cssi/SciSciGPT-SciSciNet huggingface dataset:
Chemotherapeutic nucleoside analogues and DNA polymerase β

1369 DNA polymerase β (pol β) was used as a model system to study the mechanism of nucleoside analogues Cytosine Arabinoside (AraC), Cytosine 2’-Fluorodeoxyriboside (2F-dC), and Cytosine 2’, 2’-difluorodeoxyriboside (Gemcitabine). AraC and Gemcitabine are widely used for the treatment of human cancers, and must be incorporated into the nascent DNA strand by DNA polymerases for optimal anti-tumor activity. Nucleoside analogues are often administered in combination with alkylating agents that can result in up-regulation of DNA repair enzymes such as pol β. This project used a structure-function approach to investigate the mechanism of nucleotide analogue discrimination by DNA pol β. The pol βvariants studied were located both in the active site (Tyr-271), and the loop region of the palm domain (Arg-253 and Pro-242). Discrimination of incoming nucleosides by these variants was examined using an in vitro HSV-thymidine kinase forward mutation assay, mutational spectra, and steady-state kinetic analyses. Active site variants Y271L and Y271G have a similar enzymatic activity relative to wild type (WT) pol β. The HSV-tk assay showed a three-fold higher mutation frequency for the Tyr to Gly change, implying a steric role of the Tyr-271 in pol β nucleoside incorporation. This is especially interesting because other family X polymerases, pol λ and μ, have a highly conserved glycine in the corresponding position. The loop variant P242R is the only identified human polymorphism in the pol βgene coding region, and its effect on nucleoside discrimination is yet to be determined. We constructed the variant by PCR site-directed mutagenesis and determined that its inherent enzymatic activity is similar to WT. P242R has a four-fold decreased mutation frequency and an altered mutation spectra, relative to WT. R253M, also in the loop, is known to confer an AZT-resistant in vivo phenotype (Kosa, et. al, 1999) and we confirmed this anti-mutator tendency. By in vitro incorporation assays, R253K and R253C showed similar enzymatic activity compared to WT, while R253G was relatively inactive. The catalytic activity (Vmax/Km) for AraCTP incorporation by pol β WT and variants P242R and R253M were two- to three- fold lower compared to dCTP incorporation, while the catalytic activity for 2F-dCTP incorporation was seven- to twelve- fold lower compared to dCTP. This study established that pol β recognizes AraCTP and 2F-CTP to different extents, although both nucleotide analogues have 2’-ribose modifications. Our results support the hypothesis that the loop of the palm domain region of pol β is involved in pre-selection of incoming nucleotides prior to basepairing, and a polymorphism involving this region can potentially result in an altered response to chemotherapeutic nucleoside analogues.
Building a better way to mend a broken heart

A novel hybrid pulsatile ventricular assist device uses an endothelialized pump surface to achieve biocompatibility.
Potential amelioration of waterborne iron toxicity in channel catfish (Ictalurus punctatus) through dietary supplementation of vitamin C.

Abstract Iron overload in water is a problem in many areas of the world, which could exert toxic effects on fish. To achieve maximum growth and overall fitness, iron induced toxicity must be alleviated. Therefore, this research was undertaken to investigate the potential mitigation of iron toxicity by dietary vitamin C supplementation in channel catfish (Ictalurus punctatus). Two doses of vitamin C (143 and 573 mg/kg diet) were tested against high environmental iron (HEI, 9.5 mg/L representing 25% of 96 h LC50). Fish were randomly divided into six groups with four replicated tanks. The groups were Control (vitamin C deficient feed), LVc (143 mg vitamin C supplemented per kg diet), HVc (573 mg vitamin C supplemented per kg diet), Con + Fe (control exposed to HEI), LVc + Fe (LVc exposed to HEI) and HVc + Fe (HVc exposed to HEI). Following an 8 week trial, there was a significant reduction in weight gain (WG%) in Con + Fe compared to the control, indicating a toxic effect of HEI on fish growth performance. Interestingly, WG% in both LVc + Fe and HVc + Fe groups were significantly higher than Cont + Fe, signifying that HEI inhibited growth, but this was alleviated by vitamin C. Both hemoglobin content and hematocrit were higher in LVc + Fe compared to the control and Con + Fe. In addition, exposure to HEI (Con + Fe) incited hepatic oxidative stress based on an over-accumulation of malondialdehyde (MDA) along with a significant inhibition in superoxide dismutase (SOD) and catalase (CAT) activities; whereas in LVc + Fe and HVc + Fe, the MDA content restored to basal level. A series of histopathological alterations were observed in the liver and gills, with the most severe lesions in Con + Fe, which was also complemented with a remarkable increase in hepatic iron accumulation. Vitamin C supplementations reduced the augmented concentrations of iron accumulation to that of the control. No effect, regardless of the treatments, was noted for fatty acid composition of muscle. Overall, our findings suggest that the vitamin C supplementation can be an effective therapeutic approach for boosting growth as well as alleviating iron toxicity in catfish.
Microbial composition, diversity, and activity varies across different types of basal ice

