gebhart/patrepeval huggingface dataset:
Spatially Resolved Metabolic Phenotyping of Breast Cancer by Desorption Electrospray Ionization Mass Spectrometry (2015)

Breast cancer is a heterogeneous disease characterized by varying responses to therapeutic agents and significant differences in long-term survival. Thus, there remains an unmet need for early diagnostic and prognostic tools and improved histologic characterization for more accurate disease stratification and personalized therapeutic intervention. This study evaluated a comprehensive metabolic phenotyping method in breast cancer tissue that uses desorption electrospray ionization mass spectrometry imaging (DESI MSI), both as a novel diagnostic tool and as a method to further characterize metabolic changes in breast cancer tissue and the tumor microenvironment. In this prospective single-center study, 126 intraoperative tissue biopsies from tumor and tumor bed from 50 patients undergoing surgical resections were subject to DESI MSI. Global DESI MSI models were able to distinguish adipose, stromal, and glandular tissue based on their metabolomic fingerprint. Tumor tissue and tumor-associated stroma showed evident changes in their fatty acid and phospholipid composition compared with normal glandular and stromal tissue. Diagnosis of breast cancer was achieved with an accuracy of 98.2% based on DESI MSI data (PPV 0.96, NVP 1, specificity 0.96, sensitivity 1). In the tumor group, correlation between metabolomic profile and tumor grade/hormone receptor status was found. Overall classification accuracy was 87.7% (PPV 0.92, NPV 0.9, specificity 0.9, sensitivity 0.92). These results demonstrate that DESI MSI may be a valuable tool in the improved diagnosis of breast cancer in the future. The identified tumor-associated metabolic changes support theories of de novo lipogenesis in tumor tissue and the role of stroma tissue in tumor growth and development and overall disease prognosis.
Self-Positioning Robot Navigation Using Ceiling Image Sequences (1995)

This paper presents the analysis of a vision-based homing behavior that provides self-positioning for a mobile robot using ceiling structures as landmarks. This new behavior enters the navigation approach we developed for mobile robots, which basic idea is to represent the robot spatial knowledge in a topological map, where nodes consist of self-positioning sites and edges may be any reactive behavior moving the robot between two nodes. 1.
0.6 mu m high speed BiCMOS technology with emitter-base self-aligned structure (2003)

A high-speed BiCMOS technology called emitter-base self-aligned BiCMOS (ESBiC) has been developed. This process combines the polysilicon emitter-base self-aligned bipolar transistor with a 0.6- mu m-gate CMOS transistor. With this process, a 15-GHz cutoff frequency and an ECL (emitter-coupled logic) basic delay time of 60 ps at I/sub cs/=1 mA are achieved. For the BiCMOS gate, a 200-ps basic delay and a 330-ps delay time with 0.5-pF load capacitance are obtained.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Phase 1/1B trial to assess the activity of entrectinib in children and adolescents with recurrent or refractory solid tumors including central nervous system (CNS) tumors. (2019)

