jimnoneill/paper-to-field-training huggingface dataset:
POL5551, a novel and potent CXCR4 antagonist, enhances sensitivity to chemotherapy in pediatric ALL

Field: Pharmacology, Toxicology and Pharmaceutics (Life Sciences)

// Edward Allan R. Sison 1 , Daniel Magoon 2 , Li Li 2 , Colleen E. Annesley 2 , Barbara Romagnoli 3 , Garry J. Douglas 3 , Gerald Tuffin 3 , Johann Zimmermann 3 , Patrick Brown 2 1 Pediatric Hematology/Oncology, Texas Children's Cancer and Hematology Centers, Baylor College of Medicine, Houston, TX, USA 2 Oncology and Pediatrics, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA 3 Polyphor, Ltd., Allschwil, Switzerland Correspondence to: Edward Allan R. Sison, e-mail: sison@bcm.edu Keywords: acute lymphoblastic leukemia, CXCR4, microenvironment, chemokines, pediatric Received: July 14, 2015 Accepted: August 21, 2015 Published: September 03, 2015 ABSTRACT The importance of the cell surface receptor CXCR4 and the chemokine stromal cell-derived factor-1 (SDF-1/CXCL12) is well-established in normal and malignant hematopoiesis. The Protein Epitope Mimetic POL5551 is a novel and potent antagonist of CXCR4. POL5551 efficiently mobilizes hematopoietic stem and progenitor cells, but its effects in acute lymphoblastic leukemia (ALL) have not been reported. Here, we demonstrate that POL5551 is a potent antagonist of CXCR4 in pre-B and T cell ALL cell lines and pediatric ALL primary samples. POL5551 has activity at nanomolar concentrations in decreasing CXCR4 antibody binding, blocking SDF-1α-mediated phosphorylation of ERK1/2, inhibiting SDF-1α-induced chemotaxis, and reversing stromal-mediated protection from chemotherapy. POL5551 is significantly more effective at inhibiting CXCR4 antibody binding than the FDA-approved CXCR4 inhibitor plerixafor in ALL cell lines and primary samples. We also show that treatment with POL5551 in vitro and cytarabine +/− POL5551 in vivo modulates surface expression of adhesion molecules, findings that may guide the optimal clinical use of POL5551. Finally, we demonstrate that POL5551 increases sensitivity to cytarabine in a xenograft model of a high-risk pediatric ALL, infant MLL- rearranged ( MLL- R) ALL. Therefore, disruption of the CXCR4/SDF-1 axis with POL5551 may improve outcomes in children with high-risk ALL.
Determining strategic focus for De Groene Zaak

Field: Business, Management and Accounting (Social Sciences)

Over the last three years, the organisations activities have expanded along with its growth. Comparing literature to insights has led us to conclude that De Groene Zaak should increase strategic focus. By assessing core values, strengths and weaknesses, success factors for societal influence, trends and the market we developed a new organizational strategy. We suggest De Groene Zaak to become a business accelerator, by brokering between ventures and large firms. In providing post-startups with the means to scale, De Groene Zaak directly contributes to advancing the sustainability of the economy.
Effects of funding and its return on product quality in new ventures

Field: Business, Management and Accounting (Social Sciences)

Most entrepreneurs must rely on external financing when their new venture is based on the development of a new product. External financing, however, is usually uncertain in magnitude and timing, thus creating tradeoff between the advantage of waiting-to generate more money-and improve the product versus releasing the product before competition increases. This tradeoff is investigated through a dynamic programming framework for which a simple, easy-to-implement optimal stopping rule is identified for a special class of revenue functions. The model is utilized to characterize how the amount of funding and its variability are expected to affect the quality of the product at time to market. The model also studies how the release-time strategy is affected by the expectation and the variability of the effect that each unit of funding has on the quality of the product under development. The author shows that an increment in funding does not always lead to a product of higher quality. He also shows that an improvement in the effect of investment on quality does not necessarily lead to an enhanced product.
Dehydrated brewery residue for pigs in the growth phase under high temperature conditions

Field: Agricultural and Biological Sciences (Life Sciences)

