cssi/SciSciGPT-SciSciNet huggingface dataset:
CRISPR Activation Enhances In Vitro Potency of AAV Vectors Driven by Tissue-Specific Promoters.

Validation of gene transfer vectors containing tissue-specific promoters in cell-based functional assays poses a formidable challenge for gene therapy product development. Here, we describe a novel approach based on CRISPR/dCas9 transcriptional activation to achieve robust transgene expression from transgene cassettes containing tissue or cell type-specific promoters after infection with AAV vectors in cell-based systems. Guide RNA sequences targeting two promoters that are highly active within mammalian photoreceptors were screened in a novel promoter activation assay. Using this screen, we generated and characterized stable cell lines that co-express dCas9.VPR and top-performing guide RNA candidates. These cells exhibit potent activation of proviral plasmids after transfection or after infection with AAV vectors delivering transgene cassettes carrying photoreceptor-specific promoters. In addition, we interrogated mechanisms to optimize this platform through the addition of multiple guide RNA sequences and co-expression of the universal adeno-associated virus receptor (AAVR). Collectively, this investigation identifies a rapid and broadly applicable strategy to enhance in vitro expression and to evaluate potency of AAV vectors that rely upon cell or tissue-specific regulatory elements.
The Conundrum of Diagnosing Cutaneous Composite Lymphoma in the Molecular Age.

Introduction Cutaneous composite lymphoma (CCL) is extremely rare. When 2 potentially distinct lymphoid lesions occur at one skin site, distinguishing between one neoplastic clone and a secondary reactionary lymphoid response versus a second neoplasm is difficult. In this study, we describe a unique case of CCL along with a review of reported cases in literature to identify clues and discuss issues that are relevant to the diagnosis of CCL. Design Review of a CCL case from our institution and a systematic review of reported cases of CCL in the literature. Results A total of 18 studies describing 22 cases and a case report from our institution are included. The mean age at diagnosis was 68 years. Most cases herein presented with multiple skin lesions (67%) and reported a history of immune suppression (76%). Nineteen cases (83%) had a combination of T-cell and B-cell neoplasms, whereas the remaining cases had 2 distinct B-cell clones. Clonal differentiation was confirmed based on morphology and immunohistochemistry in all cases, and by polymerase chain reaction studies in 19 cases. Complete remission was achieved in only one quarter of reported cases. Conclusion Diagnosing CCL can be challenging because accurate differentiation of 2 or more clonal populations at 1 site is tedious. A stepwise approach and integration of clinical, morphologic, immunohistochemistry, and molecular data along with an understanding of the prognosis of the lymphomas in question is essential for an accurate diagnosis and necessary because of therapeutic and prognostic implications.
Shared Decision Making: Moving from Concerns about Restrooms to Concerns about Classrooms:

Whilesome schools dive head first into shared governance, others struggle with issues and processes that frustrate both faculty and administrators. Here the author describes selected experiences of...
Acceptance of Cancer Screening

The purpose of cancer screening is to detect cancer in its preclinical phase when the disease is most likely to be curable (Hennekens & Buring, 1987) and thereby enable achievement of the ultimate goal of screening—a reduction in morbidity and mortality from cancer. To be appropriate for screening, a disease should have high prevalence in the population (e.g., hypertension or breast cancer) and must have serious consequences, and there should be an effective screening intervention. The test should be sensitive and specific and have high predictive validity. The definition of effective is often a matter of debate, but the gold standard for determining effectiveness is usually a randomized clinical trial with a statistically significant reduction in mortality. The screening characteristics will be described in more detail, but even if a test were 100% sensitive and specific, the benefits would be achieved only to the degree to which everyone at risk received the test. This is the issue of compliance with or adherence to cancer screening.
Risk factors and incidence of 90-day readmission for diverticulitis after an acute diverticulitis index admission.

Acute diverticulitis is the third most frequent cause of gastrointestinal admission in the USA. We sought to determine the incidence of recurrence within a 90-day period and determine its impact on mortality and hospital utilization. Nationwide Readmission Database (NRD) 2016 was used to identify patients ≥ 18 years old with a principal diagnosis of acute diverticulitis who were readmitted for recurrence within 90 days. The primary outcome was 90-day readmission rate for acute diverticulitis, and predictors were analyzed using a multivariate regression analysis. Secondary outcomes were mortality and hospital resource utilization. A total of 171,238 admissions were included which met inclusion criteria. Ninety-day readmission for acute diverticulitis after index diverticulitis hospitalization was 8.9%. Readmissions were associated with in-hospital additional total cost of $444,726,560 and 65,685 total hospital days and mortality rate of 4.69% compared with mortality rate of 5.20% on index hospitalization (p < 0.01). In multivariable analysis, increased odds of readmission were associated with disposition against medical advice (OR 1.75, 95% CI 1.31–2.33), younger age (OR 0.98, 95% CI 0.98–0.99), and shorter length of stay (OR 0.99, CI 0.98–0.99). Acute diverticulitis is frequently associated with recurrence within 90 days and bears a substantial financial and mortality burden. Targeted interventions are needed to minimize readmissions in identified subpopulations.
A Disorder-to-Order Transition Activates an ATP-Independent Membrane Protein Chaperone.

