cssi/SciSciGPT-SciSciNet huggingface dataset:
Insights into dental mineralization from three heritable mineralization disorders

Teeth are comprised of three unique mineralized tissues, enamel, dentin, and cementum, that are susceptible to developmental defects similar to those affecting bone. X-linked hypophosphatemia (XLH), caused by PHEX mutations, leads to increased fibroblast growth factor 23 (FGF23)-driven hypophosphatemia and local extracellular matrix disturbances. Hypophosphatasia (HPP), caused by ALPL mutations, results in increased levels of inorganic pyrophosphate (PPi), a mineralization inhibitor. Generalized arterial calcification in infancy (GACI), caused by ENPP1 mutations, results in vascular calcification due to decreased PPi, later compounded by FGF23-driven hypophosphatemia. In this perspective, we compare and contrast dental defects in primary teeth associated with XLH, HPP, and GACI, briefly reviewing genetic and biochemical features of these disorders and findings of clinical and preclinical studies to date, including some of our own recent observations. The distinct dental defects associated with the three heritable mineralization disorders reflect unique processes of the respective dental hard tissues, revealing insights into their development and clues about pathological mechanisms underlying such disorders.
Requiring Civics Then and Now: Potentials and Pitfalls of Mandated Civics Curriculum:

BackgroundIn recent years, the United States has seen a resurgence in calls for mandating civics coursework across the country. For decades, scholars have identified classroom practices that help m...
The New Bailments

The rise of cloud computing has dramatically changed how consumers and firms store their belongings. Property that owners once managed directly now exists primarily on infrastruc-ture maintained by intermediaries. Consumers entrust their photos to Apple instead of scrap-books; businesses put their documents on Amazon’s servers instead of in file cabinets; seemingly everything runs in the cloud. Were these belongings tangible, the relationship between owner and intermediary would be governed by the common-law doctrine of bailment. Bailments are mandatory relationships formed when one party entrusts their property to another. Within this relationship, the bailees owe the bailors a duty of care and may be liable if they failed to return the property. The parties can use contract to customize the relationship but not to disclaim entirely. Tracing the law of bailment relationships from its ancient roots to the present, this Article argues that cloud storage should be understood as creating a bailment relationship. The law of bailment, though developed in the Middle Ages, provides a robust framework for govern-ing twenty-first century electronic intermediaries. Though the kind of stored property has changed, the parties’ expectations and incentives have not. Yet the decline of litigation, the rise of arbitration, federal diversity jurisdiction, and the ever-growing dominance of contract has thus far prevented courts from applying the law of bailments to these new services. Recognizing cloud storage as a bailment would have significant implications. Most immedi-ately, it would suggest that important provisions in many cloud storage services’ contracts are unenforceable. A hand-collected dataset of 61 cloud storage contracts, reveals that most have include general disclaimers for any liability for lost data. These disclaimers are inconsistent with the duty of care that is the foundation of the law of bailment. In addition, understand-ing cloud storage as a bailment would have important implications for both the law of con-sumer protection and Fourth Amendment protections.
Resuscitative Endovascular Balloon Occlusion of the Aorta ( REBOA) Resuscitative endovascular balloon occlusion of the aorta (REBOA)

Resuscitative endovascular balloon occlusion of the aorta (REBOA) is an adjunct in the management of critically ill patients with non-compressible torso hemorrhage. REBOA is a less invasive alternative to resuscitative thoracotomy, designed to sustain central circulation until hemostasis can be achieved. This chapter outlines the brief history of REBOA and the steps required when placing the device as well as potential complications.
Identification, Shiga toxin subtypes and prevalence of minor serogroups of Shiga toxin-producing Escherichia coli in feedlot cattle feces.

Shiga toxin-producing Escherichia coli (STEC) are foodborne pathogens that cause illnesses in humans ranging from mild to hemorrhagic enteritis with complications of hemolytic uremic syndrome and even death. Cattle are a major reservoir of STEC, which reside in the hindgut and are shed in the feces, a major source of food and water contaminations. Seven serogroups, O26, O45, O103, O111, O121, O145 and O157, called ‘top-7’, are responsible for the majority of human STEC infections in North America. Additionally, 151 serogroups of E. coli are known to carry Shiga toxin genes (stx). Not much is known about fecal shedding and prevalence and virulence potential of STEC other than the top-7. Our primary objectives were to identify serogroups of STEC strains, other than the top-7, isolated from cattle feces and subtype stx genes to assess their virulence potential. Additional objective was to develop and validate a novel multiplex PCR assay to detect and determine prevalence of six serogroups, O2, O74, O109, O131, O168, and O171, in cattle feces. A total of 351 strains, positive for stx gene and negative for the top-7 serogroups, isolated from feedlot cattle feces were used in the study. Of the 351 strains, 291 belonged to 16 serogroups and 60 could not be serogrouped. Among the 351 strains, 63 (17.9%) carried stx1 gene and 300 (82.1%) carried stx2, including 12 strains positive for both. The majority of the stx1 and stx2 were of stx1a (47/63; 74.6%) and stx2a subtypes (234/300; 78%), respectively, which are often associated with human infections. A novel multiplex PCR assay developed and validated to detect six serogroups, O2, O74, O109, O131, O168, and O171, which accounted for 86.9% of the STEC strains identified, was utilized to determine their prevalence in fecal samples (n = 576) collected from a commercial feedlot. Four serogroups, O2, O109, O168, and O171 were identified as the dominant serogroups prevalent in cattle feces. In conclusion, cattle shed in the feces a number of STEC serogroups, other than the top-7, and the majority of the strains isolated possessed stx2, particularly of the subtype 2a, suggesting their potential risk to cause human infections.
Understanding Interest on Overpayments and Underpayments

