1977 — 1987 |
Laskowski, Michael |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Syntheses of Peptide Bonds Catalyzed by Proteinases |
1 |
1982 — 1985 |
Laskowski, Michael Coscia, Carmine [⬀] |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Subcellular Localization of Opiate Receptors |
0.961 |
1985 — 1996 |
Laskowski, Michael |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Protein Proteinase Inhibitors @ Purdue University West Lafayette
We are attempting to determine the influence on each amino acid residue in an approximately 60 residue Kazal type inhibitory domain upon the inhibitory activity of the domain. To this end we are determining the amino acid sequences of numerous avian ovomucoids, crocodilian ovomucoids, avian and crocodilian ovoinhibitors and of pancreatic trypsin inhibitors and seminal acrosin inhibitors. We are particularly focusing our attention upon finding domains, which differ by only one amino acid residue, but show differences in inhibitory activity. When this task proves too difficult we attempt to prepare the needed domains by semisynthetic enzymatic replacement of individual amino acid residues. When the needed domains are available we determine for them the value of the equilibrium constant for peptide bond hydrolysis, K-hyd and the association equilibrium constant, K-assoc, as well as the kinetic rate constants for association k-assoc and k-assoc and dissociation k-off and k-off. We are presently developing techniques for very rapid determination of these parameters since we are interested in at least 100 inhibitory domains and in about 10 serine proteinases (trypsin, kallikrein, acrosin, chymotrypsins A, B, C, elastases 1 and 2, subtilisins Carlsberg and BPN').
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1 |
1988 — 2004 |
Laskowski, Michael B. |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Development of Innervation Topography in Muscle
Over the last several years, the PI and his colleagues have shown that motoneuron pools map onto muscles with a rostrocaudal positional bias. Detailed studies from their lab revealed that this topographic map is detectable in embryonic muscles upon first contact between nerve and muscle, and is partially restored after denervation. They have developed and important model of synaptic competition during reinnervation, where they can predict with 95% accuracy the survivor between two competing nerve terminals. They have also developed an in vitro model to identify muscle membrane-bound labels that may be responsible for the positional bias. They have bound selective growth of embryonic spinal cord neurites on membranes derived from embryonic rostral or caudal muscles. They have also found selective growth of embryonic spinal cord neurites on membrane derived from transgenic muscle cell lines bearing a heritable memory for rostrocaudal position. They propose a series of experiments to extend these observations. First, using the serratus anterior (SA) muscle as a model of synaptic competition during reinnervation, they will use activity-dependent fluorescent dyes to differentially label nerve terminals in dually- innervated end-plates receiving inputs from both C6 and C7 ventral roots. Second, building upon their observations that embryonic caudal spinal cord neurites grow selectively on caudal muscle membranes, they will determine the period of expression of a label during development, and whether a continuous gradient of the label is expressed along the rostrocaudal axis. Third, they will experimentally manipulate the spinal cord neurites or substrate to test the behavior of neurites on gradients of membranes or carpets of only one membrane type. They will also ask whether sensory neurites respond to a positional label expressed by muscle membranes. Fourth, they will ask whether the label is expressed in rostral or caudal membranes (or both). Whether recognition of the label occurs between rat and chick tissues, and whether it leads to growth cone collapse. They will also extend their observations of selective growth of neurites on membranes derived from transgenic muscle cells. Finally, they will begin a series of experiments in an attempt to isolate and characterize the positional label such as developing and testing antibodies against the label, and determining its molecular mature, as a prelude to its isolation. Results of these studies will provide unique insight into how neurites in the peripheral nervous system recognize and synapse with their positionally matched partners. We will also learn whether positional labels in the neuromuscular system are part of a general scheme for encoding position in the nervous system.
