cssi/SciSciGPT-SciSciNet huggingface dataset:
Current approaches and future directions in the treatment of HER2-positive breast cancer.

Human epidermal growth factor receptor 2 (HER2), a member of the ErbB family of transmembrane receptor tyrosine kinases, is amplified in 20–30% of invasive breast cancers. HER2 amplification is associated with metastasis and reduced survival. Two HER2-directed therapies have been approved by the United States Food and Drug Administration for the treatment of HER2-overexpressing breast cancer: trastuzumab, a humanized monoclonal antibody against the extracellular portion of HER2; and lapatinib, a dual HER2- and epidermal growth factor receptor-specific tyrosine kinase inhibitor. Despite the improvement in overall survival with the addition of HER2-targeted agents to chemotherapy, many patients do not benefit from these agents because of inherent resistance. In addition, many patients who achieve an initial response eventually acquire drug resistance. Currently, several mechanisms of resistance have been described, including mutations in other signaling pathways, expression of a truncated form of HER2, receptor crosstalk, and autophagy. There are several approaches under study to target these pathways of resistance, including blocking PI3 kinase and mammalian target of rapamycin signaling, blocking neoangiogenesis and the vascular endothelial growth factor axis, using monoclonal antibody targeting of the HER2 dimerization site, and using HER2 monoclonal antibody-drug conjugates. Here we will review the current scientific rationale for these agents and how combinations of these agents may yield additive or synergistic effects and lead to improved outcomes for patients with HER2-amplified breast cancer.
Contraction theorem for the algebraic reduction of (anti)commutators involving operator strings

A proof by induction is given of the so-called contraction theorem for the evaluation of (anti)commutators of strings of Fermion creation and annihilation operators. This theorem bears some formal similarity to Wick's theorem but is essentially simpler and its applications do not lead to any disconnected diagrams. Examples of applications to configuration-interaction and coupled-cluster methods are presented.
Expression and induction of cytochrome P-450 1A1 and P-450 2D subfamily in the rat glioma C6 cell line

Abstract The cytochrome P -450 ( P -450) monooxygenase system can catalyze the oxidation of a wide variety of endogenous and exogenous compounds, including steroid hormones, fatty acids, drugs and pollutants. The functions of this system are as diverse as the substrates. Though this enzyme system has the highest level of activity in the liver, it is present in other tissues, including brain. In this study, we have established the rat glioma C6 cell line as an in vitro model system to examine the expression and induction of P -450 1A1 and the P -450 2D subfamily. Rat glioma C6 cells were treated with P -450 inducers phenobarbital (PB) or benzo[ a ]anthracene (BA). The presence of P -450 1A1 and 2D1–5 was detected by reverse transcription followed by polymerase chain reaction (RT–PCR) and confirmed by restriction enzyme digestion. The induction of P -450 1A1 and 2D1–5 was quantified using competitive PCR. Although P -450 2D1–5 do not seem to be affected by PB or BA treatment, tenfold induction of P -450 1A1 mRNA after BA treatment was detected. Western blot analysis of microsomal preparations of glioma C6 cells demonstrated the presence of P -450 1A1 at the protein level. ELISAs showed that BA induces P -450 1A1 proteins 7.3-fold. These experiments provide further evidence that the rat glioma C6 cell line contains an active cytochrome P -450 monooxygenase system which can be induced by P -450 inducers. In summary, we believe the presence of the cytochrome P -450 monooxygenase system in glial cells of the brain may be important in chemotherapy and carcinogenesis of brain tumors.
CD8+ T Cells in Tuberculosis

This chapter focuses on CD8 T cells, with an emphasis on the major histocompatibility complex (MHC) Ia-restricted T cells in tuberculosis, and also touches upon the unconventional CD8 T cells restricted by β2m-associated nonclassical MHC Ib or MHC I-like molecules. Although the T cells which recognize mycobacterial glycolipids in the context of group I CD1 molecules are not only CD8+ but also double negative and sometimes even CD4+, they are considered in this chapter where appropriate. Importantly, dendritic cells (DC) can capture an antigen at the site of infection and transport it to draining lymph nodes, where T-cell stimulation takes place. The possible functions of CD8 T cells in the control of tuberculosis include cytokine production, macrophage activation, killing of infected cells, and killing of M. tuberculosis. The memory response to M. tuberculosis in the lungs is weak compared to that of some viral infections. A model that has been used to study memory responses is infection of mice followed by antimycobacterial drug treatment beginning 4 weeks after infection. In summary, CD8 T cells that recognize mycobacterial antigens on macrophages or DC are induced following M. tuberculosis. Given the potential for effective immune responses mediated by CD8 T cells, more researchers are using strategies that include the induction of CD8 T cells in vaccine candidates for tuberculosis. The results of these studies may provide important data on the ability of CD8 T cells to contribute to protection against this disease.
Studies on the formation of circular λ DNA

Abstract A circular form of λ DNA is synthesized within 5 minutes after phage infection of sensitive and lysogenic cells of Escherichia coli K12 at phage multiplicities of 5 and 0.8 phage per bacterium. The amount of circular λ DNA formed in infected lysogenic cells is 2 to 3 times that found in sensitive cells infected under comparable conditions. The circular DNA species is also synthesized when λ phage superinfects lysogenic cells which had previously been induced by ultraviolet light or thymine deprivation. Although the mechanism for synthesis of the circular λ DNA species is not known, evidence is presented that it does not involve the incorporation of thymine or inorganic phosphate.
Lateral hypothalamus: site involved in pain modulation.

