cssi/SciSciGPT-SciSciNet huggingface dataset:
Identification and characterization of two proximal elements in the rat osteocalcin gene promoter that may confer species‐specific regulation

The rat osteocalcin gene encodes a 6-kD osteoblast-specific protein that is expressed postproliferatively. The developmental and steroid hormone responsive expression of the osteocalcin gene is transcriptionally regulated by a promoter with multiple basal and enhancer elements that exhibit activity controlled by a series of physiological mediators (e.g., 1,25(OH)2D3, glucocorticoids). In this study, we established the contribution of the rat osteocalcin (OC) box domain ( −99 to −76), a proximal basal element with a CCAAT motif as a central core, to transcriptional activity of the rat osteocalcin gene with in vivo co-transfection assays. By this same assay, however, the highly homologous (22 of 24 nt) human OC box element was unable to compete for transcription factor binding with the rat OC promoter. In vitro protein/DNA interaction studies confirm the presence of two protein binding sites in the OC box region, one of which overlaps the CCAAT motif and, at least in part, accounts for species-specific expression. Competition analysis established that the single nucleotide substitution of adenine for thymine, which converts the core motif of the rat OC box (CCAAT) to the core motif of the human OC box (CCAAA), accounts for observed species differences in transcription factor interactions. The CCAAT-specific protein/DNA interactions are heat stable and insensitive to phosphatase treatment. A second protein/DNA interaction located upstream of the CCAAT motif includes two steroid-like half-elements. These interactions are heat labile and sensitive to phosphatase treatment in contrast to the CCAAT-specific interactions. The human OC promoter contains only a single steroid-like half-element, while two steroid half-elements with an 11 nucleotide spacer are present in the rat OC promoter. These observed variations in sequence organization and transactivation factor binding in analogous proximal basal regulatory regions of the OC gene promoter may provide a basis for species-restricted variations in responsiveness to physiological mediators of OC gene expression at the transcriptional level.
Beryllium is an inhibitor of cellular GSK-3β that is 1,000-fold more potent than lithium

Glycogen synthase kinase 3β (GSK-3β) is a key regulator in signaling networks that control cell proliferation, metabolism, development, and other processes. Lithium chloride is a GSK-3 family inhibitor that has been a mainstay of in vitro and in vivo studies for many years. Beryllium salt has the potential to act as a lithium-like inhibitor of GSK-3, but it is not known whether this agent is effective under physiologically relevant conditions. Here we show that BeSO4 inhibits endogenous GSK-3β in cultured human cells. Exposure to 10 µM Be2+ produced a decrease in GSK-3β kinase activity that was comparable to that produced by 10 mM Li+, indicating that beryllium is about 1,000-fold more potent than the classical inhibitor when treating intact cells. There was a statistically significant dose-dependent reduction in specific activity of GSK-3β immunoprecipitated from cells that had been treated with either agent. Lithium inhibited GSK-3β kinase activity directly, and it also caused GSK-3β in cells to become phosphorylated at serine-9 (Ser-9), a post-translational modification that occurs as part of a well-known positive feedback loop that suppresses the kinase activity. Beryllium also inhibited the kinase directly, but unlike lithium it had little effect on Ser-9 phosphorylation in the cell types tested, suggesting that alternative modes of feedback inhibition may be elicited by this agent. These results indicate that beryllium, like lithium, can induce perturbations in the GSK-3β signaling network of treated cells.
Streptavidin and its biotin complex at atomic resolution.

Atomic resolution crystallographic studies of streptavidin and its biotin complex have been carried out at 1.03 and 0.95 A, respectively. The wild-type protein crystallized with a tetramer in the asymmetric unit, while the crystals of the biotin complex contained two subunits in the asymmetric unit. Comparison of the six subunits shows the various ways in which the protein accommodates ligand binding and different crystal-packing environments. Conformational variation is found in each of the polypeptide loops connecting the eight strands in the β-­sandwich subunit, but the largest differences are found in the flexible binding loop (residues 45–52). In three of the unliganded subunits the loop is in an ‘open’ conformation, while in the two subunits binding biotin, as well as in one of the unliganded subunits, this loop ‘closes’ over the biotin–binding site. The ‘closed’ loop contributes to the protein’s high affinity for biotin. Analysis of the anisotropic displacement parameters included in the crystallographic models is consistent with the variation found in the loop structures and the view that the dynamic nature of the protein structure contributes to the ability of the protein to bind biotin so tightly.
The use of Silastic Prosthetics in the Reconstruction of Nasal Facial Deformities

Maxillofacial deformities resulting from the loss of tissue from the midfacial region may cause serious disfigurement. Modern facial plastic reconstructive techniques have been able to produce sati...
Concurrent expression of procoagulant and plasminogen activator activities by rabbit alveolar macrophages in vitro: Opposite modulating effects of prostaglandin E2

