cssi/SciSciGPT-SciSciNet huggingface dataset:
Individual Heterogeneity in the Probability of Hospitalization, Skilled Nursing Facility Admission, and Mortality.

BACKGROUND Multimorbidity is common in adults aged 65 and older and is associated with health care utilization and mortality, but most methods ignore the interrelationship among concurrent outcome nor provide person-specific probabilities. METHOD A longitudinal cohort of 5300 older Americans from the 2011-2015 rounds of the National Health and Aging Study was linked to Center for Medicare and Medicaid Services claims. Odds ratios for 15 chronic conditions adjusted for sociodemographic factors were estimated using a joint model of hospitalization, skilled nursing facility (SNF) admission, and mortality. Additionally, we estimated the person-specific probability of an outcome while currently at risk for other outcomes for different chronic disease combinations demonstrating the heterogeneity across persons with identical chronic conditions. RESULTS During the 4-year follow-up period, 2867 (54.1%) individuals were hospitalized, 1029 (19.4%) were admitted to a SNF, and 1237 (23.3%) died. Chronic kidney disease, dementia, heart failure, and chronic obstructive pulmonary disease had significant increased odds for all 3 outcomes. By incorporating a person-specific random intercept, there was considerable range of person-specific probabilities for individuals with hypertension, diabetes, and depression with dementia, (hospitalization: 0.14-0.61; SNF admission: 0.04-0.28) and without dementia (hospitalization: 0.07-0.44; SNF admission: 0.02-0.15). Such heterogeneity was found among individuals with heart failure, ischemic heart disease, chronic kidney disease, hypertension, hyperlipidemia, and osteoarthritis with and without Medicare. CONCLUSIONS This approach of joint modeling of interrelated concurrent health care and mortality outcomes not only provides a cohort-level odds and probabilities but addresses the heterogeneity among otherwise similarly characterized persons identifying those with above-average probability of poor outcomes.
Air Pollution, Regulatory Reforms, and Impacts on Corporate Policies: Selective Review with Recent Evidence from China

We review the new approaches of managing air pollution and the impact of air pollution on corporate activities in China. The Chinese government’s new approaches, such as ecological conservation red...
Fighting Antibiotic Resistance: Marrying New Financial Incentives to Meeting Public Health Goals

The world faces a worsening public health crisis: A growing number of bacteria are resistant to available antibiotics. Yet there are few new antibiotics in the development pipeline to take the place of these increasingly ineffective drugs. We review a number of proposals intended to bolster drug development, including such financial incentives for pharmaceutical manufacturers as extending the effective patent life for new antibiotics. However, such strategies directly conflict with the clear need to reduce unnecessary antibiotic prescriptions and could actually increase prescription use. As an alternative, we recommend a two-prong, "integrated" strategy. This would increase reimbursement for the appropriate, evidence-based use of antibiotics that also met specific public health goals - such as reducing illness levels while limiting antibiotic resistance.
Rights in the Balance

Francisco J. Urbina’s Critique of Proportionality and Balancing promises “a comprehensive critique of the proportionality test.” The critique of proportionality offered in this important book is thoughtful and wide-ranging. Certainly it won’t settle the debates over proportionality, but by making his case in detail, Urbina throws into relief some core differences that underlie the disagreements between proportionality fans and critics. Ultimately, in my view, proportionality comes out looking better than the alternative. Urbina’s critique ends up highlighting features of his own conception of rights and rights review that I anticipate many readers will reject as unreasonable.
Analysis of Machine Learning Techniques for Lightweight DDoS Attack Detection on IoT Networks

As botnet style distributed denial of service (DDoS) attacks continue to proliferate the Internet of Things (IoT) landscape, researchers have struggled to provide a definitive way of addressing concerns related to the IoT’s security. In this paper, we work from the axiom that DDoS attacks are easiest to detect at the target of the attack but are best mitigated closer to the attacker by implementing four machine learning models that detect botnet-infected DDoS attackers on their access network. These models operate on network packet counts, which can easily be gathered by an access router, and run in real-time or near real-time, even on a low power device, namely a Raspberry Pi. We introduce a novel method for visualizing network activity as graphical heatmaps and use convolutional neural network (CNN) models designed for embedded devices and mobile platforms to classify network traffic as benign or malicious. We compare this approach using a support vector machine (SVM) and a long short-term memory recurrent neural network (LSTM). Based on our results, we conclude that the use of lightweight CNNs to analyze network traffic through graphical heatmaps provides highly accurate botnet-based DDoS attack detection for IoT access networks, with an average accuracy of 99.8%, despite our training dataset being between 73×–2170× smaller than those seen in related works, and runtimes ranging from 334 ms to 2 s on a Raspberry Pi.
In the Best Interest of Children: A Proposal for Corporate Guardians Ad Litem

