cssi/SciSciGPT-SciSciNet huggingface dataset:
Reducing the Prevalence of Immune-Based Chronic Disease

As described in prior chapters of this book, chronic diseases connected to immune and inflammatory dysfunction are often categorized based on the affected tissues and, as a result, can be overlooked as being immune-mediated diseases. These diseases are numerous in nature, costly to individuals, families and nations, and pervasive. They represent an emerging global health threat where effective strategies capable of reducing disease prevalence have been slow to emerge. This concluding chapter includes information on four additional immune/inflammatory-based diseases or conditions: psoriasis, autoimmune thyroiditis, frailty, and an isolation-withdrawal state. It also provides an overview of plans for reducing the risk of immune-based chronic disease and emphasizes the importance of acting early in life and using safety data that are directly relevant to priority chronic diseases. The risk-reduction strategy combines four key components: widespread outcome-based safety testing that precedes human exposure, whole-life-considered therapeutic interventions, strategic research, and effective public health policies.
Neubewertung der Wirkung der totalen Colektomie und der intestinalen Sterilisation nach portocavalem Shunt

Der therapeutische Effekt der “intestinalen Sterilisation” und der Colektomie bei Patienten mit hepataler Encephalopathie ist in zahlreichen, auch prospektiven Untersuchungen nachgewiesen. Beiden Verfahren wurde allgemein eine Verminderung der Urease-produzierenden Bakterienflora und des Ammoniakspiegels zugesprochen, was als indirekte Bestatigung des Konzeptes uber die Pathogenese aufgefast wurde, das der Ammoniak schlechthin die Substanz ist, die vor allem durch Interferenz mit dem Energiestoffwechsel fur die cerebralen Ausfalle verantwortlich ist. Diese Auffassung hat in Klinik und im Experiment kritischen Prufungen kaum entsprochen, weswegen nach Alternativen gesucht wurde. Einen wesentlichen Beitrag dazu leisteten die Ergebnisse von Fischer, Baldessarini u, Ma. (1), die neben den Veranderungen der neutralen Aminosauren im Gehirn eine Storung der Transmit -terfunktion als gemeinsame Ursache der vielfaltigen klinischen Ausfalle im Coma hepaticum nachgewiesen haben. Die Akkumulation von falschen Neurotransmittern und die Abnahme der physiologischen Katecholamine Noradrenalin und Dopamin verursachen durch verminderte Impulsweitergabe die Abschwachung des neuralen Erregungsablaufes im Gehirn, was sich klinisch als Encephalopathie ausert. Beide therapeutischen Masnahmen sollten daher den cerebralen Gehalt an falschen Neurotransmittern senken und einen Einflus auf die aromatischen Aminosauren Phenylalanin, Tryptophan und Tyrosin, die alle Prakursor sub stanzen aktiver Amine sind, ausuben.
Protein sulfenylation by oxidized lipid signaling promotes activation of platelets

Thrombosis during atherosclerotic plaque erosion or rupture is a major cause of death and disability in individuals with cardiovascular disease. Oxidized lipids in lipoproteins (oxLDL) are risk factors for this event and are recognized by platelet receptor CD36. oxLDL binding to CD36 promotes platelet activation and thrombosis by generating reactive oxygen species (ROS). The downstream signaling events initiated by ROS in this setting are largely unknown. We hypothesize that ROS generation by oxLDL signaling promotes cysteine oxidation of cellular regulators of thrombosis. Platelets from human donors were stimulated with oxLDL and ROS levels were measured using peroxide oxidation of coumarin boronic acid to 7-hydroxycoumarin. OxLDL showed time- and concentration-dependent ROS formation; control “native” LDL showed no ROS formation. To mimic physiologic conditions, platelets were sensitized with oxLDL before stimulating with classic activators adenosine diphosphate (ADP) or collagen-related peptide (CRP). Sensitization showed synergistic ROS formation by the collagen receptor, but not through ADP receptors. To assay cysteine sulfenylation, an alkyne-containing benzothiazine-based (BTD) probe was used and detected by click-chemistry with biotin-azide followed by blotting with streptavidin-HRP. OxLDL promotes a rapid, within 5 minutes, increase in sulfenylation in the platelet proteome, which was not present at 60 minutes; LDL stimulation showed no increase in sulfenylation. To determine the functional impact of sulfenylation, platelet aggregation was determined turbidometrically by light transmission. OxLDL promoted ~60% platelet aggregation, which was concentration-dependently prevented by modifying sites of sulfenylation with BTD. Mechanistically, aggregation is driven by integrin activation and α-granule secretion. OxLDL-stimulation showed integrin activation and α-granule secretion, which was partially prevented by BTD. BTD had no impact on aggregation by ADP or CRP, suggesting these classic activators do not generate sufficient ROS to promote sulfenylation. In conclusion, oxLDL present in cardiovascular disease promotes platelet activation by functional and transient sulfenylation of the proteome.
Process reasoning

