Search

One of the principal goals of glycoprotein research is to correlate glycan structure and function. Such correlation is necessary in order for one to understand the mechanisms whereby glycoprotein structure elaborates the functions of myriad proteins. The accurate comparison of glycoforms and quantification of glycosites are essential steps in this direction. Mass spectrometry has emerged as a powerful analytical technique in the field of glycoprotein characterization. Its sensitivity, high dynamic range, and mass accuracy provide both quantitative and sequence/structural information. As part of the 2012 ABRF Glycoprotein Research Group study, we explored the use of mass spectrometry and ancillary methodologies to characterize the glycoforms of two sources of human prostate specific antigen (PSA). PSA is used as a tumor marker for prostate cancer, with increasing blood levels used to distinguish between normal and cancer states. The glycans on PSA are believed to be biantennary N-linked, and it has been observed that prostate cancer tissues and cell lines contain more antennae than their benign counterparts. Thus, the ability to quantify differences in glycosylation associated with cancer has the potential to positively impact the use of PSA as a biomarker. We studied standard peptide-based proteomics/glycomics methodologies, including LC-MS/MS for peptide/glycopeptide sequencing and label-free approaches for differential quantification. We performed an interlaboratory study to determine the ability of different laboratories to correctly characterize the differences between glycoforms from two different sources using mass spectrometry methods. We used clustering analysis and ancillary statistical data treatment on the data sets submitted by participating laboratories to obtain a consensus of the glycoforms and abundances. The results demonstrate the relative strengths and weaknesses of top-down glycoproteomics, bottom-up glycoproteomics, and glycomics methods.

Using tenant-level data from 18 states that represent almost 40% of all Low-Income Housing Tax Credit units, this article examines tenant incomes, rental assistance, and rent burdens to shed light on key questions about our largest federal supply-side affordable housing program. Specifically, what are the incomes of the tenants, and does this program reach those with extremely low incomes? What rent burdens are experienced, and is economic diversity within developments achieved? We find that approximately 45% of tenants have extremely low incomes, and the overwhelming majority of such tenants also receive some form of rental assistance. Rent burdens are lower than that for renters with similar incomes nationally but generally higher than that presumed for housing programs of the U.S. Department of Housing and Urban Development. Rent burdens vary greatly by income level and are lowered by the sizable share of owners who charge below federal maximum rents. Finally, we find evidence of both economically diverse developments and those with concentrations of households with extremely low incomes.

BackgroundMechanical thrombectomy has become the accepted treatment for large vessel occlusion in acute ischemic stroke. Unfortunately, a large cohort of patients do not achieve functional independence with treatment, even though the results are more robust than with medical management. The hyperintense acute reperfusion marker (HARM) on MRI is an indication of the breakdown of the blood–brain barrier and reperfusion injury.ObjectiveTo examine the hypothesis that the presence of HARM on MRI correlates with worse neurological recovery after reperfusion therapy.MethodsWe retrospectively reviewed 35 consecutive patients who between February 24, 2016 and April 23, 2016 underwent MRI to determine the presence of HARM after thrombectomy for anterior circulation large vessel occlusion. Demographic, radiographic imaging, and outcome data were collected. Univariate and binary logistic regression models were performed to assess predictors for improvement of the National Institutes of Health Stroke Scale (NIHSS) score by ≥8 points at 24 hours.ResultsThe 35 patients studied had an average age of 64±14 years of age with a median NIHSS score of 15 (IQR 9–20). Eighteen patients (51%) were found to have a HARM-positive MRI. In univariate analysis, patients with HARM were older, had lower reperfusion rates and more postprocedural hemorrhages. In binary logistic regression modeling, the absence of HARM was independently associated with a ≥8-point NIHSS score improvement at 24 hours (OR=7.14, 95% CI 1.22 to 41.67).ConclusionsThis preliminary analysis shows that the presence of HARM may be linked to worse neurological recovery 24 hours after thrombectomy. Reperfusion injury may affect the number of patients achieving functional independence after treatment.

