gebhart/patrepeval huggingface dataset:
Oncogenic PIK3CA mutations occur in epidermal nevi and seborrheic keratoses with a characteristic mutation pattern (2007)

Activating mutations of the p110 α subunit of PI3K ( PIK3CA ) oncogene have been identified in a broad spectrum of malignant tumors. However, their role in benign or preneoplastic conditions is unknown. Activating FGF receptor 3 ( FGFR3 ) mutations are common in benign skin lesions, either as embryonic mutations in epidermal nevi (EN) or as somatic mutations in seborrheic keratoses (SK). FGFR3 mutations are also common in low-grade malignant bladder tumors, where they often occur in association with PIK3CA mutations. Therefore, we examined exons 9 and 20 of PIK3CA and FGFR3 hotspot mutations in EN ( n = 33) and SK ( n = 62), two proliferative skin lesions lacking malignant potential. Nine of 33 (27%) EN harbored PIK3CA mutations; all cases showed the E545G substitution, which is uncommon in cancers. In EN, R248C was the only FGFR3 mutation identified. By contrast, 10 of 62 (16%) SK revealed the typical cancer-associated PIK3CA mutations E542K, E545K, and H1047R. The same lesions displayed a wide range of FGFR3 mutations. Corresponding unaffected tissue was available for four EN and two mutant SK: all control samples displayed a WT sequence, confirming the somatic nature of the mutations found in lesional tissue. Forty of 95 (42%) lesions showed at least one mutation in either gene. PIK3CA and FGFR3 mutations displayed an independent distribution; 5/95 lesions harbored mutations in both genes. Our findings suggest that, in addition to their role in cancer, oncogenic PIK3CA mutations contribute to the pathogenesis of skin tumors lacking malignant potential. The remarkable genotype–phenotype correlation as observed in this study points to a distinct etiopathogenesis of the mutations in keratinocytes occuring either during fetal development or in adult life.
Evaluation of a bivalent (CVD 103-HgR/CVD 111) live oral cholera vaccine in adult volunteers from the United States and Peru (1997)

To provide optimum protection against classical and El Tor biotypes of Vibrio cholerae O1, a single-dose, oral cholera vaccine was developed by combining two live, attenuated vaccine strains, CVD 103-HgR (classical, Inaba) and CVD 111 (El Tor, Ogawa). The vaccines were formulated in a double-chamber sachet; one chamber contained lyophilized bacteria, and the other contained buffer. In the first study, 23 U.S. adult volunteers received CVD 103-HgR at 10(8) CFU plus CVD 111 at 10(8), 10(7), or 10(6) CFU, CVD 111 alone at 10(7) CFU, or placebo. In the second study, 275 Peruvian adults were randomized to receive CVD 103-HgR at 10(9) CFU plus CVD 111 at 10(9) or 10(8) CFU, CVD 111 alone at 10(9) CFU, CVD 103-HgR alone at 10(9) CFU, or placebo. Three of 15 U.S. volunteers who received CVD 111 at 10(7) or 10(8) CFU developed mild diarrhea, compared to none of 4 who received CVD 111 at 10(6) CFU and 1 of 4 who received placebo. Twelve (63%) of 19 vaccine recipients shed the El Tor vaccine strain. All but one volunteer developed significant Ogawa and Inaba vibriocidal antibody titers. Volunteers who received CVD 111 at 10(7) CFU had geometric mean Ogawa titers four to five times higher than those of volunteers who received the lower dose. In the second study, all dosage regimens were well tolerated in Peruvians. About 20% of volunteers who received CVD 111 at the high dose excreted the El Tor organism, compared to 7% in the low-dose group. CVD 111 was detected in the stools of two placebo recipients, neither of whom had symptoms or seroconverted. In all vaccine groups, 69 to 76% developed fourfold rises in Inaba vibriocidal antibodies. Among those who received the bivalent vaccine, 53 to 75% also developed significant rises in Ogawa vibriocidal antibodies. We conclude that it is feasible to produce a single-dose, oral bivalent vaccine that is safe and immunogenic against both biotypes (El Tor and classical) and both serotypes (Inaba and Ogawa) of cholera for populations in both developed and developing parts of the world.
Electrically Controllable All-Fiber PMD Emulator Using a Compact Array of Thin-Film Microheaters (2004)

