cssi/SciSciGPT-SciSciNet huggingface dataset:
A molecular model for mechanosensation in Caenorhabditis elegans.

Sensory signaling by chemicals and light are fairly well understood in molecular terms, but the molecules needed for mechanical signaling, which underlies the senses of touch, hearing, and balance, are not known. By analyzing the genes needed for mechanosensation in the nematode Caenorhabditis elegans, we hope to gain this molecular understanding. Six touch receptor neurons respond to gentle touch in C. elegans. Mutations producing touch insensitivity have identified 12 mec (mechanosensory abnormal) genes needed for touch cell function (Chalfie and Sulston, 1981; Chalfie and Au, 1989). Eight of these genes have been cloned by ourselves and others. Two genes (mec-4 and mec-10) encode similar subunits (degenerins) of a channel needed for mechanosensation (Driscoll and Chalfie, 1991; Huang and Chalfie, 1994). Gene interaction studies suggest that many of the remaining mec genes interact with this channel (Huang and Chalfie, 1994; Gu et al., 1996). Predicted protein sequences, gene interactions, and ultrastructural studies of the touch receptor neurons suggest the following model for mechanosensation in these cells (Gu et al., 1996). Mechanosensation requires the degenerin channel formed from MEC-4, MEC-10, and
Interactive transfer function modification for volume rendering using compressed sample runs

We describe a software-based method for interactive transfer function modification. Our approach exploits the fact that, in general, a user will rarely want to modify the viewpoint and the transfer functions at the same time. In that spirit, we optimize the latter by first fixing the viewpoint and then storing a compressed list of samples along each ray. Then, each time the transfer function is modified, the algorithm traverses the compressed sample lists, decompressing the runs and compositing the newly colored samples along each ray until full opacity is reached. Since the expensive sample interpolation and shading is no longer necessary, we can obtain near-interactive framerates for a variety of datasets, while our RLE-based compression of linearly varying sample runs helps keep the storage complexity down, with little decompression overhead. Decompression cost is reduced by storing decompression results in an on-the-fly constructed 2D table.
Dynamics of docosahexaenoic acid metabolism in the central nervous system: lack of effect of chronic lithium treatment.

Using a method and model developed in our laboratory to quantitatively study brain phospholipid metabolism, in vivo rates of incorporation and turnover of docosahexaenoic acid in brain phospholipids were measured in awake rats. The results suggest that docosahexaenoate incorporation and turnover in brain phospholipids are more rapid than previously assumed and that this rapid turnover dilutes tracer specific activity in brain docoshexaenoyl-CoA pool due to release and recycling of unlabeled fatty acid from phospholipid metabolism. Fractional turnover rates for docosahexaenoate within phosphatidylinositol, choline glycerophospholipids, ethanolamine glycerophospholipids and phosphatidylserine were 17.7, 3.1, 1.2, and 0.2 %.h−1, respectively. Chronic lithium treatment, at a brain level considered to be therapeutic in humans (0.6 μmol.g−1), had no effect on turnover of docosahexaenoic acid in individual brain phospholipids. Consistent with previous studies from our laboratory that chronic lithium decreased the turnover of arachidonic acid within brain phospholipids by up to 80% and attenuated brain phospholipase A2 activity, the lack of effect of lithium on docosahexaenoate recycling and turnover suggests that a target for lithium's action is an arachidonic acid-selective phospholipase A2.
Utility and Safety of Combined Interventional Catheterization and Electrophysiology Procedures in a Children's Hospital.

BACKGROUND Interventional cardiac catheterization (cath) and electrophysiology (EP) procedures are not routinely performed together. There are several perceived barriers affecting this practice, though there are also advantages for both the patient and practitioner to a combined approach. METHODS This was a single-center retrospective study reviewing combined cath and EP procedures with a preprocedural intention to intervene at Texas Children's Hospital from 2001 to 2014. We excluded procedures in which the intended procedure was purely diagnostic in nature. RESULTS A total of 121 patients requiring 125 procedures were identified, of which 61 patients underwent 62 procedures that met our inclusion criteria. Potential subgroups of interest included adult congenital heart disease patients (26% of cohort), single ventricle anatomy (34%), and heterotaxy (19%) and collectively 58% of procedures involved a patient in one of these groups. The combined nature of the procedure did not preclude a cath or EP intervention in any patient. There were no mortalities. There were three adverse events, affecting 4.8% of procedures. CONCLUSIONS Combined interventional cardiac cath and EP procedures in pediatric patients and those with congenital heart disease can be performed safely in a high-volume center. These combined procedures save patients the risk and inconvenience of multiple procedures, and further investigation into cost savings is warranted.
Effects of substrate stiffness on the tenoinduction of human mesenchymal stem cells.

