Absolute molecular transition frequencies measured by three cavity-enhanced spectroscopy techniques.

Absolute frequencies of unperturbed (12)C(16)O transitions from the near-infrared (3-0) band were measured with uncertainties five-fold lower than previously available data. The frequency axis of spectra was linked to the primary frequency standard. Three different cavity enhanced absorption and dispersion spectroscopic methods and various approaches to data analysis were used to estimate potential systematic instrumental errors. Except for a well established frequency-stabilized cavity ring-down spectroscopy, we applied the cavity mode-width spectroscopy and the one-dimensional cavity mode-dispersion spectroscopy for measurement of absorption and dispersion spectra, respectively. We demonstrated the highest quality of the dispersion line shape measured in optical spectroscopy so far. We obtained line positions of the Doppler-broadened R24 and R28 transitions with relative uncertainties at the level of 10(-10). The pressure shifting coefficients were measured and the influence of the line asymmetry on unperturbed line positions was analyzed. Our dispersion spectra are the first demonstration of molecular spectroscopy with both axes of the spectra directly linked to the primary frequency standard, which is particularly desirable for the future reference-grade measurements of molecular spectra.

BAX inhibitor-1 is a Ca(2+) channel critically important for immune cell function and survival.

The endoplasmic reticulum (ER) serves as the major intracellular Ca(2+) store and has a role in the synthesis and folding of proteins. BAX (BCL2-associated X protein) inhibitor-1 (BI-1) is a Ca(2+) leak channel also implicated in the response against protein misfolding, thereby connecting the Ca(2+) store and protein-folding functions of the ER. We found that BI-1-deficient mice suffer from leukopenia and erythrocytosis, have an increased number of splenic marginal zone B cells and higher abundance and nuclear translocation of NF-κB (nuclear factor-κ light-chain enhancer of activated B cells) proteins, correlating with increased cytosolic and ER Ca(2+) levels. When put into culture, purified knockout T cells and even more so B cells die spontaneously. This is preceded by increased activity of the mitochondrial initiator caspase-9 and correlated with a significant surge in mitochondrial Ca(2+) levels, suggesting an exhausted mitochondrial Ca(2+) buffer capacity as the underlying cause for cell death in vitro. In vivo, T-cell-dependent experimental autoimmune encephalomyelitis and B-cell-dependent antibody production are attenuated, corroborating the ex vivo results. These results suggest that BI-1 has a major role in the functioning of the adaptive immune system by regulating intracellular Ca(2+) homeostasis in lymphocytes.

Low-pressure line-shape study in molecular oxygen with absolute frequency reference.

We present a line-shape analysis of the rovibronic R1 Q2 transition of the oxygen B band resolved by the Pound-Drever-Hall-locked frequency-stabilized cavity ring-down spectroscopy technique in the low pressure range. The frequency axis of the spectra is linked by the ultra-narrow diode laser to the optical frequency comb in order to measure the absolute frequency at each point of the recorded spectra. Experimental spectra are fitted with various line-shape models: the Voigt profile, the Galatry profile, the Nelkin-Ghatak profile, the speed-dependent Voigt profile, and the speed-dependent Nelkin-Ghatak profile with quadratic and hypergeometric approximations for the speed dependence of collisional broadening and shifting. The influences of Dicke narrowing, speed-dependent effects, and correlation between phase- and velocity-changing collisions on the line shape are investigated. Values of line-shape parameters, including the absolute frequency of the transition 435685.24828(46) GHz, are reported.

Comb-linked, cavity ring-down spectroscopy for measurements of molecular transition frequencies at the kHz-level.

We present a low uncertainty measurement technique for determining molecular transition frequencies. This approach is complementary to sub-Doppler saturation spectroscopies and is expected to enable new frequency measurements for a wide variety of molecular species with uncertainties at the kHz-level. The technique involves measurements of Doppler broadened lines using cavity ring-down spectroscopy whereby the probe laser is actively locked to the ring-down cavity and the spectrum frequencies are linked directly to an optical frequency comb that is referenced to an atomic frequency standard. As a demonstration we have measured the transition frequency of the (30012) ← (00001) P14e line of CO2 near 1.57 µm with a combined standard uncertainty of ~9 kHz. This technique exhibits exceptional promise for measurements of transition frequencies and pressure shifting parameters of many weak absorbers, and indicates the potential for substantially improved measurements when compared to those obtained with conventional spectroscopic methods.

