gebhart/patrepeval huggingface dataset:
Single Cell Insights Into Cancer Transcriptomes: A Five-Part Single-Cell RNAseq Case Study Lesson (2021)

There is a growing need for integration of &ldquo;Big Data&rdquo; into undergraduate biology curricula. Transcriptomics is one venue to examine biology from an informatics perspective. RNA sequencing has largely replaced the use of microarrays for whole genome gene expression studies. Recently, single cell RNA sequencing (scRNAseq) has unmasked population heterogeneity, offering unprecedented views into the inner workings of individual cells. scRNAseq is transforming our understanding of development, cellular identity, cell function, and disease. As a &lsquo;Big Data,&rsquo;&nbsp;scRNAseq can be intimidating for students to conceptualize and analyze, yet it plays an increasingly important role in modern biology. To address these challenges, we created an engaging case study that guides students through an exploration of scRNAseq technologies. Students work in groups to explore external resources, manipulate authentic data and experience how single cell RNA transcriptomics can be used for personalized cancer treatment. This five-part case study is intended for upper-level life science majors and graduate students in genetics, bioinformatics, molecular biology, cell biology, biochemistry, biology, and medical genomics courses. The case modules can be completed sequentially, or individual parts can be separately adapted. The first module can also be used as a stand-alone exercise in an introductory biology course. Students need an intermediate mastery of Microsoft Excel but do not need programming skills. Assessment includes both students&rsquo; self-assessment of their learning as answers to previous questions are used to progress through the case study and instructor assessment of final answers. This case provides a practical exercise in the use of high-throughput data analysis to explore the molecular basis of cancer at the level of single cells.
Effect of Aliskiren and Valsartan Combination Versus Aliskiren Monotherapy on Hemostatic Biomarkers in Hypertensive Diabetics (2013)

Valsartan is known to inhibit platelet activity in both in vitro and ex vivo clinical setting, whereas aliskiren in vitro modulates antithrombin-III in plasma. The authors tested how aliskiren and valsartan combination versus aliskiren monotherapy will affect hemostatic biomarkers in mild-to-moderate hypertensive diabetics in the frame of the Aliskiren and Valsartan Impact in Diabetics (AVID) trial. A total of 52 patients with type 2 diabetes and mild-to-moderate hypertension were equally randomized to aliskiren (150-300 mg/d) and valsartan (160 mg/d) versus aliskiren (150-300 mg/d) alone for 4 weeks. A total of 25 biomarkers were serially measured, of which 16 are related to platelet function, 6 to coagulation, and 3 to fibrinolysis. Aliskiren monotherapy has no significant impact on any of the assessed biomarkers. In contrast, valsartan on top of aliskiren provided significant inhibition of ADP-induced platelet aggregation (P=0.032), decreased shear-induced activation measured with PFA-100 analyzer (P=0.041), and diminished expression of GP IIb/IIIa activity (P=0.027) measured by PAC-1 antibody, GP Ib (CD42b, P=0.033), vitronectin receptor (CD51/61, P=0.046), P-selectin (CD62p, P=0.026), lysosome-associated membrane protein (CD107a, P=0.042), and CD40-ligand (CD154, P=0.048). In AVID trial, valsartan in combination with aliskiren mildly but significantly inhibited platelets, confirming previous observations. In contrast, aliskiren monotherapy does not enhance antithrombin activity, suggesting that previous data probably represent a laboratory artifact. Importantly, these randomized data were generated on top of low-dose daily aspirin, supporting extra benefit for combination use of angiotensin receptor blockers and renin inhibitors in high-risk diabetic population.
Evaluation of glycosylation for quality assurance of antibody pharmaceuticals by capillary electrophoresis (2008)

The development of monoclonal antibody (mAb) pharmaceuticals has rapidly generated in this decade, and there are currently 23 FDA-approved mAb pharmaceuticals. Carbohydrate chains in mAb pharmaceuticals play important roles for the expression of their biological activities such as antibody-dependent cellular cytotoxicity, whereas the oligosaccharide profile is easily changed depending on the manufacturing conditions. Therefore, the evaluation of carbohydrate chains in detail is quite important for quality control in the development of mAb from early phases, but oligosaccharides in mAb have high heterogeneity and full characterization of oligosaccharide moiety in mAb has been a challenging target. Capillary electrophoresis (CE) is a powerful tool for the evaluation of glycan occupancy and oligosaccharide profile. This review focuses mainly on the application of CE to the analytical studies on glycosylation in mAb pharmaceuticals developed in our laboratory. The related techniques including the full-image microchip isoelectric focusing and the newly developed mass spectrometry technologies are also shown. The combination of the techniques described in this review will be a good guide for the evaluation of glycosylation for quality assurance of antibody pharmaceuticals by CE from the early stage of the development to the marketing stage.
Design of a Tip Appendage for the Control of Tip Leakage Vortices in Axial Flow Fans (2021)

