gebhart/patrepeval huggingface dataset:
KRN8602 (MX2-Hydrochloride): An Active New Agent for the Treatment of Recurrent High-Grade Glioma (1999)

KRN8602 is an active new agent with minimal toxicity in the treatment of relapsed or refractory high-grade glioma. Further studies with KRN8602 in combination with other cytotoxics and in adjuvant treatment of gliomas are warranted.
FMT: First Step in a Long Journey (2013)

1 Montefiore Medical Center, Division of Gastroenterology, Bronx, New York, USA Correspondence: Lawrence J. Brandt, MD, Montefiore Medical Center, Division of Gastroenterology, 111 East 210 Street, Bronx, New York, New York 10467, USA. E-mail: [email protected]
Prevention of group B meningococcal disease by vaccination: a difficult task. (2004)

New Zealand has embarked on an immunisation program to reduce the incidence of disease caused by serogroup B Neisseria meningitidis. Similar immunisation programs in Norway and South America have shown good efficacy in older vaccinees (ie, persons receiving vaccinations), but variable efficacy in younger vaccinees. Protective efficacy correlates well with the ability of the vaccine to stimulate a fourfold rise in serum bactericidal antibodies. Unfortunately, second and third doses of serogroup B N. meningitidis vaccines do not boost serum bactericidal antibody titres to very high levels; consequently protective efficacy wanes within a few years of immunisation. The overall outcome of the immunisation program will reflect both the immunogenicity of the vaccine and the uptake of the vaccine by the target population. The especially high incidence of meningococcal disease in Pacific and Maori children means that particular efforts will need to be made to reach these groups.
Production of beta-carotene in Zymomonas mobilis and Agrobacterium tumefaciens by introduction of the biosynthesis genes from Erwinia uredovora (1991)

The Erwinia uredovora crtB, crtE, crtI, and crtY genes required for beta-carotene biosynthesis were introduced by conjugal transfer into an ethanol-producing bacterium, Zymomonas mobilis, and a phytopathogenic bacterium, Agrobacterium tumefaciens, in which no carotenoid is synthesized. The transconjugants of Z. mobilis and A. tumefaciens carrying these genes appeared as yellow colonies and produced 220 and 350 micrograms of beta-carotene per g of dry weight, respectively, in the stationary phase in liquid culture.
Droplets as Microreactors for High‐Throughput Biology (2007)

Inspired by the principles of biological evolution, biologists--and others--have in recent decades harnessed the power of "natural" selection to sift through huge libraries of genes and find those with desirable properties. At the same time, the demand for high-throughput biochemical and genetic assays and screens has driven the development of increasingly miniaturised assay systems. An exciting synergy is now emerging between these two fields, whereby the tools of ultrahigh-throughput screening promise to open up new directions in molecular engineering.
Photoaffinity labeling of serum vitamin D binding protein by 3-deoxy-3-azido-25-hydroxyvitamin D3 (1987)

3-Deoxy-3-azido-25-hydroxyvitamin D3 was covalently incorporated in the 25-hydroxyvitamin D3 binding site of purified human plasma vitamin D binding protein. Competition experiments showed that 3-deoxy-3-azido-25-hydroxyvitamin D3 and 25-hydroxyvitamin D3 bind at the same site on the protein. Tritiated 3-deoxy-3-azido-25-hydroxyvitamin D3 was synthesized from tritiated 25-hydroxyvitamin D3, retaining the high specific activity of the parent compound. The tritiated azido label bound reversibly to human vitamin D binding protein in the dark and covalently to human vitamin D binding protein after exposure to ultraviolet light. Reversible binding of tritiated 3-deoxy-3-azido-25-hydroxyvitamin D3 was compared to tritiated 25-hydroxyvitamin D3 binding to human vitamin D binding protein. Scatchard analysis of the data indicated equivalent maximum density binding sites with a KD,app of 0.21 nM for 25-hydroxyvitamin D3 and a KD,app of 1.3 nM for the azido derivative. Covalent binding was observed only after exposure to ultraviolet irradiation, with an average of 3% of the reversibly bound label becoming covalently bound to vitamin D binding protein. The covalent binding was reduced 70-80% when 25-hydroxyvitamin D3 was present, indicating strong covalent binding at the vitamin D binding site of the protein. When tritiated 3-deoxy-3-azido-25-hydroxyvitamin D3 was incubated with human plasma in the absence and presence of 25-hydroxyvitamin D3, 12% of the azido derivative was reversibly bound to vitamin D binding protein. After ultraviolet irradiation, four plasma proteins covalently bound the azido label, but vitamin D binding protein was the only protein of the four that was unlabeled in the presence of 25-hydroxyvitamin D3.
Effects of α2-Adrenoceptor Agonists on Perinatal Excitotoxic Brain Injury (2002)

