gebhart/patrepeval huggingface dataset:
An oligonucleotide hybridization approach to DNA sequencing (1989)

We have proposed a DNA sequencing method based on hybridization of a DNA fragment to be sequenced with the complete set of fixed-length oligonucleotides (e.g., 4(8) = 65,536 possible 8-mers) immobilized individually as dots of a 2-D matrix [(1989) Dokl. Akad. Nauk SSSR 303, 1508-1511]. It was shown that the list of hybridizing octanucleotides is sufficient for the computer-assisted reconstruction of the structures for 80% of random-sequence fragments up to 200 bases long, based on the analysis of the octanucleotide overlapping. Here a refinement of the method and some experimental data are presented. We have performed hybridizations with oligonucleotides immobilized on a glass plate, and obtained their dissociation curves down to heptanucleotides. Other approaches, e.g., an additional hybridization of short oligonucleotides which continuously extend duplexes formed between the fragment and immobilized oligonucleotides, should considerably increase either the probability of unambiguous reconstruction, or the length of reconstructed sequences, or decrease the size of immobilized oligonucleotides.
Differential strand separation at critical temperature: A minimally disruptive enrichment method for low-abundance unknown DNA mutations (2012)

Detection of low-level DNA variations in the presence of wild-type DNA is important in several fields of medicine, including cancer, prenatal diagnosis and infectious diseases. PCR-based methods to enrich mutations during amplification have limited multiplexing capability, are mostly restricted to known mutations and are prone to polymerase or mis-priming errors. Here, we present Differential Strand Separation at Critical Temperature (DISSECT), a method that enriches unknown mutations of targeted DNA sequences purely based on thermal denaturation of DNA heteroduplexes without the need for enzymatic reactions. Target DNA is pre-amplified in a multiplex reaction and hybridized onto complementary probes immobilized on magnetic beads that correspond to wild-type DNA sequences. Presence of any mutation on the target DNA forms heteroduplexes that are subsequently denatured from the beads at a critical temperature and selectively separated from wild-type DNA. We demonstrate multiplexed enrichment by 100- to 400-fold for KRAS and TP53 mutations at multiple positions of the targeted sequence using two to four successive cycles of DISSECT. Cancer and plasma-circulating DNA samples containing traces of mutations undergo mutation enrichment allowing detection via Sanger sequencing or high-resolution melting. The simplicity, scalability and reliability of DISSECT make it a powerful method for mutation enrichment that integrates well with existing downstream detection methods.
Multimedia MedNet: a medical collaboration and consultation system (1995)

MedNet and its predecessor, NeuroNet, have been in use since 1985. The current system provides real-time monitoring and multiparty consultation during 1,600 brain surgeries per year.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
A monoclonal antibody against the c-erbB-2 protein enhances the cytotoxicity of cis-diamminedichloroplatinum against human breast and ovarian tumor cell lines. (1991)

A monoclonal antibody (TAb 250) specific to an extracellular epitope of the c-erbB-2 protein (gp185) inhibited the in vitro proliferation of human breast tumor cell lines that overexpress c-erbB-2 in a dose-dependent manner. Treatment of cells with combinations of cis-diammedichloroplatinum (CDDP) and TAb 250 resulted in a significantly enhanced cytotoxic effect. This synergistic cytotoxicity was apparent over a wide range of antibody concentrations (200 pg/ml-100 micrograms/ml) including concentrations that showed no inhibitory effect alone. TAb 250 did not increase the cytotoxic effect of CDDP in a cell line exhibiting no detectable level of gp185. Athymic mice bearing s.c. xenografts of human tumor cells expressing high levels of gp185 showed a greatly enhanced inhibition of tumor growth when treated with TAb 250 and CDDP compared to treatment with the antibody or CDDP alone. This effect was specific inasmuch as TAb 250 did not enhance the growth-inhibitory effect of CDDP on tumor xenografts which were not expressing gp185.
Develop gap-fill process of shallow trench isolation in 450mm wafer by advanced Flowable CVD technology for sub-20nm node (2016)

In this study, a novel Flowable CVD process using non-carbon silicon based precursor has been developed for gap filling in 450mm wafer level, sub-20nm STI structure. To achieve 450mm wafer with aspect ratio 5:1 STI structure, guided DSA patterning and a-carbon hard-mask are applied. The various conditions have been screened in deposition, cure and anneal processes in order to result a void free and less Si damage performance. By SEM viewing and FT-IR analysis, the gap-fill profile and mechanism of film conversion are discussed.
Majorana fermions in semiconductor nanowires (2011)

