cssi/SciSciGPT-SciSciNet huggingface dataset:
Health Care Reform Sets the Standard Under the Federal Anti-Kickback Statute, But How Much Longer Will it Apply?

Under its aegis, the 2010 Patient Protection and Affordable Care Act (PPACA, more commonly referred to as Health Care Reform, Pub. L. No. 111-148) clarified the criminal intent requirement under the federal Anti-Kickback Statute ('AKS'). Before PPACA, federal courts applied different standards of intent, both general and specific, in determining the existence of violations under the AKS. Section 6402(f)(2) of PPACA amends the AKS (42 U.S.C. § 1320a-7b) by stating, in part: 'With respect to violations of this section, a person need not have actual knowledge of this section or specific intent to commit a violation of this section.'Like it or not, Congressional design is clear, and this general intent threshold now serves as the national standard for the AKS after PPACA. While constitutional scholars may take aim at this seemingly benign amendment when they eventually tire of health care reform’s individual insurance mandate, health care and criminal law practitioners are better served by understanding the historical landscape leading up to section 6402(f)(2). By tracing the evolution of the AKS, as well as the companion False Claims Act ('FCA', 31 U.S.C. § 3729, et seq.) and the Ethics in Patient Referrals Act (more commonly referred to as Stark I and Stark II, 42 U.S.C. § 1395nn), practitioners may have a stronger perspective with which to offer their clients advice within the rapidly changing climate of health care reform, rather than relying upon cautionary missives that speak to this watered-down standard of scienter.
A Circuit Model for Energy Synchronous Direct Antenna Modulation Using an Electrically Small Loop

A simple circuit model for a broadband electrically small loop transmitter using energy synchronous direct antenna modulation (DAM) is presented. The concept of energy-synchronous DAM using a loop antenna is briefly described and compared to a conventional narrowband transmitter, via time domain simulations of the current on the loop. A brief analysis of the affect of ohmic loss on the stored current is presented. Initial results suggest that the dissipation in the loop is negligible over short symbol durations, but motivates a discussion about the need for a more comprehensive parametric study for this class of DAM transmitters.
Partially Optimal Edge Fault-Tolerant Spanners.

Recent work has established that, for every positive integer $k$, every $n$-node graph has a $(2k-1)$-spanner on $O(f^{1-1/k} n^{1+1/k})$ edges that is resilient to $f$ edge or vertex faults. For vertex faults, this bound is tight. However, the case of edge faults is not as well understood: the best known lower bound for general $k$ is $\Omega(f^{\frac12 - \frac{1}{2k}} n^{1+1/k} +fn)$. Our main result is to nearly close this gap with an improved upper bound, thus separating the cases of edge and vertex faults. For odd $k$, our new upper bound is $O_k(f^{\frac12 - \frac{1}{2k}} n^{1+1/k} + fn)$, which is tight up to hidden $poly(k)$ factors. For even $k$, our new upper bound is $O_k(f^{1/2} n^{1+1/k} +fn)$, which leaves a gap of $poly(k) f^{1/(2k)}$. Our proof is an analysis of the fault-tolerant greedy algorithm, which requires exponential time, but we also show that there is a polynomial-time algorithm which creates edge fault tolerant spanners that are larger only by factors of $k$.
Fixed-Priority Scheduling for Reliable and Energy-Aware (m,k)-Deadlines Enforcement with Standby-Sparing

For real-time computing systems, energy efficiency, Quality of Service, and fault tolerance are among the major design concerns. In this work, we study the problem of reliable and energy-aware (m,k)-deadlines enforcement using standby-sparing under fixed-priority assignment. The standby-sparing systems adopt a primary processor and a spare processor to provide fault tolerance for both permanent and transient faults. In order to reduce energy consumption for such kind of systems, we proposed two novel scheduling schemes under the QoS constraint of (m,k)-deadlines: one for task sets partitioned with deeply-red pattern and one for task sets partitioned with evenly distributed pattern. The evaluation results demonstrate that our proposed approaches significantly outperformed the previous research in energy conservation while assuring (m,k)-deadlines and fault tolerance for real-time systems.
Analysis of a ceramic bimorph piezoelectric gyroscope

The mechanism of piezoelectric transformers for producing high voltage is incorporated into a ceramic beam bimorph piezoelectric gyroscope for generating high voltage sensing signal. For the analysis of the gyroscope, one-dimensional equations of beam piezoelectric bimorphs are derived from the three-dimensional equations of linear piezoelectricity. The equations are employed in the analysis of the bimorph gyroscope. Free and forced vibration solutions are obtained showing high voltage sensitivity.
Immunoglobulin response to Salmonella enteritidis outer membrane proteins. Use for evaluating infectious status.

