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At least 253 records · Page 14Linked to original sources

PLayer-FL: A Principled Approach to Personalized Layer-wise Cross-Silo Federated Learning.

Non-identically distributed data is a major challenge in Federated Learning (FL). Personalized FL tackles this by balancing local model adaptation with global model consistency. One variant, partial FL, leverages the observation that early layers learn more transferable features by federating only early layers. However, current partial FL approaches use predetermined, architecture-specific rules to select layers, limiting their applicability. We introduce Principled Layer-wise-FL (PLayer-FL), which uses a novel federation sensitivity metric to identify layers that benefit from federation. This metric, inspired by model pruning, quantifies each layer's contribution to cross-client generalization after the first training epoch, identifying a transition point in the network where the benefits of federation diminish. We first demonstrate that our federation sensitivity metric shows strong correlation with established generalization measures across diverse architectures. Next, we show that PLayer-FL outperforms existing FL algorithms on a range of tasks, also achieving more uniform performance improvements across clients.

Journal Article↗

An outcomes model of medical decision making.

In the traditional 'fix-it' model of medical decision making, the identified problem is typically characterized by a diagnosis that indicates a deviation from normalcy. When a medical problem is multifaceted and the available interventions are only partially effective, a broader vision of the health care endeavor is needed. What matters to the patient, and what should matter to the practitioner, is the patient's future possibilities. More specifically, what is important is the character of the alternative futures that the patient could have and choosing among them so as to achieve the best future possible, with the ranking of outcomes determined by the patient's preferences. This paper describes the fix-it model, presents and defends the outcomes-based model, and demonstrates that the latter is useful in developing normative conceptions of informed consent and decision making and in establishing a basis for societal involvement in the decision making process. Finally, several shortcomings of the model will be acknowledged.

Attitude of Health Personnel↗

Intrapleural treatment with recombinant gamma-interferon in early stage malignant pleural mesothelioma.

BACKGROUND: This report presents the results of a prospective multi-institutional study of intrapleural treatment with gamma-interferon in patients with Butchart's Stages I and II epithelial or mixed malignant pleural mesothelioma. METHODS: Interferon was administered at a dose of 40 million units twice a week for 8 weeks intrapleurally via a catheter or an implantable port. Thoracoscopic or surgical biopsy was performed if computed tomography scan 2 weeks after the end of treatment demonstrated a reduction in tumor size. Survival was calculated after a follow-up of at least 18 months. Prognostic factors were identified by univariate and multivariate analyses (Cox model). RESULTS: Eighty-nine patients were included over 46 months. Eight histologically confirmed complete responses and nine partial responses with at least a 50% reduction in tumor size were obtained. The overall response rate was 20%. Most responses were achieved in patients with early stage disease. The response rate for patients with Stage I disease was 45%. Tolerance of interferon was good. Treatment was performed on an outpatient basis. The main side effects were hyperthermia, liver toxicity, neutropenia, and catheter-related infection. CONCLUSIONS: Gamma-interferon is effective mainly in Stage I mesothelioma, especially if the tumor is confined to the parietal or diaphragmatic pleura (Stage IA).

Aged↗

Predicting children's sunscreen use: application of the theories of reasoned action and planned behavior.

BACKGROUND: Skin cancer remains the most common form of cancer in the United States despite the fact that most cases can be prevented by limiting sun exposure. Childhood and adolescence are periods of life during which prolonged sun exposure is particularly common. Accordingly, promoting sun-protective behaviors during these formative years can be of critical importance in preventing skin cancer. The present study applied the theories of reasoned action and planned behavior to the understanding of children's sunscreen use. Based on these theories, it was hypothesized that attitudes, subjective norms, and perceived behavioral control would be related to intentions to use sunscreen, which, in turn, would be related to actual sunscreen use. METHODS: Questionnaires measuring sun-related attitudes, beliefs, perceived control, and intentions were administered to 199 fourth graders (ages 9 to 13, mean = 10.3) attending public schools in Florida. Self-report measures of sun-related behavior were administered to the same subjects 1 month later. RESULTS: Results of correlational analyses were consistent with study hypotheses. Higher rates of sunscreen use at follow-up were predicted by stronger intentions to use sunscreen assessed 1 month previously. In addition, stronger intentions to use sunscreen were found to be related to more favorable attitudes toward sunscreen use, stronger beliefs that peers and parents favored sunscreen use, and greater perceptions of personal control in using sunscreen. Path and multiple regression analyses identified direct and indirect relationships among study variables that partially confirmed those predicted by the theories and provided support for the use of an expanded model that included perceived behavioral control. CONCLUSIONS: The present study confirmed hypotheses derived from the theories of reasoned action and planned behavior regarding the relation of attitudes, subjective norms, and perceived behavioral control to sunscreen use among fourth graders. In addition to their theoretical significance, these findings suggest ways to intervene at the individual, classroom, and family levels to promote greater sunscreen use in this age group.

