gebhart/patrepeval huggingface dataset:
Bridging the Valley (2016)

The withdrawal of large company support for early stage research, combined with shrinking Federal expenditures, has created a “Valley of Death” in drug discovery that creates both pressing challenges and extraordinary opportunities. This chapter details the opportunities that could be created by incentivizing new innovative and entrepreneurial research into novel medicines. Many “experiments” are currently under way to identify novel means of addressing the Valley of Death and successful examples include a partnership between Yale University and Gilead Sciences, a California biotechnology company. We also explore the potential and limitations of academia rising as a means to address the need for early-stage drug research and conclude the chapter and the book with the idea that the Federal government could play a key role were it to more actively and creatively function as both the largest source of public venture capital as well as the key regulator of new medicines.
Word-for-word glossing with contextually similar words (2000)

Many corpus-based machine translation systems require parallel corpora. In this paper, we present a word-for-word glossing algorithm that requires only a source language corpus. To gloss a word, we first identify its similar words that occurred in the same context in a large corpus. We then determine the gloss by maximizing the similarity between the set of contextually similar words and the different translations of the word in a bilingual thesaurus. 1 Introduction Word-for-word glossing is the process of directly translating each word or term in a document without considering the word order. Automating this process would benefit many NLP applications. For example, in cross-language information retrieval, glossing a document often provides a sufficient translation for humans to comprehend the key concepts. Furthermore, a glossing algorithm can be used for lexical selection in a fullfledged machine translation (MT) system. Many corpus-based MT systems require parallel corpora [1][2][3...
Observed Phase-locking Between a Rubidium Raman Laser and its Pump Laser (2018)

We have observed that the beat-note between a rubidium Raman ring laser and its gain pump is much narrower than the spectral width of the pump laser itself, indicating that they are mutually phase-locked.
Update and Mutational Analysis ofSLC20A2: A Major Cause of Primary Familial Brain Calcification (2015)

Primary familial brain calcification (PFBC) is a heterogeneous neuropsychiatric disorder, with affected individuals presenting a wide variety of motor and cognitive impairments, such as migraine, parkinsonism, psychosis, dementia, and mood swings. Calcifications are usually symmetrical, bilateral, and found predominantly in the basal ganglia, thalamus, and cerebellum. So far, variants in three genes have been linked to PFBC: SLC20A2, PDGFRB, and PDGFB. Variants in SLC20A2 are responsible for most cases identified so far and, therefore, the present review is a comprehensive worldwide summary of all reported variants to date. SLC20A2 encodes an inorganic phosphate transporter, PiT-2, widely expressed in various tissues, including brain, and is part of a major family of solute carrier membrane transporters. Fifty variants reported in 55 unrelated patients so far have been identified in families of diverse ethnicities and only few are recurrent. Various types of variants were detected (missense, nonsense, frameshift) including full or partial SLC20A2 deletions. The recently reported SLC20A2 knockout mouse will enhance our understanding of disease mechanism and allow for screening of therapeutic compounds. In the present review, we also discuss the implications of these recent exciting findings and consider the possibility of treatments based on manipulation of inorganic phosphate homeostasis.
Non-uniform sampling point selection in OFDM receiver with fractional sampling (2009)

To achieve diversity with a single antenna, a fractional sampling (FS) scheme in OFDM has been proposed. In the previous literatures for FS, the sampling interval is fixed. An oversampling rate needs to be large to obtain more path diversity gain through FS. This leads to the increase of a circuit size for demodulation in a mobile terminal. In this paper, sampling point selection according to the frequency response of a channel has been proposed. The proposed scheme reduces the number of demodulation branches to a half as compared to the conventional FS scheme to achieve the same bit error rate. Moreover, by eliminating the specific sets of the sampling points, the computational complexity for sampling point selection is also reduced by a factor of 2.
Functional characterization of two anti‐estradiol antibodies as deduced from modelling and site‐directed mutagenesis experiments (2001)