There has been a steady increase in the incidence of Salmonellosis in humans over the past decade in part due to consumption of eggs and poultry products contaminated with Salmonella enteritidis (SE). Identifying the SE infectious status of flocks is critical for maintaining safety in food production and the economic welfare of poultry producers. Traditionally, bacterial cultures of fecal drag swabs, organs and egg samples are used to monitor the status of flocks for SE. Despite the high sensitivity and specificity of bacterial culture techniques, the extremely low incidence of SE shedding in eggs (<0.03%) may preclude detection by culture. Although published reports have indicated that environmental cultures may have predictive value for an older flock’s potential to produce contaminated eggs, results of environmental cultures may hold little predictive value for young flocks and instead result in the diversion of large numbers of eggs when the risk of SE positive eggs is still very low (Schlosser et al., 1995). Evaluation of the immune status of birds by the enzyme linked immunosorbent assay (ELISA) has the potential to predict SE infectious status with a sensitivity comparable to the low incidence of SE shedding in eggs. This research focuses on the development of a diagnostic ELISA used for detecting anti-Salmonella enteritidis outer membrane protein (OMP) antibodies in egg yolk samples that may reliably predict the likelihood of SE shedding in eggs. Results of egg yolk and serum OMP ELISAs are correlated with a commercial ELISA kit and culture data from egg and tissue samples from the same birds.
Diseconomies of Scale in Employment Contracts

A central question in industrial organization is what determines the size of firms. This question is closely linked to a central assumption in microeconomics generally, that "managerial diseconomies of scale" limit the size of firms. If such diseconomies of scale did not exist, many industries would be natural monopolies because average cost declines with output for any technology with a fixed cost and constant marginal cost. This was noted by Sraffa and Kaldor, who concluded that perfect competition was unrealistic. Modern textbook theory, rejecting the premise of constant marginal cost, notes that if marginal cost rises with output, then a large firm is inefficient and a competitive market is feasible. The combination of rising marginal cost and a fixed cost generates the Vinerian U-shaped average cost curve, not natural monopoly. The commonly given reason for increasing long-run marginal cost, a reason mentioned as far back as Kaldor, is that a larger firm is harder to manage.
NZB serum factor (NZB-SF): B precursor cell maturation factor identified in murine lupus: I. Identification of 60-kDa glycoprotein as the major component from both spleen cell supernatant and serum

Abstract NZB serum factor (NZB-SF), initially identified in sera of very young NZB mice, can enhance maturation and proliferation of sIg pre-B cells in marrow. In the present study, spleen cell supernatant from young NZB mice was used as a source of NZB-SF. NZB mice were treated with Corynebacterium parvum 2 weeks prior to sacrifice, and harvested spleen cells obtained at sacrifice were cultured for 24 hr in serum-free medium. One liter of spleen cell supernatant prepared in this way contained NZB-SF-like activity equivalent to that present in 10 ml of serum collected from young NZB mice. NZB-SF was purified on an affinity Chromatographie column conjugated with mouse IgG 1 monoclonal antibody (mAb) against NZB-SF. The purified NZB-SF had pI 7.8 and showed one major band of 60 kDa and a faintly stained 35-kDa band upon SDS-PAGE under nonreducing conditions. The 60-kDa NZB-SF extracted from the gel slice was also more potent in dot blot ELISA (>100 times) than the 35 kDa NZB-SF and was biologically active. After endoglycosidase F treatment, but not after treatment with a reducing agent (2-ME), the two bands merged into a single band at the 15-kDa position. Amino acid sequence analysis of endo-F treated NZB-SF indicated that the N-terminus of this protein is blocked. Serological and functional studies of affinity-purified NZB-SF have revealed that NZB-SF is distinguishable from IL-1α, IL-2, IL-3, IL-4, IL-5. IL-6, CSF-GM, IFN-γ, and TNFα. Therefore, a major component of NZB-SF(s) in the spleen cell supernatant may be an apparently novel 60-kDa glycoprotein with a single amino acid backbone. Sera and spleen cell supernatants from normal strains of mice (DBA/2, B6. or BALB/c) were also applied to the immuno-affinity column used to purify NZB-SF. It was found that trace amounts of NZB-SF are present also in serum of normal strains of mice and that spleen cells of these mice can also produce NZB-SF in vitro following stimulation with C. parvum - In SDS-PAGE, the 60-kDa NZB-SF is also the major component of NZB-SF in normal strains of mice. These results suggest that the 60-kDa NZB-SF may be of physiological importance in B cell differentiation and that this physiological factor is overproduced in autoimmune-prone NZB mice.
A comparison of hypoxemia and exercise electrocardiography in coronary artery disease. Diagnostic precision of the methods correlated with coronary angiography.

Exercise and hypoxemia electrocardiography were done when the resting ECG was normal in 35 normal control subjects, in 25 with atypical chest pain not believed clinically to be angina pectoris, and in 43 patients with typical angina pectoris. Coronary arteriography was done in all 68 patients of the latter two groups. Two of the patients believed clinically to have no coronary disease had minimal angiographic evidence of arteriosclerosis. Six of the patients with typical symptoms of angina pectoris had normal coronary arteriography. In both the normal controls and those with angiographically normal vessels, about 10 per cent had “ischemic” ST depression (segment flat for ≥ 0.08 second) ≥ 0.5 mm. with hypoxemia. Depression of the R-ST junction alone was rare. In the 39 patients with coronary disease, hypoxemia produced “ischemic” ST depression ≥ 0.5 mm. in 67 per cent, J depression in 7 per cent, and no ST change in 26 per cent. The in-exercise ECG showed J depression averaging 1.0 mm. in 83 per cent of the controls and in 48 per cent of the angiographically normal patients. “Ischemic” ST depression ≥ 1.0 mm. occurred in only 5 per cent. In the 39 patients with coronary disease, exercise produced segmental ST depression < 1.0 mm. in 8 per cent, “ischemic” depression ≥ 1.0 mm. in 46 per cent, J depression in 36 per cent, and no ST change in 10 per cent. The QXQT and QT ratios were “abnormal” in the majority of cases with coronary artery disease, but also in half of the normals, and were unreliable in the evaluation of ST depression. This study has shown the relatively high incidence of J depression with exercise in both normal subjects and those with coronary disease. While false-positive tests could be held to a minimum by accepting only “ischemic” ST depression ≥ 1.0 mm. as the criterion of a positive test, this finding occurred with exercise in less than half of the patients with documented coronary disease. Hypoxemia testing produced “ischemic” ST-segment depression ≥ 0.5 mm. in 23 of the patients with documented coronary disease. Although this test was less sensitive than exercise, the ST alterations which occurred were more discriminating.
A Multi-Faceted Approach is Necessary to Protect Endangered Species: A Case Study of the Critically Imperiled North Atlantic Right Whale

