cssi/SciSciGPT-SciSciNet huggingface dataset:
Development and Clinical Applications of Nucleic Acid Therapeutics

In the past decade, our new understanding of post-transcriptional gene silencing (PTGS) has opened up new vistas that can help us to decipher the function of genes and thus to unravel the basic mechanistic principles and genetic networks in biology. This enormous potential of PTGS to selectively turn off genes either by antisense or RNA interference pathways has made a huge impact on research in basic science. Further, we can apply this knowledge and new set of rules in biomedical research for the development of more potent therapeutics. With a plethora of advantages of PTGS, there are still certain obstacles that need to be addressed to enable translation of this technology to the clinic. This article will focus on a brief history of the discovery and evolution of PTGS and its potential as a technology. We will also discuss the importance of target availability and some strategies for identification of the target sequence. Further, we will give an overview of some past experiences in the development of this technology in the clinic for cancer therapy, with a recent update on clinical development and trials on nucleic acid therapeutics.
Chapter 5 Sodium Dependence of Cation Permeabilities and Transport

Publisher Summary Unlike excitable membranes, which contain a mixture of Na' and K + channels and Na',K'-ATPase (sodium pump) within the same membrane, epithelia have an asymmetric distribution of channels and transporters, with specific channel and transporter populations confined to either the apical or basal pole of the cell. This asymmetric distribution is a consequence of the tight junction, a continuous loop of lipoprotein, which binds individual cells together to form an epithelial sheet. The tight junction acts as the demarcation line between apical and basolateral membranes and serves as a barrier that prohibits the intermixing of the apical and basolateral domains. It is this localization of specific channels and transporters to specific membrane domains that produces the vectorial transport of electrolytes and nonelectrolytes from one compartment (e.g., the one bathing the apical membrane) to the opposing compartment (the one bathing the basolateral membrane). The classic example is the vectorial transport across the frog skin.
Erlitou and the Search for the Xia

This article places the recent literature on archaeological manifestations of the Xia in context, describes and analyzes the published data for the Erlitou typesite in some detail, and examines broader issues implicit in the debate on this contentious topic. The positivism that animates so much recent literature is linked to the Anyang excavations and the promise of scientific archaeology more generally. Particular attention is given to certain of the data from the Erlitou site—its layout, architectural features, burials, and prestige craft products (ritual bronze vessels and jades)—because these have figured prominently in most discussion of the nature and identity of the site and its eponymous culture. Broader issues are addressed, albeit more briefly, as a series of nested concepts: culture and subculture, periodization, cultural succession, developmental stage, ethnicity, and dynasty. Until the formal report of the Erlitou typesite reaches print, this article proposes a “minimal” definition of the current archaeological data, one that does not assume the historicity of the Xia.
TRANSCRIPTIONAL ACTIVATION AND NUCLEAR TARGETING SIGNALS OF THE HUMAN ANDROGEN RECEPTOR

The androgen receptor (AR) is a signal-transducing protein required for sexual differentiation, development, and expression of the male phenotype. A series of human AR deletion mutants were created either by site-directed mutagenesis using restriction enzyme digestion, the polymerase chain reaction, or, for a series of unidirectional NH2-terminal deletions, exonuclease III digestion. Receptor mutants were expressed in monkey kidney COS cells as truncated AR proteins between 20 and 107 kDa as revealed on immunoblots, where wild type AR was a doublet of 114 and 108 kDa. Subcellular localization by immunocytochemical staining demonstrated androgen-dependent nuclear uptake of AR from a perinuclear region of the cytoplasm. A nuclear targeting signal similar in sequence and position to the glucocorticoid receptor and homologous to the SV40 large T antigen was required for androgen-induced nuclear uptake of wild type AR. AR mutants lacking the NH2-terminal and/or steroid binding domains were constitutively nuclear with reduced transcriptional activity. Transcriptional activation by wild type AR was androgen-dependent in cotransfection studies of CV1 cells using the chloramphenicol acetyltransferase reporter gene linked to the mouse mammary tumor virus promoter. Deletion mutagenesis revealed within the NH2-terminal region a domain required for full transcriptional activity and within the steroid binding domain, an inhibitory function, deletion of which yielded a constitutively active receptor. Inhibition of wild type AR by coexpression with an inactive NH2-terminal fragment suggested competition for nuclear factors required for transcriptional regulation. These studies demonstrate a concerted interplay among the domains of the AR protein in regulating gene transcription.
Evaluation of mesenchymal stem cell contribution to adipose health in the context of high fat diet and exercise (673.2)

Objective: To investigate the role of mesenchymal stem cells (MSCs) in adipose tissue (AT) inflammation and fibrosis during high fat diet and exercise training. Methods: C57BL/6 mice were fed high fat (HF, 60%) or low fat (LF, 10%) diets for 8 weeks. Half of the mice were then exercised for 16 weeks. Sca1+CD45- MSCs were extracted from epididymal fat, isolated by FACS and analyzed by Q-PCR. AT inflammation and fibrosis were evaluated using Q-PCR and histology. Results: HF diet (HFD) increased body weight and exercise attenuated weight gain. AT F4/80, TNFα, and IL-10 gene expression increased with HF (p<0.05). Exercise did not attenuate this increase. Genes associated with fibrosis (TGFβ1 and Col1α) increased with HFD, and Col1α expression was attenuated with exercise (p<0.05). HFD decreased the percentage of MSCs in AT, but the total number was higher compared to LF fed mice (p<0.05). Exercise did not impact MSC content in AT. MSC gene expression was altered by HFD, but not by exercise. Specifically, Col1...
Differences in knowledge of hepatitis B among Vietnamese, African-American, Hispanic, and white adolescents in Worcester, Massachusetts.