Monoclonal antibodies are now widely used to measure the concentration of steroid hormones in human serum samples. The great development of molecular engineering techniques over the past 10 years has made possible the improvement of specificity and/or sensitivity of selected antibodies. We have obtained two monoclonal antibodies, 17E12E5 and 10G6D6, using estradiol-6-ethyl methoxy carbonyl (EMC)-bovine serum albumin (BSA) as immunogen. To tentatively improve their affinities for natural estradiol, we have initiated their structural and functional studies. For this purpose, we have cloned and sequenced the genes encoding the variable fragments of each antibody. Single chain variable fragments (scFv) were produced into the periplasmic space of E. coli using the pLIP6 expression vector. Mapping of the functional structures of both antibodies was obtained by combination of modelling and mutational analyses together with cross-reaction studies. The two binding pockets are described and models of estradiol complexed to 17E12E5 and 10G6D6 are proposed.
A novel technique for the preparation of secondary fatty amides (1994)

Abstract A low‐temperature synthesis of fatty alkanolamides, fatty diamides and fatty aralkylamides directly from triglycerides and primary amines provides essentially quantitative yields of the various products. The reactions run to completion in 3–12 h at temperatures of 50–60°C, approximately 100°C lower than employed in present conventional practice. The amines are used in excess and serve as solvent, reagent and, perhaps, as catalyst. The amides were characterized by melting point and spectroscopic (infrared and nuclear magnetic resonance) methods. If the mixed amides produced from the various natural triglyceride mixtures of fats and oils are acceptable products, this synthetic method provides these products in satisfactory quality while conserving energy and avoiding the intermediate production of free fatty acids or their esters.
Screening for new macrophage therapeutics (2019)

Myeloid derived macrophages play a key role in many human diseases, and their therapeutic modulation via pharmacological means is receiving considerable attention. Of particular interest is the fact that these cells are i) dynamic phenotypes well suited to therapeutic manipulation and ii) phagocytic, allowing them to be efficiently targeted with nanoformulations. However, it is important to consider that macrophages represent heterogeneous populations of subtypes with often competing biological behaviors and functions. In order to develop next generation therapeutics, it is therefore essential to screen for biological effects through a combination of <i>in vitro</i> and <i>in vivo</i> assays. Here, we review the state-of-the-art techniques, including both cell based screens and <i>in vivo</i> imaging tools that have been developed for assessment of macrophage phenotype. We conclude with a forward-looking perspective on the growing need for noninvasive macrophage assessment and laboratory assays to be put into clinical practice and the potential broader impact of myeloid-targeted therapeutics.
Guiding Synthesis of Polymorphs of Materials Using Nanometric Phase Diagrams (2018)

Conventionally, phase diagrams serve as road maps for the design and synthesis of materials. However, bulk phase diagrams are often not as predictive for the synthesis of nanometric materials, mainly due to the increased significance of surface energy. The change of surface energy can drastically alter the total energy of the nanocrystals and thus yields a polymorph or metastable phase different from the stable phase in bulk, providing a means for controlling the synthesis of metastable phases. To achieve a theoretical and systematical understanding on the polymorphism of nanomaterials, metallic cobalt was chosen as a model system, where the two polymorphs, fcc and hcp phases, can be tuned with 100% selectivity in a solvothermal reaction. Advanced in situ synchrotron X-ray diffraction (XRD) technique and density functional theory (DFT) calculations were complementarily employed to reveal the size- and surface-dependent polymorphism at nanometer scale. The nanometric phase diagram provides a general predictive approach to guide the synthesis of metastable materials.
CAMAP: Artificial neural networks unveil the role of codon arrangement in modulating MHC-I peptides presentation (2021)

MHC-I associated peptides (MAPs) play a central role in the elimination of virus-infected and neoplastic cells by CD8 T cells. However, accurately predicting the MAP repertoire remains difficult, because only a fraction of the transcriptome generates MAPs. In this study, we investigated whether codon arrangement (usage and placement) regulates MAP biogenesis. We developed an artificial neural network called Codon Arrangement MAP Predictor (CAMAP), predicting MAP presentation solely from mRNA sequences flanking the MAP-coding codons (MCCs), while excluding the MCC per se. CAMAP predictions were significantly more accurate when using original codon sequences than shuffled codon sequences which reflect amino acid usage. Furthermore, predictions were independent of mRNA expression and MAP binding affinity to MHC-I molecules and applied to several cell types and species. Combining MAP ligand scores, transcript expression level and CAMAP scores was particularly useful to increase MAP prediction accuracy. Using an in vitro assay, we showed that varying the synonymous codons in the regions flanking the MCCs (without changing the amino acid sequence) resulted in significant modulation of MAP presentation at the cell surface. Taken together, our results demonstrate the role of codon arrangement in the regulation of MAP presentation and support integration of both translational and post-translational events in predictive algorithms to ameliorate modeling of the immunopeptidome.
Interleukin-2 Receptors (1985)

