Miracle-dz/UniFAR-FTUs huggingface dataset:
TACCLE: a methodology for object-oriented software testing at the class and cluster levels

Object-oriented programming consists of several different levels of abstraction, namely, the algorithmic level, class level, cluster level, and system level. The testing of object-oriented software at the algorithmic and system levels is similar to conventional program testing. Testing at the class and cluster levels poses new challenges. Since methods and objects may interact with one another with unforeseen combinations and invocations, they are much more complex to simulate and test than the hierarchy of functional calls in conventional programs. In this paper, we propose a methodology for object-oriented software testing at the class and cluster levels. In class-level testing, it is essential to determine whether objects produced from the execution of implemented systems would preserve the properties defined by the specification, such as behavioral equivalence and nonequivalence. Our class-level testing methodology addresses both of these aspects. For the testing of behavioral equivalence, we propose to select fundamental pairs of equivalent ground terms as test cases using a black-box technique based on algebraic specifications, and then determine by means of a white-box technique whether the objects resulting from executing such test cases are observationally equivalent. To address the testing of behavioral nonequivalence, we have identified and analyzed several nontrivial problems in the current literature. We propose to classify term equivalence into four types, thereby setting up new concepts and deriving important properties. Based on these results, we propose an approach to deal with the problems in the generation of nonequivalent ground terms as test cases. Relatively little research has contributed to cluster-level testing. In this paper, we also discuss black-box testing at the cluster level. We illustrate the feasibility of using contract, a formal specification language for the behavioral dependencies and interactions among cooperating objects of different classes in a given cluster. We propose an approach to test the interactions among different classes using every individual message-passing rule in the given Contract specification. We also present an approach to examine the interactions among composite message-passing sequences. We have developed four testing tools to support our methodology.
Minimal Residual Disease Detection and Evolved IGH Clones Analysis in Acute B Lymphoblastic Leukemia Using IGH Deep Sequencing

Acute B lymphoblastic leukemia (B-ALL) is one of the most common types of childhood cancer worldwide and chemotherapy is the main treatment approach. Despite good response rates to chemotherapy regiments, many patients eventually relapse and minimal residual disease (MRD) is the leading risk factor for relapse. The evolution of leukemic clones during disease development and treatment may have clinical significance. In this study, we performed immunoglobulin heavy chain (IGH) repertoire high throughput sequencing (HTS) on the diagnostic and post-treatment samples of 51 pediatric B-ALL patients. We identified leukemic IGH clones in 92.2% of the diagnostic samples and nearly half of the patients were polyclonal. About one-third of the leukemic clones have correct open reading frame in the complementarity determining region 3 (CDR3) of IGH, which demonstrates that the leukemic B cells were in the early developmental stage. We also demonstrated the higher sensitivity of HTS in MRD detection and investigated the clinical value of using peripheral blood in MRD detection and monitoring the clonal IGH evolution. In addition, we found leukemic clones were extensively undergoing continuous clonal IGH evolution by variable gene replacement. Dynamic frequency change and newly emerged evolved IGH clones were identified upon the pressure of chemotherapy. In summary, we confirmed the high sensitivity and universal applicability of HTS in MRD detection. We also reported the ubiquitous evolved IGH clones in B-ALL samples and their response to chemotherapy during treatment.
Control of Rectification and Gating of Cloned KATP Channels by the Kir6.2 Subunit

KATP channels are a functional complex of sulphonylurea receptor (SUR1, SUR2) and inward rectifier K+ (Kir6.1, Kir6.2) channel subunits. We have studied the role of the putative pore forming subunit (Kir6.2) in regulation of rectification and gating of KATP channels generated by transfection of SUR1 and Kir6.2 cDNAs in COSm6 cells. In the absence of internal polyvalent cations, the current-voltage relationship is sigmoidal. Mg2+ or spermine4+ (spm) each induces a mild inward rectification. Mutation of the asparagine at position 160 in Kir6.2 to aspartate (N160D) or glutamate (N160E) increases the degree of rectification induced by Mg2+ or spermine4+, whereas wild-type rectification is still observed after mutation to other neutral residues (alanine–N160A, glutamine–N160Q). These results are consistent with this residue lining the pore of the channel and contributing to the binding of these cations, as demonstrated for the equivalent site in homomeric ROMK1 (Kir1.1) channels. Since Kir6.2 contains no consensus ATP binding site, whereas SUR1 does, inhibition by ATP has been assumed to depend on interactions with SUR1. However, we found that the [ATP] causing half-maximal inhibition of current (K i) was affected by mutation of N160. Channels formed from N160D or N160Q mutant subunits had lower apparent sensitivity to ATP (K i,N160D = 46.1 μM; K i,N160Q = 62.9 μM) than wild-type, N160E, or N160A channels (K i = 10.4, 17.7, 6.4 μM, respectively). This might suggest that ATP binding to the channel complex was altered, although examination of channel open probabilities indicates instead that the residue at position 160 alters the ATP-independent open probability, i.e., it controls the free energy of the open state, thereby affecting the “coupling” of ATP binding to channel inhibition. The results can be interpreted in terms of a kinetic scheme whereby the residue at Kir6.2 position 160 controls the rate constants governing transitions to and from the open state, without directly affecting ATP binding or unbinding transitions.
Sex in the Morning or in the Evening? Females Adjust Daily Mating Patterns to the Intensity of Sexual Harassment

