cssi/SciSciGPT-SciSciNet huggingface dataset:
Ligand discrimination and gating in cyclic nucleotide-gated ion channels from apo and partial agonist-bound cryo-EM structures

Ion channels are essential for transmitting signals in the nervous system and brain. One large group of ion channels includes members that are activated by cyclic nucleotides, small molecules used to transmit signals within cells. These cyclic nucleotide-gated channels play an important role in regulating our ability to see and smell. The activity of these ion channels has been studied for years, but scientists have only recently been able to look into their structure. Since structural biology methods require purified, well-behaved proteins, the members of this ion channel family selected for structural studies do not necessarily match those whose activity has been well established. There is a need for a good model that would allow both the structure and activity of a cyclic nucleotide-gated ion channel to be characterized. The cyclic nucleotide-gated ion channel, SthK, from bacteria called Spirochaeta thermophila, was identified as such model because both its activity and its structure are accessible. Rheinberger et al. have used cryo electron microscopy to solve several high-resolution structures of SthK channels. In two of the structures, SthK was bound to either one of two types of activating cyclic nucleotides – cAMP or cGMP – and in another structure, no cyclic nucleotides were bound. Separately recording the activity of individual channels allowed the activity states likely to be represented by these structures to be identified. Combining the results of the experiments revealed no activity from channels in an unbound state, low levels of activity for channels bound to cGMP, and moderate activity for channels bound to cAMP. Rheinberger et al. show that the channel, under the conditions experienced in cryo electron microscopy, is closed in all of the states studied. Unexpectedly, the binding of cyclic nucleotides produced no structural change even in the cyclic nucleotide-binding pocket of the channel, a region that was previously observed to undergo such changes when this region alone was crystallized. Rheinberger et al. deduce from this that the four subunits that make up the channel likely undergo the conformational change towards an open state all at once, rather than one by one. The structures and the basic functional characterization of SthK channels provide a strong starting point for future research into determining the entire opening and closing cycle for a cyclic nucleotide-gated channel. Human equivalents of the channel are likely to work in similar ways. The results presented by Rheinberger et al. could therefore be built upon to help address diseases that result from deficiencies in cyclic nucleotide-gated channels, such as loss of vision due to retinal degradation (retinitis pigmentosa or progressive cone dystrophy) and achromatopsia.
How Does Social Media Use Relate to Adolescents’ Internalizing Symptoms? Conclusions from a Systematic Narrative Review

The growing prominence of social media use among teenagers has prompted researchers in psychology and communication science to consider connections between social media activities and youths’ development and well-being. This systematic, narrative review evaluated associations between social media use and the internalizing symptoms of depression, anxiety, and loneliness among 12–18-year-olds, based on 68 qualifying empirical studies conducted between 2000 and 2017. For each symptom, analyses assessed the theoretical underpinnings of studies; the strength, direction, and consistency of associations with social media use; and factors mediating or moderating these associations. Investigators often reported positive associations between social media use and internalizing symptoms, but more nuanced studies pointed to individual, contextual, or media-based factors qualifying these direct effects. Future research would benefit from more theory-driven approaches, consistent measurements of key constructs, and a combination of longitudinal and experimental designs to identify causal associations. Integrating concepts from developmental psychology, clinical psychology, and communication science would aid in understanding the seemingly complex relationships between social media use and adolescents’ internalizing symptoms.
TCT-524 Results of self-expanding nitinol stents post-dilated with drug-coated balloon in treatment of femoropoplitial disease

Bare metal stents (BMS) have better patency results in the femoropopliteal (FP) arterial segments than conventional percutaneous balloon angioplasty (PTA). More recently, drug-coated balloons (DCB) have shown superior outcomes compared to PTA. DCB inhibit neointimal hyperplasia, but unlike BMS,
A Time Series of Water Column Distributions and Sinking Particle Flux of Pseudo-Nitzschia and Domoic Acid in the Santa Barbara Basin, California

Water column bulk Pseudo-nitzschia abundance and the dissolved and particulate domoic acid (DA) concentrations were measured in the Santa Barbara Basin (SBB), California from 2009⁻2013 and compared to bulk Pseudo-nitzschia cell abundance and DA concentrations and fluxes in sediment traps moored at 147 m and 509 m. Pseudo-nitzschia abundance throughout the study period was spatially and temporally heterogeneous ( 1000 cells L-1 and tDA = 200 ng L-1) measured as deep as 150 m. Our results highlight that dDA should not be ignored when examining bloom toxicity. Although water column abundance and pDA concentrations were poorly correlated with sediment trap Pseudo-nitzschia abundance and fluxes, DA toxicity is likely associated with senescent blooms that rapidly sink to the seafloor, adding another potential source of DA to benthic organisms.
Role for a Filamentous Nuclear Assembly of IFI16, DNA, and Host Factors in Restriction of Herpesviral Infection

