Miracle-dz/UniFAR-FTUs huggingface dataset:
Mechanism of action of ozone on the human lung.

Fourteen healthy normal volunteers were randomly exposed to air and 0.5 ppm of ozone (O3) in a controlled exposure chamber for a 2-h period during which 15 min of treadmill exercise sufficient to produce a ventilation of approximately 40 l/min was alternated with 15-min rest periods. Before testing an esophageal balloon was inserted, and lung volumes, flow rates, maximal inspiratory (at residual volume and functional residual capacity) and expiratory (at total lung capacity and functional residual capacity) mouth pressures, and pulmonary mechanics (static and dynamic compliance and airway resistance) were measured before and immediately after the exposure period. After the postexposure measurements had been completed, the subjects inhaled an aerosol of 20% lidocaine until response to citric acid aerosol inhalation was abolished. All of the measurements were immediately repeated. We found that the O3 exposure 1) induced a significant mean decrement of 17.8% in vital capacity (this change was the result of a marked fall in inspiratory capacity without significant increase in residual volume), 2) significantly increased mean airway resistance and specific airway resistance but did not change dynamic or static pulmonary compliance or viscous or elastic work, 3) significantly reduced maximal transpulmonary pressure (by 19%) but produced no changes in inspiratory or expiratory maximal mouth pressures, and 4) significantly increased respiratory rate (in 5 subjects by more than 6 breaths/min) and decreased tidal volume. (ABSTRACT TRUNCATED AT 250 WORDS)
Constitutive Activation of the β2 Adrenergic Receptor Alters the Orientation of Its Sixth Membrane-spanning Segment*

The binding site of the β2adrenergic receptor, like that of other homologous G-protein-coupled receptors, is contained within a water-accessible crevice formed among its seven membrane-spanning segments. Methanethiosulfonate ethylammonium (MTSEA), a charged, hydrophilic, lipophobic, sulfhydryl-specific reagent, had no effect on the binding of agonist or antagonist to wild-type β2 receptor expressed in HEK 293 cells. This suggested that no endogenous cysteines are accessible in the binding site crevice. In contrast, in a constitutively active β2 receptor, MTSEA significantly inhibited antagonist binding, and isoproterenol slowed the rate of reaction of MTSEA. This implies that at least one endogenous cysteine becomes accessible in the binding site crevice of the constitutively active β2receptor. Cys-285, in the sixth membrane-spanning segment, is responsible for the inhibitory effect of MTSEA on ligand binding to the constitutively active mutant. The acquired accessibility of Cys-285 in the constitutively active mutant may result from a rotation and/or tilting of the sixth membrane-spanning segment associated with activation of the receptor. This rearrangement could bring Cys-285 to the margin of the binding site crevice where it becomes accessible to MTSEA.
Long-term outcome and growth rate of subtotally resected petroclival meningiomas: experience with 38 cases.

OBJECTIVE To evaluate the long-term outcome of a subtotally resected residual tumor and to assess its growth rate, we analyzed the records of 38 patients with residual petroclival meningioma. METHODS Clinical records and radiological findings of 38 cases of petroclival meningioma that were diagnosed and subtotally resected at Seoul National University Hospital between 1981 and 1997 were carefully reviewed. Follow-up imaging studies were reviewed, and Karnofsky performance scale scores at the last follow-up were recorded. The duration of follow-up ranged from 6 to 141 months (mean, 47.5 mo; median, 30 mo). Tumor progression and progression-free survival rates were assessed. The growth rate of a residual tumor was evaluated by measuring the equivalent diameter and the tumor volume serially; the tumor doubling time was calculated, and the predictive factors for determining the growth pattern in residual tumors and the prognosis were analyzed. RESULTS In 33 (87%) of the 38 patients, Karnofsky performance scale scores at the last follow-up were 80 or above. The median progression-free survival time among patients with subtotally resected tumors was 66 months, and the 5-year progression-free survival rate was 60%. The growth rate of residual tumors was low (volume increase, 4.94 cc/yr; diameter increase, 0.37 cm/yr). The mean tumor doubling time was 8 years. Although there were no significant predictive factors, age and extent of tumor resection seemed to influence the progression-free survival rate. Significant factors affecting the growth rate were age and occurrence of menopause. CONCLUSION Subtotal resection with or without radiation or radiosurgery should be considered as a suitable treatment option for patients with petroclival meningiomas, especially the elderly, because the growth rate of residual tumors is low.
Diaspora, memory and identity : a search for home

