cssi/SciSciGPT-SciSciNet huggingface dataset:
Targeting unique biological signals on the fly to improve MS/MS coverage and identification efficiency in metabolomics

Abstract When using liquid chromatography/mass spectrometry (LC/MS) to perform untargeted metabolomics, it is common to detect thousands of features from a biological extract. Although it is impractical to collect non-chimeric MS/MS data for each in a single chromatographic run, this is generally unnecessary because most features do not correspond to unique metabolites of biological relevance. Here we show that relatively simple data-processing strategies that can be applied on the fly during acquisition of data with an Orbitrap ID-X, such as blank subtraction and well-established adduct or isotope calculations, decrease the number of features to target for MS/MS analysis by up to an order of magnitude for various types of biological matrices. We demonstrate that annotating these non-biological contaminants and redundancies in real time during data acquisition enables comprehensive MS/MS data to be acquired on each remaining feature at a single collision energy. To ensure that an appropriate collision energy is applied, we introduce a method using a series of hidden ion-trap scans in an Orbitrap ID-X to find an optimal value for each feature that can then be applied in a subsequent high-resolution Orbitrap scan. Data from 100 metabolite standards indicate that this real-time optimization of collision energies leads to more informative MS/MS patterns compared to using a single fixed collision energy alone. As a benchmark to evaluate the overall workflow, we manually annotated unique biological features by independently subjecting E. coli samples to a credentialing analysis. While credentialing led to a more rigorous reduction in feature number, on-the-fly annotation with blank subtraction on an Orbitrap ID-X did not inappropriately discard unique biological metabolites. Taken together, our results reveal that optimal fragmentation data can be obtained in a single LC/MS/MS run for >90% of the unique biological metabolites in a sample when features are annotated during acquisition and collision energies are selected by using parallel mass spectrometry detection.
Ultrafast optical switching and power limiting in intersubband polaritonic metasurfaces

Highly nonlinear optical materials with fast third-order nonlinear optical response are crucial for the operation of all-optical photonic devices, such as switches for signal processing and computation, power limiters, and saturable absorbers. The nonlinear response of traditional optical materials is weak, thus requiring large light intensities to induce significant changes in their properties. Here we show that optical control of the coupling rate in subwavelength patch antennas coupled to intersubband transitions in multi-quantum-well semiconductor heterostructures can provide a giant third-order nonlinear response, on the order of ${{3.4 \times 10}}^{- 13}{{{m}}^2}/{{\rm{V}}^2}$, with a response time ${\lt}{{2}}\;{\rm{ps}}$. We utilize this effect to realize intersubband polaritonic metasurfaces and demonstrate their operation as highly nonlinear saturable and reverse saturable absorbers, enabling optical power limiters and other elements for all-optical modulation and control. Our approach enables a plethora of compact, low-power, highly nonlinear devices with spectral, temporal, and structured wavefront responses tailored by design.
Fic and non-Fic AMPylases: protein AMPylation in metazoans

Protein AMPylation refers to the covalent attachment of an AMP moiety to the amino acid side chains of target proteins using ATP as nucleotide donor. This process is catalysed by dedicated AMP transferases, called AMPylases. Since this initial discovery, several research groups have identified AMPylation as a critical post-translational modification relevant to normal and pathological cell signalling in both bacteria and metazoans. Bacterial AMPylases are abundant enzymes that either regulate the function of endogenous bacterial proteins or are translocated into host cells to hijack host cell signalling processes. By contrast, only two classes of metazoan AMPylases have been identified so far: enzymes containing a conserved filamentation induced by cAMP (Fic) domain (Fic AMPylases), which primarily modify the ER-resident chaperone BiP, and SelO, a mitochondrial AMPylase involved in redox signalling. In this review, we compare and contrast bacterial and metazoan Fic and non-Fic AMPylases, and summarize recent technological and conceptual developments in the emerging field of AMPylation.
Bidirectional reflectance capabilities of the NIST Robotic Optical Scattering Instrument.

The National Institute of Standards and Technology (NIST) Robotic Optical Scattering Instrument (ROSI) serves as the national reference instrument for specular and diffuse bidirectional reflectance measurements in the ultraviolet to short-wave infrared wavelength regions. This paper gives a comprehensive overview of the design, operation, and capabilities of ROSI. We describe measurement methods for diffuse and specular reflectance, identify and quantify the elements of the uncertainty budget, and validate the reflectance scale through comparison with NIST’s previous reference instrument, the Spectral Tri-function Automated Reference Reflectometer. Examples of the range of ROSI’s capabilities, including the limits for low-reflectance measurements and a research application using out-of-plane measurements of bidirectional reflectance for remote sensing reference reflectors, are also covered.
The Petrogenesis of modern and ophiolitic lavas reconsidered: Ti-V and Nb-Th