Clonidine and dexmedetomidine are potent neuroprotectors that act by stimulating the alpha(2) adrenoceptors. These results obtained in a murine model of perinatal excitotoxic injury may be relevant to some forms of neonatal brain damage in humans.
Developmental regulation of Foxp3 expression during ontogeny (2005)

Thymectomy of neonatal mice can result in the development of autoimmune pathology. It has been proposed that thymic output of regulatory T (T reg) cells is delayed during ontogeny and that the development of autoimmune disease in neonatally thymectomized mice is caused by the escape of self-reactive T cells before thymectomy without accompanying T reg cells. However, the kinetics of T reg cell production within the thymus during ontogeny has not been assessed. We demonstrate that the development of Foxp3-expressing T reg cells is substantially delayed relative to nonregulatory thymocytes during ontogeny. Based on our data, we speculate that induction of Foxp3 in developing thymocytes and, thus, commitment to the T reg cell lineage is facilitated by a signal largely associated with the thymic medulla.
Cellular and Biochemical Differences between Two Attenuated Poxvirus Vaccine Candidates (MVA and NYVAC) and Role of the C7L Gene (2006)

The poxvirus strains NYVAC and MVA are two candidate vectors for the development of vaccines against a broad spectrum of diseases. Although these attenuated virus strains have proven to be safe in animals and humans, little is known about their comparative behavior in vitro. In contrast with MVA, NYVAC infection triggers greater cytopathic effect in a range of permissive and nonpermissive cell lines. The yields of NYVAC cell-associated virus in permissive cells (BHK-21) were slightly reduced compared with those of MVA infection. During the course of infection in HeLa cells, there is a translational block induced by NYVAC late in infection, which correlated with a marked increase in phosphorylation levels of the initiation factor eIF-2alpha. In contrast to MVA, the synthesis of certain late viral proteins was only blocked in NYVAC-infected HeLa cells. Electron microscopy (EM) analysis revealed that morphogenesis of NYVAC in HeLa cells was blocked at the stage of formation of immature viral forms. Phase-contrast microscopy, EM, flow cytometry, and rRNA analyses demonstrated that contrary to MVA, NYVAC infection induces potent apoptosis, a phenomenon dependent on activation of caspases and RNase L. Apoptosis induced by NYVAC was prevented when the virus gene C7L was placed back into the NYVAC genome, recovering the ability of NYVAC to replicate in HeLa cells and maintaining the attenuated phenotype in mice. Overall, our findings demonstrate distinct behavior between NYVAC and MVA strains in cultured cells, as well as a new role for the C7L viral gene as an inhibitor of apoptosis in NYVAC infection.
Palladium-Catalyzed Reactions of Hypophosphorous Compounds with Allenes, Dienes, and Allylic Electrophiles:  Methodology for the Synthesis of Allylic H-Phosphinates (2008)

Hypophosphorous compounds (MOP(O)H(2), M = H, R(3)NH) effectively participate in metal-catalyzed C-P bond-forming reactions with allenes, dienes, and activated allylic electrophiles under mild conditions. The catalytic system Pd(2)dba(3)/xantphos is crucial to avoid or minimize the competitive reductive transfer-hydrogenation pathway available to hypophosphorous acid derivatives. Further investigation into the allylation mechanism provided access to the analogy allylic acetate-allylic phosphinate, which then led to the development of a Pd-catalyzed rearrangement of preformed allylic phosphinates esters and, ultimately, to a catalytic dehydrative allylation of hypophosphorous acid with allylic alcohols. The reactions disclosed herein constitute efficient synthetic approaches, not only to prepare allylic H-phosphinic acids but also their esters via one-pot tandem processes. In addition, the potential of H-phosphinates as useful synthons for the preparation of other organophosphorus compounds is demonstrated.
Telemedicine Technology and Clinical Applications (1995)