To properly advise a client, the tax practitioner needs a basic understanding of how interest is imposed and computed on both underpayments and overpayments. Interest calculations in most commercial applications is straight-forward. As tax law and tax practice have evolved and become more complex, so have the interest provisions in the Internal Revenue Code. The IRS may make errors in its calculations or have insufficient information to compute interest accurately; in addition, there are some disputed issues or areas where the law is uncertain. For large corporations or high-income taxpayers, disputes can involve millions of dollars. Some errors can even affect low-income taxpayers with seemingly simple facts.
18FDG-PET/CT Specificity for the Detection of Lymphoma Recurrence in the Tonsils.

Objective In patients with a history of lymphoma who demonstrate palatine tonsil uptake on posttreatment PET/CT (positron emission tomography/computed tomography), tonsillectomy is often performed to evaluate for lymphoma recurrence. However, predictive clinical and imaging factors for true tonsil recurrence in this setting are not well established; this will be explored herein. Study design Retrospective case series. Setting Patients treated at a tertiary medical center from January 2008 to May 2020. Methods Chart review was performed on all patients with a history of treated lymphoma in clinical remission who presented for evaluation of abnormal PET/CT imaging findings and subsequently underwent tonsillectomy. Results Among 15 patients who met inclusion criteria, 14 had benign findings on surgical pathology, yielding a false-positive rate of 93%. The patient with malignancy was identified on biopsy after inconclusive surgical pathology and is the only documented case of recurrence in this specific patient population throughout the literature. The patient presented with B symptoms, irregularly shaped tonsils, increased lymph node activity on PET/CT, and uptrending bilateral tonsil activity but with one of the lowest maximum standardized uptake values of the cohort. The singular distinguishing feature for the patient with recurrent disease was a prior tonsil biopsy suspicious for recurrence, which prompted the otolaryngology referral. Conclusion PET/CT lacks specificity in identifying lymphoma recurrence in the oropharynx. Clinical and radiographic features that were previously considered concerning for recurrence are most likely not indicative of malignancy in this patient population. Our findings call into question whether tonsillectomy should be routinely performed in this patient population.
Sensor Integration in the Mechatronic Environment

Next generation car architecture will be marked by seamless component integration. The „Mechatronics Concept“ enables composable architectures in the car and will lead to increased development quality. The upcoming of LIN™ and FlexRay™ based networking systems in the car is in line with this new development paradigm, marked by model based system development, where the system design is supported by component modelling at each stage. This will lead to results which are „correct-by-construction“ and will shorten the qualification cycle times concurrently with a significant increase in quality and reliability. Sensor design will have to comply with the new integration paradigms into the car electronic system. This will ultimately result into a software centric car architecture, which is being defined by the newly established AutOsar consortium. It will ultimately resolve the lifecycle disconnects between the semiconductor industry and the car industry and ensure a steady stream of innovation as well as assured spare parts supply.
Optic flow is used to control human walking

How is human locomotion visually controlled? Fifty years ago, it was proposed that we steer to a goal using optic flow, the pattern of motion at the eye that specifies the direction of locomotion. However, we might also simply walk in the perceived direction of a goal. These two hypotheses normally predict the same behavior, but we tested them in an immersive virtual environment by displacing the optic flow from the direction of walking, violating the laws of optics. We found that people walked in the visual direction of a lone target, but increasingly relied on optic flow as it was added to the display. The visual control law for steering toward a goal is a linear combination of these two variables weighted by the magnitude of flow, thereby allowing humans to have robust locomotor control under varying environmental conditions.
Oak tree and grazing impacts on soil properties and nutrients in a California oak woodland