Basal ice often contains entrained subglacial debris and sediment which can serve as a source of nutrients and organic matter and provide habitat for microorganisms adapted to frozen conditions. However, basal ice comes in many different forms and comparatively little is known about how microbial composition, diversity, and activity vary across different types of basal ice. Here, we investigated these parameters in four different types of basal ice from two different glaciers and then used a meta-analysis to compare our findings with microbiome studies of other permanently frozen environments. We found microbiome composition varies substantially between basal ice types, even within the same glacier. Further, the microbiomes of sediment-rich basal ices were distinct from those found in glacial ice and instead were most like those found in permafrost. Consistent with this, microbial diversity was also comparable to that found in permafrost and was much higher relative to glacial ice. Patterns of 16S rRNA read abundance from RNA relative to DNA implicated certain taxa as potentially active in basal ice with ice temperature appearing to be an important predictor for the diversity of taxa inferred to be active. Our results improve our understanding of the microbial ecology of different basal ice types and provide insight into which types are likely habitats for metabolizing microbial communities.
Bio-FlatScope: a flat, lensless microscope for fluorescence imaging

We developed a lensless microscope with small, inexpensive form factor, large field-of-view (FOV) and cellular resolution for fluorescence imaging. Proof-of-principle measurements with “Bio-FlatScope” are presented in fixed biological samples.
Symptomatic contralateral osteophyte fracture with migration causing lumbar plexopathy during oblique lumbar interbody fusion: illustrative case

BACKGROUND While performing lateral lumbar interbody fusion surgery, one of the surgical goals is to release the contralateral side with a Cobb elevator, allowing distraction of the interbody space. Many times, there are large osteophytes on the contralateral side, and the osteophytes can be split open with the Cobb or blunt instrument. It is extremely rare for the actual osteophyte to break off from the vertebral body into the contralateral psoas muscle and lumbar plexus. OBSERVATIONS The authors report a case of symptomatic lumbar plexopathy caused by an osteophyte fracture after an oblique lumbar interbody fusion requiring a right-sided anterior approach to excise the bony fragment. They illustrate the case with imaging that the radiologist did not comment on, and they also show a video of the surgical excision of the osteophyte through a right-sided anterior lumbar retroperitoneal approach. The authors also show how the patient had spontaneous right-sided electromyography (EMG) firing before excision of the osteophyte and how the EMG firing resolved after excision. LESSONS Although the literature is plentiful with regard to ipsilateral approach–related complications, the authors discuss the literature with regard to contralateral complications after minimally invasive lateral lumbar interbody fusion.
Dynamic interactions between two axially aligned threaded joints undergoing loosening

Abstract Maintaining effective preload in bolted joints is critical for ensuring long-term performance and safety throughout the operation of any assembled structure, vehicle, or machine. The loosening of bolted joints has been studied since the Industrial Revolution, but modeling approaches have only emerged over the past three decades. Although existing approaches are capable of simulating or predicting loosening in a single joint consisting of a single bolt, they are too computationally expensive to be used to model loosening in large built-up structures consisting of dozens to thousands of joints. Recently, a new reduced-order modeling approach has been proposed for the reproducing the behavior of axially aligned threaded joints undergoing loosening due to shock excitation. The objective of this research is to apply this new approach to investigate how multiple joints can interact with each other through the global dynamics of the structure during loosening. Specifically, the new approach is applied to model the behavior of three rods connected together using two axially aligned threaded joints. The results demonstrate that the behavior of the three-rod system can be divided into five regimes based on applied loading: first, a low-amplitude (low-energy) regime where the evolution of each joint is independent of the other; second, a regime where the joints exhibit weak dependence on each other; third, a regime of strong dependence; fourth, a regime where bands of mitigation arise corresponding to only one joint loosening; and fifth, a regime corresponding to complete rapid loosening of the first joint. The third and fourth regimes reveal that when the joints are torqued to the same initial preload, regardless of the actual value, both joints will always loosen completely. However, when the joints are tightened to different amounts, there exist combinations where only one joint loosens completely, such that the other joint maintains some of the initial preload.
LIGHTNING TALK: The Rural And Diverse Student Scholars Program At Mason

Session LOCATION: George's (3rd Floor of the Johnson Center) The Rural and Diverse Student Scholars Program at Mason is a strategic initiative to recruit and retain rural and diverse Virginia students in STEM. Funded by an NSF S-STEM grant, the RADSS program bridged the College of Science and the Office of Admissions, enabling new recruiting methods and a special population of students to be welcomed to Mason. We will describe the program components that recruited these students and support their retention in STEM.
Effect of dexmedetomidine on the QT interval in pediatric patients undergoing general anesthesia.