With the increasing levels of automation in factories, production management systems need increasingly sophisticated models of manufacturing processes. A framework is presented for the design and implementation of process reasoning modules which characterize processes within a manufacturing environment. Each reasoning module describes a process in terms of its effects, constraints, and process parameters. The effects include intended objectives, such as material removal, and side effects such as burr production. Constraints include specific limits on process parameters, and preconditions to the invocation of a process. These preconditions can require the execution of several other processes, leading to the chaining of events. The process parameters provide qualitative and quantitative information necessary to execute a process. To implement a reasoning module, a process is classified in terms of the underlying physics taking place. This immediately generates a number of effects, and possibly some necessary process parameters to be associated with the process. This approach, described in this paper, relies heavily on concepts of object-oriented programming and artificial intelligence techniques. If one of the effects is a change in geometry, an interface to a geometry modeling system will be inherited. Use of a modular, inheritance approach to construct these reasoning modules means that new processes may be quickly defined. The implications of a physical process are inherited, automatically leading to constraints, side effects, etc. A process reasoning module can play many roles. It can be queried as an expert to determine the feasibility of achieving a given goal, expected side effects, and optimum process parameters. A module can also simulate a process, given specific parameter settings.
Bile salt hydrolases: Gatekeepers of bile acid metabolism and host-microbiome crosstalk in the gastrointestinal tract.

Research on bile acids has increased dramatically due to recent studies demonstrating their ability to significantly impact the host, microbiome, and various disease states [1–3]. Although these liver-synthesized molecules assist in the absorption and digestion of dietary fat in the intestine, their reabsorption and recirculation also gives them access to peripheral organs [4] (Fig 1A). Bile acids serve as substrates for bile acid receptors (BARs) found throughout the body that control critical regulatory and metabolic processes and therefore represent an important class of bioactive molecules [5]. Despite the importance of bile acids to host health, there remain gaps in our knowledge about the bacterial enzymes driving their composition and modification. Open in a separate window Fig 1 Bile salt hydrolases act on circulating conjugated bile acids in the gut-liver axis. (A) Bile acids synthesized in the liver and stored in the gall bladder enter the small intestine through the duodenum where they reach millimolar concentrations. The majority of bile acids (95%) are reabsorbed in the ileum and recirculate to the liver through the portal vein. The remaining population transit to the colon as they continue to be reabsorbed, and a small (<5%) amount exit through the feces. Recirculating bile acids access host tissues outside the intestines to impart systemic effects on host physiology. (B) BSHs cleave the amide bond in conjugated bile acids to open up the bile acid pool to increased complexity. The gut microbiota performs additional chemistry on deconjugated bile acids to generate the secondary bile acid pool, which can undergo enterohepatic circulation and be reconjugated in the liver. These transformations are illustrated to the right as conjugated CA is deconjugated, subjected to 7 α-dehydroxylation to become DCA, and subsequently reconjugated. (C) Monomeric BSH overlay from Bifidobacterium longum (PDB ID 2HEZ), Enteroccocus faecalis (PDB ID 4WL3), Lactobacillus salivarius (PDB ID 5HKE), and Clostridium perfringens (PDB ID 2BJF). Hydrolyzed TDCA in the CpBSH active site is coordinated by several loops that contain the most variation in the peptide backbone compared to the other structures. BSH, bile salt hydrolase; CA, cholic acid; CpBSH, C. perfringens BSH; DCA,; TDCA, taurodeoxycholic acid; PDB ID, Protein Data Bank ID.
Clean Engineered Steels - Progress at the End of the Twentieth Century

The Timken Company, a manufacturer of alloy steel and bearings, has developed a 15 MHz ultrasonic inspection method that correlates steel cleanness to bearing fatigue performance. It is used to qualify worldwide bearing steel suppliers for cleanness requirements, to monitor their compliance and qualify process changes. This method has permitted the appropriate steel cleanness to be selected for bearing applications. Through Continuous Improvement (CI) methodology, steelmaking productivity advancements have occurred along with advancement in steel cleanness. These efforts have led to 4 orders of magnitude steel cleanness improvement, and nearly 20 times bearing performance improvement over the past 15 years.
Bystander Selection for Antimicrobial Resistance: Implications for Patient Health

Antimicrobial therapy promotes resistance emergence in target infections and in off-target microbiota. Off-target resistance emergence threatens patient health when off-target populations are a source of future infections, as they are for many important drug-resistant pathogens. However, the health risks of antimicrobial exposure in off-target populations remain largely unquantified, making rational antibiotic stewardship challenging. Here, we discuss the contribution of bystander antimicrobial exposure to the resistance crisis, the implications for antimicrobial stewardship, and some novel opportunities to limit resistance evolution while treating target pathogens.
A1C Underperforms as a Diagnostic Test in Africans Even in the Absence of Nutritional Deficiencies, Anemia and Hemoglobinopathies: Insight From the Africans in America Study.

