cssi/SciSciGPT-SciSciNet huggingface dataset:
PC-based molecular modeling in the classroom: applications to medicinal chemistry biochemistry

Among the most difficult aspects of medicinal chemistry and biochemistry for the student to master are the three-dimensional (3D) nature of drugs and bio-organic substances and the interaction of these substances with 3D targets. Compounding this problem is the fact that such relationships are very difficult to illustrate in a lecture or discussion format. While skeletal molecular models serve a useful role in the learning process, the techniques of PC-based desktop molecular visualization provide a more powerful and effective alternative to the lecture format. These techniques can be implemented on standard MS-DOS PC hardware using one of the commonly available data projection systems. The approach has found considerable use in several areas, including the generation of computer-based lecture aids, the illustration of the molecular shapes of drugs and biochemical structures, the superposition and comparison of drug substances with common pharmacophores, and the illustration of enzyme-substrate interactions. Another related technique, molecular animation, has proven to be quite successful at illustrating the essentials of enzyme mechanisms in the classroom. The "film clips" resulting from this technique may have use beyond the classroom, and further work in this area is underway.
Rhetorical pedagogy as a postal system: Circulating subjects through Michael Warner's “publics and Counterpublics”

(2002). Rhetorical pedagogy as a postal system: Circulating subjects through Michael Warner's “publics and Counterpublics”. Quarterly Journal of Speech: Vol. 88, No. 4, pp. 434-443.
Risk stratification and short-term prognosis in acute heart failure syndromes: A review of novel biomarkers

Background: Early risk stratification of patients with acute heart failure syndrome (AHFS) can guide the decision to admit the patient to hospital and the choice of therapy.Methods: Standard review methodology using Medline and Google scholar from the years 2006–present. Papers before 2006 were reviewed when necessary.Results: Biomarkers used in AHFS are broadly classified based on their mechanism of action: inflammation, renal stress, extracellular matrix remodeling, oxidative stress, cardiac myocyte stress, and neurohormonal regulation.Conclusion: This paper provides a review for clinicians and medical scientists highlighting the most recent advances in biomarkers with application in AHFS.
Has socialism failed? An analysis of health indicators under socialism

This article analyzes the widely held assumption in academia and the mainstream press that capitalism has proven superior to socialism in responding to human needs. The author surveys the health conditions of the world's populations, continent by continent, and shows that, contrary to dominant ideology, socialism and socialist forces have been, for the most part, better able to improve health conditions than have capitalism and capitalist forces. In the underdeveloped world, socialist forces and regimes have, more frequently than not, improved health and social indicators better than capitalist forces and regimes, and in the developed world, countries with strong socialist forces have been better able to improve health conditions than those countries lacking or with weak socialist forces. The socialist experience has, of course, also included negative developments that have negated important components of the socialist project. Still, the evidence presented in this article shows that the historical experience of socialism has not been one of failure. To the contrary: it has been, for the most part, more successful than capitalism in improving the health conditions of the world's populations.
Persistence, immune specificity, and functional ability of murine mutant ras epitope-specific CD4(+) and CD8(+) T lymphocytes following in vivo adoptive transfer.

Abstract Adoptive T-cell transfer has been shown to be a potentially effective strategy for cellular immunotherapy in some murine models of disease. However, several issues remain unresolved regarding some of the basic features involved in effective adoptive transfer, such as the influence of specific peptide antigen (Ag) boost after T-cell transfer, the addition of IL-2 post-T-cell transfer, the trafficking of transferred T cells to lymphoid and nonlymphoid tissues, and the functional stability of recoverable CD4 + and CD8 + T cells. We investigated several of these parameters, particularly as they relate to the persistence and maintenance of effector functions of murine CD4 + and/or CD8 + T lymphocytes after adoptive cellular transfer into partially γ-irradiated syngeneic hosts. Our laboratory previously identified murine (H-2 d ) immunogenic CD4 + and CD8 + T-cell peptide epitopes reflecting codon 12 ras mutations as tumor-specific Ag. Therefore, the model system chosen here employed epitope-specific MHC class II-restricted CD4 + T cells and MHC class I-restricted CD8 + T cells produced from previously immunized BALB/c mice. Between 2 and 7 days after T-cell transfer, recipient mice received various combinations of peptide boosts and/or IL-2 treatments. At different times after the T-cell transfer, spleen and lung tissues were analyzed phenotypically to monitor the persistence of the immune T cells and functionally (via proliferation or cytotoxicity assays) to assess the maintenance of peptide specificity. The results showed that immune donor T lymphocytes (uncultured immune T cells or cloned T cells) were recoverable from the spleens and lungs of recipient mice after transfer. The recovery of Ag-specific T-cell responses was greatest from recipient mice that received peptide boosts and IL-2 treatment. However, mice that received a peptide boost without IL-2 treatment responded nearly as well, which suggested that including a peptide boost after T-cell transfer was more obligatory than exogenous IL-2 treatment to sustain adoptively transferred T cells in vivo. Ag-specific T-cell responses were weak in mice that either received IL-2 alone or did not receive the cognate peptide boost after T-cell transfer. The T-cell clones were also monitored by flow cytometry or RT-PCR based on expression of the T-cell receptor Vβ-chain, which was previously characterized. Ag-specific T cells were recovered from both spleens and lungs of recipient mice, demonstrating that the T-cell clones could localize to both lymphoid and nonlymphoid tissues. This study demonstrates that both uncultured and in vitro -cloned T lymphocytes can migrate to lymphoid tissues and nonlymphoid (e.g., lung) tissues in recipient hosts and that their functional activities can be maintained at these sites after transfer, if they are exposed to peptide Ag in vivo.
Disrupted mitochondrial electron transport function increases expression of anti-apoptotic Bcl-2 and Bcl-XL proteins in SH-SY5Y neuroblastoma and in Parkinson disease cybrid cells through oxidative stress