Children are corporate stakeholders without a direct voice in corporate decision-making. Other stakeholders, like employees, customers, and suppliers, can and do influence corporate strategy, but children lack the organization, standing, and legal capacity to assert similar influence. Instead of treating children as a coherent stakeholder group with rights and interests to be respected and supported, firms tend to view children only as potential victims or coveted consumers. Yet, that view is short sighted. Recent international norm-building related to children’s rights and business point toward a more comprehensive consideration of children’s interests in the broad range of business activities. Moreover, children’s best interests substantially overlap with sustainable business practices and implicate human rights generally. Firms must develop expertise in order to identify and give voice to the best interest of children, a capacity which most currently lack. This Article introduces the first corporate model that can effectively advocate for children’s best interests, which is an adapted version of the long-utilized guardian ad litem model used in family court proceedings. Courts appoint guardians ad litem when their decisions impact children who cannot adequately represent themselves because they lack the sophistication or capacity to advocate or state their own best interests. Guardians ad litem serve as objective and impartial officials whose duty is to protect and advocate for the best interest of the children—and they serve only the children. This Article therefore asserts that companies should embed “corporate guardians ad litem” within their organizations to ensure that the best interests of children are considered in the development of corporate strategy and decision-making. The Article introduces three versions of the corporate guardian ad litem, namely, director-level, officer-level, and project-level.
Die operative Behandlung des Klumpfußes

Von den 3 Kollagentypen, die den Hauptteil des menschlichen Bindegewebes ausmachen, interessieren in diesem Zusammenhang die Typen 1 und 3. Wahrend Kollagentyp 3 mit wenigen Cross-links und dunnen Fibrillen elastischer ist als Typ 1, verschwindet viel von ihm wahrend der fruhen Kindheit, um durch Typ 1 ersetzt zu werden. Biochemisch ist der Zeitplan dieses Austausches bisher nicht untersucht worden. Klinisch dagegen findet wahrend des 4. bis 6. Lebensmonats eine Straffung des Bindegewebes statt, die die konservative Behandlung des Klumpfuses immer schwerer macht. Die Theorie des Klumpfuses als Extremhaltung des Fuses durch Banderverkurzung verlangt daher einen Abschlus der konservativen Behandlung mit dem Ende des 6. Lebensmonats.
A three tier architecture for LiDAR interpolation and analysis

Emerging Grid technologies enable solving scientific problems that involve large datasets and complex analyses. Coordinating distributed Grid resources and computational processes requires adaptable interfaces and tools that provide a modularized and configurable environment for accessing Grid clusters and executing high performance computational tasks. In addition, it is beneficial to make these tools available to the community in a unified framework through a shared cyberinfrastructure, or a portal, so scientists can focus on their scientific work and not be concerned with the implementation of the underlying infrastructure. In this paper we describe a scientific workflow approach to coordinate various resources as data analysis pipelines. We present a three tier architecture for LiDAR interpolation and analysis, a high performance processing of point intensive datasets, utilizing a portal, a scientific workflow engine and Grid technologies. Our proposed solution is available through the GEON portal and, though focused on LiDAR processing, is applicable to other domains as well.
Age and sex differences in reward behavior in adolescent and adult rats

Compared to adults, adolescents are at heightened risk for drug abuse and dependence. One of the factors contributing to this vulnerability may be age-dependent differences in reward processing, with adolescents approaching reward through stimulus-directed, rather than goal-directed, processes. However, the empirical evidence for this in rodent models of adolescence, particularly those that investigate both sexes, is limited. To address this, male and female rats that were adolescents (P30) or adults (P98) at the start of the experiment were trained in a Pavlovian approach (PA) task and were subsequently tested for the effects of reward devaluation, extinction, and re-acquisition. We found significant interactions between age and sex: females had enhanced acquisition of PA and poorer extinction, relative to males, while adolescents and females were less sensitive to reward devaluation than male adults. These results suggest that females and adolescents exhibit reward behavior that is more stimulus-directed, rather than goal-directed.
The Value of Larval Connectivity Information in the Static Optimization of Marine Reserve Design

Marine reserve design often involves a tradeoff between meeting conservation goals (persistence of fished populations) and minimizing economic costs (lost fishing grounds). Optimization tools such as Marxan navigate that tradeoff by finding reserve configurations that minimize economic costs while protecting some minimum fraction of fish habitat. However, typical Marxan implementations do not account for patterns of larval connectivity among reserves, a factor known to be the key to population dynamics. We show how connectivity information (self-recruitment and network centrality) can be incorporated into the optimization. We then used a spatially explicit population model to compare the performance of reserves designed using habitat information alone or including connectivity. Incorporating connectivity information improved reserve performance for some species but not others. We conclude that including connectivity information can improve reserve design algorithms, but it is essential to evaluate species’ population dynamics to determine which species will benefit from a given reserve network.
Recent advances in the classification of hepatocellular carcinoma

Abstract Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide and its prognosis depends largely on early detection and management. The diagnosis of HCC can be challenging, especially when dealing with scant biopsy specimens and unusual morphology. This review describes HCC subtypes with emphasis on their distinguishing histological features. Furthermore, it incorporates recently described immunohistochemical markers into an algorism for the initial approach of challenging HCC cases.
Functional School Refusal Subtypes: Anxiety, Avoidance, and Malingering.

