cssi/SciSciGPT-SciSciNet huggingface dataset:
Modulation of macrophage phenotype to treat liver fibrosis—Current approaches and future possibilities

Liver fibrosis is a leading cause of death worldwide, accounting for approximately 2 million deaths annually. Despite its wide prevalence, there are currently no pharmacological therapies that directly reverse the fibrotic process in patients. Studies over the last decade have revealed that liver fibrosis is reversible in patients and in animal models. Further, studies aimed at elucidating the mechanism of fibrosis reversal have revealed that macrophages are central to this process. During resolution of fibrosis, proinflammatory macrophages shift phenotype to pro-resolution macrophages which produce matrix degrading enzymes and mediators that inactivate hepatic stellate cells, the cell type principally involved in matrix production during fibrosis development. Since fibrosis reversal begins when disease-causing macrophages transition to disease-reversing macrophages, studies have focused on identifying pharmacological agents that stimulate this process to occur. If successful, these "drugs" would constitute a first-in-class, macrophage-targeted therapeutic approach to reverse liver fibrosis. In the following review, we summarize the current approaches under investigation to modify macrophage phenotype for liver disease treatment. Further we discuss the potential of other approaches to identify novel macrophage-targeted drugs that modify the phenotype of these cells.
Lifelong Learning of Instructional Design and Educational Technology Professionals: a Heutagogical Approach

Lifelong learning is an important but often implicit part of the job for instructional designers and educational technologists (ID/ETs). While literature discusses improving on-the-job learning experiences of others, relatively little has been written on the lifelong learning practices of ID/ETs. We interviewed 31 professionals to explore ID/ETs’ attitudes towards lifelong learning, motivation for seeking learning opportunities, and learning approaches. The Constant Comparative Method for Naturalistic Inquiry was used to analyze the transcripts. As predicted by heutagogy, the study of self-determined learning, participants demonstrated traits of capable learners who view learning as part of their job and use a range of approaches to plan and continuously reflect on their learning. We recommend that employers promote self-determined learning practices within their organization, and that educators prepare students to be self-determined learners. We further recommend that academia, practitioners, and students contribute to repositories of resources and examples to learn from each other.
Supercritical Fluid Chromatography in Clinical Chemistry

Supercritical fluid chromatography (SFC) employs a gas taken above its critical temperature and critical pressure to where it forms a supercritical fluid (SF). SFs have properties of both gases and liquids. They have lower densities and viscosities and higher diffusion coefficients than liquids, but they also have the solvating power of a liquid and can dissolve nonpolar and many polar compounds. As such, these favorable properties combine to make SFs an excellent mobile phase for column chromatography. The SFC technique is highly versatile in that it can be used with either packed columns (similar to high-performance liquid chromatography (HPLC) columns with the same variety of stationary phases available) or open-tubular columns (similar to gas chromatography (GC) columns and employing the same types of coatings) which can be interfaced with a very wide array of detectors. In addition, SFC avoids high temperatures during the chromatographic separation and in most cases the need to derivatize analyzed compounds. These features make SFC particularly well suited to the separation and assay of clinically important biomolecules. As SFC instruments have become commercially available, numerous applications have been explored in the areas of drug monitoring, toxicology, environmental contaminants, and the measurement of physiological biomolecules. Despite its potential, SFC enjoys limited use in clinical chemistry laboratories currently. Greater efforts are needed to improve sensitivity, standardize and validate assays, and work toward high-volume throughput capabilities.
Hydrogen bonding interactions with the Schiff base of bacteriorhodopsin : resonance Raman spectroscopy of the mutants D85N and D85A

Abstract The bacteriorhodopsin (bR) mutants Asp-85-->Asn (D85N) and Asp-85-->Ala (D85A) have a red-shifted chromophore absorption and exhibit no proton pumping (Otto, H., Marti, T., Holz, M., Mogi, T., Stern, L., Engel, F., Khorana, H. G., and Heyn, M. P. (1990) Proc. Natl. Acad. Sci. U.S.A. 87, 1018-1022) consistent with the hypothesis that Asp-85 functions as a counterion and proton acceptor for the retinal Schiff base (Braiman, M. S., Mogi, T., Marti, T., Stern, L. J., Khorana, H. G., and Rothschild, K. J. (1988) Biochemistry 27, 8516-8520). Resonance Raman spectroscopy reveals that these mutants contain a mixture of all-trans and 13-cis/C = N syn chromophores, similar to dark-adapted purple membrane and acid-induced or deionized blue membrane. At high NaCl concentrations, both mutants adopt a predominantly all-trans chromophore structure similar to acid purple membrane. A comparison of the Schiff base C = NH+ stretch frequency (vC = N) and deuterium isotope shift for D85N, D85A as well as various forms of bR, including light-adapted bR, blue membrane, and acid purple membrane, provides information about hydrogen bonding interactions to the Schiff base. D85N has as strong a hydrogen bond as light-adapted bR despite the loss of the negative charge at residue 85. In contrast, D85A has a weaker hydrogen bond. These results can be explained if a direct interaction exists between the Schiff base and Asn-85 in D85N and between the Schiff base and a substituted water molecule in D85A. Many of the properties of wild type bR, D85N, D85A, blue membrane, and acid purple membrane can be explained on the basis of changes in the local hydrogen bonding near the Schiff base.
The efficacy of chemotherapeutic agents in the management of disseminated gynecologic cancer.

