cssi/SciSciGPT-SciSciNet huggingface dataset:
Abstract 3439: Suppression of pancreatic cancer cell growth by NISC-6 through activation of Par-4 and death receptor 5.

Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC Pancreatic cancer is one of the deadliest cancers, with a median survival of 6 months and a 5 year survival rate of 3-5%. The poor prognosis of pancreatic cancer is attributable to its tendency for late presentation, aggressive local invasion, early metastases, and poor response to chemotherapy. Currently used drugs result in marginal survival advantage and are associated with multiple adverse events and drug resistance. Thus, there is a need for novel therapeutic agents and strategies involving less toxic agents that can sensitize pancreatic cancer cells to chemotherapy. Through extensive structure-activity relationship studies, we have recently developed an Akt pathway inhibitor, NISC-6, designed by incorporating an isoselenocyanate (-N=C=Se) functionality into naphthalimide structure, rendering it lethal to cancer cells at a dose that is non-toxic to normal cells. Our hypothesis is that the Akt inhibitor, NISC-6, in conjunction with Prostate apoptosis response protein 4 (Par-4), will induce apoptosis in pancreatic tumor cells through the TRAIL pathway. This is based on the observation that Par-4 causes apoptosis in cancer, but not in normal, cells, often in response to an apoptotic agent and is often inactivated in cancer cells through interaction with Akt1. In pancreatic cancer, Par-4 expression is often reduced through deletion of a chromosome segment containing 12q21, the location of the PAR-4 gene. Activation of Par-4 through inhibition of Akt by NISC-6 thus holds promise as a possible strategy for pancreatic cancer treatment. Our studies have shown NISC-6 to be effective in reducing cell proliferation in three different pancreatic cancer cell lines e.g. MiaPaCa-2, Panc-1, and BxPC-3. The treatments of NISC-6 for 48 h reduced the cell viabilities of pancreatic cancer cells with an IC50 of between 1-2.5 μM. In addition, treatment of MiaPaCa-2 cells with NISC-6 for 24 h showed significant activation of Par-4 and death receptor 5 (DR5). This activation was associated with the down-regulation of anti-apoptotic protein Bcl-xL and Survivin. Furthermore, NISC-6 potentiated the apoptotic effects of tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL/APO-2L). Taken together, these results suggest that NISC-6 may represent a novel therapeutic agent to sensitize pancreatic cancer cells to TRAIL and chemotherapeutic drugs. Detailed results of these investigations will be presented. Citation Format: Deepkamal Karelia, Manoj K. Pandey, Rosalyn Irby, Shantu Amin, Arun K. Sharma. Suppression of pancreatic cancer cell growth by NISC-6 through activation of Par-4 and death receptor 5. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3439. doi:10.1158/1538-7445.AM2013-3439
Abstract A215: Antitumor activity of an antibody-drug conjugate targeting 5T4, a putative tumor-initiating cell antigen.

5T4 (also known as TPBG) is a transmembrane, tumor-associated protein that rapidly internalizes. In preclinical models of NSCLC, 5T4 was identified as a marker of undifferentiated tumorigenic cells that express properties of tumor-initiating cells (TICs) and was associated with a highly proliferating (Ki67 positive) cell phenotype. In addition, 5T4 has been associated with a worse clinical outcome in NSCLC (Damelin et al, Cancer Res, 2011). We constructed an ADC with a humanized anti-5T4 Ab (A1) linked to the tubulin inhibitor monomethylauristatin F through the noncleavable maleimidocaproyl (mc) linker attached to cysteine residues (A1mcMMAF) with a DAR of approximately 4 in order to target 5T4 expressing tumor cells. Anti-5T4 A1 Ab has a Kd of 0.9 nM against the 5T4 antigen, binds to a broad range of 5T4 expressing cell lines, and rapidly internalizes (66% internalized within 4h). As an ADC, A1mcMMAF retains similar properties to the unconjugated Ab. In vitro, A1mcMMAF exhibited receptor-density dependent cytotoxic activity against a panel of 5T4 + cell lines with an IC50 of 5 ng Ab/ml against high 5T4 expressing cells. A1mcMMAF exerts no inhibitory effect on 5T4 negative cells demonstrating it does not exert off-target activity in vitro. In vivo, A1mcMMAF causes long-term (100 days) tumor regressions at 10 mg Ab/kg in MDAMB435/5T4 tumor xenografts (Q4d×2, high 5T4 expression by IHC) and in the NSCLC patient-derived xenograft 37622A model (Q4d×4, high 5T4 expression by IHC though only a portion of the cells express 5T4). Significant anti-tumor activity was demonstrated at 1 mg/kg. Against the low 5T4 expressing H1975 tumor xenograft, A1mcMMAF causes potent tumor regression in spite of its lack of in vitro inhibitory activity against this cell line. Bioimaging of the H1975 tumor demonstrated good penetration of Alexa 750 labeled A1 Ab into the xenograft. A1mcMMAF exhibited no overt toxicities when administered at 10 mg Ab/kg/cycle × 2 to cynomolgus macques and possessed a half-life of 4 to 7 days. The observation that A1mcMMAF regresses H1975 tumor xenografts while demonstrating poor activity against H1975 in vitro demonstrates the attractiveness of targeting 5T4 in the tumor environment and may be explained by 5T49s principal association with proliferating cells in the tumor. It is also interesting that A1mcMMAF was able to completely regress 37622A xenografts since this patient-derived xenograft presents heterogeneous 5T4 expression, i.e. not all cells demonstrate detectable levels of 5T4. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2011 Nov 12-16; San Francisco, CA. Philadelphia (PA): AACR; Mol Cancer Ther 2011;10(11 Suppl):Abstract nr A215.
Low liquid loading gas/liquid pipe flow