While protection of endangered species in the United States is mandated for listed species under the Endangered Species Act and the Marine Mammal Protection Act, both require ancillary efforts to ensure their intents are enforced. Science, negotiation, litigation, and lobbying for political solutions are all tools that can be brought to bear to ensure compliance with protective laws. However, there is a right and wrong time for the use of each of these tools. This paper provides a short discussion of the available tools, the likelihood of success or failure of each depending on when and how they are used, and it makes the case for a multifaceted approach to protection of endangered species, using critically endangered right whales as a case study.
β-catenin loss-of-function and its putative role as a tumor suppressor in sarcomagenesis

Proc Amer Assoc Cancer Res, Volume 47, 2006 4609 The goal of this project is the elucidation of the Wnt/β-catenin pathway in sarcomagenesis, specifically that of malignant fibrous histiocytoma (MFH), a common high grade form of sarcoma. The cell of origin of sarcomas is unknown, and the issue of whether a mature differentiated mesenchymal cell becomes transformed, or whether a mesenchymal stem cell is the precursor to all sarcomas, with differentiation pathways a bystander effect of the transforming event, is as yet unexplored. As a result, neither the cell of origin nor the pathways involved in the tumorigenicity of MFH are known. Using an in vitro mesenchymal stem cell differentiation model system and a novel gene expression analysis approach in which sarcomas are compared not to their normal mature tissue/cell counterparts, but to their normal developing tissue/cell counterparts, we have been able to identify the human mesenchymal stem cell (hMSC) as the apparent precursor cell of MFH. Building on the hMSC-MFH connection we have further observed that Dickkopf-1 (Dkk1), a specific secreted inhibitor of the Wnt/β-catenin pathway, is elevated in MFH as compared to other sarcomas. This is a vital observation, since DKK1 has been shown to be necessary for hMSC cell cycle re-entry. In hMSCs Dkk1 levels decline and nuclear β-catenin accumulates as hMSCs reach confluence, a prerequisite for initiation of in vitro differentiation. However, in an MFH cell line no nuclear β-catenin accumulation was noted. We therefore hypothesized that β-catenin’s loss of function, as determined by its failure to accumulate in the nucleus in MFH cells, leads to inhibition of differentiation and maintenance of the tumor phenotype of MFH. We tested this hypothesis by treating the MFH cell line with an antibody to DKK1 (capable of sequestering secreted DKK1) and lithium (a Wnt pathway activator) which resulted in accumulation of nuclear β-catenin and expression of early markers of mesenchymal differentiation in the presence of hMSC differentiation medium. Taken together, these data suggest a model of sarcomagenesis in which a key event is the lack of nuclear β-catenin accumulation. This work suggests a novel function of β-catenin as a tumor suppressor and also identifies its central role in sarcomagenesis, suggesting novel therapeutic targets and a differentiation therapy approach for MFH and potentially other sarcomas.
ISOLATION OF RUBELLA VIRUS FROM A MOTHER AND FETUS.

This study reports isolation of rubella virus from a primagravida in the first month of pregnancy and subsequent recovery of the agent from viable fetal tissue delivered by uterine curettage 57 days after onset of the maternal exanthem.
Synergistic Effect of Ethanol to α-Pinene in Primary Attraction of the Larger Pine Shoot Beetle, Tomicus piniperda

α-Pinene and ethanol were released in the approximate proportions 1:0.1, 1:0.9 and 1:9 (at 21°C). Ethanol, released in the range of 3–279 mg/day, generally synergized the attraction of T. piniperda to α-pinene (30 mg/day at 21°C), although attraction to the mixtures varied within and between years. The low release rate of ethanol together with α-pinene attracted a significantly higher number of beetles than α-pinene alone in 1995, April of 1996, and in 1997. Lures with the medium release rate of ethanol were the most attractive only in March of 1996. The high dose of ethanol significantly synergized attraction to α-pinene in 1995 and 1997. The variable attraction of T. pinipeda to ethanol and α-pinene at various release rates and proportions may be due to the temperature dependent nature of beetle antennal sensitivity. At ambient temperatures of 10–13°C. T. piniperda was most attracted to the lures with α-pinene and high release rates of ethanol, at 14–17°C it was most attracted to those with medium release rates of ethanol, and at 18°C and higher it was most attraacted to those with low release rates of ethanol.
Status and Prospects of Minority Students in Traditional Medical Schools