An electrically controllable, all-fiber polarization-mode dispersion (PMD) emulator is constructed using thin-film microheaters to temperature tune the birefringence of 30 PM-fiber sections spliced at 45/spl deg/ angles. Compact packaging is achieved by mounting the fiber heaters onto an array of silicon V-grooves. The advantages of this electrically tunable emulator design are low loss, negligible PDL, simple construction, no internal reflections, and no moving parts.
An essential role for Langerhans cell-derived IL-1 beta in the initiation of primary immune responses in skin (1993)

Langerhans cells (LC) are Ag-presenting cells required for induction of primary immune responses in skin. After activation by Ag, LC express increased levels of MHC class II Ag, exhibit increased accessory cell activity, and migrate to regional lymph nodes where they stimulate T cells. One of the earliest manifestations of LC activation is the accumulation of increased amounts of IL-1 beta mRNA in LC within 15 min after exposure to contact allergens in vivo. To determine if enhanced IL-1 beta production by LC could be causally linked to epicutaneous sensitization, we injected IL-1 beta intradermally into the ears of BALB/c mice and extracted total epidermal RNA 4 h later. A quantitative reverse transcriptase-polymerase chain reaction technique was used to compare changes in IL-1 alpha, IL-1 beta, macrophage inflammatory protein 2, IL-10, TNF-alpha, and 1-A alpha chain mRNA signals caused by intradermally-injected IL-1 beta to those caused by intradermal IL-1 alpha or TNF alpha, or by topical application of the contact allergen trinitrochlorobenzene (3% TNCB). Intradermal injection of 25 ng IL-1 beta resulted in 5-to 100-fold enhancement of mRNA signals for IL-1 alpha, IL-1 beta, MIP-2, IL-10, TNF alpha, and class II I-A alpha, mimicking the changes caused by allergen. In contrast, injection of equivalent amounts of IL-1 alpha or TNF alpha did not significantly alter the epidermal cytokine pattern. Simulating the effects of topically applied TNCB, intradermally-injected IL-1 beta (but not IL-1 alpha or TNF alpha) also caused enhancement of LC MHC class II expression. In addition, LC derived from IL-1 beta-injected skin were 2 to 3 times more potent accessory cells in an anti-CD3 proliferation assay than LC from IL-1 alpha or sham-injected skin. Finally, injection of hamster anti-mIL-1 beta mAb into the skin prior to TNCB treatment completely prevented sensitization to this allergen, although injections of similar amounts of hamster anti-mIL-1 alpha mAb or PBS were without effect. Taken together, our data indicate that dendritic cell-derived IL-1 beta may be a critical molecule required for initiation of primary immune responses in skin.
An Introduction to 3D Microscopy Techniques (2008)

Abstract In the earliest years of microscopy, it was well understood that visualization of the finest details was often limited by the ‘intrusion’ of light from out-of-focus planes. For many decades the only solution to this dilemma was to limit microscopic studies to very thin samples or to physically squash or slice thicker samples. More recently, biomedical research has driven the need for microscopes that can resolve very fine detail in 3 dimensions within intact, and often living, specimens. The use of fluorescence labeling further exacerbates the problem of out-of-focus light because signal is generated throughout the volume of the sample. The following article describes the most prevalent techniques for 3D imaging and important optical considerations for achieving highest image quality.
Maximizing Non-monotone Submodular Functions (2011)

Submodular maximization generalizes many important problems including Max Cut in directed and undirected graphs and hypergraphs, certain constraint satisfaction problems, and maximum facility location problems. Unlike the problem of minimizing submodular functions, the problem of maximizing submodular functions is NP-hard. In this paper, we design the first constant-factor approximation algorithms for maximizing nonnegative (non-monotone) submodular functions. In particular, we give a deterministic local-search $\frac{1}{3}$-approximation and a randomized $\frac{2}{5}$-approximation algorithm for maximizing nonnegative submodular functions. We also show that a uniformly random set gives a $\frac{1}{4}$-approximation. For symmetric submodular functions, we show that a random set gives a $\frac{1}{2}$-approximation, which can also be achieved by deterministic local search. These algorithms work in the value oracle model, where the submodular function is accessible through a black box returning $f(S)$ for a given set S. We show that in this model, a $(\frac{1}{2}+\epsilon)$-approximation for symmetric submodular functions would require an exponential number of queries for any fixed $\epsilon>0$. In the model where f is given explicitly (as a sum of nonnegative submodular functions, each depending only on a constant number of elements), we prove NP-hardness of $(\frac{5}{6}+\epsilon)$-approximation in the symmetric case and NP-hardness of $(\frac{3}{4}+\epsilon)$-approximation in the general case.
Recombinant immunotoxins containing the VH or VL domain of monoclonal antibody B3 fused to Pseudomonas exotoxin (1993)

