bluuebunny/crossref_metadata_2025 huggingface dataset:
Improvements in a Non-Proprietary Radiometric Medium to Allow the Detection of Some
Pseudomonas
Species and
Alcaligenes faecalis
Authors: Previte Joseph J. , Rowley D. B. , Wells R.
Published: December 2020

The addition of [5-
14
C]glutamate and [
14
C]formate to a non-proprietary medium containing [
14
C]glucose, Trypticase, yeast extract, thiotone, and salts enabled the radiometric detection of the presence of nonfermenters of glucose. It did not interfere with the rapid detection of the presence of aerobic and anaerobic sporeforemers and nonsporeformers.
Efficacy of the Inactivation of Bacterial Spores in White Petrolatum and a Hydrophilic Ointment by Gamma Irradiation
Authors: Øie Signe Holta , Fystro Doris
Published: December 2020

To evaluate the possibilities of using gamma irradiation for the sterilization of ointments, the effect of irradiation on spores of
Bacillus pumilus
and
Bacillus sphaericus
in dry material and in two different kinds of ointments was studied. The results indicate that for sterilization purposes irradiation was less effective in white petrolatum as compared to irradiation in the dry state. No such protective effect was found in a hydrophilic ointment. Accordingly, the sterilization dose needed for the sterilization of an ointment can be decided upon only after inactivation experiments with suitable test organisms in the actual preparation.
Inhibitor of
Clostridium perfringens
Formed by Heating Sodium Nitrite in a Chemically Defined Medium
Authors: Moran Dennis M. , Tannenbaum Steven R. , Archer Michael C.
Published: December 2020

An inhibitor of
Clostridium perfringens
formed when low levels of nitrite were autoclaved with a defined chemical medium. A systematic study of the medium revealed that only amino acids and mineral salts were involved in the production of this inhibitor, which was proven to be a toxic compound formed from cysteine, ferrous sulfate, and sodium nitrite. The inhibitor was compared to several known compounds.
S
-nitrosocysteine inhibited the test organism, but would not form in the test system in amounts large enough to explain the observed inhibition. Roussin red salt was unstable in the test system and therefore was not the inhibitor. Roussin black salt, which was also inhibitory, could form in sufficient amounts to explain the inhibition. A complex of cysteine, iron, and nitrie oxide was detected in the autoclaved solution of cysteine, ferrous sulfate, and sodium nitrite; this cysteine complex did not appear to be inhibitory, however, at levels which could form in the autoclaved medium. The observed inhibition may have been due to the combined effects of sublethal concentrations of each compound.
Effect of Some Inhibitors Derived from Nitrite on Macromolecular Synthesis in
Bacillus cereus
Authors: Hansen J. N. , Levin R. A.
Published: December 2020

The effect of several inhibitors derived from nitrite on incorporation of [
14
C]uracil into ribonucleic acid of
Bacillus cereus
during outgrowth and vegetative growth has been determined. A heat-induced inhibitor presumably of the Perigo type was compared with the nitrosothiols of thioglycolate and β-mercaptoethanol. All were found to effectively inhibit uracil incorporation at all stages tested. Phase-contrast microscopy revealed that inhibition of morphological events occurred either before germination or during early outgrowth, depending on inhibitor concentration. It was also found that a precursor to the heat-induced inhibitor could be isolated from dialyzable tryptone (a pancreatic digest of casein), which chromatographed as a single species on diethylaminoethyl-cellulose and Sephadex G-25, with an apparent molecular weight of about 2,000.
Comparative Effects of β-Propiolactone on Mice, Mouse-derived Cell Cultures, and Venezuelan Equine Encephalomyelitis Virus
Authors: Hearn Henry J. , Dawson Frederick W.
Published: December 2020

Studies were made comparing the toxicity of β-propiolactone (BPL) for mammalian (mouse) cells in vitro and for mice and for Venezuelan equine encephalomyelitis (VEE) virus which is highly cytopathogenic for each. The mammalian cells grown in tissue culture were found to be adversely affected by BPL in concentrations ranging from 0.001 to 0.1 mg/ml of supernatant fluid. The difference in response was influenced by the menstruum in which the BPL was suspended and the difference in cell types tested. Tenfold less BPL appeared to be required to destroy the cells when it was suspended in a balanced salt solution than when it was suspended in protein-containing solutions such as beef heart infusion broth or medium 199 plus 20% horse serum. Secondary embryonic mouse lung cells seemed slightly more adversely affected by BPL than the established embryonic lung or L cells. BPL given to mice by intranasal instillation and by intracerebral injection was lethal to half of the animals within 2 days at doses of 0.31 and 0.39 mg, respectively. Higher concentrations of BPL were required to rapidly inactivate the virus in vitro than were required to kill mice or to cause a toxic effect on cells in culture. It required 10 mg/ml of BPL to completely inactivate a high-titered VEE virus preparation in 5 min and 1 mg/ml to inactivate most, but not all, of the virus in 15 min. A concentration of 0.1 mg/ml of BPL had only a slight effect on the virus after a period as long as 60 min. Evidence is presented indicating that simultaneous inactivation of all of the properties of the VEE virus particles by BPL aerosols did not occur at the same time but that, after treatment, the virus possessed a limited ability to immunize mice despite a loss in infectivity.
Production of Extracellular and Total Invertase by
Candida utilis, Saccharomyces cerevisiae
, and Other Yeasts
Authors: Dworschack Robert G. , Wickerham Lynferd J.
Published: December 2020

Some strains of
Candida utilis
produce exceptionally large amounts of extracellular and total invertase. Strain Y-900 of
C. utilis
produces high yields whether the carbon source is sucrose, glucose, maltose, or xylose and still higher yields with lactic acid, glycerol, and ethyl alcohol. Approximately 20 to 30% of the total invertase of
C. utilis
is extracellular.