The long allele of a functional promoter polymorphism in the serotonin transporter (SERT) is associated with an increased risk of some forms of pulmonary arterial hypertension. We hypothesized that the long allele or other polymorphisms in SERT would be associated with an increased risk of portopulmonary hypertension (PPHTN) in patients with advanced liver disease.

Right ventricular function is a key determinant of exercise capacity and survival in pulmonary arterial hypertension (PAH). We aimed to study the predictors of right ventricular ejection fraction (RVEF) in patients with newly diagnosed PAH.

Objective.In September 2006, the Centers for Disease Control and Prevention was notified of cases of gram-negative bloodstream infection (BSI) occurring among outpatients who received an intravenous formulation of the prostanoid treprostinil. An investigation was conducted to determine rates of prostanoid-associated BSI in this patient population and possible risk factors for infection.Methods.We performed a retrospective cohort study of patients who had received intravenous formulations of at least 1 of the 2 approved prostanoids (epoprostenol and treprostinil) from January 1, 2004, through late 2006. Chart reviews were conducted at 2 large centers for pulmonary arterial hypertension, and a survey of infection control practices was conducted at 1 center.Results.A total of 224 patients were given intravenous prostanoid treatment, corresponding to 146,093 treatment-days during the study period. Overall, there were 0.55 cases of BSI and 0.18 cases of BSI due to gram-negative organisms per 1,000 treatment-days. BSI rates were higher for patients who received intravenous treprostinil than for patients who received intravenous epoprostenol (1.13 vs. 0.42 BSIs per 1,000 treatment-days; P< .001), as were rates of BSI due to gram-negative organisms (0.81 vs. 0.04 BSIs per 1,000 treatment-days; P< .001). Adjusted hazard ratios for all BSIs and for BSIs due to gram-negative organisms were higher among patients given treatment with intravenous treprostinil. The survey identified no significant differences in medication-related infection control practices.Conclusion.At 2 centers, BSI due to gram-negative pathogens was more common than previously reported and was more frequent among patients given treatment with intravenous treprostinil than among patients given treatment with intravenous epoprostenol. Whether similar results would be found at other centers for pulmonary arterial hypertension warrants further investigation. This investigation underscores the importance of surveillance and evaluation of healthcare-related adverse events in patients given treatment primarily as outpatients.

The article features Jim Sproul, one of the most talented young hybridizers of roses. Sproul is a physician who engages in rose hybridizing for the love of it. He calls his breeding enterprise Roses by Design, which he operates from his home in Bakersfield, California. He planted his first seeds in 1988, but did not have real success until 1997. His rose breeding program had produced some wonderful exhibition roses such as the Honey Dijon, Stainless Steel and Singing in the Rain.

Scope of the Investigation This article discusses aspects of the reception history of the Protoevangelium of James in relationship to certain passages in the Qur 'ān that concern themselves with Mary and the birth of Jesus.1 There is no direct evidence that the author of the passages of Qur 'ān sūra 3 and sūra 19 used as a documentary source any text of the genre of Christian infancy gospels. Nevertheless, there are striking parallels between the verses of Qur 'ān sūra 3, sūra 19, and the Protoevangelium of James. In the light of that observation, the present investigation considers the text-critical problems of Qur 'ān sūra 19 following the proposal of the pseudonymous Christoph Luxenberg, some of whose work attempts to clarify key words in sūra 19.24 and provides a new reading of the text, one that suggests a closer dependence of Qur 'ān sūra 3 and sūra 19 on elements of the story attested in the Protoevangelium of James. In the proposal of the present article, the Protoevangelium of James is a witness to a story of which the author of the relevant verses of Qur 'ān sūra 19, also known as sūra Maryam, took cognizance. Whether the Protoevangelium of James is the original source of this story, or whether it attests to a story, the original of which has been lost, or which was in its earliest stages of a primarily oral nature, is a choice that cannot be made given the reach of present knowledge. This article concludes with a brief discussion of the method by which the question might be resolved through future research.

