gebhart/patrepeval huggingface dataset:
Inhibitors of Intracellular Gram-Positive Bacterial Growth Synthesized via Povarov–Doebner Reactions (2019)

<i>Staphylococcus aureus</i> can survive both inside and outside of phagocytic and nonphagocytic host cells. Once in the intracellular milieu, most antibiotics have reduced ability to kill <i>S. aureus</i>, thus resulting in relapse of infection. Consequently, there is a need for antibacterial agents that can accumulate to lethal concentrations within host cells to clear intracellular infections. We have identified tetrahydrobenzo[<i>a</i> or <i>c</i>]phenanthridine and tetrahydrobenzo[<i>a</i> or <i>c</i>]acridine compounds, synthesized via a one-flask Povarov-Doebner operation from readily available amines, aldehydes, and cyclic ketones, as potent agents against drug-resistant <i>S. aureus</i>. Importantly, the tetrahydrobenzo[<i>a</i> or <i>c</i>]phenanthridine and tetrahydrobenzo[<i>a</i> or <i>c</i>]acridine compounds can accumulate in macrophage cells and reduce the burden of intracellular MRSA better than the drug of choice, vancomycin. We observed that MRSA could not develop resistance (by passage 30) against tetrahydrobenzo[<i>a</i> or <i>c</i>]acridine compound <b>15</b>. Moreover, tetrahydrobenzo[<i>c</i>]acridine compound <b>15</b> and tetrahydrobenzo[<i>c</i>]phenanthridine compound <b>16</b> were nontoxic to red blood cells and were nonmutagenic. Preliminary data indicated that compound <b>16</b> reduced bacterial load (MRSA USA300) in mice (thigh infection model) to the same degree as vancomycin. These observations suggest that compounds <b>15</b> and <b>16</b> and analogues thereof could become therapeutic agents for the treatment of chronic MRSA infections.
Small Molecules That Modulate Quorum Sensing and Control Virulence inPseudomonas aeruginosa (2010)

Bacteria use small molecule signals to access their local population densities in a process called quorum sensing (QS). Once a threshold signal concentration is reached, and therefore a certain number of bacteria have assembled, bacteria use QS to change gene expression levels and initiate behaviors that benefit the group. These group processes play central roles in both bacterial virulence and symbiosis and can have significant impacts on human health, agriculture, and the environment. The dependence of QS on small molecule signals has inspired organic chemists to design non-native molecules that can intercept these signals and thereby perturb bacterial group behaviors. The opportunistic pathogen Pseudomonas aeruginosa has been the target of many of these efforts due to its prevalence in human infections. P. aeruginosa uses at least two N-acyl l-homoserine lactone signals and three homologous LuxR-type receptors to initiate a range of pathogenic behaviors at high cell densities, including biofilm formation and the production of an arsenal of virulence factors. This perspective highlights recent chemical efforts to modulate LuxR-type receptor activity in P. aeruginosa and offers insight into the development of receptor-specific ligands as potential antivirulence strategies.
Patterning of sub-50 nm dense features with space-invariant 157 nm interference lithography (2000)

We have implemented a space-invariant interference lithography tool for 157 nm F2 lasers, capable of creating dense line and space patterns with a spatial period of 91 nm. No gratings or curved optics are required, allowing a simple and inexpensive tool for resist and process development at 157 nm. Initial patterning of several commercial and experimental resists has resulted in high contrast features with little line edge roughness and good cross-sectional profiles, indicating that the fundamental performance of acid-catalyzed resists patterned at 157 nm may meet lithography requirements for sub-50 nm features.
15N and 13C NMR spectroscopy of 1,2,6‐thiadiazine 1,1‐dioxide derivatives and fused systems (1986)

Abstract The natural abundance 15 N NMR spectra of sulphamide, sixteen 1,2,6‐thiadiazine and two 1,2,4,6‐thiatriazine derivatives, phenylbutazone and antipyrine have been recorded for the first time. The influence of substituents on nitrogen chemical shifts and the effect of intercalation of SO 2 and CO groups between two nitrogen atoms are discussed. Prototropic tautomerism was also studied. 13 C NMR data for some of the 1,2,6‐thiadiazine and thiatriazine derivatives are reported.
Production of crosslinked gelatin beads in inverse suspension processes (2018)