There is great interest in understanding how rangeland management practices affect the long-term sustainability of California oak woodland ecosystems through their influence on nutrient cycling. This study examines the effects of oak trees and low to moderate intensity grazing on soil properties and nutrient pools in a blue oak (Quercus douglasii H.&A.) woodland in the Sierra Nevada foothills of northern California. Four combinations of vegetation and management were investigated: oak with grazing, oak without grazing, open grasslands with grazing, and open grasslands without grazing. Results indicate that oak trees create islands of enhanced fertility through organic matter incorporation and nutrient cycling. Compared to adjacent grasslands, soils beneath the oak canopy have a lower bulk density, higher pH, and greater concentrations of organic carbon, nitrogen, total and available P, and exchangeable Ca, Mg, and K, especially in the upper soil horizons (0-35 cm). In contrast, the light grazing utilized at this site had minimal effects on soil properties which included an increase in the bulk density of the surface horizon and an increase in available P throughout the entire soil profile. While low to moderate intensity grazing has little effect at this study site, there could be much larger impacts under the more intensive grazing practices utilized on many rangelands. The lack of oak regeneration and oak tree removal to enhance forage production may eventually lead to large losses of nutrients and soil fertility from these ecosystems. Results of this study have important implications for predicting how management practices may potentially affect oak regeneration, water quality, and ecosystem sustainability.
Availability of Credit and Loan Default: A Look at the Commercial Mortgage Supply Cycle

This study uses a structural equation approach to assess the presence of a credit supply effect in the commercial mortgage market and the lenders’ ability to incorporate expectations about this effect into their lending policies. A credit supply effect is defined as the effect of mortgage supply on the level of loan defaults. The empirical analysis shows two important results. First, changes in loan defaults appear to be preceded by changes in commercial mortgage supply with a lag of approximately four to five years. Second, lenders tend to behave myopically, failing to incorporate expectations about the credit supply effect into their lending policies. Additionally, a simulation suggests that adequate timing of the mortgage supply cycle is crucial in limiting the incidence of mortgage default.
Evaluating Neutralizing Antibodies Against HIV, SIV, and SHIV in Luciferase Reporter Gene Assays

Neutralizing antibody assays are powerful tools for assessing humoral immunity in AIDS virus infection and vaccine development. Although many different assays have been described, all are based on the same principle, measuring reductions in virus infectivity. This unit describes two assays utilizing a genetically engineered cell lines that are susceptible to infection by most strains of HIV-1, SIV, and SHIV. One assay is designed for optimal performance with uncloned viruses produced in either PBMC or CD4+ T cell lines. A second assay is designed for single-cycle infection with molecularly cloned pseudoviruses produced by transfection in 293T cells. Both assays are performed in a 96-well format and use tat-responsive luciferase reporter gene expression as readout.
A New Deal in Professional Preparation

(1974). A New Deal in Professional Preparation. Journal of Health, Physical Education, Recreation: Vol. 45, No. 5, pp. 65-66.
Kinship Foster Care and Its Impact on Grandmother Caregivers

Summary Kinship foster care programs are designed to address the needs of relatives, usually grandparents, who have taken in children who have been removed from their homes voluntarily, or following a substantiated report of neglect and/or abuse. The author reviews the history of kinship foster care nationally and examines related research. Reported are findings on a survey of kinship foster care programs nationwide and from qualitative interviews with nine grandmothers from New York City who were kinship foster care providers. Particular attention was paid in these surveys to the impact of kinship foster care on families caring for children with disabilities.
Identification of a candidate regulatory element within the 5' flanking region of the mouse Igh locus defined by pro-B cell-specific hypersensitivity associated with binding of PU.1, Pax5, and E2A.

The Igh locus is controlled by cis -acting elements, including Eμ and the 3′ IgH regulatory region which flank the C region genes within the well-studied 3′ part of the locus. Although the presence of additional control elements has been postulated to regulate rearrangements of the V H gene array that extends to the 5′ end of the locus, the 5′ border of Igh and its flanking region have not been characterized. To facilitate the analysis of this unexplored region and to identify potential novel control elements, we physically mapped the most D-distal V H segments and scanned 46 kb of the immediate 5′ flanking region for DNase I hypersensitive sites. Our studies revealed a cluster of hypersensitive sites 30 kb upstream of the most 5′ V H gene. Detection of one site, HS1, is restricted to pro-B cell lines and HS1 is accessible to restriction enzyme digestion exclusively in normal pro-B cells, the stage defined by actively rearranging Igh-V loci. Sequence motifs within HS1 for PU.1, Pax5, and E2A bind these proteins in vitro and these factors are recruited to HS1 sequence only in pro-B cells. Transient transfection assays indicate that the Pax5 binding site is required for the repression of transcriptional activity of HS1-containing constructs. Thus, our characterization of the region 5′ of the V H gene cluster demonstrated the presence of a single cluster of DNase I hypersensitive sites within the 5′ flanking region, and identified a candidate Igh regulatory region defined by pro-B cell-specific hypersensitivity and interaction with factors implicated in regulating V(D)J recombination.
EIFs: When it works, when it does not