Recent years have seen an increase in the use of dexmedetomidine in pediatric patients presenting for surgical procedures. However, only a limited number of studies have evaluated its effects on the QT interval in this patient group. To address this lack of knowledge, we have evaluated the effects of dexmedetomidine on the QT interval in children receiving sevoflurane anesthesia. This study was a prospective case–control study in which pediatric patients presenting for anesthetic care were divided into two groups—the dexmedetomidine (D) and control (C) groups. Three electrocardiograms (ECGs) were obtained on each patient, including a baseline ECG (T1) prior to anesthetic induction and an ECG after the induction of anesthesia with sevoflurane (T2). In group D, the third ECG was obtained 2 min after the administration of dexmedetomidine, which in turn was started immediately after the T2 ECG reading (T3D); in group C, it was obtained 2 min after the T2 reading (T3C). Statistical analysis was performed using analysis of variance to compare the QT intervals at the three time points outlined above. A total of 50 patients were recruited to the study, ranging in age from 1 to 16 [mean 7.9 ± 4.1 (SD) years]. There were 25 patients in group C and 25 in group D. There were no statistical differences in the demographics between the 2 groups. In group C, the QTc was noted to increase progressively with the administration of sevoflurane (T3C vs. T1; P = 0.006). In group D, following the administration of dexmedetomidine, there was a significant decrease in the QTc relative to the post-induction value [436 ± 25 (T2) vs. 418 ± 17 ms (T3D); P < 0.01]. A progressive lengthening of the QTc interval following the administration of sevoflurane was observed in the control group. In the dexmedetomidine group, there was a significant shortening of the QTc interval following the administration of dexmedetomidine compared to the length of the post-induction QTc interval and when compared to the control group.
Nevus lipomatosus superficialis on the face.

A 17-year-old woman presented with asymptomatic, multiple plaques around the right mandibular area of the face extending from the cheek to the neck. These lesions had gradually increased in size and number for 8 years, and then were stationary. When she came to us, there were a few skin-colored or pale yellowish papules and plaques ranging from 0.2 to 1 cm in diameter (Fig. 1). The patient stated that initially the papules developed discretely, and then these papules were confluent and grouped slowly with new lesions. The most recent lesions were skin-colored papules which were soft to the touch, the older lesions were yellowish plaques with firm consistency and a smooth shiny surface. The patient's general condition had been good at the initial visit and the laboratory findings including blood cell counts, urinalysis, and routine blood chemistry tests were all within normal limits. A roentgenogram of the mandibular area did not reveal any significant findings. The presumptive clinical diagnosis of connective tissue nevus was made. Histologic examination of biopsy specimen taken from the neck showed lobules of fat cells embedded among the collagen bundles at the level of papillary dermis and collagen bundles were proliferated irregularly (Fig. 2). The individual fat cells were mature and of normal size. The lobules were not encapsulated and did not communicate with the subcutaneous fat tissue. The epidermal changes of the lesions consisted of mild hyperkeratosis with follicular plugging and slightly increased numbers of capillaries were observed around the dermal fat cells (Fig. 3). Therefore, it was diagnosed as nevus lipomatosus superficialis (NLS) which developed multiple lesions very rarely on the face. After surgical removal of the lesion, no evidence of recurrence has been observed 1 year postoperatively.
Magnet design issues for ITER

The ITER magnetics design has been an iterative process with a trend toward features which enhance reliability and facilitate assembly. The design will continue to evolve and there remain several design issues which will be best resolved through the R&D program.
Changes in microstructure and thermal properties of thermally processed cornstarch/soy protein isolate model food systems

Abstract Fluorescent microscopy and differential scanning calorimetry were used to study the influence of thermal processing on the microstructure and thermal properties of cornstarch/soy protein model food systems. Both analytical methods showed that extrusion thermal processing at 50°C affected the physical characteristics of cornstarch/soy protein samples almost to the same extent as conventional heating at 150°C. For example, the enthalpies of transition were 0.8J/g for samples conventionally processed at 150°C and 0.6J/g for samples extruded at 50°C. The micrographs also showed that the starch granules were not completly disrupted by conventional thermal processing at 150°C but extrusion thermal processing gelatinized the starch granules at 50°C. Overall, the greatest microstructure modifications of starch or protein were clearly shown to be due to extrusion when compared to conventional thermal processing.
Steady-State Spheromak Reactor Studies

After summarizing the essential elements of a gun-sustained spheromak, the potential for a steady-state reactor is explored by means of a comprehensive physics/engineering/costing model. A range of...
Tacit Subjects: Belonging and Same-Sex Desire among Dominican Immigrant Men by Carlos U. Decena

While the anthropological and sociological literature has begun to productively examine the mainstream formation and maintenance of U.S. same-sex identities, relatively little ethnographic data has...
PCR-based gut content analysis of insect predators: using ribosomal ITS-1 fragments from prey to estimate predation frequency.

We used polymerase chain reaction to determine whether Ostrinia nubilalis (Hubner) (Lepidoptera: Crambidae) DNA was present in the guts of larvae and adult males and females of the generalist predator Coleomegilla maculata De Geer (Coleoptera: Coccinellidae). The predators were fed Ostrinia nubilalis egg masses and allowed to digest at either 20 degrees C or 27 degrees C for time spans ranging from 0 to 12 h. Four primer pairs, specific for O. nubilalis were developed, using a nuclear ribosomal RNA sequence including part of the 18S gene, the complete internal transcribed spacer (ITS-1) region and part of the 5.8S gene. These primers amplified four sequences that were 492, 369, 256 and 150 base pairs long. We found a significant negative effect of time since feeding on the number of bands that could be detected. The shortest fragment was detected for the longest time after feeding (up to 12 h). We found no effect of predator weight, sex, developmental stage, or meal size on the time course over which bands of varying lengths could be detected.
Chromatic dispersion measurement in graded-index multimode optical fibers

The chromatic dispersion observed in a graded-index multimode optical fiber is a function of the radial position of the launched light. When a graded-index multimode optical fiber is overfilled spatially and angularly, the chromatic dispersion observed is an average (composite) chromatic dispersion over all of the possible launches. Under certain assumptions, the relationship between the chromatic dispersion observed for the overfilled fiber and the chromatic dispersion of any restrictive launch can be determined. This relationship can be used to predict the composite graded-index multimode optical fiber chromatic dispersion from the measurement of the chromatic dispersion of a single simplified launch, such as a single-mode fiber launch. Preliminary experimental results confirm this approach. >
Characterization of a Drosophila proximal-sequence-element-binding protein involved in transcription of small nuclear RNA genes.