Strains of
Saccharomyces cerevisiae
and
Saccharomyces carlsbergensis
are generally inferior to
C. utilis
in production of extracellular and total invertase, the difference being accentuated in shaken cultures.

The industrial yeasts are generally superior in invertase production to the other yeasts included in the survey.
Rifomycin
Authors: Margalith P. , Pagani H.
Published: December 2020

Rifomycin complex, a mixture of at least five different antibiotic principles, has been produced by submerged fermentation procedures in the laboratory and on pilot plant scale, using a semisynthetic medium. Difficulties were met with, due to the heterogeneity of the antibiotic principles. Mutation work led to the isolation of a strain that produced fractions C and D in greater amounts.
Characterization of
Clostridium perfringens (welchii)
Isolated from Market Poultry
Authors: Yamamoto Richard , Sadler Walter W. , Adler Henry E. , Stewart George F.
Published: December 2020

Strains of
Clostridium perfringens
capable of producing heat-resistant spores, characteristic of the food-poisoning types, were not recovered in a random survey of feces and livers of market poultry. Favorable growth response with a known food-poisoning strain indicated that the media and methods employed were adequate. Spores produced in vitro from this strain survived at 100 C for several hours. Animal feeding experiments with this strain showed that heat-resistant spores (surviving for 1 hr at 100 C) could be readily demonstrated 24 hr after oral instillation of vegetative cells in mouse feces, but not in chicken feces. One experiment suggests that this strain might adapt to the environment of the intestinal tract of chickens, but not all of the spores recovered were as heat resistant as those of the parent culture.
Oxidation of Alkyl-substituted Cyclic Hydrocarbons by a Nocardia during Growth on
n
-Alkanes
Authors: Davis J. B. , Raymond R. L.
Published: December 2020

Nocardia 107-332, a soil isolate, oxidizes short-chain alkyl-substituted cyclic hydrocarbons to cyclic acids while growing on
n
-alkanes. Cyclic acids are produced also from relatively long-chain alkyl-substituted cyclics such as
n
-nonylbenzene or
n
-dodecylbenzene which alone support growth in a mineral-salts medium. ω-Oxidation of the alkyl substituents is followed by β-oxidation. It is of particular interest that cyclic acids such as cyclohexaneacetic and phenylacetic with C
2
residual carboxylic acid substituents are resistant to further oxidation by the nocardia but cyclic acids with C
1
or C
3
substituents are readily oxidized and utilized for growth.

The specificity of microbial oxidations is demonstrated by the conversion of
p
-isopropyltoluene (
p
-cymene) to
p
-isopropylbenzoic acid in
n
-alkane, growth-supported nocardia cultures.
Studies on Induced Variation in the Rhizobia
Authors: Schwinghamer E. A. , Dalmas R. L.
Published: December 2020

The relation between survival and dose of ultraviolet (UV) light or X rays was, with only one exception, nonlinear for late-log-phase cultures of four species of
Rhizobium
. The
ld
90
for different bacterial strains ranged from 400 to 3,000 ergs per mm
2
for UV treatment, and from 3.0 to 7.5 kr for X-ray treatment.

Minor existing differences in response to some antibacterial compounds (disc tests) were usable as secondary markers for genetic experiments. Spontaneous and radiation-induced mutants, resistant to high levels of several antibiotics, notably dihydrostreptomycin and erythromycin, were isolated for primary marker purposes. A significant phenotypic lag for mutation to dihydrostreptomycin resistance was noted for UV-irradiated cells. The UV-induced frequency exceeded the X-ray-induced frequency by a factor of at least three, at a comparable level of lethality. No significant change in the symbiotic capability was observed in rhizobial strains marked with antibiotics resistance.
Production of
l
-Threonine by Auxotrophic Mutants of
Escherichia coli
Authors: Huang H. T.
Published: December 2020

Two auxotrophic mutants of
Escherichia coli
have been shown to accumulate significant amounts of
l
-threonine in the culture medium. One mutant, 13071, is deficient in α,ε-diaminopimelic acid (DAP), and the other, 13070, is deficient in both DAP and methionine.

Accumulation of
l
-threonine by 13071 in a synthetic medium with mannitol as the carbon source at 37 C incubation temperature was greatly influenced by initial DAP concentration. At an optimal level of DAP a yield of 1.5 g/liter
l
-threonine was obtained in 28 hr.
l
-Threonine accumulation by 13070 with sorbitol as the carbon source at 28 C incubation temperature was dependent upon the initial concentration of both DAP and methionine. At optimal levels of the two deficient amino acids, a yield of 2.0 g/liter
l
-threonine was obtained in 44 to 48 hr. By adding to the medium suitable quantities of beet molasses or sucrose supplemented with corn steep liquor the yield could be raised to almost 4 g/liter.

l
-Threonine of extremely high purity was isolated from fermentation broth from both mutants. The product was not contaminated with any detectable amounts of
d
-threonine or allothreonine.
Lysine-Iron Agar in the Detection of Arizona Cultures
Authors: Edwards P. R. , Fife Mary A.
Published: December 2020