Abstract Extracellular matrix modulus plays an important role in regulating cell morphology, proliferation and differentiation during regular and diseased states. Although the effects of substrate topography and modulus on MSC differentiation are well known with respect to osteogenesis and adipogenesis, there has been relatively little investigation on the effects of this phenomenon on tenogenesis. Furthermore, relative roles of topographical factors (matrix alignment vs. matrix modulus) in inducing tenogenic differentiation is not well understood. In this study we investigated the effects of modulus and topographical alignment of type I collagen substrate on tendon differentiation. Type I collagen sheet substrates with random topographical alignment were fabricated with their moduli tuned in the range of 0.1, 1, 10 and 100 MPa by using electrocompaction and controlled crosslinking. In one of the groups, topographical alignment was introduced at 10 MPa stiffness, by controlled unidirectional stretching of the sheet. RT-PCR, immunohistochemistry and immunofluorescence results showed that mimicking the tendon topography, i.e. increasing the substrate modulus as well as alignment increased the tenogenic differentiation. Higher substrate modulus increased the expression of COLI, COLIII, COMP and TSP-4 about 2–3-fold and increased the production of COLI, COLIII and TSP-4 about 2–4-fold. Substrate alignment up regulated COLIII and COMP expression by 2-fold. Therefore, the tenoinductive collagen material model developed in this study can be used in the research and development of tissue engineering tendon repair constructs in future. Statement of Significance Although the effects of substrate topography and modulus on MSC differentiation are well known with respect to osteogenesis and adipogenesis, there has been relatively little investigation on the effects of this phenomenon on tenogenesis. Furthermore, a relative role of topographical factors (matrix alignment vs. matrix modulus) in inducing tenogenic differentiation is not well understood. We investigated the effects of modulus and topographical alignment of type I collagen substrate on tendon differentiation. This study showed mimicking the tendon topography, i.e. increasing the substrate modulus as well as alignment increased the tenogenic differentiation. Therefore, the tenoinductive collagen material model developed in this study can be used in the research and development of tissue engineering tendon repair constructs in future.
Improving Gene Therapy Efficiency through the Enrichment of Human Hematopoietic Stem Cells

Lentiviral vector (LV)-based hematopoietic stem cell (HSC) gene therapy is becoming a promising clinical strategy for the treatment of genetic blood diseases. However, the current approach of modifying 1 × 10 8 to 1 × 10 9 CD34 + cells per patient requires large amounts of LV, which is expensive and technically challenging to produce at clinical scale. Modification of bulk CD34 + cells uses LV inefficiently, because the majority of CD34 + cells are short-term progenitors with a limited post-transplant lifespan. Here, we utilized a clinically relevant, immunomagnetic bead (IB)-based method to purify CD34 + CD38 − cells from human bone marrow (BM) and mobilized peripheral blood (mPB). IB purification of CD34 + CD38 − cells enriched severe combined immune deficiency (SCID) repopulating cell (SRC) frequency an additional 12-fold beyond standard CD34 + purification and did not affect gene marking of long-term HSCs. Transplant of purified CD34 + CD38 − cells led to delayed myeloid reconstitution, which could be rescued by the addition of non-transduced CD38 + cells. Importantly, LV modification and transplantation of IB-purified CD34 + CD38 − cells/non-modified CD38 + cells into immune-deficient mice achieved long-term gene-marked engraftment comparable with modification of bulk CD34 + cells, while utilizing ∼7-fold less LV. Thus, we demonstrate a translatable method to improve the clinical and commercial viability of gene therapy for genetic blood cell diseases.
Poster: Camera Images Offloading in Low-resource Wireless Networks

Camera snapshot images are widely used in IoT applications. However, when the applications are deployed in rural areas or poorly-performing networks, the images offloading usually exhausts the limited network resources. While we can certainly revamp the network links, we can also optimize the payload at the same time. In this paper, we propose a middlebox system design that exploits the patterns of similarity between consecutive camera snapshots to alleviate the network load. Our preliminary results show that despite of small errors introduced in the images, the amount of reduced payloads could be a valuable choice to alleviate poorly performing networks.
Untersuchungen über die personellen und finanziellen Entlastungsmöglichkeiten der Krankenhausversorgung durch Differenzierung der Krankenhausaktivitäten nach vollstationärer und semistationärer Versorgung

Ausgehend von der Struktur der Aufgaben und des Aufwandes im Gesundheitswesen ergibt sich, das das Krankenhauswesen einen wichtigen Ansatz fur eine Begrenzung der Ausgaben fur die Gesundheit bietet. Dabei steht fest, das es nicht genugt, alle betrieblichen, baulichen und technischen Masnahmen zur Rationalisierung der Krankenhauser auszuschopfen. Es wird daruber hinaus unumganglich sein, das Krankenhauswesen als einen der kostenverursachenden Zweige des Gesundheitswesens quantitativ soweit wie moglich zu entlasten.
Paramagnetic Resonance of High-Spin Co(II) in Biologically-Relevant Environments: Models to Metalloproteins

The use of Co(II) as a spectroscopic surrogate for Zn(II) is now a well-established protocol in metallobiochemistry. The d7 Co(II) ion usually adopts a high-spin (S = 3/2) configuration and a coordination geometry similar to the native Zn(II) ion, often returning an active enzyme. However, the complicated electronic structure that gives rise to easily detectable signals in a wide array of optical and magnetic spectroscopies simultaneously hampers data interpretation in terms of structure. Nowhere is this more evident than in the EPR spectra of Co(II) complexes, particularly at X-band. Some alternatives to common practice in the assignment and simulation of high-spin Co(II) EPR are presented. Our intent is to shed light on the sources of spectral complexity, and address some of the remaining issues confounding the successful application of more advanced techniques, such as ENDOR (CW or pulsed) and ESEEM. The importance of spin sub-level mixing into the magnetic ground state, leading to possible intensity stealing and the appearance of signals from both spin doublets, is discussed in terms of available zero-field splitting data, and the identity of the ground doublet.
Modeling to Predict Biodegradability

