Miracle-dz/UniFAR-FTUs huggingface dataset:
Mechanistic studies of the effects of the retinoid N‐(4‐hydroxyphenyl)retinamide on prostate cancer cell growth and apoptosis

To explore the mechanisms underlying the chemopreventive effects of the synthetic retinoid N‐(4‐hydroxyphenyl)retinamide (4‐HPR) in prostate cancer, we evaluated the anti‐proliferative and apoptosis‐inducing effects of 4‐HPR in the androgen‐sensitive human prostate cancer cell line LNCaP. 4‐HPR decreased the number of viable LNCaP cells (as measured by the 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide assay) in a dose‐dependent manner. Although 4‐HPR exerted a modest G1 cell‐cycle block (as determined by flow cytometry), its effect on reduced cell number appeared to result primarily from induction of apoptosis (as measured by an enzyme‐linked immunosorbent assay and flow‐cytometric assays). The mitogenic effects of R1881, a non‐metabolizable androgen that potently induces LNCaP cell proliferation, was completely blocked by greater than 0.5 μM 4‐HPR. Furthermore, increasing the R1881 concentration in the presence of 2.0 μM 4‐HPR increased apoptotic cell death. 4‐HPR decreased prostate‐specific antigen (PSA) protein levels in conditioned medium and decreased PSA mRNA expression. 4‐HPR also decreased the ratio of bcl‐2 to bax mRNA expression in LNCaP cells by approximately 45%, indicating that the apoptotic effects of 4‐HPR may be mediated, at least in part, by alterations in the bcl‐2/bax–regulated apoptotic pathway. N‐acetylcysteine (4 mM) completely blocked the anti‐proliferative and apoptotic‐inducing effects of 4‐HPR, suggesting that an oxidative mechanism may be involved. We concluded that (i) 4‐HPR exerts growth‐suppressive and apoptotic effects on LNCaP cells, (ii) 4‐HPR can interact with androgen to suppress proliferation and induce apoptosis, (iii) the apoptotic effects of 4‐HPR may be mediated in part by the bcl‐2/bax pathway, and (iv) a pro‐oxidant mechanism may contribute to the anti‐proliferative and apoptotic‐inducing effects of 4‐HPR. Mol. Carcinog. 24:160–168, 1999. © 1999 Wiley‐Liss, Inc.
Effects of task lighting on visual function in age‐related macular degeneration

The purpose was to investigate the effects of the spectral power distribution (SPD) and illuminance of task lighting on visual function in age‐related macular degeneration (ARMD) compared to normal healthy eyes. Twenty‐eight subjects with ARMD and 18 age‐matched normal subjects were studied. The effects on visual function were determined for four common task light sources: standard pearl coat incandescent (SP), daylight blue incandescent (DL), warm white fluorescent (WW) and cool white fluorescent (CW). Apart from a small, statistically significant improvement in contrast sensitivity with DL compared to SP lighting (0.5 dB, p = 0.01), there were no significant effects of SPD on other visual functions and no differences in the effects for subjects with ARMD and those with normal vision. Thus, for task lighting typically used in low vision rehabilitation, the SPD would seem to be of minimal clinical importance to visual function. However, increasing the task illuminance had a greater effect on visual function, in particular for subjects with ARMD (p < 0.01). For an increase in illuminance from 300 to 3000 lux, the mean increase in contrast sensitivity and near visual acuity was 1.5 dB and 0.13 log MAR, respectively. Although this effect is not large, we suggest that it is clinically relevant and supports the provision of additional task illuminance as an important part of low vision rehabilitation for patients with ARMD.
Oral Antimicrobial Therapy for Diabetic Foot Osteomyelitis