Abstract Low liquid loading gas/liquid flow is frequently encountered in natural gas production and wet gas transmission through long distance pipelines. In this review the typical flow phenomena of low liquid loading gas/liquid pipe flow are described based on the experimental measurements and observations conducted by different authors during the past several decades. The proposed models for flow pattern, pressure gradient and liquid holdup predictions, and closure relationships developed in the previous literatures are introduced and discussed.
The common invariant subspace problem: an approach via Gröbner bases

Let A be an n × n matrix. It is a relatively simple process to construct a homogeneous ideal (generated by quadrics) whose associated projective variety parametrizes the one-dimensional invariant subspaces of A. Given a finite collection of n × n matrices, one can similarly construct a homogeneous ideal (again generated by quadrics) whose associated projective variety parametrizes the one-dimensional subspaces which are invariant subspaces for every member of the collection. Grobner basis techniques then provide a finite, rational algorithm to determine how many points are on this variety. In other words, a finite, rational algorithm is given to determine both the existence and quantity of common one-dimensional invariant subspaces to a set of matrices. This is then extended, for each d, to an algorithm to determine both the existence and quantity of common d-dimensional invariant subspaces to a set of matrices. © 2004 Published by Elsevier Inc.
Open, laparoscopic and robotic radical prostatectomy: Optimizing the surgical approach

As advances in the understanding of prostatic anatomy led to improvements in functional and oncologic outcomes after prostatectomy of the past few decades, advances in technology and surgical technique have made minimally-invasive prostate surgery a reality. Today patients diagnosed with clinically localized prostate cancer have more surgical treatment options than in the past including open, laparoscopic and robot-assisted laparoscopic radical prostatectomy. Advantages and disadvantages exist for each modality and lead to subtle differences in the technical execution of the procedure. Evidence from centers of excellence and from experienced surgeons demonstrates that both laparoscopic and robotic-assisted laparoscopic radical prostatectomy appear to be comparable to outcomes achieved with open radical retropubic prostatectomy series. Individual surgeon skill, experience and clinical judgment are likely the stronger predictors of outcome rather than the technique chosen. However, learning curves, oncologic outcomes and cost-efficacy remain important considerations in the dissemination of minimally-invasive prostate surgery. A greater appreciation of the periprostatic anatomy and further modification of surgical technique will result in continued improvement in functional outcomes and oncological control for patients undergoing radical prostatectomy, whether by open or minimally-invasive surgery.
Living With Epileptic Seizures

Summary 1. Some of the significant problems which the epileptic patient encounters, such as difficulty in securing employment, proper education, and the like, are presented and discussed. 2. Recommendations and advice which the physician can offer to the patient in order to assist him in coping with his difficulties are presented.
DNA structure and flexibility in the sequence-specific binding of papillomavirus E2 proteins

The papillomavirus E2 proteins are transcriptional regulators that bind to a consensus DNA sequence ACCG NNNN CGGT. Multiple copies of this binding site are found in the viral genomes. The affinities of the naturally occurring binding sites for the E2 proteins are predominantly dependent upon the sequence of the NNNN spacer. The hierarchies of binding site affinities among the sites present in the viral genomes result in differential occupancy during the viral life-cycle. In turn, this differential binding regulates transcription from viral promoters, including those for the oncogenes E6 and E7. Structural and biochemical studies have shown that E2 proteins bend the DNA to which they specifically bind. Atomic resolution structures of complexes of the bovine papillomavirus strain 1 (BPV-1) E2 protein and DNA show that the protein does not contact the spacer DNA. A direct comparison of the binding of the DNA-binding domains of the E2 proteins from BPV-1 and human papillomavirus strain 16 (HPV-16) to a series of binding sites as a function of the sequence of their central spacer and/or the presence of a nick or gap in one strand of the spacer DNA is presented in this paper. The BPV-1 E2 DNA-binding domain is only moderately sensitive to the nature of the central spacer; less than several fold differences in affinity were observed when the DNA sequence of the spacer was varied and/or a nick or gap was introduced. In contrast, the HPV-16 E2 DNA-binding domain binds to sites containing A:T-rich central spacers with significantly increased affinity. The introduction of a nick or gap into the spacer of these high affinity sequences is very detrimental to HPV-16 E2 binding while comparable nicks or gaps have only small effects in the low affinity sequences. These results suggest that the HPV-16 E2 protein recognizes the structure of the DNA spacer and that the mechanism of DNA-sequence specific binding of the homologous HPV-16 E2 and BPV-1 E2 proteins is significantly different.
Calculating the cost of an undergraduate Initial Teacher Education (ITE) course

