gebhart/patrepeval huggingface dataset:
Computerized features of spatial interplay of tumor-infiltrating lymphocytes predict disease recurrence in p16+ oropharyngeal squamous cell carcinoma: A multisite validation study. (2020)

6559 Background: While overall, patients with p16+ oropharyngeal squamous cell carcinoma (OPSCC) have a favorable prognosis, subsets of patients experience disease recurrence (DR) and death despite aggressive multimodality treatment. Aside from routine staging criteria, there are no biomarkers of tumor behavior routinely employed in OPSCC to identify patients at higher risk of DR. In this study we sought to evaluate whether the interplay between tumor-infiltrating lymphocytes (TILs) &amp; cancer cells, in both stromal and epithelial compartments from digitized H&amp;E-stained slides, can predict DR in OPSCC patients. Methods: OPSCC resected specimens from 354 patients (66 with DR) were retrospectively collected from 3 different sites. 107 (16 DR) patients from site 1 formed the training set and 247 (50 DR) patients from sites 2 &amp; 3 formed the independent validation cohort. Computerized algorithms automatically identified 4 types of nuclei (TILs &amp; non-TILs in both stromal &amp; epithelial regions), defined clusters for each nuclei type based on cell proximity, and used network graph concepts to capture measurements relating to the arrangement of these clusters. The top 10 features determined by a statistical selection method (LASSO) were used to train a Cox regression model that assigns a risk of DR to each patient on the training set. The median risk score was used as threshold for stratifying patients on the validation set into low and high-risk of DR. Survival analysis was used to evaluate the stratification given by the trained model. Results: Patients identified by the TIL interplay model as high risk for DR had statistically worse disease specific survival. Univariate analysis yielded an HR=2.49 (95% CI: 1.22-5.07, p=0.04) for site 2 and HR=3.62 (95% CI: 1.39-9.43, p=0.03) for site 3. Multivariate analysis controlling the effect of different clinical variables is shown in the attached table. Conclusions: We introduce a prognostic model based on the automated quantification of the interplay between tumor microenvironment cells that is able to help distinguish OPSCC patients with higher DR risk from those who will experience longer disease-free survival. [Table: see text]
Reflectance-based detection for long term environmental monitoring (2017)

Here, the potential of colorimetric sensors utilizing porphyrin indicators for long term environmental monitoring is demonstrated. Prototype devices based on commercial color sensing chips (six per device) were combined with in-house developed algorithms for data analysis. The devices are intended to provide real-time sensing of threats. An initial outdoor data set was collected using prototype devices with occasional spiked exposure to targets. This data was supported by similar data collected in a controlled indoor environment. Weaknesses in the noted performance of the devices during these experiments were addressed through altering device parameters, algorithm parameters, and array element composition. Additional outdoor data sets totaling 1,616 h and indoor data sets totaling 728 h were collected in support of assessing these changes to the system configuration. The optimized system provided receiver operating characteristics (ROC) of specificity 0.97 and sensitivity 1.0.
High Glucose Variability in Hospitalized Patients with Type 1 Diabetes Mellitus (2017)

GV is high in hospitalized T1D patients admitted at our tertiary care center. Review of the literature shows paucity of data regarding GV in hospitalized patients with T1D.
Advances in immunomodulatory strategies for host-directed therapies in combating tuberculosis (2023)

Tuberculosis (TB) maintains its infamous status regarding its detrimental effect on global health, causing the highest mortality by a single infectious agent. The presence of resistance and immune compromising disease favours the disease in maintaining its footing in the health care burden despite various anti-TB drugs used to fight it. Main factors contributing to resistance and difficulty in treating disease include prolonged treatment duration (at least 6 months) and severe toxicity, which further leads to patient non-compliance, and thus a ripple effect leading to therapeutic non-efficacy. The efficacy of new regimens demonstrates that targeting host factors concomitantly with the Mycobacterium tuberculosis (M.tb) strain is urgently required. Due to the huge expenses and time required of up to 20 years for new drug research and development, drug repurposing may be the most economical, circumspective, and conveniently faster journey to embark on. Host-directed therapy (HDT) will dampen the burden of the disease by acting as an immunomodulator, allowing it to defend the body against antibiotic-resistant pathogens whilst minimizing the possibility of developing new resistance to susceptible drugs. Repurposed drugs in TB act as host-directed therapies, acclimatizing the host immune cell to the presence of TB, improving its antimicrobial activity and time taken to get rid of the disease, whilst minimizing inflammation and tissue damage. In this review, we, therefore, explore possible immunomodulatory targets, HDT immunomodulatory agents, and their ability to improve clinical outcomes whilst minimizing the risk of drug resistance, through various pathway targeting and treatment duration reduction.
Spin diffusion on a lattice: Classical simulations and spin coherent states (1995)

