gebhart/patrepeval huggingface dataset:
Mismatched single stranded antisense oligonucleotides can induce efficient dystrophin splice switching (2011)

This raises the possibility that mismatched AOs could still be therapeutically applicable in some cases, negating the necessity to produce patient-specific compounds.
Tumor necrosis factor receptor superfamily. (1997)

Tumor necrosis factor (TNF) is a powerful cytokine which is involved in the immune and pro-inflammatory response. The TNF receptors (TNF-R1 and TNF-R2) are the sole mediators of TNF signaling. The receptors consist of a disulfide rich domain which recognizes TNF, a transmembrane helix, and a cytoplasmic domain. Signaling occurs when a TNF trimer binds two or three receptors in an extracellular complex which permits aggregation and activation of the cytoplasmic domains. The complex is then endocytosed where it dissociates at low pH. We have now determined the structure of the soluble extracellular domain of TNF-R1 in two crystal forms at pH 3.7 in addition to our earlier report of one form at pH 7.5. One low pH form diffracts to 1.85 A and the entire polypeptide sequence has now been traced for this protein. The C-terminal 20 residues of the protein which were disordered in all previous structures show a different topology and disulfide connectivity to that seen in the remainder of the structure. In all crystal forms, the uncomplexed soluble extracellular domain of the type I TNF-R (sTNF-R1) exists as a dimer. At low pH the dimer buries a large amount of solvent accessible surface (2,900 A2), over 800 A2 greater than the area buried by TNF complexation. This dimer at low pH is different than both dimers observed in our previous pH 7.5 structure of unliganded sTNF-R1. We suggest that the low pH dimer forms during endocytosis and as the dimer completely buries the TNF interaction surface, the dimer would break up the receptor TNF complex. We have identified two distinct structural modules in sTNF-R1, a type A and a type B module. We suggest that these modules are the unit of structural conservation rather than the 6 cysteine subdomain. Although the orientation of these modules with respect to each other is sensitive to crystal packing, complexation, and pH, the modules themselves are structurally well conserved between and within the known sTNF-R1 structures. This modular approach will allow us to build accurate models for all members of the TNF-R superfamily.
A novel monoclonal antibody for detection of galectin-9 in tissue sections: application to human tissues infected by oncogenic viruses (2012)

The 1G3 monoclonal antibody will be a powerful tool to assess galectin-9 expression and distribution especially in diseases related to oncogenic viruses.
Measurement of Localized Cartilage Volume and Thickness of Human Knee Joints by Computer Analysis of Three-Dimensional Magnetic Resonance Images (1998)

Standard resolution MR images with fat-suppressed contrast lead to an objective and reproducible measurement of spatial dimensions of articular cartilage when analyzed semi-automatically using computerized edge-detection methods.
Protein A immunoadsorption in the treatment of malignant disease. (1988)

Circulating immune complexes (CIC) are known to be present in cancer patients and are responsible for much of the cancer-associated immunosuppression. Removal or modulation of these "blocking factors" can reverse the immunosuppression. Protein A from Staphylococcus aureus has the unusual property of binding to CIC with high avidity. Use of protein A as an immunoadsorbent in extracorporeal immunotherapy affinity columns has resulted in antitumor and antiviral responses in animals. Our group developed a multicenter trial to assess toxicity and antitumor response with this biologic response modifier alone. Overall, 24% (21 of 87 patients) had objective tumor regressions including both partial responses (PR) and less than PR. No complete responses (CR) were observed. Responses were observed in acquired immune deficiency syndrome (AIDS)-related Kaposi's sarcoma (six of 17 PR; two of 17 less than PR; overall, 47%), breast adenocarcinoma (five of 22 PR; three of 22 less than PR; overall response, 36%), colon adenocarcinoma, (one PR, one less than PR; overall response, 11%), and non-oat cell lung carcinoma (two of seven less than PR). The procedure was well tolerated and could be performed on an outpatient basis. No adverse reaction was observed in 735 of 1,113 treatments (66%). The most common adverse effect was an "influenza-like" syndrome consisting of fever and chills. Pain was present in 12% of the patients. There were no study-related deaths. Serum IgG and CIC levels did not statistically change due to therapy in responding or nonresponding patients. Complement levels remained within the normal range. Liver and renal tests remained stable throughout the study. In summary, protein A immunoadsorption of plasma is well tolerated in the outpatient clinic, has demonstrated antitumor activity in resistant solid tumors, and functions as a biologic response modifier.
Cytokine Gene Expression After Myocardial Infarction in Rat Hearts (1998)

