Filament conductivity enhancement through nonlinear beam interaction.

Laser filament applications relying on filament plasma conductivity are limited by their low electron densities and corresponding short lifetimes. Filament plasma formation, an intensity-dependent process, is limited by the clamping of the filament core intensity. Consequently, increasing initial beam energy results in the breakup of the beam into multiple filaments rather than the enhancement of the electron density and conductivity of an individual filament. However, we demonstrate here the augmentation of the filament plasma density up to three times the typical value through the energy exchange between two co-propagating femtosecond beams with total powers between 1.7 and 2.2 Pfil.

Morphology dependent field emission of acid-spun carbon nanotube fibers.

Acid spun carbon nanotube (CNT) fibers were investigated for their field emission properties and performance was determined to be dependent on fiber morphology. The fibers were fabricated by wet-spinning of pre-made CNTs. Fiber morphology was controlled by a fabrication method and processing conditions, as well as purity, size, and type of the CNT starting material. The internal fiber structure consisted of CNT fibrils held together by van der Waals forces. Alignment and packing density of the CNTs affects the fiber's electrical and thermal conductivity. Fibers with similar diameters and differing morphology were compared, and those composed of the most densely packed and well aligned CNTs were the best field emitters as exhibited by a lower turn-on voltage and a larger field enhancement factor. Fibers with higher electrical and thermal conductivity demonstrated higher maximum current before failure and longer lifetimes. A stable emission current at 3 mA was obtained for 10 h at a field strength of <1 V µm(-1). This stable high current operation makes these CNT fibers excellent candidates for use as low voltage electron sources for vacuum electronic devices.

T-Lymphocyte precursors. I. Synergy between precursor and mature T lymphocytes in the response to concanavalin A.

When mouse bone marrow cells are mixed with cortisol-resistant thymocytes and stimulated in vitro with concanavalin A, the mitogenic response observed is much greater than additive, that is, it is synergistic. Between 94 and 96% of responding cells could be identified as T cells (Thy-1 positive) and of these, 79-100% derived from the cortisol-resistant thymocyte population, not from the bone marrow. Purified macrophages could not replace bone marrow; and marrow depleted of mature T or B cells worked as well as normal marrow. Thus, T and B cells and macrophages were ruled out as the synergizing cell of bone marrow. Nude spleen contained 10 times as many precursors of T cells as did nude marrow and was 10 times better at synergy with cortisol-resistant thymocytes. This implication of the pre-T cell as synergizer was supported by the finding that the synergistic activity of marrow was lost on preincubation, but maintained if the preincubation medium contained thymosin or cyclic AMP. Thus, the ability to enhance the response of relatively mature T cells to Con A is a property of pre-T cells. It is anticipated that this property will allow more detailed studies of T-cell precursor development in mice, and possibly in man.

Rationale for routine collection of patient reported outcomes during integrative medicine consultation visits.

OBJECTIVES: Integrative medicine (IM) is whole-person care utilizing complementary health approaches to address numerous physical or emotional influences that can impact an individual's health. Patient-reported outcomes (PRO) are subjective measures that quantify patients' perception of their quality of life. While PRO measures have been routinely assessed in specific oncology clinics, our objective was to assess the ability and utility of routine collection of PRO measures in an IM clinic. DESIGN/SETTING/MAIN OUTCOME: Patients receiving a clinical consultation in an ambulatory IM clinic completed the PROMIS Global Health Form in the clinic waiting room. RESULTS: From November 2013 through October 2016, the PROMIS Global Health Form (PROMIS-10) was administered during 59% of IM provider consultation visits (7172/12,207), representing 3473 unique patients. Most patients were female (81%), White (93%), middle-aged (49.2; SD 15.4) and had commercial health insurance (66%). Baseline Mental (44.9; SD 9.1) and Physical Health (44.2; SD 8.6) scores were roughly 0.5 standard deviation below the national mean values (50; SD 10). Factors such as age, race and non-commercial insurance were associated with lower PROMIS-10 scores. Patients completing at least two PROMIS-10 questionnaires (n = 1541) exhibited increases of 2.3% and 2.8% from first to last PROMIS-10 assessment in Mental and Physical Heath scores respectively. CONCLUSIONS: It is possible to routinely collect PRO measures in large IM clinic and longitudinal improvements in Mental and Physical Health scores were observed. Future research should focus on understanding how providers can utilize PRO results in real-time to improve patients' clinical outcomes and potentially decrease healthcare utilization.

