cssi/SciSciGPT-SciSciNet huggingface dataset:
Glial cells, the myelinated axon, and the blood-brain barrier

Abstract There are three types of glial cells: astrocytes, oligodendrocytes, and microglia. Astrocytes have many functions in both the developing and mature brain. They mature after the neurons and completely fill the spaces between them. They surround the synapses and take up released transmitters. Glu uptake prevents overstimulation of the postsynaptic cell producing excitotoxic death. Also astrocytes release glutamine that is used by Glu neurons to resynthesize Glu. They contain transporters crucial to maintaining the correct ionic environment. Also astrocytes destroy silent synapses by phagocytosis followed by lysosomal degradation. Oligodendrocytes are the brain cells that synthesize myelin, the insulating membrane that surrounds projection axons. One oligodendrocyte’s membrane can insulate many axons. They also differentiate after neurons. Schwann cells are the myelinating cells of the peripheral nervous system. However, one Schwann cell can insulate only one axon. Microglia migrate into the brain before birth from the bone marrow. They are the major immunological cell in the brain and destroy unneeded or damaged cells or organelles, including silent synapses. To produce a big brain, the myelinated axon evolved. Oligodendrocytes produce membranes that wrap around a projection neuron’s axon, thus insulating it and allowing an electrical current to very rapidly flow down the axon. The myelin membrane is composed of 70% lipid and 30% protein. Two major proteins comprise the myelin sheath proteins: myelin basic protein, a cytosolic protein, and proteolipid protein (PLP), an integral membrane protein. Interactions between PLPs on adjacent myelin membranes anchor the myelin sheath. For an electric current to flow down a long axon, a gap in the myelin every 20 µm is required. These gaps contain Na + channels to depolarize the axon and K + channels to repolarize it. Myelin forms after neuronal development is completed. The mechanism is not completely characterized but involves interactions between secreted trophic substances and receptors. With the evolution of a large brain, a barrier between it and the rest of the body was required. Capillary endothelial cells (CECs) provide the main constituent of the blood–brain barrier (BBB) forming extremely tight junctions that don’t allow the passage of even H + . Two other cell types are involved in BBB formation: astrocytes, whose end feet contact the brain side of the CECs, and pericytes, which wrap around the brain side of the CECs, providing an extracellular matrix. Two families of molecules, the occludins and the claudins, bind tightly to one another to form the tight junctions. There is also very little vesicular trafficking across the BBB. Three molecules can cross by transcytosis: transferrin bound to Fe +++ , insulin, and amylin. The CECs also have transporters that pump glucose into the brain and toxic materials out. The development of the BBB is quite complex and involves the interaction of the Wnts with their receptors.
Is Colorectal Cancer in Patients Younger Than 50 Years of Age the Same Disease as in Older Patients

The incidence of colorectal cancer (CRC) has declined steadily in persons over age 50 years of age, largely due to screening. In contrast, incidence rates have increased rapidly in younger adults (<50 years of age),1 raising the question of whether young-onset CRC is a distinct disease with unique biologic features or if it is the same disease occurring at a younger age. Studies comparing younger and older patients diagnosed with CRC have reported differences in clinical and molecular features, including tumor location, stage, and histology.2-6 However, increasing use of screening colonoscopy in the population has changed characteristics of CRC diagnosed over 50 years of age (eg, higher proportion now diagnosed with proximal tumors and/or at an earlier stage),7 so it is challenging to draw conclusions about the importance of these findings. To address this challenge, we compared characteristics of younger and older CRC patients in a predominantly unscreened population.
Derivation and Application of a Tool to Estimate Benefits From Multiple Therapies That Reduce Recurrent Stroke Risk

Background and Purpose- Lowering blood pressure and cholesterol, antiplatelet/antithrombotic use, and smoking cessation reduce risk of recurrent stroke. However, gaps in risk factor control among stroke survivors warrant development and evaluation of alternative care delivery models that aim to simultaneously improve multiple risk factors. Randomized trials of care delivery models are rarely of sufficient duration or size to be powered for low-frequency outcomes such as observed recurrent stroke. This creates a need for tools to estimate how changes across multiple stroke risk factors reduce risk of recurrent stroke. Methods- We reviewed existing evidence of the efficacy of interventions addressing blood pressure reduction, cholesterol lowering, antiplatelet/antithrombotic use, and smoking cessation and extracted relative risks for each intervention. From this, we developed a tool to estimate reductions in recurrent stroke risk, using bootstrapping and simulation methods. We also calculated a modified Global Outcome Score representing the proportion of potential benefit (relative risk reduction) achieved if all 4 individual risk factors were optimally controlled. We applied the tool to estimate stroke risk reduction among 275 participants with complete 12-month follow-up data from a recently published randomized trial of a healthcare delivery model that targeted multiple stroke risk factors. Results- The recurrent stroke risk tool was feasible to apply, yielding an estimated reduction in the relative risk of ischemic stroke of 0.36 in both the experimental and usual care trial arms. Global Outcome Score results suggest that participants in both arms likely averted, on average, 45% of recurrent stroke events that could possibly have been prevented through maximal implementation of interventions for all 4 individual risk factors. Conclusions- A stroke risk reduction tool facilitates estimation of the combined impact on vascular risk of improvements in multiple stroke risk factors and provides a summary outcome for studies testing alternative care models to prevent recurrent stroke. Registration- URL: https://www.clinicaltrials.gov; Unique identifier: NCT00861081.
The Role of Religion and Spirituality in Conceptualizing Reproductive Loss: Clinical Implications of the Narratives of Gestational Surrogates in the USA.

