Universality of Critical Dynamics with Finite Entanglement.

When a system is swept through a quantum critical point, the quantum Kibble-Zurek mechanism makes universal predictions for quantities such as the number and energy of excitations produced. This mechanism is now being used to obtain critical exponents on emerging quantum computers and emulators, which in some cases can be compared to matrix product state (MPS) numerical studies. However, the mechanism is modified when the divergence of entanglement entropy required for a faithful description of many quantum critical points is not fully captured by the experiment or classical calculation. In this Letter, we study how low-energy dynamics of quantum systems near criticality are modified by finite entanglement, using conformally invariant critical points described approximately by a MPS as an example. We derive that the effect of finite entanglement on a Kibble-Zurek process is captured by a dimensionless scaling function of the ratio of two length scales, one determined dynamically and one by the entanglement restriction. Numerically we confirm first that dynamics at finite bond dimension χ is independent of the algorithm chosen, then obtain scaling collapses for sweeps in the transverse field Ising model and the three-state Potts model. Our result establishes the precise role played by entanglement in time-dependent critical phenomena and has direct implications for quantum state preparation and classical simulation of quantum states.

Leveraging metabolic modeling to identify functional metabolic alterations associated with COVID-19 disease severity.

OBJECTIVE: Since the COVID-19 pandemic began in early 2020, SARS-CoV2 has claimed more than six million lives world-wide, with over 510 million cases to date. To reduce healthcare burden, we must investigate how to prevent non-acute disease from progressing to severe infection requiring hospitalization. METHODS: To achieve this goal, we investigated metabolic signatures of both non-acute (out-patient) and severe (requiring hospitalization) COVID-19 samples by profiling the associated plasma metabolomes of 84 COVID-19 positive University of Virginia hospital patients. We utilized supervised and unsupervised machine learning and metabolic modeling approaches to identify key metabolic drivers that are predictive of COVID-19 disease severity. Using metabolic pathway enrichment analysis, we explored potential metabolic mechanisms that link these markers to disease progression. RESULTS: Enriched metabolites associated with tryptophan in non-acute COVID-19 samples suggest mitigated innate immune system inflammatory response and immunopathology related lung damage prevention. Increased prevalence of histidine- and ketone-related metabolism in severe COVID-19 samples offers potential mechanistic insight to musculoskeletal degeneration-induced muscular weakness and host metabolism that has been hijacked by SARS-CoV2 infection to increase viral replication and invasion. CONCLUSIONS: Our findings highlight the metabolic transition from an innate immune response coupled with inflammatory pathway inhibition in non-acute infection to rampant inflammation and associated metabolic systemic dysfunction in severe COVID-19.

The timing of molecular and morphological changes underlying reproductive transitions in wild tomatoes (Solanum sect. Lycopersicon).

Molecular mechanisms underlying the transition from genetic self-incompatibility to self-compatibility are well documented, but the evolution of other reproductive trait changes that accompany shifts in reproductive strategy (mating system) remains comparatively under-investigated. A notable exception is the transition from exserted styles to styles with recessed positions relative to the anthers in wild tomatoes (Solanum Section Lycopersicon). This phenotypic change has been previously attributed to a specific mutation in the promoter of a gene that influences style length (style2.1); however, whether this specific regulatory mutation arose concurrently with the transition from long to short styles, and whether it is causally responsible for this phenotypic transition, has been poorly investigated across this group. To address this gap, we assessed 74 accessions (populations) from 13 species for quantitative genetic variation in floral and reproductive traits as well as the presence/absence of deletions at two different locations (StyleD1 and StyleD2) within the regulatory region upstream of style2.1. We confirmed that the putatively causal deletion variant (a 450-bp deletion at StyleD1) arose within self-compatible lineages. However, the variation and history of both StyleD1 and StyleD2 was more complex than previously inferred. In particular, although StyleD1 was statistically associated with differences in style length and stigma exsertion across all species, we found no evidence for this association within two species polymorphic for the StyleD1 mutation. We conclude that the previous association detected between phenotypic and molecular differences is most likely due to a phylogenetic association rather than a causal mechanistic relationship. Phenotypic variation in style length must therefore be due to other unexamined linked variants in the style2.1 regulatory region.

