Antisense Oligonucleotides from the Stage-specific Myeloid Zinc Finger Gene MZF-1 Inhibit Granulopoiesis In Vitro

Zinc finger proteins are transcriptional regulators of other genes, often controlling developmental cascades of gene expression. A recently cloned zinc finger gene, MZF-1, was found to be preferentially expressed in myeloid cells. Using complementary radiolabeled MZF-1 RNA hybridized to human bone marrow smears in situ, it was discovered that the expression of MZF-1 is essentially limited to the myelocyte and metamyelocyte stages of granulopoiesis. Antisense but not sense oligonucleotides from MZF-1 significantly inhibited granulocyte colony-stimulating factor-driven granulocyte colony formation in vitro

A local Sidereal Time Clock to Facilitate Remote Observations

Undergraduate students in ARCC at UWM often remotely operate two of the world’s largest radio telescopes: the Arecibo telescope and the Green Bank telescope. However, in order to plan and execute observations students require knowledge of the Local Sidereal Time at each observatory. This determines which astronomical targets will be visible at a given time. We describe the design, construction, and operation of an Observing Clock. This clock is based on the open-source Raspberry Pi system and is easily extendable and modifiable

Mechanistic and Kinetic Measurements of Elementary Surface Reactions Using Temperature-Programmed X‑ray Photoelectron Spectroscopy

This paper describes a method by which surface-reaction kinetics can be measured by slowly and precisely ramping up the surface temperature at a constant rate while simultaneously collecting X-ray photoelectron spectra (XPS). This approach results in the collection of a large amount of data over relatively small temperature steps to produce quasi-continuous kinetic data. The method is illustrated for the desorption and reaction of diethyl disulfide (DEDS) on a Au(111) substrate in ultrahigh vacuum, where the results can be compared with previous conventional temperature-programmed desorption (TPD) data from Au(111). Experiments were carried out using a double-pass cylindrical-mirror analyzer with a channeltron detector to demonstrate how this approach can be implemented in a routine, multitechnique vacuum chamber. The approach will be even more effective in a more modern, specialized XPS apparatus with high-transmission hemispherical analyzers with multichannel array detectors, which will enable the spectra of several elements to be measured simultaneously. The results yielded an activation energy for multilayer desorption of DEDS of 41 ± 1 kJ/mol, with a pre-exponential factor of 8 ± 7 × 1012 s–1, an activation energy of 53 ± 6 kJ/mol and pre-exponential factor of 9 ± 8 × 1013 s–1 for monolayer desorption and an activation energy of 90 ± 6 kJ/mol with a prefactor of 1.0 ± 0.3 × 1015 s–1 for the reaction of adsorbed ethyl thiolate species to adsorbed DEDS. While these results were collected for a system for which the kinetic data could have been obtained using conventional TPD, this method can be more usefully applied to those surface reaction processes that do not rely on the formation of desorption products. This system, having been previously studied by TPD, facilitates a comparison with results obtained by conventional methods

Searching and Solving Pulsar Puzzles

Pulsars are a type of evolved star that are extremely dense and rotate with an extremely reliable period producing an intense beam of radiation, similar to a lighthouse pulse. This unique pulse allows for novel ways to study the universe, the most exciting of which being the potential to detect low frequency gravitational waves. The Arecibo Remote Command Center (ARCC) was formed as a way for undergraduate students to be involved in the search for new pulsars. Students remotely observe from UWM with two of the world’s largest radio telescopes, the Arecibo Observatory in Puerto Rico, and the Green Bank Telescope in West Virginia, and analyze the resulting data to discover and study these incredible neutron stars. Once a pulsar is discovered, it must be timed regularly in order to determine various parameters describing the system with astounding precision. These timing proposals can require ~1000 hours per year of observing, which undergraduates can easily do in the place of faculty and senior researchers. Students are also learning to “solve” pulsars themselves, an effort which will likely lead to authorship on a refereed journal paper. UWM students collaborate with students at a number of other US institutions, including the University of Texas - Rio Grande Valley, and Franklin & Marshall College, and with researchers across the globe

