cssi/SciSciGPT-SciSciNet huggingface dataset:
The Src inhibitor AZD0530 cooperates with antiestrogens to inhibit human breast cancer growth in vitro and in vivo

AACR Centennial Conference: Translational Cancer Medicine-- July 20-23, 2008; Monterey, CA A41 Estrogen plays an important role in human breast cancer development and progression. It is a mitogen for estrogen receptor (ER) positive breast cancers. Upon estrogen binding, estrogen receptor- alpha (ER) recruits and activates Src leading to activation of MEK/MAPK and PI3K/Akt. Activation of these signaling kinases modulates cell cycle regulators to stimulate cell cycle progression. In this study, we investigated whether a novel Src inhibitor drug could synergize with antiestrogens (feslodex, tamoxifen and anastrozole) to inhibit cell proliferation in cell culture and in xenograft tumors in vivo . Aromatase inhibitors (AI) are used to block estrogen synthesis as an important treatment for postmenopausal women with estrogen receptor positive breast cancer. The AI anastrozole alone caused an incomplete cell cycle arrest in ER positive human breast cancer cells stably transfected with the aromatase gene (MCF-Arom5). Although the Src inhibitor, AZD0530 alone had no effect on cell cycle, it enhanced the antiproliferative effect of anastrozole on cultured MCF-AROM5. Using a dose of AZD0530 that on its own did not affect cell proliferation, it took 10 fold less anastrozole to arrest these cells when the anastrozole was used together with AZD0530. Treatment with anastrozole alone stimulated Src and MAPK activity, whereas treatment with anastrozole and AZD0530 together inhibited their activities. The two drugs together caused a greater p27 increase and cyclin E-Cdk2 inhibition than observed with either drug alone reflecting a more profound cell cycle arrest with the combination therapy. We also provide evidence for synergy between anastrozole and AZD0530 in vivo in MCF-AROM5 xenograft tumors in athymic mice. Without androstenedione, tumor growth was minimal through the whole experiment. In contrast, tumor volume increased rapidly with androstenedione treatment, reflecting the mitogenic effect of intracellular aromatase producing estrogen in this model. Daily oral AZD0530 (50mg/kg) had no effect on tumor growth compared with the androstenedione. Anastrozole alone suppressed tumor growth, with 0.25mg/kg anastrozole yielding a treated/control (%) of 62.1%. The combination therapy significantly delayed tumor growth, yielding a treated/control (%) of 46.7%. Our calculations indicate synergism between AZD0530 and anastrozole on xenograft tumors in vivo. All animals survived and showed no signs of toxicity or weight loss throughout the whole experiment. We also found that faslodex and tamoxifen, these two important estrogen blockers, could synergize with AZD0530 to inhibit the cell cycle by causing an upregulation of p27 levels, bingding of p27 to cyclinE-Cdk2 and kinase inhibition. These data show that antiestrogens cooperates with AZD0530 to inhibit ER positive breast cancer growth and support further clinical investigation of this combination for women with ER-positive breast cancer.
Compact solid state pulsed power architecture for biomedical workflows: Modular topology, programmable pulse output and experimental validation on Ex vivo platelet activation

We describe a system based on a Marx generator approach using all solid state components in a modular topology that enables higher voltages by simply adding more modules. This novel system maximizes parameter flexibility, including electric pulse amplitude, duration and repetition rate. Example of pulses generated by this all solid state generator of ∼20 kV/cm, ∼ 600 ns pulse width, and more than 300 A per pulse are shown to activate platelets by stimulating human PRP (platelet rich plasma) in a 2 mm cuvette. Two growth factors released during platelet activation were identical whether nsPEFs (nanosecond pulsed electric fields) or bovine thrombin, the standard clinical platelet activator, was used. Future in vivo studies will assess the effectiveness of nsPEFs activated platelet gels compared to those activated by bovine thrombin.
On estimating the phase of a periodic waveform in additive Gaussian noise, part 1

Motivated by recent advances in technology, a new look is taken at the problem of estimating the phase of a periodic waveform in additive Gaussian noise. The maximum a posteriori probability criterion with signal space interpretation is used to obtain the structures of optimum and some suboptimum phase estimators for the following cases: (1) known constant frequency and unknown constant phase with an a priori distribution; (2) unknown constant frequency and phase with a joint a priori distribution; (3) frequency a parameterized function of time with a joint a priori distribution on parameters and phase and (4) frequency a Gaussian random process.
Two faces of nitric oxide: lessons learned from the NOS2 knockout.