Several host cell nuclear factors are known to restrict herpes simplex virus 1 (HSV-1) replication, but their mechanisms of action remain to be defined. Interferon-inducible protein 16 (IFI16) and the nuclear domain 10-associated proteins, such as promyelocytic leukemia (PML) protein, localize to input viral genomes, but they are also capable of restricting progeny viral transcription. In this study, we used structured illumination microscopy to show that after HSV DNA replication, IFI16 forms nuclear filamentous structures on DNA within a subset of nuclear replication compartments in HSV-1 ICP0-null mutant virus-infected human cells. The ability to form filaments in different cell types correlates with the efficiency of restriction, and the kinetics of filament formation and epigenetic changes are similar. Thus, both are consistent with the filamentous structures being involved in epigenetic silencing of viral progeny DNA. IFI16 filaments recruit other restriction factors, including PML, Sp100, and ATRX, to aid in the restriction. Although the filaments are only in a subset of the replication compartments, IFI16 reduces the levels of elongation-competent RNA polymerase II (Pol II) in all replication compartments. Therefore, we propose that IFI16 filaments with associated restriction factors that form in replication compartments constitute a "restrictosome" structure that signals in cis and trans to silence the progeny viral DNA throughout the infected cell nucleus. The IFI16 filamentous structure may constitute the first known nuclear supramolecular organizing center for signaling in the cell nucleus.IMPORTANCE Mammalian cells exhibit numerous strategies to recognize and contain viral infections. The best-characterized antiviral responses are those that are induced within the cytosol by receptors that activate interferon responses or shut down translation. Antiviral responses also occur in the nucleus, yet these intranuclear innate immune responses are poorly defined at the receptor-proximal level. In this study, we explored the ability of cells to restrict infection by assembling viral DNA into transcriptionally silent heterochromatin within the nucleus. We found that the IFI16 restriction factor forms filaments on DNA within infected cells. These filaments recruit antiviral restriction factors to prevent viral replication in various cell types. Mechanistically, IFI16 filaments inhibit the recruitment of RNA polymerase II to viral genes. We propose that IFI16 filaments with associated restriction factors constitute a "restrictosome" structure that can signal to other parts of the nucleus where foreign DNA is located that it should be silenced.
Novel PRACH Scheme for 5G Networks Based on Analog Bloom Filter

5G is expected to support far higher user density and far lower latency than LTE. PRACH is an important procedure for a User Equipment (UE) to initiate a connection with the base station. In this paper, a novel PRACH scheme is proposed, which outperforms the current LTE PRACH in many cases by an order of magnitude measured by the total error ratio. The new scheme is based on the Analog Bloom Filter (ABF), with which a UE transmits multiple orthogonal sequences to the base station, instead of only one sequence according to LTE. The collision probability is greatly reduced, because the number of combinations of sequences is much larger than the number of sequences. The challenges addressed in this paper include a signal processing algorithm that can cope with peak shift and peak energy spreading, as well as a novel scheme that allows the UE to piggyback multiple bits along with the PRACH signal, which will further improve the efficiency of the network.
Predicting kernel processing score of harvested and processed corn silage via image processing techniques

Abstract An image processing algorithm was developed to characterize the size distribution of corn kernel particles from Whole Plant Corn Silage (WPCS). The algorithm determines particle cross sectional area and maximum inscribed circle diameter as well as cumulative undersize percent, dimensions of significance, and key characteristics of the distribution including mean particle size, skewness, and kurtosis. Kernel Possessing Score (KPS) was derived from the area-weighted cumulative undersize percent of 4.75 mm. Samples of WPCS harvested using self-propelled forage harvester with crop processing roll gap clearance of 1, 2, 3, and 4 mm were analyzed in their fresh, dry, and sieved states. Algorithm results were compared with the standard method of mechanical sieving and found to be well correlated r(23) = 0.8, p
Novel Methodological Considerations Regarding the Use of Visual Analog Scale (VAS) Appetite Questionnaires in Tightly Controlled Feeding Trials.

Visual analog scale (VAS) questionnaires are widely used in nutrition research to assess appetite and subsequent food intake. However, a number of methodological considerations exist. The study aims were to test whether 1) appetite VASs alter subsequent food intake and 2) viewing previous appetite responses influences subsequent responses. Twelve healthy adults (age: 22 ± 3 y; BMI: 22.0 ± 3.1 kg/m2) completed the randomized crossover study. On separate days, participants were provided breakfast preloads and completed appetite VASs every 30 min for 4 h or did not complete the questionnaires. When completing VASs, the participants were shown their previous responses (PR) or were not (No-PR). After 4 h, an ad libitum lunch was provided. Hunger, fullness, desire to eat, and prospective food consumption were not different between PR and No-PR. All data are reported as mean ± SEM. VASs did not affect lunch intake (484 ± 50 kcal) compared with no VASs (500 ± 53 kcal, nonsignificant). Thus, neither past appetite responses nor the use of appetite VASs influenced ingestive behavior in healthy adults. This trial was part of a larger acute, randomized crossover trial registered at clinicaltrials.gov as NCT03154606.
Affirmative action subcontracting regulations in dynamic procurement auctions

I study affirmative action subcontracting regulations in a model where governments use auctions to repeatedly procure goods and services at the lowest possible price. Through using disadvantaged subcontractors, prime contractors build relationships over time, resulting in lower subcontracting costs in future periods. I find that regulation in the form of a minimum subcontracting requirement expands bidder asymmetries, favoring prime contractors with stronger relationships over those with weaker ones. Simulations show that the manner in which relationships evolve determines not only the utilization of disadvantaged subcontractors but also the procurement costs attained under affirmative action.
Pre-clinical Stress Management Workshops Increase Medical Students' Knowledge and Self-awareness of Coping with Stress.

