Superluminal Molecular and Nanomaterial Probes Based on Fast Ions or Electrons.

This work reviews the progression of chemical analysis via Cherenkov emissions, i.e., Cherenkov Photometry and Cherenkov Emission Spectroscopy, from its introduction in the literature up to modern developments. In presenting the history of this field, we aim to consolidate the literature, both for reference and contextualization. We present an argument aiming to untangle why this corner of research has seen little progress while so many other directly related aspects of Cherenkov research have flourished, as well as speak to the progress of the field in recent years and prospective direction in years to come.

Development of the Mentoring in Undergraduate Research Survey.

Here we present the development of the Mentoring in Undergraduate Research Survey (MURS) as a measure of a range of mentoring experienced by undergraduate science researchers. We drafted items based on qualitative research and refined the items through cognitive interviews and expert sorting. We used one national dataset to evaluate the internal structure of the measure and a second national dataset to examine how responses on the MURS related to theoretically relevant constructs and student characteristics. Our factor analytic results indicate seven lower order forms of mentoring experiences: abusive supervision, accessibility, technical support, psychosocial support, interpersonal mismatch, sexual harassment, and unfair treatment. These forms of mentoring mapped onto two higher-order factors: supportive and destructive mentoring experiences. Although most undergraduates reported experiencing supportive mentoring, some reported experiencing absence of supportive as well as destructive experiences. Undergraduates who experienced less supportive and more destructive mentoring also experienced lower scientific integration and a dampening of their beliefs about the value of research. The MURS should be useful for investigating the effects of mentoring experienced by undergraduate researchers and for testing interventions aimed at fostering supportive experiences and reducing or preventing destructive experiences and their impacts.

Muon Irradiation of ZnO Rods: Superparamagnetic Nature Induced by Defects.

In this work, through a combination of photoluminescence spectroscopy, X-ray powder diffraction and magnetic measurements, it is determined that ZnO rods, made hydrothermally using a combination of magnetic field with respect to the force of gravity, exhibit superparamagnetic properties which emerge from Zn defects. These Zn defects result in a size-dependent superparamagnetic property of the rods. Red emissions, characteristic of Zn vacancies, and magnetic susceptibility both increased with decreasing rod size. The ZnO rods have significantly larger superparamagnetic cluster sizes (one order of magnitude) and lower fluctuation rates when compared to other superparamagnetic particles.

Sufficiency of CD40 activation and immune checkpoint blockade for T cell priming and tumor immunity.

Innate immune receptors such as toll-like receptors (TLRs) provide critical molecular links between innate cells and adaptive immune responses. Here, we studied the CD40 pathway as an alternative bridge between dendritic cells (DCs) and adaptive immunity in cancer. Using an experimental design free of chemo- or radiotherapy, we found CD40 activation with agonistic antibodies (⍺CD40) produced complete tumor regressions in a therapy-resistant pancreas cancer model, but only when combined with immune checkpoint blockade (ICB). This effect, unachievable with ICB alone, was independent of TLR, STING, or IFNAR pathways. Mechanistically, αCD40/ICB primed durable T cell responses, and efficacy required DCs and host expression of CD40. Moreover, ICB drove optimal generation of polyfunctional T cells in this "cold" tumor model, instead of rescuing T cell exhaustion. Thus, immunostimulation via αCD40 is sufficient to synergize with ICB for priming. Clinically, combination αCD40/ICB may extend efficacy in patients with "cold" and checkpoint-refractory tumors.

"Where's My Mentor?!" Characterizing Negative Mentoring Experiences in Undergraduate Life Science Research.

Undergraduate research experiences in science, technology, engineering, and mathematics fields are championed for promoting students' personal and professional development. Mentorship is an integral part of undergraduate research, as effective mentorship maximizes the benefits undergraduates realize from participating in research. Yet almost no research examines instances in which mentoring is less effective or even problematic, even though prior research on mentoring in workplace settings suggests negative mentoring experiences are common. Here, we report the results of a qualitative study to define and characterize negative mentoring experiences of undergraduate life science researchers. Undergraduate researchers in our study reported seven major ways they experienced negative mentoring: absenteeism, abuse of power, interpersonal mismatch, lack of career support, lack of psychosocial support, misaligned expectations, and unequal treatment. They described some of these experiences as the result of absence of positive mentoring behavior and others as actively harmful behavior, both of which they perceive as detrimental to their psychosocial and career development. Our results are useful to mentors for reflecting on ways their behaviors might be perceived as harmful or unhelpful. These findings can also serve as a foundation for future research aimed at examining the prevalence and impact of negative mentoring experiences in undergraduate research.