These findings suggest the possible involvement of cytokines during the remodeling process of the noninfarcted left ventricular myocardium.
Designing incentive compatible contracts for effective demand management (2000)

Demand relief from customers can help a utility (or any "load serving entity") solve a variety of problems. There exist all sorts of different demand management programs that utilities use. A critical issue is the incentive paid to the customer to participate in demand management programs and provide load relief. The utility has to design cost effective yet attractive demand management contracts. The main goal is to get load relief when needed, and to do so in a cost effective way. Customers sign up for programs when the benefits they derive in the form of up front payments, demand discounts and interruption payments exceed their cost of interruption. In order to design such contracts, mechanism design with the revelation principle is adopted from game theory and applied to the interaction between a utility and its customers. The idea behind mechanism design is to design an incentive structure that encourages customers to sign up for the right contract and reveal their true value of power (and thus, the value of power interruptibility).
Stretchable gold conductors embedded in PDMS and patterned by photolithography: fabrication and electromechanical characterization (2010)

Stretchable gold conductors embedded in polydimethylsiloxane (PDMS) films were successfully prepared using standard photolithography. The minimum feature sizes patterned in the metal film and PDMS encapsulation are 10 µm and 20 µm, respectively. The micro-patterned conductors are robust to uni-axial (1D) and radial (2D) stretching with applied strains of tens of percent. The electrical response of the conductors follows a nonlinear increase with strain, and is reversible. The extensive stretchability of the conductors relies on a randomly and independently distributed network of micro-cracks (∼100 nm long) in the metal film on PDMS. The micro-cracks elongate to a few microns length both in the stretching and normal directions in 1D stretching but during 2D stretching, the micro-cracks grow and form 'dry mud' islands leaving the gold microstructure inside the islands intact. Patterning metallic thin films directly onto elastomeric substrates opens a promising route for microelectrodes and interconnects for soft and ultra-compliant MEMS and electronic devices.
Oogenesis in cultures derived from adult human ovaries (2005)

Ten years ago, we reported that in adult human females the ovarian surface epithelium (OSE) is a source of germ cells. Recently, we also demonstrated that new primary follicles are formed by assembly of oocytes with nests of primitive granulosa cells in the ovarian cortex. The components of the new primary follicles, primitive granulosa and germ cells, differentiated sequentially from the OSE, which arises from cytokeratin positive mesenchymal progenitor cells residing in the ovarian tunica albuginea. In the present study, we investigated the possibility that the oocytes and granulosa cells may differentiate in cultures derived from adult human ovaries. Cells were scrapped from the surface of ovaries and cultured for 5 to 6 days, in the presence or absence of estrogenic stimuli [phenol red (PhR)]. The OSE cells cultured in the medium without PhR differentiated into small (15 micron) cells of granulosa phenotype, and epithelial, neural, and mesenchymal type cells. In contrast, OSE cells cultured in the presence of PhR differentiated directly into large (180 micron) cells of the oocyte phenotype. Such cells exhibited germinal vesicle breakdown, expulsion of the polar body, and surface expression of zona pellucida proteins, i.e. characteristics of secondary oocytes. These in vitro studies confirm our in vivo observations that in adult human ovaries, the OSE is a bipotent source of oocytes and granulosa cells. Development of numerous mature oocytes from adult ovarian stem cells in vitro offers new strategies for the egg preservation, IVF utilization, and treatment of female infertility. In addition, other clinical applications aiming to utilize stem cells, and basic stem cell research as well, may employ totipotent embryonic stem cells developing from fertilized oocytes.
Quantitative and sensitive in vitro assay for osteoinductive activity of demineralized bone matrix (2003)