Abstract The 43 kDa subunit of the chloroplast signal recognition particle, cpSRP43, is an ATP-independent chaperone essential for the biogenesis of the light harvesting chlorophyll-binding proteins (LHCP), the most abundant membrane protein family on earth. cpSRP43 is activated by a stromal factor, cpSRP54, to more effectively capture and solubilize LHCPs. The molecular mechanism underlying this chaperone activation is unclear. Here, a combination of hydrogen–deuterium exchange, electron paramagnetic resonance, and NMR spectroscopy experiments reveal that a disorder-to-order transition of the ankyrin repeat motifs in the substrate binding domain of cpSRP43 drives its activation. An analogous coil-to-helix transition in the bridging helix, which connects the ankyrin repeat motifs to the cpSRP54 binding site in the second chromodomain, mediates long-range allosteric communication of cpSRP43 with its activating binding partner. Our results provide a molecular model to explain how the conformational dynamics of cpSRP43 enables regulation of its chaperone activity and suggest a general mechanism by which ATP-independent chaperones with cooperatively folding domains can be regulated.
AdaPool: An Adaptive Model-Free Ride-Sharing Approach for Dispatching using Deep Reinforcement Learning

Deep Reinforcement Learning (RL) suffer from catastrophic forgetting due to being agnostic to the timescale of changes in the distribution of experiences. Although, RL algorithms are guaranteed to converge to optimal policies in Markov decision processes, this only holds in the presence of static environments. However, this assumption is very restrictive. In many real world problems like ridesharing, traffic control, etc., we are dealing with highly dynamic environments, where RL methods yield only sub-optimal decisions. In this paper, we introduce an adaptive model-free deep reinforcement approach that can recognize diurnal patterns in the ridesharing environment. To achieve this, we (1) adopt a change point detection algorithm to detect the changes in the distribution of experiences, then (2) we develop a Deep Q Network (DQN) agent that is capable of recognizing diurnal patterns and making informed dispatching decisions according to the changes in the underlying environment. Based on the demand, our DQN approach re-balances idle vehicles by dispatching them to the areas of anticipated high demand using Deep Reinforcement Learning. This approach can be adopted in various domains through tuning the RL agent's objective function, where it will still capture the changes in the corresponding underlying environment. Our framework is validated using the New York City Taxi public dataset. Experimental results show the effectiveness of our approach in real-time and large scale settings.
The Information Politics of COVID-19 in China

This chapter documents two information failures in China in early stages of the coronavirus that became the COVID-19 pandemic. First is the failure of timely and truthful upward reporting from Wuhan in December 2019 and early January 2020, which kept Beijing ignorant of the outbreak and spread of the virus. Second is the official misinformation to ordinary citizens in mid-January, even after Beijing understood the risk of transmission; this was accompanied by an aggressive campaign of censorship and intimidation of netizens who posted news about the virus on social media. Both failures were also evident in China’s SARS crisis of 2002–2003 and stem from systemic problems of information politics. China followed these failures with responses that are unusually sensitive to the tradeoffs between centralization and decentralization. With the draconian lockdown of Wuhan, Beijing exercised effective leadership by directly taking charge. Then, by invoking the Emergency Response Law, which mandates highly localized response, it permitted localities down to the county level to exercise discretion in choosing a policy response suited to local conditions and report upward ex post. With its capable response, Beijing has deflected attention from early failures, especially by comparison with bungling by governments elsewhere in the world.
Correlation of venous symptoms with iliac vein stenosis on magnetic resonance imaging

OBJECTIVE Magnetic resonance imaging (MRI) is used in patients with lower extremity venous disease to screen for iliac vein stenosis. The objective of the present study was to determine the prevalence of iliac vein stenosis and associated lower extremity venous symptoms in consecutive patients undergoing MRI of the pelvis. METHODS A retrospective study of all consecutive adult patients who had undergone MRI of the pelvis for various indications from March 2012 to June 2016 was performed. The electronic medical records (EMRs) were reviewed for patient characteristics and, specifically, for the presence and laterality of venous symptoms. All MRI scans were reviewed, and the maximal degree of iliac vein stenosis was recorded. All the patients also responded to a brief telephone survey inquiring about the presence of venous symptoms. Two thresholds of venous stenosis, ≥50% and ≥70%, were used to correlate its presence with the presence of venous symptoms determined from the EMR review and telephone survey results. RESULTS A total of 120 patients were included, with a mean age of 53 ± 14 years; 79% were women and 79% were white. The prevalence of iliac vein stenosis ≥50% was significantly greater on the left than on the right (34.2% vs 16.7%; P < .001). The survey demonstrated that 44 of the 120 patients (36.7%) had had venous symptoms compared with only 30 patients (25%) according to the EMR review (P = .001). No differences were found between patients with positive vs negative survey results for venous symptoms and the occurrence of iliac vein stenosis ≥50% on the right (17.2% vs 15.2%; P = .78) or the left (38% vs 26.8%; P = .22). We also found no differences when the occurrence of iliac vein stenosis ≥70% was used as threshold between the right (2.3% vs 3%; P = .99) and the left (10.1% vs 2.4%; P = .16). Analysis of the venous symptoms from the EMR review yielded similar results. CONCLUSIONS In our study, iliac vein stenosis was more common on the left and was encountered in up to one third of patients who had undergone MRI of the pelvis. No correlation was found in our study between the presence of iliac vein stenosis and the occurrence of ipsilateral venous symptoms. Venous symptoms were underreported in the EMRs. Further studies are necessary to identify the predictors of pathologic iliac vein stenosis.
Interpersonal emotion regulation while at work: a test of differences