In a wide variety of eukaryotic organisms, transcription of small nuclear RNA (snRNA) genes is dependent upon a proximal sequence element (PSE) located upstream of position –40 relative to the transcription start site. There is little or no existent knowledge concerning the PSE-binding proteins of organisms other than human. Here, we report the purification of a fraction enriched in the Drosophila melanogaster PSE-binding protein (Dw PBP). Dm PBP forms a highly specific complex with the PSE. The protein stimulates transcription from the Ul gene promoter by RNA polymerase II and from the U6 gene promoter by RNA polymerase III in Drosophila nuclear extracts, and activation is dependent upon the presence of a PSE. The molecular mass of native Dm PBP as measured by gel-filtration chromatography is 375 kDa. Two polypeptides (apparent molecular masses 59 kDa and 61 kDa) appear to be in close contact with the DNA in that they can be very efficiently and specifically crosslinked to the PSE sequence by ultraviolet irradiation.
Robust embedded data from wavelet coefficients

An approach to embedding gray scale images using a discrete wavelet transform is proposed. The proposed scheme enables using signature images that could be as much as 25% of the host image data and hence could be used both in digital watermarking as well as image/data hiding. In digital watermarking the primary concern is the recovery or checking for signature even when the embedded image has been changed by image processing operations. Thus the embedding scheme should be robust to typical operations such as low-pass filtering and lossy compression. In contrast, for data hiding applications it is important that there should not be any visible changes to the host data that is used to transmit a hidden image. In addition, in both data hiding and watermarking, it is desirable that it is difficult or impossible for unauthorized persons to recover the embedded signatures. The proposed scheme provides a simple control parameter that can be tailored to either hiding or watermarking purposes, and is robust to operations such as JPEG compression. Experimental results demonstrate that high quality recovery of the signature data is possible.
DEVELOPMENT OF GLOMERULAR PERFUSION RATE (GPR) IN FETAL AND NEWBORN LAMBS

The developmental pattern of regional glomerular density (GD) and glomerular perfusion rate (GPR) was studied in 29 fetal kidneys between 103-142 days of gestation (term 145 days) and in 8 newborn kidneys (3 to 19 days) using 15μ microspheres. The relative distribution of GD, measured in four cortical zones (zone 1 being the most outer portion) decreased in zone 1 from 44±3% in fetuses <120 days to 31±1.5% in newborns (p<0.01) and increased from 17±1.5% to 25±1.2% in zone 3 (p<0.05). No significant changes were seen in GD in zones 2 or 4. GPR values (nl/min), computed for each cortical zone, did not increase during fetal life (see Table). However, after birth, GPR increased three times in zones 1 and 2, doubled in zone 3 and did not change in zone 4 when compared to mean fetal GPR values. The increase in GPR in zones 1 and 2 followed the increase in glomerular filtration rate (GFR) very closely (r=0.82 and 0.86) in newborns. The present results suggest that the rapid increase in GFR following birth may depend on the increase in GPR in the outer portion of the cortex.
Parallel psychometric and cognitive modeling analyses of the Penn Face Memory Test in the Army Study to Assess Risk and Resilience in Servicemembers

Objective: The psychometric properties of the Penn Face Memory Test (PFMT) were investigated in a large sample (4,236 participants) of U.S. Army Soldiers undergoing computerized neurocognitive testing. Data were drawn from the initial phase of the Army Study to Assess Risk and Resilience in Servicemembers (Army STARRS), a large-scale study directed towards identifying risk and resilience factors for suicidal behavior and other stress-related disorders in Army Soldiers. In this paper, we report parallel psychometric and cognitive modeling analyses of the PFMT to determine whether ability estimates derived from the measure are precise and valid indicators of memory in the Army STARRS sample. Method: Single-sample cross-validation methodology combined with exploratory factor and multidimensional item response theory techniques were used to explore the latent structure of the PFMT. To help resolve rotational indeterminacy of the exploratory solution, latent constructs were aligned with parameter estimates der...
High-throughput analysis of mammalian olfactory receptors: measurement of receptor activation via luciferase activity.

