cssi/SciSciGPT-SciSciNet huggingface dataset:
Abstract 30: Small molecule profiling uncovers the landscape of combinatorial PI3K inhibitor responses in HNSCC

Recent sequencing studies of head and neck squamous cell carcinomas (HNSCCs) have identified the phosphatidylinositol 3-kinase (PI3K) pathway as the most frequently mutated oncogenic pathway in this cancer type. Although activating mutations or amplification in PIK3CA (the gene encoding the catalytic subunit of PI3K) are frequently observed in HNSCC, monotherapies targeting PI3K have shown limited clinical efficacy. We tested a panel of more than 20 patient-derived oral cavity squamous cell carcinoma (OCSCC) cell lines, which were profiled by Nimblegen V3 exome sequencing. Despite PIK3CA copy number amplification and/or mutations, we observed resistance to PI3K inhibitors in these models. Of six inhibitors tested, the only agents with marginal effects were alpha-isoform selective and pan-PI3K agents; these inhibitors, despite on-target and downstream activity, did not cause an appreciable reduction in cell viability when administered at submicromolar concentrations. We hypothesized that other oncogenic pathways, such as the Ras-MEK-ERK pathway, might still be functional in the presence of PI3K inhibitors and serve as compensatory mechanisms of resistance to these drugs. In order to more fully characterize other novel co-dependent pathway in PI3K inhibitor resistant HNSCC models, we have developed a high-throughput screening approach that utilizes a resazurin cell viability assay. This approach is an unbiased means of testing ~1400 inhibitors as monotherapies and in combination with alpha-isoform selective PI3K inhibitor HS-173 and pan-PI3K inhibitor BKM120 and has been utilized in several in vitro models of OCSCC to date. Testing of additional cellular models and validation of “hits” from this screen, which are drugs that are effective in combination but not as monotherapies, may identify additional resistance mechanisms and are currently ongoing. Developing a better understanding of these combination therapies and the patients in which they might be most effective may lead to improved prognosis for this disease. Citation Format: Nicole L. Michmerhuizen, Elizabeth Leonard, Micah Harris, Susan K. Foltin, Aditi Kulkarni, Thomas E. Carey, Carol R. Bradford, Jiang Hui, J. Chad Brenner. Small molecule profiling uncovers the landscape of combinatorial PI3K inhibitor responses in HNSCC [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Optimizing Survival and Quality of Life through Basic, Clinical, and Translational Research; April 23-25, 2017; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(23_Suppl):Abstract nr 30.
Ground-Based Weather Radar to Investigate Thunderstorms

Weather radars are considered an essential tool to identify and analyze rapidly evolving phenomenon like thunderstorms that are related to threats like high precipitation rates or wind speeds. Depending on the characteristics of radar, different features of a thunderstorm can be detected to highlight important characteristics such its severity, trajectory evolution and particle type distribution within the storm cloud. This chapter describes how different radar measurements (reflectivity, Doppler measurements, and dual-polarization measurements) are usually exploited by radar experts to identify important characteristics of such phenomena. In particular, dual-polarization weather radar allows to identify and quantify the presence of graupel particles that can be present within a cumulonimbus and can be associated with electrical activity, which is the unique characteristic of a thunderstorm.
Regulation of Autoimmune Diseases

The field of autoimmunity, like immunology itself, is undergoing rapid change due to progress in molecular biology and technology. Autoimmunity is traditionally defined as the body’s immune system turning against itself to produce lymphocytes reactive with self-components. These lymphocytes may be B cells secreting autoantibodies like those responsible for hemolytic anemia, T cells attacking and destroying target organs such as the thyroid, or most often, a combination of both.
A Perspective on Titanium Biocompatibility

The widespread and successful application of titanium (Ti) in medical implants is unquestionable. If, each year, Ti is used with good outcomes in hundreds of thousands of clinical implants, surely it must be biocompatible? This supposition will be examined in light of the definition of biocompatibility, ideas on the foreign body reaction and new developments in surface modification.
Postamputation Orthopedic Surgery in Canine Amputees: Owner Satisfaction and Outcome.

Abstract Surgical management of postamputation orthopedic disease (PAOD) in canine amputees has rarely been documented, and no reports describing outcome of stifle surgery in canine amputees are available. The objective of this multisite retrospective case series was to describe cases and evaluate satisfaction with and outcome of postamputation orthopedic surgery in canine amputees. Data was obtained through medical records and owner survey responses; data included signalment, amputation cause, diagnosis, surgical treatment, timeframes, and outcome assessment. Outcome was categorized as acceptable or unacceptable, and complications were classified as catastrophic, major, or minor. Eleven thoracic limb amputees and 6 pelvic limb amputees with surgically treated PAOD were identified. Surgically treated PAOD was reported at a median of 9.7 months (range 0.5-110 months) after amputation. All 17 amputees were treated for pelvic limb disease, predominantly for cranial cruciate ligament disease that occurred in 11 of 17 dogs. Major complications following orthopedic surgeries performed in 3 thoracic limb amputees consisted of infection (n = 2) and uncontrolled pain (n = 1). No major complications were reported following orthopedic surgeries performed in pelvic limb amputees. Acceptable mid-to-long-term outcome was achieved in 16 of the 17 canine amputees. Surgical treatment of pelvic limb disease did not appear to be associated with a high number of major complications in this case series. These findings suggest that orthopedic surgery, specifically stifle surgery, in canine amputees might be considered a feasible treatment option. Although there are inherent methodological limitations of retrospective studies and owner surveys, our case series provides new information that might help guide surgical treatment decisions in canine amputees suffering from orthopedic disease. Prospective studies using objective outcome measures evaluating surgical management of PAOD are necessary to confirm the provided information.
Micromorphology of Hydrocharis dubia (Blume) Backer (Hydrocharitaceae) Plants from the Far East of Russia