Nitric oxide synthases (NOSs) comprise a family of enzymes that generate the freely diffusible, free radical gas NO, by the conversion of l-arginine to l-citrulline in the presence of O2 and NADPH. Bioactive derivatives of NO (NOx) are produced depending on the redox state of the cell and the availability of substrates and cofactors.1 The three NOSs arise from separate genes, but each NOS molecule is composed of a calmodulin binding domain that links a carboxyl terminal flavin-containing reductase domain with an amino terminal heme-containing oxygenase domain.1 Neuronal NOS (or NOS1) and endothelial NOS (or NOS3) are constitutively active isoforms with calmodulin binding (and, consequently, enzyme activity) regulated by physiological [Ca2+], whereas inducible NOS (iNOS or NOS2) binds calmodulin tightly, even at physiological [Ca2+].1 Each of the three NOS isoforms is present in the heart, undergoes posttranslational modification, and is spatially constrained within the cell. NOS1 expression is limited and its physiological role is unclear. The largest sources in the heart of the cytokine (interleukin-1β [IL-1β], tumor necrosis factor-α [TNF-α], interferon-γ [IFN-γ], interleukin-6 [IL-6]) and lipopolysaccharide-inducible NOS2 are from cardiac myocytes, endothelial cells, and infiltrating macrophages. NOS3 is found in the endocardial and coronary arterial endothelium, myocytes, and specialized cardiac conduction tissue.1 Constitutive expression of NO is protective. Vascular effects include vasodilatation, inhibition of platelet adhesion and neutrophil infiltration, prevention of neointimal proliferation, and inhibition of vascular remodeling in heart. Cardiac effects of constitutive NO include regulation of the coronary circulation, heart rate, and contractility. In …
Healthcare Can Change from Within: Sustained Improvement in the Healthcare Response to Intimate Partner Violence

There is a great need to demonstrate sustained improvement in healthcare-based inquiry, intervention, and prevention provided to patients exposed to intimate partner violence (IPV). We evaluated implementation of the Healthcare Can Change from Within model (HCCW) in three primary care clinics and an emergency department within a large healthcare system, using two other primary care clinics for a usual-care comparison on selected variables. Outcome measures included individual-level variables (staff knowledge and attitudes) and system characteristics (clinic policies, procedures, patient education materials, and IPV documentation in patient records). Doctors and nurses reported increased self-efficacy, understanding of referral resources, and understanding of legal issues; IPV knowledge was unchanged. Intervention clinics implemented new policies and procedures, increased patient education, and increased documentation of IPV screening, an improvement which was sustained at 2-year follow-up. Results suggest HCCW is a promising practice for improving the healthcare response to IPV.
An improved automatic isotropic color edge detection technique

Abstract In many image processing applications, edge detection is a useful method for obtaining a simplified image that preserves the domain geometric structures and spatial relationships among variant image components. For providing automatic edge detection, two problems should be solved: one is feature extraction for calculating the edge strength, another is feature classification for automatic edge detection. For solving these two problems, we propose an improved automatic edge detection technique. Three color components of a color image and more potential edge patterns are integrated for solving the feature extraction problem. A fast entropic thresholding technique is also developed for solving the feature classification problem. Experimental results have confirmed that this proposed edge detector can provide more reasonable results as compared with the traditional isotropic edge operators, and its calculation cost has been reduced as compared with the complex edge detectors. Good balance between the calculation cost and the edge detection accuracy is achieved.
Estimating the likelihood of severe coronary artery disease

Purpose: To determine which clinical characteristics obtained by a physician during an initial clinical examination are important for estimating the likelihood of severe coronary artery disease, and to determine whether estimates based on these characteristics remain valid when applied prospectively and in different patient groups. Patients and Methods: We examined clinical characteristics predictive of severe disease in 6,435 consecutive symptomatic patients referred for suspected coronary artery disease between 1969 and 1983. Results: Eleven of 23 characteristics were important for estimating the likelihood of severe coronary artery disease. A model using these characteristics accurately estimated the likelihood of severe disease in an independent sample of 2,342 patients referred since 1983. The model also accurately estimated the prevalence of severe disease in large series of patients reported in the literature. Conclusions: These findings suggest that the clinician's initial evaluation can identify patients at high or low risk of anatomically severe coronary artery disease. Cost-conscious quality care is encouraged by identifying patients at higher risk for severe coronary artery disease who are most likely to benefit from further evaluation.
Time Course of Eosinophilic Recruitment and Pulmonary Toxicity Biomarkers in an Allergic Asthma Model in Brown Norway Rats.

Allergic asthma is a pulmonary disease characterized by antigen-induced pulmonary eosinophilia, airway hyperresponsiveness, antigen-specific IgE antibody responses, and broncho-constriction. In attempting to elucidate mechanisms associated with the pathogenesis of this disease, a number of animal models have been developed. The current studies were undertaken to develop a model of allergic asthma model in Brown Norway rats. Unlike the neutrophilic inflammatory response to inhaled particles in most strains of rats, inhalation of antigens in sensitized Brown Norway rats results in a complex cellular response which is characterized by a variety of inflammatory cell types, and is dependent on the time course of inflammatory cell recruitment. In characterizing this ovalbumin-challenge model of allergic asthma, it was important to assess the time course of pulmonary inflammation, cell proliferation, and apoptosis. Male Brown Norway rats were sensitized and boosted with intraperitoneal injections of ovalbumin in aluminum hydroxide on experimental days 1 and 8. On days 15-17, rats were challenged by an inhalation exposure to 5% ovalbumin and were evaluated by bronchoalveolar lavage (BAL) at 24 or 48 h postexposure (PE). Control rats were similarly treated to ovalbumin aerosol exposures; however, these animals had been sensitized and boosted with aluminum hydroxide (minus the ovalbumin). Cell differential evaluations demonstrated that the rats exposed for 3 days/24 h postexposure and for 2 days/ 48 h postexposure produced the greatest numbers of BAL eosinophils and corresponding indicators of pulmonary toxicity. It was interesting to note that earlier exposure time periods (i.e., 1 day/24 h PE) generated a predominantly neutrophilic inflammatory response, while longer exposure/postexposure time periods (i.e., 3 days/48 h) produced a predominant mononuclear inflammatory response. Subsequent studies demonstrated that the 2-day/ 48-h protocol produced the optimum eosinophilic, cytotoxic, cell proliferative, and apoptotic response. Histopathological evaluations demonstrated a chronically active alveolitis and bronchiolitis, characterized by epithelial cell proliferation in the airways and inflammatory cell proliferation in the alveoli. Studies are ongoing to assess the cell types undergoing apoptosis in both the airway and parenchymal regions to fully characterize this model in order to assess its relevance and utility for studying asthma in humans.
Blacks, Hispanics, and Others Decentralization and Ethnic Succession