Abstract 1. 1. The results of chemotherapy in 206 patients with disseminated gynecologic cancer have been reviewed. 2. 2. About 15 per cent of the patients with advanced ovarian cancer treated by alkylating agents showed an objective response that lasted at least 6 months. 3. 3. There was also an objective response in 3 out of 10 patients with disseminated endometrial cancers treated by massive doses of progestational drugs for 3 or more months. 4. 4. There was, however, no evidence that the drugs used increased the total life expectancy of the patient.
Crystal: a Timing Analyzer for nMOS VLSI Circuits

Crystal is a timing analyzer for nMOS circuits designed in the Mead-Conway style. Based on the circuit extracted from a mask set, Crystal determines the length of each clock phase and pinpoints the longest paths. The analysis is independent of specific data values and uses critical path techniques along with s simple RC model of delays. Several additional techniques are used to improve the speed and accuracy of the program, including separate up/down timing, static level assignment, flow control for pass transistors, and precharging.
STARCH HYDROLYSIS BY STREPTOCOCCUS EQUINUS

Dunican, Lawrence K. (Cornell University, Ithaca, N. Y.) and Harry W. Seeley. Starch hydrolysis by Streptococcus equinus. J. Bacteriol. 82:264-269. 1962.-In a study of starch hydrolysis by strains of Streptococcus equinus, 52 isolates were obtained and their amylolytic abilities determined. It was found that all the strains could hydrolyze starch to some extent when grown in the presence of an easily fermentable carbohydrate, viz., glucose. Without this carbohydrate the organisms did not hydrolyze starch. The hydrolysis of starch was inhibited when the organisms were grown in an atmosphere of 5% CO(2) and 95% N(2), even if grown in the presence of a fermentable monosaccharide. S. bovis, which was used as a reference organism, readily hydrolyzed starch in the absence of monosaccharides and in atmospheres containing CO(2). In no instance did S. equinus hydrolyze the starch to the level of reducing sugars. Negligible amounts of reducing sugars were recovered when the cell-free filtrates of S. equinus were incubated with starch. With S. bovis, the yield of reducing sugars under such conditions was almost quantitative. These facts extend further the differences between these related organisms. The ability to synthesize an internal starchlike polysaccharide was noted in most of the strains of S. equinus. Synthesis was found when the organisms were grown on maltose or on a starch medium containing a small amount of fermentable monosaccharide.
The Effectiveness of Interactivity in Computer-Based Instructional Diagrams

This study investigates if interaction between a student and instructional diagrams displayed on a computer can be effective in significantly improving understanding of the concepts the diagrams represent over viewing animated or static instructional diagrams. Participants viewed either interactive, animated, or static versions of multimedia tutorials that taught how a simple mechanical system, a lock, worked and how a complex mechanical system, an automobile clutch, worked. Participants were tested on recall and comprehension to determine which presentation style; static, animated, or interactive; greater impacts learning, and whether that impact is mediated by the complexity of the mechanical system. Participants who studied from interactive multimedia presentations demonstrating how simple and complex mechanical systems work performed significantly better on comprehension tests for both mechanical systems than those who studied from static or animated presentations. However, all participants performed similarly on recall tests. Research on the effectiveness of computer learning environments and how to optimize their potential for effective instruction through improved multimedia design is important as computers are increasingly being used for training and education.
Modeling learner affect with theoretically grounded dynamic bayesian networks

Evidence of the strong relationship between learning and emotion has fueled recent work in modeling affective states in intelligent tutoring systems. Many of these models are based on general models of affect without a specific focus on learner emotions. This paper presents work that investigates the benefits of using theoretical models of learner emotions to guide the development of Bayesian networks for prediction of student affect. Predictive models are empirically learned from data acquired from 260 students interacting with the game-based learning environment, CRYSTAL ISLAND. Results indicate the benefits of using theoretical models of learner emotions to inform predictive models. The most successful model, a dynamic Bayesian network, also highlights the importance of temporal information in predicting learner emotions. This work demonstrates the benefits of basing predictive models of learner emotions on theoretical foundations and has implications for how these models may be used to validate theoretical models of emotion.
16,16-Dimethyl prostaglandin E2 suppresses the increases in the proliferative activity of rat colonic epithelium induced by indomethacin and aspirin