To investigate the effects of a stress management workshop on medical students’ knowledge of stress and potential coping strategies. A panel discussion with small group breakouts on stress in clinical medicine, learning challenges, competition with colleagues, handling stressful events, and recognizing burnout symptoms was conducted with medical students entering clerkships. A longitudinal survey design was utilized to measure pre-, post-, and long-term (3-month) changes in knowledge (impact of stress on personal health, learning, and patient care), confidence, perceived skills, and attitude (towards utilizing adaptive coping strategies) among participating students (N = 135). Paired t test and multivariate analyses were performed to assess the differences between survey responses on a 5-point Likert scale. Survey response rates were pre-90.4%, post-77%, and long-term post-71.1%. Compared to pre-workshop, students reported significant improvement in all four domains immediately post-workshop: knowledge (4.4 vs. 4.7, p < 0.05), confidence (3.6 vs. 3.9, p < 0.05), perceived skills (3.3 vs. 3.7, p < 0.05), and attitude (2.6 vs. 2.8, p < 0.05). Compared to immediate post-workshop, students’ scores slightly decreased at 3 months but were overall significantly higher than the pre-workshop scores. A stress management workshop can improve medical students’ knowledge of the impact of stress as well as the use of adaptive stress coping strategies.
"Holes-in-one": A case of concurrent windsock mitral valve, root abscess, and Gerbode defect

Infective endocarditis is a heterogeneous disease with a wide array of pathological lesions. We present a 55-year-old man with severe mitral and aortic regurgitation on transthoracic echocardiography. Transesophageal echocardiogram characterized the mechanisms detecting a windsock mitral valve perforation, aortic root abscess, and Gerbode ventricular septal defect, with the deep transgastric view showing all three pathologies concurrently. The etiologies of mitral valve perforation and Gerbode defects are discussed. Transesophageal echocardiography remains a critical imaging modality to diagnose and evaluate the extent of infective endocarditis with superior sensitivity to transthoracic echocardiography.
Hematopoietic stem cell transplantation for primary immune deficiencies

Abstract Pluripotent self-replicating stem cells harvested from bone marrow, from peripheral blood following mobilization with granulocyte-colony stimulating factor (G-CSF), or from umbilical cord and placental blood develop into erythrocytes, and megakaryocyte and leukocyte precursors, and thus can be used to replace malignant, absent, or defective cells. Hematopoietic stem cell transplant aims to give stable donor stem cell engraftment after partial or full ablation of the recipient's marrow and immune system using a combination of chemotherapy, antibody therapy, and a graft-versus-marrow effect. For patients with primary immune deficiency, replacement of defective or absent granulocytes, monocytes, or T and B cells can cure the immunodeficiency.
Blocking palmitoylation of Toxoplasma gondii myosin light chain 1 disrupts glideosome composition but has little impact on parasite motility

Toxoplasma gondii is a widespread apicomplexan parasite that causes severe disease in immunocompromised individuals and the developing fetus. Like other apicomplexans, T. gondii uses an unusual form of gliding motility to invade cells of its hosts and to disseminate throughout the body during infection. It is well established that a myosin-based motor consisting of a Class XIVa heavy chain (TgMyoA) and two light chains (TgMLC1 and TgELC1/2) plays an important role in parasite motility. The ability of the motor to generate force at the parasite periphery is thought to be reliant upon its anchoring and immobilization within a peripheral membrane-bound compartment, the inner membrane complex (IMC). The motor does not insert into the IMC directly; rather, this interaction is believed to be mediated by the binding of TgMLC1 to the IMC-anchored protein, TgGAP45. The binding of TgMLC1 to TgGAP45 is therefore considered a key element in the force transduction machinery of the parasite. TgMLC1 is palmitoylated, and we show here that palmitoylation occurs on two N-terminal cysteine residues, C8 and C11. Mutations that block TgMLC1 palmitoylation disrupt the association of TgMLC1 with the membrane fraction of the parasite in phase partitioning experiments and completely block the binding of TgMLC1 to TgGAP45. Surprisingly, the loss of TgMLC1 binding to TgGAP45 in these mutant parasites has little effect on their ability to initiate or sustain movement. These results question a key tenet of the current model of apicomplexan motility and suggest that our understanding of gliding motility in this important group of human and animal pathogens is not yet complete. ImportanceGliding motility plays a central role in the life cycle of T. gondii and other apicomplexan parasites. The myosin motor thought to power motility is essential for virulence but distinctly different from the myosins found in humans. Consequently, an understanding of the mechanism(s) underlying parasite motility and the role played by this unusual myosin may reveal points of vulnerability that can be targeted for disease prevention and treatment. We show here that mutations that uncouple the motor from what is thought to be a key structural component of the motility machinery have little impact on parasite motility. This finding runs counter to predictions of the current, widely-held "linear motor" model of motility, highlighting the need for further studies to fully understand how apicomplexan parasites generate the forces necessary to move into, out of and between cells of the hosts they infect.
Clinical Experience With a Multidisciplinary Model of Vascular Ultrasound for the Evaluation for Giant Cell Arteritis.

