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Integrion Financial Network plans to announce today that its chief executive officer, William M. Fenimore Jr., will be leaving at the end of the year. The plan calls for Christopher [...]

WASHINGTON -- Apr-27 -- (CongressDaily) A veteran New York House Democrat said Monday he has told First Lady Hillary Rodham Clinton that while she would be the strongest candidate for [...]

Corporations are not driven to sustainable development by an overwhelming desire to be altruistic, but rather by their fiduciary responsibility to create shareholder value. In other words, sustainable development is [...]

Democratic lawmakers and a public-interest group are asking the Federal Communications Commission (FCC) to open to public comment its plans to ease media ownership rules. A group of 100 House [...]

Rep. Maurice Hinchey (D-N.Y.) last week introduced a bill that would massively reregulate the media. Chances for its passage are nearly nil, and it should be seen more as a [...]

À partir d’un cas de reconstruction du palais dur après exérèse carcinologique, les auteurs précisent les points clefs de la réalisation du lambeau myo-muqueux de buccinateur à charnière postérieure dit de Bozola et détaillent les limites et les indications de ce lambeau local de translation lors de la chirurgie carcinologique des tumeurs de la cavité buccale et/ou de l’oropharynx.

Macrocycles are of increasing interest as chemical probes and drugs for intractable targets like protein–protein interactions, but the determinants of their cell permeability and oral absorption are poorly understood. To enable rational design of cell-permeable macrocycles, we generated an extensive data set under consistent experimental conditions for more than 200 non-peptidic, de novo–designed macrocycles from the Broad Institute's diversity-oriented screening collection. This revealed how specific functional groups, substituents and molecular properties impact cell permeability. Analysis of energy-minimized structures for stereo- and regioisomeric sets provided fundamental insight into how dynamic, intramolecular interactions in the 3D conformations of macrocycles may be linked to physicochemical properties and permeability. Combined use of quantitative structure–permeability modeling and the procedure for conformational analysis now, for the first time, provides chemists with a rational approach to design cell-permeable non-peptidic macrocycles with potential for oral absorption.

Congressman Maurice Hinchey (D-NY) has secured a $6-million federal investment for Endicott Interconnect Technologies (EI) to develop microelectronic chips that safeguard against the foreign tampering of weapons. With this chip, [...]

Representative Maurice Hinchey (D., NY) has introduced legislation that would reinstate the Superfund tax charged to oil and chemical companies that expired December 31, 1995. The Superfund Equity and Megasite [...]

REP. MAURICE Hinchey (DNY) says Congress has refused to act on several bills to reform the FDA, 'because members are comfortably obliged to the pharmaceutical industry.' But Pharmaceutical Research and [...]

Representative Maurice Hinchey (D., NY) has stepped up pressure on the New York State Department of Health (NYSDOH; Albany) for not revising its air quality standards for exposure to trichloroethylene [...]

WASHINGTON -- Attention Brian Roberts and Steve Burke: A member of Congress is messing with your plan to buy The Walt Disney Co. Rep. Maurice Hinchey (D-N.Y.) last Tuesday introduced [...]

Longtime dereg foe Rep. Maurice Hinchey (D-N.Y.) is taking his best shot at bringing down Big Media. In a sweeping new bill, he proposes to roll back the FCC's June [...]

Democratic-led critics of media consolidation in the U.S. House of Representatives are vowing to keep up pressure to reverse the Federal Communication Commission's decision to loosen media ownership regulations. The [...]

The Savings and Community Bankers of America is upset about an amendment passed by the House Banking Subcommittee that may deny the Savings Association Insurance Fund (SAIF) access to $12 billion approved by the subcommittee. The amendment introduced by Maurice D. Hinchey sliced $5 billion from the $17 billion the Clinton administration approved for SAIF. Hinchey's amendment does not allow the Federal Deposit Insurance Corp to release funds unless an increase in insurance premiums would cause losses., WASHINGTON - The leading thrift industry trade group complained Friday that the Savings Association Insurance Fund may not be able to tap the $12 billion approved by a House Banking [...]

Profiles Democrat freshman Rep. Maurice D. Hinchey from New York's 26th District. Includes statistics on his election, birthdate, home, education, occupation, family, religion, political career and committee assignments.

Profiles freshman Rep. Maurice D. Hinchey (D-N.Y.) from the 26th District. Includes information on the election, his birthdate, home, occupation, family, religion, highest degree and last elected office. His efforts on reviving the district's economy; His support of federal assistance for defense-oriented businesses seeking to convert to production of civilian goods; Advocate of the `reindustrialization' of America; More.

