cssi/SciSciGPT-SciSciNet huggingface dataset:
CRISPR-SKIP: programmable gene splicing with single base editors

CRISPR gene editing has revolutionized biomedicine and biotechnology by providing a simple means to engineer genes through targeted double-strand breaks in the genomic DNA of living cells. However, given the stochasticity of cellular DNA repair mechanisms and the potential for off-target mutations, technologies capable of introducing targeted changes with increased precision, such as single-base editors, are preferred. We present a versatile method termed CRISPR-SKIP that utilizes cytidine deaminase single-base editors to program exon skipping by mutating target DNA bases within splice acceptor sites. Given its simplicity and precision, CRISPR-SKIP will be broadly applicable in gene therapy and synthetic biology.
Lower Pretreatment Gut Integrity Is Independently Associated With Fat Gain on Antiretroviral Therapy.

BACKGROUND Fat accumulation and insulin resistance remain a threat to the success of antiretroviral therapy (ART). The role of gut dysfunction in metabolic complications associated with ART initiation is unclear. METHODS Human immunodeficiency virus (HIV)-infected ART-naive participants were randomized to tenofovir disoproxil fumarate/emtricitabine plus atazanavir/ritonavir, darunavir/ritonavir, or raltegravir (RAL). Changes in the gut integrity markers zonulin, lipopolysaccharide-binding protein (LBP), and intestinal fatty acid and ileal bile acid binding proteins (I-FABP and I-BABP) were assessed over 96 weeks. Wilcoxon rank-sum tests were used to compare changes between groups and linear regression models to quantify associations between gut markers, insulin resistance, body mass index (BMI), and visceral, subcutaneous, and total adipose tissue (VAT, SAT, and TAT). RESULTS : 90% were male and 48% were White non-Hispanic. The median age was 36 years, HIV-1 ribonucleic acid was 4.56 log10 copies/mL, and CD4 count was 338 cells/µL. An overall 1.7-fold increase in I-FABP was observed throughout 96 weeks, with no difference between arms. Zonulin levels increased with RAL compared to protease inhibitor-based regimens (week 96, P = .02); minimal changes in I-BABP or LBP levels were observed. Higher baseline I-FABP levels were associated with increases in VAT, TAT, and BMI (16%, 9%, and 2.5%, respectively; P < .04) over 96 weeks. CONCLUSIONS While ART induces changes in the markers of gut barrier dysfunction, the extent to which they improve or worsen the gut barrier function remains unclear. Nevertheless, markers of gut barrier dysfunction in ART-naive individuals predict increases in total and visceral abdominal fat with treatment initiation.
The Rise of the Machines: 1918–1941

The volume of cipher traffic that was made possible by radio showed the need for vastly increased security, speed and accuracy in both enciphering and deciphering messages. The use of mechanical and electromechanical machines to do the encipherment was a logical outgrowth of this need. The first electromechanical rotor cipher machines began to appear right after World War I and the next three decades saw their steady improvement in both complexity and speed. The Enigma, the Typex and the M-134C/SIGABA were the epitome of these machines and the efforts to create and cryptanalyze them led us into the computer age. This chapter examines the history of cipher machines in the first part of the twentieth century and looks in some detail at the cryptographic construction of the Enigma and the Japanese Purple machine.
Long-term results of robotic anatomical segmentectomy for early-stage non-small-cell lung cancer.

Objectives Anatomical segmentectomy is advocated for curative resection in select patients. We investigated the long-term results of robotic anatomical segmentectomy with mediastinal nodal dissection in patients with early-stage lung cancer. Methods We retrospectively reviewed patients who underwent robotic anatomical segmentectomy for early-stage non-small-cell lung cancer (NSCLC). The follow-up data were obtained to determine survival and statistically significant risk factors in both univariable and multivariable models. Results Seventy-one patients had clinical stage I NSCLC (36 men, 35 women, mean age 70 ± 12 years). All patients underwent R0 resection. The mean operating time was 134 min. Ten of 71 (14%) patients were upstaged. Eight of 71 (11%) patients were upstaged due to the size of tumour in the pathological specimen, and 2 of 71 (3%) patients were upstaged due to microscopic N2 nodal metastasis. Median hospitalization was 4 days (2-31 days). Complication rate was 29%. There were no complications attributable to the surgical robot. No patient died within 90 days. Mean follow-up was 54 months (range 2 months to 9 years). The overall 5-year survival was 43%, whereas lung cancer-specific 5-year survival was 55%. The 5-year lung cancer-specific survival for pathological stage I disease was 73%. Local or mediastinal recurrence occurred in 4 of 71(5%) patients. Pathological upstaging or recurrence resulted in 0% 5-year survival. The univariable and multivariable analyses showed that advanced age and pathological upstaging were statistically significant risk factors for lung cancer-specific death. Conclusions Robotic anatomical segmentectomy with mediastinal nodal dissection is a safe and feasible procedure. Accurate preoperative clinical staging is of critical importance for long-term survival.
Sampling the Central Channel Provides Additional Information on Fish Assemblages in a Large Boatable River in the U.S. Midwest