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0.919 |
1994 — 1997 |
Laskowski, Michael Chris [⬀] |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Mathematical Sciences: Inevitability in Model Theory @ University of Maryland College Park
9403701 Laskowski Dr. Michael Laskowski will continue his research in the field of model theory, a branch of mathematical logic. He expects to obtain more information as to the possible mechanisms making a type inevitable in the setting of superstable theories that do not have the Dimensional Order Property (DOP). Laskowski expects to complete his classification of those countable theories for which there are two non-isomorphic models that can be forced isomorphic by a forcing with the countable chain condition. Finally, he will continue his research into an inherent asymmetry between two new methods of constructing models of small, superstable theories. Most of the field of model theory (as a branch of mathematical logic) is concerned with developing methods for building algebraic structures with certain properties. The problem of whether there is a structure having an element satisfying an infinite set of properties (i.e., realizing a type) is well understood: such a structure exists if and only if, for every finite subset of the type, there is an element satisfying each of these properties. However, it is a much more subtle question to ask whether a given type is inevitable, i.e., whether EVERY structure contains an element realizing the type. Without adding additional restrictions to the class of structures under consideration, it is known that there can be no satisfactory criterion for which types are inevitable. Laskowski will continue his research on what additional constraints must be placed on the algebraic structure to yield a natural characterization of inevitability. ***
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0.919 |
1997 — 2007 |
Laskowski, Michael Chris [⬀] |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Topics in Model Theory @ University of Maryland College Park
The Principal Investigator proposes to continue his research on five problems of model theory, a branch of mathematical logic. The first three problems are connected with extending and generalizing Shelah's dichotomy theorem. Specifically, the PI proposes to study the possible types of branching that can occur in decomposition trees of models of classifiable theories, inherent limitations on extending Shelah's theorem to uncountable languages, and those theories whose models are characterized by systems of invariants involving finite subsets of the model. The first of these problems emanated from the completion of the classification of the uncountable spectra of countable theories. The last two problems deal with new methods of constructing models that are reminiscent of forcing constructions. In work with Shelah, the PI defined two new methods of constructing models of small, stable theories with a type of infinite multiplicity, one based on choosing realizations of the type with positive measure and the other based on choosing non-meager realizations. Whereas the notions of measure and category typically go hand in hand throughout mathematics, there is an essential asymmetry between the notions in this context. The final problem is to investigate the feasibility of obtaining an o-minimal expansion of the reals containing a function whose growth rate exceeds any exponential polynomial. It seems possible that by using new results of Wilkie and Macintyre, such an expansion could be constructed in the manner of Cohen forcing. As the term is used here, "model theory" is essentially the systematic study of algebraic structures. A theory is simply a set of sentences and its class of models consists of the possible universes in which each of the sentences of the theory is true. It turns out that if one asks rather general questions about the class of models of a theory (such as the number of models of a certain size) the answer depends only on a small set of combinations of elements. Tha t is, the number of models of a certain size is determined by which of these combinations are permitted by the theory and which are prohibited. Much of the focus of this proposal is to better understand what these sets of combinations look like in various contexts. The study of some of these sets of combinations has recently found applications in PAC learning theory and in the study of the expressive power of neural network architectures.
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0.919 |
2001 — 2003 |
Laskowski, Michael |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Predicting Protein Reactivity From the Sequence Alone @ Purdue University West Lafayette
The increased availability of sequences raises the need for sequence to reactivity algorithms, SRA, which quantitatively predict the reactivity of members of a family of proteins from their sequence alone. An algorithm for predicting the standard free energies of association between six selected serine proteinases and a large subset of Kazal family inhibitors was just developed in our laboratory. It was tested by comparing its predictions to already known results for 92 natural avian ovomucoid third domains and on five other, quite unrelated, Kazal family inhibitors. The SRA allows us to predict the best possible, most specific possible and least specific possible sequences for the six enzymes. We plan to express these and test them as an additional important test. Numerous other design objectives are possible. This should be highly useful in drug design either directly as proteins or as models for peptidomimetics. The SRA is additivity based and the tests confirm that additivity holds very well for most residue pairs. However, the pair P2 and P1' is a clear exception and at this time, we cannot predict for pairs that we did not measure. We propose to remove this restriction thus greatly widening the SRA. A number of other restrictions will also be eliminated. The SRA will be more useful to biologists when it is extended to more enzymes. Additivity within a family is called intrascaffolding additivity. Additivity between families is called as interscaffolding additivity and will continue to be studied. Aside from the standard free energy of association, the enthalpy, entropy, heat capacity change, the on and off rate constants, the pH dependence and the equilibrium constant for the reactive site peptide bond hydrolysis are expected to be largely additive. These will be studied on the existing variant set. About 10 percent of the cases tested are nonadditive. These will be selected for detailed study with the aim of elucidating how additivity fails and incorporating corrections into the SRA for such failures. It is anticipated that the ability to correct will be even more important when defining SRAs for other less additive systems.