Objective. To assess the level of knowledge about hepatitis B of Vietnamese adolescents, a group at high risk for hepatitis B, and compare it to the knowledge of adolescents of other races and ethnicities. Methods. A sample of 2816 adolescents was surveyed in 1993 in 2 middle schools and 2 high schools in Worcester, Massachusetts, using a self-administered multilingual questionnaire. Results. Knowledge of hepatitis B was low overall. Vietnamese respondents were more likely than were other students to know that hepatitis B affects the liver (35.6% vs 22.6%). However, they were much less likely than were other students to correctly identify sex with an infected person as a risk factor for infection (13.7% vs 32.8%). Independent predictors of this knowledge were: white race; older age; attending high school versus middle school; having been taught about hepatitis B in school; knowing the definition of hepatitis B; reporting better grades; having a family member with hepatitis B; and being more highly acculturated. Conclusions. Adolescent knowledge about risk of infection was low in this study. Attention should be directed at providing health education on hepatitis B to adolescents, particularly to Vietnamese. Health care providers, community health educators, and others engaged in the effort to control and eradicate hepatitis B should be sensitive to the unique educational and cultural needs of high-risk southeast Asian adolescent populations.
Quantum Universality from Magic States Distillation Applied to CSS Codes

Given Clifford group operations and the ability to repeatedly prepare a single-qubit mixed state ?, can one do universal quantum computation? We show a sharp threshold in the Hadamard "magic" direction of the Bloch sphere between those ? allowing universal quantum computation, and those for which any calculation can be efficiently classically simulated. As a corollary, the ability to repeatedly prepare any pure state which is not a stabilizer state (e.g., any single-qubit pure state which is not a Pauli eigenstate), together with Clifford group operations, gives quantum universality. As motivation for this question, "magic state" distillation procedures can reduce the general fault-tolerance problem to that of performing fault-tolerant Clifford group circuits.
De novo design of heat-repressible RNA thermosensors in E. coli

RNA-based temperature sensing is common in bacteria that live in fluctuating environments. Most naturally-occurring RNA thermosensors are heat-inducible, have long sequences, and function by sequestering the ribosome binding site in a hairpin structure at lower temperatures. Here, we demonstrate the de novo design of short, heat-repressible RNA thermosensors. These thermosensors contain a cleavage site for RNase E, an enzyme native to Escherichia coli and many other organisms, in the 5' untranslated region of the target gene. At low temperatures, the cleavage site is sequestered in a stem-loop, and gene expression is unobstructed. At high temperatures, the stem-loop unfolds, allowing for mRNA degradation and turning off expression. We demonstrated that these thermosensors respond specifically to temperature and provided experimental support for the central role of RNase E in the mechanism. We also demonstrated the modularity of these RNA thermosensors by constructing a three-input composite circuit that utilizes transcriptional, post-transcriptional, and post-translational regulation. A thorough analysis of the 24 thermosensors allowed for the development of design guidelines for systematic construction of similar thermosensors in future applications. These short, modular RNA thermosensors can be applied to the construction of complex genetic circuits, facilitating rational reprogramming of cellular processes for synthetic biology applications.
Analysis on response to public health events in security ensuring of important activities

[Objective]To understand the effect of the establishment of disease control workstation in Chaoyang District on response to public health events in security ensuring of important activities.[Methods]The article takes the response to public health events during Beijing Olympic Games for example.By using the retrospective survey,effect analysis of field application and interviews,the data were collected and analyzed.[Results]The establishment of disease control workstation changed the organizational system,working methods and efficiency in response to public health events in security ensuring of important activities.(1) The organizational system: adding the processing link of disease control workstation.(2) The working methods: the public health emergencies had been responded by CDC alone in the past,and now are dealt with by CDC and disease control workstation according to designated regional processing.(3) The application during the Olympic period: ① There were a total of 91 public health events from July to September 2008,which increased by 1.12 times as compared with that in the same period of 2007(43 events).② Among the public health events responded by Chaoyang CDC from July to September 2008,the average time from receiving a report to staff arrived at the scene was(20.5±9.4) min,which was shorten by 20.9 min as compared with that in the same period of 2007(41.4±16.1) min.③ From July to September 2008,the staff arrived at the scene within 10 min after receiving a report in 16.5% of public health emergencies,47.3% were within 10-20 min,and 27.5% were within 20-30 min after receiving a report.In 91.2% of events,the staff arrived at the scene within 30 min.(4) Interviews: 100%(48/48) of the respondents believed that the establishment of disease control workstation mode is feasible,which can solve some problems in the emergency response.93.75%(30/32) of the respondents believed that disease control workstation plays an important role in ensuing city running during the Olympic Games,and 6.25%(2/32) of the respondents believed that its effect is not satisfactory.[Conclusion]The establishment of disease control workstation is an innovation of the Chaoyang District,it improves the existing mechanism of public health emergency response,and overall increases the comprehensive capability of public health emergency response in security ensuring of important activities.
Activation of bovine leukemia virus transcription in lymphocytes from infected sheep: rapid transition through early to late gene expression.