Abstract It is a challenge to adequately characterize the fish assemblages of large rivers because of their sizes and high spatial–temporal habitat heterogeneity. Multiple sampling methods are ofte...
How fast does product market reform pay off? New evidence from non-manufacturing industry deregulation in advanced economies

Abstract The paper sheds light on the issue of how fast product market deregulation pays off and whether it entails any transitory costs by using a unique mapping between a new narrative dataset of major reform events and sector-level outcomes for 5 major non-manufacturing industries in 26 advanced economies over the period 1975–2011. Using a local projection method, we find that deregulation pays off only gradually: its positive effect on output becomes statistically significant three to four years after the reform, consistent with the notion that entry takes time due to real frictions. At the same time, there is no evidence of any significant transitory cost. Over the medium term, these product market reforms eventually yield large, highly significant increases in output, concomitant with a relative price decline. The typical major historical reform in advanced economies increased real value added and employment in the deregulated industry by about 10 percent and over 5 percent, respectively, and lowered relative prices by some 8 to 10 percent, after five years.
Occlusive thrombosis in arteries

Thrombus formation in major arteries is life threatening. In this review article, we discuss how an arterial thrombus can form under pathologically high shear stresses, with bonding rates estimated to be the fastest K o n values in biochemistry. During occlusive thrombosis in arteries, the growth rate of the thrombus explodes to capture a billion platelets in about 10 min. Close to 100% of all platelets passing the thrombus are captured by long von Willebrand factor (vWF) strands that quickly form tethered nets. The nets grow in patches where shear stress is high, and the local concentration of vWF is elevated due to α-granule release by previously captured platelets. This rapidly formed thrombus has few red blood cells and so has a white appearance and is much stronger and more porous than clots formed through coagulation. Understanding and modeling the biophysics of this event can predict totally new approaches to prevent and treat heart attacks and strokes.
Countering grey market threat using service effort

Grey markets are likely when there is a significant price difference of the same product in two different markets. A grey marketer can buy the product in the low-price market and sell it in the high-price market starting an unauthorised channel. This paper studies the role of service effort in the authorised channels in fighting grey market under two scenarios. One is when the prices are not under the manufacturer's control and second, when they are. We find that the manufacturer's profit is significantly improved when he proactively adjusts the service levels in different markets. When service provision can be used in conjunction with pricing strategies, the manufacturer's profit is further improved. One surprising finding is that, when certain conditions are satisfied, the manufacturer actually benefits more from grey market than from the authorised channel in the high price market.
Face-Saving and Depressive Symptoms Among U.S. Chinese Older Adults

Face-saving represents a unique culturally salient construct among Chinese. However, our understanding regarding its relationship with psychological distress in this population remains limited. The objective of this cross-sectional study is to examine (1) the relationship between face-saving and depressive symptoms among U.S. Chinese older adults; and (2) whether face-saving mediates the relationship between acculturation and depressive symptoms. Data were from the Population Study of Chinese Elderly in Chicago (N = 3132), the largest epidemiologic study of Chinese older adults in Western countries. The relationship between face-saving and self-reported depressive symptoms was investigated by step-wise multivariable linear regression models. The Sobel test was used to test the mediating effect of face-saving. U.S. Chinese older adults with higher face-saving values experienced greater levels of depressive symptoms (B = 0.05, p < 0.001) than those with lower face-saving values, even after sociodemographic factors, health characteristics, and social support were accounted for. The mediation effect of face-saving was not statistically significant. The study findings underscore the significance of a unique cultural factor, specifically face-saving, in understanding U.S. Chinese older adults’ experience of depressive symptoms. Depression screening and treatment programs should pay attention to face-saving issues among U.S. Chinese older adults. Future studies need to incorporate cultural factors in mental health research in diverse populations.
Electron Crystallography of a Prokaryotic Potassium Channel

Potassium channels are ubiquitous ion channel proteins which play a crucial role in a broad spectrum of important cell functions. KcsA is a potassium channel found in the bacterium, Streptomyces lividan, and is believed to have only two transmembrane helices.The KcsA protein has been cloned, overexpressed and purified to homogeneity, and reconstituted with phospholipids to form two-dimensional (2-D) crystals. Crystal samples were embedded in trehalose and examined in a cryo-holder (-170 °C) using a JEOL 4000EX electron microscope operated at 400kV in low dose mode. Images were recorded in spot scan-mode at a magnification of 60,000X, then digitized on a Perkin Elmer PDS flat bed microdensitometer and processed by using the MRC program suite. Processed images were brought to a common phase origin, and the amplitudes and phases from individual images were vectorially combined.
Anti-Axl antibody treatment reduces the severity of experimental autoimmune encephalomyelitis