Chronic school refusal has traditionally been classified under broad categories such as school phobia and truancy. However, the need for improved recognition and treatment of school refusal has heightened efforts to identify subtypes of school refusal behavior. Recent efforts have focused on functional subtypes of school refusal. This article purposes to extend recent efforts by showing that the three basic subtypes of anxiety, avoidance, and malingering are not only functional, but consistent with refusal characteristics, empirical evidence from factor analysis and clinical diagnosis over the past decade, and treatment approaches. Such extension is intended to aid practitioners in further understanding and using functional subtypes. © 2000 John Wiley & Sons, Inc.
Professional accountability and certification in internal medicine.

THE AMERICAN BOARD OF INTERNAL MEDICINE (ABIM) should be considered accountable professionally to two material and two immaterial referents. The first of the material is the publ ic , the source of the mandate that allows a private, self-consti tuted body to evaluate and certify the potent ial of the physicians to provide excel lent care in their discipline. The pub l i c ' s trust in physicians, other than their own, is at a low point . We are considered overpaid, impatient , poo r listeners, and insensitive to the nonurgent aspects of the pat ient ' s illness. Physicians are increasingly h e m m e d in by regulation, util ization review, and third-party dictates. It would not be surprising for publ ic skepticism to extend to the Board and be at tached to the ABIM's efforts. The ABIM could be chal lenged on the basis that l icensure and certification are not truly different. Thus the Board's first target of accountabi l i ty is to expand its at tention to the publ ic and be p repared to explain certification in terms that are clear, fair, and convincing, x The second group to which the Board must be accountable is the appl icants for certification in internal m e d i c i n e y o u n g physicians who fulfill our training requi rements and prepare to take an expensive examination of great impor t to their subsequent careers. Students entering internal medic ine n o w are different f rom those of pr ior years in important ways. They are more inclined to pursue other interests, to plan for dual careers in their families, to be in debt and, thus, to quest ion major expenses. The Board must be seen as fair, perhaps demanding, but clearly justified in its approaches, and responsive to the personal and professional goals of the young internist. In particular, candidates will expec t to see a "value added" to being certified. To both the publ ic and the applicant , then, the Board owes a process that is fair, rational, and valid. In addition, however , the Board owes accountability to two immaterial standards. One is that of " B o a r d n e s s " a term I shall use to represent the principle of the Board p h e n o m e n o n as distinct f rom any immediate example . 2 In this sense, as in any philosophic ideal, there are universal attributes of Board identity that the ABIM must honor. These include a dedicat ion to the standards of a profession, a p r imary bel ief in the intellectual process, a will ingness to learn
Microtubule recognition: a curvy attraction.

Summary While many proteins specifically associate with microtubule ends, the mechanisms underlying these associations remain largely undetermined. A new study demonstrates that doublecortin may localize to microtubule tips through preferential binding to regions of microtubule curvature.
The shape of things to come: importance of design in nanotechnology for drug delivery

The design of nanoparticle (NP) size, shape and surface chemistry has a significant impact on their performance. While the influences of the particle size and surface chemistry on drug delivery have been studied extensively, little is known about the effect of particle shapes on nanomedicine. In this perspective article, we discuss recent progress on the design and fabrication of NPs of various shapes and their unique delivery properties. The shapes of these drug carriers play an important role in therapeutic delivery processes, such as particle adhesion, distribution and cell internalization. We envision that stimuli-responsive NPs, which actively change their shapes and other properties, might pave way to the next generation of nanomedicine.
Spin bags and quasiparticles in doped La2CuO4.

Limited configuration-interaction calculations beyond Hartree-Fock are reported for an ab initio derived eight-band effective Hamiltonian for ${\mathrm{La}}_{2}$${\mathrm{CuO}}_{4}$. These results clearly implicate two important types of configurations, as well as the role of apical-O ${\mathrm{p}}_{\mathrm{z}}$ states, in the nature and dispersion of quasiparticle states associated with one hole doped into the parent insulator. The two types of configurations are spatially inhomogeneous ``spin bags'' centered about a flipped spin relative to the host antiferromagnetic order, and ``doped N\'eel'' configurations that leave the host spin order intact. Taken together these complementary parts are suggestive of the local singlet of Zhang and Rice. It is, however, the latter doped N\'eel configurations that carry those apical-O ${\mathit{p}}_{\mathit{z}}$ components that are primarily responsible for very shallow quasiparticle dispersion from k=(\ensuremath{\pi}/2,\ensuremath{\pi}/2), where the first holes are doped, towards (\ensuremath{\pi},0).
The Response to Reform in a Growing Economy: The Role of Rent‐Seeking Technology

Individuals engaged in rent seeking accumulate sector-specific human capital through learning-by-doing. If agents specialize, small reforms of the trade regime may fail to reduce the level of the rent-seeking activity. The size of the reform necessary to induce movement out of rent seeking is increasing in the time that controls have been in place. If rent seeking and production are complementary activities, agents will not specialize in either, and will fully respond to a small reform of the trade regime. This is true even though they accumulate human capital specific to rent seeking.
Coping, Stress, and the Psychological Symptoms of Children of Divorce: A Cross‐sectional and Longitudinal Study