Treatment of rats with indomethacin rapidly increased ornithine decarboxylase (4 h) of colonic mucosa and [3H]thymidine incorporation into colonic mucosal deoxyribonucleic acid (DNA) (1 or 5 days) when this parameter was examined in vivo and ex vivo. The changes in colonic mucosal ornithine decarboxylase and DNA synthesis induced by indomethacin were correlated temporally with suppression of colonic prostaglandin synthesis, as assessed from ex vivo colonic production of prostaglandin E, the dominant prostaglandin product of colon. Autoradiographic studies indicated that the enhancement of proliferative activity of colonic epithelium after treatment with indomethacin for 1 day was confined to the lower third of the colonic crypt (normal proliferative zone). After 5 days of indomethacin treatment, however, there was an extension of the proliferative zone to the upper third of the colonic crypts. Concurrent treatment of rats with the stable prostaglandin E2 analogue, 16,16-dimethyl prostaglandin E2, suppressed indomethacin-induced increases in colonic mucosal ornithine decarboxylase and DNA synthesis. Concurrent administration of 16,16-dimethyl prostaglandin E2 also prevented the extension of the proliferative zone of colonic epithelium induced by 5 days of indomethacin administration. 16,16-Dimethyl prostaglandin E2 alone for 1-5 days had no detectable effects on colonic mucosal ornithine decarboxylase and DNA synthesis compared with corresponding control values. Increases in colonic mucosal DNA synthesis were also induced by treatment of rats for 5 days with aspirin (ASA). The stimulation of colonic mucosal DNA synthesis induced by ASA was significantly suppressed by concurrent administration of 16,16-dimethyl prostaglandin E2 and was also correlated with the inhibition of colonic prostaglandin synthesis by ASA. The colons of rats treated with indomethacin for 1 day or ASA for 5 days appeared normal by light microscopy. However, treatment of rats for 5 days with indomethacin resulted in mild to moderate inflammation of the lamina propria and some goblet cell depletion at the mucosal surface, but no loss of surface epithelium. The ultrastructure of the surface epithelium of the colons of rats treated with indomethacin or ASA was normal as assessed by electron microscopy. The results thus demonstrate that inhibition of local colonic prostaglandin synthesis is associated with increases in the proliferative activity of colonic epithelium, and that these increases are suppressed by administration of 16,16-dimethyl prostaglandin E2.(ABSTRACT TRUNCATED AT 400 WORDS)
Determination of isosmolar blood anticoagulant solutions by the freezing-point method.

Freezing-point depressions of several anticoagulants were determined from which concentrations isosmolar with the blood of any species may be computed. The method is not applicable to solutes of high molecular weight.
Prevention of acute aspirin-induced gastric mucosal injury by 15-R-15 methyl prostaglandin E2: an endoscopic study.

Abstract The deleterious effects of aspirin on gastric mucosa have been well documented in experimental and clinical studies. Prostaglandins offer a potential method by which this injury may be prevented. In these studies, we developed a single-dose endoscopic assay system of aspirin-induced gastric mucosal injury in normal volunteers. With this system, 27 of 30 volunteers (90%) demonstrated severe mucosal injury after ingestion of aspirin. Subsequently, we evaluated whether pretreatment with 15-R-15 methyl prostaglandin E 2 prevented severe injury after ingestion of aspirin. Following an initial dose-response study, a double-blind crossover trial was performed using pretreatment with placebo or with 10-μg doses of 15-R-15 methyl prostaglandin E 2 for 24 h before treatment with aspirin. The results of this trial indicate that prostaglandin pretreatment significantly prevented the occurrence of endoscopically visible severe gastric mucosal injury after single-dose aspirin administration.
A study of the 3,5,3'-triiodothyronine sulfation activity in the adult and the fetal rat

We have employed a new in vitro assay for study of the T3 sulfation activity in rat tissues. The assay measures by RIA the generation of T3 sulfate (T3S) during incubation of T3 with cytosol of rat tissues as the source of phenol sulfotransferase(s) and 3-phosphoadenosine-5'-phosphosulfate as the sulfate donor. The conversion of T3 to T3S proceeded rapidly for 30 min at 37 C, and the optimal pH of the reaction was 8.0. Heating the cytosol at 44 C for 15 min decreased T3S production to 63% of its value at 37 C. T3 sulfation activity was plentiful in rat liver, brain, and kidney, but little activity was demonstrable in other tissues. The Km and maximum velocity of the hepatic conversion of T3 to T3S were 114 microM and 159 pmol/mg protein.h, respectively. There was a marked inhibition of the conversion of T3 to T3S with salicylamide, 3'-monoiodothyronine, thyronine, and rT3; the IC50 of these inhibitors approximated 15, less than 0.1, 9.5, and 43 microM, respectively. On day 17 of gestation, the T3 to T3S c...
On the bernstein conjecture in approximation theory

WithE 2n (|x|) denoting the error of best uniform approximation to |x| by polynomials of degree at most 2n on the interval [−1, +1], the famous Russian mathematician S. Bernstein in 1914 established the existence of a positive constantβ for which lim 2nE 2n (|x|)=β.n→∞ Moreover, by means of numerical calculations, Bernstein determined, in the same paper, the following upper and lower bounds forβ: 0.278<β<0.286. Now, the average of these bounds is 0.282, which, as Bernstein noted as a “curious coincidence,” is very close to 1/(2√π)=0.2820947917... This observation has over the years become known as the Bernstein Conjecture: Isβ=1/(2√π)? We show here that the Bernstein conjecture isfalse. In addition, we determine rigorous upper and lower bounds forβ, and by means of the Richardson extrapolation procedure, estimateβ to approximately 50 decimal places.
Global Indices for Kinematic and Force Transmission Performance in Parallel Robots