Gelatin is a natural protein of low cost and high availability that can be regarded as a promising material for manufacture of microcapsules intended for applications in the medical, pharmaceutical, and food industries. For this reason, in the present work gelatin beads were produced in inverse suspension processes at distinct operation conditions, using glucose as a non‐toxic crosslinking agent. Particularly, the effects of reaction time and crosslinking agent on the final properties of the produced gelatin beads were analyzed. The obtained results showed that the properties of the suspended beads, including the particle size distribution, the viscosity and the thermal resistance, can change considerably during the reaction course, being also affected by the crosslinking agent and indicating that crosslinking takes place at slow rates during the entire reaction trajectory. POLYM. ENG. SCI., 59:519–525, 2019. © 2018 Society of Plastics Engineers
Is FLT3 Internal Tandem Duplication an Unfavorable Risk Factor for High Risk Children with Acute Myeloid Leukemia? - Polish Experience (2013)

According to the AML-BFM 2004 Interim, a treatment protocol used in Poland since 2005, presence of FLT3 internal tandem duplication (FLT3/ITD) qualifies a patient with acute myeloid leukemia (AML) to a high-risk group (HRG). The present study was aimed to identify the prevalence of FLT3/ITD in children with AML in Poland and to evaluate its prognostic significance in the HRG patients. Out of 291 children with de novo AML treated in 14 Polish centers between January 2006 and December 2012, samples from 174 patients were available for FLT3/ITD analysis. Among study patients 108 children (61.7%) were qualified to HRG. Genomic DNA samples from bone marrow were tested for identification of FLT3/ITD mutation by PCR amplification of exon 14 and 15 of FLT3 gene. Clinical features and treatment outcome in patients with and without FLT3/ITD were analyzed in the study. The FLT3/ITD was found in 14 (12.9%) of 108 HRG children. There were no significant differences between children with and without FLT3/ITD in age and FAB distribution. The white blood cells count in peripheral blood at diagnosis was significantly higher (p &lt;0.01) in the children with FLT3/ITD. Over 5-year overall survival rate for FLT3/ITD positive children was worse (42.4%) comparing to FLT3/ITD negative children (58.9%), but the statistical difference was not significant. However, over 5-year survivals free from treatment failures were similar. The FLT3/ITD rate (12.9%) observed in the study corresponded to the published data. There was no significant impact of FLT3/ITD mutation on survival rates, although further studies are needed on this subject.
Supplementary Materials, Figures 1-7, Table 1 from Novel Designs of Multivalent Anti-CD20 Humanized Antibodies as Improved Lymphoma Therapeutics (2023)

Supplementary Materials, Figures 1-7, Table 1 from Novel Designs of Multivalent Anti-CD20 Humanized Antibodies as Improved Lymphoma Therapeutics
Scalable Dry Processing of Binder-Free Lithium-Ion Battery Electrodes Enabled by Holey Graphene (2019)

To address the multitude of issues that accompany wet electrode fabrication techniques, composite lithium-ion battery (LIB) electrodes composed of solely active components (active battery material and conductive additive) are fabricated using a scalable and eco-friendly dry processing method known as dry pressing. To accomplish this, a nanoporous carbon allotrope (i.e., holey graphene or hG) acts as the compressible and conductive matrix to accommodate incompressible cathode and anode battery powders. The inherent nanoporosity facilitates the escape of trapped gases upon compression, enabling the successful formation of binderless and solventless composite electrodes independent of selected active battery powder, fabrication pressure, or pressing time. Dry pressed LIB electrodes fabricated with different processing parameters (e.g., hydraulic pressure, pressing time) are evaluated structurally and electrochemically using a model cathode material (lithium iron phosphate, LFP) in order to demonstrate the potential of dry pressing as a viable LIB electrode manufacturing method.
Optimizing the Cloud Data Center Availability Empowered by Surrogate Models (2020)