This study utilised the interpersonal emotion regulation questionnaire (IERQ) to examine the work environment by determining the interpersonal emotion regulation (IER) of employee's differences based upon employee and supervisor roles. A quantitative study design, utilising social medians was employed to sample 122 managers and non-mangers (n = 122). Testing analysis utilised ordinal regression and ANOVA analyses. The soothing subscale of IERQ was the only significant difference. The implications of the findings conceivably relate to the trainings of employees. The study points to the need for longitudinal studies of interpersonal emotion regulation in the workplace. This study has important implications for the business sector, as there is a lack of literature discerning the importance of the supervisory role with regard to the need for individuals in supervisory roles to regulate their own emotions as well as those of their subordinates. The IERQ has been utilised clinically to study patients. The study is the first, however, that the author is aware of, to utilise the IERQ to test organisational employees' intrinsic and extrinsic interpersonal emotional regulation.
The use of hysteroscopic endometrectomy in the conservative treatment of early endometrial cancer and atypical hyperplasia in fertile women.

To illustrate the effectiveness of hysteroscopic endometrial resection in conservative treatment of early endometrial cancer/atypical hyperplasia in women of reproductive age. Review of outcomes of women of reproductive age who underwent fertility sparing treatment (hysteroscopic superficial endometrectomy followed by progestin therapy) in early endometrial cancer. Eight women with Stage I endometrial cancer and three with atypical endometrial hyperplasia underwent hysteroscopic superficial endometrial resection, followed by 1-year treatment with oral megestrol acetate. One patient had a synchronous endometrioid ovarian carcinoma. One patient with Grade 2 carcinoma opted for conservative treatment and had hysterectomy 3 months later for persisting disease. Ten patients showed no evidence of residual disease during a 12-month follow-up period with regular hysteroscopy. Five patients had seven pregnancies without assisted reproductive technology. One patient got pregnant after one attempt of in-vitro fertilization and oocyte donation. Pregnancy rate was 54.5%; two patients had two successful pregnancies and deliveries. Average time to pregnancy was 16 months from the end of treatment. All babies were delivered vaginally. Total superficial endometrial resection followed by progestin can be considered in patients with early endometrial cancer/atypical hyperplasia who still want to conceive. It does not seem to impair fertility nor pregnancy outcomes in women of reproductive age.
Correlation of older age with severity of lymphedema in breast cancer survivors: A systematic review.

BACKGROUND Breast cancer is the most frequent cause of secondary lymphedema. Besides being progressive and chronic, lymphedema is usually hard to treat. That is why the clinicians are more focused on the prevention of its development and progression. OBJECTIVE The aim of this study is to evaluate the possible relationship between the age of patients and the severity of breast cancer-related lymphedema (BCRL). METHODS PubMed, Scopus, and Ovid MEDLINE databases were searched for articles, which described the relationship between aging and BCRL development. Two authors searched for and selected articles independently. RESULTS Out of 562 studies selected, 8 studies met the inclusion criteria. However, 2 papers had the same study population, so only 7 were included in the final analysis. The total number of patients in those 7 studies was 3,904. Five out of 7 studies included in our review depicted the association of more severe forms of BCRL with older age. CONCLUSION The final analysis showed that aging is related to the severity of BCRL. However, due to heterogeneity in study outcome reporting, the cause and effect relationship could not be determined.
Impact of Weight on Anti-Xa Attainment in High-Risk Trauma Patients on Enoxaparin Chemoprophylaxis.

Abstract Background Serum anti-factor Xa (anti-Xa) concentration may guide low molecular weight heparin chemoprophylaxis in trauma patients. Higher total body weight (TBW) is a risk factor for subprophylactic anti-Xa and venous thromboembolism (VTE). The purpose of this study was to evaluate TBW differences in patients with subprophylactic versus prophylactic trough anti-Xa. Methods This retrospective study included adults admitted to the trauma service who received enoxaparin chemoprophylaxis, trough anti-Xa assessment, and screening duplex ultrasound. Initial enoxaparin dose was determined per trauma team weight-tiered protocol with subsequent 10 mg increase if anti-Xa was subprophylactic. Patients were stratified into subprophylactic (anti-Xa Results A total of 887 patients were included with 681 (76.8%) having subprophylactic anti-Xa. The subprophylactic group had significantly younger age, higher proportion male sex, higher Injury Severity Score (ISS), higher BMI, and longer length of hospital stay. The subprophylactic group had higher TBW (median [IQR], 87.8 [74-102] kg vs. 78.9 [68-91.8] kg; P Conclusions TBW is higher and weight-adjusted enoxaparin dose is lower in high-risk trauma patients with subprophylactic anti-Xa concentrations. These data suggest TBW should be considered when determining the optimal prophylactic enoxaparin dose in high-risk trauma patients.
PERSPECTIVES ON ECOLOGICAL AND EVOLUTIONARY SYSTEMS BIOLOGY