Introduction: To improve detection of undiagnosed diabetes in Africa, there is movement to replace the OGTT with A1C. The performance of A1C in the absence of hemoglobin-related micronutrient deficiencies, anemia and heterozygous hemoglobinopathies is unknown. Therefore, we determined in 441 African-born blacks living in America (male: 65% (281/441), age: 38±10y (mean±SD), BMI: 27.5±4.4 kg/m2): (1) nutritional and hematologic profiles and; (2) glucose tolerance categorization by OGTT and A1C. Methods: Hematologic and nutritional status were assessed. Hemoglobin <11g/dL occurred in 3% (11/441) and led to exclusion. A1C and OGTT were performed in the remaining 430 participants. ADA thresholds for A1C and OGTT were used. Diagnosis by A1C required meeting either A1C-alone or A1CO but OGTT-alone detected 68% (22/32). Overall prediabetes prevalence was 41% (178/430). A1C detected 57% (102/178); but OGTT-alone identified 43% (76/178). After excluding individuals with heterozygous hemoglobinopathies, the rate of missed diagnosis by A1C of abnormal glucose tolerance did not change (OR:0.99, 95% CI: 0.61, 1.62). Conclusions: In nutritionally replete Africans without anemia or heterozygous hemoglobinopathy, if only A1C is used, ~60% with diabetes and ~40% with prediabetes would be undiagnosed.
A Survey of Intrusion Detection Systems Leveraging Host Data

This survey focuses on intrusion detection systems (IDS) that leverage host-based data sources for detecting attacks on enterprise network. The host-based IDS (HIDS) literature is organized by the input data source, presenting targeted sub-surveys of HIDS research leveraging system logs, audit data, Windows Registry, file systems, and program analysis. While system calls are generally included in audit data, several publicly available system call datasets have spawned a flurry of IDS research on this topic, which merits a separate section. To accommodate current researchers, a section giving descriptions of publicly available datasets is included, outlining their characteristics and shortcomings when used for IDS evaluation. Related surveys are organized and described. All sections are accompanied by tables concisely organizing the literature and datasets discussed. Finally, challenges, trends, and broader observations are throughout the survey and in the conclusion along with future directions of IDS research. Overall, this survey was designed to allow easy access to the diverse types of data available on a host for sensing intrusion, the progressions of research using each, and the accessible datasets for prototyping in the area.
Development and Validation of a Machine Learning Model to Aid Discharge Processes for Inpatient Surgical Care.

Importance Inpatient overcrowding is associated with delays in care, including the deferral of surgical care until beds are available to accommodate postoperative patients. Timely patient discharge is critical to address inpatient overcrowding and requires coordination among surgeons, nurses, case managers, and others. This is difficult to achieve without early identification and systemwide transparency of discharge candidates and their respective barriers to discharge. Objective To validate the performance of a clinically interpretable feedforward neural network model that could improve the discharge process by predicting which patients would be discharged within 24 hours and their clinical and nonclinical barriers. Design, Setting, and Participants This prognostic study included adult patients discharged from inpatient surgical care from May 1, 2016, to August 31, 2017, at a quaternary care teaching hospital. Model performance was assessed with standard cross-validation techniques. The model’s performance was compared with a baseline model using historical procedure median length of stay to predict discharges. In prospective cohort analysis, the feedforward neural network model was used to make predictions on general surgical care floors with 63 beds. If patients were not discharged when predicted, the causes of delay were recorded. Main Outcomes and Measures The primary outcome was the out-of-sample area under the receiver operating characteristic curve of the model. Secondary outcomes included the causes of discharge delay and the number of avoidable bed-days. Results The model was trained on 15 201 patients (median [interquartile range] age, 60 [46-70] years; 7623 [50.1%] men) discharged from inpatient surgical care. The estimated out-of-sample area under the receiver operating characteristic curve of the model was 0.840 (SD, 0.008; 95% CI, 0.839-0.844). Compared with the baseline model, the neural network model had higher sensitivity (52.5% vs 56.6%) and specificity (51.7% vs 82.6%). The neural network model identified 65 barriers to discharge. In the prospective study of 605 patients, causes of delays included clinical barriers (41 patients [30.1%]), variation in clinical practice (30 patients [22.1%]), and nonclinical reasons (65 patients [47.8%]). Summing patients who were not discharged owing to variation in clinical practice and nonclinical reasons, 128 bed-days, or 1.2 beds per day, were classified as avoidable. Conclusions and Relevance This cohort study found that a neural network model could predict daily inpatient surgical care discharges and their barriers. The model identified systemic causes of discharge delays. Such models should be studied for their ability to increase the timeliness of discharges.
Association of Strawberries and Anthocyanidin Intake with Alzheimer's Dementia Risk.