Through a documentary analysis approach, the data included in the validation documentation for a new course designed for undergraduate Initial Teacher Education are used in an attempt to calculate the direct costs of the course. The portion of the costs that are visible are then compared to the pricing policy of the funding agency involved. The devolution of financial responsibility within higher education is suggested as a means of making courses more responsive to market trends.
Biological Factors in Alcohol Use and Abuse: implications for recognizing and preventing alcohol problems in adolescence

Some, but not all alcoholism, ‘runs in families’—about half of hospitalised alcoholics give a positive family history. Characteristics can be identified which distinguish the ‘familial’ or ‘primary...
Transcervical intrauterine bupivacaine for the management of postoperative pain following endometrial balloon ablation—a pre-trial toxicity study

The success of second-generation endometrial ablation performed as day case or outpatient procedure is often hampered by severe postoperative pain. We administered dilute bupivacaine solution into the uterine cavity soon after balloon ablation in ten consecutive women, looking at the safety profile of bupivacaine. Three hours postoperative serum bupivacaine levels were well below the toxic level in all women with no side effects reported.
Subsurface Drip and Overhead Irrigation: A Comparison of Plant Boll Distribution in Upland Cotton

Although subsurface drip (SSD) is used as a water-efficient alternative to overhead irrigation in many crops, the effects of SSD on the distribution of bolls on cotton plants (Gossypium hirsutum L.) have not been thoroughly examined. The purpose of this study was to add to the current knowledge about the effects of SSD on cotton yield dynamics. Cultivar DP 488 BG/RR was grown in three studies during 2 yr with irrigation treatments consisting of overhead irrigation (Overhead), a nonirrigated control (Nonirrigated), SSD matched to overhead irrigation amounts and frequency (SSD Matched), and SSD based on soil moisture (SSD Fed) irrigated cotton. The cotton was grown in two locations in 2004 and one location in 2005 in Georgia. Crop height, maturity, and soil moisture status were monitored throughout the growing season in each location. At harvest, a subplot consisting of one harvest row measuring 3 m in length was removed from each plot and handpicked to determine cotton boll distribution in each plot. Irrigation method had a significant impact on boll distribution on the plants, with the overhead irrigation treatment consistently having less cotton near the bottom of the plant and more cotton near the top than either of the SSD methods. We conclude that SSD irrigation decreases early-season fruit loss, resulting in heavier carbohydrate sinks and decreasing overall growth and upper boll filling on the crop.
Family planning service delivery: Options and trends

Abstract Although family planning programs differ in their objectives, some being concerned primarily with improving the health of mothers and children and others aimed at reducing fertility, their common goal is to make available safe and effective methods for the regulation of human fertility. A variety of service delivery systems has evolved. Services may be provided through specialized family planning clinics or through hospitals and maternal health centers as part of the official health system. The private sector is frequently involved through private physicians or by using commercial distribution of contraceptives at subsidized prices. More recently, the trend has been towards local distribution programs involving the community and establishing family planning as a normal part of daily village life. Based on an assessment of the various approaches to service delivery, a seven-point strategy is suggested. It is concluded that an ambitious, well-managed, multimethod, multichanneled family planning program can have a significant impact on health and fertility.
Reproductive toxicity of methyl-1-(butylcarbamoyl)-2-benzimidazole carbamate (benomyl) in male wistar rats

Methyl-1-(butylcarbamoyl)-2-benzimidazole carbamate (benomyl) is a systemic fungicide which has been implicated in producing damage to the testes. The present investigation was undertaken to evaluate the functional and behavioral significance of this reported benomyl-induced damage to male rats using a 70-day feeding study followed by a 70-day recovery study. Adult male Wistar rats were fed laboratory chow containing 1.0, 6.3, or 203 ppm benomyl, with control animals receiving standard laboratory chow. Ejaculate sperm counts were significantly depressed (P less than or equal to 0.05) in male ingesting 203 ppm benomyl during the 70 day feeding phase. A significant decrease in relative testicular weights and a lowered male fertility index were observed in all benomyl-treatment groups. No significant alterations in plasma testosterone, LH, or FSH levels were observed during the feeding phase. Benomyl ingestion did not alter male copulatory behavior, nor was benomyl found to be an inducer of dominant lethal mutations. Identical studies performed during the recovery phase demonstrated that the benomyl-induced alterations in testicular function were reversible. The male fertility index, ejaculate sperm content, and testicular weights returned to control values during this phase.
Oceanography: Century of phytoplankton change.

