Miracle-dz/UniFAR-FTUs huggingface dataset:
Tropomodulin caps the pointed ends of actin filaments

Many proteins have been shown to cap the fast growing (barbed) ends of actin filaments, but none have been shown to block elongation and depolymerization at the slow growing (pointed) filament ends. Tropomodulin is a tropomyosin-binding protein originally isolated from red blood cells that has been localized by immunofluorescence staining to a site at or near the pointed ends of skeletal muscle thin filaments (Fowler, V. M., M. A., Sussman, P. G. Miller, B. E. Flucher, and M. P. Daniels. 1993. J. Cell Biol. 120: 411-420). Our experiments demonstrate that tropomodulin in conjunction with tropomyosin is a pointed end capping protein: it completely blocks both elongation and depolymerization at the pointed ends of tropomyosin-containing actin filaments in concentrations stoichiometric to the concentration of filament ends (Kd < or = 1 nM). In the absence of tropomyosin, tropomodulin acts as a "leaky" cap, partially inhibiting elongation and depolymerization at the pointed filament ends (Kd for inhibition of elongation = 0.1-0.4 microM). Thus, tropomodulin can bind directly to actin at the pointed filament end. Tropomodulin also doubles the critical concentration at the pointed ends of pure actin filaments without affecting either the rate of extent of polymerization at the barbed filament ends, indicating that tropomodulin does not sequester actin monomers. Our experiments provide direct biochemical evidence that tropomodulin binds to both the terminal tropomyosin and actin molecules at the pointed filament end, and is the long sought-after pointed end capping protein. We propose that tropomodulin plays a role in maintaining the narrow length distributions of the stable, tropomyosin-containing actin filaments in striated muscle and in red blood cells.
Obstructive lung disease and low lung function in adults in the United States: data from the National Health and Nutrition Examination Survey, 1988-1994.

BACKGROUND Obstructive lung disease (OLD) is an important cause of morbidity and mortality in the US adult population. Potentially treatable mild cases of OLD often go undetected. This analysis determines the national estimates of reported OLD and low lung function in the US adult population. METHODS We examined data from the Third National Health and Nutrition Examination Survey (NHANES III), a multistage probability representative sample of the US population. A total of 20,050 US adults participated in NHANES III from 1988 to 1994. Our main outcome measures were low lung function (a condition determined to be present if the forced expiratory volume in 1 second-forced vital capacity ratio was less than 0.7 and the forced expiratory volume in 1 second was less than 80% of the predicted value), a physician diagnosis of OLD (chronic bronchitis, asthma, or emphysema), and respiratory symptoms. RESULTS Overall a mean (SE) of 6.8% (0.3%) of the population had low lung function, and 8.5% (0.3%) of the population reported OLD. Obstructive lung disease (age-adjusted to study population) was currently reported among 12.5% (0.7%) of current smokers, 9.4% (0.6%) of former smokers, 3.1% (1.1%) of pipe or cigar smokers, and 5.8% (0.4%) of never smokers. Surprisingly, 63.3% (0.2%) of the subjects with documented low lung function had no prior or current reported diagnosis of any OLD. CONCLUSIONS This study demonstrates that OLD is present in a substantive number of US adults. In addition, many US adults have low lung function but no reported OLD diagnosis, which may indicate the presence of undiagnosed lung disease.
Rural Water Supply in Africa: Building Blocks for Handpump Sustainability

Rural water supplies in sub-Saharan Africa, particularly those relying on handpumps, often demonstrate low levels of sustainability. This book is designed to assist those responsible for planning, implementing and supporting rural water supply programmes to increase sustainability. Its primary aims are to raise awareness of issues that affect sustainability and the interrelationship between them, provide options for addressing these using examples, and describe how these options can be implemented. The importance of a programmatic approach to the delivery of rural water services is emphasized, as is the need for ongoing institutional support for community management and consideration of alternative management models. The book does not prescribe a 'one size fits all' solution but encourages a flexible, holistic approach to decision-making to achieve sustainable outcomes.
Hydra viridis: transfer of metabolites between Hydra and symbiotic algae.