Design of a Tip Appendage for the Control of Tip Leakage Vortices in Axial Flow FansThis article reports on numerical investigations of passive control techniques used for the performance enhancement of a large diameter axial flow cooling fan through modification of the blade tip geometry.Using open-source software, a novel meshing strategy is developed to carry out both steady and unsteady numerical computations of a periodic section of an axial flow fan.Analyzing the flow near the blade tip with a reduction in tip clearance, two predominant flow phenomena are identified.These two flow phenomena are further investigated with the aim of controlling them through implementation of a tip appendage design.Both introduced end-plate designs indicate effective control of each relevant flow phenomena.The constant thickness (CT) end-plate design is found to increase all fan performance characteristics at lower than design point (DP) flowrates, while increasing the fan's peak efficiency plateau toward the rotor stall margin.However, none of the CT end-plate designs are able to improve the fan's performance characteristics at its DP.The introduction of a novel trailing-edge (TE) end-plate design is found to increase all fan performance characteristics across the entire evaluated stable operating range, with an indicated increase of 37.3 percent in total-to-static pressure rise and a 2.9 percentage point increase in total-to-static efficiency at the fan's DP flowrate.The aerodynamic performance results attest to the associated benefits of the investigated passive control techniques.
TRIM5 genotypes in cynomolgus monkeys primarily influence inter-individual diversity in susceptibility to monkey-tropic human immunodeficiency virus type 1 (2013)

TRIM5α restricts human immunodeficiency virus type 1 (HIV-1) infection in cynomolgus monkey (CM) cells. We previously reported that a TRIMCyp allele expressing TRIM5-cyclophilin A fusion protein was frequently found in CMs. Here, we examined the influence of TRIM5 gene variation on the susceptibility of CMs to a monkey-tropic HIV-1 derivative (HIV-1mt) and found that TRIMCyp homozygotes were highly susceptible to HIV-1mt not only in vitro but also in vivo. These results provide important insights into the inter-individual differences in susceptibility of macaques to HIV-1mt.
Antibody‐dependent cellular cytotoxicity and disease course in North American patients with nasopharyngeal carcinoma: A prospective study (1984)

It has previously been reported that antibody-dependent cellular cytotoxicity (ADCC) levels determined at diagnosis against Epstein-Barr virus (EBV)-specific membrane antigens (MA) are predictive of disease course following therapy in patients with nasopharyngeal carcinoma (NPC). In general, survival was significantly shorter following therapy in patients with low ADCC titers at diagnosis versus those with high titers. To examine this further, a prospective study on North Americans with different histopathological types of this disease was initiated approximately 5 years ago. The results to date tend to support the conclusions drawn from the retrospective study for patients with the more poorly differentiated types (WHO 2 and WHO 3) of this disease. Over the first 3 years of this study, approximately 75% of the patients in the "high" category have remained clinically disease-free for 3 years or longer as opposed to approximately 35% of the patients in the "low" group. Disease progression rates were calculated to be approximately four times higher in the low group. Similar trends were noted in actual survival rates over a 3-year period. ADCC titers were in general found to be relatively stable in sequential serum samples from the same patient, with some exceptions. With the exceptions, however, changes in ADCC titers also reflected disease course. These results indicate, therefore, that anti-EBV ADCC titers are predictive of disease course in patients with the poorly differentiated types of NPC.
Enhancement of electron mobility in ultrathin-body silicon-on-insulator MOSFETs with uniaxial strain (2005)