Towards effective phosphorus recycling from wastewater: quantity and quality.

Precipitation in the Mg-Ca-NH3-PO4 system has been explored to improve understanding of likely phases recoverable from complex wastewaters. Over a range of Mg/Ca combinations (0-100%) and pH 5-11, at least seven identifiable crystalline phases could be precipitated from artificial wastewater including: struvite, hydroxylapatite, newberyite, brushite, merrilite/whitlockite, octocalcium phosphate, and monetite. This experimental study has outlined the physicochemical conditions required to produce various phosphate products from synthetic wastewater, and found that large differences exist between experimentally formed phases and thermodynamical predictions. Struvite formation is the most desirable precipitate for the recovery of phosphate based upon purity, growth characteristics, dewatering properties, phosphate removal efficiency, and its ability to simultaneously remove ammonia. This study has also demonstrated that in specific cases the preliminary precipitation of brushite is a possible means of decreasing calcium content such that subsequent struvite formation could achieve higher-purity. Utilising experimental results and information on current commodity prices, discussion on the choice of Mg and Ca sources for phosphorus recovery provides guidance on appropriate means to optimise the formation and yield of high quality cost-optimised products.

The current use of neuromodulation for bladder dysfunction.

Neuromodulation utilizes electrical stimulation to alter the function of an organ. Recent advances in technology and improved knowledge of micturition physiology have coincided with the growth of neuromodulation for the treatment of urinary urgency/frequency, urge incontinence and non-obstructive urinary retention. Currently, the most common modality for bladder neuromodulation involves stimulation through the S3 foramen, or sacral neuromodulation. This review will highlight the current indications, patients selection, implantation options/techniques, outcomes and complications of sacral neuromodulation. In addition, other methods of neuromodulation will be discussed.

Purification and characterization of an esterase isozyme involved in hydrolysis of organophosphorus compounds from an insecticide resistant pest, Helicoverpa armigera (Lepidoptera: Noctüidae).

An esterase isozyme was purified from the insecticide resistant pest, Helicoverpa armigera collected from field crops. Purification involved ammonium sulfate precipitation, hydrophobic interaction and ion exchange chromatography followed by gel filtration chromatography. The purification was 212-fold with 1% yield of the enzyme. The optimum pH of the isozyme was found to be 10.5 and 8.5 for p-nitrophenyl phosphate and paraoxon, respectively. The enzyme was unstable at temperature >50 degrees C. The molecular mass determined by SDS-PAGE was 66 kDa. Cations such as Hg(+2), Ag(+2), Cd(+2) inhibited the activity while Zn(+2) stimulated it. Kinetic studies indicated that the enzyme had low K(m) values of 0.238 and 0.348 mM for p-nitrophenyl phosphate and paraoxon, respectively. The enzyme had broad substrate specificity with high K(m) values for ATP, ADP and beta-glycerophosphate. This enzyme was partially sequenced and identified as an alkaline phosphatase.

Evidence for paternal transmission and heteroplasmy in the mitochondrial genome of Silene vulgaris, a gynodioecious plant.

Gynodioecy refers to the co-occurrence of females and hermaphrodites in the same population. In many gynodioecious plants, sex is determined by an epistatic interaction between mitochondrial and nuclear genes, resulting in intragenomic evolutionary conflict, should the mitochondrial genome be maternally inherited. While maternal inheritance of the mitochondrial genome is common in angiosperms, few gynodioecious species have been studied. Here, the inheritance of the mitochondrial genes atpA and coxI was studied in 318 Silene vulgaris individuals distributed among 23 crosses. While maternal inheritance was indicated in 96% of the individuals studied, one or more individuals from each of four sib groups displayed a genotype that was identical to the father, or that did not match either parent. Given evidence that inheritance is not strictly maternal, it was hypothesized that some individuals could carry a mixture of maternally and paternally derived copies of the mitochondrial genome, a condition known as heteroplasmy. Since heteroplasmy might be difficult to detect should multiple versions of the mitochondrial genome co-occur in highly unequal copy number, a method was devised to amplify low-copy number forms of atpA differentially. Evidence for heteroplasmy was found in 23 of the 99 individuals studied, including cases in which the otherwise cryptic form of atpA matched the paternal genotype. The distribution of shared nucleotide sequence polymorphism among atpA haplotypes and the results of a population survey of the joint distribution of atpA and coxI haplotypes across individuals supports the hypothesis that heteroplasmy facilitates formation of novel mitochondrial genotypes by recombination.