Endogenous ligands selecting T cells expressing particular V beta elements.

It has recently become clear that the minor lymphocyte stimulatory antigens (Mls) and other endogenous ligands which lead to the partial or total deletion of T cells bearing particular V beta segments are encoded by mouse mammary tumor virus (MMTV). We review here the genetic analyses of multiple V beta 11 and V beta 3 deletion ligands and demonstrate the involvement of MMTV in all examples. Several features of Mls and the V beta 11/V beta 3 deleting ligands identify them as members of the superantigen family. Bacterial superantigens are known to bind both MHC class II and the TCR in regions distinct from conventional peptide antigens. Within the MMTV genome, the 3' LTR has been identified as encoding superantigen function. We present data demonstrating that in vitro translation identifies the major product of the open reading frame (ORF) within the 3' LTR as a type II integral membrane glycoprotein. It is proposed that the type II membrane glycoprotein interacts with MHC and TCR in a manner analogous to the bacterial superantigens and distinct from conventional peptide antigen. Several unanswered questions regarding superantigen action remain; what determines total or partial deletion? How is Mls transferred between cells? These questions are addressed in the discussion.

An immature rat lymphocyte marker CD157: striking differences in the expression between mice and rats.

We have established a novel monoclonal antibody that recognises mouse and rat CD157, and uncovered striking differences in both the level and stage of expression of this antigen in the primary lymphoid organs between these two species. Unlike mouse, the majority of rat thymocytes express CD 157. SHR and WKY rats were the exception, having unusually low levels (similar to those of the mouse) of these cells. However, in both species, a subset of CD3- CD4- CD8- thymocytes exhibited high levels of CD157. Surprisingly, these CD157high cells temporarily upregulated MHC class I molecules in both species. Furthermore, a third of CD157high rat thymocytes were CD45RC+, a marker found on immature thymocytes with regenerative capacity. Examination of the bone marrow lymphoid population shows that the expression of rat CD157 is largely observed at the CD45R+ IgM- pre-B-II cell stage, and unlike mouse, extension of expression into the IgM+ immature B cell stage was marginal. Similar to CD157high immature thymocytes, these immature B cells also expressed high levels of MHC class I. With the exception of the LEC, SHR and WKY rat strains, which have three- to four-fold less CD157+ bone marrow myeloid cells, percentages of these cells are similar between these two species. Thus, marked differences in the level and stage(s) of CD157 expression on lymphoid cells in mouse and rat indicate that CD157 may not, as previously thought, have a direct role in T or B cell differentiation.

Prevalence of behavior disorder and disturbance to family and staff in a sample of adult day health care clients.

Latent class-derived prevalence estimates of behavior disorder are provided for adult day health care (ADHC) clients; informal and formal caregivers reported 11% and 14%, respectively, of these clients as engaging in severe disturbed behavior (95% confidence intervals across sources are from 7% to 18%). The prevalences, estimated for informal and formal caregivers respectively, were 12% and 16% for affective disorder, 15% and 18% for cognitive disorders, 16% and 13% for verbal-vocal agitation, and 6% and 8% for socially inappropriate behavior. These rates can be contrasted with those of the institutional population which, while higher, overlap with the distribution of behavior disorder for ADHC community residents. The degree of reported disturbance to family and staff was similar across items.

Enhancing geriatric nursing scholarship: specialization versus generalization.

This article explores the relative merits of encouraging preparation of more nurses with specialization in geriatrics as compared to encouraging geriatric preparation among nurses whose major field of study is outside geriatrics. The article explores two approaches to examining capacity for geriatric nursing scholarship among nurse scholars not involved in geriatrics, and in schools of nursing with strength in research but with little geriatric research. The findings show an ongoing need to strengthen geriatric nursing as an area of specialization. Faculty prepared in geriatric nursing are underrepresented in schools of nursing, and only a small number of doctoral students specialize in geriatric nursing. Academic nursing programs with strength in geriatric nursing need ongoing support to maintain and expand current geriatric programs. Data support that encouraging individual non-geriatric nurse faculty and doctoral candidates to focus their work on areas of concern to geriatric nursing, and strengthening geriatrics in research-intensive schools of nursing that have not heavily invested in geriatric scholarship are viable options for strengthening academic geriatric nursing. Establishing mechanisms to attract nurse scholars working outside the scope of geriatric nursing to address clinical issues of concern to older adults offers promise in rapidly attracting new scholars to geriatric nursing.