In the US, the safety of specific chemical substances is evaluated primarily under three statutes. Substances used as food additives, drugs and cosmetics are regulated by the Food and Drug Administration (FDA) under the Federal Food, Drug and Cosmetic Act (FFDCA). Chemical substances proposed for use as pesticides are regulated by the US Environmental Protection Agency (USEPA) under the Federal Insecticide, Fungicide and Rodenticide Act (FIFRA), which imposes a host of data requirements for any submitter seeking to register the substance as an active ingredient. Industrial chemicals are regulated under the Toxic Substances Control Act (TSCA; Public Law 94–469), which was enacted by Congress in 1976 in response to a perceived need to limit exposure to “environmental chemicals” such as polychlorinated biphenyls (PCBs). As stated in the Act, its primary purpose is “to assure that…innovation and commerce in…chemical substances and mixtures do not present an unreasonable risk of injury to health or the environment” (TSCA, section 2(b)). TSCA requirements are different for existing substances and substances not yet in production (“new” chemicals). One of the first tasks of the newly created Office of Toxic Substances (now the Office of Pollution Prevention and Toxics; OPPT) was to assemble and publish a list of chemical substances already in commerce. This was accomplished in July, 1979 as the TSCA Chemical Substance Inventory, which listed approximately 50,000 substances then in production or being imported into the US. Since that time the Inventory has grown to include over 70,000 substances by the addition of new chemicals.
Closing the practice gap: Studying boundary spanning in engineering practice to inform educational practice

How to adequately prepare engineering graduates for careers in industry has long been a concern for academics, policymakers, and employers. However, the realities of engineering practice remain somewhat mysterious to many students and instructors, often leaving engineering graduates underprepared for the workplace, and employers dissatisfied with new employees. In this work, we seek to better understand the job expectations and realities of working life as experienced by early career engineers. In this paper, we more specifically focus on three engineering practice scenarios drawn from three interviews to demonstrate the complex, sociotechnical nature of engineering work in large corporations. Our analysis of workplace boundaries, boundary spanning activities, and personal attributes revealed an inextricably linked set of concepts that we present in a new conceptual framework. We conclude with a discussion of implications for both how we understand engineering practice and approach the teaching of engineering. It is expected that this paper can help students, faculty, and industry affiliates reflect on the realities of engineering work.
Meta-Invariant Structure in Stimulus Arrays: A Response to Mace's Zetetic Challenge to Ecological Perceptual Researchers

Ecological perception, per James Gibson's theory, avows that perception depends on informative structure in stimulus arrays, where information is defined as stimulus array invariants. Gibson, howev...
A COMPARISON OF ALFAXALONE AND TRICAINE METHANESULPHONATE (MS-222) IN TWO FISH SPECIES

Abstract The purpose of this study was to evaluate the effectiveness of the alfaxalone formulation Alfaxan™ as an immersion anesthetic in tropical fish species compared to that of tricaine methanesulfonate (MS-222). 22 black spot barbs (Puntius filamentosis) measuring (mean±SD) 11.4 ±1.4 cm in body length and 22 peacock cichlids (Aulonocara spp.) (measuring 8.4 ± 1.6cm were anesthetized in water baths containing 100 mg/L of MS-222 buffered with 200 mg/L of bicarbonate or 5 mg/L of alfaxalone following a 2-week washout period. Time to maximum effect, recovery periods, self-righting, spontaneous swimming movements, opercular movements, and response to noxious stimuli were recorded. The following results are for the black spot barbs following MS-222 and alfaxalone anesthesia, respectively: mean times (±SD) to surgical anesthesia were 5.5 ± 2.11 and 3.27 ± 1.72 minutes and mean recovery times were 2.95 ± 0.9 and 9.14 ± 3.15 minutes. The peacock cichlid anesthetic protocols for MS-222 (20 of 22 cichlids) and alfaxalone (20 of 21 cichlids) produced the following results, respectively: mean times (±SD) to surgical anesthesia were 14.75 ±5.43 and 11.1 ± 9.84 minutes and mean recovery times were 3.6 ±0.82 and 22.4 ±11.3 minutes. Median recovery time from 5 mg/L alfaxalone was significantly longer (P
Assessing the Performance Level of Air Quality Models

The air quality management process relies heavily on an ability to predict the impact of control decisions on ambient pollutant concentrations.1 Air quality models are a fundamental component of this management process. In fact, control decisions based on these models have a major effect on the siting of air pollution sources and on the costs of control. Accordingly, air quality managers need to know the accuracy of model estimates, and modelers need a measure by which to evaluate and compare the performance of alternative models.
Freshwater Cyanobacteria (blue-green algae) Toxins