Multiple sclerosis is an immune-mediated disease of the central nervous system (CNS) characterized by inflammation, oligodendrocytes loss, demyelination, and damaged axons. Tyro3, Axl, and MerTK belong to a family of receptor tyrosine kinases that regulate innate immune responses and CNS homeostasis. During experimental autoimmune encephalomyelitis (EAE), the mRNA expression of MerTK, Gas6, and Axl significantly increase, whereas Tyro3 and ProS1 remain unchanged. We have shown that Gas6 is neuroprotective during EAE, and since Gas6 activation of Axl may be necessary for conferring neuroprotection, we sought to determine whether α-Axl or α-MerTK antibodies, shown by others to activate their respective receptors in vivo, could effectively reduce inflammation and neurodegeneration. Mice received either α-Axl, α-MerTK, IgG isotype control, or PBS before the onset of EAE symptoms. EAE clinical course, axonal damage, demyelination, cytokine production, and immune cell activation in the CNS were used to determine the severity of EAE. α-Axl antibody treatment significantly decreased the EAE clinical indices of female mice during chronic EAE and of male mice during both acute and chronic phases. The number of days mice were severely paralyzed also significantly decreased with α-Axl treatment. Inflammatory macrophages/microglia and the extent of demyelination significantly decreased in the spinal cords of α-Axl-treated mice during chronic EAE, with no differences in the production of pro-inflammatory cytokines. α-MerTK antibody did not influence EAE induction or progression. Our data suggests that the beneficial effect of Gas6/Axl signaling observed in mice administered with Gas6 can be partially preserved by administering an activating α-Axl antibody, but not α-MerTK.
When more is more: redundant modifiers can facilitate visual search

According to the Gricean Maxim of Quantity, speakers provide the amount of information listeners require to correctly interpret an utterance, and no more (Grice in Logic and conversation, 1975). However, speakers do tend to violate the Maxim of Quantity often, especially when the redundant information improves reference precision (Degen et al. in Psychol Rev 127(4):591–621, 2020). Redundant (non-contrastive) information may facilitate real-world search if it narrows the spatial scope under consideration, or improves target template specificity. The current study investigated whether non-contrastive modifiers that improve reference precision facilitate visual search in real-world scenes. In two visual search experiments, we compared search performance when perceptually relevant, but non-contrastive modifiers were included in the search instruction. Participants (NExp. 1 = 48, NExp. 2 = 48) searched for a unique target object following a search instruction that contained either no modifier, a location modifier (Experiment 1: on the top left, Experiment 2: on the shelf), or a color modifier (the black lamp). In Experiment 1 only, the target was located faster when the verbal instruction included either modifier, and there was an overall benefit of color modifiers in a combined analysis for scenes and conditions common to both experiments. The results suggest that violations of the Maxim of Quantity can facilitate search when the violations include task-relevant information that either augments the target template or constrains the search space, and when at least one modifier provides a highly reliable cue. Consistent with Degen et al. (2020), we conclude that listeners benefit from non-contrastive information that improves reference precision, and engage in rational reference comprehension. This study investigated whether providing more information than someone needs to find an object in a photograph helps them to find that object more easily, even though it means they need to interpret a more complicated sentence. Before searching a scene, participants were either given information about where the object would be located in the scene, what color the object was, or were only told what object to search for. The results showed that providing additional information helped participants locate an object in an image more easily only when at least one piece of information communicated what part of the scene the object was in, which suggests that more information can be beneficial as long as that information is specific and helps the recipient achieve a goal. We conclude that people will pay attention to redundant information when it supports their task. In practice, our results suggest that instructions in other contexts (e.g., real-world navigation, using a smartphone app, prescription instructions, etc.) can benefit from the inclusion of what appears to be redundant information.
Fabrication and Characterization of Cross-Linked Phenyl-Acrylate-Based Ion Exchange Membranes and Performance in a Direct Urea Fuel Cell

Ion exchange membranes (IEMs) are crucial for direct fuel cells, including direct methanol and direct urea fuel cells (DUFCs). While commercially available IEMs (e.g., FAA-3-50) show decent power d...
Conjugation and Genetic Exchange in Enterococci

The medical importance of the enterococci is closely related to the propensity of these organisms to participate in the horizontal transfer of determinants for antibiotic resistance and virulence. Conjugative plasmids in enterococci tend to fall into two main groups. Members of one group encode recognition of recipient-produced peptide pheromones that initiate the mating process; the others do not make use of such signals. The pheromone-responding plasmids usually transfer efficiently in broth (liquid) matings, whereas the others transfer relatively poorly under these conditions. An exception is pMGl, a resistance plasmid in Enterococcus faecium that transfers well in broth despite the apparent absence of a pheromone system. Those plasmids that make use of sex pheromones (e.g., pADl and pCFlO) thus far appear to exhibit a narrow host range—primarily Enterococcus faecalis and closely related species-although information on this point is very limited. A partial list of pheromone-responding plasmids is presented in this chapter. The formation of mating aggregates relates to the induction of a protein "aggregation substance" (AS), which appears extensively over the donor surface and binds to "enterococcal binding substance" (EBS) on the recipient surface. Conjugative transposons are particularly common in enterococci and streptococci and play an important role in the dissemination of antibiotic resistance in these organisms. It is likely that the enterococci play a significant role as a hardy facultative reservoir of genetic information available to a variety of other genera.
Testing the suffixoidization of German -mann '-man'

