Miracle-dz/UniFAR-FTUs huggingface dataset:
Fighting an old disease with modern tools: characteristics and molecular detection methods of drug-resistant Mycobacterium tuberculosis

Tuberculosis (TB) is an ancient disease, but not a disease of the past. The increasing prevalence of drug-resistant strains of Mycobacterium tuberculosis, the causative agent of TB, demands new measures to combat the situation. Rapid and accurate detection of the pathogen, and its drug susceptibility pattern, is essential for timely initiation of treatment, and ultimately, control of the disease. Molecular-based methods offer a great chance to improve detection of drug-resistant TB; however, their development and usage should be accompanied with a profound understanding of drug resistance mechanisms and circulating M. tuberculosis strains in specific settings, as otherwise, the usefulness of such tests may be limited. This review gives an overview of the history of TB treatment and drug resistance, drug resistance mechanisms for the most commonly used drugs and molecular methods designed to detect drug-resistant strains.
Identification of the λ integrase surface that interacts with Xis reveals a residue that is also critical for Int dimer formation

Lambda integrase (Int) is a heterobivalent DNA-binding protein that together with the accessory DNA-bending proteins IHF, Fis, and Xis, forms the higher-order protein–DNA complexes that execute integrative and excisive recombination at specific loci on the chromosomes of phage λ and its Escherichia coli host. The large carboxyl-terminal domain of Int is responsible for binding to core-type DNA sites and catalysis of DNA cleavage and ligation reactions. The small amino-terminal domain (residues 1–70), which specifies binding to arm-type DNA sites distant from the regions of strand exchange, consists of a three-stranded β-sheet, proposed to recognize the cognate DNA site, and an α-helix. We report here that a site on this α-helix is critical for both homomeric interactions between Int protomers and heteromeric interactions with Xis. The mutant E47A, which was identified by alanine-scanning mutagenesis, abolishes interactions between Int and Xis bound at adjacent binding sites and reduces interactions between Int protomers bound at adjacent arm-type sites. Concomitantly, this residue is essential for excisive recombination and contributes to the efficiency of the integrative reaction. NMR titration data with a peptide corresponding to Xis residues 57–69 strongly suggest that the carboxyl-terminal tail of Xis and the α-helix of the aminoterminal domain of Int comprise the primary interaction surface for these two proteins. The use of a common site on λ Int for both homotypic and heterotypic interactions fits well with the complex regulatory patterns associated with this site-specific recombination reaction.
Effect of GnRHa 3.75 mg subcutaneously every 6 weeks on adult height in girls with idiopathic central precocious puberty

Abstract Objective: To evaluate the long-term efficacy of triptorelin 3.75 mg subcutaneously every 6 weeks on the final height in girls with idiopathic central precocious puberty (ICPP). Methods: Forty females with ICPP received triptorelin 3.75 mg every 6 weeks subcutaneously in our hospital from 2002 to December 2010 and reached their final heights were enrolled. These patients were treated with triptorelin alone (group A, n=17) or triptorelin+recombinant human growth hormone (rhGH) (group B, n=23). Height, weight, annual growth velocity (GV), sexual development, predicted adult height (PAH), and adverse effects were observed. Bone age (BA) and height standard deviation score (SDS) were monitored yearly. Results: Final adult heights (FAHs) were 159.81±1.20 cm and 161.01±1.02 cm in group A vs. group B, which exceeded target height (THt) by 1.51±1.04 cm, 4.86±0.94 cm, respectively. The values of (FAH-THt), (FAH-PAH posttreatment) showed significant difference between the two groups (p<0.05). FAH was positively correlated with Ht SDS-BA at the end of treatment, THt, course of rhGH treatment, and age of menarche (r2=0.66). Body mass index (BMI) increased after treatment in group B. However, there was no significant tendency of increase compared with healthy children at the same age. Ages of menarche and time to menarche from discontinuation were 11.74±0.16 vs. 12.18±0.15 years and 17.41±1.69 vs. 14.71±1.04 months in two groups. Conclusion: The FAH was improved effectively by triptorelin 3.75 mg subcutaneously every 6 weeks, and more height gain could be achieved when rhGH was used concomitantly. BMI maintained steadily and ovarian function restored quickly after treatment discontinuation with the age of menarche similar to that of normal children. Neither significant side effect nor polycystic ovary syndrome was observed.
A Premature Termination Codon Mutation at the C Terminus of Foamy Virus Gag Downregulates the Levels of Spliced pol mRNA