10009 Background: Entrectinib is a CNS-penetrant oral inhibitor of TrkA/B/C, ROS1 and ALK tyrosine kinases. We report the efficacy of entrectinib in children with recurrent/refractory solid or CNS tumors. Methods: Patients ≤ 20y old with recurrent/refractory solid tumors were eligible. After determination of the recommended dose in all-comers, disease-specific expansion cohorts of CNS and solid tumors harboring target aberrations in NTRK1/2/3, ROS1 or ALK, and neuroblastoma (NBL), regardless of mutation spectrum, were enrolled. Response, assessed by Investigator, was classified as complete response (CR), partial response (PR), stable disease (SD) or progressive disease (PD) using RANO for CNS tumors, RECIST for solid tumors, and Curie score for NBL. Results: Between May 2016 and October 2018, 29 patients aged 4.9m–20y (median 7y) were enrolled and 28 were evaluated for response. Entrectinib was well tolerated. Dose limiting toxicities were elevated creatinine, dysgeusia, fatigue and pulmonary edema. The recommended dose was 550 mg/m 2 daily. All responses occurred at doses ≥ 400 mg/m 2 . In CNS tumors (n = 6), all high-grade with gene fusions: 1 achieved a CR ( ETV6-NTRK3); 3 achieved a PR ( TPR-NTRK1, EEF1G-ROS1, EML1-NTRK2); 1 achieved an unconfirmed PR ( GOPC-ROS1); and 1 has yet to be evaluated ( KANK1-NTRK2). In extracranial solid tumors (n = 8), 6 had a fusion of whom 1 achieved a CR ( DCTN1-ALK) and 5 achieved a PR ( TFG1-ROS1, EML4-NTRK3, ETV6-NTRK3, KIF5B-ALK, ETV6-NTRK3). In NBL (n = 15): 1 achieved a CR ( ALK F1174L). Median duration of therapy was 85d (6–592d) for all patients; 56d (6–338d) for non-responders; and 281d (56–592d) for responders. Median time to response was 57d (30–58d). Conclusions: Entrectinib produced striking, rapid and durable responses in all children with refractory CNS and solid tumors harboring NTRK1/2/3, ROS1 or ALK fusions (11 out of 11) as well as in an ALK-mutated NBL. No responses were seen in tumors lacking aberrations in target kinases. These results support the continued evaluation of entrectinib as a targeted therapeutic in solid tumors with NTRK1/2/3, ROS1 and ALK fusions, especially in high-grade CNS neoplasms. Clinical trial information: NCT02650401.
Genetic diversity of the human immunoglobulin heavy chain VHregion (2002)

The human immunoglobulin heavy chain VH region is one of the most complex regions in the human genome. The high level of diversity of this region has been shown by a number of studies. However, because of the limitations of the conventional experimental methods, it has been difficult to learn the extent of the diversity and the underlying mechanisms. This review describes a number of new genetic approaches developed in the authors' laboratory. By using these approaches, significant progress has been made in assigning different VH sequences to their respective loci, in learning the diversity of gene segment number and composition among the VH haplotypes, and in learning VH gene segment organization in individual haplotypes. Information obtained toward this direction could help in understanding the mechanisms underlying VH region diversity and the biological impact of the VH region diversity.
On the Current Saturation Observed in Electrochemical Polymer Transistors (2006)

Electrochemical transistors based on conjugated polymers are proposed as a path to printed electronics on paper. The electrochemical doping/dedoping of conjugated polymers clearly plays a role in the current vs potential characteristics of these devices, however, the mechanism of current saturation (often referred to as pinch-off) is not clearly understood, and the relationship between electrochemical devices and field-effect transistors is unclear. This paper offers a semiempirical model of the steady-state behavior of electrochemical transistors and compares this model with experimental observations of potential and electrochromic measurements within a device to illustrate the science behind the functionality observed.
A Mutant Cell in Which Association of Class I Heavy and Light Chains Is Induced by Viral Peptides (1989)

Association of the Db heavy chain with beta 2-microglobulin and expression of Db and Kb at the surface of the cell are induced by specific peptides in the mutant RMA-S. Association of antigenic peptides with the binding site of class I molecules may be required for correct folding of the heavy chain, association with beta 2-microglobulin, and transport of the antigen-MHC complex to the cell surface.
Ras signaling in prostate cancer progression (2003)

When prostate cancer is first detected it generally is dependent on the presence of androgens for growth, and responds to androgen ablation therapies. However, the disease often recurs in a disseminated and apparently androgen independent (AI) form, and in this state is almost invariably fatal. Considerable evidence indicates that the Androgen receptor (AR) continues to be required even in androgen independent (AI) disease. Thus, a key to understanding hormone independent prostate cancer is to determine the mechanism(s) by which the AR can function even in the absence of physiologic levels of androgen. In this article, we argue that growth factors and receptors that utilize Ras family members drive prostate cancer progression to a state of androgen hypersensitivity; and that post-translational modifications (e.g., phosphorylations) of transcriptional cofactors might be responsible for modulating the function of the AR so that it is active even at low concentrations of androgen.
MOLECULAR ANALYSIS OF V(D)J RECOMBINATION (1992)

We have made rapid progress in recent years in identifying the genetic causes of many human diseases. However, despite this recent progress, our mechanistic understanding of these diseases is often incomplete. This is a problem because it limits our ...Read More
Experimental identification of friction and its compensation in precise, position controlled mechanisms (1992)