Phytoplankton biomass is a crucial measure of the health of ocean ecosystems. An impressive synthesis of the relevant data, stretching back to more than 100 years ago, provides a connection with climate change.
Sleep deprivation: A call for institutional rules

In accordance with ACCME regulations, the American College of Surgeons, as the accredited provider of this journal CME, must ensure that anyone in a position to control the content of the educational activity has disclosed all relevant financial relationships with any commercial interest. The editor and author(s) of this article were required to complete disclosures and any reported conflicts have been managed to our satisfaction. However, if you perceive a bias within the article, please advise us of the circumstances on the evaluation form. The requirement for disclosure is not intended to imply any impropriety of such relationships, but simply to identify such relationships through full disclosure, and to allow readers to form their own judgments regarding the material.
0.8V ultralow-power CMOS analog multiplexer for remote biological and chemical signal processing

A CMOS analog multiplexer circuit has been designed for operation at 0.8 V. The circuit consists of transmission gates as switches and an inverter. MOSFETs in the design of multiplexer use the dynamic body bias method. The forward body bias is limited to no more than 0.4 V to avoid CMOS latch-up. The reverse body bias is limited to 0.4 V and allows the MOSFET to turn-off fully and suppresses the sub-threshold leakage. The improved dynamic threshold MOSFET (DTMOS) inverter is engaged to achieve low voltage operation. The CMOS multiplexer chip was designed in standard 1.5 μm n-well CMOS technology and simulated using SPICE. Excellent agreement was obtained between the simulated output waveform and corresponding experimentally measured behavior. The power dissipation is close to 70 nW and signal-to-leakage ratio is 120 dB. The proposed low voltage, ultra-low power analog multiplexer would find application for on-chip neural microprobes and other applications.
Effects of pH, chloride and Calcium(II) on adsorption of monomethylmercury by soils

Adsorption of monomethylmercury (MMHg) by soil from 2 {times} 10{sup {minus}7} and 1 {times} 10{sup {minus}6} M solutions was investigated to understand soil-water partitioning of MMHg. The effects of three factors--pH, Cl{sup {minus}}, and Ca{sup 2+}--on adsorption were examined. Adsorption as a function of pH followed a concave downward profile with the maximum adsorption occurring at pH between 5 and 6. Less adsorption at low pH values mainly resulted from the proton competition for surface sites and Cl{sup {minus}} complexation for MMHg. Decreases in adsorption at high pH values are attributed to the complexation of MMHg with soluble organic ligands whose concentrations increase with pH. Addition of 1.0 {times} 10{sup {minus}3} M Cl{sup {minus}} decreased adsorption at low pH where CH{sub 3}HgCl was dominant over CH{sub 3}HgOH, and exhibited no effect on adsorption at high pH when CH{sub 3}HgOH became predominant. The presence of a low concentration of Ca{sup 2+} (1.0 {times} 10{sup {minus}4} M) had no effect on MMHg adsorption; however, a high concentration of Ca{sup 2+} (3.3 {times} 10{sup {minus}3} M) increased adsorption at pH 6. This is ascribed to the combined effects of pH and Ca{sup 2+} onmore » the solubility of organic ligands.« less
Minimum “safe cycle time”: Selecting the frozen layer thickness

Predicting the minimum safe cycle time in injection molding is complicated by the cyclic nature of the process. The mold thermal state changes with continuous molding until a quasi steady state is achieved. In the first part of these series, we presented and experimentally tested a simple approach to predict part and mold surface temperature during continuous molding. In this work, we evaluate the minimum frozen layer thickness required before the part can be demolded and how the growth of this frozen layer is affected as the mold thermal state changes with continuous molding cycles. Experiments are used to relate the minimum frozen layer thickness to dimensional stability. Based on these experiments, statistical tools are used to select an ejection criterion to obtain a minimum safe cooling time. We show that the ejection criteria should be adjusted depending on the precision required from the molded parts. POLYM. ENG. SCI., 2009. © 2009 Society of Plastics Engineers
Chloride inhibition of ethanol electrooxidation at a platinum electrode in aqueous acid solution

Abstract The effect of adsorbed chloride ion on the electrooxidation of ethanol at a platinum electrode in 0.5 M H 2 SO 4 at 25°C has been studied in order to determine if adsorbed species are important in this electrooxidation. The cyclic voltammogram for this system exhibits three anodic waves, one of which is unusual in that it occurs during the cathodic going potential sweep. The data indicate that adsorbed species are involved in all three waves. Mechanisms proposed in the literature for ethanol electrooxidation are discussed in terms of these results. The most likely mechanism for the first wave during the anodic going potential sweep includes a chemical reaction between chemisorbed CH 3 ĊHOH and OH (ads) , while a reaction between CH 3 CH 2 OH (ads) and PtO is involved in the second wave. The cathodic going potential sweep wave is acounted for by the electrooxidation of CH 3 CH 2 OH (ads) on a surface free of oxide and chemisorbed species.
Organizational Policy and Women's Socialization in Administration

Contradictions of feminine and administrator roles and norms often lead to role strain, and sometimes to failure.
The Calibration of Photographic it for the Measurement of Q-Switched Ruby-Laser Energy

Photographic film was calibrated for energy measurements of pulsed ruby lasers. The film can be used to obtain energy values accurate to about 20%. The method works under field conditions when the use of electronic instruments may be impractical.
Towards a rigorous framework for studying 2-player continuous games

The use of 2-player strategic games is one of the most common frameworks for studying the evolution of economic and social behavior. Games are typically played between two players, each given two choices that lie at the extremes of possible behavior (e.g. completely cooperate or completely defect). Recently there has been much interest in studying the outcome of games in which players may choose a strategy from the continuous interval between extremes, requiring the set of two possible choices be replaced by a single continuous equation. This has led to confusion and even errors in the classification of the game being played. The issue is described here specifically in relation to the continuous prisoners dilemma and the continuous snowdrift game. A case study is then presented demonstrating the misclassification that can result from the extension of discrete games into continuous space. The paper ends with a call for a more rigorous and clear framework for working with continuous games.
Rat plasma cholesterol after particulate triacylglycerol clearance.