We examined the effects of arachidonic acid metabolites on the simultaneous expression of procoagulant (PC) and plasminogen activator (PA) activities by rabbit alveolar macrophages. Incubation with lymphocyte-conditioned medium (LCM) caused a significant increase in cell-associated PC activity. Co-treatment with indomethacin (1 @I) reduced this augmentation in PC activity by 33% (p < 0.05). In contrast, indomethacin caused a 42% increase in PA activity released into incubation medium (p < .OS). Both effects of indomethacin were reversed by the addition of PGE2 in concentrations as low as 1 nM. Addition of 100 nM PGE2 to these cells caused an increase in PC activity 2.7-fold greater than that achieved by LCM alone, while PGE2 suppressed released PA activity by 62%. PGE2 and indomethacin had similar but less pronounced effects on phorbol myristate acetate-treated cells. These effects of PGE2 could be duplicated by PGEr, but not by any other arachidonic acid metabolite (PGFza, PGI2, PGD2, ddPGFzcc, LTB4, or LTC4). While PGE2 increases intracellular levels of CAMP, the observed effects on PC and PA activities could not be reproduced fully by treatment with dibutyryl CAMP. We conclude that PGE2 amplifies the augmentation of PC activity by stimulated alveolar macrophages while concurrently inhibiting expression of plasminogen activator. This suggests that PGE2 may be a significant mediator in regulating the highly interactive processes of inflammation and coagulation/fibrinolysis.
Unaltered Cleavage and Secretion of Angiotensin-converting Enzyme in Tumor Necrosis Factor-α-converting Enzyme-deficient Mice

Abstract Mammalian angiotensin-converting enzyme (ACE) is one of several biologically important ectoproteins that exist in both membrane-bound and soluble forms as a result of a post-translational proteolytic cleavage. It has been suggested that a common proteolytic system is responsible for the cleavage of a diverse group of membrane ectoproteins, and tumor necrosis factor-α-converting enzyme (TACE), a recently purified disintegrin-metalloprotease, has been implicated in the proteolytic cleavage of several cell surface proteins. Mice devoid of TACE have been developed by gene targeting. Such mice could provide a useful system to determine if TACE is responsible for the cleavage of other ectoproteins. Cultured fibroblasts without TACE activity, when transfected with cDNA encoding for the testicular isozyme of ACE (ACET), synthesized and secreted ACETnormally after a proteolytic cleavage near the C terminus. In addition, similar quantities of the soluble, C-terminally truncated somatic isozyme of ACE (ACEP) were present in the serum of wild-type and TACE-deficient mice. These results demonstrate that TACE is not essential in the generation of soluble ACE under physiological conditions. Finally, we also report solubilization of ACE-secretase, the enzyme that cleaves ACE, from mouse ACE89 cells and from rabbit lung. We demonstrate that soluble ACE-secretase from both sources failed to cleave its substrate in solution, suggesting a requirement for anchoring to the membrane.
A longitudinal study of scholars attitudes and behaviors toward open-access journal publishing

This research applies statistical time series analysis to examine the changing pattern of scholars' attitudes toward open-access (OA) journal publishing from the early 1990s. By synthesizing survey results in existing studies, this research focuses on representative aspects of the attitudes and behaviors recorded through the years. It finds that although an increase in the publishing and awareness rates of scholars with regard to OA journals has been observed, scholars have been consistently concerned with the low prestige of such journals and their lack of peer review, which is not the case in practice. It is hoped that the findings will provide useful information for the improvement of OA advocacy. © 2010 Wiley Periodicals, Inc.
Bariatric surgery, hyperoxaluria, and nephrolithiasis: A plea for close postoperative management of risk factors

Hyperoxaluria contributes significant risk for kidney stone development. It can result from disordered metabolism, excessive intake of oxalate or other nutrients, or alterations of bowel flora and function. Sinha et al. show that individuals undergoing Roux-en-Y bypass have high rates of stone disease, both before and after their procedure. Whether or not the incidence of stone events is increased after surgery, hyperoxaluria should be addressed. After Roux-en-Y, it is important for patients to maintain high urine outputs, to limit fat intake, and to ingest adequate amounts of calcium.
Clinicopathologic and molecular analysis of disseminated appendiceal mucinous neoplasms: identification of factors predicting survival and proposed criteria for a three-tiered assessment of tumor grade

Previous studies have demonstrated that the prognosis of disseminated mucinous appendiceal neoplasms is highly dependent upon tumor grade. Reflecting this, the 7th edition of the American Joint Committee on Cancer (AJCC) staging system now incorporates a three-tier grading system for prognostic staging of mucinous appendiceal tumors. However, the grading criteria are not well described. In order to address this issue, we evaluated clinicopathologic and molecular features of 219 cases from 151 patients with widely disseminated appendiceal mucinous neoplasia treated at our institution between 2004 and 2012. We identified histologic features that were associated with worse overall survival on univariate analysis: destructive invasion, high cytologic grade, high tumor cellularity, angiolymphatic invasion, perineural invasion, and signet ring cell component (all with P<0.0001). We used these morphologic characteristics to classify neoplasms into three grades: AJCC grade G1 lacked all adverse histologic features; AJCC grade G2 had at least one adverse histologic feature (except a signet ring cell component); and AJCC grade G3 were defined by the presence of a signet ring cell component. Patients with AJCC grade G2 and grade G3 adenocarcinomas had a significantly worse prognosis compared with AJCC grade G1 (P<0.0001 for each). A trend toward worse overall survival was identified for patients with AJCC grade G3 adenocarcinomas compared with AJCC grade G2 adenocarcinomas (P=0.07). Our multivariate analysis found that this three-tier grading system was a significant predictor of outcome (P=0.008), independent of other prognostic variables. After controlling for other prognostic variables, AJCC grade G2 was associated with a 2.7-fold increased risk of death (95% confidence interval (CI), 1.2-6.2) and AJCC grade G3 was associated with a 5.1-fold increased risk of death (95% CI, 1.7-14) relative to grade G1 tumors. Our results indicate that evaluation of a limited set of adverse histologic features allows for the separation of disseminated mucinous neoplasms of appendiceal origin into three morphologically defined and prognostically relevant grades as advocated by the AJCC.
Maternal meal quality alters fetal rat brain serotonin concentrations