Abstract Tectonic discrimination diagrams are a key tool for understanding ancient volcanic rock origins. In this contribution we compile over 15,000 whole rock compositions to re-evaluate the Ti-V discrimination diagram and compare it to another commonly used tool, the Nb/Yb-Th/Yb diagram. We have reformulated the Ti-V diagram into a log-log plot to distinguish samples more clearly at lower concentrations. The compilation shows that MORB are dominated by Ti/V=20–43, whereas juvenile arc tholeiites and boninites are characterized by Ti/V 43, although there may be significant overlap with MORB-like ratios for ridge-centered OIB and for some oceanic plateaux. About 56% of alkaline OIB have Ti/V>70. Back-arc basins are dominantly MORB-like. Melt models show that MORB and juvenile arc volcanics most likely formed under different ƒO2 conditions, but are permissive of similar ƒO2 if the arc rocks form by much higher melt fractions. The Nb/Yb vs. Th/Yb plot clearly distinguishes most oceanic basalts (MORB, plateaux, OIB) from subduction-related volcanic rocks (boninite, juvenile arc tholeiite, calc-alkaline) and from flood basalts. We propose here a new two-proxy diagram of Ti/V vs. Th/Nb, which incorporates the advantages of both.
The Diary of James C. Hagerty: Eisenhower in Mid-Course, 1954-1955.

(1984). The Diary of James C. Hagerty: Eisenhower in Mid-Course, 1954-1955. American Journalism: Vol. 1, No. 2, pp. 86-88.
Coastal to inland: Expansion of prawn farming for adaptation to climate change in Bangladesh

Abstract The practice of prawn (Macrobrachium rosenbergii) farming is widespread in coastal Bangladesh due to favorable biophysical resources. However, export-oriented prawn farming is particularly vulnerable to climate change in coastal Bangladesh. This study identified different climatic variables, including salinity, coastal flooding, cyclone, sea-level rise, water temperature, drought, and rainfall have profound effects on prawn farming in the Bagerhat area of southwest Bangladesh. Considering extreme vulnerability to the effects of climate change on prawn production, one of the adaptation strategies is to translocate prawn culture from coastal to inland (i.e., Bagerhat–Gopalganj) that appear less vulnerable to climate change. Although the prospects for prawn–carp polyculture and integrated prawn–fish–rice farming are positive in Gopalganj, a number of challenges were identified for the expansion of prawn culture. We suggest that institutional support would help to adopt prawn production.
Electronic Theory of Phase Stability in Substitutional Alloys: A Comparison Between the Connolly-Williams Scheme and the Generalized Perturbation Method

A detailed analysis of the tendencies toward ordering and phase separation and more generally the stability properties at T ≠ 0 K in substitutional alloys is carried out using the presciption proposed by Connolly and Williams and the Generalized Perturbation Method. This enables a discussion of the viability and the basic assumptions of both approaches. The effective cluster interactions which enter such a study are derived from a simple but realistic tight binding model.
Deductive multi-valued model checking

Model checking is a widely used technique for verifying complex concurrent systems. The models used in classical model checking methods are assumed to be complete and consistent. However, a recent body of work has shown that this is not always the case, and multi-valued logics have been proposed to represent such models, spawning an extension of classical model checking, known as, multi-valued model checking. In this paper, we define a multi-valued set based semantics for the multi-valued modal μ-calculus and present a novel interpretation of logic programs to support multi-valued sets as first-class entities, that can be used as a practical deductive multi-valued model checking framework. This framework provides a semantics preserving encoding of multi-valued transition systems, and allows verification of arbitrary multi-valued modal μ-calculus properties. A prototype implementation of this framework has also been realized.
Nested PCR Biases in Interpreting Microbial Community Structure in 16S rRNA Gene Sequence Datasets

Background Sequencing of the PCR-amplified 16S rRNA gene has become a common approach to microbial community investigations in the fields of human health and environmental sciences. This approach, however, is difficult when the amount of DNA is too low to be amplified by standard PCR. Nested PCR can be employed as it can amplify samples with DNA concentration several-fold lower than standard PCR. However, potential biases with nested PCRs that could affect measurement of community structure have received little attention. Results In this study, we used 17 DNAs extracted from vaginal swabs and 12 DNAs extracted from stool samples to study the influence of nested PCR amplification of the 16S rRNA gene on the estimation of microbial community structure using Illumina MiSeq sequencing. Nested and standard PCR methods were compared on alpha- and beta-diversity metrics and relative abundances of bacterial genera. The effects of number of cycles in the first round of PCR (10 vs. 20) and microbial diversity (relatively low in vagina vs. high in stool) were also investigated. Vaginal swab samples showed no significant difference in alpha diversity or community structure between nested PCR and standard PCR (one round of 40 cycles). Stool samples showed significant differences in alpha diversity (except Shannon’s index) and relative abundance of 13 genera between nested PCR with 20 cycles in the first round and standard PCR (P 27% of total OTUs in stool). Conclusions Nested PCR introduced bias in estimated diversity and community structure. The bias was more significant for communities with relatively higher diversity and when more cycles were applied in the first round of PCR. We conclude that nested PCR could be used when standard PCR does not work. However, rare taxa detected by nested PCR should be validated by other technologies.
Pioneer 10 Observations of the Solar Wind and Its Interaction with Jupiter: Plasma Electron Results

Previously we reported (Wolfe et al., 1974a) that during the inbound portion of the Jovian flyby (see Hall, 1974 for a description of the Pioneer 10 flyby geometry) the Jovian magnetosheath was encountered for two extended time intervals: from 2031 UT (Ground Received Time) on November 26, 1973 to 2038 UT on November 27, 1973, corresponding in radial distance from Jupiter of 109 R J and 96 R J, respectively; and then from 0318 UT on December 1, 1973 to 1415 UT on December 1, 1973, corresponding in radial distance from Jupiter of 54 R J and 46.5 R J. In Wolfe et al. (1974b) we summarize the general features of the solar wind interaction with Jupiter. In Intriligator (1975) we summarize the plasma electron observations obtained in the Jovian magnetosphere. In this paper we summarize the plasma electron data obtained in the Jovian magnetosheath.
A TRAFfic cop for host defense.

