gebhart/patrepeval huggingface dataset:
Discovery of Sulfonamide-Derived Agonists of SOS1-Mediated Nucleotide Exchange on RAS Using Fragment-Based Methods (2020)

The nucleotide exchange factor Son of Sevenless (SOS) catalyzes the activation of RAS by converting it from its inactive GDP-bound state to its active GTP-bound state. Recently, we have reported the discovery of small-molecule allosteric activators of SOS1 that can increase the amount of RAS-GTP in cells. The compounds can inhibit ERK phosphorylation at higher concentrations by engaging a feedback mechanism. To further study this process, we sought different chemical matter from an NMR-based fragment screen using selective methyl labeling. To aid this process, several Ile methyl groups located in different binding sites of the protein were assigned and used to categorize the NMR hits into different classes. Hit to lead optimization using an iterative structure-based design paradigm resulted in compounds with improvements in binding affinity. These improved molecules of a different chemical class increase SOS1<sup>cat</sup>-mediated nucleotide exchange on RAS and display cellular action consistent with our prior results.
Selective and Brain‐Permeable Polo‐like Kinase‐2 (Plk‐2) Inhibitors That Reduce α‐Synuclein Phosphorylation in Rat Brain (2013)

Polo-like kinase-2 (Plk-2) has been implicated as the dominant kinase involved in the phosphorylation of α-synuclein in Lewy bodies, which are one of the hallmarks of Parkinson's disease neuropathology. Potent, selective, brain-penetrant inhibitors of Plk-2 were obtained from a structure-guided drug discovery approach driven by the first reported Plk-2-inhibitor complexes. The best of these compounds showed excellent isoform and kinome-wide selectivity, with physicochemical properties sufficient to interrogate the role of Plk-2 inhibition in vivo. One such compound significantly decreased phosphorylation of α-synuclein in rat brain upon oral administration and represents a useful probe for future studies of this therapeutic avenue toward the potential treatment of Parkinson's disease.
Ïnfïnïty (2007)

Personal mobile devices, such as cell phones and PDAs, are undergoing continual improvements in computing power, storage, and connectivity. This trend presents many opportunities for information sharing and collaboration among massively distributed data sources. However, the current mobile environment, which consists of incompatible operating systems, development models, and communication options, has hindered application development and data sharing over ad hoc networks of mobile devices. In this paper, we present a middleware framework, called Ïnfïnïty, that unifies techniques for local (and remote) device data access, automatic communication channel selection, and application deployment across heterogeneous platforms. Ïnfïnïty enables information sharing and collaboration among mobile devices in a privacy-preserving manner. We describe the prototype implementation of Ïnfïnïty and demonstrate how it eases application development and supports a wide variety of application scenarios.
Examining the information retrieval process from an inductive perspective (2010)

Term-weighting functions derived from various models of retrieval aim to model human notions of relevance more accurately. However, there is a lack of analysis of the sources of evidence from which important features of these term weighting schemes originate. In general, features pertaining to these term-weighting schemes can be collected from (1) the document, (2) the entire collection and (3) the query. In this work, we perform an empirical analysis to determine the increase in effectiveness as information from these three different sources becomes more accurate.
Optimal Source-Based Filtering of Malicious Traffic (2010)

In this paper, we consider the problem of blocking malicious traffic on the Internet, via source-based filtering. In particular, we consider filtering via access control lists (ACLs): these are already available at the routers today but are a scarce resource because they are stored in the expensive ternary content addressable memory (TCAM). Aggregation (by filtering source prefixes instead of individual IP addresses) helps reduce the number of filters, but comes also at the cost of blocking legitimate traffic originating from the filtered prefixes. We show how to optimally choose which source prefixes to filter, for a variety of realistic attack scenarios and operators' policies. In each scenario, we design optimal, yet computationally efficient, algorithms. Using logs from Dshield.org, we evaluate the algorithms and demonstrate that they bring significant benefit in practice.
The Effect of Piperine Pro-Nano Lipospheres on Direct Intestinal Phase II Metabolism: The Raloxifene Paradigm of Enhanced Oral Bioavailability (2018)