"Back transfer" of metabolites from food to endosymbiotic algae in the digestive cells of Hydra viridis was demonstrated. Brine shrimp nauplii labeled with tritiated precursors of protein and nucleic acids (DNA and RNA) were fed to light and dark grown hydras. The fate of the label after a single feeding with radioactive material in hydra and algal fractions was followed by scintillation counting and autoradiographic techniques. Labeled thymidine was incorporated into DNA in both light- and dark-grown hydras. Although the symbiosis persists indefinitely in hydras in darkness (7-10 days) the number of algae per cell is reduced. Tritiated orotic acid and tritiated uridine, RNA precursors, were incorporated into peptides and proteins, and to a lesser extent into simple sugars, oligosaccharides, and oligonucleotides in hydra and algal fractions. Thus the metabolites of the brine shrimp food are available to both partners. A decrease over time in label introduced as 3H-orotic acid and 3H-uridine and incorporated into hydra RNA is compensated for by an increase in label in the algae, implying competition for constant quantities of metabolites from the single feeding. Although food availability, light, number of algae per cell, and other factors influence the quantity and rate of nutrient transfer between the partners, in both light and dark grown hydras the amount of "back transfer" of metabolites to the symbiotic algae is impressive.
Structure of Apaf-1 in the Auto-Inhibited Form: A Critical Role for ADP

The pathway of apoptosis is conserved in the three model species: mammals, Drosophila, and C. elegans. The apoptotic protease-activating factor 1, an essential protein conserved in all three species, is responsible for the activation of the initiator caspase-9 in mammalian cells. The structure of the auto-inhibited form of Apaf-1 reveals a critical role for ADP, which serves as an organizing center for four adjoining domains. The ADP-binding pocket contains features that are important for designing other nucleotide analogs. ATP binding is a pre-requisite for the formation of the apoptosome. Despite strong sequence conservation between Apaf-1 and its orthologues in Drosophila and C. elegans, it is unclear whether they employ similar mechanisms for their own activation and for activating caspases. Much of the underlying mechanisms remain to be investigated by structural biology and biochemistry.
Virtual Blinds: Finding Online Privacy in Offline Precedents

A person in a building shows a desire for privacy by pulling her blinds shut or closing her curtains. Otherwise, she cannot complain when her neighbor sees her undressing from the window, or when a policeman looks up from the street and sees her marijuana plants. In the online context, can we find an analogy to these privacy blinds? Or is the window legally bare because of the nature of the internet? This Article argues that by analyzing the privacy given to communications in the offline context, and in particular, by analyzing case law recognizing privacy in an otherwise public place when the individual engages in affirmative efforts to ensure her privacy, the law can find a sensible foundation for recognizing privacy online. This Article proposes a framework that incorporates the following factors in the reasonable expectations of privacy context. First is the existence of a user agreement or employer policy governing the use of the specific communication mechanism or providing for monitoring of that use. Second is the extent to which third parties have access to or protect the communications. The third factor is the notice given to the user of the user agreement, employer policy, or practice of giving access to or protection from third parties. Finally, the fourth factor is the availability and use of privacy enhancing controls which increase the likelihood of the communication being protected from disclosure to people other than the chosen recipient(s), including but not limited to (a) passwords, (b) encryption technology, (c) network configuration, and (d) privacy settings limiting disclosure to certain people.Courts can adapt this test to a civil tort or Fourth Amendment context, to employment and non-employment cases, and to statutory privacy claims. It is a logical evolution from the practical factors that courts have looked at in offline cases — like closing doors and securing lockers — and it is consistent with the growing weight of authority that finds a reasonable expectation of privacy in online communications where the Internet user avails herself of privacy ensuring measures.
Tax reform 1986 and marginal welfare changes for labor