The micromorphology of Hydrocharis dubia (Blume) Backer (Hydrocharitaceae) from the Far East of Russia has been studied. A detailed description of anatomical structure diversity is given for the vegetative organs, and species-specific and adaptive traits of the plant are assessed. The elongated submerged vegetative shoot of the plant is shown to have a metamorphosed anatomical structure.
The truth and fiction in aspiration physics: may the forces be with you.

Recently, a number of authors, including us, have bemoaned inaccurate nomenclature and poorly described techniques throughout the acute ischemic stroke intervention literature. Such limitations adversely affect communication and may mislead readers and researchers alike about important and fundamental features of embolectomy procedures. This is particularly true of aspiration embolectomy, which remains poorly understood as a mechanistic and physical technique. Moreover, some investigations into the technique have seemed both misguided and confusing, probably because of a conceptual disconnection between the angiography suite and the laboratory benchtop. First, we would like to focus attention on an ongoing misunderstanding about what we are actually doing during these procedures, particularly the term ‘aspiration embolectomy'. Modern aspiration embolectomy encompasses two completely separate phenomena—‘aspiration-mediated retrieval’ and ‘clot ingestion’. Although many people think that the clot is continuously sucked through the entire length of the catheter, what is actually going on during many ‘aspiration’ procedures, is retrieval , not clot ingestion. In other words, we aspirate the face of the clot into the distal tip of the embolectomy catheter. We then start pulling (ie, retrieving) the clot out of the patient using the clot-engaged aspiration catheter—exactly as with a stent retriever. The suction force within the catheter, plus any friction between the ingested clot and the distal catheter inner wall, serve to hold onto the clot while we apply a considerable retrieval force (not suction force) with our hands, all of this to counteract the friction force and pressure …
Exploring obstacles faced by gifted minority students through Bronfenbrenner’s bioecological systems theory

For the past several decades, issues such as underrepresentation of racial/ethnic minority students in gifted programming, as well as the widening of the existing achievement gap between specific m...
The interactive effect of cultural self-construal and social exclusion on consumers' impression management goal pursuit

Abstract Four studies suggested that social exclusion (vs. inclusion) by ingroups leads interdependents to discard impression management goals because of a lower tendency to identify with ingroups. In contrast, independents do not change their impression management goals when socially excluded (vs. included) by ingroups. Consequently, when included (but not when excluded), interdependents (vs. independents) are willing to pay more, and are willing to expend more effort in the purchase of publicly (but not privately) consumed products. Hence, when promoting publicly consumed products, managers should strive to include interdependent consumers (e.g., via ads or promotional campaigns). Similarly, on social media (Facebook, Twitter), it is easier than ever before to determine whether consumers have been included or excluded by their friends and families at a given time. With that information, managers may be able to selectively target consumers who are likely to pay more for publicly consumed products.
MathemAntics: a model for computer-based mathematics education for young children / MathemAntics: un modelo de enseñanza de matemáticas asistida por ordenador para niños

Computer-based early mathematics education, especially when implemented on a touchscreen device, can help young children learn basic concepts of number and operations in deep and engaging ways. We ...
Scalable Space-And-Wavelength Selective Switch Architecture Using Microring Resonators

A new architecture for space-and-wavelength selective switch fabrics is proposed. This class of designs built with a combination of microring-based channel-selectors and comb-aggregators completely blocks first-order in-band crosstalk enabling highly-scalable and flexible interconnection networks. © 2019 The Author(s)
The Associations of Neighborhood Availability of Marijuana Dispensaries and DATA-2000 Waivered Providers with Hospital Stays Related to Opioids.

Background: Evidence is emerging on how state-wide marijuana legalization and increased supply of DATA-2000 waivered providers may be associated with outcomes related to opioids. It is unknown whether such associations remain at the neighborhood level. Objectives: This study examined the associations of neighborhood availability of marijuana dispensaries and DATA-2000 waivered providers with opioid-related hospital stays. Methods: Discharge-level records of inpatient (N = 264,013) and observation stays (N = 12,621) were obtained from the Washington Comprehensive Hospital Abstract Reporting System from January through June 2016. Outcomes were indicators for inpatient stays related to opioid use disorder (OUD), inpatient stays related to opioid overdose, and observation stays related to OUD. Primary predictors were the density of marijuana dispensaries and DATA-2000 waivered providers at the zip code level. Multilevel logistic regressions with random intercepts were used to examine the cross-sectional associations, controlling for other patient and neighborhood characteristics. Results: Patients living in neighborhoods with one more recreational marijuana dispensaries per square mile were more likely (OR = 1.54, p = .017) to be diagnosed with OUD in inpatient stays. Living in neighborhoods with increased density of medical marijuana dispensaries or DATA-2000 waivered providers was not associated with being diagnosed with OUD or opioid overdose in inpatient or observation stays. Conclusions: Recreational and medical marijuana dispensaries were differentially associated with opioid-related hospital stays. Further investigations are warranted to explore the causal pathways of the findings.
Safety of Tiered-Dispatch for 911 Calls for Abdominal Pain.