The function of TRAF3, a member of the family of tumor necrosis factor receptor–associated factors, has remained an enigma. Two recent Nature papers now show that TRAF3 regulates interferon and interleukin 10 production.
Microsensors vs. ICs: a study in contrasts

Significant differences between microsensors and micromechanisms, on the one hand, and integrated circuits, on the other, are examined from the design viewpoint. Microelectronic sensors, micromachining processes, and micromechanisms and micro-actuators are discussed. The principal technological forces driving microsensor development, namely lithography and planar technology, are considered, and some cautionary advice is given regarding the development of so-called smart sensors. Two issues in regard to the partitioning of measurement systems-device partitioning and calibration-are addressed. Technology constraints and packaging considerations are examined. >
ANTHOCYANINS AS FOOD COLORANTS: EFFECT OF pH ON THE FORMATION OF ANTHOCYANIN‐RUTIN COMPLEXES

Complex formation of anthocyanins with rutin stabilize their color under conditions similar to those of grape juices. This color intensification results in both the increase in intensity and a batho-chromic shift in the color of their solutions. The changes in the color intensity of the anthocyanin solutions are not uniform throughout the pH range 1–7, but are influenced by the substitution patterns of the B-ring, and by the nature of substituent in the 3- and 5-position. Thus maximum complex formation occurs with the 3-glucosides at around pH 4.2, with the 3,5-diglucoside at around pH 3.1, with the 3-acylglucosides around pH 4.0–4.5 and at around pH 3.1 with the 3-acylglucoside+glucosides: The obtained data further support the involvement of the anhydro base of anthocyanins in the complex formation with rutin in the pH range 1–7.
Distribution of nodes of a tree by degree

Two types of random trees, “static” and “growing,” are studied. The “growing” type of trees is constructed with an ordering bias imposed on its population of N nodes. Exact formulas for the expected number of nodes of degree i are derived in each case. Asymptotic behavior of such formulas is determined for large values of N.
Cortical processing of dynamic sound envelope transitions

Slow envelope fluctuations in the range of 2-20 Hz provide important segmental cues for processing communication sounds. For a successful segmentation, a neural processor must capture envelope features associated with the rise and fall of signal energy, a process that is often challenged by the interference of background noise. This study investigated the neural representations of slowly varying envelopes in quiet and in background noise in the primary auditory cortex (A1) of awake marmoset monkeys. We characterized envelope features based on the local average and rate of change of sound level in envelope waveforms and identified envelope features to which neurons were selective by reverse correlation. Our results showed that envelope feature selectivity of A1 neurons was correlated with the degree of nonmonotonicity in their static rate-level functions. Nonmonotonic neurons exhibited greater feature selectivity than monotonic neurons in quiet and in background noise. The diverse envelope feature selectivity decreased spike-timing correlation among A1 neurons in response to the same envelope waveforms. As a result, the variability, but not the average, of the ensemble responses of A1 neurons represented more faithfully the dynamic transitions in low-frequency sound envelopes both in quiet and in background noise.
Compact Radiative Control Structures for Millimeter Astronomy

We have designed, fabricated, and tested compact radiative control structures, including antireflection coatings and resonant absorbers, for millimeter through submillimeter wave astronomy. The antireflection coatings consist of micromachined single crystal silicon dielectric sub-wavelength honeycombs. The effective dielectric constant of the structures is set by the honeycomb cell geometry. The resonant absorbers consist of pieces of solid single crystal silicon substrate and thin phosphorus implanted regions whose sheet resistance is tailored to maximize absorption by the structure. We present an implantation model that can be used to predict the ion energy and dose required for obtaining a target implant layer sheet resistance. A neutral density filter, a hybrid of a silicon dielectric honeycomb with an implanted region, has also been fabricated with this basic approach. These radiative control structures are scalable and compatible for use large focal plane detector arrays.
Chemical mass-wasting of the northern Yucatan Peninsula by groundwater dissolution

The northern part of the Yucatan Peninsula is a relatively flat, low-lying carbonate terrane with no geomorphic expressions of stream channels. It is estimated that mean annual recharge to the groundwater system is 150 mm. For the 65,500 km 2 study area, mean annual discharge (equivalent to recharge) is 9.8 × 10 9 m 3 , or 8.6 × 10 6 m 3 for each 1 km of the 1,100-km-long coastline. In the interior of the peninsula, the recharging water annually dissolves about 37.5 t (metric tons) of calcite per 1 km 2 . When the groundwater has become saturated with calcite, little additional water-rock interaction occurs until the active mixing (dispersion) zone is reached near the coastline. Theoretical calculations and laboratory experiments have shown that when two waters, each calcite saturated and with different salinities, are mixed, the resulting solution generally becomes undersaturated with calcite and, therefore, is capable of dissolving additional calcite. On the basis of our study of the Xel Ha lagoon on the east coast of Yucatan, we calculate that as much as 1.2 mmol/L additional calcite can be dissolved in the brackish groundwater zone of dispersion. This indicates that if the total solution potential of the amount of water discharging at Xel Ha has focused within the lagoon area, the lagoon could be chemically incised in less than 3,000 yr. We postulate that chemical mass wasting by dissolution in the zone of groundwater mixing is an important geomorphic process in coastal areas of limestone terranes.
A Robust Analysis of Crossover Designs using Multisample Generalized L-Statistics