Comparison of finasteride and alpha-blockers as independent risk factors for erectile dysfunction.

There are insufficient data on the effects of alpha-blockers and finasteride on erectile function in men who have other risk factors for erectile dysfunction (ED). This study was conducted to compare the relative effects of these medications on ED in men who may be on other medications or have other risk factors for ED. Patients attending urology and primary care clinics were asked to complete an IRB-approved questionnaire that combined the validated Sexual Health Inventory for Men (SHIM) and a detailed medical history. A total of 123 patients completed the questionnaire. The age range was 28-88 years (mean: 68 years). Eighty-one per cent of patients had SHIM scores <21, indicating some degree of ED. The average SHIM scores in a population of patients with similar age and risk factors who had been on finasteride or alpha-blockers indicated the presence of ED but did not reveal a significant difference between the two groups. The scores were no different from an age-matched group of patients who were not on either medication, demonstrating the relatively greater importance of various other risk factors for ED. There was an inverse linear relationship between the number of ED risk factors and SHIM scores. There does not appear to be a significant difference between alpha-blockers and finasteride as independent risk factors for ED. Age and other risk factors (heart disease, diabetes, hypertension, smoking, and hypercholesterolaemia) tend to have a much stronger influence on the severity of ED as assessed by SHIM scores.

Disgust sensitivity and attitudes toward organ donation among African-American college students.

241 African-American college students (94 men and 147 women, mean age = 20.3 +/- 3.4 yr.) completed the 1994 Disgust Scale of Haidt, McCauley, and Rozin and a modified form of Parisi-Rizzo's 1987 Attitudes Toward Organ Donation Scale (negative subscale only) as well as a behavioral measure of intention to donate organs after death. Analyses indicated that the higher the disgust sensitivity, the more negative the attitude toward organ donation and the less likely the student was to indicate intent to donate organs. It was further shown that negative attitudes toward organ donation mediated the relationship between disgust sensitivity and the behavioral intention measure. Results highlight the complexity of the issues surrounding organ donation within an African-American population and provide additional empirical evidence for the development of a theoretical model to explain the organ donation phenomenon.

Bucillamine prevents myocardial reperfusion injury.

Injury during reperfusion can partially offset the benefit of relief of ischemia in myocardial infarctions rapidly treated with thrombolytic drugs or angioplasty. We assessed whether bucillamine (N-[2-mercapto-2-methylpropionyl]-L-cysteine) is potentially useful to treat myocardial reperfusion injury. Bucillamine is a potent sulfhydryl donor not previously tested as a treatment of reperfusion injury. Cardiac myocytes were exposed to hydrogen peroxide or a xanthine/xanthine oxidase system resulting in injury-induced release of lactate dehydrogenase. Bucillamine (125-500 microM) prevented lactate dehydrogenase release in a concentration-dependent manner. Bucillamine, which has two donatable thiol groups, was twice as protective as N-2-mercaptopropionyl glycine, which contains a single donatable thiol group. Dogs were then exposed to 90 min of coronary artery occlusion and 48 h of reperfusion before sacrifice. Beginning at the onset of reperfusion, bucillamine, 11 or 22 mg/kg per hour, or vehicle (saline) was administered intravenously for 3 h. There was a dose-related response to bucillamine for infarct size, normalized for size of the region at risk and adjusted for collateral blood flow to the ischemic region. Infarct size was reduced by 41% in the group treated with bucillamine 22 mg/kg per hour, compared with the vehicle group. Bucillamine, probably through an antioxidant mechanism, reduced infarct size when administered during reperfusion.

High-molecular-mass receptors for ammodytoxin in pig are tissue-specific isoforms of M-type phospholipase A(2) receptor.

