Statement of William J. Kilberg Before the Commission on the Future of Worker-Management Relations

Testimony_Kilberg_022494.pdf: 233 downloads, before Oct. 1, 2020

TechSat 21 and Revolutionizing Space Missions using Microsatellites

The Air Force Research Laboratory (AFRL) TechSat 21 flight experiment demonstrates a formation of three microsatellites flying in formation to operate as a “virtual satellite.” X-band transmit and receive payloads on each of the satellites form a large sparse aperture system. The satellite formation can be configured to optimize such varied missions as radio frequency (RF) sparse aperture imaging, precision geolocation, ground moving target indication (GMTI), single-pass digital terrain elevation data (DTED), electronic protection, single-pass interferometric synthetic aperture radar (IF-SAR), and high data-rate, secure communications. Benefits of such a microsatellite formation over single large satellites include unlimited aperture size and geometry, greater launch flexibility, higher system reliability, easier system upgrade, and low cost mass production. Key research has focused on the areas of formation flying and sparse aperture signal processing and been sponsored and guided by the Air Force Office of Scientific Research (AFOSR). The TechSat 21 Program Preliminary Design Review (PDR) was held in April 2001 and incorporated the results of extensive system trades to achieve a light-weight, high performance satellite design. An overview of experiment objectives, research advances, and satellite design is presented

Design principles for higher education teacher development: the Teknosofikum course/concept

This study moves from the research question: how to design a professional course/concept for the development of higher education teachers’ digital competences? It presents Teknosofikum, a project funded by the Danish Ministry of Higher Education and Science between 2020 and 2023. The outcome of the project is a course for higher education teachers with a focus on digital competence. Grounded in sociomaterial theories, digital competence refers here to the capacity to develop agency towards professional changes driven by technology. It comprises teachers’ abilities to evaluate why, when, how and with what effects to include digital technologies in teaching. The study draws on qualitative and quantitative data gathered through design-based research along the first three course iterations, with a total of 64 participants. The findings show the emergence of three design principles: (i) relational approach to technology; (ii) praxis; and (iii) organized non-linearity. These principles will guide the final format of Teknosofikum course/concept.  This study moves from the research question: how to design a professional course/concept for the development of higher education teachers’ digital competences? It presents Teknosofikum, a project funded by the Danish Ministry of Higher Education and Science between 2020 and 2023. The outcome of the project is a course for higher education teachers with a focus on digital competence. Grounded in sociomaterial theories, digital competence refers here to the capacity to develop agency towards professional changes driven by technology. It comprises teachers’ abilities to evaluate why, when, how and with what effects to include digital technologies in teaching. The study draws on qualitative and quantitative data gathered through design-based research along the first three course iterations,with a total of 64 participants. The findings show the emergence of three design principles: (i) relational approach to technology; (ii) praxis; and (iii)organized non-linearity. These principles will guide the final format of Teknosofikum course/concept

Asparagine Synthetase in Cancer: Beyond Acute Lymphoblastic Leukemia

Asparagine Synthetase (ASNS) catalyzes the synthesis of the non-essential amino acid asparagine (Asn) from aspartate (Asp) and glutamine (Gln). ASNS expression is highly regulated at the transcriptional level, being induced by both the Amino Acid Response (AAR) and the Unfolded Protein Response (UPR) pathways. Lack of ASNS protein expression is a hallmark of Acute Lymphoblastic Leukemia (ALL) blasts, which, therefore, are auxotrophic for Asn. This peculiarity is the rationale for the use of bacterial L-Asparaginase (ASNase) for ALL therapy, the first example of anti-cancer treatment targeting a tumor-specific metabolic feature. Other hematological and solid cancers express low levels of ASNS and, therefore, should also be Asn auxotrophs and ASNase sensitive. Conversely, in the last few years, several reports indicate that in some cancer types ASNS is overexpressed, promoting cell proliferation, chemoresistance, and a metastatic behavior. However, enhanced ASNS activity may constitute a metabolic vulnerability in selected cancer models, suggesting a variable and tumor-specific role of the enzyme in cancer. Recent evidence indicates that, beyond its canonical role in protein synthesis, Asn may have additional regulatory functions. These observations prompt a re-appreciation of ASNS activity in the biology of normal and cancer tissues, with particular attention to the fueling of Asn exchange between cancer cells and the tumor microenvironment

Effects of sodium and amino acid substrate availability upon the expression and stability of the SNAT2 (SLC38A2) amino acid transporter

The SNAT2 (SLC38A2) System A amino acid transporter mediates Na+-coupled cellular uptake of small neutral α-amino acids (AAs) and is extensively regulated in response to humoral and nutritional cues. Understanding the basis of such regulation is important given that AA uptake via SNAT2 has been linked to activation of mTORC1; a major controller of many important cellular processes including, for example, mRNA translation, lipid synthesis, and autophagy and whose dysregulation has been implicated in the development of cancer and conditions such as obesity and type 2 diabetes. Extracellular AA withdrawal induces an adaptive upregulation of SNAT2 gene transcription and SNAT2 protein stability but, as yet, the sensing mechanism(s) that initiate this response remain poorly understood although interactions between SNAT2 and its substrates may play a vital role. Herein, we have explored how changes in substrate (AA and Na+) availability impact upon the adaptive regulation of SNAT2 in HeLa cells. We show that while AA deprivation induces SNAT2 gene expression, this induction was not apparent if extracellular Na+ was removed during the AA withdrawal period. Furthermore, we show that the increase in SNAT2 protein stability associated with AA withdrawal is selectively repressed by provision of SNAT2 AA substrates (N-methylaminoisobutyric acid and glutamine), but not non-substrates. This stabilization and substrate-induced repression were critically dependent upon the cytoplasmic N-terminal tail of SNAT2 (containing lysyl residues which are putative targets of the ubiquitin-proteasome system), because “grafting” this tail onto SNAT5, a related SLC38 family member that does not exhibit adaptive regulation, confers substrate-induced changes in stability of the SNAT2-5 chimeric transporter. In contrast, expression of SNAT2 in which the N-terminal lysyl residues were mutated to alanine rendered the transporter stable and insensitive to substrate-induced changes in protein stability. Intriguingly, SNAT2 protein stability was dramatically reduced in the absence of extracellular Na+ irrespective of whether substrate AAs were present or absent. Our findings indicate that the presence of extracellular Na+ (and potentially its binding to SNAT2) may be crucial for not only sensing SNAT2 AA occupancy and consequently for initiating the adaptive response under AA insufficient conditions, but for enabling substrate-induced changes in SNAT2 protein stability

Intensified gradients for endogenous amino acid substrates for transport system L on injecting a specific competitor for that system

The injection into the rat of 8.1 mmoles of amino(+/-) -2- aminobicycloheptane-2-carboxylic acid per kg body weight intensified in 2 hr the gradients of several System L substrates characteristically maintained by the liver with respect to the blood plasma. The gradients of amino acids predominantly transported by systems other than L were not, with the exception of proline, significantly influenced. We interpret this effect on System L substrates as supporting the principal service of System L in net cellular exodus of these amino acids, although other factors in the effects are not necessarily excluded.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/24279/1/0000545.pd