Miracle-dz/UniFAR-FTUs huggingface dataset:
In vitro spatially organizing the differentiation in individual multicellular stem cell aggregates

Abstract With significant potential as a robust source to produce specific somatic cells for regenerative medicine, stem cells have attracted increasing attention from both academia and government. In vivo, stem cell differentiation is a process under complicated regulations to precisely build tissue with unique spatial structures. Since multicellular spheroidal aggregates of stem cells, commonly called as embryoid bodies (EBs), are considered to be capable of recapitulating the events in early stage of embryonic development, a variety of methods have been developed to form EBs in vitro for studying differentiation of embryonic stem cells. The regulation of stem cell differentiation is crucial in directing stem cells to build tissue with the correct spatial architecture for specific functions. However, stem cells within the three-dimensional multicellular aggregates undergo differentiation in a less unpredictable and spatially controlled manner in vitro than in vivo. Recently, various microengineering technologies have been developed to manipulate stem cells in vitro in a spatially controlled manner. Herein, we take the spotlight on these technologies and researches that bring us the new potential for manipulation of stem cells for specific purposes.
Identification of Peptides That Mimic the Pertussis Toxin Binding Site on Bovine Fetuin

ABSTRACT The introduction of acellular pertussis vaccines has greatly enhanced the safety profile of vaccines to prevent whooping cough. Pertussis toxin (Ptx) is one component produced by Bordetella pertussis that is contained in all of these vaccines, either in combination with other known pertussis virulence factors or as the sole pertussis component, combined with tetanus and diphtheria toxoids. A hydrogen peroxide toxoid of Ptx has been shown to be efficacious in preventing pertussis infections in a mass vaccination trial and is presently licensed in the United States and Europe (B. Trollfors, J. Taranger, T. Lagergard, L. Lind, V. Sundh, G. Zackrisson, C. U. Lowe, W. Blackwelder, and J. B. Robbins, N. Engl. J. Med. 333:1045-1050, 1995). The industrial production of Ptx can be performed through the cultivation of B. pertussis in well-defined growth media, in which the components can be well characterized and their origins can be documented. Once the bacteria are removed from the culture, Ptx can be isolated from the supernatant and purified by using the technique described by Sekura et al. (R. D. Sekura, F. Fish, C. R. Manclark, B. Meade, and Y. L. Zhang, J. Biol. Chem. 258:14647-14651, 1983). The only drawback of this procedure, which combines two affinity chromatography steps, one with Blue Sepharose and a second with matrix-bound bovine fetuin (BF), is the source and purity of the BF. Concern about vaccine preparations that may possibly risk contamination by material associated with bovine spongioform encephalopathy has continued to increase. We thus sought a replacement for the BF affinity chromatography and, more specifically, for the glycosidic moiety on BF. We describe here the identification of a seven-amino-acid peptide that mimics the glycosidic moiety on BF to which Ptx binds. Furthermore, we have constructed an affinity column containing this peptide that can be used to replace BF in Ptx purification. Finally, we used the X-ray crystallographic structure of Ptx bound to the oligosaccharide moiety of BF as a scaffold and replaced the oligosaccharide with the peptide.
New insights from immunohistochemistry for the characterization of epidural scar tissue.

BACKGROUND The association between epidural fibrosis and recurrent symptoms after lumbar spine surgery remains a matter of debate in scientific literature and the underlying pathophysiological mechanism has not been clearly elucidated. OBJECTIVE To investigate the presence of nerve fibers and the expression of osteopontin in epidural fibrous tissue after lumbar surgery in humans. STUDY DESIGN Laboratory study of human tissue samples. METHODS Twenty-four patients with persistent or recurrent low back and/or leg pain after lumbar spine surgery, in whom no relevant findings were present on magnetic resonance imaging (MRI) besides epidural scar tissue, were submitted to epiduroscopy. Biopsy samples of epidural scar tissue resting in the posterior epidural and periradicular space were obtained from 15 patients, using an endoscopic grasping forceps, in locations where the stimulation with the tip of a Fogarty consistently reproduced pain. Biopsy samples were processed for examination under optical and transmission electron microscopes and under a fluorescence microscope after incubation in primary antibodies against beta3-tubulin or against osteopontin. RESULTS Optical and transmission electron microscopy revealed a homogeneous fibrous tissue rich in collagen and lacking nerve fibers. No immunofluorescence was present in any of the samples immunoreacted against beta3-tubulin. In the samples immunoreacted against osteopontin, a punctate signal was detected around the collagen fibers. LIMITATIONS Being a human study, there was no control group, so it is not possible to determine the contribution of osteopontin in the formation of epidural fibrosis and its relation to the patients' symptoms. Additional animal studies are needed to investigate these issues. CONCLUSION Rather than direct stimulation of nociceptors in the epidural scar tissue, other factors should relate epidural fibrosis and recurrent symptoms after lumbar spine surgery. Osteopontin seems to play a role in the formation of epidural fibrosis.
Manufacture and Acceptance Test of the Full Size ITER PF5 Conductor Sample