A lysine-iron agar is described and recommended for the detection of Arizona strains which ferment lactose rapidly. Black colonies which appear on bismuth sulfite agar should be transferred to the medium. Salmonellae and Arizona cultures produce a distinctive reaction since they are the only recognized groups of enteric bacteria which regularly produce lysine decarboxylase rapidly and form large amounts of hydrogen sulfide. Use of the medium is particularly recommended in the examination of specimens from enteric infections in which shigellae and salmonellae are not detected.
A Note on the Flora and Fauna in the Rumen of Steers Fed a Feedlot Bloat-provoking Ration and the Effect of Penicillin
Authors: Bryant M. P. , Robinson I. M. , Lindahl Ivan L.
Published: December 2020

A study was made of the predominant culturable bacteria and ciliate protozoa present in the rumen of two steers that were regularly bloating on a pelleted ratio containing 22% alfalfa meal, 16% soybean oil meal, 61% barley, and 1% common salt. The ruminal microorganisms in the two animals differed as indicated by a high total culture count of bacteria, an almost complete absence of ciliate protozoa, a low pH, and a difference in the proportions of presumptively identified predominant bacterial groups in one animal (steer 26) as compared with the other (steer 32). The first exposure of the animals to procaine penicillin (75 or 150 mg per day on 2 successive days) resulted in an abnormal ruminal flora 31 hr after the first treatment as indicated by drastic drops in total and cellulolytic bacterial counts and a change in the proportions of predominant bacterial groups. The animals refused feed for 32 to 48 hr after the first treatment. After feed consumption resumed, further treatment with 75 mg penicillin on 4 successive days did not appear to greatly alter the flora and did not result in feed refusal in animal 32. In animal 26, amounts of penicillin progressing from 50 to 200 mg per day did not result in feed refusals and observations on rumen ingesta samples during this period indicated a decrease in total bacterial count, a great increase in numbers of ciliate protozoa, a higher pH, and a change in the proportions of predominant bacterial groups so that the ruminal picture was much more similar to that of animal 32 than to its own during the pre-penicillin period. Bloat was not relieved except during the period of feed refusal.

The results indicate that the ruminal flora rapidly adapts to penicillin and that bloat of the feedlot type can occur in animals with widely differing numbers and kinds of bacteria and protozoa. Feedlot bloat does not appear to be correlated with the occurrence or numbers of any of the individual predominant groups of bacteria cultured.
In Vitro Activity of Actinospectacin in Human Whole Blood
Authors: Sokolski W. T. , Chidester C. G. , Schadewald L. K.
Published: December 2020

A method for testing antibacterial substances in whole blood is described. The test agent for the method was actinospectacin which reportedly has good in vivo activity, approximately in the range with chloramphenicol, but relatively poor in vitro activity in the common media. In human whole blood, however, the in vitro activity compares favorably with chloramphenicol thus indicating that whole blood may predict in vivo activity better than the usual bacteriological media.
Regulation by proteolysis: energy-dependent proteases and their targets
Authors: Gottesman S , Maurizi M R
Published: December 2020

A number of critical regulatory proteins in both prokaryotic and eukaryotic cells are subject to rapid, energy-dependent proteolysis. Rapid degradation combined with control over biosynthesis provides a mechanism by which the availability of a protein can be limited both temporally and spatially. Highly unstable regulatory proteins are involved in numerous biological functions, particularly at the commitment steps in developmental pathways and in emergency responses. The proteases involved in energy-dependent proteolysis are large proteins with the ability to use ATP to scan for appropriate targets and degrade complete proteins in a processive manner. These cytoplasmic proteases are also able to degrade many abnormal proteins in the cell.
Translocation of DNA across bacterial membranes
Authors: Dreiseikelmann B
Published: December 2020

DNA translocation across bacterial membranes occurs during the biological processes of infection by bacteriophages, conjugative DNA transfer of plasmids, T-DNA transfer, and genetic transformation. The mechanism of DNA translocation in these systems is not fully understood, but during the last few years extensive data about genes and gene products involved in the translocation processes have accumulated. One reason for the increasing interest in this topic is the discussion about horizontal gene transfer and transkingdom sex. Analyses of genes and gene products involved in DNA transfer suggest that DNA is transferred through a protein channel spanning the bacterial envelope. No common model exists for DNA translocation during phage infection. Perhaps various mechanisms are necessary as a result of the different morphologies of bacteriophages. The DNA translocation processes during conjugation, T-DNA transfer, and transformation are more consistent and may even be compared to the excretion of some proteins. On the basis of analogies and homologies between the proteins involved in DNA translocation and protein secretion, a common basic model for these processes is presented.
Gravitational lensing by charged black hole in regularized 4D Einstein–Gauss–Bonnet gravity
Authors: Kumar Rahul , Islam Shafqat Ul , Ghosh Sushant G.
Published: December 2020

Among the higher curvature gravities, the most extensively studied theory is the so-called Einstein–Gauss–Bonnet (EGB) gravity, whose Lagrangian contains Einstein term with the GB combination of quadratic curvature terms, and the GB term yields nontrivial gravitational dynamics in $$ D\ge 5$$

D
≥
5

. Recently there has been a surge of interest in regularizing, a $$ D \rightarrow 4 $$

D
→
4

limit of, the EGB gravity, and the resulting regularized 4D EGB gravity valid in 4D. We consider gravitational lensing by Charged black holes in the 4D EGB gravity theory to calculate the light deflection coefficients in strong-field limits $$\bar{a}$$

a

¯

and $$\bar{b}$$

b

¯

, while former increases with increasing GB parameter $$\alpha $$
α
and charge q, later decrease. We also find a decrease in the deflection angle $$\alpha _D$$