Abstract Bovine leukemia virus (BLV) expression is mostly silent in peripheral blood mononuclear cells (PBMCs) of infected animals. However, when infected cells are cultured, they are stimulated to produce virus. We studied viral transcription in PBMCs taken from BLV-infected sheep because the pattern of transcriptional activation in these cells should closely mimic activation of virus expression within mononuclear cells in vivo. BLV transcription was activated as early as 30 min after PBMCs were cultured. Expression was characterized by early and late stages, each distinguished by a unique pattern of cytoplasmic RNAs. In early expression, cytoplasmic viral RNA was exclusively the doubly spliced tax/rex transcript, although all transcripts were present in the nucleus. Early expression gave way rapidly to late expression, in which all viral transcripts accumulated in the cytoplasm. The polyclonal B-cell activator lipopolysaccharide increased the amount of viral RNA by at least twofold but did not alter the pattern of transcription. The transition from early to late expression required new protein synthesis and was blocked by the inhibitor cycloheximide. This requirement reflects the essential role of the viral Rex protein in the transition, but synthesis of cellular factors may be required as well. These results provide the first demonstration of staged viral expression in lymphocytes naturally infected by either BLV or the closely related human T-cell leukemia virus (HTLV) and validate the model of BLV and HTLV gene expression that previously was derived from transfection experiments performed mainly in nonlymphoid cells.
Mechanisms Mediating the Effects of Prepubertal (n-3) Polyunsaturated Fatty Acid Diet on Breast Cancer Risk in Rats

Dietary exposures during childhood may influence later breast cancer risk. We tested in an animal model the hypothesis that prepubertal intake of (n-3) PUFAs, present mainly in fish, reduces susceptibility to breast cancer. Between postnatal days 5 to 25, rat pups were fed (n-3) PUFA-containing diets at a 2:1 ratio of (n-6):(n-3) PUFAs (typical of prehistoric societies) or a control (n-6) PUFA diet at a 17:1 ratio of (n-6):(n-3) PUFAs (comparable with current Western societies). These fatty acids were given in a low- or high-fat context (16 or 39% energy from fat). The low-(n-3) PUFA diet reduced while the high-(n-3) PUFA diet increased carcinogen-induced mammary tumorigenesis. The low-(n-3) PUFA diet reduced mammary cell proliferation and increased apoptosis, particularly in the terminal end buds (the mammary source of malignant breast tumors). The high-(n-3) PUFA diet had opposite effects on these 2 key biomarkers and increased phospho-Akt levels, a survival factor. Microarray analyses identified genes that were permanently upregulated in the low-(n-3) PUFA-exposed glands and function in oxidative damage repair. Serum levels of 8-hydroxy-2'deoxyguanosine, a marker of DNA damage, were significantly reduced in these low-(n-3) PUFA-fed rats, and increased in the high-(n-3) PUFA-exposed group. The latter group exhibited reduced expression of BRCA1, a DNA repair gene. Our results indicate that the opposing susceptibilities to mammary tumorigenesis between the low- versus high-fat (n-3) PUFA-exposed groups were associated with altered DNA damage repair and gene expression linked to proliferation, survival, and differentiation.
Atmospheric pressure drives changes in the vertical distribution of biogenic free‐phase gas in a northern peatland

[1] Atmospheric pressure (Patm) is known to regulate methane emissions from northern peatlands. However, recent conceptual models differ in how gas production and release occurs in shallow (defined here as less than 1 m depth) versus intermediate to deep peat soils (i.e., more than 1 m depth). We used ground penetrating radar (GPR) measurements to non-invasively estimate the vertical distribution of free-phase gas and the dependence of this distribution on atmospheric pressure in a northern peatland. Variations in the travel time of the electromagnetic wave to three interfaces in the peat column were used in conjunction with deformation rod data and a petrophysical model relating electromagnetic wave velocity to free-phase gas content to model changes in the vertical distribution of free-phase gas over time. We found a negative linear relation between changes in free-phase gas content and changes in Patm for shallow peat soils and a positive linear relation for deeper soils. Our results suggest that (1) free-phase gas content confined in deep peat soils is larger and less variable to changes in Patm than gas in shallow/intermediate peat soils; (2) increases in Patm result in gas release from shallow peat soils into the atmosphere (i.e., rapid ebullition); and (3) decreases in Patm result in upward gas movement from intermediate layers to replenish shallow layers. Our results suggest that changes in Patm drive changes in the vertical distribution of free phase gas in peat soil and regulate methane ebullition from peat soils to the atmosphere. Our data shows a relationship between free phase gas and depth that may be due to changes in peat properties or increasing water pressure with depth.
A cross-sectional test of the effect and conceptualization of service value