Abstract In a crossover study, some or all subjects receive more than one treatment sequentially. Using a clinical example as motivation, we develop multisample generalized L-statistics (GL-statistics) to estimate and test for treatment effects in crossovers when the distribution of the response data deviates from normality. The basic idea is to adapt simple L-statistics, such as the trimmed mean and median, to data with dependencies. GL-statistics may be applied to crossovers with more than two periods and/or sequences. These designs are useful for experiments with two treatments in which carryover and treatment effects might be aliased in the commonly used two-period, two-sequence design, as well as for experiments with more than two treatments. For data analysis with large samples, the asymptotic properties of the GL-statistics suggest that the generalized trimmed mean and generalized median often should be strongly consistent and normal. A simulation study of a four-sequence, two-period crossover desi...
Regulation of interleukin-6-induced hepatic insulin resistance by mammalian target of rapamycin through the STAT3-SOCS3 pathway.

The proinflammatory cytokine interleukin (IL)-6 has been proposed to be one of the mediators that link obesity-derived chronic inflammation with insulin resistance. Signaling through the mammalian target of rapamycin (mTOR) has been found to impact insulin sensitivity under various pathological conditions, through serine phosphorylation and inhibition of insulin receptor substrate by the downstream effector of mTOR, ribosomal S6 kinase 1 (S6K1). However, an involvement of mTOR in IL-6-induced insulin resistance has not yet been reported. Here we show that rapamycin, the inhibitor of mTOR signaling, rescues insulin signaling and glycogen synthesis from IL-6 inhibition in HepG2 hepatocarcinoma cells as well as in mouse primary hepatocytes. IL-6 activates S6K1 in these cells, but unexpectedly, S6K1 is not involved in IL-6 inhibition of insulin signaling, since the effect of IL-6 persists in cells with drastically reduced S6K1 levels induced by RNA interference, suggesting that the function of mTOR signaling is through a mechanism different from the prevailing model of S6K1 phosphorylation of insulin receptor substrate-1. Interestingly, we find that the phosphorylation of STAT3 on Ser727 and STAT3 transcriptional activity are regulated by mTOR upon IL-6 stimulation and that STAT3 is required for IL-6 inhibition of insulin signaling. Furthermore, IL-6-induced SOCS3 expression is inhibited by rapamycin, and ectopic expression of SOCS3 blocks the ability of rapamycin to enhance insulin sensitivity in the presence of IL-6. Taken together, we propose that mTOR plays a key role in IL-6-induced hepatic insulin resistance by regulating STAT3 activation and subsequent SOCS3 expression.
Identification of a Stress-Induced Protein During Human Trophoblast Differentiation by Differential Display Analysis

Differentiation of human placental trophoblast is characterized by a process during which mononuclear villous cytotrophoblasts fuse to form a multinucleate syncytium. This event is associated with dramatic changes in gene expression. In the present study, we have applied a sensitive approach-differential display analysis-to evaluate changes in gene expression during in vitro forskolin-induced differentiation of a model of human trophoblast, the choriocarcinoma BeWo. We identified seven genes that were up-regulated; their expression and function have not previously been reported in trophoblast. Four up-regulated genes were novel upon comparison of their sequences to the GenBank database. The other three genes encode human cytochrome p450 IIC, inosine monophosphate dehydrogenase type II, and reducing agent and tunicamycin-responsive protein (RTP). Northern blot analysis revealed that RTP mRNA expression was induced to 3-fold in BeWo after 24-h incubation with forskolin and increased up to 11-fold by 72 h of forskolin treatment. The expression pattern of RTP was further investigated by in situ hybridization on second trimester and term placenta tissues. RTP mRNA was predominantly expressed in syncytiotrophoblasts in both second trimester and term placentae. The expression of RTP gene in BeWo cells was protein kinase C dependent. This is the first description of RTP gene expression in placenta and the first study elucidating the signaling pathway involved in the regulation of RTP gene expression. These results suggest that RTP may play a role in trophoblast cell proliferation and differentiation.
Leukopheresis for profound hyperleukocytosis.

Abstract Background Leukocytoreduction by leukopheresis is recommended for hyperleukocytosis with leukemia, especially when accompanied by neurologic or respiratory symptoms. A single 1–1.5 blood volume leukocytopheresis is expected to reduce the leukocyte count by 30–60%. Case Report A 35 year old man presented with a 2 month history of hearing and visual loss and was found to have chronic myelogenous leukemia (CML) in chronic phase with 700,000 WBC/μL. The blast count was 1%. The spleen was markedly enlarged. He was referred for leukocytopheresis and treatment of his leukemia. Despite the extremely high white cell count, he had a hematocrit of 24, platelets of 161,000/μL, and normal lung, liver and renal function. Results A 15 L leukocytapheresis was performed with a Cobe Spectra with the removal of 1.86 L of bloody fluid with a hematocrit of 10% and a leukocrit of 28%. The blood white cell count decreased from 599,000 to 498,500/μL, and the patient felt better. He was started on hydroxyuria and 8 days later his WBC was 7000/μL. Discussion The patient’s oncologists were initially concerned by the only 17% reduction in his white cell count. However, calculations based on his hematocrit and leukocrit in blood and waste bag suggested that he was 140% blood volume expanded by his leukemia and that the cytopheresis removed about half of the extra volume along with an additional 250 mL of leukocytes, about 35% of his pre-treatment WBC volume. The case and its implications for similar patients are discussed.
Methyl mercury: its effect on eggshell thickness.

