Miracle-dz/UniFAR-FTUs huggingface dataset:
Sheet-scanned dual-axis confocal (SS-DAC) microscopy using Richardson-Lucy deconvolution

We have previously developed a line-scanned dual-axis confocal (LS-DAC) microscope with subcellular resolution suitable for high-frame-rate diagnostic imaging at shallow depths. Due to the loss of confocality along one dimension, the contrast (signal-to-background ratio) of a LSDAC microscope is deteriorated compared to a point-scanned DAC microscope. However, by using a sCMOS camera for detection, a short oblique light-sheet is imaged at each scanned position. Therefore, by scanning the light sheet in only one dimension, a thin 3D volume is imaged. Both sequential two-dimensional deconvolution and three-dimensional deconvolution are performed on the thin image volume to improve the resolution and contrast of one en face confocal image section at the center of the volume, a technique we call sheet-scanned dual-axis confocal (SS-DAC) microscopy. Confocal microscopy is one of the most important advances in optical imaging and has become an essential tool in the biological sciences as well as for medical diagnostics in recent decades. Using point illumination and pinhole detection, confocal microscopes provide a means of non-destructively imaging intact biological samples in three dimensions (i.e., optical sectioning) with subcellular resolution. Due to the high cost and time demands of the current diagnostic gold standard of histopathology, the ability to rapidly obtain diagnostic images with minimal tissue processing at a low cost is highly desirable. Therefore, by using miniaturized optics and mechanics, along with low-power fiber-coupled laser sources, portable confocal microscopes have been developed for use in clinics and surgical suites [1-10]. Previously, our group developed and miniaturized a dual-axis confocal (DAC) microscope for clinical applications [11, 12]. The DAC architecture differs from a conventional confocal microscope (referred to as a single-axis confocal, or SAC, microscope) in that the illumination and collection paths do not overlap except at the focus. Using diffraction theory and Monte-Carlo simulations, it has been shown that the DAC microscope exhibits superior optical-sectioning capabilities compared with its SAC counterpart [11, 13, 14]. In addition, Corresponding author miss.danni. wang@gmail.com. 3Current address: University of Washington, Department of Mechanical Engineering, Seattle, WA 98195 HHS Public Access Author manuscript Opt Lett. Author manuscript; available in PMC 2015 October 16. Published in final edited form as: Opt Lett. 2014 September 15; 39(18): 5431–5434. A uhor M anscript
Clustering Co-occurrence Graph based on Transitivity

Word co-occurrences form a graph, regarding words as nodes and co-occurrence relations as branches. Thus, a co-occurrence graph can be constructed by co-occurrence relations in a corpus. This paper discusses a clustering method of the co-occurrence graph, the decomposition of the graph, from a graph-theoretical viewpoint. Since one of the applications for the clustering results is the ambiguity resolution, each output cluster is expected to have no ambiguity and be specialized in a single topic. We observed that a graph has no ambiguity if its branches representing co-occurrence relations are transitive. An algorithm to extract such graphs are proposed and its uniqueness of the output is discussed. The effectiveness of our m e t h o d is examined by an experiment using co-occurrence graph obtained from a 30M bytes corpus. 1 I n t r o d u c t i o n Clustering is t h e operation to group words by some criterion. Thesauri and synonym dictionaries are some of its manual examples. Automatic outputs can be used not only to revise them, but also to aid ambiguity resolution, an essential problem in natural language processing. For instance, the m e ~ i n g of an ambiguous word can be decided by e.xamln'i~g the duster it belongs to. Furthermore, clusters grouped according to topics have many application areas such as automatic document classification. The input in this paper is the word co-occurrence graph obta~ued from corpus. The output is its subgraphs with the condition that each subgraph is specialized in a topic. Many automatic clustering methods have been already proposed. Most of them are based on the statistical similarity between two words. Our approach is different; it is graph theoretical. We tried to find out the special structure in linguistic graph. Having a huge co-occurrence graph obtained from a corpus, we first tried to decompose it to analyze its graph structure using graph theoretical tools, such as maximum strongly connected components, or biconnected components. Although both tools decompose a graph into tightly connected subgraphs, these trials resulted in vain. The question arose; what must be taken into account to decompose the cooccurrence graph. 7 The answer is the ambiguity. Furthermore, we reached to the conclusion that the ambiguity can be explained in terms of intransitivity. This feature is developed into an algorithm for clustering. This paper is organized as follows. The following chapter describes the relationship between the transitivity in the graph and the ambiguity resolution. Chapter 3 shows the relationships between clustering and transitivity. Chapter 4 proposes and discusses an algorithm for clustering. Related work is resumed in Chapter 5. Our method is examined in Chapter 6 by some experiments. 2 W o r d A m b i g u i t y a n d T r a n s i t i v i t y Two words are said to co-occur when they frequently appear close to each other within texts. Regarding words as nodes and co-occurring re-
Molecular Cloning of the Human Goodpasture Antigen