Abstract The present study is an attempt to examine the neuronal circuitry of a supraspinal site engaged in pain modulation. Five physiological measures were postulated as the criteria for defining a central nervous system site engaged in the circuitry of pain modulation. The lateral hypothalamus met these five measures: (i) 81% of the lateral hypothalamus neurons (247/304) responded to noxious stimuli using a single cell recording procedure; (ii) stimulation of the periaqueductal gray-dorsal raphe area or the habenula modulated 98% and 87% of the lateral hypothalamus noxious-evoked activity; (iii) microiontophoretically applied morphine modulated 77% of the lateral hypothalamus noxious evoked activity; (iv) electrical stimulation of the lateral hypothalamus produced behavioral analgesia proportional to the stimulus integrity as assessed by the tail flick assay; and (v) morphine application into the lateral hypothalamus produced behavioral analgesia in a dose-response manner using the tail flick assay. In conclusion, the lateral hypothalamus can be considered one of the pain modulation sites.
Communication and computing technology in biocontainment laboratories using the NEIDL as a model

The National Emerging Infectious Diseases Laboratories (NEIDL), Boston University, is a globally unique biocontainment research facility housing biosafety level 2 (BSL-2), BSL-3, and BSL-4 laboratories. Located in the BioSquare area at the University's Medical Campus, it is part of a national network of secure facilities constructed to study infectious diseases of major public health concern. The NEIDL allows for basic, translational, and clinical phases of research to be carried out in a single facility with the overall goal of accelerating understanding, treatment, and prevention of infectious diseases. The NEIDL will also act as a center of excellence providing training and education in all aspects of biocontainment research. Within every detail of NEIDL operations is a primary emphasis on safety and security. The ultramodern NEIDL has required a new approach to communications technology solutions in order to ensure safety and security and meet the needs of investigators working in this complex building. This article discusses the implementation of secure wireless networks and private cloud computing to promote operational efficiency, biosecurity, and biosafety with additional energy-saving advantages. The utilization of a dedicated data center, virtualized servers, virtualized desktop integration, multichannel secure wireless networks, and a NEIDL-dedicated Voice over Internet Protocol (VoIP) network are all discussed.
Morbidity of Staged Proctectomy After Hepatectomy for Colorectal Cancer: A Matched Case–Control Analysis

Proctectomy after hepatectomy, or the reverse approach, is an alternative to traditional sequencing for advanced liver metastases with asymptomatic colorectal primary tumors. We sought to evaluate the surgical morbidity of proctectomy for colorectal cancer after previous liver surgery. A single-institution colorectal database was queried for patients treated with proctectomy after previous hepatectomy from 2003 to 2011. Reverse-approach patients (n = 31) were matched 1:2 with a cohort of standard proctectomy patients (n = 62) using operation, age, gender, and surgeon. Perioperative factors were analyzed by univariate/multivariate models for associations with complications graded by Dindo–Clavien criteria. Thirty-one patients with adenocarcinoma ≤20 cm from the anal verge underwent proctectomy after hepatectomy. Median time from hepatectomy to proctectomy was 5.1 months. Median tumor distance was 8.5 cm. Before proctectomy, patients underwent 28 (90 %) major hepatectomies and 7 (22 %) portal vein embolizations. There were no perioperative deaths. Reverse-approach patients did not differ from control patients in operation, demographics, body mass index (BMI), comorbidities, tumor distance, operative time, estimated blood loss, length of stay, or complication rates (p > 0.05). Grade 2 or higher complications developed in 42 % of reverse-approach and 27 % of standard proctectomies (p = 0.17). Grade 3 or higher complications developed in 10 % and 8 %, respectively (p = 1.00). Independent predictors of complications of grade 2 or higher were BMI ≥30 kg/m2 (p = 0.007), operative time ≥300 min (p = 0.012), intraoperative transfusion (p = 0.044), concurrent procedures (p = 0.024), and age ≥50 years (p = 0.030). Risk factors for morbidity of staged proctectomy are similar to those for standard proctectomy. In selected patients, the reverse-approach proctectomy is safe with acceptable morbidity.
Lymphoma-associated versus lymphocytic-variant hypereosinophilia.