Background: Strawberries have been identified to have antioxidant and anti-inflammatory properties that improve neuronal function and cognition, mostly in animal studies. It is unknown if the consumption of strawberries or related bioactives may reduce the risk of Alzheimer’s dementia risk. Material and Methods: The study was conducted in 925 participants, aged 58–98 years of the Rush Memory and Aging Project. Participants were dementia-free at baseline, completed a food frequency questionnaire, and had at least two annual neurological evaluations. The diagnosis of Alzheimer’s dementia was based on structured clinical neurological examination and standardized diagnostic criteria. The association of strawberry intake and incident Alzheimer’s dementia was analyzed using proportional hazard models adjusted for age, sex, education, physical activity, participation in cognitive activities, APOE-ɛ4 genotype, dietary intake of other fruits, and total calorie intake. Results: A total of 245 participants developed Alzheimer’s dementia over the mean follow-up of 6.7 (±3.6) years. Higher strawberry intake was associated with reduced risk of Alzheimer’s dementia (HR = 0.76, 95% CI: 0.60–0.96). In separate adjusted models, highest vs. lowest quartile intakes of Vitamin C (HR = 0.64, 95% CI: 0.45, 0.92), Pelargonidin (0.63, 95% CI: 0.43, 0.92), total anthocyanidins (0.69, 95% CI: 0.48, 0.99), and total flavonoids (0.67, 95% CI: 0.46, 0.98) were each associated with lower Alzheimer’s dementia risk. These associations remained after further adjustment for cardiovascular conditions. Conclusion: Consumption of strawberries and foods rich in vitamin C, pelargonidin, anthocyanidins, and total flavonoids may reduce the risk of Alzheimer’s dementia.
Investigating Boundary Layer Flashback of a High Turbulence Intensity Jet Flame at Gas Turbine Conditions

Author(s): Auwaijan, Nicolas | Advisor(s): Samuelsen, Scott; McDonell, Vincent | Abstract: Hydrogen derived from non-fossil sources is an attractive candidate to replace carbon based fuels in gas turbines, as it is inherently carbon free. Yet the unusual combustion properties of hydrogen requires some care to successfully use it in gas turbines. To attain the lowest NOx emissions, uniformly low reaction temperatures must be assured thus the reactants must be well mixed. This is accomplished in low emission gas turbines by mixing the reactants within a pre-mixer section prior to entry into the combustor. With the addition of hydrogen into the fuel, certain issues arise such as higher flame speeds compared to carbon based fuels. Flashback is a phenomena that occurs when the flame no longer propagates downstream of the injector but instead retracts and propagates upstream towards the pre-mixer and injector. Flashback occurs when the flame speed exceeds the local flow velocity. In the present work, studies are conducted under different levels of turbulence intensity. Higher turbulence intensity is known to increase turbulent burning velocity, hence the question of how flashback propensity is affected is raised. Studies are conducted at pressures from 3 to 8 atm. with preheated reactants up to 750 K utilizing hydrogen as the fuel. The results show that even with significantly different turbulence intensities (ratio of flow centerline turbulence to centerline axial velocity) boundary layer flashback is not strongly affected. This is attributed to the role of the quenching distance in connection with the boundary layer. Core flow flashback or other flashback mechanisms may be affected differently.
How Are We Measuring Cost-Effectiveness in Total Joint Arthroplasty Studies? Systematic Review of the Literature.

Abstract Background As volumes of total hip arthroplasty (THA) and total knee arthroplasty (TKA) continue to rise, it is important to understand their economic impact. No systematic review on cost-effectiveness of THA/TKA has been performed since 2016 despite recent changes in the healthcare environment. The purpose of the study is to provide a contemporary analysis of the cost-effectiveness of total joint arthroplasty and the use of quality-adjusted life years (QALYs). Methods A systematic review was performed from 2005 to 2020. Online databases (OVID Medline, PubMed, Cost-Effectiveness Analysis Registry, Google Scholar, Elton B. Stephens Co) were queried to identify economic analyses that evaluated the cost-effectiveness of THA/TKA. Results In total, 38 studies met the screening criteria. Study designs were primarily Markov models (68%), cohort studies (16%), and randomized trials (8%). Most studies adopted either a societal perspective (45%) or a health system perspective (39%). Analysis revealed that THA/TKA was strongly cost-effective compared to nonsurgical treatment. THA/TKA procedures that were not delayed were more cost-effective than delayed intervention. The majority of studies used QALYs as the primary quality metric (82%); in all these studies there was a significant improvement in QALYs gained. Conclusion Given the high economic impact of arthroplasty, ongoing assessment of cost-effectiveness is needed. Twenty-four percent of studies included in this systematic review were published in the last 4 years of this 15-year study period, highlighting the need for continuous assessment of aggregate data. Future studies should incorporate the cost-effectiveness of THA and TKA with respect to the work-value provided by surgeon providers to support health policy and reimbursement.
Documenting #MeToo in Public Transportation: Sexual Harassment Experiences of University Students in Los Angeles:

