gebhart/patrepeval huggingface dataset:
A heuristic platform for clinical interpretation of cancer genome sequencing data. (2012)

10502 Background: The ability to identify and effectively sort the full spectrum of biologically and therapeutically relevant genetic alterations identified by massively parallel sequencing may improve cancer care. A major challenge involves rapid and rational categorization of data-intensive output, including somatic mutations, insertions/deletions, copy number alterations, and rearrangements into ranked categories for clinician review. Methods: A database of clinically actionable alterations was created, consisting of over 100 annotated genes known to undergo somatic genomic alterations in cancer that may impact clinical decision-making. A heuristic algorithm was developed, which selectively identifies somatic alterations based on the clinically actionable alterations database. Remaining variants are sorted based on additional heuristics, including high priority alterations based on presence in the Cancer Gene Census, biologically significant cancer genes based on presence in COSMIC or MSigDB, and low priority alterations in the same gene family as biologically significant cancer genes. The heuristic algorithm was applied to whole exome sequencing data of clinical samples and whole genome sequencing data from a cohort of prostate cancer samples processed using established Broad Institute pipelines. Results: Application of the heuristic algorithm to the prostate cancer whole genome rearrangement data identified 172 (out of 5978) rearrangements involving actionable genes (averaging 2-3 events per tumor). Furthermore, two clinical samples processed prospectively were analyzed, yielding three potentially actionable alterations for clinical review. Conclusions: The heuristic model for clinical interpretation of next generation sequencing data may facilitate rapid analysis of tumor genomic information for clinician review by identifying and prioritizing alterations that can directly impact care. Our platform can also be applied to research data to prospectively explore clinically relevant findings from existing cohorts. Future analytical approaches using heuristic or probabilistic algorithms should underpin a robust prospective assessment of clinical cancer genome data.
Using machine learning techniques to enhance the performance of an automatic backup and recovery system (2010)

A typical disaster recovery system will have mirrored storage at a site that is geographically separate from the main operational site. In many cases, communication between the local site and the backup repository site is performed over a network which is inherently slow, such as a WAN, or is highly strained, for example due to a whole-site disaster recovery operation.The goal of this work is to alleviate the performance impact of the network in such a scenario, and to do so using machine learning techniques. We focus on two main areas, prefetching and read-ahead size determination. In both cases we significantly improve the performance of the system.Our main contributions are as follows: We introduce a theoretical model of the system and the problem we are trying to solve and bound the gain from prefetching techniques. We construct two frequent pattern mining algorithms and use them for prefetching. A framework for controlling and combining multiple prefetch algorithms is presented as well. These algorithms, as well as various simple prefetch algorithms, are compared on a simulation environment. We introduce a novel algorithm for determining the amount of read ahead on such a system that is based on intuition from online competitive analysis and on regression techniques. The significant positive impact of this algorithm is demonstrated on IBM's FastBack system.Much of our improvements have been applied with little or no modification of the current implementation's internals. We therefore feel confident in stating that the techniques are general and are likely to have applications elsewhere.
Identification of Common CD8+T Cell Epitopes from Lassa Fever Survivors in Nigeria and Sierra Leone (2020)

