The Implementation of Bankruptcy Code Section 707(b): The Law and the Reality

The introduction of section 707(b) to the bankruptcy code has raised many difficult interpretational issues. This article focuses on those issues concerning the implementation of section 707(b). Under the law, only the courts and the U.S. Trustees are permitted to raise the issue of substantial abuse. Therefore, to determine how section 707(b) is actually being administered, a survey was distributed to the U.S. Bankruptcy Courts and the U.S. Trustees. The results of the survey are integrated into a discussion of the current status of the law and presented in this article. This analysis identifies serious shortcomings with the law that can only be remedied through congressional action. The article concludes with a proposal for solving the problems created by section 707(b)

The Red Flour Beetle as a Model for Bacterial Oral Infections

Experimental infection systems are important for studying antagonistic interactions and coevolution between hosts and their pathogens. The red flour beetle Tribolium castaneum and the spore-forming bacterial insect pathogen Bacillus thuringiensis (Bt) are widely used and tractable model organisms. However, they have not been employed yet as an efficient experimental system to study host-pathogen interactions. We used a high throughput oral infection protocol to infect T. castaneum insects with coleopteran specific B. thuringiensis bv. tenebrionis (Btt) bacteria. We found that larval mortality depends on the dietary spore concentration and on the duration of exposure to the spores. Furthermore, differential susceptibility of larvae from different T. castaneum populations indicates that the host genetic background influences infection success. The recovery of high numbers of infectious spores from the cadavers indicates successful replication of bacteria in the host and suggests that Btt could establish infectious cycles in T. castaneum in nature. We were able to transfer plasmids from Btt to a non-pathogenic but genetically well-characterised Bt strain, which was thereafter able to successfully infect T. castaneum, suggesting that factors residing on the plasmids are important for the virulence of Btt. The availability of a genetically accessible strain will provide an ideal model for more in-depth analyses of pathogenicity factors during oral infections. Combined with the availability of the full genome sequence of T. castaneum, this system will enable analyses of host responses during infection, as well as addressing basic questions concerning host-parasite coevolution

The Incidence of Highly-Obscured Star-Forming Regions in SINGS Galaxies

Using the new capabilities of the Spitzer Space Telescope and extensive multiwavelength data from the Spitzer Infrared Nearby Galaxies Survey (SINGS), it is now possible to study the infrared properties of star formation in nearby galaxies down to scales equivalent to large HII regions. We are therefore able to determine what fraction of large, infrared-selected star-forming regions in normal galaxies are highly obscured and address how much of the star formation we miss by relying solely on the optical portion of the spectrum. Employing a new empirical method for deriving attenuations of infrared-selected star-forming regions we investigate the statistics of obscured star formation on 500pc scales in a sample of 38 nearby galaxies. We find that the median attenuation is 1.4 magnitudes in H-alpha and that there is no evidence for a substantial sub-population of uniformly highly-obscured star-forming regions. The regions in the highly-obscured tail of the attenuation distribution (A_H-alpha > 3) make up only ~4% of the sample of nearly 1800 regions, though very embedded infrared sources on the much smaller scales and lower luminosities of compact and ultracompact HII regions are almost certainly present in greater numbers. The highly-obscured cases in our sample are generally the bright, central regions of galaxies with high overall attenuation but are not otherwise remarkable. We also find that a majority of the galaxies show decreasing radial trends in H-alpha attenuation. The small fraction of highly-obscured regions seen in this sample of normal, star-forming galaxies suggests that on 500pc scales the timescale for significant dispersal or break up of nearby, optically-thick dust clouds is short relative to the lifetime of a typical star-forming region.Comment: Accepted for publication in ApJ; emulateapj style, 30 pages, 18 figures (compressed versions), 3 table

Fast index based algorithms and software for matching position specific scoring matrices