Secondary eosinophilia may be seen with various lymphoid neoplasms as a result of non-clonal expansion of normal eosinophils mediated by eosinophilopoietic growth factors/ cytokines, such as interl...
Low velocity impact behavior of composite sandwich panels

Abstract Composite sandwich structures are susceptible to low velocity impact damage and thorough characterization of the loading and damage process during impact is important. The objective of this work is to study experimentally the low velocity impact behavior of sandwich panels consisting of woven carbon/epoxy facesheets and a PVC foam core. Instrumented panels were impacted with a drop mass setup and the load, strain, and deflection histories were recorded. Damage was characterized and quantified after the test. Results were compared with those of an equivalent static loading and showed that low velocity impact was generally quasi-static in nature except for localized damage. A straightforward peak impact load estimation method gave good agreement with experimental results. A contact force–indentation relationship was also investigated for the static loading case. Experimental results were compared with analytical and finite element model analysis to determine their effectiveness in predicting the indentation behavior of the sandwich panel.
Vortex-induced vibrations of a flexibly-mounted inclined cylinder

The majority of studies on vortex-induced vibrations of a flexibly-mounted rigid cylinder are for the cases where the flow direction is perpendicular to the long axis of the structure. However, in many engineering applications, such as cable stays in bridges and mooring lines of floating offshore wind turbines, the flow direction may not be perpendicular to the structure. To understand the vortex shedding behind a fixed inclined cylinder, the Independence Principle (IP) has been used. The IP assumes that an inclined cylinder behaves similarly to a normal-incidence case, if only the component of the free stream velocity normal to the cylinder axis is considered. The IP neglects the effect of the axial component of the flow, which seems reasonable for small angles of inclination, but not for large angles. In the present study, a series of experiments have been conducted on a flexibly-mounted rigid cylinder placed inclined to the oncoming flow with various angles of inclination (0°<θ<75°) in a range of Reynolds numbers from 500 to 4000 to investigate how the angle of inclination affects VIV. A rigid cylinder was mounted on springs, and air bearings were used to reduce the structural damping of the system. The system was placed in the test-section of a recirculating water tunnel and the crossflow displacements were measured at each flow velocity. Even at high angles of inclination, large-amplitude oscillations were observed. As the angle of inclination was increased, the lock-in range (the range of reduced flow velocities for which the cylinder oscillates with a large amplitude) started at a higher reduced velocity. When only the normal component of the oncoming flow was considered, the onset of lock-in was observed to be at the same normalized flow velocity for all angles of inclination except for 75°. However, the width of the lock-in region, its pattern, the maximum amplitude of oscillations and its corresponding normalized reduced velocity were not following the results of a normal-incidence case entirely. Flow visualizations showed a vortex shedding parallel to the cylinder′s axis for all the angles of inclination considered. The influence of a slight change in the added mass as well as the direction of the inclined cylinder on the response was studied as well.
Effect of pH, Calcium, and Heat Treatment on Curd Tension of Casein Fraction Fortified Skim Milk

Abstract The effect of α- or β-casein fortification (12 to 28% above control at 3.3% total protein) on skim milk curd strength was studied. After addition of 1N hydrochloric acid to pH 6.0, α-casein fortified skim milk produced a weaker curd than β-casein fortification. With added calcium chloride (.01M), both fractions formed a firmer curd with α-casein slightly stronger than β-casein. Alpha and β-casein fortified skim milk cultured with Streptococcus lactis had similar curd tension within a pH range of 5.20 to 5.85. Calcium addition (.01M) increased α-casein fortified skim milk curd tension but had a depressing effect on β-casein as compared to their respective curd strengths without added calcium. However, as pH approached 5.20, β-casein curd strength increased faster per pH unit than that of the α-casein fortified samples. Heat treatments within an effective heat range of .05 to .42 (holding time 10min) allowed α-casein fortified skim milk to form a stronger curd than that fortified with β-casein. When compared to unfortified skim milk, the greatest difference in curd tension between the α- and β-casein fortifications was at effective heat .42. Alpha casein curd tension was reduced nearly three times as fast as β-casein when skim milk fortified samples were heated at .42 in the presence of .005M calcium chloride addition.
Prepartum milking effects on parlour behaviour, endocrine and immune responses in Holstein heifers.

Transition of primiparous heifers to the milking herd is a period with multiple stressors. The objective of these studies was to determine effects of parlour experience and prepartum milking (pre-milking) on behavioural and physiological indicators of stress after calving. Two experiments were conducted, one was in a free-stall housing confinement system and the second was in a modified grazing system. Forty-eight first-calf heifers were assigned to three treatments: control; experienced heifers taken through the parlour without milking; or pre-milk heifers milked for 3 weeks prior to estimated parturition. Blood was collected within 24 h of parturition and on days 3, 5, 7, 10 and 14 following parturition for cortisol and acute phase protein determination. In the grazing system, 20 heifers were assigned to a prepartum milked or control group as in the confinement system and behaviour observations included days −21, −14, −7, −5, −3 and −1 relative to calving and days 1, 3, 7, 9, 14, and 16 post-calving. Milk production was greatest for prepartum milked heifers in both housing systems. However, somatic cell score was reduced by prepartum milking only in the confinement system. Balking occurred least in parlour-experienced heifers. In confinement housing, shifting while in the parlour was the only behaviour that was greater at first milking in control heifers. Kicking was most frequent for parlour experienced heifers on day 2. Grazing system pre-milked heifers shifted more at their first milking (day −21) than did the controls at their first milking (day 1). Shifting within cow was greatest on day −21 compared with day −5 (P<0·05). Pre-milked heifers shifted more on day 1 post-calving than did the control heifers (P<0·05). These results showed that shifting was the most indicative behaviour of restlessness, was transient, and decreased by day 5 prior to calving. Cortisol and α1-acid glycoprotein concentrations were not different; however, haptoglobin increased for all treatments up to and including day 3 and haptoglobin concentrations of pre-milked heifers began to decrease by day 5 post-calving. Pre-milked heifers had lower haptoglobin concentrations than the control heifers and tended to have lower concentrations than experienced heifers on day 10 post partum. By day 14 post partum, all haptoglobin concentrations were <200 μg/ml, but the haptoglobin concentration of control heifers was greater than that of pre-milked and experienced heifers. These results showed that prepartum milking and parlour experience shorten some acute phase protein responses, but minimally affect early parlour behaviours.
Deletion of a disease resistance nucleotide-binding-site leucine-rich- repeat-like sequence is associated with the loss of the Phytophthora resistance gene Rps4 in soybean.