There is a need to increase the number and the success rate of minority students enrolling in medical careers. Although an increasing number of minorities enter the freshman year of undergraduate education in Wisconsin, the rate at which they enter is still substantially less than that for all students in the state as a whole (USDHEW, 1970, 1972a,b; see Table 1).
Scattering, Resonance, Creeping Wave, Traveling Wave and All That: UWB Measurements of Various Targets

Ultra Wide Band (UWB) impulse radar has the potential to perform target identification. In order to realize this potential, target signatures must be measured and understood from the stand point of electromagnetic scattering. This paper discusses measurements of target “echoes” using an impulse UWB system.
Promoting Critical Thinking Through Discussion

Being able to think and speak effectively and thoughtfully is a valuable commodity to function successfully with civility in a democratic society and must be practiced. A form of discussion called Socratic seminaring, enhances teaching and learning at the college level in this regard by encouraging the development of thinking skills and student voice. In this article, readers are offered an opportunity to view the author’s initial experience with this form of discussion at the college level within a teacher education program from theoretical and practical lenses.
The ecology of macroinvertebrates inhabiting native grasslands and their role in the feeding ecology of sandhill cranes

6 INTRODUCTION 8 STUDY AREAS 10 METHODS 13 Data Collection 13 Data Analysis 16 RESULTS 18 site Characteristics 18 Macroinvertebrate Composition and Diversity 22 Environmental Factors Affecting Earthworms 28 Environmental Factors Affecting Other Macroinvertebrates 37 DISCUSSION 45 Macroinvertebrate Response to Drought Conditions 45 Macroinvertebrate Response to Abiotic and Biotic Factors 47 MANAGEMENT IMPLICATIONS 53 LITERATURE CITED 54
Addicts, Fences, and the Market for Stolen Goods:

Examination of the literature of the heroin problem in the United States Reveals that there has been scant attention paid to the type of property crime specialized in by addicts or to the marketing network of addict-stolen goods. This paper begins to remedy both neglects by focusing on merchandise theft as a primary source of income for the heroin addict. A methodology is developed for estimating the income addicts receive for merchandise that they steal. Next a method is discussed for determining the type of middlemen who purchase stolen merchandise from addicts and how much they mark up the items before retailing them in the secondhand goods market. This yields estimates for the retail value of goods stolen and the gross revenue to middlemen. Since addicts tend to sell stolen items to otherwise legitimate businessmen, not underground fences as is widely believed, there appears to be substantial scope for reducing merchandise theft by instituting stricter regulations on the sale of secondhand goods. A sy...
Occlusion of the transverse sinus by meningioma simulating pseudotumor cerebri

The authors report a case of meningioma obstructing the transverse sinus simulating pseudotumor cerebri. CT was negative but brain scan was abnormal. The radiological diagnosis of meningioma in the region of the transverse sinus proved to be difficult. In suspected cases, radioactive isotope brain scan, digital subtraction angiography or magnetic resonance imaging are important supplementary tests to confirm the diagnosis of sinus obstruction. Evidence of rerouting of cortical venous drainage should be sought when angiography is performed.
Macrocyclic Inhibitors of β-Secretase: Functional Activity in an Animal Model.

A macrocyclic inhibitor of β-secretase was designed by covalently cross-linking the P1 and P3 side chains of an isophthalamide-based inhibitor. Macrocyclization resulted in significantly improved potency and physical properties when compared to the initial lead structures. More importantly, these macrocyclic inhibitors also displayed in vivo amyloid lowering when dosed in a murine model.
Pion production and the higher resonances in pion-nucleon scattering☆

The reaction π + N → 2π + N has been studied in the vicinity of the higher resonances in the pion-nucleon cross section. The Low equation for the production amplitude is transformed into an integral equation by isolating the true one-meson intermediate states and discarding higher order contributions. The only part kept in the inhomogeneous term corresponds to the collision of a pion in the nucleon cloud with the incident pion in the resonant T = J = 1 state, which is simulated by an unstable vector Boson. Crossed terms are neglected and the 2π-N state is described by the static model. The terms kept in the sum over states describe the rescattering (off the nucleon) of one of the outgoing pions. The required off-the-energy-shell elastic scattering amplitude is approximated by the 3-3 resonance formula of Chew and Low. With these simplifications the Low equation for the production amplitude reduces to an easily soluble linear integral equation. The rescattering amplitude, which dominates the inhomogeneous term in the resonance region, is proportional to the 3-3 scattering amplitude of one of the outgoing pions. Although the result provides some support for the conventional isobar model, it is important to note that the largeness of the rescattering term arises from scattering far off the energy shell, rather than by “real” excitation as in the phenomenological isobar model. Quantitative calculations for the D32 channel leading to a p-wave (J = 32) and an s-wave pion produce a maximum in the cross section near 600 Mev incident pion lab energy. For a π-π resonance energy squared S = 10, agreement with experiment is obtained with a width about one third that suggested by nucleon electromagnetic structure. In our approximation, the well known 600 Mev D32 isospin 12 resonance occurs at the same energy as the 800 Mev D32 isospin 32 resonance. It is assumed, but not proved, that the neglected terms are responsible for the splitting of the resonance energies. When this splitting is taken into account, the predicted charge state ratios near the second resonance agree well with existing data. The “third” resonance occurs for the state having two p-wave pions, according to the present theory, although no numerical calculations were made for this case. This point of view suggests that the F32, P32, and P12 incident channels contribute to the third resonance.
Vibrational excitation and dissociative attachment of a triatomic molecule: CO 2 in the collinear approximation