We prepared recombinant immunotoxins in Escherichia coli in which the VH or VL domains of mAb B3 were fused to a truncated form of Pseudomonas exotoxin (PE) (PE38KDEL). mAb B3 binds to a carbohydrate Ag found on the surfaces of many types of cancers and only a few normal tissues. PE38KDEL is a 38-kDa form of PE (66 kDa) that is missing the cell-binding domain of PE and has the carboxyl end changed from REDLK to KDEL. We show that immunotoxins in which the H chain or the L chain V region is fused to PE38KDEL bind to and kill carcinoma cells containing the B3 Ag. B3 Ag-negative cells were not affected. The cytotoxicity of these molecules is between 20- and 100-fold less than B3(Fv)-immunotoxins, containing both the H and L chain V regions. The VL-containing toxin was more active than the VH-containing toxin, indicating that the L chain of mAb B3 probably contributes more to Ag-binding than the H chain. Refolding experiments show that B3(VL)-PE38KDEL aggregates less than the VH-derivative or than a single chain immunotoxin B3(Fv)-PE38KDEL, which contains both domains in a single chain form. Furthermore, in addition to monomers, active homodimers of B3(VH)- and B3(VL)-PE38KDEL were obtained from renaturation experiments. The VL-toxin dimers, which might have their binding regions arranged in a manner similar to Bence Jones proteins (L chain homodimers), were found to have almost the same cytotoxicity as the monomers, whereas the VH-toxin dimers had decreased cytotoxic activity.
Suppression of experimental uveitis with monoclonal antibodies to ICAM-1 and LFA-1. (1994)

These findings indicate that ICAM-1, LFA-1-dependent pathways are involved in the pathogenesis of EAU. In addition, these pathways seem to be required for both the induction and the development of this disease.
Uncooled thermal imaging using a piezoresistive microcantilever (1996)

The operation of an uncooled, microcantilever-based infrared (IR) imaging device is demonstrated. Bending of the microcantilever is a function of the IR radiation intensity incident on the cantilever surface. The infrared image of the source is obtained by rastering a microfabricated cantilever over the image formed at the focal plane of a concave mirror. The bending variation of the microcantilever, as it scanned the focal plane of the mirror, is used to construct an infrared image of the source in front of the mirror. The thermal image obtained by scanning a single element cantilever is presented.
Cell Squeezing as a Robust, Microfluidic Intracellular Delivery Platform (2013)

Rapid mechanical deformation of cells has emerged as a promising, vector-free method for intracellular delivery of macromolecules and nanomaterials. This technology has shown potential in addressing previously challenging applications; including, delivery to primary immune cells, cell reprogramming, carbon nanotube, and quantum dot delivery. This vector-free microfluidic platform relies on mechanical disruption of the cell membrane to facilitate cytosolic delivery of the target material. Herein, we describe the detailed method of use for these microfluidic devices including, device assembly, cell preparation, and system operation. This delivery approach requires a brief optimization of device type and operating conditions for previously unreported applications. The provided instructions are generalizable to most cell types and delivery materials as this system does not require specialized buffers or chemical modification/conjugation steps. This work also provides recommendations on how to improve device performance and trouble-shoot potential issues related to clogging, low delivery efficiencies, and cell viability.
Inhibition of Platelet Aggregation by Inhaled Nitric Oxide in Patients with Acute Respiratory Distress Syndrome (1995)

In patients with ARDS and without preexisting coagulation disorders, the beneficial effects of inhaled nitric oxide on arterial oxygenation and pulmonary circulation are associated with a significant inhibition of platelet aggregation. This antithrombotic effect is not associated with a significant prolongation of the bleeding time.
Wavelet and footprint sampling of signals with a finite rate of innovation (2004)