The authors have examined the effect of mono- and di-methyl mercury on the shell thickness of two species, the Ring Dove (Streptopelia risoria) and American Kestrel (Falco sparverius). Two clutches (two eggs each) were collected from each pair of doves before the administration of mercury. The length and breadth of each egg was measured before the shell was ashed overnight at 1000/sup 0/. Ashed weight was considered to be a more accurate assay of calcium content than thickness for a species laying small eggs. The results for the Ring Doves are given and it is clear than no effect was observed. The kestrels' diet consisted of one day old dead chicks. The dead chicks were injured with dimethyl mercury dissolved in semane oil in the breast region immediately before being fed to the hawk. The kestrels were on diet for about three months before egg-laying commenced. The thickness of the shells remained exactly constant at 0.172 mm and the Ratcliffe Index (1) was 1.00 +/- 0.03 (10) for controls and 0.95 +/- 0.04 (x12) for those fed mercury. 11 references, 1 table.
Current Practice And Future Directions In Digital Subtraction Angiography

Digital x-ray systems used thus far for non-film subtraction angiography may be divided into two main categories, those using image intensified video fluoroscopy apparatus and those using scanned linear detectors. On each type of system energy subtraction and time subtraction have been investigated. And, even if we limit ourselves to subtraction angiography, several types of energy and time subtraction algorithms have been tried.
Milgrom's revision of Newton's laws - Dynamical and cosmological consequences

Milgrom's (1983) recent revision of Newtonian dynamics was introduced to eliminate the inference that large quantities of invisible mass exist in galaxies. It is shown by simple examples that a Milgrom acceleration, in the form presented so far, implies other far-reaching changes in dynamics. The momentum of an isolated system is not conserved, and the usual theorem for center-of-mass motion of any system does not hold. Naive applications require extreme caution. The model fails to provide a complete description of particle dynamics and should be thought of as a revision of Kepler's laws rather than Newton's. The Milgrom acceleration also implies fundamental changes in cosmology. A quasi-Newtonian calculation adapted from Newtonian cosmology suggests that a 'Milgrom universe' will recollapse even if the classical closure parameter Omega is much less than unity. The solution, however, fails to satisfy the cosmological principle. Reasons for the breakdown of this calculation are examined. A new theory of gravitation will be needed before the behavior of a Milgrom universe can be predicted.
Concerning the phakellin substructure of palau’amine

Abstract The phakellin ( 6 ) subunit of palau’amine ( 1 ) has been synthesized and found to be devoid of antibacterial activity, resolving the question of whether 1 is simply an elaborate phakellin in terms of its antimicrobial properties.
USE OF SPECTRAL SEARCH FOR IDENTIFICATION OF THE VOLATILES IN A SYNTHETIC MEAT FLAVOR SYSTEM

Volatiles from a synthetic meat flavor mixture were isolated and concentrated using the Likens-Nickerson apparatus. After separation by gas chromatography-mass spectrometry (GC-MS), the spectra were fed into a forward spectral-search computer program containing the spectra of over 70,000 catalogued compounds. Tentative identifications were made of the following compounds: 1-undecene, 2,4-dimethyl-undecane, 2,2,4-trimethyl-heptane, acetyl pyrrolidine, furna, 2,2,5,5,-tetramethyl tetrahydrofuran, 2-methyl-thiophene, 2,2-dimethyl-3,4-pentadienal, methylethyl ether, 2-butyl-1-octanol, 2,4-bis-(methyl-butyl)-phenol, and 5-methyl-2-furfural. Four of these compounds have not been identified in meal volatiles. The spectral-search procedure offers many advantages for identification of flavor volatiles, but could be further refined by using only classes of compounds believed to be involved in meat flavor development.
A rapid, quantitative, and selective estimation of radioactively labeled peptidoglycan in gram-positive bacteria

Abstract The Park and Hancock procedure for the isolation of bacterial cell wall peptidoglycans has been modified. The method developed permits rapid and accurate determination of small quantities of radioactively labeled material. The principal modifications consist of carrying out the procedure on glass-fiber filters after a vigorous hydrolysis of the cells with TCA (96°C, 30 min) and using Pronase in place of trypsin.
Chronic graft-versus-host disease: a prospective cohort study.