The effective R-matrix model and the R-matrix propagative method applied earlier to elec- tron\char21{}diatomic-molecule scattering are extended to treat dissociative attachment of collinear triatomic molecules. To describe the vibrational excitation and dissociative attachment of ${\mathrm{CO}}_{2}$ in the 4-eV region, the nuclear dynamics is solved on a Wall-Porter potential-energy surface. A hybrid approach is developed in which the ${L}^{2}$ and R-matrix propagation methods are combined to evaluate the global R matrix. Our calculations show that it is easier to excite the symmetric mode vibrations than the asymmetric mode vibrations. Our results also show that the observed structures in the energy dependence of the dissociative attachment cross sections are due to the vibrational states of the negative ion (${\mathrm{CO}}_{2}$${\mathrm{}}^{\mathrm{\ensuremath{-}}}$) and not to the vibrational states of the CO fragment.
Towards clinical trials of lie detection with fMRI

Recent reports of successful fMRI-based discrimination between lie and truth in single subjects raised the interest of prospective users and a public concern about the potential scope of this technology. The increased scrutiny highlighted the lack of controlled "real life", i.e. prospective clinical trials of this technology that conform to the common standards of medical device development. The ethics of conducting such trials given the paucity of data on fMRI-based lie detection has also been questioned. To probe the potential issues of translating the laboratory research into practice, we conducted a case study in which we adapted the standard Guilty Knowledge Test (GKT), a well-established model of producing deception, to the common scenario of lying on a resume. The task consisted of questions about pertinent items on the subject's resume, three of which could be independently verified as truth (KNOWN) and three that could not be verified and were thus termed UNKNOWN. The subject had an incentive to lie on all UNKNOWN items, and on debriefing confirmed that he had done so. Data was preprocessed, masked with a priori regions of interest, thresholded, and qualitatively evaluated for consistency with the previously reported prefronto-parietal Lie > Truth pattern. Deceptive responses to two out of the three UNKNOWN items were associated with the predicted prefronto-parietal fMRI pattern. In the third UNKNOWN this pattern was absent, and instead, increased limbic (amygdala and hippocampus) response was observed. Based on published prefronto-parietal Lie response pattern, only the first two items could be categorized as Lie. If confirmed, this demonstration of amygdala and hippocampus activation in a Lie > Truth contrast illustrates the need to integrate the limbic system and its emotional and cognitive correlates into the existing model of deception. Our experiment suggests an approach to a naturalistic scenario and the research questions that need to be answered in order to set the stage for prospective clinical trials of fMRI-based lie detection.
Chromatin Modulation by Oncogenic Transcription Factors: New Complexity, New Therapeutic Targets

Oncogenic transcription factors such as PML-RARα, RUNX1-MTG8, and others work in large part by the recruitment of inhibitors of gene transcription to target promoters leading to aberrant repression of gene expression. PML-RARα, an archetypal chimeric oncoprotein, was previously shown to bring complexes of histone deacetylases (HDACs), histone methyltransferases (HMTases), and DNA methyl transferases (DNMTs) to target genes. In this issue of Cancer Cell , Villa et al. show that the full complement of chromatin machinery can be commandeered by these transcription factors with the polycomb group of proteins representing the newest identified recruit.
Effects of bars and blanks on recognition of words and nonwords embedded in a row of letters

Solid bars or blank spaces placed before, after, or on both sides of a pronounceable four-letter string embedded in a longer string of letters facilitated recognition of the embedded string. This effect was equal whether bar or blanks were used, and whether the embedded string was a word or a pronounceable nonword. The effect of bars or blanks on pronounceable strings was interpreted in terms of a multiletter processing operation.
Implication of multiple mechanisms in apoptosis induced by the synthetic retinoid CD437 in human prostate carcinoma cells.

The synthetic retinoid 6-[3-(1-adamantyl)-4-hydroxyphenyl]-2-naphthalene carboxylic acid (CD437) induces apoptosis in several types of cancer cell. CD437 inhibited the growth of both androgen-dependent and -independent human prostate carcinoma (HPC) cells in a concentration-dependent manner by rapid induction of apoptosis. CD437 was more effective in killing androgen-independent HPC cells such as DU145 and PC-3 than the androgen-dependent LNCaP cells. The caspase inhibitors Z-VAD-FMK and Z-DEVD-FMK blocked apoptosis induced by CD437 in DU145 and LNCaP cells, in which increased caspase-3 activity and PARP cleavage were observed, but not in PC-3 cells, in which CD437 did not induce caspase-3 activation and PARP cleavage. Thus, CD437 can induce either caspase-dependent or caspase-independent apoptosis in HPC cells. CD437 increased the expression of c-Myc, c-Jun, c-Fos, and death receptors DR4, DR5 and Fas. CD437's potency in apoptosis induction in the different cell lines was correlated with its effects on the expression of oncogenes and death receptors, thus implicating these genes in CD437-induced apoptosis in HPC cells. However, the importance and contribution of each of these genes in different HPC cell lines may vary. Because CD437 induced the expression of DR4, DR5 and Fas, we examined the effects of combining CD437 and tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) and Fas ligand, respectively, in HPC cells. We found synergistic induction of apoptosis, highlighting the importance of the modulation of these death receptors in CD437-induced apoptosis in HPC cells. This result also suggests a potential strategy of using CD437 with TRAIL for treatment of HPC.
A "Go With the Winners" approach to finding frequent patterns

