cssi/SciSciGPT-SciSciNet huggingface dataset:
Abstract A25: Differentiation of human naive T cells to various effector memory cell subtypes correlates with increased binding of the B subunit of Type-IIb heat-labile enterotoxin (LT-IIb-B5) to its cognate ganglioside receptors

The initial antigenic activation of T cells involves localization of the T-cell receptor to lipid rafts, of which gangliosides are major components. To understand the role of lipid rafts in the activation and differentiation of CD4+ and CD8+ T cells, it is necessary to dissect the ganglioside composition in each respective T-cell subset. In the present study, we used the B subunits of type-II heat-labile enterotoxins (LT-IIa-B5, LT-IIb-B5 and LT-IIc-B5), which possess defined ganglioside-binding specificities, as molecular probes to dissect the membrane ganglioside composition of human T cell subsets. Peripheral blood mononuclear cells isolated from leukocyte reduction filters by Ficoll density gradient centrifugation were stained with recombinant LT-IIa-B5, LT-IIb-B5, mutant LT-IIb-B5(T13I) or LT-IIc-B5 and with monoclonal antibodies to CD4, CD8, CD27, CD45RA, CD45RO and CD62L followed by flow cytometric analysis. Our results show that ligands for LT-IIa (gangliosides GD1b, GM1, and GT-1b), LT-IIb (gangliosides GD1a, GT1b and GM2), and LT-IIc (gangliosides GM1, GM2, and GM3) are increasingly expressed during differentiation from naiIˆve (CD4+ or CD8+CD45RO-CD27+) to memory (CD4+ or CD8+CD45RO+CD27+) T cells, and that discrete subsets of central memory (CD4+ or CD8+CD45RA-CD62L+), effector memory (CD4+ or CD8+CD45RA-CD62L-), and terminally differentiated effector memory (CD4+ or CD8+CD45RO+CD27-) T cells express the highest ganglioside levels, particularly of LT-IIb-ligands. On the other hand, mutant LT-IIb-B5(T13I), which had negligible binding in vitro to gangliosides GD1a, GT1b, and GM2, exhibited no detectable binding to naive or central memory T cells, but significantly bound subsets of terminally differentiated effector memory (CD4+ and CD8+) T cells. Our results suggest an important role for gangliosides GD1b and GM1 in naive T-cell responses, while central memory, effector memory, and terminally differentiated effector memory T-cell responses may be more dependent upon gangliosides GD1a and GT1b. Furthermore, the lymphocyte-binding activities of LT-IIb-B5(T13I) confirm that its parental B-pentameter essentially recognizes gangliosides GD1a, GT1b, and GM2 on T cells and suggest that LT-IIb-B5 (T13I) may bind to one or more unknown receptor(s) expressed on subsets of terminally differentiated effector memory (CD4+ and CD8+) T cells. Citation Format: Taylor A. Johnson, Madison K. Ritter, Mary-Peyton A. Knapp, Robert O. Rainer, Nathalie D. King-Lyons, Terry D. Connell, Sergio Arce. Differentiation of human naive T cells to various effector memory cell subtypes correlates with increased binding of the B subunit of Type-IIb heat-labile enterotoxin (LT-IIb-B5) to its cognate ganglioside receptors [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2019 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2020;8(3 Suppl):Abstract nr A25.
A 54-Year-Old Woman With Shortness of Breath After Nephrolithotomy.

Case Presentation A 54-year-old woman was admitted to the general medical floor after undergoing percutaneous nephrolithotomy via the supracostal approach. On postprocedure day 1, she developed low-grade fever, dry cough, shortness of breath, and palpitations.
Sociodemographic factors associated with high risk for firearm suicide among US adults

This cohort study assesses the association of firearm suicide risk with sociodemographic characteristics among US adults.
Negative accounting earnings and gross domestic product

Konchitchki and Patatoukas Journal of Accounting and Economics 57 (1-2), 76–88, (2014a) show that aggregate accounting earnings growth predicts future nominal gross domestic product (GDP) growth and that professional macro forecasters do not fully incorporate the information contained in aggregate accounting earnings. Based on results from prior literature, which find that accounting earnings reflect bad economic news in a timelier manner than good news, we condition Konchitchki and Patatoukas’s GDP growth forecast model on the sign of earnings changes. We show that negative changes in aggregate earnings predict future GDP growth while positive changes in earnings do not. Furthermore, we show that professional macro forecasters underreact to the information contained in negative changes in aggregate earnings about future GDP growth. Additional tests suggest our findings are a result of conservative accruals in earnings.
The association between breastfeeding during late pregnancy and the occurrence of small for gestational age and prolonged active phase of labor among Peruvian women