Making data centers highly available remains a challenge that must be considered since the design phase. The problem is selecting the right strategies and components for achieving this goal given a limited investment. Furthermore, data center designers currently lack reliable specialized tools to accomplish this task. In this paper, we disclose a formal method that chooses the components and strategies that optimize the availability of a data center while considering a given budget as a constraint. For that, we make use of stochastic models to represent a cloud data center infrastructure based on the TIA-942 standard. In order to improve the computational cost incurred to solve this optimization problem, we employ surrogate models to handle the complexity of the stochastic models. In this work, we use a Gaussian process to produce a surrogate model for a cloud data center infrastructure and we use three derivative-free optimization algorithms to explore the search space and to find optimal solutions. From the results, we observe that the Differential Evolution (DE) algorithm outperforms the other tested algorithms, since it achieves higher availability with a fair usage of the budget.
The immune microenvironment shapes transcriptional and genetic heterogeneity in chronic lymphocytic leukemia (2022)

In chronic lymphocytic leukemia (CLL), B-cell receptor signaling, tumor-microenvironment interactions, and somatic mutations drive disease progression. To better understand the intersection between the microenvironment and molecular events in CLL pathogenesis, we integrated bulk transcriptome profiling of paired peripheral blood (PB) and lymph node (LN) samples from 34 patients. Oncogenic processes were upregulated in LN compared with PB and in immunoglobulin heavy-chain variable (IGHV) region unmutated compared with mutated cases. Single-cell RNA sequencing (scRNA-seq) distinguished 3 major cell states: quiescent, activated, and proliferating. The activated subpopulation comprised only 2.2% to 4.3% of the total tumor bulk in LN samples. RNA velocity analysis found that CLL cell fate in LN is unidirectional, starts in the proliferating state, transitions to the activated state, and ends in the quiescent state. A 10-gene signature derived from activated tumor cells was associated with inferior treatment-free survival (TFS) and positively correlated with the proportion of activated CD4+ memory T cells and M2 macrophages in LN. Whole exome sequencing (WES) of paired PB and LN samples showed subclonal expansion in LN in approximately half of the patients. Since mouse models have implicated activation-induced cytidine deaminase in mutagenesis, we compared AICDA expression between cases with and without clonal evolution but did not find a difference. In contrast, the presence of a T-cell inflamed microenvironment in LN was associated with clonal stability. In summary, a distinct minor tumor subpopulation underlies CLL pathogenesis and drives the clinical outcome. Clonal trajectories are shaped by the LN milieu, where T-cell immunity may contribute to suppressing clonal outgrowth. The clinical study is registered at clinicaltrials.gov as NCT00923507.
Adaptive small-animal SPECT/CT (2008)

We are exploring the concept of adaptive multimodality imaging, a form of non-linear optimization where the imaging configuration is automatically adjusted in response to the object. Preliminary studies suggest that substantial improvement in objective, task-based measures of image quality can result. We describe here our work to add motorized adjustment capabilities and a matching CT to our existing FastSPECT II system to form an adaptive small-animal SPECT/CT.
Abstract 2698: In vivo imaging of human pancreatic tumor and melanoma models in NOD/SCID mice: Preclinical evaluation of metastases and inhibition by anti-DLL4 treatment (2011)