TELEMEDICINE can be broadly defined as the use of telecommunications technologies to provide medical information and services. Although this definition includes medical uses of the telephone, facsimile, and distance education,<i>telemedicine</i>is increasingly being used as shorthand for remote electronic clinical consultation. Interest in the field has increased dramatically in the 1990s. State and federal allocations for telemedicine and related technologies are likely to exceed $100 million in fiscal 1994-1995.<sup>1</sup>At least 13 federal agencies, including the US Department of Commerce, Health Care Financing Administration (HCFA), Office of Rural Health Policy, and US Department of Defense, have begun telemedicine research and demonstration programs. Many states are using their own resources to build state-of-the-art telemedicine systems, some with capital investments exceeding $50 million. Faith in this technology is not universal, however. Depending on one's viewpoint, telemedicine may be seen as a valuable tool for providing badly needed specialty care services
The differential expression of SPARC in esophageal squamous cell carcinoma (2006)

Secreted protein, acidic and rich in cysteine (SPARC) is a matricellular protein that modulates cell adhesion and growth. The aim of this study was to assess the prevalence of SPARC mRNA and protein expression in esophageal squamous cell carcinoma (ESCC) and to investigate the role of SPARC in proliferation and metastasis of ESCC. The differential expression of SPARC between esophageal squamous cell carcinoma and its corresponding normal esophageal mucosa was analyzed by semiquantitative reverse transcription-polymerase chain reaction (RT-PCR), immunohistochemistry, as well as Western blotting. The expression of SPARC in ESCC was significantly higher than that in the corresponding normal esophageal mucosa as shown by semi-quantitative RT-PCR, immunohistochemistry and Western blotting. Meanwhile, SPARC protein was also significantly up-regulated in ESCC compared with the corresponding normal esophageal mucosa. SPARC protein was located in the cytoplasm and nuclei of ESCC cells. The results of Western blotting showed that out of 18 paired samples, SPARC was up-regulated in 13 cases, no significant differences were found for the other 5 cases. These findings revealed that SPARC was up-regulated in ESCC and was closely associated with ESCC metastasis. This study provides new insights into nuclei location of SPARC.
Effect of induced transient arousal on obstructive apnea duration (1995)

Six untreated male patients (age 19-55 yr) with obstructive sleep apnea underwent nocturnal polysomnography with acoustic stimulation to determine the effect of transient arousal on obstructive apneas during sleep. Binaural tone bursts (25-95 dB) were delivered in late expiration during the second obstructive apnea of a cycle consisting of four consecutive apneas. For the group, stimulated apneas were significantly shorter (P < 0.05, Fisher's protected least significant difference test) than were the unstimulated apneas when transient electrocortical arousal was elicited in both non-rapid-eye-movement (non-REM) sleep [mean 17 +/- 7 (SD) vs. 26 +/- 9, 23 +/- 10, and 26 +/- 12 s for 2nd vs. 1st, 3rd, and 4th apnea, respectively, of each cycle] and REM sleep (mean 19 +/- 10 vs. 35 +/- 15, 45 +/- 18, and 39 +/- 20 s). Without electrocortical arousal, the stimulated apnea was significantly shortened in non-REM (23 +/- 9 vs. 25 +/- 7, 24 +/- 8, and 26 +/- 8 s) but not in REM (32 +/- 16 vs. 37 +/- 12, 32 +/- 15, and 30 +/- 16 s). Tones delivered relatively early and late in the apnea were equally likely to be associated with resolution of the apnea. The nadir of arterial oxygen saturation of hemoglobin was inversely proportional to apnea length, with higher saturation nadirs associated with the stimulated apneas. These data indicate that transient arousal, induced by nonrespiratory stimulation, influences the resolution of obstructive apneas during sleep.
Security and encryption optical systems based on a correlator with significant output images (2000)

An improved optical security system based on two phase-only computer-generated masks is proposed. The two transparencies are placed together in a 4f correlator so that a known output image is received. In addition to simple verification, our security system is capable of identifying the type of input mask according to the corresponding output image it generates. The two phase masks are designed with an iterative optimization algorithm with constraints in the input and the output domains. A simulation is presented with the resultant images formed by the two phase-only elements. Various mask combinations are compared to show that a combination is unique and cannot be duplicated. This uniqueness is an advantage in security systems.
Inhibition of hamster melanoma growth by estrogen. (1987)