Methodologies developed for experimentally determining accurate models for the nonlinear friction inherent in most mechanisms are presented. Alternative closed-loop controller strategies for decoupling the effect of friction in order to improve positioning accuracy are also given. The identification methodology is novel in the manner in which it extracts the nonlinear friction properties from the closed-loop errors via an iterative signal processing technique. The discussion is based on both theoretical modeling and on a practical position control problem that was substantially resolved in developing the methodologies. The application was a robotic gripper with a highly preloaded rack-and-pinion mechanism. Both measurement and control design methodologies to help systematically circumvent the problems of nonlinear friction in precise, position-controlled mechanisms are given.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Defects in coatomer protein I (COPI) transport cause blood feeding-induced mortality in Yellow Fever mosquitoes (2011)

Blood feeding by vector mosquitoes provides the entry point for disease pathogens and presents an acute metabolic challenge that must be overcome to complete the gonotrophic cycle. Based on recent data showing that coatomer protein I (COPI) vesicle transport is involved in cellular processes beyond Golgi-endoplasmic reticulum retrograde protein trafficking, we disrupted COPI functions in the Yellow Fever mosquito Aedes aegypti to interfere with blood meal digestion. Surprisingly, we found that decreased expression of the γCOPI coatomer protein led to 89% mortality in blood-fed mosquitoes by 72 h postfeeding compared with 0% mortality in control dsRNA-injected blood-fed mosquitoes and 3% mortality in γCOPI dsRNA-injected sugar-fed mosquitoes. Similar results were obtained using dsRNA directed against five other COPI coatomer subunits (α, β, β', δ, and ζ). We also examined midgut tissues by EM, quantitated heme in fecal samples, and characterized feeding-induced protein expression in midgut, fat body, and ovary tissues of COPI-deficient mosquitoes. We found that COPI defects disrupt epithelial cell membrane integrity, stimulate premature blood meal excretion, and block induced expression of several midgut protease genes. To study the role of COPI transport in ovarian development, we injected γCOPI dsRNA after blood feeding and found that, although blood digestion was normal, follicles in these mosquitoes were significantly smaller by 48 h postinjection and lacked eggshell proteins. Together, these data show that COPI functions are critical to mosquito blood digestion and egg maturation, a finding that could also apply to other blood-feeding arthropod vectors.
ProtoFlex (2009)

Functional full-system simulators are powerful and versatile research tools for accelerating architectural exploration and advanced software development. Their main shortcoming is limited throughput when simulating large multiprocessor systems with hundreds or thousands of processors or when instrumentation is introduced. We propose the ProtoFlex simulation architecture, which uses FPGAs to accelerate full-system multiprocessor simulation and to facilitate high-performance instrumentation. Prior FPGA approaches that prototype a complete system in hardware are either too complex when scaling to large-scale configurations or require significant effort to provide full-system support. In contrast, ProtoFlex virtualizes the execution of many logical processors onto a consolidated number of multiple-context execution engines on the FPGA. Through virtualization, the number of engines can be judiciously scaled, as needed, to deliver on necessary simulation performance at a large savings in complexity. Further, to achieve low-complexity full-system support, a hybrid simulation technique called transplanting allows implementing in the FPGA only the frequently encountered behaviors, while a software simulator preserves the abstraction of a complete system. We have created a first instance of the ProtoFlex simulation architecture, which is an FPGA-based, full-system functional simulator for a 16-way UltraSPARC III symmetric multiprocessor server, hosted on a single Xilinx Virtex-II XCV2P70 FPGA. On average, the simulator achieves a 38x speedup (and as high as 49×) over comparable software simulation across a suite of applications, including OLTP on a commercial database server. We also demonstrate the advantages of minimal-overhead FPGA-accelerated instrumentation through a CMP cache simulation technique that runs orders-of-magnitude faster than software.
Pathogenicity of morphological and auxotrophic mutants of Candida albicans in experimental infections (1985)

