cssi/SciSciGPT-SciSciNet huggingface dataset:
From states to secretariats: delegation in the African Union Peace and Security Council

ABSTRACTAfrican Union member states are formally responsible for deciding on peace operation mandates, yet evidence from the African Union Peace and Security Council indicates that states informally delegate some decision-making autonomy to the commission. Given the commission’s formal responsibilities in implementation, why have member states delegated any decision-making in international security? This article argues that, faced with resource limitations, African Union states surrender some decision-making autonomy to access relevant information, make informed decisions, and strengthen mandates. The argument challenges assertions that delegation does not occur in security decision-making. Findings draw on interviews with African Union ambassadors, commission staff, and other regional organization elites.
A combined data-driven, robust-estimator and parameter-learning methodology for sensor fault compensation

This paper studies the sensor fault compensation problem on the basis of recorded process input/output data. The main contribution is to construct an unified framework for fault compensation law by combing the subspace model identification (SMI) technique, measurement disturbance estimator (MDE) theory and iterative learning approach (ILA). Firstly, the considered unknown process dynamic is modeled as a discrete-time state-space model via utilizing SMI. Secondly, based on the identified system, a simultaneous estimator with Hœ optimization performance is designed to monitor the system state and output disturbance that includes the possible measurement noise and sensor fault. Thirdly, a suitable online parameter update law is provided for the purpose of correcting the SMI identification error influence on disturbance estimation. Finally, the sensor fault compensation can be achieved by dismantling the iteratively appropriated disturbance estimation from the actual measured output signal. An numerical example is given to illustrate the effectiveness of the proposed compensation procedure.
The Role of Ipsilateral and Contralateral Transrectal Ultrasound-guided Systematic Prostate Biopsy in Men With Unilateral Magnetic Resonance Imaging Lesion Undergoing Magnetic Resonance Imaging-ultrasound Fusion-targeted Prostate Biopsy

Objective To determine how ipsilateral (ipsi) and contralateral (contra) systematic biopsies (SB) impact detection of clinically significant vs insignificant prostate cancer (PCa) in men with unilateral magnetic resonance imaging (MRI) lesion undergoing MRI-ultrasound fusion-targeted biopsy (MRF-TB). Materials and Methods A total of 211 cases with 1 unilateral MRI lesion were subjected to SB and MRF-TB. Biopsy tissue cores from the MRF-TB, ipsi-SB, and contra-SB were analyzed separately. Results A direct relationship was observed between MRI suspicion score and (1) detection of any cancer, (2) Gleason 6 PCa, and (3) Gleason >6 PCa. MRF-TB alone, MRF-TB + ipsi-SB, and MRF-TB + contra-SB detected 64.1%, 89.1%, and 76.1% of all PCa, respectively; 53.5%, 81.4%, and 69.8% of Gleason 6 PCa, respectively; and 73.5%, 96.0%, and 81.6% of Gleason >6 PCa, respectively. MRF-TB + ipsi-SB detected 96% of clinically significant PCa and avoided detection of 18.6% of clinically insignificant PCa. MRF-TB + contra-SB detected 81.6% of clinically significant PCa and avoided detection of 30.2% of clinically insignificant PCa. Conclusion Our study suggests that ipsi-SB should be added to MRF-TB, as detection of clinically significant PCa increases with only a modest increase in clinically insignificant PCa detection. Contra-SB in this setting may be deferred because it primarily detects clinically insignificant PCa.
Factor VII Deficiency - A Restrospective Case Review.

Factor VII deficiency is a rare autosomal recessive disorder. Its incidence is thought to be 1 in 500,000. Symptoms vary from mild to severe. Factor VII deficient patients usually do not experience bleeding if their level of factor VII is less than 10%. Manifestations are seen with levels less than 5%, and severe bleeding can occur with levels less than 1%. Surgical hemostasis is obtained with levels greater than 25%. Factor VII deficiency is notable for causing a prolonged PT with a normal aPTT, making the diagnosis easy to determine. This is a descriptive study based on a population of patients from our community based teaching hospital with severe Factor VII deficiency. We reviewed lab data and found any patients with less than a 5% factor deficiency from March 2004- June 2006. In our experience we have noted varying manifestations in moderate factor deficiency patients. We describe four patients with varying symptoms, all with factor levels less than 3%. Their charts were reviewed, and three of the patients were available for a telephone interview. Patient A is a 75 yo African American female found to have factor deficiency after an increased Prothrombin time (PT) of 31.2 seconds, INR 5.9, and Partial thromboplastin time (PTT) of 34.9 seconds on routine blood work. This patieny’s factor level was found to be 1.86%. Patient A denied any history of bleeding complications, including an uncomplicated tooth extraction. Patient B is a 46 yo African American female with a long history of bleeding complications. Laboratory data revealed a PT of 26 seconds, INR 4.2, PTT 22 seconds and a Factor level of 1%. She experienced years of heavy menstrual periods and nose bleeds. A hysterectomy was performed secondary to bleeding fibroids. She required multiple doses of novoseven as well as FFP. Patient C was diagnosed at the age of 11. Laboratory results revealed a factor level of 1.87 %, and a PT of 25.1 seconds and an INR of 4.1. She has had minor bleeding events, such as gum bleeding. She did receive FFP prior to a foot surgery, and tooth extraction. Patient D is a 46 year old Hispanic man found to have and INR of 4.3 and, factor VII 1.45. Pt had an uncomplicated cholocystectomy. This is a descriptive study of four different patients with factor VII levels of less than 2%. These four cases demonstrate the wide range of clinical manifestations that factor VII patients may experience. One patient did require novoseven prior to a hysterectomy. Though, as our cases illustrate, some patients do not experience any bleeding manifestations, and therefore, prophylactic plasma may not be required. Furthermore, treatment of factor VII deficient patients needs to be individualized, and guided by personal history.
Gesture and Power: Religion, Nationalism, and Everyday Performance in Congo, by Yolanda Covington-Ward, Durham, Duke University Press, 2016, xi+287 pp., US$25.95 (paperback), ISBN 978 0 8223 6036 0

