Taber Vibration Isolator for Vacuum and Cryogenic Applications

We present a procedure for the design and construction of a passive, multipole, mechanical high-stop vibration isolator. The isolator, consisting of a stack of metal disks connected by thin wires, attenuates frequencies in the kilohertz range, and is suited to both vacuum and cryogenic environments. We derive an approximate analytical model and compare its predictions for the frequencies of the normal modes to those of a finite element analysis. The analytical model is exact for the modes involving only motion along and rotation about the longitudinal axis, and it gives a good approximate description of the transverse modes. These results show that the high-frequency behavior of a multi-stage isolator is well characterized by the natural frequencies of a single stage. From the single-stage frequency formulae, we derive relationships among the various geometrical parameters of the isolator to guarantee equal attenuation in all degrees of freedom. We then derive expressions for the attenuation attainable with a given isolator length, and find that the most important limiting factor is the elastic limit of the spring wire material. For our application, which requires attenuations of 250 dB at 1 kHz, our model specifies a six-stage design using brass disks of approximately 2 cm in both radius and thickness, connected by 3 cm steel wires of diameters ranging from 25 to 75 microns. We describe the construction of this isolator in detail, and compare measurements of the natural frequencies of a single stage with calculations from the analytical model and the finite element package. For translations along and rotations about the longitudinal axes, all three results are in agreement to within 10% accuracy.Comment: 11 pages, 13 figures, REVTe

Fatty Acid Synthase Impacts the Pathobiology of Candida parapsilosis In Vitro and during Mammalian Infection

Cytosolic fungal fatty acid synthase is composed of two subunits α and β, which are encoded by Fas1 and Fas2 genes. In this study, the Fas2 genes of the human pathogen Candida parapsilosis were deleted using a modified SAT1 flipper technique. CpFas2 was essential in media lacking exogenous fatty acids and the growth of Fas2 disruptants (Fas2 KO) was regulated by the supplementation of different long chain fatty acids, such as myristic acid (14∶0), palmitic acid (16∶0), and Tween 80, in a dose-specific manner. Lipidomic analysis revealed that Fas2 KO cells were severely restricted in production of unsaturated fatty acids. The Fas2 KO strains were unable to form normal biofilms and were more efficiently killed by murine-like macrophages, J774.16, than the wild type, heterozygous and reconstituted strains. Furthermore, Fas2 KO yeast were significantly less virulent in a systemic murine infection model. The Fas2 KO cells were also hypersensitive to human serum, and inhibition of CpFas2 in WT C. parapsilosis by cerulenin significantly decreased fungal growth in human serum. This study demonstrates that CpFas2 is essential for C. parapsilosis growth in the absence of exogenous fatty acids, is involved in unsaturated fatty acid production, influences fungal virulence, and represents a promising antifungal drug target

RIPK1 is a critical modulator of both tonic and TLR-responsive inflammatory and cell death pathways in human macrophage differentiation

In this study, we took advantage of human-induced pluripotent stem cells (hiPSC) and CRISPR/Cas9 technology to investigate the potential roles of RIPK1 in regulating hematopoiesis and macrophage differentiation, proinflammatory activation, and cell death pathways. Knock-out of RIPK1 in hiPSCs demonstrated that this protein is not required for erythro-myeloid differentiation. Using a well-established macrophage differentiation protocol, knock-out of RIPK1 did not block the differentiation of iPSC-derived macrophages, which displayed a similar phenotype to WT hiPSC-derived macrophages. However, knock-out of RIPK1 leads to a TNFα-dependent apoptotic death of differentiated hiPSC-derived macrophages (iPS-MΦ) and progressive loss of iPS-MΦ production irrespective of external pro-inflammatory stimuli. Live video analysis demonstrated that TLR3/4 activation of RIPK1 KO hiPSC-derived macrophages triggered TRIF and RIPK3-dependent necroptosis irrespective of caspase-8 activation. In contrast, TLR3/4 activation of WT macrophages-induced necroptosis only when caspases were inhibited, confirming the modulating effect of RIPK1 on RIPK3-mediated necroptosis through the FADD, Caspase-8 pathway. Activation of these inflammatory pathways required RIPK3 kinase activity while RIPK1 was dispensable. However, loss of RIPK1 sensitizes macrophages to activate RIPK3 in response to inflammatory stimuli, thereby exacerbating a potentially pathological inflammatory response. Taken together, these results reveal that RIPK1 has an important role in regulating the potent inflammatory pathways in authentic human macrophages that are poised to respond to external stimuli. Consequently, RIPK1 activity might be a valid target in the development of novel therapies for chronic inflammatory diseases.España, MINECO/FEDER SAF2015-64171