Interleukin-2 (IL-2) is a lymphokine synthesized by some T-cells following activation. Resting T-cells do not express IL-2 receptors but receptors are rapidly expressed on T-cells following the interaction of antigens, mitogens, or monoclonal antibodies with the antigen specific T-cell receptor complex. Using anti-Tac a monoclonal antibody that recognizes the IL-2 receptor, the receptor has been purified. The receptor is a 33kd peptide that is posttranslationally glycosylated to a 55kd mature form. Mature receptors contain both N-linked and O-linked sugars and are both sulfated and phosphorylated. Using an oligonucleotide probe, based on the N-terminal amino acid sequence, cDNAs encoding this receptor have been cloned, sequenced and expressed. The addition of anti-Tac to in vitro culture systems blocks the IL-2 induced DNA synthesis of IL-2 dependent T-cell lines and inhibits soluble auto- and alloantigen induced T-cell proliferation. Furthermore, it prevents the generation of cytotoxic and suppressor effector T cells. The anti-receptor antibody also inhibits lectin stimulated immunoglobulin synthesis and the sequential expression of late appearing activation antigens on T-cells. Normal resting T-cells and most leukemic T-cell populations do not express IL2 receptors however the leukemic cells of all patients with human T-cell leukemia/lymphoma virus (HTLV-1) associated, adult T-cell leukemia (ATL) examined expressed the Tac antigen. In HTLV-I infected cells the 42kd LOR protein encoded in part, by the pX region of HTLV-I may act as a transacting transcriptional activator that induces transcription of the IL-2 receptor gene thus providing an explanation for the constant association of HTLV-I infection of lymphoid cells and IL-2 receptor expression. The constant display of large numbers of IL-2 receptors which may be aberrant in the ATL cells may play a role in the uncontrolled growth of these leukemic T-cells. Patients with the Tac positive adult T-cell leukemia are being treated with the anti-Tac monoclonal antibody directed towards this growth factor receptor.
Abstract 1494: Hepatocyte Growth Factor Attenuates Angiotensin II Induced Renal Fibrosis through TGF-β1 Suppression by Anoikis of Myofibroblasts (2008)

Progression of chronic kidney disease (CKD) is characterized by the persistent accumulation of extracellular matrix. Especially, α-SMA positive myofibroblast which produce high amounts of TGF-β1 are considered to play a key role in interstitial fibrosis. Previous studies demonstrated that hepatocyte growth factor (HGF) improved kidney fibrosis in murine models, where direct molecular mechanisms of myofibroblasts have not yet been understood. We tested the hypothesis in vivo using cardiac specific overexpression HGF mice (HGF-Tg), which showed a significant increase in serum HGF concentration. Angiotensin II (Ang II) infusion significantly induced renal fibrosis in wild type mice, while renal fibrosis was significantly decreased in HGF-Tg mice accompanied by the degrease in interstitial myofibroblasts (P&lt;0.05). Quantitative analysis demonstrated 1.69-folds induction of profibrtic cytokine, TGF-β1 mRNA in HGF-Tg with Ang II group compared with wild type with Ang II, and Collagen type I and IV mRNA expression was significantly decreased in HGF-Tg mice with Ang II. The antifibotic action of HGF-Tg mice was concordant with an increase in MMP-2, MMP-9 expression (1.32-fold, 1.33-fold vs wild type with Ang II infusion, P&lt;0.05, respectively), and decreased TIMP-1, TIMP-2 expression (1.5-fold, 1.28-fold vs wild type with Ang II infusion, P&lt;0.05, respectively). To further investigate the anti-fibrotic effect of HGF, we used cultured human mesangial cells (HMC). When HMC were treated with TGF-β1, cells underwent to phenotypic change similar to myofibroblasts, accompanied by the significant increase in c-Met/HGF receptor (P&lt;0.05). Under such conditions, HGF induced anoikis-induced apoptosis of myofibroblasts. It also linked with FAK phosphorylation especially p-FAK (Y925) (P&lt;0.05). When GM6001 (a broad-spectrum MMP inhibitor) was added with HGF, HGF-induced apptosis was significantly decreased. It was suggested that increased activities of MMPs underlie the major mechanism of HGF mediated anoikis induced apoptosis. The present study demonstrated that HGF elicited myofibroblast anoikis. Activation of MMPs in fibrotic kidney might be considered as a target to attenuate the progression of CKD.
New Polydentate Ligand and Catalytic Properties of the Corresponding Ruthenium Complex During Sulfoxidation and Alkene Epoxidation (2008)

