Extreme ultraviolet time-resolved photoelectron spectroscopy of adenine, adenosine and adenosine monophosphate in a liquid flat jet.

Time-resolved photoelectron spectroscopy using an extreme-ultraviolet (XUV) probe pulse was used to investigate the UV photoinduced dynamics of adenine (Ade), adenosine (Ado), and adenosine-5-monophosphate (AMP) in a liquid water jet. In contrast to previous studies using UV probe pulses, the XUV pulse at 21.7 eV can photoionize all excited states of a molecule, allowing for full relaxation pathways to be addressed after excitation at 4.66 eV. This work was carried out using a gas-dynamic flat liquid jet, resulting in considerably enhanced signal compared to a cylindrical jet. All three species decay on multiple time scales that are assigned based on their decay associated spectra; the fastest decay of ∼100 fs is assigned to ππ* decay to the ground state, while a smaller component with a lifetime of ∼500 fs is attributed to the nπ* state. An additional slower channel in Ade is assigned to the 7H Ade conformer, as seen previously. This work demonstrates the capability of XUV-TRPES to disentangle non-adiabatic dynamics in an aqueous solution in a state-specific manner and represents the first identification of the nπ* state in the relaxation dynamics of adenine and its derivatives.

"They Just Helped Save My Life:" Client Perspectives on the Los Angeles County Full Service Partnership (FSP) Program for Serious Mental Illness.

The purpose of this qualitative study was to elicit client perspectives on the Los Angeles County Full Service Partnership (FSP) program - an adaptation of Assertive Community Treatment (ACT). Semi-structured interviews were conducted with 20 FSP clients. Qualitative data were analyzed using thematic analysis. Two major themes were identified from the interview data: (1) Clients' acknowledgement of the material benefits of the FSP program; and (2) FSP's impact on restoring and stabilizing clients' social and treatment relationships. Interviewees greatly valued the material (i.e., basic needs, housing assistance) and relational (i.e., relationships with providers, restored personal relationships) aspects of the program, but did not ascribe the same degree of value to mental health treatment. Interviewees' emphases on material and relational aspects reflect the status of assertive mental health treatment as an intervention on intermediary determinants of health in the lives of persons diagnosed with serious mental illness.

Relaxation Dynamics of Hydrated Thymine, Thymidine, and Thymidine Monophosphate Probed by Liquid Jet Time-Resolved Photoelectron Spectroscopy.

The relaxation dynamics of thymine and its derivatives thymidine and thymidine monophosphate are studied using time-resolved photoelectron spectroscopy applied to a water microjet. Two absorption bands are studied; the first is a bright ππ* state which is populated using tunable-ultraviolet light in the range 4.74-5.17 eV and probed using a 6.20 eV probe pulse. By reversing the order of these pulses, a band containing multiple ππ* states is populated by the 6.20 eV pulse and the lower energy pulse serves as the probe. The lower lying ππ* state is found to decay in ∼400 fs in both thymine and thymidine independent of pump photon energy, while thymidine monophosphate decays vary from 670 to 840 fs with some pump energy dependence. The application of a computational quantum mechanical/molecular mechanical scheme at the XMS-CASPT2//CASSCF/AMBER level of theory suggests that conformational differences existing between thymidine and thymidine monophosphate in solution account for this difference. The higher lying ππ* band is found to decay in ∼600 fs in all three cases, but it is only able to be characterized when the 5.17 eV probe pulse is used. Notably, no long-lived signal from an nπ* state can be identified in either experiment on any of the three molecules.

Time-resolved photoelectron spectroscopy of adenosine and adenosine monophosphate photodeactivation dynamics in water microjets.

The excited state relaxation dynamics of adenosine and adenosine monophosphate were studied at multiple excitation energies using femtosecond time-resolved photoelectron spectroscopy in a liquid water microjet. At pump energies of 4.69-4.97 eV, the lowest ππ* excited state, S1, was accessed and its decay dynamics were probed via ionization at 6.20 eV. By reversing the role of the pump and probe lasers, a higher-lying ππ* state was excited at 6.20 eV and its time-evolving photoelectron spectrum was monitored at probe energies of 4.69-4.97 eV. The S1 ππ* excited state was found to decay with a lifetime ranging from ∼210 to 250 fs in adenosine and ∼220 to 250 fs in adenosine monophosphate. This lifetime drops with increasing pump photon energy. Signal from the higher-lying ππ* excited state decayed on a time scale of ∼320 fs and was measureable only in adenosine monophosphate.

Combined Electron-Diffraction and Spectroscopic Determination of the Structure of Spiropentane, C5H8.

Gas-phase electron-diffraction (GED) data have been combined with recent spectroscopic rotational constants to determine the rα0 structural parameters for spiropentane, C5H8. The structure has D2d symmetry, and the results yield values of 1.105(2) Å for the CH bond length, 1.557(3) Å for the distal CC bond length, and a smaller value of 1.482(1) Å for the four lateral CC bonds that connect to the central carbon atom. The HCH angle is 113.7(13)°, and the HCH flap angle, defined as the angle of the HCH bisector and the distal CC bond, is 150.2(16)°. Corresponding rg values are 1.122(2) Å, 1.560(3) Å, 1.485(1) Å, 115.1(13)°, and 148.9 (16)°. The results are in good accord with values from density functional calculations (B3LYP/cc-pVTZ) and resolve some questions about the structure reported in an earlier GED study, in particular about the HCH angle and anomalous rotational constants calculated for the structure.