A malignant hamster melanoma cell line HM-1 derived from the heterogenous malignant hamster melanoma MM1 contains a specific, high affinity binding protein for estrogens. Partial purification of the binding protein with ammonium sulfate (40% saturation) increased mean binding content (3.1 +/- 1.2 (SD) fmol/mg protein) 15-fold without any change in affinity (10(10) M-1). The binding protein sedimented at 8-9S on 10-30% low salt sucrose gradients and 9-10S in the presence of 20 mM molybdate ion. Addition of 0.4 M KCl shifted the 8S peak to 4S. Binding was specific, saturable, and indicative of a single class of high affinity sites over a concentration range of 0.01-10.0 nM [3H]estradiol. Estradiol produced a dose related inhibition of HM-1 growth in vitro without altering the growth of an additional line (HM-2) which did not bind estrogen. The antiestrogen tamoxifen (10(-7) M) also significantly inhibited HM-1 melanoma growth in vitro, which was reversed by the addition of estradiol (10(-9) M). HM-1 xenografts grew faster in female BALB/c-nu/nu mice than male mice while there was no sex difference in HM-2 growth. Pharmacological doses of estradiol and the antiestrogen nafoxidine significantly inhibited HM-1 growth without altering tumor incidence or latency. Our observations suggest that HM-1 cell lines bind estrogens specifically and with high affinity and that hamster melanoma cells positive for this binding protein respond to estrogen.
Developing 3D microscopy with CLARITY on human brain tissue: Towards a tool for informing and validating MRI-based histology (2017)

Recent breakthroughs in magnetic resonance imaging (MRI) enabled quantitative relaxometry and diffusion-weighted imaging with sub-millimeter resolution. Combined with biophysical models of MR contrast the emerging methods promise in vivo mapping of cyto- and myelo-architectonics, i.e., in vivo histology using MRI (hMRI) in humans. The hMRI methods require histological reference data for model building and validation. This is currently provided by MRI on post mortem human brain tissue in combination with classical histology on sections. However, this well established approach is limited to qualitative 2D information, while a systematic validation of hMRI requires quantitative 3D information on macroscopic voxels. We present a promising histological method based on optical 3D imaging combined with a tissue clearing method, Clear Lipid-exchanged Acrylamide-hybridized Rigid Imaging compatible Tissue hYdrogel (CLARITY), adapted for hMRI validation. Adapting CLARITY to the needs of hMRI is challenging due to poor antibody penetration into large sample volumes and high opacity of aged post mortem human brain tissue. In a pilot experiment we achieved transparency of up to 8 mm-thick and immunohistochemical staining of up to 5 mm-thick post mortem brain tissue by a combination of active and passive clearing, prolonged clearing and staining times. We combined 3D optical imaging of the cleared samples with tailored image processing methods. We demonstrated the feasibility for quantification of neuron density, fiber orientation distribution and cell type classification within a volume with size similar to a typical MRI voxel. The presented combination of MRI, 3D optical microscopy and image processing is a promising tool for validation of MRI-based microstructure estimates.
Interleukin-17 promotes angiogenesis and tumor growth (2002)

Interleukin-17 (IL-17) is a CD4 T-cell-derived proinflammatory cytokine. We investigated the effects of locally produced IL-17 by tumors as a means to evaluate its biologic function. Although recombinant IL-17 protein or retroviral transduction of IL-17 gene into tumors did not affect in vitro proliferation, IL-17 transfectants grew more rapidly in vivo when compared with controls. Immunostaining for Factor VIII revealed that tumors transduced with IL-17 had significantly higher vascular density when compared with controls. IL-17 indeed elicited neovascularization in rat cornea. In addition, angiogenic activity present in the conditioned media of CD4 T cells was markedly suppressed by neutralizing monoclonal antibody to IL-17. IL-17 had no direct effect on the growth of vascular endothelial cells, whereas IL-17 significantly stimulated migration. IL-17 also markedly promoted the cord formation of vascular endothelial cells. In addition, IL-17 up-regulated elaboration of a variety of proangiogenic factors by fibroblasts as well as tumor cells. These findings reveal a novel role for IL-17 as a CD4 T-cell-derived mediator of angiogenesis that stimulates vascular endothelial cell migration and cord formation and regulates production of a variety of proangiogenic factors. Furthermore, they suggest that inhibition of biologic action of IL-17 may have therapeutic benefits when applied to angiogenesis-related disorders.
Targeted genome modification of crop plants using a CRISPR-Cas system (2013)