We study multiband semiconducting nanowires proximity coupled with an $s$-wave superconductor and calculate the topological phase diagram as a function of the chemical potential and magnetic field. The nontrivial topological state corresponds to a superconducting phase supporting an odd number of pairs of Majorana modes localized at the ends of the wire, whereas the nontopological state corresponds to a superconducting phase with no Majoranas or with an even number of pairs of Majorana modes. Our key finding is that multiband occupancy not only lifts the stringent constraint of one-dimensionality, but also allows having higher carrier density in the nanowire. Consequently, multiband nanowires are better suited for stabilizing the topological superconducting phase and for observing the Majorana physics. We present a detailed study of the parameter space for multiband semiconductor nanowires focusing on understanding the key experimental conditions required for the realization and detection of Majorana fermions in solid-state systems. We include various sources of disorder and characterize their effects on the stability of the topological phase. Finally, we calculate the local density of states as well as the differential tunneling conductance as functions of external parameters and predict the experimental signatures that would establish the existence of emergent Majorana zero-energy modes in solid-state systems.
Single-frequency thulium-doped distributed-feedback fiber laser (2004)

We have successfully demonstrated a single-frequency distributed-feedback (DFB) thulium-doped silica fiber laser emitting at a wavelength of 1735 nm. The laser cavity is less than 5 cm long and is formed by intracore UV-written Bragg gratings with a phase shift. The laser is pumped at 790 nm from a Ti:sapphire laser and has a threshold pump power of 59 mW. The laser has a maximum output power of 1 mW in a single-frequency, single-polarization radiation mode and is tunable over a few nanometers. To the best of the authors' knowledge, this is the first report of a single-frequency DFB fiber laser that uses thulium as the amplifying medium. The lasing wavelength is the longest demonstrated with DFB fiber lasers and yet is among the shortest obtained for thulium-doped silica fiber lasers.
Investigating the limits of SOAP performance for scientific computing (2003)

The growing synergy between Web Services and Grid-based technologies will potentially enable profound, dynamic interactions between scientific applications dispersed in geographic, institutional, and conceptual space. Such deep interoperability requires the simplicity, robustness, and extensibility for which SOAP was conceived, thus making it a natural lingua franca. Concomitant with these advantages, however is a degree of inefficiency that may limit the applicability of SOAP to some situations. We investigate the limitations of SOAP for high-performance scientific computing. We analyze the processing of SOAP messages, and identify the issues of each stage. We present a high-performance SOAP implementation and a schema-specific parser based on the results of our investigation. After our SOAP optimizations are implemented, the most significant bottleneck is ASCII/double conversion. Instead of handling this using extensions to SOAP we recommend a multiprotocol approach that uses SOAP to negotiate faster binary protocols between messaging participants.
Dissection of Influenza A Virus M1 Protein: pH-Dependent Oligomerization of N-Terminal Domain and Dimerization of C-Terminal Domain (2012)

Oligomerization of M1 involves both the N- and C-terminal domains. The N-terminal domain determines the pH-dependent oligomerization characteristic, and C-terminal domain forms a stable dimer, which contributes to the dimerization of M1. The present study will help to unveil the mechanisms of influenza A virus assembly and uncoating process.
Redox Control of the Catalytic Cycle of Flavocytochrome P-450 BM3 (1997)

Flavocytochrome P-450 BM3 from Bacillus megaterium is a 119 kDa polypeptide whose heme and diflavin domains are fused to produce a catalytically self-sufficient fatty acid monooxygenase. Redox potentiometry studies have been performed with intact flavocytochrome P-450 BM3 and with its component heme, diflavin, FAD, and FMN domains. Results indicate that electron flow occurs from the NADPH donor through FAD, then FMN and on to the heme center where fatty acid substrate is bound and monooxygenation occurs. Prevention of futile cycling of electrons is avoided through an increase in redox potential of more than 100 mV caused by binding of fatty acids to the active site of P-450. Redox potentials are little altered for the component domains with respect to their values in the larger constructs, providing further evidence for the discrete domain organization of this flavocytochrome. The reduction potentials of the 4-electron reduced diflavin domain and 2-electron reduced FAD domain are considerably lower than those for the blue FAD semiquinone species observed during reductive titrations of these enzymes and that of the physiological electron donor (NADPH), indicating that the FAD hydroquinone is thermodynamically unfavorable and does not accumulate under turnover conditions. In contrast, the FMN hydroquinone is thermodynamically more favorable than the semiquinone.
“Chemical aminoacylation” of tRNA's (1978)

