A QM/MM approach for the study of monolayer-protected gold clusters

We report the development and implementation of hybrid methods that combine quantum mechanics (QM) with molecular mechanics (MM) to theoretically characterize thiolated gold clusters. We use, as training systems, structures such as Au25(SCH2-R)18 and Au38(SCH2-R)24, which can be readily compared with recent crystallographic data. We envision that such an approach will lead to an accurate description of key structural and electronic signatures at a fraction of the cost of a full quantum chemical treatment. As an example, we demonstrate that calculations of the 1H and 13C NMR shielding constants with our proposed QM/MM model maintain the qualitative features of a full DFT calculation, with an order-of-magnitude increase in computational efficiency.Comment: Journal of Materials Science, 201

The next generation of target capture technologies - large DNA fragment enrichment and sequencing determines regional genomic variation of high complexity

Abstract Background The ability to capture and sequence large contiguous DNA fragments represents a significant advancement towards the comprehensive characterization of complex genomic regions. While emerging sequencing platforms are capable of producing several kilobases-long reads, the fragment sizes generated by current DNA target enrichment technologies remain a limiting factor, producing DNA fragments generally shorter than 1 kbp. The DNA enrichment methodology described herein, Region-Specific Extraction (RSE), produces DNA segments in excess of 20 kbp in length. Coupling this enrichment method to appropriate sequencing platforms will significantly enhance the ability to generate complete and accurate sequence characterization of any genomic region without the need for reference-based assembly. Results RSE is a long-range DNA target capture methodology that relies on the specific hybridization of short (20-25 base) oligonucleotide primers to selected sequence motifs within the DNA target region. These capture primers are then enzymatically extended on the 3’-end, incorporating biotinylated nucleotides into the DNA. Streptavidin-coated beads are subsequently used to pull-down the original, long DNA template molecules via the newly synthesized, biotinylated DNA that is bound to them. We demonstrate the accuracy, simplicity and utility of the RSE method by capturing and sequencing a 4 Mbp stretch of the major histocompatibility complex (MHC). Our results show an average depth of coverage of 164X for the entire MHC. This depth of coverage contributes significantly to a 99.94 % total coverage of the targeted region and to an accuracy that is over 99.99 %. Conclusions RSE represents a cost-effective target enrichment method capable of producing sequencing templates in excess of 20 kbp in length. The utility of our method has been proven to generate superior coverage across the MHC as compared to other commercially available methodologies, with the added advantage of producing longer sequencing templates amenable to DNA sequencing on recently developed platforms. Although our demonstration of the method does not utilize these DNA sequencing platforms directly, our results indicate that the capture of long DNA fragments produce superior coverage of the targeted region

Improving Clinician Competence to Screen for Suicide Risk: An Organizational Change

MHBH is on a journey to implement Zero Suicide across the organization. Zero Suicide is a quality improvement model that transforms system-wide 0% 10% 20% 30% 40% 50% 60% Outpatient Staff Inpatient Staff September 2021 May 2024 Project Life Worth Living is supported by a grant from Substance Abuse and Mental Health Services Administration (SAMHSA), Center for Mental Health Services (CMHS), under Grant No. 1H79SM088556 % who strongly agree: “I have the knowledge and skills to screen for suicide risk” prevention and care with an aspirational goal of zero suicide deaths among the people we serve.https://knowledgeconnection.mainehealth.org/lambrew-retreat-2025/1021/thumbnail.jp

Versatile Coordination of Cyclopentadienyl-Arene Ligands and Its Role in Titanium-Catalyzed Ethylene Trimerization

Cationic titanium(IV) complexes with ansa-(η5-cyclopentadienyl,η6-arene) ligands were synthesized and characterized by X-ray crystallography. The strength of the metal-arene interaction in these systems was studied by variable-temperature NMR spectroscopy. Complexes with a C1 bridge between the cyclopentadienyl and arene moieties feature hemilabile coordination behavior of the ligand and consequently are active ethylene trimerization catalysts. Reaction of the titanium(IV) dimethyl cations with CO results in conversion to the analogous cationic titanium(II) dicarbonyl species. Metal-to-ligand backdonation in these formally low-valent complexes gives rise to a strongly bonded, partially reduced arene moiety. In contrast to the η6-arene coordination mode observed for titanium, the more electron-rich vanadium(V) cations [cyclopentadienyl-arene]V(NiPr2)(NC6H4-4-Me)+ feature η1-arene binding, as determined by a crystallographic study. The three different metal-arene coordination modes that we experimentally observed model intermediates in the cycle for titanium-catalyzed ethylene trimerization. The nature of the metal-arene interaction in these systems was studied by DFT calculations.