Early and robust T cell responses have been associated with survival from Lassa fever (LF), but the Lassa virus-specific memory responses have not been well characterized. Regions within the virus surface glycoprotein (GPC) and nucleoprotein (NP) are the main targets of the Lassa virus-specific T cell responses, but, to date, only a few T cell epitopes within these proteins have been identified. We identified GPC and NP regions containing T cell epitopes and HLA haplotypes from LF survivors and used predictive HLA-binding algorithms to identify putative epitopes, which were then experimentally tested using autologous survivor samples. We identified 12 CD8-positive (CD8<sup>+</sup>) T cell epitopes, including epitopes common to both Nigerian and Sierra Leonean survivors. These data should be useful for the identification of dominant Lassa virus-specific T cell responses in Lassa fever survivors and vaccinated individuals as well as for designing vaccines that elicit cell-mediated immunity.<b>IMPORTANCE</b> The high morbidity and mortality associated with clinical cases of Lassa fever, together with the lack of licensed vaccines and limited and partially effective interventions, make Lassa virus (LASV) an important health concern in its regions of endemicity in West Africa. Previous infection with LASV protects from disease after subsequent exposure, providing a framework for designing vaccines to elicit similar protective immunity. Multiple major lineages of LASV circulate in West Africa, and therefore, ideal vaccine candidates should elicit immunity to all lineages. We therefore sought to identify common T cell epitopes between Lassa fever survivors from Sierra Leone and Nigeria, where distinct lineages circulate. We identified three such epitopes derived from highly conserved regions within LASV proteins. In this process, we also identified nine other T cell epitopes. These data should help in the design of an effective pan-LASV vaccine.
A protocol to replace dedication to either normal phase or polar organic mode for chiral stationary phases containing amylose tris(3,5-dimethylphenylcarbamate) (2022)

Alteration of the enantiorecognition ability of polysaccharide-based chiral columns in the shipping normal phase (NP) eluent after exposition to polar organic (PO) mode eluents can be conceived as an incomplete hysteresis cycle. Non-standard solvents provide a solution to overcome this issue with immobilized stationary phases, but a procedure was missing so far to regenerate coated stationary phases from the altered state. Recent results with alcohol mixtures within the PO mode showed that an appropriate order of standard solvents may also be suitable to complete hysteresis. Using an analogous approach, a simple protocol was established to regenerate the original NP retentions on various stationary phases containing amylose tris(3,5-dimethylphenylcarbamate) (ADMPC) chiral selector after the change induced by flushing with 2-propanol or ethanol. The members of a chemically diverse compound set indicated that alterations in retentions and selectivities using different brands and types of ADMPC-based stationary phases can be quite different, but the recovery of the original state was very good for all of them. The proposed protocol eliminates the need of the costly dedication of a chiral column with ADMPC selector to either NP or PO mode. Furthermore, the limits of the alcohol content in the mobile phase compositions where the system is free of hysteresis were determined.
Organocatalytic asymmetric transfer hydrogenation of imines (2011)

The asymmetric organocatalytic transfer hydrogenation of imines can be accomplished in good yields with high enantioselectivities through the use of BINOL-derived phosphoric acids as catalysts and Hantzsch esters or benzothiazoles as the hydride source. The same method can also be applied to the enantioselective reduction of benzo-fused heterocycles, such as quinolines, benzoxazines, benzothiazines, benzoxazinones, quinoxalines, quinoxalinones and a limited number of pyridines containing electron-withdrawing groups. Cascade reactions involving multiple reductions and rearrangements have been reported as well as combinations of metal-catalysed reactions, such as gold-catalyzed hydroaminations of alkynes combined with the reduction of the ensuing enamine. Although turnover frequencies of the organocatalytic imine hydrogenations are still lower than those of metal-catalyzed hydrogenations, there are several advantages. Mild and environmentally friendly conditions as well as excellent selectivity make this method a valuable approach to enantiopure amine building blocks.
Biochemical and immunologic characterization of a major surface antigen of Dirofilaria immitis infective larvae. (1986)