This paper defines, develops, and demonstrates new indices for quantifying kinematic and force transmission performance of parallel robotic mechanisms. Conventional indices are first analyzed and shown to be insufficient for characterizing common design specifications based on worst-case performance. New indices are then developed, analyzed, and extended to simply and intuitively quantify global worst-case kinematic and force performance. These new tools are then successfully applied to the design, optimization, and analysis of a linear delta robot for medical applications.
Toxicity of the novel animal-derived anticancer agent, VRCTC-310: acute and subchronic studies in beagle dogs

Abstract Acute and subchronic toxicities of VRCTC-310, a combination product of crotoxin (CT) and cardiotoxin (CD), which has shown antitumor activity in vivo, have been studied in Beagle dogs. Single i.m. doses of 0.25, 0.5 and 1.0 mg/kg resulted in dose-dependent local muscular toxicity consisting of myofiber atrophy, interstitial edema and macrophage infiltration. Also, AST, ALT and LDH levels increased on day 2, returning to normal values on days 6–8. Local lesions were absent after recovery on day 45. At 2.0 mg/kg, signs of neurotoxicity (ataxia) appeared, in addition to vomitus, salivation, hematuria and myotoxicity in tongue and diaphragm on day 8. Local lesions healed with fibrosis at the site of injection on day 45. Administration of fixed (0.025 and 0.05 mg/kg) or escalating (0.025–0.1 mg/kg) daily doses for 30 days also produced local muscular damage, which was absent at day 75. The increases in AST, ALT and LDH serum activities on days 2–4 were independent of dosing schedule and sharply decreased on day 8, despite continuation of treatment. An escalating dose schedule of 0.025-2.0 mg/kg showed local muscle damage at the site of injection on day 31, however, there were no lesions of myotoxicity in the tongue or diaphragm and no clinical signs of neurotoxicity were observed. Animals tolerated the subchronic treatment better than the acute. The resolution of serum enzymes to normal values during treatment may be attributed to a decrease of sensitivity to VRCTC-310-mediated myotoxic effects.
Piezoelectret foam–based vibration energy harvesting:

The use of energy harvesting to provide power to low-power electronic devices has the potential to create autonomous, self-powered electronics. This article presents the investigation of a novel ma...
The Nature and Probable Cause of Rough Egg Shells Laid by Two Lines of White Leghorns

Abstract Rough, pebbly-textured eggs were found fifteen times as frequently in one line of White Leghorns as in another even at six and one-half months of age. The rough, pimple-like shell texture was caused by foreign masses attached to the outer wall of the outer shell membrane before onset of shell secretion. It is suggested that in the lines of Leghorns studied, these masses are albumen-like debris produced in the magnum. Injections of oestrogen did not cause hens laying smooth-shelled eggs to lay eggs with rough shells. Hens laying rough-shelled eggs continued to lay rough-shelled eggs after two feedings of a drug antagonistic to oestrogen. That a rough shell texture is not necessarily indicative of shell thinness was demonstrated by means of (1) specific gravity tests, (2) microscopic comparisons of smooth and rough areas of shells and (3) measurements of shell thickness in successive rough-shelled eggs laid by individual hens.
Opioids increase laryngeal resistance and motoneuron activity in the recurrent laryngeal nerve.

Abstract [D-Ala2, Met5]enkephalinamide (DAME), [D-Ala2, Leu5]enkephalinamide (DALE) and morphine sulfate (MS) increase activity in the recurrent laryngeal nerve (RLN) within 1 s subsequent to right atrial administration. The activation of the RLN was correlated with a large increase in the resistance to airflow in the in situ isolated larynx. Single unit recurrent laryngeal motoneuron recordings showed that the increase in laryngeal resistance was caused by the continuous activation and recruitment of expiratory motoneurons. Results obtained with opioids mimicked those of phenydiguanide (20–40 μg/kg RA), an agent known to stimulate pulmonary J-receptors. Opioid-induced increases in laryngeal resistance were blocked by bilateral section of the RLN and pretreatment with naloxone (100 μg/kg RA). Naloxone had no effect on PDG responses. During the initial period of laryngeal motoneuron activation, the phrenic nerve (PN) was inhibited, however, the activation of the RLN was not dependent upon PN inhibition. It was concluded that stimulation of pulmonary opiate receptors, which may be associated with vagal afferents, elicit a reflex activation of expiratory recurrent laryngeal motoneurons resulting in an increase in laryngeal resistance.
Efficient Strategies for Accurate Calculations of Electronic Excitation and Ionization Energies: Theory and Application to the Dehydro-m-xylylene Anion

In the dehydro-m-xylylene (DMX) anion [Munsch; et al. J. Org. Chem. 2004, 69, 5735], three nearly degenerate orbitals host four electrons, which results in a large number of nearly-degenerate electronic states. By using this challenging example, we assess the performance of the multireference "brute force" approach and the two-step schemes based on single-reference methods for calculating accurate energy differences. Different schemes for calculating adiabatic ionization potential (IP) of DMX- are also investigated. IP calculated by single-reference based schemes is in excellent agreement with experiment.
Spectral representation of higher-order localization relationships for elastic behavior of polycrystalline cubic materials