Reproductive losses experienced by gestational surrogates, who do not share a genetic connection to the child they are carrying, may not be acknowledged or treated as compassionately as women who lose their “own” pregnancies. In-depth, semi-structured interviews were conducted with 17 gestational surrogates from diverse religious backgrounds. Grounded theory analysis of data included line-by-line coding, and emergent themes were identified. The results suggest that understanding and utilizing the religious/spiritual beliefs of a gestational surrogate may be one way for health professionals to provide implications counseling prior to surrogacy and also as a means to help process and grieve losses that may occur within surrogacy.
Latent brain state dynamics distinguish behavioral variability, impaired decision-making, and inattention.

Children with Attention Deficit Hyperactivity Disorder (ADHD) have prominent deficits in sustained attention that manifest as elevated intra-individual response variability and poor decision-making. Influential neurocognitive models have linked attentional fluctuations to aberrant brain dynamics, but these models have not been tested with computationally rigorous procedures. Here we use a Research Domain Criteria approach, drift-diffusion modeling of behavior, and a novel Bayesian Switching Dynamic System unsupervised learning algorithm, with ultrafast temporal resolution (490 ms) whole-brain task-fMRI data, to investigate latent brain state dynamics of salience, frontoparietal, and default mode networks and their relation to response variability, latent decision-making processes, and inattention. Our analyses revealed that occurrence of a task-optimal latent brain state predicted decreased intra-individual response variability and increased evidence accumulation related to decision-making. In contrast, occurrence and dwell time of a non-optimal latent brain state predicted inattention symptoms and furthermore, in a categorical analysis, distinguished children with ADHD from controls. Importantly, functional connectivity between salience and frontoparietal networks predicted rate of evidence accumulation to a decision threshold, whereas functional connectivity between salience and default mode networks predicted inattention. Taken together, our computational modeling reveals dissociable latent brain state features underlying response variability, impaired decision-making, and inattentional symptoms common to ADHD. Our findings provide novel insights into the neurobiology of attention deficits in children.
Illicit Drug Use, Cognitive Distortions, and Suicidal Ideation Among Homeless Youth: Results From a Randomized Controlled Trial

Abstract Illicit drug use and cognitive distortions confer significant risks to youth suicidal thoughts and behaviors. However, there has been limited evidence regarding the efficacy of suicide prevention interventions with homeless youth, especially studies testing whether such interventions can reduce the risk for suicidal ideation associated with illicit drug use. Suicidal homeless youth (N = 150) between the ages of 18 to 24 years were recruited from a drop-in center. Youth were randomly assigned to Cognitive Therapy for Suicide Prevention (CTSP) + Treatment as Usual (TAU) or TAU alone. Youth reported their illicit drug use, cognitive distortions, and suicidal ideation 4 times over 9 months. A multiple-group multilevel structural equation model showed that higher illicit drug use at baseline predicted a slower reduction in cognitive distortions and suicidal ideation in the TAU group. These associations were not found in the CTSP + TAU group, suggesting an interruption of such risk from illicit drug use. Findings suggest that CTSP can reduce the risk of illicit drug use as a treatment barrier towards cognitive distortions and suicidal ideation among homeless youth, with implications to improve treatment efforts and to reduce premature mortality in a vulnerable population.
Modulation of Neuroinflammation by the Gut Microbiota in Prion and Prion-Like Diseases

The process of neuroinflammation contributes to the pathogenic mechanism of many neurodegenerative diseases. The deleterious attributes of neuroinflammation involve aberrant and uncontrolled activation of glia, which can result in damage to proximal brain parenchyma. Failure to distinguish self from non-self, as well as leukocyte reaction to aggregation and accumulation of proteins in the CNS, are the primary mechanisms by which neuroinflammation is initiated. While processes local to the CNS may instigate neurodegenerative disease, the existence or dysregulation of systemic homeostasis can also serve to improve or worsen CNS pathologies, respectively. One fundamental component of systemic homeostasis is the gut microbiota, which communicates with the CNS via microbial metabolite production, the peripheral nervous system, and regulation of tryptophan metabolism. Over the past 10–15 years, research focused on the microbiota–gut–brain axis has culminated in the discovery that dysbiosis, or an imbalance between commensal and pathogenic gut bacteria, can promote CNS pathologies. Conversely, a properly regulated and well-balanced microbiome supports CNS homeostasis and reduces the incidence and extent of pathogenic neuroinflammation. This review will discuss the role of the gut microbiota in exacerbating or alleviating neuroinflammation in neurodegenerative diseases, and potential microbiota-based therapeutic approaches to reduce pathology in diseased states.
A Bayesian group lasso classification for ADNI volumetrics data