Author(s): Abramson, Tiffany M.; Sanko, Stephen; Kashani, Saman; Eckstein, Marc | Abstract: Introduction: Many dispatch systems send Advanced Life Support (ALS) resources to patientscomplaining of abdominal pain even though the majority of these incidents require only Basic LifeSupport (BLS). With increasing 911-call volume, resource utilization has become more important toensure that ALS resources are available for time-critical emergencies. In 2015, a large, urban firedepartment implemented an internally developed, tiered-dispatch system. Under this system, patientsreporting a chief complaint of abdominal pain received the closest BLS ambulance dispatched aloneemergency if located within three miles of the incident. The objective of this study was to determine thesafety of BLS-only dispatch to abdominal pain by determining the frequency of time-sensitive events.Methods: This was a retrospective review of electronic health records of one emergency medicalservice provider agency from May 2015-2018. Inclusion criteria were a chief complaint of abdominalpain from a first- or second-party caller, age over 15, and the patient was reported to be alert andbreathing normally. The primary outcome was the prevalence of time-sensitive events, includingcardiopulmonary resuscitation (CPR), defibrillation, or airway management. Secondary outcomeswere hypotension (systolic blood pressure l 90 mmHg); or a prehospital 12 lead-electrocardiogram(ECG) demonstrating ST-elevation myocardial infarction (STEMI) criteria or a wide complex arrhythmia.Descriptive statistics were used.Results: During the study period, there were 1,220,820 EMS incidents, of which 33,267 (2.72%) metinclusion criteria. The mean age was 49.9 years (range 16-111, standard deviation [SD] 19.6); 14,556patients (56.2%) were female. Time-sensitive events occurred in seven cases (0.021%), mean age was75.3 years (range 30-86, SD18.7); 85.7% were female. Airway management was required in sevencases (0.021%), CPR in six cases (0.018%), and defibrillation in one case (0.003%). Two of the seven(28.6%) cases involved dispatch protocol deviations. Hypotension was present in 240 (0.72%) cases;six (0.018%) cases had 12-lead ECGs meeting STEMI criteria; and no cases demonstrated widecomplex arrhythmia.Conclusion: Among adult 911 patients with a dispatch chief complaint of abdominal pain, time-sensitiveevents were exceedingly rare. Dispatching a BLS ambulance alone appears to be safe.
Tuning Crystal Structures of Iron-Based Metal–Organic Frameworks for Drug Delivery Applications

Iron-based metal–organic frameworks (Fe-MOFs) have emerged as promising candidates for drug delivery applications due to their low toxicity, structural flexibility, and safe biodegradation in a physiological environment. Here, we studied two types of Fe-MOFs: MIL-53 and MIL-88B, for in vitro drug loading and releasing of ibuprofen as a model drug. Both Fe-MOFs are based on the same iron clusters and organic ligands but form different crystal structures as a result of two different nucleation pathways. The MIL-53 structure demonstrates one-dimensional channels, while MIL-88B exhibits a three-dimensional cage structure. Our studies show that MIL-53 adsorbs more ibuprofen (37.0 wt %) compared to MIL-88B (19.5 wt %). A controlled drug release was observed in both materials with a slower elution pattern in the case of the ibuprofen-encapsulated MIL-88B. This indicates that a complex cage structure of MIL-88 is beneficial to control the rate of drug release. A linear correlation was found between cumulative dru...
Age moderates the association between psychological distress and engagement in mindfulness among cancer patients and survivors: A population-based study

We aim to evaluate the relationship between psychological distress and engagement in mindfulness among a national representative sample of cancer survivors. Using the 2017 National Health Interview...
Fe–Ni foams self-heal during redox cycling via reversible formation/homogenization of a ductile Ni scaffold

We investigate the degradation mechanisms during redox cycling of directionally freeze-cast, lamellar Fe foams containing 0, 7, 19, or 25 at% Ni, relevant to applications in solid-oxide Fe–air batteries and chemical looping processes. In pure Fe, the oxidation/reduction cycle causes a net outward Fe mass flux. This imbalance, left untreated, leads to irreversible microstructural changes: growth of internal microporosity in Fe lamellae and formation of a dense, gas-blocking shell at the foam exterior surface. We propose and demonstrate a novel strategy of alloying Fe with Ni to make reversible the oxidation and reduction pathways, creating a self-healing effect for redox cycling by H2O/H2 at 800 °C (representative of a solid-oxide Fe–air battery). During oxidation, each Fe–Ni lamella transforms, in situ, into a composite structure with a Ni-rich alloy core and FeO/Fe3O4 surfaces. The internal Ni-rich scaffold imparts mechanical stability against oxide fracture and spallation typical of Fe redox materials. During subsequent reduction, the Ni-rich scaffold maintains adhesion to the FeO/Fe3O4 surfaces, and Ni catalyzes Fe reduction at the metal/oxide interface. From this interface, Fe diffuses inward to the Ni-rich core, reversing the diffusive flux of the oxidation half-cycle, and Fe–Ni re-homogenization eliminates the microporosity formed within the lamellae during oxidation. Foams are redox-cycled and their microstructural changes are examined by metallography, SEM/EDS, and X-ray diffraction. In pure–Fe foams, the channel porosity necessary for gas flow decreases from 63 to 27 vol% after 5 redox cycles, while the deleterious microporosity increases from 3.6 to 13.7% of the lamellae volume. In contrast, Fe–25Ni foams maintain 54 vol% channel porosity and develop microporosity of only 6.7% of the lamellae volume, with mechanically stable microstructures for at least 20 redox cycles.
Sexual dimorphism of synaptonemal complex length among populations of threespine stickleback fish