ABSTRACT Worldwide in natural or man induced eutrophic water bodies certain fresh/brackish water cyanobacteria (blue-green algae) species and strains in the genera Anabaena. Aphanizomenon. Microcystis. Nodularia and Oscillatoria are known to produce potent biotoxins. Two chemical groups of toxins are recognized, the first is a related family of hepatotoxic cyclic heptaand pentapeptides, termed microcystin and nodularin. These peptide toxins produce similar gross and ultrastructural effects on hepatocytes resulting in hemorrhagic necrosis and death by hemorrhogic shock. Research suggests that the toxins are taken up via the bile acid transport systems and that the toxins exert an effect on the cytoskeletal system of the cell. The second group contains at least three types of neurotoxic alkaloids produced by strains of the species Anabaena (anatoxins) and Aphanizomenon (aphantoxins). Anatoxin-a (a bicyclic secondary amine) is a potent nicotinic agonist acting as a depolarizing neuro-muscular blocking agent. Anatoxin-a(s) (a cyclic organo-phosphate) has been shown to act as a potent irreversible acetylcholinesterase inhibitor. The mechanism of inhibition is similar to known irreversible organophosphorus anti-cholinesterases such as diisopropylfluorophosphate (DFP). Aphantoxins have been shown to be the same as saxitoxin and neosaxitoxin, the potent sodium channel blockers, produced by species of marine dinoflagellates such as Protogonvaulax . The range of toxicity for these peptide and alkaloid toxins is between 10 and 500 /ig/kg body weight (based on intraperitoneal mouse assay).
Acute stroke treated with tissue plasminogen activator in a patient with GBM (P6.134)

Objective: To report a case of acute stroke treated with tPA in a patient with history of Glioblastoma Multiforme (GBM). Background: Among all primary brain tumors in humans, GBM is the most common and also has the worst prognosis. It is a very vascular tumor and patients are at higher risk for getting ischemic strokes and intracerebral hemorrhage. Design/Methods: We present a case report of a patient with a history of GBM who was treated with tPA for her Ischemic stroke. Results: Our patient is a 62 year old female with history of GBM WHO grade IV: Ki- 67 of 50%, IDH1 negative, ATRX positive, p53 positive, MGMT unmethylated, MYC translocation negative who had undergone right temporal craniotomy and resection of the tumor followed by radiation therapy and chemotherapy with temozolomide. Four months after her initial surgery the patient had progression of GBM and underwent a redo right temporal craniotomy for resection. Three months after her second surgery she presented to us with left sided weakness. She had dense left sided hemiplegia and her NIHSS was 7. She was given alteplase bolus 6.5 mg bolus followed by alteplase infusion 58.9 mg/hr. Her NIHSS improved after getting tPA. MRI brain showed a small right Basal Ganglia stroke. Her post tPA CT head was stable. She was discharged to inpatient rehab and from there she went home. Conclusions: GBM is a very vascular tumor and overexpresses the vascular endothelial growth factor. Patients with GBM are at higher risk for getting ischemic strokes and intracerebral hemorrhage. It can cause stroke by occluding the blood vessel by direct compression or infiltration. Radiation vasculopathy is also a risk factor. Currently there no guidelines on treatment of stroke in patients with GBM. In this case report we demonstrate how we safely treated ischemic stroke in a patient with GBM with tPA. Disclosure: Dr. Hinduja has nothing to disclose. Dr. Rauf has nothing to disclose.
Conflicts of Interest in Patent Practice

Addresses conflicts of interest in patent practice, including patent prosecution, patent opinion work, and patent litigation.
Le base ball, Assimilation, and Ethnic Identity: The National Pastime in Franco-America

This article explores the meaning of baseball in areas of New England where immigrants of French-Canadian descent settled permanently. It examines representations of the sport in the French-languag...
Response to Technical Comment on Rickles, Heppen, Allensworth, Sorensen, and Walters (2018):

In response to the concerns White raises in his technical comment on Rickles, Heppen, Allensworth, Sorensen, and Walters (2018), we discuss whether it would have been appropriate to test for nomina...
Tradition Versus Value: Is There Utility in Protocolized Postoperative Laboratory Testing After Elective Colorectal Surgery?

Objective Determine if routine ordering of postoperative day 1 (POD 1) serum laboratory tests after elective colorectal surgery are clinically warranted and valuable given the associated costs of these lab tests. Summary of background data Routine postoperative serum laboratory tests are a part of many colorectal surgery order sets. Whether these protocolized lab tests represent cost-effective care is unknown. Methods Patients undergoing elective colorectal surgery between January 1, 2015 and December 31, 2017 at our institution were identified. The protocolized POD 1 lab tests obtained as part of the postoperative order set were reviewed to determine the rate of abnormal values and any intervention in response. Costs associated with protocolized laboratory testing were calculated using dollar amounts representing 2017 outpatient Medicare reimbursement. Results A total of 2252 patients were identified with 8205 total lab test values. Of these, only 4% were abnormal (3% of hemoglobin values, 6% of creatinine values, 3% of potassium of values, and 3% of glucose values), and only 1% were actively intervened upon. The total aggregate cost of the protocolized POD 1 laboratory tests in these years was $64,000 based on Medicare outpatient reimbursement dollars. Conclusions Routine POD 1 lab tests after elective colorectal surgery are rarely abnormal, and they even less frequently require active intervention beyond rechecking. This results in increased resource utilization and cost of care without appreciable impact on clinical care, and is not cost-effective. Protocolized POD 1 laboratory testing should be replaced with clinically-based criteria to trigger serum laboratory investigations.
Defining thyroid spherules: A benign cytomorphologic feature that mimics microfollicles