This research was developed to evaluate the nutritional, digestible (DE) and metabolizable (ME) energy values of dehydrated brewery residue (DBR) for growing pigs, as well as to evaluate the performance of these animals, subjected to five levels of DBR inclusion (0, 5, 10, 15 and 20%). The experimental design was of randomized blocks, based on animal weight. In the digestibility assay, 12 male piglets of average weight of 34.8±4.8 kg were utilized, while the performance assay had 40 piglets with average weight of 26.7±3.3 kg. Digestible and metabolizable protein values of dehydrated brewery residue for growing pigs reared in an environment of high temperatures were 22.47 and 22.06%, respectively, whereas digestible and metabolizable energy values of DBR were 3,371 and 3,364 kcal/kg, respectively. Dehydrated brewery residue can be included in diets for growing pigs up to the level of 20%.
One‐step Fabrication of π‐Conjugated Polymer Thin Films from Naphthalenes via Plasma Polymerization for Efficient Optoelectronic Devices: White Polymer Light‐emitting Diodes

Field: Materials Science (Physical Sciences)

Abstract We describe a facile one‐step fabrication process of thin film conjugated polymers for efficient optoelectronic devices from naphthalenes by plasma polymerization through a new monomer feeding method. The resulting 3‐D aromatic chain networks of the polymerized films were in good agreement with the predictions based on monomer bond rupture routes analysis. The photoluminescence (PL) spectra of plasma‐polymerized films featured short‐lived inter‐molecular emissions arising from self‐assembly of the naphthalene units in the crosslinked architectures. When functioning between the electrodes for light emitting, the plasma films manifested electroluminescence (EL) spectra that showed a steep rise at the threshold wavelength red‐shifted relative to the PL spectra, indicating prevailing charge tunneling to lower excited states by the accumulated interfacial charges. The wide distribution of conjugation lengths in the plasma films provided the subsequent energy transfer routes and gave rise to the broad EL emission band that produced stable pure white light of CIE coordinates of (0.34, 0.33) with excellent efficiencies. This dry deposition process allows the use of multiple monomers for property tailoring and may be used for large‐area depositions. magnified image
Birth defects: Risk factors and consequences

Field: Medicine (Health Sciences)

Birth defects (BDs) or congenital anomalies include all structural and functional alterations in embryonic or fetal development resulting from genetic, environmental or unknown causes, which result in physical and/or mental impairment. BDs occur in about 3% of newborn babies and in most cases of pregnancy loss. BDs are a very complex and heterogeneous group of single or multiple changes that, in most cases, are of unknown etiology. Among the risk factors are advanced maternal and paternal ages, parental consanguinity, teratogenic agents such as infectious agents and drugs, and poor nutrition, in particular folic acid deficiency. One of the consequences of these defects is the high death rate within the first year of life. Information on BDs is becoming increasingly more important throughout the world so that preventive measures can be taken. Knowledge of BDs enables the development of therapeutic and preventive strategies besides adequate genetic counseling.
A departure from history: Kashmiri Pandits, 1990-2001

Field: Social Sciences (Social Sciences)

Abstract Most Kashmiri Pandits living in the Kashmir Valley left in 1990 as militant violence engulfed the state. Some 95% of the 160,000-170,000 community left in what is often described as a case of ethnic cleansing. Why did they leave? What political movements have followed? Much of the present focus is on those who have left, but the small minority who remain in the Kashmir Valley may be more important in determining what kind of society Kashmir becomes.
Geology of the Panamint silver district, California

Field: Earth and Planetary Sciences (Physical Sciences)

This paper is concerned with the geology of the Panamint mining \ndistrict, situated in the Panamint Range, southeastern California. \nThe numerous clean-cut silver-bearing fissure veins of \nthis district which occur largely in limestone, have received but \nslight attention from geologists in the past. The geology of the district and the mineralogy of the deposits are relatively simple. \nThere is much conflict in the many more or less indefinite accounts \nof the extent of production from the several mines, but \nit seems safe to state that the gross value of the output was over \n$2,000,000. \nThe work upon which this paper is based was done in the \ngraduate school of the California Institute of Technology. I am \nindebted to Dr. F. L. Ransome for the reading of the manuscript \nof this report and for accompanying me on a brief field trip \nto the region.
Essays on european natural gas market