Chronic graft-versus-host disease (CGVHD) is a major cause of morbidity and mortality following allogeneic bone marrow transplantation (BMT). We studied 159 patients with CGVHD longitudinally to characterize the natural history of CGVHD and identify reliable predictors of response and long-term mortality. Rates of response to treatment were 61%, 53%, and 50% at 6 months, 1 year, and 2 years, respectively. A high incidence of infections (7 of 1000 patient-days at 0 to 6 months, 2.5 of 1000 patient-days at 6 months to 1 year, and 0.6 of 1000 patient-days at 1 to 2 years) was observed. After a median follow-up of 8.4 years, an overall survival rate of 40% was observed. The overall survival rate was 63% (95% confidence interval [CI], 56%-71%) at 1 year, 51% (95% CI, 43%-59%) at 2 years, and 39% (95% CI, 31%-47%) at 10 years. In multivariate analysis, age older than 20 years (RR = 1.5; 95% CI, 0.9%-2.5%; P = .09), progressive onset of CGVHD (RR = 1.6; 95% CI, 1.0%-2.4%; P = .04), platelet count of <100,000/μL (RR = 2.1; 95% CI, 1.3%-3.4%; P = .001), and GI involvement (RR = 1.5; 95% CI, 1.0%-2.4%; P = .05) were associated with increased mortality. Among patients surviving more than 6 months, no response (RR = 4.5; 95% CI, 1.9%-10.5%; P = .0006) and partial response (RR = 2.5; 95% CI, 1.1%-6.1%; P = .04) to treatment at 6 months also were significant predictors of mortality. The prevalence of active CGVHD was 33% at 2 years. However, the cumulative incidence of successful discontinuation of therapy was only 13% at 2 years. Among patients with clinical resolution of CGVHD, only 18% were off immunosuppressive therapy by 2 years, and 89% by 4 years. Despite high initial response rates, a large majority of patients had active disease requiring prolonged immunosuppression. This requires improved infection prevention for a longer time. Recognition of a high-risk group should facilitate assignment of more intensified regimens. Better treatment regimens need to be identified to improve survival and limit toxicity of prolonged immunosuppression. © 2003 American Society for Blood and Marrow Transplantation Biology of Blood and Marrow Transplantation 9:38-45 (2003)
Melanin, nutrition, and the lion's mane.

In their report on the sexually selected function of the lion's mane ( Panthera leo ), P. M. West and C. Packer “(Sexual selection, temperature, and the lion's mane,” 23 Aug., p. [1339][1]) assert that “[m]ane darkness indicates nutrition and testosterone and influences both female choice and
The Inner-Sphere Process in the Enantioselective Tsuji Allylation Reaction with (S)-t-Bu-phosphinooxazoline Ligands

We propose an inner-sphere mechanism explaining the unique performance of the Tsuji asymmetrical allylation reaction using hard prochiral enolate nucleophiles and non-prochiral allyl groups. Using first principles quantum mechanics (B3LYP density functional theory), we find that the pathway for this reaction involves nucleophilic attack followed by interconversion from a five-coordinate Pd complex to a four-coordinate complex. This intermediate is trapped in a potential well and escapes via reductive elimination that proceeds through a seven-membered transition state to generate the product and a Pd0 complex. This seven-membered transition state contrasts dramatically from the usual three-centered C−C reductive elimination paradigm generally associated with C−C coupling reactions. This inner-sphere asymmetric allylation pathway involving hard enolates is energetically more favorable than outer-sphere nucleophilic attack, a process understood to occur in asymmetric allylic alkylations with soft enolates.
Risk and the relationship among strategy organizational processes, and performance

Performance is an important variable in strategic management research. But, although managers must deal with performance on two dimensions, its level return and the variation in that level risk, performance has traditionally been studied only in terms of return. This paper reports the results of a study of business strategy content and processes where performance was operationalized as both return and risk. In a field study of 20 firms in the banking industry in one state, different strategies were found to be associated with differences in risk but not in return. The effects of processes on performance were varied; some processes were associated with risk only, some with return only, and others with both risk and return. These results suggest that the relationships among strategy, processes and performance are more complex than most researchers have acknowledged. Further theoretical and managerial insights may be gained into these relationships if risk is included as a dimension of performance in strategic management research.
Do RANKL inhibitors (denosumab) affect inflammation and immunity

Receptor activator of nuclear factor kappa B ligand (RANKL) and its natural antagonist, osteoprotegerin (OPG), are, respectively, an indispensable factor and a potent inhibitor for osteoclast differentiation, activity, and survival. The development of a human monoclonal antibody to RANKL, denosumab, constitutes a novel approach to prevent fragility fractures in osteoporosis, skeletal complications of malignancy, and potentially bone erosions in rheumatoid arthritis (RA). In addition to being expressed by osteoblasts, RANKL is abundantly produced by activated T cells, and synoviocytes in RA, whereas its receptor, RANK, is also expressed by monocytes/macrophages and dendritic cells. However, in preclinical and clinical studies of RA—including patients with some degree of immunosuppression—RANKL inhibitors did not significantly alter inflammatory processes. RANKL, RANK, and OPG deficiency in murine models highlights the important role of this pathway in the development and maturation of the immune system in rodents, including functions of T and/or B cells, whereas OPG overexpression in mice and rats seems innocuous with regard to immunity. In contrast, loss-of-function mutations in humans have more limited effects on immune cells. In clinical studies, the overall rate of infections, cancer, and death was similar with denosumab and placebo. Nevertheless, the risk of severe infections and cancer in some specific tissues remains to be carefully scrutinized.
Maspin regulates hypoxia-mediated stimulation of uPA/uPAR complex in invasive breast cancer cells.

