cssi/SciSciGPT-SciSciNet huggingface dataset:
ALTRE: workflow for defining ALTered Regulatory Elements using chromatin accessibility data

Regulatory elements regulate gene transcription, and their location and accessibility is cell-type specific, particularly for enhancers. Mapping and comparing chromatin accessibility between different cell types may identify mechanisms involved in cellular development and disease progression. To streamline and simplify differential analysis of regulatory elements genome-wide using chromatin accessibility data (e.g. DNase-seq, ATAC-seq), we developed ALTRE (ALTered Regulatory Elements), an R-package and associated R Shiny web app. ALTRE makes such analysis accessible to a wide range of users - from novice to practiced computational biologists.
UKA TO TKA: IS IT AS GOOD AS A PRIMARY RESULT?

As with any revision knee arthroplasty, the first rule of revision is to ensure that the reason for failure has been identified, as revision for pain alone is associated with poor results. This is particularly important when considering revision of a UKA, as surgeons may have a lower threshold for revision than following TKA given the perception that the revision is “easy” and that the pain is “probably from the unresurfaced compartments”. In a multi-center study, we found that many patients undergoing revision of a failed UKA do not have an appropriate evaluation for infection. Evaluation should include a screening ESR and CRP and if abnormal, an aspiration of the knee joint for synovial fluid WBC count, differential and culture. To revise a UKA to a TKA, we perform the revision as we would a primary TKA, ignoring the implanted femoral component and using it to assist with reference of femoral component rotation and for the distal femoral cut; the component is not removed until it must for the final preparation. After finishing the femoral component cuts, the tibia is completely exposed prior to carefully removing the tibial component and re-cutting the tibia. In our experience of 45 consecutive both component revisions of UKA to TKA at Rush, 44 used primary implants (98%), including cruciate retaining implants in 36 of these 44 knees (82%; the balance were PS implants) and tibial stems were utilised in 6 of 44 knees (14%). In order to better understand the outcomes of revision of failed UKA we studied 49 patients revised from UKA to TKA and 43 revised from HTO to TKA and matched them to 43 aseptic, both component revision TKA and 97 primary TKA. At a mean of 4.8 years, the KSS and Function Scores in the UKA to TKA, HTO to TKA and primary TKA cohorts were similar. Total operative times were significantly higher in the HTO to TKA and revision TKA groups. Length of hospital stay was shorter in the primary TKA cohort. The rate of complications and reoperations were higher in the HTO to TKA and revision TKA groups compared to the UKA to TKA and primary TKA groups. Based on these results, we believe that revising an HTO and UKA to a TKA both had functional outcomes more similar to a primary than a revision TKA, however, the complication rate of revising an HTO was more similar to a revision than a primary TKA.
A National Study of Online Learning Leaders in US Higher Education

Online learning in US higher education continues to grow dramatically. The most recent estimates indicate that about 30% of all students enroll in at least one online course (Allen & Seamen, 2016). As this important type of academic offering has become increasingly important to institutions of higher education, Presidents and Provosts have frequently established leadership positions to coordinate and direct their efforts in this area. But what do we know about the leaders who have been charged with managing this academic transformation? This systematic national study, a first of its kind, sheds light on the leadership that is guiding this new teaching and learning environment.
Rapid amino acid analysis of beers using flow-gated capillary electrophoresis coupled with side-by-side calibration

Amino acid analysis is an important procedure to measure free amino acids (AAs) in various samples including proteins, blood plasma, urine, foods and beverages. Due to the complexity of these samples, chemical separations are required to determine the composition and quantities of AAs. Here, we report a fast and accurate approach to quantify AAs in beers. This method was based on a flow-gated capillary electrophoresis (CE) system coupled with alternate injections enabled by a micro-fabricated switch. AAs in beer samples and standard solutions were fluorogenically derivatized with 2,3-naphthalenedicarboxaldehyde (NDA) in the presence of cyanide. The two derivatized mixtures were then loaded into two separate micro-syringes and were alternately delivered to the flow gate for rapid injections and separations. Here, the standards functioned as side-by-side calibration and quantitation references. The separation of 21 AA derivatives was achieved within 90 seconds under an electric field of 1470 V cm−1 by using optimized background electrolytes consisting of 40 mM sodium tetraborate, 60 mM sodium dodecyl sulfate, and 2 mM 2-hydroxypropyl-β-cyclodextrin, and theoretical plates of >300k for most AAs were obtained. The beer matrix effect was studied, and the quantitation of AAs was conducted by directly comparing the peak heights of analytes with those of their individual self-standards. The method was validated with respect to the linearity, precision, and accuracy, and was applied to the measurements of 21 AAs in eight different beer samples. The results demonstrated the quantitative capability of flow-gated CE coupled with alternate injections for side-by-side calibration that was able to compensate for potential drift of the CE system. The developed method is expected to be valuable for high-throughput amino acid analysis of a variety of samples.
Fundamental Concepts of Distributed Computing Used in Big Data Analytics