Field: Economics, Econometrics and Finance (Social Sciences)

La presente tesis ha cubierto diferentes aspectos de los mercados europeos del gas natural y la electricidad, en particular algunas propiedades que afectan a la efectividad de la cobertura, como la estacionalidad en varianza y en precios. Asimismo, se ha realizado un estudio de la prima de riesgo del gas natural, su relacion con las variables de riesgo y su descomposicion en una prima de riesgo de reinversion o ‘rollover’ y una prima de ‘preferencia por liquidez’ relacionada con el plazo. La tesis se compone de tres capitulos: el Capitulo I estudia la estacionalidad en los precios y la volatilidad y como mejora la efectividad de la cobertura teniendo en cuenta dicha estacionalidad; el Capitulo II analiza la prima de riesgo convencional y de rollover y su diferencia y como se relacionan con factores de riesgo especificos a lo largo del tiempo; y el Capitulo III evalua la efectividad de la cobertura del ‘spark spread’ usando conjuntamente los precios de futuros de electricidad y gas natural. Las conclusiones mas importantes de la tesis son: en el calculo de los ratios de cobertura de minima varianza, se han obtenido mejoras significativas en la efectividad de la cobertura de las estrategias consideradas en la gestion del riesgo de precio cuando se considera el cambio esperado en los precios al contado con el enfoque de Ederington y Salas (2008). Otro resultado a resaltar es que las primas de riesgo en los futuros de gas natural del Reino Unido estan dominadas por el 'componente spot' (las primas de riesgo de rollover exceden las primas de riesgo convencionales). Tambien se han detectado patrones estacionales en media y volatilidad en las primas de riesgo de rollover, en las primas de riesgo convencionales y en la diferencia entre ellos. Y por ultimo, en el tercer capitulo, aplicando el enfoque de Ederington y Salas (2008) para los rendimientos del spark spread se consiguen mejoras en la efectividad de la cobertura respecto al enfoque de minima varianza clasico, ya que la reduccion del riesgo se infraestima con este ultimo.
Exome Sequencing Identifies Carriers of the Autosomal Dominant Cancer Predisposition Disorders Beyond Current Practice Guideline Recommendations

Field: Medicine (Health Sciences)

PURPOSE The autosomal dominant cancer predisposition disorders hereditary breast and ovarian cancer (HBOC) and Lynch syndrome (LS) are genetic conditions for which early identification and intervention have a positive effect on the individual and public health. The goals of this study were to determine whether germline genetic screening using exome sequencing could be used to efficiently identify carriers of HBOC and LS. METHODS Participants were recruited from three geographically and racially diverse sites in the United States (Rochester, MN; Phoenix, AZ; Jacksonville, FL). Participants underwent Exome+ sequencing (Helix Inc, San Mateo, CA) and return of results for specific genetic findings: HBOC ( BRCA1 and BRCA1) and LS ( MLH1, MSH2, MSH6, PMS2, and EPCAM). Chart review was performed to collect demographics and personal and family cancer history. RESULTS To date, 44,306 participants have enrolled in Tapestry. Annotation and interpretation of all variants in genes for HBOC and LS resulted in the identification of 550 carriers (prevalence, 1.24%), which included 387 with HBOC (27.2% BRCA1, 42.8% BRCA2) and 163 with LS (12.3% MSH6, 8.8% PMS2, 4.5% MLH1, 3.8% MSH2, and 0.2% EPCAM). More than half of these participants (52.1%) were newly diagnosed carriers with HBOC and LS. In all, 39.2% of HBOC/LS carriers did not satisfy National Comprehensive Cancer Network (NCCN) criteria for genetic evaluation. NCCN criteria were less commonly met in underrepresented minority populations versus self-reported White race (51.5% v 37.5%, P = .028). CONCLUSION Our results emphasize the need for wider utilization of germline genetic sequencing for enhanced screening and detection of individuals who have LS and HBOC cancer predisposition syndromes.
Kinship, ectoparasites, and reproductive success in Cape ground squirrel (Xerus inauris) social networks

