jimnoneill/paper-to-field-training huggingface dataset:
Identification of mannose 6-phosphate in glycoproteins that inhibit the assimilation of β-galactosidase by fibroblasts

Field: Biochemistry, Genetics and Molecular Biology (Life Sciences)

Bovine testicular β-galactosidase (β-D-galactoside galactohydrolase, EC 3.2.1.23) is rapidly and selectively assimilated by human skin fibroblasts. The assimilation of the enzyme is strongly inhibited by mannose 6-phosphate and by a glycoprotein fraction isolated from bovine testes (glycoprotein inhibitors). These results suggest that β-galactosidase and the glycoprotein inhibitors have a common recognition marker that contains mannose 6-phosphate. The presence of mannose phosphate in the glycoprotein inhibitors was demonstrated by acid hydrolysis of the glycoproteins to liberate mannose phosphate followed by reduction with NaB 3 H 4 to give [ 3 H]mannitol phosphate. The 3 H-labeled compound was identified by paper electrophoresis and by the release of [ 3 H]mannitol on treatment with phosphatase. The [ 3 H]mannitol phosphate was oxidized with periodate and the resulting phosphorylated fragment, on reduction with NaB 3 H 4 , yielded [ 3 H]ethylene glycol phosphate, indicating substitution of phosphate on carbon 6 of mannitol. Mannose 6-phosphate was also found in a major carbohydrate-containing fraction of peptides produced from the glycoprotein inhibitors by tryspin digestion. It was estimated that about 2% of the mannose residues were present as mannose 6-phosphate. Phosphorylated oligosaccharides were also identified in hydrolysates of the glycoprotein inhibitors. One, a disaccharide, was identified as α-(mannosyl-6-phosphate)-(1 → 2)-mannose. These observations suggest that the recognition marker of β-galactosidase contains α1,2-linked mannose 6-phosphate; terminal α1,2-linked mannose residues are known to occur in the high-mannose type oligosaccharides present on β-galactosidase.
TH‐D‐BRC‐03: Panel Member

Field: Medicine (Health Sciences)

Interest in proton therapy has increased dramatically in the past couple of years, especially in the United States. There certainly is an important place for proton therapy in the arsenal of cancer treatments. Its dosimetric advantage and potential for low toxicity makes it the perfect partner for photons and other cancer treatment modalities. Often there is a belief that the new technology ought to be better but many believe that they should be widely adopted in the clinic only after evidence has shown that they are at least as safe and efficacious as existing technologies, which are often less expensive. This is the case for proton radiotherapy. This session being both educational and debate will provide a good review of basics and technological advancement as well as a comprehensive clinical update for both proton and photon therapy. Future technology developments and how they will impact the potential dosimetric advantage of proton therapy will be discussed. Particularly the debate will focus on whether these developments will close or widen the gap between photon and proton therapy. Learning Objectives: To review challenges, limitations, and recent and future developments in proton therapy. To review challenges, limitations, recent and future developments in photon radiotherapy. To review current clinical trials and challenging clinical cases. C. Yu, No company or organization that my presentation mentions provided me with financial support. I am the Founder and CEO of Xcision Medical Systems, LLC. However, my presentation will not mention any product or technology developed by Xcision.
Abstract 1775: Characterization of new highly selective and potent PARP-1 inhibitors

Field: Pharmacology, Toxicology and Pharmaceutics (Life Sciences)