Abstract Crossover frequencies often differ substantially between sexes (i.e. heterochiasmy). Although this phenomenon is widespread throughout taxa, the mechanisms that lead to heterochiasmy remain unclear. One pattern that has emerged is that the overall length of the synaptonemal complex likely has a direct influence on the total number of crossovers in each sex. However, this has only been investigated in a handful of species. The threespine stickleback fish (Gasterosteus aculeatus) is an excellent species to explore whether synaptonemal complex length is associated with differences in the total number of crossovers, as females have much longer linkage maps than males. We used an immunocytological approach to quantify synaptonemal complex length in late pachytene female and male meiocytes in two different populations of threespine stickleback fish. Overall, the freshwater population had shorter synaptonemal complex lengths than the marine population. In both populations we observed sexual dimorphism, with females possessing longer axes. Our results support a model where chromosome axis length determines overall crossover frequency and establish the threespine stickleback as a useful species to explore the mechanistic basis of heterochiasmy as well as the genetic basis underlying variation in synaptonemal complex length.
Recurrent rhabdomyomatous mesenchymal hamartoma: An uncommon benign lesion

Abstract Rhabdomyomatous mesenchymal hamartoma (RMH) is an interesting, often unexpected, benign cutaneous lesion that can present in children. Surgical excision is the intervention of choice. This case report describes a case of RMH and is unique in that it is the first instance of a recurrence. A review of the literature is included.
Prediction of tumor hypoxia using paired images of tumor proliferation and glucose metabolism in rodent breast cancers

1100 Objectives Imaging tumor hypoxia is very important not only to predict prognosis but also to select the appropriate therapy. The goal of this study is to estimate hypoxic areas in vivo using images of tumor perfusion and glucose metabolism. Methods Rats bearing syngeneic mammary tumor (RMT) in their interscapular subcutaneous region were prepared. One of the well-established hypoxia markers, pimonidazole (60mg/kg) was injected i.p. six hours before sacrifice, and 14C-deoxy-d-glucose (10μCi) and a perfusion marker, Hoechst 33342 (10mg/kg) were injected i.v. two hours and one minute before sacrifice, respectively. We removed the tumors and made sections of three or four different parts of each tumor. Digital autoradiography for 14C and immunofluorescent staining using a confocal microscope were performed with the same frozen sections. The images of the distribution of the three tracers were quantitatively assessed for density on tumor sections using ImageJ. Correlation among the tracers was analyzed. Furthermore, the data was classified into groups according to Hoechst 33342 and 14C-deoxy-d-glucose density, and 3D graphs were created to analyze the correlation among the three agents. Results Pimonidazole and Hoechst 33342 (flow) showed a mild negative correlation (r=-0.29, p Conclusions Our results suggest that the combination of perfusion and glucose metabolism images is more helpful to predict tumor hypoxia than either metric alone and that the most hypoxic tissues are those with a signature of high FDG accumulation and relatively low tumor blood flow
Thermal Stresses Near the Interface of a Bimaterial Joint

The state of elastic strains and stresses in a bimaterial joint subjected to a uniform change of temperature was analyzed by moire interferometry.1,2 The specimen configuration is illustrated in Fig. 8.1. The steel and brass plates were joined by a very thin, high-temperature silver-solder film along the mating surfaces. The experimental analysis measured the deformations caused by a change of temperature of -133°C.
CLINICAL CONFERENCE: Ulcerative Colitis

Dr. Wright: I shall describe a boy with ulcerative colitis whom we have been following for the last 15 years. His father is of Swedish extraction, American born. He is a very placid, long-suffering gentleman who enters very little into the picture which follows. His education extended slightly beyond the high school level as he went to college for 2 years at a technical school. The boy9s mother, by contrast, was born in Italy. Her family migrated to this country when she was only 9 months. They settled in Chicago and set up a closely knit family unit which spoke Italian most of the time. His mother grew up under circumstances which made her feel considerably inferior to persons around her. She had a younger sister of whom she was very jealous during the early part of her life. She also had many feelings of resentment toward her mother from whom she apparently received little or no affection. During her early childhood she had clubbed feet which were corrected by her mother by the application of an apparatus which was painful and which caused her to cry a good ideal without receiving much solace from her mother. Her education extended only through grammar school, with the addition of 2 years of secretarial training. After this, she never held a job for any length of time. She worked sporadically as a waitress. She lived at home with her family and became closely attached to them. In spite of her feeling toward her mother, she was quite dependent upon her.
A scalable algorithm for clustering protein sequences