The study of distributed computing started in late 70s and many fundamental concepts has been proposed and successfully used in this area since then. Those concepts are used in various Big Data Technologies of present time, which are in turn the key building blocks of the Big Data Analytics used today in various businesses and industries. So it is essential for practitioners of Big Data Analytics to understand these fundamental concepts related to Distributed Computing. In this chapter we cover these fundamental concepts of Distributed Computing along with the Quality of Service aspects associated with them with examples wherever applicable.
Revisiting the four C's of managing a successful simulation project

This paper aims to discuss four key elements imperative to conducting an effective simulation study and how they impact the progress of the study. • The Clue: determining when and why to use simulation and what issues will be addressed • The Cash: understanding the financial costs and the impact of the project • The Commitment and the Courage: the importance of having a team committed to the endeavor and having the courage to make hard decisions so that the project will be successful Each of these key factors are critical to starting a successful project and keeping it on track towards proposing effective solutions for the problems the model was designed to address.
An off-target effect of BX795 blocks herpes simplex virus type 1 infection of the eye

Herpes simplex virus type 1 (HSV-1) causes recurrent mucocutaneous lesions in the eye that may advance to corneal blindness. Nucleoside analogs exemplified by acyclovir (ACV) form the primary class of antiherpetic drugs, but this class suffers limitations due to the emergence of viral resistance and other side effects. While studying the molecular basis of ocular HSV-1 infection, we observed that BX795, a commonly used inhibitor of TANK-binding kinase 1 (TBK1), strongly suppressed infection by multiple strains of HSV-1 in transformed and primary human cells, cultured human and animal corneas, and a murine model of ocular infection. Our investigations revealed that the antiviral activity of BX795 relies on targeting Akt phosphorylation in infected cells, leading to the blockage of viral protein synthesis. This small-molecule inhibitor, which was also effective against an ACV-resistant HSV-1 strain, shows promise as an alternative to existing drugs and as an effective topical therapy for ocular herpes infection. Collectively, our results obtained using multiple infection models and virus strains establish BX795 as a promising lead compound for broad-spectrum antiviral applications in humans.
Does Subcutaneous Infiltration of Liposomal Bupivacaine Following Single-Level Transforaminal Lumbar Interbody Fusion Surgery Improve Immediate Postoperative Pain Control?

Study design Retrospective case-control study using prospectively collected data. Purpose Evaluate the impact of liposomal bupivacaine (LB) on postoperative pain management and narcotic use following standardized single-level low lumbar transforaminal lumbar interbody fusion (TLIF). Overview of literature Poor pain control after surgery has been linked with decreased pain satisfaction and increased economic burden. Unfortunately, opioids have many limitations and side effects despite being the primary treatment of postoperative pain. LB may be a form of pre-emptive analgesia used to reduce the use of postoperative narcotics as evidence in other studies evaluating its use in single-level microdiskectomies. Methods The infiltration of LB subcutaneously during wound closure was performed by a single surgeon beginning in July 2014 for all single-level lumbar TLIF spinal surgeries at Landstuhl Regional Medical Center. This cohort was compared against a control cohort of patients who underwent the same surgery by the same surgeon in the preceding 6 months. Statistical analysis was performed on relevant variables including: morphine equivalents of narcotic medication used (primary outcome), length of hospitalization, Visual Analog Scale pain scores, and total time spent on a patient-controlled analgesia (PCA) pump. Results A total of 30 patients were included in this study; 16 were in the intervention cohort and 14 were in the control cohort. The morphine equivalents of intravenous narcotic use postoperatively were significantly less in the LB cohort from day of surgery to postoperative day 3. Although the differences lost their statistical significance, the trend remained for total (oral and intravenous) narcotic consumption to be lower in the LB group. The patients who received the study intervention required an acute pain service consult less frequently (62.5% in LB cohort vs. 78.6% in control cohort). The amount of time spent on a PCA pump in the LB group was 31 hours versus 47 hours in the control group (p=0.1506). Conclusions Local infiltration of LB postoperatively to the subcutaneous tissues during closure following TLIF significantly decreased the amount of intravenous narcotic medication required by patients. Well-powered prospective studies are still needed to determine optimal dosing and confirm benefits of LB on total narcotic consumption and other measures of pain control following major spinal surgery.
Global Warming in Asheville, North Carolina

As predicted by Svante Arrhenius in 1896, global warming is taking place as evidenced by documented rises in average sea level of about 1.7 mm/year during the 20th century. There have been naturally occurring cycles of global warming and cooling throughout the history of the world. Much has been written about the catastrophe that global warming would present to humankind, but the effects of elevated atmospheric carbon dioxide concentrations upon ambient annual mean temperatures at the local level in western North Carolina are not easily recognized at this time. Observation of annual mean temperatures in western NC did not immediately indicate a detectable temperature increase over the period of analysis. However, annual weather data for Asheville, North Carolina from 1965 until 2006 indicated an upward trend in annual mean surface temperatures of about 1.3°F (0.72°C) while global atmospheric carbon dioxide concentrations have risen about 62 ppm. This paper will present an examination of regional ambient annual surface temperature trends in western North Carolina relative to global atmospheric carbon dioxide concentrations. The focus will be on analysis of data to determine cyclical patterns.
Reliability of new indices of radiographic osteoarthritis of the hand and hip and lumbar disc degeneration