In the R&D process of the International Thermonuclear Experimental Reactor (ITER) Poloidal Field (PF) coils, 16 m PF5 Cable-in-Conduit Conductor (CICC) was integrated at Institute of Plasma Physics, Chinese Academy of Sciences (ASIPP). The manufacture process of the qualification conductor was according to the ITER design. As required by the ITER Procurement Arrangement (PA), full size PF5 qualification conductor sample was manufactured and delivered to SULTAN facility (CRPP Villigen, Switzerland) for acceptance test. The PF5 conductor sample was made of two legs by one conductor bending, bottom hairpin box, upper terminations, support clamps, insulation, cryogenic piping and instrumentations. The concept of hairpin box and comb-type terminations configuration for ITER PF conductor sample which was co-contributed by ENEA and CEA was successfully verified by the first China PF2 conductor sample tested in SULTAN facility May 2010. The PF5 conductor sample test was initiated at the end of Feb. 2011. The test program included DC performance, cyclic loading, AC loss and MQE test. The conductor manufacture process, conductor sample assembly and test results were presented in this paper.
Substrate Specificities of Caspase Family Proteases*

The caspase family represents a new class of intracellular cysteine proteases with known or suspected roles in cytokine maturation and apoptosis. These enzymes display a preference for Asp in the P1 position of substrates. To clarify differences in the biological roles of the interleukin-1β converting enzyme (ICE) family proteases, we have examined in detail the specificities beyond the P1 position of caspase-1, −2, −3, −4, −6, and −7 toward minimal length peptide substrates in vitro We find differences and similarities between the enzymes that suggest a functional subgrouping of the family different from that based on overall sequence alignment. The primary specificities of ICE homologs explain many observed enzyme preferences for macromolecular substrates and can be used to support predictions of their natural function(s). The results also suggest the design of optimal peptidic substrates and inhibitors.
Plant C-N Hydrolases and the Identification of a Plant N-Carbamoylputrescine Amidohydrolase Involved in Polyamine Biosynthesis*

A nitrilase-like protein from Arabidopsis thaliana (NLP1) was expressed in Escherichia coli as a His6-tagged protein and purified to apparent homogeneity by Ni2+-chelate affinity chromatography. The purified enzyme showed N-carbamoylputrescine amidohydrolase activity, an enzyme involved in the biosynthesis of polyamines in plants and bacteria. N-carbamoylputrescine amidohydrolase activity was confirmed by identification of two of the three occurring products, namely putrescine and ammonia. In contrast, no enzymatic activity could be detected when applying various compounds including nitriles, amines, and amides as well as other N-carbamoyl compounds, indicating the specificity of the enzyme forN-carbamoylputrescine. Like the homologousβ-alanine synthases, NLP1 showed positive cooperativity toward its substrate. The native enzyme had a molecular mass of 279 kDa as shown by blue-native polyacrylamide gel electrophoresis, indicating a complex of eight monomers. Expression of the NLP1 gene was found in all organs investigated, but it was not induced upon osmotic stress, which is known to induce biosynthesis of putrescine. This is the first report of cloning and expression of a plantN-carbamoylputrescine amidohydrolase and the first time that N-carbamoylputrescine amidohydrolase activity of a recombinant protein could be shown in vitro. NLP1 is one of the two missing links in the arginine decarboxylase pathway of putrescine biosynthesis in higher plants.
A Murine Retrovirus Co-Opts YB-1, a Translational Regulator and Stress Granule-Associated Protein, To Facilitate Virus Assembly