The subject areas identified at the top of the back cover of this wonderful book are ‘RELIGION/AFRICAN STUDIES/ANTHROPOLOGY,’ and Yolanda Covington-Ward’s Gesture and Power makes significant contri...
Research note: A rock mulch layer supported little vegetation in an arid reclamation setting

Rosemont Copper Company [2013 -1]; University of Arizona Agricultural Experiment Station [ARZT-1361260-H12-217]
Co-production in global sustainability: Histories and theories

Abstract Co-production is one of the most important ideas in the theory and practice of knowledge and governance for global sustainability, including ecology and biodiversity conservation. A core challenge confronting the application of co-production has been confusion over differences in definition and practice across several disciplinary traditions, including sustainability science, public administration, and science and technology studies. In this paper, we review the theoretical foundations of these disciplinary traditions and how each has applied co-production. We suggest, at the theoretical level, the differences across disciplines are, in fact, more apparent than real. We identify several theoretical convergences that allow us to synthesize a strong conceptual foundation for those seeking to design and implement co-production work in programs of global sustainability research and policy.
Diminished Economic Return of Socioeconomic Status for Black Families.

Background: According to the Minorities’ Diminished Return theory, socioeconomic status (SES) systemically generates larger gains for Whites compared to Blacks. It is, however, unknown whether the effects of baseline SES on future family income also varies between Blacks and Whites. Aims: Using a national sample, this study investigated racial variation in the effects of family SES (i.e., family structure, maternal education, and income) at birth on subsequent household income at age 15. Methods: This 15-year longitudinal study used data from the Fragile Families and Child Wellbeing Study (FFCWS), which followed 1471 non-Hispanic Black or White families from the time of birth of their child for 15 years. Two family SES indicators (maternal education and income) at birth were the independent variables. Family income 15 years later was the outcome. Maternal age, child gender, and family structure at baseline were covariates. Race was the focal moderator. Linear regression models were used for data analysis. Results: In the pooled sample, maternal education (b = 11.62, p < 0.001) and household income (b = 0.73, p < 0.001) at baseline were predictive of family income 15 years later. Race, however, interacted with maternal education (b = −12,073.89, p < 0.001) and household income (b = −312.47, p < 0.001) at birth on household income 15 years later, indicating smaller effects for Black compared to White families. These differential gains were independent of family structure, mother age, and child gender. Conclusions: The economic return of family SES is smaller for Black compared to White families, regardless of the SES indicator. Policies should specifically address structural barriers in the lives of racial and ethnic minorities to minimize the diminished return of SES resources across racial minority groups. Policies should also reduce extra costs of upward social mobility for racial minorities. As the likely causes are multi-level, solutions should also be also multi-level. Without such interventions, it may be very difficult if not impossible to eliminate the existing Black–White economic gap.
Variable decelerations and the nonstress test: Anindication of cord compromise

Thirty-seven women with high-risk pregnancies who were undergoing antenatal fetal surveillance with the nonstress test (NST) were observed to have persistent mild variable decelerations. Intrapartum umbilical cord problems were observed in 35 women. These observations were found to be statistically significant. (Am. J. Obstet. Gynecol. 137:704, 1980.)
Assessing the Impact of Federal Industrial R&D Expenditure on Private R&D Activity in the United States

A number of studies have attempted to determine the effect of US government expenditures on research and development (R&D) performed in industry on the quantity of private investment in R&D, by analysing the statistical relationship betweed federal and company R&D spending at the firm, industry, and aggregate levels(l). These studies are restricted to the US case owing to the lack of comparable data for other countries. The possibility that private decisions to invest in R&D may be influenced by federal industrial R&D spending is regarded as worthy of careful investigation, in part because numerous studies have demonstrated that private R&D expenditure has a significant, positive impact on total factor productivity (TFP). Although most analysts have failed to find evidence of a similar direct productivity impact of federal R&D expenditure(2), federal R&D may nevertheless have a considerable indirect impact (positive or negative) on TFP if it influences private R&D investment decisions.
Automated Smartphone Audiometry: A Preliminary Validation of a Bone-Conduction Threshold Test App:

