cssi/SciSciGPT-SciSciNet huggingface dataset:
Intensive care unit admission for patients with pulmonary hypertension presenting to U.S. Emergency Departments.

Abstract Introduction Pulmonary hypertension (PH) is an important contributor to morbidity and mortality in patients seeking emergency care, resulting in high acuity presentations and resource utilization. The objective was to characterize the rate of intensive care unit (ICU) admission for PH among adult patients presenting to the emergency department (ED) along with other important clinical outcomes. Methods We analyzed data from the State Emergency Department Databases (SEDD) and State Inpatient Databases (SID) from two geographically separated U.S. states (New York and Nebraska). The primary outcome measure was admission to an ICU. Other measures of interest included the hospital admission rate, hospital length of stay (LOS), inpatient mortality, and rate of critical care procedures performed. Results From 2010 to 2014, in a sample of 34 million ED visits, patients with a diagnosis of PH accounted for 0.71% of all ED visits. Of the PH visits, 20.2% were admitted to the ICU, compared to 2.6% of all other visits (P Conclusions In this study, patients with PH who sought emergency care in U.S. EDs from 2010 to 2014 were significantly more likely to require ICU admission than all other patients. They were also significantly more likely to be admitted to the hospital than all other patients, had longer hospital LOS, increased risk of inpatient mortality, and underwent more critical care procedures. These findings indicate the high acuity of PH patients seeking emergency care and demonstrate the need for additional research into this population.
Epithelial-to-Mesenchymal Transition Signaling Pathways Responsible for Breast Cancer Metastasis

Breast carcinoma is highly metastatic and invasive. Tumor metastasis is a convoluted and multistep process involving tumor cell disseminating from their primary site and migrating to the secondary organ. Epithelial-mesenchymal transition (EMT) is one of the crucial steps that initiate cell progression, invasion, and metastasis. During EMT, epithelial cells alter their molecular features and acquire a mesenchymal phenotype. The regulation of EMT is centered by several signaling pathways, including primary mediators TGF-β, Notch, Wnt, TNF-α, Hedgehog, and RTKs. It is also affected by hypoxia and microRNAs (miRNAs). All these pathways are the convergence on the transcriptional factors such as Snail, Slug, Twist, and ZEB1/2. In addition, a line of evidence suggested that EMT and cancer stem like cells (CSCs) are associated. EMT associated cancer stem cells display mesenchymal phenotypes and resist to chemotherapy or targeted therapy. In this review, we highlighted recent discoveries in these signaling pathways and their regulation in breast cancer metastasis and invasion. While the clinical relevance of EMT and breast cancers remains controversial, we speculated a convergent signaling network pivotal to elucidating the transition of epithelial to mesenchymal phenotypes and onset of metastasis of breast cancer cells.
Tracheal Ulcer Development From Low Pressure Cuffed Flexible Endotracheal Tubes

Background: Endotracheal intubation is a life-saving intervention performed in the setting of respiratory failure. While injury to the vocal cords is known, there is limited information in the literature on tracheal injuries secondary to endotracheal intubation. Patient positioning, cuff pressure, tube positioning, and pressure exerted on the tube by the tongue can cause the endotracheal tube to follow a sigmoidal path through the airway, causing the tip of the endotracheal tube to rest on the tracheal wall and potentially putting the patient at risk of injury. However, the development of low pressure cylindrical cuffed flexible endotracheal tubes can mitigate injuries found at the tip and cuff of the endotracheal tube. This study investigates the development of endotracheal tip and cuff ulcers in ICU patients as observed at the time of tracheostomy placement. Methods: An IRB approved retrospective cohort study was conducted on 1,355 patients who underwent tracheostomy from 2002–2018. Tracheal ulcers were documented during percutaneous tracheostomy placement. Patients were excluded if tracheal ulcers were not documented by bronchoscopy. Demographic data was collected. Primary outcome measures included length of time on a ventilator until tracheostomy (LOVT), length of hospitalization (LOH), and mortality. Data was reported as n (%) and median (IQR). Differences in means between groups were analyzed by ANOVA with alpha of 0.05. Results: Chart review of 206 patients revealed 65 subjects without tracheal ulcers and 141 patients with tracheal ulcers. Patients with tracheal ulcers were grouped by severity: no ulcer, mild - minimal mucosal erosion with exudate, moderate - mucosal erosion, severe - tracheal ring exposure. Comparison of demographic data revealed no statistically significant differences in age (P = 0.99), gender (P = 0.83), BMI (P = 0.44), LOH (P = 0.88), LOVT (P = 0.93), and mortality (P = 0.306) between patients with differing severity of ulcers. The average yearly incidence of clinically significant ulcers (moderate and severe) was 2.2%. Conclusions: In our limited cohort, there was no statistically significant difference in age, gender, LOH, LOVT, BMI, and mortality between patients with different severity of tracheal ulcers due to intubation. The lack of statistical difference amongst severity and demographic data, along with a low average yearly incidence of 2.2%, supports the safety of low pressure cylindrical cuffed flexible endotracheal tubes on tracheal injuries.
MODELS FOR INTERACTION OF THE TEAR FILM WITH THE CORNEAL AND CONJUNCTIVAL EPITHELIA

