Miracle-dz/UniFAR-FTUs huggingface dataset:
Physiological Evidence for Isopotential Tunneling in the Electron Transport Chain of Methane-Producing Archaea

ABSTRACT Many, but not all, organisms use quinones to conserve energy in their electron transport chains. Fermentative bacteria and methane-producing archaea (methanogens) do not produce quinones but have devised other ways to generate ATP. Methanophenazine (MPh) is a unique membrane electron carrier found in Methanosarcina species that plays the same role as quinones in the electron transport chain. To extend the analogy between quinones and MPh, we compared the MPh pool sizes between two well-studied Methanosarcina species, Methanosarcina acetivorans C2A and Methanosarcina barkeri Fusaro, to the quinone pool size in the bacterium Escherichia coli. We found the quantity of MPh per cell increases as cultures transition from exponential growth to stationary phase, and absolute quantities of MPh were 3-fold higher in M. acetivorans than in M. barkeri. The concentration of MPh suggests the cell membrane of M. acetivorans, but not of M. barkeri, is electrically quantized as if it were a single conductive metal sheet and near optimal for rate of electron transport. Similarly, stationary (but not exponentially growing) E. coli cells also have electrically quantized membranes on the basis of quinone content. Consistent with our hypothesis, we demonstrated that the exogenous addition of phenazine increases the growth rate of M. barkeri three times that of M. acetivorans. Our work suggests electron flux through MPh is naturally higher in M. acetivorans than in M. barkeri and that hydrogen cycling is less efficient at conserving energy than scalar proton translocation using MPh. IMPORTANCE Can we grow more from less? The ability to optimize and manipulate metabolic efficiency in cells is the difference between commercially viable and nonviable renewable technologies. Much can be learned from methane-producing archaea (methanogens) which evolved a successful metabolic lifestyle under extreme thermodynamic constraints. Methanogens use highly efficient electron transport systems and supramolecular complexes to optimize electron and carbon flow to control biomass synthesis and the production of methane. Worldwide, methanogens are used to generate renewable methane for heat, electricity, and transportation. Our observations suggest Methanosarcina acetivorans, but not Methanosarcina barkeri, has electrically quantized membranes. Escherichia coli, a model facultative anaerobe, has optimal electron transport at the stationary phase but not during exponential growth. This study also suggests the metabolic efficiency of bacteria and archaea can be improved using exogenously supplied lipophilic electron carriers. The enhancement of methanogen electron transport through methanophenazine has the potential to increase renewable methane production at an industrial scale.
Fitness‐related differences in the rate of whole‐body total heat loss in exercising young healthy women are heat‐load dependent

What is the central question of this study? Aerobic fitness modulates heat loss, albeit the heat load at which fitness‐related differences occur in young healthy women remains unclear. What is the main finding and its importance? We demonstrate using direct calorimetry that fitness modulates heat loss in a heat‐load dependent manner, with differences occurring between young women of low and high fitness and matched physical characteristics when the metabolic heat load is at least 400 W in hot, dry conditions. Although fitness has been known for some time to modulate heat loss, our findings define the metabolic heat load at which fitness‐related differences occur.
A novel dynamic spectrum access algorithm for cognitive radio networks

This paper proposes a new dynamic spectrum access (DSA) algorithm for cognitive radio networks. Once initialized, this algorithm works without the need of coordination overhead and hence can be used when no control channel is available. Secondary user (SU) lists and predetermined access control are used in this algorithm. We analyze the probability of no SU collision with primary user and the throughput of our proposed algorithm. Extensive simulations show that our algorithm outperforms the existing DSA algorithm in terms of both the aggregate throughput and the traffic distribution fairness. Furthermore, the validity of our analysis is confirmed by simulation results.
Sensory and fatty acid profile of eggs from commercial hens fed rendered spent hen meal.

