Miracle-dz/UniFAR-FTUs huggingface dataset:
Role of Glycosylation and Disulfide Bond Formation in the β Subunit in the Folding and Functional Expression of Na,K-ATPase*

Initial folding is a prerequisite for subunit assembly in oligomeric proteins. In this study, we have compared the role of co-translational modifications in the acquisition of an assembly-competent conformation of the β subunit, the assembly of which is required for the structural and functional maturation of the catalytic Na,K-ATPase α subunit. Cysteine or asparagine residues implicated in disulfide bond formation or N-glycosylation, respectively, in the Xenopus β1 subunit were eliminated by site-directed mutagenesis, and the assembly efficiency of the mutants and the functional expression of Na+,K+ pumps were studied after expression in Xenopus oocytes. Our results show that lack of each one of the two most C-terminal disulfide bonds indeed permits short term but completely abolishes long term assembly of the β subunit. On the other hand, lack of the most N-terminal disulfide bonds allows the expression of a small number of functional Na+,K+ pumps at the cell surface. Elimination of all three but not of one or two glycosylation sites produces β subunits that remain stably expressed in the endoplasmic reticulum, in association with binding protein but not as irreversible aggregates. The assembly efficiency of nonglycosylated β subunits is decreased but a reduced number of functional Na+,K+ pumps is expressed at the cell surface. The lack of sugars does not influence the apparent K+ or ouabain affinity of the Na+,K+ pumps. Thus, these data show that disulfide bond formation and N-glycosylation may play important but qualitatively distinct roles in the initial folding of oligomeric protein subunits. Moreover, the results suggest that an endoplasmic reticulum degradation pathway exists, which is glycosylation-dependent.
Intraocular Lens Implantation in Myopic Eyes

Purpose. To assess the results of posterior chamber lens implantation in myopic eyes with cataract. Methods. Retrospective study of postoperative results ranging from 4 to 89 months (mean 35 months) in 54 myopic patients (62 eyes with axial length of 26 mm or more) who had undergone PC IOL implantation in the Department of Ophthalmology, Medical Academy of Bydgoszcz, Poland. Outcome measure. Best corrected distance and near visual acuity, operative complications, early and late postoperative complications. Results. in 95% of patients with eye length 26–28 mm visual acuity of 0.5 or more was achieved. The mean postoperative spherical equivalent was -0.8 D. Posterior capsule opacification which required Nd:YAG capsulotomy developed in 19% of eyes, on average after one year of follow-up. No complications such as retinal detachment, glaucoma or corneal dystrophy were observed. Conclusions. PC IOL implantation in myopic eyes with cataract appears to be an efficacious, satisfactory and safe procedure.
Testing the current paradigm for space weather prediction with heliospheric imagers

Predictions of the arrival of four coronal mass ejections (CMEs) in geospace are produced through use of three CME geometric models combined with CME drag modeling, constraining these models with the available Coronagraph and Heliospheric Imager data. The efficacy of these predications is assessed by comparison with the Space Weather Prediction Center (SWPC) numerical MHD forecasts of these same events. It is found that such a prediction technique cannot outperform the standard SWPC forecast at a statistically meaningful level. We test the Harmonic Mean, Self‐Similar Expansion, and Ellipse Evolution geometric models, and find that, for these events at least, the differences between the models are smaller than the observational errors. We present a new method of characterizing CME fronts in the Heliospheric Imager field of view, utilizing the analysis of citizen scientists working with the Solar Stormwatch project, and we demonstrate that this provides a more accurate representation of the CME front than is obtained by experts analyzing elongation time maps for the studied events. Comparison of the CME kinematics estimated independently from the STEREO‐A and STEREO‐B Heliospheric Imager data reveals inconsistencies that cannot be explained within the observational errors and model assumptions. We argue that these observations imply that the assumptions of the CME geometric models are routinely invalidated and question their utility in a space weather forecasting context. These results argue for the continuing development of more advanced techniques to better exploit the Heliospheric Imager observations for space weather forecasting.
Role of methionine adenosyltransferase 2A and S-adenosylmethionine in mitogen-induced growth of human colon cancer cells.

