover, we found that the changes in gene expression profile of leukemic cells upon Sox4 knockdown or overexpression significantly overlap with the changes in response to the presence of bone marrow stromal cells in co-culture, indicating that Sox4 pathways are involved in leukemic cell response to stromal cell signaling. Based on these findings we hypothesize that deletion of Sox4 abolishes the interaction between the developing lymphocytes and their niches during lymphopoiesis. Conversely, overexpression of Sox4 may enforce these cells to over-interact with the niches so that they are overexposed to local growth factor stimuli. If superimposed with other genetic and/or epigenetic changes in the developing lymphocytes, such over-interaction may result in the development of leukemia. In case of established leukemia, such over-interaction may lead to the enhanced protection of leukemic cells by their niches. Therefore, the role of Sox4 in the interaction of developing lymphocytes or leukemic cells with their niches is like “rooting into the soil” of a growing tree, abbreviated as “rooting”.

Why do some El Niños have no impact on tropical North Atlantic SST?

Warming of the Tropical North Atlantic (TNA) in boreal spring and early summer (April–June) following El Niño peaks in boreal winter is a well‐known phenomenon that involves formation of the so‐called atmospheric bridge (or teleconnection) from the Pacific. However, the existence of an El Niño in boreal winter does not guarantee a warm TNA in the following April–June (AMJ): for sixteen observed El Niño events that occurred during 1950–2005, the TNA (AMJ) remained neutral in six of them. A careful examination of the sixteen El Niño events leads to a hypothesis that if an El Niño ends before April, the TNA remains neutral. Here, we test this working hypothesis by performing multiple sets of ensemble model experiments using the NCAR atmospheric general circulation model coupled to a slab mixed layer ocean model. Analysis of the model experiments indicates that January–March (JFM) are the crucial months for the El Niño‐induced warming of TNA. Therefore, if an El Niño does not continue throughout JFM, the atmospheric bridge connecting the tropical Pacific to the TNA is not persistent enough to force the TNA, thus the TNA remains neutral. Finally, our model experiments indicate even if an El Niño continues beyond JFM, the El Niño‐induced warming of TNA in AMJ can be greatly reduced by Atlantic internal variability, and vice versa.

Early Pharmacological Treatment of Autism: A Rationale for Developmental Treatment

Autism is a dynamic neurodevelopmental syndrome in which disabilities emerge during the first three postnatal years and continue to evolve with ongoing development. We briefly review research in autism describing subtle changes in molecules important in brain development and neurotransmission, in morphology of specific neurons, brain connections, and in brain size. We then provide a general schema of how these processes may interact with particular emphasis on neurotransmission. In this context, we present a rationale for utilizing pharmacologic treatments aimed at modifying key neurodevelopmental processes in young children with autism. Early treatment with selective serotonin reuptake inhibitors (SSRIs) is presented as a model for pharmacologic interventions because there is evidence in autistic children for reduced brain serotonin synthesis during periods of peak synaptogenesis; serotonin is known to enhance synapse refinement; and exploratory studies with these agents in autistic children exist. Additional hypothetical developmental interventions and relevant published clinical data are described. Finally, we discuss the importance of exploring early pharmacologic interventions within multiple experimental settings in order to develop effective treatments as quickly as possible while minimizing risks.

Molecular Identification and Characterization of a Family of Kinases with Homology to Ca2+/Calmodulin-dependent Protein Kinases I/IV

Despite the critical importance of Ca(2+)/calmodulin (CaM)-dependent protein kinase (CaMK) II signaling in neuroplasticity, only a limited amount of work has so far been available regarding the presence and significance of another predominant CaMK subfamily, the CaMKI/CaMKIV family, in the central nervous system. We here searched for kinases with a core catalytic structure similar to CaMKI and CaMKIV. We isolated full-length cDNAs encoding three mouse CaMKI/CaMKIV-related kinases, CLICK-I (CL1)/doublecortin and CaM kinase-Like (DCAMKL)1, CLICK-II (CL2)/DCAMKL2, and CLICK-I,II-related (CLr)/DCAMKL3, the kinase domains of which had an intermediate homology not only to CaMKI/CaMKIV but also to CaMKII. Furthermore, CL1, CL2, and CLr were highly expressed in the central nervous system, in a neuron-specific fashion. CL1alpha and CL1beta were shorter isoforms of DCAMKL1, which lacked the doublecortin-like domain (Dx). In contrast, CL2alpha and CL2beta contained a full N-terminal Dx, whereas CLr only possessed a partial and dysfunctional Dx. Interestingly, despite a large similarity in the kinase domain, CL1/CL2/CLr had an impact on CRE-dependent gene expression distinct from that of the related CaMKI/CaMKIV and CaMKII. Although these were previously shown to activate Ca(2+)/cAMP-response element-binding protein (CREB)-dependent transcription, we here show that CL1 and CL2 were unable to significantly phosphorylate CREB Ser-133 and rather inhibited CRE-dependent gene expression by a dominant mechanism that bypassed CREB and was mediated by phosphorylated TORC2.