The objective of the study was to determine sensory characteristics and fatty acid profile of eggs from commercial laying hens fed rendered spent hen meal (RSHM). Eggs were collected on a daily basis from Single Comb White Leghorn hens between 43 and 60 wk of age. The hens were fed a layer diet containing either 0, 2.5, 5.0, 7.5, or 10.0% RSHM from 48 to 60 wk in Trial 1, and from 43 to 55 wk in Trial 2. Eggs were evaluated for sensory characteristics and fatty acid profile from hens fed the higher levels of RSHM (i.e., 7.5 and 10.0%). The RSHM treatments had no adverse effects (P > 0.05) on flavor, texture, and overall acceptability of the hard-boiled eggs. Fatty acid profile and total fat content of the eggs were similar for all treatments. Data demonstrated that up to 10% RSHM could be incorporated into the diets of laying hens, without altering the acceptability and fatty acid profile of the eggs produced.
LACE1 interacts with p53 and mediates its mitochondrial translocation and apoptosis

p53 is a major cellular tumor suppressor that in addition to its nuclear, transcription-dependent activity is also known to function extranuclearly. Cellular stressors such as reactive oxygen species can promote translocation of p53 into mitochondria where it acts to protect mitochondrial genome or trigger cell death via transcription-independent manner. Here we report that the mammalian homologue of yeast mitochondrial Afg1 ATPase (LACE1) promotes translocation of p53 into mitochondria. We further show that LACE1 exhibits significant pro-apoptotic activity, which is dependent on p53, and that the protein is required for normal mitochondrial respiratory function. LACE1 physically interacts with p53 and is necessary for mitomycin c-induced translocation of p53 into mitochondria. Conversely, increased expression of LACE1 partitions p53 to mitochondria, causes reduction in nuclear p53 content and induces apoptosis. Thus, LACE1 mediates mitochondrial translocation of p53 and its transcription-independent apoptosis.
Population genetics of immune-related multilocus copy number variation in Native Americans

While multiallelic copy number variation (mCNV) loci are a major component of genomic variation, quantifying the individual copy number of a locus and defining genotypes is challenging. Few methods exist to study how mCNV genetic diversity is apportioned within and between populations (i.e. to define the population genetic structure of mCNV). These inferences are critical in populations with a small effective size, such as Amerindians, that may not fit the Hardy–Weinberg model due to inbreeding, assortative mating, population subdivision, natural selection or a combination of these evolutionary factors. We propose a likelihood-based method that simultaneously infers mCNV allele frequencies and the population structure parameter f, which quantifies the departure of homozygosity from the Hardy–Weinberg expectation. This method is implemented in the freely available software CNVice, which also infers individual genotypes using information from both the population and from trios, if available. We studied the population genetics of five immune-related mCNV loci associated with complex diseases (beta-defensins, CCL3L1/CCL4L1, FCGR3A, FCGR3B and FCGR2C) in 12 traditional Native American populations and found that the population structure parameters inferred for these mCNVs are comparable to but lower than those for single nucleotide polymorphisms studied in the same populations.
Geographic Information Retrieval: Progress and Challenges in Spatial Search of Text

Significant amounts of information available today contain references to places on earth. Traditionally such information has been held as structured data and was the concern of Geographic Information Systems (GIS). However, increasing amounts of data in the form of unstructured text are available for indexing and retrieval that also contain spatial references. This monograph describes the field of Geographic Information Retrieval (GIR) that seeks to develop spatially-aware search systems and support user’s geographical information needs. Important concepts with respect to storing, querying and analysing geographical information in computers are introduced, before user needs and interaction in the context of GIR are explored. The task of associating documents with coordinates, prior to their indexing and ranking forms the core of any GIR system, and different approaches and their implications are discussed. Evaluating the resulting systems and their components, and different paradigms for doing so continue to be an important area of research in GIR and are illustrated through several examples. The monograph provides an overview of the research field, and in so doing identifies key remaining research challenges in GIR.
Phase 1 study of quizartinib in combination with induction and consolidation chemotherapy in patients with newly diagnosed acute myeloid leukemia