BACKGROUND & AIMS Two genes (MAT1A and MAT2A) encode for methionine adenosyltransferase, an essential enzyme responsible for S-adenosylmethionine (SAMe) biosynthesis. MAT1A is expressed in liver, whereas MAT2A is widely distributed. In liver, increased MAT2A expression is associated with growth, while SAMe inhibits MAT2A expression and growth. The role of MAT2A in colon cancer in unknown. The aims of this study were to examine whether MAT2A expression and SAMe and its metabolite methylthioadenosine (MTA) can modulate growth of colon cancer cells. METHODS Studies were conducted using resected colon cancer specimens, polyps from Min mice, and human colon cancer cell lines RKO and HT-29. MAT2A expression was measured by real-time polymerase chain reaction and cell growth by the 3-(4,5-dimethylthiazolyl-2-yl)-2,5-diphenyltetrazolium bromide assay. RESULTS In 12 of 13 patients and all 9 polyps from Min mice, the MAT2A messenger RNA levels were 200%-340% of levels in adjacent normal tissues, respectively. Epidermal growth factor, insulin-like growth factor 1, and leptin increased growth and up-regulated MAT2A expression and MAT2A promoter activity in RKO and HT-29 cells. SAMe and MTA lowered the baseline expression of MAT2A and blocked the growth factor-mediated increase in MAT2A expression and growth in colon cancer cell lines. Importantly, the mitogenic effect of these growth factors was inhibited if MAT2A induction was prevented by RNA interference. SAMe and MTA supplementation in drinking water increased intestinal SAMe levels and lowered MAT2A expression. CONCLUSIONS Similar to the liver, up-regulation of MAT2A also provides a growth advantage and SAMe and MTA can block mitogenic signaling in colon cancer cells.
Post‐transplant lymphoproliferative disorder following kidney transplantation: a population‐based cohort study

Post‐transplant lymphoproliferative disorder (PTLD) incidence is difficult to determine, mainly because both early and other lesions may go unrecognized and unregistered. Few studies have included systematic pathology review to maximize case identification and decide more accurately PTLD frequency after long‐term post‐transplantation follow‐up. A retrospective population‐based cohort study including all kidney transplant recipients at two Danish centres (1990–2011; population covered 3.1 million; 2175 transplantations in 1906 patients). Pathology reports were reviewed for all patient biopsies to identify possible PTLDs. Candidate PTLDs underwent histopathological review and classification. Seventy PTLD cases were identified in 2175 transplantations (3.2%). The incidence rate (IR) after first transplantation was 5.4 cases per 1000 patient‐years (95% CI: 4.0–7.3). Most PTLDs were monomorphic (58.5%), or early lesions (21.5%). Excluding early lesions and patients <18 years, IR was 3.7 (95% CI: 2.9–5.5). Ten patients with PTLD were retransplanted, 2 developing further PTLDs. Post‐transplant patient survival was inferior in patients with PTLD, while death‐censored graft survival was not. Using registry data together with extensive pathological review and long follow‐up, a rather high incidence of PTLD was found.
Fighting against Malaria: Prevent Wars while Waiting for the Miraculous Vaccine

The World Health Organization estimates that 300 million clinical cases of malaria occur annually and observed that during the 80s and part of the 90s its incidence increased. In this paper, we explore the influence of refugees from civil wars on the incidence of malaria in the refugee-receiving countries. Using civil wars as an instrumental variable, we show that for each 1,000 refugees there are between 2,000 and 2,700 cases of malaria in the refugee-receiving country. On average 13 of the cases of malaria reported by the WHO are caused by forced migration as a consequence of civil wars.
Cancer registries in Africa 2014: A survey of operational features and uses in cancer control planning