A sensitive, rapid, reliable and quantitative method to check the bone forming potential of demineralized bone matrix (DBM) has been developed. The osteoinductivity of the bone morphogenetic proteins (BMPs), present in DBM, can be measured in vitro using a pluripotent myoblast C2C12 cell line. Alkaline phosphatase activity induced by co-incubation of DBM with C2C12 cells was dose-responsive and corresponds to the amount of active BMPs in DBM. Bone forming potential was simultaneously tested in vivo by implanting DBM intra-muscularly in nude rats. ALP activity induced in C2C12 cells, correlated with bone formation in vivo (r=0.88), determined by alkaline phosphatase activity, mineralization density and histomorphology of the DBM explants. Results from DBM batches, originating from five established Bone Banks, showed good consistency between in vitro and in vivo assays. However, DBM activity varied widely from bank to bank as well as from batch to batch within the same bank.
Ligand mediated iron catalyzed dimerization of terminal aryl alkynes: scope and limitations (2014)

Regioselective dimerization of terminal aryl alkynes to produce conjugated enynes has been achieved using FeCl3 and KO(t)Bu in the presence of either DMEDA or dppe. The reaction proceeds smoothly in toluene at 145 °C for 2 h to give the corresponding head-to-head dimers in good to excellent yields (54 to 99%) with high E-selectivity (67 : 33 to 83 : 17 E/Z). Both strongly electron-donating and electron-withdrawing groups are compatible with this procedure. The bidentate phosphine (dppe) ligand exhibits better catalytic activity than the bidentate amine (DMEDA). The aliphatic acetylene fails to react under this catalytic system which suggests that potassium tertiary butoxide activates the conjugated system of aryl acetylene through cation-pi interaction and pi-pi interaction. A radical inhibitor (galvinoxyl or TEMPO) completely suppresses the reaction. Employing FeCl2 as a catalyst instead of FeCl3, only phenyl acetylene afforded the corresponding head to head dimer in good yield. Mechanistic pathways for both FeCl3 catalyzed dimerization of aryl alkynes and FeCl2 catalyzed dimerization of phenyl acetylene have been proposed.
Using timestamping to optimize two phase commit (2002)

The two-phase commit (2PC) protocol is used to guarantee the serializability of distributed transactions. The message cost of the standard 2PC has led to efforts to optimize the protocol and reduce the number of messages required. The common optimizations require that each cohort of a transaction be terminated (finished with normal accessing of data) in order for these optimizations to lead to serial schedules. The use of timestamps is suggested as a substitute for knowing when cohorts are terminated, and it is shown how the 2PC protocol itself can be used to choose the timestamps. The key to this is to permit cohorts to vote transaction time ranges within which the transaction must commit or else be aborted. Using time ranges, the read only optimization and early release of read locks can be supported. The transaction times chosen are appropriate for identifying versions of data in a multiversion rollback database.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Concise Drug Review: Pazopanib and Axitinib (2012)

Pazopanib and axitinib are both U.S. Food and Drug Administration approved ATP-competitive inhibitors of the vascular endothelial growth factor receptor. Pazopanib and axitinib have been shown to be effective and tolerable treatment options for patients with metastatic renal cell cancer and therefore have enlarged the armamentarium for this disease. This concise drug review discusses the clinical benefits, clinical use, mechanism of action, bioanalysis, pharmacokinetics, pharmacogenetics, pharmacodynamics, drug resistance, toxicity, and patient instructions and recommendations for supportive care for these two drugs.
THE ISOLATION AND CYTOLOGY OF TWO PIGMENT CELL STRAINS FROM B-16 MOUSE MELANOMAS. (1964)