α
D

, angular position $$\theta _{\infty }$$

θ
∞

decreases more slowly and impact parameter for photon orbits $$u_{m}$$

u
m

more quickly, but angular separation s increases more rapidly with $$\alpha $$
α
and charge q. We compare our results with those for analogous black holes in General Relativity (GR) and also the formalism is applied to discuss the astrophysical consequences in the case of the supermassive black holes Sgr A* and M87*.
Towards Higgs masses and decay widths satisfying the symmetries in the (N)MSSM
Authors: Domingo Florian , Paßehr Sebastian
Published: December 2020

In models with an extended Higgs sector, such as the (N)MSSM, scalar states mix with one another. Yet, the concept of Higgs mixing is problematic at the radiative level, since it introduces both a scheme and a gauge dependence. In particular, the definition of Higgs masses and decay amplitudes can be impaired by the presence of gauge-violating pieces of higher order. We discuss in depth the origin and magnitude of such effects and consider two strategies that minimize the dependence on the gauge-fixing parameter and field-renormalization of one-loop order in the definition of the mass and decay observables, both in degenerate and non-degenerate scenarios. In addition, the intuitive concept of mixing and the simplicity of its definition in terms of two-point diagrams can make it tempting to include higher-order corrections on this side of the calculation, irrespectively of the order achieved in vertex diagrams. Using the global $$SU(2)_{\mathrm{L}}$$

S
U

(
2
)

L

-symmetry in the decoupling limit, we show that no improvement can be expected from such an approach at the level of the Higgs decays, but that, on the contrary, the higher-order terms may lead to numerically large spurious effects.
Radially and azimuthally excited states of a soliton system of vortex and Q-ball
Authors: Loginov A. Yu. , Gauzshtein V. V.
Published: December 2020

In the present paper, we continue to study the two-dimensional soliton system that is composed of vortex and Q-ball components interacting with each other through an Abelian gauge field. This vortex-Q-ball system is electrically neutral as a whole, nevertheless it possesses a nonzero electric field. Moreover, the vortex-Q-ball system has a quantized magnetic flux and a nonzero angular momentum, and combines properties of topological and nontopological solitons. We investigate radially and azimuthally excited states of the vortex-Q-ball system along with the unexcited vortex-Q-ball system at different values of gauge coupling constants. We also ascertain the behaviour of the vortex-Q-ball system in several extreme regimes, including thin-wall and thick-wall regimes.
Real-time warm pions from the lattice using an effective theory
Authors: Gupta Sourendu , Sharma Rishi
Published: December 2020

Lattice measurements provide adequate information to fix the parameters of long-distance effective field theories in Euclidean time. Using such a theory, we examine the analytic continuation of long-distance correlation functions of composite operators at finite temperature from Euclidean to Minkowski space–time. We show through an explicit computation that the analytic continuation of the pion correlation function is possible and gives rise to nontrivial effects. Among them is the possibility, supported by lattice computations of Euclidean correlators, that long distance excitations can be understood in terms of (very massive) pions even at temperatures higher than the QCD crossover temperature.
Deep learning for quark–gluon plasma detection in the CBM experiment
Authors: Sergeev Fedor , Bratkovskaya Elena , Kisel Ivan , Vassiliev Iouri
Published: December 2020

Classification of processes in heavy-ion collisions in the CBM experiment (FAIR/GSI, Darmstadt) using neural networks is investigated. Fully-connected neural networks and a deep convolutional neural network are built to identify quark–gluon plasma simulated within the Parton-Hadron-String Dynamics (PHSD) microscopic off-shell transport approach for central Au+Au collision at a fixed energy. The convolutional neural network outperforms fully-connected networks and reaches 93% accuracy on the validation set, while the remaining only 7% of collisions are incorrectly classified.
Experimental Study on Dynamic Amplification Factor of Simple-Supported Reinforced Concrete Beams Under Impact Loading Generated by an Impulse Hammer
Authors: Wu Xue-Qian , Zhong Bo , Lv Yang , Li Zhong-Xian , Chouw Nawawi
Published: December 2020

The empirical formulas of dynamic amplification factor (DAF) specified in current bridge codes only consider the span or fundamental frequency of reinforced concrete (RC) girders in highway. Although investigations have been carried out on different bridges with considering the road roughness, vehicle–bridge interactions and travelling velocity, but most of them have been done numerically. In this study, experimental study of DAF was carried out on three simple-supported RC beams with different fundamental frequencies and different damage stages, i.e. without damage, cracked and yielded. Impulse hammer with four hammer heads of different hardness, i.e. black, red, green and brown, were used to generate impact forces with increasing duration. The impact tests were first carried out on the RC beams without any damage by impact hammer with different hammer heads. Then the RC beams were loaded by a concentrated static force at the mid-span to crack. Impact tests with different hammer heads were repeated on the cracked RC beams. Finally, the cracked beams were further loaded by a concentrated static force to yield of the longitudinal reinforcement. The impact tests were repeated on the yielded beams again. Load cells installed at the supports of the RC beams were used to measure the reaction force generated by the hammer, then DAF was calculated directly by dividing the peak reaction force with the peak impact force. Data obtained from tests, theoretical analysis and specification in codes were compared to examine the DAFs. Results show that the ratio of duration of the impact force and the period of the beams performed a significant effect on the DAFs of the beams.
Rethinking Decimalization: The Impact of Increased Tick Sizes on Trading Activity, Volatility, and Price Clustering
Authors: Blau Benjamin , Whitby Ryan
Published: December 2020