Background: Osteomyelitis in the foot of a diabetic individual is a common complication of peripheral neuropathy, peripheral vascular disease, and infection. Operative facilities and home intravenous antibiotic therapy programs may not be available in remote or rural communities. Limited data are available regarding the treatment results of oral antimicrobial therapy, with or without limited office debridement for diabetic foot osteomyelitis. Methods: This retrospective medical record review of 325 consecutive diabetic patients who were evaluated at a multidisciplinary foot clinic identified 94 (29%) patients with 117 episodes of osteomyelitis. The most common group of organisms isolated were aerobic gram-positive cocci, and the single most frequent organism was Staphylococcus aureus. A mean of 1.6 ± 0.8 (range 1 to 4) pathogens were recovered per episode of osteomyelitis. Therapy was guided by culture results. There were 93 episodes of osteomyelitis (79 patients) that were treated with a mean of 3 ± 1 oral antimicrobial agents (with or without an initial short course of intravenous antimicrobial agents) and had adequate followup to evaluate outcome of treatment; office treatment included bone debridement in 26 (28%) and toe amputation in nine (10%) of the 93 episodes (79 patients). Results: Of the 93 episodes treated with oral antimicrobial agents (with or without an initial short course of intravenous antimicrobial agents), 75 (80.5%) episodes were put into remission. Mean duration of oral antimicrobial therapy was 40 ± 30 weeks. Mean relapse-free followup duration was 50 ± 50 weeks. Conclusions: Diabetic foot osteomyelitis was effectively managed with oral antimicrobial therapy with or without limited office debridement in most patients. This regimen may be especially useful in communities where infectious disease specialists and operative resources are limited.
B-cell–independent sialylation of IgG

Significance Sialylation of Fc domain glycans on IgG is now a recognized functional switch between pro- and anti-inflammatory antibody function. Creation and analysis of a B-cell–specific knockout of β-galactoside α-2,6-sialyltransferase 1 (ST6Gal1) revealed that IgG sialylation occurs independently of the B-cell secretory pathway and within the bloodstream after IgG secretion. This finding supports a paradigm for exogenous posttranslational modification of glycoproteins that has profound functional significance for IgG functions modulated by the conserved N-linked glycan within the Fc domain. IgG carrying terminal α2,6-linked sialic acids added to conserved N-glycans within the Fc domain by the sialyltransferase ST6Gal1 accounts for the anti-inflammatory effects of large-dose i.v. Ig (IVIg) in autoimmunity. Here, B-cell–specific ablation of ST6Gal1 in mice revealed that IgG sialylation can occur in the extracellular environment of the bloodstream independently of the B-cell secretory pathway. We also discovered that secreted ST6Gal1 is produced by cells lining central veins in the liver and that IgG sialylation is powered by serum-localized nucleotide sugar donor CMP-sialic acid that is at least partially derived from degranulating platelets. Thus, antibody-secreting cells do not exclusively control the sialylation-dependent anti-inflammatory function of IgG. Rather, IgG sialylation can be regulated by the liver and platelets through the corresponding release of enzyme and sugar donor into the cardiovascular circulation.
Management of upper extremity bone metastases

Metastatic bone disease represents a significant burden of disease. Metastatic disease can seed in any bone of the body, but one of the most common long bones affected is the humerus. Although painful and often disabling, metastatic bone disease of the upper extremity often can be treated more conservatively than the lower extremity because of lower weight-bearing demands. However, the surgical management of upper extremity metastatic bone disease is an evolving field, and recent clinical studies have demonstrated several key principles. Intramedullary nailing and whole bone irradiation may be an optimal combination for prophylactic fixation. The addition of polymethyl methacrylate cement adds immediate stabilization to internal fixation and decreases postoperative pain. Plate and screw fixation can be used in lesions that cannot be treated with intramedullary nailing, but caution is necessary to avoid complications related to surgical technique. Finally, periarticular and intraarticular lesions may be managed with a hemi- or total-joint prosthesis for both the shoulder and elbow to provide the maximal functional outcome. Surgical intervention together with appropriate adjunctive therapies can decrease patient-important pain and skeletal-related events while improving quality of life in patients living with metastatic bone disease of the upper extremity.
A comparison of recalled date of last menstrual period with prospectively recorded dates.