The primary objective of this paper is to develop a statistically valid classification procedure for analyzing brain image volumetrics data obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) in elderly subjects with cognitive impairments. The Bayesian group lasso method thereby proposed for logistic regression efficiently selects an optimal model with the use of a spike and slab type prior. This method selects groups of attributes of a brain subregion encouraged by the group lasso penalty. We conduct simulation studies for high- and low-dimensional scenarios where our method is always able to select the true parameters that are truly predictive among a large number of parameters. The method is then applied on dichotomous response ADNI data which selects predictive atrophied brain regions and classifies Alzheimer's disease patients from healthy controls. Our analysis is able to give an accuracy rate of 80% for classifying Alzheimer's disease. The suggested method selects 29 brain subregions. The medical literature indicates that all these regions are associated with Alzheimer's patients. The Bayesian method of model selection further helps selecting only the subregions that are statistically significant, thus obtaining an optimal model.
SIRPα sequesters SHP-2 to promote IL-4 and IL-13 signaling and the alternative activation of macrophages.

The cytokines interleukin-4 (IL-4) and IL-13 bind to their shared receptor subunit IL-4Rα to direct the alternative activation of macrophages to promote immunosuppression and wound healing. Activat...
Snapdown: A Text-Based Snapshot Diagram Language for Programming Education

Snapshot diagrams, which visualize in-memory program state, are frequently used in programming education to demonstrate new concepts and help students develop a better understanding of program functionality. In this paper we introduce Snapdown, a textual language for drawing snapshot diagrams, designed for use by both students and instructors of programming courses. Snapdown is designed with an emphasis on learnability and simplicity: both to be picked up by students in a classroom setting in a matter of minutes, and to enable creation and maintenance of diagrams in instructional content with minimal overhead. We introduce several use cases of Snapdown and describe the design and features of its textual language. We also describe a deployment of Snapdown during two semesters of emergency remote teaching in 6.031 Software Construction at MIT, a software engineering course intended for sophomore- and junior-level undergraduate students.
The Spectrum of Alcohol Use: Epidemiology, Diagnosis, and Treatment

In the United States, alcohol is the most common substance used and the spectrum of unhealthy alcohol use is highly prevalent. Complications of unhealthy alcohol use affect nearly every organ system. One of the most frequent and potentially life-threatening of these complications is alcohol withdrawal syndrome for which benzodiazepines remain first-line therapy. Pharmacologic treatment of alcohol use disorder, the most severe form of unhealthy alcohol use, is underutilized despite the availability of multiple effective medications. Although behavioral therapies are an important component of treatment, they are overemphasized at the expense of pharmacotherapy.
Exclusivity of Strength‐Limiting Extrinsic Surface and Hybrid Flaws

Flexure strength-limiting flaw populations were examined in a sintered alpha-SiC having ∼6 vol% porosity comprised of homogenously distributed monosized (∼60-70 μm) pores. Bend bars were coarse-, medium-, and fine-finish ground with the intent to produce concurrent activity of intrinsic strength-limiting flaws (pores) and extrinsic strength-limiting flaws (machining damage) populations. However, this was not achieved as fractography showed that strength was always limited by a pore independent of the depth of machining damage in this material. The effects of strength-limiting flaw hybridization on 2-Parameter Weibull were then examined by positioning Knoop indents either directly on a pore present at the ground surface of the bend bars or away from them, and flexure loading those specimens to fracture. Fractography confirmed the suggestion in this case that a negative curvature in the Weibull distribution curve was associated with exclusive strength-limiting flaw populations (hybrid and surface flaw types). The interpretation of intrinsic and extrinsic exclusive flaw distributions is discussed in reference to the prospective selection of a ceramic for structural applications.
A 2.5-D scalar Helmholtz wave solution employing the spectral Lanczos decomposition method (SLDM)

It is demonstrated that the SLDM may be used to solve the 2.5-D scalar Helmholtz equation efficiently in O(N/sup 1.5/) operations with a high degree of accuracy. The Lanczos method is used to build discrete orthogonal polynomials that approximate the solution to the scalar Helmholtz wave equation. The advantage to using the SLDM for the 2.5-D problem is that only the 2-D solution needs to be computed numerically, while the z-variation may be computed analytically. The particular numerical example considered consists of the computation of the point source response in a rectangular waveguide with a Dirichlet boundary condition. >
Purification and characterization of a multicomponent AP-1.junD complex from T cells. Dependence on a separate cellular factor for enhanced DNA binding activity.

TAP-1 (T-cell AP-1) is a previously identified DNA-binding activity that is rapidly induced in activated T cells in the absence of protein synthesis. This activity has been purified over 2,000-fold from the T-cell line MLA144. Purified TAP-1 is a multicomponent complex composed of 38-kDa and 43-kDa junD polypeptides in association with a separate factor(s), distinct from fos, that partly dissociate from the complex during affinity purification but is required for full TAP-1 DNA-binding activity. When reconstituted with TAP-1, this partly dissociated component strongly enhances the DNA-binding activity of the TAP-1 complex. UV-cross-linking analysis identifies the dissociable component of the TAP-1 complex as a separate class of low molecular mass (23-29-kDa) DNA-binding polypeptide(s). 23-29-kDa polypeptides have been partially purified from nuclear extracts derived from MLA144 that enhance TAP-1 DNA-binding activity over 100-fold and increase its contacts with flanking DNA sequence. These results define TAP-1 as a distinct AP-1.junD-containing complex in T cells whose DNA-binding activity is regulated by the interaction of distinct and separate cellular factor(s).
Current Status of Nucleon Decay Searches with Super-Kamiokande