Class and Kinetics of Weakly Reactive Pretransplant Donor-specific HLA Antibodies Predict Rejection in Kidney Transplant Recipients.

BACKGROUND: The clinical impact of weakly reactive pretransplant donor-specific antibody (DSA) in kidney transplantation is controversial. While some evidence suggests that weakly reactive DSA can lead to rejection, it is unclear which patients are at risk for rejection and whether posttransplant changes in weakly reactive DSA are clinically meaningful. METHODS: We retrospectively studied 80 kidney transplant recipients with weakly reactive pretransplant DSA between 2007 and 2014. We performed a multivariate Cox regression analysis to identify immunologic factors most associated with risk of biopsy-proven rejection. RESULTS: Biopsy-proven rejection occurred in 13 of 80 (16%) patients. The presence of both class I and II DSA before transplant (hazards ratio 17.4, P < 0.01) and any posttransplant increase in DSA reactivity above a mean fluorescence intensity of 3000 (hazards ratio 7.8, P < 0.01) were each significantly associated with an increased risk of rejection, which primarily occurred within the first 18 months. CONCLUSIONS: Pretransplant DSA class and DSA kinetics after transplantation are useful prognostic indicators in patients with weak DSA reactivity. These results identify a small, high-risk patient group that warrants aggressive posttransplant DSA monitoring and may benefit from alternative donor selection.

Immunotherapy and Prevention of Pancreatic Cancer.

Pancreatic cancer is the third-leading cause of cancer mortality in the USA, recently surpassing breast cancer. A key component of pancreatic cancer's lethality is its acquired immune privilege, which is driven by an immunosuppressive microenvironment, poor T cell infiltration, and a low mutational burden. Although immunotherapies such as checkpoint blockade or engineered T cells have yet to demonstrate efficacy, a growing body of evidence suggests that orthogonal combinations of these and other strategies could unlock immunotherapy in pancreatic cancer. In this Review article, we discuss promising immunotherapies currently under investigation in pancreatic cancer and provide a roadmap for the development of prevention vaccines for this and other cancers.

Pregnancy-Induced Sensitization Promotes Sex Disparity in Living Donor Kidney Transplantation.

The presence of sex disparity in living donor kidney transplantation (LDKT) remains controversial. To determine if women fall behind men in LDKT evaluation, we performed an intention to treat study of 2587 candidates listed for kidney transplant at a single transplant center over 7 years. We found that women and men kidney transplant candidates engaged an equivalent type and number of prospective living donors. However, sex-specific differences in sensitization history and histocompatibility reduced the rate of LDKT for women by 30%. Pregnancy-induced incompatibility with spouse donors was limiting given that spouses were among the individuals most likely to complete donation. Notably, participation in a kidney paired exchange program eliminated sex-based differences in LDKT. Collectively, these data suggest that pregnancy is a formidable biologic barrier for women and contributes uniquely to sex disparity in LDKT. Targeted efforts to improve transplant center participation in paired kidney exchanges may increase sex equity in LDKT.

Propargyl + O2 reaction in helium droplets: entrance channel barrier or not?

A combination of liquid He droplet experiments and multireference electronic structure calculations is used to probe the potential energy surface for the reaction between the propargyl radical and O2. Infrared laser spectroscopy is used to probe the outcome of the low temperature, liquid He-mediated reaction. Bands in the spectrum are assigned to the acetylenic CH stretch (ν1), the symmetric CH2 stretch (ν2), and the antisymmetric CH2 stretch (ν13) of the trans-acetylenic propargyl peroxy radical ((•)OO-CH2-C≡CH). The observed band origins are in excellent agreement with previously reported anharmonic frequency computations for this species [Jochnowitz, E. B.; Zhang, X.; Nimlos, M. R.; Flowers, B. A.; Stanton, J. F.; Ellison, G. B. J. Phys. Chem. A 2010, 114, 1498]. The Stark spectrum of the ν1 band provides further evidence that the reaction leads only to the trans-acetylenic species. There are no other bands in the CH2 stretching region that can be attributed to any of the other three propargyl peroxy isomers/conformers that are predicted to be minimum energy structures (gauche-acetylenic, cis-allenic, and trans-allenic). There is also no evidence for the kinetic stabilization of a van der Waals complex between propargyl and O2. A combination of multireference and coupled-cluster electronic structure calculations is used to probe the potential energy surface in the neighborhood of the transition state connecting reactants with the acetylenic adduct. The multireference based evaluation of the doublet-quartet splitting added to the coupled-cluster calculated quartet state energies yields what are likely the most accurate predictions for the doublet potential curve. This calculation suggests that there is no saddle point for the addition process, in agreement with the experimental observations. Other calculations suggest the possible presence of a small submerged barrier.