Objective To develop a method for assessing the presence and severity of radiographic features of osteoarthritis (OA) of the hip and hand, and thoracic and lumbar disc degeneration. Methods An atlas illustrating scoring of individual radiographic features and summary grades for individual joints was developed. Three readers evaluated 31 pelvic films, 27 hand films, and 25 lateral lumbar and thoracic spine films selected from a community based sample of healthy elderly women. Interrater agreement between the 3 readers, and test-retest agreement for one of the readers, were estimated by the intraclass correlation coefficient (ICC) and kappa statistic. Results Interrater agreement (ICC, unless otherwise noted) for individual radiographic features of the hip ranged from 0.66 for osteophytes to 0.80 for narrowing. For the 9 interphalangeal (IP) joints of the hand, agreement ranged from 0.42 (kappa) for sclerosis to 0.93 for narrowing, and for the lumbar spine from 0.55 (kappa) for sclerosis to 0.95 for narrowing. Interrater agreement for summary grades of radiographic findings was as follows: hip, 0.81; 5 distal interphalangeal joints (DIP), 0.89; 4 proximal interphalangeal joints (PIP), 0.82; and lumbar spine, 0.93. Intrarater agreement for summary grades was as follows: hips, 0.79; 5 DIP, 0.86; 4 PIP, 0.81; and lumbar spine, 0.90. Conclusion We have developed reliable indices of the presence and severity of radiographic features of hip and hand OA and spinal disc degeneration for use in epidemiologic studies. The assessment includes grading of individual radiographic features, which allows for the independent variation in these features often found in OA and a summary grade of disease that is derived from the presence and severity of individual features.
Responses to the Ten Questions [On National Security Posed by the Journal of National Security Forum Board of Editors]

In 2009, the Journal of the National Security Forum Board of Editors posed ten questions on national security to a group of national-security law experts. Contributors were free to answer as many of the ten questions as they wished. All responses were published in a special issue of the William Mitchell Law Review. I answered the following three questions: 3. What are the lessons from detaining non-U.S. citizens, labeled enemy combatants, at Gitmo? 4. What is left for the Supreme Court to decide after the Boumediene decision? 10. What is the most important issue for American national security?The SSRN download includes the list of all ten questions and my three answers. This document is also available on the William Mitchell Law Review website.
Quadratic Forms in n Variables

In Chapter 3.8 we considered a quadric surface in ℝ3 with the equation $$ a{x^2}\;{\rm{ + }}\;2bxy\; + \;2cxz\;{\rm{ + }}\;d{y^2}\;{\rm{ + }}\;2eyz\;{\rm{ + }}\;f{z^2}\;{\rm{ = }}\;{\rm{1,}} $$ (1) where a, b, c, d, e, f are constants.
Customer retention in freemium applications

Over the last decade, many software companies have moved away from selling traditional packaged goods and toward providing “freemium” services. Under this business model, companies give away their basic product and generate revenue by repeatedly selling additional features and content. With this movement, away from one-off transactions and toward longer-term, repeated customer relationships, businesses are increasingly using analytics to understand their customers’ behavior, with retention—a measure of the likelihood that a customer will return—being of particular importance. However, despite the value of measuring customer retention, there is no consensus on its definition. Using a unique dataset of freemium mobile games, this study compares and contrasts four commonly used retention measures and finds that a measure that takes into account when a user interacts with an application provides the highest correlation with future monetization. This study also provides empirical evidence of a positive relationship between customer retention and future monetization.
Marcus Rediker, The Fearless Benjamin Lay: The Quaker Dwarf Who Became the First Revolutionary Abolitionist

Marcus Rediker, The Fearless Benjamin Lay: The Quaker Dwarf Who Became the First Revolutionary Abolitionist (Boston: Beacon Press, 2017), 212 pp., $26.95 (hardcover), ISBN: 978-0-8070-3592-4.
Heterogeneous Integrations on Fan-Out RDL Substrates