Resistance of soybean against the oomycete pathogen Phytophthora sojae is conferred by a series of Rps genes. We have characterized a disease resistance gene-like sequence NBSRps4/6 that was introgressed into soybean lines along with Rps4 or Rps6. High-resolution genetic mapping established that NBSRps4/6 cosegregates with Rps4. Two mutants, M1 and M2, showing rearrangements in the NBSRps4/6 region were identified from analyses of 82 F1’s and 201 selfed HARO4272 plants containing Rps4. Fingerprints of these mutants are identical to those of HARO4272 for 176 SSR markers representing the whole genome except the NBSRps4/6 region. Both mutants showed a gain of race specificities, distinct from the one encoded by Rps4. To investigate the possible mechanism of gain of Phytophthora resistance in M1, the novel race specificity was mapped. Surprisingly, the gene encoding this resistance mapped to the Rps3 region, indicating that this gene could be either allelic or linked to Rps3. Recombinant analyses have shown that deletion of NBSRps4/6 in M1 is associated with the loss of Rps4 function. The NBSRps4/6 sequence is highly transcribed in etiolated hypocotyls expressing the Phytophthora resistance. It is most likely that a copy of the NBSRps4/6 sequence is the Rps4 gene. Possible mechanisms of the deletion in the NBSRps4/6 region and introgression of two unlinked Rps genes into Harosoy are discussed.
Time Travel: Double Your Fun

I start off by relating the standard philosophical account of what time travel is to models of time travel that have recently been discussed by physicists. I then discuss some puzzles associated with time travel. I conclude that philosophers’ arguments against time travel are relevant when assessing the likelihood of the occurrence time travel in our world, and are relevant to the assessment whether time travel is physically possible.
Inside multi-disciplinary science and engineering research centers: The impact of organizational climate on invention disclosures and patents

a b s t r a c t Much past research on commercialization activities by university scientists and engineers has focused on the role of resources in the extra-organizational commercialization environment, such as the availability of venture capital funding. By contrast, our theoretical and empirical interest was in intra-organizational dynamics impacting the context in which scientists and engineers work. Drawing upon organizational psychology literature on the construct of organizational climate, we posited that researchers working in an intra-organizational climate that supports commercialization and encourages intra-organizational boundary-spanning will be more likely to produce invention disclosures and patents. Our data from 218 respondents at 21 engineering research centers was both multi-method (i.e., qualitative data from interviews, longitudinal archival data, and survey data) and multi-level. Our results showed that an orga- nizational climate characterized by support for commercialization predicted invention disclosures one year later and an organizational climate characterized by boundary-spanning predicted patent awards two years later.
An approach to software reliability prediction and quality control

The increase in importance of software in command and control and other complex systems has not been accompanied by commensurate progress in the development of analytical techniques for the measurement of software quality and the prediction of software reliability. This paper presents a rationale for implementing software reliability programs; defines software reliability; and describes some of the problems of performing software reliability analysis. A software reliability program is outlined and a methodology for reliability prediction and quality control is presented. The results of initial efforts to develop a software reliability methodology at the Naval Electronics Laboratory Center are reported.
Glycolysis Inhibitors Among Compounds Containing the CON Structure

Abstract Over 400 organic substances possessing a CON grouping were studied for their ability to exert residual inhibitory action on glycolysis by oral microorganisms, when the organisms were present in a thin film resembling the dental plaque.Among amides inhibitory structures were frequently found for alkyl monoamides and lact- amides containing 7 to 21 carbon atoms.Only two inhibitory substances were found among 154 carbamates, and none of 71 derivatives of urea were inhibitory when tested in aqueous solution.
Combining norepinephrine and serotonin reuptake inhibition mechanisms for treatment of depression: a double-blind, randomized study