A computationally efficient higher-order spectral framework has been formulated for the calculation of the elastic localization tensors for polycrystalline material systems using the generalized spherical harmonics as the Fourier basis. This new approach offers tremendous potential for rapid analysis of the elastic performance of a very large set of microstructures in any selected polycrystalline material system. The spectral framework transforms the complex integral relations for local stress and strain fields (derived from established generalized composite theories) into relatively simple algebraic expressions involving polynomials of structure parameters and morphology-independent influence coefficients. These coefficients need to be established only once for a given material system. In this paper, we formulate and demonstrate a viable approach to establishing the values of the second-order influence coefficients for cubic polycrystals by calibration to the results of micromechanical finite element models.
Gender identity and gender transposition: longitudinal outcome study of 24 male hermaphrodites assigned as boys.

Abstract The longitudinal case histories of 32 female-assigned male hermaphrodites aged 18 or older were indexed and abstracted for evidence of variables related to gender transposition, i.e., bisexualism, lesbianism, or sex reassignment to live as male. The prevalence of transposition was biased because of the referral of cases selected for reassignment. Childhood stigmatization, either subtle or blatant, because of the birth defect of the sex organs correlated with gender transposition (p <.00l) and was related to the age of feminizing surge? (p<.05), which often coincided with the age of gonadectomy. Variables not significantly correlated with gender transposition were: neonatal ambivalence regarding the sex of announcement; feminizing or masculinizing puberty; presence or absence of mullerian organs; and gross family pathology. Physicians encountered no moral problem with sex reassignment as the chromosomal and god 1 sex were male.
Criteria for the reduction of the effective manifold of states in models of laser-induced dissociation and chemistry.

A laser-driven molecular species A, represented as a two-level system, is taken to react forming a finite-level molecular species B. Criteria are developed that, when satisfied, enable this model to be approximated by a two-level molecular A system reacting to form a single-level molecular species B. Further criteria are then developed that, when satisfied, enable this model to be approximated by a two-level molecular species A with irreversible population loss.
Ab initio high-pressure structural and electronic properties of ZnS.

The total energy of ZnS as a function of unit-cell volume has been calculated for the zinc-blende and rocksalt structures by the first-principles Hartree-Fock linear-combination-of-atomic-orbitals method. The calculated structural properties of both phases and the transition pressure between them agree very well with experiment. The band structure of the high-pressure phase is obtained and discussed in relation to zinc-blende ZnS and other IIB-VIA semiconductors.
MRI-Based Segmentation of Pubic Bone for Evaluation of Pelvic Organ Prolapse

Pelvic organ prolapse (POP) is a major women's health problem. Its diagnosis through magnetic resonance imaging (MRI) has become popular due to current inaccuracies of clinical examination. The diagnosis of POP on MRI consists of identifying reference points on pelvic bone structures for measurement and evaluation. However, it is currently performed manually, making it a time-consuming and subjective procedure. We present a new segmentation approach for automating pelvic bone point identification on MRI. It consists of a multistage mechanism based on texture-based block classification, leak detection, and prior shape information. Texture-based block classification and clustering analysis using K-means algorithm are integrated to generate the initial bone segmentation and to identify leak areas. Prior shape information is incorporated to obtain the final bone segmentation. Then, the reference points are identified using morphological skeleton operation. Results demonstrate that the proposed method achieves higher bone segmentation accuracy compared to other segmentation methods. The proposed method can also automatically identify reference points faster and with more consistency compared with the manually identified point process by experts. This research aims to enable faster and consistent pelvic measurements on MRI to facilitate and improve the diagnosis of female POP.
Functional language compiler experiences at Intel

For five years Intel's Programming Systems Lab (PSL) has been collaborating with an external partner on a new functional programming language designed for productivity on many-core processors. While the language is not yet public, this talk outlines motivations behind the language and describes our experiences in implementing it using a variety of functional languages. The reference interpreter is written in Haskell and compiled with GHC while PSL's performance implementation is written in SML and compiled with Mlton. We have also generated Scheme code compiled with PLT Scheme as part of a prototyping effort.At several points, the project has had several contributors that did not have a background in functional languages working on the compiler and on writing benchmarks. We describe their experiences working in SML and with functional languages in general. Specifically:•what they liked and disliked about using functional languages•what was easy and hard about learning and using functional languages•what worked/didn't work for helping them learn to program in functional languages•which functional features they used and didn't use•general observations about the code that they wrote•what (if anything) they took away from the experienceA design principle of the implementation effort was to by default avoid the use of imperative features. Previous experience and review of the literature suggested that many parts of a compiler could be written as well or better using primarily functional code, but that restricting ourselves entirely to the functional fragment of SML was probably not reasonable. We describe our experiences with this, and the tradeoffs that we encountered. Specifically:•During the project we experimented with both immutable and mutable intermediate representations (IRs). We describe and motivate some of the scenarios where we used one or the other, explain our experiences with this, and describe cases where we feel that we made an inappropriate initial choice.•We chose to avoid all global mutable state in the compiler. Most notably, symbol tables and global configuration information are always passed explicitly as parameters to parts of the compiler that require them. This choice had benefits and costs, and we discuss our experience with this.We also describe some of the features of SML that we found useful, and discuss some of the lack of features and quirks of SML that annoyed us. Specifically:•We discuss places where we encountered limitations in the module system. These include the lack of uniformity between the signature and structure language, and the lack of recursive modules.•We describe some of the ways in which we believe that better syntactic support could have lessened the programming burden, especially with respect to attempting to be purely functional. Examples of this include a type class mechanism and/or monadic syntax to lessen the burden of passing around explicit state, better syntactic support for using the imperative features of the language, and better support for custom control operators.
Cystic pancreatic neuroendocrine tumors: Is preoperative diagnosis possible?