Acknowledgments Introduction VIJAY AGNEW Part 1: Diaspora and Memory * Language Matters VIJAY AGNEW * Memories of Internment: Narrating Japanese-Canadian Women's Life Stories PAMELA SUGIMAN * Wounding Events and the Limits of Autobiography MARLENE KADAR Part 2: History and Identity * Memoirs of a Sirdar's Daughter in Canada: Hybridity and Writing Home RISHMA DUNLOP * Ghosts and Shadows: Memory and Resilience among the Eritrean Diaspora ATSUKO MATSUOKA and JOHN SORENSON * A Diasporic Bounty: Cultural History and Heritage VIJAY AGNEW Part 3: Community and Home * Diaspora and Cultural Memory ANH HUA * Gendered Nostalgia: The Experiences of New Chinese Skilled Immigrants in Canada IZUMI SAKAMOTO and YANQIU RACHEL ZHOU * 'I Feel Like a Trini': Narrative of a Generation-and-a-Half Canadian 230 CARL E. JAMES * The 'Muslim' Diaspora and Research on Gender: Promises and Perils HAIDEH MOGHISSI * The Quest for the Soul in the Diaspora VIJAY AGNEW Afterword SUSAN E. BABBITT Contributors
Plasma concentrations of sVCAM‐1 and severity of dengue infections

Adhesion molecules are essential for the immune response. They are involved in the regulation of cell‐to‐cell contact, thereby enabling leukocytes to communicate. Circulating forms of adhesion molecules are found in the serum of healthy individuals. Raised levels have been associated with disease severity in HCV and other infections and thus appear to be good markers of endothelial damage. The levels of soluble Vascular Cell Adhesion Molecule‐1 (sVCAM‐1) and of sP and sL‐selectin in the plasma of children hospitalised for dengue in French Polynesia were monitored. Studies from the 1996/1997 dengue‐2 outbreak, showed that levels of sVCAM‐1 increase steadily during the febrile period, peak on day 7, and then decline relatively rapidly. Disregarding the time frame within the febrile period, sVCAM‐1 levels were always higher compared to controls. There was a significant association between sVCAM‐1 levels and dengue haemorrhagic fever, a severe manifestation of dengue virus infection characterised by plasma leakage. No association was apparent between sVCAM‐1 levels and primary vs. secondary dengue virus infections. Levels of sP‐selectin and sL‐selectin were significantly higher in primary compared with secondary infection but were not different in patients presenting with plasma leakage. Lastly, sVCAM‐1 levels were significantly higher in an outbreak of severe disease in 1989/1990 (dengue‐3) when compared to a non‐severe outbreak in 1988/1989 (dengue‐1) and a mild outbreak in 1996/1997 (dengue‐2). The results suggested that levels of sVCAM‐1 production might prove to be a useful marker in the management of severe dengue. J. Med. Virol. 65:97–104, 2001. © 2001 Wiley‐Liss, Inc.
Stimulation of Ebola virus production from persistent infection through activation of the Ras/MAPK pathway

Human infections with Ebola virus (EBOV) result in a deadly viral disease known as Ebola hemorrhagic fever. Up to 90% of infected patients die, and there is no available treatment or vaccine. The sporadic human outbreaks are believed to result when EBOV “jumps” from an infected animal to a person and is subsequently transmitted between persons by direct contact with infected blood or body fluids. This study was undertaken to investigate the mechanism by which EBOV can persistently infect and then escape from model cell and animal reservoir systems. We report a model system in which infection of mouse and bat cell lines with EBOV leads to persistence, which can be broken with low levels of lipopolysaccharide or phorbol-12-myristate-13-acetate (PMA). This reactivation depends on the Ras/MAPK pathway through inhibition of RNA-dependent protein kinase and eukaryotic initiation factor 2α phosphorylation and occurs at the level of protein synthesis. EBOV also can be evoked from mice 7 days after infection by PMA treatment, indicating that a similar mechanism occurs in vivo. Our findings suggest that EBOV may persist in nature through subclinical infection of a reservoir species, such as bats, and that appropriate physiological stimulation may result in increased replication and transmission to new hosts. Identification of a presumptive mechanism responsible for EBOV emergence from its reservoir underscores the “hit-and-run” nature of the initiation of human and/or nonhuman primate EBOV outbreaks and may provide insight into possible countermeasures to interfere with transmission.
An eco-friendly Cu-Zn wetting layer for highly reliable solder joints