Summary Two cell lines (HFH-14, HFH-18) isolated from B16 mouse melanomas were established as monolayer cultures. These cells retained their capacity of melanin pigment formation after repeated passages in vitro. According to their morphology and developmental history, various cell types, namely, melanoblasts, melanocytes, and mature melanocytes, are identified. These cells when inoculated into C57BL mice produced typical melanotic tumors which closely resembled the original melanomas from which the cell strains were derived. These cells have all the characteristics of melanocytes and are considered to be true pigment cell strains.
Routing in High-Speed Networks (1993)

In the 1990s, significant advances in fiber optic and switching technology have precipitated the current explosion in the amount of research in future high-speed networks. The challenges facing high-speed network researchers result not just from the high data transmission rate but also from other new characteristics not previously encountered in traditional circuit-switched or packet-switched networks. For example, features such as large propagation delay as compared to transmission delay, diverse application demands, constraints on call processing capacity, and quality-of-service (QOS) support for different applications all present new challenges which arise from the new technology and new applications. Thus, much research is needed not just to improve existing technologies, but to seek a fundamentally different approach toward network architectures and protocols. In particular, new flow control and routing algorithms need to be developed to meet these new challenges. The goal of this dissertation is to solve routing problems in the context of high-speed networks taking into account the new network environment. In order to better understand the influence of these new network characteristics on the routing problem; we first study the computational delays associated with call admission, routing and call setup in future high-speed networks. This study also leads us to explore the similarity between call setup in high-speed networks and circuit-switched networks and to study how approaches toward routing in circuit-switched networks can be adapted for routing in high-speed networks. Specifically, based on the Markov Decision Process (MDP) framework, we next design and evaluate state-dependent routing algorithms for high-speed networks which account for these new network characteristics. Finally, we consider a Virtual Path (VP) concept that has been proposed to simplify traffic control and resource management in future high-speed networks. Thus, in the last part of this dissertation, we also demonstrate the efficiency of MDP-based routing algorithms in virtual path-based networks.
Hepatocarcinogenesis in FXR−/− Mice Mimics Human HCC Progression That Operates through HNF1α Regulation of FXR Expression (2012)

Farnesoid X receptor (FXR) (nuclear receptor subfamily 1, group H, member 4) is a member of nuclear hormone receptor superfamily, which plays essential roles in metabolism of bile acids, lipid, and glucose. We previously showed spontaneously hepatocarcinogenesis in aged FXR(-/-) mice, but its relevance to human hepatocellular carcinoma (HCC) is unclear. Here, we report a systematical analysis of hepatocarcinogenesis in FXR(-/-) mice and FXR expression in human liver cancer. In this study, liver tissues obtained from FXR(-/-) and wild-type mice at different ages were compared by microarray gene profiling, histological staining, chemical analysis, and quantitative real-time PCR. Primary hepatic stellate cells and primary hepatocytes isolated from FXR(-/-) and wild-type mice were also analyzed and compared. The results showed that the altered genes in FXR(-/-) livers were mainly related to metabolism, inflammation, and fibrosis, which suggest that hepatocarcinogenesis in FXR(-/-) mice recapitulated the progression of human liver cancer. Indeed, FXR expression in human HCC was down-regulated compared with normal liver tissues. Furthermore, the proinflammatory cytokines, which were up-regulated in human HCC microenvironment, decreased FXR expression by inhibiting the transactivity of hepatic nuclear factor 1α on FXR gene promoter. Our study thereby demonstrates that the down-regulation of FXR has an important role in human hepatocarcinogenesis and FXR(-/-) mice provide a unique animal model for HCC study.
Host Specificity and Tomato-Related Race Composition of Phytophthora infestans Isolates in Taiwan During 2004 and 2005 (2008)