Abstract Poly (ADP-ribose) polymerase 1 (PARP-1) is a key nuclear enzyme that is activated by DNA-strand breaks; activation of PARP-1 protects DNA breaks and chromatin structure and recruits DNA repair and checkpoint proteins to the sites of damage, by modification with poly(ADP-ribose) (PAR) polymers. PARP-2, another nuclear member of the PARP family with largely unknown functions, shares homology with PARP-1 and is also activated by DNA breaks. Embryonic knock out of either PARP-1 or PARP-2 is well tolerated; however, double knockout is embryonic lethal suggesting that inhibiting both PARPs could enhance toxicity. PARP inhibitors in clinical development generally inhibit more than one PARP isoforms. These compounds are synthetic lethal with defects in homologous recombination (HR), and are currently being tested in combination as well as in monotherapy for hereditable cancers deficient in the BRCA1 or BRCA2 genes. Here we describe the in vitro and in vivo properties of a novel class of potent and selective PARP-1 small molecule inhibitors. Starting from a series of derivatives that were found to be active against PARP-1 and PARP-2, an expansion and optimization program was undertaken. This led to the identification of inhibitors with single digit nM affinity for PARP-1 and negligible crossreactivity against PARP-2. Members of this sub-series display single agent cytotoxicity with IC50s below 1 μM in cell lines harboring BRCA mutations, or in cells stably transfected with BRCA-1 short harpin RNA, and more than 100 times selectivity against BRCA wild-type tumor cell lines. Furthermore, these compounds are highly active in other repair deficient backgrounds such as ATM and Mre11 mutated acute leukemias and lymphomas and they compared favorably with reference PARP inhibitors which are in clinical development. Expected mechanism of action was confirmed by observed modulation of PAR induction, in vitro and in vivo. These compounds show high oral bioavailability, good ADME properties and high tolerability. Selection of the candidate most suitable for further development is underway. 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 1775. doi:1538-7445.AM2012-1775
Developing Methods and Measures to Assess Progress in Achieving Access Goals of the Americans with Disabilities Act: A Case Study of Small Towns in Montana

Field: Social Sciences (Social Sciences)

The Americans with Disabilities Act (ADA) was enacted without any baseline data against which to measure progress on achieving its public access goals. To date, no one has collected local, state, or national data to establish such a baseline or to assess progress in achieving those goals empirically. We developed a simple accessibility assessment tool that can aggregate data across businesses and communities. We then established a sampling frame for all Montana incorporated communities with populations of 2,500 – 10,000. We randomly selected 327 businesses to observe from a universe of 2,151 businesses that met inclusion criteria, and we trained accessibility advocates across the State to conduct observations. These advocates observed 236 businesses in 19 communities. Combining ratings across nine categories of accessibility, the State’s small cities and towns achieved an overall accessibility rating of 66.5% (2.66 on a 4-point scale), including average ratings of 2.74 for municipal parking availability, 1.91 for municipal parking accessibility, 2.28 for private parking availability, 1.98 for private parking accessibility, 2.91 for the safety and accessibility of municipal routes to businesses, 3.01 for private routes to businesses, 2.80 for accessibility of business entries, 2.42 for accessibility of business doorways, and 3.09 for accessibility of business interiors. Using these data, we identified 86 businesses (35.9% of the sample) that had at least one barrier that would likely preclude a person using a wheelchair from doing business there. This report presents exploratory analyses of the relationship between accessibility ratings and demographic and economic variables. Results are discussed in terms of the value of having longitudinal data that can represent the accessibility of communities over time.
Drone Detection and Classification using Computer Vision

Field: Computer Science (Physical Sciences)

Drones, also known as Unmanned Aerial Vehicles (UAVs) are based on the principle of rotor torque pushing the air down which results in the upward lift of the drone. UAVs are used in tasks such as rescue operations and item delivery in remote areas, surveillance, agriculture, wildlife conservation, outer space and photography. Due to their low cost and high efficiency, it is used by diverse groups for both better and worse causes. The cases of malicious uses of military drones and spy drones employed are on a rise. The malicious activities deployed by the military drones may include air strikes at enemy military bases, army troops and in some cases end up causing the death of civilians in proximity. Drones that are used for espionage can retrieve valuable information regarding the different strategies of the military, can track the location of the army personnel and spy upon unsuspecting civilians. These drones are eliminated after being detected by the persons involved but sometimes in order to reduce risks, harmless delivery drones are also discarded. In order to aid against the malicious drone activity while making sure that unnecessary panic over the delivery drones and material-loss is not caused, a real-time computer vision system is proposed that can identify the drone in the given region of interest, give its relative location and classify the drone. The Convolutional Neural Network (CNN) architecture, You Only Look Once Algorithm (YOLOV5), is used to classify the drone into one of the categories: Army, Surveillance and Delivery drones.
Formation and Operation of the Histidine-degrading Pathway in Pseudomonas aeruginosa