Decentralization in New York City has opened administrative careers for Hispanic and Black Americans.
Computer-aided retinal photocoagulation system.

Researchers at the University of Texas at Austin's Biomedical Engineering Laser Laboratory and the U. S. Air Force Academy’s Department of Electrical Engineering are developing a computer-assisted prototype retinal photocoagulation system. The project goal is to rapidly and precisely automatically place laser lesions in the retina for the treatment of disorders such as diabetic retinopathy and retinal tears while dynamically controlling the extent of the lesion. Separate prototype subsystems have been developed to control lesion parameters (diameter or depth) using lesion reflectance feedback and lesion placement using retinal vessels as tracking landmarks. Successful subsystem testing results in vivo on pigmented rabbits using an argon continuous wave laser are presented. A prototype integrated system design to simultaneously control lesion parameters and placement at clinically significant speeds is provided.
Gamma irradiation for control of insects in wheat flour.

When naturally or artificially infested wheat flour was packed in metal cans or multiwall paper bags and treated with doses of gamma irradiation ranging from 31.8–48.0 krad, populations of mixed stages and species of insects were not eliminated within 1 month. However, doses averaging as low as 15.0 krad did cause 100% mortality within 3 months of irradiation among eggs and young larvae of those species most likely to be present in flour. The results showed that if mortality of all eggs and young larvae is to be complete by the end of 1 month, the dose selected must be higher than the maximum dose used in the tests reported here.
Systemic lupus erythematosus in three ethnic groups: IX. Differences in damage accrual

Objective To determine the factors predictive of damage in a multiethnic (Hispanic, African American, and Caucasian) LUMINA (lupus in minority populations, nature versus nurture) cohort of patients with systemic lupus erythematosus (SLE) with disease duration of ≤5 years at enrollment (T0). Methods Variables (socioeconomic/demographic, clinical, immunologic, immunogenetic, behavioral, and psychological) were measured at T0 and annually thereafter. Disease damage was measured with the Systemic Lupus International Collaborating Clinics Damage Index (SDI), and disease activity was measured with the Systemic Lupus Activity Measure. The relationship between the different variables and the SDI at the last visit (TL) was examined (mean followup from diagnosis to TL 61 months; adjusted for disease duration). Poisson regression was used to identify the independent association between the different variables and SDI scores at TL. Results Seventy-two Hispanics, 104 African Americans, and 82 Caucasians were included. One-half of patients had not accrued any damage. Caucasians had the lowest SDI scores at T0, and Hispanics had the highest scores at TL. Renal damage occurred more frequently among Hispanics and African Americans, while integument damage was more frequent among African Americans. Neuropsychiatric (20%), renal (16%), and ocular (15%) damage occurred most frequently among all patients. Independent predictors of SDI at TL were age, corticosteroid use (maximum dose at T0), number of American College of Rheumatology (ACR) criteria met, disease activity, and abnormal illness-related behaviors. Other variables were less consistently associated with damage accrual (poverty in African Americans, lack of HLA–DRB1*0301 in Hispanics, presence of HLA–DQB1*0201 and acute onset of SLE in Caucasians). Conclusion Damage in SLE occurs from the outset in some, but not all, patients; Hispanics accrue damage more rapidly. Disease factors (corticosteroid use, number of ACR criteria met, disease activity, and acute-onset type) are important, but age and abnormal illness-related behaviors also contribute to overall damage in SLE.
Structure-Function Relationships in Aquaporins

The identification of members of the aquaporin family as the primary water channels of cell membranes has been followed up by an intense effort to determine how these channels work. Specifically, investigators have sought to learn why these channels are selective for water and how they exclude proton trafficking. Molecular-dynamics studies using elegant, extremely detailed computer models based on accurate crystallographic maps of the channels show the basis for the selectivity of the channel. Channel size, the location of hydrophobic amino-acid side chains, and specific interactions of water dipoles with a charged residue near the most constricted point of the channel indicate that water molecules travel in single file through the center of the channel, and that the orientation of water molecules is manipulated to prevent the formation of a water wire spanning the channel. Finally, the number of water molecules calculated to be aligned in single file in the channel constriction fits predictions based on classic studies of the osmotic permeability: diffusive permeability ratios in water-permeable membranes.
Leak after Whipple resection: preventable?