Incubation of abbreviated tRNA's (tRNA-C-COH's) with (chemically) preaminoacylated P1, P2-di(adenosine 5'-)diphosphates in the presence of purified RNA ligase effected transfer of an aminoacyladenylate moiety to the 3'-terminus of the abbreviated tRNA's in good yield. Aminoacylated (or misacylated) tRNA's may thus be prepared from fractionated or unfractionated tRNA-C-COH's; each of the five aminoacylated dinucleoside diphosphates tested was utilized as a substrate by RNA ligase. That the resulting "chemically aminoacylated" tRNA's were identical with those prepared by enzymatic aminoacylation was judged by comparison of 1) chromatographic properties on benzolated diethylaminoethyl-cellulose, 2) rates of chemical deacylation, and 3) affinities for elongation factor Tu, as well as 4) the ability of misacylated tRNA's so derived to be deacylated chemically and then reactivated enzymatically with their cognate amino acids.
Lidocaine patch: double-blind controlled study of a new treatment method for post-herpetic neuralgia (1996)

Post-herpetic neuralgia (PHN) is a common and often intractable neuropathic pain syndrome predominantly affecting the elderly. Topical local anesthetics have shown promise in both uncontrolled and controlled studies. Thirty-five subjects with established PHN affecting the torso or extremities completed a four-session, random order, double-blind, vehicle-controlled study of the analgesic effects of topically applied 5% lidocaine in the form of a non-woven polyethylene adhesive patch. All subjects had allodynia on examination. Up to 3 patches, covering a maximum of 420 cm2, were applied to cover the area of greatest pain as fully as possible. Lidocaine containing patches were applied in two of the four 12-h-long sessions, in one session vehicle patches were applied, and one session was a no-treatment observation session. Lidocaine containing patches significantly reduced pain intensity at all time points 30 min to 12 h compared to no-treatment observation, and at all time points 4--12 h compared to vehicle patches. Lidocaine patches were superior to both no-treatment observation and vehicle patches in averaged category pain relief scores. The highest blood lidocaine level measured was 0.1 micrograms/ml, indicating minimal systemic absorption of lidocaine. Patch application was without systemic side effect and well tolerated when applied on allodynic skin for 12 h. This study demonstrates that topical 5% lidocaine in patch form is easy to use and relieves post-herpetic neuralgia.
Clinical Implication of Hot SpotBRAFMutation, V599E, in Papillary Thyroid Cancers (2003)

Activating mutations in the BRAF kinase gene have recently been reported in human cancers. The aim of the present study was to determine the frequency of BRAF mutations in thyroid cancer and their correlation with clinicopathological parameters. We analyzed exons 11 and 15 of BRAF gene in six human thyroid cancer cell lines and 207 paraffin-embedded thyroid tumor tissues. A missense mutation was found at T1796A (V599E) in exon 15 in four of the six cell lines and 51 of 207 thyroid tumors (24.6%; 0 of 20 follicular adenoma, 0 of 11 follicular carcinoma, 49 of 170 papillary carcinomas, and 2 of 6 undifferentiated carcinomas). Activation of MAPK kinase-MAPK pathway was observed in cell lines harboring BRAF mutation. BRAF mutation-associated enhanced cell growth was suppressed by MAPK kinase inhibitor, U0126. Examination of 126 patients with papillary thyroid cancer showed that BRAF mutation correlated significantly with distant metastasis (P = 0.033) and clinical stage (P = 0.049). Our results indicate that activating mutation of BRAF gene could be a potentially useful marker of prognosis of patients with advanced thyroid cancers.
Comparison of healing process following ligation with sutures and bipolar vessel sealing. (2002)