A 35 kD major surface antigen of Dirofilaria immitis third-stage larvae was characterized biochemically and immunologically. Living larvae were iodinated by using Iodo-gen, iodosulfanilic acid, lactoperoxidase-glucose oxidase, and Bolton-Hunter reagents. Detergent extracts of larvae labeled by the first three methods showed one major 35 kD component and a number of smaller components of about 6 kD, as analyzed by one-dimensional SDS-PAGE. In contrast, extracts from larvae labeled with the Bolton-Hunter reagent showed multiple bands on gels. The 35kD molecule was shown to be exposed on the larval surface, insofar as it was accessible to trypsin-proteolysis on living radiolabeled larvae. Two-dimensional gel electrophoresis resolved the 35 kD band into two components: a major one with a pI of 3.8, and a minor one of pI 7.3. The lower m.w. bands were resolved into about 12 constituents with pI values from 3.5 to 8.0. Of all these surface molecules, the only one that was antigenic was the 35 kD component. It could be immunoprecipitated with sera from dogs carrying an occult experimental D. immitis infection or with sera from dogs immunized with irradiated third-stage larvae of this parasite. Similarly, sera from rabbits immunized repeatedly with normal unirradiated larvae also precipitated the 35 kD antigen. None of these sera, however, contained detectable antibodies to the surface-labeled low m.w. molecules. Sera from rabbits immunized with D. immitis adult worms and microfilariae precipitated the 35 kD antigen, which is therefore not stage specific. In contrast, sera from dogs experimentally infected with Toxocara canis and Ancylostoma caninum or with Uncinaria stenocephala (a canine hookworm) did not contain antibodies to the 35 kD antigen, but did cross-react with many other D. immitis adult and microfilarial antigens. This molecule may therefore be species specific. Evidence for glycosylation of the 35 kD molecule was not found: it did not bind to peanut, wheat germ, lentil, or Ulex europeus lectins, and its electrophoretic mobility was not altered after treatment with endoglycosidase-F or mild alkali solutions.
Effect of Multiple–Nodal Basin Drainage on Cutaneous Melanoma (2008)

Multiple-nodal basin drainage does not confer a worse prognosis for patients with cutaneous melanoma. In fact, single-nodal basin drainage appears to be associated with a greater risk of locoregional recurrence.
Lineage restriction analyses in CHIP indicate myeloid bias for TET2 and multipotent stem cell origin for DNMT3A (2018)

We analyzed DNA from polymorphonuclear (PMN) cells, monocytes, B cells, and T cells of 107 individuals with clonal hematopoiesis of indeterminate potential (CHIP) to perform lineage restriction analysis of different gene mutations. Three lineage categories were defined: myeloid (PMN with or without monocytes), myelolympho-B (myeloid and B cells), and multipotent (myeloid, B and T cells). Six individuals with aberrant patterns were excluded from analysis. Ninety-four had a single mutation (56 in <i>DNMT3A</i>, 24 in <i>TET2</i>, 7 in other genes [<i>JAK2</i>, <i>ASXL1</i>, <i>CBL</i> or <i>TP53</i>]). Fourteen had multiple mutations. The lineage restriction patterns of single <i>DNMT3A</i>- or <i>TET2</i>-mutated individuals were different. The proportion of myeloid restricted mutations was higher for <i>TET2</i> (54.2%, 13 of 24) than for <i>DNMT3A</i> (23.2%, 13 of 56) (<i>P</i> < .05). It was similar for myelolympho-B category but with a 1.5 fold greater proportion of myeloid cells for <i>TET2</i> individuals (<i>P</i> < .05). Importantly, 0% (0 of 24) of the individuals with <i>TET2</i> mutation in the multipotent category in contrast to 35.7% (20 of 56) for <i>DNMT3A</i> (<i>P</i> < .01). The clone size predicted multipotent pattern for <i>DNMT3A</i> suggesting a time delay for extensive lineage clonal dominance. These distinctive features may be important in deciphering the transformation mechanisms of these frequent mutations.
Stochastic batch size for adaptive regularization in deep network optimization (2020)

We propose a first-order stochastic optimization algorithm incorporating adaptive regularization applicable to machine learning problems in deep learning framework. The adaptive regularization is imposed by stochastic process in determining batch size for each model parameter at each optimization iteration. The stochastic batch size is determined by the update probability of each parameter following a distribution of gradient norms in consideration of their local and global properties in the neural network architecture where the range of gradient norms may vary within and across layers. We empirically demonstrate the effectiveness of our algorithm using an image classification task based on conventional network models applied to commonly used benchmark datasets. The quantitative evaluation indicates that our algorithm outperforms the state-of-the-art optimization algorithms in generalization while providing less sensitivity to the selection of batch size which often plays a critical role in optimization, thus achieving more robustness to the selection of regularity.
Flat and conformal optics with dielectric metasurfaces (2017)