The enormous growth of public sequence databases and continuing addition of fully sequenced genomes has created many challenges in developing novel and scalable computational techniques for searching, comparing, and analyzing these databases. Over the years, many methods have been developed for clustering proteins according to their sequence similarity. However, most of these methods tend to have a computational complexity that is at least quadratic on the number of sequences. In this paper we present an entirely different approach to protein clustering that does not require an all-against-all analysis and uses a near-linear complexity K-means based clustering algorithm. Our experimental evaluation on three different data sets containing up to 43,569 protein sequences, show that this approach leads to reasonably good clusters.
Mechanisms of hTERT up-regulation during immortalization of human mammary epithelial cells

4987 Immortality is a prerequisite for the accumulation of multiple malignant changes in a single cell lineage during human breast carcinogenesis. We use cultured human mammary epithelial cells (HMEC) to study changes contributing to immortalization. Following treatment with carcinogen, benzo(a)pyrene, extremely rare HMEC achieved immortalization. Early passages of the immortal HMEC line 184A1, expressing wild-type p53, initially displayed very low telomerase activity, but continued to divide until the cells attained mean TRF lengths of 3 kb or less. At this point, the cultured cells reproducibly entered a period of slow, heterogeneous growth termed conversion, which was accompanied by accumulation of the cyclin-dependent kinase inhibitior p57KIP2. When the p53-inhibiting genetic suppressor element 22 (GSE22) was transduced into the cells prior to the onset of conversion, hTERT mRNA was rapidly induced and telomerase activity was up-regulated, indicating that telomerase expression in the newly immortalized HMEC was suppressed by endogenous p53. As conversion of 184A1 progressed, p57KIP2 was dowregulated, and p53-mediated repression of hTERT was presumably alleviated. Current experiments include: 1) investigating the role of p57KIP2 in hTERT regulation by introducing shRNA to p57KIP2 into 184A1 HMEC before and during conversion, 2) measuring the timing of hTERT activation following inhibition of p53 by GSE22, as a first step in determining the mechanism of p53-mediated repression of hTERT, and 3) testing the hypothesis that alterations in chromatin configuration of the hTERT promoter may be necessary for de-repression of hTERT as 184A1 cells undergo conversion to full immortality. In the latter experiments, we are examining the effects of the histone deacetylase inhibitor, trichostatin A (TSA), on pre-conversion 184A1 cells in the presence and absence of transcriptional regulators such as c-myc. By examining the mechanisms of hTERT de-repression during HMEC immortalization, we expect to gain further understanding of rate-limiting processes taking place during early breast carcinogenesis.
Idiopathic Peripheral Neuropathy and Subsequent Development of Diabetes Mellitus (P6.095)

OBJECTIVE: To ascertain the percentage of patients with idiopathic sensorimotor axonal peripheral neuropathy diagnosed via nerve conduction studies that subsequently develop diabetes mellitus. BACKGROUND: Peripheral neuropathy causes significant morbidity due to pain, gait instability, and injury. Diabetes mellitus is considered the most common cause amongst many, but approximately 1/3rd of patients never have an identifiable cause and the term idiopathic peripheral neuropathy is applied. METHODS: 421 patients from the New Mexico VA Health Care System (NMVAHCS) electrodiagnostic laboratory were diagnosed with idiopathic peripheral neuropathy in last 16 years. Hemoglobin A1c (HgbA1c) both around the time of nerve studies and at subsequent visits was gathered retrospectively. Classification of diabetes was based on 2010 American Diabetes Association guidelines (HgBA1c <5.7% normo-glycemic, 5.7- 6.4% pre-diabetic and 蠅6.5% diabetic). Patients with initial HgbA1c 蠅 6.5%, another cause for neuropathy and those taking anti-diabetic medications were excluded. SAS software used for statistical analysis. RESULTS: At final analysis 283 patients (269 males, 14 females) with a median age of 65 years (38 to 95) were included. Around the time of the nerve study, 156 (55.1%) patients were normo-glycemic and 127 (44.9%) pre-diabetic. On follow-up of 156 normo-glycemic patients, 36.5% converted to pre-diabetes, 10.3% to diabetes, 37.2% remained normo-glycemic and data was unavailable for 16%. Of the 127 initially pre-diabetic patients, 54.3% remain pre-diabetic, 18.9% converted to diabetes, 7.9% returned back to normo-glycemic, and data was unavailable for 18.9%. Overall, 46.8% of the initially normo-glycemic patients converted to pre-diabetes or diabetes and survival analysis shows 50% of them took 78 months (6.5 years) to convert. CONCLUSION: Peripheral neuropathy may precede the actual diagnosis of pre-diabetes/diabetes mellitus. These patients should be routinely monitored for development of diabetes mellitus and make early lifestyle modifications to decrease future complications. Disclosure: Dr. Mahajan has nothing to disclose. Dr. King has received personal compensation for activities with Demos Publishing as an author.
The interposition operation.

Abstract One hundred cases treated by the interposition operation between the years 1926 and 1951 are reported. The indications are stressed and it is pointed out that if these are intelligently followed excellent results may be expected. A plea is made for the retention of this procedure in the armamentarium of the gynecological surgeon.
Dopamine D1 receptor behavioral responsitivity following selective lesions of the striatal patch compartment during development.