Abstract The quality of food eaten by pregnant animals may influence fetal neurotransmitter biosynthesis by altering the relative availability of precursor amino acids. Fetal brain concentrations of tryptophan and the neurotransmitter serotonin increase following the consumption of a carbohydrate-fat meal or after the injection of insulin in fasting animals; in contrast, the fetal concentrations of these compounds are reduced in animals whose mothers eat a meal containing casein protein or amino acids which compete with tryptophan for uptake from maternal blood into the placenta and fetus.
Nonsurgical septal reduction therapy for hypertrophic obstructive cardiomyopathy: short-term results in 50 consecutive procedures.

Background: Nonsurgical septal reduction therapy (NSRT) has been shown to improve left ventricular outflow tract (LVOT) gradients, decrease septal thickness, and improve symptoms in patients with hypertrophic obstructive cardiomyopathy (HOCM). The major complication of this procedure has been the development of complete heart block (CHB) requiring permanent pacemaker implantation, which has been reported in up to 33% of patients in early studies. Since this procedure was first reported, there have been refinements in the technique such as the use of echocardiographic contrast material to localize the site of infarction, slower injection of alcohol, as well as improvement in balloon technology. Hypothesis: We sought to determine the results of NSRT using echocardiographic contrast localization, slow injection of alcohol, and short balloon length. We theorized that the incidence CHB would be lower than earlier reported results using these refined techniques. Methods: We performed 50 NSRT procedures on 46 patients using echocardiographic contrast localization, slow alcohol injection, and currently available balloons. Patients had an echocardiogram before, immediately after NSRT, and at 3 months, and a treadmill test before and at 3 months after NSRT. In the hospital, patients were observed for the development of CHB or other complications, and infarct size was determined by serial creatine kinase (CK) measurements. Results: There was a decrease in the LVOT gradient from 84.2 (± 30.8) mmHg at baseline, to 18.5 (± 14.8) mmHg immediately after NSRT (p < 0.001). At 3 months, the gradient was not statistically different at 22.7 (± 22.2) mmHg (p = 0.27). The septal thickness decreased from 2.21 (± 0.66) cm at baseline, to 1.67 (± 0.51) cm at 3 months (p < 0.001). New York Heart Association symptom class improved from 3.2 (± 0.4) at baseline, to 1.1 (± 0.6) at 3 months (p < 0.001). Mean treadmill time in 30 patients was 235 (± 142) s at baseline, to 367 (± 159) s at 3 months (p < 0.001). Of the 50 procedures, 45 were performed in patients without a previously placed permanent pacemaker or intracardiac cardioverter defibrillator; only 3 (6.7%) of the 45 developed complete heart blocks required permanent pacing. While only three patients in the series had a preexisting left bundle-branch block (LBBB), two of the three patients who required a permanent pacemaker had an LBBB before the procedure. Conclusion: Using contrast echocardiographic localization, slow injection of alcohol, and shorter balloon catheters, there continues to be excellent improvement in LVOT gradients, septal thickness, and symptoms, with a reduced incidence of CHB requiring permanent pacemaker implantation. Left bundle-branch block appears to be a strong predictor for the development of CHB after NSRT.
SU-E-T-273: Radiation Shielding for a Fixed Horizontal-Beam Linac in a Shipping Container and a Conventional Treatment Vault

Purpose: A fixed horizontal-beam linac, where the patient is treated in a seated position, could lower the overall costs of the treatment unit and room shielding substantially. This design also allows the treatment room and control area to be contained within a reduced space, such as a shipping container. The main application is the introduction of low-cost, high-quality radiation therapy to low- and middle-income regions. Here we consider shielding for upright treatments with a fixed-6MV-beam linac in a shipping container and a conventional treatment vault. Methods: Shielding calculations were done for two treatment room layouts using calculation methods in NCRP Report 151: (1) a shipping container (6m × 2.4m with the remaining space occupied by the console area), and (2) the treatment vault in NCRP 151 (7.8m by 5.4m by 3.4m). The shipping container has a fixed gantry that points in one direction at all times. For the treatment vault, various beam directions were evaluated. Results: The shipping container requires a primary barrier of 168cm concrete (4.5 TVL), surrounded by a secondary barrier of 3.6 TVL. The other walls require between 2.8–3.3 TVL. Multiple shielding calculations were done along the side wall. The results show that patient scatter increases in the forward direction and decreases dramatically in the backward direction. Leakage scatter also varies along the wall, depending largely on the distance between the gantry and the wall. For the treatment room, fixed-beam requires a slightly thicker primary barrier than the conventional linac (0.6 TVL), although this barrier is only needed in the center of one wall. The secondary barrier is different only by 0–0.2 TVL. Conclusion: This work shows that (1) the shipping container option is achievable, using indigenous materials for shielding and (2) upright treatments can be performed in a conventional treatment room with minimal additional shielding. Varian Medical Systems
Primary hyperparathyroidism after Roux-en-Y gastric bypass.