Abstract Pre-existing metastases at the time of diagnosis are often the cause of death in patients suffering from a number of malignancies, including pancreatic cancer and melanoma. Successful development of effective anti-metastatic cancer therapies requires preclinical metastasis models that mimic the clinical condition of human cancer, sensitive methods of metastasis detection in mice bearing orthotopic tumors, and real-time evaluation of anti-metastatic activity of novel treatments. We have developed orthotopic tumor models in NOD/SCID mice utilizing pancreatic and melanoma tumor cells that are derived directly from human cancer patient specimens. These tumors retain much of the original human cancer heterogeneity, phenotype, and the ability to form metastases in the lungs, liver, intestines, and brain _ recapitulating the metastatic invasiveness seen in the clinic. Since the ability of optical imaging methods to detect tumors and metastases in deep tissues is limited by tumor size and light penetration depth, we employed Zymera's Bioluminescence Resonance Energy Transfer-Quantum Dot (BRET-Qdot®) nanoprobes conjugated with streptavidin ([BRET-Qdot]-SA) to improve sensitivity for detection of both early stage primary tumors and small metastases. The cell surface proteins, MCAM in melanoma and EpCAM in pancreatic tumors, were targeted with human specific biotinylated anti-MCAM or -EpCAM antibodies, (respectively) delivered intravenously or intraperitoneally into NOD/SCID mice and detected with the [BRET-Qdot®]-SA nanoprobe. Light emission from the tumor-bound [BRET-Qdot®]-SA was activated by the catalytic conversion of the luciferase substrate coelenterazine. The novel and highly sensitive BRET-Qdot® technology emits 655 nm bioluminescence light for in vivo imaging of deep tissues. This technology allowed the growth of primary tumors and metastases to be measured overtime in the same mice. Moreover, in efficacy studies we have treated the mice with antibodies developed against the human and the murine DLL4 to target both tumor cells and vasculature that cooperate for the formation and growth of primary tumor and metastases. Treatment with anti-DLL4 inhibits metastases in the lungs, liver, intestine and brain. Finally, we have developed a more clinically relevant melanoma metastasis model consisting of the surgical excision of the primary tumor. This model, characterized by an enrichment of aggressive growth of metastases in the lungs, has been also utilized to evaluate the inhibitory activity of anti-DLL4 antibodies. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2698. doi:10.1158/1538-7445.AM2011-2698
Jinn (2010)

Programming language specifications mandate static and dynamic analyses to preclude syntactic and semantic errors. Although individual languages are usually well-specified, composing languages is not, and this poor specification is a source of many errors in multilingual programs. For example, virtually all Java programs compose Java and C using the Java Native Interface (JNI). Since JNI is informally specified, developers have difficulty using it correctly, and current Java compilers and virtual machines (VMs) inconsistently check only a subset of JNI constraints. This paper's most significant contribution is to show how to synthesize dynamic analyses from state machines to detect foreign function interface (FFI) violations. We identify three classes of FFI constraints encoded by eleven state machines that capture thousands of JNI and Python/C FFI rules. We use a mapping function to specify which state machines, transitions, and program entities (threads, objects, references) to check at each FFI call and return. From this function, we synthesize a context-specific dynamic analysis to find FFI bugs. We build bug detection tools for JNI and Python/C using this approach. For JNI, we dynamically and transparently interpose the analysis on Java and C language transitions through the JVM tools interface. The resulting tool, called Jinn, is compiler and virtual machine independent . It detects and diagnoses a wide variety of FFI bugs that other tools miss. This approach greatly reduces the annotation burden by exploiting common FFI constraints: whereas the generated Jinn code is 22,000+ lines, we wrote only 1,400 lines of state machine and mapping code. Overall, this paper lays the foundation for a more principled approach to developing correct multilingual software and a more concise and automated approach to FFI specification.
Hidroclorinación regioselectiva, estereoselectiva y catalítica de alquinos (2018)

La presente invención describe un procedimiento de obtención de cloruros de vinilo que puede comprender, al menos, las siguientes etapas: - Una primera etapa en la que, al menos, un alquino seleccionado entre acetileno, un derivado del acetileno y combinaciones de los mismos, y cloruro de hidrógeno se pone en contacto con un catalizador que contiene, al menos, nanopartículas de oro en presencia de un aditivo polar no prótico. - Una segunda etapa de calentamiento de la mezcla obtenida. - Una tercera etapa de recuperación del producto
Selective vulnerability in Alzheimer's disease: Amyloid precursor protein and p75NTR interaction (2009)

These results provide new insight into the emerging signaling network that mediates the Alzheimer's phenotype and into the mechanism of basal forebrain cholinergic neuronal selective vulnerability. In addition, the results argue that the interaction between APP and p75(NTR) may represent a therapeutic target in Alzheimer's disease.
Reinforced Imitation in Heterogeneous Action Space (2019)