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1 |
2001 — 2003 |
Laskowski, Michael B. |
P20Activity Code Description: To support planning for new programs, expansion or modification of existing resources, and feasibility studies to explore various approaches to the development of interdisciplinary programs that offer potential solutions to problems of special significance to the mission of the NIH. These exploratory studies may lead to specialized or comprehensive centers. |
Biomedical Research Infrastructure Network in Idaho |
0.919 |
2002 |
Laskowski, Michael B. |
P20Activity Code Description: To support planning for new programs, expansion or modification of existing resources, and feasibility studies to explore various approaches to the development of interdisciplinary programs that offer potential solutions to problems of special significance to the mission of the NIH. These exploratory studies may lead to specialized or comprehensive centers. |
Supplement to Idaho Brin Program--P20 Rr16454-01
DESCRIPTION (provided by applicant): The people of the State of Idaho recognize the need for training in science and technology. They further realize the importance of biomedical research to the State's economy and the overall quality of their lives. The NIH BRIN Program offers the State of Idaho an opportunity to build its infrastructure network, and to align biomedical research in Idaho with its importance to the citizens of the State. The design of the Idaho BRIN Program centers around three cores: an Administrative Core, a Bioinformatics Core and a Research Core. In the five months since the BRIN grant was awarded to the State of Idaho, there has developed a collaborative link between the faculty of Idaho's three universities that is unprecedented. Working cooperatively we have already made significant progress in each of the cores. Our proposal for supplementary funding has two principal objectives. First, we will extend the network that now consists of the University of Idaho (UI), Idaho State University (ISU) and Boise State University (BSU) to include the six undergraduate colleges in Idaho. The goal is to provide research opportunities for students and faculty from these colleges, and to create a pipeline for the best undergraduate students into Idaho's graduate programs. The second objective of the supplement request is to direct research infrastructure funds in proportion to their likelihood of generating new NIH support. Thus a three-tier system is proposed for the support of initiatives by BRIN. Tier 1 consists of those initiatives that are most likely to achieve success in receiving NIH grant support within 12 - 18 months. Tier 2 is directed at those programs designed for an intermediate return on investment within 2 - 4 years. Tier 3 programs consist of a long-term investment yielding dividends 4 to 10 years into the future. Support for all three tiers is requested in the Supplement, but funds are apportioned according to their likelihood of generating new NIH funding in the short-term. Taken together, the initial BRIN grant has enabled Idaho to develop an unprecedented network among its universities, using resources judiciously to improve research infrastructure. The supplement will allow us to extend the network and create greater opportunities for research while retaining a clear focus on the primary goal of BRIN: to increase NIH support in Idaho. The UI, BSU and ISU working cooperatively envision a time when we will be receiving much more NIH research funding, and support from infrastructure programs such as BRIN will no longer be necessary.
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0.919 |
2004 |
Laskowski, Michael B. |
P20Activity Code Description: To support planning for new programs, expansion or modification of existing resources, and feasibility studies to explore various approaches to the development of interdisciplinary programs that offer potential solutions to problems of special significance to the mission of the NIH. These exploratory studies may lead to specialized or comprehensive centers. |
Core--Undergraduate College Outreach Program |
0.919 |
2004 |
Laskowski, Michael B. |
P20Activity Code Description: To support planning for new programs, expansion or modification of existing resources, and feasibility studies to explore various approaches to the development of interdisciplinary programs that offer potential solutions to problems of special significance to the mission of the NIH. These exploratory studies may lead to specialized or comprehensive centers. |
Core--Brin: Enhancing Core Research Facilities |
0.919 |
2004 — 2005 |
Laskowski, Michael B. |
P20Activity Code Description: To support planning for new programs, expansion or modification of existing resources, and feasibility studies to explore various approaches to the development of interdisciplinary programs that offer potential solutions to problems of special significance to the mission of the NIH. These exploratory studies may lead to specialized or comprehensive centers. |
Idaho Inbre Program
DESCRIPTION (provided by applicant): The Idaho BRIN Program has had a profound effect on biomedical research at every level and in all regions of the state. In the brief eighteen month period since the BRIN Program was implemented in Idaho, a network of research core facilities now enables researchers from all parts of the state to have access to state-of-the-art technology. This has fostered new inter-disciplinary research collaborations between faculty at the University of Idaho, Idaho State University, and Boise State University. Such inter-institutional collaborations are unprecedented in the history of Idaho, and have allowed us to focus on a single statewide theme for biomedical research, Cell Signaling. Bioinformatics, a research tool used sparsely prior to BRIN, is now applied extensively as a result of new facilities, targeted training sessions and undergraduate and graduate level courses. BRIN has enabled us to assemble an educational pipeline, beginning at K-12 levels, and continuing through college and graduate schools, while offering progressively greater research experiences at each level. The INBRE Program would allow us to build on these successes, and extend the Network to undergraduate colleges and institutions throughout the state. The INBRE Program will continue the three cores established under BRIN: Administrative, Bioinformatics, Research, plus add a fourth Outreach Core. These cores will support five fundamental goals: 1) To continue to build an interdisciplinary research network under the theme of Cell Signaling; 2) To support a Network of Research Partners consisting of colleges with developing research missions; 3) To expand the Outreach Core and enhance science education and training at undergraduate colleges; and 5) To create an educated workforce that will sustain a developing biomedical industry in Idaho. All network universities, colleges, and institutions recognize the BRIN and INBRE Programs as a unique opportunity to build Idaho's research infrastructure so that our faculty can become more competitive for NIH awards. But our approach is designed to build a lasting change in the biomedical research culture in Idaho, reaching to the next generation of researchers and to the public. We anticipate that by the end of the INBRE Program the fundamental changes being made in Idaho's biomedical research enterprise will be sustainable, so that support from infrastructure programs such as INBRE will no longer be necessary.