Odorants create unique and overlapping patterns of olfactory receptor activation, allowing a family of approximately 1,000 murine and 400 human receptors to recognize thousands of odorants. Odorant ligands have been published for fewer than 6% of human receptors1-11. This lack of data is due in part to difficulties functionally expressing these receptors in heterologous systems. Here, we describe a method for expressing the majority of the olfactory receptor family in Hana3A cells, followed by high-throughput assessment of olfactory receptor activation using a luciferase reporter assay. This assay can be used to (1) screen panels of odorants against panels of olfactory receptors; (2) confirm odorant/receptor interaction via dose response curves; and (3) compare receptor activation levels among receptor variants. In our sample data, 328 olfactory receptors were screened against 26 odorants. Odorant/receptor pairs with varying response scores were selected and tested in dose response. These data indicate that a screen is an effective method to enrich for odorant/receptor pairs that will pass a dose response experiment, i.e. receptors that have a bona fide response to an odorant. Therefore, this high-throughput luciferase assay is an effective method to characterize olfactory receptors—an essential step toward a model of odor coding in the mammalian olfactory system.
Characterization of a protein in mid-term human amniotic fluid which reacts in the somatomedin-C radioreceptor assay.

Amniotic fluid contains materials other than insulin which react in a somatomedin C radioreceptor assay using human placental membranes. The material in mid-gestational amniotic fluid which reacted with the somatomedin C radioreceptor assay eluted slightly after albumin from a Sephadex G-150 column equilibrated with 0.1M NH4HCO3. Neither boiling nor treatment of this fraction with 1%formic acid yielded small molecular weight somatomedin- Iike peptides. Separation of the somatomedin reactive material (Sm RM) from albumin was achieved by gel filtration through Ultrogel AcA44 in 0.1M NH4HCO3. The active product had an apparent molecular weight of 33,000 to 35,000 Daltons; its isoelectric point determined by focusing was between 4.1 and 5.1. The purified amniotic fluid protein displaced somatomedin C in the somatomedin C radioreceptor assay but did not compete with insulin in the insulin radioreceptor assay. Sm RM produced only a slight stimulation thymidine uptake in human fibroblasts but was inactive in sti...
Allyl alcohol partially protects murine hepatic mitochondria against carbon tetrachloride.

Male CD-1 mice were treated with carbon tetrachloride (CCl4, 1 ml/kg, i.p.), or allyl alcohol (AA, 0.05 ml/kg, i.p.) or both 24 h prior to sacrifice. The livers were removed, homogenized and mitochondrial preparations were fractionated. Electron micrographs of the mitochondrial pellet from the livers of mice treated with CCl4 showed lysed and fragmented mitochondria as well as a few condensed mitochondria. No normal intact mitochondria were observed. The mitochondrial pellet from AA-treated livers was characterized by a preponderance of condensed mitochondria whether CCl4 was given also or not. The mitochondrial fraction from CCl4-treated mice failed to utilize oxygen whereas that fraction from mice given AA did not differ from control in either its basal oxygen consumption (state 4) or oxygen utilization after the addition of adenosine diphosphate (state 3). State 4 respiration differed slightly but significantly from control in mitochondria from mice given both AA and CCl4 whereas state 3 respiration was greatly and significantly decreased from that of control values. Electron micrographs of liver slices from mice given AA or the combination of AA and CCl4 showed normal mitochondrial morphology. Thus, AA appears to exert an influence, perhaps at the level of the mitochondrial membrane, which is manifested only after their isolation. This effect which results in the condensation of isolated mitochondria serves to partially protect them against CCl4, but it did not prevent the characteristic CCl4-induced centrilobular necrosis.
Geometric programming and mechanism design for air traffic conflict resolution

We develop certain extensions of optimization-based conflict resolution methods in air traffic control. The problem considered concerns the scheduling of the crossing times of a set of aircraft through a metering fix, while maintaining aircraft separation. First, we show how to solve this combined path planning and scheduling problem using mixed-integer geometric programming. Second, the objective function used to determine the aircraft ordering at the fix is not given a priori but needs to be obtained from the airlines, which are strategic profit maximizing agents and could lie about their true cost. In order to realign individual and global objectives, we study the use of the Clarke-Groves mechanism in this context, which aims at extracting the true utility functions from the airlines using side-payments to the FAA.
Polymers with Very Low Polydispersities from Atom Transfer Radical Polymerization

A radical polymerization process that yields well-defined polymers normally obtained only through anionic polymerizations is reported. Atom transfer radical polymerizations of styrene were conducted with several solubilizing ligands for the copper(I) halides: 4,4′-di-tert-butyl, 4,4′-di-n-heptyl, and 4,4′-di-(5-nonyl)-2,2′-dipyridyl. The resulting polymerizations have all of the characteristics of a living polymerization and displayed linear semilogarithmic kinetic plots, a linear correlation between the number-average molecular weight and the monomer conversion, and low polydispersities (ratio of the weight-average to number-average molecular weights of 1.04 to 1.05). Similar results were obtained for the polymerization of acrylates.
Exploring polyethylenimine-mediated DNA transfection and the proton sponge hypothesis.