Focusses attention on service value as a construct which may help explain consumer decision making; however, to date this attention has been largely conceptual. Finds from the results of two empirical studies that models of consumer decision‐making which include service value explain significantly more variance in purchase intentions than models which include only service quality or cost factors, and the means by which consumers form service value perceptions is best depicted as a cognitive addition process.
Evaluation of various properties of alternative salt forms of sulfobutylether-β-cyclodextrin, (SBE)7M-β-CD

Abstract The goal of this study was to evaluate alternative salt forms of (SBE) 7M -β-CD (currently the sodium salt). The potential salt form would ideally decrease the rate of (SBE) 7M -β-CD release from osmotic pump formulations and result in an increase in the rate and extent of drug release in osmotic pump tablet and pellet dosage forms. Several (SBE) 7M -β-CD salt forms (potassium, calcium, and two ethylene diamine salt forms) were prepared by either titration or ultrafiltration and characterized by elemental analysis and capillary electrophoresis, CE. The physical properties (water uptake behavior, osmolality, complexation characteristics, etc.) were then compared to the sodium salt form. Although the water isotherm and the binding characteristics using various model drugs were similar among all the salt forms, the calcium salt form appeared to be the best alternative candidate due to its lower osmolality and slower intrinsic dissolution rate.
Quality as critique: promoting critical reflection among youth in structured encounter programs

In this manuscript, I interrogate the concept of ‘quality’ encounter programs for youth in conflict zones. I focus on two Israeli organizations implementing encounters for Jewish and Palestinian citizens, and draw upon narratives of former participants as articulated during life history narratives to illustrate divergent emphases in each organization’s goals and implementation strategies. Through my comparison of the organizations and their work, I highlight the importance in encounter programs of providing opportunities not only for legitimizing the collective narrative of the ‘other’ side, but also for critical reflection upon in-group narratives and policies, and suggest that ‘quality’ peace education programs are those that provide these opportunities.
Attitudinal and structural factors contributing to challenges in the work of the scholarship of teaching and learning

Much progress has been made in efforts to conduct, support, value, and use the scholarship of teaching and learning in higher education. Nevertheless, to further enhance student learning, many challenges remain.
Information content of scattering measurements and characterization of spheroids

Characterization of small particles ubiquitously involves scattering measurements at multiple wavelengths or at multiple angles. Such measurements are desired to provide the maximum amount of information regarding the particles. This paper develops a method to analyze the information content of scattering measurements when applied to characterize the shape and size distribution function of spheroidal particles. For a specific application, this method enables the selection of the optimal set of conditions (in terms of the wavelengths and the scattering angles) to perform the scattering measurements. Numerical simulations have demonstrated that this method can significantly improve the determination of the shape and size distribution function of spheroidal particles based on multispectral scattering measurements. The results obtained here provide valuable insights into the optimal design of techniques and instruments for particle characterization using scattering measurements.
A Note on the Ocean Surface Roughness Spectrum

Abstract In a recent study, the dimensionless surface roughness spectrum has been empirically parameterized as a power-law function of the dimensionless wind speed expressed as the ratio of wind friction velocity and phase speed of the surface roughness wave component. The wave-number-dependent proportionality coefficient, A, and exponent, a, of the power-law function are derived from field measurements of the short-wave spectrum. To extend the roughness spectrum model beyond the wavenumber range of field data, analytical functions are formulated such that A and a approach their asymptotic limits: A0 and a0 toward the lowest wavenumber, and A∞ and a∞ toward the highest wavenumber. Of the four asymptotic values, A∞ is considered most questionable for the lack of reference information. When applied to the normalized radar cross-section (NRCS) computation, the results are in good agreement (within about 2 dB) with field data or geophysical model functions (GMFs) for incidence angles between 20° and 40° but s...
Successful plastic procedures of the perineum.

Abstract Three flap procedures and reference to a fourth are described for use in the perineal area. These are advocated as they have been uniformly successful. Other plastic procedures are mentioned.
Detection of Clonal Rearrangement of the T-cell Receptor Gamma Gene by Polymerase Chain Reaction and Single-strand Conformation Polymorphism (PCR-SSCP).

Background: Diagnosis of T-lymphoid neoplasms frequently requires molecular studies of T-cell receptor (TCR) gene rearrangements. The Southern blot technique traditionally used for these analyses lacks the sensitivity and speed necessary for the routine clinical laboratory. The authors have developed a method using polymerase chain reaction (PCR) amplification with single-strand conformation polymorphism (SSCP) analysis that is rapid, sensitive, and semiautomated. Methods and Results: Polymerase chain reaction of the TCR gamma gene is done with consensus primers to the V and J regions. Amplicons thus include the N region, which serves as a marker of clonal T-cell population. Clonal populations having identical N-region sequences are identified by SSCP analysis, using a semiautomated electrophoresis system with silver staining for gel visualization. A series of 46 DNA samples from normal controls and various hematopoietic malignancies was comparatively analyzed by both Southern blot of the TCR beta locus and PCR-SSCP of the of the TCR gamma gene. The PCR-SSCP technique was rapid and reproducible, and detected clonal T-cell populations constituting 1% of the cell sample: The PCR-SSCP technique detected clones in eight cases that were negative by Southern blot. Conclusions: PCR-SSCP analysis of the TCR gamma gene is a rapid and sensitive method for the detection of clonal T-cell populations.
Factorial Invariance, Scale Reliability, and Construct Validity of the Job Control and Job Demands Scales for Immigrant Workers: The Multi-Ethnic Study of Atherosclerosis