Objective:To develop and validate an automated smartphone app that determines bone-conduction pure-tone thresholds.Methods:A novel app, called EarBone, was developed as an automated test to determi...
Enantioselective metal carbene transformations with polyethylene-bound soluble recoverable dirhodium(II) 2-pyrrolidone-5(S)-carboxylates

Ligand displacement of methyl 2-pyrrolidone-5(S)-carboxylate (5(S)-MEPYH) from Rh 2 -(5(S)-MEPY) 4 by a soluble polyethylene-bound 2-pyrrolidone-5(S)-carboxylate produced a recoverable dirhodium(II) catalyst whose effectiveness was demonstrated by high enantioselection for intramolecular cyclopropanation of 3-methyl-2-buten-1-yl diazoacetate (98% ee) and intramolar C-H insertion of 2-methoxyethyl diazoacetate (72% ee) as well as by catalyst recovery and reuse seven times
David Oliver: Nurses, degrees, and the workforce crisis.

The biggest threat to the NHS’s existence is its workforce crisis. And, although modern healthcare is a team venture reliant on interdisciplinary working, nursing is the NHS’s most numerous, visible, and trusted clinical workforce group. One with a workforce crisis even more pressing than that in medicine.1 Against this backdrop, the zombie trope I’ve mentioned before in this column2—that “overeducated nurses” lead to declining standards of care—has made an unwelcome return in parts of the media. It seems a peculiarly British obsession, as graduate nursing is established in most developed nations—but it’s hard to kill off. In a 2014 study in nine European countries, every 10% increase in degree educated nurses was associated with a 7% reduction in patient mortality. England had one of the lowest percentages of graduate nurses in …
Diabetes and Hepatocellular Carcinoma: Incidence Trends and Impact of Liver Disease Etiology

Background/Aims Hepatocellular carcinoma (HCC) remains the leading cause of cancer-related death among patients with type 2 diabetes mellitus (T2DM). We aimed to assess the independent role of T2DM on HCC risk among patients with different liver disease etiologies. Methods We analyzed the United Network for Organ Sharing database of all adults registered for liver transplantation (LT) between February 27, 2002 and December 31, 2017. For initial analyses, patients were divided into four groups: nonalcoholic steatohepatitis (NASH) and all other etiologies with or without T2DM. For additional analyses, we divided them based on underlying etiology. Logistic regression was used to evaluate the impact of T2DM with NASH and other etiologies on HCC risk. Results Overall, 24,149 (21.6%) of the listed patients had HCC. Of those, 23.9% had T2DM. When compared with nondiabetics, patient with NASH and T2DM had the highest risk of HCC (odds ratio [OR] 1.68; 95% confidence interval [CI] 1.52–1.86), followed by patients with other etiologies and diabetes. After adjusting for other risk factors, these associations remained unchanged. Registrants with T2DM and NASH, cryptogenic cirrhosis, hepatitis C, and alcoholic liver disease were at higher risk of HCC than those without diabetes, but in patients with chronic hepatitis B or primary biliary cholangitis, diabetes did not increase the HCC risk. Between 2004 and 2016, the annual percentage change of HCC incidence increased for all patients with NASH and hepatitis C regardless of their diabetes status. For those with hepatitis B, this trend was significant only for diabetics. Conclusions The additive risk of T2DM for HCC development was highest in patients with NASH. HCC risk may vary depending on the underlying etiology.
Voices Speaking Truths from Our Past and Our Present

This introductory chapter situates homeschooling in an African American educational history context and in the context of today’s Black education. The chapter demonstrates the connections between African American legacy of self-agency and self-determination as well as resistance in the pursuit of education. Additionally, the chapter reviews the literature on Black homeschooling and demonstrates the corroboration between existing homeschool literature and issues in Black education including low expectations, discipline disproportionality, limited access to gifted education, marginalization of Black parents, and excessive referrals to special education. In addition, the chapter critiques the existing Black homeschool literature for excluding the voices of single Black mothers and perpetuating the myth of Black families as a monolith.
The Progressive Mutagenic Effects of Acidic Bile Refluxate in Hypopharyngeal Squamous Cell Carcinogenesis: New Insights.

Cancers of the laryngopharynx represent the most devastating of the head and neck malignancies and additional risk factors are now epidemiologically linked to this disease. Using an in vivo model (Mus musculus C57Bl/6J), we provide novel evidence that acidic bile (pH 3.0) progressively promotes invasive cancer in the hypopharynx. Malignant lesions are characterized by increasing: (i) oxidative DNA-damage, (ii) γH2AX expression, (iii) NF-κB activation, and (iv) p53 expression. Histopathological changes observed in murine hypopharyngeal mucosa exposed to acidic bile were preceded by the overexpression of Tnf, Il6, Bcl2, Egfr, Rela, Stat3, and the deregulation of miR-21, miR-155, miR-192, miR-34a, miR-375, and miR-451a. This is the first study to document that acidic bile is carcinogenic in the upper aerodigestive tract. We showed that oxidative DNA-damage produced by acidic bile in combination with NF-κB-related anti-apoptotic deregulation further supports the underlying two-hit hypothesized mechanism. Just as importantly, we reproduced the role of several biomarkers of progression that served as valuable indicators of early neoplasia in our experimental model. These findings provide a sound basis for proposing translational studies in humans by exposing new opportunities for early detection and prevention.
Clean cooking for all? A critical review of behavior, stakeholder engagement, and adoption for the global diffusion of improved cookstoves