Maternal nutritional status is considered an important risk factor for the progression of labor and birth weight. Poor birth outcomes, such as experiencing a prolonged labor or being small for gestational age, represent a risk factor for maternal as well as infant morbidity and mortality. Understanding the factors that may affect maternal nutritional status is necessary. The objective of the present study was to examine the association between the practice of breastfeeding during late pregnancy and the risk of having a prolonged active phase of labor (PAPL) or giving birth to a small for gestational age (SGA) baby. A case-control study was conducted with two matched controls for each case of SGA or PAPL. Between March 2006 and April 2007 three Peruvian hospitals were visited daily. Mothers who met the inclusion criteria were interviewed and information regarding maternal as well as newborn characteristics was extracted from their clinical charts. Hair samples for zinc analysis were collected on a subsample of mothers. The association between the overlap of breastfeeding during late pregnancy and the risk of SGA or PAPL was tested with conditional logistic regression. No differences were found in the proportion of mothers who breastfed during late pregnancy between the cases of SGA or PAPL and their respective controls. In addition, there was no difference in maternal hair zinc concentration between cases and controls. Our findings do not support the hypothesis that the practice of breastfeeding during late pregnancy represents a risk for having a small for gestational age infant or experiencing a prolonged active phase of labor. However, research to confirm these results is needed since negative birth and postnatal consequences have been previously associated with this practice.
Pediatric Spontaneous Pneumothorax: Does Initial Treatment Affect Outcomes?

Abstract Background Primary spontaneous pneumothorax (PSP) commonly occurs in adolescents, most commonly in males, and has recurrence rates between 20% and 60%. Surgical therapy has long been debated regarding its role in preventing recurrence, with no current consensus on guidelines for care. The purpose of this study is to examine the effect of treatment type on recurrence rates in pediatric PSP. Methods This is a single-institution, institutional review board–approved retrospective analysis of patients aged 1 to 18 diagnosed with their first occurrence of PSP between 2009 and 2017. Patient demographics, hospital course, and outcomes over a 2-y period were collected. Patients were divided into nonoperative (oxygen therapy only) management, chest tube placement, and surgical management. The primary outcome was the recurrence rate. Results Sixty-four patients diagnosed with PSP met inclusive criteria. The mean age was 15.5, and 48 (75%) of patients were men. Twenty-one patients (33%) underwent nonoperative treatment, 24 patients (37.5%) underwent operative treatment with video-assisted thoracoscopic surgery or open thoracotomy, and 19 patients (30%) underwent chest tube or pigtail placement alone. Fifteen patients (23.4%) experienced a recurrence within 2 y: 6 patients (29%) from the nonoperative treatment group, 4 (21%) who were treated with the chest tube only, and 5 (21%) who underwent video-assisted thoracoscopic surgery or open thoracotomy. No statistically significant difference in recurrence rates was found between treatment groups. Pneumothorax size was found to differ between treatment type; larger pneumothoraces were more likely to undergo surgical intervention (P = 0.0003). Smaller pneumothoraces were associated with higher rates of recurrence on multivariate logistic regression analysis (P = 0.046). Conclusions Recurrence of PSP in adolescents was found to be 23.4% after 2-y follow-up. Smaller-sized pneumothoraces were associated with higher rates of recurrence, but treatment type did not significantly affect recurrence rates.
Mobile Bat Acoustic Routes Indicate Cavity-Roosting Species Undergo Compensatory Changes in Community Composition Following White-Nose Syndrome

Emerging pathogens can cause mass mortalities in susceptible species. High host mortality, in turn, can alter species composition, community structure and function. White-nose syndrome (WNS) is an emerging wildlife disease introduced to North America that has decimated millions of cave-dependent bats. For areas affected by WNS, there have been reports of community compositional changes, but compensatory changes to species composition following WNS has only been suggested, not reported. To determine if compensatory changes to species composition occur following WNS, we used seven years of data from statewide citizen science mobile bat acoustic routes initiated by the Ohio Division of Wildlife in 2011. We hypothesized that migratory bat abundance increased and cave-dependent bat abundance decreased following the emergence of WNS in the study period (2011–2017). Our hypothesis was based on the higher susceptibility of cave-dependent bats than migratory bats to infection and WNS mortality. We used two sets of models to identify abundance trends of each species found in Ohio and species grouped by wintering and roosting behaviors that are putatively important to changes in species composition post-WNS. Following WNS, we found a compensatory change in species in summer months from cave-dependent, cavity-roosting species (Myotis species and Eptesicus fuscus) to migratory, cavity-roosting species (Nycticeius humeralis and Lasionycteris noctivagans). However, for species that roost in foliage in the summer, we did not detect an increase in migratory species (Lasiurus borealis and Lasiurus cinereus) paired with a decrease in cave-dependent species (Perimyotis subflavus). The observed post-WNS trends in bat populations could suggest shifts in bat species composition in other areas where WNS is established.
Evaluating Soil Water Redistribution under Mobile Drip Irrigation, Low-Elevation Spray Application, and Low-Energy Precision Application Using HYDRUS

AbstractA study to assess soil water redistribution under mobile drip irrigation (MDI), low-energy precision application (LEPA), and low-elevation spray application (LESA) was conducted under a cen...
Alternatives to Perpetual Chemotherapy for Metastatic Pancreatic Cancer.