BACKGROUND Distinctive rounded structures termed spherules have been observed in thyroid fine-needle aspiration (FNA) samples. Although they are often small and interpreted as microfollicles, spherules are notable for the even spacing of the follicular cells along the perimeter of the structure. Because they have an orderly architectural arrangement, it has been hypothesized that spherules are benign and do not carry the same risk of malignancy that traditional microfollicles do. The aim of this study was to identify the clinical significance and histopathologic correlate of spherules. METHODS Thyroid FNAs (n = 637) with an interpretation of atypia of undetermined significance (AUS) were reviewed for the presence of spherules, which were defined as small follicles with a rounded, smooth, sharply defined outer contour, evenly spaced nuclei, and a 3-dimensional appearance. Cases were included if spherules accounted for >50% of follicular cell arrangements. Clinical, histopathologic, molecular, and sonographic follow-up data were obtained. RESULTS Twenty-five spherule cases were identified, and they represented 3.9% of all AUS cases reviewed. All 24 cases with follow-up had a benign outcome. Eleven were tested with the Afirma gene expression classifier; 8 were benign according to the gene expression classifier, and 3 were suspicious but histologically benign after surgical resection. Four additional cases were histologically benign after surgery. Five patients had repeat benign cytology. Four patients had repeat stable ultrasound findings. CONCLUSIONS Thyroid nodules diagnosed as AUS, if composed predominantly of spherules, are associated with a benign outcome. Recognizing this distinctive cytomorphologic finding may help to reduce the number of FNAs interpreted as AUS and save patients from unnecessary additional testing and surgery.
Analyzing system software components using API model guided symbolic execution

Analyzing real-world software is challenging due to complexity of the software frameworks or APIs they depend on. In this paper, we present a tool, PROMPT, that facilitates the analysis of software components using API model guided symbolic execution. PROMPT has a specification component, PROSE, that lets users define an API model, which consists of a set of data constraints and life-cycle rules that define control-flow constraints among sequentially composed API functions. Given a PROSE model and a software component, PROMPT symbolically executes the component while enforcing the specified API model. PROMPT has been implemented on top of the KLEE symbolic execution engine and has been applied to Linux device drivers from the video, sound, and network subsystems and to some vulnerable components of BlueZ, the implementation of the Bluetooth protocol stack for the Linux kernel. PROMPT detected two new and four known memory vulnerabilities in some of the analyzed system software components.
Biomechanical assessment while using production tables on mast climbing work platforms

The objective of this study was to assess the impact of using alternative mast climbing work platform (MCWP) designs on trunk motion and postural stability with masonry workers while performing bricklaying and stepping down tasks using a conventional MCWP setting (i.e. with a step deck) as well as two types of production tables (straight- and L-shaped). The trunk angles and postural sway parameters of twenty-five masonry workers were recorded for the following tasks: (1) standing on a simulated MCWP and laying bricks on an adjacent wall, and (2) stepping down onto the step deck to get into position for doing the bricklaying task. Results indicated that the use of the L-shaped production table resulted in the lowest trunk ranges of motion and significantly reduced the workers' trunk angles in all three planes when compared to both the straight-shaped production table and the conventional approach of not using a production table. Data showed that both body sway velocity and area were significantly reduced when using either one of the production tables. The use of production tables significantly reduced impact sway forces when workers stepped from the main platform to the step deck. The use of production tables on MCWPs improved workers' postures and overall stability, which could reduce the risk of injury.
User Scheduling and Beam Alignment in mmWave Networks With a Large Number of Mobile Users

In this paper, we study an optimal user scheduling with minimum beam alignment overhead in millimeter wave networks. The problem is posed as constrained Markov decision process (CMDP) with the goal of minimizing the average beam alignment overhead subject to the average rate constraint on each user. Under a certain assumption on the rate function of the users, by using a structural result derived from the Lagrangian formulation of the CMDP, we show that the optimal policy should keep scheduling the users that are scheduled in the previous time slot unless an abrupt change in the beam direction occurs. Using this result, the complexity of the problem decreases to polynomial in the number of users. In addition, we provide a heuristic deterministic algorithm that achieves $({1}+\epsilon)$ approximation of the optimal solution, with smaller $\epsilon $ at the cost of longer transmission interval of each user. Lastly, to deal with the case where the assumption on the rate function does not hold due to beam conflicts between the users, we consider a system model that accounts for an angular channel information. A new CMDP is formulated for the problem and a heuristic algorithm based on the age information is proposed.
Engineered Split Reporter Systems for Molecular Imaging of Protein-Protein Interactions in Living Subjects