Abstract Improved cookstoves and solar cookers have been positioned as a socio-technical strategy for improving household health and economics, and for reducing the negative impacts on the environment associated with the combustion of residential solid fuels in low- and middle-income countries. However, adoption and sustained use of these technologies have not been realized. This critical review examines the ways in which cookstove programs use information-sharing and education-related Behavior Change Communication techniques to engage all stakeholders within a household to promote long-term cookstove usage. Findings indicate that few cookstove and solar cooker adoption studies (n = 18) report such strategies, and of those that do, rarely are men (n = 4), often the primary financial decision makers of a household, or children (n = 3), current and future users of cookstoves, purposefully engaged. Included papers report cookstove adoption metrics in a variety of ways, preventing direct comparisons between studies, by stakeholder, or behavior change strategy. Despite the lack of standardized adoption metrics, this review finds that comprehensive educational initiatives, as opposed to training or simple information provision, as part of a behavior change strategy may advance sustained use of cooking technologies. This represents an unexplored area of improved energy research.
Chapter 4 – Transport Kinetics

Publisher Summary This chapter discusses several reasons why neither hydrophilic nor lipophilic solutes or the solvent are likely to migrate across biomembranes by ordinary diffusion. Nevertheless, diffusion is an important mechanism by which these ions and molecules may reach the membrane for transport. Moreover, concepts developed under the assumption that diffusion occurs across biomembranes can be used to help us to understand mechanisms of transport regulation. For example, it is proposed on the basis of such data that water channels may open in response to osmotic gradients across the plasma membrane. Although it remains controversial whether hydrophobic solutes cross biomembranes primarily via lipid- or protein-mediated processes, there appears to be little doubt that protein-mediated processes catalyze most of the migration of hydrophilic solutes. Even the relatively rapid migration of water through the lipid bilayers of biomembranes is usually several orders of magnitude slower than the migration that occurs via water channels. The ability of each of different types of transport processes to produce new total chemical potential gradients of solutes by kinetically different mechanisms probably relates to their similar fundamental structures, each of which provides a saturable pathway for substrate migration across a biomembrane. The reliance of the functions of transport proteins on their underlying asymmetric structures leads naturally to detailed considerations of the structures of transport proteins that form, propagate, or dissipate solute gradients.
Postoperative Pulmonary Complications in the Morbidly Obese: The Role of Tidal Volume and the Type of Abdominal Surgery

BACKGROUND: The patient who is morbidly obese is not adequately represented in the evidence recommending intraoperative low tidal volume (VT) ventilation. We aimed to explore the association between VT adjusted for ideal body weight (IBW) and the occurrence of postoperative pulmonary complications in subjects who were morbidly obese and undergoing abdominal surgery, as well as its implications on intraoperative ventilatory variables. METHODS: We included 734 subjects with a body mass index of at least 40 kg/m2, undergoing open or laparoscopic abdominal surgery that lasted for at least 120 min. Clinical variables were obtained to estimate the preoperative pulmonary risk as well as intraoperative ventilator data to perform associations. Outcomes were defined by medical billing code diagnoses and oxygen use. All data were collected electronically by using Structured Query Language. RESULTS: The subjects received a mean VT/IBW of 9.41 mL/kg IBW, and postoperative pulmonary complications occurred in 7.5% of the subjects. The occurrence of complications was correlated with the presence of several preoperative risk factors for postoperative pulmonary complications. VT/IBW was not associated with postoperative pulmonary complications. This finding remained present after separating different levels of VT/IBW. In a multivariate analysis, only laparoscopic surgery was an independent protective factor against postoperative pulmonary complications (odds ratio 0.07, 95% CI 0.01–0.55). CONCLUSIONS: VT/IBW was not associated with the occurrence of postoperative pulmonary complications in subjects who were morbidly obese and undergoing prolonged abdominal surgery. Future prospective studies are indicated to guide the optimum ventilation strategy for patients who are morbidly obese.
Convolutional Neural Networks for Predicting the Strength of the Near-Earth Magnetic Field Caused by Interplanetary Coronal Mass Ejections