Adolescent↗

Characterisation and partial purification of a novel prohormone processing enzyme from ovine adrenal medulla.

An enzymatic activity has been identified which is capable of generating a product chromatographically identical with adrenorphin from the model substrate BAM12P. This enzyme was purified by gel filtration and ion-exchange chromatography and characterised as having a molecular mass between 30 and 45 kDa and an acidic pI. The enzyme is active at the acid pH expected in the secretory vesicle interior and is inhibited by EDTA, suggesting that it is a metalloprotease. This activity could not be mimicked by incubation with lysosomal fractions and it meets the criteria to be considered as a possible prohormone processing enzyme.

Adrenal Medulla↗

Correlation of histology and sensibility after nerve repair.

The partially denervated human fingertip was used as a model to correlate results of a detailed evaluation of sensibility with the presence of reinnervated sensory corpuscles identified by light and electron microscopy. In each of the three patients studied, the histologically identified reinnervated mechanoreceptors were appropriate to provide the neurophysiologic basis for the observed results of clinically tested sensibility.

Adult↗

Development and evaluation of an in silico model for hERG binding.

It has been recognized that drug-induced QT prolongation is related to blockage of the human ether-a-go-go-related gene (hERG) ion channel. Therefore, it is prudent to evaluate the hERG binding of active compounds in early stages of drug discovery. In silico approaches provide an economic and quick method to screen for potential hERG liability. A diverse set of 90 compounds with hERG IC(50) inhibition data was collected from literature references. Fragment-based QSAR descriptors and three different statistical methods, support vector regression, partial least squares, and random forests, were employed to construct QSAR models for hERG binding affinity. Important fragment descriptors relevant to hERG binding affinity were identified through an efficient feature selection method based on sparse linear support vector regression. The support vector regression predictive model built upon selected fragment descriptors outperforms the other two statistical methods in this study, resulting in an r(2) of 0.912 and 0.848 for the training and testing data sets, respectively. The support vector regression model was applied to predict hERG binding affinities of 20 in-house compounds belonging to three different series. The model predicted the relative binding affinity well for two out of three compound series. The hierarchical clustering and dendrogram results show that the compound series with the best prediction has much higher structural similarity and more neighbors of training compounds than the other two compound series, demonstrating the predictive scope of the model. The combination of a QSAR model and postprocessing analysis, such as clustering and visualization, provides a way to assess the confidence level of QSAR prediction results on the basis of similarity to the training set.

Cell Line↗

Semi-mechanistic partial buffer approach to modeling pH, the buffer properties, and the distribution of ionic species in complex solutions.

In many biological science and food processing applications, it is very important to control or modify pH. However, the complex, unknown composition of biological media and foods often limits the utility of purely theoretical approaches to modeling pH and calculating the distributions of ionizable species. This paper provides general formulas and efficient algorithms for predicting the pH, titration, ionic species concentrations, buffer capacity, and ionic strength of buffer solutions containing both defined and undefined components. A flexible, semi-mechanistic, partial buffering (SMPB) approach is presented that uses local polynomial regression to model the buffering influence of complex or undefined components in a solution, while identified components of known concentration are modeled using expressions based on extensions of the standard acid-base theory. The SMPB method is implemented in a freeware package, (pH)Tools, for use with Matlab. We validated the predictive accuracy of these methods by using strong acid titrations of cucumber slurries to predict the amount of a weak acid required to adjust pH to selected target values.