Bis(diimine)-ruthenium complexes constitute a class of catalysts with good activity for oxidation reactions, such as sulfoxidation and epoxidation. The synthesis and the full characterization of a new ruthenium complex bearing an original pentadentate ligand (L5pyr for 2,6-bis-(6-ethyl-2,2'-bipyridyl)-pyridine) is reported. Comparison of its activity with regard to[Ru(bpy)2(CH3CN)2](2+) and [Ru(bpy)2(py)(CH3CN)](2+) during alkene and sulfide oxidation allowed us to conclude that the addition of a fifth pyridine ligand in the coordination sphere improves the efficiency of the catalyst. Moreover, under these oxidation conditions a hydroxylation of the ligand L5pyr led to a better activity than its analogue [Ru(bpy)2(py)(CH3CN)](2+), especially during epoxidation of alkenes by PhI(OAc)2.
MO-FG-CAMPUS-TeP2-04: Optimizing for a Specified Target Coverage Probability (2016)

Purpose: The purpose of this work is to develop a method for inverse planning of radiation therapy margins. When using this method the user specifies a desired target coverage probability and the system optimizes to meet the demand without any explicit specification of margins to handle setup uncertainty. Methods: The method determines which voxels to include in an optimization function promoting target coverage in order to achieve a specified target coverage probability. Voxels are selected in a way that retains the correlation between them: The target is displaced according to the setup errors and the voxels to include are selected as the union of the displaced target regions under the x% best scenarios according to some quality measure. The quality measure could depend on the dose to the considered structure alone or could depend on the dose to multiple structures in order to take into account correlation between structures. Results: A target coverage function was applied to the CTV of a prostate case with prescription 78 Gy and compared to conventional planning using a DVH function on the PTV. Planning was performed to achieve 90% probability of CTV coverage. The plan optimized using the coverage probability function had P(D98 > 77.95 Gy) = 0.97 for the CTV. The PTV plan using a constraint on minimum DVH 78 Gy at 90% had P(D98 > 77.95) = 0.44 for the CTV. To match the coverage probability optimization, the DVH volume parameter had to be increased to 97% which resulted in 0.5 Gy higher average dose to the rectum. Conclusion: Optimizing a target coverage probability is an easily used method to find a margin that achieves the desired coverage probability. It can lead to reduced OAR doses at the same coverage probability compared to planning with margins and DVH functions.
Spectral characterization of fiber gratings with high resolution (1998)

We demonstrate a high-resolution technique to measure the optical magnitude and phase responses of fiber gratings. The technique employs single-sideband modulation of an optical source and has spectral resolution in the hertz regime. The technique is demonstrated by measurement of the phase ripples of unapodized and apodized chirped gratings as well as the transmission spectrum of a pi-phase-shifted grating. Although it is demonstrated on fiber gratings, the technique is applicable to any optical device.
Virus infectivity detection by effective refractive index using optofluidic imaging (2014)

This paper presents an optofluidic imaging system to detect influenza virus infection via co-culture of Madin Darby Canine Kidney (MDCK) cells. Influenza flu virus is a serious threat that can cause contagious infections in people in epidemic proportions. Hence, it is crucial to accurately detect and understand the morphological changes that occur in the cells when infected by the influenza virus. Recently, researchers are investigating the biophysical properties of cells and correlating them to biomedical conditions. For example, a decrease in refractive index (RI) is observed in bacterial infected cells [1]. In this paper, an optofluidic imaging system is developed to observe the change of RI in virus infected cells based on scattering signature.
Platform-aware bottleneck detection for reconfigurable computing applications (2011)