A questionnaire survey of all active population based cancer registries in sub‐Saharan Africa obtained information on their characteristics (size, staffing, funding), methods of working, the nature of any links between registries and their respective Health Authorities (national and/or local), and the use of their data in research or cancer control planning. 23/25 registries (92%) responded. Sources of direct funding and estimated amounts from each source were established, and suggest that it is approximately US$8‐9 per case registered. Almost half of the funding is used for routine data collection, processing and analysis. Staffing levels vary, partly as a function of the registry size (approximately one FTE per 300 cases registered). Most data collection is active, using multiple sources (median 10 per registry), and is largely paper‐based (abstraction onto paper forms), although all use the computer system CanReg© for data entry, storage and analysis. Most reporting by the registries is remarkably timely, and in general, their results are widely used by health authorities and other stakeholders in planning and evaluating services, while research output is much more variable. These registries are the source of almost all the existing information on cancer incidence and mortality in sub‐Saharan Africa, as published in IARC's “Globocan”.
Neuropsychological scores and WeeFIM cognitive ratings of children with traumatic brain injury: A brief report

Abstract Primary objective and hypothesis: To test the hypothesis that there is a significant relationship between WeeFIM ratings of cognitive functioning and performance on neuropsychological tests of children with traumatic brain injury (TBI). Design: Retrospective analysis of archival data. Participants: Data from 52 children with severe TBI collected during inpatient rehabilitation. Main outcome measures: Multiple regression analysis with Neuropsychological test scores from Wechsler Abbreviated Scale of Intelligence (WASI) and Children’s Memory Scale (CMS) entered as predictor variables and WeeFIM cognitive ratings as criteria variables. Results: Analyses revealed significant relationships between WeeFIM cognitive rating and neuropsychological test scores. Delayed verbal memory was most highly associated with WeeFIM cognitive ratings. Conclusions: Results support the hypothesis of significant relationships between neuropsychological performance and WeeFIM ratings of children with TBI and support generalizability of neuropsychological performance to daily cognitive functioning.
Influence of sex on P300: an event-related potential electrophysiological study

The primary objective of this study was to further characterize the role of sex, if any, in event-related potentials (ERPs). More specifically, we aimed to investigate sex sensitivity with respect to the P300 ERP. Each female and male study participant underwent an oddball paradigm electroencephalography ERP session. ERP data were subjected to preprocessing and postprocessing, as well as statistical analysis. The results of the study showed that men had larger P300 amplitudes on average for both low-probability and high-probability stimuli compared with women (P<0.001). Men also showed shorter P300 latencies on average than did women (P<0.001). Significant differences in ERPs between men and women were observed in this study. The results indicate the existence of sex sensitivity to the P300 ERP, which may be because of men eliciting higher response inhibition compared with women.
Long-term risk of local failure after proton therapy for choroidal/ciliary body melanoma.

PURPOSE To quantitate long-term risk of local treatment failure after proton irradiation of choroidal/ciliary body melanomas and to evaluate risk of metastasis-related deaths after local failure. METHODS We followed prospectively 1,922 patients treated at the Harvard Cyclotron between January 1975 and December 1996 for local recurrences of their tumors. Mortality surveillance was completed through June 1999. For analysis, patient follow-up continued until tumor regrowth was detected or, in patients without recurrence, until the date of the last dilated examination prior to April 1998. Actuarial methods were used to calculate rates of recurrence and metastatic deaths. Cox regression models were constructed to evaluate risk factors for these outcomes. RESULTS Median ocular follow-up after irradiation was 5.2 years. Local recurrence was documented in 45 patients by ultrasound and/or sequential fundus photographs; in 17 more patients, the eye was enucleated due to suspected but unconfirmed tumor growth. Recurrences were documented between 2 months and 11.3 years after irradiation. The 5- and 10-year rates of regrowth, including suspected cases, were 3.2% (95% confidence interval [CI], 2.5%-4.2%), and 4.3% (95% CI, 3.3%-5.6%). Among the 45 documented recurrences, about one half (21) occurred at the margin, presumably due to treatment planning errors. The remaining cases represented extrascleral extensions (nine cases), ring melanomas (six cases), or uncontrolled tumor (nine cases). Recurrence of the tumor was independently related to risk of tumor-related death. CONCLUSION These data, based on relatively long-term follow-up, demonstrate that excellent local control is maintained after proton therapy and that patients with recurrences experience poorer survival.
Associations Between Youth Risk Behavior and Exposure to Violence