During the 1980s in the United States, before-tax income shifted away from the poor and toward the upper income groups. Changing the distribution of tax burdens or after-tax income is one way to redress a growing imbalance in before-tax income. Pechman [14], Feldstein [6], and Wallace et al. [17] have all shown that the Tax Reform Act of 1986 (TRA86) increased the progressivity of the combined personal and corporate income taxes, an achievement not accomplished in the last two decades of income tax reform [14]. Tax reform can also increase or decrease the welfare of individuals in an economy through its effect on the allocation of labor supply resources. TRA86 reduced the highest marginal income tax rates from 50 percent to 28 percent for high income persons and removed some lower-income persons from the tax roles. Such large marginal tax rate changes introduce significant potential for increased economic efficiency in labor supply and for welfare gains for the rich and poor alike. These changes should be part of the benefit analysis of tax reform. Indeed, Hausman and Poterba [10] report welfare cost changes that result from TRA86 for the average male and female. Their estimates, however, do not account for welfare cost changes throughout the income distribution. In addition to our use of microdata to estimate the marginal welfare cost of tax reform, we use more precise measures of marginal tax rates than other researchers. In this paper, we use Browning's partial equilibrium framework to examine the influence of the reduction in marginal tax rates from TRA86 on the distribution of welfare gains from labor supply reallocation for males by population decile and for females by population decile and by marital status. The empirical results illustrate how the tax reform affected low-income female household heads, where poverty is so heavily concentrated, as well as other household heads and spouses. The results indicate that TRA86 reduced welfare costs in the economy, but these welfare
The MAPK Pathway Is a Predominant Regulator of HLA-A Expression in Esophageal and Gastric Cancer

Downregulation of HLA class I expression may contribute to a poor prognosis in cancer patients. There is limited information about epigenetic and oncogenic regulation of HLA class I, and multiple mechanisms may be involved. In the current study, we examined the relationship between the HER2-signaling pathway (MAPK and PI3K-Akt) and the expression of HLA class I and Ag-processing machinery (APM) components. A panel of gastric and esophageal cancer cell lines was treated with wortmannin as an Akt-signal inhibitor; the MAPK signal inhibitor PD98059; lapatinib, which inhibits both the epidermal growth factor receptor and HER2 tyrosine kinase; or siRNA for MAPK. The levels of HER2-signaling molecules, APM components, and HLA class I were evaluated by Western blot, quantitative PCR, and flow cytometry. Resected gastric tumor tissues (n = 102) were analyzed for p-Erk and HLA class I expression by immunohistochemistry. As a result, inhibition of the MAPK pathway induced upregulation of HLA-A02 and HLA-A24 expression in parallel with an increase in APM components and enhanced target sensitivity to tumor Ag–specific CTL lysis. HLA-A expression was predominantly regulated by the MAPK pathway, but it was also influenced, in part, by the Akt pathway. There was a strong inverse correlation between p-Erk expression and HLA class I expression in clinical tumor samples. In conclusion, HLA-A expression is predominantly regulated by the MAPK pathway in gastric and esophageal cancer.
Novel Broadband Bandpass Filters Using Y-Shaped Dual-Mode Microstrip Resonators

A Y-shaped dual-mode microstrip bandpass filter (BPF) with input-output cross-coupling is presented. The characteristic of the Y-shaped dual-mode resonator has been investigated. The resonance frequencies of the degenerate modes can be adjusted easily to satisfy the bandwidth of the BPF. A parallel-coupling feed structure with a cross coupling has been used to generate two transmission zeros at the lower and upper stopband, which can improve the out-of-band performance. A broadband dual-mode microstrip BPF has been designed, fabricated, and measured. The simulated and measured results are in agreement generally. Within the 3.1 to 5.4 GHz bandwidth, the measured insertion loss, return loss and group delay variation are below 0.5 dB, above 15 dB, and below 0.2 ns, respectively.
System Integration of Electronic Functions in Smart Packaging Applications