Sitaxsentan is an orally active, selective endothelin-A receptor antagonist that may benefit patients with pulmonary arterial hypertension by blocking the vasoconstrictive effects of endothelin-A receptors, while maintaining the vasodilator and endothelin-1 clearance functions of the endothelin-B receptors. In its first randomized, placebo-controlled study, sitaxsentan improved exercise capacity assessed by the 6-min walk test, New York Heart Association functional class, cardiac index and pulmonary vascular resistance in New York Heart Association Class II, III and IV patients with idiopathic pulmonary arterial hypertension and pulmonary arterial hypertension related to connective tissue disease or congenital heart disease. Although doses of 100 and 300 mg once daily demonstrated equivalent efficacy, the lower dose had a better safety profile. Additional studies are ongoing to assess the relative safety and efficacy of 50 and 100 mg once-daily dosing. The most common side effects include rhinitis, headache, peripheral edema, chest pain, nausea, constipation, increased prothrombin time/international normalized ratio (in patients on warfarin), flushing and insomnia. As with other endothelin receptor antagonists, increases in hepatic transaminases have been observed with sitaxsentan. Initial studies using the selective oral endothelin-A receptor antagonist sitaxsentan in pulmonary arterial hypertension patients have revealed a favorable risk–benefit therapeutic profile with the 100 mg once-daily dose.

We hypothesized that higher plasma levels of von Willebrand factor (vWF) and reduced ristocetin cofactor activity (RCA)/vWF ratios at baseline and follow-up would be associated with an increased risk of death in patients with pulmonary arterial hypertension (PAH).

ObjectiveTo investigate the quality of the smoking cessation advice on over‐the‐counter (OTC) nicotine replacement treatment (NRT) provided by community and hospital pharmacies in Norway and to assess any change in customer services and pharmaceutical smoking cessation advice after a change in legislation deregulating NRT from pharmacy‐only to general sale.

Sitaxsentan, a highly selective endothelin-A (ETA) receptor antagonist (6500-fold more selective for ETA receptors than endothelin-B (ETB) receptors), may benefit patients with pulmonary artery hypertension (PAH) by blocking the vasoconstrictor effects of ETA receptors while maintaining the vasodilator/clearance functions of ETB receptors. In its first randomised, placebo-controlled study, Sitaxsentan to Relieve Impaired Exercise-1 (STRIDE-1), sitaxsentan improved exercise capacity assessed by 6 min walk, New York Heart Association functional class, cardiac index and pulmonary vascular resistance in New York Heart Association class II, III and IV patients with idiopathic PAH, PAH related to connective tissue disease or PAH related to congenital heart disease. In STRIDE-1, doses of 100 and 300 mg/day p.o. were evaluated. Although both doses showed equivalent efficacy, the lower dose had a more tolerable safety profile. Additional studies are ongoing to assess the relative safety and efficacy of 50 and 100 mg/day doses, both in de novo patients and in patients previously treated with the ETA/ETB receptor antagonist bosentan. Long-term comparative studies are necessary to determine whether there is a clinically meaningful difference between selective ETA receptor antagonism and ETA/ETB receptor antagonism.

The inferior olivary nucleus is the sole source of an entire afferent system to the cerebellum, the climbing-fiber system. Inferior olivary neurons are very sensitive to the appropriate sensory stimuli, such as light contact to the paw. Yet, when animals move about, olivary cells show little change in discharge rate. Apparently some mechanism prevents the cells from discharging to stimuli generated by the animal's own movement. The inferior olive receives a massive inhibitory input from small cells in the cerebellar and vestibular nuclei. This article reviews the results from several experiments that suggest that the inferior olive is specifically targeted by inhibitory inputs that prevent responses to stimuli resulting from self-produced movement. Oscarsson proposed that the inferior olive provides the cerebellum with information about errors of motor performance and about spinal reflexes. We argue that it is unlikely that the inferior olive provides information about movement errors, although the olive may signal the occurrence of sensory events that are likely to elicit reflex movements. Another popular theory of climbing-fiber action argues that the climbing fibers play a role in altering the strength of the parallel fiber-Purkinje cell synapse. The cerebellum is important for the formation of classically conditioned responses, and input generated by the unconditioned stimulus does provide effective stimulation of olivary neurons. Although the olive does not generate the unconditioned response, it may provide the cerebellum with information necessary for the formation of conditioned responses.