With the advent of multi-agent chemotherapy for metastatic pancreatic cancer, subgroups of patients whose disease responds durably to treatment are emerging. Although this is wonderful progress in the face of a deadly illness, cumulative toxicities of perpetual chemotherapy over months or even years of treatment degrade quality of life and organ function, in addition to fueling eventual therapeutic resistance. The POLO trial demonstrated a benefit of maintenance olaparib compared to placebo in patients with germline pathogenic variants in BRCA1 or BRCA2. The success of this trial, albeit in a limited subset of patients, suggests that there may be opportunity to study this alternative treatment strategy as a paradigm for a broader group of patients with advanced pancreatic cancer. This article discusses the phenotypic and genotypic signatures of patients with pancreatic cancer that may provide the basis upon which to design rational maintenance clinical trials.
Surgical Treatment of Upper Extremity Segmental Myoclonus in an Adolescent with Chiari Malformation and Cervicothoracic Syrinx.

Background Myoclonus is an involuntary movement disorder characterized by semirhythmic jerking movements of muscle groups but is rarely seen in association with Chiari malformation type I (CM-1). CM-1 is a frequently encountered clinical entity in pediatric neurosurgery characterized by caudal displacement of the cerebellar tonsils with or without syringomyelia. We report a pediatric patient who presented with upper extremity myoclonus and was found to have CM-1 and a complex septated cervicothoracic syrinx eccentric to the left. Case presentation A 12-year-old female presented with 6 months of headaches and upper extremity paresthesias who subsequently developed a left upper extremity segmental myoclonus after a fall. MRI demonstrated a CM-1 and a large complex cervicothoracic syrinx with a midline and left paracentral cavities. Her myoclonus was nonepileptic and refractory to clonazepam, cyclobenzaprine, and gabapentin. She underwent an intradural Chiari decompression and duraplasty. Postoperatively, she had complete resolution of her segmental myoclonus. Discussion This case demonstrates a durable resolution of posttraumatic upper extremity segmental myoclonus after surgical decompression of a CM-1 with syringomyelia. Thus, Chiari decompression should be considered in cases of myoclonus with CM-1 and syringomyelia.
The economic reality of the forest and fuel management deficit on a fire prone western US national forest.

Abstract Recent extreme wildfire seasons in the United States (US) have rekindled policy debates about the underlying drivers and potential role forest management can play in reducing fuels and future wildfire. Most US western national forests face a substantial backlog of treatments and manifold management issues related to wildfire, forest health, and wildfire protection and constitute the major part of the wildfire problem. However, the precise schedule and detailed assessments that map the type and amount of treatments needed, as well as the associated cost are rarely assessed. We simulated restoration trajectories on the US fire prone Umatilla National Forest that faces complex management challenges related to wildfire and forest resiliency. The treatments were targeted to specific ecological conditions based on a decision tree developed in consultation with specialists. Planning areas were then prioritized based on fire protection of the wildland-urban interface (WUI), forest products, and stand resiliency. The results revealed a backlog of 211,893 ha, that when treated would generate $320 million in revenue from forest products, and cover 80% of the forest. The treatment area estimate was more than double prior estimates based on ecological departure from historic condition. Financial sensitivity analysis showed that high priority fuel treatments were revenue positive on 22% of the planning areas. The study established a restoration blueprint in terms of amount, location, and treatment type to support funding requests to the agency and schedule internal and external capacity to complete the work. The work also contributes to ongoing collaborative restoration planning to help stakeholders understand the opportunity cost of specific restoration objectives. The case study and framework can be widely extrapolated to the national forests in the western US to improve financial evaluation of forest and fuel management and estimate future management inputs. This work represents a rare instance of a bottom-up spatially explicit assessment of a restoration backlog, and prioritization of planning areas to reduce that backlog on a US national forest.
Conceptualization and Assessments of the Consumers’ Meta-Cognitive Awareness with Respect to Purchase Decision

The current study has attempted to conceptualize consumers’ meta-cognitive awareness while making purchase decision this is also attempting to validate the instrument measuring consumer’s Meta cognition awareness. The study has performed the review of the literature on meta-cognition and its respective construct dimensions in relation to consumer psychology. Subscale of six dimensions covering the consumers’ knowledge and regulation have been explored and examined through the survey data participated by 1156 individuals. Using structural equation modeling the study has attempted to test, validate and cross-validate the measurement with three homogeneous groups of consumers. This has attempted to examine internal consistency, confirm factor structure, convergent and discriminate validity and structural reliability of the scale. The study has further given theoretical and practical implication.
Gastrointestinal Surgical Emergencies in the Neutropenic Immunocompromised Patient.