Phase II biotransformation reactions have been gaining more attention due to their acknowledged significance in drug bioavailability, drug development, and drug-drug interactions. However, the predominant role of phase I metabolism has always overshadowed phase II metabolism, resulting in insufficient data regarding its mechanisms. In this paper, we investigate the effect of an advanced lipid based formulation on the phase II metabolism process of glucuronidation, occuring in the enterocytes monolayer. The investigated formulation is a self-emulsifying drug delivery system, termed pro-nano lipospheres, which contains the natural absorption enhancer piperine. To evaluate the effect of this formulation on direct glucuronidation we chose the model molecule raloxifene. First, glucuronidation is the main clearance pathway of this compound without involvement of preceding mechanisms. Second, raloxifene's extensive glucuronidation site is primarily at the intestine. Raloxifene's oral bioavailability was determined in a series of pharmacokinetic experiments using the freely moving rat model. In order to test the effect of the formulation on the relevant UGT enzymes reported in the clinic, we used the in vitro method of UGT-Glo Assay. Coadministration of raloxifene and piperine pro-nano lipospheres to rats resulted in a 2-fold increase in the relative oral bioavailability of raloxifene. However, coadministration of raloxifene with blank pro-nano lipospheres had no effect on its oral bioavailability. In contrast to the difference found in vivo between the two vehicles, both formulations extended an inhibitory effect on UGT enzymes in vitro. Ultimately, these findings prove the ability of the formulation to diminish intestinal direct phase II metabolism which serves as an absorption obstacle for many of today's marketed drugs. Pro-nano lipospheres is a formulation that serves as a platform for the simultaneous delivery of the absorption enhancer and a required drug. The discrepancy found between the in vivo and in vitro models demonstrates that the in vitro method may not be sensitive enough to distinguish the difference between the formulations.
A New Methodology for Quantifying the Impact of Direct and Diffuse Solar Radiation on Energy Savings in Commercial Office Spaces (2015)

In this paper, we describe a new methodology for quantifying how direct and diffuse solar radiation impact total energy consumption in a standard perimeter office room by optimizing the allowed daylight penetration for achieving overall energy reduction. Our methodology is different from standard studies that focus on modification of window glazing geometrical, optical and/or thermal parameters and their impact on energy consumption. In our study, we consistently use the same window glazing geometry, and modify the weather file by varying the direct and/or diffuse components of solar radiation. This combination emulates the effect of an advanced dynamic glazing on the incoming solar radiation and is independent of the technology used. Such a glazing would regulate the proportions of direct and diffuse solar radiation to achieve overall energy reduction. In other words, our approach does not try to qualify or evaluate a particular glazing technology, but rather to generate specifications for advanced dynamic glazings that can manage the incoming radiation and hence help drive the development of such advanced dynamic glazing technology. To achieve our goal, we use EnergyPlus to simulate a 6m×3m×3m (length×width×height) office space with a 40% WWR, at all four cardinal orientations. To eliminate any effects that could arise from heat transfer from adjacent rooms — e.g., through walls — we treat those surfaces as adiabatic. In addition, since the front façade wall is the host surface of the window and thus cannot be defined as adiabatic, we intentionally set the façade wall at very high R-value, thus minimizing any thermal impact from that surface too. As a result, the only element responsible for daylight and thermal impact in the office space is the glazing. We present the results by comparing the energy requirements under various solar radiation penetrations into the office, as they are managed by the glazing. We compare the results under non-dynamic and dynamic glazing operation and offer recommendations on the optimum glazing operation for achieving year around energy savings. By investigating the interplay between managed solar radiation, via the emulated advanced dynamic glazing, and energy consumption in the room, we identify and quantify opportunities for energy savings.
Loss of Ranbp2 in motor neurons causes the disruption of nucleocytoplasmic and chemokine signaling and proteostasis of hnRNPH3 and Mmp28, and the development of amyotrophic lateral sclerosis (ALS)-like syndromes (2017)