Pulmonary artery hypertension is a life-threatening disease characterised by a pulmonary vasculopathy and progressive right ventricular failure. Major advances were made with the development of continuous intravenous epoprostenol (Flolan™) as a treatment modality. Nevertheless, it is far from ideal as treatment for this disease. Subcutaneous treprostinil has been FDA approved for the treatment of New York Heart Association Functional Class II – IV pulmonary artery hypertension. It is a longer acting subcutaneous prostacyclin analogue that offers an additional mode of therapy for this disease. A discussion of the pharmacology of this prostacyclin analogue as compared to its related compounds, the clinical studies which led to its approval, a review of some additional basic studies and the practical use of this drug in the treatment modalities for precapillary pulmonary artery hypertension in 2002 in light of other available therapies is discussed.

In electron-capture dissociation (ECD), a multiply-protonated protein ion, trapped in a Fourier transform-ion cyclotron resonance (FT-ICR) cell, captures a low-energy electron at a protonated site. In a major reaction pathway, the resulting hydrogen atom attacks a backbone carbonyl oxygen to form a hypervalent species that immediately dissociates into a complementary c, z•ion pair. For larger proteins, the reduced odd-electron ion (M + nH)(n−1)+•is a major product, as shown here using isotopically isolated precursors. In addition, a hydrogen atom can be lost without further reaction, yielding the [M + (n−1)H](n−1)+even-electron ions. The large effect of charge state on the yield of these ions suggests that the 9+ to 11+ charge states have novel charge-solvated secondary structures.

Magnocellular (RNm) and parvicellular (RNp) divisions of the cat red nucleus (RN) project to the cervical spinal cord. RNp projects more heavily to upper cervical levels and RNm projects more heavily to lower levels. The cells in RN are active during reaching and grasping, and the differences in termination suggest that the divisions influence different musculature during this behavior. However, the spinal termination may not reflect function because most rubrospinal terminations are to interneuronal regions, which can influence motor neurons at other spinal levels. To test for functional differences between RNm and RNp, we selectively stimulated RNm and RNp as well as the efferent fibers from each region. Electromyographic activity was recorded from seven muscles of the cat forelimb during reaching. The activity from each muscle was averaged over several thousand stimuli to detect influences of stimulation on muscle activity. Stimulation within the RN produced a characteristic pattern of poststimulus effects. The digit dorsiflexor, extensor digitorum communis (edc), was most likely to show facilitation, and several other muscles showed suppression. The pattern of activation did not differ between RNm and RNp. In contrast, stimulation of RNp fibers favored facilitation of shoulder muscles (spinodeltoideus and supraspinatus), and stimulation of RNm fibers favored facilitation of digit and wrist muscles (edc, palmaris longus, and extensor carpi ulnaris). Fiber stimulation produced few instances of poststimulus suppression. The results from fiber stimulation indicate that the physiological actions of RNm and RNp match their levels of spinal termination. The complex pattern of facilitation and suppression seen with RN stimulation may reflect synaptic actions within the nucleus.

Traditionally, the red nucleus of the cat is divided into two parts: a large-celled, magnocellular, division (RNm) and a small-celled, parvicellular, division (RNp). The RNm projects to the spinal cord and receives input from the cerebellar interpositus nucleus. The RNp projects to the inferior olive and receives input from the cerebellar dentate nucleus. In this report, we reexamine the connections of the red nucleus using the bidirectional tracer wheat germ agglutinin-horseradish peroxidase (WGA-HRP). Our findings demonstrate that the cat RNp has a large caudal and lateral region that projects to contralateral spinal cord and not to the inferior olive. The spinally projecting region of RNp receives input from the dentate nucleus and a lateral segment of anterior interpositus. Cervical projections from the red nucleus show a topography with the rostral portion of RNp favoring upper segments and the caudal portion of RNm favoring lower segments. The results show that dentate output can influence spinal activity without passing through the cerebral cortex. For the control of movements such as reaching and grasping, we suggest that RNp and dentate focus on the control of proximal limb musculature, whereas RNm and the anterior interpositus focus on the control of distal limb musculature. We also suggest that other species are likely to have a small-celled area of red nucleus projecting to the spinal cord.