Death of dopamine neurons in Parkinson disease (PD) may arise from consequences of the complex I (C-I) defect in the mitochondrial electron transport chain (ETC). Whether cells activate programmed death (apoptosis) pathways derives, in part, from relative activities of proteins such as bcl-2 and bcl-X(L), that have anti-apoptotic actions. We studied the responses of bcl-2 and bcl-X(L) genes in pharmacologic (acute incubation with methylpyridinium (MPP+)) and mitochondrial transgenic ("cybrid") models of Parkinson disease C-I defects. MPP+ incubation increased levels of bcl-2 and bcl-X(L) proteins in native SH-SY5Y cells but not in rho(0) cells devoid of ETC activity. MPP+ increased bcl-2 mRNA levels by 40% at 8 hr. Confocal microscopic imaging showed that the intracellular distribution of immunoreactive bcl-2 was not significantly associated with mitochondrial membranes at baseline but was associated with mitochondria after 12 hr of MPP+. Immunoreactive bcl-X(L) protein was significantly and equally associated with mitochondrial membranes both at baseline and after MPP+. PD cybrids showed increased basal levels of bcl-2 and bcl-X(L) proteins, similar to the maximum levels found after MPP+ treatment of control SY5Y cells. After MPP+ exposure, bcl-2 protein levels increased in control cybrids but did not increase further in PD cybrids. Both pharmacologically generated and transgenically induced C-I inhibition increases levels of anti-apoptotic bcl proteins, possibly from increased gene transcription. Augmentation of bcl-2 and bcl-X(L) expression may delay neurodegeneration in PD.
Diagnosis of Sanfilippo type A syndrome by estimation of sulfamidase activity using a radiolabelled tetrasaccharide substrate.

Abstract 1. 1. A radiolabelled tetrasaccharide mixture (GlcNS-UA-GlcNS-UOA) containing GlcNSO3-UA-GlcNSO3- l -[6,3H]idonic acid, GlcNSO3-UA-GlcNSO3-anhydro- l -[6,3H]idonic acid and GlcNSO3-UA-GlcNSO3- l -[6,3H]gulonic acid was evaluated together with a radiolabelled disaccharide O-(α-2- sulfamino -2- deoxy - d -glucopyranosyl )-(1→3)- l -[6, 3 H]idonic acid (GlcNS-IdOA) and a trisaccharide GlcNSO3-UA- d -[1,3H]glucosaminitol N-sulfate (GlcNS-UA-GlcitolNS) as diagnostic substrates for sulfamidase present in cultured human skin fibroblasts and leucocytes. 2. 2. Sulfamidase activity assessed with GlcNS-UA-GlcNS-UOA was up to 10 times higher than the value obtained for GlcNS-IdOA and the trisaccharide. These results demonstrate that an adjacent GlcNS-UOA disaccharide residue to the sulfaminoglucosamine under attack may play a role in the mechanism of action or binding of sulfamidase toward its substrates. 3. 3. Sulfamidase activity in fibroblast and leucocyte homogenates with GlcNS-UA-GlcNS-UOA exhibited a pH optimum at pH 5.0, an apparent Km of 27 to 50 μmol/l and inhibition by both NaCl and Na2SO4. 4. 4. No detectable sulfamidase activity toward the tetrasaccharide, trisaccharide and disaccharide substrates could be detected using homogenates of fibroblast cultures from Sanfilippo A patients (sulfamidase deficient). Sulfamidase activity assayed with GlcNS-UA-GlcNS-UOA clearly distinguished Sanfilippo A patients from normal controls, heterozygotes and other mucopolysaccharidosis types. Because of the higher activity of sulfamidase toward the tetrasaccharide substrate, compared to that observed for the other substrates evaluated, we recommend its use for the routine enzymic detection of the Sanfilippo A syndrome.
Percutaneous sclerotherapy in neonatal and infant head and neck lymphatic malformations: a single center experience