Surgeons encounter neutropenic patients through elective or emergency consultation with increasing regularity. As medical management continues to extend the lives of patients with benign hematologic diseases, hematologic malignancies, solid malignancies, or iatrogenic neutropenia, more patients are presenting with infectious complications caused and/or complicated by their neutropenia. This leaves surgeons in the difficult position of managing medically fragile patients with unusual presentations of common disease processes. These patients often fall outside of classical guidelines and treatment pathways. Many studies addressing these issues are retrospective and non-randomized. Here, we review common emergency gastrointestinal surgery scenarios and their management in the setting of a neutropenic patient. While biliary disease, appendicitis, anorectal disease, and perforations will be covered in detail, an extensive appreciation of a patient’s medical or oncologic disease course and appropriate utilization of consultants such as interventional radiology, gastroenterology, and hematology is often necessary.
Conceptions of the Natural and the Social in Walras's Economic Thought

Neoclassical economics is sometimes said to overlook the institutional character of markets, treating them as ‘natural.’ I address whether this criticism applies to Leon Walras. Walras's position i...
Influence of Menopausal Hormone Therapy on the Breast: Counseling Your Patients Before You Prescribe

Menopausal hormone therapy (HT) aims to improve a woman's quality of life by treating bothersome menopausal symptoms associated with low estrogen levels. Although HT is prescribed to millions of wo...
Aerodynamics of Blasts-Diffraction of Blast Around Finite Corners

The reflection and diffraction of strong shocks around corners of arbitrary, finite angle, and the resulting pressure and density fields have been calculated by two different methods. The second method, which is a hyperbolic procedure, appears to be useful in various types of nonlinear problems. At the end a modified procedure of the second method is outlined which promises faster convergence.
Professional and bureaucratic organization in large public accounting firms

TEE growth of the public accounting T profession has been at a time in history characterized by phenomenal changes in organizational structures. The work of the certified public accountant has been so inextricably tied to these organizational changes that his own mode of professional association has been adapted to meet the new demands created by these changes. Primarily the demand for professional audits by large and widely dispersed corporations has wrought the CPA's professional, yet bureaucratic,' mode of organization, i.e., the large, complex multi-office firm. Within the theoretical modes of professional and bureaucratic organization there are common and mutually exclusive characteristics.2 The impact of these characteristics within the firm may confront the individual CPA with divergent organizational orientations. More specifically, an individual within the firm may be faced with norms (guides to behavior) that support alternative forms of organization. If an individual is expected to behave as a "professional" and as an "employee" (more broadly a bureaucrat) at the same time, he may experience a conflict in selecting which behavior to follow. Large public accounting firms appear to be unique since no other currently known profession has been able to develop professionally through the widespread use of nationally or regionally organized offices. Blending and maintaining partially conflicting organizational modes as "going concerns" is undoubtedly a testimonial to the professional CPA's perseverance and ingenuity. In general, this study3 seeks to identify and to analyze an organizational disagree-
Handling Disaggregate Spatiotemporal Travel Data in GIS

Disaggregate travel data is not new to urban transportation planning studies, but it is infrequently handled in a GIS environment. With the evolution of urban travel demand models from aggregate models to disaggregate models and from a trip-based paradigm to an activity-based paradigm, there is a growing need of managing disaggregate travel data with spatial and temporal components in a GIS environment. At the data organization level, the main challenge is to efficiently store the data by minimizing redundancy while maintaining the complex relationships among the data items. The data organization should allow users to retrieve and visualize disaggregate travel data according to various possible combinations of spatial, temporal, and attribute criteria. This paper presents an implementation that employs a relational database approach and dynamic segmentation to organize the spatial, temporal, and attribute components in a sample travel diary data set. Discussions of the benefits and shortcomings associated with this approach are provided, along with suggestions for future research.
Drop Phenomena Affecting Liquid Extraction

Publisher Summary A liquid–liquid mass-transfer operation proceeds in several distinguishable steps. Dispersion of one phase into the other creates a large interfacial area. It may be accomplished by mixing impellers, nozzles, orifices, perforated plates, drip points or edges, tower packings, eductors, centrifugal pumps, or by the turbulence created when the two phases are forced at high speed through a pipeline. There are certain conditions under which drops of one phase, surrounded by a film of another phase and the whole moving in a field of the first phase, can come together to form a layer that can best be described as a liquid–liquid foam. The shape of a drop forming slowly at a submerged orifice is the basis for the hanging-drop method for determining interfacial tension. The shape of a liquid drop moving in a liquid field is dependent upon the balance between the hydrodynamic pressure exerted because of the relative velocities of drop and field and the surface forces, which tend to make the drop a sphere. As the drop size in a given system is increased above the laminar-flow region, a size is reached at which the drop flattens and assumes a generally oblate ellipsoidal shape. This chapter explores shape, oscillation, and layers of different types of drop. Flocculation and coalescence and field–fluid currents are also discussed in the chapter.
The corporate control job: Breaking the mold: The function has broadened—and will broaden more

Abstract Many company controllers—especially if they are accounting or finance men—have lost part of their jobs by choosing to work only within familiar financial channels. They fail to see that the modern concept of business control has broadened and will continue to do so. It now covers a wide range of tasks—from the managing of a typing pool to the over-all financial control of the company. In companies where control continues to have a narrow meaning, financial controls are emphasized, whether or not they are the best ones to use. The author presents an approach that can help controllers recognize new control areas and deal with them.
vPath: precise discovery of request processing paths from black-box observations of thread and network activities