Reconfigurable Computing (RC) has the potential to provide substantial performance benefits and yet simultaneously consume less power than traditional microprocessors or GPUs. While experimental performance analysis of RC applications has previously been shown crucial for achieving this potential, existing methods still require application designers to manually locate bottlenecks and determine appropriate optimizations, typically requiring significant designer expertise and effort. Worse, the diversity of platforms employed by RC applications further complicates the process of detecting bottlenecks and formulating optimizations. To address these shortcomings, we first discuss our platform-template system, which enables a performance analysis tool to perform more accurate bottleneck detection and achieve a higher degree of portability across diverse FPGA systems. We then provide details for our implementation of these concepts and techniques in the Reconfigurable Computing Application Performance (ReCAP) tool. Next, we present a taxonomy of common RC bottlenecks, providing associated detection and optimization strategies for each bottleneck, which we use to populate ReCAP's knowledge base for bottleneck detection. Finally, we demonstrate the utility of our approach via two application case studies across a total of three platforms.
Functional imaging by optical tomography (2004)

Maintenance of appropriate interactions between tissue and its blood supply is critical to health and continuation of normal body function. Time-series optical imaging is a highly effective method for exploring and monitoring these interactions. For this purpose, we have developed a complete temporo-spectral optical imaging system, comprising instrumentation and software.
Induction by a Lactic Acid Bacterium of a Population of CD4+T Cells with Low Proliferative Capacity That Produce Transforming Growth Factor β and Interleukin-10 (2001)

We investigated whether certain strains of lactic acid bacteria (LAB) could antagonize specific T-helper functions in vitro and thus have the potential to prevent inflammatory intestinal immunopathologies. All strains tested induced various levels of both interleukin-12 (IL-12) and IL-10 in murine splenocytes. In particular, Lactobacillus paracasei (strain NCC2461) induced the highest levels of these cytokines. Since IL-12 and IL-10 have the potential to induce and suppress Th1 functions, respectively, we addressed the impact of this bacterium on the outcome of CD4(+) T-cell differentiation. For this purpose, bacteria were added to mixed lymphocyte cultures where CD4(+) T-cells from naive BALB/c mice were stimulated weekly in the presence of irradiated allogeneic splenocytes. In these cultures, L. paracasei NCC2461 strongly inhibited the proliferative activity of CD4(+) T cells in a dose-dependent fashion. This was accompanied by a marked decrease of both Th1 and Th2 effector cytokines, including gamma interferon, IL-4, and IL-5. In contrast, IL-10 was maintained and transforming growth factor beta (TGF-beta) was markedly induced in a dose-dependent manner. The bacteria were not cytotoxic, because cell viability was not affected after two rounds of stimulation. Thus, unidentified bacterial components from L. paracasei NCC2461 induced the development of a population of CD4(+) T cells with low proliferative capacity that produced TGF-beta and IL-10, reminiscent of previously described subsets of regulatory cells implicated in oral tolerance and gut homeostasis.
Role of Metal–Semiconductor Contact in Nanowire Field-Effect Transistors (2009)

In this paper, we present a systematic study of the role of metal/semiconductor nanowire (NW) contact in back-gated Ge and Si NW Schottky-barrier (SB) FETs. Our results show that the performance of such devices is largely dominated by the carrier injection efficiency at the source contact, which, in turn, is controlled by metal contact depth and gate bias. Using low-temperature annealing of back-gated Ge and Si NW SB FETs with nickel (Ni) contacts as source and drain, we monitor the evolution of the device current as the contact metal progressively diffuses into the NWs. The drain current, which is measured at a given gate and drain bias, first increases as the contact metal diffuses into the NW, reaches a maximum, and subsequently decreases. These results can be explained by the interplay between carrier injection efficiency through the metal/NW SB, which increases with the metal contact depth, and the number of available states in the NW between contact and the bottom oxide, which decreases with the metal contact depth.