Pancreatic neuroendocrine tumors rarely undergo cystic degeneration leading to a radiologic appearance, which is often interpreted as a pancreatic mucinous cystadenoma or pseudocyst. We reviewed our experience with 38 neuroendocrine tumors, four of which were cystic, and 24 other cystic pancreatic tumors (mucinous cystadenoma [n = 5], cystadenocarcinoma [n = 6], serous cystadenoma [n = 3], solid/cystic papillary neoplasm [n = 3], intraductal papillary mucinous tumor [n = 6], and mucinous adenocarcinoma [n = 1]) managed operatively between 1990 and 2000. This review was undertaken to identify clinical and pathologic features useful for preoperative diagnosis of cystic neuroendocrine tumors. Two of the four patients with cystic neuroendocrine tumors presented with abdominal pain, one patient was asymptomatic, and one patient had hypoglycemia. Three of the four cystic neuroendocrine tumors were identified by CT scan, and none were biopsied preoperatively. Preoperative diagnoses included mucinous cystadenoma in two patients (n = 2), pancreatic cystic neoplasm in one patient, (n = 1) and insulinoma in one patient (n = 1). All four cystic neuroendocrine tumors were benign and were completely resected (distal pancreatectomy [n = 2], enucleation [n = 2]). Cystic neuroendocrine tumors are difficult to diagnose preoperatively because the majority of these tumors are nonfunctional, and CT does not differentiate these tumors from other cystic neoplasms. Cystic neuroendocrine tumors represent a subgroup of pancreatic cystic and neuroendocrine tumors with malignant potential. Their high resectability rate further supports the role of surgical exploration and resection in the treatment of pancreatic cystic neoplasms.
Regulation of steroid receptor subcellular trafficking.

Cellular responses to external signals often reflect alterations in gene expression. The activation of cell surface hormone or growth factor receptors upon the binding of appropriate ligands mobilizes signal transduction cascades that can ultimately impact the activity of defined sets of transcription factors. The interpretation of hormonal signals can also be initiated intracellularly, as is the case for steroid hormone receptors. In addition to recognizing specific hormones, steroid hormone receptors also function as transcription factors and directly transduce hormonal signals to activation or repression of unique target genes. The delivery of activated steroid receptors to high-affinity genomic sites must be efficient to account for the rapidity and selectivity of many transcriptional responses to steroid hormones. Thus, the signal transduction capacity of steroid hormone receptors will be affected by the efficiency of receptor trafficking both between different subcellular compartments (i.e., the cytoplasm and nucleus) and within a specific compartment (i.e., the nucleus). This article will highlight the recent advances in our understanding of subcellular and subnuclear trafficking of steroid receptors.
The effects of source, rate and placement of nitrogen and phosphorus fertilizers on growth of Spartina alterniflora transplants in North Carolina

The effects of rate of N and P fertilizer, type of fertilizer material and application method on establishment, growth and tissue nutrient concentrations of Spartina alterniflora were evaluated on an eroding estuarine shoreline. Both N and P were growth limiting factors at the test site. Biomass increased with increasing rates of N and P up to 224 kg per ha N and 49 kg per ha P when ammonium sulfate and concentrated superphosphate were banded at planting. There were only slight increases in growth when either N or P were applied alone. Placement of fertilizer below ground was necessary; there was no growth response to surface application at transplanting time. The slow-release fertilizers, Mag Amp and Osmocote, supplied N over a longer period of time and produced more growth than the other sources of N which were tested. Urea and urea-formaldehyde were ineffective sources of N. Concentrated superphosphate was as effective as the slow-release fertilizers as a source of P. Nitrogen concentrations in fertilized plants which produced more biomass were lower than in those plants stunted by lack of N or P except where near optimum amounts of N were supplied by the slow-release fertilizers. Residual effects of the fertilizer were evident the second growing season but top-dressing with N and P was necessary to maintain a vigorous stand. Accumulation of up to 28 cm of sand in 2 years was evidence of reduction of shoreline erosion.
Diltiazem for long-term therapy of coronary arterial spasm