To characterize the autoantigen of Goodpasture's (anti-glomerular basement membrane) disease, a molecule of 26-kD reactive with autoantibodies from patients' sera was purified from collagenase digests of sheep glomerular basement membrane. Short internal amino acid sequences were obtained after tryptic or cyanogen bromide cleavage, and used to deduce redundant oligonucleotides for use in the polymerase chain reaction on cDNA derived from sheep renal cortex. Molecules of 175 bp were amplified and found to come from two cDNA sequences. One was identical to that of a type IV collagen chain (a5) cloned from human placenta and shown to be expressed in human kidney. The other was from a type IV collagen chain with close similarities to al and a5 chains, and was used to obtain human cDNA sequences by cDNA library screening and by further polymerase chain reaction amplifications. The correspondence of the derived amino acid sequence of the new chain with published protein and cDNA sequences shows it to be the a3 chain oftype IV collagen. Its gene, COL4A3, maps to 2q36-2q37. The primary sequence and other characteristics of this chain confirm that it carries the Goodpasture antigen. (J. Clin. Invest. 1992. 89:5924601.)
Ca2+-Dependent Contraction by the Saponoside Escin in Rat Vena Cava. Implications in Venotonic Treatment of Varicose Veins

Background—Saponosides (horse chestnut seed extract, escin) and flavonoids (diosmin, Daflon 500) exhibit venotonic properties that have been utilized in treatment of varicose veins. However, the cellular mechanisms underlying the venotonic properties of escin and diosmin are unclear. Because Ca2+ is a major regulator of venous smooth muscle (VSM) function, we tested the hypothesis that escin and diosmin promote Ca2+-dependent venous contraction. Methods—Rings of inferior vena cava (IVC) from male rats were suspended in a tissue bath for measurement of isometric contraction. Following control contraction to 96 mM KCl, the effects of escin and diosmin (10−10 to 10−4 M) on vein contraction were measured. To test the role of intracellular Ca2+ release, the vein response to escin and diosmin was measured in Ca2+-free (2mM EGTA) Krebs. To test for Ca2+-dependent effects, IVC segments were pretreated with escin or diosmin (10−4 M) in 0 Ca2+ Krebs, then extracellular CaCl2 (0.1, 0.3, 0.6, 1, 2.5 mM) was added and the [Ca]e-contraction relationship was constructed. To test for synergistic effects of diosmin, IVC segments were pretreated with diosmin (10−4 M) then stimulated with KCl (16 to 96 mM) or escin (10−10 to 10−4 M) and vein contraction was measured. Contraction data were presented as mg/mg tissue (means±SEM). Results—In IVC segments incubated in normal Krebs (2.5 mM Ca2+), escin caused concentration-dependent contraction (max 104.3±19.6 at 10−4 M). Escin-induced contraction was not a rigor state, because after washing with Krebs the veins returned to a relaxed state. In Ca2+free Krebs, there was essentially no contraction to escin. In escin-treated veins incubated in 0 Ca2+ Krebs, stepwise addition of extracellular CaCl2 caused corresponding increases in contraction (max 80.0±11.1 at 2.5 mM). In the absence of escin, the α-adrenergic agonist phenylephrine (PHE, 10−5 M), angiotensin II (AngII, 10−6 M), and membrane depolarization by KCl (96 mM) caused significant contraction (122.5±45.1, 114.2±12.2 and 221.7±35.4, respectively). In IVC segments pretreated with escin (10−4 M), the contractile response to PHE (9.7±2.6), AngII (36.0±9.1) and KCl (82.3±10.2) was significantly reduced. Diosmin (10−4 M) caused small contraction in normal Krebs (11.7±1.9) and Ca2+-free Krebs (4.2±2.2). In diosmin-treated veins incubated in 0 Ca2+ Krebs, addition of extracellular CaCl2 caused minimal contraction. Diosmin did not enhance the IVC contraction to PHE, AngII, or escin, but enhanced the contractile response to KCl (24 to 51 mM). Conclusion—In rat IVC, escin induces extracellular Ca2+-dependent contraction, but disrupts αadrenergic and AT1R receptor-mediated pathways, and depolarization-induced contraction. The Correspondence and Reprints: Raouf A Khalil, MD, PhD, Harvard Medical School, Brigham and Women’s Hospital, Division of Vascular Surgery, 75 Francis Street, Boston, MA 02115, Tel: (617) 525-8530, Fax: (617) 264-5124, raouf_khalil@hms.harvard. edu. NIH Public Access
Minimal Identifiable Disease and the Role of Conditioning Intensity in Hematopoietic Cell Transplantation for MDS and AML evolving from MDS