Objective Vascular ultrasound (VUS) is a first-line test for giant cell arteritis (GCA) in Europe but has been of limited use in the United States. We report clinical experience with a multidisciplinary model of VUS for the evaluation of GCA at a large US medical center. Methods Patients who underwent VUS for evaluation of GCA between 2013 and 2017 were reviewed. Trained vascular technologists followed a standardized protocol to visualize bilateral temporal, carotid, subclavian, and axillary arteries. Vascular medicine physicians interpreted VUS as no arteritis, hyperechoic wall thickening, or acute arteritis. Characteristics of patients with versus without acute arteritis (no arteritis or hyperechoic wall thickening) were compared. Among patients with suspected new-onset GCA, the treating physician's pretest and posttest suspicion for GCA were compared. Results Of 530 patients, 10.6% had prior-onset GCA, 31.7% had polymyalgia rheumatica, and 57.6% were taking glucocorticoids. Most patients had no arteritis on VUS (84.3%); 10.6% had acute arteritis, and 5.1% had hyperechoic wall thickening. Typical GCA symptoms, such as jaw claudication and scalp tenderness, were significantly more frequent in patients with acute arteritis. For all 42 patients with suspected new-onset GCA and acute arteritis, posttest suspicion was unchanged or increased. Of 415 patients with suspected new-onset GCA and VUS without acute arteritis, suspicion decreased (76.4%) or was unchanged (20.2%). Conclusion We describe a multidisciplinary model for incorporating VUS into GCA care. When pretest suspicion was low and VUS did not reveal acute arteritis, posttest suspicion typically decreased, whereas when pretest suspicion was high and VUS revealed acute arteritis, posttest suspicion was reinforced.
Late effects in a high-risk population of breast cancer survivors.

To better understand the impact of cancer and treatment on outcomes and guide program development, we evaluated breast cancer survivors at risk for long-term medical and psychosocial issues who participated in survivorship care visits (SVs) at Johns Hopkins Hospital. We conducted a prospective survey study of women with stage I-III breast cancer who participated in SVs from 2010–2016. The same 56-item questionnaire administered at SV and follow-up included an assessment of symptoms, social factors, demographics, anxiety, depression, and comorbidities. We added the Godin Exercise questionnaire to the follow-up. In 2018, 74 participants were identified as disease-free and mailed a follow-up survey; 52 (70.3%) completed the survey. At a median follow-up time of 3.1 years after diagnosis, participants were less likely to be employed (54% vs. 67%) than at the SV. About two-thirds were sedentary, and this was associated with high body mass index (p = 0.02). Sufficiently active participants (≥ 150 min per week of moderate-intensity activity) were less likely to report pain (p = 0.02) or fatigue (p = 0.001). Although 19% had moderate/severe anxiety or depression at follow-up, participants who reported employment satisfaction were less likely to be depressed (p = 0.02). Awareness of issues faced by survivors is critical for enhancing care and developing models to identify patients who might benefit most from targeted long-term interventions. Interventions to address physical activity, persistent symptoms, and mental health are critical for breast cancer survivors.
Assessing the Concordance Between Urogenital and Vaginal Microbiota: Can Urine Specimens Be Used as a Proxy for Vaginal Samples?

Background: The vaginal microbiota play a key role in defense against reproductive tract infections; however, many population-based women’s health studies do not collect vaginal samples. Molecular examinations of urine samples have revealed common vaginal bacteria. We sought to assess the extent that community state type assignments of archived random-catch and clean-catch urine samples agreed with the paired vaginal samples in both reproductive-age and peri/post-menopausal women. Results: Using archived samples, we evaluated the microbiota concordance among women in three studies: two with paired mid-vaginal/random-catch urine (N=91 reproductive-age participants and N=13 peri/post-menopausal participants), and one with paired mid-vaginal/clean-catch urine (N=99 reproductive-age participants). Microbiota composition was characterized by sequencing amplicons of the 16S rRNA gene V3-V4 regions and assigned to community state types. Similarity of paired samples was gauged using agreement of community state types and Yue-Clayton  indices. Analysis of Composition of Microbiomes II indicated which taxa were differently relatively abundant in paired vaginal and urine samples. In reproductive-age women, random-catch and clean-catch urines were 89.0% and 86.9% concordant on five community state types with paired mid-vaginal swabs, and Kappa statistics indicated almost perfect agreement (random-catch=.85, clean-catch=.81, p<0.0001). A small number of pairs of samples were discordant (23/190, 12%), and discordant pairs tended to be between samples classified to L. iners-dominated and/or low-Lactobacillus states. Concordance and agreement remained similar when dichotomizing the microbiota to Lactobacillus-dominated versus low-Lactobacillus microbiota, as well as when evaluating separately the three subtypes of the low-Lactobacillus community state type IV. Median similarity of paired urine/vaginal samples was high (random-catch=.85, clean-catch=.88), and a comparison of the random-catch and clean-catch similarity scores showed no significant difference (p=.80). Concordance and similarity were lower for peri/post-menopausal women, but agreement remained substantial (76.9% concordant, random-catch= 0.64, random-catch=.62). Taxonomic-level analysis confirmed these findings. Conclusions: Random-catch and clean-catch urine samples showed substantial agreement on bacterial composition to paired mid-vaginal samples, indicating that the genitourinary microbiota may be a reliable proxy for assessing the overall composition of the vaginal microbiota via community state types. This data suggests that urine samples can, with proper interpretation, be utilized as a surrogate for developing preliminary data and hypothesis-generating studies.
Why Black Voters Chose Biden