Abstract Purpose To evaluate the clinical outcomes of percutaneous sclerotherapy for congenital head and neck lymphatic malformations in our institution. Materials and Methods Over a 7-year period, 17 children (10 M, 7 F) mean age 5.8 months (5 days to 13 months) underwent 49 sclerotherapy procedures for congenital head and neck malformations. The imaging and clinical records were reviewed for each patient. Ten of 17 had macrocystic disease; 7 of 17 had microcystic disease. Imaging response was categorized by volume reductions of 0% to 25%, 25% to 50%, 50% to 75%, or 75% to 100%. A concentration of 10 mg/mL doxycycline was used routinely via catheter in 3 instillations with a dose range of 50 to 500 mg per session as per our standard protocol in 17 of 17 patients. In more recent patients, systemic doxycycline levels were obtained after instillations. Additional treatments included direct injection doxycycline (10/17), instillation of absolute ethanol (7/17) or sodium tetradecyl sulfate (4/17), or a combination of these methods. Results Imaging improvement of ≥76% was noted in 11 of 17. Of these, 8 of 11 had macrocystic disease. Four of 17 had 51% to 75% resolution, of which 3/4 were mixed. Two of 17 children had 25% to 50% resolution with a mixed lesion. Seven of 49 peri-procedural complications: hemolytic anemia in 2 infants, hypoglycemic and metabolic acidosis in 3 neonates aged 7 to 10 days, transient hypotension during absolute alcohol instillation in 1 neonate, and self-limiting skin excoriation secondary to peri-catheter leakage of doxycycline in one neonate. Neonates prone to these systemic complications had doxycycline doses of greater than 250 mg and resulted in serum levels of >5 μ g/mL but as high as 21 μ g/mL. Delayed neural complications occurred in 7 of 49 procedures, Horner's syndromes in 4 of 49 procedures, transient left lip weakness in 1 of 49 procedures, right facial nerve palsy in 1 of 49 procedures, and transient left hemidiaphragm paralysis in 1/49 procedures. Conclusion Our experience with catheter directed doxycycline sclerotherapy provides excellent results for large macrocystic head and neck lymphatic malformations. Microcystic and mixed lesions continue to provide a therapeutic challenge.
GABAA receptor regulation of kyphotic nursing and female sexual behavior in the caudal ventrolateral periaqueductal gray of postpartum rats

Bilateral lesions of the ventrolateral caudal periaqueductal gray inhibit lordosis and kyphosis, the postures of female sexual receptivity and maternal nursing that are characterized respectively by dorsoflexion and ventroflexion of the spinal column. These lesions also inhibit the solicitation behaviors that accompany lordosis, but they do not impair retrieval or licking of pups. We tested the hypothesis that reproductive behaviors affected by these lesions are tonically inhibited by activity of the GABA(A) receptor via site-specific manipulations of receptor activity. Rats were bilaterally implanted during pregnancy with guide cannulae aimed at the caudal periaqueductal gray and ovariectomized on day 1 postpartum. Microinfusions (0.25 microl/side) of saline or drug took place on days 5 and 7 postpartum into the dorsolateral column and on days 9 and 11 into the ventrolateral column. Five minutes post-infusion dams were reunited with their pups and their maternal behavior was observed for 30 min. Feminine sexual behaviors were evaluated post-weaning after another set of microinfusions in the ventrolateral caudal periaqueductal gray. Potential facilitation of kyphosis and lordosis was tested with the GABA(A) antagonist bicuculline (15 ng/side) during sub-threshold conditions, i.e., non-suckling pups or sub-threshold ovarian hormone dosages; potential inhibition of these postures was tested with the GABA(A) agonist muscimol (125 ng/side) during optimal conditions, i.e., suckling pups or supra-threshold ovarian hormone treatments. Dorsolateral drug manipulations were ineffective. In the ventrolateral periaqueductal gray bicuculline significantly increased and muscimol significantly decreased kyphosis, lordosis, and sexual solicitations compared with saline. Retrieval and licking of pups were not altered by GABA(A) manipulations. These findings suggest that the reproductive postures of female rats, lordosis and kyphosis, as well as sexual solicitations, are tonically inhibited by the neurotransmitter GABA within the ventrolateral caudal periaqueductal gray in the midbrain. In contrast, retrieval and licking of pups appear to be under separate neurochemical or neuroanatomical control, or both. Further, this tonic inhibition is likely relieved by excitatory somatosensory inputs to this site, from mounting and suckling respectively.
Detection of aortic tear in the acute trauma patient using MRI

Traumatic aortic tears are life threatening and, therefore, need to be evaluated urgently. Typically, a thoracic aortogram is conducted; however, aortography occasionally demonstrates nonspecific abnormalities. These equivocal examinations can lead to unnecessary thoracotomies, or repeated angiography and catastrophic delays in aortic repair. We report a case in which magnetic resonance (MR) imaging was very useful in the diagnosis of aortic tear.
Preferential localization of varying forms of photoactive 1, 8-naphthalimide compounds within the atheromatous arterial wall.

Background and Objective We are currently working with a novel class of photoactivated 4-amino substituted 1,8-naphthalimide compounds for tissue bonding. With promising results in other tissues, we are pursuing potential vascular applications. This study focused on determining the appropriate compound formulation(s), concentration, and exposure times to optimize penetration of the heterogeneous arterial wall. Study Design/Materials and Methods Segments of atheromatous rabbit carotid artery were immersed in hydrophilic or lipophilic forms of the compound, then frozen, cryosectioned, and examined by confocal microscopy. Results The hydrophilic compound exhibited preferential localization within the intima and media and limited presence in the adventitia. Conversely, the lipophilic compound concentrated in the intima and adventitia with virtual exclusion from the media. Exposure to both forms resulted in complete penetration of the arterial wall. Conclusion These results extend our knowledge and permit a more practical approach to potential vascular applications using these photoactivated compounds for tissue bonding. Lasers Surg. Med. 26:316–322, 2000. © 2000 Wiley-Liss, Inc.
Progressive systemic sclerosis and meralgia paraesthetica.

Excerpt To the editor: A patient recently came to us with a burning pain in her left anterolateral thigh. She had a long history of progressive systemic sclerosis characterized by Raynaud's phenome...
The association between pre-operative PSA and prostate cancer-specific mortality in patients with long-term follow-up after radical prostatectomy.