Algorithms↗

A rapid computational filter for cytochrome P450 1A2 inhibition potential of compound libraries.

QSAR models for a diverse set of compounds for cytochrome P450 1A2 inhibition have been produced using 4 statistical approaches; partial least squares (PLS), multiple linear regression (MLR), classification and regression trees (CART), and bayesian neural networks (BNN). The models complement one another and have identified the following descriptors as important features for CYP1A2 inhibition; lipophilicity, aromaticity, charge, and the HOMO/LUMO energies. Furthermore all models are global and have been used to predict a diverse independent set of compounds. For the first time in the field of QSAR, the kappa index of agreement has comprehensively been used to assess the overall accuracy of the model's predictive power. The models are statistically significant and can be used as a rapid computational filter for cytochrome P450 1A2 inhibition potential of compound libraries.

Bayes Theorem↗

Evidence for neuromelanin involvement in MPTP-induced neurotoxicity.

Exposure to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) reproduces certain clinical, pathological, and neurochemical features of Parkinson's disease. MPTP is metabolized by monoamine oxidase Type B to 1-methyl-4-phenylpyridine (MPP+), which is selectively accumulated by high-affinity uptake mechanisms into dopaminergic neurons. Lyden et al. described low-affinity binding of MPTP to synthetic and retinal melanin. We showed that MPP+ binds to neuromelanin with high affinity, suggesting that in MPTP neurotoxicity, MPP+ enters nigral neurons by the dopamine uptake system and binds to neuromelanin, which serves as a depot, continuously releasing MPP+ until it destroys the cells. This model predicts that agents which compete with MPP+ binding to neuromelanin should partially protect the dopamine neurons from MPTP-induced toxicity. The most potent identified competitor for MPP+ binding to melanin is the antimalarial drug chloroquine, which has a high affinity for melanins. In the present study, chloroquine, administered to monkeys in conventional anti-malarial doses before MPTP, protects them from MPTP-induced parkinsonian motor abnormalities, dopamine depletion in the striatum, and neuropathological changes in the substantia nigra.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

The risk of mortality among older adults over an eight-year period.

Mortality risks over an 8-year period are assessed among the 7,527 older adults interviewed as part of the Longitudinal Study on Aging. Using a modified version of the behavioral model, hierarchical methods are used to sequentially introduce the predisposing and enabling characteristics, disease history, disabilities and functional limitations, perceived health, and health services utilization both at and after baseline. Based on their partial r statistics (shown in parentheses), the proportional hazard analyses identify the mean annual number of hospital episodes after baseline (.13), age (.07), female gender (-.05), non-kin social supports (-.03), body mass (-.03), and having a history of diabetes (.03) as the six most salient predictors. These six variables account for 80% of the overall model fit.

Activities of Daily Living↗

Activation of murine macrophages by Neisseria meningitidis and IFN-gamma in vitro: distinct roles of class A scavenger and Toll-like pattern recognition receptors in selective modulation of surface phenotype.

Innate and adaptive immune activation of macrophages (Mphi) by microorganisms and antigen-activated lymphoid cells, respectively, plays an important role in host defense and immunopathology. Antigen-presenting cells express a range of pattern recognition receptors including the class A types I and II scavenger receptors (SR-A) and Toll-like receptors (TLR). Recognition of microbial products by SR-A and TLR controls uptake, killing, altered gene expression, and the adaptive immune response; however, the contribution of each receptor and interplay with cytokine stimuli such as interferon-gamma (IFN-gamma) are not defined. We used Neisseria meningitidis (NM), a potent activator of innate immunity, and IFN-gamma, a prototypic T helper cell type 1 proinflammatory cytokine, to compare surface antigens, secretion of mediators, and receptor functions in elicited peritoneal Mphi from wild-type and genetically modified mouse strains. We show that these stimuli regulate major histocompatibility complex type II (MHC-II) and costimulatory molecules differentially, as well as expression of the mannose receptor and of Mphi receptor with collagenous structure (MARCO), a distinct SR-A, which provides a selective marker for innate activation. In combination, NM inhibited up-regulation of MHC-II by IFN-gamma while priming enhanced release of tumor necrosis factor alpha and nitric oxide. The SR-A contributes to phagocytosis of the organisms but not to their ability to induce CD80, CD86, and MARCO or to inhibit MHC-II. Conversely, studies with lipopolysaccharide (LPS)-deficient organisms and/or TLR-4 mutant mice showed that LPS and TLR-4 are at least partially required to induce CD80, CD86, and MARCO, but LPS is not required to inhibit MHC-II. These studies provide an experimental model and identify surface markers for analysis of innate and acquired immune activation of Mphi.

