gebhart/patrepeval huggingface dataset:
Intracellular amplification of proviral DNA in tissue sections using the polymerase chain reaction. (1992)

We developed a new method to amplify cell DNA in situ using the polymerase chain reaction (PCR). Proviral sequences of mouse mammary tumor virus (MMTV) contained in cultured cells and tissue sections were amplified intracellularly using a thermal cycler. Two techniques were employed to maintain the localization of the amplified DNA. First, complementary tails at the 5' ends of the oligonucleotide primers resulted in the synthesis of high molecular weight concatamers containing the target sequences. Second, the PCR was carried out in a thin film of agarose solidified over the tissue sections. The specifically amplified and localized DNA was then detected by in situ hybridization (ISH). Our results demonstrate that (a) DNA in tissue sections can serve as the target for the polymerase chain reaction in situ, (b) cell morphology is maintained, and (c) a target of 167 BP can be specifically detected in individual cells. This technique should be generally applicable to amplifying cellular DNA targets in tissue sections for detection in situ.
Hypermethylation of the DAP-Kinase CpG Island Is a Common Alteration in B-Cell Malignancies (1999)

Abstract Death-associated protein kinase (DAP-Kinase) is a novel serine/threonine kinase whose expression is required for γ interferon-induced apoptosis. A previous study suggested that DAP-Kinase expression may be lost epigenetically in cancer cell lines, because treatment of several nonexpressing cell lines with 5-aza-2′-deoxycytidine resulted in the expression of DAP-Kinase. Using methylation-specific polymerase chain reaction (MSP), we examined the DAP-Kinase CpG island for hypermethylation in cancer. Normal lymphocytes and lymphoblastoid cell lines are unmethylated in the 5′ CpG island of DAP-Kinase. However, in primary tumor samples, all Burkitt’s lymphomas and 84% of the B-cell non-Hodgkin’s lymphomas were hypermethylated in the DAP-Kinase CpG island. In contrast, none of the T-cell non-Hodgkin’s lymphoma samples and 15% or less of leukemia samples examined had hypermethylated DAP-Kinase alleles. U937, an unmethylated, DAP-Kinase–expressing leukemia cell line, was treated with γ interferon and underwent apoptosis; however, Raji, a fully methylated, DAP-Kinase nonexpressing Burkitt’s lymphoma cell line, only did so when treated with 5-aza-2′-deoxycytidine followed by γ interferon. Our findings in cell lines and primary tumors suggest that hypermethylation of the DAP-Kinase gene and loss of γ interferon-mediated apoptosis may be important in the development of B-cell malignancies and may provide a promising biomarker for B-cell–lineage lymphomas.
Fiber-based frequency combs with millihertz-level relative linewidths for optical lattice clocks (2010)

We have been developing a new clock laser system for Yb and Sr optical lattice clocks. The system is based on an infrared laser with a narrow linewidth, and a fiber-based frequency comb transferring the linewidth to required plural wavelengths. We demonstrate that fiber-based frequency combs with a multi-branch configuration can transfer laser linewidth to another wavelength at the millihertz level. An intra-cavity electro-optic modulator is employed to obtain a broad servo bandwidth for repetition rate control.
Implantable electromagnetic middle-ear bone-conduction hearing aid device (1989)

First Page
[C<sub>6</sub>H<sub>3</sub>(CH<sub>3</sub>)<sub>3</sub>][BiCl<sub>3</sub>] and [C<sub>6</sub>(CH<sub>3</sub>)<sub>6</sub>][BiCl<sub>3</sub>]<sub>2</sub>, Arene Complexes of Bismuth with Half‐Sandwich and “Inverted” Sandwich Structures (1986)

The title compounds 1 and 2 display fascinating structures. They were prepared by simply dissolving BiCl3 in mesitylene and hexamethylbenzene/toluene, respectively, followed by crystallization. The layer structure of the 1 : 1 complex 1 is characterized by η6-coordination of the mesitylene to the metal atom. The same holds true for the novel “inverted” sandwich structure of 2, in which ring-shaped Bi4Cl12 structural units are linked through the arenes to form a three-dimensional network.
THE MICROWAVE SPECTRUM OF 2-CHLOROETHANOL (1966)

This research was supported in part by a Contract extended to Harvard University by the Office of Naval Research, Nonr-1866(14). Raymond G. Azrak is a NIH Predoctoral Fellow.
Comparison of Non-hurricane and Hurricane Induced Near Inertial Oscillations in Deep Water of Gulf of Mexico (2007)

By using oil platform based ADCPs on the continental slope, some time series and spectrum analyses are implemented to examine the general flow distributions including those of the near inertial oscillations and their temporal variations along the vertical water columns for the Gulf of Mexico during different time periods in the year of 2005 and 2006, particularly in 2005, when a few hurricanes struck the Gulf of Mexico coast of the US, causing tremendous amount of damages. Among these hurricanes are the infamous Hurricanes Katrina and Rita. However, during the Hurricanes Katrina and Rita, most of the acoustic Doppler current profilers from oil platforms and moorings were not functioning and only a couple of the deep water ADCPs were collecting data during the storms. This paper presents some preliminary studies analyzing the ADCP data using different methods, such as rotary spectra and wavelet analysis. The rotary spectra of the velocity showed interesting patterns of inertial oscillations before, during, and after the hurricanes.
Identification of Novel Keratinocyte Differentiation Modulating Compounds by High-Throughput Screening (2006)