Selection on males to mate at a higher rate than females often results in male harassment of females and counteracting female responses. When the reproductive value of copulation changes over time, these mating strategies are expected to be time dependent. Here, we demonstrate that variation in the intensity of male harassment leads to drastic changes in female daily mating patterns. In feral populations of fowl Gallus gallus domesticus, male harassment is intense, particularly in the evening when inseminations are most likely to result in fertilization. We experimentally manipulated the intensity of male harassment through similar‐sized groups of different sex ratios. Male mating propensity was always higher than females’, particularly in male‐biased groups and in the evening, when males were closer to and more likely to approach females. Females counteracted male harassment by escalating resistance to mating and—crucially—by shifting their daily mating pattern: in strongly female‐biased groups with relaxed sexual harassment, females solicited sex in the evening, while in male‐biased groups, they solicited sex in the morning, thus avoiding harassment in the evening. Together, these results indicate that intersexual conflict may occur not only over mating rates but also over when in the day to copulate.
Asynchronous parallel disk sorting

We develop an algorithm for parallel disk sorting, whose I/O cost approaches the lower bound and that guarantees almost perfect overlap between I/O and computation. Previous algorithms have either suboptimal I/O volume or cannot guarantee that I/O and computations can always be overlapped. We give an efficient implementation that can (at least) compete with the best practical implementations but gives additional performance guarantees. For the experiments we have configured a state of the art machine that can sustain full bandwidth I/O with eight disks and is very cost effective.
A comparative analysis of HGSC and Celera human genome assemblies and gene sets

MOTIVATION Since the simultaneous publication of the human genome assembly by the International Human Genome Sequencing Consortium (HGSC) and Celera Genomics, several comparisons have been made of various aspects of these two assemblies. In this work, we set out to provide a more comprehensive comparative analysis of the two assemblies and their associated gene sets. RESULTS The local sequence content for both draft genome assemblies has been similar since the early releases, however it took a year for the quality of the Celera assembly to approach that of HGSC, suggesting an advantage of HGSC's hierarchical shotgun (HS) sequencing strategy over Celera's whole genome shotgun (WGS) approach. While similar numbers of ab initio predicted genes can be derived from both assemblies, Celera's Otto approach consistently generated larger, more varied gene sets than the Ensembl gene build system. The presence of a non-overlapping gene set has persisted with successive data releases from both groups. Since most of the unique genes from either genome assembly could be mapped back to the other assembly, we conclude that the gene set discrepancies do not reflect differences in local sequence content but rather in the assemblies and especially the different gene-prediction methodologies.
Transmission-line broadband GaN FET class-E power amplifier

A transmission-line loading network for class-E amplifiers is presented. In this work, a GaN FET device with a parasitic drain capacitance of 4-pF is used at 1-GHz design frequency for 20-W output power at 20-V DC supply voltage. A finite inductive reactance DC-feed class-E amplifier output network is designed based upon wire-lines and then modified using transmission-line transforms. The final network topology is managed so that it contains specific transmission-line impedances suitable for breadboarding employing air-suspended brass-bars so that no dielectric is used. The network presents the proper impedance at the device intrinsic drain and at the same time serves as broadband matching to 50-Ohms. The resultant measured performance of 80% efficiency or higher and flat output power over wide bandwidth (760-1060 MHz) is presented.
The shape and arrangement of the cholinergic neurons in the rabbit retina