The results of computational studies of classical spin diffusion on a lattice are presented, and the validity of these results in the quantum regime is explored using a general theoretical framework. First, classical simulations of spin diffusion are used to identify conservation principles required for adherence to a traditional diffusion equation. The breakdown of diffusive behavior for magnetization in zero applied field is tied to nonconservation of spin angular momentum by the dipole-dipole interaction. The effects of dilution upon the spin diffusion constant are also studied for lattices of various dimensionalities. At low concentrations and low dimensionality, the results are suggestive of percolation. Next, with considerations of spin diffusion serving as a model, classical spin dynamics on a lattice are linked to quantum dynamics using the interpolating properties of spin coherent states. For systems with initial disturbances characterized by slow spatial variation, and in the limit of high temperature and large particle number, and a full quantum treatment of the spin diffusion problem is shown to reduce to the classical paradigm used in numerical simulations. The equivalence of quantum and classical behaviors under these conditions is shown to result from the cancellation of quantum interference terms in the coherent-state representations of expectation values.
MELTING MAPPING IN NANOCHANNELS (2008)

We demonstrate direct visualization of melting mapping of DNA stretched in nanoscale channels[1] using standard staining methods and epifluorescence microscopy to gain information on the local AT/GC ratio along large DNA molecules. Our development opens up a novel route to mapping of large-scale genomic variations.
Synthesis and Characterization of Potential Impurities of Canagliflozin (2017)

Abstract Multiple sources of anticipated process and degradation impurities of canagliflozin drug has been identified during its laboratory optimization and later in commercial scale manufacturing process. The structure of these impurities were confirmed by their independent synthesis as well as by their complete spectral characterization including 2D NMR, 19 F NMR, and their chromatographic retention time profile. As a part of these investigations, three new impurities such as Hydroperoxide (Impurity‐D), Sulfone (impurity‐F) and Dimer (impurity‐C) were characterized. The present work describe our detailed investigations on the structural characterization of canagliflozin impurities, and further their independent synthesis.
Measurement of the Effect of Fixed Wing on Flapping Flight (2017)

In this paper, we evaluated the effect of fixed wings of a beetle-inspired ornithopter during flapping flight. The fixed wings of the fabricated beetle-inspired ornithopter were attachable to either the leading or tailing side of the flapping wings. MEMS differential pressure sensors were attached to both fixed and flapping wings surfaces to evaluate the aerodynamic performance of the wings. We performed flight experiments with 3 types of ornithopter; fixed wings in leading side of the flapping wings, fixed wings tailing side the flapping wings, without fixed wings. The result suggested the fixed wings of the leading side enhanced lift force and stabilized pitching comparing with the other types during flapping flight.
Studies on the Bisoxazoline‐ and (−)‐Sparteine‐Mediated Enantioselective Addition of Organolithium Reagents to Imines (2008)

The enantioselective addition of organolithium reagents to N-anisyl aldimines promoted by chiral bisoxazolines and (-)-sparteine as external ligands is described. This reaction proceeds readily with a wide range of aldimine substrates (aliphatic, aromatic, olefinic) and organolithium nucleophiles (Me, n-Bu, Ph, vinyl) in excellent yields (81-99%) and with high enantioselectivities (up to 95.5:4.5 er). The external ligands can be used in substoichiometric amounts albeit with slightly attenuated enantioselectivities. A systematic evaluation of the structural features of the bisoxazolines revealed a primary contribution from the substituent at C(4) and a secondary influence from the bridging substituents. A computational analysis (PM3) provided a clear rationalization for the origin of enantioselectivity.
Continuous Soluble Ziegler‐Natta Ethylene Polymerizations in Reactor Trains, 3 – Influence of Operating Conditions upon Process Performance (2008)