Animals↗

Differentiation of normal and malignant human squamous epithelium in vivo and in vitro: a morphologic study.

We report a light microscopic and ultrastructural analysis of the comparative degrees of differentiation seen in keratinocytes derived from the tongue and epidermis with those of a well-differentiated human squamous carcinoma cell line (LICR-LON-HN5). When growing on plastic substrates, all cultures had a similar morphology, with multilayering and the production of cornified envelopes. When cultured on collagen gels the structure was more organized, with keratohyalin granules and keratin whorl formation in both the normal and the malignant cultures. Normal keratinocytes injected into athymic mice produced epidermal cysts, while cells from the cell line produced well-differentiated squamous cell carcinomas, which were partially solid and partially cystic. the tumor was well organized, with identifiable basal cells, spinous cells, keratohyalin granules, and a prominent basal lamina at the stromal/epithelial interface. This model is to be developed for comparative studies between normal and malignant cells, with particular reference to basement membrane production and to investigations of the relative importance of extrinsic and intrinsic factors in the control of squamous differentiation.

Animals↗

Different residues mediate recognition of 1-O-oleyllysophosphatidic acid and rosiglitazone in the ligand binding domain of peroxisome proliferator-activated receptor gamma.

Here we showed that a naturally occurring ether analog of lysophosphatidic acid, 1-O-octadecenyl-2-hydroxy-sn-glycero-3-phosphate (AGP), is a high affinity partial agonist of the peroxisome proliferator-activated receptor gamma (PPARgamma). Binding studies using the PPARgamma ligand binding domain showed that [32P]AGP and [3H]rosiglitazone (Rosi) both specifically bind to PPARgamma and compete with each other. [32P]AGP bound PPARgamma with an affinity (Kdapp 60 nm) similar to that of Rosi. However, AGP displaced approximately 40% of bound [3H]Rosi even when applied at a 2000-fold excess. Activation of PPARgamma reporter gene expression by AGP and Rosi showed similar potency, yet AGP-mediated activation was approximately 40% that of Rosi. A complex between AGP and PPARgamma was generated using molecular modeling based on a PPARgamma crystal structure. AGP-interacting residues were compared with Rosi-interacting residues identified within the Rosi-PPARgamma co-crystal complex. These comparisons showed that the two ligands occupy partially overlapping positions but make different hydrogen bonding and ion pairing interactions. Site-specific mutants of PPARgamma were prepared to examine individual ligand binding. H323A and H449A mutants showed reduced binding of Rosi but maintained binding of AGP. In contrast, the R288A showed reduced AGP binding but maintained Rosi binding. Finally, alanine replacement of Tyr-473 abolished binding and activation by Rosi and AGP. These observations indicate that the endogenous lipid mediator AGP is a high affinity ligand of PPARgamma but that it binds via interactions distinct from those involved in Rosi binding. These distinct interactions are likely responsible for the partial PPARgamma agonism of AGP.

Adenoviridae↗

Refined structure of the chitinase from barley seeds at 2.0 a resolution.