The electrostatics of fully depleted MOS devices such as double- and triple-gate MOSFETs are highly dependent on the thickness of the silicon-on-insulator film in the channel. Scaling these devices to their ultimate limits makes it necessary to scale the channel thickness into a regime where quantum confinement effects negatively impact the electrical transport properties of the film. We use the application of uniaxial mechanical strain to investigate electron mobility in films where mobility has been degraded by quantum size effects. We find that these films exhibit more mobility enhancement from strain than do thick films, indicating that the strain increases mobility conventionally and mitigates the mechanism that causes mobility degradation in thin films.
Evaluation of a Lyophilized CRISPR-Cas12 Assay for a Sensitive, Specific, and Rapid Detection of SARS-CoV-2 (2021)

We evaluated a lyophilized CRISPR-Cas12 assay for SARS-CoV-2 detection (Lyo-CRISPR SARS-CoV-2 kit) based on reverse transcription, isothermal amplification, and CRISPR-Cas12 reaction. From a total of 210 RNA samples extracted from nasopharyngeal swabs using spin columns, the Lyo-CRISPR SARS-CoV-2 kit detected 105/105 (100%; 95% confidence interval (CI): 96.55-100) positive samples and 104/105 (99.05%; 95% CI: 94.81-99.97) negative samples that were previously tested using commercial RT-qPCR. The estimated overall Kappa index was 0.991, reflecting an almost perfect concordance level between the two diagnostic tests. An initial validation test was also performed on 30 nasopharyngeal samples collected in lysis buffer, in which the Lyo-CRISPR SARS-CoV-2 kit detected 20/21 (95.24%; 95% CI: 76.18-99.88) positive samples and 9/9 (100%; 95% CI: 66.37-100) negative samples. The estimated Kappa index was 0.923, indicating a strong concordance between the test procedures. The Lyo-CRISPR SARS-CoV-2 kit was suitable for detecting a wide range of RT-qPCR-positive samples (cycle threshold range: 11.45-36.90) and dilutions of heat-inactivated virus (range: 2.5-100 copies/µL); no cross-reaction was observed with the other respiratory pathogens tested. We demonstrated that the performance of the Lyo-CRISPR SARS-CoV-2 kit was similar to that of commercial RT-qPCR, as the former was highly sensitive and specific, timesaving (1.5 h), inexpensive, and did not require sophisticated equipment. The use of this kit would reduce the time taken for diagnosis and facilitate molecular diagnosis in low-resource laboratories.
From production to acoustics to perception: The case of fricatives. (2008)

Although the acoustics of speech mediate production and perception, few studies have examined the entire chain. English fricatives present an interesting case because they are realized by multiple cues. Previously, 20 speakers were recorded producing the eight English fricatives with six vowels. Twenty-one cues were measured [Jongman et al., J. Acoust. Soc. Am. 108, (2000)]. Fricatives were presented (with and without the vowel) to 20 listeners for identification. Listeners were better at identifying fricatives in context (M=91%) than isolation (M=75%), and sibilants (M=94%) than nonsibilants (M=72%). Acoustic measurements were analyzed with a regression model of cue-parsing [McMurray et al. (unpublished)]. The model approximated listeners' performance in context (M=87%). However, this was only true when speaker-specific variance could be parsed out; significant speaker variation was observed in every cue. Thus, vowel context may aid perception by helping listeners identify the speaker. While parsing speaker and vowel from the cues was helpful, this was not true for voicing. Voicing and place cues overlapped, but knowing the voicing did not improve identification of place (and vice versa). Finally, when cue weightings based on perception and articulation were computed independently, subtle differences emerged, suggesting that perception is similar, but not isomorphic, to production
Current Advances in the Development of Anticancer Drugs Targeting Tyrosine Kinases of the Src Family (2008)