Understanding the emergent properties inherent to genome function requires an integrated approach of data from all levels of biology. Molecular biol- ogy data alone does not describe the complex interacting functions of organisms, while studies at the level of ecological communities and ecosystems have provided little insight into the molecular underpinnings of adaptation. Merging ecology and evolution into systems biology allows researchers to exploit a wealth of genomic information by incorporating the natural phenotypic, genetic and epigenetic diver- sity of model systems as well as their diverse ecologies and evolutionary histories. Here, we suggest that systems biology could more fully address the question of how organisms respond to environment if studies incorporated real field settings or experimental manipulation of relevant environmental factors. In addition, al- though the application of genomic approaches to non-model systems has been slow, we highlight some of the significant progress that has been made. Ecological and evolutionary systems biology will lead to a much more sophisticated under- standing of the origins and functions of biological diversity, and serve as a critical component in deciphering how organisms respond to complex environments.
Interventions for hazard control in foods during harvesting.

This chapter discusses the interventions applied during harvest of different food commodities. Current interventions applied in order to reduce hazards during the harvesting of beef cattle include physical and chemical treatments. Chemical dehairing is a decontamination process that involves the removal of hair from animals by using a sodium sulfide solution followed by a rinse with a hydrogen peroxide solution and water prior to dehiding. The approved methods to meet this requirement are knife trimming and vacuuming beef carcasses with hot water or steam, when such contamination is less than 1 square inch. Steam pasteurization treatments have been used in meat processing. Several chemicals with antimicrobial activity have been tested for usefulness as carcass sanitizers. The steps in poultry slaughter for which contamination is most likely to occur are the scalding and defeathering points. High-pressure processing is an alternative treatment used to eliminate pathogens from foods with no thermal pasteurization and extend the shelf life of foods. Some studies developed to test the effectiveness of radiation in decontamination of seafood have demonstrated that doses of 3 kGy or below are enough to eliminate pathogenic bacteria. There are multiple interventions for hazard control during harvest that are capable of reducing pathogenic bacteria in foods of different origin. Overall, the proper use of approved interventions/ decontamination methods will continue to enhance the safety of the food supply and allow producers to meet the demands and expectations of the consumers.
Telecommunications Investment and Traffic in Developing Countries: The Effects of International Settlement Rate Reforms

In 1997 the FCC ordered sharp decreases in international settlement rates (bilaterally negotiated telecommunication rates) between the U.S. and other countries. Developing countries, which received about $35 billion in net settlement payments from U.S. carriers between 1985 and 1998, claim that payments finance telecom investment and that reduced rates, and therefore payments, will harm investment. Using a panel dataset of 179 countries from 1985–1998, I find settlement rates negatively correlated with international telecom traffic, suggesting that reduced rates will stimulate traffic. I also find no evidence that payments finance investment as measured by telephone penetration and telecommunications equipment imports.
Quantization = Integration over Function Space

The construction of P(φ)2 fields begins with this chapter; Chapters 11–12 conclude the construction. We develop efficient methods for computing and estimating integrals $$ \int {A\;d\phi = \sum\limits_{G = graph} {I\left( G \right)} } $$ (8.1.1) of polynomials A = A(φ) with respect to a Gaussian measure dφ. There are a variety of equivalent methods for computing Gaussian integrals of polynomials, such as integration by parts, expansion in Hermite polynomials, or the use of annihilation and creation (raising and lowering) operators.
2MASS and the Tully-Fisher Relation

The major advantage of studying galaxies in the near infrared (NIR), is the minimization of dust extinction. The NIR is the region of the stellar emission spectrum which is least affected by both dust emission and extinction. Dust emission becomes more of a factor at longer wavelengths while dust extinction is more significant at shorter ones. The other important advantage of a NIR study is that it probes the bulk of the stellar mass in the galaxies. Since Tully-Fisher (T-F) is a relationship between a galaxy’s total stellar content and its rotation speed, minimizing the biases in the measurement of the bulk of the stellar emission provides a significant advantage.
Important Research Questions in Innovation and Technology

Researchers in a variety of disciplines have studied various aspects of technological innovation. However, those in marketing have a unique advantage. Adopting a consumer orientation helps in understanding technological innovation because all innovations ultimately aim to produce better products for consumer welfare. Thus researchers in marketing have a unique vantage point in researching and understanding this phenomenon. This essay outlines ten important research questions in technological innovation from a marketing perspective.
Consumption, Technology, and Development: The “Poor” as “Consumer”