Growth and Dissolution of Calcite in the Presence of Adsorbed Stearic Acid.

The interaction of organic molecules with the surface of calcite plays a central role in many geochemical, petrochemical, and industrial processes and in biomineralization. Adsorbed organics, typically fatty acids, can interfere with the evolution of calcite when immersed in aqueous solutions. Here we use atomic force microscopy in liquid to explore in real-time the evolution of the (1014) surface of calcite covered with various densities of stearic acid and exposed to different saline solutions. Our results show that the stearic acid molecules tend to act as "pinning points" on the calcite's surface and slow down the crystal's restructuring kinetics. Depending on the amount of material adsorbed, the organic molecules can form monolayers or bilayer islands that become embedded into the growing crystal. The growth process can also displaces the organic molecules and actively concentrate them into stacked multilayers. Our results provide molecular-level insights into the interplay between the adsorbed fatty acid molecules and the evolving calcite crystal, highlighting mechanisms that could have important implications for several biochemical and geochemical processes and for the oil industry.

Polyplex exposure inhibits cell cycle, increases inflammatory response, and can cause protein expression without cell division.

We sought to evaluate the relationship between cell division and protein expression when using commercial poly(ethylenimine) (PEI)-based polyplexes. The membrane dye PKH26 was used to assess cell division, and cyan fluorescent protein (CFP) was used to monitor protein expression. When analyzed at the whole population level, a greater number of cells divided than expressed protein, regardless of the level of protein expression observed, giving apparent consistency with the hypothesis that protein expression requires cells to pass through mitosis in order for the transgene to overcome the nuclear membrane. However, when the polyplex-exposed population was evaluated for the amount of division in the protein-expressing subpopulation, it was observed that substantial amounts of expression had occurred in the absence of division. Indeed, in HeLa S3 cells, this represented the majority of expressing cells. Of interest, the doubling time for both cell lines was slowed by ~2-fold upon exposure to polyplexes. This change was not altered by the origin of the plasmid DNA (pDNA) transgene promoter (cytomegalovirus (CMV) or elongation factor-1 alpha (EF1α)). Gene expression arrays in polyplex-exposed HeLa S3 cells showed upregulation of cell cycle arrest genes and downregulation of genes related to mitosis. Chemokine, interleukin, and toll-like receptor genes were also upregulated, suggesting activation of proinflammatory pathways. In summary, we find evidence that a cell division-independent expression pathway exists, and that polyplex exposure slows cell division and increases inflammatory response.

A Rapid Review of "Low-Threshold" Psychiatric Medication Prescribing: Considerations for Street Medicine and Beyond.

OBJECTIVE: No widely accepted clinical guidelines, and scant directly applicable pragmatic research, are available to guide the prescription of psychiatric medications in "low-threshold" outpatient settings, such as street outreach, urgent care, and crisis care, as well as walk-in, shelter, and bridge and transition clinics. Providers frequently prescribe medications in these settings without patients' having firm psychiatric diagnoses and without medical records to guide clinical decision making. Persons who receive medications in these settings often seek help voluntarily and intermittently for mental illness symptoms. However, because of structural and individual factors, such patients may not engage in longitudinal outpatient psychiatric care. The authors reviewed the literature on psychiatric medication prescribing in low-threshold settings and offer clinical considerations for such prescribing. METHODS: The authors conducted a rapid literature review (N=2,215 abstracts), which was augmented with up-to-date clinical prescribing literature, the authors' collective clinical experience, and DSM-5 section II diagnostic criteria to provide considerations for prescribing medications in low-threshold settings. RESULTS: For individuals for whom diagnostic uncertainty is prominent, a symptom-based diagnostic and treatment approach may be best suited to weigh the risks and benefits of medication use in low-threshold settings. Practical considerations for treating patients with clinical presentations of psychosis and trauma, as well as mood, anxiety, and substance use disorders, in low-threshold settings are discussed. CONCLUSIONS: An urgent need exists to invest in pragmatic research and guideline development to delineate best-practice prescribing in low-threshold settings.

A Case for Psychiatric Leadership in Dispositional Capacity Assessment.

Dispositional capacity assessment, which evaluates a patient's ability for self-care after hospital discharge, is a novel concept with important implications for work in consultation-liaison, inpatient, and emergency psychiatric settings. In this Open Forum, the authors present an illustrative case, review literature relevant to dispositional capacity, and explore social theory that elucidates the concept. Psychiatrists are specifically positioned to provide leadership in this area. Psychiatrists should consider further developing and formalizing criteria for dispositional capacity assessment.

Failure to Appear: Mental Health Professionals' Role Amidst Pretrial Justice Reform.