Abstract Following clearance of plasma cholesterol-rich triacylglycerol emulsions, lower-density lipoprotein cholesterol increased minimally in chow and considerably in cholesterol-fed rats. Cholesterol-poor chylomicrons and enterai triacylglycerol produced similar lipoprotein cholesterol increases in cholesterol-fed rats indicating tissue cholesterol recruitment after particulate triacylglycerol clearance. No plasma cholesterol increment was found after chylomicron clearance in anhepatic cholesterol fed rats demonstrating the liver as the major tissue source. The post triacylglycerol clearance was not due to the influx of fatty acid into the liver since larger hepatic free fatty acid loads produced no plasma cholesterol increment. This plasma cholesterol response to particulate triacylglycerol flux occurs only when the liver has excess cholesterol and if applicable to man, may be a factor explaining the large plasma cholesterol differences between diets rich and poor in lipid.
Complications of indwelling chemotherapy catheters

Fifty consecutive chemotherapeutic infusions for cancer via precutaneously introduced arterial catheters were reviewed to determine the frequency of angiographic and clinical complications related to the indwelling catheter. Fibrin cloaking along the catheter was found in 20 patients studied by pull-out arteriography and was unassociated with clinical symptoms. Major thrombus formation occurred around the catheter tip in 28% of the infused vessels, all within the hepatic artery. Clinical symptoms developed in only three patients where thrombosis of the hepatic artery had propagated into the celiac axis. Systemic heparinization did not reduce the incidence of thrombus formation but did increase the incidence of mild gastrointestinal bleeding. Several factors may reduce the incidence of complications, such as puncture of a large artery, use of soft, pliable, and small diameter catheters, proper free position of the catheter in the infused vessel, regular angiographic checkups for catheters position, and early evidence of thrombus formation.
Do the benefits of anti-arrhythmic drugs outweigh the associated risks? A tale of treatment goals in atrial fibrillation

Atrial fibrillation (AF) is the most common cardiac rhythm disorder and places a substantial burden on the US healthcare system. Unfortunately, there is no consensus as to whether patients should be treated with a primary rate- or rhythm-control strategy. The use of anti-arrhythmic drugs in the treatment of AF is discussed in the broader context of AF disease-management strategies with a focus on rhythm control. Outside of rhythm/ECG, AF treatment targets and cardiovascular outcomes are highlighted.
The new approach to assignment of ASFA categories--introduction to the fourth special issue: clinical applications of therapeutic apheresis.

The American Society for Apheresis (ASFA) Apheresis Applications Committee is responsible for a review and categorization of indications for therapeutic apheresis. The results of the review process were previously published in 1986, 1993, and 2000 as the ASFA Special Issues. The ASFA categories consist of categories I through IV, and category P (pending). This article describes the novel methodology, based on structured systematic review of the published literature, used to assign categories for indications for therapeutic apheresis. This is the first time each entity is presented as a fact sheet, which summarizes the evidence for the use of therapeutic apheresis. A detailed description of the fact sheet format and the individual fact sheets for categories I through III and category P are presented in the main article of this Special Issue. The diseases assigned to category IV are discussed in a separate article in this issue. Information on how the Apheresis Applications Committee proposes to include new diseases for category assignment is also provided. J. Clin. Apheresis. 22:96–105, 2007 V C 2007 Wiley-Liss, Inc.
Collection and interpretation of respiratory cytology

Advances in pulmonary cytological sampling have helped establish a more accurate diagnosis and better therapeutic choices for the respiratory patient. Choosing the appropriate test is necessary to maximize the potential diagnostic yield and should be based on the clinical presentation of the patient as well as the minimum database. This article describes several methods of collection of cytological samples for the canine and feline upper and lower respiratory tracts, defines normal respiratory cytology, and discusses normal cytological characterization of various respiratory diseases. Categorization of cytological findings may aid the clinician in narrowing the potential etiologies for the pulmonary disorder. The authors focus on cytological recovery and analysis from transtracheal wash (TTW), bronchial brushing, transthoracic lung aspiration (TTLA), bronchoalveolar lavage (BAL), and open chest biopsy. Indications, complications, and contraindications for each procedure are discussed. Variation in expected findings among BAL, TTW, TTLA, and bronchial brushings are described. Appropriate sampling technique, transport, and processing are also emphasized.
Lower gastrointestinal disease in women.