We successfully fabricated an eco-friendly Cu-Zn wetting layer for Sn-Ag-Cu (SAC) solders by electroplating in a cyanide-free solution. The reliabilities of solder joints formed on the Cu-Zn solder wetting layer were evaluated through the drop impact test and thermal cycling (T/C) test. First, board-level drop impact test was performed with the SAC solder joints formed on electroplated Cu or Cu-Zn layers. Drop test samples were fabricated by connecting SAC solders with Cu or Cu-20 wt% Zn wetting layer formed on printed circuit boards (PCBs). Cu-20 wt% Zn layers were electroplated in cyanide and cyanide-free solutions. Drop impact resistance of Cu-Zn/SAC/Cu-Zn solder joints was superior to that of Cu/SAC/Cu solder joints. Next, for T/C test, Cu pillar bumps with Sn-2.5 wt% Ag capping layers were fabricated on Si chip and joined with Cu or Cu-Zn layer on PCB substrate by flip chip bonding. T/C test was carried out between -55°C and 125°C up to 3000 cycles. The flip chip joints formed on either Cu or Cu-Zn layer showed excellent T/C reliability in the underfilled condition. The failure was not observed in both samples after 3000 cycles. When underfill was not applied in the flip chip joints, Cu-Zn samples exhibited better results than Cu samples even though both samples had short thermal fatigue life. The improvement of reliability in Cu-Zn samples was ascribed to the beneficial effect of Zn. Our results implied that electroplating of Cu-Zn layers in a cyanide-free solution was successful and the reliability of solder joints can be enhanced by applying a Cu-Zn solder wetting layer.
Comparison of Autologous Serum Eye Drops with Different Diluents

Purpose: To compare the effect of autologous serum eye drops with different diluents in patients with dry eyes and persistent epithelial defects. Methods: Patients of Sjögren’s syndrome (Group I), non-Sjögren’s syndrome (group II) with dry eye, and persistent epithelial defects (Group III) were included. The eyes of each group were randomly treated with one of the following autologous serum eye drops: 100% serum (AS100), 50% serum with normal saline (AS50NS); 50% serum with sodium hyaluronate (AS50HA); or 50% serum with ceftazidime (AS50CEF). The differences in dry eye symptoms, Schirmer test I, tear break-up time (TBUT), corneal staining, and speed in epithelial healing were studied. Results: In Group I, AS100 showed fewer symptoms than AS50NS, AS50HA and AS50CEF (all p < 0.01). AS100 showed significantly better effect than AS50NS, AS50HA and AS50CEF in decreasing corneal staining at the time point of 12-week post-treatment (p = 0.041, p < 0.001 and p < 0.001, respectively). In Group II, AS100 was more effective than AS50CEF in decreasing symptoms and decreasing corneal staining (all p < 0.05). There was no significant difference in symptom and corneal staining between AS100 and AS50NS. In Group III, AS100 was the most effective in achieving quick epithelial closure. Conclusion: In the eyes with Sjögren syndrome and persistent epithelial defects, AS100 was the most effective in decreasing symptoms, corneal epitheliopathy and promoting fast closure of wound. In the eyes with non-Sjögren syndrome, AS100 and AS50NS have similar effects in decreasing symptoms and corneal epitheliopathy.
CD47–signal regulatory protein-α (SIRPα) interactions form a barrier for antibody-mediated tumor cell destruction

Monoclonal antibodies are among the most promising therapeutic agents for treating cancer. Therapeutic cancer antibodies bind to tumor cells, turning them into targets for immune-mediated destruction. We show here that this antibody-mediated killing of tumor cells is limited by a mechanism involving the interaction between tumor cell-expressed CD47 and the inhibitory receptor signal regulatory protein-α (SIRPα) on myeloid cells. Mice that lack the SIRPα cytoplasmic tail, and hence its inhibitory signaling, display increased antibody-mediated elimination of melanoma cells in vivo. Moreover, interference with CD47–SIRPα interactions by CD47 knockdown or by antagonistic antibodies against CD47 or SIRPα significantly enhances the in vitro killing of trastuzumab-opsonized Her2/Neu-positive breast cancer cells by phagocytes. Finally, the response to trastuzumab therapy in breast cancer patients appears correlated to cancer cell CD47 expression. These findings demonstrate that CD47–SIRPα interactions participate in a homeostatic mechanism that restricts antibody-mediated killing of tumor cells. This provides a rational basis for targeting CD47–SIRPα interactions, using for instance the antagonistic antibodies against human SIRPα described herein, to potentiate the clinical effects of cancer therapeutic antibodies.
Prediction of missed proteolytic cleavages for the selection of surrogate peptides for quantitative proteomics.