Primary hyperparathyroidism (PHPT) in the setting of previous roux-en-Y gastric bypass (RYGBP) is not well described. The diagnosis can be difficult, as secondary hyperparathyroidism (SHPT) commonly occurs in patients after RYGBP due to calcium malabsorption and vitamin D deficiency. All patients from 2000 to 2012 who underwent cervical exploration for diagnosis of primary hyperparathyroidism with history of preceding RYGBP were identified and analyzed retrospectively. Ten patients were identified. The average age was 58.4 and all patients were female. Time interval between RYGBP and cervical exploration was 67 months with median follow-up of 19 months. Average preoperative calcium was 10.8 mg/dL, PTH 155 pg/mL, and 25-vitamin-D 32 ng/mL. Eighty percent of patients presented with symptoms and 90 % underwent preoperative imaging. Seventy percent underwent initial focused parathyroidectomy with 20 % being converted to four-gland exploration. Seventy percent of patients had a single adenoma with two patients having multi-gland disease. Intraoperative PTH was used in seven patients with successful drop to 50 % of baseline in all. Ninety percent of patients had greater then 6-month follow-up without evidence of persistent or recurrent PHPT. Average 6-month calcium was 9.3 mg/dL, PTH 73 pg/mL, and 25-vitamin-D 44 ng/ML. Four patients had evidence of persistently elevated PTH despite normalization of calcium. PHPT after RYGBP is rare but surgery with either a focused approach following successful localization or four-gland exploration is indicated when the biochemical diagnosis holds true. The presence of SHPT can make diagnosis and follow-up difficult and may predispose them to severe post-operative hypocalcemia.
A flexible data to L2 cache mapping approach for future multicore processors

This paper proposes and studies a distributed L2 cache management approach through page-level data to cache slice mapping in a future processor chip comprising many cores. L2 cache management is a crucial multicore processor design aspect to overcome non-uniform cache access latency for high program performance and to reduce on-chip network traffic and related power consumption. Unlike previously studied "pure" hardware-based private and shared cache designs, the proposed OS-microarchitecture approach allows mimicking a wide spectrum of L2 caching policies without complex hardware support. Moreover, processors and cache slices can be isolated from each other without hardware modifications, resulting in improved chip reliability characteristics. We discuss the key design issues and implementation strategies of the proposed approach, and present an experimental result showing the promise of it.
Serial Transmission of Information: A Study of the Grapevine.

(1977). Serial transmission of information: A study of the grapevine. Journal of Applied Communication Research: Vol. 5, No. 2, pp. 61-72.
Dynamics of density equilibration near the liquid-vapor critical point of3He

The density change σρ(t) was measured as a function of time at two locations in the upper and the lower half of a flat cell, after a temperature step ΔT≪(T−Tc), whereTc is the critical temperature. The series of measurements were made along the critical isochore. Direct observation of the sharp response from adiabatic energy transfer into the bulk fluid (“piston effect”), and the effect of slow diffusive relaxation to equilibrium are reported. The relaxation time is found to diverge asTc is approached. The onset of convection for a step ΔT beyond a critical value could be observed, with a dramatic change of the temporal profile of σρ(t). Computer simulations of this profile in the absence of convection have been carried out and are compared with the experiment.
Interaction of D2O with CeO2(001) Investigated by Temperature-Programmed Desorption and X-ray Photoelectron Spectroscopy

The interaction of D{sub 2}O with the CeO{sub 2}(001) surface was studied with temperature-programmed desorption (TPD) and X-ray photoelectron spectroscopy (XPS). It was found with TPD that D{sub 2}O desorption occurs in three states with temperatures of 152, 200, and 275 K, which are defined as multilayer D{sub 2}O weakly bound surface D{sub 2}O, and hydroxyl recombination, respectively. O 1s XPS measurements for high D{sub 2}O exposures, where multilayer water desorption was observed in the TPD, resulted in emission from only the substrate and surface hydroxyls. This is likely due to a nonwetting behavior of D{sub 2}O on this surface with the formation of nanosized clusters. An analysis of the O1s XPS data indicates that the surface has a hydroxyl coverage of 0.9 monolayers for large water exposures at 85 K. This is consistent with a model in which the polar CeO{sub 2}(001) surface can be stabilized by a reduction of the dipole in the top layer by the formation of a full monolayer of hydroxyls.
Long-term reworking of volcanic ash deposited in the abyssal ocean based on uranium and thorium isotope measurements

Abstract A red-clay core from north of New Zealand contains a 21 cm-thick layer of the 340 thousand-year old Rangitawa ash. Uranium and thorium isotope measurements on this core show that ash continuously contributes to sediments overlying the ash layer, ranging from ~ 58% immediately above the ash to ~ 8% at the core top. Rather than from an upward bioturbation or subsequent volcanic eruptions, the ash in sediments is most likely sourced from suspended Rangitawa ash in the nepheloid layer that has steadily re-deposited at the core site ever since the Whakamaru super-eruption. We suggest that this lateral transport bears important influence on interpreting marine sediment proxy records.
A comparison of alternative serum biomarkers with creatinine for predicting allograft function after kidney transplantation.