Late blight, caused by Phytophthora infestans, is a major disease of tomato in cool and wet environments. In this study, we report on the host specificity, race composition, and variation among races revealed by amplified fragment length polymorphism (AFLP) of P. infestans isolated from tomato production areas in Taiwan. In all, 177 P. infestans isolates were collected in Taiwan during 2004 and 2005. All were aggressive on both potato and tomato. Nine physiological races were identified based on disease response on a set of tomato differentials developed by the Asian Vegetable Research and Development Center–The World Vegetable Center. Eighty-seven polymorphic bands from 32 isolates of four races were detected by AFLP. No significant correlation between the polymorphism and the races was found using cluster analysis. This study revealed that a high variability of race composition among the asexual population of P. infestans isolates existed in Taiwan during 2004 and 2005. Breeding new tomato cultivars for resistance to P. infestans is an urgent and ongoing need because new races of the pathogen appeared continuously in Taiwan in past years. Further analysis of the genomic diversity is necessary to determine whether the high genetic variation of P. infestans is related to the complex race composition.
Oral Testosterone in Oil Plus Dutasteride in Men: A Pharmacokinetic Study (2005)

Testosterone (T) is not administered orally, because it has been reported to be rapidly metabolized by the liver. We hypothesized that sufficient doses of T or T enanthate (TE), administered orally in oil, would result in clinically useful elevations in serum T. We also hypothesized that coadministration of dutasteride (D) with T or TE would minimize increases in serum DHT seen previously with oral administration. Therefore, we conducted a pharmacokinetic study of oral T and TE in oil, with and without concomitant D, in normal men whose T production had been temporarily suppressed by the GnRH antagonist acyline. Thirteen healthy men (mean age, 24 +/- 6 yr) were enrolled and assigned to oral T (n = 7) and oral TE (n = 6) groups and were administered 200, 400, or 800 mg of either T or TE in sesame oil in the morning on 3 successive days 24 h after receiving acyline. Blood samples for measurement of serum T and dihydrotestosterone were obtained before T or TE administration and 0.5, 1, 2, 4, 6, 8, 10, 12, and 24 h after administration. Subjects were then administered D for 4 d before repeating the sequence of T or TE doses with D. Serum T was significantly increased in a dose-dependent fashion with the administration of oral T or TE in oil. Coadministration of D with oral T or TE significantly increased the 24-hr average serum T levels compared with administration of T or TE alone [average serum T after 400 mg dose, 8.7 +/- 3.0 nmol/l (T) and 8.3 +/- 5.7 nmol/l (TE) vs. 16.1 +/- 5.8 nmol/l (T +D) and 15.0 +/- 8.8 nmol/l (TE + D); P < 0.05 for T vs. T and D]. The administration of oral T or TE in oil combined with D results in unexpected and potentially therapeutic increases in serum T. Additional studies of this combination as a novel form of oral androgen therapy are warranted.
Ectopic regeneration of whiskers in the hooded rat from implanted lengths of vibrissa follicle wall (1967)

ABSTRACT A method is described for isolating and removing lengths of follicle wall, composed of the inner root sheath, outer root sheath and mesenchymal layer, from vibrissa follicles. These segments of follicle wall were transplanted into ear skin and, in one case, into an ovarian capsule. Seven of the thirteen implants originally dissected from the lower third of the follicle produced short whiskers up to 6 mm in length. Two further implants had also regenerated dermal papillae but not whiskers. The dermal papillae regenerated at the proximal end of the implants and appeared to derive from cells from the mesenchymal layer. None of the four implants obtained from above the lower third of the follicle regenerated dermal papillae or produced whiskers. The outer root sheaths of all of the implants which did not regenerate papillae or whiskers did, however, maintain their typical histological character. The possibility that maintenance of the implants was dependent on the presence of the mesenchymal layer is discussed. Whisker growth from transplanted lengths of follicle wall logically isolates the outer root sheath and/or the mesenchymal layer as the essential prerequisites for papilla regeneration.