Discovering end-to-end request-processing paths is crucial in many modern IT environments for reasons varying from debugging and bottleneck analysis to billing and auditing. Existing solutions for this problem fall into two broad categories: statistical inference and intrusive instrumentation. The statistical approaches infer request-processing paths in a "most likely" way and their accuracy degrades as the workload increases. The instrumentation approaches can be accurate, but they are system dependent as they require knowledge (and often source code) of the application as well as time and effort from skilled programmers. We have developed a discovery technique called vPath that overcomes these shortcomings. Unlike techniques using statistical inference, vPath provides precise path discovery, by monitoring thread and network activities and reasoning about their causality. Unlike techniques using intrusive instrumentation, vPath is implemented in a virtual machine monitor, making it agnostic of the overlying middleware or application. Our evaluation using a diverse set of applications (TPC-W, RUBiS, MediaWiki, and the home-grown vApp) written in different programming languages (C, Java, and PHP) demonstrates the generality and accuracy of vPath as well as its low overhead. For example, turning on vPath affects the throughput and response time of TPC-W by only 6%.
Cultivating Strategic Imagination in the Next Generation Engineering Systems Transportation Professional

Potentially the biggest failure in transportation planning is a failure of imagination. How many times have we heard, “we did not see it coming,” “it wasn’t on our radar,” “nobody could have planned for THAT?” The increasing complexity and interconnectedness of transportation systems worldwide and the connectedness of those systems with other critical infra-structure, such as telecommunications, and electricity, as well as the changing nature of land-use planning demands that the next generation transportation professional have an intellectual toolkit that is broader and more strategically oriented than today’s tactical and operational perspective. The ability to understand the complicated dynamics of transportation systems as complex, large-scale, socio-technical systems requires the cultivation of an ability to imagine the possible and understand the consequences of what sometimes are called low probability, high impact events. Although one cannot plan for every remote possibility, one does need to develop a framework for interpreting the potentially far-reaching implications of seemingly minor events and to craft strategies that can effectively respond to these possibilities. One may think of this capacity as strategic imagination. In this paper we explore scenario planning for cultivating strategic imagination and, in particular, examine the use of scenario planning as a way to enable the individual transportation professional to think more creatively and, through the incorporation of this technique into the transportation planning process, create a common medium for multiple stakeholders to think collaboratively and reflect upon the deeper connections among socio-technical systems. We report on a case study of a scenario planning exercise for the Centre Region, Centre County, Pennsylvania held in cooperation with the U. S. Department of Transportation to illustrate how scenario planning may be used to think imaginatively, but practically, of the connections between land-use and transportation. In this context, scenario planning may be seen as an effective tool to be used for strategic engineering leadership.
Acute Presentation of Chiari I Malformation with Hemiparesis in a Pediatric Patient.

Background Chiari I malformation (CM-I) is defined by cerebellar tonsillar herniation through the foramen magnum. Patients typically present with chronic complaints, including headache, dizziness, and numbness, although there are few reports in the literature of pediatric patients presenting acutely with neurological deficit caused by CM-I. We report a child who presented acutely with hemiparesis and magnetic resonance imaging findings consistent with CM-I and spinal cord edema. Case Description A 3-year old boy with normal development presented with difficulty walking and increased drooling. His mother stated he was running into objects and had balance issues for several days. Neurological examination showed ataxia with falling to the right after a few steps and weakness of the right arm and leg. His medical history was remarkable only for mild asthma, although he had recently been treated for an upper respiratory viral infection. Computed tomography of the head demonstrated no brainstem mass. Magnetic resonance imaging of the head and cervical spine showed tonsillar ectopia approximately 2 cm below the craniocervical junction with increased T 2 signal in the spinal cord from C1 to C3 consistent with syringomyelia and cord edema. The patient underwent suboccipital craniectomy with removal of the posterior arch of C1 and dural patch graft. His postoperative course was unremarkable, with complete resolution of his symptoms at his 1-month follow-up visit. Conclusions This case highlights an unusual presentation of CM-I with neurological deficit related to spinal cord edema, possibly precipitated by the "water-hammer" effect of this patient's coughing fits. Providers should be aware of the acute presentations of CM-I.
American Muslim Women Challenging Conventional Understanding of Islam

This lecture was presented at Kendal of Ithaca on September 28, 2009. The Streaming Video File is provided by cdnapi.katura.com
The Epstein-Barr virus BMLF1 promoter contains an enhancer element that is responsive to the BZLF1 and BRLF1 transactivators.

Abstract We have previously shown that the Epstein-Barr virus (EBV) immediate-early gene product, BZLF1, can activate expression of the EBV BMLF1 immediate-early promoter in EBV-positive, but not EBV-negative, B cells, suggesting that the BZLF1 effect may be mediated through another EBV gene product (S. Kenney, J. Kamine, E. Holley-Guthrie, J.-C. Lin, E.-C. Mar, and J. S. Pagano, J. Virol. 63:1729-1736, 1989). Here, we show that the EBV BRLF1 immediate-early gene product transactivates the BMLF1 promoter in either EBV-positive or EBV-negative B cells. Deletional analysis revealed that both the BZLF1-responsive region and the BRLF1-responsive region of the BMLF1 promoter are contained within the same 140-base-pair FokI-PvuII fragment located 300 base pairs upstream of the mRNA start site. This FokI-PvuII fragment functions as an enhancer element in the presence of the BRLF1 transactivator and contains the sequence CCGTGGAGA ATGTC, which is strikingly similar to the BRLF1-responsive region of the EBV DR/DL enhancer (A. Chevallier-Greco, H. Gruffat, E. Manet, A. Calender, and A. Sergeant, J. Virol. 63:615-623, 1989). The effect of BZLF1 on the BMLF1 promoter is likely to be indirect and mediated through the BRLF1 transactivator.
Legislative Behavior in Romania: The Effect of the 2008 Romanian Electoral Reform