Background. The role of serum cystatin C (Scyc), neutrophil gelatinase-associated lipocalin, and interleukin-18 in predicting early graft function after kidney transplant is poorly defined. Methods. We conducted a multicenter prospective cohort study of deceased-donor kidney transplants. We collected serial blood samples for the first 3 days of transplant and monitored need for dialysis within 1 week and graft function at 3 months after transplant. Results. Among 78 recipients with serum biomarker measurements, 26 had delayed graft function (DGF; hemodialysis within 1 week of transplant). Of those not dialyzed, 29 had slow graft function (serum creatinine [Scr] reduction from transplantation to day 7 <70%), and 23 had immediate graft function (IGF; reduction in Scr ≥70%). Scyc levels were statistically different between groups by the first postoperative day (POD), whereas Scr levels were not. Serum neutrophil gelatinase-associated lipocalin and serum interleukin-18 levels were not different between groups. Scyc on the first POD demonstrated good utility for predicting DGF and non-IGF (DGF or slow graft function) with areas under the receiver-operating characteristic curve of 0.83 and 0.85, respectively. Areas under the receiver-operating characteristic curve for predicting DGF and non-IGF using Scr on the first POD were 0.65 and 0.53, respectively. Substituting Scyc for Scr in a clinical algorithm improved its utility for predicting DGF or non-IGF, with adjusted odds ratios of 2.4 and 3.3 for Scyc levels on the first POD. The change in Scyc during the first POD demonstrated a dose-response relationship with 3-month graft function. Conclusions. Scyc outperforms Scr as a predictor of early graft function after deceased-donor kidney transplant.
Gender Bias in an Occupational Therapy Text

Willard and Spackman's Occupational Therapy does not create an awareness and understanding of the role of women in the field of occupational therapy. Nor does the text include general policy statements or reflections on how gender bias affects our work. What is our true consciousness as women therapists? Maria Mies (1983) wrote that women consent to their own oppression or subordination through silence. "Only when there is a rupture in the 'normal' life of a woman, a divorce, an end of a relationship, is there a chance for her to become conscious of her true condition which had been unconsciously submerged in a patriarchal system" (p. 125). True consciousness occurs in occupational therapy when practitioners avoid the use of activities or occupation in therapy. This is our "rupture". I believe the profession needs to develop a policy statement discussing gender concerns in our theory and practice linked to the progress made by women scientists in anthropology, psychology, sociology, history, and literature. It is critical to good treatment that the gender role factor be included in our research on the generic impact of activity on the individual and small group. As female occupational therapists we have the opportunity to make a significant imprint on a gender-based understanding of the health value of activities in our daily lives.
Development: Creator and destroyer of values

Abstract The terminology and practice of development are ambiguous. The term is used both descriptively and normatively, and it refers either to goals or to means for reaching these. Moreover, the practice has oscillated from one-dimensional pursuit of economic growth to comprehensive social engineering to transform societal structures. Development was long considered an unalloyed good. As attendant social, cultural, ecological and human costs become more evident, however, it is increasingly viewed as a two-edge sword, simultaneously creating and destroying values. It brings material and technological gains and new freedoms, but also breeds injustice, destroys cultures, damages environments and generalizes anomie . More importantly, development engenders value conflicts over the meaning and content of the good life, the basis of justice in society, and the criteria governing the stance of human societies toward nature. In thinking about, and acting upon, development we need “a wisdom to match our sciences.” This essay explores possible roads leading to such wisdom.
Incidence of fungi in the stools of non-specific Ulcerative Colitis preliminary report

We are presenting our findings in ulcerative colitis without making any claims that fungi are of etiologic importance in ulcerative colitis. However, we know of no studies along these lines and, therefore, consider the evidence of interest. Our ability to culture fungi in 87.5 per cent of the stools of “non-specific” ulcerative colitis as compared to 33.3 per cent of controls may be significant. The comparatively pure cultures of geotrichum grown in the stools of ulcerative colitis as compared with the few scant colonies grown from the stools of normals or from those with diarrhea due to other causes is also very significant. Apparently the presence of monilia albicans in the stools is of prognostic significance, denoting a malignant course and a possible fatality. At present, further clinical and experimental studies are being carried out to further elucidate the importance of fungi in ulcerative colitis.
Mutations and polymorphisms in the human N-acetylglutamate synthase (NAGS) gene.

N-acetylglutamate synthase (NAGS) deficiency, an autosomal recessive disorder, is the last urea cycle disorder for which molecular testing became available. This is the first comprehensive report of 21 mutations that cause NAGS deficiency and of commonly found polymorphisms in the NAGS gene. Five mutations are reported here for the first time. A total of 10 disease-causing mutations are associated with acute neonatal hyperammonemia; the remaining mutations were found in patients with late onset disease. Residual enzymatic activities are included in this report and the deleterious effects of eight mutations were confirmed by expression studies. Mutations in the NAGS gene are distributed throughout its reading frame. No mutations have been found in exon 1, which encodes for the putative mitochondrial targeting signal and variable segment of NAGS. Three polymorphisms have been found. Early, accurate, and specific diagnosis of NAGS deficiency is critical since this condition can be successfully treated with N-carbamylglutamate (NCG, Carbaglu®; Orphan Europe). Treatment with NCG should be initiated as soon as a patient is suspected of having NAGS deficiency. Molecular testing represents the most reliable method of diagnosis. Hum Mutat 28(8), 754–759, 2007. Published 2007 Wiley-Liss, Inc.
The central distinction in the theory of corporate moral personhood