We consider classes of not bandlimited signals, namely streams of Diracs and piecewise polynomial signals, and show that these signals can be sampled and perfectly reconstructed using wavelets as sampling kernel. Due to the multiresolution structure of the wavelet transform, these new sampling theorems naturally lead to the development of a new resolution enhancement algorithm based on wavelet footprints (Dragotti, P.L. and Vetterli, M., IEEE Trans. Sig. Process., vol.51, no.5, p.1306-23, 2003). Preliminary results show the potentiality of this algorithm.
Locked nucleic acids: a promising molecular family for gene-function analysis and antisense drug development. (2001)

Locked nucleic acids (LNAs) are a family of conformationally locked oligonucleotide analogs inducing unprecedented binding affinity towards DNA/RNA target sequences. Importantly, by virtue of the structural resemblance of LNAs to natural nucleic acid monomers, a combination of LNA chemistry with other oligonucleotide chemistries can be exploited to fine-tune the properties towards optimized antisense drug development and target validation technology. The first promising antisense results from experiments with LNA in living animals are described.
Effect of Stress in the Deposited Silicon Nitride Films on Boron Diffusion of Silicon (1995)

The effect of stress in silicon nitride films on boron diffusion of silicon has been studied. During annealing in nitrogen, the degree of the retardation in boron diffusion becomes larger as the temperature becomes lower and the thickness of nitride films increases. On the other hand, boron diffusion of Si covered with very thin nitride films is enhanced for long diffusion times. These results suggest that nitride film stress makes the region near the surface of the silicon substrate compressed and changes vacancy and interstitial concentrations.
Unexpected High Response Rate to Traditional Therapy after Dendritic Cell‐Based Vaccine in Advanced Melanoma: Update of Clinical Outcome and Subgroup Analysis (2010)

We reviewed the clinical results of a dendritic cell‐based phase II clinical vaccine trial in stage IV melanoma and analyzed a patient subgroup treated with standard therapies after stopping vaccination. From 2003 to 2009, 24 metastatic melanoma patients were treated with mature dendritic cells pulsed with autologous tumor lysate and keyhole limpet hemocyanin and low‐dose interleukin‐2. Overall response (OR) to vaccination was 37.5% with a clinical benefit of 54.1%. All 14 responders showed delayed type hypersensitivity positivity. Median overall survival (OS) was 15 months (95% CI, 8–33). Eleven patients underwent other treatments (3 surgery, 2 biotherapy, 2 radiotherapy, 2 chemotherapy, and 4 biochemotherapy) after stopping vaccination. Of these, 2 patients had a complete response and 5 a partial response, with an OR of 63.6%. Median OS was 34 months (range 16–61). Our results suggest that therapeutic DC vaccination could favor clinical response in patients after more than one line of therapy.
Nanocellulose: a new ageless bionanomaterial (2013)

Owing to the hierarchical structure of cellulose, nanoparticles can be extracted from this naturally occurring polymer. Multiple mechanical shearing actions allow the release of more or fewer individual microfibrils. Longitudinal cutting of these microfibrils can be achieved by a strong acid hydrolysis treatment, allowing dissolution of amorphous domains. The impressive mechanical properties, reinforcing capabilities, abundance, low density, and biodegradability of these nanoparticles make them ideal candidates for the processing of polymer nanocomposites. With a Young's modulus in the range 100–130 GPa and a surface area of several hundred m2 g−1, new promising properties can be considered for cellulose.
Acrylamide Formation Mechanism in Heated Foods (2003)

Recent findings of a potential human carcinogen, acrylamide, in foods have focused research on the possible mechanisms of formation. We present a mechanism for the formation of acrylamide from the reaction of the amino acid asparagine and a carbonyl-containing compound at typical cooking temperatures. The mechanism involves formation of a Schiff base followed by decarboxylation and elimination of either ammonia or a substituted imine under heat to yield acrylamide. Isotope substitution studies and mass spectrometric analysis of heated model systems confirm the presence of key reaction intermediates. Further confirmation of this mechanism is accomplished through selective removal of asparagine with asparaginase that results in a reduced level of acrylamide in a selected heated food.
Infectious bursal disease virus structural proteins expressed in a baculovirus recombinant confer protection in chickens (1993)