The soybean GmSNAP18 gene underlies two types of resistance to soybean cyst nematode

Two types of resistant soybean (Glycine max (L.) Merr.) sources are widely used against soybean cyst nematode (SCN, Heterodera glycines Ichinohe). These include Peking-type soybean, whose resistance requires both the rhg1-a and Rhg4 alleles, and PI 88788-type soybean, whose resistance requires only the rhg1-b allele. Multiple copy number of PI 88788-type GmSNAP18, GmAAT, and GmWI12 in one genomic segment simultaneously contribute to rhg1-b resistance. Using an integrated set of genetic and genomic approaches, we demonstrate that the rhg1-a Peking-type GmSNAP18 is sufficient for resistance to SCN in combination with Rhg4. The two SNAPs (soluble NSF attachment proteins) differ by only five amino acids. Our findings suggest that Peking-type GmSNAP18 is performing a different role in SCN resistance than PI 88788-type GmSNAP18. As such, this is an example of a pathogen resistance gene that has evolved to underlie two types of resistance, yet ensure the same function within a single plant species

Automated Motion of a Radiation Source for Testing Micromegas Detectors & Modeling QGP Flow Coefficients Using a Particle Transport Model

This thesis consists of two independent parts. In the first section, an automated system for moving a radiation source for testing micromegas detectors was designed, assembled, and programmed. Micromegas amplify the signal from incident radiation through the ionization of the gas filling the detectors. They are reliable and maintain high accuracy under high incident particle flux conditions, but remain vulnerable to ion backflow, which reduces tracking accuracy. To characterize ion backflow, the current drawn by the detector's drift mesh can be measured. However, due to the current's picoamp scale it is very sensitive to noise and drift, which necessitates a time-consuming process of repeated, alternating measurements with a radiation source present and a control with none present. The work presented here automates the motion of the radiation source using code that is easily integrable into existing data-collection programs, in order to facilitate the measurement of ion backflow in micromegas. In the second section, a particle transport model is used to examine flow coefficients of quark-gluon plasma. These coefficients describe the modes of flow of the medium produced in collisions of relativistic nuclei. Studies using AMPT, a particle transport model, have shown that lower-order flow coefficients can be produced due to differential particle escape from the medium. This project uses a simplified particle transport model to investigate whether the escape mechanism can contribute to the quadrangular (fourth-order) flow coefficient

The Role of Integrins in HIV-1 Infection of Intestinal Endothelial Cell Stimulated Resting CD4+ T Cells

A major barrier to eradicating HIV is latent reservoirs in resting CD4+ T cells. Antiretroviral therapy is effective in bringing the viral load down to undetectable levels but is unable to eradicate the latent reservoir. Previous data from our lab revealed that when stimulated by intestinal endothelial cells (IEC), resting CD4+ T cells can be directly infected while remaining in a resting state, allowing formation of latent reservoirs. An additional study found that integrins, which are cell surface molecules, play a role in the interactions between endothelial cells (EC) and T cells. Our research further examines the role of integrins (rhICAM & rhVCAM) in the context of HIV infection. Resting CD4+ T cells were stimulated with integrins, and increased levels of HIV infection were observed. A pro-inflammatory cytokine, IL-6, was previously found to increase productive infection rates in resting CD4+ T cells, and when combined with integrins, infection rates of resting CD4+ T Cells reached those of IEC, indicating that these may be two of the main mechanisms by which HIV-1 infects resting CD4+ T cells. Our studies show that IEC allow HIV infection of resting CD4+ T cells through an integrin dependent manner in conjunction with IL-

Preferential infection of CCR6+ CD4+ T Cells by HIV is increased by human intestinal endothelial cells

Th17 cells are found to be heavily depleted in the gut of HIV patients. Even after successful antiretroviral therapy, HIV patients exhibit a smaller Th17 population for years after treatment. Previous research has found human intestinal endothelial cells (IEC) to increase HIV infection of helper T cells. Using CCR6 as a marker for Th17, we investigated the effect of IEC on HIV infection of Th17 cells. IECs were found to increase the preferential infection of resting and activated CCR6+ cells. Th17 cells are known to be more susceptible to HIV infection than other types of CD4+ T cells. IEC stimulation increased the infection of all resting and activated CD4+ T cells, but had a greater effect on CCR6+ T helper cells. Moreover, coculturing CD4+ T cells with IEC reduced the proportion of CCR6+ T helper cells upon infection with HIV, suggesting that IECs facilitate preferential death of CCR6+ T cells. IEC’s role in CCR6+ T cell infection could be involved in the depletion of Th17 cells in HIV patients