In their seminal work on Go With the Winners (GWW) algorithms, D. Aldous and U. Vazirani [3] proved a sufficient condition for the number of particles needed for reaching the bottom of a tree with high probability via a GWW random walk. However, to use this result in practice would require knowledge of the entire search tree which is infeasible for most problems. In this paper we improve slightly on this situation by deriving a recurrence relation that provides an upper-bound for a tree's imbalance in terms of the imbalance between tree levels that are close to one another, provided that these latter imbalances can be measured with sufficient accuracy.We then turn our attention to the problem of finding both frequent and infrequent patterns in a database. One of the most widely used algorithms for finding frequent patterns in memory-resident databases is a randomized algorithm first proposed by Gunopulos et al. [12]. We show that such an algorithm is precisely one for which the GWW paradigm was designed to improve on. Experimental results using the Splice-junction Gene Sequences Database [4] are also provided and lend empirical evidence of the benefits of using GWW.
Inhibition of DNA synthesis in cultured hepatocytes by endotoxin-conditioned medium of activated stellate cells is transforming growth factor-β and nitric oxide-independent

Activated hepatic stellate cells play a major role in the pathophysiology of chronic liver disease. They can influence the metabolism of hepatocytes by producing a variety of cytokines and growth factors. Upon stimulation with endotoxin, stellate cells also synthesize nitric oxide (NO), a potent mediator of growth of several cell types including hepatocytes. We investigated the effect of serum-free medium conditioned by activated stellate cells in the absence and presence of endotoxin on NO and DNA synthesis in hepatocytes. Stellate cells and hepatocytes were isolated by enzymatic digestion of the liver. Stellate cells were cultured for 10 days after which the majority exhibited alpha-smooth muscle actin (a marker for activated cells); hepatocytes were used after overnight culture. While the medium conditioned by stellate cells in the absence of endotoxin stimulated DNA synthesis in hepatocytes, medium conditioned in its presence inhibited this process in an endotoxin concentration-dependent manner (10 - 1000 ng ml(-1)). Endotoxin-conditioned stellate cell medium also stimulated NO synthesis in hepatocytes; the effect was consistent with increased protein and mRNA expression of inducible NO synthase (iNOS). However, inhibition of DNA synthesis in hepatocytes caused by endotoxin-conditioned stellate cell medium was unaffected by the NOS inhibitor, L-N(G)-monomethylarginine (L-NMMA), guanylyl cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), and neutralizing antibodies for TGF-beta, IL-1beta, IL-6 and TNF-alpha. These results indicate that factors other than these cytokines produced by activated stellate cells upon stimulation with endotoxin or by hepatocytes challenged with endotoxin-conditioned stellate cell medium inhibit DNA synthesis in hepatocytes.
Postnatal development of N-methyl-D-aspartate receptor subunits 2A, 2B, 2C, 2D, and 3B immunoreactivity in brain stem respiratory nuclei of the rat

Previously, we reported that a critical period in respiratory network development exists in rats around postnatal days (P; P12-P13), when abrupt neurochemical, metabolic, and physiological changes occur. Specifically, the expressions of glutamate and N-methyl-d-aspartate (NMDA) receptor (NR) subunit 1 in the pre-Botzinger complex (PBC), nucleus ambiguus (Amb), hypoglossal nucleus (XII), and ventrolateral subnucleus of solitary tract nucleus (NTS(VL)) were significantly reduced at P12. To test our hypothesis that other NR subunits also undergo postnatal changes, we undertook an in-depth immunohistochemical study of NR2A, 2B, 2C, 2D, and 3B in these four respiratory nuclei in P2-P21 rats, using the non-respiratory cuneate nucleus (CN) as a control. Our results revealed that: (1) NR2A expression increased gradually from P2 to P11, but fell significantly at P12 in all four respiratory nuclei (but not in the CN), followed by a quick rise and a relative plateau until P21; (2) NR2B expression remained relatively constant from P2 to P21 in all five nuclei examined; (3) NR2C expression had an initial rise from P2 to P3, but remained relatively constant thereafter until P21, except for a significant fall at P12 in the PBC; (4) NR2D expression fell significantly from P2 to P3, then plateaued until P12, and declined again until P21; and (5) in contrast to NR2D, NR3B expression rose gradually from P2 to P21. These patterns reflect a dynamic remodeling of NMDA receptor subunit composition during postnatal development, with a distinct reduction of NR2A expression during the critical period (P12), just as NR1 did in various respiratory nuclei. There was also a potential switch between the neonatal NR2D and the more mature NR3B subunit, possibly around the critical period. Thus, during the critical period, NMDA receptors are undergoing greater adjustments that may contribute to attenuated excitatory synaptic transmission in the respiratory network.
Continuous warfarin versus periprocedural dabigatran to reduce stroke and systemic embolism in patients undergoing catheter ablation for atrial fibrillation or left atrial flutter