Spectroscopic measurement of the vapour pressure of ice.

We present a laser absorption technique to measure the saturation vapour pressure of hexagonal ice. This method is referenced to the triple-point state of water and uses frequency-stabilized cavity ring-down spectroscopy to probe four rotation-vibration transitions of at wavenumbers near 7180 cm(-1). Laser measurements are made at the output of a temperature-regulated standard humidity generator, which contains ice. The dynamic range of the technique is extended by measuring the relative intensities of three weak/strong transition pairs at fixed ice temperature and humidity concentration. Our results agree with a widely used thermodynamically derived ice vapour pressure correlation over the temperature range 0°C to -70°C to within 0.35 per cent.

Spontaneous burrowing behaviour in the rat is reduced by peripheral nerve injury or inflammation associated pain.

Pain influences many aspects of daily living and effective analgesics should reinstate normal spontaneous daily behaviours. Experiments are described herein which show that the innate, spontaneous behaviour of burrowing by rats, which can be simply and objectively assessed by measuring the amount of gravel left in a hollow tube 1 h after presentation to the rat, is reduced by peripheral nerve injury (tibial nerve transection (TNT), L5 spinal nerve transection (SNT) and partial sciatic nerve ligation (PSNL)) and also following inflammation induced by intra-plantar injection of Complete Freund's Adjuvant (CFA). Gabapentin (100 mg/kg sc) but not at 30 mg/kg sc significantly reduced burrowing activity in naive rats. All peripheral nerve injuries and CFA reduced burrowing compared with shams and rats naive to surgery. The level of mechanical hypersensitivity in rats with peripheral nerve injury did not correlate with the deficit in burrowing indicating that different parameters of the holistic pain experience are measured in these paradigms. Gabapentin at 30 mg/kg sc, but not 100 mg/kg sc, reversed the deficit in burrowing induced by TNT and ibuprofen (30 mg/kg sc) reversed the effect of CFA on burrowing. These experiments show that measurement of burrowing is a simple, objective assay of innate rodent behaviour affected by pain that is ethologically relevant to the rat, does not rely wholly on evoking a reflex and can dissociate a selective analgesic dose of gabapentin from one inducing motor impairment in the same animal.

Cavity ring-down spectroscopy of the oxygen B-band with absolute frequency reference to the optical frequency comb.

Absolute positions of several oxygen B-band lines were measured with the Pound-Drever-Hall-locked frequency-stabilized cavity ring-down spectrometer. The frequency axis of spectra was linked to the optical frequency comb. Achieved uncertainties of line positions are between 0.9 and 2.9 MHz. Self-pressure shifts coefficients are also reported.

Pound-Drever-Hall-locked, frequency-stabilized cavity ring-down spectrometer.

We describe a high sensitivity and high spectral resolution laser absorption spectrometer based upon the frequency-stabilized cavity ring-down spectroscopy (FS-CRDS) technique. We used the Pound-Drever-Hall (PDH) method to lock the probe laser to the high-finesse ring-down cavity. We show that the concomitant narrowing of the probe laser line width leads to dramatically increased ring-down event acquisition rates (up to 14.3 kHz), improved spectrum signal-to-noise ratios for weak O(2) absorption spectra at λ = 687 nm and substantial increase in spectrum acquisition rates compared to implementations of FS-CRDS that do not incorporate high-bandwidth locking techniques. The minimum detectable absorption coefficient and the noise-equivalent absorption coefficient for the spectrometer are about 2×10(-10) cm(-1) and 7.5×10(-11) cm(-1)Hz(-1/2), respectively.

Expression of urokinase plasminogen activator receptor on monocytes from patients with relapsing-remitting multiple sclerosis: effect of glatiramer acetate (copolymer 1).