Throughout its history in Old High German (OHG), Middle High German, Early New High German, and Modern German (ModG), the word Mann "man" has exhibited a high degree of productivity and linguistic flexibility. It has ranged morphosyntactically from a full noun (OHG man "man"), compounded noun (OHG werolt.man "human, mortal"), affixoid (ModG Sports.mann "athlete"), indefinite pronoun (ModG man "one"), to something approaching zero (undergoing demorphologization in the OHG compound gom.man "husband, man"). The affixoid notion and its usefulness in morphology have been controversial in the literature (e.g., Schmidt 1987). Relatively recently, Stevens (2005) proposed criteria for the category affixoid, and a number of standard German grammatical and etymological references (e.g., Duden 1995) have been utilizing this term. This study involves examining modern usage of the form -mann as found in the online Spiegel newsmagazine's database, as well as the collection of historical data primarily on the forms of German -mann from the robust Titus database in Frankfurt. Stevens' (2005) criteria are evaluated and used to measure the validity of German -mann's membership in the category of suffixoid.
Event Detection in Wireless Sensor Networks – Can Fuzzy Values Be Accurate?

Event detection is a central component in numerous wireless sensor network (WSN) applications. In spite of this, the area of event description has not received enough attention. The majority of current event description approaches rely on using precise values to specify event thresholds. However, we believe that crisp values cannot adequately handle the often imprecise sensor readings. In this paper we demonstrate that using fuzzy values instead of crisp ones significantly improves the accuracy of event detection. We also show that our fuzzy logic approach provides higher detection precision than a couple of well established classification algorithms.
MPI datatype marshalling: a case study in datatype equivalence

MPI datatypes are a convenient abstraction for manipulating complex data structures and are useful in a number of contexts. In some cases, these descriptions need to be preserved on disk or communicated between processes, such as when defining RMA windows. We propose an extension to MPI that enables marshalling and unmarshalling MPI datatypes in the spirit of MPI_Pack/MPI_Unpack. Issues in MPI datatype equivalence are discussed in detail and an implementation of the new interface outside of MPI is presented. The new marshalling interface provides a mechanism for serializing all aspects of an MPI datatype: the typemap, upper/lower bounds, name, contents/envelope information, and attributes.
Why have some countries on international rivers been successful negotiating treaties? A global perspective

[1] This paper presents a typology of international rivers based on asymmetries in economic and political power among riparian states. This typology is then used, along with other factors such as the spatial location of riparians on the river, to explore the question of why some riparians on international rivers have been able to successfully negotiate treaties and others have not. The findings lend support to both economic and political economy explanations of cooperative action on international rivers. International rivers with riparians with countervailing economic and political power are far more likely to have negotiated treaties than other river types. Riparian states on international rivers sharing a “western civilization” were much more likely to have concluded treaties than riparian states on rivers in other civilizations. Somewhat surprisingly, rivers that cross “civilization boundaries” appear no less likely to have treaties than international rivers than run entirely through riparian states that share a single civilization. Adjacent upstream/downstream or “side-by-side” riparians were less likely to have concluded treaties than “country pairs” with other spatial relationships.
Membrane protein stability as the energy sink for sorting in the periplasm (224.3)

We will present novel measurements of folding free energies for the transmembrane proteins PagP and OmpW from E. coli. Our data were collected in the same lipid bilayer and buffer system we previously employed to determine those parameters for E. coli OmpLA. From a biophysical perspective, our results suggest that the stabilities of these proteins may be strongly correlated to the water-to-bilayer transfer free energy of the lipid-facing residues in their transmembrane regions. From a biological perspective, our findings suggest that the folding free energies for these membrane proteins may be the thermodynamic sink that establishes an energy gradient across the periplasm. This potential thus drives the sorting of outer membrane proteins by chaperones to the outer membranes in living bacteria. Binding free energies of these outer membrane proteins with periplasmic chaperones support this energy sink hypothesis.
S(+)amphetamine induces a persistent leak in the human dopamine transporter: molecular stent hypothesis