The acetylcholine-synthesizing neurons of the rabbit retina were selectively stained by intraocular injection of the fluorescent dye 4, 6-diamidino-2-phenylindole (DAP1). Retinas were then isolated from the eye, fixed for 10-30 min with 4% paraformaldehyde, and mounted flat on the stage of a fluorescence microscope. The acetylcholine-synthesizing cells were penetrated under visual control by microelectrodes filled with lucifer yellow CH. When the dye was electrophoretically injected into the cells, complete filling of their dendrites often occurred. Cells were successfully injected as long as one month after fixation of the tissue. Complete or nearly complete filling of 281 cells was accomplished, at retinal locations systematically covering the retinal surface. The cells stained with DAPI were found to form a single morphological population. They have two to seven primary dendrites, which branch repeatedly within a narrow plane and form a round or slightly oval dendritic tree. The branching becomes very fine for the distal one third of the dendritic tree, and the dendrites there are studded with small swellings. The distal dendritic tree lies mainly within one of the two thin strata of the inner plexiform layer where acetylcholine is present. The shape and size of the dendritic tree are continuously graded across the retina ; the dendritic tree is narrower and the branching denser in the central retina, wider and sparser in the periphery. From knowledge of the population density and the shape of the neurons, one can reconstruct the array of dendrites that exists within the inner plexiform layer. The overlap of the dendritic fields is an order of magnitude greater than of any other retinal neuron previously described. Because the cells not only overlap widely but branch quite profusely, a very dense plexus of cholinergic dendrites is created.
THE NEUROLOGY OF HIV INFECTION

Since the onset of the AIDS pandemic in 1981, infection with the human immunodeficiency virus (HIV) has spread exponentially throughout the world with currently an estimated 40 million adults and children affected. Worldwide there are approximately 16 000 new infections per day. Every day 8000 HIV infected patients die. In the UK, there are currently about 50 000 individuals living with HIV/AIDS. Since the introduction of highly active anti-retroviral therapy (HAART), in communities where this is available, HIV/AIDS has become a chronic disorder with dramatic reductions in mortality and morbidity both from the effects of HIV itself as well as from opportunistic infections and tumours. In the UK, the clinician will encounter two broad groups of patients. The first group comprises individuals who have been infected with HIV for a number of years and are receiving HAART. This group is composed largely of homosexual men and those who acquired their infection in the UK. The second group consists of patients who present with opportunistic infections and tumours and who have late stage HIV infection. This is a situation that was previously encountered in the late 1980s and early 1990s. This cohort largely consists of men and women infected by heterosexual intercourse outside Europe. HIV is neuro-invasive (with invasion occurring early in the course of the infection), neuro-virulent (causing a neuropathy, myopathy, myelopathy, and dementia), but it is not especially neurotrophic. The virus is rarely isolated from neurones either in the peripheral or central nervous system. Productive infection is usually found within the associated inflammatory infiltrate, predominantly macrophages. Since all areas of the neuro-axis in an HIV infected individual may be affected by different aetiological agents, the clinical assessment of this group of patients may be more complex than assessment of the immune competent patient—the principle of “Ocam’s Razor” may not …
A Novel Approach for Untargeted Post-translational Modification Identification Using Integer Linear Optimization and Tandem Mass Spectrometry*

A novel algorithm, PILOT_PTM, has been developed for the untargeted identification of post-translational modifications (PTMs) on a template sequence. The algorithm consists of an analysis of an MS/MS spectrum via an integer linear optimization model to output a rank-ordered list of PTMs that best match the experimental data. Each MS/MS spectrum is analyzed by a preprocessing algorithm to reduce spectral noise and label potential complimentary, offset, isotope, and multiply charged peaks. Postprocessing of the rank-ordered list from the integer linear optimization model will resolve fragment mass errors and will reorder the list of PTMs based on the cross-correlation between the experimental and theoretical MS/MS spectrum. PILOT_PTM is instrument-independent, capable of handling multiple fragmentation technologies, and can address the universe of PTMs for every amino acid on the template sequence. The various features of PILOT_PTM are presented, and it is tested on several modified and unmodified data sets including chemically synthesized phosphopeptides, histone H3-(1–50) polypeptides, histone H3-(1–50) tryptic fragments, and peptides generated from proteins extracted from chromatin-enriched fractions. The data sets consist of spectra derived from fragmentation via collision-induced dissociation, electron transfer dissociation, and electron capture dissociation. The capability of PILOT_PTM is then benchmarked using five state-of-the-art methods, InsPecT, Virtual Expert Mass Spectrometrist (VEMS), Modi, Mascot, and X! Tandem. PILOT_PTM demonstrates superior accuracy on both the small and large scale proteome experiments. A protocol is finally developed for the analysis of a complete LC-MS/MS scan using template sequences generated from SEQUEST and is demonstrated on over 270,000 MS/MS spectra collected from a total chromatin digest.
Reputation Risk Management: A Corporate Social Responsibility Reporting Perspective