Purpose Left atrial catheter ablation for patients with atrial fibrillation (AF) requires periprocedural anticoagulation to minimize thromboembolic complications. High rates of major bleeding complications using dabigatran etexilate for periprocedural anticoagulation have been reported, raising concerns regarding its safety during left atrial catheter ablation. We sought to evaluate the safety and efficacy of a dabigatran use strategy versus warfarin, at a single high-volume AF ablation center.
Vascular Dendritic Cells in Giant Cell Arteritis

Giant cell arteritis (GCA) is a granulomatous vasculitis that selectively targets medium-sized and large arteries, especially the cranial branches of the aorta. The inflammatory activity of vascular lesions is driven by adaptive immune responses, with CD4 T cells undergoing clonal expansion in the vessel wall and releasing interferon gamma. Recent studies have described a distinctive population of dendritic cells (DCs) localized at the adventitia-media border of normal medium-sized arteries that appear to play a critical role in the initiation of vasculitis. Immune effector functions of this DC population are being examined in human artery-severe combined immunodeficient (SCID) mouse chimeras. In their constitutive form, CD11c+ fascin+ adventitial DCs are not recognized by alloreactive T cells. Triggering with Toll-like receptor (TLR) ligands is sufficient to break this state of tolerance and initiate DC activation, T-cell recruitment, T-cell activation, and T-cell retention in the arterial wall. Systemic administration of ligands for TLR2 or -4 in human artery-SCID chimeras drives differentiation of adventitial DCs into chemokine-producing effector cells with high-level expression of both CD83 and CD86 and mediates T-cell regulatory function through release of interleukin 18. In established vasculitis, fully matured DCs retain antigen-presenting function; antibody-mediated DC depletion disrupts T-cell and macrophage activation and has marked anti-inflammatory effects. We conclude that adventitial DCs, an indigenous cell population of the arterial wall, are responsive to pathogen-derived macromolecules and have gatekeeper function in regulating T-cell recruitment and retention to the arterial adventitia. A switch of adventitial DCs from being nonstimulatory to T-cell activating emerges as a critical event in the initiation of vasculitis.
Basolateral Sorting of Syntaxin 4 Is Dependent on Its N-terminal Domain and the AP1B Clathrin Adaptor, and Required for the Epithelial Cell Polarity

Generation of epithelial cell polarity requires mechanisms to sort plasma membrane proteins to the apical and basolateral domains. Sorting involves incorporation into specific vesicular carriers and subsequent fusion to the correct target membranes mediated by specific SNARE proteins. In polarized epithelial cells, the SNARE protein syntaxin 4 localizes exclusively to the basolateral plasma membrane and plays an important role in basolateral trafficking pathways. However, the mechanism of basolateral targeting of syntaxin 4 itself has remained poorly understood. Here we show that newly synthesized syntaxin 4 is directly targeted to the basolateral plasma membrane in polarized Madin-Darby canine kidney (MDCK) cells. Basolateral targeting depends on a signal that is centered around residues 24–29 in the N-terminal domain of syntaxin 4. Furthermore, basolateral targeting of syntaxin 4 is dependent on the epithelial cell-specific clathrin adaptor AP1B. Disruption of the basolateral targeting signal of syntaxin 4 leads to non-polarized delivery to both the apical and basolateral surface, as well as partial intercellular retention in the trans-Golgi network. Importantly, disruption of the basolateral targeting signal of syntaxin 4 leads to the inability of MDCK cells to establish a polarized morphology which suggests that restriction of syntaxin 4 to the basolateral domain is required for epithelial cell polarity.
Effects of Sunflower Hulls on Digestibility and Performance by Growing Dairy Heifers Fed Varying Amounts of Protein and Fiber

A digestion trial involving 10 Holstein heifers evaluated rations containing 0, 10, 20, 30, and 40% sunflower hulls. Five experimental rations were isonitrogenous at 15% crude protein and 40% acid detergent fiber which was supplied primarily by alfalfa hay and sunflower hulls. Increasing the quantity of sunflower hulls in the ration decreased nutrient digestibility for dry matter, acid detergent fiber, and protein. Each 10% increment of sunflower hulls up to 40% of the experimental ration resulted in a reduction of digestibility coefficients for dry matter and acid detergent fiber, respectively, of 7.7% (linear regression coefficient; square correlation .90) and 4.9% (square correlation .78). Eight Holstein heifers were used for the feeding trial in two replicates of a 4 × 4 Latin square experiment to determine the nutritive value of sunflower hulls as a roughage source in growing ruminant rations. Treatment variables were two concentrations of crude protein, 12 or 18%, and two concentrations of acid detergent fiber, 19 or 30% of ration dry matter. Heifers fed rations containing 18% protein, 19% acid detergent fiber (27% sunflower hulls) achieved the highest gain (1.36 kg/day) and efficiency of growth (gain/feed, 20.5%). Animals on 27% sunflower hull rations consumed less feed and gained more than those on 50% sunflower hulls.
The temperature-composition phase diagram and the miscibility gap of Hg 1−x Cd x Te solid solutions by dynamic mass-loss measurements