The behavioral effects of selective destruction of the dopamine (DA) input to the patch compartment of rat striatum early in development was investigated. Rat pups were given bilateral intrastriatal (i.s.) injections of the neurotoxin 6-hydroxydopamine (6-OHDA) on day of birth (P0) or postnatal day 1 (P1), which resulted in selective behavioral alterations following DA agonist treatment in adulthood. Neonatally-lesioned rats exhibited self-biting behavior following treatment with the DA precursor L-dihydroxyphenylalanine (L-DOPA). In response to treatment with the selective D1 agonist SKF38393, there was an increased incidence of abnormal perioral movements. The cataleptogenic effects of the D1 antagonist SCH23390 and the D2 antagonist haloperidol were also studied. Neonatally-lesioned rats were significantly less cataleptic compared to control rats following D1 antagonist treatment, but not following D2 antagonist treatment. Autoradiographs of [3H]mazindol binding to DA uptake sites (a measure of DA terminal density) showed a 'patchy' loss of approx. 40-50% in striatal tissue sections derived from the i.s. lesioned rats. These data suggest that injections of 6-OHDA into the striatum during this early postnatal period cause a DA lesion that results in long-term effects on a D1 receptor system.
Adjustment costs and indeterminacy in perfect foresight models

Abstract This paper suggests a method for resolving indeterminacy of equilibrium in perfect foresight models and applies it to several existing models. Quadratic adjustment costs are introduced into models with multiple equilibria, and the limiting behavior of the resulting solutions is studied as the adjustment costs go to zero. The method is shown to be useful in selecting among feasible equilibria in examples in which there is local indeterminacy.
Corrigendum to “Design and synthesis of a novel pyrrolidinyl pyrido pyrimidinone derivative as a potent inhibitor of PI3Kα and mTOR” [Bioorg. Med. Chem. Lett. 22 (2012) 5098–5103]

Corrigendum Corrigendum to ‘‘Design and synthesis of a novel pyrrolidinyl pyrido pyrimidinone derivative as a potent inhibitor of PI3Ka and mTOR’’ [Bioorg. Med. Chem. Lett. 22 (2012) 5098–5103] Phuong T. Le a,⇑, Hengmiao Cheng , Sacha Ninkovic , Michael Plewe , Xiaojun Huang , Hai Wang , Shubha Bagrodia , Shaoxian Sun , Daniel R. Knighton , Caroline M. LaFleur Rogers , Andrew Pannifer , Samantha Greasley , Deepak Dalvie , Eric Zhang c Cancer Chemistry, Pfizer Worldwide Research & Development, La Jolla Laboratories, Pfizer Inc., La Jolla, CA 92121, United States Oncology Research Unit, Pfizer Worldwide Research & Development, La Jolla Laboratories, Pfizer Inc., La Jolla, CA 92121, United States PDM, Pfizer Worldwide Research & Development, La Jolla Laboratories, Pfizer Inc., La Jolla, CA 92121, United States d Pfizer Worldwide Research & Development, Sandwich Laboratories, Pfizer Inc., UK
Aerosol size distribution from ion mobility

Abstract Constructional details of one ion chamber design are presented. A typical ion current versus voltage curve is shown. The theory pertinent to the interpretation of such curves in terms of mobility distribution and size distribution for aerosols is presented in detail. Experimental results are presented and are compared with those obtained using the electron microscope.
Studies on the activities and properties of lysosomal hydrolases in fractionated populations of human peripheral blood cells.

Abstract Studies have been carried out on the activities and properties of the isozymes of α-mannosidase, α-glucosidase and β-glucosidase in granulocytes, monocytes, lymphocytes and platelets from peripheral blood of healthy adult donors. The findings reveal the differences in activities as well as a characteristic distribution of the different molecular forms of these lysosomal hydrolases in specific cell types. Therefore, the results obtained with unfractionated total leukocyte samples from different subjects may vary according to the distribution of cell types in the circulation. Granulocytes and monocytes show only the acid α-mannosidase activity whereas lymphocytes and platelets show both acid and neutral activities. The specific activity of acid α-mannosidase in granulocytes and monocytes is higher than in lymphocytes and platelets. By DEAE-cellulose chromatography, the acid α-mannosidase in granulocyte and monocyte extracts elutes as two peaks, but only one peak is seen in lymphocytes. All cell types show both acid and neutral α-glucosidase activities. The specific activities of both isozymes are higher in granulocytes and monocytes than in lymphocytes and platelets. Monocytes show a higher acid than neutral activity. All other cell types show a higher neutral activity. β-Glucosidase in all cell types is mainly membranebound and it can be released by Triton X-100 and sodium taurocholate. Taurocholate also stimulates the β-glucosidase activity of granulocytes, monocytes and lymphocytes whereas it inhibits the activity of this enzyme in platelets. These results indicate that variations in the total number of leukocytes and in the relative proportion of the various cell types in health and disease may yield inconsistent or unreliable values for enzyme activity in the diagnosis of ly sosomal storage disease and in carrier detection
Neuroprotective effects of moderate aerobic exercise on the spastic Han-Wistar rat, a model of ataxia.