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system in which peripheral blood monocytes play an important role. We have previously reported that patients with chronic progressive MS (CPMS) have significantly increased numbers of circulating monocytes which express the urokinase plasminogen activator receptor (uPAR). In the present study, we examined the expression of uPAR on monocytes in patients with relapsing-remitting multiple sclerosis (RRMS) not currently participating in a clinical trial and in patients with RRMS who were enrolled in a double-blind multicenter clinical trial designed to examine the effect of glatiramer acetate (copolymer 1; Copaxone) on relapsing disease. Patients with CPMS have sustained high levels of circulating uPAR-positive (uPAR(+)) monocytes. In comparison, patients with RRMS displayed variable levels of circulating uPAR(+) monocytes. Mean values for uPAR in patients with RRMS were above those seen for controls but were not as high as those observed for patients with secondary progressive MS. Patients with RRMS in the clinical trial also had variable levels of monocyte uPAR. However, patients in the treatment group displayed lower levels following 2 years of treatment. In both placebo-treated and glatiramer acetate-treated patients, the percentage of circulating uPAR(+) monocytes, as well as the density of uPAR expressed per cell (mean linear fluorescence intensity), increased just prior to the onset of a clinically documented exacerbation. Values fell dramatically with the development of clinical symptoms. uPAR levels in all groups correlated with both clinical activity and severity. Results indicate that monocyte activation is impatient in MS and that glatiramer acetate may have a significant effect on monocyte activation in patients with RRMS.

Overview of symptomatic management of multiple sclerosis.

Multiple sclerosis (MS) is a chronic, inflammatory, demyelinating, and often disabling disease of the central nervous system. Permanent disability may relate to axonal damage. The etiology of MS remains elusive; treatment may be episodic, symptomatic, and designed for partial disease modification. Its hallmark is unpredictability marked by relapses and remissions or disease progression. Despite the new immunomodulating agents that diminish some individuals' relapse rates and clinical worsening, there is no cure for MS. Thus symptom management is a key feature of MS nursing care. Adequate control of symptoms can result in maximal function, prevention of injury or trauma, restoration of a sense of control, and promotion of an acceptable quality of life. The nurse plays a vital role in the spectrum of MS care, none so critical as in the effort to moderate and modulate the symptomatic problems related to the disease.

Effect of monthly intravenous cyclophosphamide in rapidly deteriorating multiple sclerosis patients resistant to conventional therapy.

Fourteen consecutive clinically definite relapsing-remitting multiple sclerosis (MS) patients were treated with monthly intravenous cyclophosphomide (CTX) for 6 months. All had experienced severe dinical deterioration during the 12 months prior to treatment with CTX despite treatment with conventional immunomodulating agents and intravenous methylprednisolone. Treatment with CTX led to improvement and neurologic stability within 6 months which was sustained for at least 18 months after the onset of treatment with CTX. Therapy with CTX was well tolerated. CTX may be of benefit in MS patients who experience rapid clinical worsening and are resistant to conventional therapy.

Long-term therapy with glatiramer acetate in multiple sclerosis: effect on T-cells.

Glatiramer acetate (GA) is an immunotherapeutic drug for multiple sclerosis (MS). Several mechanisms of action have been demonstrated which target and affect T-cells that are specific for myelin antigen epitopes. We measured the in vitro proliferation of GA-responsive T-cells from untreated MS patients and from normal healthy subjects; in addition, we determined the effect of prolonged GA therapy or interferon-beta therapy on the in vitro proliferation of GA-responsive T-cells of MS patients. We found that GA induces the proliferation of T-cells isolated from individuals who have not been previously exposed to GA, and that long-term in vivo therapy of MS patients with GA abrogates the GA-induced proliferative response of T-cells. In GA-treated patients, there is no evidence of generalized immunosuppression; both tetanus toxoid and anti-CD3 induced proliferative responses remain unaffected. We propose that prolonged in vivo exposure to GA may result in the eventual induction of anergy or deletion of a population of GA-responsive cells that may also be T-cells that are pathogenic in MS. This mechanism of action, in addition to other mechanisms that have been demonstrated, suggests that GA has pleiotropic effects on the immune system in MS.