In the last decade, there has been a veritable explosion in the field of reporter gene imaging, with the aim of determining the location(s), duration, and extent of gene expression within living subjects. An important application of this is in molecular imaging of interacting protein partners, an area that could pave the way to functional proteomics in living animals and provide a tool for whole-body evaluation of new pharmaceuticals targeted to modulate protein–protein interactions. We review the main methods currently available for imaging protein–protein interactions in living subjects using molecularly engineered and rationally designed split reporter gene and protein systems tailored to various protein complementation and reconstitution strategies.
Chapter 13. Antineoplastic Agents

Publisher Summary This chapter examines the synthesis and clinical studies of the antineoplastic agents. 5-Aziridinyl-2,4-dinitrobenamide has the exceptional activity against the Walker carcinoma. Its antitumor activity is reversed by 4-amino-5-imidazolecarboxamide. Suppression of cell membrane transport plays a role in the resistance to nitrogen mustard by the Yoshida sarcoma cells. Metabolism of cyclophosphamide by rat hepatic microsomes has been reported. Enzymatic phosphorylation studies confirm that ara-C and its phosphorylated derivatives are deoxycytidine antagonists rather than cytidine antagonists. Inhibition of DNA polymerase activity is considered more significant to antineoplastic properties than either blocking the uptake of thymidinel or the inhibition of the conversion of cytidine diphosphate to deoxycytidine diphosphate. 5-Fluorouracil (5-FU) might be more effective in patients with liver metastases when given orally, due to high drug concentrations in the portal system. Oral dosage with 5-FU is safe and effective in metastatic colorectal carcinoma and it enhances the antitumor effect of irradiation in bronchogenic carcinoma.
A Cockpit Display Designed to Enable Limited Flight Deck Separation Responsibility

Cockpit displays need to be substantially improved to serve the goals of situational awareness, conflict detection, and path replanning, in Free Flight. This paper describes the design of such an advanced cockpit display, along with an initial simulation based usability evaluation. Flight crews were particularly enthusiastic about color coding for relative altitude, dynamically pulsing predictors, and the use of 3-D flight plans for alerting and situational awareness.
Cesarean delivery and risk of herpes simplex virus infection.

To the Editor: Based on 18 cases of neonatal herpes, Dr Brown and colleagues argue that “development of a strategy to reduce this disease burden seems imperative.” What, though, is the actual disease burden? The authors provided no clinical outcome details about the neonatal herpes cases they observed and did not acknowledge that theirs is among the highest incidence ever to be reported. Before broad neonatal herpes preventive efforts (eg, serologic screening) are instituted, the incidence and severity of neonatal herpes should be better defined and categorized on a populationwide basis. In California, during the 10-year period of 1985-1995, the incidence of neonatal herpes was stable at 1.1 per 10000 births, a rate 3 times lower than that reported by Brown et al. It is difficult to imagine that screening and treatment for such an uncommon disease would ever be efficient or cost-effective.
Thermal-mechanical behavior of oceanic transform faults: Implications for the spatial distribution of seismicity

[1] To investigate the spatial distribution of earthquakes along oceanic transform faults, we utilize a 3-D finite element model to calculate the mantle flow field and temperature structure associated with a ridge-transform-ridge system. The model incorporates a viscoplastic rheology to simulate brittle failure in the lithosphere and a non-Newtonian temperature-dependent viscous flow law in the underlying mantle. We consider the effects of three key thermal and rheological feedbacks: (1) frictional weakening due to mantle alteration, (2) shear heating, and (3) hydrothermal circulation in the shallow lithosphere. Of these effects, the thermal structure is most strongly influenced by hydrothermal cooling. We quantify the thermally controlled seismogenic area for a range of fault parameters, including slip rate and fault length, and find that the area between the 350°C and 600°C isotherms (analogous to the zone of seismic slip) is nearly identical to that predicted from a half-space cooling model. However, in contrast to the half-space cooling model, we find that the depth to the 600°C isotherm and the width of the seismogenic zone are nearly constant along the fault, consistent with seismic observations. The calculated temperature structure and zone of permeable fluid flow are also used to approximate the stability field of hydrous phases in the upper mantle. We find that for slow slipping faults, the potential zone of hydrous alteration extends greater than 10 km in depth, suggesting that transform faults serve as a significant pathway for water to enter the oceanic upper mantle.
In Memoriam: John Shannon (1931–2015)

John Meeks Shannon, museum director, historian, and longtime fixture in the Denver and Tucson mineral shows, passed away in Lakewood, Colorado, on 4 March 2015. He was born in Pampa, Texas, to Cleo...
Breast DCE-MRI Kinetic Heterogeneity Tumor Markers: Preliminary Associations With Neoadjuvant Chemotherapy Response