In this study, we examine the trading activity and volatility of stocks influenced by the U.S. Securities and Exchange Commission’s pilot program that increases tick sizes for various samples of stocks. The objective of the program is to improve the market quality of small-cap stocks, which have historically been relatively less liquid than other stocks. Using a difference-in-differences approach, we find that, relative to control stocks, the trading activity of pilot stocks does not appear to be meaningfully affected by the increase in tick sizes. Volatility, however, increases markedly for the pilot stocks compared to non-pilot stocks. These results are robust to the three different sets of pilot stocks, various rollout periods, and different control groups. We also find that pilot stocks tend to cluster on round increments of $0.05 more frequently than non-pilot stocks after the rollout periods. This is true particularly for pilot stocks that quote on $0.05 but trade on $0.01. To the extent that prices convey important information to market participants, these latter results suggest that the discreteness in prices imposed by the pilot program may adversely affect the informativeness of prices in equity markets.
Volcanic geology and petrochemistry of Ashikule volcanic field in western Kunlun Mountains of the Tibetan plateau
Authors: Xu Jiandong , Zhao Bo , Yu Hongmei , Wei Feixiang , Chen Zhengquan
Published: December 2020

Ashikule volcanic field, developed in the western Kunlun mountain of north Tibet, is composed of approximately 10 volcanoes, and covers a total area of about 200 km
2
at an average altitude of approximately 5000 m, one of the highest volcanic fields in the world. In this study, we conducted detailed field investigations of the geological and geomorphological features of volcanic rocks and volcanic edifices in Ashikule basin, and compiled a large-scale geological map of the study area for the first time. We also collected a series of samples for petrochemistry analysis, as well as a high-precision
40
Ar/
39
Ar geochronology study of selected lavas from Ashikule volcanic field. Finally, we refined the eruption history for the volcanic activity in the basin, which provides some new volcanological evidence for the study of the tectonic evolution of the Northern Tibetan Plateau.
Minimization of WCRT with Recovery Assurance from Hardware Trojans for Tasks on FPGA-based Cloud
Authors: Saha Debasri , Sur-Kolay Susmita
Published: December 2020

Dynamic partial reconfiguration (DPR) enabled FPGA-based Cloud architecture acts as a flexible and efficient shared environment to facilitates application support to users’ request at low cost. While on one hand we need to handle a variety of tasks, such as periodic or sporadic, deadline or non-deadline, high or low critical tasks from the point of producing correct results, on the other hand we are constrained to use untrusted FPGA-based application IP blocks procured from various third-party vendors, which may contain hardware Trojan horse (HTH) affecting throughput and reliability of the Cloud. We propose Trojan-aware processing of tasks by monitored execution of a task on different untrusted cores, and then one more execution is done upon detection of hardware Trojan effects. For this stringent scheduling environment, the proposed dynamic scheduling algorithm is also properly extended to guarantee successful recovery from Trojan effects for all accepted tasks. Experimental results show that our algorithm improves worst-case-response-time for all tasks including non-deadline tasks and achieves lower task rejection rate for the deadline tasks, through judicious non-uniform partitioning of FPGAs based on supported jobs and subsequent better resource utilization, compared to that for existing Trojan-aware scheduling techniques.
Multi-Stage Network Embedding for Exploring Heterogeneous Edges
Authors: Huang Hong , Song Yu , Ye Fanghua , Xie Xing , Shi Xuanhua , Jin Hai
Published: December 2020

The relationships between objects in a network are typically diverse and complex, leading to the heterogeneous edges with different semantic information. In this article, we focus on exploring the heterogeneous edges for network representation learning. By considering each relationship as a view that depicts a specific type of proximity between nodes, we propose a multi-stage non-negative matrix factorization (MNMF) model, committed to utilizing abundant information in multiple views to learn robust network representations. In fact, most existing network embedding methods are closely related to implicitly factorizing the complex proximity matrix. However, the approximation error is usually quite large, since a single low-rank matrix is insufficient to capture the original information. Through a multi-stage matrix factorization process motivated by gradient boosting, our MNMF model achieves lower approximation error. Meanwhile, the multi-stage structure of MNMF gives the feasibility of designing two kinds of non-negative matrix factorization (NMF) manners to preserve network information better. The united NMF aims to preserve the consensus information between different views, and the independent NMF aims to preserve unique information of each view. Concrete experimental results on realistic datasets indicate that our model outperforms three types of baselines in practical applications.
Combinatorial Algorithms for String Sanitization
Authors: Bernardini Giulia , Chen Huiping , Conte Alessio , Grossi Roberto , Loukides Grigorios , Pisanti Nadia , Pissis Solon P. , Rosone Giovanna , Sweering Michelle
Published: December 2020

String data are often disseminated to support applications such as location-based service provision or DNA sequence analysis. This dissemination, however, may expose sensitive patterns that model confidential knowledge (e.g., trips to mental health clinics from a string representing a user’s location history). In this article, we consider the problem of sanitizing a string by concealing the occurrences of sensitive patterns, while maintaining data utility, in two settings that are relevant to many common string processing tasks.