Abstract The behavior of continuous solution ethylene/but‐1‐ene polymerizations through Ziegler‐Natta catalysts is analyzed, based on a previously developed mathematical model. In order to do that, dynamic simulations are carried out and process responses are analyzed as functions of process operating policies and flowsheet configuration, at conditions that resemble the actual operation of industrial sites. It is shown that system responses are highly nonlinear and very sensitive to disturbances of the operating conditions and that catalyst decay is of fundamental importance for proper understanding of process behavior. Results indicate that mixing conditions inside the reactor vessels exert a significant impact upon the final polymer quality and can be manipulated for in‐line control of final resin properties. Finally, it is shown that the development of feed policies, based on the use of lateral feed streams, allows the simultaneous control of melt flow index, stress exponent and polymer density of the final polymer resin. magnified image
Aerobic bacteria associated with chronic suppurative otitis media in Angola (2018)

The infection of the middle ear in CSOM is highly polymicrobial, and isolates found in nasopharynx do not correspond well with those found in ear discharge. Pathogens associated with CSOM in Angola are dominated by gram-negatives including Enterobacteriaceae and P. aeruginosa, while gram-positive enterococci also are common. Based on the results of antimicrobial susceptibility testing topical quinolones would be the preferred antibiotic therapy of CSOM in Angola. Topical antiseptics such as aluminium acetate, acetic acid or boric acid, however, may be more feasible options due to a possibly emerging antimicrobial resistance.
Synthesis, characterization, and biodistribution of [113mIn]TE-BAT: a new myocardial imaging agent. (1989)

In order to develop a new myocardial perfusion agent, new lipid-soluble complexes containing a net charge of +1 were evaluated. Synthesis, radiolabeling, characterization, and biodistribution of a unique indium complex, [113mIn]TE-BAT (tetraethyl-bis-aminoethanethiol), are described. The complex formation between In +3 and TE-BAT ligand is rapid, simple, and of high yield (greater than or equal to 95%). This process is amenable to kit formulation. The complex has a net charge of +1 and an In/ligand ratio of 1:1. Biodistribution in mice shows higher heart uptake and longer retention as compared to 201TI. This complex, when labeled with 111In, shows promise as a possible tracer for myocardial perfusion imaging.
Physics of Inertial Fusion: Beam Plasma Interaction, Hydrodynamics, Hot Dense Matter, Stafano Atzeni and Jürgen Meyer-ter-Vehn (2005)

Physics of Inertial Fusion: Beam Plasma Interaction, Hydrodynamics, Hot Dense Matter , Stafano Atzeni and Jürgen Meyer-ter-Vehn, Clarendon Press, 2004, 458 pages, ISBN: 0198562640 This book has several remarkable highlights summarized on laser produced plasmas and particle beam driven fusion energy. In contrast to the usual books, the nuclear fusion reactions are presented with very detailed experience, including pycnonuclear reactions, spin polarization, and mentioning the 25 orders of magnitude less probable weak force pp-reaction than DT. There is a rather comprehensive collection of the conditions of confinement, spherical implosion, ignition burn, and gain. Hydrodynamics is based on a one fluid model, not Schlüter's space charge quasi-neutral two-fluid model nor the genuine two-fluid treatment. Hohlraum targets are covered and the fast ignition (FI) contains the forte of the authors' own achievements though the entire problems shown experimentally or theoretically (Mulser et al. , 2004) are not discussed nor the new aspects on FI known before finishing the book (Hora, 2004). The 36 pages for the entire physics of (laser- and particle-) beam-target interaction are used to sketch at least the most important aspects.
Discovery of 1-Butyl-3-chloro-4-(4-phenyl-1-piperidinyl)-(1 H )-pyridone (JNJ-40411813): A Novel Positive Allosteric Modulator of the Metabotropic Glutamate 2 Receptor (2014)