Exterior Insulation Finish System clad projects perform well when they are properly designed and constructed and they have had problems when they were not. As with all manufactured systems and products, there are proper uses and methods of application that must be understood and used by the designer, contractor and the owner. The author's first use of an Exterior Insulation Finish System was designed and constructed in 1978. That project's success and condition today exemplifies the proper design and use of the material. The author has investigated several projects in the last four years that have had problems. Through study of the problems, the design and the installation, the reasons for the problems were defined. The problems were of the type that do not condemn the system. They were the result of inadequate design, lack of understanding of the system use, and its interface with other materials or the failure of the installers to perform their work properly. These reasons for the failures and the way they could have been avoided are explained through the use of specific examples from the 1978 building and the problem projects.
Quantitative Methods for Determining U.S. Air Force Crew Cushion Comfort

Abstract : Designing a single cushion to address the physiological problems of the entire aircrew population is a significant challenge. Often the cushion itself is the only item that can be replaced to improve comfort. In this study 22 subjects were tested on Operational and prototype cushions, including one dynamic cushion. Tests were conducted over eight-hour durations, during which subjective survey data, cognitive performance data, seated pressures and contact areas, muscular fatigue levels, and lower extremity oxygen saturation were recorded. Peak seated pressures range from 1.22 - 3.22 psi. Oxygen saturation in the lower extremities decreased over the eight hours. Cognitive performance increased over time. Muscle fatigue increased throughout the eight hours regardless of cushion, with the exception of the dynamic cushion which promoted muscular recovery. Subjective comfort levels declined over the eight hours. Subjective measurements correlated with objective parameters for the static cushions. Trade-offs in performance and fatigue mitigation were apparent in the dynamic cushion which also highlighted differences between genders.
fMRI of Language Systems: Methods and Applications

Language functions were among the first to be ascribed a specific location in the human brain1 and have been the subject of intense research for over a century. Many researchers across the globe—working in disciplines as varied as linguistics, psychology, neurology, anthropology, and philosophy—have devoted their careers to understanding language processes and their biological bases.
Teaching Elementary Students with Moderate Intellectual Disabilities How to Shop for Groceries

A multiple probe across participants design assessed the effectiveness of an instructional strategy to teach 10 elementary-aged students with moderate intellectual disabilities how to shop for grocery items. Following the intervention, which consisted of in vivo training using constant time delay and simulation training using a pictorial storyboard, 6 students achieved criterion. Two other students' shopping performances improved considerably during training, but the students did not achieve criterion as training was discontinued due to the end of the school year. Maintenance data indicate that the students who achieved criterion retained their skills for 6 weeks, and generalization data indicate that they could shop for the same items in a novel store.
Characterization of an 18,000-molecular-weight outer membrane protein of Haemophilus ducreyi that contains a conserved surface-exposed epitope.

Abstract Identification of antigenically conserved surface components of Haemophilus ducreyi may facilitate the development of reagents to diagnose and prevent chancroid. A hybridoma derived from a mouse immunized with nontypeable Haemophilus influenzae produced a monoclonal antibody (MAb), designated 3B9, that bound to 35 of 35 H. ducreyi strains isolated from diverse geographic regions. The MAb 3B9 bound to a non-heat-modifiable H. ducreyi outer membrane protein (OMP) whose apparent molecular weight was 18,000 (the 18K OMP), and the 3B9 epitope did not phase vary at a rate of greater than 10(-3) in H. ducreyi. In immunoelectron microscopy, the 3B9 epitope was surface exposed, and there was intrastrain and interstrain variability in the amount of 3B9 labelling of whole cells. The MAb 3B9 cross-reacted with many species of the family Pasteurellaceae and bound to the 16.6K peptidoglycan-associated lipoprotein (P6 or PAL) of H. influenzae. Unlike P6, the 18K OMP did not copurify with peptidoglycan. In Western blots (immunoblots), five of seven serum samples obtained from patients with chancroid and four of five serum samples obtained from patients with other genital ulcer diseases at the time of presentation contained antibodies that bound to the 18K OMP. In a competition enzyme-linked immunosorbent assay, four of these serum samples inhibited the binding of 3B9 to H. ducreyi by more than 50%. We conclude that members of Pasteurellaceae expressed a conserved epitope on OMPs that sometimes had different physical characteristics. Patients with chancroid usually have antibodies to the 18K OMP and the 3B9 epitope that may have resulted from infection with H. ducreyi or previous exposure to other Haemophilus or Actinobacillus sp. strains.
EU Cohesion Policy and the Europeanization of Central and East European Regions

This article probes the extent to which politics in Central and Eastern European (CEE) regions are becoming Europeanized. Existing analyses suggest that Europeanization and regionalization in CEE have been loosely related phenomena. These claims, along with broader forecasts about the waning post-accession influence of the European Union (EU), generate predictions that the politics of the regions will be ‘lightly Europeanized’. The article presents evidence to refute these predictions. It shows that EU norms, incentives and discourses are being transmitted through EU cohesion policy and becoming deeply embedded in the identities and strategies of Polish, Czech and Slovak regional officials. It further suggests that subnational actors are drawing on EU resources to reinforce their traditionally weak positions vis-a-vis their respective central states.
Scaling functions and equations of state for nonlinear sigma models