Plasmids were prepared that contained cDNA segments of the large genomic segment A of infectious bursal disease virus (IBDV) strain GLS-5. The genes encoding the IBDV structural proteins (VP2, VP3 and VP4) were introduced into the baculovirus transfer vector pBlueBacI to obtain a recombinant baculovirus vIBD-7. When insect cells were infected with recombinant viruses, the result was synthesis of IBDV precursor proteins which were processed by the viral protease. The recombinant IBDV antigens were characterized by immunoprecipitation with monoclonal antibodies (MAbs) and polyclonal antiserum to IBDV, and by antigen-capture ELISA using a panel of IBDV-specific MAbs. The recombinant IBDV antigens closely resembled the native IBDV proteins and reacted with all the GLS-5 strain-specific neutralizing MAbs that recognize only conformational epitopes of IBDV. When susceptible chickens were inoculated with the recombinant IBDV antigens, virus-neutralizing antibodies were induced that conferred up to 79% protection against IBDV challenge.
Conjugation of Ligands at the 5‘-End of CpG DNA Affects Immunostimulatory Activity (2002)

Bacterial DNA and synthetic oligonucleotides containing unmethylated CpG dinucleotides (CpG DNA) activate the vertebrate immune system and promote Th1-like immune responses. Several CpG DNAs are currently being tested in clinical trials as either alone or in combination with vaccines, antibodies, and allergens separately or as conjugates for a number of disease indications including cancers, allergies, and asthma. In this paper, we show that conjugation of an oligonucleotide and a CpG DNA through their 5'-ends (5'-5'-linked DNA) significantly reduces the immunostimulatory activity of the CpG DNA. In addition, we found that the reduction in immunostimulatory activity of 5'-5'-linked CpG DNA depends on the size of the oligonucleotide conjugated to CpG DNA. Conjugation of a smaller group or molecule, such as a phosphorothioate group, at the 5'-end of CpG DNA has an insignificant effect on immunostimulatory activity. However, conjugation of a mononucleotide, tetra- or longer oligonucleotide or a fluorescein molecule to the 5'-end of a CpG DNA (5'-5'-linked DNA) significantly suppresses the immunostimulatory activity of CpG DNA. Surprisingly, conjugation of an oligonucleotide or a ligand through the 3'-end of CpG DNA (3'-3'-linked DNA) has an insignificant effect on immunostimulatory activity. Studies of cellular uptake and activation of transcription factor NF-kappaB in J774 cells using fluorescein-conjugated CpG DNAs suggest that the differences in the immune stimulation of 5'- and 3'-end-conjugated CpG DNAs is not as a result of differences in their cellular uptake properties. These results suggest that for optimal immunostimulatory activity, ligands should not be attached at the 5'-end of the CpG DNA.
The checkerboard tissue block. An improved multitissue control block. (1990)

We describe an improved method of embedding a large number of tissue samples in a single, normal-sized paraffin block. Because the tissues are evenly distributed in a checkerboard arrangement, they can be readily identified by their position in the resulting sections. This device permits rapid and inexpensive screening of new histologic reagents, and facilitates intra- and interlaboratory quality control.
Vanadium compounds as insulin mimics. (1995)

That vanadium compounds act in an insulin-mimetic fashion both in vitro and in vivo has been well established. Both inorganic and organic vanadium compounds have been shown to lower plasma glucose levels, increase peripheral glucose uptake, improve insulin sensitivity, decrease plasma lipid levels, and normalize liver enzyme activities in a variety of animal models of both type I and type II diabetes. Vanadium treatment of diabetic animals does not restore plasma insulin levels but may spare pancreatic insulin. Elucidation of the mechanism(s) of action and potentiation of vanadium's insulin-mimetic effect by appropriate ligand binding would seem to be the highest priorities for future investigation.
Treating Patients with Severe Sepsis (1999)

Sepsis is an infection-induced syndrome defined as the presence of two or more of the following features of systemic inflammation: fever or hypothermia, leukocytosis or leukopenia, tachycardia, and tachypnea or a supranormal minute ventilation.1 When an organ system begins to fail because of sepsis, the sepsis is considered severe. Each year, sepsis develops in more than 500,000 patients in the United States, and only 55 to 65 percent survive.2,3 Fortunately, the death rates in some subgroups of patients with sepsis-induced organ failure have decreased, even though there is no specific therapy for sepsis.3,4 The reduced mortality may be . . .