BACKGROUND: In biological sequence analysis, position specific scoring matrices (PSSMs) are widely used to represent sequence motifs in nucleotide as well as amino acid sequences. Searching with PSSMs in complete genomes or large sequence databases is a common, but computationally expensive task. RESULTS: We present a new non-heuristic algorithm, called ESAsearch, to efficiently find matches of PSSMs in large databases. Our approach preprocesses the search space, e.g., a complete genome or a set of protein sequences, and builds an enhanced suffix array that is stored on file. This allows the searching of a database with a PSSM in sublinear expected time. Since ESAsearch benefits from small alphabets, we present a variant operating on sequences recoded according to a reduced alphabet. We also address the problem of non-comparable PSSM-scores by developing a method which allows the efficient computation of a matrix similarity threshold for a PSSM, given an E-value or a p-value. Our method is based on dynamic programming and, in contrast to other methods, it employs lazy evaluation of the dynamic programming matrix. We evaluated algorithm ESAsearch with nucleotide PSSMs and with amino acid PSSMs. Compared to the best previous methods, ESAsearch shows speedups of a factor between 17 and 275 for nucleotide PSSMs, and speedups up to factor 1.8 for amino acid PSSMs. Comparisons with the most widely used programs even show speedups by a factor of at least 3.8. Alphabet reduction yields an additional speedup factor of 2 on amino acid sequences compared to results achieved with the 20 symbol standard alphabet. The lazy evaluation method is also much faster than previous methods, with speedups of a factor between 3 and 330. CONCLUSION: Our analysis of ESAsearch reveals sublinear runtime in the expected case, and linear runtime in the worst case for sequences not shorter than | [Formula: see text] |(m )+ m - 1, where m is the length of the PSSM and [Formula: see text] a finite alphabet. In practice, ESAsearch shows superior performance over the most widely used programs, especially for DNA sequences. The new algorithm for accurate on-the-fly calculations of thresholds has the potential to replace formerly used approximation approaches. Beyond the algorithmic contributions, we provide a robust, well documented, and easy to use software package, implementing the ideas and algorithms presented in this manuscript

Infection routes matter in population-specific responses of the red flour beetle to the entomopathogen Bacillus thuringiensis

Background: Pathogens can infect their hosts through different routes. For studying the consequences for host resistance, we here used the entomopathogen Bacillus thuringiensis and the red flour beetle Tribolium castaneum for oral and systemic (i. e. pricking the cuticle) experimental infection. In order to characterize the molecular mechanisms underpinning the two different infection routes, the transcriptomes of beetles of two different T. castaneum populations – one recently collected population (Cro1) and a commonly used laboratory strain (SB) – were analyzed using a next generation RNA sequencing approach. Results: The genetically more diverse population Cro1 showed a significantly larger number of differentially expressed genes. While both populations exhibited similar reactions to pricking, their expression patterns in response to oral infection differed remarkably. In particular, the Cro1 population showed a strong response of cuticular proteins and developmental genes, which might indicate an adaptive developmental flexibility that was lost in the SB population presumably as a result of inbreeding. The immune response of SB was primarily based on antimicrobial peptides, while Cro1 relied on responses mediated by phenoloxidase and reactive oxygen species, which may explain the higher resistance of this strain against oral infection. Conclusions: Our data demonstrate that immunological and physiological processes underpinning the two different routes of infection are clearly distinct, and that host populations particularly differ in responses to oral infection. Furthermore, gene expression upon pricking infection entailed a strong signal of wounding, highlighting the importance of pricking controls in future infection studies

Monomer-on-Monomer (MoM) Mitsunobu Reaction: Facile Purification Utilizing Surface-Initiated Sequestration

A monomer-on-monomer (MoM) Mitsunobu reaction utilizing norbornenyl-tagged (Nb-tagged) reagents is reported, whereby purification was rapidly achieved by employing ring-opening metathesis polymerization which is initiated by any of three methods utilizing Grubbs catalyst (i) free catalyst in solution, (ii) surface-initiated catalyst-armed silica or (iii) surface-initiated catalyst-armed Co/C magnetic nanoparticles

Phenotypic dissection of the mouse Ren-1(d) knockout by complementation with human renin

Normal renin synthesis and secretion is important for the maintenance of juxtaglomerular apparatus architecture. Mice lacking a functional Ren-1d gene are devoid of renal juxtaglomerular cell granules and exhibit an altered macula densa morphology. Due to the species-specificity of renin activity, transgenic mice are ideal models for experimentally investigating and manipulating expression patterns of the human renin gene in a native cellular environment without confounding Renin-angiotensin-system interactions. A 55 kb transgene encompassing the human renin locus was crossed onto the mouse Ren-1d-null background, restoring granulation in juxtaglomerular cells.  Correct processing of human renin in dense core granules was confirmed by immunogold labelling. After stimulation of the renin-angiotensin system, juxtaglomerular cells contained rhomboid protogranules with paracrystalline contents, dilated rough endoplasmic reticulum and electron-lucent granular structures. However, complementation of Ren-1d-/- mice with human renin was unable to rescue the abnormality seen in macula densa structure. The juxtaglomerular apparatus was still able to respond to tubuloglomerular feedback in isolated perfused juxtaglomerular apparatus preparations, although minor differences in glomerular tuft contractility and macula densa cell calcium handling were observed. This study reveals that the human renin protein is able to complement the mouse Ren-1d-/- non-granulated defect and suggests that granulopoiesis requires a structural motif that is conserved between the mouse Ren-1d and human renin proteins. It also suggests that the altered macula densa phenotype is related to the activity of the renin-1d enzyme in a local juxtaglomerular renin-angiotensin system