Abstract Background Although several antidepressants are now available, all have limited efficacy and a delayed onset of action. The current study was undertaken as a proof of the concept that combining norepinephrine and serotonin reuptake inhibition would be more effective and act more rapidly than either drug alone. Methods Inpatients with nonpsychotic unipolar major depression and a Hamilton Depression Rating Scale (HAMD) score of at least 18 after 1 week of hospitalization without antidepressant medication were randomized to 6 weeks of treatment with fluoxetine (FLX) 20 mg/day, desipramine (DMI) adjusted to an adequate plasma level, or the combination of FLX 20 mg/day and DMI, given under double-blind conditions. Twenty-four-hour DMI levels were used to rapidly adjust DMI dose to achieve a therapeutic level and to anticipate the enzyme-inhibiting effects of FLX. Treatment-resistant patients were stratified. Patients were rated with the HAMD and the Montgomery-Asberg Depression Rating Scale (MADRS). Results Thirty-nine patients began treatment. One patient withdrew consent. The DMI–FLX combination was significantly more likely to result in remission on the MADRS than either FLX or DMI alone [53.8% vs. 7.1% and 0%, respectively; χ 2 (2) = 13.49, p = .001]. The advantage for combined treatment was not explained by history of treatment resistance or by drug plasma concentrations. Rapid response, at 1 or 2 weeks, was neither statistically nor meaningfully greater with combined treatment. Conclusions This study supports the hypothesis that the combination of a noradrenergic and serotonergic agent is more likely to result in remission than either selective agent alone during a 6-week treatment period.
It is not the parts, but how they interact that determines the behaviour of circadian rhythms across scales and organisms

Biological rhythms, generated by feedback loops containing interacting genes, proteins and/or cells, time physiological processes in many organisms. While many of the components of the systems that generate biological rhythms have been identified, much less is known about the details of their interactions. Using examples from the circadian (daily) clock in three organisms, Neurospora, Drosophila and mouse, we show, with mathematical models of varying complexity, how interactions among (i) promoter sites, (ii) proteins forming complexes, and (iii) cells can have a drastic effect on timekeeping. Inspired by the identification of many transcription factors, for example as involved in the Neurospora circadian clock, that can both activate and repress, we show how these multiple actions can cause complex oscillatory patterns in a transcription-translation feedback loop (TTFL). Inspired by the timekeeping complex formed by the NMO-PER-TIM-SGG complex that regulates the negative TTFL in the Drosophila circadian clock, we show how the mechanism of complex formation can determine the prevalence of oscillations in a TTFL. Finally, we note that most mathematical models of intracellular clocks model a single cell, but compare with experimental data from collections of cells. We find that refitting the most detailed model of the mammalian circadian clock, so that the coupling between cells matches experimental data, yields different dynamics and makes an interesting prediction that also matches experimental data: individual cells are bistable, and network coupling removes this bistability and causes the network to be more robust to external perturbations. Taken together, we propose that the interactions between components in biological timekeeping systems are carefully tuned towards proper function. We also show how timekeeping can be controlled by novel mechanisms at different levels of organization.
Microglial response to degeneration of serotonergic axon terminals

The neurotoxic drug p-chloramphetamine (PCA) causes widespread degeneration of fine, unmyelinated serotonergic (5-HT) axons in the forebrain. PCA toxicity is selective for 5-HT axon terminals; preterminal axons and cell bodies are spared. Degeneration is followed by slowly progressive axonal sprouting and partial reinnervation. PCA is injected subcutaneously; this route of administration avoids mechanical disruption of the blood brain barrier. The present study analyzed the response of microglia and astrocytes in rat brain to selective ablation of 5-HT axons by PCA. Several microglial markers were analyzed with immunocytochemical methods. An increase in the number of microglial processes and in immunoreactive staining was observed with antibodies directed against CR-3, MHC-I, CD4, and rat LCA. The microglial response was maximal 3 weeks after PCA treatment, became less evident 6 weeks after treatment, and by 9 weeks no difference was observed between treated and control rats. No change was detected in MHC-II or the macrophage marker ED1, nor in expression of GFAP by astrocytes. Thus, degeneration of 5-HT axon terminals affects only a subset of the microglial markers examined; in comparison, retrograde reaction to facial nerve transection causes a robust increase in all of these markers and in GFAP. The microglial response to PCA-induced axon loss is slow in onset and small in magnitude. These findings indicate that CNS microglia are activated by degeneration of fine, unmyelinated 5-HT axon terminals; furthermore, sensitive microglial markers can detect a subtle axonal lesion that provokes no detectable increase in GFAP expression by astrocytes.
Clinical use of a solid-phase radioimmunoassay specific for human chorionic gonadotropin.