Allogeneic hematopoietic cell transplantation (HCT) is the only known treatment with curative potential for myelodysplastic syndromes (MDS), but relapse is a major cause of failure. We studied results in 289 patients transplanted between June 2004 and December 2013. Minimal Identifiable Disease (MID) markers pre-HCT were determined by multiparameter flow cytometry Corresponding Author: Bart L. Scott, MD, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue N, Mail Stop D1-100, PO Box 19024, Seattle, WA 98109-1024. bscott@fredhutch.org. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Authors’ Contributions: M.F. , H.J.D. , and B.L. S. designed the study. M.F. collected and assembled data. M.F. , H.J.D. , T.A. G. , K.B. , B.L. W. , M.Fa. , B.M.S., and B.L. S. analyzed and interpreted data. H.J.D. and B.L. S. provided study material or patients. M.F. , H.J.D. , T.A. G. , K.B. , B.L. W. , M.Fa. , B.M.S., and B.L. S. wrote the manuscript. Authors’ Disclosures of Potential Conflicts of Interest Moreno Festuccia No relationship to disclose H. Joachim Deeg Consulting or Advisory Role: MEDAC Research Funding: MEDAC Travel, Accommodations, Expenses: MEDAC Theodore A. Gooley No relationship to disclose Kelsey Baker No relationship to disclose Brent L. Wood Honoraria: Abbvie, Seattle Genetics Consulting or Advisory Role: Abbvie, Seattle Genetics Research Funding: Seattle Genetics, Amgen, Coronado, Pfizer Travel, Accommodations, Expenses: Abbvie, Seattle Genetics Min Fang Research Funding: Affymetrix (Inst) Brenda M. Sandmaier Stock or Other Ownership: Blaze Bioscience (I), EpiThany (I) Honoraria: Gilliad, ArevaMed, Jazz Pharmaceuticals; Seattle Genetics Consulting or Advisory Role: Frazier (I) Research Funding: Ambit, Bellicum Patents, Royalties, Other Intellectual Property: Gilliad(I) Bart L. Scott No relationship to disclose HHS Public Access Author manuscript Biol Blood Marrow Transplant. Author manuscript; available in PMC 2017 July 01. Published in final edited form as: Biol Blood Marrow Transplant. 2016 July ; 22(7): 1227–1233. doi:10.1016/j.bbmt. 2016.03. 029. A uhor M anscript
Escherichia coli: 11. Site-directed sulfhydryl modification

Cys-scanning mutagenesis of putative transmembrane helix VI11 in the lactose permease of Escherichia coli (Frillingos S , Ujwal ML, Sun J, Kaback HR, 1997, Protein Sci 6:431-437) indicates that, although helix VI11 contains only one irreplaceable residue (Glu 269), one face is important for active lactose transport. In this study, the rate of inactivation of each N-ethylmaleimide (NEM)-sensitive mutant is examined in the absence or presence of P,D-galactopyranosyl 1 -thio-P,D-galactopyranoside (TDG). Remarkably, the analogue affords protection against inactivation with mutants Val 264 -+ Cys, Gly 268 + Cys, and Asn 272 -+ Cys, and alkylation of these singlecys mutants in right-side-out membrane vesicles with [ I4C]NEM is attenuated by TDG. In contrast, alkylation of Thr 265 -+ Cys, which borders the three residues that are protected by TDG, is enhanced markedly by the analogue. Furthermore, NEM-labeling in the presence of the impermeant thiol reagent methanethiosulfonate ethylsulfonate demonstrates that ligand enhances the accessibility of position 265 to solvent. Finally, no significant alteration in NEM reactivity is observed for mutant Gly 262 + Cys, Glu 269 + Cys, Ala 273 + Cys, Met 276 + Cys, Phe 277 + Cys, or Ala 279 -+ Cys. The findings indicate that a portion of one face of helix VI11 (Val 264, Gly 268, and Asn 272), which is in close proximity to Cys 148 (helix V), interacts with substrate, whereas another position bordering these residues (Thr 265) is altered by a ligandinduced conformational change.
Neuroimaging in Pediatric Patients with Mild Traumatic Brain Injury: Relating the Current 2018 Centers for Disease Control Guideline and the Potential of Advanced Neuroimaging Modalities for Research and Clinical Biomarker Development