Immigrants have a different social context from those who stay in their home country or those who were born to the country that immigrants now live. Cultural theory of risk perception suggests that social context influences one’s interpretation of questionnaire items. We examined psychometric properties of job control and job demand scales with US- and foreign-born workers who preferred English, Spanish, or Chinese (n = 3,114, mean age = 58.1). Across all groups, the job control scale had acceptable Cronbach’s alpha (0.78–0.83) and equivalent factor loadings (ΔCFI < 0.01). Immigrants had low alpha (0.42–0.65) for the job demands scale regardless of language, education, or age of migration. Two job-demand items had different factor loadings across groups. Among immigrants, both scales had inconsistent associations with perceived job stress and self-rated health. For a better understanding of immigrants’ job stress, the concept of job demands should be expanded and immigrants’ expectations for job control explored.
An Entropy Approach to the Hard-Core Model on Bipartite Graphs

We use entropy ideas to study hard-core distributions on the independent sets of a finite, regular bipartite graph, specifically distributions according to which each independent set I is chosen with probability proportional to λ∣I∣ for some fixed λ > 0. Among the results obtained are rather precise bounds on occupation probabilities; a ‘phase transition’ statement for Hamming cubes; and an exact upper bound on the number of independent sets in an n-regular bipartite graph on a given number of vertices.
Topological Edge States in Silicon Photonics

We demonstrate the robustness of topological edge states in a photonic system of coupled microring resonators. Using direct imaging and transmission analysis, we show that the edge states are robust to lattice disorders.
A clinical comparison of two forms of the card sorting test

Abstract This study examined 67 older adults with dementia and 157 predominantly younger individuals with HIV-1 infection to determine the comparability of two commonly used forms of the Card Sorting Test: the traditional Wisconsin Card Sorting Test (WCST) and Nelson's Modified Card Sorting Test (MCST). Three frequently used clinical outcome measures were examined: the total number of categories achieved; the ratio of perseverative errors to total trials; and the number of failures to maintain set exhibited in the protocol. Our results indicated that when the number of perseverative errors relative to total trials is used as a clinical indicator, the WCST and MCST appear to be comparable. For the number of categories achieved, the forms appear comparable only in the non-elderly, non-demented sample. Finally, we did not find comparable results between the two forms for the number of failures to maintain set.
Does early intervention increase latency to relapse in major depressive disorder?: re-evaluation with cognitive behavior therapy

Abstract Background: Major depressive disorder (MDD) has been studied in relation to its propensity for remission and likelihood of relapse. While the general clinical lore suggests that early intervention benefits treatment outcome, the empirical validation of this assumption is inconclusive. Specifically, no studies have been conducted concerning Time to Treatment Entry and long-term clinical course for MDD. Methods: For the current study, 53 participants received 16-weeks of cognitive behavioral therapy (CBT). Participants who remitted ( n =41) from their depression were then inducted into a longitudinal follow-up protocol. Results: Longer Time to Treatment Entry was predictive of longer time to relapse. A greater number of previous depressive episodes was associated with decreased Time to Treatment Entry. Limitations: A more elaborate protocol could be designed in order to explore the nature of treatment effects and Time to Treatment Entry within one study. Conclusions: CBT may be the most effective for patients who have delayed seeking treatment. Although the present study adds to the developmental neurobiological assumptions of Post [Severe depressive disorders (1994) 23–65] concerning affective ‘kindling,’ it also challenges the kindling theory’s assumptions concerning early intervention.
Rising mortality due to Parkinson's disease and amyotrophic lateral sclerosis: a manifestation of the competitive nature of human mortality.

Over the past 15 yr, a marked increase in crude mortality rates from Parkinson's disease (PD) and amyotrophic lateral sclerosis (ALS) has occurred in the U.S. This is often attributed to as yet undefined environmental factors. The deterministic risk of general mortality and mortality due to PD, ALS, ischemic heart disease (IHD), and stroke for the years 1963, 1977, and 1986 in the U.S., as defined by the method of longitudinal Gompertzian analysis, were calculated and compared. When the rise in PD and ALS mortality is viewed from the perspective of deterministic and competitive mortality dynamics, it becomes evident that the major force increasing mortality from these two neurologic diseases is the declining mortality from IHD and stroke. Consequently, there is no need to invoke intrinsic etiologic alterations in the environment to account for the observed increases in PD and ALS mortality. Recognition of the competitive nature of human mortality illustrates the inherent risk of making etiopathogenic conclusions based upon single disease mortality data.
Inhibition of lymphocytic choriomeningitis virus multiplication by 2-(α-hydroxybenzyl)benzimidazole