Novel therapies have potential to improve outcomes in patients with acute myeloid leukemia (AML) harboring FLT3‐ITD mutations that have high risk of relapse and poor survival following standard of care (SOC) cytarabine/anthracycline‐based induction/consolidation chemotherapy. Quizartinib is a selective and highly potent FLT3 inhibitor that has shown strong single‐agent activity in relapsed or refractory (R/R) AML. This phase 1, open‐label, sequential group dose‐escalation trial (NCT 01390337) is the first evaluating safety and tolerability of quizartinib in combination with SOC chemotherapy in newly diagnosed AML (ndAML). Nineteen patients unselected for FLT3 mutational status received one of three quizartinib dihydrochloride dose levels (DL): 60 mg/d for 7 days (DL1; n = 6), 60 mg/d for 14 days (DL2; n = 7), and 40 mg/d for 14 days (DL‐1; n = 6); administered orally starting on day 4 of chemotherapy. Median age was 43.8 years. Ten patients completed induction and consolidation. Three patients experienced dose‐limiting toxicities (DLTs): 2 at DL2 (1 pericardial effusion; 1 febrile neutropenia, decreased platelet count, and QT prolongation); 1 at DL‐1 (pericarditis). Maximum tolerated dose (MTD) was identified as DL‐1. Most common grade 3/4 adverse events were febrile neutropenia (47%), neutropenia (42%), thrombocytopenia (32%), and anemia (26%). There were no apparent additional toxicities with addition of quizartinib to chemotherapy although grade ≤1 QT prolongation was observed at MTD. Sixteen patients (84%) achieved a response; 14 (74%) composite complete response; 2 (11%) morphologic leukemia‐free state. The phase 3 QuANTUM‐First trial (NCT02668653) is further evaluating the effect of quizartinib plus SOC chemotherapy in ndAML FLT3‐ITD mutated patients.
Competitive gut exclusion of avian pathogens by Lactobacillus acidophilus in gnotobiotic chicks.

A total of 205 Grey Leghorn chicks were hatched germfree for separate trials to determine the effects of Lactobacillus acidophilus treatment on pathogenic Salmonella typhimurium and Staphlococcus aureus. Prophylactic and therapeutic treatments with L. acidophilus were administered either before or after the pathogens were introduced. Prophylactic treatments significantly reduced chick mortality (P less than .01) and shedding of the pathogens (P less than .05). The L. acidophilus prophylactic treatments were also effective qualitatively in reducing the isolation of S. typhimurium and Staph. aureus from crop contents but not, to a great extent, from cecal or rectal contents of gnotobiotic chicks at postmortem. The average surface pH values for the crop, proventriculus, duodenum, cecum, and rectum for gnotobiotic chicks were 5.43, 5.02, 6.18, 6.56, and 6.71, respectively. The L. acidophilus treatments did not significantly affect surface pH of the various segments of the intestinal tract.
Estimates by sex of genetic parameters for body weight and skeletal dimensions in a random bred strain of meat type fowl.

Abstract RELATIVELY few of the many reported estimates of genetic parameters for traits in the fowl have been based on control or unselected populations. In addition to characterizing the population itself, estimates based on such populations can be very useful in quantitative inheritance studies. King (1961) has pointed out that estimates on unselected populations based on the commonly used variance component analyses, are free of the bias that could result from selection of parents. Establishing changes, if any, in genetic parameters of selected lines drawn from the control population has been mentioned by King as being an important use for such estimates. The estimates reported in this study are based on a population of meat-type chickens maintained as a random bred control strain. The history and development of this strain have been previously reported by Merritt and Gowe (1962). Only traits, namely body weights and skeletal dimensions, obtained on both sexes …
Efficient Algorithms for the Dynamic Pricing Problem with Reference Price Effect

We analyze a finite-horizon dynamic pricing model in which demand at each period depends on not only the current price but also past prices through reference prices. A unique feature but also a significant challenge in this model is the asymmetry in reference price effect, which implies that the underlying optimization problem is nonsmooth and no standard optimization methods can be applied. We identify a few key structural properties of the problem, which enable us to develop strongly polynomial-time algorithms to compute the optimal prices for several plausible scenarios. We complement our exact algorithms by proposing an approximation heuristic and provide an upper bound on the optimal objective value. Finally, we conduct numerical experiments to study the optimal price path and demonstrate the value of dynamic pricing when demands are seasonal. We further compare numerically one of the exact algorithms with the heuristic and offer managerial suggestions. This paper was accepted by Yinyu Ye, optimization.
Impact of institutional accreditation by the Japan Society of Gynecologic Oncology on the treatment and survival of women with cervical cancer