This paper explores one of the reputation risk management (RRM) processes through which corporate social responsibility (CSR) reporting can help companies achieve reputation gains, or at least mitigate reputation losses. The paper presents and analyzes a case study of Nippon Steel Sustainability Report 2008, which is a CSR report published by Nippon Steel Corporation (NSC). The key elements revealed in the report were (1) financial performance; (2) quality of management; (3) social and environmental responsibility performance; (4) employee quality and (5) the quality of the goods/services provided. These five elements played a crucial role in ranking companies according to their reputation scores. The paper analyzes the report with content analysis. In addition, an image restoration framework is employed in the paper. The analysis leads to two conclusions about the CSR reporting which companies can use to manage reputation risk. First, CSR reporting as a communication tool can deliver information on five elements of reputation which would enhance reputation capital. Second, some image restoration strategies are employed in CSR reporting, which implies that CSR reporting could work as part of RRM process.
Copper economy in Chlamydomonas: Prioritized allocation and reallocation of copper to respiration vs. photosynthesis

Significance Many inorganic elements, because they are required for catalysis or as structural components in biomolecules, are essential nutrients for life. In a situation of poor nutrition, organisms economize on the use of these elements by choosing alternate chemistries to achieve the same function. The mechanism of copper economy in Chlamydomonas involves replacement of copper-containing plastocyanin with heme-containing cytochrome (Cyt) c6. The copper that is saved by this substitution is used instead for Cyt oxidase biosynthesis. Copper recycling requires proteolysis of plastocyanin dependent on a copper-sensing transcription factor. A candidate protease has been identified. Inorganic elements, although required only in trace amounts, permit life and primary productivity because of their functions in catalysis. Every organism has a minimal requirement of each metal based on the intracellular abundance of proteins that use inorganic cofactors, but elemental sparing mechanisms can reduce this quota. A well-studied copper-sparing mechanism that operates in microalgae faced with copper deficiency is the replacement of the abundant copper protein plastocyanin with a heme-containing substitute, cytochrome (Cyt) c6. This switch, which is dependent on a copper-sensing transcription factor, copper response regulator 1 (CRR1), dramatically reduces the copper quota. We show here that in a situation of marginal copper availability, copper is preferentially allocated from plastocyanin, whose function is dispensable, to other more critical copper-dependent enzymes like Cyt oxidase and a ferroxidase. In the absence of an extracellular source, copper allocation to Cyt oxidase includes CRR1-dependent proteolysis of plastocyanin and quantitative recycling of the copper cofactor from plastocyanin to Cyt oxidase. Transcriptome profiling identifies a gene encoding a Zn-metalloprotease, as a candidate effecting copper recycling. One reason for the retention of genes encoding both plastocyanin and Cyt c6 in algal and cyanobacterial genomes might be because plastocyanin provides a competitive advantage in copper-depleted environments as a ready source of copper.
Genetic control of cytolytic T-lymphocyte responses. I. Ir gene control of the specificity of cytolytic T-lymphocyte responses to trinitrophenyl-modified syngeneic cells

The ability of cytotoxic T lymphocytes (CTL) induced in vitro to trinitrophenyl (TNP)-modified syngeneic cells to cross-reactively lyse a TNP allogeneic spleen target varies among inbred mouse strains. The cross-reactive CTL phenotype was found to be histocompatibility 2 (H-2) linked and to be dominant in F1 hybrid mice. All strains investigated demonstrated cross-reactivity except for some strains bearing portions of the H-2k haplotype. The gene(s) controlling this response maps to the K and/or I-A region of the H-2 complex. We have termed the immune response (Ir) gene responsible for controlling the specificity of CTL induced to TNP-modified syngeneic cells Ir-X-TNP.
Acquired Resistance of Escherichia coli to Complement Lysis by Binding of Glycophosphoinositol-Anchored Protectin (CD59)

ABSTRACT Protectin (CD59) is a glycophosphoinsitol (GPI)-anchored defender of human cells against lysis by the membrane attack complex of complement. In this study, we examined whether protectin released from human cell membranes can incorporate into the surface of gram-negative bacteria. Analysis by using radiolabeled protectin, immunofluorescence, flow cytometry, and whole-cell enzyme-linked immunosorbent assay demonstrated that protectin bound to nonencapsulated Escherichia coli EH237 (Re) and EH234 (Ra) in a calcium-dependent manner. The incorporation required the GPI-phospholipid moiety since no binding of a phospholipid-free soluble form of protectin was observed. Mg2+ did not enhance the binding, and a polysialic acid capsule prevented it (strain IH3080 [O18:K1:H8]). Bound protectin inhibited the C5b-9 neoantigen expression on complement-treated bacteria. Protection against complement lysis was observed in both a colony counting assay and a bioluminescence assay, where viable EH234 bacteria expressing the luciferase gene emitted green light in the presence of the luciferine substrate. In general, two- to four-times-higher serum concentrations were needed to obtain 50% lysis of protectin-coated versus noncoated bacteria. The results indicate that protectin can incorporate in a functionally active form into the cell membranes of the two nonencapsulated deep rough E. coli strains studied.