The relative pathogenicities of yeast and mycelial forms of Candida albicans were determined after intravenous injection of the two forms into mice. Yeast and mycelial forms of C. albicans CMI45348 were prepared in chemostat culture. Both morphological forms were pathogenic, but the histology of kidney sections always showed a mixture of the yeast and mycelial elements of the organism. Similarly, infection of mice with prototrophic strains produced a mixture of morphological forms at the site of infection. The yeast (CA2) and mycelial (hOG301) morphological mutants of C. albicans were pathogenic, and sections from the kidneys of the infected mice showed that the mutants retained their original morphological forms. These data indicate that both the yeast and mycelial forms of C. albicans can adhere, invade, and proliferate in an infected host. Auxotrophic diploid mutants were nonpathogenic. However, construction of a prototrophic tetraploid strain from two auxotrophs restored the pathogenicity of the organism.
Electrospinning of poly(ethylene‐co‐vinyl acetate)/clay nanocomposite fibers (2009)

Abstract Poly(ethylene‐ co ‐vinyl acetate)/clay nanocomposite fibers were fabricated using electrospinning. The fiber diameters were controlled by varying the polymer/chloroform concentration, which resulted in fibers with diameters ranging from 1 to 15 μm. The clay concentration was varied from 0.35 to 6.6 wt %. Scanning electron microscopy revealed that the fiber diameter increased with increasing clay concentration, whereas beading decreased. Transmission electron microscopy revealed a disruption of the spherulite structures by clay, which is consistent with heterogeneous nucleation. Shear modulus force microscopy indicated a reduction in melting point ( T m ) with decreasing diameter for fibers thinner than 15 μm, which was confirmed by temperature dependent X‐ray diffraction data. For fibers thinner than 8 μm, the presence of clay further enhanced the reduction of T m . © 2009 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 47: 2501–2508, 2009
Continuous deployment at Facebook and OANDA (2016)

Continuous deployment is the software engineering practice of deploying many small incremental software updates into production, leading to a continuous stream of 10s, 100s, or even 1,000s of deployments per day. High-profile Internet firms such as Amazon, Etsy, Facebook, Flickr, Google, and Netflix have embraced continuous deployment. However, the practice has not been covered in textbooks and no scientific publication has presented an analysis of continuous deployment.
Rep protein of tomato yellow leaf curl geminivirus has an ATPase activity required for viral DNA replication. (1995)

The Rep protein of geminiviruses is the sole viral protein required for their DNA replication. The amino acid sequence of Rep protein contains an NTP binding consensus motif (P-loop). Here we show that purified Rep protein of tomato yellow leaf curl virus expressed in Escherichia coli exhibits an ATPase activity in vitro. Amino acid exchanges in the P-loop sequence of Rep causes a substantial decrease or loss of the ATPase activity. In vivo, mutant viruses carrying these Rep mutations do not replicate in plant cells. These results show that ATP binding by the Rep protein of geminiviruses is required for its function in viral DNA replication.
The expression of the adhesion molecules ICAM‐1, VCAM‐1, PECAM, and E‐selectin in human atherosclerosis (1993)

The expression of PECAM, ICAM-1, VCAM-1, and E-selectin was studied in 64 samples of human coronary arteries taken from 15 explanted hearts obtained within 5 min of transplantation. Normal artery (n = 12), predominantly fibrous plaques (n = 23), and plaques containing extracellular lipid (n = 26) and three segments showing recanalization channels were studied. All endothelial cells strongly and equally expressed PECAM; positive staining was used to check that artefactual denudation of the endothelial surface had not occurred. PECAM was also present in some lipid-filled macrophages. Normal arteries showed no VCAM-1 staining but focal segments of the endothelium were positive for ICAM-1 and E-selectin. ICAM-1 was strongly and constantly expressed by the endothelium over all types of plaques and in macrophages. E-selectin expression was confined to endothelial cells and occurred on the surface in 35 per cent of fibrous and 22 per cent of lipid-containing plaques. VCAM-1 staining of surface endothelium occurred in 39 per cent of fibrous and 20 per cent of lipid-containing plaques. A population of spindle-shaped cells of macrophage type (positive for EMB11 antigen) expressed VCAM-1 in lipid-containing plaques. Adventitial vessels adjacent to plaques showed endothelial expression of ICAM-1 and E-selectin. VCAM-1 staining of adventitial vessel endothelium was associated with local lymphoid aggregation. In conclusion, the expression of cell adhesion molecules is an important element in the inflammatory component of atherosclerosis and contributes to both monocyte and lymphocyte activation and recruitment from adventitial vessels and the arterial lumen.
Calories and carcinogenesis: lessons learned from 30 years of calorie restriction research (2009)