Pretrial detention reform is keeping people who have been arrested on low-level charges out of jail while they await trial. This reform has implications for people with serious mental illnesses who are overrepresented in the criminal legal system and who can now stay connected to families, employment, community supports, and treatment providers while their cases are processed. However, such reforms may have uniquely negative consequences for those with serious mental illnesses. In this Open Forum, the authors argue that it is critical for mental health professionals to understand what pretrial reform entails and to incorporate planning around clients' criminal legal system involvement into their routine clinical work.

Type I collagen exists as a distribution of nanoscale morphologies in teeth, bones, and tendons.

This study demonstrates that collagen, the most abundant protein in animals, exists as a distribution of nanoscale morphologies in teeth, bones, and tendons. This fundamental characteristic of Type I collagen has not previously been reported and provides a new understanding of the nanoscale architecture of this ubiquitous and important biological nanomaterial. Dentin, bone, and tendon tissue samples were chosen for their differences in cellular origin and function, as well as to compare mineralized tissues with a tissue that lacks mineral in a normal physiological setting. A distribution of morphologies was present in all three tissues, confirming that this characteristic is fundamental to Type I collagen regardless of the presence of mineral, cellular origin of the collagen (osteoblast versus odontoblast versus fibroblast), anatomical location, or mechanical function of the tissue.

Reducing uncertainties in energy dissipation measurements in atomic force spectroscopy of molecular networks and cell-adhesion studies.

Atomic force microscope (AFM) based single molecule force spectroscopy (SMFS) is a valuable tool in biophysics to investigate the ligand-receptor interactions, cell adhesion and cell mechanics. However, the force spectroscopy data analysis needs to be done carefully to extract the required quantitative parameters correctly. Especially the large number of molecules, commonly involved in complex networks formation; leads to very complicated force spectroscopy curves. One therefore, generally characterizes the total dissipated energy over a whole pulling cycle, as it is difficult to decompose the complex force curves into individual single molecule events. However, calculating the energy dissipation directly from the transformed force spectroscopy curves can lead to a significant over-estimation of the dissipated energy during a pulling experiment. The over-estimation of dissipated energy arises from the finite stiffness of the cantilever used for AFM based SMFS. Although this error can be significant, it is generally not compensated for. This can lead to significant misinterpretation of the energy dissipation (up to the order of 30%). In this paper, we show how in complex SMFS the excess dissipated energy caused by the stiffness of the cantilever can be identified and corrected using a high throughput algorithm. This algorithm is then applied to experimental results from molecular networks and cell-adhesion measurements to quantify the improvement in the estimation of the total energy dissipation.

Evaluation of the Mental Health Services Act in Los Angeles County: Implementation and Outcomes for Key Programs.

Los Angeles County used Mental Health Services Act (MHSA) funds to greatly expand access to Full-Service Partnership (FSP) services and offer new prevention and early intervention (PEI) services. This study examines the reach of key MHSA-funded activities and what the impact of those activities has been, with a focus on PEI programs for children and transition-age youth (TAY) and FSP programs for children, TAY, and adults. The evaluation found evidence that the Los Angeles County Department of Mental Health (LAC DMH) is reaching the highly vulnerable population it seeks to reach with its FSP and youth PEI programs. Furthermore, those reached by the programs experience improvements in their mental health and life circumstances. Refining data collection will enable more-thorough evaluation of processes of care and would inform the program's quality-improvement efforts.

Harnessing the damping properties of materials for high-speed atomic force microscopy.

The success of high-speed atomic force microscopy in imaging molecular motors, enzymes and microbes in liquid environments suggests that the technique could be of significant value in a variety of areas of nanotechnology. However, the majority of atomic force microscopy experiments are performed in air, and the tapping-mode detection speed of current high-speed cantilevers is an order of magnitude lower in air than in liquids. Traditional approaches to increasing the imaging rate of atomic force microscopy have involved reducing the size of the cantilever, but further reductions in size will require a fundamental change in the detection method of the microscope. Here, we show that high-speed imaging in air can instead be achieved by changing the cantilever material. We use cantilevers fabricated from polymers, which can mimic the high damping environment of liquids. With this approach, SU-8 polymer cantilevers are developed that have an imaging-in-air detection bandwidth that is 19 times faster than those of conventional cantilevers of similar size, resonance frequency and spring constant.

Studying biological membranes with extended range high-speed atomic force microscopy.

High-speed atomic force microscopy has proven to be a valuable tool for the study of biomolecular systems at the nanoscale. Expanding its application to larger biological specimens such as membranes or cells has, however, proven difficult, often requiring fundamental changes in the AFM instrument. Here we show a way to utilize conventional AFM instrumentation with minor alterations to perform high-speed AFM imaging with a large scan range. Using a two-actuator design with adapted control systems, a 130 × 130 × 5 µm scanner with nearly 100 kHz open-loop small-signal Z-bandwidth is implemented. This allows for high-speed imaging of biologically relevant samples as well as high-speed measurements of nanomechanical surface properties. We demonstrate the system performance by real-time imaging of the effect of charged polymer nanoparticles on the integrity of lipid membranes at high imaging speeds and peak force tapping measurements at 32 kHz peak force rate.