ABSTRACT The Gag protein of the murine retrovirus mouse mammary tumor virus (MMTV) orchestrates the assembly of immature virus particles in the cytoplasm which are subsequently transported to the plasma membrane for release from the cell. The morphogenetic pathway of MMTV assembly is similar to that of Saccharomyces cerevisiae retrotransposons Ty1 and Ty3, which assemble virus-like particles (VLPs) in intracytoplasmic ribonucleoprotein (RNP) complexes. Assembly of Ty1 and Ty3 VLPs depends upon cellular mRNA processing factors, prompting us to examine whether MMTV utilizes a similar set of host proteins to facilitate viral capsid assembly. Our data revealed that MMTV Gag colocalized with YB-1, a translational regulator found in stress granules and P bodies, in intracytoplasmic foci. The association of MMTV Gag and YB-1 in cytoplasmic granules was not disrupted by cycloheximide treatment, suggesting that these sites were not typical stress granules. However, the association of MMTV Gag and YB-1 was RNA dependent, and an MMTV RNA reporter construct colocalized with Gag and YB-1 in cytoplasmic RNP complexes. Knockdown of YB-1 resulted in a significant decrease in MMTV particle production, indicating that YB-1 plays a role in MMTV capsid formation. Analysis by live-cell imaging with fluorescence recovery after photobleaching (FRAP) revealed that the population of Gag proteins localized within YB-1 complexes was relatively immobile, suggesting that Gag forms stable complexes in association with YB-1. Together, our data imply that the formation of intracytoplasmic Gag-RNA complexes is facilitated by YB-1, which promotes MMTV virus assembly. IMPORTANCE Cellular mRNA processing factors regulate the posttranscriptional fates of mRNAs, affecting localization and utilization of mRNAs under normal conditions and in response to stress. RNA viruses such as retroviruses interact with cellular mRNA processing factors that accumulate in ribonucleoprotein complexes known as P bodies and stress granules. This report shows for the first time that mouse mammary tumor virus (MMTV), a mammalian retrovirus that assembles intracytoplasmic virus particles, commandeers the cellular factor YB-1, a key regulator of translation involved in the cellular stress response. YB-1 is essential for the efficient production of MMTV particles, a process directed by the viral Gag protein. We found that Gag and YB-1 localize together in cytoplasmic granules. Functional studies of Gag/YB-1 granules suggest that they may be sites where virus particles assemble. These studies provide significant insights into the interplay between mRNA processing factors and retroviruses.
A Retrospective Analysis of Psychosocial Risk Factors Modulating Adolescent Alcohol Binge Drinking

Background/Aims: Adolescent alcohol binge-induced hospital admissions (BIHAs) are an increasing problem in Europe. We investigated whether psychosocial factors (e.g., drinking situations, drinking occasions and neighborhood unemployment) are associated with particularly risky patterns of alcohol or substance use. Method: We performed a systematic retrospective chart review of all the respective cases in 2003-2008 (n = 586; age range: 12-17 years) from both pediatric hospitals in the city of Dresden, Germany. Results: The vast majority of adolescent BIHAs were associated with drinking together with peers at weekend parties. Compared to this ‘typical' drinking pattern, adolescents drinking ‘atypically' (i.e., drinking either alone, to cope or despite the fact that the next day was a school/work day) more often had already used alcohol and illegal substances before and were more often diagnosed with substance use disorders and other mental disorders prior to BIHA. The unemployment rate in the patients' neighborhood was positively related to the incidence proportion of adolescent BIHAs in the respective subdistricts (rs = 0.61). Conclusion: Adolescent atypical drinking may indicate an increased risk for the development of alcohol and substance use disorders. This information is quickly accessible and can alert clinicians to initiate psychosocial aftercare; their infrastructure should address the strong relation between BIHA probability and neighborhood unemployment rates.
Cost effectiveness of intraperitoneal compared with intravenous chemotherapy for women with optimally resected stage III ovarian cancer: a Gynecologic Oncology Group study.