Calorie restriction (CR) is arguably the most potent, broadly acting dietary regimen for suppressing the carcinogenesis process, and many of the key studies in this field have been published in Carcinogenesis. Translation of the knowledge gained from CR research in animal models to cancer prevention strategies in humans is urgently needed given the worldwide obesity epidemic and the established link between obesity and increased risk of many cancers. This review synthesizes the evidence on key biological mechanisms underlying many of the beneficial effects of CR, with particular emphasis on the impact of CR on growth factor signaling pathways and inflammatory processes and on the emerging development of pharmacological mimetics of CR. These approaches will facilitate the translation of CR research into effective strategies for cancer prevention in humans.
An Alternative Synthesis of HPMPC and HPMPA Diphosphoryl Derivatives (2001)

In ( S )-1-[3-hydroxy-2-(phosphonomethoxy)propyl]cytosine (HPMPC) and ( S )-9-[3-hydroxy-2-(phosphonomethoxy)propyl]adenine (HPMPA) with 3-hydroxy functions protected with 4,4'-dimethoxytrityl (DMTr) groups, phosphonate groups were transformed to the morpholides and treated with bis(tributylammonium) diphosphate. Selective cleavage of the DMTr group in the presence of the labile diphosphate residue was achieved in water at pH 2.5. Purification by charcoal adsorption followed by anion exchange chromatography afforded phosphonate-diphosphate compounds (HPMPCpp, HPMPApp).
Pattern recognition. II. Linear and nonlinear methods for displaying chemical data (1973)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPattern recognition. II. Linear and nonlinear methods for displaying chemical dataB. R. Kowalski and C. F. BenderCite this: J. Am. Chem. Soc. 1973, 95, 3, 686–693Publication Date (Print):February 1, 1973Publication History Published online1 May 2002Published inissue 1 February 1973https://pubs.acs.org/doi/10.1021/ja00784a007https://doi.org/10.1021/ja00784a007research-articleACS PublicationsRequest reuse permissionsArticle Views218Altmetric-Citations151LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Efficient Total Synthesis of Ammosamide B (2010)

A total synthesis of ammosamide B, a metabolite of the marine-derived Streptomyces strain CNR-698, has been executed in nine steps and 6.9% overall yield. The key step involves the condensation of a 4,6-diBoc-protected 1,3,4,6-tetraaminobenzene derivative with dimethyl 2-ketoglutaconate, which effectively constructs the pyrrolidinone ring and the quinoline ring in a single step. This contributes a unique approach to the synthesis of pyrroloquinoline alkaloids that offers the advantages of brevity and relatively high overall yield.
Staphylococcus aureusAccessory Gene Regulator(agr)Group II: Is There a Relationship to the Development of Intermediate‐Level Glycopeptide Resistance? (2003)

We previously determined that all 6 Staphylococcus aureus strains with confirmed intermediate-level resistance to glycopeptides (glycopeptide intermediate S. aureus [GISA]) from the United States that we tested belonged to accessory gene regulator (agr) group II. In the present study, we found that 56% of surveyed bloodstream methicillin-resistant S. aureus isolates (n = 148) at our hospital were agr group II, whereas only 24% of methicillin-susceptible S. aureus isolates (n = 33) were agr group II (P = .001). Population analysis of genetically engineered agr-null and parent wild-type strains of groups I, II, and IV revealed that, when agr function is lost, the agr group II knockout S. aureus was most likely to develop glycopeptide heteroresistance after growth in 1 microg/mL but not 16 microg/mL vancomycin. This strain was unique in showing decreased autolysis after growth in these conditions. This study suggests that some S. aureus strains have an intrinsic survival advantage under a glycopeptide selective pressure, which is possibly related to reduced autolysis after exposure to subinhibitory concentrations of glycopeptide.