BACKGROUND The clinical and pathologic predictors of prostate cancer-specific mortality (PCSM) many years after radical prostatectomy (RP) remain to be fully elucidated. We explored the association between pre-operative prostate-specific antigen (PSA) and other pathologic predictors and PCSM in men who have undergone (RP). METHODS We report on 459 patients with PCSM data after RP who were followed prospectively over a 23-year period between 1987 and 1997. Cox regression and Kaplan–Meier analysis were used to evaluate pre-operative PSA, pathologic Gleason sum, pathologic stage, and surgical margin status as predictors of PCSM. RESULTS The median PSA was 6.6 ng/ml (±9.9) and the median follow-up time was 9.4 (±4.9) years. Fourteen patients (3.1%) died of PC. On multivariate analysis, only PSA (HR: 1.050; P = 0.001) and binary Gleason sum (HR: 3.402; P = 0.043) remained significant predictors of PCSM. The predicted 10-year PCSM was significantly worse in those patients in the highest PSA tertile compared to those in other tertiles [PSA > 9.9: 87% (82–92%) vs. PSA = 4–9.9: 95% (93.0–97.0%) vs. PSA = 0–3.9: 100.0% (100.0–100.0%)]. CONCLUSIONS We have highlighted the importance of pre-operative PSA in predicting PCSM many years after RP. It is a more significant predictor than Gleason sum and pathologic stage. Thus, PSA may help identify patients with life-threatening PC at a time when their disease is curable with definitive therapy. Prostate 72:24–29, 2012. © 2011 Wiley Periodicals, Inc.
Diagnosis and management of condylar resorption.

Purpose: This article discusses the cause, appropriate diagnostic evaluation, and management of progressive condylar resorption. Patients and Methods: This retrospective study evaluated 28 adult patients with bilateral progressive condylar resorption. Investigation included serial clinical examination, lateral cephalograms, tomograms, and a technetium isotope bone scan when indicated. Twenty-two patients were managed by either condylectomy and reconstruction with a costochondral graft (n = 5 patients) or orthognathic surgery (n = 18 patients). One patient initially had orthognathic surgery and subsequently underwent condylectomy and costochondral grafting, making a total of 23 procedures on 22 patients. Six patients received no surgical treatment. All patients were observed at least 2 years postoperatively. Results: Of the 18 patients who underwent orthognathic surgery, four again demonstrated condylar resorption with recurrence of open bite and retrognathism. Four patients had a stable result, but currently have temporomandibular joint (TMJ) symptoms, whereas 10 patients had a stable result (no change in postoperative occlusion or jaw position) without TMJ symptoms. The five cases receiving condylectomy and costochondral grafting were stable and asymptomatic, with good mandibular function. Analysis of the 18 orthognathic surgery patients showed that relapse occurred in patients having bimaxillary surgery with mandibular advancements greater than 5 mm and with a preoperative posterior ramus height of less than 35 mm. Conclusion: The management of progressive condylar resorption remains controversial. Orthognathic surgery in this small sample was associated with a complication rate (relapse or TMJ dysfunction) of approximately 45% (8 of 18). In contrast, condylectomy and costochondral grafting appeared to produce stable and functional results. Further long-term outcome studies for patients with condylar resorption are needed to corroborate these results.
Ribosyl-trans-Zeatin, A Major Cytokinin Produced by Crown Gall Tumor Tissue

A cell division factor in crystalline form has been isolated from ethanolic extracts of cultured Vinca rosea L. crown gall tumor tissue. The crystalline material shows the melting point, mass spectrum, ultraviolet-light absorbancy spectra, solubilities, chromatographic migration values, ion-exchange behavior, and growth activities expected of ribosyl-trans-zeatin, that is, 6-(4-hydroxyl-3-methyl-trans-2-butenylamino)-9-β-D- ribofuranosylpurine. This compound, which appears to be a major cell-division factor in the extracts, has also been crystallized from liquid media in which the tumor tissue had been growing and apparently was the only active compound in such media.
Genetics of Sjögren's syndrome in the genome-wide association era.

While Sjogren’s syndrome (SS) is more common than related autoimmune disorders, such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA), scientific and medical research in SS has lagged behind significantly. This is especially true in the field of SS genetics, where efforts to date have relied heavily on candidate gene approaches. Within the last decade, the advent of the genome-wide association (GWA) scan has altered our understanding of disease pathogenesis in hundreds of disorders through the successful identification of novel risk loci. With strong evidence for a genetic component in SS as evidenced by familial aggregation of SS as well as similarities between SS and SLE and RA, the application of GWA approaches would likely yield numerous novel risk loci in SS. Here we review the fundamental scientific principles employed in GWA scans as well as the limitations of this tool, and we discuss the application of GWA scans in determining genetic variants at play in complex disease. We also examine the successful application of GWA scans in SLE, which now has more than 40 confirmed risk loci, and consider the possibility for a similar trajectory of SS genetic discovery in the era of GWA scans. Ultimately, the GWA studies that will be performed in SS have the potential to identify a myriad of novel genetic loci that will allow scientists to begin filling in the gaps in our understanding of the SS pathogenesis.
Cournot Equilibrium with Free Entry