PURPOSE To determine the cost effectiveness of intraperitoneal versus intravenous regimens for adjuvant treatment of optimally resected stage III ovarian cancer. PATIENTS AND METHODS A decision model was developed to compare the cost effectiveness at 7-, 11.5-, and 35-year horizons of intravenous carboplatin and paclitaxel (IV-CARBO/PAC), intravenous cisplatin and paclitaxel (IV-CIS/PAC), or intravenous paclitaxel followed by intraperitoneal cisplatin and paclitaxel (IP-CIS/PAC). Survival data were from women participating in representative Gynecologic Oncology Group (GOG) protocols. Medicare reimbursement rates and the Agency for Healthcare Research and Quality Database were used to estimate costs for treatment regimens and grade 3 to 4 adverse effects, respectively. RESULTS Median predicted survival was 66, 57, 51, and 48 months for IP-CIS/PAC, IV-CARBO/PAC, IV-CIS/PAC (GOG 172), or IV-CIS/PAC (GOG 158), respectively. Across a range of analyses, IV-CIS/PAC was more costly and had lower life expectancy than IV-CARBO/PAC. Compared with IV-CARBO/PAC, IP-CIS/PAC had an incremental cost-effectiveness ratio (ICER) of $180,022 per quality-adjusted life year (QALY) saved at a 7-year time horizon, $71,835/QALY at 11.5 years, and $32,053/QALY over a lifetime. Extending the survival advantage of IP-CIS/PAC over 11.5 years and a lifetime results in ICERs of $26,249 and $23,973, respectively. Assuming IP-CIS/PAC and IV-CIS/PAC were equally effective when administered on an outpatient basis, the ICER of IP-CIS/PAC compared with IV-CARBO/PAC was $26,311. CONCLUSION Inpatient IP-CIS/PAC, while not cost effective compared with IV-CARBO/PAC at 7 years, becomes cost effective if a longer time horizon is modeled and/or a survival benefit can be assumed to persist longer than currently available data. Outpatient IP-CIS/PAC may also be cost effective compared with IV-CARBO/PAC if proven as effective as inpatient IP-CIS/PAC.
Graph-based clustering for identifying region of interest in eye tracker data analysis

Localization of a viewer's region of interest (ROI) on eye gaze signal trajectories acquired by eye trackers is a widely used approach in scene analysis, image compression, and quality of experience assessment. In this paper, we propose a novel clustering approach for ROI estimation from potentially noisy raw eye gaze data, based on signal processing on graphs. The clustering approach adapts graph signal processing (GSP)-based classification by first cleverly selecting a starting data sample, and then classifying the remaining samples. Furthermore, Graph Fourier Transform is used to adjust GSP parameters on-the-fly to maximise accuracy. Experimental results show competitive clustering accuracy of our proposed scheme compared to Density-based spatial clustering of applications with noise (DB-SCAN), Distance-Threshold Identification (I-DT), and Mean-Shift on publicly available Shape Dataset and the potential of estimating ROI accurately on true eye tracker data1.
Myths and plain truths about schizophrenia epidemiology – the NAPE lecture 2004

Objective: Science needs to constantly match research models against the data. With respect to the epidemiology of schizophrenia, the widely held belief that the incidence of schizophrenia shows little variation may no longer be supported by the data. The aims of this paper are (i) to explore data‐vs.‐belief mismatch with respect to the incidence of schizophrenia, and (ii) to speculate on the causes and consequences of such discrepancies.
Retrieval of important concepts from generalized one-sided concept lattice

One of the approaches used in data analysis area is related to the theory of concept lattices. It is known as formal concept analysis (FCA), which is used for analysis of object-attribute input data models. The output of FCA is represented by concept lattice, which is the hierarchically organized structure of groups of objects with shared attributes (concepts). One of the main issues of FCA is a large number of concepts in generated concept lattice. In this paper, we present a solution based on information retrieval methods, where on the input is user query of what he/she wants to find in concept lattice and on the output we get concepts which best fits input query. Also, some interactive methods for visualization of best concepts are presented. Our approach is applied on concept lattice generated by the model of Generalized One-Side Concept Lattices (GOSCL), which against classical FCA models is suitable to work with different types of attributes used in input data tables. In order to work with this model, the modified Hamming distance was introduced for comparison of values of complex types of attributes.
Construction of a URA3 deletion strain from the allotetraploid bottom‐fermenting yeast Saccharomyces pastorianus