In the first setting, we aim to generate the minimal-length string that preserves the order of appearance and frequency of all non-sensitive patterns. Such a string allows accurately performing tasks based on the sequential nature and pattern frequencies of the string. To construct such a string, we propose a time-optimal algorithm, TFS-ALGO. We also propose another time-optimal algorithm, PFS-ALGO, which preserves a partial order of appearance of non-sensitive patterns but produces a much shorter string that can be analyzed more efficiently. The strings produced by either of these algorithms are constructed by concatenating non-sensitive parts of the input string. However, it is possible to detect the sensitive patterns by “reversing” the concatenation operations. In response, we propose a heuristic, MCSR-ALGO, which replaces letters in the strings output by the algorithms with carefully selected letters, so that sensitive patterns are not reinstated, implausible patterns are not introduced, and occurrences of spurious patterns are prevented. In the second setting, we aim to generate a string that is at minimal edit distance from the original string, in addition to preserving the order of appearance and frequency of all non-sensitive patterns. To construct such a string, we propose an algorithm, ETFS-ALGO, based on solving specific instances of approximate regular expression matching.

We implemented our sanitization approach that applies TFS-ALGO, PFS-ALGO, and then MCSR-ALGO, and experimentally show that it is effective and efficient. We also show that TFS-ALGO is nearly as effective at minimizing the edit distance as ETFS-ALGO, while being substantially more efficient than ETFS-ALGO.
Verifying the Safety of Autonomous Systems with Neural Network Controllers
Authors: Ivanov Radoslav , Carpenter Taylor J. , Weimer James , Alur Rajeev , Pappas George J. , Lee Insup
Published: December 2020

This article addresses the problem of verifying the safety of autonomous systems with neural network (NN) controllers. We focus on NNs with sigmoid/tanh activations and use the fact that the sigmoid/tanh is the solution to a quadratic differential equation. This allows us to convert the NN into an equivalent hybrid system and cast the problem as a hybrid system verification problem, which can be solved by existing tools. Furthermore, we improve the scalability of the proposed method by approximating the sigmoid with a Taylor series with worst-case error bounds. Finally, we provide an evaluation over four benchmarks, including comparisons with alternative approaches based on mixed integer linear programming as well as on star sets.
Exercise intolerance in kidney diseases: physiological contributors and therapeutic strategies
Authors: Kirkman Danielle L. , Bohmke Natalie , Carbone Salvatore , Garten Ryan S. , Rodriguez-Miguelez Paula , Franco Robert L. , Kidd Jason M. , Abbate Antonio
Published: December 2020

Exertional fatigue, defined as the overwhelming and debilitating sense of sustained exhaustion that impacts the ability to perform activities of daily living, is highly prevalent in chronic kidney disease (CKD) and end-stage renal disease (ESRD). Subjective reports of exertional fatigue are paralleled by objective measurements of exercise intolerance throughout the spectrum of the disease. The prevalence of exercise intolerance is clinically noteworthy, as it leads to increased frailty, worsened quality of life, and an increased risk of mortality. The physiological underpinnings of exercise intolerance are multifaceted and still not fully understood. This review aims to provide a comprehensive outline of the potential physiological contributors, both central and peripheral, to kidney disease-related exercise intolerance and highlight current and prospective interventions to target this symptom. In this review, the CKD-related metabolic derangements, cardiac and pulmonary dysfunction, altered physiological responses to oxygen consumption, vascular derangements, and sarcopenia are discussed in the context of exercise intolerance. Lifestyle interventions to improve exertional fatigue, such as aerobic and resistance exercise training, are discussed, and the lack of dietary interventions to improve exercise tolerance is highlighted. Current and prospective pharmaceutical and nutraceutical strategies to improve exertional fatigue are also broached. An extensive understanding of the pathophysiological mechanisms of exercise intolerance will allow for the development of more targeted therapeutic approached to improve exertional fatigue and health-related quality of life in CKD and ESRD.
Genetic Variants Associated with Therapy-Related Cardiomyopathy among Childhood Cancer Survivors of African Ancestry
Authors: Sapkota Yadav , Qin Na , Ehrhardt Matthew J. , Wang Zhaoming , Chen Yan , Wilson Carmen L. , Estepp Jeremie , Rai Parul , Hankins Jane S. , Burridge Paul W. , Jefferies John L. , Zhang Jinghui , Hudson Melissa M. , Robison Leslie L. , Armstrong Gregory T. , Mulrooney Daniel A. , Yasui Yutaka
Published: December 2020

Cardiomyopathy occurs at significantly higher rates in survivors of childhood cancer than the general population, but few studies have evaluated racial or ethnic disparities, and none have assessed potential genetic factors contributing to this outcome. In this study, childhood cancer survivors of African ancestry exposed to cardiotoxic therapies (anthracyclines and/or heart radiotherapy; n = 246) were compared with cardiotoxic-exposed survivors of European ancestry (n = 1,645) in the St. Jude Lifetime Cohort. Genetic variants were examined using whole-genome sequencing data among survivors of African ancestry, first based on ejection fraction (EF) as a continuous outcome, followed by clinical history of cardiomyopathy. Survivors of African ancestry showed 1.53- and 2.47-fold risks of CTCAE grade 2–4 and grade 3–4 cardiomyopathy than survivors of European ancestry. A novel locus at 1p13.2 showed significant association with EF (rs6689879*C: EF reduction = 4.2%; P = 2.8 × 10−8) in 246 survivors of African ancestry, which was successfully replicated in 1,645 survivors of European ancestry but with attenuated magnitude (EF reduction = 0.4%; P = 0.042). In survivors of African ancestry, rs6689879*C showed a 5.43-fold risk of cardiomyopathy and 1.31-fold risk in those of European ancestry. Among survivors of African ancestry with rs6689879*C and CTCAE grade 2–4 cardiomyopathy, the PHTF1 promoter region was hypomethylated. Similar results were observed in survivors of European ancestry, albeit with reduced magnitudes of hypomethylation among those with rs6689879*C and CTCAE grade 2–4 cardiomyopathy. PHTF1 was upregulated in human-induced pluripotent stem cell-derived cardiomyocytes from patients with doxorubicin-induced cardiomyopathy. These findings have potential implications for long-term cardiac surveillance and up-front cancer care for patients of African ancestry.