BACKGROUND AND PURPOSE Wherever they are located, dopamine transporters (DATs) clear dopamine (DA) from the extracellular milieu to help regulate dopaminergic signalling. Exposure to amphetamine (AMPH) increases extracellular DA in the synaptic cleft, which has been ascribed to DAT reverse transport. Increased extracellular DA prolongs postsynaptic activity and reinforces abuse and hedonic behaviour. EXPERIMENTAL APPROACH Xenopus laevis oocytes expressing human (h) DAT were voltage-clamped and exposed to DA, R(-)AMPH, or S(+)AMPH. KEY RESULTS At -60mV, near neuronal resting potentials, S(+)AMPH induced a depolarizing current through hDAT, which after removing the drug, persisted for more than 30 min. This persistent leak in the absence of S(+)AMPH was in contrast to the currents induced by R(-)AMPH and DA, which returned to baseline immediately after their removal. Our data suggest that S(+)AMPH and Na+ carry the initial S(+)AMPH-induced current, whereas Na+ and Cl- carry the persistent leak current. We propose that the persistent current results from the internal action of S(+)AMPH on hDAT because the temporal effect was consistent with S(+)AMPH influx, and intracellular S(+)AMPH activated the effect. The persistent current was dependent on Na+ and was blocked by cocaine. Intracellular injection of S(+)AMPH also activated a DA-induced persistent leak current. CONCLUSIONS AND IMPLICATIONS We report a hitherto unknown action of S(+)AMPH on hDAT that potentially affects AMPH-induced DA release. We propose that internal S(+)AMPH acts as a molecular stent that holds the transporter open even after external S(+)AMPH is removed. Amphetamine-induced persistent leak currents are likely to influence dopaminergic signalling, DA release mechanisms, and amphetamine abuse.
High density area array module connector

The increase in circuits per module chip has also increased the demand for the quantity of contacts per module. Ideally, this increase should be accomplished by an increase in contact density and not an expansion in module size. Furthermore, the ever-increasing shift from single chip to multiple chip modules is accomplished by a shift from permanently attached to plugable modules. This paper describes a newly developed module-to-card array connector that uses a unique contact system which provides high density, and high reliability at an affordable cost. Connector and contact design details, as well as theoretical and actual test data, are presented. >
The Implications of State Fiscal Policies for Community Colleges.

A variety of policies and practices, including those developed by local boards and administrations, as well as those mandated by state and federal governments, affect budgets and finances at community colleges. Examples include tuition policies, fee structures, performance-based funding, and personnel policies. This chapter explores some of the reasons for policy changes and provides a framework for incorporating effectiveness into the community college mission, thereby avoiding unintended negative consequences for students or the fiscal viability of the institution.
Fluorescence Based Characterization of Calcium Sensitizer Action on the Troponin Complex

Calcium sensitizers enhance the transduction of the Ca(2+) signal into force within the heart and have found use in treating heart failure. However the mechanisms of action for most Ca(2+) sensitizers remain unclear. To address this issue an efficient fluorescence based approach to Ca(2+) sensitizer screening was developed which monitors cardiac troponin C's (cTnC's) hydrophobic cleft. This approach was tested on four common Ca(2+) -sensitizers, EMD 57033, levosimendan, bepridil and pimobendan with the aim of elucidating the mechanisms of action for each as well as proving the efficacy of the new screening method. Ca(2+) -titration experiments were employed to determine the effect on Ca(2+) sensitivity and cooperativity of cTnC opening, while stopped flow experiments were used to investigate the impact on cTnC relaxation kinetics. Bepridil was shown to increase the sensitivity of cTnC for Ca(2+) under all reconstitution conditions, sensitization by the other drugs was context dependent. Levosimendan and pimobendan reduced the rate of cTnC closing consistent with a stabilization of cTnC's open conformation while bepridil increased the rate of relaxation. Experiments were also run on samples containing cTnT(T204E), a known Ca(2+) -desensitizing phosphorylation mimic. Levosimendan, bepridil, and pimobendan were found to elevate the Ca(2+) -sensitivity of cTnT(T204E) containing samples in this context.
China, the United States and a “power shift” in Asia

Recent signs of assertiveness by the Chinese administration in relations with the United States have been seen as reflecting a broader shift of power in Asian and world affairs where China is superseding the United States. Closer examination of the Chinese posture toward the United States and power dynamics in Asia shows that China has not the will nor the ability to challenge US leadership in Asia.
(−)-Bacillamide C: the convergent approach

The newly discovered natural product bacillamide C and several derivatives were convergently synthesized for the first time and in only three steps. The key transformation constitutes a thiazole Ugi multicomponent reaction. These compounds will serve to elucidate chemical biology and SAR of this potent anti-algae natural product and shows the synthetic pathway to related natural products.
Improving the quality of evaluation participation: a meta-evaluation

This study presents a meta-evaluation of a beta-test undertaken of a customer service training programme. The initial evaluation showed a low level of participation in the beta-test evaluations. Therefore, the meta-evaluation (or an evaluation of the evaluation) focused on issues related to the conduct of the initial evaluation and reasons for non-response. The meta-evaluation identified solutions to the participation problem as related to authority, capacity and motivation.
Evaluation of matrix-assisted laser desorption ionization-time-of-flight mass measurement accuracy by using delayed extraction.