The first 36 patients with coronary arterial spasm treated with diltiazem and followed up at the Stanford University Coronary Artery Spasm Clinic for 6 months or longer are described. There were 13 men and 23 women with a mean age of 50.2 years; the mean duration of angina was 36.1 months. All patients had angina at rest with a good or fair response to sublingual nitroglycerin. During a mean of 17.5 months of diltiazem therapy, the frequency of angina was reduced from a mean of 21.5 to 1.3 attacks/week. This 94 percent reduction in pain frequency occurred when either 240 or 360 mg of diltiazem was administered daily. Sixteen patients required the addition of isosorbide dinitrate to achieve a painfree state. Pain breakthrough occurred a mean of 1.7 times during the 17.5 month follow-up period but tended to be of short duration. Six patients had trace to 1+ pedal edema and no other adverse effects occurred. It is concluded that diltiazem is highly effective and well tolerated for the long-term prophylaxis and treatment of angina in patients with coronary spasm.
Violence, law, and the informal polity

It is the purpose of this essay to elaborate a conceptual framework which views the social process, its institutions, prevailing norms, and the circumstances of social disorder as related phenomena. Violence is not usefully viewed as strictly pathological, exceptional, and spasmodic. To look for its sources and to seek its forms apart from normative social processes is to ignore the intrinsic continuum between peaceable and disruptive behavior; it is to deny the role of violence in creating and testing political legitimacy and conditioning the terms of all social bargaining and adjustments. The function of the police power of the state is to maintain a threshold of force to deter and/or contain the ever-present margin of anti-social acts by individuals and groups. Some element of personal dislocation and anomie exists in the best managed and most equitable societies. Even when isolated outbreaks contain germs of larger social issues (they usually do), they may be contained at acceptable costs by the appropriate and measured application of police power. This constitutes the normal function of the state in dealing with private violence. So long as this task is managed at acceptable risk and cost, police power protects most of the members of the community and enjoys general support. This kind of violence may be termed fractionall." To minimize and control it is the legitimate purpose of the police power. Political grievances are forced into peaceable channels and eventual adjustment through debate, legislation, public policy, and private contract. However, the characteristic pattern of contemporary riots has shown a tendency toward violent counter-escalation against police action by elements of both black and white communities. While the white violence has been limited, the black violence escalates in response to police action, often with general support from the black community and with enhanced responsiveness, organization, and danger of future out.breaks. This phenomenon is different in kind from frictional violence. The capability of infinite escalation heightens the risk and increases the cost to society beyond acceptable levels; most important, it destroys the efficacy of normal methods of police power. This kind of violence must be termed "political." It addresses itself to changing the very system of social norms which police power is designed to protect. It focuses grievances in recurring, deliberate, or spontaneous acts of violence, even at great risk and cost to the actors. The peaceable procedures of political adjustment fail to divert the escalation, whether because they are closed, discredited, halting, or simply untried. The peculiar pattern of major social upheaval and political confrontation arises from the fact that the normal police security methods become counter-productive; they merely solidify the capability and likelihood
Velocity vs. momentum — A new relativistic paradox

Abstract A new paradox is posed and resolved, concerning the relativistic and quantum mechanical concepts of velocity and momentum. The statement of the problem depends on the existence of the neutron interferometer, and of the Borrmann effect in a very thick, perfect crystal, a field pioneered by the work of professor Cliff Shull and his laboratory.
The single-staged approach to the surgical management of abdominal wall hernias in contaminated fields.

The surgical treatment of large ventral hernias with accompanying contamination is challenging. We have reviewed our institution's experience with single-staged repair of complex ventral hernias in the setting of contamination. We retrospectively reviewed the medical records of all patients who underwent ventral hernia repairs in the setting of a contaminated field. Pertinent details included baseline demographics, reason for contamination, operative technique and details, postoperative morbidity, mortality and recurrence rates. Between December 1999 and January 2006, 19 patients were identified with ventral hernia repairs performed in contaminated fields. There were 6 males and 13 females with a mean age of 61 years (40–82), ASA 3.2 (2–4), and BMI of 34 kg/m2 (20–65). Fourteen patients had prior mesh: prolene (9), composix (3), goretex (1), and alloderm (1). Reasons for contamination included: mesh infection (14), enterocutaneous fistula (7), concomitant bowel resection (8), chronic non-healing wound (2), and necrotizing fasciitis (1). Operative approaches included primary repair (3), component separation without reinforcement (2), and with prosthetic reinforcement (9). In five patients the fascia could not be reapproximated in the midline and the defect was bridged with surgisis (1), Marlex (1), lightweight polypropylene (1) placed in the retrorectus space, and alloderm (2). Mean operative time was 260 min (90–600). Twelve postoperative complications occurred in nine (47%) patients and included wound infection (6), respiratory failure (1), ileus (2), postoperative hemorrhage (1), renal failure (1), and atrial fibrillation (1). One patient died in this series. During routine follow-up two recurrences were identified by physical exam. This study shows that single-stage treatment of ventral hernias in contaminated fields can be accomplished with a low recurrence rate and acceptable morbidity in these extremely challenging patients.
Mexican American Biographies: A Historical Dictionary, 1836-1987

Preface Mexican American Biographies Appendix A: List of Biographees by Field of Professional Activity Appendix B: List of Biographees by State Index
Cortical Specializations Underlying Fast Computations