In this paper, we explore the potential of neural networks for making space weather predictions based on near-Sun observations. Our second goal is to determine the extent to which coronal polarimetric observations of erupting structures near the Sun encode sufficient information to predict the impact these structures will have on Earth. We focus on predicting the maximal southward component of the magnetic field ("-Bz") inside an interplanetary coronal mass ejection (ICME) as it impacts the Earth. We use Gibson&Low (G&L) self-similarly expanding flux rope model (Gibson&Low 1998), which allows to consider CMEs with varying location, orientation, size, and morphology. We vary 5 parameters of the model to alter these CME properties, and generate a large database of synthetic CMEs (over 36k synthetic events). For each model CME, we synthesize near-Sun observations, as seen from an observer in quadrature (assuming the CME is directed Earthwards), of either three components of the vector magnetic field (“Experiment 1”), or of synthetic Stokes images, (“Experiment 2”). We then allow the flux rope to expand and record max(-Bz) as the ICME passes 1AU. We further conduct two separate machine learning experiments and develop two different regression-based deep convolutional neural networks (CNNs) to predict max(-Bz) based on these two kinds of the near-Sun input data. Experiment 1 is a proof of concept, to see if a 3-channel CNN (hereafter CNN1), similar to those used in RGB image recognition, can reproduce the results of the self-similar (i.e. scale-invariant) expansion of the G&L model. Experiment 2 is less trivial, as Stokes vector is not linearly related to B, and the line-of-sight integration in the optically thin corona presents additional difficulties for interpreting the signal. This second CNN (hereafter CNN2), although resembling CNN1 in Experiment 1, will have a different number of layers and set of hyperparameters due to a much more complicated mapping between the input and output data. We find that, given vector B, CNN1 can predict max(-Bz) with 97% accuracy, and for the Stokes vector as input, CNN2 can predict max(-Bz) with 95%, both measured in the relative root square error.
Cochlear spiral ganglion neuron degeneration following cyclodextrin-induced hearing loss.

Abstract Because cyclodextrins are capable of removing cholesterol from cell membranes, there is growing interest in using these compounds to treat diseases linked to aberrant cholesterol metabolism. One compound, 2-hydroxypropyl-beta-cyclodextrin (HPβCD), is currently being evaluated as a treatment for Niemann-Pick Type C1 disease, a rare, fatal neurodegenerative disease caused by the buildup of lipids in endosomes and lysosomes. HPβCD can reduce some debilitating symptoms and extend life span, but the therapeutic doses used to treat the disease cause hearing loss. Initial studies in rodents suggested that HPβCD selectively damaged only cochlear outer hair cells during the first week post-treatment. However, our recent in vivo and in vitro studies suggested that the damage could become progressively worse and more extensive over time. To test this hypothesis, we treated rats subcutaneously with 1, 2, 3 or 4 g/kg of HPβCD and waited for 8-weeks to assess the long-term histological consequences. Our new results indicate that the two highest doses of HPβCD caused extensive damage not only to OHC, but also to inner hair cells, pillar cells and other support cells resulting in the collapse and flattening of the sensory epithelium. The 4 g/kg dose destroyed all the outer hair cells and three-fourths of the inner hair cells over the basal two-thirds of the cochlea and more than 85% of the nerve fibers in the habenula perforata and more than 80% of spiral ganglion neurons in the middle of basal turn of the cochlea. The mechanisms that lead to the delayed degeneration of inner hair cells, pillar cells, nerve fibers and spiral ganglion neurons remain poorly understood, but may be related to the loss of trophic support caused by the degeneration of sensory and/or support cells in the organ of Corti. Despite the massive damage to the cochlear sensory epithelium, the blood vessels in the stria vascularis and the vestibular hair cells in the utricle and saccule remained normal.
Fracture of tibial tuberosity in an adult with Paget's disease of the bone – An interesting case and review of literature

Abstract Introduction Paget's disease of the bone is a non-malignant skeletal disorder characterized by focal abnormalities in bone remodelling at one or more skeletal sites. Pathological fractures occurring from trivial injuries are a well-known clinical presentation in patients with Paget's disease. An avulsion fracture of the tibial tuberosity is an infrequent injury and has an extremely low occurrence in adults, with only a few cases reported in literature. We describe a case of a patient with undiagnosed Paget's Disease of the bone, sustaining a pathological avulsion fracture of the tibial tuberosity. Case report A 54-year-old male presented with right knee pain after his knee gave way whilst standing in the goal area during a game of football, twisting his right ankle and falling. Plain radiographs of the knee revealed an avulsion fracture of the tibial tuberosity with abnormal modelling of the proximal half of the tibia. An MRI confirmed a diagnosis of Paget's disease of the bone. The patient underwent open reduction internal fixation. At 3 months follow up, the patient had good knee range of motion from 0 to 100 degrees and by 6 months he had returned to his usual activities. Conclusion We describe a unique case of tibial tuberosity avulsion fracture in an adult with PDB. Treatment was successful with cannulated screws and tension band wiring. Patients with PDB who fracture present with diagnostic and operative challenges, it is vital to progress with caution in the postoperative rehabilitation phase.
The HIV-1 antisense gene ASP: The new kid on the block

Viruses have developed incredibly creative ways of making a virtue out of necessity, including taking full advantage of their small genomes. Indeed, viruses often encode multiple proteins within the same genomic region by using two or more reading frames in both orientations through a process called overprinting. Complex retroviruses provide compelling examples of that. The human immunodeficiency virus type 1 (HIV-1) genome expresses sixteen proteins from nine genes that are encoded in the three positive-sense reading frames. In addition, the genome of some HIV-1 strains contains a tenth gene in one of the negative-sense reading frames. The so-called Antisense Protein (ASP) gene overlaps the HIV-1 Rev Response Element (RRE) and the envelope glycoprotein gene, and encodes a highly hydrophobic protein of ~190 amino acids. Despite being identified over thirty years ago, relatively few studies have investigated the role that ASP may play in the virus lifecycle, and its expression in vivo is still questioned. Here we review the current knowledge about ASP, and we discuss some of the many unanswered questions.
The use of experimental models of human medulloblastoma in the design of rational therapy