Mathematical models that connect the tear film with the underlying epithelia of the cornea and conjunctiva were developed. The tear film is assumed to be a spatially uniform evaporating aqueous layer with a concentration variable representing the osmolarity in the tear film. In the first model, the underlying epithelia are approximated as in Levin and Verkmann [6], with a few layers of cells of varying thickness that are linked via osmosis between each of the cells and with the tear film. Loss of water due to evaporation from the tear film causes increased osmolarity there, leading to osmotic flow from the epithelium to the tear film, and between the epithelial cells. The parameters are set by comparison with thinning rate measurements from human subjects in vivo. In those experiments, 5% fluorescein solution is instilled in the tear film, and the thickness of the tear film is deduced from subsequent intensity measurements in the concentrated flourescein regime. These measurements were used to calibrate the model parameters for osmosis. A second model is proposed that includes the molecules involved in metabolism in the epithelial cell of the cornea. This model is based on the Leung et al model [3]. The proposed model includes differential and algebraic equations to represent the concentrations of the metabolites in the cells and their effects over time. Both models are used to predict tear film thickness and osmolarity, as well as epithelial cell layer thicknesses and osmolarities. The first model predicts thickness and osmolarity changes for single interblinks and for extended periods of many blink cycles with constant interblink duration. Cumulative effects from multiple blink cycles are seen that are significantly more than for single interblinks. We interpret the results in light of biochemical response and the rate of progression of apoptosis in squamous cells.
Advances in Genome Sequencing and Genotyping Technology for Soybean Diversity Analysis

Publisher Summary The completion of a soybean draft whole genome sequence along with advances in sequencing and genotyping technologies are creating a revolution in soybean genomics. The draft whole genome sequence of soybean is allowing researchers to fully take advantage of the new technology and is rapidly changing how soybean germplasm is mined. Genetic markers can be quickly identified by using next generation sequencing and assayed on a large number of materials using advanced technologies that can genotype tens of thousands of markers on thousands of individuals very rapidly. The ability to quickly identify and genotype genetic diversity is allowing researchers to identify beneficial genetic diversity and rapidly transfer it into elite cultivars for increased soybean production, biotic and abiotic protection, and improved seed quality. As all the genetic variation is mapped out within soybean germplasm, new and novel methods would be developed that would better link the genetic variation to phenotype variation. That would help in the abilities to improve soybean.
Developing Scientific Applications with Loosely-Coupled Sub-tasks

The Simple API for Grid Applications (SAGA) can be used to develop a range of applications which are in turn composed of multiple sub-tasks. In particular SAGA is an effective tool for coordinating and orchestrating the many sub-tasks of such applications, whilst keeping the application agnostic to the details of the infrastructure used. Although developed primarily in the context of distributed applications, SAGA provides an equally valid approach for applications with many sub-tasks on single high-end supercomputers, such as emerging peta-scale computers. Specifically, in this paper we describe how SAGA has been used to develop applications from two types of applications: the first with loosely-coupled homogeneous sub-tasks and, applications with loosely-coupled heterogeneous sub-tasks. We also analyse and contrast the coupling and scheduling requirements of the sub-tasks for these two applications. We find that applications with multiple sub-tasks often have dynamic characteristics, and thus require support for both infrastructure-independent programming models and agile execution models. Hence attention must be paid to the practical deployment challenges along with the theoretical advances in the development of infrastructure-independent applications.
Complete leading order analysis in chiral perturbation theory of the decays KL → γγ and KL → ℓ+ℓ−γ

Abstract The decays K L → γγ and K L → l + l − γ are studied at the leading order p 6 in chiral perturbation theory. One-loop contributions stemming from the odd intrinsic parity | ΔS | = 1 effective Lagrangian of order p 4 are included and shown to be of possible relevance. They affect the decay K L → γγ adding to the usual pole terms a piece free of counterterm uncertainties. In the case of the K L → l + l − γ decays the dependence of the form factor on the dilepton invariant mass requires a counterterm. The form factor may receive a sizeable contribution from chiral logarithms. Including considerations from the K L → π + π − γ direct emission amplitude, we obtain two consistent scenarios. In one scenario the long distance contributions from the one-loop terms are important, while in the other they are marginal. In both cases the counterterm is shown to be significant.
OATPs, OATs and OCTs: the organic anion and cation transporters of the SLCO and SLC22A gene superfamilies