Abstract A simple method is presented which allows for a systematic extrapolation and resummation of the loop expansion for nonlinear σ-models. The results guarantees renormalizability, the correct critical exponents to the order the loop expansion was carried out exactly, and a physical solution in the high-temperature phase. As applications we use recent four-loop results to calculate the equation of state for the Heisenberg ferromagnet, and the scaling function for the Anderson transition, both with and without time-reversal invariance.
Latent Effects of Pesticides and Toxic Substances On Sexual Differentiation of Rodents

In humans and rodents, exposure to hormonally active chemicals during sex differentiation can produce morphological pseudohermaphrodism (Schardein, 1993; Gray, 1992). For example, hormonally active drugs like DES (estrogenic), Danazol (androgenic), and progestins cause urogenital malformations in the reproductive tracts of humans and rodents. The current discussion will present new information on the effects of toxic chemicals and pesticides that act on reproductive development via novel mechanisms, including germ cell toxicity, antiandrogenicity, and Ah-receptor binding. Information will be presented that describes how exposure during critical stages of life to synthetic chemicals present in our environment, such as benzidine-based dyes, antiandrogenic fungicides, 2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD), and PCB congener 169, result in abnormal rodent sex differentiation. In rodents, perinatal exposure to fetal germ cell toxicants reduced the reproductive potential of female, and permanently reduced sperm production in male progeny. Phenotypic sex differentiation, however, was unaffected by these germ cell toxicants. In contrast, antiandrogenic drugs and fungicides induced profound alterations in phenotypic sex differentiation. Effects such as hypospadias, ectopic testes, vaginal pouches, agenesis of the ventral prostate, and nipple retention in male rats were observed commonly. Although these antiandrogens induced no permanent effects in female progeny, another class of chemicals, the Ah-receptor mediated toxicants, did reduce fertility in both male and female rat offspring. Cauda epididymal sperm numbers were reduced permanently in TCDD-exposed male rat and hamster progeny, and female progeny displayed malformations of the external genitalia. Other toxicants produced dramatic alterations of sex differentiation (uterus unicornis, agenesis of the vas and epididymis, and undescended testes), via mechanisms that have not been characterized yet. Since these adult/pubertal alterations resulted from gestational and/or neonatal exposures, future studies should include a comprehensive assessment of reproductive function after perinatal exposure because the developing animal is extremely sensitive to toxicants during sex differentiation, and many of the effects are difficult to detect until late in life.
Abraham Lincoln as Authentic Reproduction: A Critique of Postmodernism

L'A. va a l'encontre du courant postmoderniste (et plus particulierement de J. Baudrillard et U. Eco) qui critique la nature inauthentique des sites construits aux Etats-Unis. Il definit dans un premier temps l'authenticite (quasi-similitude, similitude, originalite et autorite) avant de prendre l'exemple du site historique reconstitue de New Salem (village illinois ou vecu Lincoln dans les annees 1930). Il explique en quoi ces reconstitutions ne sont pas uniquement negatives
Carcinoma of prostate metastasizingto vocal cord

Metastatic involvement of the larynx by carcinoma of the prostate is a rare event: only 5 cases are recorded in the English literature. We report a case of prostatic carcinoma with symptomatic metastasis to the right vocal cord. Five months after the diagnosis of metastatic disease in the vocal cord the patient died of widespread metastases. We report the sixth case of this event and review the reported cases in the literature.
The role of water in the petrogenesis of Mariana trough magmas

Most variations in composition among primitive basalts from the Mariana back-arc trough can be explained by melting mixtures of an NMORB-type mantle source and an H_2O-rich component, provided the degree of melting is positively and approximately linearly correlated with the proportion of the H_2O-rich component in the mixture. We conclude that the degrees of melting by which Mariana trough magmas are generated increase from magmas similar to NMORB, through more H_2O-enriched basalts, to ‘arc-like’ basalts, and that this increase is due to the lowering of the solidus of mantle peridotite that accompanies addition of the H_2O-rich component is likely to be ultimately derived from fluid from a subducting slab, but we propose that by the time fluids reach the source regions of Mariana trough basalts, they have interacted with sufficient mantle material that for all but the most incompatible of elements (with respect to fluid-mantle interaction), they are in equilibrium with the mantle. In contrast, fluids added to the source regions of Mariana island-arc magmas have typically interacted with less mantle and thus retain the signature of slab-derived fluids to varying degrees for all but the most compatible elements. Primitive Mariana arc basalts can be generated by melting mixtures of such incompletely exchanged slab-derived fluids and sources similar to NMORB-type mantle sources, but the degrees of melting are typically higher than those of Mariana trough NMORB and the sources have been variably depleted relative to the back-arc sources by previous melt extraction. This depletion may be related to earlier extraction of back-arc basin magmas or may evolve by repeated fluxing of the sources as fluid is continually added to them in the regions of arc magma generation. If fluid with partitioning behavior relative to the solid mantle similar to that deduced for the H_2O-rich component involved in the generation of Mariana trough basalts were extracted from primitive mantle, the residual mantle would have many of the minor and trace element characteristics of typical oceanic upper mantle; primitive mantle enriched in such fluid would be a satisfactory source for the continental crust in terms of its trace and minor element chemical composition.
Performance of genomic medicine