The authors conducted a cross-sectional and prospective longitudinal study of stress, coping, and psychological symptoms in children of divorce. The sample consisted of 258 children (mean age = 10.1; SD = 1.2), of whom 196 were successfully followed 5.5 months later. A 4-dimensional model of coping was found using confirmatory factor analysis, with the factors being active coping, avoidance, distraction, and support. In the cross-sectional model avoidance coping partially mediated the relations between negative events and symptoms while active coping moderated the relations between negative events and conduct problems. In the longitudinal model significant negative paths were found from active coping and distraction Time 1 to internalizing symptoms Time 2, while Time 1 support coping had a positive path coefficient to Time 2 depression. Positive paths were found between negative events at Time 1 and anxiety at Time 2, and between all symptoms at Time 1 and negative events at Time 2.
Surface features and residual strains in AlON grinding

Aluminum Oxynitride (AlON) is a material of interest to the military for a variety of optical applications, including conformal optics and transparent armor. However, its high hardness and large grain size (on the order of 100-200 micrometers s) produced by current powder metallurgy processes present challenges to deterministic microgrinding. For example, typical contact areas between the tool and work surface for contour grinding are on the order of the AlON grain size. Therefore, individual grains often appear in surface relief (orange peel effect) following contour grinding. In addition, small pits, on the order of 10 micrometers diameter and up to a few microns deep have been observed throughout the grain structure after fine grinding with a 2-4 micrometers diamond tool. In this paper, an overview is given of our experience micro-grinding AlON. First, some of the features observed in fine ground AlON surfaces are described in detail. A theory, based on micro-indentation, is presented to explain the generation of the surface pits. Finally, an estimate of the residual surface stresses after grinding, using x-ray diffraction techniques to measure the strains, is presented.
Data Assimilation Experiments Using Quality Controlled AIRS Version 5 Temperature Soundings

The AIRS Science Team Version 5 retrieval algorithm has been finalized and is now operational at the Goddard DAAC in the processing (and reprocessing) of all AIRS data. The AIRS Science Team Version 5 retrieval algorithm contains two significant improvements over Version 4: 1) Improved physics allows for use of AIRS observations in the entire 4.3 mum CO2 absorption band in the retrieval of temperature profile T(p) during both day and night. Tropospheric sounding 15 mum CO2 observations are now used primarily in the generation of cloud cleared radiances Rcirci. This approach allows for the generation of accurate values of Rcirci and T(p) under most cloud conditions. 2) Another very significant improvement in Version 5 is the ability to generate accurate case-by-case, level-by-level error estimates for the atmospheric temperature profile, as well as for channel-by-channel error estimates for Rcirci. These error estimates are used for quality control of the retrieved products. We have conducted forecast impact experiments assimilating AIRS temperature profiles with different levels of quality control using the NASA GEOS-5 data assimilation system. Assimilation of quality controlled T(p) resulted in significantly improved forecast skill compared to that obtained from analyses obtained when all data used operationally by NCEP, except for AIRS data, is assimilated. We also conducted an experiment assimilating AIRS radiances uncontaminated by clouds, as done operationally by ECMWF and NCEP. Forecast resulting from assimilated AIRS radiances were of poorer quality than those obtained assimilating AIRS temperatures.
The aggregation states of spinach phosphoribulokinase.

Phosphoribulokinase (PRK; EC 2.1.7.19) is active in illuminated chloroplasts and inactive in darkened chloroplasts. This regulatory mechanism is mediated by thioredoxin-dependent reduction of a kinase disulfide in vivo. Extracts of spinach (Spinacia oleracea L.) leaves in the presence of 10 mM dithiothreitol contain a single 80-kDa form of PRK as judged by gel filtration. Gel filtration of thiol-free extracts of light-harvested tissue shows the presence of two inactive forms of PRK, the 80-kDa form and an aggregate (> 550 kDa) form, but treatment of both forms with dithiothreitol restores kinase activity. Gel filtration following extraction of dark-harvested tissue in the absence of dithiotreitol demonstrates the presence of only the heavier form. Inclusion of 400 mM (NH4)2SO4 in the homogenization buffer during extraction of light-harvested tissue suppresses the formation of the high-M r form of PRK, but does not eliminate the aggregate form observed in extracts of dark-harvested leaves. However, prolonged treatment of extracts from dark-harvested tissue with 400 mM (NH4)2SO4 results in conversion of the high-M r form of phosphoribulokinase to the low-M r form. The data are consistent with the heavier form of phosphoribulokinase being the normal in-vivo aggregation state in the dark, while the lighter form is the normal aggregation state in the light. This research was sponsored jointly by the science and education administration of the U.S. Department of Agriculture under Grant No. 88-37130-3722 from the Competitive Research Grants Office and by the Office of Health and Environmental Research, U.S. Department of Energy under Contract DE-AC05-84OR21400 with Martin Marietta Energy Systems Inc., Oak Ridge, Tenn., USA. The author is Postdoctoral Investigator supported by the U.S. Department of Agriculture through Subcontract No. 88-37130-3722 from the Biology Division of Oak Ridge National Laboratory to the University of Tennessee.
Irrigation and Nitrogen Effects on Tall Wheatgrass Yield in the Southern High Plains