Field: Agricultural and Biological Sciences (Life Sciences)

Sociality – or living in groups among members of the same species – can have both costs and benefits for survival and reproductive success. Inclusive fitness theory suggests organisms might behaviourally favour closer kin if they can identify and act to benefit them. In promiscuous social species, average relatedness may be too low to maintain costly social behaviours like cooperative breeding without kin discrimination. Animals that are more central in social networks may gain fitness benefits and costs similar to those of sociality generally, but particularly those effects that arise from indirect social connections. Increased social network centrality is often linked to improved fitness, but also greater ectoparasite abundance. Exploring whether fitness correlates to social network position under low rates of aggression or hierarchy remains a key challenge for comparative evolutionary ecology. Cape ground squirrels (Xerus inauris) are facultatively cooperative breeders with high promiscuity. They are a social species that rarely exhibit aggressive behaviours towards conspecifics and show no evidence of dominance hierarchies. A previous study that removed their parasites dramatically increased female reproductive success. Our objective was to examine whether kinship influences social structure and whether ectoparasite abundance and centrality influence survival and reproductive success in adult female Cape ground squirrels. We predicted kinship increases affiliative and decreases agonistic interactions, that centrality increases ectoparasites, and that ectoparasites and centrality reduce reproductive success but not survival. We studied Cape ground squirrels on S.A. Lombard Nature Reserve, South Africa in 2017. We followed 14 social groups, collected interaction data through all-occurrence sampling, and collected ectoparasite abundance data from trapping. We found that kinship increased both affiliative and agonistic interactions. Since agonistic interactions are relatively mild in this species, greater agonistic interaction frequencies with closer kin may have insignificant fitness costs. More central adult females had more ectoparasites, but eigenvector centrality and ectoparasite abundance did not affect survival or reproductive success. Our study shows that Cape ground squirrels are nepotistic with their interactions within their social groups, and that the costs and benefits of group living in species with low rates of aggression can have novel implications for the relationships between fitness and sociality.
Mitochondrial DNA and the origins of the domestic horse

Field: Agricultural and Biological Sciences (Life Sciences)

The place and date of the domestication of the horse has long been a matter for debate among archaeologists. To determine whether horses were domesticated from one or several ancestral horse populations, we sequenced the mitochondrial D-loop for 318 horses from 25 oriental and European breeds, including American mustangs. Adding these sequences to previously published data, the total comes to 652, the largest currently available database. From these sequences, a phylogenetic network was constructed that showed that most of the 93 different mitochondrial (mt)DNA types grouped into 17 distinct phylogenetic clusters. Several of the clusters correspond to breeds and/or geographic areas, notably cluster A2, which is specific to Przewalski's horses, cluster C1, which is distinctive for northern European ponies, and cluster D1, which is well represented in Iberian and northwest African breeds. A consideration of the horse mtDNA mutation rate together with the archaeological timeframe for domestication requires at least 77 successfully breeding mares recruited from the wild. The extensive genetic diversity of these 77 ancestral mares leads us to conclude that several distinct horse populations were involved in the domestication of the horse.
Davis-Christopher Textbook of Surgery: The Biological Basis of Modern Surgical Practice

Field: Medicine (Health Sciences)

Smith'sPapyrus, Osler'sMedicine, and Sabiston'sSurgery—these are probably the three most widely read medical texts in history. The 1977 edition of the latter has been translated into six languages besides English. The obvious question is, Why a 12th edition written only four years after the last? Justification for the new edition lies primarily in the first half of this massive (2,481 pages) new testament. If it were merely an atlas of operative surgery or a standard surgical text, a stately edition every ten to 15 years would serve. But as the subtitle indicates, the objective of this text is to describe the biological basis of modern surgical practice—a field where the doubling time approaches that of a rabbit. This remarkable text, which is almost as much a medical as a surgical textbook, is therefore among other things a summary of "what's new in surgical biology?" The answer is,
Ocular Tension in Glaucoma Simplex