The pathogenic drivers of sporadic and familial motor neuron disease (MND), such amyotrophic lateral sclerosis (ALS), are unknown. MND impairs the Ran GTPase cycle, which controls nucleocytoplasmic transport, ribostasis and proteostasis; however, cause-effect mechanisms of Ran GTPase modulators in motoneuron pathobiology have remained elusive. The cytosolic and peripheral nucleoporin Ranbp2 is a crucial regulator of the Ran GTPase cycle and of the proteostasis of neurological disease-prone substrates, but the roles of Ranbp2 in motoneuron biology and disease remain unknown. This study shows that conditional ablation of <i>Ranbp2</i> in mouse Thy1 motoneurons causes ALS syndromes with hypoactivity followed by hindlimb paralysis, respiratory distress and, ultimately, death. These phenotypes are accompanied by: a decline in the nerve conduction velocity, free fatty acids and phophatidylcholine of the sciatic nerve; a reduction in the g-ratios of sciatic and phrenic nerves; and hypertrophy of motoneurons. Furthermore, Ranbp2 loss disrupts the nucleocytoplasmic partitioning of the import and export nuclear receptors importin β and exportin 1, respectively, Ran GTPase and histone deacetylase 4. Whole-transcriptome, proteomic and cellular analyses uncovered that the chemokine receptor Cxcr4, its antagonizing ligands Cxcl12 and Cxcl14, and effector, latent and activated Stat3 all undergo early autocrine and proteostatic deregulation, and intracellular sequestration and aggregation as a result of Ranbp2 loss in motoneurons. These effects were accompanied by paracrine and autocrine neuroglial deregulation of hnRNPH3 proteostasis in sciatic nerve and motoneurons, respectively, and post-transcriptional downregulation of metalloproteinase 28 in the sciatic nerve. Mechanistically, our results demonstrate that Ranbp2 controls nucleocytoplasmic, chemokine and metalloproteinase 28 signaling, and proteostasis of substrates that are crucial to motoneuronal homeostasis and whose impairments by loss of Ranbp2 drive ALS-like syndromes.
Spark-based large-scale matrix inversion for big data processing (2016)

Matrix inversion is a fundamental operation to solve linear equations for many computational applications. However, it is a challenging task to invert large-scale matrices of extremely high order (several thousands), which are common in most of web-scale systems like social networks and recommendation systems. In this paper, we present a LU decomposition based block-recursive algorithm for large-scale matrix inversion, and its well-designed implementation with optimized data structure, reduction of space complexity and effective matrix multiplication on the Spark parallel computing platform. The experimental evaluation results show that the proposed algorithm is efficient to invert large-scale matrices on a cluster composed of commodity servers and scalable to invert even larger matrices. The proposed algorithm and implementation will be a solid base to build a high-performance linear algebra library on Spark for big data processing.
Maspin. A tumor suppressing serpin. (1997)

Maspin, a serpin found in mammary epithelial cells, has been shown to have tumor suppressor activity. The gene is expressed in normal human mammary epithelial cells but down-regulated in invasive breast carcinomas. Similar patterns of expression at the RNA and protein levels are seen by Northern analysis with cells grown in culture and by immunostaining of tissues. Biological assays of invasion by tumor cells through Matrigel membranes and of motility have shown that recombinant maspin inhibits both processes, and that its inhibitory action is totally lost by a single cleavage at the reaction center. Tumor transfectants expressing maspin are inhibited in growth and metastasis in nude mice. Maspin is located in the cell membrane and extracellular matrix, and does not behave as a classical inhibitory serpin against any known target protease. Its mode of action is presently unknown.
Gaussian distortion-rate function under sub-nyquist nonuniform sampling (2014)

A bound on the amount of distortion in the reconstruction of a stationary Gaussian process from its rate-limited samples is derived. The bound is based on a combined sampling and source coding problem in which a Gaussian stationary process is described from a compressed version of its values on an infinite discrete set. We show that the distortion in reconstruction cannot be lower than the distortion-rate function based on optimal uniform filter-bank sampling using a sufficient number of sampling branches. This can be seen as an extension of Landau's theorem on a necessary condition for optimal recovery of a signal from its samples, in the sense that it describes both the error as a result of sub-sampling and the error incurred due to lossy compression of the samples.
Computer-aided diagnosis of breast lesions in medical images (2000)