Protein kinases, either membrane-embedded receptorial or cytosolic non-receptorial ones, are important transducers of cell proliferation signals. In almost all tumor cells, the activity of some kinases is deregulated, either because of the presence of cancer-specific aberrant forms, or as a consequence of alterations in regulatory pathways, at the transcriptional or post-transcriptional level, which increase the activity of protein kinases with respect to normal cells. The study of the non-receptor tyrosine kinase Src plays a pivotal role in the field of the molecular genetics of cancer. The Src family of kinases (SFKs) comprises nine members, Src, Fyn, Yes, which are expressed in most tissues, and Blk,Yrk, Fgr, Hck, Lck and Lyn, which are more selectively expressed in particular tissues. To date, cellular (c-) Src has been implicated in the development of human cancer. Like oncogenic v-Src, activated mutants of c-Src can transform cells in culture and induce tumours in chickens. In addition, Src protein expression and/or activity is elevated in epithelial cancers, or cell lines derived from these, and there is often an association with advancement of disease or with malignancy. During the past decade, examples of tyrosine kinases inhibitors have been reported. Many of these compounds were highly active in vitro, but only a few demonstrated in vivo activity. These approaches led to the characterization of the PP1/PP2 derivatives as very strong and selective inhibitors of the c-Src family of kinases. Unfortunately, attempts to improve the biological profile of the latter compounds have so far met little success. Following these studies, some other inhibitors, possessing different chemical structures and interesting c-Src inhibitory activity, have been recently reported. Some of these molecules showed potent inhibition of tumor cell proliferation, which was due to the interference with the signalling pathway at the level of Src tyrosine kinase, providing proof-of-principle for the targeting of Src in anticancer chemotherapy. Keywords: Anticancer Drugs, Tyrosine Kinases, cell proliferation signals, tumor cells, Src family, inhibitors, anticancer chemotherapy, Angiogenesis, Signal Transduction
Incidence of cranial nerve paralysis in poliomyelitis in relation to presence or absence of tonsils. I. In a metropolitan area. (1958)

Evidence is presented from data covering the period 1940 to 1952 which corroborates the conclusion of previous studies that prior tonsillectomy probably adversely affects the occurrence of brainstem paralysis (bulbar and bulbospinal) in poliomyelitis. Neither this study nor any preceding studies relating to this problem have proved the contention. On the basis that the hypothesis is correct, an attempt is made to find an answer by studying the incidence of the common paralysis of cranial nerves (VII, IX and X and XI) in bulbar and bulbospinal cases of poliomyelitis on the basis of presence or absence of tonsils. Rates of incidence of paralysis of cranial nerves, not adjusted for age, indicate a decidedly higher proportion of paralysis of the facial nerve (VII) among nontonsillectomized patients whereas tonsillectomized persons are preportionately more affected by palatal and pharyngeal paralysis (nerves IX and X). Paralysis of the facial nerve appears from two studies to occur more commonly at earlier ages, particularly in the age group 0 to 4 years. However, age adjustment did not erase, although it did somewhat lower, the TR/TP ratio. This finding lends credence to a real difference but can only be applied to this study, as Paffenbarger in a smaller study found no significant difference in frequencies of paralysis of the facial nerve between groups with tonsils removed and tonsils present, and Southcott, also in a small study, found paralysis of the facial nerve more common among tonsillectomized patients with bulbar (includes bulbospinal) involvement. The differences noted for palatal and pharyngeal paralyses (nerves IX and X) in the unadjusted rates as between tonsillectomized and nontonsillectomized patients remain statistically different and in some instances significant when corrections for age are made. The results of this study are suggestive but give no entirely satisfactory explanation for the differences noted. Various explanations previously offered are cited and briefly discussed. Perhaps more definitive studies in animals along the approach suggested by Southcott will prove more fruitful, namely, labelling virus by some radioactive element in order to trace the route it takes to the central nervous system.
α-Sheet secondary structure in amyloid β-peptide drives aggregation and toxicity in Alzheimer’s disease (2019)

Alzheimer's disease (AD) is characterized by the deposition of β-sheet-rich, insoluble amyloid β-peptide (Aβ) plaques; however, plaque burden is not correlated with cognitive impairment in AD patients; instead, it is correlated with the presence of toxic soluble oligomers. Here, we show, by a variety of different techniques, that these Aβ oligomers adopt a nonstandard secondary structure, termed "α-sheet." These oligomers form in the lag phase of aggregation, when Aβ-associated cytotoxicity peaks, en route to forming nontoxic β-sheet fibrils. De novo-designed α-sheet peptides specifically and tightly bind the toxic oligomers over monomeric and fibrillar forms of Aβ, leading to inhibition of aggregation in vitro and neurotoxicity in neuroblastoma cells. Based on this specific binding, a soluble oligomer-binding assay (SOBA) was developed as an indirect probe of α-sheet content. Combined SOBA and toxicity experiments demonstrate a strong correlation between α-sheet content and toxicity. The designed α-sheet peptides are also active in vivo where they inhibit Aβ-induced paralysis in a transgenic Aβ <i>Caenorhabditis elegans</i> model and specifically target and clear soluble, toxic oligomers in a transgenic APPsw mouse model. The α-sheet hypothesis has profound implications for further understanding the mechanism behind AD pathogenesis.
Metal particle manipulation by laser irradiation in borosilicate glass (2010)