This article assesses the relation between health risk behaviors and varying levels of exposure to violence in an effort to inform assessment and intervention efforts of a school-based mental health program serving inner-city youth. Health risk behaviors such as involvement in violence, risky sexual behavior, and substance use are clearly associated, both with each other and with violence exposure. However, differential relationships were observed depending on the nature of violence exposure. Knowledge of violence was associated with substance use and sexual behavior variables. Witnessing violence was associated with violence involvement, substance use, and exercise variables. Finally, violent victimization was associated with violence involvement and sexual behavior variables. A more complete understanding of the associations among health risk factors and violence exposure variables has the potential to improve implementation of school mental health services for urban youth.
Hair cell alteration prevalence rates in students of a school in Distrito Federal

Exposure to loud music is increasing among young people, and so could be the number of hearing impairment cases in this population. Otoacoustic emission tests are sensitive in capturing the effects of exposure to noise, and allow the detection of early cochlear disorders. Objective: This study aims to look into the prevalence rates of injuries to outer hair cells in a population of students through otoacoustic emission testing. Materials and Method: One-hundred and thirty-four subjects were submitted to transient evoked and distortion product otoacoustic emission tests. Subjects were assessed on a “pass/fail” scale. This is a cross-sectional descriptive study on prevalence rates. Results: More than four fifths (80.6%) of the 134 subjects had altered transient otoacoustic emissions, most of whom were males; 97.8% had altered distortion product otoacoustic emissions and 79.9% had altered test results in both transient evoked and distortion product OAEs; most were males; 94.0% reported they used earphones; and 82.8% stated they frequented places where loud music was played. Conclusion: The high prevalence rates of altered test results seem to indicate the presence of early cochlear disorders in the studied subjects. A significant number of subjects reported exposure to loud music, a habit that may be conducive to the onset of cochlear disorders.
The apolipoprotein E epsilon 2 allele and decline in episodic memory.

OBJECTIVES The apolipoprotein E (apoE) epsilon 4 allele is related to decline in multiple cognitive domains, especially episodic memory, but the effect of the epsilon 2 allele on change in different forms of cognitive function has been difficult to establish. METHODS Participants are from the Religious Orders Study. At baseline, they were at least 65 years old and free of clinical evidence of dementia. For up to eight years, they underwent annual clinical evaluations that included detailed cognitive function assessment from which previously established summary measures of episodic memory, semantic memory, working memory, perceptual speed, and visuospatial ability were derived. Growth curve models were used to assess change in each measure and its relation to apoE genotype, controlling for age, sex, education, and baseline level of cognition. Follow up data were available in 669 persons (98% of those eligible). We treated those with the epsilon 3/3 genotype as the reference group (n=425), which was contrasted with epsilon 2 ( epsilon 2/2, epsilon 2/3; n=86), and epsilon 4 ( epsilon 3/4, epsilon 4/4; n=158) subgroups. RESULTS Rate of episodic memory change in the three subgroups significantly differed, with an average annual increase of 0.016 units in the epsilon 2 subgroup and annual decreases of 0.022 units in those with epsilon 3/3 and of 0.073 units in the epsilon 4 subgroup. The epsilon 2 subgroup did not differ from those with epsilon 3/3 in rate of decline in other cognitive systems. The epsilon 4 subgroup declined more rapidly than those with epsilon 3/3 in semantic memory and perceptual speed but not in working memory or visuospatial ability. CONCLUSION Possession of one or more apoE epsilon 2 alleles is associated with reduced decline in episodic memory in older persons.
All-Units Discounts: Experimental Evidence from the Vending Industry