A report on the Cold Spring Harbor Laboratory meeting on Precision Medicine: Personal Genomes and Pharmacogenomics, held in Cold Spring Harbor, New York, USA, November 13–16, 2013.
Vaccination Against Murine γ-Herpesvirus Infection

The γ-herpesviruses establish life-long latency in the host and are important human pathogens. T cells play a major role in controlling the initial acute infection and subsequently maintaining the virus in a quiescent state. However, the nature of the T-cell response to γ-herpesvirus infection and the requirements for effective vaccination are poorly understood. The recent development of a murine γ-herpesvirus (murine herpesvirus-68 [MHV-68]) has made it possible to analyze T-cell responses and test vaccination strategies in a small animal model. Intranasal infection with MHV-68 induces an acute infection in the lung and the subsequent establishment of long-term latency, which is associated with splenomegaly and an infectious mononucleosis-like syndrome. Here we review the T-cell response to different phases of the infection and the impact of vaccination against either lytic-cycle, or latency-associated T-cell epitopes.
Growth factors in ulcer healing: lessons from recent studies.

Abstract Growth factors such as epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), platelet-derived growth factor (PDGF) and more recently vascular endothelial growth factor (VEGF) have been used extensively to heal experimental gastric, duodenal and colonic ulcers in animal models. Encouraging results have been reported in clinical trials with EGF and bFGF. Since our laboratory has been involved with the initial ulcer healing studies with bFGF, PDGF and VEGF, we summarize here the major lessons from these studies and from literature data. These conclusions relate to the role of: 1) gastrointestinal (GI) secretion; 2) epithelial versus vascular components of the healing; 3) efficacy in the upper and lower GI tract; 4) quality of ulcer healing; as well as 5) the endogenous origin; and 6) molar potency of growth factors. Namely, among these growth factors only EGF inhibits gastric acid and stimulates duodenal bicarbonate secretion, while chronic administration of bFGF slightly enhances gastric secretion and PDGF has no effect demonstrating that potent ulcer healing can be achieved without influencing acid base and mucus secretion. This might be related to the fact that these growth factors stimulate with varying potency virtually all the cellular elements needed for ulcer healing, e.g., epithelial cell proliferation and migration by EGF > bFGF > PDGF, fibroblast proliferation by bFGF > PDGF and angiogenesis by VEGF > bFGF >> PDGF >> EGF. Conceptually, the most interesting results were obtained recently with VEGF which is virtually specific for angiogenesis, illustrating that stimulation of vascular factors is sufficient for ulcer healing because epithelial cells apparently spontaneously proliferate and migrate over a dense granulation tissue to complete the healing process. Since these growth factors directly stimulate the cell components of ulcer healing, it is probably not surprising that they are active in both upper and lower GI tract lesions, produce good quality of ulcer healing in comparison with spontaneously healed duodenal ulcers which are hypovascular and muscle regeneration is not part of natural healing. Contrary to other antiulcer drugs, these growth factors are endogenously derived and play a role in the natural history of ulcer healing, and since these relatively large peptides (18–45 kDa) are active in ng quantities, their molar potency is 2–7 million times superior to cimetidine-like drugs. Thus growth factors are endogenously derived very potent antiulcer drugs which act independently of GI secretion, are active in upper and lower GI lesions, and since they stimulate virtually all the cells of the healing process, they produce an excellent quality of ulcer healing.
Experimental studies and population balance equation models for breakage prediction of emulsion drop size distributions

A population balance equation (PBE) model for pure drop breakage processes was developed from homogenization experiments and used to investigate model extensibility over a range of emulsion formulation and homogenizer operating variables. Adjustable parameters in the mechanistic breakage functions were estimated from measured drop volume distributions by constrained nonlinear least-squares optimization. Satisfactory prediction of measured bimodal distributions was achieved by the incorporation of two different breakage functions that accounted for large drop breakage due to turbulent shear and for small drop breakage due to collisions between drops and turbulent eddies. Model extensibility to different emulsion compositions and homogenizer pressures was investigated by comparing model predictions generated with the base case parameters to drop volume distributions measured under different conditions. The PBE model satisfactorily accounted for changes in the dispersed phase volume fraction and the interfacial tension with the base case parameters. By contrast, significantly improved predictions for the continuous phase viscosity or multiple formulation variables were obtained through re-estimation of the model parameters using multiple data sets in which the associated variables were systematically varied. The model was not able to satisfactorily predict drop volume distributions resulting from homogenizer pressure changes, perhaps due to the assumption of a constant pressure throughout the homogenizer. We conclude that PBE models of drop breakage can be used to reasonably predict the effects of emulsion formulation variables on drop volume distributions and have the potential for guiding experimental efforts aimed at the design of novel emulsified products.
A Model for mechanotransduction in bone cells: The load‐bearing mechanosomes