Individual peptides with lysine at the C‐terminus as well as protein tryptic digests were reacted with 2‐methoxy‐4,5‐dihydro‐1H‐imidazole, converting lysine residues to their 4,5‐dihydro‐1H‐imidazol‐2‐yl derivatives. The mass spectra of derivatized digests exhibit a greater number of more intense features than their underivatized counterparts, thus increasing the information obtained in peptide mapping experiments. Additionally, MS/MS spectra of the derivatized peptides are greatly simplified in comparison to their native species, yielding primarily an easily interpretable series of y‐ions. Finally, this novel label also enables differential quantitation studies, as a stable isotopic form containing four deuterium atoms can readily be produced. Copyright © 2001 John Wiley & Sons, Ltd.

Blackbody infrared radiative dissociation (BIRD), demonstrated originally with ions as large as 17 kDa, has been applied to larger proteins in a 6 T Fourier-transform mass spectrometer. For carbonic anhydrase (29 kDa), ThiF (27 kDa), and thiazole kinase (29 kDa), ion cell temperatures of 60–110 °C give mostly uninformative H2O loss, but 145 °C gives extensive backbone dissociation. For carbonic anhydrase ions at 70 °C, H2O loss continues for >240 s; thermalizing ions for ∼30 s reduces H2O loss eightfold. For thiaminase I (42 kDa), H2O loss is not observed, with backbone dissociation occurring above 150 °C. For these proteins, BIRD has effected cleavages of 34, 41, 23, and 28, respectively, backbone bonds. Although most are the same as those cleaved by infrared multiphoton dissociation and collisionally activated dissociation, some BIRD cleavages do provide additional and complementary sequence information. Carbonic anhydrase also shows extensive H2O loss from its fragment ions that compromises their validity for sequencing.

We present the results of a study that offers an observing scenario that can significantly enhance the scientific return from the Stratospheric Observatory for Infrared Astronomy (SOFIA). By examining atmospheric data from a satellite mission, we found that at typical SOFIA flight altitudes from 37,000 to 45,000 feet, it can be advantageous to fly into high-latitude regions-for example, north of +40°. This is because of the fact that the water vapor overburden (WVO) and the frequency of cloud occurrence at these latitudes are less than if the flights are centered above Moffett Field, California, where the SOFIA base will be located. It has also been shown that for certain science projects, the amount of time on target can be considerably extended with high-latitude flights. Compared to flights on the Kuiper Airborne Observatory (KAO), SOFIA's predecessor, which typically took 6.5-8 hours, an increase of up to 50% of target time is possible without exceeding the often required very low line-of-sight (LOS) WVO of ?10 ?m. When flying into northern latitudes where the tropopause, and hence the major water vapor distribution, is lower than over the tropics, it becomes possible to observe at correspondingly lower altitudes, for example, 37,000 or 39,000 feet. This permits longer but fewer flights, which include legs at lower altitudes, and makes observatory operations easier. Therefore, we have studied flights from Moffett Field, California, to Canada, as well as week-long flight series out of Anchorage, Alaska. In the winter months, the air over Canada and Alaska is very dry at SOFIA altitudes. Those flights demonstrate that the LOS WVO is almost always below 10 ?m. Additionally, the study shows that the LOS WVO for a fixed set of Galactic plane objects is about the same for north-shifted SOFIA flights-elevation range 20°-60°-as for the Moffett-centered KAO flights-elevation range 35°-75°.