Black voters are primarily responsible for having propelled former Vice President Joseph R. Biden to become the Democratic Party presidential nominee in 2020. They voted for him in large numbers, starting with the South Carolina election onward. Given the historic nature of the national political context in which Biden emerged as frontrunner, plus controversy surrounding some of his past involvements with momentous racial issues, a question of interest is: why did blacks vote for him? A look at the data on black primary voter policy priorities and positions versus the plans and promises of candidates during the 2020 election season suggests that Biden’s vision came closest to black voter policy interests. The takeaway lesson from this chapter’s look at the degree of substantive synchronicity between the black Democratic electorate and the candidate Biden platform is that issue voting best explains the otherwise odd choice of Biden over the rest of the diverse field. More broadly, black voters utilize their voting power in ways that are based more on substance, than on skin color, political elite cues, retrospective assessment, or liberal ideology.
Outcomes in Exceptionally Poor-Responders to Neoadjuvant Chemotherapy.

PURPOSE/OBJECTIVE(S) The use of neoadjuvant chemotherapy (NAC) in patients with operable breast cancer allows for assessment of treatment response, and subsequent tailoring of adjuvant therapy. While there is robust evidence demonstrating worse prognosis with residual disease versus path CR after NAC, there is little data regarding outcomes among patients with a heavy residual tumor burden after NAC. We report outcomes in patients who have exceptionally poor responses to NAC-those with > 9 nodes after NAC or with 5 cm or more of residual disease in the breast. MATERIALS/METHODS Between 06/2014 and 04/2020, 1511 patients received NAC followed by surgery at our institution. Poor responders, defined as those with positive nodes or residual tumor in the breast, were identified for analysis. Those with 1-3 positive nodes after NAC were used as a comparison cohort. Recurrence and survival outcomes were compared based on residual disease burden after NAC. Clinicopathologic parameters were summarized with descriptive statistics. Overall survival and recurrence-free survival estimates were calculated using Kaplan Meier methodology. RESULTS Among 517 poor-responders, 315 patients had 1-3 positive nodes (N1a), 108 had 4-9 positive nodes (N2a), and 62 had > 9 positive nodes (high-volume residual, HVR); 32 patients with > 5cm of residual tumor in the breast were categorized as HVR. With a median follow-up of 39 months (IQR 27-50), the 5-year overall survival rate was 90% among N1a, 72% among N2a, and 78% among HVR patients (P = 0.003). The 5-year distant recurrence-free survival and local recurrence-free survival rates were 87%/87% among N1a vs. 59%/71% among N2a vs. 68%/75% among HVR (P < 0.001 and P = 0.009), respectively. 5-year local-regional and distant recurrence cumulative incidence rates, stratified by residual disease burden and by breast cancer subtype, are shown in Table 1. CONCLUSION Our work confirms that patients with high-volume residual are at high risk for LR and distant recurrence as well as death, despite best available standard-of-care treatment. ypN2a patients appear to perform as bad as HVR patients in terms of DM and death, but better in terms of local-regional recurrence. Triple-negative patients with residual disease had high rates of recurrence and death compared to other subtypes. Treatment intensification efforts are urgently needed.
New concepts in the treatment of uterine leiomyomas

Uterine leiomyomas are a common clinical occurrence for gynecologists. The current approach to treating these neoplasms is shaped by classic surgical principles and the knowledge that these tumors are responsive to the gonadal steroids estrogen and progesterone. As knowledge of leiomyomas advances through the techniques of molecular biology and molecular genetics, new concepts are developed that go beyond just myomas as steroid-responsive tumors. Understanding the molecular events involved in the transformation of a normal myometrial cell into a neoplastic cell and the subsequent growth of these leiomyoma cells will be important in determining the pathogenesis of these tumors and providing new targets for treatment. Knowing the role of peptide growth factors, including basic fibroblast growth factor and transforming growth factor-beta, in the pathogenesis of leiomyoma-related symptoms might lead to new treatments targeting these molecules or their receptors. As the effects of genes, including HMGIC and HMGI(Y), are determined; new treatments to prevent leiomyoma formation or growth may be developed. As we gain understanding of the molecular events that cause benign gynecologic conditions such as leiomyomas, safer and more effective treatments might be found as we enter the 21st century.
Binding of human factors VII and VIIa to a human bladder carcinoma cell line (J82): Implications for the initiation of the extrinsic pathway of blood coagulation