Abstract A rapid radioimmunoassay specific for human chorionic gonadotropin (hCG) has been developed. Elimination of cross-reactivity with luteinizing hormone (hLH) was obtained by utilizing an antiserum with a specificity for the beta subunit of hCG. A solid-phase system, in which the antibody was bound to CNBR-activated sepharose in a preliminary step, reduced the minimum incubation time of the assay to two hours. The assay has been found to be of particular value in those conditions where in the concentration of hCG as measured by previously described assays would be affected by circulating levels of hLH: i.e., early implantation, unruptured ectopic pregnancy, threatened abortion, and trophoblastic disease under chemotherapy.
Bromadiolone, a New Anticoagulant Rodenticide

A search for more effective anticoagulant rodenticides has brought about the development of a new compound, coded LM-637, and temporarily named bromadiolone. Results of efficacy tests on 10 rodent species are discussed in detail. The compound was found to be a very potent and highly palatable anticoagulant which is capable of achieving 100% mortality in Norway rats, Rattus norvegicus (Berkenhout), with 1-day feeding. Efficacy was demonstrated on all 3 commensal rodents and several important agricultural rodent pests native to the United States. A relatively few feedings (1 to 5 days) of bait containing 0.005 % bromadiolone produced death in most species tested. These rodenticidal properties make bromadiolone a most promising control agent.
MOSES: exploring new ground in media and post-conflict reconciliation

While the history of traditional media in post-conflict peace building efforts is rich and well studied, the potential for interactive new media technologies in this area has gone unexplored. In cooperation with the Truth and Reconciliation Commission of Liberia, we have constructed a novel interactive kiosk system, called MOSES, for use in that country's post-conflict reconciliation effort. The system allows the sharing of video messages between Liberians throughout the country, despite the presence of little or no communications infrastructure. In this paper, we describe the MOSES system, including several innovative design elements. We also present a novel design methodology we employed to manage the various distances between our design team and the intended user group in Liberia. Finally, we report on a qualitative study of the system with 27 participants from throughout Liberia. The study found that participants saw MOSES as giving them a voice and connecting them to other Liberians throughout the country; that the system was broadly usable by low-literate, novice users without human assistance; that the embodied conversational agent used in our design shows considerable promise; that users generally ascribed foreign involvement to the system; and that the system encouraged heavily group-oriented usage.
Social support reduces the impact of partner violence on health: application of structural equation models.

Background Intimate partner violence (IPV) is associated with poorer health, yet pathways through which IPV affects either mental or physical health are not well characterized. Methods Structural equation modeling was used to test a model in which physical-IPV and battering were considered as separate independent variables. The sample included 191 women currently experiencing either physical IPV or battering. Emotional support provided to women experiencing IPV was hypothesized to mediate the impact of IPV on current mental and physical health (dependent variables). Results Higher scores on emotional support were associated with better physical (s = -0.23, P < 0.01) and mental health (s = -0.27, P < 0.001). Physical IPV was directly associated with poorer mental health (s = .023, P < 0.01) and indirectly associated with poorer physical health (s = 0.18, P < 0.001) and mental health (s = -0.04, P < 0.05), primarily through battering. Higher battering scores were directly associated with less emotional support (s = -0.33, P < 0.001) and indirectly associated with poorer physical (s = 0.12, P < 0.01) and mental health (s = 0.09, P < 0.01), primarily through emotional support. Model diagnostics indicated a good fit (?2 = 20.44, P = 0.37, GFI = 0.98, CFI = 0.99, RMSEA = 0.02). Conclusions Higher levels of emotional support may modify the effect of IPV on health. Interventions to increase social and emotional support to abused women may reduce mental and physical health consequences.
Directional Wave Spectra from Wave Sensors

The measurement of directional ocean wave spectra with in situ instruments in the ocean environment requires arrays consisting of relatively few sensors. More elaborate systems are difficult and costly to maintain.
Cohomology of Coherent Sheaves

In this chapter, we continue the study of coherent sheaves, by studying their cohomology. The first key result is that the higher cohomology groups for coherent sheaves vanish for affine schemes. Using this we can compute cohomology for projective spaces using the Cech complex for the standard open affine cover, and establish finite-dimensionality and other basic results. We also consider analogous statements for complex manifolds. With these results in hand, we complete our discussion of the GAGA theorems. The second basic result is that if 蒖 is a coherent algebraic sheaf on ℙ n ℂ, its cohomology is isomorphic to the cohomology of 蒖an. Thus the calculation of the latter reduces to a purely algebraic problem. This cohomological result is also needed for the proof of the first GAGA theorem stated in the previous chapter.
IGF1 receptor expression protects against microenvironmental stress found in the solid tumor.

Abstract Peretz, S., Kim, C., Rockwell, S., Baserga, R. and Glazer, P. M. IGF1 Receptor Expression Protects against Microenvironmental Stress Found in the Solid Tumor. Radiat. Res. 158, 174–180 (2002). The insulin-like growth factor 1 receptor (IGF1R) is a tyrosine kinase, transmembrane receptor expressed in most body tissues and required for normal growth of cells. In cell culture, overexpression of the receptor has been shown to promote transformation and enhance cell survival in response to selected cytotoxic agents. As tumors develop, abnormalities in vascularization lead to a heterogeneous environment that includes areas of hypoxia, low pH and low glucose. Here we report that the overexpression of the IGF1R promotes increased survival in cells exposed to hypoxia, low pH and low glucose. Furthermore, cells lacking the receptor due to targeted disruption of the IGF1R gene do not survive as well as normal cells in such conditions. In addition, we find that cells can activate the IGF1R gene promoter in r...
Computational prediction and experimental validation of novel Hedgehog-responsive enhancers linked to genes of the Hedgehog pathway