Field: Biochemistry, Genetics and Molecular Biology (Life Sciences)

Histidine ammonia lyase (histidase), urocanase, and the capacity to degrade formiminoglutamate, which are respectively involved in steps I, II, and IV in the catabolism of histidine, were induced during growth of Pseudomonas aeruginosa on histidine or urocanate, and were formed gratuitously in the presence of dihydro-urocanate. Urocanase-deficient bacteria formed enzymes I and IV constitutively; presumably they accumulate enough urocanate from the breakdown of endogenous histidine to induce formation of the pathway. Urocanate did not satisfy the histidine requirement of a histidine auxotroph, indicating that it probably acted as an inducer without being converted to histidine. The results imply that urocanate is the physiological inducer of the histidine-degrading enzymes in P. aeruginosa . Enzymes of the pathway were extremely sensitive to catabolite repression; enzymes I and II, but not IV, were coordinately repressed. Our results suggest a specific involvement of nitrogenous metabolites in the repression. Mutant bacteria with altered sensitivity to repression were obtained. The molecular weight of partially purified histidase was estimated at 210,000 by sucrose gradient centrifugation. Its K m for histidine was 2 × 10 −3 m in tris(hydroxymethyl)aminomethane chloride buffer. Sigmoid saturation curves were obtained in pyrophosphate buffer, indicating that the enzyme might have multiple binding sites for histidine. Under certain conditions, histidase appeared to be partially inactive in vivo. These findings suggest that some sort of allosteric interaction involving histidase may play a role in governing the operation of the pathway of histidine catabolism.
N-Heterocyclic 3-Pyridyl Carboxamide Inhibitors of DHODH for the Treatment of Acute Myelogenous Leukemia

Field: Pharmacology, Toxicology and Pharmaceutics (Life Sciences)

Acute myelogenous leukemia (AML), a disease of the blood and bone marrow, is characterized by the inability of myeloblasts to differentiate into mature cell types. Dihydroorotate dehydrogenase (DHODH) is an enzyme well-known in the pyrimidine biosynthesis pathway; however, small molecule DHODH inhibitors were recently shown to induce differentiation in multiple AML subtypes. Using virtual screening and structure-based drug design approaches, a new series of N-heterocyclic 3-pyridyl carboxamide DHODH inhibitors were discovered. Two lead compounds, 19 and 29, have potent biochemical and cellular DHODH activity, favorable physicochemical properties, and efficacy in a preclinical model of AML.
Age‐related changes of proinsulin processing in diabetic and non‐diabetic Japanese individuals

Field: Medicine (Health Sciences)

Aim The present study was carried out to examine whether the insulin secretory mechanism deteriorates during the aging process using the new intact proinsulin assay system in non‐diabetic and diabetic individuals. Methods A total of 172 participants were separated into four groups according to their age (<64 years and >65 years) and an association of type 2 diabetes; that is, 46 older diabetics (mean age 74.5 ± 6.2 years, glycated hemoglobin [National Glycohemoglobin Standardization Program] 7.5 ± 1.3%), 27 older non‐diabetics (mean age 76.9 ± 7.5 years), 48 middle‐aged diabetics (mean age 50.8 ± 10.4, glycated hemoglobin 7.8 ± 1.5%) and 51 middle aged non‐diabetics (mean age 46.6 ± 13.0 years) participants were enrolled. Results The proinsulin/insulin (PI/I) ratio of the diabetic group was higher than that of the non‐diabetic group in the older group (0.19 ± 0.12 vs 0.11 ± 0.06, P = 0.002). In the middle‐aged groups, the PI/I ratio of the diabetic group was higher than that of the non‐diabetic group (0.16 ± 0.15 vs 0.09 ± 0.09, P = 0.003). Simple regression analysis showed that male sex (95% CI 0.02–0.01, P = 0.004), age (95% CI 0.00–0.002, P = 0.03), lower body mass index (95% CI −0.06 to 0.00, P = 0.02) and the presence of diabetes mellitus (95% CI 0.04–0.012, P < 0.0001) were significantly associated with the increase in the PI/I ratio. Multivariate regression analysis showed that male sex and age were the independent factors determining the increase in the PI/I ratio in the non‐diabetic group. After adjusted for body mass index, the PI/I ratio correlated significantly with age only in the non‐diabetic group ( r = 0.5, P = 0.004). Conclusions The proinsulin processing system might deteriorate not only in diabetics, but also in non‐diabetic Japanese individuals with age. Also, sex‐related hormones can be protective for the proinsulin processing system. Geriatr Gerontol Int 2018; 18: 1046–1050 .
Lightning Current Tests to Evaluate Vulnerability of Electronics in Composite Structures