This article analyzes the impact of electoral rules on legislators’ rate of vote defection from their party position in legislatures while accounting for how party-leadership strength mediates this impact. To this end it looks at the effect of the 2008 Romanian electoral reform. The reform shifted the electoral system from a closed-list proportional representation to one in which all candidates run in single-member districts. The analysis finds that because party leaders have maintained their leverage intact, the impact of the reform was minimal, with legislators being more likely to defect in less important votes only, in which party leaders allow defection. Also, after the reform legislators are more likely to use other means to impress their voters, such as legislative initiation and cabinet questioning. These forms of behavior are more accepted by party leaders.
Scaffolding Informal Learning in Science Museums: How Much Is Too Much?.

This research follows on a previous study that investigated how digitally augmented devices and knowledge building could enhance learning in a science museum. In this study, we were interested in understanding which combination of scaffolds could be used in conjunction with the unique characteristics of informal participation to increase conceptual and cognitive outcomes. Three hundred seven students from nine middle schools participated in the study. Six scaffolds were used in various combinations. The first was the digital augmentation. The next five were adaptations of knowledge-building scaffolds. Results demonstrated that digital augmentations, posted questions, and participation in collaborative groups may be the optimal design for improving conceptual learning (content knowledge) while preserving informal participation behaviors. However, our results also showed that obtaining deeper cognitive gains such as ability to theorize only occurred in the most highly scaffolded condition in which students demonstrated much decreased informal participation behaviors. We discuss the implications of our results with respect to the broader research on improving learning in informal science learning environments.
EGFR inhibits DNA mismatch repair

Safeguarding the integrity of the genome should not be left to chance. Indeed, all organisms have highly effective mechanisms to detect and remove errors and lesions in DNA. DNA mismatch repair (MMR) serves as the final safeguard in assuring the fidelity of DNA replication from bacteria to humans and backstops the nucleotide selection and exonuclease proofreading activities of replicative polymerases (Fig. 1) (1⇓–3). The loss of MMR results in greatly elevated rates of spontaneous mutation, is the underlying cause of Lynch syndrome colon cancer, and is implicated in a subset of sporadic tumors. In its postreplication capacity, MMR functions during S phase in close association with the replication fork. This process is mediated by proliferating cell nuclear antigen protein (PCNA), a lynchpin in regulating access and activity of DNA polymerases and other proteins involved in replication, repair, and recombination (4). EGFR, a member of the HER family of receptor tyrosine kinases (RTKs) that span the plasma membrane, regulates cell proliferation, differentiation, and motility in response to extracellular ligands (e.g., EGF) (5, 6). Ligand binding promotes dimerization and allosteric activation of cytoplasmic kinase domains. Autophosphorylation initiates signaling cascades involving RAS/MAPK, PI(3)K/Akt, Jak/STAT, and others. EGFR also translocates to the nucleus where it influences replication, repair, and transcription and is linked to poor prognoses in several malignancies, but molecular mechanisms are largely unknown (7, 8). In the nucleus, EGFR phosphorylates PCNA, increasing its stability (9). This would be expected to have important consequences, but the functional significance was unclear until now. In PNAS, Ortega et al. reveal that phosphorylation of PCNA by EGFR inhibits MMR in cells and switches DNA synthesis in vitro from high-fidelity to error-prone (Fig. 2 … [↵][1]1To whom correspondence should be addressed. Email: peggyh{at}niddk.nih.gov. [1]: #xref-corresp-1-1
Action, movement, and neurophysiology

Action is to be distinguished from (mere) bodily movement not by reference to an agent's intentions, or his conscious control of his movements (Sect. I), but by reference to the agent as cause of those movements, though this needs to be understood in a way which destroys the alleged distinction between agent‐causation and event‐causation (Sect. II). It also raises the question of the relation between an agent and his neurophysiology (Sect. III), and eventually the question of the compatibility of purposive and mechanistic accounts of human behaviour (Sect. IV). For the two to be compatible it is necessary that, e.g., intentions and brain states be not merely co‐existent but also causal equivalents, in a way which allows for the mechanical explanation of teleological states — or vice versa.
Chronic Management of Seizures in the Syndromes of Idiopathic Generalized Epilepsy