1. Jinek, M. et al. Science 337, 816–821 (2012). 2. Cho, S.W., Kim, S., Kim, J.M. & Kim, J.S. Nat. Biotechnol. 31, 230–232 (2013). 3. Cong, L. et al. Science 339, 819–823 (2013). 4. Mali, P. et al. Science 339, 823–826 (2013). 5. Hwang, W.Y. et al. Nat. Biotechnol. 31, 227–229 (2013). 6. Jiang, W., Bikard, D., Cox, D., Zhang, F. & Marraffini, L.A. Nat. Biotechnol. 31, 233–239 (2013). 7. Wang, H. et al. Cell 153, 910–918 (2013). 8. Geurts, A.M. et al. Science 325, 433 (2009). 9. Tong, C., Li, P., Wu, N.L., Yan, Y. & Ying, Q.L. Nature 467, 211–213 (2010). 10. Tesson, L. et al. Nat. Biotechnol. 29, 695–696 (2011). 11. Wu, H. & Zhang, Y. Genes Dev. 25, 2436–2452 (2011). 12. Gu, T.P. et al. Nature 477, 606–610 (2011). 13. Dawlaty, M.M. et al. Dev. Cell 24, 310–323 (2013). revision process of this work, an independent study reported the simultaneous generation of multiple mutations in mice7. Our work, together with the mice work, demonstrates that it should be feasible to produce genetargeted models in rodents and probably other mammalian species using the CRISPRCas systems.
Poly(ethylene oxide)-Based Delivery Systems (1994)

The release kinetics of monolithic drug delivery devices based on poly(ethylene oxide) (PEO) was investigated. Water soluble PEO's with molecular weights of 600,000 and 4,000,000 and two blends were studied. The water-swelling and dissolution characteristics of the two polymers and two blends, along with the diffusivity of the drug etofylline in the water-penetrated polymer gels were analyzed. The higher molecular weight PEO and the two blends underwent swelling rather than polymer dissolution. As a result, a non-constant release induced by the prevailing diffusive control was observed. Conversely, the drug release from the lower molecular weight PEO was a result of equal rates of swelling and dissolution, which gave a constant release rate.
Diffractive and holographic optics as optical combiners in head mounted displays (2013)

We review in this paper the various architectures that have been developed in industry to implement see-through head-mounted display (HMD) optics, especially for the consumer electronics market. We will focus our investigations on holographic and diffractive optics.
All-optical processing in coherent nonlinear spectroscopy (2004)

In spectroscopy, the fingerprint of a substance is usually comprised of a sequence of spectral lines with characteristic frequencies and strengths. Identification of substances often involves postprocessing, where the measured spectrum is compared with tabulated fingerprint spectra. Here we suggest a scheme for nonlinear spectroscopy, where, through coherent control of the nonlinear process, the information from the entire spectrum can be practically collected into a single coherent entity. We apply this for all-optical analysis of coherent Raman spectra and demonstrate enhanced detection and effective background suppression using coherent processing.
Novel Synthetic Antimicrobial Peptides against Streptococcus mutans (2007)

Streptococcus mutans, a common oral pathogen and the causative agent of dental caries, has persisted and even thrived on the tooth surface despite constant removal and eradication efforts. In this study, we generated a number of synthetic antimicrobial peptides against this bacterium via construction and screening of several structurally diverse peptide libraries where the hydrophobicity and charge within each library was varied incrementally in order to generate a collection of peptides with different biochemical characteristics. From these libraries, we identified multiple peptides with robust killing activity against S. mutans. To further improve their effectiveness, the most bactericidal peptides from each library were synthesized together as one molecule, in various combinations, with and without a flexible peptide linker between each antimicrobial region. Many of these "fusion" peptides had enhanced killing activities in comparison with those of the original nonconjoined molecules. The results presented here illustrate that small libraries of biochemically constrained peptides can be used to generate antimicrobial peptides against S. mutans, several of which may be likely candidates for the development of anticaries agents.