The non-thiol angiotensin-converting enzyme inhibitor quinapril suppresses inflammatory arthritis.

OBJECTIVES: In addition to its vasoactive effects, angiotensin II has proinflammatory properties. Angiotensin-converting enzyme (ACE) inhibitors reduce the production of angiotensin II and could therefore act as anti-inflammatory agents. Here we investigated the capacity of the ACE inhibitor quinapril to modulate inflammatory arthritis. METHODS: We studied the effect of quinapril on disease activity in mice with collagen-induced arthritis (CIA). Mice received oral quinapril (10 mg/kg/day) at the time of arthritis induction (prophylaxis protocol) or at the onset of mild arthritis (therapy protocol). Concentrations of immunoglobulin G (IgG) subtypes specific for bovine Type II collagen and TNF-alpha were measured by enzyme-linked immunoassay. RESULTS: Quinapril significantly diminished the activity of CIA when given as prophylaxis or therapy (prophylaxis protocol, P<0.001; therapy protocol P=0.002). Antigen-specific IgG2a antibodies were reduced by 52% (P=0.02) in the quinapril prophylaxis protocol. Suppression of arthritis by quinapril was associated with reduced articular expression of TNF-alpha by 68% (P=0.01) in the prophylaxis protocol and 27% (P=0.06) in the therapy protocol. Quinapril therapy also inhibited expression of splenocyte TNF-alpha production following lipopolysaccharide (LPS) in vitro stimulation by 59% (P=0.02). In parallel human in vitro experiments, ACE inhibition suppressed LPS-stimulated production of TNF-alpha by monocytes. In order to confirm that the action of quinapril occurred predominantly through suppression of angiotensin II, parallel experiments with the angiotensin receptor antagonist candesartan cilexetil demonstrated that this agent also inhibited disease activity in CIA. CONCLUSIONS: These data suggest that angiotensin II is a mediator of chronic inflammation and that ACE inhibition may have therapeutic effects in human inflammatory arthritis.

Inflammatory arthritis and dermatitis in thymectomized, CD25+ cell-depleted adult mice.

OBJECTIVE: To investigate the effect of CD25+ or CTLA-4(+) cell depletion on the natural history of collagen-induced and spontaneous arthritis in male DBA1/J mice. METHODS: Male DBA/1J mice were treated with anti-CD25 depleting antibody (PC61) or isotype control (GL113), or with anti-CTLA-4 depleting antibody (4F10) at various time-points peri- and post-immunization with bovine collagen type II, emulsified in adjuvant. In order to develop a model system in which long-term depletion of CD25+ regulatory T cells can be achieved prior to immunization, adult male DBA/1J mice were thymectomized prior to administration of either PC61 or GL113. An ELISA demonstrated that PC61 and GL113 antibodies were undetectable by 21 days after administration and FACS analysis confirmed the long-term depletion of CD25+ cells in peripheral blood. RESULTS: In the thymectomized mice treated with PC61, the CD25+ population was depleted and a spontaneous arthritis developed (P = 0.03). In the non-thymectomized mice, administration of CTLA-4-depleting antibody prior to immunization exacerbated arthritis in mice immunized with bovine collagen type II emulsified in incomplete Freund's adjuvant (P < 0.01). However, no significant difference in the natural history of arthritis was evident in mice treated with CD25-depleting antibody (PC61) compared with control antibody (GL113). CONCLUSIONS: Two separate models implicate CD25+ CTLA-4(+) constitutive cells in suppression of arthritis in susceptible DBA/1 males: exacerbation of collagen-induced arthritis following CTLA-4 depletion at the start of induction and spontaneous arthritis in the thymectomy/CD25+ depletion model.

The genetic basis of negative selection of Tcrb-V11+ T cells.