As a group, idiopathic generalized epilepsies (IGEs) have the highest rates of complete seizure control with medication. However, there are little evidence-based data to guide drug choice for treatment. Examples of IGE include absence epilepsy, generalized tonic-clonic epilepsy, and juvenile myoclonic epilepsy. Generalized epilepsies seem to be particularly vulnerable to seizure aggravation, and medications that are primarily effective against partial seizures are more commonly involved in seizure aggravation than other medications. A review of current research has shown that only a few medications can control IGE without potentially causing seizure aggravation. Broad-spectrum antiepileptic drugs such as valproate (VPA), lamotrigine, and topiramate are extremely effective at controlling a variety of seizures without causing excessive seizure aggravation. Among these drugs, VPA has the longest clinical experience history and the largest body of published data.
Insulin Sensitivity and Variability in Hepatitis C Virus Infection Using Direct Measurement

Studies investigating insulin resistance (IR) in chronic hepatitis C virus (HCV) infection have used surrogate measures of IR that have limited reliability. We aimed to describe the distribution and risk factors associated with IR and its change over time in HCV using direct measurement. One hundred two non-cirrhotic, non-diabetic, HCV-infected subjects underwent clinical, histologic, and metabolic evaluation, and 27 completed repeat evaluation at 6 months. Insulin-mediated glucose uptake was measured by steady-state plasma glucose (SSPG) concentration during the insulin suppression test. Three subjects with diabetes were excluded and 95 completed all testing. SSPG ranged from 39 to 328 mg/dL (mean 135 mg/dL) and was stable over time (mean SSPG change −0.3 mg/dL). SSPG was associated with Latino ethnicity (Coef 67, 95 % CI 37–96), BMI (Coef 19 per 5 kg/m2, 95 % CI 5–32), ferritin (Coef 1.4 per 10 ng/ml, 95 % CI 0.2–2.5), male gender (Coef −48, 95 % CI −80 to −16), and HDL (Coef −16, 95 % CI −28 to −5 mg/dL). Current tobacco use (Coef 55, 95 % CI 19–90), steatosis (Coef −44, 95 % CI −86 to −3), and increases in BMI (Coef 30 per 5 kg/m2, 95 % CI 6–53) and triglyceride (Coef 3.5 per 10 mg/dL, 95 % CI 0.3–6.7) predicted change in SSPG. There was a wide spectrum of insulin resistance in our HCV population. Host factors, rather than viral factors, appeared to more greatly influence insulin action and its change in HCV.
Do investors overreact to earnings warnings

Abstract This study shows that contrary to what many managers argue, there is no overreaction to earnings warnings. Our sample consists of 986 firms that had significantly lower fourth-quarter earnings than analysts' forecasts during the period of 1983 to 1998. About 9% of these firms released quantitative earnings information while 6.5% of the firms disclosed qualitative earnings information prior to the formal earnings report dates. We find that although these firms experience significant stock price declines during the warning period, their share prices are still higher than the economic values, calculated using Ohlson's residual income model. Further, long-run operating and stock performance of these firms are not more positive than the performance of firms that do not warn. We also find that investor reaction to both warning and non-warning firms is positively related to the firms' long-run stock and operating performance. These findings support the argument that investors do not overreact to the warnings but base their reaction on anticipated long-term performance of the firms.
Determination of fatigue related discontinuity state of 7000 series of aerospace aluminum alloys

Abstract The current methods of fatigue life estimation do not model the interaction of stress with microstructural discontinuities. An experimental study of fatigue crack nucleation in 7075-T6 and 7079-T6 aluminum alloy sheet was performed to obtain more information on the role of discontinuities in the microstructure and to determine the relative contributions of each type of discontinuity. Some specimens were machined from recently manufactured material without any coating (cladding or anodizing). Some were fabricated from old clad-anodized material from an aircraft fuselage and old anodized material from a stock of unused wing panels. In the uncoated materials, large constituent particles and the surface roughness were found to be important factors in fatigue crack nucleation. In the coated materials, discontinuities related to the cladding and anodizing appeared to be the controlling factors in crack nucleation and particles did not play any role. The coated specimens showed a low scatter and a relatively low fatigue life. Multiple nucleation sites were observed in the coated materials.
Vitreoscilla hemoglobin aids respiration under hypoxic conditions in its native host.

Summary When Vitreoscilla were grown in medium containing 60 mM sodium nitrite under both normal and limited aeration conditions, the levels of Vitreoscilla hemoglobin (VHb) were decreased by greater than 90%, while the levels of the terminal respiratory oxidase, cytochrome bo , were increased 350% under normal aeration and 7–23% under limited aeration. Cytochrome function, as measured by both NADH and ubiquinol oxidases for cells grown under both conditions, increased in parallel (by 150–222% and 8–56%, respectively, for the two activities). Nitrite in the medium inhibited Vitreoscilla growth at both normal and limited aeration. The inhibition of VHb at 60 mM nitrite decreased whole cell respiration to the greatest degree in stationary phase for growth in limited aeration conditions, which was the most oxygen poor condition tested. These results are consistent with the originally proposed role for VHb, as an aid to respiration under hypoxic conditions.
Instabilities in deeply supersaturated systems.