Despite the fact that the assumptions underlying perfect competition never actually hold, the use of the competitive model, as an idealization, is justified if the predictions of the model approximate the outcomes of situations it is used to represent. In partial equilibrium analysis, this justification is embodied in the " Folk Theorem " which states that if firms are small relative to the market, then the market outcome is approximately competitive. This paper provides a precise statement and proof of the " Folk Theorem " for competitive markets with a single homogeneous good, and free entry and exit. It is shown that if firms are small relative to the market then there is a Cournot equilibrium with free entry; furthermore, any Cournot equilibrium with free entry is approximately competitive. More specifically, if we consider an appropriate sequence of markets in which firms become arbitrarily small relative to the market, then there is a Cournot equilibrium with free entry for all markets in the tail of the sequence, and aggregate equilibrium output converges to perfectly competitive output. If firms have strictly U-shaped average cost curves, then individual firm behaviour converges to competitive behaviour. The treatment of free entry distinguishes this paper from other papers dealing with the " Folk Theorem ", where either the number of firms is exogeneous, ruling out free entry, or free entry is treated as being equivalent to a zero profit condition, ignoring the integer problem that arises when the number of firms is finite but unspecified. Firms may become small relative to the market in two ways: through changes in technology, absolute firm size (the smallest output at which minimum average cost is attained) may become small, or, through shifts in demand, the absolute size of the market (the market demand at competitive price) may become large. We allow both types of changes here, though shifts in demand, especially in the form of replication of the consumer sector, may be more familiar. In his conclusion, Ruffin (1971) presents a verbal argument for the " Folk Theorem " which is based on replication of demand and entry. Hart (1979), though not concerned with existence, shows that in a general equilibrium model with differentiated products and free entry, equilibria are approximately competitive (Pareto optimal) when consumers have been replicated a sufficient number of times. The paper is organized as follows: Section 1 contains the perfectly competitive model and its assumptions, Section 2 contains the assumptions and definitions for the imperfectly competitive model, Section 3 contains an example contrasting the usual treatment of the " Folk Theorem" and the present approach, Section 4 contains the proofs of the main results, and Section 5 contains remarks on the results and indicates how some of the assumptions that are used can be weakened.
Prospective evaluation of a critical care pathway for clearance of the cervical spine using the bolster and active range-of-motion flexion/extension techniques.

Background: Clearance of the cervical spine after blunt trauma remains controversial in patients with normal radiologic evaluation. Methods: Blunt trauma patients with midline boney cervical tenderness and plain films that disclose no abnormalities and computed tomography (CT) scans were entered into a care pathway for spinal clearance using the Bolster or active range-of-motion (AROM) flexion/extension techniques. The quality of films between the two techniques was then compared. Results: In all, 159 patients entered the pathway with 14 patients (9%) unable to complete the examination secondary to pain. The Bolster was used in 129 patients (89%) and AROM was used in 16 (11%). The total range of motion was significantly better with AROM at 51.4 ± 19.4 degrees of motion compared with 32.0 ± 13.0 degrees with the Bolster (p ≤ 0.05). The most distal level visualized was not different between groups with 6.6 ± 0.8 cervical vertebrae visualized on average in the Bolster group and 6.8 ± 0.7 in the AROM group. Positive findings occurred in five patients (3.4%) in the Bolster group. Conclusion: The incidence of occult cervical injury in patients with boney cervical pain despite normal plain films and CT scans in this study was 3.4%. The AROM technique has better total range of motion than the Bolster, although results of the Bolster technique remain within acceptable standards. The present care pathway appears to be an effective screening tool for evaluation of this population of patients. Additional evaluation of the obtunded patient is necessary before broad implementation of this technique.
Modeling Science Teaching on Science Practice? Painting a More Accurate Picture through an Ethnographic Lab Study.

This article reports an ethnographic study of a molecular biology research laboratory, “Sally's Lab.” By studying the daily practices of the lab members, and interpreting these observations through an anthropological lens grounded in practice theory, I portray the social and cultural construction of a scientific community. Findings include an examination of how good science practice was operationalized, status in the lab was constructed, members gained or lost interest in continuing on in careers in research science, and individual members conformed to and resisted localized norms of scientific practice. These issues have direct relevance to our work as science educators, in terms of how we present science practice to our students. For example, when K–16 science students engage in activities based on authentic science practice, upon whose experiences are these simulations based? The current study shows that there is not just one acceptable way to do science, nor one set of experiences that pertain to all members within a given community of science practice. Likewise, there should not be just one way that science is presented in school, nor one set of experiences we expect all our students to take from our classes. © 2001 John Wiley & Sons, Inc. J Res Sci Teach 38: 387–407, 2001
Zscan4 interacts directly with human Rap1 in cancer cells regardless of telomerase status