ABSTRACTPenciclovir (PCV), an antiherpesvirus agent in the same class as acyclovir (ACV), is phosphorylated in herpes simplex virus (HSV)-infected cells by the viral thymidine kinase (TK). Resistance to ACV has been mapped to mutations within either the TK or the DNA polymerase gene. An identical activation pathway, the similarity in mode of action, and the invariant cross-resistance of TK-negative mutants argue that the mechanisms of resistance to PCV and ACV are likely to be analogous. A total of 48 HSV type 1 (HSV-1) and HSV-2 isolates were selected after passage in the presence of increasing concentrations of PCV or ACV in MRC-5 cells. Phenotypic analysis suggested these isolates were deficient in TK activity. Moreover, sequencing of the TK genes from ACV-selected mutants identified two homopolymeric G-C nucleotide stretches as putative hot spots, thereby confirming previous reports examining Acvrclinical isolates. Surprisingly, mutations identified in PCV-selected mutants were generally not in these regions but distributed throughout the TK gene and at similar frequencies of occurrence within A-T or G-C nucleotides, regardless of virus type. Furthermore, HSV-1 isolates selected in the presence of ACV commonly included frameshift mutations, while PCV-selected HSV-1 mutants contained mostly nonconservative amino acid changes. Data from this panel of laboratory isolates show that Pcvrmutants share cross-resistance and only limited sequence similarity with HSV mutants identified following ACV selection. Subtle differences between PCV and ACV in the interaction with viral TK or polymerase may account for the different spectra of genotypes observed for the two sets of mutants.

Neurons in the caudal hypothalamus (CH) are responsible for the modulation of various processes including respiratory and cardiovascular output. Previous results from this and other laboratories have demonstrated in vivo that these neurons have firing rhythms matched to the respiratory and cardiovascular cycles. The goal of the present study was to characterize the biophysical properties of neurons in the CH with particular emphasis in those properties responsible for rhythmic firing behavior. Whole cell, patch-clamped CH neurons displayed a resting membrane potential of −58.0 ± 1.1 mV and an input resistance of 319.3 ± 16.6 MΩ when recorded in current-clamp mode in an in vitro brain slice preparation. A large proportion of these neurons displayed postinhibitory rebound (PIR) that was dependent on the duration and magnitude of hyperpolarizing current as well as the resting membrane potential of the cell. Furthermore these neurons discharged tonically in response to a depolarizing current pulse at a depolarized resting membrane potential (more positive than −65 mV) but switched to a rapid burst of firing to the same stimulus when the resting membrane potential was lowered. The PIR observed in these neurons was calcium dependent as demonstrated by the ability to block its amplitude by perfusion of Ca2+-free bath solution or by application of Ni2+(0.3–0.5 mM) or nifedipine (10 μM). These properties suggest that low-voltage-activated (LVA) calcium current is involved in the PIR and bursting firing of these CH neurons. In addition, high-voltage-activated calcium responses were detected after blockade of outward potassium current or in Ba2+-replacement solution. In addition, almost all of the CH neurons studied showed spike frequency adaptation that was decreased following Ca2+removal, indicating the involvement of Ca2+-dependent K+current (IK,Ca) in these cells. In conclusion, CH neurons have at least two different types of calcium currents that contribute to their excitability; the dominant current is the LVA or T-type. This LVA current appears to play a significant role in the bursting characteristics that may underlie the rhythmic firing of CH neurons.