Lower gastrointestinal tract complaints are a common part of the practice of obstetrics and gynecology. Women are disproportionately affected by lower gastrointestinal tract disease. Functional gastrointestinal symptoms are identified in as many as 20% of women, and 70% of patients with irritable bowel syndrome (IBS) are women. Gynecologists are most likely to see gastrointestinal conditions of an indolent or chronic course or with vague nonspecific symptoms. Consequently, any physician who cares for women must be aware of the scope and impact of these conditions to provide timely diagnosis and efficacious therapy.
Taking Aim at Good Targets: Inter-rater Agreement of Listening Competency

Abstract An examination of listening competency using the Organizational Listening Survey (OLS) demonstrated significant inter-rater agreement in assessments of their co-workers' listening abilities (Cooper & Buchanan, 1999). However, the fact that there was variability in the amount of agreement across individual items and OLS subscales raises the question, why? Do independent raters tend to agree more when assessing targets who are better (or worse) listeners? We hypothesized that inter-rater agreement would be highest among multiple raters for both the best and worst listeners, with targets in the middle receiving less agreement. This assumes that the clear targets (good and bad) would be good targets when it came to agreement. The findings suggested that inter-rater agreement is strongest with the worst listeners.
Feature subspace transformations for enhancing k-means clustering

Unsupervised classification typically concerns identifying clusters of similar entities in an unlabeled dataset. Popular methods include clustering based on (i) distance-based metrics between the entities in the feature space (K-Means), and (ii) combinatorial properties in a weighted graph representation of the dataset (Multilevel K-Means). In this paper, we present a force-directed graph layout based feature subspace transformation (FST) scheme to transform the dataset before the application of K-Means. Our FST-K-Means method utilizes both distance-based and combinatorial attributes of the original dataset to seek improvements in the internal and external quality metrics of unsupervised classification. We demonstrate the effectiveness of FST-K-Means in improving classification quality relative to K-Means and Multilevel K-Means (GraClus). The quality of classification is measured by observing internal and external quality metrics on a test suite of datasets. Our results indicate that on average, the internal quality metric (cluster cohesiveness) is 20.2% better than K-Means, and 6.6% better than GraClus. More significantly, FST-K-Means improves the external quality metric (accuracy) of classification on average by 14.9% relative to K-Means and 23.6% relative to GraClus.
Enantioselective construction of natural (+)-pallescensin A. A sigmatropic pathway to furanosesquiterpenes

Addition of the cerium reagent derived from 3-lithiofuran and anhydrous CeCl 3 to optically pure bicyclic ketone 2 affords alcohol 4 selectively. Anionic oxy-Cope rearrangement of 4 in hot diglyme results in conversion to keto aldehyde 6, a consequence of β-elimination following upon the [3,3]sigmatropic event. Advantage was then taken of chemoselective acetalization and unidirectional introduction of an enone double bond. Regio- and stereoselective epoxidation of 8 was a prelude to formation of the furan ring by BF 3 .etherate-promoted cyclization. Once the carbonyl group was reduced with alane, catalytic hydrogenation in the presence of diethylamine gave the title compound
Some Ruminations about Prison Mental Health Work.

In this article. the author refers to incidents involving mental health services in prison facilities that illustrate Catch-22 situations, in many of which inmates perceive clinicians as people who "come to watch you drown instead of throwing you a rope." The author proposes a supplementation of what he calls "administrative clinical" thinking with non-bureaucratic, collaborative efforts to assist inmates.
Elimination of Na+ and GTP regulation of α2-adrenoceptor-agonist interactions in rat kidney membranes by 4,4'-diisothiocyano-2,2'-stilbene disulfonic acid (DIDS)

Abstract Pretreatment of rat kidney membranes with 4,4′-diisothiocyano-2,2′-stilbene disulfonic acid (DIDS) did not affect the Bmax but reduced the affinity of the receptors for antagonist by less than 2-fold. However, such treatment reduced the affinity of the receptors for agonist by several fold by preventing the formation of agonist-receptor-Gi-protein complex. The modulatory effects of GTP and Na+ on α2-adrenoceptor-agonist interactions were also abolished. These results suggest that DIDS acts at multiple sites on α2-adrenoceptor-adenylate cyclase complex.
Photoperiodic responsiveness of hamsters with lesions of the lateral geniculate nucleus is related to hippocampal damage

We tested the hypothesis that the geniculohypothalamic tract is important for hamster photoperiodism. Adult male hamsters, maintained in a long photoperiod (LD 14:10), received either large bilateral neurotoxic lesions of the lateral geniculate nucleus (LGN) or sham lesions. One week later, half of the animals from each group were transferred to a short photoperiod (LD 8:16) where they were maintained for 15 weeks. Most lesions effectively destroyed the intergeniculate leaflet (IGL) and much of the lateral geniculate complex. They also caused substantial damage to the overlying hippocampus. The lesions had no effect on long-day animals, but significantly reduced the extent of testicular regression during short photoperiod exposure. This effect, however, appeared to be the result of hippocampal, rather than geniculate, damage. Four individuals with complete IGL lesions, but minimal hippocampal damage, underwent a pattern of regression that was indistinguishable from controls. Body weight was increased by lesions in short-day, but not long-day, animals. This effect was not related to the extent of hippocampal damage. We conclude that geniculate input to the suprachiasmatic nuclei is not essential for hamster photoperiodism and that hippocampal damage may modify the effect of short daylengths on testes size.
Synthesis of β-silyl ketones via reaction of trimethylsilyllthium with unsaturated hydrazones. Application to the synthesis of brevicomin