The bottom‐fermenting lager yeast Saccharomyces pastorianus has been proposed to be allotetraploid, containing two S. cerevisiae (Sc)‐type and two S. bayanus (Sb)‐type chromosomes. This chromosomal constitution likely explains why recessive mutants of S. pastorianus have not previously been reported. Here we describe the construction of a ura3 deletion strain derived from the lager strain Weihenstephan34/70 by targeted transformation and subsequent loss of heterozygosity (LOH). Initially, deletion constructs of the Sc and Sb types of URA3 were constructed in laboratory yeast strains in which a TDH3p‐hygro allele conferring hygromycin B resistance replaced ScURA3 and a KanMX cassette conferring G‐418 resistance replaced SbURA3. The lager strain was then transformed with these constructs to yield a heterozygous URA3 disruptant (ScURA3+/Scura3Δ::TDH3p‐hygro, SbURA3+/Sbura3Δ::KanMX), which was plated on 5‐fluoroorotic acid (5‐FOA) plates to generate the desired Ura– homozygous disruptant (Scura3Δ::TDH3p‐hygro/Scura3Δ::TDH3p‐hygro Sbura3Δ::KanMX/Sbura3Δ::KanMX) through LOH. This ura3 deletion strain was then used to construct a bottom‐fermenting yeast transformant overexpressing ATF1 that encodes an enzyme that produces acetate esters. The ATF1‐overexpressing transformant produced significantly more acetate esters than the parent strain. The constructed ura3∆ lager strain will be a useful host for constructing strains of relevance to brewing. Copyright © 2012 John Wiley & Sons, Ltd.
Catecholamine Excretion in Spontaneously Occurring Asymptomatic Neonatal Hypoglycemia

Extract: Twenty-six full-term infants delivered vaginally were studied. There were 16 males and 10 females. Capillary blood samples for glucose were obtained hourly. When the infant voided spontaneously, the urine collection for determination of epinephrine (E), norepinephrine (NE), metanephrine (M), normetanephrine (NM), and vanillylmandelic acid (VMA) was discontinued. Using the value of 30 mg/100 ml as the lower limit of normal for glucose in blood, the study patients were divided into three groups: group A (16 subjects), all values over 30 mg/100 ml; group B (5 subjects), one value under 30 mg/100 ml; group C (5 subjects), two or more values less than 30 mg/100 ml.Comparison of the means by groups revealed no significant differences in individual or total catecholamine excretions. The two patients who were judged to be the most severely hypoglycemic, however, showed the lowest epinephrine excretions of the entire study group. Nonparametric statistical analysis was used to compare the epinephrine excretion of the 16 patients who maintained a normal glucose level with that of the 10 patients of groups B and C. A P value of less than 0.05 was obtained, suggesting that the ability to maintain adequate blood glucose was associated with a higher epinephrine excretion. Nonparametric statistical analyses did not show a significant difference in E+M or E+M+VMA excretion among the study groups. This negative finding does not support our hypothesis of deficient epinephrine release as a contributory factor in spontaneous neonatal hypoglycemia.Catecholamines in urine were determined in nine newborns who were treated in a fashion similar to the study groups except that they were not subjected to heel punctures as repeated unpleasant stimuli. The results, expressed as mean ± SD were: E, 7.73 ± 5.36; NE, 35.3 ± 22.9; M, 52.8 ± 33.9; NM, 201 ± 140; and VMA, 899 ± 356 ng/kg/h. The only significant difference between these values and those of the study group lay in the levels of epinephrine excretion where significant differences were found between these subjects and those in group A. It appears reasonable to attribute the observed difference to the lack of stimulation by heel punctures.A rise in blood glucose concentrations was observed after epinephrine injection in all groups, with no differences between them.Speculation: These results suggest that in certain instances failure of endogenous epinephrine release may play a role in spontaneous hypoglycemia of the newborn. A major unresolved question is whether this failure of epinephrine release is itself primary, or whether asymptomatic hypoglycemia is not a sufficient stimulus for adrenal activation in these children.