The human organic anion and cation transporters are classified within two SLC superfamilies. Superfamily SLCO (formerly SLC21A) consists of organic anion transporting polypeptides (OATPs), while the organic anion transporters (OATs) and the organic cation transporters (OCTs) are classified in the SLC22A superfamily. Individual members of each superfamily are expressed in essentially every epithelium throughout the body, where they play a significant role in drug absorption, distribution and elimination. Substrates of OATPs are mainly large hydrophobic organic anions, while OATs transport smaller and more hydrophilic organic anions and OCTs transport organic cations. In addition to endogenous substrates, such as steroids, hormones and neurotransmitters, numerous drugs and other xenobiotics are transported by these proteins, including statins, antivirals, antibiotics and anticancer drugs. Expression of OATPs, OATs and OCTs can be regulated at the protein or transcriptional level and appears to vary within each family by both protein and tissue type. All three superfamilies consist of 12 transmembrane domain proteins that have intracellular termini. Although no crystal structures have yet been determined, combinations of homology modelling and mutation experiments have been used to explore the mechanism of substrate recognition and transport. Several polymorphisms identified in members of these superfamilies have been shown to affect pharmacokinetics of their drug substrates, confirming the importance of these drug transporters for efficient pharmacological therapy. This review, unlike other reviews that focus on a single transporter family, briefly summarizes the current knowledge of all the functionally characterized human organic anion and cation drug uptake transporters of the SLCO and the SLC22A superfamilies. LINKED ARTICLES BJP recently published a themed section on Transporters. To view the papers in this section visit http://dx.doi.org/10.1111/bph.2011.164.issue-7
On the Complexity of Single Row Routing Problems

We consider single row routing problems in VLSI. Previous work has left open, for all k≥3, whether or not there is an efficient algorithm to route interconnections on the minimum number of layers when only k channels are permitted per layer. We show that deciding whether such a routing exists is NP-complete even when k=3 and the interconnections are 2-pin nets. This solves an important open problem often cited in the literature. We also improve the running times of previously described algorithms for obtaining optimal single row routings by showing how to eliminate several paths in exhaustive search. Although this result still yields an exponential time algorithm (which presumably is necessary, as the problem is NP-complete), it solves routings instances with more channels than could be handled before.
Proportionate Mortality Study of Workers in the Grain Industry

The proportionate mortality experience and proportionate cancer mortality experience were examined for 1,114 white male members of the American Federation of Grain Millers' life insurance plan. Mortality was significantly elevated for accidents and cancers of the lymphatic and hematopoietic systems, particularly from lymphosarcoma and reticulum cell sarcoma, other neoplasms of lymphoid tissue (i.e., giant follicular lymphoma and other primary malignant neoplasms of lymphoid tissue), and multiple myeloma. No increased mortality was seen for cancer of the respiratory tract, and nonmalignant diseases of the digestive tract were significantly lower than expected. Employees of grain mills showed higher mortality ratios of lymphatic and hematopoietic cancers as compared to other grain industry categories. A preliminary survey of pesticide usage suggested that grain mills were generally associated with greater use of pesticides than other industrial categories with considerable variation among the many facilities encompassed in this study.
Design of a Medical Triage Evidence-Based Clinical Management Protocol and Implementation of Medical Triage On-Line Training for Use by Mission of Mercy Volunteers

Evidence-based protocols in safety net settings can help standardize care practices, increase organizational workflow, and enhance quality outcomes for those receiving services. The purpose of this quality improvement project is two-fold: to design an evidence-based medical triage clinical management protocol, and, to influence adherence to that protocol by safety net medical triage volunteers through an on-line volunteer orientation. Leadership skills were required to help translate evidence-based practice recommendations into useful tools to assist in directing practice. Project outcomes included successful multidisciplinary practice change, significantly improved volunteer knowledge surrounding medical triage protocol parameters, increased organizational workflow, and enhanced quality client outcomes.
Pharmacists' role in facilitating evidence-based prescribing for unlabeled use of medications.

In the United States, up to 80% of prescription drugs are prescribed for indications not approved by the Food and Drug Administration (FDA).[1][1] Unlabeled use is often the mainstay of therapy in patient populations for whom less conclusive evidence is available, such as pediatric,[2][2] oncology,[
Characteristics of the relationship between plasma ketamine concentration and its effect on the minimum alveolar concentration of isoflurane in dogs

Objective To characterize the shape of the relationship between plasma ketamine concentration and minimum alveolar concentration (MAC) of isoflurane in dogs.
Mechanical transmission of bovine leukemia virus by horse flies (Diptera: Tabanidae).

Bovine leukemia virus was transmitted mechanically to goats and sheep from a cow with persistent lymphocytosis and an infectious titer between 103 and 104 doses/ml by groups of 50 and 100 horse flies, Tabanus fuscicostatus Hine, but not by groups of 25 and 10 flies. A total of 185 flies did not transmit BLV to goats from a cow with a normal lymphocyte count. Transmission trials indicated at least 20% of the 10 nl blood residue on the mouthparts of T. fuscicostatus may be deposited upon a second probe.
Vasopressin location and relative quantification within the vampire bat (Desmodus rotundas) brain

Vasopressin was localized in the supraoptic nucleus (SON), paraventricular nucleus, amygdala, habenula, and the posterior pituitary. Microdensitometry analysis revealed an inversely proportionate relationship between the relative vasopressin levels in the SON and the posterior pituitary when exposed to varying periods of dehydration. Short term dehydrated bats displayed increased vasopressin in the SON and decreased levels in the posterior pituitary. Chronically dehydrated bats displayed decreased vasopressin in the SON with increased levels in the posterior pituitary.
Carotid Endarterectomy Prior to Ventricular Assist Device Placement

While there has been considerable debate regarding the timing of carotid endarterectomy (CEA) with respect to coronary artery bypass grafting, the ventricular assist device (VAD) patient population presents possible new concerns, given the implications of stroke while on mechanical support as a bridge to transplant. We present the first report in the literature of CEA in a patient with severe carotid disease prior to elective VAD placement.
Commentary on "Diagnosis of Alzheimer's disease: two decades of progress". Alzheimer's disease research: new opportunities for early diagnosis and drug discovery.