ABSTRACT Foamy viruses (FV) comprise a subfamily of retroviruses. Orthoretroviruses, such as human immunodeficiency virus type 1, synthesize Gag and Pol from unspliced genomic RNA. However, FV Pol is expressed from a spliced mRNA independently of Gag. FV pol splicing uses a 3′ splice site located at the 3′ end of gag, resulting in a shared exon between gag and pol. Previously, our laboratory showed that C-terminal Gag premature termination codon (PTC) mutations in the 3′ shared exon led to greatly decreased levels of Pol protein (C. R. Stenbak and M. L. Linial, J. Virol. 78:9423-9430, 2004). To further characterize these mutants, we quantitated the levels of unspliced gag and spliced pol mRNAs using a real-time PCR assay. In some of the PTC mutants, the levels of spliced pol mRNA were reduced as much as 30-fold, whereas levels of unspliced gag RNA were not affected. Substitutions of a missense codon in place of a PTC restored normal levels of spliced pol mRNA. Disrupting Upf proteins involved in nonsense-mediated mRNA decay (NMD) did not affect Pol protein expression. Introduction of an exonic splicing enhancer downstream of the PTC mutation restored pol splicing to the wild-type level. Taken together, our results show that the PTC mutation itself is responsible for decreased levels of pol mRNA but that mechanisms other than NMD might be involved in downregulating Pol expression. The results also suggest that normal pol splicing utilizes a suboptimal splice site seen for other spliced mRNAs in most retroviruses, in that introduced exonic enhancer elements can increase splicing efficiency.
Versatile Dual-Technology System for Markerless Allele Replacement in Burkholderia pseudomallei

ABSTRACT Burkholderia pseudomallei is the etiologic agent of melioidosis, a rare but serious tropical disease. In the United States, genetic research with this select agent bacterium is strictly regulated. Although several select agent compliant methods have been developed for allelic replacement, all of them suffer from some drawbacks, such as a need for specific host backgrounds or use of minimal media. Here we describe a versatile select agent compliant allele replacement system for B. pseudomallei based on a mobilizable vector, pEXKm5, which contains (i) a multiple cloning site within a lacZα gene for facile cloning of recombinant DNA fragments, (ii) a constitutively expressed gusA indicator gene for visual detection of merodiploid formation and resolution, and (iii) elements required for resolution of merodiploids using either I-SceI homing endonuclease-stimulated recombination or sacB-based counterselection. The homing endonuclease-based allele replacement system is completed by pBADSce, which contains an araC-PBAD-I-sceI expression cassette for arabinose-inducible I-SceI expression and a temperature-sensitive pRO1600 replicon for facile plasmid curing. Complementing these systems is the improved Δasd Escherichia coli mobilizer strain RHO3. This strain is susceptible to commonly used antibiotics and allows nutritional counterselection on rich media because of its diaminopimelic acid auxotrophy. The versatility of the I-SceI- and sacB-based methods afforded by pEXKm5 in conjunction with E. coli RHO3 was demonstrated by isolation of diverse deletion mutants in several clinical, environmental, and laboratory B. pseudomallei strains. Finally, sacB-based counterselection was employed to isolate a defined chromosomal fabD(Ts) allele that causes synthesis of a temperature-sensitive FabD, an essential fatty acid biosynthesis enzyme.
Genetic analysis of the Erwinia chrysanthemi 3937 chrysobactin iron‐transport system: characterization of a gene cluster involved in uptake and biosynthetic pathways