Abstract Trimethylsilyllithium undergoes conjugate addition to dimethylhydrazones of α,β-unsaturated ketones. The resulting metalloenamine intermediates can be alkylated, and the resulting hydrazone products cleaved to give α-substituted-β-silyl ketones. These reactions, together with a silicon-directed Baeyer-Villiger reaction, have been applied to the synthesis of brevicomin.
Transformed Eulerian-Mean Theory. Part I: Nonquasigeostrophic Theory for Eddies on a Zonal-Mean Flow

A theoretical formalism for nongeostrophic eddy transport in zonal-mean flows, using a transformed Eulerian-mean (TEM) approach in z coordinates, is discussed. By using Andrews and McIntyre’s coordinate-independent definition of the “quasi-Stokes streamfunction,” it is argued that the surface boundary condition can be dealt with more readily than when the widely used quasigeostrophic definition is adopted. Along with the “residual mean circulation,” the concept of “residual eddy flux” arises naturally within the TEM framework, and it is argued that it is this residual eddy flux, and not the “raw” eddy flux, that might reasonably be expected to be downgradient. This distinction is shown to be especially important for Ertel potential vorticity (PV). The authors show how a closed set of transformed mean equations can be generated, and how the eddy forcing appears in the TEM momentum equations. Under adiabatic conditions, the “eddy drag” is just proportional to the residual eddy flux of PV along the mean isopycnals; in the diabatic layer close to the surface, it is more complicated, but becomes very simple for small Rossby number (without any assumption of small isopycnal slope).
Proposed Signal Transduction Role for Conserved CheY Residue Thr87, a Member of the Response Regulator Active-Site Quintet

CheY serves as a structural prototype for the response regulator proteins of two-component regulatory systems. Functional roles have previously been defined for four of the five highly conserved residues that form the response regulator active site, the exception being the hydroxy amino acid which corresponds to Thr87 in CheY. To investigate the contribution of Thr87 to signaling, we characterized, genetically and biochemically, several cheY mutants with amino acid substitutions at this position. The hydroxyl group appears to be necessary for effective chemotaxis, as a Thr→Ser substitution was the only one of six tested which retained a Che+ swarm phenotype. Although nonchemotactic, cheY mutants with amino acid substitutions T87A and T87C could generate clockwise flagellar rotation either in the absence of CheZ, a protein that stimulates dephosphorylation of CheY, or when paired with a second site-activating mutation, Asp13→Lys, demonstrating that a hydroxy amino acid at position 87 is not essential for activation of the flagellar switch. All purified mutant proteins examined phosphorylated efficiently from the CheA kinase in vitro but were impaired in autodephosphorylation. Thus, the mutant CheY proteins are phosphorylated to a greater degree than wild-type CheY yet support less clockwise flagellar rotation. The data imply that Thr87 is important for generating and/or stabilizing the phosphorylation-induced conformational change in CheY. Furthermore, the various position 87 substitutions differentially affected several properties of the mutant proteins. The chemotaxis and autodephosphorylation defects were tightly linked, suggesting common structural elements, whereas the effects on self-catalyzed and CheZ-mediated dephosphorylation of CheY were uncorrelated, suggesting different structural requirements for the two dephosphorylation reactions.
Childhood socioeconomic disadvantage and prediabetes and diabetes in later life: a study of biopsychosocial pathways.

Objective We examined the relationship between childhood socioeconomic status (SES) and glucoregulation in later life and used a life-course framework to examine critical periods and underlying pathways.
Human Lyme disease vaccines: past and future concerns.

The development of a vaccine for Lyme disease was intensely pursued in the 1990s. However, citing a lack of demand, the first human Lyme disease vaccine was withdrawn from the market less than 5 years after its approval. The public’s concerns about the vaccine’s safety also likely contributed to the withdrawal of the vaccine. Nearly a decade later, no vaccine for human Lyme disease exists. The expansion of Lyme disease’s endemic range, as well as the difficulty of diagnosing infection and the disease’s steady increase in incidence in the face of proven preventative measures, make the pursuit of a Lyme disease vaccine a worthwhile endeavor. Many believe that the negative public perception of the Lyme disease vaccine will have tarnished any future endeavors towards its development. Importantly, many of the drawbacks of the Lyme disease vaccine were apparent or foreseeable prior to its approval. These pitfalls must be confronted before the construction of a new, effective and safe human Lyme disease vaccine.
The Gene-Duplication Problem: Near-Linear Time Algorithms for NNI-Based Local Searches