As mentioned in Chap. 4 that TSV (through-silicon via) interposer is very expensive (Selvanayagam et al. in IEEE Trans Adv Pack 32(4), 2009, [1]; Chai et al. in IEEE Trans CPMT 1(5), 2011, [2]; Chien et al. in IMAPS Trans J Microelectron Pack 9, 2012, [3]; Chaware et al. in IEEE/ECTC Proc, 2012, [4]; Banijamali et al. in IEEE/ECTC Proc, 2011, [5]; Banijamali et al. in IEEE/ECTC Proc, 2012, [6]; Banijamali et al. in IEEE/ECTC Proc, 2013, [7]; Lau in 3D IC integration and packaging. McGraw-Hill, New York, 2016 [8]; Lau in Through-silicon via (TSV) for 3D integration. McGraw-Hill, New York, 2013, [9]; Lau in Reliability of RoHS compliant 2D & 3D IC interconnects. McGraw-Hill, New York, 2011, [10]) and a few silicon bridges have been proposed to replace the TSV interposers for heterogeneous integration applications. Recently, using the fan-out wafer/panel packaging technology (Lau in Fan-out wafer-level packaging. Springer, New York, 2018, [11]; Ko et al. in IEEE Trans CPMT, pp. 1561–1572, 2018, [12]; Lau et al. in IEEE Trans CPMT, pp. 1544–1560, 2018, [13]; Lau et al. in IMAPS Trans J Microelectron Electron Packag 15(4):148–162, 2018, [14]; Ko et al. in IEEE IMAPS Trans J Microelectron Electron Packag 15(4):141–147, 2018, [15]; Yoon et al. in IEEE/ECTC Proc: 1250–1254, 2012, [16]; Lau et al. in IEEE Trans CPMT 4(9):1407–1419, 2014, [17]; Lau et al. in IMAPS Trans J Microelectron Electron Packag:123–131, 2017, [18]; Lau et al. in IEEE Trans CPMT:991–1002, 2018, [19]; Lin et al. in IEEE/ECTC Proc:13–18, 2016, [20]) to make RDLs (redistribution-layers) on substrates to eliminate the TSV-interposer for heterogeneous integrations has been getting traction. At ECTC2013, Statschippac proposed using the fan-out flip chip to make the RDLs for the chips to perform mostly lateral communications. During ECTC2016, ASE and Mediatek used a similar technology to fabricate the RDLs with FOWLP and showed that the TSV interposer, wafer bumping, fluxing, chip-to-wafer bonding, cleaning, and underfill dispensing and curing are eliminated, i.e., TSV-less interposers. At ECTC2018, Samsung used chip-last or RDL-first to make the RDLs for the TSV-interposer. During SEMICON Taiwan 2018, TSMC also mentioned this technology and called it InFO_oS (integrated fan-out on substrate).
Memory-efficient, Global Phase-retrieval of Fourier Ptychography with Alternating Direction Method

We propose to use alternate direction method of multipliers (ADMM), to improve computational robustness of Fourier ptychographic microscopy (FPM). This method is highly parallel so it can be run efficiently on GPU or distributed CPUs.
Song production by the North Pacific right whale, Eubalaena japonica

This paper describes song production by the eastern North Pacific right whale (NPRW, Eubalaena japonica) in the southeastern Bering Sea. Songs were localized in real-time to individuals using sonobuoys. Singers whose sex could be determined were all males. Autonomous recorder data from 17 year-long deployments were analyzed to document and characterize song types. Four distinct song types were documented over eight years (2009-2017) at five distinct locations. Each song type consists of a hierarchical structure of 1-3 different repeating phrases comprised predominantly of gunshot sounds; three of the four songs contained additional sound types (downsweep, moan, and low-frequency pulsive call). Songs were detected annually (July-January); all song types remained consistent over eight years. Two different songs often occurred simultaneously, produced by different individuals; the same song was never detected simultaneously at the same location. The same song type was detected on the same day and time at two distant locations, indicating multiple individuals can produce the same song. These findings provide support that males produce song; it remains unknown if females also sing. NPRW is the first right whale species documented to produce song. Based on current knowledge about song in mysticetes, it is hypothesized that these songs are reproductive displays.
Mycobacterium abscessus Prosthetic Joint Infections of the Knee

M. abscessus complex prosthetic joint infections (PJI) of the knee are rare. We present a patient with an M. abscessus subsp. massiliense, a nontuberculous mycobacterium (NTM), peri-prosthetic knee infection who presented with wound drainage followed by sepsis. The published peer-reviewed literature on knee PJIs due to this organism is reviewed to highlight its clinical presentation,symptomatology, microbiology, surgical interventions, antimicrobial regimens, and outcomes.
Sustainable Crop Protection and Farming

Annually, between 20% and 40% of global crop production is lost due to pests. The sustainable protection of crops has immense relevance for the security of the food supply chain, in a world of growing population and shrinking resources. In the last decades, the increasing awareness of serious drawbacks coming from the use of pesticides stimulated studies aimed at identifying and developing new biological substances for crop protection, which are safer and more sustainable. Nonetheless, the global use of pesticides increased less than expected. Despite the positive results and the effectiveness and readiness of several products, biopesticides still represent a niche in the global pesticides market. This chapter discusses the main factors constraining the widespread adoption of biological pesticides and poses the urgent need to identify and standardize the most effective and efficient methods for the extraction and stabilization of biopesticide formulations, towards which intense research efforts should be directed. This chapter also illustrates the current trends of organic farming, its main differences and gaps compared to the conventional farming, the insufficient inclusion of benefits from organic farming and its drawbacks, and externalities affecting conventional intensive farming, as well as the potential of expanding the area covered by low-input farming to achieving multiple Sustainable Development Goals (SDGs).
Proving the shalls: Early validation of requirements through formal methods

Incomplete, inaccurate, ambiguous, and vola-tile requirements have plagued the software industry since its inception. The convergence of model-based development and formal methods offers developers of safety-critical systems a powerful new approach to the early validation of requirements. This paper describes an exercise conducted to determine if formal methods could be used to validate system requirements early in the lifecycle at reasonable cost. Several hundred functional and safety requirements for the mode logic of a typical flight guidance system were captured as natural language “shall” statements. A formal model of the mode logic was written in the RSML−e language and translated into the NuSMV model checker and the PVS theorem prover using translators developed as part of the project. Each “shall” statement was manually translated into a NuSMV or PVS property and proven using these tools. Numerous errors were found in both the original requirements and the RSML−e model. This demonstrates that formal models can be written for realistic systems and that formal analysis tools have matured to the point where they can be effectively used to find errors before implementation.
Sarcopenia is Distinct from Physical Frailty and Significantly Associated with Length of Stay after Transplantation