Models were established to study the biology and therapeutic sensitivity of medulloblastoma using two continuous human medulloblastoma-derived cell lines. TE-671, derived from a cerebellar medulloblastoma, grew in vitro in plastic dishes and soft agar, and grew both subcutaneously and intracranially in athymic mice. Studies were conducted to evaluate in vitro therapeutic sensitivity using a clonogenic assay and in vivo sensitivity using growth inhibition of subcutaneous and intracranial tumors. Agents tested in vitro included Adriamycin, vincristine, AZQ, 4-hydroperoxycyclophosphamide, BCNU and methotrexate, allowing calculation of respective ID75 values. Agents studied in vivo included cyclophosphamide, melphalan, vincristine, PCNU, Asta Z 7557, Azacytidine, cisplatinum, AZQ, Fludarabine, Adriamycin, methotrexate, AraC, AD32, MGBG, BW-301U, BCNU, procarbazine and abrin. Agents with ID75 less than the in vivo murine plasma drug concentrations were all active in vivo, whereas two of the three agents with an ID75 greater than the murine plasma drug concentrations showed no in vivo activity. The most effective agents studied to date include Melphalan, cyclophosphamide, Asta Z 7557 and vincristine. D283 Med, derived from the peritoneal implant and ascitic fluid of a child with metastatic medulloblastoma, grew in vitro only in suspension culture and is similarly tumorigenic in athymic mice. Therapeutic sensitivity studies utilizing D283 Med are now in progress. The use of TE-671, D283 Med and other medulloblastoma-derived cell lines will allow demonstration of a spectrum of therapeutic sensitivity for human medulloblastoma.
Evaluation and optimization of bio‐optical inversion algorithms for remote sensing of Lake Superior's optical properties

[1] Satellite remote sensing offers one of the best spatial and temporal observational approaches. However, well-validated satellite imagery has remained elusive for Lake Superior. Lake Superior's optical properties are highly influenced by colored dissolved organic matter (CDOM), which has hindered the retrieval of chlorophyll concentration through band-ratio algorithms. This study evaluated seven existing inversion algorithms. The top-performing inversion algorithm was tuned to a Lake Superior optical data set and applied to satellite imagery. The retrieval of chlorophyll concentration via inversion algorithms was not possible due to errors in derived CDOM absorption being greater than phytoplankton absorption values and the very small contribution of phytoplankton absorption to the overall absorption budget. However, the retrieval of absorption due to CDOM from satellite imagery was encouraging. To ensure that the best satellite remotely sensed reflectance estimates were used in the retrieval of absorption due to CDOM, several atmospheric correction schemes were evaluated. The absorption due to CDOM was greatest in the western arm of Lake Superior and near river mouths and decreased with distance offshore. The absorption due to CDOM had a bimodal distribution over the annual cycle with the greatest peak in fall and a smaller peak in spring.
Neurogliaform cells in cortical circuits.

Local circuit GABAergic inhibitory interneurons regulate almost all aspects of cortical and hippocampal circuitry. In this Review, Overstreet-Wadiche and McBain discuss how neurogliaform cells are emerging as an inhibitory interneuron type with unique cellular and signalling properties that diverge from canonical roles for interneurons.
Lasers for Optogenetics and Multimodal Microscopy

A new type of short-pulse ultrafast laser sources provides extremely wide (680 – 1300 nm) wavelength tunability of the primary output as well as simultaneous high power (1.5 watts) output at 1040 nm. This combination makes lasers such as the Chameleon Discovery ideal for demanding multiphoton excitation applications in optogenetics, multimodal imaging, and other microscopy applications that need two independent wavelengths. In this article we will see why these applications benefit from this performance.
Mitochondrial Signaling: The Retrograde Response

Abstract Mitochondrial retrograde signaling is a pathway of communication from mitochondria to the nucleus that influences many cellular and organismal activities under both normal and pathophysiological conditions. In yeast it is used as a sensor of mitochondrial dysfunction that initiates readjustments of carbohydrate and nitrogen metabolism. In both yeast and animal cells, retrograde signaling is linked to TOR signaling, but the precise connections are unclear. In mammalian cells, mitochondrial dysfunction sets off signaling cascades through altered Ca 2+ dynamics, which activate factors such as NFκB, NFAT, and ATF. Retrograde signaling also induces invasive behavior in otherwise nontumorigenic cells implying a role in tumor progression.
Abstract 18960: Anti-PCSK9 VLP Immunization Reduces Cholesterol Levels in Mice and Non-human Primates