This article focuses on the case of M-PESA mobile payments service in Kenya. It critically analyzes the assumptions and cultural contradictions that underpin notions of the low-income consumer and their implications in practice for business strategy. The poor-as-consumer model assumes that, in order to target low-income groups, one needs to design products, services, and marketing specifically for the poor. We find a unifying notion of the consumer that is not based on income. Being an M-PESA consumer can enable low-income Kenyans to seemingly cross class boundaries and assume identities not linked to their traditional class status. Although the poor are price sensitive, our research shows the importance of not making them “feel” like they are, as a class, “the poor.” By examining and building on these assumptions and contradictions, Safaricom successfully tapped into market messages that met individual consumers’ desires and aspirations.
Microsomal oxidases. 3. Comparison of species and organ distribution of dialkylarylamine N-oxide dealkylase and dialkylarylamine N-oxidase.

Abstract Microsomes isolated from hepatic tissue of different species and from different tissues of the same species have been examined for heat-labile and SKF-525A-sensitive N-oxide dealkylase activity. This activity is most concentrated in hepatic tissue and appears to be restricted to vertebrates. The distribution of this enzyme follows the distribution of the oxidative N-dealkylation system in all of the different tissues studied. The N-oxide dealkylase activity, like oxidative N-dealkylation activity, is markedly increased in tissues obtained from rats pretreated with diethylbarbital. The N-oxide dealkylase activity of all the microsomal fractions obtained from vertebrates is heat-labile. This activity in hepatic microsomes from most species is inhibited by SKF-525A. However, this compound does not affect the N-oxide dealkylase activity of raccoon liver microsomes, and only partially inhibits this enzyme in bovine, rabbit, or armadillo liver microsomes.
Chapter 14. Assessment of arteriogenesis

Assessment of arterial circulation development and function in mice is a frequent experimental challenge. A number of techniques including micro-CT angiography, fluorescent angiography, laser-Doppler perfusion imaging electron pramagnetic resonance and nuclear magnetic resonance can be used to assess the anatomic extent and functional state of an arterial circulation in a given organ. The chapter discusses the application of these tools in adult mice.
Body Image and Body Type Preferences in St. Kitts, Caribbean: A Cross- Cultural Comparison with U.S. Samples Regarding Attitudes Towards Muscularity, Body Fat, and Breast Size

We investigated body image in St. Kitts, a Caribbean island where tourism, international media, and relatively high levels of body fat are common. Participants were men and women recruited from St. Kitts (n = 39) and, for comparison, U.S. samples from universities (n = 618) and the Internet (n = 438). Participants were shown computer generated images varying in apparent body fat level and muscularity or breast size and they indicated their body type preferences and attitudes. Overall, there were only modest differences in body type preferences between St. Kitts and the Internet sample, with the St. Kitts participants being somewhat more likely to value heavier women. Notably, however, men and women from St. Kitts were more likely to idealize smaller breasts than participants in the U.S. samples. Attitudes regarding muscularity were generally similar across samples. This study provides one of the few investigations of body preferences in the Caribbean.
Cellular Adaptation: Journey from Smooth Muscle Cells to Neurons

In the 1960s, it became clear that the adaptation of smooth muscle to denervation was different from that of skeletal muscle. The supersensitivity of denervated smooth muscle extended to agonists unrelated to the lost neurotransmitter and developed on a tissue-dependent time course of several days to several weeks. Several procedures, in addition to denervation, that interrupted excitatory transmission, elicited the phenomenon. The supersensitivity occurred without changes in density or affinity of receptors but correlated with a partial depolarization of the smooth muscle cells. The phenomenon could be mimicked by procedures that acutely depolarized the cells. Electrophysiological, biochemical, and molecular data established that the depolarization was due to reduced electrogenic pumping and reduced density of the Na + ,K + pump. The triggering event for the development of such supersensitivity is not interruption of contact of neurotransmitter with its receptor, but rather the decreased activity of the adapting cells. This is clear from the fact that the inhibitory action of opioids produces similar sensitivity changes in several different populations of guinea pig neurons, including S-type neurons of the myenteric plexus. Subcutaneous implantation of morphine pellets in guinea pigs induces adaptation of S neurons expressed as nonspecific subsensitivity to inhibitory agonists (opioids, α 2 -adrenoceptor agonists, 2-chloroadenosine) and supersensitivity to excitatory agonists (nicotine, 5-hydroxytryptamine, K + ). These changes are accompanied by a partial depolarization of the S neurons and decreased electrogenic Na + ,K + pumping. Chronic implantation of morphine pellets also produces similar nonspecific changes in sensitivity in neurons of the nucleus tractus solitarius and locus ceruleus. It is suggested that depressed activity of these neurons leads to an electrophysiological adaptation, presumably due to reduced density of Na + ,K + pump proteins, as demonstrated in smooth muscle.
The sweet, sweet smell of diacetyl