Local hemostasis is critical for successful surgical intervention and may be accomplished with a variety of techniques ranging from direct pressure to lasers. Critical assessment of the clinical situation is required to determine the appropriate technology necessary to achieve effective hemostasis. As a general rule, ligatures remain the mainstay for effecting hemostasis in all but the smallest isolated vessels. Although ligatures have been in use since the first century AD, both the applications as well as their sophistication have increased dramatically. As sutures are foreign material to the human body, tissue reaction is unavoidable. This response may be mitigated, but not eliminated completely, through the use of non-absorbable sutures. The body's inflammatory response triggers a complex cascade of cellular and biochemical events that lead to fibrinogenesis and coagulation. This process, in turn, results in an increased deposition of collagen that may result in formation of adhesions.
Antiandrogenic effects of novel androgen synthesis inhibitors on hormone-dependent prostate cancer. (2000)

We have found that in addition to being potent inhibitors of 17alpha-hydroxylase/C17,20-lyase and/or 5alpha-reductase, some of our novel androgen synthesis inhibitors also interact with the mutated androgen receptor (AR) expressed in LNCaP prostate cancer cells and the wild-type AR expressed in hormone-dependent prostatic carcinomas. The effects of these compounds on the proliferation of hormone-dependent human prostatic cancer cells were determined in vitro and in vivo. L-2 and L-10 are delta4-3-one-pregnane derivatives. L-35 and L-37 are delta5-3beta-ol-androstane derivatives, and L-36 and L-39 are delta4-3-one-androstane-derived compounds. L-2, L-10, and L-36 (L-36 at low concentrations) stimulated the growth of LNCaP cells, indicating that they were interacting agonistically with the mutated AR expressed in LNCaP cells. L-35, L-37, and L-39 acted as LNCaP AR antagonists. To determine whether the growth modulatory effects of our novel compounds were specific for the mutated LNCaP AR, competitive binding studies were performed with LNCaP cells and PC-3 cells stably transfected with the wild-type AR (designated PC-3AR). Regardless of AR receptor type, all of our novel compounds were effective at preventing binding of the synthetic androgen methyl-trienolone[17alpha-methyl-(3H)-R1881 to both the LNCaP AR and the wildtype AR. L-36, L-37, and L-39 (5.0 microM) prevented binding by >90%, whereas L-35 inhibited binding by 30%. To determine whether the compounds were acting as agonists or antagonists, LNCaP cells and PC-3AR cells were transfected with the pMAMneoLUC reporter gene. When luciferase activity was induced by dihydrotestosterone, all of the compounds were found to be potent inhibitors of transcriptional activity, and the pattern of inhibition was similar for both receptor types. However, L-2, L-10, and L-36 were determined to be AR agonists, and L-35, L-37, and L-39 were wild-type AR antagonists. When tested in vivo, L-39 was the only AR antagonist that proved to be effective at inhibiting the growth of LNCaP prostate tumor growth. L-39 slowed tumor growth rate in LNCaP tumors grown in male SCID mice to the same level as orchidectomy, significantly reduced tumor weights (P < 0.05), significantly lowered serum levels of prostate-specific antigen (P < 0.02), and significanty lowered serum levels of testosterone (P < 0.05). L-39 also proved to be effective when tested against the PC-82 prostate cancer xenograft that expresses wild-type AR. These results show that some of our compounds initially developed to be inhibitors of androgen synthesis also interact with the human AR and modulate the proliferation of hormone-dependent prostatic cancer cells. Therefore, compounds such as L-39, which have multifunctional activities, hold promise for the treatment of androgen-dependent prostate tumors.
The plurifunctional nucleolus (1998)

The nucleolus of eukaryotic cells was first described in the early 19th century and was discovered in the 1960s to be the seat of ribosome synthesis. Although rRNA transcription, rRNA processing and ribosome assembly have been clearly established as major functions of the nucleolus, recent studies suggest that the nucleolus participates in many other aspects of gene expression as well. Thus, the nucleolus has been implicated in the processing or nuclear export of certain mRNAs. In addition, new results indicate that biosyntheses of signal recognition particle RNA and telomerase RNA involve a nucleolar stage and that the nucleolus is also involved in processing of U6 RNA, one of the spliceosomal small nuclear RNAs. Interestingly, these three nucleolus-associated small nuclear RNAs (signal recognition particle RNA, telomerase RNA and U6 RNA) are components of catalytic ribonucleoprotein machines. Finally, recent work has also suggested that some transfer RNA precursors are processed in the nucleolus. The nucleolus may have evolutionarily descended from a proto-eukaryotic minimal genome that was spatially linked to vicinal RNA processing and ribonucleoprotein assembly events involved in gene read-out. The nucleolus of today's eukaryotes, now surrounded by the chromatin of over 2 billion years of genome expansion, may still perform these ancient functions, in addition to ribosome biosynthesis. The plurifunctional nucleolus concept has a strong footing in contemporary data and adds a new perspective to our current picture of the spatial-functional design of the cell nucleus.
The Contrasting Effects on Bone Histology of Vitamin D and of Calcium Carbonate in the Osteomalacia of Chronic Renal Failure (1974)