Twenty of the twenty‐two MudII1734 insertions impairing the chrysobactin iron‐assimilation system of Erwinia chrysanthemi 3937 were localized to a 50kbp genomic insert contained in the R‐prime plasmid, R′4 (Enard et al., 1988). Using the conjugative plasmid pULB1 10 (RP4::mini‐Mu) and the generalized transducing phage ΦEC2, we located this iron‐transport region and the two unlinked mutations on the chromosome linkage map. Chrysobactin is a catechol‐type siderophore and, as we have previously observed with the entA locus of Escherichia coli, the E. chrysanthemi‐derived R′4 was found to complement E. coli entB and entE mutations. A 2.9 kb Eco Ri and a 4.8kb BamHI fragment in the R′4 sharing homology with the E. coli entCEBAP15 operon DNA were subcloned. These fragments were used as DNA/DNA hybridization probes to screen a wild‐type gene library, yielding a recombinant cosmid (pEC7) able to complement mutations disrupting the 2,3‐drhydroxy‐benzoic acid biosynthetic pathway in both Erwinia and Escherichia spp. as well as the E. coli entE mutation. Physical mapping of the genomic MudII1734 insertions corresponding to these mutations led to the identification of a cluster of genes confined to a DNA sequence of about 10 kb required for both biosynthetic and receptor functions.
Mnogoznal: An unsupervised system for word sense disambiguation

In this paper, we present Mnogoznal, an unsupervised system for word sense disambiguation. Given a sentence, the system chooses the most relevant sense of each input word w.r. t. to the semantic similarity between the given sentence and the synset constituting the sense of the target word. Mnogoznal has two modes of operation. The sparse mode uses the traditional vector space model to estimate the most similar word sense corresponding to its context. The dense mode, instead, uses synset embeddings to cope with the sparsity problem. We describe the architecture of the present system and also conduct its preliminary evaluation on three different lexical semantic resources for Russian. We found that the dense mode substantially outperform the sparse one on all the datasets as according to the adjusted Rand index computed on a gold standard dataset.
Directed Mutations in the Poorly Defined Region of Porcine Liver Fructose-1,6-bisphosphatase Significantly Affect Catalysis and the Mechanism of AMP Inhibition*

Asn64, Asp68, Lys71, Lys72, and Asp74 of porcine liver fructose-1,6-bisphosphatase (FBPase) are conserved residues and part of a loop for which no electron density has been observed in crystal structures. Yet mutations of the above dramatically affect catalytic rates and/or AMP inhibition. The Asp74 → Ala and Asp74 → Asn mutant enzymes exhibited 50,000- and 2,000-fold reductions, respectively, in k catrelative to wild-type FBPase. The pH optimum for the catalytic activity of the Asp74 → Glu, Asp68 → Glu, Asn64 → Gln, and Asn64 → Ala mutant enzymes shifted from pH 7.0 (wild-type enzyme) to pH 8.5, whereas the Lys71 → Ala mutant and Lys71,72 → Met double mutant had optimum activity at pH 7.5. Mg2+cooperativity, K m for fructose 1,6-bisphosphate, and K i for fructose 2,6-bisphosphate were comparable for the mutant and wild-type enzymes. Nevertheless, for the Asp74 → Glu, Asp68 → Glu, Asn64→ Gln, and Asn64 → Ala mutants, the binding affinity for Mg2+ decreased by 40–125-fold relative to the wild-type enzyme. In addition, the Asp74 → Glu and Asn64 → Ala mutants exhibited no AMP cooperativity, and the kinetic mechanism of AMP inhibition with respect to Mg2+ was changed from competitive to noncompetitive. The double mutation Lys71,72 → Met increasedK i for AMP by 175-fold and increased Mg2+ affinity by 2-fold relative to wild-type FBPase. The results reported here strongly suggest that loop 51–72 is important for catalytic activity and the mechanism of allosteric inhibition of FBPase by AMP.
Bahasa Slang di Angkringan Kabupaten Ponorogo