I discuss our dielectric metasurface platform based on high index nano-posts on a low index substrate, and its applications in imaging, dispersion control, retroreflection and conformal optics.
Conformation‐function relationships in LHRH analogs (1993)

A systematic conformational build-up procedure was performed for the LHRH molecule, pGlu1-His2-Trp3-Ser4-Tyr5-Gly6-Leu7-Arg8-Pro9-Gly10-NH 2. The results showed a very high flexibility of the LHRH backbone, with 300 conformers being regarded as having low energy. At the same time, the conformational flexibility of LHRH differs among the fragments of the molecule. The most rigid fragments of LHRH are the Ser4-Tyr5-Gly6-Leu7 and Tyr5-Gly6-Leu7-Arg8 central tetrapeptides, the latter possessing only eight different types of low-energy backbone conformers. These eight conformer types belong to different kinds of chain reversals which are stabilized by different systems of intramolecular hydrogen bonds. Some of them resemble the beta-II' turn, which was derived as the LHRH structure from energy calculations by others. The results obtained are in good agreement with the experimental data on LHRH flexibility in solution.
Cross Point Test Arrays for Development and Yield Ramp of Emerging Memories (2019)

New non-volatile memory types are becoming increasingly attractive for embedded and storage-class applications. Among the development challenges to insert memory elements between upper interconnect metals are long learning cycles and high wafer cost. We propose a short-flow based characterization of Memory Arrays using a Cross Point Array approach, which significantly reduces the Turn-Around Time and processing cost.
Constraints (2015)

Every good scientific theory is a prohibition: it forbids certain things to happen. The more a theory forbids, the better it is– Karl Popper
Lens Design of Compatible Objective Lens for Blu-ray Disc and Digital Versatile Disk with Diffractive Optical Element and Phase Steps (2004)

A two-element objective lens which is compatible with for digital versatile disk (DVD) and Blu-ray Disc (BD) and has adequate optical performances in terms of off-axis wavefront and on-axis chromatic aberration for both optical heads has been designed. The first-order diffracted light is used for DVD and the second-order one is used for BD. We analyzed chromatic spherical aberration and found that using first- and second-diffracted lights causes 20 mλ/nm chromatic spherical aberration at a wavelength of 400 nm. However, using 5λ and 10λ phase steps can reduce chromatic spherical aberration to 7 mλ/nm. The designed two-element lens consists of the first plastic lens, on which there is diffractive optical element, and the second plano-convex glass molded lens.
FAILURE OF ACETALDEHYDE OR ACETATE TO MIMIC THE SPLANCHNIC ARTERIOLAR OR VENULAR DILATOR ACTIONS OF ETHANOL: DIRECT in situ STUDIES ON THE MICROCIRCULATION (1981)

The effects of acetaldehyde and sodium acetate on rat mesenteric arterioles (17-25 micron i.d.) and muscular venules (35-50 micron i.d.) were examined in situ, at the microcirculatory level, by use of a high-resolution closed circuit television microscope recording system. Local, intravenous or intra-arterial administration of acetaldehyde (1.8-3600 mumol) and sodium acetate (0.25-250 mumol) to mesenteric arterioles and muscular venules of the anaesthetized rat induced dose-dependent vasoconstriction. Systemic administration of a variety of pharmacological antagonists (i.e., phentolamine, diphenhydramine, methysergide, atropine and indomethacin) did not attenuate or prevent the dose-dependent vasoconstrictor actions of these metabolites of ethanol. Our findings do not support the concept that some or all of the peripheral vasodilator actions of ethanol can be attributed to its metabolites, acetaldehyde and acetate.
Focusing Images through Large-Core Multimode Fibers and a Multimode Fiber Endoscope (2020)