This study presents findings from a survey with 1,284 students at three Los Angeles area universities, exploring their experiences with sexual harassment in transit environments, and how these diff...
Kinematic Age Estimates for Four Compact Symmetric Objects from the Pearson-Readhead Survey

Based on multiepoch observations at 15 and 43 GHz with the Very Long Baseline Array (VLBA), we detect significant angular expansions between the two hot spots of four compact symmetric objects (CSOs). From these relative motions we derive kinematic ages of between 300 and 1200 yr for the radio emission. These ages lend support to the idea that CSOs are produced in a recent phase of activity. These observations also allow us to study the evolution of the hot spots dynamically in individual sources. In all four sources the hot spots are separating along the source axis, but in 1031+567 the tip of the hot spot appears to be moving almost orthogonally to the source axis. Jet components, seen in three of the four sources observed, are found to be moving relativistically outward from the central engines toward the more slowly moving hot spots.
Efficacy of an Asynchronous Online Preparatory Chemistry Course: An Observational Study.

In an ongoing effort to increase student retention and success in the undergraduate general chemistry course sequence, a fully online preparatory chemistry course was developed and implemented at a large public research university. To gain insight about the efficacy of the online course, an observational study was carried out in which student performance on final exams and performance in the subsequent general chemistry course were compared between the online cohort and a previous student cohort which completed the preparatory chemistry course in a traditional lecture format. Multiple linear regression analyses were used to compare final exam scores and general chemistry course grades between the online and in-person student cohorts, while statistically controlling for incoming student academic achievement. Results from these analyses suggest the fully online course resulted in statistically significant increases in both the preparatory chemistry final exam scores and course grades in the subsequent general chemistry course. Because the retention of less academically prepared students in STEM majors is a historical problem at the institution in which the online preparatory chemistry course was implemented, the analyses also aimed to determine if this at-risk group demonstrated similar achievement relative to the population at large. Notably, it was determined that students with the lowest incoming Math SAT scores appeared to perform better in the online course relative to the analogous group of students in the in-person course. Though the observational nature of this study does not allow for the determination of causality, these results suggest a fully online course can result in improved performance for large populations of students, without resulting in a negative achievement gap for less academically prepared students. The structure and implementation of the online course and the results from the statistical analyses will be described herein.
How Does Perseverance of Effort Influence the University Outcomes of Historically Underrepresented Students

Grit has become a popular concept in the education field and is characterised by consistency of interest and perseverance of effort. This study focuses on one dimension of grit, perseverance of effort, to examine if it has compensatory effects for historically underrepresented students. Using a large, diverse sample of undergraduates, the results indicate that perseverance of effort has a stronger relationship with some process indicators of student learning than for traditional students. Additionally, we did not observe any stronger relationships for traditional students relative to non-traditional populations. Consequently, the results suggest that perseverance of effort can have compensatory effects that can help historically underrepresented students overcome obstacles to student success.
The Effects of Marine Microplastics on Marine Life and Human Health in the Bay of Bengal

Marine microplastics are an emerging pollutant that has already shown adverse effects in fish, mice, and other lower-order organisms. Based on the impact microplastics have on these organisms, human health will likely be affected, especially in areas where fish and other marine life are a significant part of the diet. A wide range of previously conducted research was used to study the effects and predict the dangers of microplastic consumption on human health. The sources covered three general topics: the effects of microplastics on commonly consumed European and Mediterranean fish, their effects on the gut microbiome of mice, and the transmission of microplastics across trophic levels. A prediction was made using the presented data, stating that there will be and there is already a likely effect on the human neuroendocrine and digestive systems. This assumption was drawn from the known health effects of microplastics on fish and mice and the processes of bioaccumulation and biomagnification. In conclusion, it was predicted that the regular consumption of contaminated fish is likely already affecting human health in the region. Furthermore, the current policies and regulations focused on plastic pollution in India and Bangladesh are either not strong enough or not enforced well enough to reduce the amount of plastic pollution in the bodies of water in the region.
Patient Perceptions of Telephonic Visits during the COVID-19 Pandemic-Is Video Connectivity Imperative?

AbstractIntroduction:We characterize patient perceptions of telemedicine (video-enabled) and telephonic (audio-only) visits conducted during the COVID-19 pandemic.Methods:A single-center cohort of ...
Living With Survival Analysis in Orthopedics

Abstract Time-to-event data occur commonly in orthopedics research and require special methods that are often called “survival analysis”. These data are complex because both a follow-up time and an event indicator are needed to correctly describe the occurrence of the outcome of interest. Common pitfalls in analyzing time-to-event data include using methods designed for binary outcomes, failing to check proportional hazards, ignoring competing risks, and introducing immortal time bias by using future information. This article describes the concepts involved in time-to-event analyses as well as how to avoid common statistical pitfalls.
Congenital extremity anomalies with a TBX5 pathogenic variant in consecutive IVF assisted pregnancies: a case report of Holt-Oram Syndrome.