Abstract It has been reported that 2-(α-hydroxybenzyl)-benzimidazole (HBB) selectively inhibits only the picornaviruses. However, we have found that three stains of LCM virus—Traub, WCP, and CA1371—when grown in HeLa cells, are inhibited by HBB. In all cases HBB, at 55 μ M , inhibited virus production by 70–90%. HBB at 220 μ M did not affect the multiplication rate of noninfected cells, but did noticeably inhibit multiplication 2 days after infection. Furthermore, 220 μ M HBB did not change the in vitro inactivation rate of the virus, nor its adsorption to cells. It would appear then that inhibition of virus multiplication by HBB is not entirely restricted to defined picornaviruses. However, unlike other HBB-sensitive viruses, the multiplication of LCM was not inhibited by 700 μ M guanidine hydrochloride.
Reiterative template switching: The effect of single-strand homopolymeric DNA on non-template-directed nucleotide addition by DNA polymerase

Template switching occurs when DNA polymerase juxtaposes two discontinuous DNA molecules with 3'-terminally complementary ends generated through non-template-directed nucleotide addition. We examined whether juxtaposition of homopolymeric single-stranded oligonucleotides affects non-templated addition. We hypothesized that if DNA polymerase first juxtaposed the two substrates, then the non-template-directed nucleotide addition of any deoxynucleotide would decrease in the presence of its non-complementary template. For dATP, product formation was unaffected by non-complementary substrates. In contrast, dCTP and dGTP incorporation decreased to varying degrees while dTTP incorporation increased in the presence of oligodeoxythymidine but decreased for other non-complementary homopolymers. Interestingly, the presence of complementary templates strongly influenced the formation of highly periodic products indicative of reiterative template switching. Transient template synapsis was observed and found to be dependent on the non-templated sequence added: 3-4 A:T or 1-2 G:C base pairs were needed for stable synapsis, suggesting that base pairing plays a more important role in the active site of the enzyme than previously thought.
Effect of mercury toxicity on serum osmolality, plasma sodium and potassium, and serum proteins in the chicken

Juvenile male chickens were exposed continuously to 300μg/ml of mercury (Hg) in the form of mercuric chloride (HgCl2),via the drinking water, from hatching through six weeks of age. Serum osmolality and plasma potassium were increased significantly as a result of the Hg treatment. Plasma sodium was increased numerically in two of the three trials. Of the serum proteins, only albumin and the transferrins exhibited a consistent significant increase. It is concluded that alterations in serum ions and proteins account for the significant increase in plasma osmolality. The increase in transferrins may represent a mechanism to bind and detoxify Hg.
On first-person narrative scholarship: Autoethnography as acts of meaning

Social science writing can be construed as a form of discourse that puts meaning into motion. This article reviews the cultural conditions that inspired the burgeoning interest in autoethnography, the kinds of truth to which it aspires, and the opportunities it opens to invite readers into conversation with the possibilities of happiness in the presence of human suffering. Autoethnographies attempt to make social science something more than an end in itself.
Defining the role of the epidermal growth factor receptor in pancreatic cancer grown in vitro

Abstract Background The purpose of this study was to determine the effect of a novel epidermal growth factor (EGF) receptor tyrosine kinase inhibitor, Erlotinib, on pancreatic cancer cell lines of varying differentiation in vitro. Methods Six pancreatic cancer cell lines (AsPc-1, CAPAN-1, HPAC, HPAF-II, Mia PaCa-2, PANC-1) were grown in the presence of 50 μM or 100 μM of Erlotinib or recombinant EGF. Cell proliferation was determined using the MTT assay over 72 hours. The EGF receptor gene and protein expression were determined by polymerase chain reaction and immunohistochemistry respectively. Results All cell lines demonstrated the presence of the EGF receptor gene and its gene product. Five of six cell lines showed significant growth inhibition at 72 hours compared with controls (P Conclusions Inhibition of EGF receptor is a valid therapeutic strategy in pancreatic cancer.
Strial dysfunction in the MRL-Faslpr mouse

Abstract The MRL-Faslpr mouse, a model of multisystemic autoimmune disease, has been proposed as a potential model of autoimmune inner ear disease. Cochlear pathology, consisting of hydropic degeneration of the stria vascularis, has been documented to occur coincident with the establishment of systemic disease in this animal. Because the cochlear pathology is restricted to the stria, this study was designed to evaluate whether the endocochlear potential (EP) would be diminished in these animals because of a loss in strial Na,K-ATPase. Experimental (MRL-Faslpr) mice, with established systemic disease, had auditory brain stem response thresholds and EPs recorded. MRL-+/+ mice served as controls. Animals were then euthanized, and their cochleas were processed for immunohistologic assay for the α1 and β2 subunits of Na,K-ATPase. Density of staining was evaluated by use of quantitative means with densitometry image analysis of digitized images. MRL-Faslpr mice revealed significant elevations in auditory brain stem response thresholds and reductions in EPs but no reductions in Na,K-ATPase levels, as evidenced by immunohistochemical assay. The reduction of EP likely occurs as a result of cellular degeneration within the stria vascularis and likely results from an abrogation of the strial perilymph/endolymph barrier and not from a reduction in strial Na,K-ATPase levels. (Otolaryngol Head Neck Surg 1999;121:452-6.)
MEASURING LINE CENTERS FROM DIGITALLY RECORDED SPECTRA USING A MINICOMPUTER