The gene-duplication problem is to infer a species supertree from a collection of gene trees that are confounded by complex histories of gene-duplication events. This problem is NP-complete and thus requires efficient and effective heuristics. Existing heuristics perform a stepwise search of the tree space, where each step is guided by an exact solution to an instance of a local search problem. A classical local search problem is the {\tt NNI} search problem, which is based on the nearest neighbor interchange operation. In this work, we 1) provide a novel near-linear time algorithm for the {\tt NNI} search problem, 2) introduce extensions that significantly enlarge the search space of the {\tt NNI} search problem, and 3) present algorithms for these extended versions that are asymptotically just as efficient as our algorithm for the {\tt NNI} search problem. The exceptional speedup achieved in the extended {\tt NNI} search problems makes the gene-duplication problem more tractable for large-scale phylogenetic analyses. We verify the performance of our algorithms in a comparison study using sets of large randomly generated gene trees.
Research on Policy: Shadow Elite: How the Study of Post‐Communist Societies Illuminates US Power Structures

: Janine R Wedel is contributing editor of “Research on Policy,” the AAA Interest Group for the Anthropology of Public Policy column in Anthropology News.
Advances in follicular lymphoma

Follicular lymphoma is a usually indolent lymphoma that responds well to chemotherapy. While multiple treatments show a good response rate, most patients relapse. Emerging therapies, such as antibody therapy and stem cell transplantation, are increasingly being used to try to lengthen response time. This article will review the available treatments for follicular lymphoma and discuss the studies supporting newer strategies of treatment.
Rapid torque development in older female fallers and nonfallers: A comparison across lower-extremity muscles

Abstract The objective of this study was to compare reaction time, joint torque, rate of torque development, and magnitude of neuromuscular activation of lower-extremity muscles in elderly female fallers and nonfallers. Participants included 11, elderly, female fallers (71.3±5.4years) and twelve nonfallers (71.3±6.2years) who completed a fall risk questionnaire. Then, maximal, voluntary, isometric contractions of the knee and ankle muscles were performed in reaction to a visual cue to determine joint torque, rate of torque development, reaction time, and nervous activation of agonists and antagonists. Results indicated that significantly more fallers reported "dizziness upon rising", "use of balance altering medications", "stress or depression", "not enough sleep", "arthritis in lower body", "chronic pain in lower body", and "tiring easily while walking" (all P P P
Core Concepts: Respiratory Distress Syndrome

Respiratory distress syndrome (RDS) is seen primarily in the preterm neonate and is due mostly to pulmonary surfactant deficiency. Lung atelectasis leads to ventilation-perfusion mismatching, hypoxia, and eventual respiratory failure in the untreated infant who has RDS. RDS is diagnosed by physical findings consistent with respiratory distress and characteristic radiographic findings. Treatment of RDS begins antenatally with the administration of maternal steroids to women at risk of preterm delivery between 24 and 34 weeks’ gestation. The use of repeat doses of antenatal steroids is under investigation but is currently not recommended outside of randomized, controlled trials. SRT has been approved for use since 1990 and has been successful in decreasing rates of RDS. Natural surfactant is currently recommended for use, but synthetic surfactant that contains proteins to mimic surfactant proteins is being investigated. In general, prophylactic use of surfactant is recommended over rescue treatment in infants at high risk for developing RDS, but the determination of which infants are at high risk for developing RDS remains a clinical one. The push toward use of less invasive ventilation strategies in the treatment of RDS has led to several trials of nasal continuous positive airway pressure (nCPAP). Results of the SUPPORT trial are pending, but the COIN trial has concluded that nCPAP use in infants who have RDS is not detrimental. Inhaled nitric oxide for RDS still requires investigation on safety and efficacy. Several other treatments have been studied, but as of yet, only inositol administration shows promise in the treatment of RDS. Several complications of the recommended treatments for RDS have been identified, but the benefits far outweigh the risks. Finally, there remains a need for long-term follow-up studies on preterm infants treated for RDS to assess neurodevelopmental outcomes.
In vivo footprinting of a muscle specific enhancer by ligation mediated PCR

In vivo protein-DNA interactions at the developmentally regulated enhancer of the mouse muscle creatine kinase (MCK) gene were examined by a newly developed polymerase chain reaction (PCR) footprinting procedure. This ligation mediated, single-sided PCR technique permits the exponential amplification of an entire sequence ladder. Several footprints were detected in terminally differentiated muscle cells where the MCK gene is actively transcribed. None were observed in myogenic cells prior to differentiation or in nonmuscle cells. Two footprints appear to correspond to sites that can bind the myogenic regulator MyoD1 in vitro, whereas two others represent muscle specific use of apparently general factors. Because MyoD1 is synthesized by undifferentiated myoblasts, these data imply that additional regulatory mechanisms must restrict the interaction between this protein and its target site prior to differentiation.
Lung Herniation Secondary to Minimally Invasive Direct Coronary Artery Bypass Grafting

Lung herniation after thoracotomy is rare. We report a 66-year-old man who presented with this complication after undergoing attempted minimally invasive direct coronary artery bypass grafting. The defect was repaired with a composite of Marlex mesh and methyl methacrylate.