Purpose Our previous studies demonstrated an association between physical frailty by Fried frailty phenotype (FFP) with waitlist death and length of stay (LOS) after lung transplantation. We sought to evaluate the predictive ability of sarcopenia in patients undergoing evaluation for lung transplantation. Methods We identified 68 patients, ages 60-71, who had frailty evaluation by FFP or short performance physical battery (SPPB) with chest CT available for review during transplant evaluation. Using the software Osirix (Pixmeo, Switzerland), we determined the total area (in cm2) and average attenuation (in HU) of the right and left pectoralis muscle at the level of one slice above the aortic arch (Figure). Pectoralis was chosen as it resulted in more reproduceable measurements compared with intercostal muscles. Results Sarcopenia, as measured by either total pectoral area or average attenuation, was not significantly associated with patient age or physical frailty by FFP or SPPB. Sarcopenia was not associated with death on the waiting list or death in the first year after transplantation. Notably, however, patients with less sarcopenia were more likely to be transplanted (p= 0.022), a clinical outcome that was not associated with age, sex, or physical frailty. For patients who underwent transplantation during the period of study (n= 46), both lower total pectoral area and average attenuation were significantly associated with increased LOS after transplantation (p=0.002 and p=0.034, respectively). Conclusion Sarcopenia represents an attractive avenue for patient assessment, where chest CT evaluation is part of routine evaluation. No association was seen between physical frailty and sarcopenia, although both measures were predictive of clinical outcomes. This suggests the possibility of applying multiple assessments for patient risk stratification. Future studies are needed to determine the impact of optimizing nutrition and physical therapy in waitlisted patients.
Glycogen Synthase Kinase 3 Beta Regulates the Human Aryl Hydrocarbon Receptor Cellular Content and Activity

The aryl hydrocarbon receptor (AHR) is a cytosolic receptor which is involved in diverse cellular events in humans. The most well-characterized function of AHR is its ability to upregulate gene transcription after exposure to its ligands, such as environmental toxicants, dietary antioxidants, drugs, and endogenous ligands. The cellular content of AHR is partly controlled by its degradation via the ubiquitin–proteasome system and the lysosome-dependent autophagy. We used human cervical cancer (HeLa) cells to investigate how AHR undergoes protein degradation and how its activity is modulated. Since the glycogen synthase kinase 3 beta (GSK3β)-mediated phosphorylation can trigger protein degradation and substrates of GSK3β contain stretches of serine/threonine residues which can be found in AHR, we examined whether degradation and activity of AHR can be controlled by GSK3β. We observed that AHR undergoes the GSK3β-dependent, LC3-mediated lysosomal degradation without ligand treatment. The AHR can be phosphorylated in a GSK3β-dependent manner at three putative sites (S436/S440/S444, S689/S693/T697, and S723/S727/T731), which leads to lysosomal degradation of the AHR protein. Inhibition of the GSK3β activity suppresses the ligand-activated transcription of an AHR target gene in HeLa, human liver cancer (Hep3B), and human breast cancer (MCF-7) cells. Collectively, our findings support that phosphorylation of AHR by GSK3β is essential for the optimal activation of its target gene transcription and this phosphorylation may partake as an “off” switch by subjecting the receptor to lysosomal degradation.
Recalibrating Reform: The Limits of Political Change

Part I. Introduction: Introduction. Reconstructing governance 1. The theory and political processes of recalibration 2. The Supreme Court and transformative recalibration Part II. Legal Reform and its Delimitation: 3. Emancipation, the reconstruction era, and delimitation 4. Labor rights, the new deal era, and delimitation 5. Constitutional equal protection, the civil rights era, and delimitation 6. Explaining judicial delimiting behavior Part III. The Construction and Maintenance of Governance: 7. The entrenchment and maintenance of the Jim Crow order 8. The entrenchment and maintenance of industrial pluralism 9. The entrenchment and maintenance of the anti-classification order 10. Explaining order-affirming and tension-managing judicial behavior 11. Conclusion Acknowledgements Bibliography.
Interspecies Interactions Promote Multispecies Communities

Multispecies communities, not a collection of single-species colonies, compose human oral biofilms. The human oral microbiome is the most intensely studied and, perhaps, the best-characterized ecosystem in humans, but the organization of these species into multispecies communities at any point in time remains poorly understood. Genomic inquiry of community members will enable a fuller vision of each member’s metabolic contribution to the community. A central contributor to colonization of oral bacteria in biofilms is the universal ability of these species to attach to a surface: to teeth or to epithelial cell surfaces or to the bacterial surface of an already attached cell. Cells suspended in saliva are unable to multiply within a typical between-swallows interval due to the rapid salivary flow. Thus, adherence is essential before multispecies communities can develop and colonize the surface. Following coadherence and coaggregation, attached cells grow, as evidenced by incorporation of radiolabeled nucleosides and by cell division planes observed in the biofilms of intraoral mounted pieces of enamel or glass. Evidence-based two-species and three-species biofilms contribute in understanding species succession leading to a crossroad between health and disease in dental plaque biofilms. Virulence mechanisms exhibited by red complex periodontal pathogens are discussed in an inspired review of the interplay between pathogenic and commensal bacteria in disrupting host homeostasis. It is recognized that multispecies communities respond differently than pure cultures to antimicrobials.
Information Security Investment: Expected Utility Approach with Correlated Information Assets