Mass measurement accuracy of a reflectron time-of-flight mass spectrometer equipped with delayed extraction is evaluated. Mass resolution of 10,000–15,000 is achieved routinely for peptides in the mass range of 1–6 ku ionized by matrix-assisted laser desorption ionization. The mass measurement accuracy of peptides with molecular weights of 1–4 ku is 10–15 ppm by using external calibration and better than 5 ppm by using internal calibration. The mass calibration remains accurate over a broad mass-to-charge ratio range (1–4 ku), even when the calibration curve is extrapolated several thousand mass units.
Evolutionary synthesis of photographic artwork using human fitness function derived from web-based social networks

We explore the possibility of approximating the performance of a human fitness function applied to the evolutionary selection of generative artwork. Traditional generators of evolutionary artwork rely on human interactivity for selection of aesthetically pleasing art from populations of computer-generated individuals. Users of the Web-based photograph sharing site Flickr.com, through interactions with the Flickr.com web site, have produced a large set of high-quality photographs considered interesting or popular by its users. Our experimentation exploited this established data set to estimate the interestingness of artwork evolved without human interaction.
The changing conditions of zebrafish mutants

In PNAS, Ni et al. (1) describe a gene trap construct that makes conditional inactivation of genes in zebrafish a reality. This represents a major milestone in zebrafish research. The relatively recent and rapid emergence of zebrafish as a vertebrate model organism has fundamentally been because of its utility in genetic approaches. The generation of mutations and subsequent screening for phenotypes in zebrafish requires significantly fewer resources than screens of equivalent numbers in mice or other mammalian models. Because of this advantage, it prompted two major phenotypic screens in the early 1990s that generated and identified hundreds of embryonic mutations (2, 3). These chemically induced alleles became a resource that propelled scientific advances in the zebrafish research community for nearly two decades. Zebrafish mutants have contributed biological insights ranging from basic mechanisms of gastrulation (4) to human pigmentation (5). However, the Achilles' heel of classical genetics, including zebrafish genetics, is a result of what Sean Carroll describes as the “genetic toolkit” (6), i.e., the same genetic pathways are often deployed in multiple different tissues at different times during development and adult homeostasis. The result is that, if you knock out a gene that has multiple functions, the massive pleiotropic changes that occur in the organism make it difficult to impossible to understand the specific role of that gene in, say, eye development or function. Mouse researchers devised an important method for circumventing this problem: conditional inactivation (7). By using homologous recombination, researchers can flank mouse exons with loxP recombination sites; then, by expressing the cre recombinase in a temporal or tissue specific manner, inactivate the gene by deleting the targeted exon(s). Unfortunately, neither of the two essential components of this strategy, ES cells or homologous recombination, are currently options for zebrafish researchers, so other strategies need to be pursued.
Experimental hyperparathyroidism. Effects on gastric secretion

Abstract Inbred rats were made hyperparathyroid by transplantation of multiple parathyroid glands, and gastric secretion was serially estimated. Gastric secretion was not altered except during the period of marked hypercalcemia, when it was diminished.
Hot corrosion and oxidation behavior of a novel Pt + Hf-modified γ′-Ni3Al + γ-Ni-based coating

Abstract A new type of Pt + Hf-modified γ′-Ni 3 Al + γ-Ni-based coating has been developed in which deposition involves Pt electroplating followed by combined aluminizing and hafnizing using a pack cementation process. Cyclic oxidation testing of both Pt + Hf-modified γ′ + γ and Pt-modified β-NiAl coatings at 1150 °C (2102 °F), in air, resulted in the formation of a continuous and adherent α-Al 2 O 3 scale; however, the latter developed unwanted surface undulations after thermal cycling. Type I ( i.e. 900 °C/1652 °F) and Type II ( i.e. 705 °C/1300 °F) hot corrosion behavior of the Pt + Hf-modified γ′ + γ coating were studied and compared to Pt-modified β and γ + β-CoCrAlY coatings. Both types of hot corrosion conditions were simulated by depositing Na 2 SO 4 salt on the coated samples and then exposing the samples to a laboratory-based furnace rig. It was found that the Pt + Hf-modified γ′ + γ and Pt-modified β coatings exhibited superior Type II hot corrosion resistance compared to the γ + β-CoCrAlY coating; while the Pt + Hf-modified γ′ + γ and γ + β-CoCrAlY coatings showed improved Type I hot corrosion performance than the Pt-modified β.
Random sequential adsorption on a ladder

We study the asymptotic coverage of a lattice to which particles are randomly and irreversibly attached, under the constraint of nearest neighbor exclusion. After reviewing the case of a one-dimensional lattice, we extend the treatment first to a triangular ladder and then to a square ladder. The former maps onto a previously solved one-dimensional case, the latter does not. We also determine the time-dependent coverage of the square ladder. Implications as to the process on a full 2-dimensional square lattice are discussed.
Deferoxamine prevents cardiac hypertrophy and failure in the gerbil model of iron-induced cardiomyopathy.