Field: Engineering (Physical Sciences)

Protecting highly sensitive electronics housed inside composite structures against lightning is a real challenge. The direct strike represents the worst-case scenario for composite structures. The electromagnetic field generated by an indirect lightning strike in the vicinity of highly sensitive equipment can cause interference or even damage electronic components. The Military Standard MIL STD – 464A gives some indications about the characteristics of a lightning strike (negative in polarity). A first discharge of 50 to 200kA, called A Pulse followed by two subsequent B & C Pulses. The B Pulse has a current of 2 kA while Pulse C has between 200 and 800 A. A test setup capable to replicate these characteristics is used to perform various tests on structures that replicate radars.
Estimating disease burden using Internet data

Field: Health Professions (Health Sciences)

Data on disease burden are often used for assessing population health, evaluating the effectiveness of interventions, formulating health policies, and planning future resource allocation. We investigated whether Internet usage and social media data, specifically the search volume on Google, page view count on Wikipedia, and disease mentioning frequency on Twitter, correlated with the disease burden, measured by prevalence and treatment cost, for 1633 diseases over an 11-year period. We also applied least absolute shrinkage and selection operator to predict the burden of diseases. We found that Google search volume is relatively strongly correlated with the burdens for 39 of 1633 diseases, including viral hepatitis, diabetes mellitus, multiple sclerosis, and hemorrhoids. Wikipedia and Twitter data strongly correlated with the burdens of 15 and 7 diseases, respectively. However, an accurate analysis must consider each condition’s characteristics, including acute/chronic nature, severity, familiarity to the public, and the presence of stigma.
THE USE OF MODERATED REGRESSION IN JOB REDESIGN DECISIONS*

Field: Psychology (Social Sciences)

ABSTRACT This paper describes the use of moderated regression in job redesign decisions. The procedures outlined are intended to augment the job redesign strategy described by Hackman and his colleagues. Different regression models based on a theory of job design are shown to lead to different job redesign decisions. Comparisons are also made between the moderated regression procedures and the more commonly used subgroups analysis.
Three dimensional telomeric profiles in circulating tumour cells as a method of monitoring treatment response in high-risk prostate cancer patients

Field: Medicine (Health Sciences)

Prostate cancer is the second most commonly diagnosed cancer in men worldwide. Because prognosis can vary depending on tumour stage, precise diagnosis is vital. Circulating tumour cells (CTC) detach from primary and secondary tumour sites into the bloodstream. Changes in three-dimensional (3D) nuclear organization are associated with different types of cancer and were examined in this study in CTCs of high-risk prostate cancer patients. CTCs were isolated from 3mL of patient blood samples of 20 high-risk prostate cancer patients before treatment; after neoadjuvant androgen deprivation therapy (ADT) but before radiotherapy (RT); and after completing RT. Telomere-specific fluorescence in situ hybridization was performed on filters containing cells, 3D images of 30 CTCs per filter were analysed. Changes in telomere organization were observed post ADT and RT; patients fell into three groups depending on the change in CTC telomeric profiles in response to ADT. These groups displayed responses characteristic to each group upon delivery of RT. 3D nuclear telomere profiles in CTCs post-ADT may indicate both ADT response and predict RT response in high-risk prostate cancer.
The Excavations at Nimrud (Kalḫu), 1949-1950 Ivories from the N. W. Palace

Field: Arts and Humanities (Social Sciences)