Studying the molecular basis of presynaptic neurotoxicity of ammodytoxin C, a secretory phospholipase A(2) from the venom of Vipera a. ammodytes snake, we demonstrated the existence of two high-molecular-mass ammodytoxin C-binding proteins in porcine tissues, one in cerebral cortex and the other in liver. These proteins differ considerably in stability and Western blotting properties. However, as shown by immunological analysis and tandem mass spectrometry sequencing of several internal peptides derived from the purified receptors, both belong to secretory phospholipase A(2) receptors of the M type, which are Ca(2+)-dependent multilectins homologous to the macrophage mannose receptor. Based on Southern blot analysis of genomic DNA and deglycosylation of the receptors, the difference between the two proteins most likely stems from the different posttranscriptional and posttranslational modifications of a single gene product. Our findings raise the possibility that the M-type receptors for secretory phospholipases A(2) may display different physiological properties in different tissues.

Laparoscopic removal of an abdominal extralobar pulmonary sequestration.

Extralobar pulmonary sequestrations are rare congenital anomalies that fall into the spectrum of broncho-pulmonary-foregut malformations. The authors describe the laparoscopic removal of an infradiaphragmatic sequestration. The lesion initially presented as a suprarenal mass on antenatal ultrasonographic images. The mass was confirmed on postnatal ultrasonography and computer tomographic scanning. It was followed by magnetic resonance imaging until the patient was 28 months old, at which point it was resected. A review of the literature indicates that infradiaphragmatic sequestrations are readily detectable on antenatal ultrasonographic studies. Advances in imaging technology have made it possible in most cases to distinguish sequestrations from other suprarenal masses including neuroblastomas. However, resection provides a definitive diagnosis and remains the treatment of choice. A laparoscopic approach offers the additional benefits associated with minimally invasive techniques.

Co-localization of the inositol 1,4,5-trisphosphate receptor and calreticulin in the equatorial segment and in membrane bounded vesicles in the cytoplasmic droplet of human spermatozoa.

Modulation of the intracellular calcium concentration within mammalian spermatozoa is important in several pre-fertilization events including hyperactivated motility and the acrosome reaction. To identify calcium binding proteins (CBP) potentially regulating these processes, a (45)Ca overlay technique was employed on 2-D blots of human sperm extracts. Microsequencing by Edman degradation and CAD mass spectrometry identified a relatively abundant 60.5 kDa CBP with a pI of 4.2 as calreticulin (CRT). Immunofluorescent labelling with anti-CRT antibodies localized CRT to the acrosome, with highest fluorescence in the equatorial segment, and in the cytoplasmic droplets of 94 and 48% of human spermatozoa respectively. Double immunolabelling experiments demonstrated co-localization of CRT and the inositol 1,4,5-trisphosphate receptor (IP(3)R) in the acrosome, in the equatorial segment, and vesicular structures in the cytoplasmic droplets of the neck region. Electron microscopic immunogold labelling localized CRT to the equatorial segment of acrosome-reacted spermatozoa and to membrane-enclosed vesicles within the cytoplasmic droplet of both acrosome-intact and acrosome-reacted spermatozoa. Localization of the IP(3) receptor to the CRT-containing vesicles, in the sperm neck and to the acrosome, suggests that capacitative calcium entry in human spermatozoa may be regulated from these putative calcium storage sites.

Differential extraction and enrichment of human sperm surface proteins in a proteome: identification of immunocontraceptive candidates.