We have studied the binding of radioiodinated human factor VII and its activated form, factor VIIa, to monolayers of a human bladder carcinoma cell line (J82) that expresses functional cell surface tissue factor. The binding of factors VII and VIIa to these cells was found to be time-, temperature-, and calcium-dependent. In addition, the binding of each protein to J82 cells was specific, dose-dependent, and saturable. The binding isotherms for factors VII and VIIa were hyperbolic, and Scatchard plots of the binding data obtained at 37 degrees C indicated a single class of binding sites for each protein with Kd values of 3.20 +/- 0.51 and 3.25 +/- 0.31 nM, respectively. Factors VII and VIIa, respectively, interacted with 256,000 +/- 39,000 and 320,000 +/- 31,000 binding sites/cell. Competition experiments suggested a common receptor for factors VII and VIIa. Binding of factor VIIa to the cells was completely blocked by preincubation of the cells with polyclonal anti-tissue factor IgG, whereas binding of factor VII was inhibited approximately 90%, suggesting the presence of a small number of tissue factor-independent binding sites specific for factor VII on this cell. Functional studies revealed that factor X activation by increasing amounts of cell-bound factor VII or VIIa was hyperbolic in nature. Half-maximal rates of factor Xa formation occurred at factor VII and VIIa concentrations of 3.7 +/- 0.47 and 3.2 +/- 0.31 nM, respectively. No factor VII- or VIIa-mediated activation of factor X was observed when cells were preincubated with anti-tissue factor IgG. Two-chain 125I-factor VIIa recovered from the cells was identical to the offered ligand as judged by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography. In contrast, the offered single-chain 125I-factor VII was progressively converted to two-chain 125I-factor VIIa upon binding to the cells. When the J82 cells were pretreated with anti-tissue factor IgG, both factor VII recovered from the cells and factor VII in the supernatant were in the single-chain form, indicating that cell-surface tissue factor was essential for the activation of factor VII on these cells. These data indicate that binding of factor VII to tissue factor appears to be a prerequisite for its conversion to factor VIIa and the initiation of the extrinsic pathway of coagulation on these cells.
Severe cholestatic hepatitis caused by thiazolidinediones: risks associated with substituting rosiglitazone for troglitazone

Troglitazone maleate (Rezulin) has been associated with severe hepatotoxicity, which led to its withdrawal from the U.S. market in March 2000. Rosiglitazone maleate (Avandia) is being marketed as a safe alternative in the treatment of type 2 diabetes mellitus. We report a case of severe thiazolidinedione-induced cholestatic hepatitis in a 56-year-old female patient at a university hospital who was given rosiglitazone, 8 mg/day, after she developed milder hepatotoxicity while taking troglitazone. Rosiglitazone was discontinued, and the patient was treated with prednisone, azathioprine, and ursodiol. Clinical evaluation and liver biopsy were performed and liver function tests were monitored. After being switched from troglitazone to rosiglitazone the patient developed a severe cholestatic hepatitis with marked jaundice and moderate increases in serum alkaline phosphatase and γ-glutamyltranspeptidase but only mild increases in serum aminotransferases. Discontinuation of rosiglitazone and treatment with prednisone, azathioprine, and ursodiol led to improvement, albeit with residual injury, dropout of intrahepatic bile ducts, and persisting elevations of serum alkaline phosphatase. Rosiglitazone is not always a safe alternative in patients who have had hepatotoxicity to troglitazone. It is important to monitor the serum alkaline phosphatase in addition to the serum aminotransferases in patients taking thiazolidinediones.
4. Lasers, Optics, and Thermal Considerations in Ablation Experiments

Publisher Summary This chapter focuses on lasers, optics, and thermal considerations in ablation experiments. Lasers are used in a variety of materials processing applications, including melting and recrystallization, doping, and annealing, which do not involve mass removal from a target. Other processes, such as etching, micromachining, and pulsed laser deposition of thin films (PLD), are ablative. In all cases, the design of a laser processing experiment requires the consideration of the coupling of the laser energy with the target material via the optical delivery system. The chapter defines the laser intensity and fluence variables and discusses the issues pertaining to the temperature field introduced in the target material. The chapter illustrates the design of the optical components used in laser processing experiments and the measurement of laser beam characteristics. It also provides a review of experimental methods available for measuring target temperature upon pulsed laser irradiation. The spatial profile of a laser beam at the laser exit aperture is determined by the geometry of the laser cavity. When the cross section of the cavity is symmetrical, as in the case of cylindrically or rectangularly shaped cavities, the spatial profiles become simple. If a Gaussian beam of circular cross section is focused by a cylindrical lens, or if the beam is incident on the target at an oblique angle of incidence, the resulting profile is elliptical.
Congressional Investigations and Judicial Review: Kilbourn v. Thompson Revisited

