The Motion of a Body in Newtonian Theories

A theorem due to Bob Geroch and Pong Soo Jang ["Motion of a Body in General Relativity." Journal of Mathematical Physics 16(1), (1975)] provides the sense in which the geodesic principle has the status of a theorem in General Relativity (GR). Here we show that a similar theorem holds in the context of geometrized Newtonian gravitation (often called Newton-Cartan theory). It follows that in Newtonian gravitation, as in GR, inertial motion can be derived from other central principles of the theory.Comment: 12 pages, 1 figure. This is the version that appeared in JMP; it is only slightly changed from the previous version, to reflect small issue caught in proo

ECLSS advanced automation preliminary requirements

A description of the total Environmental Control and Life Support System (ECLSS) is presented. The description of the hardware is given in a top down format, the lowest level of which is a functional description of each candidate implementation. For each candidate implementation, both its advantages and disadvantages are presented. From this knowledge, it was suggested where expert systems could be used in the diagnosis and control of specific portions of the ECLSS. A process to determine if expert systems are applicable and how to select the expert system is also presented. The consideration of possible problems or inconsistencies in the knowledge or workings in the subsystems is described

Mathematically optimized cryoprotectant equilibration procedures for cryopreservation of human oocytes

Background Simple and effective cryopreservation of human oocytes would have an enormous impact on the financial and ethical constraints of human assisted reproduction. Recently, studies have demonstrated the potential for cryopreservation in an ice-free glassy state by equilibrating oocytes with high concentrations of cryoprotectants (CPAs) and rapidly cooling to liquid nitrogen temperatures. A major difficulty with this approach is that the high concentrations required for the avoidance of crystal formation (vitrification) also increase the risk of osmotic and toxic damage. We recently described a mathematical optimization approach for designing CPA equilibration procedures that avoid osmotic damage and minimize toxicity, and we presented optimized procedures for human oocytes involving continuous changes in solution composition. Methods Here we adapt and refine our previous algorithm to predict piecewise-constant changes in extracellular solution concentrations in order to make the predicted procedures easier to implement. Importantly, we investigate the effects of using alternate equilibration endpoints on predicted protocol toxicity. Finally, we compare the resulting procedures to previously described experimental methods, as well as mathematically optimized procedures involving continuous changes in solution composition. Results For equilibration with CPA, our algorithm predicts an optimal first step consisting of exposure to a solution containing only water and CPA. This is predicted to cause the cells to initially shrink and then swell to the maximum cell volume limit. To reach the target intracellular CPA concentration, the cells are then induced to shrink to the minimum cell volume limit by exposure to a high CPA concentration. For post-thaw equilibration to remove CPA, the optimal procedures involve exposure to CPA-free solutions that are predicted to cause swelling to the maximum volume limit. The toxicity associated with these procedures is predicted to be much less than that of conventional procedures and comparable to that of the corresponding procedures with continuous changes in solution composition. Conclusions The piecewise-constant procedures described in this study are experimentally facile and are predicted to be less toxic than conventional procedures for human oocyte cryopreservation. Moreover, the mathematical optimization approach described here will facilitate the design of cryopreservation procedures for other cell types.This work was supported by a National Science Foundation grant (#1150861) to Adam Higgins. This article is made openly accessible in part by an award from the Northern Illinois University Libraries’ Open Access Publishing Fund

A diagnostic prototype of the potable water subsystem of the Space Station Freedom ECLSS

In analyzing the baseline Environmental Control and Life Support System (ECLSS) command and control architecture, various processes are found which would be enhanced by the use of knowledge based system methods of implementation. The most suitable process for prototyping using rule based methods are documented, while domain knowledge resources and other practical considerations are examined. Requirements for a prototype rule based software system are documented. These requirements reflect Space Station Freedom ECLSS software and hardware development efforts, and knowledge based system requirements. A quick prototype knowledge based system environment is researched and developed

Microelectromechanical systems Coulter counter for cell monitoring and counting

This note describes the design, fabrication, and testing of a novel microelectromechanical systems Coulter counter. The Coulter counter will be used to detect and monitor impedance changes of cells as a function of time in response to different experimental extracellular environments. The device consists of SU-8 (negative photoresist ) microchannels, vertical electroplated electrodes, polydimethylsiloxane cover, and is divided into a passive mixing region, a focusing region using negative dielectrophoretic forces, and a measuring region defined by multiple electroplated electrode pairs. The devices were tested using both microbeads in saline water and fibroblast cells in phosphate buffered saline solution. The results show that the proposed microsystem is capable of monitoring impedance of cells at different positions along the Coulter microchannel

Osmotic characteristics and fertility of murine spermatozoa collected in different solutions