Maspin, a unique serine proteinase inhibitor (serpin), plays a key role in mammary gland development and is silenced during breast cancer progression. Maspin has been shown to inhibit tumor cell motility and invasion in cell culture, as well as growth and metastasis in animal models. In this study, we investigated the effect of maspin on the regulation of hypoxia-induced expression of urokinase-type plasminogen activator (uPA) and its receptor (uPAR), with respect to invasive potential in metastatic breast cells MDA-MB-231. We hypothesized that maspin can neutralize or mitigate hypoxia- induced expression of uPA/uPAR in metastatic breast cancer cells, resulting in suppression of their invasive potential. To test our hypothesis, we employed the highly invasive MDA-MB-231 breast cancer cells that are devoid of maspin, and transfected them with the maspin gene, and then determined the effect of hypoxia on uPA/uPAR expression. Normal mammary epithelial cells 1436N1 were used as a control. Our findings demonstrate that maspin downregulated the basal and hypoxia-induced uPA/uPAR expression and reduced the stimulatory effect of hypoxia on the in vitro invasive ability of MDA-MB-231-cells. In addition, maspin also inhibited the enzymatic activity of secreted and cell associated uPA in MDA-MB-231 cells. These results indicate that maspin inhibits hypoxia-induced invasion of metastatic breast cancer cells by blocking the uPA system, thus illuminating an important molecular pathway for therapeutic consideration.
Realizing the power of strategic vision

Abstract This article defines the concept of strategic vision, seeing ‘vision’ as a coherent and powerful statement of what the business should aim to become. It must be realistic about the market, competitive, economic, and regulatory conditions and reflect the values and aspirations of management, employees, and stakeholders. In uncertain and difficult times visioning is vital to establish direction.
Response of phenobarbital- and ciprofibrate-exposed hepatocytes to growth factors in type I collagen gels

The response of promoter-exposed hepatocytes to the complete hepatic mitogens hepatocyte growth factor (HGF), epidermal growth factor (EGF) and acidic fibroblast growth factor (aFGF) was studied. Male Fisher 344 rats were administered phenobarbital or ciprofibrate. Hepatocytes were isolated at various time points and cultured in type I collagen gels, a 3-dimensional culture system that allows stable long-term hepatocyte differentiation. DNA synthetic activity in response to addition of HGF, aFGF or EGF to the cultures was assayed by incorporation of [3H]thymidine. Administration of ciprofibrate to rats caused an immediate decreased growth response in hepatocytes to all three growth factors. Phenobarbital administration caused a gradual decrease in responsiveness to the growth factors: after 10 days, hepatocytes became insensitive to the mitogenic effects of HGF, EGF and aFGF. However, an early increase in responsiveness to HGF and aFGF occurred in phenobarbital-exposed hepatocytes. The results indicate that phenobarbital and ciprofibrate have similar inhibitory effects on hepatocyte DNA synthesis in culture after long-term in vivo exposure. However, their early effects on hepatocyte growth response differ considerably, suggesting that their effects on cellular proliferation occur via different mechanisms.
The TCL1 oncoprotein binds the RNase PH domains of the PNPase exoribonuclease without affecting its RNA degrading activity

TCL1 is an AKT kinase coactivator that, when dysregulated, initiates mature lymphocyte malignancies in humans and transgenic mice. While TCL1 augments AKT pathway signaling, additional TCL1 interacting proteins that may contribute to cellular homeostasis or transformation are lacking. Here, an exoribonuclease, PNPase, was identified in a complex with TCL1. The AKT interaction domain on TCL1 bound either RNase PH repeat domain of PNPase without influencing its RNA degrading activity, which was compatible with predicted docking models for a TCL1-PNPase complex. Our data provide a novel protein interaction for mammalian PNPase that may impact TCL1 mediated transformation.
The Optical Emission from Oscillating White Dwarf Radiative Shock Waves

The hypothesis that quasi-periodic oscillations (QPOs) are due to the oscillatory instability of radiative shock waves discovered by Langer et al. (1981, 1092) is examined. The time-dependent optical spectra of oscillating radiative shocks produced by flows onto magnetic white dwarfs are calculated. The results are compared with the observations of the AM Her QPO sources V834 Cen, AN UMa, EF Eri, and VV Pup. It is found that the shock oscillation model has difficulties with aspects of the observations for each of the sources. For VV Pup, AN UMa, and V834 Cen, the cyclotron luminosities for the observed magnetic fields of these systems, based on our calculations, are large. The strong cyclotron emission probably stabilizes the shock oscillations. For EF Eri, the mass of the white dwarf based on hard X-ray observations is greater than 0.6 solar mass.
Nanoliter scale microbioreactor array for quantitative cell biology