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a secretory protease involved in cholesterol homeostasis by enhancing endosomal and lysosomal degradation of cell surface low-density lipoprotein receptors (LDL-R). While increased activity of PCSK9 has been associated with hypercholesterolemia and atherosclerosis, several healthy patients have also been identified with loss-of-function PCSK9 mutations and exhibit a hypocholesterolemia phenotype (and an extremely low incidence of coronary artery disease - CAD). These observations indicate that PCSK9 is an attractive target for the purpose of lowering circulating LDL-cholesterol, and therefore decreasing the potential for CAD and atherosclerosis. To date, several different strategies are being attempted to target and reduce plasma levels of PCSK9 but they are based on expensive therapies that may be utilized only by a limited number of patients. Phase 2 clinical studies utilizing monoclonal antibodies targeting PCSK9 demonstrated a reduction in LDL-c up to 70%. To reach a much broader population and design a low cost, long-term treatment, we developed a Virus-like Particle (VLP) based vaccine that targets the LDLR binding domain of PCSK9. Immunized mice (n=20) developed high-titer anti-peptide IgG responses that cross-reacted with PCSK9. Total cholesterol, free cholesterol, phospholipid and triglyceride levels were measured after the final boost. Vaccination with PCSK9-VLPs significantly reduced all four of these measures, with total cholesterol decreasing by over 30% (relative to pre-vaccination levels). We also immunized small groups (n=3) of rhesus macaques. Vaccination resulted in changes in lipoprotein profile at week 2, and decreases in TC (14.2%), ApoB (13.4%) and LDL-p (28.4%) at week 6 were observed. The PCSK9-VLP vaccine was well tolerated with no signs of overt toxicity in both species. In conclusion, these findings suggest that VLP-PCSK9 immunization may be an accessible, low cost, and effective new therapy for hypercholesterolemia and CAD.
Calcium and cholecalciferol supplementation provides no added benefit to nutritional counseling to improve bone mineral density in survivors of childhood acute lymphoblastic leukemia (ALL)

Background We sought to improve lumbar spine bone mineral density (LS-BMD) in long-term survivors of childhood acute lymphoblastic leukemia (ALL) using calcium and cholecalciferol supplementation.
PMFastR: a new approach to multiple RNA structure alignment

Multiple RNA structure alignment is particularly challenging because covarying mutations make sequence information alone insufficient. Many existing tools for multiple RNA alignments first generate pairwise RNA structure alignments and then build the multiple alignment using only the sequence information. Here we present PMFastR, an algorithm which iteratively uses a sequence-structure alignment procedure to build a multiple RNA structure alignment. PMFastR has low memory consumption allowing for the alignment of large sequences such as 16S and 23S rRNA. The algorithm also provides a method to utilize a multi-core environment. Finally, we present results on benchmark data sets from BRAliBase, which shows PMFastR outperforms other state-of-the-art programs. Furthermore, we regenerate 607 Rfam seed alignments and show that our automated process creates similar multiple alignments to the manually-curated Rfam seed alignments.
Opponent classification in poker

Modeling games has a long history in the Artificial Intelligence community. Most of the games that have been considered solved in AI are perfect information games. Imperfect information games like Poker and Bridge represent a domain where there is a great deal of uncertainty involved and additional challenges with respect to modeling the behavior of the opponent etc. Techniques developed for playing imperfect games also have many real world applications like repeated online auctions, human computer interaction, opponent modeling for military applications etc. In this paper we explore different techniques for playing poker, the core of these techniques is opponent modeling via classifying the behavior of opponent according to classes provided by domain experts. We utilize windows of full observation in the game to classify the opponent. In Poker, the behavior of an opponent is classified into four standard poker-playing styles based on a subjective function.
Roles for proteinases in the pathogenesis of chronic obstructive pulmonary disease

Since the early 1960s, a compelling body of evidence has accumulated to show that proteinases play critical roles in airspace enlargement in chronic obstructive pulmonary disease (COPD). However, until recently the causative enzymes and their exact roles in pathologic processes in COPD have not been clear. Recent studies of gene-targeted mice in murine models of COPD have confi rmed roles for proteinases not only in airspace enlargement, but also in airway pathologies in COPD. These studies have also shed light on the specifi c proteinases involved in COPD pathogenesis, and the mechanisms by which these proteinases injure the lung. They have also identifi ed important interactions between different classes of proteinases, and between proteinases and other molecules that amplify lung infl ammation and injury. This review will discuss the biology of proteinases and the mechanisms by which they contribute to the pathogenesis of COPD. In addition, I will discuss the potential of proteinase inhibitors and anti-infl ammatory drugs as new treatment strategies for COPD patients.
Mass spectrometry-based metabolomics as a unique biochemical approach for understanding disease pathogenesis (350.3)

Metabolomics, the quantitative global analysis of endogenous metabolites from cells, tissues, fluids and whole organisms, is becoming an integral part of functional genomics efforts as well as a to...
Landscape level estimate of lands and waters impacted by road runoff in the Adirondack Park of New York State.