Winter months in the Southern High Plains of the USA have the lowest precipitation. As a result, producers using tall wheatgrass [Agropyron elongatum (Host) Beauv.] may get higher production in the spring and possibly throughout the growing season with additional irrigation. Also, growers need information about interactions between soil moisture and N fertilizer to maximize productivity. In a split-plot study conducted at the New Mexico State University Agricultural Science Center at Tucumcari from 1997 to 1999, tall wheatgrass furrow-irrigated monthly from April to September was irrigated once, twice, or not irrigated during winter as the whole-plot treatment. For subplot treatments, tall wheatgrass annually received 168 kg N ha -1 split into two, three, or four equal applications. Tall wheatgrass irrigated in the winter yielded more dry matter (DM) over the 3 yr than unirrigated tall wheatgrass (11.72, 12.10, and 13.55 Mg ha -1 for tall wheatgrass not irrigated, irrigated once, or irrigated twice, respectively). Tall wheatgrass fertilized three or four times outyielded tall wheatgrass fertilized twice (11.08, 12.85, and 13.44 Mg ha -1 for two, three, and four N applications, respectively). No interaction occurred between the irrigation and N treatments. A year x harvest x N effect existed in which a mid-December N application, preceded and followed by precipitation, produced approximately 1 Mg ha -1 more DM than unfertilized tall wheatgrass in the first harvest the following year. Both supplemental winter irrigation and N application scheduling offer opportunities for tall wheatgrass producers to increase production in the Southern High Plains of the USA.
The kernel of a research infrastructure

Infrastructure makes it easier, faster or possible for investigators to study objects of research. It does so by making available consistent and stable resources and services such as data, collaboration tools, sites of sample collection, or calibrated instruments. This paper offers the concept of the kernel of a research infrastructure as a new unit of analysis for investigating the enabling capacities of infrastructure. The kernel is the core resources and services an infrastructure makes available (called the cache), as well as the work, techniques and technologies that go into sustaining that availability (called addressing). By inspecting and comparing the kernel of two long-term scientific enterprises, this paper demonstrates how focusing on the kernel can help explain key qualities of research infrastructure such as flexibility and persistence in the face of dramatic changes to the objects, methods and practice of science.
Stretching and curvature of material lines in chaotic flows

As a streak of dye is advected by a chaotic flow, it stretches and folds and becomes indistinguishable from a one-dimensional idealized material line. The variation along a material line of the total stretching experienced by fluid elements is examined, and it is found that it can be decomposed into an overall time-dependent factor, constant along the line, and a smooth time-independent deviation. The stretching is related by a power-law to the curvature of the line near sharp bends. This is confirmed numerically and motivated by a simple model. A conservation law for Lyapunov exponents explains deviations from a power-law.
Relationship between Mycobacterium avium subspecies paratuberculosis, IL-1α, and TRAF1 in primary bovine monocyte-derived macrophages

Mycobacterium avium subspecies paratuberculosis (MAP) is a facultative intracellular pathogen that resides in host macrophage cells. Presently, little is known about how MAP is able to subvert the normal bacteriocidal functions of infected macrophages. Previously, we reported that ileal tissues from MAP infected cattle contained high levels of interleukin-1 alpha (IL-1alpha) and tumor necrosis factor receptor-associated factor 1 (TRAF1), relative to ileal tissues from uninfected cattle. High-level expression of these two proteins could have profound effects on macrophage function, intracellular signaling, and apoptosis. We now demonstrate that high levels of TRAF1 protein are located primarily within macrophages infiltrating areas of MAP infection. We have also utilized cultured bovine monocyte-derived macrophage cells (MDM) either infected with live MAP or stimulated with recombinant IL-1alpha (rIL-1alpha) to determine if there is a relationship between IL-1alpha and TRAF1 expression. These studies have identified a dose dependent increase in TRAF1 protein levels in bovine MDM in response to infection with live MAP or following treatment with rIL-1alpha. Sustained TRAF1 protein expression was dependent upon interaction of rIL-1alpha with it's receptor and rIL-1beta was also able to enhance TRAF1 gene expression. Our results suggest that MAP may use the IL-1-TRAF1 system to enhance TRAF1 protein expression in infected bovine MDM. These novel results provide evidence for a new avenue of research on the effect of MAP and other intracellular pathogens on macrophage signaling and apoptosis.
THE ULTRASTRUCTURE OF THE PARASITOPHOROUS VACUOLE FORMED BY LEISHMANIA MAJOR