New Experimental Limits on Macroscopic Forces Below 100 Microns

Results of an experimental search for new macroscopic forces with Yukawa range between 5 and 500 microns are presented. The experiment uses 1 kHz mechanical oscillators as test masses with a stiff conducting shield between them to suppress backgrounds. No signal is observed above the instrumental thermal noise after 22 hours of integration time. These results provide the strongest limits to date between 10 and 100 microns, improve on previous limits by as much as three orders of magnitude, and rule out half of the remaining parameter space for predictions of string-inspired models with low-energy supersymmetry breaking. New forces of four times gravitational strength or greater are excluded at the 95% confidence level for interaction ranges between 200 and 500 microns.Comment: 25 Pages, 7 Figures: Minor Correction

Discovery of Stable and Selective Antibody Mimetics from Combinatorial Libraries of Polyvalent, Loop-Functionalized Peptoid Nanosheets.

The ability of antibodies to bind a wide variety of analytes with high specificity and high affinity makes them ideal candidates for therapeutic and diagnostic applications. However, the poor stability and high production cost of antibodies have prompted exploration of a variety of synthetic materials capable of specific molecular recognition. Unfortunately, it remains a fundamental challenge to create a chemically diverse population of protein-like, folded synthetic nanostructures with defined molecular conformations in water. Here we report the synthesis and screening of combinatorial libraries of sequence-defined peptoid polymers engineered to fold into ordered, supramolecular nanosheets displaying a high spatial density of diverse, conformationally constrained peptoid loops on their surface. These polyvalent, loop-functionalized nanosheets were screened using a homogeneous Förster resonance energy transfer (FRET) assay for binding to a variety of protein targets. Peptoid sequences were identified that bound to the heptameric protein, anthrax protective antigen, with high avidity and selectivity. These nanosheets were shown to be resistant to proteolytic degradation, and the binding was shown to be dependent on the loop display density. This work demonstrates that key aspects of antibody structure and function-the creation of multivalent, combinatorial chemical diversity within a well-defined folded structure-can be realized with completely synthetic materials. This approach enables the rapid discovery of biomimetic affinity reagents that combine the durability of synthetic materials with the specificity of biomolecular materials

The Grizzly, April 14, 2011

Ursinus Enjoys Sixth Annual CoSA Event • Students Participate in 30 Hour Famine • Haverford Professor Guest Lectures on Physics Theory • Dr. Ruth Rosenberg Speaks on Holocaust Remembrance • Ursinus Welcomes Patti Smith • Tips on Surviving and Salvaging Bad Internships • Hypnotist Brings Laughs • How to Avoid Allergy Season • Linking Up with LinkedIn • Internship Spotlight: Lindsay Budnick • Opinions: Response to Article Segregation in the 21st Century ; Verizon\u27s DroidX-R2D2 has Cool Features But is Not for Me; President Obama Sends CIA Agents to Libya • How Far Ursinus Goes to Keep Students Safe on Main Street • New Coach and New Outlook Lead UC Softball • Gymnasts Named All-Americans at Championshipshttps://digitalcommons.ursinus.edu/grizzlynews/1834/thumbnail.jp

SDSS J092455.87+021924.9: an Interesting Gravitationally Lensed Quasar from the Sloan Digital Sky Survey

We report the discovery of a new gravitationally lensed quasar from the Sloan Digital Sky Survey, SDSS J092455.87+021924.9 (SDSS J0924+0219). This object was selected from among known SDSS quasars by an algorithm that was designed to select another known SDSS lensed quasar (SDSS 1226-0006A,B). Five separate components, three of which are unresolved, are identified in photometric follow-up observations obtained with the Magellan Consortium's 6.5m Walter Baade telescope at Las Campanas Observatory. Two of the unresolved components (designated A and B) are confirmed to be quasars with z=1.524; the velocity difference is less than 100 km sec^{-1} according to spectra taken with the W. M. Keck Observatory's Keck II telescope on Mauna Kea. A third stellar component, designated C, has the colors of a quasar with redshift similar to components A and B. The maximum separation of the point sources is 1.78". The other two sources, designated G and D, are resolved. Component G appears to be the best candidate for the lensing galaxy. Although component D is near the expected position of the fourth lensed component in a four image lens system, its properties are not consistent with being the image of a quasar at z~1.5. Nevertheless, the identical redshifts of components A and B and the presence of component C strongly suggest that this object is a gravitational lens. Our observations support the idea that a foreground object reddens the fourth lensed component and that another unmodeled effect (such as micro- or milli-lensing) demagnificates it, but we cannot rule out the possibility that SDSS0924+0219 is an example of the relatively rare class of ``three component'' lens systems.Comment: 24 pages, 6 figures, accepted by A