The time course of behaviorally relevant environmental events sets temporal constraints on neuronal processing. How does the mammalian brain make use of the increasingly complex networks of the neocortex, while making decisions and executing behavioral reactions within a reasonable time? The key parameter determining the speed of computations in neuronal networks is a time interval that neuronal ensembles need to process changes at their input and communicate results of this processing to downstream neurons. Theoretical analysis identified basic requirements for fast processing: use of neuronal populations for encoding, background activity, and fast onset dynamics of action potentials in neurons. Experimental evidence shows that populations of neocortical neurons fulfil these requirements. Indeed, they can change firing rate in response to input perturbations very quickly, within 1 to 3 ms, and encode high-frequency components of the input by phase-locking their spiking to frequencies up to 300 to 1000 Hz...
Effect of Supplemental Dietary Vitamin E and Zinc on Reproductive Performance of Dairy Cows and Heifers Fed Excess Iron

We tested the hypothesis that the incidence of retained fetal membranes could be reduced by limiting oxidative stress. Sixty-four primigravid heifers (56 Holstein and 8 Jersey) and 80 multiparous cows (64 Holstein and 16 Jersey) were used. A combination of vitamin E or Zn and Fe was fed in a 2 x 2 x 2 factorial arrangement during the last 42 d prepartum. Amounts of supplements per animal were 1000 IU of vitamin E (d, l alpha-tocopheryl acetate), 0.8 g of Zn (Zn-Met and ZnSO4), and 12 g of Fe (FeSO4.7H2O) for Holsteins and 9 g for Jerseys. Neither vitamin E nor Zn directly affected the incidence of retained fetal membranes, but plasma alpha-tocopherol was lower when fetal membranes were retained > 12 h or when vitamin E was not supplemented. Iron had no direct negative effects on reproductive performance, but cows receiving additional Fe had lower unsaturated iron-binding capacity, which, in turn, was also lower in cows that retained fetal membranes. Days to first observed estrus were reduced by supplementation with either vitamin E or Zn. Vitamin E reduced days to first artificial insemination (AI) and tended to reduce days open. Supplemental Zn tended to reduce days to first AI but did not affect days open. Milk production during the first 12 wk and AI per conception were not affected by supplementation with either vitamin E or Zn. Both vitamin E and Zn reduced days to first observed estrus, indicating improved reproductive health during the early postpartum period.
Nonlinear Absorbing Platinum(II) Diimine Complexes: Synthesis, Photophysics, and Reverse Saturable Absorption

A series of platinum(II) diimine complexes with different substituents on fluorenyl acetylide ligands (1a-1e) were synthesized and characterized. The influence of the auxiliary substituent on the photophysics of these complexes has been systematically investigated spectroscopically and theoretically (using density functional theory (DFT) methods). All complexes exhibit ligand-centered (1)π,π* transitions in the UV and blue spectral region, and broad, structureless (1)MLCT/(1)LLCT (1a, 1b, 1d and 1e) or (1)MLCT/(1)LLCT/(1)π,π* (1c) absorption bands in the visible region. All complexes are emissive in solution at room temperature, with the emitting state is tentatively assigned to mixed (3)MLCT/(3)π,π* states. The degree of (3)π,π* and (3)MLCT mixing varies with different substituents and solvent polarities. Complexes 1a-1e exhibit relatively strong singlet and triplet transient absorption from 450 to 800 nm, at which point reverse saturable absorption (RSA) could occur. Nonlinear transmission experiments at 532 nm by using nanosecond laser pulses demonstrate that 1a-1e are strong reverse saturable absorbers and could potentially be used as broadband nonlinear absorbing materials.
LIMK2 is a crucial regulator and effector of Aurora-A-kinase-mediated malignancy

Aurora A is overexpressed in majority of breast carcinomas. With the exception of BRCA1 and PHLDA1, no oncogenic Aurora A substrates are known in breast cancer. In this study, a chemical genetic approach was used to identify malignant targets of Aurora A, which revealed LIMK2 as a novel Aurora A substrate. Aurora A regulates LIMK2 kinase activity, subcellular localization and protein levels by direct phosphorylation at S283, T494 and T505. In response, LIMK2 also positively regulates the level of Aurora A, thereby engaging in a positive-feedback loop, promoting Aurora-A-mediated oncogenic pathways. Most importantly, LIMK2 ablation fully abrogates Aurora-A-mediated tumorigenesis in nude mice, suggesting that LIMK2 is a key oncogenic effector of Aurora A. Furthermore, LIMK2 ablation acts synergistically with inhibition of Aurora A in promoting cell death. Finally, Aurora-A-mediated upregulation of LIMK2 appears to be a common mechanism in many cancers. LIMK2 inhibition or ablation is therefore an alternative approach for modulating Aurora A deregulation in cancer.
Biomedical Discovery with DNA Arrays

I am grateful to Gerry Fink, David Gifford, Alex Hartemink, Mark Johnston, Seema Kumar, Jerry Nau, Nicola Rinaldi, Phil Sharp, Robert Weinberg, and Peter Young for comments that improved this manuscript and Tom Volkert and Peter Young for assistance with figures.