A legislative committee of inquiry vested with power to summon witnesses and compel the production of records and papers is an institution rivaling most legislative institutions in the antiquity of its origin. ... Prior to the adoption of our Constitution colonial assemblies frequently assumed authority to punish for contempt any person who refused to appear in answer to a summons or who failed to disclose information required for the effective administration of Government.'
Classical and Motivic Adams Charts

This document contains large-format Adams charts that compute 2-complete stable homotopy groups, both in the classical context and in the motivic context over C. The charts are essentially complete through the 61-stem and contain partial results to the 70-stem. In the classical context, we believe that these are the most accurate charts of their kind. We also include Adams charts for the motivic homotopy groups of the cofiber of tau.
Radiolabeling of Compounds

The use of compounds labeled with radionuclides has grown considerably in medical, biochemical, and other related fields. In the medical field, compounds labeled with β--emitting radionuclides are mainly restricted to in vitro experiments and therapeutic treatment, whereas those labeled with γ-emitting radionuclides have much wider applications. The latter are particularly useful for in vivo imaging of different organs.
Potentials on Special Open Sets

Throughout this book a special open subset of ℝ N is either a ball in ℝ N or ℝ N itself, but the latter only when N > 2. The Green function G D for D a ball was defined in Section II.1. The Green function G D for D = ℝ N with N > 2 is defined as G. If μ is a measure on a special open set D, define the function G D μ on D by $$ {{G}_{D}}\mu (\xi ) = \int_{D} {{{G}_{D}}(\xi ,\eta )\mu (dn)} $$ (1.1) .
Water Features on Topographic Maps

Topographic maps are a prime source of information for planning the improvement of man’s environment with respect to water. In order to utilize the tremendous amount of hydrologic information shown on these maps, the water resources planner must know what maps are available and how to interpret the map portrayal of water features. The paper explains how various features are shown and how to interpret features that are subject to change because of seasonal conditions, construction of dams, reclamation of swamps, and changes in stream courses. The classes of water features discussed include streams, lakes, ponds, reservoirs, canals, aqueducts, ditches, springs, wells, glaciers, and coasts. Methods of improving the means of presenting hydrologic information on maps are considered, with specific reference to orthophotomaps. Applications of special types of photography such as color infrared, and the use of orbiting satellites as vehicles for sophisticated sensors are mentioned.
The epidemiology of tick-borne relapsing fever in the United States.

Each year, many residents of and visitors to endemic regions of the western United States are exposed to the vector of tick-borne relapsing fever (TBRF), an underrecognized and underreported disease. Through review of report forms and literature review, we identified 450 cases of TBRF acquired in the United States in 11 western states (and in British Columbia by a U.S. resident) from January 1977 to January 2000. Exposure sites were in forested areas, at varying elevations, in mountainous regions (Cascade, Rocky Mountain, San Bernardino, and Sierra Nevada ranges) of the United States and Canada and in limestone caves in central Texas. Only 13 counties accounted for approximately 50% of all cases. Forty percent of the cases were not residents of the state where TBRF exposure occurred, including 7% from 11 states where TBRF is not endemic. TBRF is endemic in the United States and is a disease affecting travelers, who may return home with the disease to areas where physicians are not familiar with it.
Editor’s Overview: Mentoring in the Schoolhouse

Mentoring & Tutoring: Partnership in Learning, Volume 21, Issue 3, includes research from scholars representing the USA (Missouri and Washington, DC), Australia, Canada (Toronto), Sweden, and Eston...
Aurora and open magnetic flux during isolated substorms, sawteeth, and SMC events

Abstract. Using Polar UVI LBHl and IMAGE FUV WIC data, we have compared the auroral signatures and polar cap open flux for isolated substorms, sawteeth oscillations, and steady magnetospheric convection (SMC) events. First, a case study of each event type is performed, comparing auroral signatures and open magnetic fluxes to one another. The latitude location of the auroral oval is similar during isolated substorms and SMC events. The auroral intensity during SMC events is similar to that observed during the expansion phase of an isolated substorm. Examination of an individual sawtooth shows that the auroral intensity is much greater than the SMC or isolated substorm events and the auroral oval is displaced equatorward making a larger polar cap. The temporal variations observed during the individual sawtooth are similar to that observed during the isolated substorm, and while the change in polar cap flux measured during the sawtooth is larger, the percent change in flux is similar to that measured during the isolated substorm. These results are confirmed by a statistical analysis of events within these three classes. The results show that the auroral oval measured during individual sawteeth contains a polar cap with, on average, 150% more magnetic flux than the oval measured during isolated substorms or during SMC events. However, both isolated substorms and sawteeth show a 30% decrease in polar cap magnetic flux during the dipolarization (expansion) phase.
Effect of molecular weight on the spherulitic growth rate of poly(aryl ether ether ketone)