Road runoff is understood to be a significant stressor in terrestrial and aquatic ecosystems, yet the effects of this stressor are poorly understood at large spatial scales. We developed an efficient method for estimating the spatial impact of road runoff on lands and waters over large geographic areas and then applied our methodology to the 2.4 million ha Adirondack Park in New York State. We used TauDEM hydrologic modeling and a series of ESRI GIS processes to delineate surface flow downslope of paved roads, illustrating the potential movement of pollutants originating from paved roads through the USGS 10 m DEM topography. We then estimated the land and surface water areas, number of water bodies, and total stream length potentially impacted by road runoff from paved roads. We found that as much as 11 % of land area, 77 % of surface water area, 1/3 of the water bodies, and 52 % of stream length in the Adirondack Park may be impacted by road runoff. The high degree of hydrologic association between paved roads and the lands and waters of this region strongly suggests that the environmental impacts of road runoff should be evaluated along with other regional stressors currently being studied. Being able to estimate the spatial impact of road runoff is important for designing monitoring programs that can explicitly monitor this stressor while also providing opportunities to understand the interaction of multiple environmental stressors.
Delivery across the blood-brain barrier of antisense directed against amyloid beta: reversal of learning and memory deficits in mice overexpressing amyloid precursor protein.

Amyloid beta protein (Abeta) may play a causal role in Alzheimer's disease. Previous work has shown that the learning and memory deficits that develop with aging in SAMP8 mice, a strain that overproduces Abeta, can be reversed with i.c.v. injections of an Abeta antisense phosphorothiolate oligonucleotide (Olg). Here, we showed that Olg radioactively labeled with (32)P (P-Olg) was transported intact across the blood-brain barrier (BBB) of mice by a saturable system, termed oligonucleotide transport system-1 (OTS-1). Multiple-time regression analysis found a blood-to-brain unidirectional influx rate for P-Olg of 1.4 +/- 0.39 microl/g-min and capillary depletion showed that P-Olg completely crossed the BBB to enter the parenchymal space of the brain. P-Olg was also shown to enter the cerebrospinal fluid. Transport was especially high into the hippocampus, with the percentage of the i.v. dose taken up by each gram of brain (0.865 +/- 0.115%) being about 1/100 of the i.c.v. dose. An i.v. dose of Olg 100 times that of the effective i.c.v. dose reversed the learning and memory deficits of aged SAMP8 mice. These studies show for the first time that phosphorothiolate oligonucleotides can be delivered to the brain in effective doses by intravenous administration.
No Steps Forward, Two Steps Back: The Fallacy of Trying to “Eradicate” Adverse Impact?

Within the context of the 50th anniversary of the Civil Rights Act of 1964, and specifically as it pertains to the tenets of Title VII, Lindsey, King, Dunleavy, McCausland, and Jones (2013) state: “This focal article raises and addresses critical issues regarding a yet unanswered question: How can organizational researchers and practitioners contribute to the ultimate goal of eradicating employment discrimination” (p. 391). We argue that in the context of employment testing and selection, at least as per the disparate impact theory of discrimination, this question is the wrong one—certainly as framed by Lindsey et al. To the contrary, instead of holding up the "eradication of employment discrimination" as our ultimate goal, perhaps we should continue to focus on the development, implementation, and support of the best (i.e., most job-related and valid) employment practices possible.
Acne treatment with topical erythromycin and zinc: Effect on Propionibacterium acnes and free fatty acid composition

A double-blind investigation has been conducted to examine the effect of topical 4% erythromycin/1.2% zinc acetate solution and its vehicle on quantitative bacterial counts (skin surface washings) of propionibacterium acnes and the free fatty acids of the skin surface. The logarithmic counts for P. acnes in the erythromycin/zinc group showed a significant reduction (98%) following 10 weeks of therapy. This compared with a 43% change shown for the vehicle-control group. A significant reduction (69%) in the percentage of free fatty acids in the surface lipids was seen at week 4 in the erythromycin/zinc group as compared to the control group. Triglyceride levels were significantly increased at all time points for the erythromycin/zinc group as compared to the control group. There was also a significant decrease (69%) in inflammatory lesions shown for the erythromycin/zinc treatment group at week 8 as compared to a 9% reduction in the control group.
Changes in fatty acid composition of peripheral nerve myelin in essential fatty acid deficiency

Abstract Severe essential fatty acid deficiency (EFAD) was induced by feeding weanling rats a diet free of essential fatty acids 8 months after weaning. The fatty acid compositions of phospholipids and glycosphingolipids in peripheral nerve myelin were compared in rats with and without EFAD. With the deficient diet, 20:3ω9 was found in the major myelin phospholipids. The level of 18:1 was increased and the levels of 18:2ω6, 20:4ω6, and 22:4ω6 were decreased. Both sphingomyelin and cerebroside showed higher proportion of 24:1 and lower proportions of 24:0 in EFA-deficient rats than in control rats. The fatty acid chain elongating system in myelin cerebroside was also depressed by EFAD. A two- to sevenfold increase of the ratio 20:4ω6 to 20:3ω6 was found in myelin phospholipids of regenerated nerve from rats fed control diet. However, this ratio was suppressed by EFAD diet. The biochemical index (20:3ω9/20:4ω6) for EFAD was not affected by crush injury. These results suggest that dietary EFAD in postweaning rats can induce fatty acid alterations in peripheral nerve myelin without resulting in detectable changes in function or structure and that myelin lipids may be sequestered and reused during nerve degeneration and regeneration.