Quantitative proteomics experiments are usually performed using proteolytic peptides as surrogates for their parent proteins, inferring protein amounts from peptide-level quantitation. This process is frequently dependent on complete digestion of the parent protein to its limit peptides so that their signal is truly representative. Unfortunately, proteolysis is often incomplete, and missed cleavage peptides are frequently produced that are unlikely to be optimal surrogates for quantitation, particularly for label-mediated approaches seeking to derive absolute values. We have generated a predictive computational tool that is able to predict which candidate proteolytic peptide bonds are likely to be missed by the standard enzyme trypsin. Our cross-validated prediction tool uses support vector machines and achieves high accuracy in excess of 0.94 precision (PPV), with attendant high sensitivity of 0.79, across multiple proteomes. We believe this is a useful tool for selecting candidate quantotypic peptides, seeking to minimize likely loss owing to missed cleavage, which will be a boon for quantitative proteomic pipelines as well as other areas of proteomics. Our results are discussed in the context of recent results examining the kinetics of missed cleavages in proteomic digestion protocols, and show agreement with observed experimental trends. The software has been made available at http://king.smith. man.ac. uk/mcpred .
Implementation of a Service-learning Module in Medical Microbiology and Cell Biology Classes at an Undergraduate Liberal Arts University

Here we discuss the implementation of a service-learning module in two upper-division biology classes, Medical Microbiology and Cell Biology. This exciting hands-on learning experience provided our students with an opportunity to extend their learning of in-class topics to a real-life scenario. Students were required to volunteer their time (a minimum of 10 hours in a semester) at an under-served clinic in Houston, Texas. As they interacted with the personnel at the clinic, they were asked to identify the most prevalent disease (infectious for Medical Microbiology, and cellular-based for Cell) seen at the clinic and, working in groups, come up with educational material in the form of a display or brochure to be distributed to patients. The material was meant to educate patients about the disease in general terms, as well as how to recognize (symptoms), prevent and treat it. Students were required to keep a reflective journal in the form of a blog throughout the semester, and present their final materials to the class orally. Students were surveyed about their opinion of the experience at the end of the semester. The vast majority of student participants felt that the project was a positive experience and that it helped them develop additional skills beyond what they learn in the classroom and understand how lecture topics relate to every day life.
An Unusual Peptide Deformylase Features in the Human Mitochondrial N-terminal Methionine Excision Pathway*

Dedicated machinery for N-terminal methionine excision (NME) was recently identified in plant organelles and shown to be essential in plastids. We report here the existence of mitochondrial NME in mammals, as shown by the identification of cDNAs encoding specific peptide deformylases (PDFs) and new methionine aminopeptidases (MAP1D). We cloned the two full-length human cDNAs and showed that the N-terminal domains of the encoded enzymes were specifically involved in targeting to mitochondria. In contrast to mitochondrial MAP1D, the human PDF sequence differed from that of known PDFs in several key features. We characterized the human PDF fully in vivo and in vitro. Comparison of the processed human enzyme with the plant mitochondrial PDF1A, to which it is phylogenetically related, showed that the human enzyme had an extra N-terminal domain involved in both mitochondrial targeting and enzyme stability. Mammalian PDFs also display non-random substitutions in the conserved motifs important for activity. Human PDF site-directed mutagenesis variants were studied and compared with the corresponding plant PDF1A variants. We found that amino acid substitutions in human PDF specifically altered its catalytic site, resulting in an enzyme intermediate between bacterial PDF1Bs and plant PDF1As. Because (i) human PDF was found to be active both in vitro and in vivo, (ii) the entire machinery is conserved and expressed in most animals, (iii) the mitochondrial genome expresses substrates for these enzymes, and (iv) mRNA synthesis is regulated, we conclude that animal mitochondria have a functional NME machinery that can be regulated.
Significance of Increased Apoptosis and Bax Expression in Human Small Intestinal Adenocarcinoma