The ability to predict response to neoadjuvant chemotherapy for women diagnosed with breast cancer, either before or early on in treatment, is critical to judicious patient selection and tailoring the treatment regimen. In this paper, we investigate the role of contrast agent kinetic heterogeneity features derived from breast dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) for predicting treatment response. We propose a set of kinetic statistic descriptors and present preliminary results showing the discriminatory capacity of the proposed descriptors for predicting complete and non-complete responders as assessed from pre-treatment imaging exams. The study population consisted of 15 participants: 8 complete responders and 7 non-complete responders. Using the proposed kinetic features, we trained a leave-one-out logistic regression classifier that performs with an area under the receiver operating characteristic (ROC) curve (AUC) of 0.84 under the ROC. We compare the predictive value of our features against commonly used MRI features including kinetics of the characteristic kinetic curve (CKC), maximum peak enhancement (MPE), hotspot signal enhancement ratio (SER), and longest tumor diameter that give lower AUCs of 0.71, 0.66, 0.64, and 0.54, respectively. Our proposed kinetic statistics thus outperform the conventional kinetic descriptors as well as the classifier using a combination of all the conventional descriptors (i.e., CKC, MPE, SER, and longest diameter), which gives an AUC of 0.74. These findings suggest that heterogeneity-based DCE-MRI kinetic statistics could serve as potential imaging biomarkers for tumor characterization and could be used to improve candidate patient selection even before the start of the neoadjuvant treatment.
Fiswidgets: a graphical computing environment for neuroimaging analysis.

Current fMRI neuroimaging software programs offer the researcher a wealth of analysis methods and tools. However, the incompatibilities in user interface, data format, and computing environment in these tools make it difficult if not impossible for most researchers to take advantage of the full set of resources available for neuroimaging analyses. We describe a graphical computing environment, Functional Imaging Software Widgets (fiswidgets), which was developed to address these interoperability and usability problems. This environment provides a desktop style framework into which 100 subcomponents from a number of widely used fMRI analysis software packages (e.g., AFNI, AIR) are incorporated. It is an open-source, extensible environment available for reuse and modification by other software developers. A discussion of the design criteria (open architecture, modularity, wrapper technology, commercial utilities) that support such loosely integrative computing environments, and the problems entailed in maintaining them (development overhead, distribution logistics, format incompatibilities, graphics vs scripting tradeoffs, and appropriate acknowledgment of software developers) follows.
The deterioration of children in ward areas in a specialist children's hospital.

Research in adult patients, in the last decade, has highlighted suboptimal care and failures in the recognition of sick adults in ward areas. In addition, many of these patients (at least 50%) demonstrated documented evidence, on observation charts, of clinical deterioration in the 24–48 h preceding cardiopulmonary arrest or emergency intensive care unit admission. However, there is little published data on whether these findings apply to children (0–17 years). The aim of the study was to examine the extent of inpatient deterioration and critical care unit admission within a children’s hospital based in the North West of England, during a 4-month period. The design included a prospective chart review of clinical observations. As noted in adult patients, there is considerable documented evidence (in terms of abnormal vital signs) of physiological deterioration in the 24 h preceding intensive care or high-dependency unit admission. The use of a Paediatric Early Warning (PEW) tool could potentially have identified 87% of these children of being ‘at risk’ of deterioration. It is recommended that a PEW tool be incorporated into the routine paediatric ward observation charts and practice to identify children ‘at risk’ of deterioration.
THE INTERACTION BETWEEN PRICING AND UNDERWRITING SPREAD IN THE NEW ISSUE CONVERTIBLE DEBT MARKET

The objective of this research is to measure the interaction among pricing variables in new issues of convertible debt. In underwriting convertible debt issues, there is a simultaneous tradeoff among the conversion premium, yield, and underwriting spread. Since the three endogenous variables are interrelated, a simultaneous equation model is used to test for this interaction. Based on a sample of 264 new convertible debt offerings, the results indicate underpricing in terms of conversion premium and yield as well as simultaneous increases in yield and underwriting spread.
Low pressure studies of dehydrocyclization of n-heptane on platinum crystal surfaces using mass spectrometry, auger electron spectroscopy, and low energy electron diffraction

Abstract The dehydrocyclization of n-heptane on platinum crystal surfaces of area less than 1 cm2 was studied in the temperature range of 100–400 °C and at pressures in the 10−4 Torr range. The toluene formation rate was monitored in a static system by a mass spectrometer, the surface structure by low energy electron diffraction, and the surface composition by Auger electron spectroscopy. The (111) face and two types of stepped platinum crystal faces were used. The stepped surfaces exhibit a surface structure of ordered steps of monatomic height separated by terraces with (111) orientation for one face and by terraces of (100) orientation for the other. The initial rate of toluene formation on the stepped surface with (111) terraces is twice as fast as on the surface with (100) terraces and the reaction can be sustained in the presence of hydrogen for more than an hour. A new (√3 × √3)-R30 ° surface structure which develops in the course of the reaction or a (9 × 9) surface structure which appears upon heat treatment to 850 °C have no detrimental effect on the reactivity. These surface structures can be attributed to the presence of ordered carbon at the platinum surface. Under identical conditions, the toluene yield of the stepped surface with (100) terraces decreases steadily as a function of the number of doses and reaches the detection limit after about an hour. The low index (111) surface appears to be less reactive than the stepped surface with (111) terraces by at least an order of magnitude. Both of the less reactive surfaces become covered by a disordered carbon-containing layer during the reaction. The presence of hydrogen during the reaction appears to reduce the rate of dissociative chemisorption of n-heptane, so that the dehydrocyclization can successfully compete with it.
Eelgrass (Zostera marina L.) transplants in San Francisco Bay: Role of light availability on metabolism, growth and survival