Objective The Japan Society of Gynecologic Oncology (JSGO) initiated a nation-wide training system for the education and certification for gynecologic oncologists in 2005. To assess the impact of the quality of the JSGO-accredited institutions, JSGO undertook an analysis of the Uterine Cervical Cancer Registry of the Japan Society of Obstetrics and Gynecology (JSOG) to determine the effectiveness of the JSGO-accredited institutions on the treatment and survival of women with cervical cancer. Methods The effectiveness of 119 JSGO-accredited institutions and 125 non-JSGO-accredited institutions on the treatment and survival of women with cervical cancer were compared by analyzing the tumor characteristics, treatment patterns, and survival outcomes of women with stage T1B–T4 cervical cancer utilizing the data in the JSOG nation-wide registry for cervical cancer (2006–2009). Results A total of 14,185 eligible women were identified: 10,920 (77.0%) cases for 119 JSGO-accredited institutions and 3,265 (23.0%) cases for 125 non-accredited institutions. A multivariate analysis showed that age, stage, histology type, and treatment pattern were independently associated with mortality. Moreover, women who received treatment at the JSGO-accredited institutions had a significantly decreased mortality risk compared to non-accredited institutions (adjusted hazard ratio [aHR]=0.843; 95% confidence interval [CI]=0.784–0.905). Similar findings on multivariate analysis were seen among subset of women who received surgery alone (aHR=0.552; 95% CI=0.393–0.775) and among women who received radiotherapy (aHR=0.845; 95% CI=0.766–0.931). Conclusion Successful implementation of gynecologic oncology accrediting institution was associated with improved survival outcome of women with cervical cancer in Japan.
Fault Attacks Made Easy: Differential Fault Analysis Automation on Assembly Code

Over the past decades, fault injection attacks have been extensively studied due to their capability to efficiently break cryptographic implementations. Fault injection attack models are normally determined by analyzing the cipher structure and finding exploitable spots in non-linear and permutation layers. However, this level of abstraction is often too high to distinguish vulnerable parts of software implementations, due to specific operations and optimizations. On the other hand, manually analyzing the assembly code requires non-negligible amount of time and expertise. In this paper, we propose an automated approach for analyzing cipher implementations in assembly. We represent the whole assembly program as a data flow graph so that the vulnerable spots can be found efficiently. Fault propagation is analyzed in a subgraph constructed from each vulnerable spot, allowing equations for Differential Fault Analysis (DFA) to be automatically generated. We have created a tool that implements our approach: DATAC – DFA Automation Tool for Assembly Code . We have successfully used this tool for attacking PRESENT- 80, being able to find implementation-specific vulnerabilities that can be exploited in order to recover the last round key with 16 faults. Our results show that DATAC is useful in finding attack spots that are not visible from the cipher structure, but can be easily exploited when dealing with real-world implementations.
Market Structure and Productivity: A Concrete Example

Many studies have documented large and persistent productivity differences across producers, even within narrowly defined industries. This paper both extends and departs from the past literature, which focused on technological explanations for these differences, by proposing that demand‐side features also play a role in creating the observed productivity variation. The specific mechanism investigated here is the effect of spatial substitutability in the product market. When producers are densely clustered in a market, it is easier for consumers to switch between suppliers (making the market in a certain sense more competitive). Relatively inefficient producers find it more difficult to operate profitably as a result. Increases in substitutability truncate the productivity distribution from below, resulting in higher minimum and average productivity levels as well as less productivity dispersion. The paper presents a model that makes this process explicit and empirically tests it using data from U.S. ready‐mixed concrete plants, taking advantage of geographic variation in substitutability created by the industry’s high transport costs. The results support the model’s predictions and appear robust. Markets with high demand density for ready‐mixed concrete—and thus high concrete plant densities—have higher lower‐bound and average productivity levels and exhibit less productivity dispersion among their producers.
Response of broiler breeder females to feed restriction below recommended levels. 1. Growth and reproductive performance.