Protozoan parasites of Leishmania spp. invade macrophages as promastigotes and differentiate into replicative amastigotes within parasitophorous vacuoles. Infection of inbred strains of mice with Leishmania major is a well-studied model of the mammalian immune response to Leishmania species, but the ultrastructure and biochemical properties of the parasitophorous vacuole occupied by this parasite have been best characterized for other species of Leishmania. We examined the parasitophorous vacuole occupied by L. major in lymph nodes of infected mice and in bone marrow-derived macrophages infected in vitro. At all time points after infection, single L. major amastigotes were wrapped tightly by host membrane, suggesting that amastigotes segregate into separate vacuoles during replication. This small, individual vacuole contrasts sharply with the large, communal vacuoles occupied by Leishmania amazonensis. An extensive survey of the literature revealed that the single vacuoles occupied by L. major are characteristic of those formed by Old World species of Leishmania, while New World species of Leishmania form large vacuoles occupied by many amastigotes.
Frequently asked questions in drug combinations and the mass-action law-based answers

Summary Drug combinations have been widely used in the treatment of the most dreadful diseases, such as cancer and AIDS. In the search for synergistic combinations for therapy, numerous articles have been published during the past century. However, the term “synergy” has at least 20 different definitions in literature but none supports others. The confusion on synergy claims has far reaching consequences in biomedical research, drug discovery and development, regulation, and medical care of patients. This article reviews the current status and enlists the frequently occurred pit-falls, misconceptions and common errors in drug combination studies. The questions and issues are contemplated to be answered and clarified with the physico-chemical algorithms of the mass-action law, specifically with the unified theory of the median-effect equation and its combination index theorem for drug combinations. The derived theory, algorithm and its computer simulation lead to a quantitative indexed bioinformatics, and econo-green bio-research using small number of data points.
Characterization of a Rat Na+-Dicarboxylate Cotransporter

Abstract The metabolism of Krebs cycle intermediates is of fundamental importance for eukaryotic cells. In the kidney, these intermediates are transported actively into epithelial cells. Because citrate is a potent inhibitor for calcium stone formation, excessive uptake results in nephrolithiasis due to hypocitraturia. We report the cloning and characterization of a rat kidney dicarboxylate transporter (SDCT1). In situ hybridization revealed that SDCT1 mRNA is localized in S3 segments of kidney proximal tubules and in enterocytes lining the intestinal villi. Signals were also detected in lung bronchioli, the epididymis, and liver. When expressed inXenopus oocytes, SDCT1 mediated electrogenic, sodium-dependent transport of most Krebs cycle intermediates (K m = 20–60 μm), including citrate, succinate, α-ketoglutarate, and oxaloacetate. Of note, the acidic amino acids l- and d-glutamate and aspartate were also transported, although with lower affinity (K m = 2–18 mm). Transport of citrate was pH-sensitive. At pH 7.5, the K m for citrate was high (0.64 mm), whereas at pH 5.5, theK m was low (57 μm). This is consistent with the concept that the −2 form of citrate is the transported species. In addition, maximal currents at pH 5.5 were 70% higher than those at pH 7.5, and our data show that the −3 form acts as a competitive inhibitor. Simultaneous measurements of substrate-evoked currents and tracer uptakes under voltage-clamp condition, as well as a thermodynamic approach, gave a Na+to citrate or a Na+ to succinate stoichiometry of 3 to 1. SDCT1-mediated currents were inhibited by phloretin. This plant glycoside also inhibited the SDCT1-specific sodium leak in the absence of substrate, indicating that at least one Na+ binds to the transporter before the substrate. The data presented provide new insights into the biophysical characteristics and physiological implications of a cloned dicarboxylate transporter.
Optical mapping of nonmelanoma skin cancer

More than two million cases of nonmelanoma skin cancers are diagnosed every year. Therefore, there is a strong need for practical, reliable, rapid, and precise methods for tumor delineation, to guide surgery and other treatments of skin cancer. Once developed, such methods may be useful for squamous cell carcinomas of other organs. Non-invasive optical imaging techniques including polarization sensitive reflectance and fluorescence imaging were evaluated for the demarcation of nonmelanoma skin tumors. Thick freshly excised tumor specimens obtained from Mohs surgery were used for the experiments. Imaging was performed using linearly polarized incident light in the visible and near infrared spectral range from 577 nm to 750 nm. Non-toxic absorbing and fluorescent dyes (Toluidine Blue O, Methylene Blue) were employed to enhance tumor contrast in the images. The images were acquired using the remitted light polarized in the directions parallel and perpendicular to the polarization of incident light. Reflectance and fluorescence polarization images were evaluated. The data were processed and analyzed for dependence of the remitted light polarization on the tissue type (cancerous/normal). The data obtained so far from fresh tumor specimens in vitro using dye-enhanced polarized light reflectance, and exogenous fluorescence polarization imaging suggest that optical mapping can become a valuable guidance tool in nonmelanoma cancer surgery.
Maximum pressure developed by solid conveying force in screw extruders