Significance:

Childhood cancer survivors of African ancestry are at higher risk of cardiomyopathy than those of European ancestry, and a novel locus at 1p13.2 is associated with therapy-related cardiomyopathy specifically in African-American survivors.

See related commentary by Brown and Richard, p. 2272
Early-Life and Adult Adiposity, Adult Height, and Benign Breast Tissue Composition
Authors: Oh Hannah , Yaghjyan Lusine , Austin-Datta Rebecca J. , Heng Yujing J. , Baker Gabrielle M. , Sirinukunwattana Korsuk , Vellal Adithya D. , Collins Laura C. , Murthy Divya , Eliassen A. Heather , Rosner Bernard A. , Tamimi Rulla M.
Published: December 2020

Background:

Early-life and adult anthropometrics are associated with breast density and breast cancer risk. However, little is known about whether these factors also influence breast tissue composition beyond what is captured by breast density among women with benign breast disease (BBD).

Methods:

This analysis included 788 controls from a nested case–control study of breast cancer within the Nurses' Health Study BBD subcohorts. Body fatness at ages 5 and 10 years was recalled using a 9-level pictogram. Weight at age 18, current weight, and height were reported via questionnaires. A deep-learning image analysis was used to quantify the percentages of epithelial, fibrous stromal, and adipose tissue areas within BBD slides. We performed linear mixed models to estimate beta coefficients (β) and 95% confidence intervals (CI) for the relationships between anthropometrics and the log-transformed percentages of individual tissue type, adjusting for confounders.

Results:

Childhood body fatness (level ≥ 4.5 vs. 1), BMI at age 18 (≥23 vs. <19 kg/m2), and current adult BMI (≥30 vs. <21 kg/m2) were associated with higher proportions of adipose tissue [β (95% CI) = 0.34 (0.03, 0.65), 0.19 (−0.04–0.42), 0.40 (0.12, 0.68), respectively] and lower proportions of fibrous stromal tissue [−0.05 (−0.10, 0.002), −0.03 (−0.07, 0.003), −0.12 (−0.16, −0.07), respectively] during adulthood (all Ptrend < 0.04). BMI at age 18 was also inversely associated with epithelial tissue (Ptrend = 0.03). Adult height was not associated with any of the individual tissue types.

Conclusions:

Our data suggest that body fatness has long-term impacts on breast tissue composition.

Impact:

This study contributes to our understanding of the link between body fatness and breast cancer risk.

See related commentary by Oskar et al., p. 590
Phosphorylation and Driver Mutations in PI3Kα and PTEN Autoinhibition
Authors: Nussinov Ruth , Zhang Mingzhen , Tsai Chung-Jung , Jang Hyunbum
Published: December 2020

PI3K and PTEN are the second and third most highly mutated proteins in cancer following only p53. Their actions oppose each other. PI3K phosphorylates signaling lipid PIP2 to PIP3. PTEN dephosphorylates it back. Driver mutations in both proteins accrue PIP3. PIP3 recruits AKT and PDK1 to the membrane, promoting cell-cycle progression. Here we review phosphorylation events and mutations in autoinhibition in PI3K and PTEN from the structural standpoint. Our purpose is to clarify how they control the autoinhibited states. In autoinhibition, a segment or a subunit of the protein occludes its functional site. Protein–protein interfaces are often only marginally stable, making them sensitive to changes in conditions in living cells. Phosphorylation can stabilize or destabilize the interfaces. Driver mutations commonly destabilize them. In analogy to “passenger mutations,” we coin “passenger phosphorylation” to emphasize that the presence of a phosphorylation recognition sequence logo does not necessarily imply function. Rather, it may simply reflect a statistical occurrence. In both PI3K and PTEN, autoinhibiting phosphorylation events are observed in the occluding “piece.” In PI3Kα, the “piece” is the p85α subunit. In PTEN, it is the C-terminal segment. In both enzymes the stabilized interface covers the domain that attaches to the membrane. Driver mutations that trigger rotation of the occluding piece or its deletion prompt activation. To date, both enzymes lack specific, potent drugs. We discuss the implications of detailed structural and mechanistic insight into oncogenic activation and how it can advance allosteric precision oncology.
COVID-19: Bestimmung des inflammatorischen Phänotyps zur Vorhersage des klinischen Verlaufs
Authors: Krüger Stefan
Published: December 2020