A system integration scheme relevant for smart packaging applications is presented. Recent advances in printed electronics, radio frequency identification tag production, and standardization of communication protocols are factors that increase the design freedom for new applications. As in all new technology fields, the first products are expected to appear in the high-cost segment attracting early adopters in the form of niche products. A reasonable assumption is that these products will come from hybridization of different types of technologies. Such a scenario is likely since no technology solution available can provide all features that these types of applications demand. There is a need of standard solutions for hybridization of silicon devices and printed (or foil-type) components. Conductive ink technology is a powerful tool for hybridization and customization of large-area electronics, providing 3-D integration and large-area customization. However, high-performance communication and advanced processing demand the use of silicon. Smart hybridization solutions allow combination of the best from both worlds. This paper analyzes the requirements on hybridization technologies suitable for smart packaging applications and provides design examples on integration of intrusion surveillance solutions for cellulose-based packaging applications. It shows that even though the current hybridization technologies are far from optimal, they can provide a considerable design freedom and system performance.
Calcium signaling in the development and function of T‐lineage cells

Summary: Ca2+ signals are essential for diverse cellular functions including differentiation, effector function, and gene transcription in the immune system. In lymphocytes, sustained Ca2+ entry is necessary for complete and long‐lasting activation of calcineurin/nuclear factor of activated T cells (NFAT) pathways. Engagement of immunoreceptors, such as the T‐cell antigen receptor, induces store‐operated Ca2+ entry (SOCE) through plasma membrane Ca2+ channels. In lymphocytes, mast cells, and other immune cell types, SOCE through highly Ca2+‐selective Ca2+ release‐activated Ca2+ (CRAC) channels constitute the major pathway of intracellular Ca2+ increase. A recent breakthrough in our understanding of CRAC channel function is the identification of STIM and ORAI, two essential regulators of CRAC channel function. This discovery allows us to directly address the physiological role of Ca2+ entry in lymphocytes. A growing number of studies have emphasized that Ca2+/calcineurin/NFAT pathway is crucial for both development and function of all T‐cell lineage cells, such as conventional αβ+ TCR T cells, Foxp3+ regulatory T cells, and invariant natural killer T cells. This review focuses on the role of the signaling pathways upstream and downstream of Ca2+ influx in the development and function in T‐cell lineages.
The social experience of aging with a chronic illness: Perspectives of older adults with multiple sclerosis

Purpose. The purpose of this study was to explore the social experiences of older adults with multiple sclerosis (MS) in order to recognize the changes in social experience and social needs that may occur with aging with a chronic illness. Method. Analysis of qualitative data from an exploratory study utilizing a phenomenological approach with 27 older adults with MS, aged 55 – 81. Results. In-depth interviews revealed that the social experience was influenced by groups of factors including the person's social needs, experience of MS, values and expectations, characteristics of the social support system, the response of the support providers, and the accessibility of the social environment. The participants discussed concerns about the future adequacy of support. A process of negotiation was also described and was seen as an opportunity to change the social experience and social support received. Conclusion. This study provides an insider's view of the social changes that older adults living with MS experience. This study also identifies barriers to the acquisition of support and addresses the importance of appropriately responding to the changing needs of this population.
Structure and Mechanism of CTP:Phosphocholine Cytidylyltransferase (LicC) from Streptococcus pneumoniae *

Pneumococcal LicC is a member of the nucleoside triphosphate transferase superfamily and catalyzes the transfer of a cytidine monophosphate from CTP to phosphocholine to form CDP-choline. The structures of apo-LicC and the LicC·CDP-choline·Mg2+ ternary complex were determined, and the comparison of these structures reveals a significant conformational change driven by the multivalent coordination of Mg2+. The key event is breaking the Glu216·Arg129 salt bridge, which triggers the coalescence of four individual β-strands into two extended β-sheets. These movements reorient the side chains of Trp136 and Tyr190 for the optimal binding and alignment of the phosphocholine moiety. Consistent with these conformational changes, LicC operates via a compulsory ordered kinetic mechanism. The structures explain the substrate specificity of LicC for CTP and phosphocholine and implicate a direct role for Mg2+in aligning phosphocholine for in-line nucleophilic attack and stabilizing the negative charge that develops in the pentacoordinate transition state. These results provide a structural basis for assigning a specific role for magnesium in the catalytic mechanism of pneumococcal LicC.
Features of AIDS and AIDS defining diseases during the highly active antiretroviral therapy (HAART) era, compared with the pre-HAART period: a case-control study