The objective of this study was to discover previously unknown human sperm surface proteins that may be candidate contraceptive vaccinogens. To this end, methods of concentrating human sperm proteins for microsequencing by mass spectrometry were used, which increased the likelihood of identifying surface proteins. Vectorial labeling, differential extraction and two-dimensional (2-D) gel electrophoresis were employed to identify and isolate proteins accessible at the cell surface. Percoll harvested or swim-up sperm were either solubilized directly or solubilized after surface labeling with sulfo-succinimidyl-6-(biotinamido)hexanoate (sulfo-NHS-LC-biotin). Comparisons were made of proteins extracted with four lysis buffers: (i) Celis buffer containing 9.8 M urea and 2% Igepal CA-630; (ii) 1% Triton X (TX)-100; (iii) 1.7% TX-114 followed by phase partitioning; or (iv) 1 M NaCl. Blots of proteins separated by high-resolution 2-D electrophoresis were probed with avidin and antibodies to known proteins specific for three domains: the sperm surface (SAGA-1), the acrosome (SP-10), and the cytoskeleton (alpha-tubulin). Celis buffer (45 min) extracted proteins from all three major compartments. However, a 20-s extraction in Celis buffer enriched for several proteins and enabled the identification of several novel peptides by mass spectrometry. Mild extraction with TX-100 or 1 M NaCl solubilized mainly membrane and acrosomal proteins, but not cytoskeletal proteins. Comparison of biotinylated proteins extracted by each method showed that the major vectorially labeled proteins solubilized by Celis buffer were also solubilized by TX-100, TX-114, and 1 M NaCl. Extraction with TX-114 followed by phase-partitioning significantly enriched hydrophobic surface proteins and aided resolution and isolation. Eight protein spots microsequenced following all these extraction methods proved to be novel sperm molecules.

Proteolytic processing of the human T-cell lymphotropic virus 1 reverse transcriptase: identification of the N-terminal cleavage site by mass spectrometry.

Human T-cell lymphotropic virus 1 (HTLV-1) is a type C human retrovirus, which is the causative agent of Adult T-cell Leukemia and other diseases. The reverse transcriptase of HTLV-1 (E.C. 2.7.7.49) is synthesized as part of a Gag--Pro--Pol precursor protein, and the mature Gag, Pro, and Pol proteins, including the reverse transcriptase, are created by proteolytic processing catalyzed by the viral protease. The location of the proteolytic cleavage site, which creates the N-terminus of mature HTLV-1 reverse transcriptase, has not been previously identified. By using sequence comparisons of several retroviral polymerases, as well as information about the location of the ribosomal frameshift, we tentatively identified this N-terminal processing site. PCR amplification was used to construct a clone, which spans a region of the pro--pol junction of HTLV-1, to produce a recombinant Pro--Pol protein spanning the locations of those cleavage sites proposed by others as well as the one identified by our sequence alignment. Cleavage of the recombinant Pro--Pol protein by HTLV-1 protease generated a 5.5-kDa fragment. Analysis of this fragment by capillary LC-MS and MS/MS revealed the N-terminal cleavage site to be between Leu(147)--Pro(148) of the pro ORF. This is the first physical identification of the authentic amino acid sequence of the reverse transcriptase of HTLV-1. The data reported here provides a basis for further investigation of the function and structural aspects of protein-nucleic interaction.

Outer dense fiber proteins are dominant postobstruction autoantigens in adult Lewis rats.

Obstruction of the male reproductive tract commonly results in generation of antisperm autoantibodies. However, only a few of the sperm autoantigens recognized by these antibodies have been characterized. To identify postobstruction rat sperm autoantigens, sperm proteins were separated by two-dimensional(2-D) gel electrophoresis. Spots corresponding to proteins that were stained by at least 50% of postvasectomy rat sera on 2-D Western blots were removed from polyacrylamide gels and microsequenced by tandem mass spectrometry. From a total of 21 spots, 12 contained peptides that matched solely to either of two outer dense fiber proteins, odf1 or odf2. Six additional spots contained peptides comprising odf1 or odf2 and were accompanied by peptides representing other proteins. Only three spots lacked outer dense fiber peptides but did contain sequences of other known proteins. The results indicate that the outer dense fiber proteins odf1 and odf2 are dominant postobstruction autoantigens because they were detected in the majority of the immunoreactive protein spots examined. Possible explanations for this observation include the abundance of outer dense fiber proteins in spermatozoa, slow solubility, which may provide a sustained supply of antigen, and testis-specific expression during spermiogenesis.

A high affinity acceptor for phospholipase A2 with neurotoxic activity is a calmodulin.