A system is described for determining spectral positions from high resolution infrared spectra which have been recorded in digital form on magnetic tape. The system employs a minicomputer located in the laboratory and line centers are determined by an interactive procedure in which the operator makes judgments based on information displayed on the CRT screen of the computer. This information consists of the spectrum, a reflection of a local section of the spectrum at a vertical line through the center of the screen, a plot of the difference between the spectrum and its reflection, and the square of the area under the difference curve. Very high accuracy is demonstrated for locating the centers of single lines as well as the centers of the components of incompletely resolved double lines. Determinations of spectral positions (wave-number calibration) parallel operations that were previously performed as batch jobs by a much larger computer. Spectral positions are determined by standard methods of calibration of interference fringes and interpolation.
Discriminant Analysis of Psychological Judgments of Literal and Figurative Meaningfulness and Anomaly

Abstract Virtually no psycholinguistic studies have investigated components of psychological judgments of literal and figurative meaningfulness versus anomaly. In a study of 57 undergraduates, one group of 21 S s classified 120 sentences as literal or figurative in meaning or as meaningless; two groups of 18 S s each judged the truth value of the proposition in each sentence and rated the degree of similarity between subject and predicate constituents. Discriminant analysis indicated that literal, figurative, and anomalous sentences were accurately distinguished in truth value and subject-predicate similarity. In particular, metaphors reflected the literary notion of similarity between the elements of a logically false proposition.
Development of an intelligent polymerized crystalline colloidal array colorimetric reagent.

We have developed a novel colorimetric reagent for the determination of Pb2+, pH, and temperature. This colorimetric reagent consists of a dispersion of ∼100-μm particles composed of an intelligent polymerized crystalline colloidal array (IPCCA). The IPCCA particles are composed of a hydrogel polymerized around a face-centered cubic (fcc) array of monodisperse, highly charged polystyrene colloidal particles. These IPCCA particles diffract visible light because the (111) planes of the fcc polystyrene colloidal particle array have an ∼200-nm lattice constant. The IPCCA particles also contain a molecular recognition agent that actuates array volume changes as a result of changes in analyte concentration or temperature. This results in changes in the IPCCA lattice constants, which shifts the wavelength of light diffracted. We report here the use of these sensing materials in a liquid dispersion that can be poured into a sample solution. This diffraction measurement method is analogous to X-ray powder diffract...
Diurnal and circadian retinomotor movements in zebrafish.

Key indicators of circadian regulation include the persistence of physiological rhythmicity in the absence of environmental time cues and entrainment of this rhythmicity by the ambient light cycle. In some teleosts, the inner segments of rod and cone photoreceptors contract and elongate according to changes in ambient lighting and the circadian cycle. Pigment granules in the retinal pigment epithelium (RPE) disperse and aggregate in a similar manner. Collectively, these movements are known as retinomotor movements. We report the histological characterization of diurnal and circadian retinomotor movements in zebrafish, Danio rerio. Adult fish subjected to a 14:10 light:dark (LD) cycle, constant darkness (DD), or constant light (LL) were sacrificed at 1–13 h intervals and processed for semithin sectioning of the retina. Using bright-field microscopy, 15 measurements of pigment granule position and the inner segment lengths of 30 rods and 30–45 cones were collected from the central third of the dorso-optic retina per time point. In LD, rods and cones followed a clear diurnal rhythm in their inner segment movements. Short-single, UV-sensitive cones were found to contract significantly 1 h before light onset in LD conditions. In DD conditions, the inner segments movements of short-single and double cones displayed statistically significant rhythms. RPE pigment granule movements are rhythmically regulated in both LD and DD although fluctuations are damped in the absence of photic cues. No significant retinomotor movements were observed in LL. These findings indicate retinomotor movements in zebrafish are differentially regulated by an endogenous oscillator and by light-dependent mechanisms.
Modulation of MHC Class II Expression in Human Cells by Dexamethasone

Abstract The effect of dexamethasone on human MHC class II expression was examined on various cell types including lymphocytes, monocytes, and epithelial cells. Dexamethasone decreased the surface expression of HLA-DR and -DP, but not HLA-DQ, on lymphocytic cell lines that constitutively express these molecules. In addition, dexamethasome down-regulated the mRNA levels of HLA-DRA, but not of HLA-DQB, in Jijoye cells, a human lymphoblastic cell line. Similarly, dexamethasone decreased HLA-DR expression on epithelial and monocytic cell lines that express HLA-DR upon IFN-γ treatment. In total, these results suggest that dexamethasone inhibits both constitutive and IFN-γ-inducible MHC class II expression in several cell types. Moreover, these results indicate that the inhibitory effect of dexamethasone on MHC class II expression is selective for HLA-DR and -DP but not HLA-DQ. Possible mechanisms of dexamethasone-mediated regulation of MHC class II expression are discussed.
Assessing response rates in clinical trials of treatment for relapsed or refractory multiple myeloma: a study of bortezomib and thalidomide by H Prince, Brad Schenkel and Linda Mileshkin

Assessing response rates in clinical trials of treatment for relapsed or refractory multiple myeloma: a study of bortezomib and thalidomide by H Prince, Brad Schenkel and Linda Mileshkin
Prospective multicenter evaluation of cocaine-associated chest pain. Cocaine Associated Chest Pain (COCHPA) Study Group.