Abstract Research has shown that physical exercise may reduce degeneration in certain brain regions experiencing ataxia. Our laboratory utilized mutant spastic Han–Wistar rats (sHW) that display developmental abnormalities, including spastic paresis, fore limb tremors, hind limb rigidity, and a reduced life span (60–65 days of age). Concomitant neurodegeneration has been observed in the cerebellum (Purkinje cells). The purpose of this study was to investigate if moderate, aerobic exercise could reduce Purkinje cell neurodegeneration and improve the motor ability and survival of the mutant sHW rat. Mutant male littermates at the ages of 20 (n = 11 pairs) and 30 (n = 13 pairs) days old were divided into running groups and non-running groups. Mutant rats were run on a motorized treadmill at the rate of 15 m/min with a 10% slope. The “running” group ran for 30 min per day, 5 days a week; the “non-runners” remained nearby in the training facility. These conditions were held constant until the mutant runners could no longer run due to disease progression. Moderate exercise increased the lifespan of running mutant rats in both the 20-day start group (14% increase) and 30-day start group (13% increase). The rats exhibited improved motor function as open-field tests showed higher activity scores for runners after 50 days. Histological examination of the cerebellum revealed a 62% increase in Purkinje cell survival of the runners. These results suggest that aerobic exercise ameliorates, at least partially, cerebellar dysfunction in the sHW rat, an excellent model of ataxia.
Performance bounds for matched field processing in subsurface object detection applications

In recent years there has been considerable interest in the use of ground penetrating radar (GPR) for the non-invasive detection and localization of buried objects. In a previous work, we have considered the use of high resolution array processing methods for solving these problems for measurement geometries in which an array of electromagnetic receivers observes the fields scattered by the subsurface targets in response to a plane wave illumination. Our approach uses the MUSIC algorithm in a matched field processing (MFP) scheme to determine both the range and the bearing of the objects. In this paper we derive the Cramer-Rao bounds (CRB) for this MUSIC-based approach analytically. Analysis of the theoretical CRB has shown that there exists an optimum inter-element spacing of array elements for which the CRB is minimum. Furthermore, the optimum inter-element spacing minimizing CRB is smaller than the conventional half wavelength criterion. The theoretical bounds are then verified for two estimators using Monte-Carlo simulations. The first estimator is the MUSIC-based MFP and the second one is the maximum likelihood based MFP. The two approaches differ in the cost functions they optimize. We observe that Monte-Carlo simulated error variances always lie above the values established by CRB. Finally, we evaluate the performance of our MUSIC-based algorithm in the presence of model mismatches. Since the detection algorithm strongly depends on the model used, we have tested the performance of the algorithm when the object radius used in the model is different from the true radius. This analysis reveals that the algorithm is still capable of localizing the objects with a bias depending on the degree of mismatch.
Interviewing for knowledge

An expert system is an application of artificial intelligence which requires the transfer of knowledge from human to machine. The acquisition of this knowledge from experienced practitioners (domain experts) is typically inefficient. Problems associated with the subjective reporting of knowledge must be overcome. To do this, a structured rather than unstructured interviewing approach can be used by knowledge engineers. Open, closed, and probing questions as well as direction responses should be used, together with a general-to-specific technique. The goal of the knowledge acquisition interview is to obtain complete, accurate, and reliable knowledge for the expert system.
A Practical Measure of Student Motivation: Establishing Validity Evidence for the Expectancy-Value-Cost Scale in Middle School.

We present validity evidence for the Expectancy-Value-Cost (EVC) Scale of student motivation. Using a brief, 10-item scale, we measured middle school students’ expectancy, value, and cost for their math and science classes in the Fall and Winter of the same academic year. Confirmatory factor analyses supported the three-factor structure of the EVC Scale, as well as measurement invariance across gender, academic domain, and time. Predictions of the EVC Scale’s relationship with domain-specific future interest and prior achievement provide convergent and discriminant validity evidence. The practical utility of the survey is highlighted by the short administration time and the alignment between observed and latent means, indicating that practitioners can use raw scores rather than latent values. Finally, we discuss methods of how to use the EVC Scale to provide actionable information for educational practitioners, such as identifying which motivation interventions are most needed for students and if those in...
Final report of the phase I trial of continuous infusion etanidazole (SR 2508): A radiation therapy oncology group study

Seventy-eight patients have been treated on a Phase I trial using continuous infusion etanidazole while undergoing brachytherapy for locally advanced tumors. There were two sequential schemata, the first treated 63 patients with doses ranging from 8-23 g/m2 over 48 hr and the second treated 15 patients with doses ranging from 20-23 g/m2 over 96 hr. The tumor sites were: brain (n = 42), cervix (n = 22), and breast (n = 14). Patients received a loading dose of etanidazole of 2 g/m2 followed by a continuous infusion for a total of 48 or 96 hr while radioactive implants were in place. Of the 63 patients in the 48-hr study, 52 were entered at doses of less than or equal to 21 g/m2 and there were no definite neuropathies but two patients with the cramping/arthralgia syndrome. Of the 11 patients entered at 22-23 g/m2, 1 patient had symptoms of peripheral neuropathy (Grade II) and 6 had the cramping/arthralgia syndrome. This is a new syndrome, distinct from the peripheral neuropathy, characterized by transient alterations in sensations consisting of cramping, arthralgias, or tingling that resolved completely at intervals varying from a few hours to about 1 week post-treatment. The cramping/arthralgia syndrome limited dose escalation; therefore, the maximum tolerated dose over 48 hr was determined to be 20-21 g/m2. The 96-hr infusion was limited to patients with recurrent gliomas undergoing stereotactic implantation. To date, 15 patients have been treated with doses of 20-23 g/m2. No toxicity was encountered at doses less than or equal to 22 g/m2. At 23 g/m2, one patient developed Grade III neuropathy and three patients had mild cramping/arthralgia syndrome, for whom the drug was discontinued. Therefore, it appears the maximum tolerated dose at 96 hr will be approximately 23 g/m2, which is 10-15% higher than for the 48-hr infusion.
Rare earth element partitioning between hydrous ferric oxides and acid mine water during iron oxidation