BACKGROUND Women are often asked to recall the first day of their last menstrual period (LMP date) in a clinic setting (i.e., pregnancy dating, x-rays). There are no data supporting the validity of these reports. METHODS Using data from a group of 385 women ages 35-49 from a larger cohort study in the Washington, DC, area, we constructed menstrual segments from a prospective daily menstrual record. We then compared the first day of a menstrual segment to a woman's recalled LMP date at a subsequent study-related clinic appointment to assess the accuracy of recall. RESULTS More than half of the women (56%) accurately recalled their LMP date; 74% were within 1 day, and 81% were within 2 days. Women tended to underreport (25%) the length of time since their last menstrual period rather than overreport the length of time (19%). Recall accuracy did not vary significantly with education or by whether the woman usually recorded her menstrual cycle when not in the study. As one might expect, women with a shorter recall duration tended to report more accurately. DISCUSSION Women appear to recall their LMP dates fairly accurately, but inaccurate recall was not random. When length of recall was 3 weeks or longer, women tended to overestimate the time since LMP. This suggests that gestational age calculated from LMP date will tend to be overestimated. Most women can recall the date of their LMP reasonably well regardless of their education and whether they usually record their LMP dates.
The resurrection of ribonucleases from mammals: from ecology to medicine

The family of proteins related to bovine pancreatic ribonuclease A (RNase A) provided the first biomolecular system to be analyzed using experimental paleogenetics. This protein family was chosen in 1979, as it was one of only three families of protein sequences that were sufficiently well represented in the then modest database for which one might consider doing experimental resurrections. Other families that were also considered included cytochrome c, which had been developed as a paradigm for molecular evolution by Margoliash (1963, 1964), and hemoglobin, which was studied as a model for biomolecular adaptation (Riggs, 1959; Bonaventura et al., 1974). Cytochromes are substrates for cytochrome oxidases, and it was not considered possible to resurrect both ancestral cytochromes and their ancient oxidases. Hemoglobins are complicated to express, a problem solved only later. This left the RNases. Fortunately, Jaap Beintema and his colleagues in Groningen had done an excellent job of sequencing (at the level of the protein) ribonucleases from a wide range of ruminants and closely related nonruminant mammals (Beintema and Gruber, 1967, 1973; Gaastra et al., 1974; Groen et al., 1975; Welling et al., 1975; Emmens et al., 1976; Kuper and Beintema, 1976; Muskiet et al., 1976; Vandenberg et al., 1976; Vandijk et al., 1976; Welling et al., 1976; Gaastra et al., 1978; Beintema et al., 1979, 1984, 1985; Jekel et al., 1979; Lenstra and Beintema, 1979; Beintema and Martena, 1982; Breukelman et al., 2001). Done before the so-called age of the genome, this work exploited classical Edman degradation of peptide fragments derived by selective cleavage of the protein. Such work required substantial amounts of protein, making convenient the large amount of RNase found in the digestive tracts of oxen and their immediate relatives. Beintema had also inferred the sequences of the ancestral proteins throughout the recent history of the digestive enzymes, using parsimony tools that adapted the ideas that Margaret Dayhoff had laid out (Dayhoff et al., 1978).
ywfE in Bacillus subtilis Codes for a Novel Enzyme, l-Amino Acid Ligase

ABSTRACT The ATP-dependent carboxylate-amine/thiol ligase superfamily is known to contain enzymes catalyzing the formation of various types of peptide, such as d-alanyl-d-alanine, polyglutamate, and γ-peptide, but, curiously, no enzyme synthesizing α-dipeptides of l-amino acids is known. We attempted to find such an enzyme. By in silico screening based on the consensus sequence of the superfamily followed by an in vitro assay with purified enzyme to avoid the degradation of the peptide(s) synthesized, ywfE of Bacillus subtilis was found to code for the activity forming l-alanyl-l-glutamine from l-alanine and l-glutamine with hydrolysis of ATP to ADP. No AMP was formed, supporting the idea that the enzyme belongs to the superfamily. Surprisingly, the enzyme accepted a wide variety of l-amino acids. Among 231 combinations of l-amino acids tested, reaction products were obtained for 111 combinations and 44 kinds of α-dipeptides were confirmed by high-performance liquid chromatography analyses, while no tripeptide or longer peptide was detected and the d-amino acids were inert. From these results, we propose that ywfE encodes a new member of the superfamily, l-amino acid ligase.
Risk factors for primary postpartum hemorrhage in Bhumibol Adulyadej Hospital.