There are two distinct solid conveying theories that can be applied to plasticating screw extruders. One is Darnell and Mol's theory based on a solid-to-solid friction model and the other is Chung's theory based on a viscous shearing model. The two theories predict very different solid conveying performances for a same set of conditions. In this paper, the maximum pressures that can be developed inside plasticating screw extruders by the solid conveying force are calculated using each of the two theories. Comparison of the results may shed some light on the applicability of each theory for a particular extrusion operation.
An Investigation of Differential Reinforced Imitation Training on Imitative Behavior

Abstract The function of reinforcement as a performance versus a learning variable was examined with the use of a number of varying imitation training conditions. Forty white and 40 black Ss were used. The analysis consisted of five 2 (Testing Situation) × 2 (White versus Black children) × 8 (Training Conditions) factorials with the use of an analysis of variance technique. The results question the hypothesis that reinforcement is only a performance variable. Partial support is provided for the assumption that imitative behavior may be maintained through similarity of responding where imitation has been acquired through a strong history of reinforcement for imitation. Few racial differences were discovered.
Graph Database Indexing Using Structured Graph Decomposition

We introduce a novel method of indexing graph databases in order to facilitate subgraph isomorphism and similarity queries. The index is comprised of two major data structures. The primary structure is a directed acyclic graph which contains a node for each of the unique, induced subgraphs of the database graphs. The secondary structure is a hash table which cross-indexes each subgraph for fast isomorphic lookup. In order to create a hash key independent of isomorphism, we utilize a code-based canonical representation of adjacency matrices, which we have further refined to improve computation speed. We validate the concept by demonstrating its effectiveness in answering queries for two practical datasets. Our experiments show that for subgraph isomorphism queries, our method outperforms existing methods by more than an order of magnitude.
The golden ratio and super central configurations of the n-body problem

Abstract In this paper, we consider the problem of central configurations of the n-body problem with the general homogeneous potential 1 / r α . A configuration q = ( q 1 , q 2 , … , q n ) is called a super central configuration if there exists a positive mass vector m = ( m 1 , … , m n ) such that q is a central configuration for m with m i attached to q i and q is also a central configuration for m ′ , where m ′ ≠ m and m ′ is a permutation of m. The main discovery in this paper is that super central configurations of the n-body problem have surprising connections with the golden ratio φ. Let r be the ratio | q 3 − q 2 | | q 2 − q 1 | of the collinear three-body problem with the ordered positions q 1 , q 2 , q 3 on a line. q is a super central configuration if and only if 1 / r 1 ( α ) r r 1 ( α ) and r ≠ 1 , where r 1 ( α ) > 1 is a continuous function such that lim α → 0 r 1 ( α ) = φ , the golden ratio. The existence and classification of super central configurations are established in the collinear three-body problem with general homogeneous potential 1 / r α . Super central configurations play an important role in counting the number of central configurations for a given mass vector which may decrease the number of central configurations under geometric equivalence.
Medical co-morbidity, brain disease, and the future of geriatric psychiatry.

The co-occurrence of psychiatric and medical illness and the complex bi-directional relationship of disorders of the aging brain and body is the rule, rather than the exception, in geriatric psychiatry. Psychiatric illnesses ranging from affective disorders to anxiety and cognitive disorders are common in the geriatric population, and often co-occur with medical illness, which is likewiseprevalentinthispopulation.Medicalillnessmay hasten the initial presentation of psychiatric illness, affect its course, and influence response to treatment and prognosis, and psychiatric illness and its treatment may predict greater severity and poorer outcome of medical illness. Adding to this complexity, the symptoms of psychiatric and medical illness frequently overlap in the geriatric population, and are influenced by medication burden and side effects, as well as age-related biological and environmental factors, all of which necessitate the needforincreasingdiagnosticvigilanceandcollaboration with medical providers in the care of geriatric patients. This special edition of the Journal addresses the complex relationship between psychiatric and medical illness in the elderly. In this editorial we highlight examples of medicalandpsychiatricsyndromesthatareco-occurring, interrelated, and mechanistically linked, thereby providingamountingargument for achangingstandard of research and clinical practice in geriatric psychiatry.
REGIONS OF CELL WALL EXPANSION IN THE PROTONEMA OF A FERN

A B S T R A CT Protonemata of Onoclea sensibilis were grown for 7 days in darkness and were then transferred into light on new media, either liquid or agar-solidified, which contained 0.15 % colchicine. The growth of individual plants was observed on solid media in microchambers. Unequivocal evidence was obtained that cell wall expansion and an increase in cell diameter occurred in regions well behind the apex of the protonema. This finding is related to an hypothesis which proposes light-induced changes in microtubule orientation and cell wall structure as an explanation for certain changes in cell form in fern gametophytes. MILLER AND STEPHANI (1971) suggested that the increase by light in the rate of protonema elongation in fern gametophytes might result from a light-induced change in the orientation of cytoplasmic microtubules which, in turn, controlled the structure and mechanical properties of the cellulose cell wall. The walls of protonemata growing in darkness were supposed to be more mechanically isotropic and prone to yield laterally as well as longitudinally under cell turgor. Irradiation with red or far-red light was proposed to produce a wall structure which was strengthened against lateral yielding; this was indicated by the smaller diameters of the light-treated protonemata. Since both dark- and light-grown protonemata had the same rate of volume increase, the rate of elongation was, of necessity, higher in irradiated plants with smaller diameters. Some support for the basic assumption of this hypothesis has come from the work of Stetler and DeMaggio (1972). Microtubules were oriented axially in the cylindrical part of protonemata of Dryopteris filix-mas which were kept filamentous under red light, whereas microtubule orientation was random in plants placed under blue light, which initiated a bulging lateral expansion of the filament tip. Thus at least one example of a lightinduced change in cell shape in fern gametophytes is correlated with an observable change in microtubule orientation.
Coordinated synthesis and degradation of actin and myosin in a variety of myogenic and non-myogenic cells.