We previously reported the discovery of 4-aryl-substituted pyridones with mGlu2 PAM activity starting from the HTS hit 5. In this article, we describe a different exploration from 5 that led to the discovery of a novel subseries of phenylpiperidine-substituted pyridones. The optimization strategy involved the introduction of different spacers between the pyridone core and the phenyl ring of 5. The fine tuning of metabolism and hERG followed by differentiation of advanced leads that were identified on the basis of PK profiles and in vivo potency converged on lead compound 36 (JNJ-40411813). Full in vitro and in vivo profiles indicate that 36 displayed an optimal interplay between potency, selectivity, favorable ADMET/PK and cardiovascular safety profile, and central EEG activity. Compound 36 has been investigated in the clinic for schizophrenia and anxious depression disorders.
Hardware obfuscation for IP protection (2020)

The horizontal business model adopted by the semiconductor industry has resulted in a manufacturing process that has integrated various foreign entities focusing on individual production steps. However, serious trust issues have emerged with the internationalization of the semiconductor supply chain, and the trust concerns grow further with the proliferation of theft, reverse engineering (RE), and piracy of hardware intellectual property (IP). Unlike the software industry, the semiconductor supply chain cannot benefit from traditional cryptographic solutions due to the requirement of white-box accessibility to the hardware IP. Therefore, hardware obfuscation has originated as a potential countermeasure against dreaded supply chain attacks. The obfuscation process aims to hide the design intent and lock functionality by introducing structural and functional transformations to the IP, which increases the resistance against unauthorized use and potential exploitation of the design by an adversary. In this chapter, we investigate hardware obfuscation techniques that have been developed in the past decade and the limitations and challenges of these techniques. In particular, we explore the evolution of different techniques that are applicable at various supply chain stages of the semiconductor life cycle, the development of obfuscation benchmarks, and the research trends in the area of obfuscation. We also expand on the innovative attacks that have been developed to compromise the obfuscation techniques, as well as the countermeasures that are introduced to combat them. This chapter also sheds light on the lessons learned from the decade-long research on obfuscation by discussing the attack trends and unsolved challenges. Finally, we conclude by presenting a road map that aims to improve the existing solutions and provides improved security metrics for systematic evaluation.
Aggregated Bloom Filters for Intrusion Detection and Prevention Hardware (2007)

Bloom Filters (BFs) are fundamental building blocks in various network security applications, where packets from high-speed links are processed using state-of-the-art hardware- based systems. In this paper, we propose Aggregated Bloom Filters (ABFs) to increase the throughput and scalability of BFs. The proposed ABF has two methods to improve average speed and scalability. The first method leverages the query mechanism for hardware BFs. We optimize queries by removing redundant hash calculations and memory accesses. First, to remove redundancy, the hash functions for each query are calculated sequentially. As soon as we have a no match in any of the hash results, the query is immediately abandoned. We then aggregate multiple queries and query a BF with all of these queries in parallel, which maximizes the throughput of the BF. The second method addresses scalability issues regarding the on-chip memory resources. In most applications multiple BFs are required to store many sets with different numbers of elements. These sets may also be too small for the unit memory on-chip. So, most of the memory is left unused, causing low memory utilization. The second method aggregates small distributed BFs to a single BF allowing better on-chip memory utilization. For the application of Network Intrusion Detection and Prevention Systems (NIDPSs), our proposed ABF shows seven-fold improvement in the average query throughput and four times less memory usage.
UBL3 modification influences protein sorting to small extracellular vesicles (2018)

Exosomes, a type of small extracellular vesicles (sEVs), derived from multivesicular bodies (MVBs), mediate cell-to-cell communication by transporting proteins, mRNAs, and miRNAs. However, the molecular mechanism by which proteins are sorted to sEVs is not fully understood. Here, we report that ubiquitin-like 3 (UBL3)/membrane-anchored Ub-fold protein (MUB) acts as a posttranslational modification (PTM) factor that regulates protein sorting to sEVs. We find that UBL3 modification is indispensable for sorting of UBL3 to MVBs and sEVs. We also observe a 60% reduction of total protein levels in sEVs purified from Ubl3-knockout mice compared with those from wild-type mice. By performing proteomics analysis, we find 1241 UBL3-interacting proteins, including Ras. We also show that UBL3 directly modifies Ras and oncogenic RasG12V mutant, and that UBL3 expression enhances sorting of RasG12V to sEVs via UBL3 modification. Collectively, these results indicate that PTM by UBL3 influences the sorting of proteins to sEVs.
Scalable segmentation-based malicious circuitry detection and diagnosis (2010)