Background The relatively high transfection efficiency of polyethylenimine (PEI) vectors has been hypothesized to be due to their ability to avoid trafficking to degradative lysosomes. According to the proton sponge hypothesis, the buffering capacity of PEI leads to osmotic swelling and rupture of endosomes, resulting in the release of the vector into the cytoplasm. Methods The mechanism of PEI-mediated DNA transfer was investigated using quantitative methods to study individual steps in the overall transfection process. In addition to transfection efficiency, the cellular uptake, local pH environment, and stability of vectors were analyzed. N-Quaternized (and therefore non-proton sponge) versions of PEI and specific cell function inhibitors were used to further probe the proton sponge hypothesis. Results Both N-quaternization and the use of bafilomycin A1 (a vacuolar proton pump inhibitor) reduced the transfection efficiency of PEI by approximately two orders of magnitude. Chloroquine, which buffers lysosomes, enhanced the transfection efficiency of N-quaternized PEIs and polylysine by 2–3-fold. In contrast, chloroquine did not improve the transfection efficiency of PEI. The measured average pH environment of PEI vectors was 6.1, indicating that they successfully avoid trafficking to acidic lysosomes. Significantly lower average pH environments were observed for permethyl-PEI (pH 5.4), perethyl-PEI (pH 5.1), and polylysine (pH 4.6) vectors. Cellular uptake levels of permethyl-PEI and perethyl-PEI vectors were found to be 20 and 90% higher, respectively, than that of parent PEI vectors, indicating that the reduction in transfection activity of the N-quaternized PEIs is due to a barrier downstream of cellular uptake. A polycation/DNA-binding affinity assessment showed that the more charge dense N-quaternized PEIs bind DNA less tightly than PEI, demonstrating that poor vector unpackaging was not responsible for the reduced transfection activity of the N-quaternized PEIs. Conclusions The results obtained are consistent with the proton sponge hypothesis and strongly suggest that the transfection activity of PEI vectors is due to their unique ability to avoid acidic lysosomes. Copyright © 2004 John Wiley & Sons, Ltd.
Attentional selection of superimposed surfaces cannot be explained by modulation of the gain of color channels

When two differently colored, superimposed patterns of dots rotate in opposite directions, this yields the percept of two superimposed transparent surfaces. If observers are cued to attend to one set of dots, they are impaired in making judgments about the other set. Since the two sets of dots are overlapping, the cueing effect cannot be explained by spatial attention. This has led to the interpretation that the impairment reflects surface-based attentional selection. However, recent single-unit recording studies in monkeys have found that attention can modulate the gain of neurons tuned for features such as color. Thus, rather than reflecting the selection of a surface, the behavioral effects might simply reflect a reduction in the gain of color channels selective for the color of the uncued set of dots (feature-based attention), as if viewing the surfaces through a colored filter. If so, then the impairment should be eliminated when the two surfaces are made the same color. Instead, we find that the impairment persists with no reduction in strength. Our findings thus rule out the color gain explanation.
Millipeds from Dominican amber, with the description of two new species (Diplopoda: Siphonophoridae) of Siphonophora

Representatives of 11 genera ( Lophoproctus?, Glomeridesmus, Epinannolene, Siphonophora, Siphonotus, Docodesmus, lomus, Lophodesmus?, Psochodesmus, Dasyodontus , and Inodesmus? ) are reported from Dominican amber, most of them constituting the first or oldest fossils of their corresponding higher taxa. Extant species of lomus and Inodesmus have not been reported from Hispaniola; a chelodesmid seems more closely related to South American genera than to present-day Caribbean diplopods. Siphonophora hoffmani spec. nov. and S. velezi spec. nov. are described from adults embedded in Dominican amber.
Simulation of Stochastic Hybrid Systems using probabilistic boundary detection and adaptive time stepping

Abstract Modeling and simulation of biochemical systems are important tasks because they can provide insights into complicated systems where traditional experimentation is expensive or impossible. Stochastic Hybrid Systems (SHS) are an ideal modeling paradigm for biochemical systems because they combine continuous and discrete dynamics in a stochastic framework. In this work we develop an advanced simulation method for SHS that explicitly considers switching and reflective boundaries and uses probabilistic crossing detection methods to improve accuracy. We also develop an adaptive time stepping algorithm for SHS to improve efficiency. We present case studies for a water/electrolyte balance system in humans and a biodiesel production model. Simulation results are presented to demonstrate the accuracy and efficiency of the improved simulation techniques.
Reversible Carbon-Carbon Bond Cleavage of a 3-Vinyl-1-Cyclopropene by Rh(I). Molecular Structures of Two Sterically Crowded 1,2,3,5-η-Pentadienediyl Complexes of Rh(III)

1,2,3-Tri-tert-butyl-3-vinyl-1-cyclopropene 6a reacts with [RhCl(C2H4)]2 to give the dimeric 1,2,3,5-η-pentadienediyl complex 7a. The cyclopentadienyl derivative of this complex, 8a, is obtained by reaction of 7a with T1(C5H5). Crystal structures of both 7a and 8a were determined: 7a; orthorhombic, Pbcn, a = 28.136 (4) A, b = 10.637 (2) A, c = 12.154 (2) A, V = 3637.6 (1.2) A3, and Z = 4: 8a; triclinic, P 1 -bar, a = 9.906 (2) A, b = 9.736 (2) A, c = 12.126 (2) A, α = 76.07 (2)°, β = 78.21 (2)°, γ = 65.34 (2)°, V = 1024.6 (3) A3, and Z = 2. Treatment of 7a with one equivalent of PMe3 per Rh center results in regeneration of the vinylcyclopropene, demonstrating the reversibility of the ring opening reaction. Deuterium labelling studies show that both the ring opening and closing reactions proceed with retention of configuration at the vinyl olefin. Thus the trans-deuterated vinylcyclopropene 6b reacts with [RhCl(C2H4)2]2 to give 7b in which deuterium is located exclusively in the syn position. Treatment of 7b with T1(C5H5) yields 8b. Treatment of 7b with one equivalent of PMe3 per Rh center results in formation of 6b as the sole organic product. Unlike their triphenyl relative 2, the tri-Bu complexes 7a, 7b, 8a, and 8b are stereochemically rigid in solution at room temperature, and do not undergo an η3 η1 η3 isomerization on the NMR time scale. However, after prolonged heating, syn-anti site exchange of H and D slowly takes place with 8b.
The antagonism of hippocampal and cortical afterdischarge by SC-13504, a new anticonvulsant.