The clinical diagnosis of Alzheimer’s disease (AD) is imprecise with an accuracy rate currently of approximately 90% using consensus criteria in specialized AD centers. A definite diagnosis of AD requires autopsy confirmation, and diagnostic accuracy is far lower at early and presymptomatic stages of AD when confusion with other dementias is common. Although AD affects about 4.5 million Americans now, it is predicted to affect as many as 16 million Americans by 2050, and this neurodegenerative dementia is the most devastating major human disorder for which there still is no effective treatment. Because clinical trials of promising new AD medications are lengthy, involve large numbers of subjects, are difficult to conduct, thereby making AD clinical trials risky and extremely expensive to implement, there has been very modest progress in translating many of the spectacular laboratory advances in AD research over the last 2 decades into meaningful therapeutic steps forward to significantly help AD patients. Moreover, because it is now widely accepted that therapy is likely to be most effective at symptom onset, the early diagnosis of AD is highly desirable well before irreversible brain degeneration becomes severe and widespread. Thus, the essay in this issue of the Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association b yKhachaturia n[1 ]provide sa thoughtfu lpersonal perspective or review of advances in the past 2 decades that position the field of AD research to translate new understanding of AD into better strategies for early diagnosis and drug discovery. For example, AD and many other aging-related neurodegenerative disorders appear to share common disease mechanisms because they are known to be associated with the pathologic aggregation of proteins that misfold and accumulate as fibrillar amyloid deposits in selectively vul
23-year-old woman with increasing frequency of migraine headaches.

Address reprint requests and correspondence to Jimmy R. Fulgham, MD, Department of Neurology, Mayo Clinic, 200 First St SW, Rochester, MN 55905. A 23-year-old woman with a history of classic migraines presented to the emergency department because of sudden onset (45 minutes earlier) of “the worst headache of my life” with associated weakness and incoordination of her right hand and right leg, numbness and paresthesias of the right arm, and scintillating scotoma in her right superior visual field. The motor and coordination deficits resolved after approximately 30 minutes. She had noted an increase in migraine headache frequency over the past few months, from 1 or 2 episodes per month to 2 or 3 episodes per week. Her typical migraine attacks consisted of an aura of scintillating scotoma of the right visual field, followed by a unilateral throbbing headache. The patient’s medical history was remarkable for 5 to 6 episodes of mild epistaxis per year since early childhood. She was taking no medications and had no drug allergies. Her paternal grandmother died of a stroke in her 30s, and there was a strong family history of migraine. The patient’s occupational and social history were unremarkable. She was a nonsmoker. On physical examination, the patient’s blood pressure level was 122/74 mm Hg, and her pulse rate was 88/min. She was afebrile, alert, and oriented. She had no nuchal rigidity. Cardiovascular, pulmonary, abdominal, and skin examination findings were unremarkable. There were no carotid bruits. On neurologic examination, she had a right superior quadrantanopia, mildly decreased recall, and short-term memory deficit. Funduscopic findings were normal. The patient had no calf tenderness and no indications of Homan sign. Initial laboratory findings were as follows (reference ranges shown parenthetically): hemoglobin, 16.4 g/dL (12.0-15.5 g/dL); hematocrit, 45% (34.9%-44.5%); leukocytes, 7.9 × 10/L (3.5-10.5 × 10/L); platelet count, 319 × 10/L; erythrocyte sedimentation rate (ESR), 3 mm/1 h; serum sodium, 141 mEq/L (135-145 mEq/L); potassium, 3.6 mEq/L (3.6-4.8 mEq/L); and creatinine, 0.7 mg/dL (0.60.9 mg/dL). Prothrombin time, activated partial thromboplastin time, liver function test results, cholesterol profile, and antinuclear antibody test results were all within normal limits. An electrocardiogram showed sinus bradycardia.
From enhancing lesions to brain atrophy in relapsing MS.

Abstract Based on observations from MR imaging studies, the natural history of the MS lesion appears to be progression from an acute enhancing lesion, corresponding to the early inflammatory stage, with evolution to a chronic T2 hyperintense lesion, which is the non-specific `footprint' of the prior event. In addition to accumulation of these relatively non-specific lesions, we find in longitudinal evaluations that patients with only mild to modest disability are already developing significant cerebral atrophy. Atrophy, particularly that resulting from volume loss around the third ventricle, appears to be predicted by the presence of prior temporally and anatomically distant enhancing lesions. One can speculate that the initial enhancing-inflammatory lesion events in the brain, place into motion, at an early stage, the processes that ultimately lead to cerebral atrophy, and these processes may include early axonal injury.
Matrix multiplication by optical methods: experimental verification.