Chitinase from barley seeds is a monomeric enzyme with 243 amino-acid residues and it plays a role as a defense protein. Its structure, previously determined at 2.8 A resolution by multiple isomorphous replacement method, is mainly alpha-helical [Hart, Monzingo, Ready, Ernst & Robertus, (1993). J. Mol. Biol. 229, 189-193]. The crystallization and preliminary X-ray data of the same enzyme in a different crystal form has been reported independently [Song, Hwang, Kim & Suh, (1993). Proteins, 17, 107-109}, the asymmetric unit of which contains two chitinase molecules. As a step toward understanding the general principles of catalysis, reported here is the structure of chitinase from barley seeds in this crystal form, as determined by molecular replacement and subsequently refined at 2.0 A resolution, with incorporation of partial data to 1.9 A (R factor of 18.9% for 31 038 unique reflections with F(o)> 2sigma(F) in the range 8.0-1.9 A). The r.m.s. deviations from ideal stereochemistry are 0.013 A for bond lengths and 1.32 degrees for bond angles. A superposition of the two independent molecules in the asymmetric unit gives an r.m.s. difference of 0.55 A for all protein atoms (0.43 and 0.74 A for main-chain and side-chain atoms, respectively). When the refined model of each chitinase molecule in the asymmetric unit is superposed with the starting model, the r.m.s. difference for all shared protein atoms is 0.99 A for molecule 1 and 0.85 A for molecule 2, respectively. Through a sequence comparison with homologous plant chitinases as well as a structural comparison with the active sites of other glycosidases, key catalytic residues have been identified and the active site has been located in the three-dimensional structure of the barley chitinase. The present structure, refined at an effective resolution of 2.0 A with incorporation of partial data to 1.9 A, represents a significant improvement in resolution compared to the previously reported model. The improved resolution has enabled the location of solvent atoms, including water molecules near the catalytic residues, in addition to the positioning of protein atoms with greater accuracy.

Journal Article↗

Higher plant 5S rRNAs share common secondary and tertiary structure. A new three domains model.

A new model of secondary and tertiary structure of higher plant 5S RNA is proposed. It consists of three helical domains: domain alpha includes stem I; domain beta contains stems II and III and loops B and C; domain gamma consists of stems IV and V and loops D and E. Except for, presumably, a canonical RNA-A like domain alpha, the two remaining domains apparently adopt a perturbed RNA-A structure due to irregularities within internal loops B and E and three bulges occurring in the model. Bending of RNA could bring loops B and E and/or C and D closer making tertiary interactions likely. The model differs from that suggested for eukaryotic 5S rRNA, by organization of domain gamma. Our model is based on the results of partial digestion obtained with single- and double-strand RNA specific nucleases. The proposed secondary structure is strongly supported by the observation that crude plant 5S rRNA contains abundant RNA, identified as domain gamma of 5S rRNA. Presumably it is excised from the 5S rRNA molecule by a specific nuclease present in lupin seeds. Experimental results were confirmed by computer-aided secondary structure prediction analysis of all higher plant 5S rRNAs. Differences observed between earlier proposed models and our proposition are discussed.

Base Sequence↗

Yeast DNA polymerases and their role at the replication fork.

The DNA polymerases of the yeast Saccharomyces cerevisiae serve as a model system for the study of the replication fork during DNA replication. To date, six S. cerevisiae DNA polymerases have been at least partially characterized (compared with four in mammals so far), with further candidates being identified as open reading frames in the yeast genome sequencing project. Here, we review the current state of knowledge of the yeast polymerases, and discuss, where possible, their biological role during DNA replication.

DNA Polymerase II↗

Caring for the frail elderly at home: toward a theoretical explanation of the dynamics of poor quality family caregiving.

Using the grounded theory approach, 39 family caregivers were theoretically sampled using newspaper advertising to explore their perceptions of providing home care for frail elders and to generate a theoretical model that describes the dynamics of good quality and poor quality family caregiving; explains the relationships among certain contextual and perceptual variables and the behaviors exchanged by elders and caregivers; and identifies points where interventions by nurses could be effective. The model consists of five constructs that were identified from the data and were staged within the framework provided by symbolic interactionism and social exchange theory. The five constructs and two related driving forces provide a partial explanation for the quality of family caregiving and a beginning explanation for the phenomenon of elder abuse.

Adolescent↗