Abstract SC-13504, an experimental anticonvulsant agent, is more active and potent than either diphenylhydantoin or phenobarbital in antagonizing afterdischarges produced by cortical or hippocampal stimulation. It is capable of abolishing afterdischarges at doses at or below those producing minimal behavioural alterations in chronic cats. Changes observed in behaviour, EEG, and on thresholds for arousal and recruiting demonstrate that in these regards SC-13504 is more similar to known tranquilizing agents than to sedative-hypnotics. SC-13504 may be considered structurally as either a diphenylmethane derivative or as a hydrazone derivative. Because of its unique structure as compared to the majority of anticonvulsants and because of its marked anticonvulsant properties, further evaluation is indicated.
Overview of Antifungal Agents

This article is a comprehensive clinically focused review of currently available antifungals administered by way of the intravenous or inhalational route: amphotericin B and its lipid formulations, fluconazole, itraconazole, posaconazole, voriconazole, caspofungin, micafungin, anidulafungin, and flucytosine. Emphasis is placed on pharmacodynamics and kinetics, drug interactions, adverse events, and evidence for their use. Selected clinical trials demonstrating the efficacy of these agents are also reviewed.
Subcutaneous tissue approximation in relation to wound disruption after cesarean delivery in obese women

Objective: To test the hypothesis that closure of the subcutaneous fat decreases the incidence of wound disruption after cesarean delivery. Methods: Two hundred forty-five women with at least 2 cm of subcutaneous fat were randomized to closure of the Camper fascia or no closure with cesarean delivery. Results: Complications leading to disruption or opening of the incision were classified as wound seromas in 28 women (11.4%) and as wound infections in 17 (7.0%). The relative risk (RR) of seroma formation in the subcutaneous closure group was 0.3 with a 95% confidence interval (CI) of 0.1–0.7 (5.1 versus 17.2%), a statistically significant difference. There was no significant difference in the incidence of wound infections in the two study groups. Overall, there was a significant difference in the incidence of wound disruption from all causes between the two groups: 14.5% in the subcutaneous closure group compared with 26.6% when the subcutaneous tissues were not reapproximated (RR 0.5, 95% CI = 0.3–0.9). Conclusion: Closure of the subcutaneous tissue can significantly reduce the rate of postoperative wound disruption in women with at least 2 cm of subcutaneous adipose tissue.
Polyacrylamide gel staining with Fe2+-bathophenanthroline sulfonate.

Abstract The utilization of Fe2+-bathophenanthroline sulfonate for the detection and quantitation of protein bands in cylindrical polyacrylamide gels is described. Two procedures are outlined. The first procedure is used in standard disc electrophoresis and involves fixing the protein with trichloroacetic acid, staining with Fe2+-bathophenanthroline sulfonate, and destaining with an ethanol:acetic acid solution. The second protocol reported is utilized with sodium dodecyl sulfate-containing gels. After electrophoresis, the gels are incubated with a methanol: acetic acid solution to remove the sodium dodecyl sulfate. The gels are then stained with Fe2+-bathophenanthroline sulfonate and destained with a methanol: acetic acid solution. Excellent background clarity is observed with both methods. Densitometric areas of the stained protein bands are linear to 60 μg of bovine serum albumin, and the limit of detection of this protein is 1 μg. Because of its rapidity of staining and destaining, good sensitivity, and reproducibility of stain intensity, Fe2+-bathophenanthroline sulfonate is an excellent protein stain.
The use of strain rank orders in assessing equivalence of techniques

In situations where effects of previous testing make it impossible to compare putativety equivalent forms of a behavioral test, inbred strains may be useful. To a considerable extent, animals from an inbred strain represent replicate individuals. Different naive samples from the same strain may be tested in different forms of a test. There is presumptive evidence that the two forms arc assessing similar functions if samples from different strains that differ on the behavior give consistent ordinal rankings. An illustration is given of the use of this approach in assessing methods of measuring alcohol preference in mice.
A defective movement protein of TMV in transgenic plants confers resistance to multipleviruses whereas the functional analog increases susceptibility

Transgenic tobacco plants that express a gene encoding a defective mutant of the tobacco mosaic virus (TMV) movement protein which are known to be resistant to several tobamoviruses were inoculated with viruses from different taxonomic groups to determine the breadth of resistance. There were significant delays in the time of appearance of disease symptoms and/or there was reduced systemic accumulation of virus in upper leaves of plants inoculated with tobacco rattle tobravirus, tobacco ringspot nepovirus, alfalfa mosaic alfamovirus, peanut chlorotic streak caulimovirus, and cucumber mosaic cucumovirus. Conversely, tobacco plants that express a gene encoding the functional tobacco mosaic virus wild-type movement protein accelerated symptom development, enhanced the severity of symptom formation, and/or increased the accumulation of these viruses and, additionally, TMV. Our results indicate that there are similar functions among the movement proteins of a number of plant viruses despite the apparent lack of sequence similarity between them.
The Communication Complexity of Distributed Set-Joins with Applications to Matrix Multiplication