Background: Leakage of the pancreaticojejunal anastomosis has been a major complication after pancreaticoduodenectomy (Whipple operation), frequently reported in an incidence of 5 percent to 15 percent. The most widely used techniques of anastomosis have been variations of end-toend pancreaticojejunostomy. Complicating 152 end-to-end anastomoses, done by me (including 98 for carcinoma of the pancreas or ampulla), were 5 pancreatic anastomotic leaks; the fifth patient died of this complication. Study Design: The death resulting from a pancreatic anastomotic fistula led me to change my technique to an end of the pancreas to side of the jejunum, mucosa-tomucosa, pancreaticojejunostomy (intubated), a modification of the technique described by Cattell and used since 1985 by me in 56 consecutive patients. Patients were monitored for clinical evidence of a pancreatic fistula, including evaluation of amylase content in serum and, in most, in peritoneal drainage. Pancreatography through the exteriorized pancreatic catheter was possible if deemed advisable. Results: No pancreatic duct was too small or pancreas too soft to permit effective anastomosis. No clinical evidence developed of a pancreatic fistula, ＂sentinel bleed,＂ or acute pancreatitis, and no patient was recognized to have a high amylase content in the peripancreatic peritoneal drainage. Results of the pancreatogram were negative in three patients with peripancreatic infections and in one with severe cholestasis. Conclusions: Although consensus among surgeons does not exist as to technique of pancreatic anastomosis, the end-toside, mucosa-to-mucosa pancreatico-jejunostomy, intubated, has proved safer in my experience that end-to2end pancreaticojejunostomy. The experience has led me to believe that the technique may reduce the incidence of this fistula and contribute to making pancreaticojejunal leakage a preventable complication.
Fine-grained rocks: Shales or physilites

Abstract Fine-grained sediments and rocks containing a high percentage of phyllosilicate minerals have never been satisfactorily classified. Rocks names are poorly defined. The definition of many terms such as clay, clay mineral and shale are logically inconsistent. The major problems are caused by the assumption that there is a fixed relation between grain size and mineralogy and that structure is a basic parameter. Shallow-buried recent and ancient marine sediments with a high content of phyllosilicates commonly contain 60–80% clay and 20–40% silt. Phyllosilicates are present in approximately the same amounts as the clay-size material. Many fine-grained sediments that have been deeply buried commonly contain 30–40% clay; the phyllosilicate mineral content is in the range of 60–80%. In most fine-grained sediments, as deposited, the majority of the material is in the clay size. With burial and diagenesis, much of the clay-sized material grows to silt size. Thus, claystones are converted to siltstones. The term physil, an abbreviated form of phyllosilicate, is proposed to describe all sheet silicate minerals regardless of grain size. Physilites are rocks with a high content of physils. A simple classification is proposed in which size, mineralogy and structure are treated as independent variables.
Specific subclones derived from a multipotential clone of rat anterior pituitary cells.

Several functional subclones of rat anterior pituitary cells were established from our 2A8 clone which apparently contains a heterogeneous population of committed and uncommitted cells. On the basis of the hormones secreted into the culture media, as measured by radioimmunoassay, these subclones were divided into four categories, i.e., subclones which secrete (1) ACTH only, (2) prolactin only, (3) prolactin and GH or (4) ACTH, prolactin and GH. None of the subclones produced detectable amounts of thyrotrophic or gonadotrophic hormones. Subclones which secrete a single hormone have shown no change in the type of hormone produced, indicating that these subclones were each derived from a committed cell. The cells of all subclones exhibit a normal diploid karyotype and show good growth characteristics. The cells of the different subclones can be classified by phase contrast microscopy into four categories. However, no clear-cut ultrastructural features have been observed which can be correlated with the different categories of subclones. On the basis of the results a hypothesis is proposed relative to the functional cytodifferentiation of anterior pituitary cells.
Hexakis(tris(hydroxymethyl)phosphine oxide)metal(II) and (III) perchlorates [1]

Abstract Complexes of tris(hydroxymethyl)phosphine oxide (thpo) with various metal perchlorates were prepared by interaction of ligand and salt in triethyl orthoformate. Characterization of the new complexes by means of spectral, magnetic and conductance studies led to their formulation as [M(thpo) 6 ](ClO 4 ) n (M = Mg 2+ , Cr 3+ , Mn 2+ , Fe 2+ , Fe 3+ , Co 2+ , Ni 2+ , Cu 2+ , Zn 2+ , Cd 2+ , Nd 3+ ; n = 2 or 3), involving low symmetry hexacoordinated complex cations and exclusively ionic perchlorate. Thpo acts as a unidentate ligand, coordinating through the PO oxygen. The tendency of thpo to form 6:1 cationic metal complexes, in contrast to other phosphine oxides, which yield 4:1 or 5:1 complexs with the same metal perchlorates, is attributed to its lower ligand-field strength. The metal-thpo bonds are weaker than the corresponding bonds in the complexes of other phosphine oxides. This leads to a less sterically crowded environment around the central metal ion, and allows the accommodation of six thpo molecules in the first coordination sphere.
Complete Basis Set ab Initio Computational Exploration of the Lowest Energy, Unimolecular, Triplet Potential Energy Surface for Triplet Oxygen Atom Assisted Acetylene Rearrangement into Vinylidene