Editor,—To assess the features of AIDS defining illnesses during the HAART era versus those observed before the introduction of HAART, the characteristics of 72 consecutive patients, diagnosed in 1997–9, were compared with those of 144 subjects randomly selected from the 436 patients diagnosed from 1985 to 1995, in a case-control study. An impressive drop in AIDS diagnosis was seen shortly after the introduction of HAART, with only 38, 21, and 13 cases per ∼1000 patient years observed in 1997, 1998, and 1999 respectively, versus a mean frequency >60 cases per ∼1000 patient years, demonstrated during 1991–5. A tendency towards an increased incidence of female sex was shown in 1997–9 compared with 1985–95 (33.3% versus 27.1%), together with a rise of mean CD4+ lymphocyte count (86.8 (SD 99.4) versus 72.1 (93.7) cells ×106/l), while …
Sensing lysozyme rebinding on molecularly imprinted polymers by scanning electrochemical microscopy

Molecularly imprinted polymers, artificial antibodies, were synthesized by printing target biomolecules on a monomer mixture and then forming a highly selective and stable polymer. Scanning electrochemical microscopy (SECM) was employed to measure the reduction current between horseradish peroxide (HRP) conjugated lysozyme antibody and ferrocenylmethol (FMA) after different lysozyme concentrations for rebinding were applied on the molecularly imprinted polymers. We found that the reduction current increased linearly with increasing the rebinding lysozyme concentration.
Defective decidualization during and after severe preeclampsia reveals a possible maternal contribution to the etiology

Significance We provide evidence of a decidualization defect in the endometrium of women with severe preeclampsia (PE) that was detected at the time of delivery and persisted years after the affected pregnancy. We went on to link this defect to impaired cytotrophoblast invasion. The transcriptional signature of the defect could enable its detection before (or after) conception, which would aid the development of therapies focused on improving decidualization and perhaps preventing severe PE. In preeclampsia (PE), cytotrophoblast (CTB) invasion of the uterus and spiral arteries is often shallow. Thus, the placenta’s role has been a focus. In this study, we tested the hypothesis that decidual defects are an important determinant of the placental phenotype. We isolated human endometrial stromal cells from nonpregnant donors with a previous pregnancy that was complicated by severe PE (sPE). Compared with control cells, they failed to decidualize in vitro as demonstrated by morphological criteria and the analysis of stage-specific antigens (i.e., IGFBP1, PRL). These results were bolstered by global transcriptional profiling data that showed they were transcriptionally inert. Additionally, we used laser microdissection to isolate the decidua from tissue sections of the maternal–fetal interface in sPE. Global transcriptional profiling revealed defects in gene expression. Also, decidual cells from patients with sPE, which dedifferentiated in vitro, failed to redecidualize in culture. Conditioned medium from these cells failed to support CTB invasion. To mimic aspects of the uterine environment in normal pregnancy, we added PRL and IGFBP1, which enhanced invasion. These data suggested that failed decidualization is an important contributor to down-regulated CTB invasion in sPE. Future studies will be aimed at determining whether this discovery has translational potential with regard to assessing a woman’s risk of developing this pregnancy complication.
Two Distinct Actin Networks Drive the Protrusion of Migrating Cells

Cell migration initiates by extension of the actin cytoskeleton at the leading edge. Computational analysis of fluorescent speckle microscopy movies of migrating epithelial cells revealed this process is mediated by two spatially colocalized but kinematically, kinetically, molecularly, and functionally distinct actin networks. A lamellipodium network assembled at the leading edge but completely disassembled within 1 to 3 micrometers. It was weakly coupled to the rest of the cytoskeleton and promoted the random protrusion and retraction of the leading edge. Productive cell advance was a function of the second colocalized network, the lamella, where actomyosin contraction was integrated with substrate adhesion.