Community Energy, Inc (CEI), U.S. Congressman Maurice Hinchey, and the U.S. General Services Administration (GSA) recently announced that the Binghamton (NY) Federal Building is the first federal facility in the [...]

Presents several letters to the editor referencing articles and topics published in previous issues. Evaluation of the median household income; Comments on the cost analysis carried out by the United Nations to provide food, clean water, health care, shelter, and literacy for everyone on the entire planet; Views on the notion that Palestinians are culturally more ruthless and vengeful than Israelis; Information on the fact that the Palestinian Authority's new official map of Palestine includes all of Israel and shows holy sites of Muslims and Christians, but not of Jews.

The article focuses on citizen participation in school affairs. Too often, neither the laymen participants nor the educational leaders have a dear idea of just what citizen-school cooperation can accomplish or how they can best go about it. One must, first, remember that the schools are public institutions serving the community. Decisions affecting them are matters of broad public policy and, to be effective, such decisions must have the support of the whole community. There are two major alternatives to community-wide solution of school questions. One is not to solve them at all. The other is for a small group of interested--sometimes self-interested--laymen and schoolmen to impose a solution on an apathetic public. Individuals, working independently, have made many contributions to their schools. However, a dozen--or 100--individuals, working separately can never accomplish as much as the same number could working together. Therefore, organization is important. Many appointed citizens committees have been strikingly effective in working on school issues. They are likely to start out with the full confidence and cooperation of school authorities and often enjoy a sort of semi-official status which sometimes helps them more easily to gain the confidence of the community.

Brain-computer interfaces (BCIs) aim to provide a mechanism by which individuals with severe forms of paralysis can communicate their wishes to others or gain control over devices in their environment. This paper describes the evaluation of an interface designed for use with BCI, which is dedicated to providing a flexible and extensible framework for controlling multiple devices within a domestic environment. A structured format for assessing the usability aspects of this interface is presented. The goal-question-metric (GQM) approach derived from measurement in software engineering was used, providing a mechanism that can be readily adapted to assess other interfaces in assistive technology. The assessment was based on interaction of five participants currently using assistive technology who provided an initial representation of the target user group. Their input, in addition to guidance from a lead user, was used to influence subsequent design choices and directions and highlight the importance of user-centred design within BCI development.

Congress should exempt empowerment zone bonds from the state-by-state private-activity bond caps and make banks eligible buyers of the debt if the program is to become an effective economic development [...]

Reps. Maurice Hinchey, D-N.Y., and Henry B. Gonzalez, D Tex., introduced legislation Tuesday that would prohibit unsolicited loans by mail. 'Banks should not be sending unsolicited loans through the mail [...]

Given that the 104th Congress is the most anti-wilderness Capitol Hill delegation in memory, choosing its worst members is no easy task. According to the League of Conservation Voters, which […]

In a 2011 reply to our 2010 comment in this journal, Berument and Dogen maintained their challenge to the existence of the negative daylight-saving effect in stock returns reported by Kamstra, Kramer, and Levi in 2000. Unfortunately, in their reply, Berument and Dogen ignored all of the points raised in the comment, failing even to cite the Kamstra, et al.comment. Berument and Dogen continued to use inappropriate estimation techniques, over-parameterized models, and low-power tests and perhaps most surprisingly even failed to replicate results they themselves reported in their previous paper, written by Berument, Dogen, and Onar in 2010. The findings reported by Berument and Dogen, as well as by Berument, Dogen, and Onar, are neither well-supported nor well-reasoned. We maintain our original objections to their analysis, highlight new serious empirical and theoretical problems, and emphasize that there remains statistically significant evidence of an economically large negative daylight-saving effect in U.S. stock returns. The issues raised in this rebuttal extend beyond the daylight-saving effect itself, touching on methodological points that arise more generally when deciding how to model financial returns data.

It is well known that eastern oysters (Crassostrea virginica) are bio-indicators and can be used to determine the elemental composition of an estuarine system. Laser-induced breakdown spectroscopy (LIBS) has been successfully used for the detect of trace elements in various environmental matrices. In this work, LIBS was used to characterize oysters collected from a total of six sites in two different coastal estuarine reserves – Grand Bay, Mississippi (4 sites) and Apalachicola Bay, Florida (2 sites). Multiple ionic and neutral elemental species of Al, C, Ca, Cu, Fe, K, Mg, Na, Si, Sr, and Zn were observed through LIBS spectral analysis of the harvested oysters. Principal component analysis, discriminant function analysis, and hierarchical cluster analysis were applied to a data matrix of identified elemental lines resulting in intra- and inter-site clustering of the oysters according to their geographical origin.