Objective: To describe a large cohort of patients who had chest pain following cocaine use, and to determine the incidence of and clinical characteristics predictive for myocardial infarction in this group of patients. Methods: A prospective observational cohort study of consecutive patients with cocaine-associated chest pain was conducted in six municipal hospital emergency departments (EDs). Demographic variables, drug abuse patterns, medical histories, chest pain characteristics, ECG results, and laboratory data were recorded. Myocardial infarction was the primary endpoint. Results: Fourteen of 246 patients (5.7%; 95% confidence interval [CI], 2.7–8.7%) had myocardial infarction, as diagnosed by elevated CK-MB isoenzyme levels. There were two deaths (0.8%). The patients had a median age of 33 years. The majority were male (71.5%), non-white (83.3%), cigarette smokers (83.3%) who used cocaine regularly. Chest pain began a median of 60 minutes after cocaine use and persisted for a median of 120 minutes. Chest pain was most frequently described as substernal (71.3%) and pressure-like (46.7%). Shortness of breath (59.3%) and diaphoresis (38.6%) were common. There was no clinical difference between patients who had myocardial infarctions and those who did not. Twelve patients had arrhythmias and four had congestive heart failure. All cases requiring intervention were evident upon presentation. An ECG revealing ischemia or infarction had a sensitivity of 35.7% for predicting a myocardial infarction. The specificity, positive predictive value, and negative predictive value of the ECGs were 89.9%, 17.9%, and 95.8%, respectively. Conclusions: Myocardial infarction in patients who have cocaine-associated chest pain is not uncommon. No clinical parameter available to the physician can adequately identify patients at very low risk for myocardial infarction. Therefore, all patients with cocaine-associated chest pain should be evaluated for myocardial infarction.
Synecology of a Virginia salt marsh

In the spring and summer of 1964 a salt marsh in Gloucester County, Virginia, was analyzed using random quadrat sampling. Synthetic treatments were employed to evaluate data and were correlated with observed differences in elevation. Floristic data indicate the Virginia salt marshes show closer similarity to marshes north of Chesapeake Bay than those south of Chesapeake Bay. Correlation of floristic data with observed differences in elevation indicates that zonation in the marsh is dependent upon differences in elevation or some environmental factor correlated with elevation differences. Observations of sedimentation and erosion in localized areas indicate that the marsh is in a constant state of change, with extensive areas undergoing both succession and regression.
Delayed computed tomographic characterization of renal masses: preliminary experience.

Background: To evaluate the performance of delayed contrast enhanced computed tomography (DCT) in characterizing renal masses. Methods: Twenty-four patients with suspected renal masses or indeterminate renal masses on previous imaging studies were prospectively evaluated with preintravenous contrast imaging, conventional contrast-enhanced computed tomography (imaging initiated 2 min after intravenous contrast injection), and DCT (imaging initiated 13 min after injection of intravenous contrast). Only lesions larger than 1.0 cm were evaluated, with scanning parameters kept constant across the three scans. Results: All pathologically confirmed renal cell carcinomas (n= 6) were detected on DCT using a threshold attenuation decrease of 10 Hounsfield units (HU). A significant decrease (p= 0.031) in attenuation occurred in renal cell carcinomas (mean = 29.6 ± 23.6 HU) compared with the attenuation change (mean decrease = 1.1 ± 7.1 HU), which occurred in non-neoplastic renal cysts (n= 34). Non-neoplastic renal cysts were correctly classified by DCT 32 of 34 times (94%). Conclusions: In this study, DCT distinguished renal cell carcinomas from non-neoplastic cysts in a vast majority of cases and may aid in characterizing incidentally discovered renal lesions on postcontrast CT.
Synthesis and structure of a tricyclic bis(zirconacyclopentadiene) compound

Abstract 1, 5-Bis (trimethylsilyl)penta-1, 4-diyne was synthesized from trimethylsilylacetylide and 1-trimethylsilyl-3-bromo-1-propyne, and used in a reaction with “Cp2Zr”, giving as the major product 4, 6, 10, 12-tetrakis (trimethylsilyl)-5, 5, 11, 11-tetrakis ( ƞ 5 - cyclopentadienyl )-5 , 11-dizirconatricyclo[7, 3, 0, 03]dodeca-1(12), 3, 6, 9-tetraene, which was characterized by H and 13C NMR spectroscopy and x-ray diffraction studies.
Irradiations in the beam dump of an intermediate energy proton accelerator

Abstract The different types of irradiation which are present in a high beam, intermediate energy proton accelerator and means for making them available are described. A discussion is given of the factors involved in choice of elements for use as a beam stop. Estimation of neutron and proton irradiating fluxes, induced radioactivity and shielding are also presented.