Evidence for Nucleon Decay has yet to be observed. Current results from the observation of a 45 kton-year exposure of Super-Kamiokande and lifetime limits for nucleons to decay via lepton + pion, lepton + eta and lepton + kaon modes are presented.
Polarized Radiative Capture Experiments and the D-State of 4 He and 3 He

The tensor polarized capture reactions 2H(d,γ)4He and 1H(d,γ)3He are a sensitive means for measuring D-state effects in 4He and 3He. Data and recent calculations are considered. Values for the D-to-S state asymptotic ratio of −0.2 ± 0.05 for 4He and 0.032 ± 0.014 for 3He are deduced from the capture data. Results are compared to the results of other recent measurements of D-state effects in these systems. The effect of the D-state of 4He on the low energy 2H(d,γ)4He cross-section is shown to be profound.
The Effect of Aspirin on Bleeding and Transfusion in Contemporary Cardiac Surgery

Objective Despite evidence that preoperative aspirin improves outcomes in cardiac surgery, recommendations for aspirin use are inconsistent due to aspirin’s anti-platelet effect and concern for bleeding. The purpose of this study was to investigate preoperative aspirin use and its effect on bleeding and transfusion in cardiac surgery. Methods This retrospective study involved consecutive patients (n=1571) who underwent CABG, valve, or combined CABG and valve surgery at a single center between March 2007 and July 2012. Of all patients, 728 met the inclusion criteria and were divided into two groups: those using (n=603) or not using (n=125) aspirin within 5 days of surgery. Data were collected on chest tube drainage, re-operation for bleeding, and transfusion of red blood cells (RBCs), fresh frozen plasma (FFP), and platelets. Results No significant difference was observed between the two groups in chest tube drainage or re-operation for bleeding. An increase in patients transfused with RBCs was observed in the aspirin group (61.9 vs 51.2%, adjusted OR 1.77, p=0.027); however, among those transfused RBCs, no significant difference in mean units transfused or massive transfusion was observed. No significant difference was seen in transfusion requirement of FFP or platelets. Conclusions In patients undergoing CABG, valve, or combined CABG/valve surgery, preoperative aspirin, within 5 days of surgery, was associated with an increased probability of receiving an RBC transfusion. Preoperative aspirin was not associated with an increase in chest tube drainage, re-operation for bleeding complications, or transfusion of FFP or platelets.
Con Respeto: Bridging the Distances between Culturally Diverse Families and Schools, An Ethnographic Portrait

Con Respeto: Bridging the Distances between Culturally Diverse Families and Schools, An Ethnographic Portrait Guadalupe Valdes New York: Teachers College Press, 1996. 237 pp.
Accounting for group differences in appraisals of social inequality: Differential injustice standards

We tested whether differential appraisals of inequality are a function of the injustice standards used by different groups. A confirmatory standard of injustice is defined as the amount of evidence needed to arrive at the conclusion that injustice has occurred. Consistent with a motivational shifting of standards view, we found that advantaged and disadvantaged group members set different standards of injustice when judging the magnitude of gender (Study 1) and racial (Study 2) wage inequality. In addition, because advantaged and disadvantaged group members formed - based on their differential standards - divergent appraisals of wage inequality, they experienced differential desire to restore inter-group justice. We discuss the implications of promoting low confirmatory standards for changing perceptions of social reality and for motivating justice-restorative behaviour.
Novel solution of 2-D waveguides using the finite element method

A novel technique is described for solving 2-D waveguide equations using the finite element method. The full-wave equation is solved, thus automatically taking care of various inhomogeneities in the medium. The solution yields the transverse components of the field, which are useful for calculating far-field radiation patterns.
Impact of RNA-Guided Technologies for Target Identification and Deconvolution

For well over a decade, RNA interference (RNAi) has provided a powerful tool for investigators to query specific gene targets in an easily modulated loss-of-function setting, both in vitro and in vivo. Hundreds of publications have demonstrated the utility of RNAi in arrayed and pooled-based formats, in a wide variety of cell-based systems, including clonal, stem, transformed, and primary cells. Over the years, there have been significant improvements in the design of target-specific small-interfering RNA (siRNA) and short-hairpin RNA (shRNA), expression vectors, methods for mitigating off-target effects, and accurately interpreting screening results. Recent developments in RNAi technology include the Sensor assay, high-efficiency miR-E shRNAs, improved shRNA virus production with Pasha (DRGC8) knockdown, and assessment of RNAi off-target effects by using the C9-11 method. An exciting addition to the arsenal of RNA-mediated gene modulation is the clustered regularly interspaced short palindromic repeats/Cas9 (CRISPR/Cas) system for genomic editing, allowing for gene functional knockout rather than knockdown.
Newer Findings on a Unified Perspective of Copper Restriction and Cardiomyopathy

AbstractThe cuproenzymes lysyl oxidase, cytochrome-c oxidase, and superoxide dismutase are key factors in understanding the cardiac hypertrophy and cardiomyopathy associated with dietary copper res...
Thermodynamic properties of silicides IV. Molar heat capacity at temperatures from 7 K to 340 K and derived thermodynamic properties toT= 2200 K of molybdenum disilicide (MoSi2.067 ± 0.002)