Abstract This study examines the change in spherulitic growth rate of poly(aryl ether ether ketone) (PEEK) as a function of molecular weight in the range of Mn = 6900 to 60 200 and for temperatures varying between 250 and 300°C. Optical microscopy using polarized light was used to follow the growth of the spherulites. Detailed analysis of the temperature dependence of the growth rates indicates that, within this relatively narrow range of molecular weight and temperature, both the pre-exponential factor and the exponential factor involving the free energy for nucleation are affected by molecular weight. Values of Kg increase with molecular weight from ≈0.8 × 106 K2 to 1.82 × 106 K2. Values of σe, the end surface free energy, increase likewise from 41 to 101 erg cm−2 with increasing molecular weight. The results of the microscopy study and the differential scanning calorimetry study are compared and discussed in terms of the relevance of either a thermodynamic model or a kinetic model with regime behaviour for the kinetics of crystallization of PEEK.
Perspectives on How Computer Science Curricula 2013 Influences Two-Year College Programs (Abstract Only)

The ACM Computer Science Curricula 2013 (CS2013) guidance for undergraduate degrees was released in December 2013. This BOF will provide a platform for two-year and four-year computer science faculty and academic administrators to discuss CS2013 and its influence on associate-degree computer science curricula. The session will include a brief overview of the Core Tier-1 and Core Tier-2 CS2013 topics and attendees will primarily engage in an open dialog about which CS2013 topics and learning outcomes are most relevant to be included in a transfer curriculum. This CS2013 discussion will help inform the forthcoming update to Computing Curricular 2009: Guidelines for Associate-Degree Transfer Curriculum in Computer Science (www.capspace.org).
The presence of dialkylphosphates in fresh fruit juices: implication for organophosphorus pesticide exposure and risk assessments.

This study was designed to determine whether dialkylphosphates (DAPs) are present in fresh fruit juices, as a result of organophosphorus (OP) pesticides degradation. Fresh conventional and organic fruit (apple and orange) juices were purchased from local grocery stores. DAPs were found in both conventional and organic juices, and the original levels were higher, for both apple and orange juices, in conventional than in organic juices. Additional DAPs were found in OP pesticide fortified juices after 72 h of storage at 4°C, suggesting a degradation of OP pesticides in juices. Overall, 12% and 36.2% of fortified azinphosmethyl, a dimethyl OP pesticide, and the combination of fortified diazinon and chlorpyrifos, both diethyl OP pesticides, were degraded to dimethyl and diethyl DAPs, respectively. Although the exact mechanism of the degradation is unknown, hydrolysis is likely the cause of OP pesticide degradation in juice. The presence of DAPs in fresh fruit juices clouds the validity of using urinary DAP me...
Inhibitory effect of leukemic plasma on periodate-induced lymphocyte transformation

Abstract Plasma from nine out of 18 patients with untreated acute lymphoblastic leukemia (ALL) depressed the transformation of normal blood lymphocytes induced by sodium periodate (Na10 4 ) as judged by reduction of blast cell formation and [ 3 H]thymidine and [ 3 H]uridine incorporation into DNA and RNA respectively. The depressed mitogen responsiveness of lymphocytes cultured in the presence of leukemic plasma was due to the presence of inhibitory factor(s) present in the plasma rather than the absence of components present in normal plasma. The inhibitory effect of leukemic plasma on periodate-induced cell stimulation indicated that the leukemic plasma inhibitory factor(s) exert their action very rapidly and directly on the cell. Transfer of the inhibitory factor(s) from the leukemic plasma to the cultured cells was supported by the finding that the depressive action of leukemic plasma on lectin and non-lectin mitogen-induced transformation of lymphocytes was reduced if the leukemic plasma was preincubated with either resting or mitogen-treated lymphocytes prior to testing with lymphocytes not previously exposed to leukemic plasma or mitogen.
Adenolipomas of the head and neck: analysis of 6 cases

Adenolipomas are rare benign neoplasms composed of mature adipose tissue and glandular elements. We report 6 patients with adenolipomas of the head and neck region: 3 in the parathyroid, 2 in the thyroid, and 1 in the parotid gland. The patients were 4 women and 2 men, ranging in age from 21 to 70 years (mean, 62.5 years). The patients with parathyroid adenolipomas manifested signs and symptoms of hyperparathyroidism, whereas the others complained of a mass in the neck. Computed tomography and magnetic resonance imaging are useful tools for the preoperative diagnosis of adenolipomas of the head and neck. The findings of adipose tissue and benign glandular elements by fine-needle aspiration biopsy should prompt consideration of adenolipoma in the differential diagnosis. Complete surgical excision is curative.
The normalization of diffraction from porous non-crystalline systems

Abstract The usual method of normalizing diffraction data from non-crystalline systems is based on the exclusion of atoms from the immediate neighborhood of another atom. This procedure relates the structure-independent intensity to the average atomic density. Porous materials exhibit intense small angle scattering. If this scattering is ignored or removed from the data, the normalization is related to the local atom density; if the small angle data are included in the transform, the normalization is related to the bulk density. An incorrect normalization of the experimental data will produce errors in the correlation function and the measured coordination numbers.
Editor's Introduction Theoretical Directions of Environment and Behavior Research

The articles in this issue offer fundamentally new conceptions of environment and behavior. Taken together, they provide a partial but provocative glimpse of certain general, theoretical directions...