Matrix multiplication has been performed by optical analog methods using the scheme of Heinz et al. The most critical element was ℱ(a), the spatial filter corresponding to the two-dimensional Fourier transform of a. In the operation c = b × a, errors in the c elements were 1–2% when the a elements were all approximately the same. Very large errors occurred when the a elements differed significantly, and these were used directly [instead of the ℱ(a) derived values] in the numerical comparisons. These errors were attributed to the limited linear range of the amplitude transmittance characteristic of the film used. Suggestions for future work are made.
Assessment of myocardial perfusion in humans by contrast echocardiography. I. Evaluation of regional coronary reserve by peak contrast intensity.

Abstract Myocardial contrast echocardiography was performed during coronary angiography with 2 ml of sonicated meglumine diatrizoate sodium 76% (meglumine) in 40 patients (ranging in age from 25 to 79 years) before and 10 to 15 s after intracoronary injection of papaverine, 8 mg into the right coronary artery (n = 43) and 10 mg into the left (n = 46). The same protocol was repeated in 17 patients 5 to 10 min after completion of coronary angioplasty. In 13 patients with normal coronary angiograms, peak contrast intensity corrected for background myocardial intensity was measured in 36 regions and was found to increase after papaverine from 36 ± 16 to 55 ± 22 U (p
Rat neonatal beta cells lack the specialised metabolic phenotype of mature beta cells

Aims/hypothesis Fetal and neonatal beta cells have poor glucose-induced insulin secretion and only gain robust glucose responsiveness several weeks after birth. We hypothesise that this unresponsiveness is due to a generalised immaturity of the metabolic pathways normally found in beta cells rather than to a specific defect.
Electrosurgery, pacemakers and ICDs: a survey of precautions and complications experienced by cutaneous surgeons.

BACKGROUNDMinimal information is available in the literature regarding the precautions implemented or complications experienced by cutaneous surgeons when electrosurgery is used in patients with pacemakers or implantable cardioverter-defibrillators (ICDs). The literature pertinent to dermatologists
Abstract 4840: DNA methylation patterns and transcript isoform regulation in prostate cancer

Proceedings: AACR 102nd Annual Meeting 2011‐‐ Apr 2‐6, 2011; Orlando, FL In cancer, the genome undergoes global DNA methylation changes, which contributes to disease progression. We mapped the global DNA methylation patterns in prostate tissues and cells (n=19) from fifty nanograms of genomic DNA. The methylated regions enriched by Methylplex technology, were subjected -Next Generation Sequencing (M-NGS). A total of 28 lanes of next generation sequencing yielded approximately 530 million sequence reads. The reads uniquely mapped to human genome were analyzed by H-Peak program to identify 1.8 million methylated regions from the 28 runs. While twenty percent of all CpG islands (CGIs) (68,508) were methylated in tissues, the promoter CGI methylation gradually increased from ∼12.6% in benign samples to 19.3% and 21.8% in localized and metastatic cancer tissues. However surprisingly, the total methylation events in intergenic/intronic regions between benign adjacent and cancer tissues were largely comparable. We found distinct patterns in promoter methylation around transcription start sites where methylation occurred directly on the CGIs, flanking regions and on CGI sparse promoters. Among the 6,691 methylated promoters in prostate tissues, 2481 differentially methylated regions (DMRs) were cancer specific and several previously studied targets were among them. A novel cancer specific DMR in WFDC2 promoter showed 77% methylation in cancer (17/22), 100% methylation in transformed prostate cell lines (6/6), none in the benign tissues (0/10) and normal PrEC cells. Integration of LNCaP DNA methylation and H3K4me3 data suggested a role for DNA methylation in alternate transcription start site utilization. Specifically, we detail the regulation of RASSF1, a gene previously reported to be silenced through DNA methylation in PCa and NDRG2. We show that variant-1 of RASSF1, but not variant-2 or -3, is specifically silenced in LNCaP through promoter methylation, and normal cells do not exhibit this phenomenon. Treatment with 5-Aza-2-deoxycytidine preferentially induced re-expression of variant-1 of RASSF1 in LNCaP, confirming transcriptional regulation of this isoform through DNA methylation. The methylated promoters lacking CGIs showed sparse H3K4me3 modification, interestingly methylated promoters containing CGIs showed a mutually exclusive H3K4me3/DNA methylation marks. Finally, we observed a difference in the methylation of LINE-1 elements between transcription factor ERG positive and negative cancers. The comprehensive methylome map presented here will further our understanding of epigenetic regulation of the prostate cancer genome. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4840. doi:10.1158/1538-7445.AM2011-4840
Characterization of Circle Cliffs tar sands. 1. Application of the FT-i.r. technique to mineral matter