One of the high affinity binding proteins for ammodytoxin C, a snake venom presynaptically neurotoxic phospholipase A(2), has been purified from porcine cerebral cortex and characterized. After extraction from the membranes, the toxin-binding protein was isolated in a homogenous form using wheat germ lectin-Sepharose, Q-Sepharose, and ammodytoxin-CH-Sepharose chromatography. The specific binding of (125)I-ammodytoxin C to the isolated acceptor was inhibited to different extents by some neurotoxic phospholipases A(2), ammodytoxins, bee venom phospholipase A(2), agkistrodotoxin, and crotoxin; but not by nontoxic phospholipases A(2), ammodytin I(2), porcine pancreatic phospholipase A(2), and human type IIA phospholipase A(2); suggesting the significance of the acceptor in the mechanism of phospholipase A(2) neurotoxicity. The isolated acceptor was identified as calmodulin by tandem mass spectrometry. Since calmodulin is generally considered as an intracellular protein, the identity of this acceptor supports the view that secretory phospholipase A(2) neurotoxins have to be internalized to exert their toxic effect. Moreover, since ammodytoxin is known to block synaptic transmission, its interaction with calmodulin as an acceptor may constitute a valuable probe for further investigation of the role of the latter in this Ca(2+)-regulated process.

Pseudomonas aeruginosa and a proteomic approach to bacterial pathogenesis.

Pseudomonas aeruginosa is a Gram-negative bacterium that is ubiquitous in the environment and can cause a variety of diseases in compromised patients. The genome of P. aeruginosa strain PAO1 has been reported to contain 5570 potential proteins. The value of this genomic database is that new proteins can be recognized to use as diagnostic markers, novel drug targets, and to better understand the physiology of this organism. However, similar to what has been observed in other sequenced bacterial genomes, approximately one third of the potential proteins have no known function. This is somewhat surprising given the long-standing interest in P. aeruginosa as an opportunistic pathogen. Obviously new tools, in addition to sequence similarity analysis, are needed to determine the role of these proteins. Proteomics using two-dimensional gel electrophoresis followed by mass spectrometry to detect and identify P. aeruginosa proteins represents a novel approach to address this gap.

Fingerprinting Trichoderma reesei hydrolases in a commercial cellulase preparation.

Polysaccharide degrading enzymes from commercial T. reesei broth have been subjected to "fingerprint" analysis by high-resolution 2-D gel electrophoresis. Forty-five spots from 11 x 25 cm Pharmacia gels have been analyzed by LC-MS/MS and the resulting peptide sequences were compared to existing databases. Understanding the roles and relationships of component enzymes from the T. reesei cellulase system acting on complex substrates is key to the development of efficient artificial cellulase systems for the conversion of lignocellulosic biomass to sugars. These studies suggest follow-on work comparing induced and noninduced T. reesei cells at the proteome level, which may elucidate substrate-specific gene regulation and response.

A decade of experience with the primary pull-through for hirschsprung disease in the newborn period: a multicenter analysis of outcomes.

OBJECTIVE: To determine whether use of a primary pull-through would result in equivalent perioperative and long-term complications compared with the two-stage approach. SUMMARY BACKGROUND DATA: During the past decade, the authors have advanced the use of a primary pull-through for Hirschsprung disease in the newborn, and preliminary results have suggested excellent outcomes. METHODS: From May 1989 through September 1999, 78 infants underwent a primary endorectal pull-through (ERPT) procedure at four pediatric surgical sites. Data were collected from medical records and a parental telephone interview (if the child was older than 3 years) to assess stooling patterns. A similar group of patients treated in a two-stage fashion served as a historical control. RESULTS: Mean age at the time of ERPT was 17.8 days of life. Comparing primary ERPT with a two-stage approach showed a trend toward a higher incidence of enterocolitis in the primary ERPT group compared with those with a two-stage approach (42.0% vs. 22.0%). Other complications were either lower in the primary ERPT group or similar, including rate of soiling and development of a bowel obstruction. Median number of stools per day was two at a mean follow-up of 4.1 +/- 2.5 years, with 83% having three or fewer stools per day. CONCLUSIONS: Performance of a primary ERPT for Hirschsprung disease in the newborn is an excellent option. Results were comparable to those of the two-stage procedure. The greater incidence of enterocolitis appears to be due to a lower threshold in diagnosing enterocolitis in more recent years.