Hardware Trojans (HTs) pose a significant threat to the modern and pending integrated circuit (IC). Several approaches have been proposed to detect HTs, but they are either incapable of detecting HTs under the presence of process variation (PV) or unable to handle very large circuits in the modern IC industry. We develop a scalable HT detection and diagnosis scheme by using segmentation techniques and gate level characterization (GLC). In order to address the scalability issue, we propose a segmentation method which divides the large circuit into small sub-circuits by using input vector control. We propose a segment selection model in terms of properties of segments and their effects on GLC accuracy. The model parameters are calibrated by sampled data from the GLC process. Based on the selected segments we are able to detect and diagnose HTs correctly by tracing gate level leakage power. We evaluate our approach on several ISCAS85/ISCAS89/ITC99 benchmarks. The simulation results show that our approach is capable of detecting and diagnosing HTs accurately on large circuits.
A Smart Metal–Organic Framework Nanomaterial for Lung Targeting (2017)

Abstract Despite high morbidity and mortality associated with lung diseases, addressing drugs towards lung tissue remains a pending task. Particle lung filtration has been proposed for passive lung targeting and drug delivery. However, toxicity issues derived from the long‐term presence of the particles must be overcome. By exploiting some of the ignored properties of nanosized metal–organic frameworks it is possible to achieve impressive antitumoral effects on experimental lung tumors, even without the need to engineer the surface of the material. In fact, it was discovered that, based on unique pH‐responsiveness and reversible aggregation behaviors, nanoMOF was capable of targeting lung tissue. At the neutral pH of the blood, the nanoMOFs form aggregates with the adequate size to be retained in lung capillaries. Within 24 h they then disaggregate and release their drug payload. This phenomenon was compatible with lung tissue physiology.
Interim Results of a Phase 2 Clinical Study of Nusinersen (ISIS-SMNRx) in Patients with Infantile-Onset Spinal Muscular Atrophy (P5.004) (2016)

Objective:To assess the safety, tolerability, pharmacokinetics and clinical effects of nusinersen (ISIS-SMNRx) in patients with infantile-onset Spinal Muscular Atrophy (SMA). Background:Infantile-onset SMA is a devastating and relentlessly progressive neurodegenerative disease caused by the deficiency of Survival of Motor Neuron (SMN) protein in motor neurons, accounts for over half of all patients with SMA, and is the most common genetic cause of death in infancy. Nusinersen is a novel antisense oligonucleotide drug designed to alter splicing of SMN2 mRNA thereby increasing the amount of functional SMN protein. Methods:This is an interim analysis of an ongoing multicenter, open-label, Phase 2 clinical study designed to evaluate the safety/tolerability, pharmacokinetics, and clinical effects of multiple intrathecal doses of nusinersen in patients with infantile-onset SMA. Twenty participants (4 in a lower-dose cohort, 16 in a higher-dose cohort) were enrolled. Autopsy tissue in 3 participants enabled pharmacodynamic analyses. Results:As of an interim analysis performed in August 2015, the study has been ongoing for 27 months. Nusinersen has been well tolerated with no safety concerns identified. Sixteen of 19 participants in the evaluable population remain alive (median age 20.1 months) and demonstrate significant (p=0.01) improvements in motor function scores, incremental achievement of motor milestones such as head control (10 participants), rolling (9 participants), sitting (6 participants), and improvements in neuromuscular electrophysiology compared to baseline and published natural history data. Pharmacodynamic data support drug delivery, enhancement of full-length SMN2 transcript, and an increase in SMN protein in target neurons. Conclusions:In this open-label Phase 2 study, nusinersen exhibits good safety and tolerability, pharmacology that is consistent with its intended mechanism of action, and encouraging evidence supporting meaningful clinical response. Importantly, a pivotal, sham-controlled Phase 3 clinical study of nusinersen in infantile-onset SMA is currently ongoing.