The article reports on the use of radio frequency identification (RFID), simulation and other industrial engineering methods for inventory control of the National Aeronautics and Space Administration (NASA) in the U.S. It offers information on the benefits of automated inventory management using a discrete-event simulation model and by introducing an inventory policy equation known as the economic order quantity (EOQ) that determines the best amount of stored inventory given information like cost of food, amount of food consumed and frequency of shipment. A five-step approach is presented using the RFID to determine EOQ including the calculation of calories consumed by astronauts, determining safety stock values and integrating the annual demand and costs into an EOQ model.

In a recent article in this journal, Berument, Dogan, and Onar (2010) challenged the existence of the previously documented daylight-saving effect. Kamstra, Kramer, and Levi's original finding (2000) was that average stock market returns on Mondays following time changes are economically and statistically significantly lower than typical Monday returns. Kamstra, et al.hypothesized that the effect may arise due to heightened anxiety or risk aversion on the part of market participants after they experience a 1-hr. disruption in their sleep habits, in accordance with prior findings in the psychology literature linking sleep desynchronosis with anxiety. Berument, et al.replicated the original findings using ordinary least squares estimation, but when they modeled the mean of returns using a method prone to producing biased estimates, they obtained puzzling results. The analysis here, based on standard, unbiased modeling techniques, shows that the daylight-saving effect remains intact in the U.S.

Kynurenine, the major degradation product of tryptophan has been shown to directly damage tissues, but its possible contribution to posttraumatic morbidity is unknown. Here, we studied the kinetics of kynurenine in patients after major trauma and whether this correlates with the development of posttraumatic sepsis. Kynurenine and tryptophan levels of 60 multiple-injured patients with Injury Severity Score of more than 16 were quantified prospectively by high-performance liquid chromatography. Blood samples were obtained daily from admission until day 10 after admission. Significantly increased kynurenine values were detectable already at day 1 after admission in blood from patients who later developed sepsis, regardless of injury pattern (P< 0.01). In contrast, kynurenine values of nonsepsis patients remained low throughout the observation period. However, all patients exhibited significantly decreased tryptophan values versus healthy controls (P< 0.01). Moreover, significantly increased kynurenine-tryptophan ratios rapidly predicted subsequent sepsis, multiple organ failure, and death (P< 0.01). Both increased kynurenine values and kynurenine-tryptophan ratios predicted posttraumatic development of sepsis and organ failure. This ought to be validated in subsequent studies.

ABSTRACTStreptococcus mutans, a common oral pathogen and the causative agent of dental caries, has persisted and even thrived on the tooth surface despite constant removal and eradication efforts. In this study, we generated a number of synthetic antimicrobial peptides against this bacterium via construction and screening of several structurally diverse peptide libraries where the hydrophobicity and charge within each library was varied incrementally in order to generate a collection of peptides with different biochemical characteristics. From these libraries, we identified multiple peptides with robust killing activity against S. mutans. To further improve their effectiveness, the most bactericidal peptides from each library were synthesized together as one molecule, in various combinations, with and without a flexible peptide linker between each antimicrobial region. Many of these “fusion” peptides had enhanced killing activities in comparison with those of the original nonconjoined molecules. The results presented here illustrate that small libraries of biochemically constrained peptides can be used to generate antimicrobial peptides against S. mutans, several of which may be likely candidates for the development of anticaries agents.

MTHFR (methylenetetrahydrofolate reductase) catalyses the synthesis of 5-methyltetrahydrofolate, the folate derivative utilized in homocysteine remethylation to methionine. A severe deficiency of MTHFR results in hyperhomocysteinaemia and homocystinuria. Betaine supplementation has proven effective in ameliorating the biochemical abnormalities and the clinical course in patients with this deficiency. Mice with a complete knockout of MTHFR serve as a good animal model for homocystinuria; early postnatal death of these mice is common, as with some neonates with low residual MTHFR activity. We attempted to rescue Mthfr−/− mice from postnatal death by betaine supplementation to their mothers throughout pregnancy and lactation. Betaine decreased the mortality of Mthfr−/− mice from 83% to 26% and significantly improved somatic development from postnatal day 1, compared with Mthfr−/− mice from unsupplemented dams. Biochemical evaluations demonstrated higher availability of betaine in suckling pups, decreased accumulation of homocysteine, and decreased flux through the trans-sulphuration pathway in liver and brain of Mthfr−/− pups from betaine-supplemented dams. We observed disturbances in proliferation and differentiation in the cerebellum and hippocampus in the knockout mice; these changes were ameliorated by betaine supplementation. The dramatic effects of betaine on survival and growth, and the partial reversibility of the biochemical and developmental anomalies in the brains of MTHFR-deficient mice, emphasize an important role for choline and betaine depletion in the pathogenesis of homocystinuria due to MTHFR deficiency.