We propose a new technique of manipulating a metal particle in borosilicate glass. A metal particle that is heated by laser illumination heats the surrounding glass by radiation and conduction. A softened glass enabled metal particle migration. A 1-µm-thick platinum film was deposited on the back surface of a glass plate and irradiated with a green CW laser beam through the glass. As a result, the platinum film was melted and implanted into the glass as a particle. Platinum particles with diameters of 3 to 50 μm migrated at speeds up to 10 mm/s. In addition to platinum particles, nickel and austenitic stainless steel (SUS304) particles can be implanted.
Surface-Functionalized Silicon Nanoparticles as Anode Material for Lithium-Ion Battery (2018)

An epoxy group was successfully attached to the surface of silicon nanoparticle (SiNPs) via a silanization reaction between silanol-enriched SiNPs and functional silanes. The epoxy-functionalized SiNPs showed a much improved cell performance compared with the pristine SiNPs because of the increased stability with electrolyte and the formation of a covalent bond between the epoxy group and the polyacrylic acid binder. Furthermore, the anode laminate made from epoxy-SiNPs showed much enhanced adhesion strength. Post-test analysis shed light on how the epoxy-functional group affects the physical and electrochemical properties of the SiNP anode.
Comparison of Antiviral Activity between IgA and IgG Specific to Influenza Virus Hemagglutinin: Increased Potential of IgA for Heterosubtypic Immunity (2014)

Both IgA and IgG antibodies are known to play important roles in protection against influenza virus infection. While IgG is the major isotype induced systemically, IgA is predominant in mucosal tissues, including the upper respiratory tract. Although IgA antibodies are believed to have unique advantages in mucosal immunity, information on direct comparisons of the in vitro antiviral activities of IgA and IgG antibodies recognizing the same epitope is limited. In this study, we demonstrate differences in antiviral activities between these isotypes using monoclonal IgA and IgG antibodies obtained from hybridomas of the same origin. Polymeric IgA-producing hybridoma cells were successfully subcloned from those originally producing monoclonal antibody S139/1, a hemaggulutinin (HA)-specific IgG that was generated against an influenza A virus strain of the H3 subtype but had cross-neutralizing activities against the H1, H2, H13, and H16 subtypes. These monoclonal S139/1 IgA and IgG antibodies were assumed to recognize the same epitope and thus used to compare their antiviral activities. We found that both S139/1 IgA and IgG antibodies strongly bound to the homologous H3 virus in an enzyme-linked immunosorbent assay, and there were no significant differences in their hemagglutination-inhibiting and neutralizing activities against the H3 virus. In contrast, S139/1 IgA showed remarkably higher cross-binding to and antiviral activities against H1, H2, and H13 viruses than S139/1 IgG. It was also noted that S139/1 IgA, but not IgG, drastically suppressed the extracellular release of the viruses from infected cells. Electron microscopy revealed that S139/1 IgA deposited newly produced viral particles on the cell surface, most likely by tethering the particles. These results suggest that anti-HA IgA has greater potential to prevent influenza A virus infection than IgG antibodies, likely due to increased avidity conferred by its multivalency, and that this advantage may be particularly important for heterosubtypic immunity.
Application of Li2S to compensate for loss of active lithium in a Si–C anode (2018)

A battery consisting of a Li<sub>2</sub>S pre-lithiated material/cathode and Si–C anode shows both high energy density and excellent capacity retention.
Temporal Proteomic Analysis of Intestine Developing Necrotizing Enterocolitis following Enteral Formula Feeding to Preterm Pigs (2008)

Necrotizing enterocolitis (NEC), a serious gastrointestinal inflammatory disease, frequently occurs in preterm neonates that fail to adapt to enteral nutrition. A temporal gel-based proteomics study was performed on porcine intestine with NEC lesions induced by enteral formula feeding. Functional assignment of the differentially expressed proteins revealed that important cellular functions, such as the heat shock response, protein processing; and purine, nitrogen, energy metabolism, were possible involved in the early progression of NEC.