Human small intestine accounts for 75% of the gastrointestinal (GI) length but for only 1–5% of GI tumors. The reason remains as yet unclearly understood. Our study was designed to examine whether increased apoptosis and expression of related genes/proteins, especially those of the Bcl-2 family, contribute to this difference. For this purpose, 77 samples from patients were examined by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling and immunohistochemistry, including 40 cases from normal small intestine (jejunum), 7 cases from jejunum and ileum adenocarcinomas, and 30 cases from normal colon. The results showed that a significantly higher level of enterocyte apoptosis was observed in normal small intestine compared with small intestinal adenocarcinomas and normal colon (median of apoptotic index, 15.2% vs 0.1% and 1.6%, p<0.01). A similar pattern was observed for Bax (expression-positive, 77.5% vs 28.6% and 53.3%, p<0.05) but not for Bcl-2 (42.5% vs 42.9% and 46.7%, p>0.05) or Bax/Bcl-2 ratio (percent of samples having a ratio ≥1, 45.0% vs 14.3% and 36.7%, p>0.05). In conclusion, increased apoptosis and expression of Bax, not Bcl-2 or the Bax/Bcl-2 ratio, may play some role in the relatively lower incidence of human small intestinal carcinomas. However, more studies are required for a better understanding of these changes.
Improved Survival With an Intact DNA Mismatch Repair System in Endometrial Cancer

OBJECTIVE: To correlate survival and surgical-pathologic factors with DNA mismatch repair status in patients with endometrial cancer. METHODS: Specimens from 336 patients with endometrial cancer were used to create a tissue microarray. Immunohistochemistry with antibodies against the mismatch repair genes MLH1, MSH2, MSH6, and PMS2 were used to stain the tissue microarray. Clinical, pathologic, and survival data were collected and correlated with the immunohistochemistry results. RESULTS: Mismatch repair deficiency was seen in 29% (84 of 294) of cases. Correlation was noted between lack of expression of MLH1 and an increased risk for lymphvascular space involvement (32% versus 21%, P=.05) and cervical involvement (26% versus 14%, P=.02). Lack of expression of either MLH1 or MSH2 was associated with thinner patients (85% had a body mass index less than 40 versus 73% of patients with normal expression, P=.02), as well as with the absence of a history of previous primary malignancy (0 verus 13 cases [4%], P=.023). The estimated disease-free survival is 88%; despite a small number of recurrences, there was a nonsignificant improvement in disease-free survival in tumors with an intact mismatch repair system (P=.1). Significantly improved disease-free survival was seen in patients with normal MLH1 and MSH2 expression compared with those with abnormal expression (92% versus 81%, P=.035). CONCLUSION: Defects in DNA mismatch repair in endometrial cancer is correlated with negative prognostic factors and worse progression-free survival (without a difference in overall survival) compared with tumors with an intact mismatch repair system. LEVEL OF EVIDENCE: II-3
Inhibitory Effects against Pasture Weeds in Brazilian Amazonia of Natural Products from the Marine Brown Alga Dictyota menstrualis

Fractions of the acetone extract and a mixture of two diterpenes from the marine brown alga Dictyota menstrualis were prepared with the aim of identifying potential effects on the germination of seeds and on elongation of the radicle and hypocotyl of the weeds Mimosa pudica and Senna obtusifolia. The bioassay on seed germination was performed in controlled conditions of 25°C temperature and a 12 hour photoperiod, while the one concerning radicle and hypocotyl elongation was performed at the same temperature, though adopting a photoperiod of 24 hours. The results varied according to the receptor species, the fraction utilized, and its concentration. TLC analysis of the fractions and comparison with isolated products indicated that the diterpenes pachydictyol A and isopachydictyol A were the most abundant compounds in fraction HE, whereas the diterpene 6-hydroxy-dichotomano-2, 13-diene-16, 17-dial (3) was the most abundant compound in fractions DC and EA. Analysis of less polar fractions (in n-hexane, dichloromethane and ethyl acetate) revealed values of less than 30% inhibition. On the other hand, the ethanol/water fraction was the most active in all instances. The biological activity of these fractions must be due to the presence of known diterpenes and/or sulfated polysaccharides isolated in earlier studies.