Previous work from this laboratory has indicated that TTX-sensitive sodium channels are involved in the hypoxia-induced inward current response of caudal hypothalamic neurons. Since this inward current underlies the depolarization and increased firing frequency observed in these cells during hypoxia, the present study utilized more detailed biophysical methods to specifically determine which sodium currents are responsible for this hypoxic activation. Caudal hypothalamic neurons from ∼3-wk-old Sprague-Dawley rats were acutely dissociated and patch-clamped in the voltage-clamp mode to obtain recordings from fast-inactivating and persistent (noninactivating) whole cell sodium currents. Using computer-generated activation and inactivation voltage protocols, rapidly inactivating sodium currents were analyzed during normal conditions and during a brief (3–6 min) period of severe hypoxia. In addition, voltage-ramp and extended-voltage-activation protocols were used to analyze persistent sodium currents during normal conditions and during hypoxia. A polarographic oxygen electrode determined that the level of oxygen in this preparation quickly dropped to 10 Torr within 2 min of initiation of hypoxia and stabilized at <0.5 Torr within 4 min. During hypoxia, the peak fast-inactivating sodium current was significantly increased throughout the entire activation range, and both the activation and inactivation values (V1/2) were negatively shifted. Furthermore both the voltage-ramp and extended-activation protocols demonstrated a significant increase in the persistent sodium current during hypoxia when compared with normoxia. These results demonstrate that both rapidly inactivating and persistent sodium currents are significantly enhanced by a brief hypoxic stimulus. Furthermore the hypoxic-induced increase in these currents most likely is the primary mechanism for the depolarization and increased firing frequency observed in caudal hypothalamic neurons during hypoxia. Since these neurons are important in modulating cardiorespiratory activity, the oxygen responsiveness of these sodium currents may play a significant role in the centrally mediated cardiorespiratory response to hypoxia.

While conducting a purification protocol of phospholipase D (PLD) from human granulocytes, we observed that PLD activity was inhibited by a commonly-used protease inhibitor cocktail. Of the six inhibitors present in the cocktail, the serine protease inhibitor, 4-(2-aminoethyl)-benezensulfonyl fluoride (AEBSF), was found to be the sole inhibitor of PLD. AEBSF caused a loss of neutrophil and purified plant PLD activities in vitro, but not in intact cells at the concentrations used, nor did it affect the related phospholipases A2 and C, that were utilized as specificity controls. The compound AEBSNH2, which has the fluoride replaced by an -NH2 group, failed to affect PLD activity as did other compounds structurally related to AEBSF with known protease inhibitory capabilities. Finally, basal- and agonist-stimulated PLD activity was inhibited in phosphatidylcholine-specific anti-PLD immunoprecipitates (IC50 = 75 μM). These results suggest that AEBSF, in an effect probably unrelated to its anti-proteolytic ability, directly interferes with PLD enzymatic activity, making it a significant compound to begin analyzing the role of PLD in mammalian cell signaling.

We consider numerical models of accretion disks and boundary layers (BLs) around white dwarfs in cataclysmic variables (CVs). Our models include the effects of the radial viscous force and are created using the realistic OPAL opacities. We present the composite continuum spectrum of our "fiducial" BL model, which is hot and close to the primary and is a strong emitter of soft X-rays. We examine the effects on the structure of the BL of variations in the model parameters: the mass accretion rate , stellar mass M*and radius R*, stellar rotation rate ?*, and viscosity parameter ?. Finally, the ultraviolet colors of the models are computed for a range of system parameters and compared with the UV colors of observed CVs. We find that our models are consistent with the observed colors.

We present the results of a linearized perturbation analysis for the models of cataclysmic variable (CV) disks and their boundary layers (BLs), discussed in a previous companion paper. For the case of large-scale, azimuthal oscillations in the BL, we find a triplet of unstable "torsional" modes consisting primarily of perturbations of the azimuthal velocity, plus a singlet mode consisting mainly of a pressure perturbation. In the disk, the torsional modes are modified gravity waves, with rise times short enough for significant amplification before entering the BL; in the BL, the frequencies of these modes are close enough in magnitude to produce beating. In the BL region where the effective temperature has its maximum, the beat frequencies, for a star rotating at 5% of its breakup rate, span a range from the stellar rotation frequency ?*up to an order of magnitude larger than that, i.e., from periods of P~ 20 s to (2-3) × 100 s, with the underlying fundamental oscillations having much smaller periods, ~1 s. These beat-frequency oscillations of the torsional modes have attributes similar to the quasi-periodic oscillations (QPOs) observed in many CVs. Furthermore, if a particular region of the BL is excited, fairly high Q(where Q? |dP/dt|-1) beat-frequency oscillations are produced, which are similar to some observed dwarf nova oscillations (DNOs). We propose two observational tests to determine whether some QPOs can be identified with the modes studied here. The tests require an extension of the search for CV oscillations to the 0.2-2 Hz frequency range.