To evaluate the effects of the iron chelator deferoxamine on the functional and structural manifestations of iron-induced cardiac dysfunction, we measured cardiac power, left ventricular systolic, and diastolic function as (dP/dt)max and (dP/dt)min, respectively, and left ventricular and septal wall thickness in isolated heart preparations derived from the Mongolian gerbil model of iron overload. We induced iron overload with weekly subcutaneous injections of iron dextran (800 mg/kg/wk); deferoxamine (DFO; 100 mg/kg) was administered twice daily by subcutaneous injection, 5 of 7 days each week; and control animals received weekly subcutaneous injections of dextran alone. Animals administered iron alone initially exhibited, at 5 weeks, increased cardiac power but by 12 to 20 weeks, cardiac power was severely diminished, with impairment of both systolic and diastolic function of the left ventricle and marked cardiac hypertrophy (P < .001 for all vs control animals). Administration of DFO with iron did not interfere with the initial augmentation of cardiac power at 5 weeks but prevented the subsequent deterioration in cardiac performance. After 12 to 20 weeks, gerbils given DFO with iron had mean values of cardiac power indistinguishable from those of control animals; both systolic and diastolic function were significantly enhanced not only in comparison with those of animals treated with iron alone but also with respect to controls. In addition, DFO prevented cardiac hypertrophy; mean ventricular and septal wall thickness in gerbils given DFO and iron were not significantly different from those in controls. In the gerbil model of iron overload, concurrent administration of DFO with iron prevents both the development of cardiac hypertrophy and the progressive deterioration in cardiac performance that are produced by chronic iron accumulation.
Adsorption of CO on the (110) plane of tungsten electron impact, thermal desorption, and work function measurements

Abstract The adsorption of CO on the (110) plane of tungsten has been studied using electron impact desorption, thermal desorption, and work function measurements in a single apparatus combining these various techniques. It is concluded that a single molecular adsorption state exists at 20–250 K (virgin-CO). At 300–400 K, 60% of the low temperature layer desorbs, the remainder converting principally to a beta-1 state, which has very small electron impact cross section; in addition to beta-1 an O + yielding state, which we call beta-precursor is formed. The beta-1 state is stable to 900 K, where some desorption and conversion of the remaineder to a beta-2 state occurs. The O + yielding state decays with increasing T and is gone at 800 K. Readsorption on beta-1 leads to two types of adsorption states called alpha and gamma, which seem to be site specific. Electron impact desorption yields mostly CO + and CO for virgin, O + for beta-precursor, and CO + and CO for the readsorption states. There is no isotopic mixing in virgin or in readsorbed CO, nor does readsorbed CO exchange with beta-1 or beta precursor. There is complete isotopic mixing in beta desorption. In addition, massive EID creates another state, characterized by a large dipole moment, also yielding O + in EID. This state can be converted to beta-1 by heating to 400 K. The total disappearance cross sections for the various states are virgin- CO 5 × 10 −17 cm 2 ; γ - CO 1.6 × 10 −16 cm 2 ; α - CO 5 × 10 −17 cm 2 ; β - precursor 6 × 10 −18 cm 2 and 1.2 × 10 −19 cm 2 ; EID induced state 8 × 10 −18 cm 2 . In addition, cross sections for ion production are determined and found to be several orders of magnitude less than total disappearance cross sections. These results, and Leed and coverage data obtained in parallel investigations are used to formulate models of the various adsorption states. It is concluded that virgin and readsorbed CO are molecular and beta-precursor and beta dissociated, although strong interactions between C and O remain. The electron impact desorption of physisorbed CO was investigated and found to yield C + , O + , and neutral CO, but very little CO + . These results suggest primary dissociation of CO by electron impact, and desorption of neutral physisorbed CO by the energetic fragments. Physisorbed CO + , although undoubtedly created, lies on the attractive part of its potential curve relative to the surface, and thus does not desorb as CO + .
Metrology and test requirements for movement of the RAS/HOMS test facility to NASA-GSFC

The Refractive Aberrated Simulator/Hubble Opto-Mechanical Simulator (RAS/HOMS) test facility previously located at Ball Aerospace Division in Boulder (BASD), CO will be relocated to NASA Goddard Space Flight Center (GSFC). This paper will highlight the metrology and test methods used to characterize the facility prior to disassembly as well as assemble and align the facility once it has been moved to GSFC. The HOMS portion of the facility simulates the mechanical latch mechanisms that hold an axial instrument in alignment with the Hubble Space Telescope (HST) optical path. Two sets of three latches must be aligned in position on the HOMS structure to match that of the two axial bays in HST. The RAS portion of the facility is a refractive optical system that simulates the aberrations in HST's optical telescope assembly. Each mount and lens must be properly aligned within the RAS system in order to accurately simulate the aberrations of HST's optical system. The optical axis of the RAS system must be brought into alignment with the optical axis of HOMS system. Photogrammetry, theodolite auto-collimation data, theodolite coordinate data, and laser tracker coordinate data were used to characterize the system prior to disassembly. The same data will be used to bring the RAS/HOMS system as close to the original alignment as possible.
Clinical implications of velamentous cord insertion in triplet gestations.