This paper analyzes the information security investment decisions by a firm with two correlated information assets. When information assets are correlated, a firm may face additional losses compared to a loss from a single breach, and the probability of security breach on one set may increase the probability on the other. We model the security investment of a risk-taking firm as well as risk-neutral firm by taking an expected utility approach. We then compare the decisions made by a risk-taking firm to those made by a risk-neutral firm. We will also examine how decision maker allocates funds in protecting two information sets with a limited budget.
Influence of Nonionic Liposomal Composition on Topical Delivery of Peptide Drugs into Pilosebaceous Units: An in Vivo Study Using the Hamster Ear Model

Purpose. The purpose of this study was to test the hypothesis that nonionic liposomes facilitate the topical delivery of peptide drugs into pilosebaceous units. Methods. The hamster ear was used as a model for human pilosebaceous units. The deposition of a hydrophilic protein, alpha-interferon (α-IFN), into pilosebaceous units and other strata of the hamster ear 12 hours after topical in vivo application of three nonionic liposomal formulations, one composed of glyceryl dilaurate/cholesterol/polyoxyethylene-10-stearyl ether (Non-1), the second composed of glyceryl distearate/cholesterol/ polyoxyethylene-10-stearyl ether (Non-2) and the third composed of polyoxyethylene-10-stearyl ether/cholesterol (Non-3), a phospho-lipid-based liposomal formulation (PC) and an aqueous control solution (AQ) was determined. We also determined the deposition of a hydrophobic peptide, cyclosporin-A (CsA), into pilosebaceous units and other strata of the hamster ear after topical in vivo application of these liposomal formulations and a hydroalcoholic control solution (HA). Results. The deposition of α-IFN into the pilosebaceous units was in the order: Non-1 ≫ PC > Non-2 > Non-3 = AQ. The deposition of CsA into the pilosebaceous units was in the order: Non-1 ≫ HA > PC > Non-2 = Non-3. Conclusions. Despite differences in the hydrophobicities and size of the drug molecules, deposition into the various ear strata was significantly enhanced by the Non-1 liposomal system.
Maintenance, Loss, and Resurgence of T Cell Responses During Acute, Protracted, and Chronic Viral Infections

The acute phase of many viral infections is associated with the induction of a pronounced CD8 T cell response which plays a principle role in clearing the infection. By contrast, certain infections are not as readily controlled. In this study, we have used the well-defined system of lymphocytic choriomeningitis virus (LCMV) infection of mice to determine quantitative and qualitative changes in virus-specific CD8 T cell responses that rapidly resolve acute infections, more slowly control protracted infections, or fail to clear chronic infections. Acute LCMV infection elicits potent, functional, multi-epitope-specific CD8 T cell responses. Virus-specific CD8 T cells also expand, albeit to a lesser extent, during protracted LCMV infection. Under these conditions, there is a progressive diminution in the capacity to produce IL-2, TNF-alpha, and IFN-gamma. Changes in cytotoxic activities are also detectable but differ depending upon the specificity of the responding cells. As the infection is slowly resolved, a resurgence of cytokine production by virus-specific CD8 T cells is observed. CD4-deficient mice cannot control infection with certain strains of LCMV, but do mount multi-epitope-specific CD8 T cell responses that also lose effector capabilities; however, they are not maintained indefinitely in an unresponsive state as these cells become deleted over time. Overall, our findings suggest that constant high viral loads result in the progressive diminution of T cell effector functions and subsequent physical loss of the responding cells, whereas if the viral load is brought under control a partial restoration of CD8 T cell functions can occur.
A Critique of Suggested Diffuse Band Carriers

We summarize the discussions that took place on the last afternoon of the conference, on the various diffuse band carriers that were advocated by speakers during the week. This discussion was presented in the form of a “shoot-out”, in which the speakers were challenged to compare their models with a list of observational criteria that had been presented earlier in the conference. The summary given here is an attempt to reproduce the presentations that were made during the shoot-out, complete with comments on how well the proposed carriers did or did not satisfy the observational criteria. It is hoped that this summary will serve dual purposes: (1) to record the comments and ideas that were presented at the conference, since these remarks were not submitted in writing in any other format; and (2) to provide stimulation, if not inspiration, to future authors of diffuse band carrier models, who may want to see where previous suggestions have either succeeded or failed.
Postmetamorphic cell death in the nervous and muscular systems of Drosophila melanogaster