A 37-year-old, G3P0, with a pregnancy that arose after in vitro fertilisation, attended for nuchal translucency sonogram at 13 weeks and 3 days of gestation. This scan was notable for fixed deviati...
Perils, Potential and Perspectives of Bioarchaeological Analyses in the Study of Mediterranean Mobility

The resolution of bioarchaeological analyses has improved dramatically in recent years, and bioarchaeology is increasingly employed in areas of the world where preservation issues and disciplinary traditions had previously hindered its application. One such area is the Mediterranean region. Bioarchaeological analyses arguably are the most direct indicator of human behavior in the past, and as a result the full integration of bioarchaeology and archaeology into Mediterranean research shows much promise. However, several methodological, theoretical and practical challenges have emerged: (1) discrepancies between cultural and biological variability; (2) discrepancies in the dating of skeletal samples and of migration events in the two subdisciplines; (3) diverging interpretations of (collective) identities; and (4) the fostering of effective cross-disciplinary communication and collaboration. While the first two points are especially salient for Mediterranean research, the third and fourth are relevant for the archaeological discipline more generally. In this paper, we discuss each challenge in turn, focusing on the first millennium bc Greek diaspora in the Mediterranean. We believe that both disciplines would benefit from open discussion of these issues, which we hope might spur more collaborative efforts towards their resolution.
On the Chromosomal Proteins of Lens Epithelium

Chromosomal proteins of lens epithelium from bullfrogs, leopard frogs, and rabbits have been isolated and compared. Gels of frog lens histones contain one more band than those of rabbits. Qualitatively, the NHCPs of the two amphibians are nearly identical. Coupling between histone and DNA synthesis in the rabbit lens was demonstrated by use of cytosine arabinoside. The block was reversed with deoxycytidine.
Protein–Protein Interactions as Drug Discovery Targets

Protein–protein interactions (PPIs) recently have been recognized as a major class of drug targets. Many of the successful “classical” biotechnology protein drugs are agonists or antagonists of PPIs and there are established pathways for their development. However, small molecular weight compounds as antagonists of PPIs still pose a major problem to discovery due to the inherent physicochemical properties of their targets. Recently, several small molecular weight antagonists of PPIs advanced into clinical trials and thus comprise a proof-of-concept to this young area in medicinal chemistry. This chapter summarizes the area of small molecular weight antagonists of PPIs with a focus on recent success stories. After a short introduction into the structural biology of PPIs, recognized important PPI targets, discovery pathways of their inhibitors are discussed. The PPI p53-Mdm2 with potential applications in cancer is used as a case study to demonstrate to diversity of approaches leading to many different lead structures. In contrast, the discovery of IL-2/IL-2 rec. antagonists is discussed to highlight adaptive high affinity binding to hotspot regions. Keywords: computational docking; drug discovery target; FBA; HTS; PPI; protein–protein interaction
Manifolds of Preferences and Equilibria

This work is concerned with the study of local and global properties of spaces of preferences and their applications to general equilibrium, utility and demand analysis. Differential topology and global analysis tools are used to study the mathematical aspects of these problems, adding further results and techniques to an approach introduced in mathematical economics by Gerard Debreu in 1970. Spaces of smooth, not necessarily convex or increasing, preferences are shown here to be representable as differentiable Hilbert manifolds. These structures on spaces of preferences are then used to extend major results on the regularity of equilibria, based on Sard's theorem and Abraham-Thom transversality theory, to economies where agents are described by their preferences and endowments. Certain topological properties of these manifolds of preferences are studied. Applications are also given to the study of the utilities and the demands of the agents in relation to the underlying preferences. The results point to extensions and indicate new branches of research of both economic and mathematical interest; these are written as suggestions or conjectures in the text.
Synchronization of timing systems on TFTR

The Tokamak Fusion Test Reactor (TFTR) facility clock system has four related timing subsystems: the TFTR shot clock, the neutral beams clocks, the ion cyclotron range of frequencies (ICRF) system clock, and the disruption trigger system. These systems have been integrated to support increasingly fast sampling rates in data acquisition and greater accuracy in the firing of the neutral beams and ICRF systems during TFTR shots. >
99th Dahlem Conference on Infection, Inflammation and Chronic Inflammatory Disorders: Farm lifestyles and the hygiene hypothesis