Given current error rates, this article surveys various approaches and techniques for improved breast lesion diagnosis in medical images, including mammography, ultrasound and magnetic resonance imaging. The author also includes studies that compare human versus computer-aided diagnosis.
Lymphosarcoma in the laboratory woodchuck (Marmota monax). (2002)

From 1979 to 1999,28 cases of lymphosarcoma were identified in the Cornell University woodchuck colony (prevalence rate: 152/100,000/yr). The prevalence of lymphosarcoma was similar in woodchucks not infected with the woodchuck hepatitis virus (WHV) and in chronic carriers of WHV. Males (13) and females (15) alike were affected (mean +/- SD age 4.7 +/- 2.92 years; range, 0.5 to 9 years). On the basis of the major organ system involved, woodchuck lymphosarcoma was classified as multicentric (12 cases, 43%), alimentary (5 cases, 18%), cranial mediastinal (5 cases, 18%), and miscellaneous (6 cases, 21%). A cutaneous form was not observed. Morphologic criteria similar to those of the Kiel classification were used for light microscopic classification. All Kiel categories-except the immunoblastic form-were found: 17 cases (61%) were centroblastic, and 6 were lymphocytic (21%). Other categories (centrocytic and plasmacytoid) were recognized less frequently. Immunophenotyping of 27 cases revealed 15 (56%) B cell (CD3-/CD79a+ or CD3-/BLA.36+), 7 (26%) T cell (CD3+/CD79a-/BLA.36-), and 5 (18%) non-T non-B cell (CD3-CD79a-/BLA.36-) lymphosarcomas. Lymphosarcoma in woodchucks develops at a higher rate than that observed in humans or companion animals, and WHV infection has no effect on prevalence. The anatomic and Kiel classification used in domestic species also can be used in woodchucks. Commercially available alpha-CD3, alpha-CD79a, and alpha-BLA.36 antibodies were useful for immunophenotyping woodchuck lymphosarcomas.
P1183EFFECT OF DECREASE IN GLUCOSE GRADIENT ON CHANGE IN INTRAPERITONEAL VOLUME USING SEGMENTAL BIOIMPEDANCE DURING PET (2020)

Abstract Background and Aims The aim of this study was to investigate relationship of glucose gradient dynamics with change in intraperitoneal volume (IPV) measured by segmental bioimpedance analysis (SBIA). Method Ten PD patients (age 59±8.8 years, 7 females, 5 Blacks, weight 69.8±12.4 kg) were studied during standard peritoneal equilibrium test (PET). Dialysate glucose concentration (D) was measured hourly throughout the PET. IPV was monitoring continuously using SBIA (Hydra 4200; Zhu et al, Kidney Blood Press Res 2019). Hourly IPV was used to calculate (1) the difference between two conservative hours (ΔIPVt = IPVt+1 - IPVt; t=0, 1, 2 and 3) and (2) the IPVt / IPV0 ratio vs. the concurrent Dt/D0. Results IPVs were successfully measured in nine patients (1 high transporter, 6 high-average, 2 low-average). Ultrafiltration volume (UFV, 0.55±0.17 L) at the end of dwell was measured by SBIA. ΔIPV1(0.26±0.17 L) was positive during the first hour of dialysate dwell in 7 patients, their corresponding ΔD1 (calculated as D1 – D0) was -902±278 mg/dL. However, 2 patients (1 high and 1 high-average transporter) showed negative ΔIPV1(-0.13±0.1 L) and a ΔD1 of -861±367 mg/dL. The relationship between IPVt/ IPV0 and Dt/D0 is shown in Fig.1 (a) – (i). The figures indicate the dynamics of IPV and glucose concentration changes in all 9 patients. Conclusion Peak IPV appears at different time points and is associated with different glucose gradients. These findings may represent specific, individual characteristics of the peritoneal membrane. Since first hour ΔIPV represents almost half of total UFV at the end of dwell, it could emerge as an important indicator of peritoneal membrane characteristics. Monitoring IPV using SBIA provides a useful tool for further investigation.
Influence of Pokémon Go on Physical Activity: Study and Implications (2016)