Field: Neuroscience (Life Sciences)

Heterotromeric G-proteins of the Gq family are thought to transduce signals from group I metabotropic glutamate receptors (mGluRs) in central neurons. We investigated roles of this cascade in hippocampal long-term potentiation (LTP) by using null-mutant mice lacking the α subunit of Gq (Gαq) or G11 (Gα11). We found no obvious abnormalities in the morphology, layer structure, expression of NMDA receptors, and basic parameters of excitatory synaptic transmission in the hippocampus of Gαq mutant mice. We used theta burst stimulation (TBS) (3–10 burst trains at 5 Hz; each train consisted of five stimuli at 100 Hz) to induce LTP at Schaffer collateral to CA1 pyramidal cell synapses. Conventional TBS with 10 burst trains induced robust LTP in wild-type, Gαq mutant, and Gα11 mutant mice. Weak TBS with three burst trains consistently induced LTP in wild-type mice. In contrast, the same weak TBS was insufficient to induce LTP in Gαq and Gα11 mutant mice. In wild-type mice, the LTP by weak TBS was abolished by inhibiting group I mGluR or protein kinase C (PKC) but not by blocking muscarinic acetylcholine receptors. Prior activation of group I mGluR by an agonist significantly enhanced the LTP by weak TBS in wild-type mice. However, this priming effect was absent in Gαq mutant mice. These results indicate that the signaling from group I mGluR to PKC involving Gαq/Gα11 does not constitute the main pathway for LTP, but it secures LTP induction by lowering its threshold in the hippocampal area CA1.
Increasing Conversational Interactions Between Verbal High School Students With Autism and Their Peers Without Disabilities

Field: Social Sciences (Social Sciences)

Self-prompted communication books were used in combination with conversational peer orientation to increase conversational interactions of verbal high school students with autism or autistic-like behavior with their peers without disabilities. Previous investigators have used communication books only with students with autism or intellectual disability with limited or no verbal or reading skills. The six high school participants in this study could read and were verbal. We sought to determine whether the communication books would be accepted by peers without disabilities in general education classrooms or whether the books would stigmatize the students with disabilities. Finally, we assessed the effects of having a peer with a learning disability as the teacher of conversational interaction skills. We interpreted our results to conclude that the communication book package was associated with increased conversational interactions for all participants with their general education peers and that communication books were viewed positively by conversational partners.
Prenatal Detection of Ischemic Changes in the Placenta of the Growth-Retarded Fetus by Doppler Flow Velocimetry of the Maternal Uterine Artery

Field: Medicine (Health Sciences)

Objective: To determine the relationships among the pregnancy outcomes of growth-retarded fetuses, Doppler flow velocimetry of the fetomaternal circulation, and pathologic changes in the placenta. Methods: Forty-seven fetuses confirmed to be growth-retarded by ultrasonographic biometry were monitored during pregnancy in terms of the resistance indexes of the maternal uterine, fetal umbilical, and fetal middle cerebral arteries. After delivery, the placentas were examined for pathologic changes such as infarction and villous ischemia. Results: Compared with 23 fetuses with nonischemic placentas, 24 growth-retarded fetuses whose placentas showed ischemic lesions were more frequently delivered preterm (P< .001) and by cesarean for fetal distress (P< .01), and they also had lower mean pH, higher carbon dioxide pressure, and lower oxygen pressure values (P< .05). Compared with the fetal umbilical and middle cerebral artery resistance indexes, the uterine artery resistance index showed the highest sensitivity (91.7%), specificity (78.3%), and positive predictive value (81.5%) for detecting placental ischemic changes. Linear discriminative analysis also showed that the uterine artery resistance index had the strongest correlation (P< .00001) with the placental ischemic changes. Conclusion: Ischemia of the placenta is associated with an adverse pregnancy outcome in growth-retarded fetuses. The placental ischemic changes can be detected using Doppler flow velocimetry. Measurement of the uterine artery resistance index might be useful for determining the clinical management of growth-retarded fetuses.(Obstet Gynecol 1993;82:494-9)