Abstract In the first of a two-part study of mineral matter associated with tar sands, results are presented from the characterization of samples from the Circle Cliffs and P.R. Spring deposits using FT-i.r. spectroscopy. Following the collection of data for a library of minerals associated with tar sand deposits, the procedures used in the analysis were tested on mineral mixtures of known composition. Illite, dolomite, kaolinite and quartz were measured in the Circle Cliffs sample, while the only minerals present in the P.R. Spring specimen were microline feldspar and quartz.
Abstract 4243: Oncogenic K-Ras transforms three-dimensional colon epithelia through upregulation of ERK-MAPK signaling

Colorectal cancers have the third highest incidence and are the second most common cause of cancer-related death when considering tumors that affect both men and women in the United States. Interestingly, a third of these tumors harbor activating mutations in K-Ras and are associated with worse outcomes. Caco-2 cells, derived from a colorectal carcinoma, are noninvasive and do not harbor mutations in K-Ras, B-Raf or PI3KCA. This cell line has historically been used as a model to study normal, differentiated colonic epithelium in two-dimensional cell culture. Recent studies have used Caco-2 cells in a three-dimensional cell culture system to better model epithelial morphogenesis. In this study, we studied the effects of introducing oncogenic K-Ras into three-dimensionally cultured Caco-2 cells. Control Caco-2 cells seeded in extracellular matrix generate hollow, polarized structures after ten days. In contrast, Caco-2 cells expressing oncogenic K-Ras formed much larger and filled structures that lack a central lumen. Furthermore, western blot analysis of protein lysates made from day 1 and day 10 control structures revealed a strong decrease in cyclin B, suggesting a reduction in the proportion of cells undergoing mitosis. K-Ras structures, however, maintained cyclin B levels, providing evidence of prolonged proliferation. In addition, immunofluorescence of the apical marker aPKC and the tight junction protein ZO-1 revealed that K-Ras structures have disrupted polarity. Caco-2 cells expressing oncogenic B-Raf phenocopied our results with oncogenic K-Ras. Conversely, MEK inhibition with U0126 reverted K-Ras structures back to normal morphology, indicating that K-Ras acts through the ERK-MAPK signaling pathway. The expression of active versions of PI3KCA and RalGDS, other Ras effectors, in Caco-2 cells produced structures identical to control. Further work aims to elucidate a more specific mechanism of Ras downstream of the ERK-MAPK signaling pathway in our three-dimensionally cultured Caco-2 system. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4243. doi:1538-7445.AM2012-4243
Phosphorylation of the Neurospora clock protein FREQUENCY determines its degradation rate and strongly influences the period length of the circadian clock

Under free running conditions, FREQUENCY (FRQ) protein, a central component of the Neurospora circadian clock, is progressively phosphorylated, becoming highly phosphorylated before its degradation late in the circadian day. To understand the biological function of FRQ phosphorylation, kinase inhibitors were used to block FRQ phosphorylation in vivo and the effects on FRQ and the clock observed. 6-dimethylaminopurine (a general kinase inhibitor) is able to block FRQ phosphorylation in vivo, reducing the rate of phosphorylation and the degradation of FRQ and lengthening the period of the clock in a dose-dependent manner. To confirm the role of FRQ phosphorylation in this clock effect, phosphorylation sites in FRQ were identified by systematic mutagenesis of the FRQ ORF. The mutation of one phosphorylation site at Ser-513 leads to a dramatic reduction of the rate of FRQ degradation and a very long period (>30 hr) of the clock. Taken together, these data strongly suggest that FRQ phosphorylation triggers its degradation, and the degradation rate of FRQ is a major determining factor for the period length of the Neurospora circadian clock.
Cathepsin D: Regulation in mammary gland remodeling, misregulation in breast cancer.

Proteases are a large and important group of enzymes, with essential roles in a great diversity of biological processes in all living organisms.1 Proteases are classified according the mechanisms by which they catalyze hydrolysis of peptide bonds within their protein substrates: serine, cysteine, threonine, metallo- and aspartic protease classes are each named for a key functional group instrumental in their chemical mechanisms. A wide variety of proteases have been implicated throughout the development of the mammary gland, but misregulated expression of some of the same proteases has been implicated in the development and progression of breast cancer.2,3
Chemotherapy of tumors in rats with piperazine-1, 4-bis (N, N'-diethylenephosphondiamide). IV.