Peter French has argued that conglomerate collectivities such as business corporations are moral persons and that aggregate collectivities such as lynch mobs are not. Two arguments are advanced to show that French's claim is flawed. First, the distinction between aggregates and conglomerates is, at best, a distinction of degree, not kind. Moreover, some aggregates show evidence of moral personhood. Second, French's criterion for distinguishing aggregates and conglomerates is based on inadequate grounds. Application of the criterion to specific cases requires an additional judgment of a pragmatic nature which undermines any attempt to demonstrate French's thesis that actual conglomerates are moral persons and aggregates are not. Thus, French's theory is seriously lacking both empirical basis and empirical relevance.
Assessment of Patient-Reported Outcomes in Patients with Melanoma

Assessment of patient-reported outcomes (PROs) provides important information to assist with clinical decision making. There has been significant progress in the field of PROs over the past 2 decades with the introduction of validated disease- and symptom-specific instruments. The Functional Assessment of Cancer Therapy-Melanoma (FACT-M) is a melanoma-specific module to accompany the FACT-General, which was validated to assess health-related quality of life for patients with all stages of melanoma. Melanoma-specific health state utilities also have been reported from a number of studies. Assessment of PROs should be incorporated into routine clinical practice to inform clinicians and researchers of the patient perspective for clinical decision making and to evaluate the effects of psychosocial and medical interventions.
Intralesional injections of alefacept may predict systemic response to intramuscular alefacept: results from a pilot study.

Background: Alefacept (Amevive®) was the first biologic agent to be approved by the FDA for use in moderate to severe chronic plaque psoriasis and remains one of the safest systemic agents. However, alefacept is the least utilized of all the biologic agents due to the finding that it is only effective in a small proportion of patients and its maximal efficacy is not seen until approximately 6 weeks after treatment completion. Objective: To determine whether intralesional injections with a biologic agent can predict who will be a responder or a non-responder to the medication. Methods: This was a single-center 22-week study consisting of three phases: i) intralesional injection to a target plaque, ii) intramuscular alefacept injections for 12 weeks (standard dose) and iii) post-treatment follow-up. Results: There appears to be a perfect correlation between patients who show a response to an intralesional injection of alefacept to a small, target plaque and those who eventually respond to a full 12-week sys...
The physiological and clinical changes following closure of atrial septal defects by atrio-septo-pexy

Abstract 1. 1. The physiological and clinical changes following closure of atrial septal defect in fifteen patients by the atrio-septo-pexy technique are presented. 2. 2. The hemodynamic studies reveal complete elimination of the left-to-right shunt in twelve cases. In two patients the shunt was decreased, and there was no change observed in one. 3. 3. The significance of the clinical changes following surgery is discussed.
Stress-induced modulation of the immune response in the developing rat pup

Although substantial evidence has linked stressful events to immune changes in adult animals, little is known regarding the impact of stress on immune function during ontogeny. In the present study, 8-, 16-, and 20-day old rat pups were isolated from their mothers and littermates for 24 h; splenocyte responses to the mitogen Con A were assessed 72 h following reunion. A suppression of the mitogen response was obtained for 16- and 20-day old pups, but no effect was found in the 8-day-old animals, possibly due to the small sample size. These data offer a viable model from which to study further changes in immune responsiveness during ontogeny.
Revaccination of high-risk adults with pneumococcal polysaccharide vaccine.

1. Flegal KM, Carrol MD, Kuczmarski RJ, Johnson CL. Overweight and obesity in the United States: prevalence and trends, 1960-1994. Int J Obes Relat Metab Disord. 1998;22:39-47. 2. Williamson DF, Serdula MK, Anda RF, Levy A, Byers T. Current weight loss attempts in adults: goal, duration, and rate of weight loss. Am J Public Health. 1992; 82:1251-1257. 3. Levy D, Thom TJ. Death rates from coronary disease: progress and a puzzling paradox. N Engl J Med. 1998;339:915-917. 4. Kassirer JP, Angell M. Losing weight: an ill-fated New Year’s resolution. N Engl J Med. 1998;388:52-54. 5. HarrisMI, FlegalKM,CowieCC,et al. Prevalenceofdiabetes, impaired fastingglucose, and impaired glucose tolerance in US adults. Diabetes Care. 1998;21:518-524. 6. Rosamond WD, Chambless LE, Folsom AR, et al. Trends in the incidence of myocardial infarction and in mortality due to coronary heart disease, 1987 to 1994. N Engl J Med. 1998;339:861-867. 7. Bowen R, Glicklich A, Khan M, et al. Cardiac valvulopathy associated with exposure to fenfluramine or dexfenfluramine: US Department of Health and Human Services Interim Public Health Recommendations, November 1997. MMWR Morb Mortal Wkly Rep. 1997;46:1061-1066. 8. Meridia [prescribing information]. Mount Olive, NJ: Knoll Pharmaceutical Co; 1998. 9. Sjostrom L, Rissanen A, Andersen T, et al. Randomised placebo-controlled trial of orlistat for weight loss and prevention of weight regain in obese patients. Lancet. 1998;352:167-172. 10. Hollander PA, Elbein SC, Hirsch IB, et al. Role of orlistat in the treatment of obese patients with type 2 diabetes. Diabetes Care. 1998;21:1288-1294. 11. Davidson MH, Hauptman J, DiGirolamo M, et al. Weight control and risk factor reduction in obese subjects treated for 2 years with orlistat: a randomized controlled trial. JAMA. 1999;281:235-242. 12. Little R, Yau L. Intent-to-treat analysis for longitudinal studies with dropouts. Biometrics. 1996;52:1324-1333. 13. Psaty BM, Smith NL, Siscovick DS, et al. Health outcomes associated with antihypertensive therapies used as first-line agents: a systematic review and metaanalysis. JAMA. 1997;277:739-745. 14. National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health. Study of Health Outcomes of Weight loss (SHOW) Web site. Available at: http://www.ep.niddk.nih.gov/divisions/ddn/SHOW/show.htm. Accessed December 30, 1998. 15. Forster JL, Jeffery RW, Schmid TL, Kramer FM. Preventing weight gain in adults: a pound of prevention. Health Psychol. 1988;7:515-525. 16. Jeffery RW, French SA. Preventing weight gain in adults: design, methods and one year results from the Pound of Prevention study. Int J Obes Relat Metab Disord. 1997;21:457-464.
ADSORPTION OF ETHYLENE GLYCOL ON AMINE-SUBSTITUTED MONTMORILLONITES