Factors in the cycle of violence: gender rigidity and emotional constriction.

A sample of 595 men were administered self-report assessments of childhood sexual and physical abuse, perpetration history, gender rigidity and emotional constriction. Including noncontact forms of sexual abuse, 11% of the men reported sexual abuse alone, 17% reported physical abuse alone, and 17% reported both sexual and physical abuse. Of the 257 men in the sample who reported some form of childhood abuse, 38% reported some form of perpetration themselves, either sexual or physical; of the 126 perpetrators, 70% reported having been abused in childhood. Thus, most perpetrators were abused, but most abused men did not perpetrate. Both sexually and physically abused men who perpetrated manifested significantly more gender rigidity and emotional constriction than abused nonperpetrators. Men who reported abuse but not perpetration demonstrated significantly less gender rigidity, less homophobia and less emotional constriction than nonabused men.

Educational, occupational, and relationship histories of men who were sexually and/or physically abused as children.

Ninety men (mean age 26) at an urban Northeastern university were administered a self-report assessment of their early sexual and physical abuse experiences, and their educational, occupational, relationship, and substance abuse histories. Subjects were classified as sexually abused according to criteria used by Wyatt (1985) and Finkelhor (1979). Sixteen men (17.8%) experienced sexual abuse alone, 22 men (24.4%) physical abuse alone, 15 men (16.7%) both sexual and physical abuse, and 37 men (41.1%) were classified as nonabused. Of the 31 men who reported sexual abuse, 24 (77.4%) were contact, the rest noncontact. Sexually abused men reported significantly greater difficulties than nonabused men at all levels of education: grade school, high school and college. They also reported more negative job experiences and more negative experiences in relationships. Physically abused men showed a similar but less pervasive pattern of difficulties. Substance abuse was significantly more prevalent among both sexually and physically abused men than among nonabused subjects.

The psychological impact of sexual abuse: content analysis of interviews with male survivors.

Autobiographical interviews with 26 adult male survivors of childhood sexual abuse were audiotaped, transcribed verbatim and content analyzed to identify common psychological themes. Approximately equal numbers of men were abused by male and female perpetrators, almost half came from disrupted or violent homes and a majority had a history of substance abuse. Fifteen psychological themes were identified: Anger, Betrayal, Fear, Homosexuality Issues, Helplessness, Isolation and Alienation, Legitimacy, Loss, Masculinity Issues, Negative Childhood Peer Relations, Negative Schemas about People, Negative Schemas about the Self, Problems with Sexuality, Self Blame/Guilt and Shame/Humiliation. The themes are discussed and illustrated with examples drawn from the transcripts.

Motives and psychodynamics of self-reported, unincarcerated rapists.

Fifteen men, classified by self-report as rapists and attempted rapists, but who had never been arrested or convicted, were compared to a matched control group on standardized instruments and content-coded interviews. Differences in hostility toward women, power motivations, and hypermasculinity were similar to findings from studies of convicted rapists. However, results suggest a greater role for the father in the etiology of rape-associated dynamics than has previously been reported.

Motivational factors in nonincarcerated sexually aggressive men.

Research on convicted rapists has demonstrated the importance of several key motivational factors in male sexual aggression. In particular, anger at women and the need to dominate or control them have been repeatedly implicated. Although anger and power have also been shown to be important in understanding college men who report sexually aggressive behavior, there has been little research on what underlies these motives. This research combined questions assessing these underlying motivational factors, as well as questions dealing with underlying sexual motivation and disinhibition, with a slightly modified version of the Sexual Experiences Survey (Koss & Oros, 1982). In Study 1, subjects were 184 male undergraduates. Factor analysis of the questions composing the four scales yielded four slightly modified scales. Scales measuring underlying anger, underlying power, and disinhibition significantly differentiated sexually aggressive from nonaggressive men but did not distinguish between men who were coercive, manipulative, or nonaggressive. In a replication on a smaller sample (n = 70), underlying anger, underlying power, and disinhibition again differentiated sexually aggressive from nonaggressive men.