Arbor Acre broiler breeders were used to determine the effects on growth and reproductive performance of quantitative feed restriction below breeder recommended levels. Feed treatments were: 8% above standard (+8%); standard feeding program (STD); and 8 (-8%), 16 (-16%), and 24% (-24%) below standard. Proportional decreases in feed allocation resulted in corresponding decreases in body weight, frequency of double-yolked eggs, and number of days in production. Egg weight, fertility, hatchability, and female mortality to 64 wk of age were not significantly (P greater than or equal to .05) affected by the reduction in feed intake. Shell quality was significantly improved with the -16 and -24% feed treatments. A delay in sexual maturity caused a significant (P less than or equal to .05) decrease in average rate of lay (%hen-day) but not in total settable eggs for treatments -16 and -24% to 64 wk of age.
Locomotor and discriminative stimulus effects of four novel hallucinogens in rodents

There has been increasing use of novel synthetic hallucinogenic compounds, 2-(4-bromo-2,5-dimethoxyphenyl)-N-(2-methoxybenzyl)ethanamine hydrochloride (25B-NBOMe), 2-(4-chloro-2,5-dimethoxyphenyl)-N-(2-methoxybenzyl)ethanamine hydrochloride (25C-NBOMe), 2-(4-iodo-2,5-dimethoxyphenyl)-N-(2-methoxybenzyl)ethanamine hydrochloride (25I-NBOMe), and N,N-diallyl-5-methoxy tryptamine (5-MeO-DALT), which have been associated with severe toxicities. These four compounds were tested for discriminative stimulus effects similar to a prototypical hallucinogen (−)-2,5-dimethoxy-4-methylamphetamine (DOM) and the entactogen (±)-3,4-methylenedioxymethamphetamine (MDMA). Locomotor activity in mice was tested to obtain dose range and time-course information. 25B-NBOMe, 25C-NBOMe, and 25I-NBOMe decreased locomotor activity. 5-MeO-DALT dose dependently increased locomotor activity, with a peak at 10 mg/kg. A higher dose (25 mg/kg) suppressed activity. 25B-NBOMe fully substituted (≥80%) in both DOM-trained and MDMA-trained rats at 0.5 mg/kg. However, higher doses produced much lower levels of drug-appropriate responding in both DOM-trained and MDMA-trained rats. 25C-NBOMe fully substituted in DOM-trained rats, but produced only 67% drug-appropriate responding in MDMA-trained rats at doses that suppressed responding. 25I-NBOMe produced 74–78% drug-appropriate responding in DOM-trained and MDMA-trained rats at doses that suppressed responding. 5-MeO-DALT fully substituted for DOM, but produced few or no MDMA-like effects. All of the compounds, except 25I-NBOMe, fully substituted for DOM, whereas only 25B-NBOMe fully substituted for MDMA. However, the failure of 25I-NBOMe to fully substitute for either MDMA or DOM was more likely because of its substantial rate-depressant effects than weak discriminative stimulus effects. All of the compounds are likely to attract recreational users for their hallucinogenic properties, but probably of much less interest as substitutes for MDMA. Although no acute adverse effects were observed at the doses tested, the substantial toxicities reported in humans, coupled with the high likelihood for illicit use, suggests that these compounds have the same potential for abuse as other, currently scheduled compounds.
The membrane localization domains of two distinct bacterial toxins form a 4‐helix‐bundle in solution

Membrane localization domain (MLD) was first proposed for a 4‐helix‐bundle motif in the crystal structure of the C1 domain of Pasteurella multocida toxin (PMT). This structure motif is also found in the crystal structures of several clostridial glycosylating toxins (TcdA, TcdB, TcsL, and TcnA). The Ras/Rap1‐specific endopeptidase (RRSP) module of the multifunctional autoprocessing repeats‐in‐toxins (MARTX) toxin produced by Vibrio vulnificus has sequence homology to the C1‐C2 domains of PMT, including a putative MLD. We have determined the solution structure for the MLDs in PMT and in RRSP using solution state NMR. We conclude that the MLDs in these two toxins assume a 4‐helix‐bundle structure in solution.