The unimolecular triplet potential energy surface was explored with the complete basis set method with the aim being to evaluate the possibility of the triplet oxygen atom assisted acetylene rearrangement into vinylidine. Various linear and cyclic oxygen-acetylene adducts and isomers are located, and their structures are optimized at the MP2/6-31G(d′) level of theory, with the energy evaluation at the CBSQ ab initio level of theory. These stationary points are connected with 17 transition state structures. Their interconversion activation barriers were evaluated together with the enthalpies of the reactions, and for some C2H2O isomers, the selective bond dissociation energies were also estimated. The experimental feasibility of some of the reaction channels was discussed, and from all calculations presented in this paper it is a general conclusion that the oxygen assisted acetylene-vinylidene rearrangement is not possible through the unimolecular reactions of the C 2H2O isomers in their triplet states. The possibility of the existence of the two-molecule hydrogen reactions was indicated, for which additional potential energy surface exploration is required.
Quality Education Cannot Be Separated from Traditional Culture

In its "Several Opinions on Further Strengthening and Improving the Work of Moral Education in the Schools," the Central Committee of the Chinese Communist Party stated: "The quality of the ideological and intellectual ethics and the scientific and cultural outlook of students whom we produce and nurture now and for the next decade or two will directly affect the outlook of China in the twenty-first century; it will affect whether the strategic goals of socialist modernization construction in our country will be realized." This is a passage that Commissioner Zhang Qizhi cited in our conversation as he discussed the subject of quality education.
The use of drift-flux techniques for the analysis of horizontal two-phase flows

Abstract New data is presented for horizontal air/water two-phase flow having various flow regimes. It is shown that drift-flux models are able to correlate these data and that the drift velocity, V g j , is normally finite.
Ultrasonic Evaluation of Pelvic Masses

Seventy-two patients with pelvic mass lesions were examined by B-mode ultrasonic scanning. In 30 of these patients, a specific diagnosis was obtained either by operation, biopsy or laparo-scopy, and the present study is based on these patients. Echographic features of various pelvic mass lesions are described. The procedure is safe, non-invasive and universally acceptable to the patients referred for examination.
Effects of peripheral nerve lesions during pregnancy on parturition in rats.

Bilateral section of either the sensory or motor branch of the pelvic nerve or pudendal nerve was performed in rats on days 8–10 of pregnancy, and the effects on delivery were observed. Bilateral resection of the sensory branch of the pelvic nerve reduced the number of live pups per litter, and increased the number of stillbirths and the number of fetuses retained in utero per litter at day 24. Sectioning motor components of the pelvic nerve, or both motor and sensory components of the pudendal nerve, had no effects on delivery in rats. We conclude that of the peripheral nerves evaluated in this study, only the sensory branch of the pelvic nerve is required for normal vaginal delivery in this species.
Oxygen minimum expansion in the Sulu Sea, western equatorial Pacific, during the last glacial low stand of sea level

The Sulu Sea in the western equatorial Pacific is presently a shallowly-silled, dysaerobic, deep-marine basin. Deep waters in the Sulu Sea are ventilated through a single sill at 420 m depth which connects it to the China Sea. Benthic and planktonic foraminiferal oxygen and carbon isotope records, benthic and planktonic foraminiferal census data and total organic carbon measurements have been used to evaluate changes in water mass conditions in the Sulu Sea between the last glacial maximum (18,000 yrs. B.P.) and the present day. An increase in the abundance of the planktonic foraminiferaNeogloboquadrina dutertrei and relatively light planktonic foraminiferal δ18O values suggest that during the last glacial maximum surface water salinities were reduced in the Sulu Sea. Enhanced isolation of the basin due to glacio-eustatic lowering of sea level and reduced surface salinities resulted in stagnation of deep water and an expansion of the mid-water oxygen minimum layer. Increased organic carbon preservation at mid-water depths occurs at this time. Benthic carbon isotope data and an increase in the abundance of benthic foraminiferal species considered to prefer low oxygen environments support the conclusion of an oxygen-minimum expansion at mid-water depths during the last glacial maximum. At water depths greater than 4000 m, bottom waters appear to have maintained some degree of oxygenation during the last glacial maximum. Stronger Pacific Ocean trade winds at this time may have caused the influx of denser Celebes Sea surface water into the southern part of the Sulu Sea. The slow sinking of this water would have then ventilated bottom waters in this part of the basin. At the transition from glacial to interglacial conditions, rising sea level caused denser water to flow over the deepest sill into the Sulu Sea. Vertical circulation increased, resulting in a greater downward flux of oxygen and a dissipation of the oxygen minimum. Continued post-glacial sea level rise caused periodic ventilation of deep water until the present dysaerobic conditions were established.
Utility of PAX2 as a Marker for Diagnosis of Endometrial Intraepithelial Neoplasia