The most important of the rich and varied pieces of carved ivory discovered at Nimrud during 1949 and 1950 have already been illustrated and discussed in previous numbers of this Journal.1 The photographs which accompany this article, Plates XII-XVIII, illustrate the remainder of what still needed to be published from those two seasons : anything omitted is probably too much mutilated or fragmentary to be worth describing. This material falls into two groups. Plates XII-XV represent the remains of the ivories from Layard's dumps in chamber V of the N.W. Palace, and were found in 1949 together with the beautiful ivory cow shown in Iraq, XIII, Pt. 1, Plate I, Nos. 2, 3 ; Plates XVI-XV?1 represent the few pieces still unpublished from the collection of ivories found in the S.E. wing of the N.W. Palace during 1950. It will be seen that none of these pieces adds substantially to our knowledge of the Nimrud ivories, for none of them is different in style from anything previously discovered, but for the sake of completeness they have deserved illustration. Nor should it be forgotten that some of them may perhaps join with other fragments brought home by Layard a century ago and now in the British Museum. However, it is also evident that each element is but a small fraction of a very much larger whole, and such joins as could be made would not be likely to alter the picture of the already known themes which composed the repertory ?f the ancient ivory work. It may be hoped, none the Jess, that at some future time such disjecta membra will be reassembled, however little they may avail for the complete restoration of what was long ago for the most part destroyed. AH o? the ivory fragments as well as the glass and gold foil shown on Plates XII-XV were found in Layard's filling which overlay the floor of chamber V {cf. Fig. 1 for the location of this room in the N.W. Palace); a few mutilated pieces were also discovered in room W. There can be no certainty about their original position, since they come from earth which the workmen had shovelled back again on Layard's orders for the purpose of protecting the rooms after he had finished digging them. But it is most probable that the majority had in fact come from room V where Layard himself said that he found them : the passage in which he describes the discovery is of interest, cf. Nineveh and its Remains, Vol. 11, p. 8/. The chamber V is remarkable for the discovery, near the entrance a, of a number of ivory ornaments of considerable beauty and interest. These ivories, when uncovered, adhered so firmly to the soil,
Analysis of a Half-Scale Composite Floor System Test under Column Loss Scenarios

Field: Engineering (Physical Sciences)

This paper describes modeling and analysis of a half-scale steel gravity frame system with composite concrete slab on steel deck that was constructed and tested at the University of Illinois under corner, edge, and interior column removal scenarios. For each scenario, distributed floor loading was incrementally increased until the floor system could not sustain additional load. The experimental results showed that the ultimate capacity of the floor system ranged from 44 % to 62 % of the applicable gravity load combination (1.2D + 0.5L), indicating a potential vulnerability to collapse. Analyses of the floor system used a component-based modeling approach for the shear connections, with load-displacement curves for each bolt row calibrated against experimental data from half-scale connections. Girders, beams, and columns were modeled with beam elements, and alternating strips of shell elements were used to represent the ribbed profile of the concrete slab on steel deck. The model accounted for partial continuity of the steel deck, as influenced by the actual placement of shear studs and spot welds. Blind pre-test predictions are compared with experimental data for the four column removal scenarios. The modeling approach was refined after each of the first two tests, and two factors were identified as having a significant influence on the response of the system: the post-ultimate softening modulus of concrete in tension and the out-of-plane (torsional and transverse shear) behavior of the shear connections.
Influence of El Niño on Midtropospheric CO2 from Atmospheric Infrared Sounder and Model

Field: Environmental Science (Physical Sciences)

Abstract The authors investigate the influence of El Niño on midtropospheric CO2 from the Atmospheric Infrared Sounder (AIRS) and the Model for Ozone and Related Chemical Tracers, version 2 (MOZART-2). AIRS midtropospheric CO2 data are used to study the temporal and spatial variability of CO2 in response to El Niño. CO2 differences between the central and western Pacific Ocean correlate well with the Southern Oscillation index. To reveal the temporal and spatial variability of the El Niño signal in the AIRS midtropospheric CO2, a multiple regression method is applied to the CO2 data from September 2002 to February 2011. There is more (less) midtropospheric CO2 in the central Pacific and less (more) midtropospheric CO2 in the western Pacific during El Niño (La Niña) events. Similar results are seen in the MOZART-2 convolved midtropospheric CO2, although the El Niño signal in the MOZART-2 is weaker than that in the AIRS data.