Ferrous iron rapidly oxidizes to Fe (III) and precipitates as hydrous Fe (III) oxides in acid mine waters. This study examines the effect of Fe precipitation on the rare earth element (REE) geochemistry of acid mine waters to determine the pH range over which REEs behave conservatively and the range over which attenuation and fractionation occur. Two field studies were designed to investigate REE attenuation during Fe oxidation in acidic, alpine surface waters. To complement these field studies, a suite of six acid mine waters with a pH range from 1.6 to 6.1 were collected and allowed to oxidize in the laboratory at ambient conditions to determine the partitioning of REEs during Fe oxidation and precipitation. Results from field experiments document that even with substantial Fe oxidation, the REEs remain dissolved in acid, sulfate waters with pH below 5.1. Between pH 5.1 and 6.6 the REEs partitioned to the solid phases in the water column, and heavy REEs were preferentially removed compared to light REEs. Laboratory experiments corroborated field data with the most solid-phase partitioning occurring in the waters with the highest pH.
Detecting Hydrothermal Pyritic Zones along Bald Eagle Ridge Using Induced Polarization

Acid rock drainage (ARD) is a major environmental problem in Pennsylvania. ARD occurs when iron sulfides, most commonly pyrite, oxidize to form sulfuric acid. This weathering reaction typically occurs slowly in undisturbed pyritic rock. When this rock is excavated, however, the greater surface area and availability of oxygen enable iron-oxidizing bacteria to flourish, increasing the reaction rate by many orders of magnitude (e.g., Singer and Stumm, 1970). Although the majority of ARD problems are due to coal mining, ARD can also be caused by highway construction. Typical characterizations can involve drilling test holes and carrying out acid-base accounting on the cores. Pennsylvania guidelines for highway construction require a drillhole every 500 ft (152 m). However, in areas of near-vertical beds or steeply dipping veins, sizeable pyritic zones can easily be missed. Induced polarization (IP) is a geophysical method that can be used to detect pyritic zones before excavation. The purpose of this article is to report the results of IP surveys of hydrothermal pyrite veins in the sandstones and shales of the Appalachians. IP is an electrical geophysical method developed by the mining industry to prospect for disseminated sulfide deposits. IP measures chargeability, the ability of a material to retain electrical charge. In general, rocks with pyrite contents of approximately one percent or greater have elevated chargeabilities. Although the potential value of IP in screening highway corridors for potential ARD problems has been known for some time (Jones et al., 1982), the technique is not widely used. To our knowledge, all of the published case studies (Jones et al., 1982; Anderson et al., 1990; Byerly, 1996; Butler et al., 2004) discuss the detection of pyritic zones in meta-sedimentary rocks. Although these studies were successful in locating some pyritic zones, they were unable to quantify the relationship between IP response …
Use of online modules to enhance knowledge and skills application during an introductory pharmacy practice experience.

Objectives. To implement and assess the effectiveness of online instructional modules to increase the consistency of learning outcomes related to students’ patient-care practice knowledge and their...
Crystal nucleation: More than one pathway

A predictive theoretical framework that incorporates both classical and non-classical crystal-nucleation pathways explains the observed rapid aggregation of metastable clusters in the nucleation process of minerals.
OIM and Related Animal Models of Osteogenesis Imperfecta

Osteogenesis imperfecta (OI) is characterized by fragile bones, skeletal deformity, and growth retardation. This heritable disorder of connective tissue is the result of mutations affecting the COL1A1 and COL1A2 genes of type I collagen. Progress in OI research has been limited because of dependence on human fibroblast and osteoblast specimens and the absence of a naturally occurring animal model for this genetic disorder. Recent technology in molecular biology has led to the development of transgenic models of OI based on site directed mutagenesis of type I collagen genes. OIM is a naturally occurring model which incorporates both the phenotypic and biochemical defects of moderate to severe osteogenesis imperfecta. This powerful tool permits the development of models based on different type I collagen mutations. The collagen type I mutation in OIM is a C propeptide deletion which impairs the production of normal pro-alpha2(I). Tissues in OIM contain only [pro-alpha1(I)]3 homotrimer. Thus, although several animal models are now available for research in osteogenesis imperfecta few are viable or fully mimic human disease disorders. OIM duplicates the phenotype and biochemistry of human disease and has a normal life span.
An exact discretization of Michaelis–Menten type population equations

Many single population models involve the inclusion of Michaelis–Menten type terms. We derive an exact discretization for such rational functions and demonstrate how these relations may be incorporated into more complex models representing the dynamics of single populations. The Lambert W-function plays an important role in this work.