About 15 years have gone by since Strachan first proposed the idea that infections and unhygienic contact may confer protection from the development of allergic illnesses. The so-called 'hygiene hypothesis' has since undergone numerous modifications in the field of epidemiology, clinical science and immunology. Three main areas of research have been brought forward: to explore the role of overt viral and bacterial infections for the inception of allergic diseases; to investigate the significance of environmental exposure to microbial compounds on the development of allergies; and to study the effect of both exposures on underlying innate and adaptive immune responses. A concept unifying these various aspects has not been found, but various pieces of a complex interplay between immune responses of the host, characteristics of the invading microorganism, the level and variety of the environmental exposure and the interactions between an exposed subject's genetic background and the environmental exposures becomes apparent. A natural experiment relating to the hygiene hypothesis is the recurrent observation of a protective effect of growing up on a farm for asthma and allergies. This has been shown in a large number of epidemiological studies across the world among children and adults. The timing and duration of exposure are likely to play a critical role. The largest reduction in risk has been demonstrated for those exposed prenatally and continuously thereafter until adulthood. The protective factors in these farming environments have not been unravelled completely. Findings from various studies suggest that the contact with farm animals, at least in childhood, confers protection. Also the consumption of unprocessed cow's milk directly from the farm has been shown to protect from childhood asthma and allergies. Increased levels of microbial substances may, at least in part, contribute to the 'farm effect'. However, only few studies have measured microbial exposures in these environments and the results obtained so far suggest that the underlying protective microbial exposure(s) have not been identified, but a number of studies using metagenomic approaches are currently under way. The mechanisms by which such environmental exposures confer protection from respiratory allergies are also not well understood. There is good evidence for the involvement of innate immune responses, but translation into protective mechanisms for asthma and allergies is lacking. Furthermore, a number of gene x environment interactions have been observed.
Advances in Industrial Automation: Historical Perspectives

Automation is a way for humans to extend the capability of their tools and machines. Self-operation by tools and machines requires four functions: Performance detection; process correction; adjustments due to disturbances; enabling the previous three functions without human intervention. Development of these functions evolved in history, and automation is the capability of causing machines to carry out a specific operation on command from external source. In chemical manufacturing and petroleum industries prior to 1940, most processing was in batch environment. The increasing demand for chemical and petroleum products by World War II and thereafter required different manufacturing setup, leading to continuous processing and efficiencies were achieved by automatic control and automation of process, flow and transfer. The increasing complexity of the control system for large plants necessitated applications of computers, which were introduced to the chemical industry in the 1960s. Automation has substituted computer-based control systems for most, if not all, control systems previously based on human-aided mechanical or pneumatic systems to the point that chemical and petroleum plant systems are now fully automatic to a very high degree. In addition, automation has replaced human effort, eliminates significant labor costs, and prevents accidents and injuries that might occur. The Purdue enterprise reference architecture (PERA) for hierarchical control structure, the hierarchy of personnel tasks, and plant operational management structure, as developed for large industrial plants, and a frameworks for automation studies are also illustrated.
Effect of acoustic coupling on random and harmonic plate vibrations

The effect of acoustic coupling on random and harmonic plate vibrations is studied using two numerical models. In the coupled model, the plate response is obtained by integration of the nonlinear plate equation coupled with the nonlinear Euler equations for the surrounding acoustic fluid. In the uncoupled model, the nonlinear plate equation with an equivalent linear viscous damping term is integrated to obtain the response of the plate subject to the same excitation field. For a low-level, narrow-band excitation, the two models predict the same plate response spectra. As the excitation level is increased, the response power spectrum predicted by the uncoupled model becomes broader and more shifted towards the high frequencies than that obtained by the coupled model. In addition, the difference in response between the coupled and uncoupled models at high frequencies becomes larger. When a high intensity harmonic excitation is used, causing a nonlinear plate response, both models predict the same frequency content of the response. However, the level of the harmonics and subharmonics are higher for the uncoupled model. Comparisons to earlier experimental and numerical results show that acoustic coupling has a significant effect on the plate response at high excitation levels. Its absence in previous models may explain the discrepancy between predicted and measured responses.
Collaborative genres for collaboration: genre systems in digital media

Using the concept of genre, we examined the use of Team Room to facilitate collaborative work in one organization. Team Room is a collaborative application built within Lotus Notes and designed specifically to support teams within organizational settings. We studied three teams' communication in Team Room over seven months and found that some of the genres they enacted formed sets of interdependent genres or "genre systems", which facilitated collaboration among team members. The teams' use of these genre systems (meeting documentation, collaborative repository, and collaborative authoring) varied in ways that reflected differences in team size, task, and orientation towards the new technology. The three genre systems observed in Team Room demonstrate different of electronic collaboration that both build on and vary from collaboration in traditional media. Based on the notion of collaborative genres, we suggest insights for research and practical implications for system designers and users.
Information Revelation in Sequential Ascending Auctions