The Center for Disease Control and Prevention (CDC)’s 2018 Guideline for current practices in pediatric mild traumatic brain injury (mTBI; also referred to as concussion herein) systematically identified the best up-to-date practices based on current evidence and, specifically, identified recommended practices regarding computed tomography (CT), magnetic resonance imaging (MRI), and skull radiograph imaging. In this article, we discuss types of neuroimaging not discussed in the guideline in terms of their safety for pediatric populations, their potential application, and the research investigating the future use of certain modalities to aid in the diagnosis and treatment of mTBI in children. The role of neuroimaging in pediatric mTBI cases should be considered for the potential contribution to children’s neural and social development, in addition to the immediate clinical value (as in the case of acute structural findings). Selective use of specific neuroimaging modalities in research has already been shown to detect aspects of diffuse brain injury, disrupted cerebral blood flow, and correlate physiological factors with persistent symptoms, such as fatigue, cognitive decline, headache, and mood changes, following mTBI. However, these advanced neuroimaging modalities are currently limited to the research arena, and any future clinical application of advanced imaging modalities in pediatric mTBI will require robust evidence for each modality’s ability to provide measurement of the subtle conditions of brain development, disease, damage, or degeneration, while accounting for variables at both non-injury and time-post-injury epochs. Continued collaboration and communication between researchers and healthcare providers is essential to investigate, develop, and validate the potential of advanced imaging modalities in pediatric mTBI diagnostics and management.
Mutationally Activated PIK3CAH1047R Cooperates With BRAFV600E To Promote Lung Cancer Progression

Adenocarcinoma of the lung, a leading cause of cancer death, frequently displays mutational activation of the KRAS proto-oncogene but, unlike lung cancers expressing mutated EGFR, ROS1 or ALK, there is no pathway-targeted therapy for patients with KRAS mutated lung cancer. In preclinical models, expression of oncogenic KRASG12D in the lung epithelium of adult mice initiates development of lung adenocarcinoma through activation of downstream signaling pathways. By contrast, mutationally activated BRAFV600E, a KRAS effector, fails to initiate lung carcinogenesis despite highly efficient induction of benign lung tumorigenesis. To test if PI3′-kinase-α (PIK3CA), another KRAS effector, might cooperate with oncogenic BRAFV600E to promote lung cancer progression, we employed mice carrying a conditional allele of Pik3ca that allows conversion of the wild-type catalytic subunit of PIK3CA to mutationally activated PIK3CAH1047R. Whereas expression of PIK3CAH1047R in the lung epithelium, either alone or in combination with PTEN silencing, was without phenotype, concomitant expression of BRAFV600E and PIK3CAH1047R led to dramatically decreased tumor latency and increased tumor burden compared to BRAFV600E alone. Most notably, co-expression of BRAFV600E and PIK3CAH1047R elicited lung adenocarcinomas in a manner reminiscent of the effects of KRASG12D. These data emphasize a role for PI3′-kinase signaling, not in lung tumor initiation per se, but in both the rate of tumor growth and the propensity of benign lung tumors to progress to a malignant phenotype. Finally, biological and biochemical analysis of BRAFV600E/PIK3CAH1047R expressing mouse lung cancer cells revealed mechanistic clues as to cooperative regulation of the cell division cycle and apoptosis by these oncogenes.
Study Design Two-Phase, Generalized Case-Control Designs for the Study of Quantitative Longitudinal Outcomes