This research examines and discovers the variation and formation of slang in the street food court (angkringan) of the Perpek community, Ponorogo Regency, which is indicated by a variant of the slang language. This research uses a qualitative descriptive method. The research data is in the form of words from languages that contain slang forms and are spoken by sellers and buyers. Data collection uses observation techniques supported by note-taking techniques. The data analysis technique used is the equivalent method and the method of religion. The findings of this research are four processes of the formation of slang language in terms of the formation of phonological structures, namely: (1) reversing the overall arrangement of letters, for example "mahal" to "laham", (2) giving an insert at the beginning and at the end both vowels and consonants, for example "kopi" becomes "ngikop", (3) exchanges consonants and replaces one or two letters, for example "sedikit" becomes "sikit", and (4) words are shortened or cut without changing their meanings, for example "mama cantik" to be "macan". The results of the research findings indicate the formation of new slang languages that are different from the original languages, both from Indonesian and regional languages (Javanese). Penelitian ini mengkaji dan menemukan variasi dan pembentukan bahasa slang di angkringan komunitas Perpek, Kabupaten Ponorogo, yang terindikasi ditemuakan varian bahasa slang. Penelitian ini menggunakan metode diskriptif kualitatif. Data penelitian berupa kata dari bahasa yang mengandung bentuk bahasa slang dan dituturkan oleh penjual dan pembeli. Pengumpulan data menggunakan teknik observasi yang didukung dengan teknik simak-libat-catat. Teknik analisis data yang digunakan adalah metode padan dan metode agih. Dari penelitian ini diperoleh temuan berupa empat proses pembentukan variasi bahasa slang dari segi pembentukan struktur fonologis, yaitu: (1) membalikkan susunan huruf secara keseluruhan, misal "mahal" menjadi "laham", (2) memberikan sisipan di awal dan di akhir kata, baik vokal maupun konsonan, misal "kopi" menjadi "ngikop", (3) menukar konsonan dan mengganti satu atau dua huruf, misal "sedikit" menjadi "sikit", dan (4) kata dipendekkan atau dipotong tanpa mengubah maknanya, misal "mama cantik" menjadi "macan". Hasil temuan penelitian menunjukkan adanya pembentukan bahasa slang baru yang berbeda dari bahasa aslinya, baik dari bahasa Indonesia maupun bahasa daerah (bahasa Jawa).
Introduction to modern OpenGL programming

OpenGL is the most widely available library for creating interactive computer graphics applications across all of the major computer operating systems. Its applications range from creating systems for scientific visualization to computer-aided design, interactive gaming, and entertainment, and with each new version, its capabilities reveal the most up-to-date features of modern graphics hardware. This course provides an accelerated introduction to programming OpenGL, emphasizing current methods for using the library. While there have been numerous courses on OpenGL in the past, the recent sequence of revisions to the API, culminating in OpenGL version 4.2, provide a wealth of new functionality and features for creation of ever-richer content. In recent years, OpenGL has undergone numerous updates that have fundamentally changed how programmers interact with the application programming interface (API) and the skills required for being an effective OpenGL programmer. The most notable of those changes are the introduction of shader-based rendering, which has expanded to subsume almost all functionality in OpenGL, and the depracation of immediate-mode functions. Course attendees are introduced to each of the shader stages in OpenGL version 4.2, along with methods for specifying data to be used in rendering with OpenGL. The course begins with an overview of the complete OpenGL pipeline, introducing all the latest shader stages. Then it focuses on the shader-based pipeline, which requires an application to provide both a vertex shader and a fragment shader. It also includes an summary of key graphics concepts: the synthetic-camera model, transformations, viewing, and lighting.
Evaluation of the Regional Choice Initiative

This evaluation describes the Regional Choice Initiative (RCI), a large-scale initiative in 17 school districts in Pennsylvania. The RCI sought to expand school choice and offer more-rigorous courses for students in grades 7 to 12. RAND evaluated the performance of the individual programs and the RCI overall. The authors also identified aspects of implementation that facilitated or hindered the performance of the RCI.
In-air handwritten Chinese character recognition using discriminative projection based on locality-sensitive sparse representation