We study an All-Units Discount, in which a downstream firm pays a linear wholesale price up to a quantity threshold, beyond which a discount applies to all future and previous units. The result of the contract is that marginal cost downstream is effectively negative over a quantity range. Such contracts are common in many industries, and we implement a field experiment in one such industry (confections), in which we remove top-selling products from a market in order to identify the potential efficiency effect of the contract. We combine the experimental variation with a structural model of demand and a dynamic model of the retailer’s re-stocking decision to identify cases in which the contract results in either efficient or inefficient exclusion of competing products. We show how the contract allocates the cost of a stock-out between upstream and downstream firms, and find evidence of inefficient exclusion. Finally, we point out that the impact of upstream mergers in these markets is likely to be felt not through the price in the final-goods market, but rather in the wholesale market. We examine the impact of various upstream mergers on the willingness of the dominant firm to offer rebate contracts, and the impact that the rebate contracts have on social welfare. ∗We thank Mark Stein, Bill Hannon, and the drivers at Mark Vend Company for implementing the experiments used in this paper, providing data, and generally educating us about the vending industry. We thank Scott Hemphill, Michael Riordan, and seminar participants at Harvard Business School, Rochester University, SUNY Stony Brook, Universitat Autonoma de Barcelona, Universitat Pompeu Fabra, and the International Industrial Organization Conference for helpful comments. Financial support for this research was generously provided through NSF grant SES-0617896. Any remaining errors are our own. †Department of Economics, Columbia University, 420 W. 118th St., New York City, NY 10027. email: cconlon@columbia.edu ‡Department of Economics, Boston College, 140 Commonwealth Ave., Chestnut Hill, MA 02467, and NBER. email: julie.mortimer. 2@bc.edu
Parietal Lobe Lesional Epilepsy: Electroclinical Correlation and Operative Outcome

Summary: We retrospectively studied ictal behavior, extracranial EEG, and operative outcome in 10 consecutive patients with intractable partial epilepsy of presumed parietal lobe origin who received a lesionectomy, i.e., resection of the neuroimaging‐identified abnormality, at the Mayo Clinic. Nine patients had a pathologically verified foreign‐tissue lesion, e.g., tumor or vascular malformation, and 1 patient had gliosis. All patients with foreign‐tissue lesions were rendered seizure‐free. The patient with gliosis experienced a reduction in seizure tendency. There were no operative complications. The most common seizure type was a simple partial seizure with visual, motor, or sensory symptoms (n = 8). Complex partial seizures (n = 5) and secondarily generalized tonic‐clonic seizures (GTC, n = 2) were also observed. The ictal behavior was often nonspecific although useful in identifying lateralization of the epileptogenic zone. Extracranial interictal and ictal EEG changes were unreliable markers of the parietal lobe origin of seizure activity. Lesionectomy without chronic intracranial monitoring or functional mapping may be an effective and safe alternative surgical procedure in patients with partial epilepsy related to parietal lobe lesions.
Progress in Transcription of Vietnamese Broadcast News

In this paper, we report on our research and progress in Vietnamese Broadcast News transcription, with an emphasis on efficient modeling for more accurate recognition. In the acoustic modeling area, this was achieved through a re-alignment process, which considers all pronunciations for each word and outputs the pronunciation that best matches the acoustic data. The effectiveness of acoustic adaptation is greatly increased through unsupervised clustering of test data. In language modeling, we explored the use of non-broadcast-news training data as well as the adaptation to topic. Experimental results showed significant improvements in which the achieved WAR measured on a 1h test set was 84.2%, which gained absolutely 5.4% improvement over the baseline result (Nguyen and Vu, 2006 and Huynh et al., 2005).
Transcriptional Regulation of the Heterocyst Patterning Gene patA from Anabaena sp. Strain PCC 7120

ABSTRACT The filamentous cyanobacterium Anabaena sp. strain PCC 7120 forms a periodic pattern of nitrogen-fixing heterocysts when grown in the absence of combined nitrogen. PatA is necessary for proper patterning of heterocysts along filaments. In this study, apparent transcriptional start points (tsps) were identified at nucleotides −305, −614, and −645 relative to the translational start site (−305, −614, and −645 tsps). Transcriptional reporter fusions were used to show that transcription from the −305 tsp was induced in all cells of filaments in response to nitrogen deprivation, required hetR for induction, and increased in a patA mutant. Transcription from −614/−645 tsp reporter fusions was spatially regulated and occurred primarily in cells that would become heterocysts. Complementation of a patA mutant strain by alleles encoding substitutions in, or deletion of, the putative phosphoacceptor C-terminal domain indicates that the PATAN domain can function independently of the C-terminal domain of PatA. Localization of a ring of PatA-GFP at sites of cell division, as well as the formation of enlarged cells with altered cell morphology when patA was overexpressed, suggests that PatA may participate in cell division.