To investigate interindividual differences in neurobehavioral deficits during sleep deprivation, and to establish to what extent the neurobehavioral responses to sleep loss are a function of sleep history versus trait-like differential vulnerability.

Hyperhomocysteinemia, a proposed risk factor for cardiovascular disease, is also observed in other common disorders. The most frequent genetic cause of hyperhomocysteinemia is a mutated methylenetetrahydrofolate reductase (MTHFR), predominantly when folate status is impaired. MTHFR synthesizes a major methyl donor for homocysteine remethylation to methionine. We administered the alternate choline‐derived methyl donor, betaine, to wild‐type mice and to littermates with mild or severe hyperhomocysteinemia due to hetero‐ or homozygosity for a disruption of the Mthfrgene. On control diets, plasma homocysteine and liver choline metabolite levels were strongly dependent on the Mthfrgenotype. Betaine supplementation decreased homocysteine in all three genotypes, restored liver betaine and phosphocholine pools, and prevented severe steatosis in Mthfr‐deficient mice. Increasing betaine intake did not further decrease homocysteine. In humans with cardiovascular disease, we found a significant negative correlation between plasma betaine and homocysteine concentrations. Our results emphasize the strong interrelationship between homocysteine, folate, and choline metabolism. Hyperhomocysteinemic Mthfr‐compromised mice appear to be much more sensitive to changes of choline/betaine intake than do wild‐type animals. Hyperhomocysteinemia, in the range of that associated with folate deficiency or with homozygosity for the 677T MTHFRvariant, may be associated with disturbed choline metabolism.

At early stages of tumorigenesis, the transforming growth factor-beta (TGF-beta) signaling pathway is thought to have tumor suppressor activity as a result of its ability to arrest the growth of epithelial cells. Smad4 plays a pivotal role in the TGF-beta signaling pathway and has been identified as a tumor suppressor, being mutated or deleted in approximately 50% of pancreatic carcinomas and 15% of colorectal cancers. A nonsense mutation generating a C-terminal truncation of 38 amino acids in the Smad4 protein has been identified in a pancreatic adenocarcinoma (Hahn, S. A., Schutte, M., Hoque, A. T., Moskaluk, C. A., da Costa, L. T., Rozenblum, E., Weinstein, C. L., Fischer, A., Yeo, C. J., Hruban, R. H., and Kern, S. E. (1996) Science 271, 350-353), and here we investigate the functional consequences of this mutation. We demonstrate that the C-terminal truncation prevents Smad4 homomeric complex formation and heteromeric complex formation with activated Smad2. Furthermore, the mutant protein is unable to be recruited to DNA by transcription factors and hence cannot form transcriptionally active DNA-binding complexes. These observations are supported by molecular modeling, which indicates that the truncation removes residues critical for homomeric and heteromeric Smad complex formation. We go on to show that the mutant Smad4 is highly unstable compared with wild type Smad4 and is rapidly degraded through the ubiquitin-proteasome pathway. Consistent with this, we demonstrate that the pancreatic adenocarcinoma harboring this mutated allele, in conjunction with loss of the other allele, expresses no Smad4 protein. Thus we conclude that these tumors completely lack Smad4 activity.

Multiple families of cyclic nucleotide phosphodiesterases (PDE) have been described, and the regulated expression of these genes in cells is complex. Although cAMP is known to control the expression of certain PDE in cells, presumably reflecting a system of feedback on cAMP signaling, relatively little is known about the influence of non-cAMP signaling systems on PDE expression. In this study, we describe a novel mechanism by which activators of the protein kinase C (PKC)-Raf-MEK-ERK cascade regulate phosphodiesterase 4D (PDE4D) expression in vascular smooth muscle cells (VSMC) and assess the functional consequences of this effect. Whereas a prolonged elevation of cAMP in VSMC resulted in a protein kinase A (PKA)-dependent induction of expression of two PDE4D variants (PDE4D1 and PDE4D2), simultaneous activation of both the cAMP-PKA and PKC-Raf-MEK-ERK signaling cascades blunted this cAMP-mediated increase in PDE4D expression. By using biochemical, molecular biological, and pharmacological approaches, we demonstrate that this PDE4D-selective effect of activators of the PKC-Raf-MEK-ERK cascade was mediated through a mechanism involving altered PDE4D mRNA stability and markedly attenuated the cAMP-mediated desensitization that results from prolonged activation of the cAMP signaling system in cells. The data are presented in the context of activators of the PKC-Raf-MEK-ERK cascade having both short and long term effects on PDE4D activity and expression in cells that may influence cAMP signaling.