Abstract The molar heat capacity of molybdenum disilicide MoSi 2.067 ± 0.002 was measured from T = 7 K to T = 340 K by adiabetic calorimetry. Our results show that no phase transition is present, but a slight anomaly was observed in the region of T = 200 K. From our results, the standard molar entropy Δ o T S m o (MoSi 2.067 ± 0.002 ,cr)/R = 7.298.15 K; on the basis of this result, the function Φ m o (MoSi 2.067 ± 0.002 ,cr, 298.15 K)/ R = 3.002. Heat capacities derived from transient heat-pulse calorimetry from T = 0.2 K to T = 7 K, and results from high-temperature adiabatic and drop calorimetry from T = 300 K to T = 2200 K, together with the heat capacities obtained in this work, allowed the estimation of thermodynamic functions to T = 2200 K.
A MODEL OF WEAK INTERACTIONS

A picture of the weak interactions is described in which the ΔI=1/2 and ΔI=3/2 currents responsible for strangeness-changing leptonic reactions are constructed out of direct products of the strangenessconserving currents responsible for ordinary β-decays and a Δ = 1 isotopic doublet which transforms spatially as a scalar or pseudoscalar, for example, the K-meson field doublet itself. For models which invoke six intermediate bosons, this device introduces a degree of freedom that serves to get around a certain difficulty recently noted. But if the weak currentcurrent interactions are sufficiently local (i.e., if the intermediate bosons are sufficiently heavy), the scheme discussed here permits a description which requires only four intermediate bosons. The discussion is based on acceptance of the ΔI=1/2 rule for ΔS=1 nonleptonic reactions and acceptance of the notion that ΔS=2 nonleptonic transitions are effectively forbidden.
MicroRNAs in Cardiac Development

The transcriptional regulation of cardiovascular development requires precise spatiotemporal control of gene expression, and heterozygous mutations of transcription factors have frequently been implicated in human cardiovascular malformations. A novel mechanism involving post-transcriptional regulation by small, noncoding microRNAs (miRNAs) has emerged as a central regulator of many cardiogenic processes. We are beginning to understand the functions that miRNAs play during essential biologic processes, such as cell proliferation, differentiation, apoptosis, stress response, and tumorigenesis. The identification of miRNAs expressed in specific cardiac and vascular cell types has led to the discovery of important regulatory roles for these small RNAs during cardiomyocyte differentiation, cell cycle, conduction, and vessel formation. Here, we overview the recent findings on miRNA regulation in cardiovascular development. Further analysis of miRNA function during cardiovascular development will allow us to determine the potential for novel miRNA-based therapeutic strategies.
Spouse Abusers and Court Mandated Treatment

Abstract Only recently have treatment staff directed their attention to spouse abusers. However, batterers undergoing treatment typically are volunteers. They are presumably the most amenable candidates for treatment. Therefore, data about batterers secured from such programs is not from the larger volume of batterers known to the criminal justice system. It is likely that those convicted in court represent the most serious and less easily resolvable cases. Unlike previous efforts, a body of research is initiated solely on court mandated treatment program participants. These findings are not in complete agreement with recent assumptions concerning characteristics of abusers. Among the significant findings in relation to program completion are the importance of prior criminal charges, type and number of prior charges. Treatment staff and court officials can better understand the abuser population with which our criminal justice system deals, as this body of knowledge evolves.
Rapid maturation of effector T cells in tumors, but not lymphoid organs, during tumor regression.

Increasing the efficacy of adoptively transferred, tumor antigen specific T cells is a major goal of immunotherapy. Clearly, a more thorough understanding of the effector phase of T cell responses, within the tumor site itself, would be beneficial. To examine this issue, we adoptively transferred tumor antigen-specific effector T cells into tumor-bearing mice, then performed kinetic evaluations of their phenotype, function, and survival in tumors, draining lymph nodes (dLNs), and spleens during regression of murine fibrosarcomas. Effector function in tumors was quantitated through the use of a novel intratumoral cytolytic assay. This approach revealed dynamic changes in the phenotype, cytolytic capacity, and viability of tumor infiltrating effector T cells during the course of tumor regression. Over a period of days, T cells within tumors rapidly transitioned from a CD25hi/CD27hi to a CD25low/CD27low phenotype and displayed an increase in cytolytic capacity, indicative of effector maturation. Simultaneously, however, the viability of maturing T cells within tumors diminished. In contrast, transferred T cells trafficking through lymphoid organs were much more static, as they maintained a stable phenotype, robust cytolytic activity, and high viability. Therefore, there exists a marked phenotypic and functional divergence between tumor-infiltrating effector T cells and their counterparts in lymphoid organs. Our results indicate that the population of tumor-infiltrating T cells is unique in experiencing rapid effector maturation post-transfer, and suggest that strategies aimed at prolonging the survival of CD25low/CD27low full effectors, which displayed the highest levels of intratumoral cytolytic activity, should enhance the efficacy of T cell based tumor immunotherapies.
Construction of designer glycoconjugate vaccines with size-specific oligosaccharide antigens and site-controlled coupling.