Abstract Survival, metabolism and growth of Zostera marina L. transplants were examined along depth gradients in Keil Cove and Paradise Cove in the extremely turbid San Francisco Bay estuary. Water transparency was unusually high throughout 1989–1990 for San Francisco Bay. Transplant survival was strongly depth-dependent at Paradise Cove but not at Keil Cove. All transplants were lost below − 1.0 m depth within 1 year at Paradise Cove, but survived to depths of − 1.5 m at Keil Cove. Half the transplants growing in shallow water survived the first year at both sites. Shoot photosynthesis, respiration, growth, and sugar content did not differ between sites. Daily periods of irradiance-saturated photosynthesis (Hsat) were over 6 h all year. Seasonal photosynthetic acclimation to light availability maintained long Hsat periods and high ratios of daily whole-plant production to respiration through the winter, indicating a potential for net carbon gain throughout the year. Winter growth was 50% of the summer rate. Despite high initial losses, surviving transplants have persisted at both sites through 1994. Although eelgrass transplants can succeed in San Francisco Bay given sufficient light availability, the role of carbon reserves and transplant timing may influence transplant survival.
Integrating DBT-based techniques and concepts to facilitate exposure treatment for PTSD.

While considerable evidence supports the use of exposure-based treatment for PTSD, its utilization in clinical practice remains limited. This article presents a systematic and empirically grounded approach to the flexible application of PTSD treatment research in a “true” clinical setting. High rates of attrition, suicidality, dissociation, destructive impulsivity, and chaotic life problems are reasons cited by clinicians for abandoning empirically supported exposure treatment. Linehan's dialectical behavior therapy (DBT), designed to address many of these issues, offers useful strategies for addressing the needs of patients considered poor candidates for exposure therapy. This article offers a model for integrating DBT-based theory, concepts, and skills with manualized exposure-based cognitive-behavior therapy for PTSD in order to improve patient (and therapist) tolerance of this treatment.
An examination of cost structure and production performance of commercial banks in Singapore

Abstract This paper uses a parametric approach in the framework of a translog cost function and a non-parametric approach in the framework of linear programming to examine production performance and cost structure of a sample of Singaporean commercial banks. The results of the parametric methodology suggest that the average cost curve of these banks is U shaped and there are economies of scale for small and medium-size banks. Further analysis provides evidence of economies of scope for all banks regardless of their size. The non-parametric results indicate that the Singaporean banks could have reduced cost by 43% had they all been overall efficient. The sources of this cost inefficiency seem to be caused equally by allocative and technical inefficiencies.
Herbicides: Feminization of male frogs in the wild

Water-borne herbicide threatens amphibian populations in parts of the United States. Atrazine is the most commonly used herbicide in the United States and probably in the world1. Here we investigate the effects of exposure to water-borne atrazine contamination on wild leopard frogs (Rana pipiens) in different regions of the United States and find that 10–92% of males show gonadal abnormalities such as retarded development and hermaphroditism. These results are supported by laboratory observations, which together highlight concerns over the biological effects of environmental atrazine on amphibians.
Can the first pregnancy of a young adolescent be prevented? A question which must be answered.

The title of this paper is a question, and the text of the paper presents some issues and ideas which are the sources of the question. Included are notions from the literature on adolescent cognitive development and their relation with the notion of “prevention”. It is argued that the notion of prevention is taken for granted in professional thinking about adolescent pregnancy and that a fuller understanding of this idea in the context of adolescent cognitive development could have clear consequences for research action.
Inequalities for Ek(X, Y) when the marginals are fixed

When k(x, y) is a quasi-monotone function and the random variables X and Y have fixed distributions, it is shown under some further mild conditions that ℰ k(X, Y) is a monotone functional of the joint distribution function of X and Y. Its infimum and supremum are both attained and correspond to explicitly described joint distribution functions.
Genetic control of IgM responses to (T,G)-A — L: H-2 andIg-1 linkage

The primary antibody response to aqueous immunization with a low molecular-weight lot of (T,G)-A — L (#420) was studied in congenic pairs of inbred mouse strains. Two new genetic controls were identified, both of which quantitatively regulate the production of IgM anti-(T,G)-A — L antibody. Testing of F1 and F2 progeny demonstrated that one of these genes is linked to the major histocompatibility (H-2) complex, and that high response is dominant over low response. Whether this gene is identical toIr-1A is not yet known. The other gene, designatedIg-TGALM, is linked to the immunoglobulin heavy-chain allotype locus (Ig-1) and is expressed in a genedose dependent manner. Following secondary challenge with (T,G)-A — L 420, quantitative differences in IgG antibody response were observed inIr-1A high-responder congenics differing only at theIg-1 locus. Breeding studies, however, failed to demonstrate any linkage between this locus and the quantitative control of IgG anti-(T,G)-A — L antibody. These data demonstrate thatH-2-linked immune response genes can regulate IgM as well as IgG antibody responses, that genetic control of the IgM response to (T,G)-A — L is linked toIg-1, and that bothH-2-linked andIg-1-linked genes may simultaneously affect an IgM antibody response to the same antigen.