Can worms distinguish between odorants that are perceived through the same neuron? Perhaps any odorant that activates AWA or AWC smells the same to the worm, and chemoattraction results simply from the activation of those neurons. Alternatively, the worm may distinguish between odorants detected by the same cell by activating different ion conductances (hyperpolarizing versus depolarizing) or by having different odors elicit different firing patterns in that neuron. Determining the odor-induced electrical responses of these neurons by patch–clamp techniques would shed light on this issue. While patch–clamping specific neurons is technically difficult in C. elegans, the availability of worms expressing the GFP specifically in AWA cells (Sengupta et al. 1996xSengupta, P., Chou, J.H., and Bargmann, C.I. Cell. 1996; 84Abstract | Full Text | Full Text PDF | PubMed | Scopus (316)See all ReferencesSengupta et al. 1996) should facilitate this approach.The availability of an odorant receptor with a defined chemical specificity makes several interesting experiments possible. The binding affinity of ODR-10 for diacetyl and other ligands could be determined by expressing these receptors in culture. It would be interesting to determine whether ODR-10 can function in heterologous systems. For example, would transgenic expression of ODR-10 in mouse olfactory neurons generate mice with acute sensitivity to diacetyl? Expressing ODR-10 in other chemosensory neurons in C. elegans might make those cells sensitive to diacetyl. This may alter chemosensory behavior to diacetyl in ways that might provide insight into the function of those neurons (and may be less disrupting than laser ablation). If vertebrate odorant receptors could be functionally expressed in C. elegans, olfactory behavioral assays might provide a strategy to determine the odorant sensitivity of specific vertebrate receptors. Answers to these questions will provide further insight into the specificity and universality of olfactory signaling mechanisms and the nature of Lucretius's pore.
Polymerization of furandicarbonyl chloride with bisphenol A poly(2,5-furandiylcarbonyloxy-1,4-phenylenedimethylmethylene-1,4-phenyleneoxycarbonyl)

Abstract Polymerization of 2,5-furandicarbonyl chloride with bisphenol A in four systems was studied. Catalysed polymerizations in tetrachloroethane solution at 155°C using AlCl 3 or Zn dust yielded coloured polymer with intrinsic viscosities of 0.24 and 0.23, respectively in about 80% yield. Uncatalysed solution polymerization in chloroform at ambient temperature using triethylamine as an acid acceptor gave a 90% yield of a white, film-forming polymer with an intrinsic viscosity of 0.5. Interfacial polymerization in benzene yielded a polymer of the same viscosity but in reduced yield (16%). Thermal analysis by differential scanning calorimetry revealed that thermal decomposition begins at about 225°C and is superimposed on an apparent crystallization exotherm at ∼250°C and an apparent melting endotherm at ∼320°C.
Use of a novel elution regimen reveals the dominance of polyreactive antinuclear autoantibodies in lupus kidneys

Objective The autoantibody specificities that dominate the deposits in lupus kidneys remain unclear. Reasoning that previously utilized elution buffers such as acidic glycine and ammonium thiocyanate may not have been maximally effective in eluting all Ig deposits from the kidneys, this study was conducted to experiment with a stronger dissociating agent, urea-glycine. Methods Seven antinuclear antibody–positive, nephritic female (SWR × NZB)F1 (SNF1) lupus mice were selected for the elution study. Deposited Ig was eluted from their kidneys using 3 different elution buffers: 0.15M glycine-HCl buffer, 1.3M ammonia thiocyanate/0.15M glycine-HCl buffer, and 5M urea/0.15M glycine-HCl buffer. All eluates were tested for specificity against a variety of nuclear and glomerular antigens. Results Compared with conventional elution buffers, the urea-based regimen eluted severalfold more IgG and IgM antinuclear antibodies from the kidneys of nephritic SNF1 lupus mice. IgG anti–double-stranded DNA (anti-dsDNA) antibodies were not only the most prevalent species in these renal deposits, they were also heavily enriched in the kidneys, relative to the corresponding serum levels. A substantial fraction of the anti–single-stranded DNA and antihistone/DNA (but not antihistone) reactivity in these eluates was due to cross-reactive anti-dsDNA antibodies. No reactivity with SSA, SSB, Sm, RNP, Jo-1, Scl-70, or ribosomal P antigens could be demonstrated in these eluates. Importantly, the urea-glycine eluates differed from the conventional eluates in having significantly greater reactivity to glomerular substrate and laminin. Conclusion This novel urea-based elution provides further support for the dominance of antibodies in lupus kidneys, with strong polyreactivity to DNA and glomerular substrate.
Bullying perpetration and subsequent sexual violence perpetration among middle school students.