The skeleton's response to mechanical force, or load, has significance to space travel, the treatment of osteoporosis, and orthodontic appliances. How bone senses and processes load remains largely unknown. The cellular basis of mechanotransduction, however, likely involves the integration of diffusion-controlled signaling pathways with a solid-state scaffold linking the cell I membrane to the genes. Here, we integrate various concepts from models of connective membrane skeleton proteins, cellular tensegrity, and nuclear matrix architectural transcription factors, to describe how a load-induced deformation of bone activates a change in the skeletal genetic program. We propose that mechanical information is relayed from the bone to the gene in part by a succession of deformations, changes in conformations, and translocations. The load-induced deformation of bone is converted into the deformation of the sensor cell membrane. This, in turn, drives conformational changes in membrane proteins of which some are linked to a solid-state signaling scaffold that releases protein complexes capable of carrying mechanical information, " mechanosomes", into the nucleus. These mechanosomes translate this information into changes in the geometry of the 5' regulatory region of target gene DNA altering gene activity; bending bone ultimately bends genes. We identify specific candidate proteins fitting the profile of load-signaling mechanosomes.
Analysis of KIF17 distal tip trafficking in zebrafish cone photoreceptors.

Abstract Multiple proteins are targeted to photoreceptor outer segments (OSs) where they function in phototransduction. Intraflagellar transport (IFT), a highly conserved bidirectional transport pathway occurring along the microtubules of the ciliary axoneme has been implicated in OS trafficking. The canonical anterograde motor for IFT is the heterotrimeric kinesin II or KIF3 complex. Previous work from our laboratory has demonstrated a role for an additional kinesin 2 family motor, the homodimeric KIF17. To gain a better understanding of KIF17 function in photoreceptor OS we utilized transgenic zebrafish expressing zfKIF17-GFP to assess the localization and dynamics of zfKIF17. Our data indicate that both endogenous KIF17 and KIF17-GFP are associated with the axoneme of zebrafish cones at both early (5 dpf) and late (21 dfp) stages of development. Strikingly, KIF17-GFP accumulates at the OS distal tip in a phenomenon referred to as “tipping”. Tipping occurs in the large majority of photoreceptors and also occurs when mammalian KIF17-mCherry is expressed in ciliated epithelial cells in culture. In some cases KIF17-GFP is shed with the OS tip as part of the disc shedding process. We have also found that KIF17-GFP moves within the OS at rates consistent with those observed for IFT and other kinesins.
The influence of pH and methylene blue on the pathways of glucose utilization and lactate formation in erythrocytes of man.

The influence of pH on the contributions of the Embden-Meyerhof and of the oxidative pentose-phosphate pathways in the utilization of glucose by human erythrocytes in the presence and absence of methylene blue were determined from yields of 14CO2 and [14C]lactate. In the absence of methylene blue both the NADP+ concentration and the phosphofructokinase are controlling factors. At pH 7.0 the oxidative pentose-phosphate pathway accounts for nearly one-half of the metabolic flux. Its contribution nearly vanishes at pH 8.2. In the presence of methylene blue the limitation by the NADP+ concentration disappears. At pH values of 7.4 and below the phosphofructokinase is completely inhibited and is circumvented for the formation of lactate. The limitation of the glucose influx resides in the hexokinase. At pH 8.2 both the Embden-Meyerhof and the oxidative pentose-phosphate pathway participate in the metabolic flux, since the inhibition of the phosphofructokinase is released. With methylene blue metabolic pools are formed. They are derived exclusively from the oxidative pentose-phosphate pathway up to pH 7.5–7.6 and entirely from the Embden-Meyerhof pathway at pH 8.2.
Different neurons in different regions of human temporal lobe distinguish correct from incorrect identification or memory

Changes in the frequency of neural activity differentiating correct from incorrect responses were identified in extracellular recordings from 113 neurons at 62 sites in temporal lobe of 26 patients undergoing awake neurosurgery, during identification and recent explicit memory for object names, text or auditory words. Activity significantly differentiating correct from incorrect performance was identified in 22 neurons at 16 sites in 12 patients. Different neurons in different regions differentiated identification or memory performance. The 13 neurons differentiating identification performance were overrepresented in medial-basal recordings, the 9 neurons differentiating memory performance in superior temporal gyrus. All memory changes occurred during encoding. For both identification and memory there was separation of neurons showing differentiation early during perception and processing from those showing differentiation late, when output should occur, perhaps reflecting response monitoring. Early differentiating neurons were located more superior-laterally within the different regions related to accuracy of identification or memory.
Micromechanics of toughening in ductile/brittle polymeric microlaminates: Effect of volume fraction