Diagnosis of endometrial intraepithelial neoplasia (EIN) requires learning new criteria. Two trainees rendered diagnoses based on biopsy findings, and then measured the effect of reviewing PAX2 on their interpretation. Fifty-two endometrial biopsy specimens diagnosed as having EIN were evaluated using EIN criteria. Background endometrial pattern, altered differentiation, and any features complicating diagnosis were noted. PAX2 stains were scored as confusing, helpful, or noncontributory. Fifty-two cases generated 104 passes; 82% were rediagnosed as EIN. The diagnosis was complicated because of altered differentiation (14%), EIN and background separation (13%), large lesions lacking background (11%), and secretory background (8%). PAX2 was most helpful in cases with secretory backgrounds and when EIN lacked adjacent normal tissue, and most confusing when scoring was ambiguous (14%). The diagnosis of EIN can be difficult when: (1) the lesion cannot be easily compared with background; (2) there is a confounding process; and (3) gland differentiation is altered. PAX2 can be of assistance in delimiting EIN lesions.
Implantable microwave antennas for thermal therapy

The purpose of this article is to review the physical construction and power deposition characteristics of interstitial microwave antennas that may be used for highly localized heating of tissue at depth in the human body. Several different antenna designs are described and matched with potential clinical applications that range from moderate temperature Hyperthermia therapy to tissue- necrosing Thermal Ablation therapy. Typical clinical procedures are outlined for thermal treatment of target sites such as brain, prostate, heart, and gynecologic region tissues. Associated methods of implanting the antennas and coupling microwave energy into the surrounding tissue are also described, including the use of single or multi-chamber stiff, flexible or inflatable balloon type catheters, with or without circulating air or water cooling. With numerous references to the primary literature, this material should provide a framework for analyzing potential new applications for interstitial microwave antennas, as derived from the physical capabilities and limitations of the available hardware and techniques.
Isotopic enrichment by electron exchange

The importance of isotope separation has increased due to the wide use of isotopes in both energy- and life-science-oriented applications1. This, coupled with our observation2 that the solution electron affinities3 of perdeuterated hydrocarbons are less than those of corresponding undeuterated species, led us to investigate the possibility of isotopic enrichment through electron exchange equilibria. Here we report the observation that nitrobenzene containing 15N has a higher affinity for solvated electrons in liquid ammonia than does nitrobenzene containing the most common isotope of nitrogen (14N). When an equal-molar mixture of 14N-nitrobenzene (PhNO2-14N) and 15N-substituted nitrobenzene (PhNO2-15N) is added to a solution of solvated electrons in liquid ammonia, the anion radical of PhNO2−15N is formed predominantly over that of PhNO2-14N. Furthermore, as the chemical and physical properties of the resulting anion radicals (PhNO2-15N−. and PhNO2-14N−.) are very different from those of the neutral molecules, the electron exchange equilibrium between these two isotopic species can be utilized to enrich samples selectively with respect to the two isotopic species. Analogous results have been observed for the case of benzophenone-12C and benzophenone-13C (carbonyl 13C).
Inventory sharing in integrated network design and inventory optimization with low-demand parts

Abstract Service Parts Logistics (SPL) problems induce strong interaction between network design and inventory stocking due to high costs and low demands of parts and response time based service requirements. These pressures motivate the inventory sharing practice among stocking facilities. We incorporate inventory sharing effects within a simplified version of the integrated SPL problem, capturing the sharing fill rates in 2-facility inventory sharing pools. The problem decides which facilities in which pools should be stocked and how the demand should be allocated to stocked facilities, given full inventory sharing between the facilities within each pool so as to minimize the total facility, inventory and transportation costs subject to a time-based service level constraint. Our analysis for the single pool problem leads us to model this otherwise non-linear integer optimization problem as a modified version of the binary knapsack problem. Our numerical results show that a greedy heuristic for a network of 100 facilities is on average within 0.12% of the optimal solution. Furthermore, we observe that a greater degree of sharing occurs when a large amount of customer demands are located in the area overlapping the time windows of both facilities in 2-facility pools.
The paradox of pharmaceutical CSR: The sincerity nexus

Abstract Whether characterized as corporate social responsibility (CSR), business ethics, or some other name, best practices in a given industry often fall short, thus causing efforts of companies seeking to improve their own CSR practices to fall short as well. A typical CSR model uses philanthropic donations to demonstrate the company's commitment to social welfare. Even a strategic version of CSR falls short of what it could achieve. To be sure, these can be important efforts worth celebrating, but we seek to raise the bar higher. Our case study focuses on the pharmaceutical industry because of our experience working in and studying that industry. In Section 2, we identify the typical CSR efforts of pharmaceutical companies. Dissatisfied with the scope of current efforts, Section 3 switches from an inductive approach to a deductive one in which we rely on scholarly literature and some exemplary benchmarks to propose a stronger model of corporate ethics. At the heart of this model is the claim that optimum instrumental benefits accrue to corporate CSR actions when they are undertaken for sincere aims rather than for instrumental ones. Section 4 then explains how this framework provides a way for pharmaceutical companies to embrace a more robust model of corporate responsibility that could be extended to other industries as well.
Symbols and paleolithic artifacts: Style, standardization, and the imposition of arbitrary form