To determine the reason why the adsorption of ethylene glycol on organo-smectites does not result in an expansion along the c-axis of the clays, smectites containing relatively small organo-ammonium ions (lauryl-, benzyl-, dibenzyl-, and dicyclohexylammonium), larger organic cations (dimethylbenzyloc- tadeyl- and methylbenzyldioctadecylammonium), and the heterocyclic organo-ammonium ion 1,4a-di- methyl-7-isopropyl-l,2,3,4,4a,9,10,10a-octahydro-l-phenanthrenemethylammonium and the correspond- ing ethoxylated compound were exposed to ethylene glycol vapor for up to several months and examined by X-ray powder diffraction (XRD), surface area, and thermogravimetric methods. Weight loss data showed that all samples adsorbed ethylene glycol. XRD data for oriented samples indicated that lauryl-, benzyl-, dicyclohexyl-, and ethoxylated heterocyclic ammonium clays expanded by one layer of ethylene glycol and that methylbenzyldioctadecylammonium smectite expanded by two layers. Dibenzyl-, dimeth- ylbenzyloctadecyl-, and heterocyclic smectites did not expand because the clay oriented in such a manner as to leave free clay surface between the organo-ammonium cations.
Transforming growth factor-β1 inhibits tumor necrosis factor-α/lymphotoxin production and adoptive transfer of disease by effector cells of autoimmune encephalomyelitis

We previously reported that the CD4+ suppressor cells (Ts) that regulate recovery of Lewis rats from experimental autoimmune encephalomyelitis (EAE) produce transforming growth factor-beta (TGF-beta). We also reported that TGF-beta downregulates interferon-gamma (IFN-gamma), but not interleukin-2 (IL-2) production, by the CD4+ effector T cells (Te) that mediate EAE. We now report that TGF-beta also inhibits the production of tumor necrosis factor/lymphotoxin (TNF/LT) by EAE effector cells. When activated in vitro with myelin basic protein (MBP), Te produced TNF/LT, as measured using a WEHI 164 cytotoxicity assay. The specificity of cytokine action was demonstrated using neutralizing antibodies to TNF/LT. When added to the Te+MBP cultures, TGF-beta inhibited TNF/LT production in a dose-dependent fashion. Moreover, neutralizing anti-TGF-beta antibodies augmented TNF/LT production in the Te+MBP cultures. We also confirm that TGF-beta inhibits adoptive transfer of EAE. In contrast, murine IL-10 only partially inhibited TNF/LT and IFN-gamma production by Te. We conclude that TGF-beta production by Ts plays a major role in recovery from EAE in the Lewis rat by inhibiting TNF/LT and IFN-gamma production by the effector cells that mediate EAE.
Chick skeletal Muscle Proteolysis in vitro Increased by Corticosterone

Six-day-old chick skeletal muscle (extensor digitorum longus) was incubated in the presence of corticosterone (CTC; 0, 3, 30, and 300 ng/ml) for 2 h at 37°C. Tyrosine and Nτ-methylhistidine releases, as indices of total muscle and myofibrillar proteolysis, were increased by CTC but with different dose responses, indicating an independent regulation of myofibrillar and non-myofibrillar protein degradation.
39Ar and 37Ar recoil loss during neutron irradiation of sanidine and plagioclase