Background The Hedgehog (Hh) signaling pathway, acting through three homologous transcription factors (GLI1, GLI2, GLI3) in vertebrates, plays multiple roles in embryonic organ development and adult tissue homeostasis. At the level of the genome, GLI factors bind to specific motifs in enhancers, some of which are hundreds of kilobases removed from the gene promoter. These enhancers integrate the Hh signal in a context-specific manner to control the spatiotemporal pattern of target gene expression. Importantly, a number of genes that encode Hh pathway molecules are themselves targets of Hh signaling, allowing pathway regulation by an intricate balance of feed-back activation and inhibition. However, surprisingly few of the critical enhancer elements that control these pathway target genes have been identified despite the fact that such elements are central determinants of Hh signaling activity. Recently, ChIP studies have been carried out in multiple tissue contexts using mouse models carrying FLAG-tagged GLI proteins (GLIFLAG). Using these datasets, we tested whether a meta-analysis of GLI binding sites, coupled with a machine learning approach, could reveal genomic features that could be used to empirically identify Hh-regulated enhancers linked to loci of the Hh signaling pathway.
Exact Gift Wrapping to Prune the Tree of Edges of Newton Polytopes to Compute Pretropisms.

Pretropisms are candidates for the leading exponents of Puiseux series that represent solutions of polynomial systems. To find pretropisms, we propose an exact gift wrapping algorithm to prune the tree of edges of a tuple of Newton polytopes. We prefer exact arithmetic not only because of the exact input and the degrees of the output, but because of the often unpredictable growth of the coordinates in the face normals, even for polytopes in generic position. We provide experimental results with our preliminary implementation in Sage that compare favorably with the pruning method that relies only on cone intersections.
Attachment and mentoring

Purpose – The purpose of this paper is to examine the relationships between attachment styles, mentoring (psychosocial support and career support), organizational commitment, and turnover intent of proteges in formal faculty mentoring. Design/methodology/approach – An internet survey was conducted with a population of 125 proteges in a formal faculty mentoring program at a US university. Findings – Results from linear regression analyses revealed that proteges’ secure attachment was positively and significantly related with their organizational commitment and was negatively and significantly related to intent to turnover. Additional linear regression analyses revealed that psychosocial support and career support were positively and significantly related with protege organizational commitment and were negatively and significantly related to intent to turnover. Hierarchical regression showed that secure attachment alone was a unique predictor of proteges’ organizational commitment and intent to turnover. Fu...
Alcohol and Neuroimmune Interactions

Abstract Alcohol-mediated changes in neuroimmune activity have been documented in humans with alcohol use disorders and have also been shown in animal models across the lifespan. A neuroimmune response to alcohol occurs in fetal, adolescent, and adult brains with an apparent dependence on dose, age, and pattern of exposure, which supports a hypothesis of differential sensitivity. Microglia and neuroinflammatory molecules are believed to play a role in ethanol-induced neurodegeneration and long-term deficits in behavior and cognition. Anti-inflammatory agents show promise to reduce alcohol-mediated deficits. Alcohol effects on neuroimmune processes are discussed and new strategies to move anti-neuroinflammatory pharmaceuticals toward translational use to block alcohol-induced neuropathology and its long-term consequences are advanced.
Imaging of cartilage degeneration in vivo using ultrahigh resolution OCT

Ultrahigh resolution OCT is used to visualize experimentally induced osteoarthritis in a rat knee model. Using a Cr4+:Forsterite laser, ultrahigh image resolutions of 5um are achieved in vivo. Progression of osteoarthritic remodeling and cartilage degeneration are quantified. The utility of OCT for the assessment of cartilage integrity is demonstrated.
A High Order Space-time Riemann-solver-free Method for Solving Compressible Euler Equations

In this paper, a novel high-order space-time method is introduced for solving compressible Euler equations. The method is inspired by two important concepts, the staggered space-time mesh of the space-time conservation element/solution element (CE/SE) method and the local discontinuous basis functions of the space-time discontinuous Galerkin (DG) finite element method. The staggered space-time mesh is constructed using the cell-vertex structure of the underlying spatial mesh. The solution within each physical time step is updated alternately at the cell level and the vertex level. The arbitrarily high order of accuracy is achieved by employing high-order Taylor polynomials as the basis functions inside each CE. The current method exhibits many advantageous features such as Riemannsolver-free, arbitrarily high-order accuracy, point-implicitness, and compactness. Several numerical tests will demonstrate the performance of the new scheme.
Effects of elevated glucocorticoids on reproduction and development: relevance to endocrine disruptor screening