Summary1. Piperazine-1, 4-bis(N,N'-die-thylenephosphondiamide) (PDA) in doses up to 1 mg/kg/D for 4-6 weeks produced no significant toxic reaction in rats: at higher doses there was some leukopenia but it was not serious, even with doses of 3.0-4.5 mg/ kg D administered for 4-6 weeks. 2. Flex-ner-Jobling carcinoma regressed completely in 30% of rats treated with .2 mg/kg/D of PDA and in about 90% of those with 3.5 mg/ kg/D. There were no regressions among the controls 34 days after implantation. 3. Growth of sarcoma Rl in Wis tar rats was retarded about 50% by the product at 3 mg/kg/D. 4. Walker 256 carcinosarcoma was retarded in growth by doses of 1-3 mg/ kg/D and inhibited for about 2-3 weeks with a dose of 4.5 mg/kg/D. 5. After initial period of growth inhibition the Walker tumor became resistant to the drug and then grew rapidly in spite of continued therapy.
Inversion for the Attenuated Radon Transform with Constant Attenuation

An exact form of the inversion formula for the attenuated Radon transform with constant attenuation in a convex domain for use in Single-Photon Computerized Tomography is presented. This problem is reduced to solving a generalized Abel integral equation and the conditions for the existence of a unique continuous solution are given. Implementation of this method involves a preprocessing step (modified attenuated Radon transform), a convolution by an attenuation-dependent function and a weighted backprojection. Therefore, only slight modifications of existing reconstruction algorithms are needed. If the attenuation is zero, this formula reduces to Radon's original inversion formula. When attenuation is not constant, the conditions for a unique continuous solution can be established with a similar approach. Many results found empirically by previous authors are consistent with this theory.
On the Measurement of Organizational Slack

According to various writers, organizational slack serves to reduce goal conflict, to reduce information processing needs, to promote political behavior, or to facilitate certain strategic behaviors. The salient feature is that the slack construct is usually discussed without a concurrent attempt at empirical measurement. In this article I propose several operational measures, and develop one that allows the use of secondary (financial) data.
Human α2-macroglobulin structure

To localize the pair of thiol-ester-derived cysteine-949 residues within a half-molecule of α2M and estimate the internal diameter of this α2-macroglobulin trap, we have measured the separation between these cysteines. We unexpectedly found that the two cysteines of intermediate form α2M had different reactivity, which permitted selective modification of one cysteine with dansyl, and the other with fluorescein fluorophores. From fluorescence energy transfer measurements, we calculated a separation of 41 ± 10 A between these fluorophores. This indicates that the Cys-949 residues are probably located at the perimeter of the trap with an internal diameter at least as large as this separation.
PERSON–ORGANIZATION INCONGRUENCE AS A PREDICTOR OF RIGHT-WING AUTHORITARIANISM, SOCIAL DOMINANCE ORIENTATION, AND HETEROSEXISM

Using a sample of 124 incoming social work graduate students, we examined whether levels of perceived incongruence with social work values and the perceived culture of a graduate social work progra...
Raman spectra of dimethylgermanium dihydroxide in aqueous solution: Acidity trends in the sequence (CH3)2Ge(IV), (CH3)2Sn(IV), and (CH3)2Pb(IV)

Abstract Raman spectra have been obtained on aqueous solutions prepared from [(CH 3 ) 2 GeO] 4 . The solutions have been shown to contain tetrahedral (CH 3 ) 2 Ge(0H) 2 and vibrational assignments have been made. The equilibrium constants for the hydrolysis of dimethylgermanium, tin, and lead compounds have been compared and discussed in terms of the structures and hybridization of thespecies present in acidic aqueous solutions.
Relationship between Drosophila gap gene tailless and a vertebrate nuclear receptor Tlx

We report here the identification of a unique vertebrate nuclear receptor, Tlx, which is expressed exclusively in the neuroepithelium of the embryonic brain. Sequence comparison reveals striking similarity to the product of the Drosophila terminal/gap gene tailless (tll), which is expressed in the embryonic brain and is required for brain development in flies. In vitro DNA-binding assays demonstrated that Tlx and Tll proteins share a target gene specificity that is unique among the nuclear receptor superfamily. Ectopic expression of Tlx in fly embryos caused a repression of segmentation comparable to that elicited by Tll. The similarities in structure, expression pattern, target gene specificity and phenotypes in transgenic flies suggest conservation of genetic programs upstream and downstream of this Tlx/Tll class of nuclear receptors during embryogenesis.
Nonsteroidal anti-inflammatory drugs and their effects in the elderly

Management of chronic pain can often be a challenging task, especially in the elderly. Patients over the age of 65 years have altered metabolism and pharmacodynamics that increase their susceptibility to adverse side effects. Nonsteroidal anti-inflammatory drugs (NSAIDs) are a common component of pain management in this population. Nonselective NSAIDs as well as selective Cox-2 inhibitors have been associated with side effects, including renal dysfunction, heart failure, gastrointestinal toxicity and increased risk of cardiovascular side effects. These adverse effects are particularly important in the elderly, and thus use of NSAIDs in this population must be scrutinized carefully. If NSAIDs are utilized, they should be tailored to the individual patient and administered in the lowest dose and for the shortest duration possible. It is hoped that future studies will provide further insight into the safety of these agents in elderly patients.
Toward Large‐Scale Implementation of Empirically Supported Treatments for Children: A Review and Observations by the Hawaii Empirical Basis to Services Task Force