A nanoliter scale microbioreactor array was designed for multiplexed quantitative cell biology. An addressable 8 x 8 array of three nanoliter chambers was demonstrated for observing the serum response of HeLa human cancer cells in 64 parallel cultures. The individual culture unit was designed with a "C" shaped ring that effectively decoupled the central cell growth regions from the outer fluid transport channels. The chamber layout mimics physiological tissue conditions by implementing an outer channel for convective "blood" flow that feeds cells through diffusion into the low shear "interstitial" space. The 2 microm opening at the base of the "C" ring established a differential fluidic resistance up to 3 orders of magnitude greater than the fluid transport channel within a single mold microfluidic device. Three-dimensional (3D) finite element simulation were used to predict fluid transport properties based on chamber dimensions and verified experimentally. The microbioreactor array provided a continuous flow culture environment with a Peclet number (0.02) and shear stress (0.01 Pa) that approximated in vivo tissue conditions without limiting mass transport (10 s nutrient turnover). This microfluidic design overcomes the major problems encountered in multiplexing nanoliter culture environments by enabling uniform cell loading, eliminating shear, and pressure stresses on cultured cells, providing stable control of fluidic addressing, and permitting continuous on-chip optical monitoring.
Interdisciplinary research produces results in understanding planetary dunes

First International Planetary Cave Research Workshop: Implications for Astrobiology, Climate, Detection, and Exploration; Carlsbad, New Mexico, 25–28 October 2011 With the advent of high-resolution spatial imaging, the idea of caves on other planets has moved from the pages of science fiction into the realm of hard-core science—complete with hypotheses, models, experiments, and observational data. Recently acquired data from spacecraft, together with terrestrial analogs and numerical models, are providing new insights into caves on Earth as well as caves on other terrestrial planetary bodies (e.g., Moon, Mars, and Titan).
Re-visiting 1-D hypervelocity penetration

Abstract Classical, one-dimensional theory of hydrodynamic penetration is used as the basis of establishing simplified analytical relationships describing energy, momentum, and power deposition during hypervelocity impact events. A concise overview of the 1-D model is given followed by a select grouping of terms into relationships that offer first-order criteria for making engineering design considerations on relevant applications and assist in the analysis of experimental observations. Momentum, energy, and power deposition are found to be proportional to second, third and fourth power exponents, respectively. These analytical terms are presented for constant velocity gradient, i.e. fixed length, rods as well as linear velocity gradient rods, such as shaped charge jets. The role of penetrator-to-target density ratio is then examined in terms of the backflow, or reverse flow of 1-D penetration. Again, the non-dimensional ratio of penetrator-to-target mass density is used to compare the relative velocity of material flow during penetration. The relationship highlights the role of penetrator materials for achieving desired effects in these hypervelocity, terminal ballistics events. Albeit the relationships are derived on the assumptions for hydrodynamic processes, their generality of form and ease of implementation make them a useful first-order description for engineering insight and application over a broad range of velocities.
Psychopathology in substance abusing adolescents: gender comparisons

Few studies have explored gender comparisons of psychopathology in substance abusing adolescents. To expand the knowledge base in this area, we assessed 59 adolescents (34 males and 25 females) presenting for inpatient treatment in a university‐based adolescent dual diagnosis program. Subjects were interviewed for psychiatric disorders using the revised Child Schedule for Affective Disorder and Schizophrenia (K‐SADS). The Structured Clinical Interview DSM‐IV (SCID‐R) was used to diagnose substance use disorders. The subjects were primarily Caucasian, ages 12–18. Ninety‐four per cent of the sample used tobacco and females were more likely than males to meet criteria for alcohol abuse or dependence. Disruptive disorders were the most prevalent psychiatric diagnoses in both males and females. However, anxiety disorders were more prevalent in females, and social phobia was the most common anxiety disorder. Both groups had experienced physical and/or sexual abuse; however, there was a trend towards higher inci...
Disequilibrium partial melting model and its implications for trace element fractionations during mantle melting

Abstract A model to describe trace element evolutions during partial melting is proposed by assuming surface equilibrium instead of complete equilibrium between mineral grains and melt and by considering the following factors: (1) chemical diffusion in minerals; (2) melting and melt extraction. For mantle melting rates of ∼ 10 −7 yr −1 , inferred from mid-ocean ridge spreading rates, elements with diffusivities ( D ) in minerals of > 10 −15 cm 2 /s be at equilibrium between minerals of 0.5 cm in diameter and melt during mantle melting. However, the anomalous radioactive excess of 236 Ra over 230 Th (up to 300%) in young basalts which cannot be explained by equilibrium melting because of the highly incompatible nature of both elements can be accounted for by the present model only when melting rate is in the orders of 10 −6 to 10 −5 yr −1 . The disequilibrium effect cannot be ignored for elements with D −13 cm 2 /s if the melting rate is 10 −5 yr −1 . Disequilibrium melting lowers the incompatibility of an incompatible element; the high the incompatibility, the more obvious this effect is. Fractionation of trace elements during disequilibrium melting depends both on their equilibrium partition coefficients ( k ) and their diffusivities. This has two consequences: (1) fractionation of two highly incompatible elements ( k ⩽ 0.01) by more than 20% is still possible at melting degree as high as 15% if their diffusivities differ by a factor of 5 or more, as compared to the requirement for less than 5% partial melting for the same extent of fractionation by equilibrium melting; and (2) the incompatibility order of two incompatible elements can be reversed under certain circumstances (i.e., k 1 > k 2 , but D 1 > D 2 ). The Pb paradox, namely, that the U/Pb ratio in mantle sources inferred from Pb isotopes has increased during the differentiation of the Earth even though Pb is less incompatible than U, is explainable if the diffusivity of Pb is higher than that of U (e.g., by a factor of 10) and if the melting rate is in the order of 10 −5 yr −1 .