Given a set-comparison predicate P and given two lists of sets A = (A1,...,Am) and B = (B1,...,Bm), with all Ai, Bj ⊆ [n], the P-set join A bowtiePB is defined to be the set {(i, j) in [m] x [m] | P(Ai,Bj)}. When P(Ai,Bj) is the condition "Ai ∩ Bj ≠ is empty " we call this the set-intersection-notempty join (a.k.a. the composition of A and B); when P(Ai,Bj) is "Ai ∩ Bj is empty" we call it the set-disjointness join; when P(Ai,Bj) is "Ai = Bj" we call it the set-equality join; when P(Ai,Bj) is "|Ai ∩ Bj| ≥ T" for a given threshold T, we call it the set-intersection threshold join. Assuming A and B are stored at two different sites in a distributed environment, we study the (randomized) communication complexity of computing these, and related, set-joins A bowtiePB, as well as the (randomized) communication complexity of computing the exact and approximate value of their size k = |A bowtiePB|. Combined, our analyses shed new insights into the quantitative differences between these different set-joins. Furthermore, given the close affinity of the natural join and the set-intersection-not-empty join, our results also yield communication complexity results for computing the natural join in a distributed environment.Additionally, we obtain new algorithms for computing the distributed set-intersection-not empty join when the input and/or output is sparse. For instance, when the output is k sparse, we improve an O(kn) communication algorithm of (Williams and Yu, SODA 2014). Observing that the set-intersection-not-empty join is isomorphic to Boolean matrix multiplication (BMM), our results imply new algorithms for fundamental graph theoretic problems related to BMM. For example, we show how to compute the transitive closure of a directed graph in O(k3/2) time, when the transitive closure contains at most k edges. When k = O(n), we obtain a (practical) O(n3/2) time algorithm, improving a recent O(n1+(c+3)/4) time algorithm (Borassi, Crescenzi, and Habib, arXiv 2014) based on (impractical) fast matrix multiplication, where c ≥ 2 is the exponent for matrix multiplication.
Tree structures for high dimensionality nearest neighbor searching

Abstract A nearest neighbor searching algorithm which is an extension of the multidimensional binary tree ( k-d tree) for high dimensional spaces is discussed. A model of its behavior, which is applicable under restricted conditions, shows that the search time required is bounded by 0( log 2 N ) α , where N is the number of records and α is a system-dependent parameter. Experiments with a document collection show that the model provides a reasonable guide to performance, and that some savings over a sequential search can be achieved in this type of application. A probabilistic version of the algorithm is presented which provides significantly faster searching with little degradation in retrieval quality.
Experimental results of a low-power roadheader driving a gallery with different types of rock at the face

In this paper, the experimental results of a 45-kW and 15-t roadheader excavating a gallery with two different types of rock at the face using two different cutting heads are shown. It is proved that the roadheader works properly with both cutting heads. In comparison with other results in the literature, the principal parameters, i.e. specific energy, cutting rate and tool wear, are at a level that can be considered satisfactory taking into account the low power of the roadheader. On the other hand, the influence of the number of picks, which is the main difference between the two cutting heads, on the operational parameters is shown.
On the role of ion temperature anisotropy in the growth and propagation of shear‐modified ion‐acoustic waves

[1] Oblique ion-acoustic waves, excited by the combination of magnetic field-aligned (parallel) electron drift and sheared parallel ion flow, are investigated in magnetized laboratory plasma that is characterized by ion temperature anisotropy. Direct measurements of the parallel and perpendicular ion temperatures, parallel and perpendicular ion drift velocities, electron temperature and parallel electron drift velocity, parallel and perpendicular wave vector components, and mode frequency and growth rate are used to elucidate the shear-modified ion-acoustic (SMIA) instability mechanism and document an observed correlation between ion temperature anisotropy and wave propagation angle. Experimental measurements show that anisotropy significantly influences the growth rate and propagation angle of oblique ion-acoustic waves. These results support the ion-acoustic wave interpretation of broadband waves in the auroral energization region where shear and anisotropy are known to exist and may have ramifications for many space plasmas in which anisotropy exists in the electron temperature or ion temperature.
Geographic Scales and the Competition for Economic Growth: States, Subnational Governments, and Cities

One of the key features of globalization is the increase in capital mobility, which propels national and subnational governments alike into a heightened competition for investment as more locations become feasible for any particular investment. This can be seen most clearly in the case of state and local governments in the United States, where the absence of controls on development incentives allowed a rapid increase in their level during the 1990s. State and local governments are caught in a Prisoners’ Dilemma that can only be solved at the federal level. In the absence of such intervention, many local organizations have tried to at least bring more transparency and accountability to the use of development incentives, with some success in moving the deals out of the back rooms and institutionalizing clawbacks of incentives where recipients fail to produce the promised investment.