We examine a model in which buyers with single-unit demand are faced with an infinite sequence of auctions. In each period, a new buyer probabilistically arrives to the market, and is endowed with a constant private value. We demonstrate by way of a simple example the inefficiency of the second-price sealed-bid auction in this setting, and therefore focus instead on the ascending auction. We then show that the mechanism in which the objects are sold via ascending auctions has an efficient, fully revealing, and Markov perfect Bayesian equilibrium which is ex post optimal for all buyers in each period, given their expectations about the future. In equilibrium, all buyers completely reveal their private information in every period. However, equilibrium bidding behavior is memoryless. Bids depend only upon the information revealed in the current auction, and not on any information revealed in previous periods. This lack of memory is crucial, as it allows buyers to behave symmetrically, despite the informational asymmetry arising from the arrival of uninformed buyers. This provides the appropriate incentives for these new buyers to also reveal their information.
Contemporary Systemic Therapy for Urologic Malignancies in Geriatric Patients

Current data on systemic therapy in geriatric populations with genitourinary malignancies are largely derived from retrospective analyses of prospectively conducted trials or retrospective reviews. Although extrapolation of these data to real-world patients should be cautious, patients aged 65 years or older with good functional status and minimal comorbidities seem to enjoy similar survival benefit from therapy as their younger counterparts. Chronologic age alone should generally not be used to guide management decisions. Comprehensive geriatric assessment tools and prospective studies in older adults integrating comprehensive geriatric assessment can shed light on the optimal management of urologic malignancies in this population.
Extracellular signals that regulate liver transcription factors during hepatic differentiation in vitro

A complex cell culture environment has been shown to maintain the differentiated state of hepatocytes, yet the mechanisms by which environmental cues selectively maintain liver-specific gene transcription have been unknown. In this paper we show that the hepatic environment regulates the activities of at least three liver-enriched transcription factors, eE-TF, eG-TF/HNF3, and eH-TF, that activate the mouse serum albumin enhancer. eE-TF is a heat-stable factor that has a DNA-binding specificity similar to that of the liver transcription factor C/EBP, but is a distinct protein. eG-TF/HNF3 contributes to the liver-specific transcription of several other serum protein genes. eH-TF binds to a TGTTTGC sequence that occurs at regulatory sites of the albumin promoter, the hepatitis B virus enhancer, and other hepatic genes. eE-TF, eG-TF/HNF3, and eH-TF are regulated by different combinations of the following cell culture conditions: a hormonally defined serum-free medium; an extracellular matrix gel; and a transformation-competent simian virus 40 large T antigen. We propose a regulatory network model to explain how cues from the cell lineage and the extracellular environment coordinately help maintain the activities of transcription factors involved in hepatocyte differentiation.
Nonprobability Sampling in Social Work Research: Dilemmas, Consequences, and Strategies

This study critically reviews sampling procedures commonly found in social work research. Through a Monte Carlo study simulating conditions of probability and nonprobability sampling procedures, the study demonstrates consequences of using nonprobability sampling procedures and identifies conditions under which researchers should examine the issue critically and exercise caution in reporting findings. Five empirical strategies to address dilemmas are recommended. The study calls for greater efforts to fund and coordinate large-scale social work research particularly at the federal level.
Age at sexual maturity influences the response of single comb White Leghorn pullets to marginal and low levels of dietary phosphorus.

This study was designed to determine the differences in response of early-maturing (EM) and latcmaturing (LM) Single Comb White Leghorn pullets within a flock to marginal or low dietary phosphorus. Various levels of dietary phosphorus were fed to EM and LM Leghorn pullets from 18 wk of age until the age of peak egg production (24 wk). The dietary phosphorus levels were 0.40, 0.45, 0.50, 0.55 and 0.70 g total phosphorus (tP)/100 g diet, corresponding to calculated available phosphorus values of 0.18, 0.23, 0.28, 0.33 and 0.48 g/100 g, respectively. At 0.70 and 0.55 g tP/ 100 g, the plasma inorganic phosphorus, Ca ++ and urine calcium concentrations did not differ between EM and LM pullets, whereas LM pullets had a better bone status than EM pullets as reflected by bone mineral content, bone density and bone breaking strength. As dietary phosphorus was lowered from 0.55 to 0.4 g tP/100 g, the plasma concentration of inorganic phosphorus dropped and that of Ca ++ increased at greater rates in LM pullets than in LM pullets. The magnitude of decline in bone status was also greater in LM than in EM pullets when dietary phosphorus was lowered from 0.55 to 0.40 g tP/100 g. The maximum incidences of osteoporosis and mortality were observed in LM pullets fed 0.40 g tP/ 100 g, followed by LM pullets fed 0.45 g tP/100 g diet. We conclude that when early layer diets contain marginal or low levels of phosphorus, the severity of adverse effects are greater in LM pullets than in EM pullets
Maps of virtual structures in R&D

The paper presents the evolution of collaborative structures, ranging from the traditional pattern of "invisible college" to current virtual structures of R&D projects. Properties of virtual structures in R&D are described and their configurations are presented.