Abstract The turnover of myosin and actin in both muscle and non-muscle cells in culture was investigated. By the double-label criterion, myosin and actin were coordinately synthesized and degraded in replicating, mononucleated fibroblasts, chondrocytes, BUdR-suppressed myogenic cells, and in post-mitotic, multinucleated myotubes. Myosin and actin were among the most stable proteins in each cell type. In single label ‘pulse-chase’ experiments, the half-lives of myosin and actin in all replicating, mononucleated cells were 2.5–3 days; in myotubes, however, they were approx. 6 days. Myosin and actin labelled in replicating presumptive myoblasts and chased until the cells ceased replicating and fused into multinucleated myotubes retained the degradation rate of 3 days; this differed from Jhe rate of 6 days shown for myosin and actin newly-synthesized in post-mitotic myotubes. The type of myosin synthesized in the mother presumptive myoblast, then, is transmitted to the postmitotic daughters. This myosin, however, is more rapidly degraded than the definitive myosin that is synthesized in the myotube.
Coherent gestures, locomotion, and speech in life-like pedagogical agents

Life-like animated interface agents for knowledge-based learning environments can provide timely, customized advice to support students’ problem solving. Because of their strong visual presence, they hold significant promise for substantially increasing students’ enjoyment of their learning experiences. A key problem posed by life-like agents that inhabit artificial worlds is deictic believability. In the same manner that humans refer to objects in their environment through judicious combinations of speech, locomotion, and gesture, animated agents should be able to move through their environment, and point to and refer to objects appropriately as they provide problem-solving advice. In this paper we describe a framework for achieving deictic believabilityin animated agents. A deictic behavior planner exploits a world model and the evolving explanation plan as it selects and coordinates locomotive, gestural, and speech behaviors. The resulting behaviors and utterances are believable, and the references are unambiguous. This approach to spatial deixis has been implemented in a life-like animated agent, Cosmo, who inhabits a learning environment for the domain of Internet packet routing. The product of a large multidisciplinary team of computer scientists, 3D modelers, graphic artists, and animators, Cosmo provides realtime advice to students as they escort packets through a virtual world of interconnected routers.
Neonatal cavopulmonary assist: pulsatile versus steady-flow pulmonary perfusion.

Background Morbidity and mortality associated with single-ventricle physiology decrease substantially once a systemic venous, rather than systemic arterial, source of pulmonary blood flow is established. Cavopulmonary assist has potential to eliminate critical dependence on the problematic systemic-to-pulmonary shunt as a source of pulmonary blood flow in neonates. We have previously demonstrated feasibility of neonatal cavopulmonary assist under steady-flow conditions. We hypothesized that pulsatile pulmonary perfusion would further improve pulmonary hemodynamics. Methods Lambs (weight 7.2 ± 1.1 kg, age 7.9 ± 1.5 days) underwent total cavopulmonary diversion using bicaval venous-to-main pulmonary artery cannulation. A miniature centrifugal pump was used to augment cavopulmonary flow. Pulsatility was created with an intermittently compressed compliance chamber in the circuit. Hemodynamic and gas exchange data were measured for 8 hours. Pulsatile (n = 6), steady-flow (n = 13), and control (n = 6) groups were compared using two-way analysis of variance with repeated measures. Results All animals remained physiologically stable with normal gas exchange function. Mean pulmonary arterial pressure was elevated in pulsatile and steady-flow groups compared with the control group and within-group baseline values. Pulmonary vascular resistance was elevated initially in both assist groups but decreased significantly over the last 4 hours of the study and normalized after hour 4 in the pulsatile perfusion group. Pulmonary vascular resistance also normalized to control in the steady-flow group after hour 7. Conclusions Both steady-flow and pulsatile pulmonary perfusion demonstrated normalization of pulmonary vascular resistance to control in a neonatal model of univentricular Fontan circulation. These results suggest that there is no benefit to pulsatile flow in this model.
The milkweed bug electroantennogram: Milkweed bug extracts and the effect of light and temperature

Abstract Milkweed bug olfactory receptors were stimulated by extracts of adult male and female milkweed bugs. These responses, measured electrophysiologically, were independent of sex and reproductive condition. An increase in temperature above room temperature decreased the stimulus-off amplitude of the electroantennogram, but the electroantennogram was not changed by variations in light intensity.