Osmotic stress is an important factor that can result in cell damage during cryopreservation. Before ejaculation or collection for cryopreservation, murine spermatozoa are stored in epididymal fluid, a physiologically hyperosmotic environment (w415 mmol/kg). The objectives of this study were to determine the osmotic tolerance limits of sperm motion parameters of ICR and C57BL/6 mouse spermatozoa collected in isosmotic (290 mmol/kg) and hyperosmotic (415 mmol/kg) media, and the effect of the osmolality of sperm collection media on sperm fertility after cryopreservation. Our results indicate that murine spermatozoa collected in media with different osmolalities (290 and 415 mmol/kg Dulbecco’s phosphate buffered saline (DPBS)) appeared to have different osmotic tolerances for the maintenance of sperm motility and other motion parameters in both mouse strains. The hypo- and hyperosmotic treatments decreased motility and affected other motion parameters of spermatozoa collected in 290 mmol/kg DPBS. The extent of the change of motion parameters after treatments corresponded with the levels of osmotic stress. However, for spermatozoa collected in 415 mmol/kg DPBS, exposure to 290 mmol/kg DPBS tended to increase sperm motility and the quality of their motion parameters. The osmolality of sperm collection medium can affect murine sperm fertility. Spermatozoa collected in 415 mmol/kg medium showed higher fertility compared with spermatozoa collected in 290 mmol/kg as assessed by IVF. Results characterizing murine sperm osmotic tolerance collected in media with different osmolalities from different strains and the effect of collection media osmolality on sperm fertility after cryopreservation will be useful in designing cryopreservation protocols

Impact of \u3cem\u3eMYH6\u3c/em\u3e Variants in Hypoplastic Left Heart Syndrome

Hypoplastic left heart syndrome (HLHS) is a clinically and anatomically severe form of congenital heart disease (CHD). Although prior studies suggest that HLHS has a complex genetic inheritance, its etiology remains largely unknown. The goal of this study was to characterize a risk gene in HLHS and its effect on HLHS etiology and outcome. We performed next-generation sequencing on a multigenerational family with a high prevalence of CHD/HLHS, identifying a rare variant in the α-myosin heavy chain (MYH6) gene. A case-control study of 190 unrelated HLHS subjects was then performed and compared with the 1000 Genomes Project. Damaging MYH6 variants, including novel, missense, in-frame deletion, premature stop, de novo, and compound heterozygous variants, were significantly enriched in HLHS cases (P \u3c 1 × 10−5). Clinical outcomes analysis showed reduced transplant-free survival in HLHS subjects with damaging MYH6 variants (P \u3c 1 × 10−2). Transcriptome and protein expression analyses with cardiac tissue revealed differential expression of cardiac contractility genes, notably upregulation of the β-myosin heavy chain (MYH7) gene in subjects with MYH6 variants (P \u3c 1 × 10−3). We subsequently used patient-specific induced pluripotent stem cells (iPSCs) to model HLHS in vitro. Early stages of in vitro cardiomyogenesis in iPSCs derived from two unrelated HLHS families mimicked the increased expression of MYH7 observed in vivo (P \u3c 1 × 10−2), while revealing defective cardiomyogenic differentiation. Rare, damaging variants in MYH6 are enriched in HLHS, affect molecular expression of contractility genes, and are predictive of poor outcome. These findings indicate that the etiology of MYH6-associated HLHS can be informed using iPSCs and suggest utility in future clinical applications

Antigen depot is not required for alum adjuvanticity

Alum adjuvants have been in continuous clinical use for more than 80 yr. While the prevailing theory has been that depot formation and the associated slow release of antigen and/or inflammation are responsible for alum enhancement of antigen presentation and subsequent T- and B-cell responses, this has never been formally proven. To examine antigen persistence, we used the chimeric fluorescent protein EαGFP, which allows assessment of antigen presentation in situ, using the Y-Ae antibody. We demonstrate that alum and/or CpG adjuvants induced similar uptake of antigen, and in all cases, GFP signal did not persist beyond 24 h in draining lymph node antigen-presenting cells. Antigen presentation was first detectable on B cells within 6–12 h of antigen administration, followed by conventional dendritic cells (DCs) at 12–24 h, then finally plasmacytoid DCs at 48 h or later. Again, alum and/or CpG adjuvants did not have an effect on the magnitude or sequence of this response; furthermore, they induced similar antigen-specific T-cell activation in vivo. Notably, removal of the injection site and associated alum depot, as early as 2 h after administration, had no appreciable effect on antigen-specific T- and B-cell responses. This study clearly rules out a role for depot formation in alum adjuvant activity

A hybrid bipy–NHC ligand for the construction of group 11 mixed-metal bimetallic complexes

An asymmetric bipy/NHC ligand L has been used to construct Au/Au, Au/Ag and Au/Cu bimetallic complexes through prior coordination of the NHC to Au(I) and subsequent introduction of the second group 11 metal ion at the bipy donor of the hybrid ligand. The complex [Au(κC-L)2]BF4, 1, has been used as the precursor for the formation of [AuAg(κ-CAu,κ2-N,N′Ag-1)2](BF4)2, 2a, [AuCu(κ-CAu,κ2-N,N′Cu-1)2](BF4)2, 2b and [AuAu′(κ-CAu/Au′,κ1-NAu/Au′-1)2](BF4)2, 3