BACKGROUND Postpartum hemorrhage remains one of the main causes of maternal morbidity and mortality in both developed and developing countries. Hemorrhages account for 28%of all direct maternal deaths and remain the most common cause of direct maternal deaths worldwide. OBJECTIVE To study the incidence and risk factors for postpartum hemorrhage (PPH) in Bhunibol Adulyadej Hospital. MATERIAL AND METHOD Retrospective cohort study of 19,429 patients who gave birth between P' January 2004 and 31st December 2007 at Bhumibol Adulyadej Hospital. One thousand five hundred and thirty women were enrolled in the present study, three hundred and eighty five women had postpartum hemorrhage and one thousand one hundred and forty-five had no postpartum hemorrhage. The present study analyzed one postpartum hemorrhage woman compared to three women who gave birth in nearly the same period and had no postpartum hemorrhage both vaginal deliveries and cesarean section. RESULTS The PPH rate in Bhumibol Adulyadej Hospital was 1.98%. Maternal age, height and fetal birth weight were not different between the PPH group and no PPH group. The strongest risk factors for postpartum hemorrhage in the present study were prolonged 3rd stage of labor, retained placenta, lacerations of birth passage, and placenta previa. CONCLUSION The strongest risk factors for postpartum hemorrhage in the present study were prolonged 3rd stage of labor, retained placenta, lacerations of birth passage, and placenta previa.
Munc18-1 Protein Molecules Move between Membrane Molecular Depots Distinct from Vesicle Docking Sites*

Background: The molecular architecture of the secretory machinery is undefined. Results: Munc18 moves between membrane depots distinct from vesicle docking sites. Conclusion: Munc18 is not a docking factor, and the membrane environment is likely to determine fusion likelihood. Significance: It is now possible to test directly previous models of the molecular mechanisms of secretion. Four evolutionarily conserved proteins are required for mammalian regulated exocytosis: three SNARE proteins, syntaxin, SNAP-25, and synaptobrevin, and the SM protein, Munc18-1. Here, using single-molecule imaging, we measured the spatial distribution of large cohorts of single Munc18-1 molecules correlated with the positions of single secretory vesicles in a functionally rescued Munc18-1-null cellular model. Munc18-1 molecules were nonrandomly distributed across the plasma membrane in a manner not directed by mode of interaction with syntaxin1, with a small mean number of molecules observed to reside under membrane resident vesicles. Surprisingly, we found that the majority of vesicles in fully secretion-competent cells had no Munc18-1 associated within distances relevant to plasma membrane-vesicle SNARE interactions. Live cell imaging of Munc18-1 molecule dynamics revealed that the density of Munc18-1 molecules at the plasma membrane anticorrelated with molecular speed, with single Munc18-1 molecules displaying directed motion between membrane hotspots enriched in syntaxin1a. Our findings demonstrate that Munc18-1 molecules move between membrane depots distinct from vesicle morphological docking sites.
A Novel Enzyme-Linked Immunosorbent Assay for Screening HIV-1 Fusion Inhibitors Targeting HIV-1 Gp41 Core Structure

The gp41 subunit of the human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein mediates the fusion of viral and host cell membranes. As the HIV-1 enters the host cells, the 2 helical regions, HR1 and HR2, in the ectodomain of gp41 can form a 6-helix bundle, which brings the viral and target cell membranes to close proximity and serves as an attractive target for developing HIV-1 fusion inhibitors. Now, there are several cell- and molecule-based assays to identify potential HIV-1 fusion inhibitors targeting gp41. However, these assays cannot be used universally because they are time-consuming, inconvenient, and expensive. In the present study, the authors expressed and purified GST-HR121 and C43-30a proteins that were derived from the HIV-1 gp41 ectodomain region. GST-HR121 has a function similar to the HR1 peptide of gp41, whereas C43-30a is an HR2-derived peptide that added 50 amino acid residues (aa) in the N-terminal of C43. Further research found they could interact with each other, and a potential HIV-1 fusion inhibitor could inhibit this interaction. On the basis of this fact, a novel, rapid, and economic enzyme-linked immunosorbent assay was established, which can be developed for high-throughput screening of HIV-1 fusion inhibitors.
Efficient mode-matching based on closed form integrals of Pridmore-Brown modes