Abstract The 40Ar/39Ar dating technique requires the activation of 39Ar via neutron irradiation. The energy produced by the reaction is transferred to the daughter atom as kinetic energy and triggers its displacement, known as the recoil effect. Significant amounts of 39Ar and 37Ar can be lost from minerals leading to spurious ages and biased age spectra. Through two experiments, we present direct measurement of the recoil-induced 39Ar and 37Ar losses on Fish Canyon sanidine and plagioclase. We use multi-grain populations with discrete sizes ranging from 210 to We show that 39Ar loss (depletion factor) for sanidine is ∼3% for the smallest fraction. Age spectra of fractions smaller than ∼50 μm show slight departure from flat plateau-age spectrum usually observed for large sanidine. This departure is roughly proportional to the size of the grain but does not show typical 39Ar loss age spectra. The calculated thickness of the total depletion layer d0(sanidine) is 0.035 ± 0.012 (2σ). This is equivalent to a mean depth of the partial depletion layer (x0) of 0.070 ± 0.024 μm. The latter value is indistinguishable from previous values of ∼0.07–0.09 μm obtained by argon implantation experiments and simulation results. We show that it is possible to adequately correct ages from 39Ar ejection loss provided that the d0-value and the size range of the minerals are sufficiently constrained. As exemplified by similar calculations performed on results obtained in a similar study of GA1550 biotite [Paine J. H., Nomade S., and Renne P. R. (2006) Quantification of 39Ar recoil ejection from GA1550 biotite during neutron irradiation as a function of grain dimensions. Geochim. Cosmochim. Acta 70, 1507–1517.], the d0(biotite) is 0.46 ± 0.06 μm. The significant difference between empirical results on biotite and sanidine, along with different simulation results, suggests that for biotite, crystal structures and lattice defects of the stopping medium and possibly subsequent thermal degassing (due to ∼150–200 °C temperature in the reactor or extraction line bake out) must play an important role in 39Ar loss. The second experiment suggests that 37Ar recoil can substantially affect the age via the interference corrections with results that suggest up to ∼98% of 37Ar can be ejected from the ∼5 μm grain dimension. Further investigation of silicates of various compositions and structures are required to better understand (and correct) the recoil and recoil-induced effects on both 39Ar and 37Ar and their influences on 40Ar/39Ar dating.
GenBank and PubMed: How connected are they?

GenBank(R) is a public repository of all publicly available molecular sequence data from a range of sources. In addition to relevant metadata (e.g., sequence description, source organism and taxonomy), publication information is recorded in the GenBank data file. The identification of literature associated with a given molecular sequence may be an essential first step in developing research hypotheses. Although many of the publications associated with GenBank records may not be linked into or part of complementary literature databases (e.g., PubMed), GenBank records associated with literature indexed in Medline are identifiable as they contain PubMed identifiers (PMIDs). Here we show that an analysis of 87,116,501 GenBank sequence files reveals that 42% are associated with a publication or patent. Of these, 71% are associated with PMIDs, and can therefore be linked to a citation record in the PubMed database. The remaining (29%) of publication-associated GenBank entries either do not have PMIDs or cite a publication that is not currently indexed by PubMed. We also identify the journal titles that are linked through citations in the GenBank files to the largest number of sequences. Our analysis suggests that GenBank contains molecular sequences from a range of disciplines beyond biomedicine, the initial scope of PubMed. The findings thus suggest opportunities to develop mechanisms for integrating biological knowledge beyond the biomedical field.
Thermal structure of the plasmasphere

Abstract The density structure of the plasmasphere has been a subject of interest and considerable research since the discovery of the plasmapause. For a number of reasons, plasmasphere thermal structure has been examined less thoroughly. Observations show that the thermal structure is closely tied to density structure and has significant impact on the composition of the plasma. In this report, we review observations of plasmasphere temperatures, displaying their variability in space and time and their relation to the plasmasphere density structure. Primary observations are from the Retarding Ion Mass Spectrometer on the Dynamics Explorer 1 satellite. Through comparisons with numerical simulations, we can begin to test our quantitative understanding of a number of factors which either influence or respond to this thermal structure. We review several studies which compare observations with numerical simulations of plasmaspheric properties, directing particular attention to energy sources and energy transport in the inner and outer plasmasphere. We find that photoelectrons, as currently understood, do not always provide sufficient energy to plasmaspheric plasma to produce the ion temperatures observed; additional possibilities are examined. In addition to what we appear to understand fairly well, there are several areas of deficiency, which we outline briefly.
Treatment of Diabetic Neuropathy with Inhibitors of the Aldose Reductase Enzyme

Neuropathy represents the most common target organ complication in diabetes. Because criteria for diagnosis vary, however, its prevalence is impossible to state precisely. In one series, 71% of an unselected group of diabetics showed nerve conduction slowing.’ However, because electrophysiologic measurements of nerve conduction velocity reflect abnormalities only in large, myelinated nerve fibers, and thus overlook small fiber disease which is an important component of diabetic neuropathy, the prevalence of clinically relevant neuropathy is clearly higher. There are three broad categories of diabetic neuropathy. The mononeuropathies consist of dysfunction within the distribution of a single nerve, are usually of abrupt onset, tend to resolve completely, and are generally believed to result from involvement of the vasa nervorum. Peripheral sensorimotor neuropathies and the autonomic neuropathies tend to be of gradual onset and slowly but inexorably progressive. They are considered to be of metabolic origin and are therefore theoretically likely to be amenable to prophylaxis or therapy with agents such as aldose reductase inhibitors (ARls), which are designed to interfere with the metabolic pathways considered important in the pathogenesis of neuropathy.’ Osmotic forces related to polyol pathway activity may generate sufficient hydrostatic pressure in the nerve bundle to compromise or even occlude the microvessels that penetrate the perineurium from without, thereby producing the ischemic pattern of injury to nerves that has been suggested recently by several groups of investigators.3-5