Discovery of Drug-Like Ligands for the Mac1 Domain of SARS-CoV-2 Nsp3

Small molecules that bind the SARS-CoV-2 nonstructural protein 3 Mac1 domain in place of ADP-ribose could be useful as molecular probes or scaffolds for COVID-19 antiviral drug discovery because Mac1 has been linked to the ability of coronaviruses to evade cellular detection. A high-throughput assay based on differential scanning fluorimetry (DSF) was therefore optimized and used to identify possible Mac1 ligands in small libraries of drugs and drug-like compounds. Numerous promising compounds included nucleotides, steroids, β-lactams, and benzimidazoles. The main drawback to this approach was that a high percentage of compounds in some libraries were found to influence the observed Mac1 melting temperature. To prioritize DSF screening hits, the shapes of the observed melting curves and initial assay fluorescence were examined, and the results were compared with virtual screens performed using AutoDock Vina. The molecular basis for alternate ligand binding was also examined by determining a structure of one of the hits, cyclic adenosine monophosphate, with atomic resolution

Prandtl–Tomlinson-Type Models for Coupled Molecular Sliding Friction: Chain-Length Dependence of Friction of Self-assembled Monolayers

Previous work (Manzi et al. in Tribol Lett 69:147, 2021) proposed a tip–molecular interaction for calculating the friction of organic overlayers that consisted of a parabolic potential that extended to some cut-of distance when the energy reached a value of E0 sld, which represents an activation barrier for the detachment of the tip from the molecular terminus. A proposed advantage of such a potential was that it could be coupled to other degrees of freedom of the system. A method for accomplishing this is described here for the interaction between a tip and a compliant molecular chain to model the velocity, temperature, and chain-length dependences of the friction force. Analytical equations are derived for constant force sliding, such as in a ball-on-fat tribometer, and for compliant sliding, such as in an atomic force microscopy (AFM) experiment. The analytic models provided good fts to the chain-length dependence of the friction of carboxylate self-assembled monolayers (SAMs) on copper measured in an ultrahigh vacuum tribometer as part of this work and for alkyl thiolate SAMs on gold measured by an AFM taken from the literature. The results indicate that the commonly observed decrease in friction with increasing chain length has a component that is due to geometrical efects, as well as the possible participation of interchain van der Waals’ interactions that are commonly invoked as being responsible for the friction reduction.Fil: Hou, Kaiming. University Of Wisconsin. Department Of Chemistry & Biochemistry; Estados UnidosFil: Bavisotto, Robert. Universidad Nacional de San Luis; Argentina. University Of Wisconsin. Department Of Chemistry & Biochemistry; Estados UnidosFil: Manzi, Sergio Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto de Física Aplicada "Dr. Jorge Andrés Zgrablich". Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto de Física Aplicada "Dr. Jorge Andrés Zgrablich"; ArgentinaFil: Perez, Eliseo Joaquín. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto de Física Aplicada "Dr. Jorge Andrés Zgrablich". Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto de Física Aplicada "Dr. Jorge Andrés Zgrablich"; ArgentinaFil: Furlong, Octavio Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto de Física Aplicada "Dr. Jorge Andrés Zgrablich". Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto de Física Aplicada "Dr. Jorge Andrés Zgrablich"; ArgentinaFil: Kotvis, Peter. University Of Wisconsin. Department Of Chemistry & Biochemistry; Estados UnidosFil: Kenmoe, Germaine Djuidje. University Of Wisconsin. Department Of Chemistry & Biochemistry; Estados UnidosFil: Tysoe, Wilfred T.. University Of Wisconsin. Department Of Chemistry & Biochemistry; Estados Unido

The Green Bank North Celestial Cap Survey. VII. 12 New Pulsar Timing Solutions

We present timing solutions for 12 pulsars discovered in the Green Bank North Celestial Cap 350 MHz pulsar survey, including six millisecond pulsars (MSPs), a double neutron star (DNS) system, and a pulsar orbiting a massive white dwarf companion. Timing solutions presented here include 350 and 820 MHz Green Bank Telescope data from initial confirmation and follow-up, as well as a dedicated timing campaign spanning 1 ryr PSR J1122−3546 is an isolated MSP, PSRs J1221−0633 and J1317−0157 are MSPs in black widow systems and regularly exhibit eclipses, and PSRs J2022+2534 and J2039−3616 are MSPs that can be timed with high precision and have been included in pulsar timing array experiments seeking to detect low-frequency gravitational waves. PSRs J1221−0633 and J2039−3616 have Fermi Large Area Telescope gamma-ray counterparts and also exhibit significant gamma-ray pulsations. We measure proper motions for three of the MSPs in this sample and estimate their space velocities, which are typical compared to those of other MSPs. We have detected the advance of periastron for PSR J1018−1523 and therefore measure the total mass of the DNS system, m _tot = 2.3 ± 0.3 M _⊙ . Long-term pulsar timing with data spanning more than 1 yr is critical for classifying recycled pulsars, carrying out detailed astrometry studies, and shedding light on the wealth of information in these systems post-discovery