AbstractThis article reviews the influence of the hypothalamo–pituitary–adrenocortical (HPA) axis on mammalian male and female reproduction and development of offspring and its potential impact on the identification of endocrine disruptive chemicals by in vivo assays. In the adult male rat and baboon, stress suppresses testosterone secretion via a direct inhibitory effect of elevated glucocorticoids on Leydig cells. In adult female sheep, stress disrupts reproductive function via multi-stage mechanisms involving glucocorticoid-mediated suppression of LH secretion, LH action on the ovary and the action of estradiol on its target cells (e.g., uterus). While physiological concentrations of endogenous glucocorticoids are supportive of fetal development, excessive glucocorticoids in utero (i.e., maternal stress) adversely affect mammalian offspring by “programing” abnormalities that are primarily manifest postpartum. The influence of stress on reproduction and development can also be mediated by 11β-hydroxyste...
Effects of 17β-estradiol on mouse lung fibroblast cell cycle

Aim: To observe the effect of 17β-estradiol( 17β-E2) on mouse lung fibroblast cell cycle. Methods: According to the L9( 33) orthogonal experimental design,mouse lung fibroblasts were induced by SiO2( 20,50,100 mg/L),intervented by 17β-E2( 10- 6,10- 7,10- 8mol /L) for 24,48,or 72 h. The cell proliferation was determined by MTT method. Based on low proliferation activity,the best experimental condition was selected. Mouse lung fibroblasts was divided into three groups: blank control group,SiO2 induction group,and 17β-E2 intervention group. The cells were cultured under the selected experimental condition,and the cell cycle was detected using flow cytometry. Results: The selected experimental condition was as follows: 20 mg /L SiO2 induction,and followed by 10- 6mol /L 17β-E2 intervention for 24 h.There were statistical differences in G1 phase cell proportion,and S + G2 phase cell proportion among the three groups( F =50.300,29.896,P 0.001). Compared with blank control group,G1 phase cell proportion in SiO2 induction group was lower( P 0. 05),while S + G2 phase cell proportion was higher( P 0. 05). Compared with SiO2 induction group,G1 phase cell proportion in 17β-E2 intervention group was higher( P 0. 05),while S + G2 phase cell proportion was lower( P 0.05). Conclusion: 17β-E2 might inhibit mouse lung fibroblast proliferation by blocking the cells in G1 phase.
Surveillance Report on Brucellosis in 2007 in Quzhou Municipality

OBJECTIVE The present investigation was made to get an insight into the epidemic dynamics of human brucellosis in Quzhou Municipality to provide scientific basis for the prediction of the epidemic trend of Brucellosis and establishment of strategies for its prevention and control. METHODS Surveillance was made following the requirements in the Surveillance of Brucellosis in Zhejiang. "Diagnostic Standard and Management Principle of Brucellosis(GB15988—1995)" was used as reference for serologic reaults and case evaluations. RESULTS 1071 cattles in Quzhou Municipality were detected serologically in 2007, there were 26 positive subjects, and the positive rate was 2.43% (26/1071). And 304 subjects were detected serologically in 2007, there were 1 positive subject, and the positive rate was 0.33% (1/304) of human brucellosis. CONCLUSION There still exists a threat of brucellosis in Quzhou Municipality. Comprehensive preventive and therapeutic measures should be taken to control Human Brucellosis.
Letter to U.S. Senate Committee on the Judiciary Concerning Inter Partes Review and Orange Book-Listed Patents

A summary of data concerning the intersection of inter partes review challenges of Orange Book-listed patents.Data available at Harvard's Dataverse under keyword "sherkow."
Laser Sphincterotomy and Ablation of the Prostate Using a Sapphire Chisel Contact Tip Firing Neodymium:Yag Laser

AbstractI report a modified technique for use of a contact laser for urological endoscopic surgery in spinal cord injury patients. Instead of the usual technique of passing the laser probe for surface vaporization, subsurface buttonholes were drilled with subsequent incision of the overlying tissue. As a result, creation of an adequate channel was expedited with excellent hemostasis. A total of 40 spinal cord injury patients (mean age 50.1 years, range 28 to 76) underwent transurethral surgery for bladder outlet obstruction using a sapphire contact laser tip. Of the patients 50% had undergone previous transurethral surgery and were not voiding well. Urodynamic studies demonstrated detrusor-sphincter dyssynergia in 37 patients (92.5%). Avoiding cystoure- throgram was done in 83% of the patients and showed vesicoureteral reflux in 17%. On cystoscopic examination 32.5% of the patients had an associated enlarged prostate, 32% stricture of the bulbous urethra and 20% bladder neck stenosis. Apart from transuret...
Fear, Panic, and Market Returns

We recognize that markets have two personalities. One is of the rational and careful analyst, researching the fundamental ability of a firm to generate future earnings, and establishing a best match between risk and return in the marketplace and their own tolerance for risk. The other personality is bipolar, carried to new emotional heights when the market is optimistic, and sinking to deep emotional lows when the market mood turns ugly.
17. Intraoperative neurophysiologic monitoring of cerebral aneurysm surgery and endovascular procedures

Intraoperative neurophysiologic monitoring (IONM) can be used to assess the functional state of the brain during surgical and endovascular treatment of cerebrovascular disorders, including cerebral aneurysms. This is possible because evoked potentials and EEG are altered in a very predictive manner with different levels of regional cerebral blood flow (rCBF). A variety of studies have shown the following conclusions: 1. Major EEG changes occur with rCBF of