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0.919 |
2004 |
Laskowski, Michael B. |
P20Activity Code Description: To support planning for new programs, expansion or modification of existing resources, and feasibility studies to explore various approaches to the development of interdisciplinary programs that offer potential solutions to problems of special significance to the mission of the NIH. These exploratory studies may lead to specialized or comprehensive centers. |
Brin: Wami Brin Network |
0.919 |
2004 — 2005 |
Laskowski, Michael B. |
P20Activity Code Description: To support planning for new programs, expansion or modification of existing resources, and feasibility studies to explore various approaches to the development of interdisciplinary programs that offer potential solutions to problems of special significance to the mission of the NIH. These exploratory studies may lead to specialized or comprehensive centers. |
Brin: Idaho: Pipeline to Graduate Education |
0.919 |
2004 — 2005 |
Laskowski, Michael B. |
P20Activity Code Description: To support planning for new programs, expansion or modification of existing resources, and feasibility studies to explore various approaches to the development of interdisciplinary programs that offer potential solutions to problems of special significance to the mission of the NIH. These exploratory studies may lead to specialized or comprehensive centers. |
Brin: Faculty Development Program |
0.919 |
2005 |
Laskowski, Michael B. |
P20Activity Code Description: To support planning for new programs, expansion or modification of existing resources, and feasibility studies to explore various approaches to the development of interdisciplinary programs that offer potential solutions to problems of special significance to the mission of the NIH. These exploratory studies may lead to specialized or comprehensive centers. |
Undergraduate College Outreach Program |
0.919 |
2005 |
Laskowski, Michael B. |
P20Activity Code Description: To support planning for new programs, expansion or modification of existing resources, and feasibility studies to explore various approaches to the development of interdisciplinary programs that offer potential solutions to problems of special significance to the mission of the NIH. These exploratory studies may lead to specialized or comprehensive centers. |
Brin: Idaho: Bioinformatics Core Enhancements |
0.919 |
2005 |
Laskowski, Michael B. |
P20Activity Code Description: To support planning for new programs, expansion or modification of existing resources, and feasibility studies to explore various approaches to the development of interdisciplinary programs that offer potential solutions to problems of special significance to the mission of the NIH. These exploratory studies may lead to specialized or comprehensive centers. |
Brin: Enhancing Core Research Facilities |
0.919 |
2005 — 2006 |
Laskowski, Michael B. |
P20Activity Code Description: To support planning for new programs, expansion or modification of existing resources, and feasibility studies to explore various approaches to the development of interdisciplinary programs that offer potential solutions to problems of special significance to the mission of the NIH. These exploratory studies may lead to specialized or comprehensive centers. |
Administrative Core |
0.919 |
2006 |
Laskowski, Michael B. |
P20Activity Code Description: To support planning for new programs, expansion or modification of existing resources, and feasibility studies to explore various approaches to the development of interdisciplinary programs that offer potential solutions to problems of special significance to the mission of the NIH. These exploratory studies may lead to specialized or comprehensive centers. |
Outreach Core: Pipeline to Graduate Education |
0.919 |
2006 |
Laskowski, Michael B. |
P20Activity Code Description: To support planning for new programs, expansion or modification of existing resources, and feasibility studies to explore various approaches to the development of interdisciplinary programs that offer potential solutions to problems of special significance to the mission of the NIH. These exploratory studies may lead to specialized or comprehensive centers. |
Research Core: Core Research Facilities &Infrastructure |
0.919 |
2006 |
Laskowski, Michael B. |
P20Activity Code Description: To support planning for new programs, expansion or modification of existing resources, and feasibility studies to explore various approaches to the development of interdisciplinary programs that offer potential solutions to problems of special significance to the mission of the NIH. These exploratory studies may lead to specialized or comprehensive centers. |
Research Core: Faculty Development Program |
0.919 |
2006 |
Laskowski, Michael B. |
P20Activity Code Description: To support planning for new programs, expansion or modification of existing resources, and feasibility studies to explore various approaches to the development of interdisciplinary programs that offer potential solutions to problems of special significance to the mission of the NIH. These exploratory studies may lead to specialized or comprehensive centers. |
Outreach Core: Enhancements of Traditional Teaching Colleges |
0.919 |
2006 — 2013 |
Laskowski, Michael Chris [⬀] |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Structure Theorems in Model Theory @ University of Maryland College Park
This award is funded under the American Recovery and Reinvestment Act of 2009 (Public Law 111-5).