Programmed cell death occurs in the nervous and muscular system of newly emerged adult Drosophila melanogaster. Many of the abdominal muscles that were used for eclosion and wing-spreading behavior degenerate by 12 hr after eclosion. Related neurons in the ventral ganglion also die within the first 24 hr. Ligation experiments showed that the muscle breakdown is triggered by a signal from the anterior region, presumably the head, that occurs about 1 hr before adult emergence. The timing of this signal suggests that eclosion hormone may be involved. Although muscle death is triggered prior to ecdysis, it can be delayed, at least temporarily, by forcing the emerging flies to show a prolonged ecdysis behavior. In contrast to the muscles, the death of the neurons is triggered after emergence. The signal for neuronal degeneration is closely correlated with the initiation of wing inflation behavior. Ligation and digging experiments and behavioral manipulations that either blocked or delayed wing expansion behavior had a parallel effect in suppressing or delaying neuronal death.
A fuzzy logic controller view of participatory learning

The authors discuss the participatory learning model originally introduced by R.R. Yager (1990). They analyze the learning mechanism as a stable control strategy. It is shown that the learning mechanism used in participatory learning can be expressed in a rule base formulation. This rule base formulation is used to provide new learning rules. The Widrow-Hoff rule is modified to include a participatory learning mechanism. >
Systemic Levamisole-Induced Vasculitis in a Cocaine User without Cutaneous Findings: A Consideration in Diagnosis

Levamisole is a known immunomodulating agent frequently used as a cutting agent in cocaine consumed in the United States today. Numerous cases of anti-neutrophil cytoplasmic antibody (ANCA) vasculitis connected with the use of levamisole-adulterated cocaine have previously been reported in the literature, classically characterized by a retiform purpuric rash. We report a case of a crack-cocaine user without cutaneous abnormalities who developed ANCA-associated glomerulonephritis that progressed to renal failure. This case demonstrates the difficulties in solidifying the diagnosis of levamisole-induced vasculitis in the absence of cutaneous findings and the need to pursue more testing to establish causality in ANCA-associated vasculitis that has potential for severe end-organ damage in patients who continue to use cocaine.
Evaluation of the gamma dose distribution comparison method

The gamma tool was developed to quantitatively compare dose distributions, either measured or calculated. Before computing gamma, the dose and distance scales of the two distributions, referred to as evaluated and reference, are renormalized by dose and distance criteria, respectively. The renormalization allows the dose distribution comparison to be conducted simultaneously along dose and distance axes. The gamma quantity, calculated independently for each reference point, is the minimum distance in the renormalized multidimensional space between the evaluated distribution and the reference point. The gamma quantity degenerates to the dose-difference and distance-to-agreement tests in shallow and very steep dose gradient regions, respectively. Since being introduced, the gamma quantity has been used by investigators to evaluate dose calculation algorithms, and compare dosimetry measurements. This manuscript examines the gamma distribution behavior in two dimensions and evaluates the gamma distribution in the presence of data noise. Noise in the evaluated distribution causes the gamma distribution to be underestimated relative to the no-noise, condition. Noise in the reference distribution adds noise in the gamma distribution in proportion to the normalized dose noise. In typical clinical use, the fraction of points that exceed 3% and 3 mm can be extensive, so we typically use 5% and 2-3 mm in clinical evaluations. For clinical cases, the calculation time is typically 5 minutes for a 1 x 1 mm2 interpolated resolution on an 800 MHz Pentium 4 for a 14.1 x 15.2 cm2 radiographic film.
Analysis and Design of External Cavity, Strong Feedback, Semiconductor Lasers for Use with Coherent Optical Communication Systems

External cavity, strong optical feedback, semiconductor lasers are analyzed using a rotated ellipse gain(REG) model. The model considers laser diode characteristics as well as the effects of optical feedback. Theoretical calculations on this strong feedback structure are developed in terms of amplification, injection locking, and mode ratio. Threshold current is expressed as a function of wavelength and temperature. Also various formulae for threshold current reduction, effective current, amplified output power, and reduced spectral linewidth are presented. From the amplified output power we calculate the spectral linewidth. We analyze in more detail the theoretical work of Patzak et al and show that spontaneous emission is reduced by frequency selective strong optical feedback. In designing external cavity lasers with strong feedback, mode ratio has to be larger than 100 for stable output power and frequency. It is possible to obtain many characteristic properties of the solitary laser diode with the help of the REG model.
Preserving fertility during cancer treatment.

Imatinib (trade name Gleevec) preserves fertility in female mice treated with the common chemotherapeutic agent cisplatin. Imatinib seems to block an apoptotic pathway activated by cisplatin in ovarian germ cells (pages 1179– 1185). The findings could lead to new ways to protect germ cells from the damaging effects of cancer treatment.
Molecular determinants of LXRα agonism