Evaluation of the zucker diabetic fatty (ZDF) rat as a model for human disease based on urinary peptidomic profiles

Representative animal models for diabetes-associated vascular complications are extremely relevant in assessing potential therapeutic drugs. While several rodent models for type 2 diabetes (T2D) are available, their relevance in recapitulating renal and cardiovascular features of diabetes in man is not entirely clear. Here we evaluate at the molecular level the similarity between Zucker diabetic fatty (ZDF) rats, as a model of T2D-associated vascular complications, and human disease by urinary proteome analysis. Urine analysis of ZDF rats at early and late stages of disease compared to age- matched LEAN rats identified 180 peptides as potentially associated with diabetes complications. Overlaps with human chronic kidney disease (CKD) and cardiovascular disease (CVD) biomarkers were observed, corresponding to proteins marking kidney damage (eg albumin, alpha-1 antitrypsin) or related to disease development (collagen). Concordance in regulation of these peptides in rats versus humans was more pronounced in the CVD compared to the CKD panels. In addition, disease-associated predicted protease activities in ZDF rats showed higher similarities to the predicted activities in human CVD. Based on urinary peptidomic analysis, the ZDF rat model displays similarity to human CVD but might not be the most appropriate model to display human CKD on a molecular level

Incorporating multiple sets of eQTL weights into gene-by-environment interaction analysis identifies novel susceptibility loci for pancreatic cancer.

It is of great scientific interest to identify interactions between genetic variants and environmental exposures that may modify the risk of complex diseases. However, larger sample sizes are usually required to detect gene-by-environment interaction (G × E) than required to detect genetic main association effects. To boost the statistical power and improve the understanding of the underlying molecular mechanisms, we incorporate functional genomics information, specifically, expression quantitative trait loci (eQTLs), into a data-adaptive G × E test, called aGEw. This test adaptively chooses the best eQTL weights from multiple tissues and provides an extra layer of weighting at the genetic variant level. Extensive simulations show that the aGEw test can control the Type 1 error rate, and the power is resilient to the inclusion of neutral variants and noninformative external weights. We applied the proposed aGEw test to the Pancreatic Cancer Case-Control Consortium (discovery cohort of 3,585 cases and 3,482 controls) and the PanScan II genome-wide association study data (replication cohort of 2,021 cases and 2,105 controls) with smoking as the exposure of interest. Two novel putative smoking-related pancreatic cancer susceptibility genes, TRIP10 and KDM3A, were identified. The aGEw test is implemented in an R package aGE.We thank the two anonymous reviewers for their constructive comments. This research was supported by the National Institutes of Health (NIH) grant R01CA169122; P.W. was supported by NIH grants R01HL116720 and R21HL126032. S.H.O. was supported by NIH grant P30CA008748. R.E.N. and the Queensland Pancreatic Cancer Study were funded by the Australian National Health and Medical Research Council. The authors thank Ms. Jessica Swann and the National Institute of Statistical Sciences writing workshop for editorial assistance and suggestions. The authors acknowledge the Texas Advanced Computing Center at The University of Texas at Austin for providing computing resources. The authors alone are responsible for the views expressed in this article and they do not necessarily represent the views, decisions or policies of the institutions with which they are affiliated. The authors declare that there is no conflict of interest

Menstrual And Reproductive Factors, Hormone Use, And Risk Of Pancreatic Cancer: Analysis From The International Pancreatic Cancer Case-control Consortium (Panc4)

Objectives: We aimed to evaluate the relation between menstrual and reproductive factors, exogenous hormones, and risk of pancreatic cancer (PC). Methods: Eleven case-control studies within the International Pancreatic Cancer Case-control Consortium took part in the present study, including in total 2838 case and 4748 control women. Pooled estimates of odds ratios (ORs) and their 95% confidence intervals (CIs) were calculated using a 2-step logistic regression model and adjusting for relevant covariates. Results: An inverse OR was observed in women who reported having had hysterectomy (ORyesvs.no, 0.78; 95% CI, 0.67-0.91), remaining significant in postmenopausal women and never-smoking women, adjusted for potential PC confounders. A mutually adjusted model with the joint effect for hormone replacement therapy (HRT) and hysterectomy showed significant inverse associations with PC in women who reported having had hysterectomy with HRT use (OR, 0.64; 95% CI, 0.48-0.84). Conclusions: Our large pooled analysis suggests that women who have had a hysterectomy may have reduced risk of PC. However, we cannot rule out that the reduced risk could be due to factors or indications for having had a hysterectomy. Further investigation of risk according to HRT use and reason for hysterectomy may be necessary