Abstract One of the main problems in the study of human behavioral evolution is to identify the beginnings of the habitual creation and use of symbols. This study investigates the theoretical issues involved in inferring symboling in a Middle or Lower Paleolithic context from three aspects of artifact manufacture—style, imposition of arbitrary form, and standardization. Because any of these phenomena can result from nonsymbolic behavior, none can be used alone to infer symbolic behavior.
Deep-sea Researches

WHEN Prof. Wyville Thomson published his recent volume giving the results of the deep-sea researches conducted by himself and his colleagues, Dr. Carpenter, Mr. Jeffreys, and others, he also gave a sketch of the history of the subject; but he made no mention of my memoir on the Microscopic Organisms of the Levant Mud, published in 1847 in the Transactions of the Literary and Philosophical Society of Manchester, though this memoir had been referred to from time to time by Dr. Carpenter, Messrs. Parker and Rupert Jones, and others, and was, next to Ehrenberg's discovery of the microscopic structure of chalk, the starting-point of all these deep-sea investigations. It was the first to call attention to the existence of foraminiferous deposits in the sea, and to insist upon the organic origin of all limestones except a few freshwater Travertins, in opposition to the theory of chemical deposits that had previously been advocated in the works of Phillips and other geologists. I do not care very much about these questions of priority of observation, but since Dr. Wyville Thomson's article in NATURE, vol. xi. p. 116, dwells largely upon another point, which was also brought prominently forward in my memoir, I think it worth while preventing a repetition of the oversight, because the two subjects referred to, viz. the foraminiferous origin of calcareous deposits, and the subsequent modification of such deposits by the agency of carbonic acid gas, now prove, as I long ago insisted that they would do, two of the most important factors in the solution of the problem of ; the nature and origin of deep-sea deposits. Dr. Wyville Thomson, in the article in question, points out that extensive areas of the deep-sea bottom are now occupied by a reddish earth, and he has arrived at the conclusion that this earth is a residue left after all the calcareous Globigerinae and other such elements have been removed by the solvent action of carbonic acid accumulated in these deep waters. In my memoir I arrived at the same conclusion from the study of the marine Tertiary deposits, containing Diatomaceae, of Bermuda, Virginia, and elsewhere. I may perhaps be permitted to republish the following extracts from that memoir, since it is not now readily accessible to all the numerous naturalists who are interested in this question:—
The multiregional matrix growth operator and the stable interregional age structure.

Current population-forecasting efforts generally adopt minor variants of the cohort-survival projection method. This technique focuses on a population disaggregated into cohorts, a group of people having one or more common characteristics at a point in time and, by subjecting each cohort to class-specific rates of fertility, mortality, and net migration, generates a distribution of survivors and descendants of the original population, at successive intervals of time.
Allelism, non-allelism, and genetic compounds among the mucopolysaccharidoses.

Abstract On the basis of cellular studies it is proposed that the genes for the strikingly dissimilar Hurler and Scheie syndromes are allelic, and that genetic compounds of the Hurler and Scheie genes occur, presenting an intermediate phenotype. Two clinically distinct forms of X-linked mucopolysaccharidosis (Hunter syndrome) are probably determined by alleles. A case is also presented which may represent either an allelic form of Maroteaux-Lamy syndrome or a genetic compound.
Vibrotactile thresholds of the Non-Pacinian I channel: II. Predicting the effects of contactor location on the phalanx.

The firing-rate-based population model for rapidly-adapting (RA) mechanoreceptive fibers by Guclu and Bolanowski (Guclu B, Bolanowski SJ. 2002. Modeling population responses of rapidly-adapting mechanoreceptive fibers. Journal of Computational Neuroscience 12:201–218.) is extended by including temporal-response properties of RA fibers. This representation allows for the generation of action-potential (spike) times for each fiber when a sinusoidal, steady-state stimulus is applied onto the skin. Signal detection theory was used to predict human psychophysical thresholds. Specifically, the effects of sensorineural innervation pattern, stimulus-contactor location and selected decision rules on the model predictions were studied. The predicted thresholds were lowest when the decision rule was one spike and highest when many active fibers were required for detection. These predictions were empirically tested by measuring vibrotactile thresholds of the Non-Pacinian I (NP I) channel, which required the special t...
Correlation Function Method for the Transport Coefficients of Dense Gases. II. First Density Correction to the Shear Viscosity for Systems with Attractive Forces

Extending the technique presented in our earlier work, the correlation-function expression for the shear viscosity is evaluated up to the first-density correction for a classical system of particles interacting with pair and three-body forces of short range which may have attractive parts and may allow for bound states. The results contain new terms as a result of the existence of bound states, in addition to those obtained for the first-density correction to the shear viscosity for the case of purely repulsive forces. In particular, ${\ensuremath{\eta}}_{\mathrm{KU}}$, ${\ensuremath{\eta}}_{\mathrm{UK}}$, and ${\ensuremath{\eta}}_{\mathrm{UU}}$ involve genuine three-body dynamics and give rise to finite contributions to the first-density correction. Diagrams are provided which help to visualize the various processes contributing to the shear viscosity. Finally, higher order density corrections and unstable clusters are briefly discussed.
Radiologic features and anatomic basis of atypical clinical presentations of ruptured abdominal aortic aneurysms