Telomeres are repetitive sequences at the ends of chromosomes protected by DNA binding proteins of the shelterin complex that form capping structures. Through the interaction of shelterin complex-associated proteins, telomere length maintenance is regulated. Recently, the newly identified embryonic stem cell marker, Zinc finger and SCAN domain-containing 4 gene (Zscan4), was shown to be a telomere-associated protein, co-localizing to the shelterin complex. Furthermore, it was shown to play an essential role in genomic stability by regulating telomere elongation. Although it is known that Zscan4 regulates TRF2, POT1b, and Rap1 expression in embryonic stem cells, the relationship and the exact mechanism of action for ZSscan4-mediated telomere maintenance in cancer cells is unknown. In this study, we investigated Zscan4 expression and interactions with Rap1 in telomerase positive (HeLa, MCF7) and ALT pathway (SaOS2, U2OS) cancer cells. Through western, pulldown, siRNA, and overexpression assays we demonstrate, for the first time, that Zscan4 directly associates with Rap1 (physical association protein). Furthermore, by generating truncated versions of Zscan4, we identified its zinc finger domain as the Rap1 binding site. Using bimolecular fluorescence complementation, we further validate this functional interaction in human cancer cells. Our results indicate that Zscan4 functions as a mediator of telomere length through its direct interaction with Rap1, possibly regulating shelterin complex-controlled telomere elongation in both telomerase positive and alternative lengthening of telomere pathways. This direct interaction between Zscan4 and Rap1 may explain how Zscan4 rapidly increases telomere length, yielding important information about the role of these proteins in telomere biology.
Reactions of the 1-halo-7-(2-hydroxyethoxy)cycloheptenes and the 3-halo-4-(2-hydroxyethoxy)bicyclo[3.2.1]oct-2-enes with potassium t-butoxide☆

Abstract Reactions of 1 - bromo - 7 - (2 - hydroxyethoxy)cycloheptene 2 and its chloro analogue 3 with potassium t -butoxide in dimethyl sulphoxide or tetrahydrofuran gave cycloheptatriene and cis - 8,11 - dioxabicyclo[5.4.0]undec - 2 - ene 18 as the major products together with small amounts of the trans -isomer 17 ,8,11-dioxabicyclo[5.4.0]undec - 1(7) - ene 14 , 8,11 - dioxabicyclo[5.4.0] - undec - 1 - ene 19 , cyclohept - 2 - enone ethylene ketal 15 , cyclohept - 3 - enone ethylene ketal 16 , and 1- and 2 - t - butoxycyclohepta - 1,3 - diene 20 . Similar reactions of 3 - bromo - and 3 - chloro - 4 - (2 - hydroxyethoxy)bicyclo[3.2.1]oct - 2 - ene 4 and 5 gave 4,7 - dioxatricyclo[7.2.1.0 3,8 ]dodeca - 2 - ene 26 as the major product together with small amounts of 3,6 - dioxatricyclo[7.2.1.0 2,7 ]dodeca - 2(7) - ene 27 and bicyclo[3.2.1]oct - 3 - ene - 2 - one ethylene ketal 28 . Mechanisms for these transformations are discussed.
In situ fringe projector development for thermal coating deposition

Thermal barrier coatings (TBCs) and plasma spray coatings, in general, require fine control over the deposited thickness to achieve a reliable coating performance. Currently, the plasma spray industry quantifies thickness by sampling the part before and after TBC deposition. Approximate thickness is inferred from previous runs; however, process variability can cause errors in these approximations that result in wasted time and resources that can ultimately lead to nonreliant coatings. To this end, we present an in situ optical fringe projector technology that enables coating thickness measurements across a two-dimensional surface. The sensor is capable of achieving micron scale resolution in the harsh environment of a thermal spray booth. Furthermore, unlike the existing approaches, this technique is extendable to parts with complex geometries. The underlying background of the fringe projection method, including a differential measurement technique, is presented. Current results on production equipment and cylindrical parts are also discussed, showing good correlation and agreement with physical measurements captured in an industrial setting.
Haptic body-powered upper-extremity prosthesis simulator with tunable stiffness and sensitivity

In this paper, we present the design, implementation, and characterization of a haptic body-powered prosthesis simulator. A novel aspect of our design is enabling real-time adjustment of gripper stiffness and control cable sensitivity parameters via software based on a haptic teleoperation control algorithm. Adjustment of these parameters across a continuum of values can assist the user to decide on the optimal parameters that can best fulfill the user's functional needs, rendering the device a body-powered prosthesis prescription tool. Additionally, a switching capability between the voluntary-closing (VC) mode and the voluntary-opening (VO) mode is incorporated into the software interface. With design and operation characteristics that closely replicate the form and mechanics of an actual body-powered upper-extremity prosthesis, our haptic prosthesis enables parameter optimization for individual prosthesis users and various human-subject-based research experiments involving both amputees and non-amputees on task-based optimization of prosthesis parameters and selection of operation mode.
Effect of methylprednisolone on oedema formation after a major burn

Summary The mechanism of oedema formation distant from a burn site is only partially explained by an increase in capillary permeability. It has been demonstrated in quantitative terms that after a major burn, there is a large number of white blood cells (WBCs) stuck to the walls of venules in the distant microcirculation. Theoretical calculations predict a corresponding increase in post-capillary resistance, suggesting that WBC-sticking is partly responsible for oedema formation. In an attempt to discover whether the theoretical calculations persisted in vivo , the number of sticking WBCs in the mesenteric microvasculature of rats was determined at various times up to 48 h after a full-thickness scald burn to the back. The quantitative oedema formed was assessed by the wet weight/dry weight technique in burned skin, unburned skin, skeletal muscle and lung tissue. Half of the rats received methylprednisolone sodium succinate prior to burning to determine its effect on WBC-sticking and oedema formation. Conclusions from the experiment showed that a 30 per cent body surface, full-thickness burn results in significant increase in WBC-sticking in mesenteric microcirculation in animals. Pretreatment with systemic methylprednisolone sodium succinate decreased the magnitude of this change. Pretreatment with methylprednisolone was not effective in reducing oedema formation to statistically significant levels, although pretreated animals consistently showed less oedema formation than those which were untreated. Correlation between the number of adherent WBCs in the mesenteric microvasculature and the quantity of oedema formed could not be demonstrated in this model.
Problematic Situations Associated with Dating Experiences and Relationships Among Urban African American Adolescents: A Qualitative Study