Liver X receptors (LXRs) are nuclear receptors that participate in the regulation of cholesterol, bile acid, and glucose metabolism. Despite the identification of the natural oxysterol and nonsteroidal ligands for LXRalpha, little is known about the structure of the LXRalpha ligand-binding domain (LBD). We constructed a three-dimensional (3D) homology model of the LBD of LXRalpha based on the crystal structure of the retinoic acid receptor gamma (RARgamma) and all-trans retinoic acid complex. We combined molecular modeling and classical structure-function techniques to define the interactions between the LBD and three structurally diverse ligands, 22(R)-hydroxycholesterol (22RHC), N-(2,2,2-trifluoro-ethyl)-N-[4-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-phenyl]-benzenesulfonamide (T0901317) and (3-[3-[(2-chloro-3-trifluoromethyl-benzyl)-(2,2-diphenyl-ethyl)-amino]-propoxy]-phenyl)-acetic acid (GW3965). Sixteen individual amino acid point mutations were made in the predicted ligand-binding cavity of the LBD, and each of these mutant receptors was assessed for their ability to be activated by these three ligands. The majority of individual mutations resulted in lack of activation by all three ligands. Two residues were identified that resulted in a significant increase in basal activity while retaining responsiveness to the ligands. Interestingly, a number of residues were identified that appear to be selective in their response to a particular ligand, indicating that these three ligands recognize distinct structural components within the ligand-binding cavity. These data, together with our docking study, enable us to identify the amino acids that coordinate the interaction of both steroidal and non-steroidal ligands in the ligand-binding pocket of LXRalpha.
Evil humors take their toll as innate immunity makes gouty joints TREM-ble.

Acute gouty arthritis is a characteristically intense acute inflammatory reaction that erupts in response to articular tophaceous deposits of monosodium urate monohydrate (MSU) crystals. Full-blown acute gouty arthritis is dependent on the influx into the joint space of neutrophils, a cell type normally absent from this locus. Hence, the clinical term “gout,” classically described in the 5th century BC by Hippocrates, was derived in a remarkably prescient manner from the Latin word “gutta,” which literally means “drop.” Specifically, gout was named to reflect the notion of “evil humors” aberrantly seeping into affected joints. Recent advances have revealed the uncanny link between this ancient disease and innate immune inflammatory responses that are phylogenetically primeval. Innate immunity provides a first line of defense against infection via primitive responses that are nonspecific and broad in spectrum (1). Unlike adaptive immune responses, stereotypic innate immune “early induced” responses do not directly induce immunologic memory or lasting protective immunity, consistent in acute gout with the recurrent paroxysmal nature of the disease and the primary role in pathogenesis of “professional phagocytes.” Central to rapid innate immune inflammatory and killing responses is the remarkable capacity of all eukaryotic organisms to recognize the same constituents of microbes (termed pathogenassociated molecular patterns [PAMPs]). Seminal identification of Toll and Toll-like receptors (TLRs) that recognize PAMPs in Drosophila indicates that human innate immune mechanisms for discrimination of nonself PAMPs such as lipopolysaccharide (LPS) and peptidoglycan from self are phylogenetically primordial. The majority of encounters with microorganisms expressing PAMPs do not result in disease, but breaching of tissue barriers by pathogens can stimulate innate immune alternative complement pathway activation, the expression of chemokines and certain other inflammatory cytokines, and uptake of the pathogen by resident and recruited professional phagocytes in a rapid effort to eliminate the noxious agent.
Within-Plant Distribution of Spider Mites (Acari: Tetranychidae) on Cotton: A Developing Implementable Monitoring Program

The vertical distribution of spider mites, Tetranychus spp., on cotton is largely determined by the phenological stage of crop growth. Early in the season, plants have few leaves and the mites are located close to the mainstem terminal; during the rapid phase of vegetative growth, the mites are located increasingly farther from the terminal; as vegetative growth decreases late in the season, the mites are again found closer to the terminal. The small size and potentially large numbers of mites found on cotton make conventional monitoring procedures economically impractical. A presence-absence monitoring procedure is presented which relates the proportion of mite-infested mainstem node leaves at the most infested node to the number of mites per leaf which can in turn be converted to an area estimate. An optimized sampling program was developed by incorporating the spider mite distribution information into a presence-absence sequential sampling plan. Some monitoring shortcuts that result in incorrect treatment decisions are discussed.
Amino Acid Neurotransmitters in the CNS: Properties of Diaminobutyric Acid Transport

Uptake of L-2,4-diaminobutyric acid (DABA), a positively charged analogue of gamma-aminobutyric acid (GABA), by a synaptosomal fraction isolated from rat brain occurred with a Km of 54 +/- 12 microM and a Vmax of 1.3 +/- 0.2 nmol/min/mg protein. The transport of DABA was inhibited competitively by GABA whereas that of GABA was affected in the same manner by addition of DABA. The maximal accumulation of DABA ([DABA]i/[DABA]c) was observed to increase as the second power of the transmembrane electrical potential ([K+]i/[K+]e) and the first power of the sodium ion concentration gradient. These findings indicate that DABA is transported on the GABA carrier with a net charge of +2, where one charge is provided by the cotransported Na+ and the second is contributed by the amino acid itself. Since uptake of GABA, an electroneutral molecule, is accompanied by transfer of two sodium ions, the results obtained with DABA suggest that one of the sodium binding sites on the GABA transporter is in proximity to the amino acid binding site.
Elimination of Optical Discontinuity between Two Immiscible Fluids

The indices of refraction of heptane and of aqueous solutions of glycol were measured over a range of temperature. It is shown that the indices of this pair of fluids can be matched exactly and hence that the optical discontinuity at the interface of the two phases can be eliminated over a range of temperature by varying the composition of the solution. The utilization of this matched pair of fluids for light transmission measurements through dispersions is discussed.