Abstract Purpose This study examines the association between bullying experiences and sexual violence (SV) perpetration among a sample of middle school students (n = 1391; males and females in grades 5–8) across five middle schools in a Midwestern state. Methods We include waves 1 and 2 of a larger longitudinal study that aimed to track the overlap between bullying and SV victimization and/or perpetration across a 3-year period. Wave 1 data were collected in the spring of 2008, and wave 2 data were collected in the fall of 2008. Student participants completed a series of scales in a paper and pencil survey. After missing data imputation, a total sample of 1391 students was analyzed. Results Using cutoff scores, 12% of males and 12% of females could be considered bully perpetrators. Thirty-two percent of the boys (22% of girls) reported making sexual comments to other students, 5% of boys (7% of girls) spread a sexual rumor, and 4% of boys (2% of girls) pulled at someone's clothing. Bullying perpetration and homophobic teasing were significant predictors of sexual harassment perpetration over time. Conclusions Given the overlap among bullying, homophobic teasing perpetration, and SV perpetration, future studies should address the link among these forms of aggression so that prevention programs can be enhanced to address gender-based bullying and sexual harassment.
Theme: Teachers' Beliefs Helping Student Teachers Think about Teaching: Another Look at Lou

This article provides an in-depth study of one student during his two semesters of student teaching in a graduate preservice program. Data for the study were drawn from the student's dialogue jour nals, documents, interviews with supervisors, and observation and interview of the student during his first year of teaching. The interpretive focus is on how a program designed to prepare deliberative teachers can serve a student who resists reflective thinking. Findings suggest that although the dialogue journal provides an effective index of student thinking, it must be used appropriately by supervisors and may need to be supplemented with other tools for development of reflective thought, such as the personal journal.
The Effect of Amphotericin B on the Water and Nonelectrolyte Permeability of Thin Lipid Membranes

This paper reports the effects of amphotericin B, a polyene antibiotic, on the water and nonelectrolyte permeability of optically black, thin lipid membranes formed from sheep red blood cell lipids dissolved in decane. The permeability coefficients for the diffusion of water and nonelectrolytes (PDDi) were estimated from unidirectional tracer fluxes when net water flow (Jw) was zero. Alternatively, an osmotic water permeability coefficient (Pf) was computed from Jw when the two aqueous phases contained unequal solute concentrations. In the absence of amphotericin B, when the membrane solutions contained equimolar amounts of cholesterol and phospholipid, Pf was 22.9 ± 4.6 µsec-1 and PDDHDH2O was 10.8 ± 2.4 µsec-1. Furthermore, PDDi was < 0.05 µsec-1 for urea, glycerol, ribose, arabinose, glucose, and sucrose, and σi, the reflection coefficient of each of these solutes was one. When amphotericin B (10-6 M) was present in the aqueous phases and the membrane solutions contained equimolar amounts of cholesterol and phospholipid, PDDHDH2O was 18.1 ± 2.4 µsec-1; Pf was 549 ± 143 µsec-1 when glucose, sucrose, and raffinose were the aqueous solutes. Concomitantly, PDDi varied inversely, and σi directly, with the effective hydrodynamic radii of the solutes tested. These polyene-dependent phenomena required the presence of cholesterol in the membrane solutions. These data were analyzed in terms of restricted diffusion and filtration through uniform right circular cylinders, and were compatible with the hypothesis that the interactions of amphotericin B with membrane-bound cholesterol result in the formation of pores whose equivalent radii are in the range 7 to 10.5 A.
Laboratory crosses and genetic analysis of natural populations demonstrate sexual viability of invasive hybrid watermilfoils (Myriophyllum spicatum × M. sibiricum)

Abstract The hybrid offspring of invasive Eurasian watermilfoil (Myriophyllum spicatum) and native northern watermilfoil (Myriophyllum sibiricum) are highly invasive and have recently been considered to be of special management concern. Hybrid watermilfoils can reproduce asexually via fragmentation, but it is unknown if they can reproduce sexually. Here, we use laboratory crosses of hybrid watermilfoil genotypes to demonstrate that they can be sexually viable. In addition, a Bayesian analysis of Amplified Fragment Length Polymorphism (AFLP) data from natural populations of parental and hybrid watermilfoils was used to determine whether there was evidence for sexual reproduction by hybrid watermilfoils in natural populations. While many hybrid genotypes were estimated to be first generation hybrids, we found strong evidence for sexual reproduction in the form of later generation hybrids (F2 backcrosses, or later generation hybrids). Our study provides strong evidence that hybrids can, and frequently do, reproduce via sexual reproduction in natural populations. The capacity for sexual reproduction by hybrid watermilfoils has important management implications. The production of viable seeds may serve as an important source for the recolonization of previously treated lakes or areas within lakes. In addition, seeds may provide opportunities for colonization of new lakes (e.g., through water fowl). Thus, managers may consider practices that limit the production of seeds. In addition, sexual reproduction by hybrids may provide opportunities for the generation of unique genotypes through genetic recombination, some of which may be more invasive than their parental genotypes. Therefore, further consideration of sexual reproduction by hybrid watermilfoils is warranted.
E Pluribus Tres: The 2009 Nobel Prize in Chemistry

This year's Nobel Prize in Chemistry celebrates a multitude of research areas, making the difficult selection of those most responsible for providing atomic details of the nanomachine that makes proteins according to genetic instructions. The Ribosome and RNA polymerase (recognized in 2006) structures highlight a puzzling asymmetry at the origins of biology.
Investigation of calcium-induced, noncovalent association of calmodulin with melittin by electrospray ionization mass spectrometry