We propose a general class of 2-phase epidemiologic study designs for quantitative, longitudinal data that are useful when phase 1 longitudinal outcome and covariate data are available but data on the exposure (e.g., a biomarker) can only be collected on a subset of subjects during phase 2. To conduct a study using a design in the class, one first summarizes the longitudinal outcomes by fitting a simple linear regression of the response on a time-varying covariate for each subject. Sampling strata are defined by splitting the estimated regression intercept or slope distributions into distinct (low, medium, and high) regions. Stratified sampling is then conducted from strata defined by the intercepts, by the slopes, or from a mixture. In general, samples selected with extreme intercept values will yield low variances for associations of time-fixed exposures with the outcome and samples enriched with extreme slope values will yield low variances for associations of time-varying exposures with the outcome (including interactions with time-varying exposures). We describe ascertainment-corrected maximum likelihood and multiple-imputation estimation procedures that permit valid and efficient inferences. We embed all methodological developments within the framework of conducting a substudy that seeks to examine genetic associations with lung function among continuous smokers in the Lung Health Study (United States and Canada, 1986–1994).
BsiY 1 , a novel thermophilic restriction endonuclease that recognizes 5 ' CCNNNNNNNGG 3 ' and the discovery of a wrongly sequenced site in pACYC 177

A new type 11 restriction endonuclease designated BsiY I has been purified from a thermophilic soil Bacillus stearothermophilus strain. This enzyme recognizes and cleaves the highly degenerate sequence 5' CCNNNNNINNGG 3'. During the identification of the recognition sequence of BsiY 1, we discovered that there should be five G nucleotides instead of four at position 1227-1230 of the plasmid pACYCi77.
Meta-Analyses of Seven of NIDA’s Principles of Drug Addiction Treatment

Seven of the 13 Principles of Drug Addiction Treatment disseminated by the National Institute on Drug Abuse (NIDA) were meta-analyzed as part of the Evidence-based Principles of Treatment (EPT) project. By averaging outcomes over the diverse programs included in EPT, we found that five of the NIDA principles examined are supported: matching treatment to the client’s needs; attending to the multiple needs of clients; behavioral counseling interventions; treatment plan reassessment; and counseling to reduce risk of HIV. Two of the NIDA principles are not supported: remaining in treatment for an adequate period of time and frequency of testing for drug use. These weak effects could be the result of the principles being stated too generally to apply to the diverse interventions and programs that exist or of unmeasured moderator variables being confounded with the moderators that measured the principles. Meta-analysis should be a standard tool for developing principles of effective treatment for substance use disorders.
RAPID COMMUNICATION : Multi-breed validation study unraveled genomic regions associated with puberty traits segregating across tropically adapted breeds

An efficient strategy to improve QTL detection power is performing across-breed validation studies. Variants segregating across breeds are expected to be in high linkage disequilibrium (LD) with causal mutations affecting economically important traits. The aim of this study was to validate, in a Tropical Composite cattle (TC) population, QTL associations identified for sexual precocity traits in a Nellore and Brahman meta-analysis genome-wide association study. In total, 2,816 TC, 8,001 Nellore, and 2,210 Brahman animals were available for the analysis. For that, genomic regions significantly associated with puberty traits in the meta-analysis study were validated for the following sexual precocity traits in TC: age at first corpus luteum (AGECL), first postpartum anestrus interval (PPAI), and scrotal circumference at 18 months of age (SC). We considered validated QTL those underpinned by significant markers from the Nellore and Brahman meta-analysis (P ≤ 10–4) that were also significant for a TC trait, i.e., presenting a P-value of ≤10–3 for AGECL, PPAI, or SC. We also considered as validated QTL those regions where significant markers in the reference population were at ±250 kb from significant markers in the validation population. Using this criteria, 49 SNP were validated for AGECL, 4 for PPAI, and 14 for SC, from which 5 were in common with AGECL, totaling 62 validated SNP for these traits and 30 candidate genes surrounding them. Considering just candidate genes closest to the top SNP of each chromosome, for AGECL 8 candidate genes were identified: COL8A1, PENK, ENSBTAG00000047425, BPNT1, ADAMTS17, CCHCR1, SUFU, and ENSBTAG00000046374. For PPAI, 3 genes emerged as candidates (PCBP3, KCNK10, and MRPS5), and for SC 8 candidate genes were identified (SNORA70, TRAC, ASS1, BPNT1, LRRK1, PKHD1, PTPRM, and ENSBTAG00000045690). Several candidate regions presented here were previously associated with puberty traits in cattle. The majority of emerging candidate genes are related to biological processes involved in reproductive events, such as maintenance of gestation, and some are known to be expressed in reproductive tissues. Our results suggested that some QTL controlling early puberty seem to be segregating across cattle breeds adapted to tropical conditions.