Abstract Objective: The purpose of this study was to determine the incidence of velamentous cord insertion and to evaluate the association between velamentous cord insertion and small-for-gestational age infants in triplet gestations. Study design: We reviewed our computerized database to identify all cases of velamentous cord insertion in triplet gestations who were delivered at our institution from January 1995 through December 1999. Triplet gestations without velamentous cord insertion who were delivered during this period were used as control subjects. Birth weights and pregnancy outcomes were obtained from medical records. Data were analyzed with descriptive statistics, analysis of variance, and χ 2 with Fisher exact test, where appropriate. Results: Thirty-nine sets of triplets (117 infants) were delivered during the study period. Of these, 11 sets of triplets (28.2%) had a velamentous insertion of at least one umbilical cord. Infants with velamentous cord insertion were more likely to be small-for-gestational age than infants without velamentous cord insertion (33% vs 8%, P = .02). There were no significant differences in the rates of pregnancy complications between the two groups. Conclusion: Velamentous cord insertion is found frequently in triplet gestations and is significantly associated with small-for-gestational age in triplet neonates. (Am J Obstet Gynecol 2002;186:809-11.)
A generalized confidence limit for the reliability function of a two-parameter exponential distribution

Based on type II censored data, an exact lower confidence limit is constructed for the reliability function of a two-parameter exponential distribution, using the concept of a generalized confidence interval due to Weerahandi (J. Amer. Statist. Assoc. 88 (1993) 899). It is shown that the interval is exact, i.e., it provides the intended coverage. The confidence limit has to be numerically obtained; however, the required computations are simple and straightforward. An approximation is also developed for the confidence limit and its performance is numerically investigated. The numerical results show that compared to what is currently available, our approximation is more satisfactory in terms of providing the intended coverage, especially for small samples.
A Low-Cost Wireless System for Autonomous Generation of Road Safety Alerts

This paper describes an autonomous wireless system that generates road safety alerts, in the form of SMS and email messages, and sends them to motorists subscribed to the service. Drivers who regularly traverse a particular route are the main beneficiaries of the proposed system, which is intended for sparsely populated rural areas, where information available to drivers about road safety, especially bridge conditions, is very limited. At the heart of this system is the SmartBrick, a wireless system for remote structural health monitoring that has been presented in our previous work. Sensors on the SmartBrick network regularly collect data on water level, temperature, strain, and other parameters important to safety of a bridge. This information is stored on the device, and reported to a remote server over the GSM cellular infrastructure. The system generates alerts indicating hazardous road conditions when the data exceeds thresholds that can be remotely changed. The remote server and any number of designated authorities can be notified by email, FTP, and SMS. Drivers can view road conditions and subscribe to SMS and/or email alerts through a web page. The subscription-only form of alert generation has been deliberately selected to mitigate privacy concerns. The proposed system can significantly increase the safety of travel through rural areas. Real-time availability of information to transportation authorities and law enforcement officials facilitates early or proactive reaction to road hazards. Direct notification of drivers further increases the utility of the system in increasing the safety of the traveling public.
An Interactive Multiple Criteria Approach for Parameter Selection in Metal Cutting

Many real-world problems, particularly in manufacturing planning, can be expressed as multiple criteria problems. In this paper, we formulate a metal cutting operation, the turning operation, as a discrete multiple objective problem. The objectives are to minimize cost per part, production time per part, and roughness of the work surface, simultaneously. We discuss a heuristic, gradient-based multiple criteria decision making approach that we apply to parameter selection in metal cutting. The approach can be applied to any multicriteria problems with either discrete, integer, or continuous sets of alternatives. The approach is interactive and requires only paired comparisons of alternatives. For the metal cutting problem, we show how efficient alternatives can be generated by a discrete variable approach and how the gradient-based multiple objective approach can be implemented to obtain the most preferred alternative. We also discuss the software package for microcomputers as a decision support system for parameter selection. The newly developed Computer Aided Machine Parameter Selection CAMPS package is then compared to some of the recent commercial packages on the market. Some computational experiments are reported and some examples are discussed.
Crossing an Ultracritical Carotid Stenosis for Carotid Angioplasty

Carotid angioplasty requires early placement of a cerebral protection device in an effort to minimize cerebral embolization during the conduct of the subsequent angioplasty and stenting procedure. In patients who exhibit a very critical internal carotid artery (ICA) stenosis (∼99%), initial passage of the lesion may not be possible with a standard 0.014-inch wire system. In this report, the authors describe an approach using a 0.012-inch hydrophilic system to overcome this technical obstacle.
The generation of gravitational waves. II - The postlinear formalism revisited

Two different versions of the Green's function for the scalar wave equation in weakly curved spacetime (one due to DeWitt and DeWitt, the other to Thorne and Kovacs) are compared and contrasted; and their mathematical equivalence is demonstrated. Then the DeWitt-DeWitt Green's function is used to construct several alternative versions of the Thorne-Kovacs postlinear formalism for gravitational-wave generation. Finally it is shown that, in calculations of gravitational bremsstrahlung radiation, some of our versions of the postlinear formalism allow one to treat the interacting bodies as point masses, while others do not.