Laskowski is continuing his research in model theory, which is a branch of mathematical logic. The bulk of his research is organized around the theme of obtaining better structure theorems in three distinct settings. He will continue his investigations of the fine structure of models of classifiable theories with an eye on extensions to uncountable languages, look for a generalization of Shelah's notion of excellence that is applicable to more classes of structures, and seek more instances where stability theoretic assumptions automatically bound the quantifier complexity of the formulas. Additionally, Laskowski will attempt to answer specific questions about dependent formulas, elementary extensions of expansions of Archimedean ordered abelian groups, the Schroeder-Bernstein property of a theory, and a long standing decidability question from symbolic dynamics.
Model theory is concerned with the interplay between theories, i.e., sets of sentences in a very formal language, and the classes of algebraic structures (models) that satisfy these sentences. There is a well established taxonomy of theories, which is based on the embeddability or non-embeddability of certain configurations of elements into models of the theory. Laskowski has identified certain classes of theories that have direct connections to limitations on data compression and computational learning theory, and will continue his examination of these theories.
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0.919 |
2006 |
Laskowski, Michael B. |
S10Activity Code Description: To make available to institutions with a high concentration of NIH extramural research awards, research instruments which will be used on a shared basis. |
Laser Confocal Microscope |
0.919 |
2006 |
Laskowski, Michael B. |
P20Activity Code Description: To support planning for new programs, expansion or modification of existing resources, and feasibility studies to explore various approaches to the development of interdisciplinary programs that offer potential solutions to problems of special significance to the mission of the NIH. These exploratory studies may lead to specialized or comprehensive centers. |
Bioinformatics Core |
0.919 |
2013 — 2017 |
Laskowski, Michael Chris [⬀] |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Absoluteness, Stability, and Quantifier Complexity in Model Theory @ University of Maryland College Park
Laskowski is continuing his research in model theory, which is a branch of mathematical logic. The PI's research is in three areas. It is well known that almost all of the basic notions of first-order model theory are absolute, i.e., their interpretation does not change depending on the model of set theory one is working in. The situation is known to be much more complicated for similar concepts in infinitary languages, where even simple concepts such as categoricity in power can fail to be absolute, even for cardinal preserving forcings. A few years ago, it was noted that if one places extremely strong stability theoretic conditions on a theory, then these conditions limit the quantifier complexity of the elementary diagram of any model of the theory. These bounds immediately give upper bounds on the computable complexity of definable subsets of such a theory. The model theoretic notion of definability of types over finite sets is intimately related to the notion of a compression scheme in computational learning theory. This connection has beein fruitful in both directions. A number of examples of concept classes that posess compression schemes have been identified, and conversely this connection has led to a deeper model theoretic understanding of dependent theories.
Model theory is concerned with the interplay between theories, i.e., sets of sentences in a very formal language, and the classes of algebraic structures (models) that satisfy these sentences. There is a well established taxonomy of theories, which is based on the embeddability or non-embeddability of certain configurations of elements into models of the theory. Laskowski has identified certain classes of theories that have direct connections to limitations on data compression and computational learning theory, and will continue his examination of these theories.
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0.919 |