This qualitative study focused on the identification of problem situations associated with adolescent dating experiences and relationships, including those that placed youth at risk for dating violence perpetration or victimization. Interviews were conducted with 44 African American middle and high school students in an urban school system. Qualitative analysis identified 18 individual themes representing six categories of problem situations: (a) approach and initiation; (b) conflict, conflict resolution, and break-ups; (c) communication, connection, and emotion; (d) aggression and victimization; (e) the role of others; and (f) media and technology. Identification of these problem situation themes has important implications for developing and evaluating prevention efforts designed to foster healthy adolescent dating relationships.
Lipopolysaccharide stimulation of RAW 264.7 macrophages induces lipid accumulation and foam cell formation

A role for immune and inflammatory processes in the induction of atherosclerotic lesions is emerging. These studies were undertaken to determine whether activation by lipopolysaccharide (LPS) enhances the ability of macrophages to become foam cells. Since LPS activation inhibits scavenger receptor activity, we studied the ability of LPS-activated RAW 264.7 macrophages to accumulate lipid from a variety of lipid particles that are not ligands for the scavenger receptor. Macrophages activated by LPS, in the absence of lipid particles, accumulated triglyceride, but not cholesterol ester (CE). The addition of Soyacal, a triglyceride-rich particle, further enhanced this LPS-stimulated triglyceride accumulation. LPS activation similarly enhanced CE accumulation almost 3-fold from two CE-rich lipoproteins, beta VLDL and LDL, as compared with controls. The unstimulated control cells only accumulated significant CE from beta VLDL and not LDL. LPS-enhanced lipid accumulation was dependent on LPS dose and began after 8-12 h of incubation. LPS increased the degradation of 125I-labelled LDL and the cell-associated 125I-labelled LDL at 37 degrees C by 1.8-fold. Degradation remained saturable, consistent with a receptor-mediated process. Antioxidants did not inhibit LPS-induced CE accumulation from LDL. Thus, activation of RAW 264.7 macrophages enhanced their ability to accumulate lipid from a variety of lipid particles and to become foam cells. These data suggest a potential role for infections, and LPS in particular, in atherogenesis.
Influence of Strain on the Environmental Hydrogen-Assisted Cracking of a High-Strength Steel in Sodium Chloride Solution

Abstract Evidence is presented that will establish the role of mechanical strain in promoting surface absorption of hydrogen by rupturing surface films on AISI 4340 steel in alkaline 3.5% sodium ch...
HPLC Determination of Trace Hydrazine Levels in Phenelzine Sulfate Drug Substance

Abstract An HPLC procedure for the estimation of trace hydrazine levels in phenelzine sulfate drug substance has been developed. The hydrazine is derivatized at ambient temperature with salicylaldehyde, and the salazine derivative is measured using short wavelength UV (209 nm). The salazine is separated from unreacted salicylaldehyde and other compounds using a mobile phase consisting of 60:40 acetonitrile-water. The mobile phase was pumped at a flow rate of 1.0 mL/min through a 150 mm × 4.6 mm i.d. reverse phase column (5 μm octadecylsilane, 30% carbon loading). The limit of detection of salazine produced when hydrazine sulfate reacts with salicylaldehyde in an analytical sample was found to be equivalent to 10 ppm of hydrazine (based upon 100 mg of phenelzine sulfate). Absorbance and hydrazine concentration are linear over the range of 10–1000 ppm of hydrazine, with an r2 of 0.9998 (n=7) based on peak height. Five samples of phenelzine sulfate analyzed for hydrazine content with salicylaldehyde gave an ...
Reconstruction of defects caused by bisphosphonate-induced osteonecrosis of the jaws.

Reconstructive surgery of defects for any disease or injury including bisphosphonate-induced osteonecrosis of the jaws requires an understanding of the pathophysiology of the condition. Related to bisphosphonates, it is the apoptosis (programmed cell death) of the osteoclast that inhibits, and in some cases stops, bone renewal/remodeling altogether. Therefore, reconstruction begins with a debridement of resection considering this mechanism. For intravenous bisphosphonate-induced osteonecrosis defects of the mandible, most resections are immediately reconstructed with a rigid titanium plate provided that secondary infection is controlled, there is sufficient soft tissue present, and a resection margin containing variable bone marrow can be achieved. For some similar defects with significant secondary infection, a delayed rigid plate placement after the recipient site has healed and is infection free represents another option. In those defects in which there is a significant soft tissue loss, flap reconstruciton may also be necessary. The pectoralis major myocutaneous flap is the most predictable and most commonly used flap, followed by the trapezius myocutaneous flap, and stemocleidomastoid flap. Bone graft reconstructions are rarely needed, and are often not indicated due to minimal benefit for the patient, anesthetic risks, or active cancer at metastatic sites. However, in selected cases, mostly for breast cancer or prostate cancer patients with continuity defects from intravenous bisphosphonate-induced osteonecrosis, standard cancellous marrow grafting with platelet-rich plasma growth factor supplementation has been successful. Maxillary resections are treated with prosthodonic obturators as they are in primary cancer surgery. Reconstruciton of oral bisphosphonate-induced osteonecrosis defects usually takes the form of alveolar grafting and/or dental implant placements, and only rarely requires grafting of continuity defects. Standard grafting techniques and dental implant placements can be used if guided by the published serum C-terminal telopeptide (CTX) test. The guidelines are less than 100 pg/mL = high risk, 100 pg/mL to 150 mg/mL = moderate risk, and greater than 150 pg/mL = minimal risk.
Differences in perceptions by stage of fluid adherence