A new mode-matching method is developed for acoustic modes in axially sectioned lined ducts with parallel, but otherwise arbitrary mean flow. The method is evaluated in detail for a circularly symmetric configuration (where the mean flow depends only on the radial coordinate), with the so-called Pridmore-Brown modes, satisfying the radial Pridmore-Brown equation. Classically, the matching of the modal representations at the interfaces between the sections is based on continuity of pressure and velocity in combination with projection to a suitable but unrelated set of test functions by means of a standard integral inner product. The alternative proposed here uses essentially the same Pridmore-Brown modes, but instead of the standard inner product it applies a particular bilinear form that can be evaluated in closed form. Apart from numerical efficiency, this approach features also a higher accuracy because it avoids the inherently inaccurate numerical quadrature of oscillating functions. The results are co.
Musculoskeletal response to exercise is greatest in women with low initial values.

INTRODUCTION The "initial values" principle of exercise training states those with the lowest initial values of a physiologic system have the greatest capacity for improvement in response to training. We sought to determine whether initial values predicted the musculoskeletal response to training in premenopausal women (N = 31) who participated in a 1-yr program of resistance and jump training designed to improve physical indices of fracture risk. Significant improvements in trochanteric bone mineral density (BMD), hip abductor strength, power, and postural stability occurred in response to training. METHODS To determine the predictive power of initial values, we performed separate stepwise regression analyses for each variable including the following dependent variables: age, initial value, highest weight lifted during training, and total number of exercise sessions attended. RESULTS In each case, the initial value was the most significant predictor of percent change in response to training. Initial values explained 15-29% of the variance in the magnitude of the training response. For each unit lower BMD of the greater trochanter (0.01 g.cm-2), the training response was 12% greater. For each unit decrease in initial strength (1 N.m), power (1 W), and stability (1 SI unit), the training response was 1.0%, 0.2%, and 8.0% greater, respectively. When categorized by quartile of initial values, women in the lowest quartile had two- to fivefold greater improvements in musculoskeletal measures than those in the upper quartile. CONCLUSION Women who began training with the lowest initial values had the greatest improvements in hip BMD, hip abductor strength, leg power, and postural stability. These results support the training principle of initial values and suggest that this training program may be most successful in premenopausal women with lower values of musculoskeletal indices of fracture risk.
Sediment cascades : an integrated approach

Contributors. Preface. 1 Sediment Cascades in the Environment: An Integrated Approach(Timothy P. Burt, Durham University, UK and Robert J. Allison,University of Sussex, UK). 2 Mountains and Montane Channels (Michael Church, Universityof British Columbia, Canada). 3 Landslides and Rockfalls (Nick J. Rosser, DurhamUniversity, UK). 4 Sediment Cascades in Active Landscapes (Tim R. H. Davies,University of Canterbury, New Zealand and Oliver Korup, SwissFederal Institute for Forest, Snow and Landscape Research). 5 Pacific Rim Steeplands (Basil Gomez, Indiana StateUniversity, USA Michael J. Page, GNS Science, New Zealand Noel A.Trustrum, GNS Science, New Zealand). 6 Local Buffers to the Sediment Cascade: Debris Cones andAlluvial Fans (Adrian M. Harvey, University of Liverpool,UK). 7 Overland Flow and Soil Erosion (Louise J. Bracken, DurhamUniversity, UK). 8 Erosional Processes and Sediment Transport in Upland Mires(Martin G. Evans, University of Manchester, UK and Timothy P.Burt, Durham University, UK). 9 Gravel-Bed Rivers (Michael Church, University of BritishColumbia, Canada). 10 The Fine-Sediment Cascade (Pamela S. Naden, Centre forEcology and Hydrology, UK). 11 Streams, Valleys and Floodplains in the Sediment Cascade(Stanley W. Trimble, University of California at Los Angeles,USA). 12 Lakes and Reservoirs in the Sediment Cascade (Ian D.L.Foster, University of Westminster, UK). 13 Continental-Scale River Basins (David L. Higgitt, NationalUniversity of Singapore). 14 Estuaries (Tom Spencer, Cambridge University, UK andDenise J. Reed, University of New Orleans, USA). 15 The Continental Shelf and Continental Slope (David N.Petley, Durham University, UK). Index.