Dimensionality reduction methods have been shown to be effective for handwritten Chinese character recognition. In this paper, we propose discriminative projection based on locality-sensitive sparse representation (DPLSR) for in-air handwritten Chinese character recognition. DPLSR based on the locality-sensitive sparse representation based classifier (LSRC), which can provide closed-form solutions and maintain the data locality constraint during the sparse coding stage. In contrast to sparse representation classifier steered discriminative projection (SRC-DP), which did not consider global structure of data and use all training samples as dictionary atoms, DPLSR is able to use fewer atoms and spend less training time to achieve better performance. Experiments are conducted on the IAHCC-UCAS2016 dataset built by us, experimental results demonstrate the effectiveness of proposed method.
Effects of Sowing Time and Growing Density on Agronomic Traits, Grain Yield, and Grain Quality of Waxy Sorghum Cultivar Hongliangfeng 1

The aim of this study was to determine the effects of sowing time and growing density on the yield and quality of grain in waxy sorghum (Sorghum bicolor L. Moench). The main plots were two sowing time: early sowing (5 April) and late sowing (20 April), and the subplots were three growing densities: 0.8 × 105, 1.1 × 105, and 1.4 × 105 plants/ha. Results showed that sowing time and growing density had significant effects on grain yield and grain quality of waxy sorghum cultivar Hongliangfeng 1. Grain yield, plant height, spike length, culm diameter, grain number per spike, grain weight per plant, 1000-grain weight, protein content, starch content, and amylopectin content were reduced by a delay of sowing time, while the tannin content and amylose content were increased by a delay of sowing time. Grain yield, plant height, spike length, culm diameter, grain number per spike, grain weight per plant, 1000-grain weight, protein content, starch content, and amylopectin content increased and then decreased with the increase of growing density, while the tannin content and amylose content decreased and then increased with the increase of growing density. These results hinted that appropriate sowing time and growing density are key cultivation measures to ensure high yield and good quality in waxy sorghum production.
Can specific deficits in executive functioning explain the behavioral characteristics of CHARGE syndrome: A case study

I present the case of a 12‐year‐old girl diagnosed with CHARGE syndrome. As an infant she had shown typical characteristics of CHARGE. Neuroimaging revealed asymmetrical ventriculomegaly. Both her teacher and parents reported academic and psychosocial problems. Neuropsychological assessment revealed significant executive dysfunction, including attention difficulties. We discuss the possible association between executive deficits and school and psychosocial problems. This case also highlights the importance of evaluating executive function in children with CHARGE, which is particularly useful in efficiently identifying needs for direct intervention. © 2005 Wiley‐Liss, Inc.
Nucleoprotein and membrane protein genes are associated with restriction of replication of influenza A/Mallard/NY/78 virus and its reassortants in squirrel monkey respiratory tract

An avian influenza A virus, A/Mallard/NY/6750/78(H2N2), was restricted in in replication in the respiratory tract of squirrel monkeys. Avian-human influenza A reassortant viruses possessing the six RNA segments coding for nonsurface proteins (i.e., internal genes) of this avian virus were as restricted in replication in squirrel monkeys as their avian influenza parent. These findings indicated that restriction of replication of the avian influenza virus is a function of one or more of its internal genes. For an investigation of which of the avian influenza genes was responsible for restricted replication in the respiratory tract of primates, reassortant viruses were produced that contained human influenza virus surface antigens from the A/Udorn/72(H3N2) virus and one or more of the internal genes derived from the avian influenza virus parent. Avian-human reassortant influenza A viruses containing only the nucleoprotein or matrix protein RNA segment from the avian influenza virus parent were as restricted in their growth as an avian-human influenza reassortant virus containing each of the six avian influenza internal genes. In addition, an avian-human influenza reassortant virus possessing only the avian RNA 1 and nonstructural genes (which by themselves do not specify restricted replication) manifested a significant reduction of virus replication in squirrel monkey tracheas. Thus, the avian nucleoprotein and matrix genes appear to play a major role in the host range restriction exhibited by the A/Mallard/78 virus and its reassortants, but the combination of RNA 1 and nonstructural genes also contributes to restriction of replication.