Cyclic nucleotide phosphodiesterases (PDEs) are a superfamily of enzymes whose physiological role is the attenuation of the signaling mediated by the ubiquitous second messengers cAMP and cGMP. Given the myriad of physiological processes regulated by cAMP and cGMP, PDEs have long been studied as potential therapeutic targets. Although phosphodiesterase 3 (PDE3) activity is abundant in human cardiovascular tissues, and acute PDE3 inhibition, with agents such as milrinone, was beneficial in heart failure patients, prolonged treatments were associated with time-dependent reductions in hemodynamic effects and increased mortality. The molecular basis of this time-dependent reduction in efficacy has not been elucidated. In this context, we used a combination of approaches to determine PDE3 expression in human cardiovascular tissues and to elucidate the effects of prolonged elevations of cellular cAMP, as would occur with PDE3 inhibition, on this activity. Although our data confirms the expression of PDE3A in human blood vessel smooth muscle cells (HASMCs), we identify a previously unrecognized role for PDE3B in cAMP hydrolysis in human cardiovascular tissues. Specifically, although both PDE3A and PDE3B were expressed in HASMCs, their subcellular expression pattern and regulated expression by cAMP were distinct, with only expression of PDE3B being subject to cAMP-regulated expression. Thus, a paradigm emerges that allows for dual expression, with distinctive regulation, of both PDE3A and PDE3B proteins in cardiovascular tissues that may have profound significance for the rational design of molecules regulating this PDE activity.

The authors aim to facilitate the psychiatric evaluation of death-hastening decisions, such as cessation of life-support treatment or physician-assisted suicide, by deriving principles for evaluating patients from a literature review and a recently completed prospective study on dialysis discontinuation conducted by consultation psychiatrists. Factors are delineated and suggestions are provided for the evaluation of requests to accelerate dying. Included are the authors’ method for determining major depression in the context of terminal illness and their “vector analysis” in assessing patient requests to stop dialysis. As our society heatedly examines the care provided to the terminally ill, psychiatry also needs to reconsider whether actions that foreshorten life can be normative and permissible. Familiarity with competency, psychiatric diagnosis, and ease in communication and negotiation between patient, family, and staff are resources that psychiatrists can bring to these complicated assessments. Challenging areas include diagnosing depression, establishing the adequacy of palliative care, and appreciating issues related to personality features, family dynamics, and ethnic differences.

Four furanosesquiterpene β-hydroxy ketones previously isolated from Myoporumspp., and given tentative names, are now assigned complete stereostructures from n.m.r. and X-ray data. The compounds are (5R,7R,9S)-9-hydroxy-5,9-dihydromyomontanone (Woogaroo) (1a), (5S,7R,9R)-9-hydroxy-5,9-dihydro- myomontanone (Redbank) (1b), (5R,7R,9R)-9-hydroxy-5,9-dihydromyomontanone (Perillup) (1c) and (4S,7S,8R)-4-hydroxy-10,11-didehydro-4,8-dihydromyodesmone (Carney's ketol) (2a). The stereo- structures of two other previously reported compounds, Kindon ketol ((4S,7S,8R)-4-hydroxy-4,8- dihydromyodesmone) (2b), and Carr's ketol ((4S,7S,8S)-4-hydroxy-4,8-dihydromyodesmone) (2c), follow from the above results.

In this study, we describe a novel mechanism by which a protein kinase C (PKC)-mediated activation of the Raf-extracellular signal-regulated kinase kinase (MEK)-extracellular signal-regulated kinase (ERK) cascade regulates the activity and membrane targeting of members of the cyclic AMP-specific phosphodiesterase D family (PDE4D). Using a combination of pharmacological and biochemical approaches, we show that increases in intracellular cAMP cause a protein kinase A-mediated phosphorylation and activation of the two PDE4D variants expressed in vascular smooth muscle cells, namely PDE4D3 and PDE4D5. In addition, we show that stimulation of PKC via the associated activation of the Raf-MEK-ERK cascade results in the phosphorylation and activation of PDE4D3 in these cells. Furthermore, our studies demonstrate that simultaneous activation of both the protein kinase A and PKC-Raf-MEK-ERK pathways allows for a coordinated activation of PDE4D3 and for the translocation of the particulate PDE4D3 to the cytosolic fraction of these cells. These data are presented and discussed in the context of the activation of the Raf-MEK-ERK cascade acting to modulate the activation and subcellular targeting of PDE4D gene products mediated by cAMP.