Imitation learning is an effective alternative approach to learn a policy when the reward function is sparse. In this paper, we consider a challenging setting where an agent and an expert use different actions from each other. We assume that the agent has access to a sparse reward function and state-only expert observations. We propose a method which gradually balances between the imitation learning cost and the reinforcement learning objective. In addition, this method adapts the agent's policy based on either mimicking expert behavior or maximizing sparse reward. We show, through navigation scenarios, that (i) an agent is able to efficiently leverage sparse rewards to outperform standard state-only imitation learning, (ii) it can learn a policy even when its actions are different from the expert, and (iii) the performance of the agent is not bounded by that of the expert, due to the optimized usage of sparse rewards.
A memristor-based nonvolatile latch circuit (2010)

Memristive devices, which exhibit a dynamical conductance state that depends on the excitation history, can be used as nonvolatile memory elements by storing information as different conductance states. We describe the implementation of a nonvolatile synchronous flip-flop circuit that uses a nanoscale memristive device as the nonvolatile memory element. Controlled testing of the circuit demonstrated successful state storage and restoration, with an error rate of 0.1%, during 1000 power loss events. These results indicate that integration of digital logic devices and memristors could open the way for nonvolatile computation with applications in small platforms that rely on intermittent power sources. This demonstrated feasibility of tight integration of memristors with CMOS (complementary metal-oxide-semiconductor) circuitry challenges the traditional memory hierarchy, in which nonvolatile memory is only available as a large, slow, monolithic block at the bottom of the hierarchy. In contrast, the nonvolatile, memristor-based memory cell can be fast, fine-grained and small, and is compatible with conventional CMOS electronics. This threatens to upset the traditional memory hierarchy, and may open up new architectural possibilities beyond it.
Precision Cutting of Nanotubes with a Low-Energy Electron Beam (2005)

sReceived 16 September 2004; accepted 2 December 2004; published online 25 January 2005d We report on a method to locally remove material from carbon and boron nitride nanotubes using the low-energy focused electron beam of a scanning electron microscope. Using this method, clean precise cuts can be made into nanotubes, either part-way through screating hingelike geometriesd or fully through screating size-selected nanotube segmentsd. This cutting mechanism involves foreign molecular species and differs from electron-beam-induced knock-on damage in transmission electron microscopy. © 2005 American Institute of Physics. fDOI: 10.1063/1.1857081g
Plasmonische Synthese von metallischen Nanostrukturen (2013)

Abstract Edelmetall‐Nanostrukturen können in gewünschter Zusammensetzung, Größe und Form und mit ebenso maßgeschneiderten Eigenschaften hergestellt werden. Ihre Anwendungsmöglichkeiten sind äußerst vielfältig und reichen von der Medizin bis zur Elektronik. Besonders interessant ist die Möglichkeit, für ihre Synthese Licht zu verwenden. Im Prinzip kann man mit einer Anregungswellenlänge, die von den Nanostrukturen absorbiert wird, das Wachstum der Partikel gezielt steuern und z. B. aus einer heterogenen Ausgangspopulation eine homogene Endpopulation von Nanopartikeln gewinnen. Das beste Beispiel dafür ist die Synthese von Metall‐Nanopartikeln durch chemische Reduktion von Ag + durch Citrat unter Anregung von Oberflächenplasmonen durch Licht. Als erstes wurde entdeckt, dass sich mithilfe von sichtbarem Licht sphärische Ag‐Nanopartikel in trigonale Ag‐Prismen umwandeln lassen. Diese plasmonische Synthese wurde dann zu einer leistungsfähigen Technik weiterentwickelt, um Ag‐Partikel sowie zahlreiche dimetallische Au‐Ag‐Nanostrukturen mit definierten Morphologien herzustellen. Wir erörtern, welche physikalischen und chemischen Faktoren für die strukturelle Selektion ausschlaggebend sind. Aus den Studien zu den plasmonischen Reaktionen folgern wir dann, welche Überlegungen für das Design der Partikelform wichtig sind. Diese Grundlagen lassen sich auf alle Synthesemethoden für Edelmetall‐Nanokristalle übertragen.
Commercial RFV kiln drying : recent successes (2000)

Radio frequency (RF) heating is a commercial operation that has found many applications over the last fifty years in various industrial production units, and in many cases has replaced the less efficient and economic conventional methods. One of these operations is the drying of materials that contain large quantities of water, such as agricultural grains, ceramics, foodstuffs, textiles, paper products and wood.