Background: The COVID-19 pandemic has led to more than 760,000 deaths worldwide (correct as of 16th August 2020). Studies suggest a hyperinflammatory response is a major cause of disease severity and death. Identifying COVID-19 patients with hyperinflammation may identify subgroups who could benefit from targeted immunomodulatory treatments. Analysis of cytokine levels at the point of diagnosis of SARS-CoV-2 infection can identify patients at risk of deterioration. Methods: We used a multiplex cytokine assay to measure serum IL-6, IL-8, TNF, IL-1β, GM-CSF, IL-10, IL-33 and IFN-γ in 100 hospitalised patients with confirmed COVID-19 at admission to University Hospital Southampton (UK). Demographic, clinical and outcome data were collected for analysis. Results: Age > 70 years was the strongest predictor of death (OR 28, 95% CI 5.94, 139.45). IL-6, IL-8, TNF, IL-1β and IL-33 were significantly associated with adverse outcome. Clinical parameters were predictive of poor outcome (AUROC 0.71), addition of a combined cytokine panel significantly improved the predictability (AUROC 0.85). In those ≤70 years, IL-33 and TNF were predictive of poor outcome (AUROC 0.83 and 0.84), addition of a combined cytokine panel demonstrated greater predictability of poor outcome than clinical parameters alone (AUROC 0.92 vs. 0.77). Conclusions: A combined cytokine panel improves the accuracy of the predictive value for adverse outcome beyond standard clinical data alone. Identification of specific cytokines may help to stratify patients towards trials of specific immunomodulatory treatments to improve outcomes in COVID-19.
Site-Level Variability in 30-Day Patient Outcomes After Transcatheter Mitral Valve Repair in the United States
Authors: Malik Ali O. , Chhatriwalla Adnan K. , Saxon John , Hejjaji Vittal , Stebbins Amanda , Jones Philip G. , Cohen David J. , Arnold Suzanne V. , Vemulapalli Sreekanth , Wegermann Zachary K. , Kosinski Andrzej , Spertus John A.
Published: December 2020

Background:

Clinical trials have demonstrated health status benefit of transcatheter mitral valve repair (TMVr) with MitraClip in patients with mitral valve regurgitation. Real-world site-level variability in health status outcomes for TMVr, and factors associated with this variability, are unknown.

Methods:

All patients undergoing TMVr procedure with MitraClip between November 2013 and March 2019 in the Transcatheter Valve Therapy Registry were included. Health status was measured at baseline and 30 days with the Kansas City Cardiomyopathy Questionnaire (KCCQ) Overall Summary (OS) score. Site-level variability in 30-day change in KCCQ-OS was examined by calculating the median odds ratio from a hierarchical logistic regression model, with ≥20-point improvement as the dependent variable. To define the extent to which patient characteristics, procedural characteristics (residual mitral valve regurgitation, periprocedural bleeding), site volume, and patients’ baseline health status accounted for variability in outcomes, the proportion of variability (
R

2

) explained by sequentially adding these variables to the model was quantified.

Results:

Across 339 sites, 12 415 patients (mean age 79.0±9.5 years, 46.1%. females, 89.5% White) completed baseline and 30-day health status assessments. Mean KCCQ-OS score was 43.0±24.4 at baseline and 67.0±24.9 at 30-day follow-up. Across sites, the proportion of patients achieving a ≥20-point improvement in KCCQ-OS ranged from 12.5% to 100% and the adjusted median odds ratio was 1.58 (95% CI, 1.46–1.69). The greatest contribution to the variability in health status outcomes was from patients’ baseline KCCQ-OS score (
R

2

=25%) with <1% of the variability explained by patient and procedural characteristics, and annual site volume.

Conclusions:

There is moderate variation across sites in their patients’ achievement of health status benefits from TMVr, with patient’s baseline health status accounting for the largest proportion of this variation. This underscores the importance of patient selection in supporting more consistent health status benefit from TMVr.
Prediction of Preeclampsia-Related Adverse Outcomes With the sFlt-1 (Soluble fms-Like Tyrosine Kinase 1)/PlGF (Placental Growth Factor)-Ratio in the Clinical Routine
Authors: Dröge Lisa Antonia , Perschel Frank Holger , Stütz Natalia , Gafron Anna , Frank Lisa , Busjahn Andreas , Henrich Wolfgang , Verlohren Stefan
Published: December 2020

This retrospective real-world study investigated the clinical use of the sFlt-1 (soluble fms-like tyrosine kinase 1)/PlGF (placental growth factor) ratio alone or in combination with other clinical tests to predict an adverse maternal (maternal death, kidney failure, hemolysis elevated liver enzymes low platelets-syndrome, pulmonary edema, disseminated intravascular coagulation, cerebral hemorrhage, or eclampsia) or fetal (delivery before 34 weeks because of preeclampsia and/or intrauterine growth restriction, respiratory distress syndrome, necrotizing enterocolitis, intraventricular hemorrhage, placental abruption or intrauterine fetal death or neonatal death within 7 days post natum) pregnancy outcome in patients with signs and symptoms of preeclampsia. We evaluated the sFlt-1/PlGF-ratio cutoff values of 38 and 85 and evaluated its integration into a multimarker model. Of 1117 subjects, 322 (28.8%) developed an adverse fetal or maternal outcome. Patients with an adverse versus no adverse outcome had a median sFlt-1/PlGF-ratio of 177 (interquartile range, 54–362) versus 14 (4–64). Risk-stratification with the sFlt-1/PlGF cutoff values into high- (>85), intermediate- (38–85), and low-risk (<38) showed a significantly shorter time to delivery in high- and intermediate- versus low-risk patients (4 versus 8 versus 29 days). When integrating all available clinical information into a multimarker model, an area under the curve of 88.7% corresponding to a sensitivity, specificity, positive and negative predictive value of 80.0%, 87.3%, 75.0%, and 90.2% was reached. The sFlt-1/PlGF-ratio alone was inferior to the full model with an area under the curve of 85.7%. As expected, blood pressure and proteinuria were significantly less accurate with an area under the curve of 69.0%. Combining biomarker measurements with all available information in a multimarker modeling approach increased detection of adverse outcomes in women with suspected disease.