Nerve Growth Factor Translates Stress Response and Subsequent Murine Abortion via Adhesion Molecule-Dependent Pathways1

Spontaneous abortion is a frequent threat affecting 10%-25% of human pregnancies. Psychosocial stress has been suggested to be attributable for pregnancy losses by challenging the equilibrium of systems mandatory for pregnancy maintenance, including the nervous, endocrine, and immune system. Strong evidence indicates that stress-triggered abortion is mediated by adhesion molecules, i.e., intercellular adhesion molecule 1 (ICAM1) and leukocyte function associated molecule 1, now being referred to as integrin alpha L (ITGAL), which facilitate recruitment of inflammatory cells to the feto-maternal interface. The neurotrophin beta-nerve growth factor (NGFB), which has been shown to be upregulated in response to stress in multiple experimental settings including in the uterine lining (decidua) during pregnancy, increases ICAM1 expression on endothelial cells. Here, we investigated whether and how NGFB neutralization has a preventive effect on stress-triggered abortion in the murine CBA/J x DBA/2J model. We provide experimental evidence that stress exposure upregulates the frequency of abortion and the expression of uterine NGFB. Further, adhesion molecules ICAM1 and selectin platelet (SELP, formerly P-Selectin) and their ligands ITGAL and SELP ligand (SELPL, formerly P selectin glycoprotein ligand 1) respectively increase in murine deciduas in response to stress. Subsequently, decidual cytokines are biased toward a proinflammatory and abortogenic cytokine profile. Additionally, a decrease of pregnancy protective CD8alpha(+) decidual cells is present. Strikingly, all such uterine stress responses are abrogated by NGFB neutralization. Hence, NGFB acts as a proximal mediator in the hierarchical network of immune rejection by mediating an abortogenic environment comprised of classical signs of neurogenic inflammation.

Microtiter assay for glutamine synthetase biosynthetic activity using inorganic phosphate detection

A microtiter assay was developed for the improved detection of inorganic phosphate released from adenosine 5 ′-triphosphate (ATP) in the glutamine synthetase biosynthetic assay. In this assay, ascorbic acid replaces the traditionally used ferrous sulfate to reduce the phosphomolybdate complex. As a result, increased color development, linearity, and sensitivity are achieved. Additionally, in the microtiter format, multiple sets of kinetic experiments can be rapidly performed in parallel. The color that forms is rendered highly stable by the addition of sodium citrate. However, the commonly used sodium arsenite in this solution has been omitted, making the assay less hazardous. The assay is linear to 100 nmol Pi in the presence of 10 mM ATP.

Microarray analysis of xenograft-derived cancer cell lines representing multiple experimental models of human prostate cancer.

Expression analysis of 7129 transcripts was carried out in five human prostate cancer cell lines derived from orthotopic xenografts after one to five passages in nude mice and primary cultures of human normal prostate epithelial (NPE) cells. These experiments identified a consensus class of 214 genes (43 up- and 171 downregulated transcripts), expression of which was altered at least twofold in the same direction in all the cell lines relative to NPE cells. To validate the relevance of altered expression behavior of these genes for human prostate cancer, their expression pattern was evaluated in multiple additional experimental and clinical settings. Expression of 170 of these 214 genes (79%) was altered in the same direction in vivo in experimental human prostate tumors in mice. Similarly, the expression of 151 of the 214 genes (71%) was altered in the same direction in M12 cells, a variant of an SV40 large T antigen transformed normal human prostate epithelial cell line selected for increased malignancy in vivo. In clinical samples of human prostate tumors, the changes in transcript expression levels of majority of these genes (85% of downregulated and 76% of upregulated transcripts) are consistent with alterations of their expression pattern in xenograft-derived cancer cell lines. These results imply that the expression pattern of a large class of genes is consistently altered in multiple experimental models and clinical samples of human prostate cancer and underscore the potential relevance of the xenograft models and cell lines derived from them for expression analysis studies relevant to human cancer.

Inexpensive laboratory experiments for nonscience students

Students who experience acoustics rather than merely being exposed to concepts universally gain insights not otherwise available. The experience of doing rather than simply hearing greatly enhances the excitement associated with learning. With that understanding, it seems almost imperative to include a laboratory component in every acoustics course. Frequently cost precludes the use of sophisticated equipment in multiple sets of identical experiments, however, sequential use of different laboratory setups provides a simple solution to that problem. Furthermore, there are many simple devices which lend themselves to quantitative measurements, and there is available relatively low-cost computer software for rather sophisticated experiments. Among experiments to be discussed and illustrated are graphic wave addition, complex wave synthesis using a polyphonic keyboard and a computer based digital oscilloscope, standing transverse waves on a spring, standing longitudinal waves in an air column, spectral analysis using inexpensive computer software with a sound card in a PC, normal mode mapping with Chladni patterns and phase shift observation in Lissajou figures, and sound pressure level measurements.

5-Hydroxytryptamine (Serotonin): Biphasic Dose Responses

This article briefly summarizes the occurrence of biphasic dose-response relationships associated with 5-hydroxytryptamine (5-HT) receptor systems, as well as 5-HT agonists and antagonists. Such biphasic responses have been reliably reported in multiple experimental settings that explored a broad range of responses, including aggressive behavior, cardiovascular functioning, muscle relaxation, and interactions with other receptor systems such as adrenergic interaction as well as with neurotransmitters such as NMDA.

Interactions between inflammatory mediators in expression of antitumor cytostatic activity of macrophages

Antitumor properties and participation in inflammatory events are important characteristics of activated macrophages. We show here that both antitumor cytostatic function of macrophages and participation of these cells at inflammatory sites are controlled by two main groups of mediators: cytokines (IL-1, TNF alpha) and eicosanoids (prostanoids and leukotrienes). These two groups of mediators represent a complex system of mutual interactions in regulation of their production and activities. Multiple sets of experiments with murine macrophages are discussed in favor of the views that PGE2 and lipoxygenase products oppose each other's actions, and that the regulating role of PGE2 in the secretions of cytokines are of pivotal importance in antitumor cytostasis of macrophages in vitro. Such observations can be extended to a situation ex vivo, showing that human macrophages harvested from inflammatory sites have markedly augmented cytostatic expression. It thus appears that the antitumor cytostatic function of macrophages is related to the production of inflammatory mediators by these cells. Accordingly, it might be that occurrence of inflammation in tumor-bearing individuals plays a role in the promotion of antitumor activity of macrophages.