Coupling of carbohydrate antigens to protein carriers is a typical approach to enhancing the immunogenicity of carbohydrate-based vaccines. Glycoconjugates with well-defined structures are needed for studies defining the structural variables that govern antibody responses. We report a chemical strategy for preparation of an array of glycoconjugates containing saccharides of desired molecular sizes by selective depolymerization of bacterial polysaccharides and chemically controlled site-specific coupling. As an example, we synthesized and evaluated an oligosaccharide-based vaccine against type III group B Streptococcus.
17β-Estradiol modulates local cardiac renin-angiotensin system to prevent cardiac remodeling in the DOCA-salt model of hypertension in rats

Ventricular remodeling can play a detrimental role in the progression of cardiovascular diseases, leading to heart failure. The current study was designed to investigate the effects of 17beta-estradiol (E2) on cardiac remodeling. Cardiac fibrosis and hypertrophy were examined in deoxycorticosterone acetate (DOCA)-salt treated rats with chronic, six-week administration of two different doses of E2. Bilaterally ovariectomized (Ovex) female Sprague-Dawley rats were randomly assigned to one of the following groups: Ovex-control; Ovex-DOCA; Ovex-DOCA+low-dose E2 (1.66 microg/day); or Ovex-DOCA+high-dose E2 (2.38 microg/day). All DOCA-treated rats were uninephrectomized and drinking water was replaced by 0.15M NaCl solution for the remainder of the study period. DOCA-salt treatment resulted in a significant increase in blood pressure, which was not altered by estrogen replacement. Histological examinations revealed marked cardiac remodeling (both ventricular hypertrophy and interstitial fibrosis) with DOCA treatment, which was attenuated in animals receiving estrogen therapy. Western blot analysis demonstrated increased cardiac levels of angiotensin converting enzyme (ACE) with DOCA treatment, which was attenuated by E2 replacement. Furthermore, increased levels of cardiac angiotensin converting enzyme 2 (ACE2) protein were observed in animals receiving high-dose E2 replacement. These findings suggest that physiologically relevant estrogen replacement therapy has blood pressure-independent cardioprotective effects, which are possibly mediated through modulation of the cardiac renin-angiotensin system.
The Bellaire wetland: Wastewater alteration and recovery

The village of Bellaire, MI, has discharged wastewater from their stabilization lagoons to a 18 hectare wetland for eleven years at about 30 million gallons per year. For the last eight of those years, studies of hydrology, water quality, vegetation and soils have been conducted. Discharges terminated in 1981, with a resultant recovery of the ecosystem. During irrigation, wastewater parameters were dramatically improved by waste treatment standards, but not by receiving ecosystem standards. Mass balances for water and chloride agreed reasonably well. All surface inflows and outflows and precipitation were measured; and evapotranspiration was calculated from climatic data. With estimated hydrology, mass balances were possible for nutrients. Nitrogen, phosphorus, and suspended solids were retained or removed in large measure. After irrigation, no significant release occurred. Vegetation suffered major damage in the immediate vicinity of the discharge: trees were uprooted and new species invaded. Heavy growths of fungi and bacteria were noted in the immediate area of wastewater application.
Postoperative adjuvante Chemoradiotherapie beim Hochrisikomagenkarzinom

Weltweit ist das Magenkarzinom eine der haufigsten Krebsarten mit einer hohen Mortalitatsrate. Trotz potenziell kurativer Resektionen ist die lokoregionare Rezidiventwicklung zum Teil verantwortlich fur diese hohe Mortalitatsrate. Viele Versuche zur Senkung des Rezidivrisikos nach Resektion wurden unternommen. Studien, die die postoperative Chemotherapie als einzige Therapiemodalitat beinhalteten, konnten keinen klaren Benefit zeigen. Ebenso konnten die meisten Studien mit postoperativer Radiochemotherapie keinen klaren Uberlebensvorteil nachweisen. Jedoch gelang es kurzlich einer amerikanischen “intergroup-Studie”, einen Uberlebensvorteil fur Patienten mit lokal fortgeschrittenem Magenkarzinom nach Radiochemotherapie im Vergleich zur alleinigen Chirurgie aufzeigen. “Intergroup-116” ist eine grose randomisierte Studie mit dem Ziel, die Rolle der adjuvanten Chemotherapie plus Strahlentherapie nach kurativer Magenresektion zu evaluieren. Die Ergebnisse dieser Studien zeigen einen Uberlebensvorteil mit adjuvanter Radiochemotherapie, zum Grosteil wahrscheinlich bedingt durch bessere lokoregionare Tumorkontrolle. Obwohl viele Patienten keine adaquate Lymphknotendissektion erhielten, korrelierte die Art der Lymphknotendissektion nicht mit dem Uberleben. Die Toxizitat war akzeptabel. “Intergroup-116” zeigt, dass eine postoperative Radiochemotherapie die Standardtherapieoption fur Patienten mit lokal fortgeschrittenem Magenkarzinom sein konnte. Zukunftige Studien sollten weitere, noch effektivere systemische Therapien und molekularbiologisch orientierte Behandlungen evaluieren. Ein weiterer wichtiger Aspekt ware, ob eine ausreichende Lymphknotendissektion die Strahlentherapie uberflussig macht.
A parametric approach to optimal soft signal relaying in wireless parallel-relay systems