The dynamic mass-loss technique has been employed to measure Hg partial pressures over Te-saturated Hg1-xCdxTe solid solutions with x = 0.40, 0.54, and 0.70 in the 10-1 to 10-4 atm range. The relative chemical potentials of HgTe in Hg1-xCdxTe solid solutions have been calculated using the measured Hg partial pressures at temperatures below 413°C, and fitted into an analytical expression. A Gibbs-Duhem integration yielded the relative chemical potentials of CdTe. By combining the relative chemical potentials of the binary components HgTe and CdTe, an expression for the Gibbs free energy of mixing was derived. The binodal (miscibility gap) and spinodal curves of the Hg1-xCdxTe solid solutions have been established with the critical temperature and composition of 221°C and Hg0.40Cd0.60Te.
Chronotropic response to exercise predicts angiographic severity in patients with suspected or stable coronary artery disease

Inappropriate chronotropic response to exercise has been observed to correlate with poor prognosis in patients with coronary disease, but the mechanism for this association is not well defined. We attempted to examine the association between chronotropic response to exercise and angiographic severity of coronary disease in patients with suspected or stable coronary artery disease. The chronotropic response, expressed as peak heart rate, chronotropic index (ratio of heart rate reserve and metabolic reserve utilized), or percent maximal heart rate achieved, was correlated with angiographic findings obtained within 180 days of the test. Significant coronary disease was defined as > or = 1 stenosis of > or = 50% in a major epicardial artery or its main branches; severe coronary disease was defined as > or = 50% stenosis in all 3 epicardial arteries, or in the left main coronary trunk, or 2-vessel disease with > or = 70% proximal left anterior descending artery stenosis. We observed that peak heart rate and percent maximal heart rate achieved were independent negative predictors of both significant and severe coronary disease by logistic regression. The chronotropic index predicted severe coronary disease only. All 3 parameters of chronotropic response exhibited a significant gradient of abnormality across the spectrum of coronary disease (p < 0.01 for all), expressed by the number of vessels involved and correlated with left anterior descending artery involvement (p < 0.05 for all). We conclude that chronotropic response to exercise predicts the presence and angiographic severity of coronary disease. This association is likely related to the proportion of left ventricular myocardium rendered ischemic during stress.
A Microprocessor Controlled on-Line Monitor with Computed Trip Points for Long Lived Alpha Emitters in Aerosols

A four-channel microprocessor-controlled alpha-particle monitor with trip levels computed from background and source activity levels has been designed and constructed. This instrument, intended for monitoring uranium and transuranic particles contained in aerosols, uses virtual impactors to collect the particles and to provide background separation. Alpha spectrometry is subsequently used to separate the desired isotopes. The microprocessor performs trip point calculations, controls 12 four-decade counters and 12 fourdecade liquid crystal displays. It also monitors trip input information from flow and pressure monitors, a key pad for operator input, and controls a small printer used for report generation. This article covers the hardware and software techniques used to implement the device and the theoretical aspects of calculating the sliding scale trip point.
Interaction of stimulus parameters on the auditory brain stem response: a normal variant.

ABSTRACT The purpose of this investigation was to further define the effect that stimulus parameters of phase, intensity, and rate have insignificantly reducing the wave V amplitude. Two separate experiments were conducted to determine whether an interactive effect exists and how robust the effect was on wave V. Results revealed that wave V amplitude was reduced to less than half the absolute amplitude of the wave IV-V complex in 9 of the 39 subjects. The phenomenon was dependent upon stimulus parameters of rarefaction phase, high intensity, and low repetition rate. Conversely, the phenomenon was independent of cochlear integrity, sex, and test equipment. The implications to diagnostic interpretation during routine auditory brain stem response testing are discussed.
Solvent effects on geminate recombination dynamics after photodetachment

Abstract The time-dependent survival probability for photoelectrons produced following resonant excitation of I− in its first charge-transfer-to-solvent (CTTS) band is determined by femtosecond pump–probe spectroscopy. The solvent effect on localization and recombination dynamics of the detached solvated electrons in various hydroxylic solvents (H2O, CH3OH, C2H5OH, C3H7OH, C4H9OH) is studied. The data are consistent with a caged geminate pair being formed in the CTTS photodetachment step. In all solvents, the geminate recombination of the detached electron can be modeled as competition between diffusive escape from an attractive short-range potential (∼3kBT) and reverse electron transfer to reform ground state iodide.
When are intermediate processes of the same stochastic order

Abstract Let Z m ( n ) represent the m th largest order statistic in a random sample of size n . Here we study the process Z [ mt ] ( n ) , t > 0, where m ( n ) is an intermediate sequence such that m → ∞, m / n → 0 as n → ∞.
Kinetic Equation for a Dilute Gas with Short-Range Forces

Abstract : The kinetic equation for a dilute gas with short-range forces is derived by a method which we believe to be physically more transparent than other methods. We first derive a density expansion for the correlation functions, the coefficients of which are functionals of F, the first distribution function. These functionals relax to timeindependent functionals over a time interval t (which we argue to be of the order of the duration of a collision) after a time t sub o (which is characterized by the phases) from the initial time. The functionals contain F over the interval + and therefore the resulting kinetic equation is nonMarkoffian. The non-Markoffian behavior is removed by further expanding the correlation functions in a parameter that is the ratio of the duration of a collision to the mean free time. The results for the correlation functions are carried to first order and agree with those of other methods for configurations where the particles are interacting, and therefore lead to the same kinetic equation, but are otherwise different. (Author)