In a referenceless imaging setup with coherent light control based on a transmission matrix approach, an endoscope, composed of multimode fibers, is implemented in order to set focus at specific targets and enable structured illumination.
Flow Control Predictions Using Unsteady Reynolds-Averaged Navier-Stokes Modeling: A Parametric Study (2009)

T HE effective control of flow separation promises substantial performance improvements for a wide variety of air vehicles. Although the methods are well known, there is very little by way of theory or numerical models that can adequately predict lift enhancements, drag reduction, etc. An attemptwasmade to address this problem by conducting a computational fluid dynamics (CFD) validation workshop for synthetic jets and turbulent separation control [1], where one casewas dedicated to predicting the nominally two-dimensional flow over a hump. The baseline (uncontrolled) case was considered in addition to control by means of steady suction [2] and zero-net-mass flux (oscillatory) blowing [3]. The workshop determined that CFD with steady or unsteady Reynolds-averaged Navier–Stokes (RANS or URANS) consistently overpredicted the reattachment location, regardless of turbulence model or method. Within the separation bubble, most computations predicted velocity profiles well but considerably underpredicted the magnitude of turbulent shear stresses. Large-eddy simulations and other costly methods appear capable of overcoming this deficiency, but the focus of the current study is on the more affordable RANS and URANS methodologies. See, for example, Krishnan et al. [4], Morgan et al. [5], and Saric et al. [6]. Although these individual test cases were challenging to CFD codes, only a single test case was considered for both steady suction and zero-net-mass flux blowing. During the course of the experimental investigation, however, steady and unsteady surface pressures were acquired for a wide variety of control parameters, including Reynolds number, suction flow rate, and frequency and blowing amplitude in the zero-net-mass flux case. Significant variations, or changes, in control authority were observed depending upon the control input or prevailing Reynolds numbers. For example, varying the suction flow rate at different Reynolds numbers indicated an increase in the rate of drag reduction; in contrast, no Reynolds number effect could be detected with regard to zero-net-mass flux blowing. In addition, for the oscillatory case, the flow was seen to be highly dependent on control frequency and peak blowing amplitude. Different, sometimes counteracting, mechanisms dominated the separated flowfield during different parts of the control cycle. Comparisons of these changes, or trends, with numerical results will clearly facilitate more precise evaluation of CFD’s value for predictive purposes. This is because the uncontrolled, or baseline, state is usually known and hence the correct prediction of changes to the baseline state as a result of a particular control strategy would be of great value for assessing different concepts or downselection. To address this need, Rumsey and Greenblatt [7] undertook a detailed parametric study and this Note presents a summary of the main findings.
Phosphodiesterasehemmung als neues positiv-inotropes Prinzip* (1986)

Drug Prescribing for Patients with Chronic Kidney Disease in General Practice: a Cross-Sectional Study
Design Principles for Optoelectronic Applications of Extraordinary Light Transmission Effect in Plasmonics Nanoapertures (2010)

The extraordinary light transmission effect (EOT) through sub-wavelength nanoapertures in opaque metal films has lead to observation of a wide variety of exciting new optical phenomena. This remarkable effect is generally related to the interaction of the light with the extended plasmonic resonances on the surface of the metal film and localized surface plasmons in the apertures. On the other hand, there is little conceptual understanding for controlling the localized surface plasmonic behavior of the individual apertures and their coupling to the extended surface plasmons. In this letter, we present an intuitive and straightforward picture of the extra-ordinary light transmission phenomena based on basic antenna principles for plasmonic excitations and coupling of these plasmonic excitations in complex nano-apertures. Our quasi-static model remarkably well explains our experimental measurements in shape anisotropic structures with unique properties controlled by adjusting the size and the geometry of the apertures. Our approach puts forward new design principles for potential applications ranging from subwavelength optoelectronics and data storage to bio/chemical sensing.