Ruptured abdominal aortic aneurysms (AAAs) occasionally manifest with atypical clinical presentations and can be initially misdiagnosed. Symptoms are attributable either to local mass effect from the aneurysm or a contained rupture, or to the particular cavity or anatomic space into which an aneurysm bleeds. Radiologic studies obtained in this patient population often will demonstrate signs of the ruptured AAA, and these signs should be actively searched for when a ruptured AAA can be in the differential diagnosis. Emergent computed tomographic examination is indicated to confirm any clinical or radiologic suspicion of a ruptured abdominal aortic aneurysm, provided that the patient remains hemodynamically stable. The anatomic basis for a ruptured AAA presenting clinically as renal colic is discussed and illustrated, and the spectrum of clinical presentations of ruptured AAAs is reviewed.
Molding of the uterus following intrauterine contraceptive device removal: Documentation by hysterosalpingography

Intrauterine contraceptive devices (IUDs) distort the uterine cavity. We report 2 cases of endometrial molding demonstrated by hysterosalpingography (HSG) following removal of an IUD. Other processes may cause filling defects in the uterine cavity including inflammatory synechiae (Asherman's syndrome), tuberculosis, endometrial hyperplasia, and polyps. Whenever filling defects are seen, the history of IUD usage should be determined.
High rate partial-state-of-charge operation of VRLA batteries

Abstract The world market for 12 V SLI batteries currently stands at around US$ 12 billion. The lack of a serious challenge from other battery types has allowed lead–acid products to serve this market exclusively, with minimal demand for product improvement through research and development, and a sharp competition has, over time, cut sales prices to commodity levels. The electrochemical storage of energy in automobiles now faces the possibility of a major change, in the form of the proposed 36/42 V electrical systems for vehicles that remain primarily powered by internal combustion engines, and of the hybrid electric vehicle. The duty cycle for these two applications sees the battery held at a partial-state-of-charge (PSoC) for most of its life and required to supply, and to accept, charge at unprecedented rates. The remarkable advances achieved with VRLA battery technology for electric vehicles during the past 8–10 years will be of only passing value in overcoming the challenges posed by high rate PSoC service in 36/42 V and HEV duty. This is because the failure modes seen in PSoC are quite different from those faced in EV (deep cycle) use. The replacement of the 12 V SLI will not take place rapidly. However, if the applications which take its place are to be satisfied by a lead–acid product (probably VRLA), rather than by a battery of a different chemistry, a program of development as successful as that mounted for deep cycle duty will be required. The present phase of the Advanced Lead–Acid Battery Consortium (ALABC) R&D program has begun to shed light on those aspects of the function of a VRLA battery which currently limit its life in high rate PSoC duty. The program is also pursuing the several technologies which show promise of overcoming those limits, including multiple tab plate design, mass transport facilitation and minor component (both beneficial and detrimental impurity) management. This paper presents a brief review of the changes which are taking place in lead–acid battery technology in response to the challenges of the new duty cycle.
The RF Ferrite-Testing Program at NAL

Investigations at NAL on ferrite disclosed a time dependent RF loss phenomenon occuring only at high power. Ferrite toroids of two manufacturers were tested to obtain enough cores of adequate power-handling capability for both the Booster and Main Accelerator cavities. The central portion of the test apparatus was a half wave coaxial cavity impedance matched to a 5kW power amplifier. The core selection criteria for Booster and Main Accelerator tuners differed and is discussed. Tuners assembled with the selected cores have operated satisfactorily at R. F. levels above 1OOkVA per core.
Relationship of Cortical Atrophy to Fatigue in Patients With Multiple Sclerosis

Background Fatigue is a common and disabling symptom of multiple sclerosis (MS). Previous studies reported that damage of the corticostriatothalamocortical circuit is critical in its occurrence. Objective To investigate the relationship between fatigue in MS and regional cortical and subcortical gray matter atrophy. Design Case-control study. Setting National Institutes of Health. Participants Twenty-four patients with MS and 24 matched healthy volunteers who underwent 3.0-T magnetic resonance imaging and evaluations of fatigue (Modified Fatigue Impact Scale) and depression (Center for Epidemiologic Studies Depression Scale). Main Outcome Measures Relationship between thalamic and basal ganglia volume, cortical thickness of frontal and parietal lobes, and, in patients, T2 lesion volume and normal-appearing white matter volume and the extent of fatigue. Results Patients were more fatigued than healthy volunteers ( P = .04), while controlling for the effect of depression. Modified Fatigue Impact Scale score correlated with cortical thickness of the parietal lobe ( r = −0.50, P = .01), explaining 25% of its variance. The posterior parietal cortex was the only parietal area significantly associated with the Modified Fatigue Impact Scale scores. Conclusions Cortical atrophy of the parietal lobe had the strongest relationship with fatigue. Given the implications of the posterior parietal cortex in motor planning and integration of information from different sources, our preliminary results suggest that dysfunctions in higher-order aspects of motor control may have a role in determining fatigue in MS.