Dynamic interpretation of maternal inputs by the Drosophila segmentation gene network.

Patterning of body parts in multicellular organisms relies on the interpretation of transcription factor (TF) concentrations by genetic networks. To determine the extent by which absolute TF concentration dictates gene expression and morphogenesis programs that ultimately lead to patterns in Drosophila embryos, we manipulate maternally supplied patterning determinants and measure readout concentration at the position of various developmental markers. When we increase the overall amount of the maternal TF Bicoid (Bcd) fivefold, Bcd concentrations in cells at positions of the cephalic furrow, an early morphological marker, differ by a factor of 2. This finding apparently contradicts the traditional threshold-dependent readout model, which predicts that the Bcd concentrations at these positions should be identical. In contrast, Bcd concentration at target gene expression boundaries is nearly unchanged early in development but adjusts dynamically toward the same twofold change as development progresses. Thus, the Drosophila segmentation gene network responds faithfully to Bcd concentration during early development, in agreement with the threshold model, but subsequently partially adapts in response to altered Bcd dosage, driving segmentation patterns toward their WT positions. This dynamic response requires other maternal regulators, such as Torso and Nanos, suggesting that integration of maternal input information is not achieved through molecular interactions at the time of readout but through the subsequent collective interplay of the network.

Automation of an "Aculight" continuous-wave optical parametric oscillator.

We report the automation of a continuous-wave, singly resonant, optical parametric oscillator (Lockheed-Martin Aculight ARGOS 2400-SF-15). This commercially available optical parametric oscillator (OPO) is capable of producing >1 W of continuously tunable idler output between 2.2 and 4.6 µm. An algorithm based on the feedback from a high accuracy wavemeter is implemented to synchronize three separate OPO tuning elements; the translation of a fan-out type periodically poled lithium niobate crystal, the rotation of an intracavity etalon, and the continuous tuning of the pump and idler wavelengths via piezoelectric strain of the tunable fiber pump laser. This allows for several hundred wavenumbers of efficient, automatic, continuous tuning of the idler wave. Continuous feedback from the wavemeter limits the absolute frequency accuracy to ±20 MHz. The broad, automatic tuning of the OPO is demonstrated via its implementation as a probe laser for the infrared action spectroscopy of methanol solvated in helium nanodroplets. LabVIEW virtual instruments for the automation of this OPO laser system are reported, along with detailed schematics of the associated hardware developed at the University of Georgia.

Rotational dynamics of the methyl radical in superfluid 4He nanodroplets.

We report the ro-vibrational spectrum of the ν3(e') band of the methyl radical (CH3) solvated in superfluid (4)He nanodroplets. Five allowed transitions produce population in the N(K) = 0(0), 1(1), 1(0), 2(2) and 2(0) rotational levels. The observed transitions exhibit variable Lorentzian line shapes, consistent with state specific homogeneous broadening effects. Population relaxation of the 0(0) and 1(1) levels is only allowed through vibrationally inelastic decay channels, and the (P)P1(1) and (R)R0(0) transitions accessing these levels have 4.12(1) and 4.66(1) GHz full-width at half-maximum line widths, respectively. The line widths of the (P)R1(1) and (R)R1(1) transitions are comparatively broader (8.6(1) and 57.0(6) GHz, respectively), consistent with rotational relaxation of the 2(0) and 2(2) levels within the vibrationally excited manifold. The nuclear spin symmetry allowed rotational relaxation channel for the excited 1(0) level has an energy difference similar to those associated with the 2(0) and 2(2) levels. However, the (P)Q1(1) transition that accesses the 1(0) level is 2.3 and 15.1 times narrower than the (P)R1(1) and (R)R1(1) lines, respectively. The relative line widths of these transitions are rationalized in terms of the anisotropy in the He-CH3 potential energy surface, which couples the molecule rotation to the collective modes of the droplet.

Infrared laser spectroscopy of the CH3OO radical formed from the reaction of CH3 and O2 within a helium nanodroplet.

Helium nanodroplet isolation and infrared laser spectroscopy are used to investigate the CH(3) + O(2) reaction. Helium nanodroplets are doped with methyl radicals that are generated in an effusive pyrolysis source. Downstream from the introduction of CH(3), the droplets are doped with O(2) from a gas pick-up cell. The CH(3) + O(2) reaction therefore occurs between sequentially picked-up and presumably cold CH(3) and O(2) reactants. The reaction is known to lead barrierlessly to the methyl peroxy radical, CH(3)OO. The ~30 kcal/mol bond energy is dissipated by helium atom evaporation, and the infrared spectrum in the CH stretch region reveals a large abundance of droplets containing the cold, helium solvated CH(3)OO radical. The CH(3)OO infrared spectrum is assigned on the basis of comparisons to high-level ab initio calculations and to the gas phase band origins and rotational constants.