Non-H-2 genes responsible for negative selection of Tcrb-V11+ T cells were examined using backcross mice of various strains with C58, which does not delete Tcrb-V11+ T cells. Two independently segregating genes were found: one leading to partial deletion was closely linked to Ly-2/Ly-3 on chromosome 6, and the second giving virtually complete deletion has not yet been mapped. The A strain had only the former, whereas BALB/c, BALB.K, B10.BR, CBA-T6, C3H/He, and DBA/2 expressed both of these genes. Although a gene(s) of the NIH strain led only to partial deletion, the chromosomal localization of the gene(s) has not yet been determined: no informative polymorphic molecules are expressed from genes on chromosome 6 of this strain.

Positive and negative selection of Tcrb-V6+ T cells.

Tcrb-V6+ T cells are deleted by an endogenous superantigen probably encoded by a mouse mammary tumor provirus (Mtv), Mtv-7, in association with major histocompatibility complex (MHC) class II molecules. In contrast, Tcrb-V6+CD4+ T cells are positively selected by MHC class II E molecules in Mtv-7- mice. We have examined the levels of Tcrb-V6+CD4+ and Tcrb-V6+CD8+ T cells from six combinations of backcross mice. In this paper we show that: 1) Tcrb-V6+CD8+ T cells can be positively selected by MHC class I molecules; 2) MHC class II A molecules can also influence the levels of Tcrb-V6+CD4+ T cells; 3) Mtv-7- NZW mice have a new Mtv, Mtv-44, which cosegregates with a gene encoding the partial deletion ligand for Tcrb-V6+ T cells; 4) the remaining Tcrb-V6+ T cells from mice with partial deletion of these T cells appear not to be anergized in the periphery.

H-Y responses of non-obese diabetic (NOD) mice.

Female non-obese diabetic (NOD) mice were tested for their ability to make responses to the male-specific (H-Y) transplantation antigen. In vivo assessment of this ability was made using skin graft rejection. A proportion (60%) spontaneously rejected NOD male tail skin by 80 days post-transplantation. The detection of the generation of H-Y-specific cytotoxic T cells, following in vivo priming and secondary in vitro restimulation, was carried out using a conventional 51Cr release assay. Female NOD mice primed either by skin grafting, intraperitoneal (i.p.) or footpad (f.p.) injection of male NOD spleen cells could be induced to make anti-H-Y cytotoxic responses, but not every immunized mouse responded. The nature of the H-Y-reactive T cells was investigated further by the in vitro isolation of T-cell clones of which some were H-Y specific.

Thymic control of proliferation of T cell precursors in bone marrow.

The activity of T lymphocyte precursors (pre-T cells) in the bone marrow of mice was measured by the concanavalin A response synergy assay. Pre-T cell levels were low in marrow of neonatally thymectomized mice and could be restored to control values by treatment in vivo with an extract of mouse thymus. Levels of activity were also low in aging mice and again could be restored by thymic extract treatment. The most profound fall with aging was in the proliferating pre-T cell compartment as detected by tritiated thymidine suicide; and this compartment was restored by thymic extract treatment. Irradiation to the thymus, with the bone marrow shielded, caused a fall in resting pre-T cells in the bone marrow and a concomitant rise in proliferating cells. These results are consistent with a model of control of pre-T cell maturation in which the thymus senses the number of developing lymphocytes within it and responds to a fall in this number by increasing production of hormone. The hormone acts on resting pre-T cells in the marrow, stimulating some of them to proliferate, leave the bone marrow, and repopulate the thymus.

Induction of mouse homocytotropic antibodies to Timothy pollen antigens.

The IgG1 and IgE homocytotropic antibody responses of LAF and C3H mice to timothy pollen antigens are defined. Both mouse strains responded to low doses of crude timothy pollen extract (WST) or a major antigen of timothy pollen coupled to a purified fraction of Ascaris suum (Antigen B-Ascaris). Titers in LAF mice were greater than those in C3H mice. Regardless of the immunogen, antigen B was the major determinant recognized by the homocytotropic antibodies; PCA titers with WST or antigen B for challenge were equivalent and PCA activity could be inhibited by antigen D, a dialyzable fraction of timothy pollen possessing the antigen B determinant in monovalent form. The possible usefulness of antigen D for in vivo and in vitro studies of specific immune suppression of cellular activity is discussed.