Physical activity helps people maintain a healthy weight and reduces the risk for several chronic diseases. Although this knowledge is widely recognized, adults and children in many countries around the world do not get recommended amounts of physical activity. While many interventions are found to be ineffective at increasing physical activity or reaching inactive populations, there have been anecdotal reports of increased physical activity due to novel mobile games that embed game play in the physical world. The most recent and salient example of such a game is Pokémon Go, which has reportedly reached tens of millions of users in the US and worldwide. We study the effect of Pokémon Go on physical activity through a combination of signals from large-scale corpora of wearable sensor data and search engine logs for 32 thousand users over a period of three months. Pokémon Go players are identified through search engine queries and activity is measured through accelerometry. We find that Pokémon Go leads to significant increases in physical activity over a period of 30 days, with particularly engaged users (i.e., those making multiple search queries for details about game usage) increasing their activity by 1473 steps a day on average, a more than 25% increase compared to their prior activity level ($p&lt;10^{-15}$). In the short time span of the study, we estimate that Pokémon Go has added a total of 144 billion steps to US physical activity. Furthermore, Pokémon Go has been able to increase physical activity across men and women of all ages, weight status, and prior activity levels showing this form of game leads to increases in physical activity with significant implications for public health. We find that Pokémon Go is able to reach low activity populations while all four leading mobile health apps studied in this work largely draw from an already very active population.
Integration of BST varactors with surface acoustic wave device by film transfer technology for tunable RF filters (2012)

This paper presents a film transfer process to integrate barium strontium titanate (BST) metal–insulator–metal (MIM) structures with surface acoustic wave (SAW) devices on a lithium niobate (LN) substrate. A high-quality BST film grown on a Si substrate above 650 °C was patterned into the MIM structures, and transferred to a LN substrate below 130 °C by Ar-plasma-activated Au–Au bonding and the Si lost wafer process. Simple test SAW devices with the transferred BST variable capacitors (VCs) were fabricated and characterized. The resonance frequency of a one-port SAW resonator with the VC connected in series changed from 999 to 1018 MHz, when a dc bias voltage of 3 V was applied to the VC. Although the observed frequency tuning range was smaller than expected due to the degradation of BST in the process, the experimental result demonstrated that a tunable SAW filter with the transferred BST VCs was feasible.
Proceedings of the NAACL HLT 2010 Young Investigators Workshop on Computational Approaches to Languages of the Americas (2010)

Welcome to the First Young Investigators Workshop on Computational Approaches to Languages of the Americas. This workshop will be held on June 6, 2010 in Los Angeles, immediately following the 11th Annual Conference of the North American Chapter of the Association for Computational Linguistics, NAACL-HLT 2010. The goal of this workshop is to bring together researchers from all of the Americas developing human language technologies that are interested in establishing international collaborations. We believe a more interactive community within the Americas can contribute to the advancement of the field, not only with respect to the improvement of performance on specific areas of NLP but more important, with respect to motivating the growth of its community by providing a conducive collaboration infrastructure that facilitates the active involvement of researchers in the field.

We are very excited about the response to the call for papers. We received a total of 21 submissions from 8 countries. The final program brings together researchers from Argentina, Brazil, Colombia, Costa Rica, Mexico, Uruguay and the USA. The contributions in the proceedings are of three types: research papers, project overviews and opinion papers. The research papers include recent advances in topics from opinion mining, to textual entailment, to adaptation of NLP approaches to software engineering. The survey papers present an overview of larger research projects by a single university or research group. These overviews present interesting efforts in dialogue systems, text simplification, language generation, and corpus based approaches to verb subcategorization and relation extraction. The proceedings also include two opinion papers that describe the research situation of the NLP communities in Costa Rica and Brazil. All contributions describe how international collaborations can push research forward by either listing the resources and/or experience sought or what specific resources and experience can be contributed. In sum, these proceedings provide a broad coverage of research on computational linguistics south of the Rio Bravo addressing three different languages: Spanish, Brazilian Portuguese and English.