This article details the context and findings of a review conducted by a state-established panel established to examine the efficacy and effectiveness of child treatments for Anxiety Disorders, Depression, Attention Deficit Hyperactivity Disorder, Conduct and Oppositional Disorders, and Autistic Disorder. The review emphasizes not only the specific results obtained, but also the process by which a university, Department of Health, and family partnership was established to address specific issues of relevance to statewide implementation of empirically based services. The review of treatment efficacy is consistent with the recent child treatment literature, and these findings were extended through a systematic cataloguing of effectiveness parameters across more than one hundred treatment outcome studies. The importance of such findings and the process by which they were obtained are discussed in the context of a statewide effort to improve mental health practice for children through the extension and application of much of the work by Division 12 of the American Psychological Association with respect to empirically supported treatments.
Lack of appreciable species differences in nonspecific microsomal binding

ABSTRACT Species differences in microsomal binding were evaluated for 43 drug molecules in human, monkey, dog and rat liver microsomes, using a fixed concentration of microsomal protein. The dataset included 32 named drugs and 11 proprietary compounds encompassing a broad spectrum of physicochemical properties (11 acids, 24 bases, 8 neutral, c log D −1 to 7, MW 200 to 700 and free fraction f u,mic ) in monkey, dog, rat and human microsomes were highly correlated, with linear regression correlation coefficients greater than 0.97. The average fold-difference in f u,mic between monkey, dog, or rat, and human was 1.6-, 1.3-, and 1.5-fold, respectively. Species differences in f u,mic were also assessed for a range of microsomal protein concentrations (0.2-2mg/mL) for midazolam, clomipramine, astemizole, and tamoxifen, drugs with low to high microsomal binding. The mean fold species-difference in f u,mic for midazolam, clomipramine, astemizole, and tamoxifen was 1.1-, 1.2-, 1.3-, and 2.0-fold, respectively, and was independent of normalized microsomal protein concentration. For a fixed concentration of microsomal protein, greater than 76% and 90% of drugs examined in this study had preclinical species f u,mic within 1.5- and 2-fold, respectively, of experimentally measured human values.
Shelter Network: Serving Homeless Families and Individuals (1987–2007)

Shelter Network is a nonprofit organization that delivers a range of services that meet the needs of homeless families and individuals in order to help them achieve stable housing and self-sufficiency. The agency began as a grassroots community effort to respond to the growing problem of homelessness and its relationship with its external community continues to play an important role in its financing, growth, and development. Over its 20-year history, Shelter Network has overcome multiple challenges related to leadership, finance, and community support and has grown from a grassroots agency into an organization with a budget of $7 million.
Short‐chain fatty‐acid‐induced effects on the cell cycle in root meristems of Pisum sativum

Propionic acid and valeric acid at 1 mM reduced the mitotic index of root meristem cells of Pisum sativum to <1% after 12 h in aerated White's medium. After 12 h exposure to either acid, seedlings transferred to fresh medium resumed their normal mitotic index 12 h after transfer, with a burst of mitosis at 8 h. Exposure times of 8 h to either acid inhibited DNA synthesis, and nuclei released from either propionic or valeric acid inhibition were still unable to resume normal DNA synthesis after 12 h. Neither acid significantly altered the distribution of meristematic cells in G1 and G2 after 12 h. Propionic acid at 1 mM reduced the uptake of [14C]-leucin but conversion rates to protein were constant regardless of whether any acid was present. Another longer fatty acid, caprylic acid, at 1 mM did not significantly reduce the mitotic index nor did 1 mM benzoic acid, another organic acid. This information suggests that only the short-chain fatty acids, propionic acid and valeric acid, limit progression through the cell cycle by inhibiting DNA synthesis and arresting cells in G1 and G2 in a manner similar to butyric acid, a known cell arresting agent.
History, current state, and future of linear Fresnel concentrating solar collectors

Abstract Linear Fresnel collectors are a type of concentrating solar power technology. In this paper, the technology’s technical features and aspects are first described via illustrations of various design concepts; then, the past low- and intermediate-temperature applications of linear Fresnel collectors are reviewed and their state-of-the-art applications in utility-scale electricity generation are presented; finally, the performance, technical challenges, and future outlook of linear Fresnel technology in the context of utility-scale power plants are summarized.
Assessment of eptifibatide clearance by hemodialysis using an in vitro system.

Background/Aims: Eptifibatide is a parenteral glycoprotein IIb-IIIa inhibitor that prevents platelet aggregation. Although contraindicated in dialysis patients due to limited safety
Immunodiffusion and gel-electrophoretic studies of human articular cartilage proteoglycan.

Human articular cartilage proteoglycan has been prepared by non-disruptive extraction with 4M guanidine and fractionated by CsCI density gradients. Immunodiffusion studies revealed at least three antigenic components. The proteoglycan subunit (PGS) contains an antigenic component common to proteoglycan of many species. The glycoprotein link fraction (GPL) also contains a species-specific antigen identical to a component of human synovial fluid and one or more antigens in common with bovine GPL. SDS-gel electrophoresis of proteoglycan fractions from normal cartilage yielded protein bands within the gels with GPL and a protein band at the gel origin with PGS. The proteoglycan subunit from the single sample of osteoarthritic cartilage studied gave an additional metachromatically staining band within the gel.