Quantifying the Bicoid morphogen gradient in living fly embryos.

In multicellular organisms, patterns of gene expression are established in response to gradients of signaling molecules. During fly development in early Drosophila embryos, the Bicoid (Bcd) morphogen gradient is established within the first hour after fertilization. Bcd acts as a transcription factor, initiating the expression of a cascade of genes that determine the segmentation pattern of the embryo, which serves as a blueprint for the future adult organism. A robust understanding of the mechanisms that govern this segmentation cascade is still lacking, and a new generation of quantitative measurements of the spatiotemporal concentration dynamics of the individual players in this cascade is necessary for further progress. Here we describe a series of methods that represent the beginning of the use of Bcd as a quantification example. We describe the generation of a transgenic fly line expressing a Bcd-enhanced green fluorescent protein fusion protein. Using two-photon microscopy, we analyze the Bcd concentration dynamics and measure absolute Bcd expression levels in living fly embryos. These experiments have proven to be fruitful, generating new insights into the mechanisms that lead to the establishment and readout of the Bcd gradient. Generalization of these methods to other genes in the Drosophila segmentation cascade is straightforward and should further our understanding of the early patterning processes and the architecture of the underlying genetic network structure.

Quantum cascade laser spectroscopy and photoinduced chemistry of Al-(CO)n clusters in helium nanodroplets.

Helium nanodroplet isolation and a tunable quantum cascade laser are used to probe the fundamental CO stretch bands of aluminum carbonyl complexes, Al-(CO)(n) (n ≤ 5). The droplets are doped with single aluminum atoms via the resistive heating of an aluminum wetted tantalum wire. The downstream sequential pick-up of CO molecules leads to the rapid formation and cooling of Al-(CO)(n) clusters within the droplets. Near 1900 cm(-1), rotational fine structure is resolved in bands that are assigned to the CO stretch of a linear (2)Π(1/2) Al-CO species and the asymmetric and symmetric CO stretch vibrations of a planar C(2v) Al-(CO)(2) complex in a (2)B(1) electronic state. Bands corresponding to clusters with n ≥ 3 lack resolved rotational fine structure; nevertheless, the small frequency shifts from the n = 2 bands indicate that these clusters consist of an Al-(CO)(2) core with additional CO molecules attached via van der Waals interactions. A second n = 2 band is observed near the CO stretch of Al-CO, indicating a local minimum on the n = 2 potential consisting of an "unreacted" (Al-CO)-CO cluster. The line width of this band is ∼0.3 cm(-1), which is about 30 times broader than the transitions within the Al-CO band. The additional broadening is consistent with a homogeneous mechanism corresponding to a rapid vibrational excitation induced reaction within the (Al-CO)-CO cluster to form the covalently bonded Al-(CO)(2) complex. Ab initio CCSD(T) calculations and natural bond orbital (NBO) analyses are carried out to investigate the nature of the bonding in the n = 1, 2 complexes. The NBO calculations show that both π-donation (from the occupied aluminum p orbital into a π* antibonding CO orbital) and σ-donation (from CO into the empty aluminum p orbitals) play a significant role in the bonding, analogous to transition-metal carbonyl complexes. The large red shift observed for the CO stretch vibrations is consistent with this bonding analysis.

Infrared spectroscopy of (HCl)m(H(2)O)n clusters in helium nanodroplets: definitive assignments in the HCl stretch region.

Infrared spectra in the HCl stretch region (2600-2900 cm(-1)) are presented for small, mixed (HCl)(m)(H(2)O)(n) clusters solvated in helium nanodroplets. Sharp bands associated with the Cl-H...Cl stretch vibrations in m:n = 1:1, 2:1, 2:2, and 3:1 clusters are superimposed on a broad background that increases in intensity as larger clusters are grown within the droplets. The broad background is determined to be partially due to mixed clusters with m > 3 and n > 2. The sharp bands are assigned to specific cluster compositions, m:n, via pick-up pressure dependence studies and optically selected mass spectrometry. Orientation of the clusters is achieved with the application of a large electric field to the laser/droplet beam interaction region. The intensity of each band is measured as a function of the applied field strength. Simulations of this electric field dependence based on ab initio calculations of permanent dipole moments and vibrational transition moment angles leads to definitive structural assignments for each sharp band. The 2:1 complex is cyclic, and a band associated with the 2:2 cluster is determined to arise from the nonalternating cyclic structure.