We have investigated the instabilities against phase decomposition in a deeply supersaturated system based on a two-dimensional lattice-gas model. The free-energy change is evaluated using a regular solution model and is expressed as a function of both the amplitude and the wavelength of the concentration fluctuations. A unified picture which includes both classical theories of nucleation and growth and spinodal decomposition emerges naturally from the present work. As the system is quenched to nearly a classical spinodal boundary, it may take a condensation route in which both the amplitude of fluctuations (the concentration of the atoms in the condensing islands) and the wavelength of fluctuations (the size of the islands) vary simultaneously in time during condensation. The system is shown to transform smoothly from the metastable state to the unstable state without a sharp boundary, a prediction which is consistent with recent cluster-dynamics calculations. The present theory also accounts for a recently discussed phenomenon known as the ``physical spinodal.'' In addition to the familiar long-wavelength, small-density spinodal decomposition, it is shown that, in the unstable region far from the spinodal boundary, nuclei of high density can grow spontaneously without a nucleation barrier.
DHEA and cognition in HIV-positive patients with non-major depression.

Background Dihydroepiandrosterone (DHEA) has been investigated for its potential role in improving cognition in a number of patient populations. Treatment options are limited for HIV-associated neurocognitive disorders. Objective The authors tested the effect of DHEA administration on the cognitive functioning of HIV-positive subjects with non-major depression. Method The neuropsychological testing data for 60 HIV-positive patients enrolled in a clinical trial for non-major depression were analyzed to determine if DHEA-treated patients demonstrated improved cognitive functioning versus placebo. Results At baseline, 80% of the sample met criteria for asymptomatic cognitive impairment. No benefit in cognitive performance was found on 16 of 17 neuropsychological measures evaluated. One measure showed a modest benefit for placebo-treated patients over DHEA. Conclusion DHEA treatment was not associated with improved cognitive performance in HIV-positive patients with non-major depression.
Activation of C3a receptor is required in cigarette smoke-mediated emphysema

Exposure to cigarette smoke can initiate sterile inflammatory responses in the lung and activate myeloid dendritic cells (mDCs) that induce differentiation of T helper type 1 (Th1) and Th17 cells in the emphysematous lungs. Consumption of complement proteins increases in acute inflammation, but the contribution of complement protein 3 (C3) to chronic cigarette smoke-induced immune responses in the lung is not clear. Here, we show that following chronic exposure to cigarette smoke, C3-deficient (C3(-/-)) mice develop less emphysema and have fewer CD11b(+)CD11c(+) mDCs infiltrating the lungs as compared with wild-type mice. Proteolytic cleavage of C3 by neutrophil elastase releases C3a, which in turn increases the expression of its receptor (C3aR) on lung mDCs. Mice deficient in the C3aR (C3ar(-/-)) partially phenocopy the attenuated responses to chronic smoke observed in C3(-/-) mice. Consistent with a role for C3 in emphysema, C3 and its active fragments are deposited on the lung tissue of smokers with emphysema, and smoke-exposed mice. Together, these findings suggest a critical role for C3a through autocrine/paracrine induction of C3aR in the pathogenesis of cigarette smoke-induced sterile inflammation and provide new therapeutic targets for the treatment of emphysema.
MS-Xα calculations of the electron affinities and ionization potentials of some heavy metals and their hydrides and fluorides†

MS-X..cap alpha.. calculations were performed for the neutral species and the transition states for the positive and negative ions of the heavy metal atoms Mo, W, Re, Ir, Pt, and U and their diatomic hydrides and fluorides. Both nonspin-polarized and spin-polarized calculations were performed. The main purpose of this study was to gain insight into which negative ion species might be preferable to try to prepare for use in ion sources for tandem accelerators. 27 references.
Stoichiometries and Energetics of Cationic Nanoparticle-Membrane Complexes

The nanoparticle-membrane interaction is essential to nanotheraputic design and nanotoxicity concerns. The equilibrium structure was determined for phospholipid membranes interacting with one type of nanoparticle, poly(amidoamine) dendrimers, at the atomistic and molecular scale via both experimental and theoretical approaches. The resulting dendrimer-phospholipid complex depends on both the number of primary amines per dendrimer and the dendrimer size. Large dendrimers (> 7 nm diameter) induce vesicle-encased dendrimers and significant membrane disruption. In contrast, small dendrimers (< 5 nm diameter) bind to the membrane surface without individually inducing significant membrane disruption. Techniques such as isothermal titration calorimetry (ITC), molecular dynamics (MD), and differential scanning calorimetry (DSC) were used for examination of the equilibrium structures and identifying the mechanisms of nanoparticle-induced membrane disruption.Third-, fifth-, and seventh-generation poly(amidoamine) dendrimers (G3, G5, and G7, respectively) are shown here in complexes with phospholipids. The stoichiometries and dimensions of the dendrimer-lipid complexes indicate small dendrimers (G3) saturate with lipids on a planar membrane, medium-sized dendrimers (G5) induces local membrane curvature and/or binds to multiple bilayer surfaces, and each larger dendrimer (G7) becomes encased by a lipid vesicle. These understandings will guide nanoparticle design in both medical and industrial applications.View Large Image | View Hi-Res Image | Download PowerPoint Slide