Abstract Ductile/brittle microlaminates, comprised of alternating layers of ductile polymer [e.g., polycarbonate (PC)] that inelastically deform by shear yielding, and brittle polymer [e.g., styrene-acrylonitrile (SAN), polymethylmethacrylate (PMMA)] that undergo crazing in tension, offer a strategy for tensile toughening by capitalizing on the synergistic interactions between crazing and shear yielding. This work presents a micromechanical model for PC/PMMA ductile/brittle laminates that captures the constituent volume fraction dependence of the macroscopic behavior, as well as the underlying micro-mechanisms of deformation and tensile failure, in particular the synergy between crazing and shear yielding. The finite element implementation of the model considers both two-dimensional and three-dimensional representative volume elements (RVEs), and incorporates continuum-based physics-inspired descriptions of shear yielding and crazing, along with failure criteria for the ductile (PC) and brittle (PMMA) layers. The interface between the ductile and brittle layers is assumed to be perfectly bonded. The 3D RVE models successfully capture the macroscopic tensile stress–strain behavior of the ductile/brittle laminates at varying constituent volume fractions and the corresponding underlying micromechanisms of deformation and failure. The transition from brittle to ductile laminate behavior is in agreement with experimental data and is found to occur as the fraction of the ductile layer is increased to 0.60. The simulations reveal the brittle to ductile cross-over to be governed by the ability of the ductile layers to constrain the dilation and growth of crazes in the brittle layer. In particular, after the critical volume fraction of the ductile constituent is attained, surface edge crazes are inhibited from tunneling across the width of the specimen which then leads to reduced crazing/cracking and increased shear yielding. 2D RVE models are unable to adequately account for the deformation and toughness of PC/PMMA microlaminates as a function of the constituent volume fractions, as they neglect any distribution of inelastic events in the laminate-width (out-of-plane) direction.
Religious Involvement and Depression Among Korean Young Adults in the United States

Using a sample of 102 Korean church goers, this study found that a higher level of general religiosity was significantly associated with a lower level of depression only for non-visa-holding church members (U.S. citizens). The results underscore the importance of considering both the type of religiosity/spirituality assessed and sample characteristics when examining the religiosity–mental health relationship since both the dimension of religiosity measured and the visa status of the respondents qualified the relationship. A test of the mediating role of social support was not significant. Recommendations were made to explore mechanisms for the religiosity-depression relationship other than social support.
A model for the structure of the Escherichia coli SOS-regulated UmuD2 protein

Abstract The ubiquitous Y-family of DNA polymerases, exemplified by the Escherichia coli UmuC protein (the catalytic subunit of DNA Pol V), possess the remarkable ability to replicate imperfect DNA templates that cannot be replicated by other types of DNA polymerases. Since this ability comes at the cost of a reduced fidelity, it is important that organisms manage these unique polymerases to coordinate their actions with those of the replication machinery. In E. coli, it is becoming evident that a sophisticated series of protein–protein interactions involving the two forms of the umuD gene product, UmuD and UmuD′ and components of the replicative DNA polymerase serve to manage the actions of the umuC-encoded DNA polymerase. The purpose of this study was to better understand how structural differences between UmuD2 and UmuD2′ help to determine which biological role the umuDC gene products will play; the UmuD2C complex functions as a DNA damage checkpoint effector, while the UmuD2′C complex participates in translesion DNA synthesis, which serves as the mechanistic basis for most chemical and UV light mutagenesis. Based on the results of a combination of disulfide cross-linking experiments, measurements of solvent accessibility and electron paramagnetic spin resonance (EPR) studies, we have developed a refined model for the structure of the UmuD2 homodimer. In the model that we are proposing, the N-terminal arms of UmuD (residues 1–39) form an extended interface in the UmuD2 homodimer by folding down over the globular domains of their intradimer partners. As a result, significant portions of the surface of each globular domain are buried in the UmuD2 homodimer. Based on the structure of the UmuD2′ homodimer, both in the crystal and in solution, these same surfaces are exposed. Implications of these structural differences between the UmuD2 and the UmuD2′ homodimers with respect to their roles in managing the actions of the umuC-encoded DNA polymerase are discussed.
Environmental statistical process control using an augmented neural network classification approach

Abstract Shifts in the values of monitored environmental parameters can help to indicate changes in an underlying system. For example, increased concentrations of copper in water discharged from a manufacturing facility might indicate a problem in the wastewater treatment process. The ability to identify such shifts can lead to early detection of problems and appropriate remedial action, thus reducing the risk of long-term consequences. Statistical process control (SPC) techniques have traditionally been used to identify when process parameters have shifted away from their nominal values. In situations where there are correlations among the observed outputs of the process, however, as in many environmental processes, the underlying assumptions of SPC are violated and alternative approaches such as neural networks become necessary. A neural network approach that incorporates a geometric data preprocessing algorithm and identifies the need for increased sampling of observations was applied to facilitate early detection of shifts in autocorrelated environmental process parameters. Utilization of the preprocessing algorithm and the increased sampling technique enabled the neural network to accurately identify the process state of control. The algorithm was able to identify shifts in the highly correlated process parameters with accuracies ranging from 96.4% to 99.8%.