1. The histological appearances of cancellous bone from the ilium have been quantified in thirteen patients with osteomalacia due to chronic renal failure. 2. There was an excess of osteoid tissue and a reduction in the extent of the calcification front in that osteoid lamella lying next to calcified bone. 3. Administration of calcium compounds orally produced an increase of punctate calcification within the osteoid, but there was no change in the extent of the calcification front. 4. Administration of vitamin D produced a marked rise in the extent of the calcification front but no increase of punctate calcification within the osteoid. 5. This rise in the extent of the calcification front was not dependent on a rise in plasma calcium × plasma phosphorus product. 6. It is concluded that vitamin D has a direct action on the bone in patients with the osteomalacia of chronic renal failure.
Novel amyloid precursor protein gene mutation (codon 665Asp) in a patient with late‐onset Alzheimer's disease (1994)

Amyloid plaques in Alzheimer's disease contain beta-amyloid, encoded by portions of exons 16 and 17 of the amyloid precursor protein. The specific association of rare amyloid precursor protein mutations with some kindreds with early-onset familial Alzheimer's disease suggests that specific abnormalities in amyloid precursor protein may contribute to the pathogenesis of Alzheimer's disease. Until now, there has been no evidence suggesting that amyloid precursor protein mutations could be involved in late-onset or sporadic Alzheimer's disease. We used reverse transcription-polymerase chain reaction, denaturing gradient gel electrophoresis, and direct DNA sequencing to analyze amyloid precursor protein exons 16 and 17 from postmortem cerebellar samples from patients with histologically confirmed Alzheimer's disease and control subjects. We found a novel point mutation, substitution of cytosine for guanine, at nucleotide 2119 (amyloid precursor protein 770 messenger RNA transcript) in a patient with late-onset Alzheimer's disease. This substitution deletes a BglII site and substitutes aspartate for glutamine at codon 665. Denaturing gradient gel electrophoresis analysis showed that this mutation was absent in 40 control subjects and 127 dementia patients. Whether this mutation is a rare but normal variant or contributes to the development of Alzheimer's disease is not known. The BglII restriction fragment length polymorphism enables investigators to determine the frequency of this polymorphism in normal subjects and Alzheimer's disease patients.
The dnaB protein of Escherichia coli: mechanism of nucleotide binding, hydrolysis, and modulation by dnaC protein (1986)

The mechanism of nucleotide binding and hydrolysis by dnaB protein and dnaB X dnaC protein complex has been studied by using fluorescent nucleotide analogues. Binding of trinitrophenyladenosine triphosphate (TNP-ATP) or the corresponding diphosphate (TNP-ADP) results in a blue shift of the emission maximum and a severalfold amplification of the fluorescence emission of the nucleotide analogues. Scatchard analysis of TNP-ATP binding indicates that TNP-ATP binds with a high affinity (Kd = 0.87 microM) and a 8.5-fold enhancement of fluorescence emission of the nucleotide. Only three molecules of TNP-ATP or TNP-ADP bind per hexamer of dnaB protein in contrast to six molecules of ATP or ADP binding to a dnaB hexamer. TNP-ATP and TNP-ADP are both competitive inhibitors of single-stranded (SS) DNA-dependent ATPase activity of dnaB protein. TNP-AMP neither binds to dnaB protein nor inhibits the ATPase activity. Formation of dnaB X dnaC complex by dnaC protein results in diminution of the TNP-ATP fluorescence enhancement and a concomitant decrease in the SS DNA-dependent ATPase activity. Kinetic analysis of the ATPase activity of dnaB X dnaC complex indicates that the decrease in the ATPase activity on complex formation is due to a reduction of the maximal velocity (Vmax). The dnaB protein hydrolyzes both TNP-ATP and dATP, however, with an extremely slow rate in the presence of single-stranded M13 DNA. The 2'-OH group of the nucleotide most likely plays an important role in the hydrolysis reaction but not in the nucleotide binding.