This paper proposes an optimal estimate-forward strategy, termed Z-forwarding, for 2-hop parallel-relay systems. The previous tanh-forwarding strategy, which is optimized for the single-relay system is shown to be no longer optimal for a parallel-relay system. Instead, a new, parametrically-optimized Z-forwarding strategy is proposed, where the relay re-transmits a nonlinear but piece-wise linear function of the log-likelihood ratio (LLR) of the source signal. By analytically formulating the end-to-end bit error rate (BER), optimal thresholds that minimize the BER are computed as a function of all the source-relay and relay-destination channels. Maximum likelihood (ML) detector is also developed for the destination to recoup all the diversity gains from the multiple relays. It is shown that Z-forwarding strategy delivers a performance comparable to tanh-forwarding in a single relay system, but considerably better than tanh-forwarding (as well as amplify-forward and decode-forward) in a parallel-relay system.
Relation Between Repolarization and Refractoriness in the Human Ventricle: Cycle Length Dependence and Effect of Procainamide

The cycle length dependence of the action potential duration and the effective refractory period of the right ventricular endocardium were investigated in 24 patients undergoing electrophysiologic studies for suspected ventricular tachycardia. The action potential duration at 90% repolarization and the effective refractory period at twice diastolic threshold strength were measured at the same catheter site at steady state cycle lengths of 350 to 600 ms. Both measurements decreased linearly with decreasing cycle length, maintaining a parallel relation. When the relation between action potential duration and effective refractory period was expressed as the effective refractory period-action potential duration difference, nearly constant values (range −12 to −15 ms) were obtained at all cycle lengths. To determine whether sodium channel blocking drugs influence the effective refractory period-action potential duration relation in humans, measurements of these two variables were obtained in 15 patients before and during the infusion of procainamide. Procainamide prolonged the action potential duration at each cycle length by a near constant amount over baseline values (p Thus, in the human ventricle, the action potential duration and the effective refractory period have a close relation that remains fixed over a wide range of cycle lengths. The cycle length-dependent increase in the effective refractory period relative to action potential duration induced by procainamide is consistent with use dependency of sodium channel blocking drugs observed in vitro and may be a useful marker for measuring antiarrhythmic drug activity in vivo.
Development of a molecularly imprinted polymer for the analysis of avermectin.

Abstract Five molecularly imprinted polymers (MIPs) were synthesized for a large molecule, avermectin, using different preparation techniques, monomers, and polymerization solvents. Selectivities ( α ) of each were compared using HPLC and different mobile phases containing various levels of acetic acid. Selectivity ( α ) for avermectin was greatest ( α estimated ≥18) when the polymer was prepared non-covalently (utilizing only non-covalent interactions between avermectin and monomer) in chloroform using methacrylic acid (MAA) monomer and evaluated in chloroform. When evaluated in acetonitrile, an MIP prepared in acetonitrile provided better selectivity ( α = 8.4) than the polymer prepared in chloroform. Optimizing mobile phase conditions by adding acetic acid was much more important when MIPs were evaluated in chloroform than in acetonitrile. MIPs prepared with MAA provided better selectivity than a polymer prepared with acrylamide monomer. Covalent preparation of two MIPs utilizing a covalent bond between avermectin and monomer before polymerization did not improve selectivity but did improve peak shape in chromatograms. Specificity was demonstrated by comparing the selectivity of avermectin with eprinomectin ( α = 3.0), a compound with a very similar structure. Results indicate that an MIP can be prepared for the large avermectin molecule, and has the potential to simplify sample preparation and to reduce the time needed for analysis.
Legacy Divestitures: Motives and Implications

This paper investigates “legacy divestitures,” the sale or spinoff of a company’s original, or “legacy,” business. The central tension considered in this work is that the historical presence of a firm’s legacy business should simultaneously make that unit very interdependent with the company’s remaining operations and make the firm’s managers highly likely to take those same interdependencies for granted. Consistent with these predictions, the post-divestiture operating performance of firms that divest their legacy businesses falls short of that of firms that retain comparable legacy units, especially when the divested unit operates in the same industry as others of the divesting firm’s businesses. Newer chief executive officers (CEOs) are more likely to undertake legacy divestitures than their longer-tenured peers, and the most recently appointed CEOs undertake the most costly legacy divestitures. In summary, this paper provides insights into how historical interdependencies create value in diversified f...
Cost efficiency and financial flexibility in institutions of higher education

Abstract Donors frequently impose restrictions on the use of contributions to non-profit institutions. These restrictions may be imposed in an attempt to ensure that the objectives of the donors are achieved, to limit administrative accretion (lattice), and to discourage the pursuit of objectives deemed by donors to not be fundamental to the core mission. On the other hand, donor restrictions may be costly to the extent that administrators possess better knowledge of the underlying production/cost function. This study evaluates the degree to which the common perception that the lack of financial flexibility inhibits institutional efficiency is empirically valid in the context of institutions of higher education. The degree of financial flexibility (the ratio of unrestricted net assets to total assets) is used as a measure of the degree to which institutional performance may be constrained by donor restrictions. Our results show a positive relationship between the degree of financial flexibility and cost inefficiency for all types of private higher education institutions. Thus, contrary to common belief, enhanced financial flexibility appears to lead to higher cost inefficiency. Conversely, greater financial restrictions appears to lead to more cost efficiency. This finding suggests that line item budgeting, for example, may not be as ineffective a cost control mechanism as it is commonly perceived to be. More rigorous comparative studies are needed to support the anecdotal evidence often cited to show the inefficiency of line-item budgeting.
Dynamical model for pion electroproduction on the nucleon