Noncovalent association of Ca2+-loaded calmodulin with a target peptide melittin was studied by electrospray ionization mass spectrometry (ESI-MS). ESI-MS does not reveal any binding of the apocalmodulin to the melittin. Partial loading of calmodulin with calcium leads to weak association with melittin. Upon binding of two calcium ions to the protein, changes in the conformation of calmodulin occur; these changes are sufficient to promote binding of melittin. Saturation of the protein with Ca2+ (a distribution of up to seven calcium ions is detected) induces a large increase of the binding to melittin. The stoichiometry of peptide binding to calmodulin is 1:1.
Experimental evaluation of intelligent assistance for navigation

Abstract Modern user interfaces make extensive use of navigation, a metaphor based on wayfinding in a physical space. Navigation can be an effective solution for many problems in understanding and manipulating a complex information space. Unfortunately, current research toward domain-independent, intelligent assistance for navigation lacks some important conceptual and practical tools for evaluation. This article describes an empirical study of assisted navigation that investigates the relationship between the quality of the assistance and overall performance. Our definition of quality is based on the information retrieval concepts of precision and recall. We use the limitations of the study results to motivate the development of a general-purpose navigation testbed. By separating the concerns of retrieving navigational data, maintaining and managing the resulting information space, and providing different views into the space, the testbed facilitates the development of navigational mechanisms and supports their evaluation. The testbed will act as a foundation for future work toward the automated generation of intelligent tools for navigational assistance.
Strategic Biomarkers for Drug Development in Treating Rare Diseases and Diseases in Neonates and Infants

There are similar challenges in developing a product designed to treat patients with a rare disease and drugs to treat critically ill neonates and infants. Part of the challenge in developing such products as well as identifying the optimal dosing regimen for the treatment of young children arises from the complex interrelationship between developmental changes and changes in biomarkers responsive to drug therapy. These difficulties are further compounded by our lack of understanding of the key physiological factors that cause the differences in clinical responses between adults and neonates and infants. Regulatory efforts have succeeded in overcoming these challenges in many areas of pediatric and orphan drug development. Strategic applications of biomarkers and surrogate endpoints for the development and approval of a product used to treat an orphan disease will be highlighted with examples of approved products. Continued efforts are still needed to fill in our knowledge gap and to strategically link biomarkers and surrogate endpoints to clinical responses for rare diseases and diseases affecting neonates and infants.
Surfing for Problems: Advocacy Group Strategy in U.S. Forestry Policy

John Kingdon sets out a multiple streams approach to policymaking, whereby problems, solutions, and politics develop independently of one another. Kingdon's work suggests that advocates with pet policies may continually search the problem stream, looking for prominent issues to attach to their preferred solutions. I call this process “problem surfing.” This paper provides an empirical test of problem surfing through the use of a case study of environmental advocacy. The paper examines Wilderness Society and Sierra Club advocacy for sustainable forestry practices from 1971 to 1994 through an analysis of articles in member magazines and interview data. Problem surfing is revealed to be a complex strategic process. I find evidence that advocacy groups adjust the problems they associate their solutions with over time to take advantage of salient issues. However, problem surfing appears to be influenced by more than just problem salience.
Noninvasive measurement of moisture distribution in individual wheat kernels by magnetic resonance imaging

The distribution and migration of moisture in wheat kernels during storage and milling are important for controlling wheat quality and milling performance. A non-destructive microscopic magnetic resonance imaging (MRI) technique was applied to measure the 3D distribution of moisture in individual wheat kernels. Soft white winter wheat kernels at approximately 12% moisture content were measured. A 3D Fourier transform pulse sequence with a short echo time (TE) was used to acquire proton images. The image data were zero- filled to improve spatial resolution. The spatial resolution of the images was 78 micrometers X 62 micrometers X 62 micrometers . The 3D proton density images were related to the 3D moisture distribution in the wheat kernels. For wheat kernels equilibrated to a water activity of 0.53 aw, the moisture distribution in the starchy endosperm of the wheat was fairly uniform in the three principal (orthogonal) directions. To quantify moisture distribution and movement in wheat kernels during the moisture-tempering process, the microscopic MRI with a shorter TE 3D pulse sequence will be used in future research. The results of the measurements will be used to characterize the quantity and nature of kernel moisture and relate these to kernel physiology, physical-chemical properties, and milling performance.© (1995) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.
Identification and restoration of lapsed skills for primary care providers.

Objective: Individualized educational programs based upon structured comprehensive evaluations have the highest opportunity for success in addressing the needs of physicians with lapsed skills. The purpose of this article is to describe the Physician Prescribed Educational Program (PPEP), an integrated series of programs that incorporate a formalized, structured evaluation strategy. Methods: The PPEP is structured to determine: 1) The presence of deficits which are amenable to educational remediation, 2) The likelihood that an appropriate educational program can be developed, and 3) The structure of such a program. Results: Of 300 referrals, 100 have received evaluations thus far. A wide range of deficits were addressable, although there were specific exclusions to participation. Conclusions: Administrators and others who wish to undertake these efforts should avail themselves of educational and other resources but should not expect rapid results. With careful planning and execution, these programs can provide appropriate and successful experiences for participants.