Abstract Objective: The purpose of this study was to determine in a group of hemodialysis patients whether perceptions of barriers to and benefits of adherence to fluid limitations, perceived seriousness of and susceptibility to the consequences of nonadherence, self-efficacy, and thirst differed by stage of fluid adherence. Design: Cross-sectional descriptive design. Setting: There were 147 participants from rural, suburban, and urban outpatient hemodialysis units. Results: Significant differences were found in perceived benefits, barriers, seriousness, susceptibility, and thirst intensity by stage of fluid adherence. There were no significant differences in self-efficacy by stage of fluid adherence. Conclusion: Stage of fluid adherence may be important to consider when designing interventions to reduce fluid intake.
Sex Differences in Story Receipt and Story Sequencing Behaviors in Dyadic Conversations.

Recordings of 30-minute dyadic conversations between strangers were coded for the frequency of occurrence of 11 story receipt and eight story sequencing variables, for the duration of all storytellings, and for the frequency of occurrence of story sequences. Analysis of the data indicated that (1) females spent significantly more time than males as the recipients of storytelling; (2) males and females differed significantly on a linear combination of five story receipt variables (displays interest tokens, appreciates, adds or predicts details, withholds sequential talk, and withholds all talk at story's end); (3) there were no significant differences between males and females in the number of sequential stories told; (4) females and males differed significantly on a linear combination of two story sequencing devices, embedded repeat and marked repeat.
Dose‐dependent Hemodynamic Effect of Digoxin Therapy in Severe Verapamil Toxicity

UNLABELLED: Calcium chloride (CaCl(2)) alone is an ineffective antidote in severe calcium channel antagonist overdoses. Digoxin has been evaluated as a therapy to increase the effectiveness of calcium in severe calcium channel antagonist overdoses. OBJECTIVE: To determine if there is a dose-dependent hemodynamic effect of digoxin in the setting of severe verapamil toxicity treated with high-dose CaCl(2). METHODS: Eight dogs were instrumented to measure systolic and diastolic blood pressure, cardiac output, pulmonary artery pressures, and left ventricular pressures. Verapamil toxicity (50% decrease in mean arterial pressure) was induced with verapamil 6 mg/kg/hr and maintained for 30 minutes by titrating the verapamil rate. Following verapamil toxicity, each dog received one dose of digoxin equivalent to 0, 1, 1.5, 2, 3, 4, 6, or 8 times the loading dose of digoxin (0.009 mg/kg). The verapamil rate was changed to 4 mg/kg/hr and continued for the next five hours. CaCl(2) boluses were given (0.5 g immediately following verapamil toxicity and 1 g at one, two, and three hours). Measurements were compared with the loading dose of digoxin using linear regression analysis. RESULTS: Digoxin resulted in a dose-dependent increase in systolic blood pressure at 4 hours (10.23 mm Hg/loading dose of digoxin, 95% CI = 2.74 to 17.73), 4 hours, 15 minutes (13.9 mm Hg/loading dose of digoxin, 95% CI = 8.75 to 19.01), and 5 hours (17.04 mm Hg/loading dose of digoxin, 95% CI = 1.76 to 32.32). Digoxin resulted in a dose-dependent increase in maximal ventricular pressure at the end of hour 3 (8.55 mm Hg/loading dose of digoxin, 95% CI = 3.41 to 13.69), 3 hours, 15 minutes (11.81 mm Hg/loading dose of digoxin, 95% CI = 4.89 to 18.73), hour 4 (8.26 mm Hg/loading dose of digoxin, 95% CI = 1.03 to 15.48), and 4 hours, 15 minutes (9.74 mm Hg/loading dose of digoxin, 95% CI = 4.47 to 15.00). The authors were unable to detect a dose-dependent increase in other parameters, including diastolic relaxation (diastolic change in pressure over time) and time to onset of death. No ventricular arrhythmias developed in any dogs. CONCLUSIONS: There is a dose-dependent effect of digoxin on systolic blood pressure and maximal ventricular pressure in the setting of severe verapamil toxicity treated with high-dose CaCl(2).
Duration of the initial TCR stimulus controls the magnitude but not functionality of the CD8+ T cell response

CD8+ T cells only require a brief stimulation with antigen in vitro to divide and differentiate into effector and memory cells upon transfer in vivo. The efficiency of clonal expansion and the functional characteristics of memory cells derived from briefly stimulated cells are poorly defined. We developed a system that allowed us to examine programming entirely in vivo. This was achieved by rapidly killing peptide-pulsed DCs carrying a diphtheria toxin receptor transgene with timed injections of diphtheria toxin without altering the course of an accompanying infection. The magnitude of clonal expansion, but not the functionality of the effector cells, correlated directly with the duration of antigen exposure. Furthermore, memory T cells were capable of mounting a secondary response, regardless of the length of antigen encounter during the primary response. These results indicate that the duration of initial antigen encounter influences the magnitude of the primary response, but does not program responsiveness during the secondary challenge.