We develop a Lorentz- and gauge-invariant dynamical model for pion electroproduction in the resonance region. The model is based on solving the Salpeter (instantaneous) equation for the pion-nucleon interaction with a hadron-exchange potential. We find that the one-particle-exchange kernel of the Salpeter equation for pion electroproduction develops an unphysical singularity for a finite value of Q{sup 2}. We analyze two methods of dealing with this problem. Results of our model are compared with recent single-polarization data for pion electroproduction.
Atomic Effects on the Tritium ft Value

Atomic effects on the tritium $\mathrm{ft}$ value including bound-state decay, imperfect wave-function overlap, screening, and electron exchange are considered for each of the species ${\mathrm{T}}^{+}$, T, ${\mathrm{T}}_{2}$, and ${\mathrm{T}}^{\ensuremath{-}}$. Corrections to the $f$ value are tabulated and can be combined to extract an improved estimate for the axial-vector matrix element in tritium $\ensuremath{\beta}$ decay.
Effects of individual promoters on the Direct Synthesis of methylchlorosilanes

Abstract The industrially relevant Direct Synthesis involves the reaction of methyl chloride with silicon in the presence of a copper catalyst (promoted with Zn, Sn, and P), termed the contact mass, to form methylchlorosilanes. In situ attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR) coupled with flow reactor studies was used to help understand the relationship between the composition of the working catalytic surface and product selectivity during reaction (1 bar CH3Cl at 300 °C). Promotion of copper–silicon contact masses with Sn and Zn increased the selectivity of the reaction for dimethyldichlorosilane compared to P-promoted and copper–silicon (unpromoted) contact masses. Results showed that the rate of Si conversion associated with the Sn-promoted contact mass was higher than the Si conversion rate associated with the Zn and unpromoted contact masses. ATR-FTIR results suggested that Sn promotion led to a stabilization and relatively high concentration of surface methyl species. In contrast to Sn or Zn promotion, P promotion led to significant methyl fragmentation on the contact mass surface, consistent with its relatively low selectivity toward dimethyldichlorosilane.
The cellular chaperone Hsc70 is specifically recruited to reovirus viral factories independently of its chaperone function.

Mammalian orthoreoviruses replicate and assemble in the cytosol of infected cells. A viral nonstructural protein, μNS, forms large inclusion-like structures called viral factories (VFs) in which assembling viral particles can be identified. Here we examined the localization of the cellular chaperone Hsc70 and found that it colocalizes with VFs in infected cells and also with viral factory-like structures (VFLs) formed by ectopically expressed μNS. Small interfering RNA (siRNA)-mediated knockdown of Hsc70 did not affect the formation or maintenance of VFLs. We further showed that dominant negative mutants of Hsc70 were also recruited to VFLs, indicating that Hsc70 recruitment to VFLs is independent of the chaperone function. In support of this finding, μNS was immunoprecipitated with wild-type Hsc70, with a dominant negative mutant of Hsc70, and with the minimal substrate-binding site of Hsc70 (amino acids 395 to 540). We identified a minimal region of μNS between amino acids 222 and 271 that was sufficient for the interaction with Hsc70. This region of μNS has not been assigned any function previously. However, neither point mutants with alterations in this region nor the complete deletion of this domain abrogated the μNS-Hsc70 interaction, indicating that a second portion of μNS also interacts with Hsc70. Taken together, these findings suggest a specific chaperone function for Hsc70 within viral factories, the sites of reovirus replication and assembly in cells.
Amphidinium cryophilum sp. nov. (Dinophyceae) a new freshwater dinoflagellate. I. Species description using light and scanning electron microscopy.

Amphidinium cryophilum sp. nov. was found in the fall of 1979 in a small pond near Madison, Wisconsin. During the ensuing winter, it became the dominant phytoplankter. Cell numbers remained high despite a thick layer of ice and snow. After the ice melted in the spring the organism disappeared from plankton samples. A successful culture of A. cryophilum was established only when isolates were incubated at 5–7° C. It is compared with two morphologically similar species, A. amphidinioides (Geitler) Schiller and Gymnodinium inversum Nygaard. Amphidinium cryophilum is distinguished from the former by its pigmentation (golden-yellow vs. blue-green), the location of the cingulum, and its lack of an eyespot. It differs from the latter in cell shape, the route of the sulcus and position of the nucleus.
LINCAGES 2000: Latest Developments and Case Study

This paper introduces the latest development of LINCAGES 2000, a mechanism design software package available on Windows 9x/NT and 2000. A case study of a motion generation mechanism design using LINCAGES 2000 is presented. Various design options are compared and their advantages and disadvantages are discussed. This software is proved to be a powerful tool for mechanism synthesis and analysis.© 2002 ASME