The authors have designed high-throughput screens to identify compounds that promote or inhibit terminal differentiation of primary human epidermal keratinocytes. Eleven known inhibitors of signaling pathways and approximately 4000 compounds of diverse structure were screened using an In-Cell Western system based on immunofluorescent staining of the terminal differentiation marker, involucrin. Staurosporine, a nonspecific protein kinase C inhibitor, and H89, a protein kinase A inhibitor, promoted expression of involucrin. Conversely, U0126, a MEK inhibitor, and SAHA or SBHA, 2 histone deacetylase inhibitors, reduced the expression of involucrin during calcium-induced stratification. In addition, the authors found 1 novel compound that induced keratinocyte differentiation and 2 novel compounds that were inhibitory to calcium-induced differentiation. The differentiation-inducing compound also inhibited growth of a human squamous cell carcinoma line by stimulating both differentiation and apoptosis. Because the compound affected the tumor cells at a lower concentration than primary keratinocytes, it may have potential as an antitumor therapy.
Classification of voiceless speech using facial muscle activity and vision based techniques (2008)

This paper presents a silent speech recognition technique based on facial muscle activity and video, without evaluating any voice signals. This research examines the use of facial surface electromyogram (SEMG) to identify unvoiced vowels and vision-based technique to classify unvoiced consonants. The moving root mean square (RMS) of SEMG signals of four facial muscles is used to segment the signals and to identify the start and end of a silently spoken vowels. Visual features are extracted from the mouth video of a speaker silently uttering consonants using motion segmentation and image moment techniques. The SEMG features and visual features are classified using feedforward multilayer perceptron (MLP) neural networks. The preliminary results demonstrate that the proposed technique yields high recognition rate for classification of unvoiced vowels using SEMG features. Similarly, promising results are obtained in identification of consonants using visual features. The results demonstrate that the system is easy to train for a new user and suggest that such a system works reliably for voiceless, simple speech based commands for human computer interface when it is trained for a user.
Novel Modeling of Cancer Cell Signaling Pathways Enables Systematic Drug Repositioning for Distinct Breast Cancer Metastases (2013)

A new type of signaling network element, called cancer signaling bridges (CSB), has been shown to have the potential for systematic and fast-tracked drug repositioning. On the basis of CSBs, we developed a computational model to derive specific downstream signaling pathways that reveal previously unknown target-disease connections and new mechanisms for specific cancer subtypes. The model enables us to reposition drugs based on available patient gene expression data. We applied this model to repurpose known or shelved drugs for brain, lung, and bone metastases of breast cancer with the hypothesis that cancer subtypes have their own specific signaling mechanisms. To test the hypothesis, we addressed specific CSBs for each metastasis that satisfy (i) CSB proteins are activated by the maximal number of enriched signaling pathways specific to a given metastasis, and (ii) CSB proteins are involved in the most differential expressed coding genes specific to each breast cancer metastasis. The identified signaling networks for the three types of breast cancer metastases contain 31, 15, and 18 proteins and are used to reposition 15, 9, and 2 drug candidates for the brain, lung, and bone metastases. We conducted both in vitro and in vivo preclinical experiments as well as analysis on patient tumor specimens to evaluate the targets and repositioned drugs. Of special note, we found that the Food and Drug Administration-approved drugs, sunitinib and dasatinib, prohibit brain metastases derived from breast cancer, addressing one particularly challenging aspect of this disease.
Electron Paramagnetic Resonance Study of Partially Oriented Clay Platelets Intercalated with Copper(II) 1,4,8,11-Tetraazacyclotetradecane (2005)

Electron paramagnetic resonance (EPR) spectra of powder and oriented films of montmorillonite, hectorite, and saponite intercalated with [Cu(cyclam)](2+) (cyclam = 1,4,8,11-tetraazacyclotetradecane) exhibit three components: an orientation-dependent component without hyperfine features, an orientation-dependent component with hyperfine features, and an orientation-independent component without hyperfine feature. EPR spectra of [Cu(cyclam)](2+)-saponite, which exhibit only two components and the best resolved hyperfine features, were simulated. The spectra indicate that a large portion of the saponite platelets are inclined to the glass surface, although they tend to align with their basal planes parallel to the glass surface. The orientation-dependent spectra could be simulated by introducing a Gaussian distribution with a standard deviation of 20 degrees for the inclination angle. The standard deviation may be used as a disorder parameter for the microcrystals assembled on glass plates. Spectral simulation also shows that the CuN(4) plane of [Cu(cyclam)](2+) is parallel to the clay layers. EPR spectra of some other partially oriented systems are also discussed.
ChemInform Abstract: PHOTOCHEMIE 4.5‐DISUBSTITUIERTER 1,3‐DIOXOLONE‐(2) (1972)

Abstract Das Dioxolon (II) wird durch Behandlung des Acyloins (I) mit Phosgen in Gegenwart von Pyridin und nachfolgende Destillation dargestellt.
Switching mechanisms of cell death in mdm2- and mdm4-null mice by deletion of p53 downstream targets. (2003)

The p53 tumor suppressor ensures maintenance of genome integrity by initiating either apoptosis or cell cycle arrest in response to DNA damage. Deletion of either mdm2 or mdm4 genes, which encode p53 inhibitors, results in embryonic lethality. The lethal phenotypes are rescued in the absence of p53, which indicates that increased activity of p53 is the cause of lethality in the mdm2- and mdm4-null embryos. Here we show that mdm2-null embryos die because of apoptosis initiated at 3.5 days postcoitum (dpc). Partial rescue of mdm2-null embryos by deletion of bax allows survival to 6.5 dpc and alters the mechanism of death from apoptosis to cell cycle arrest, indicating that bax is a critical component of the p53 pathway in early embryogenesis. The death of mdm4-null embryos is due to p53-initiated cell cycle arrest at 7.5 dpc. Deletion of p21(p21(waf1/cip1)), a p53 downstream target partially responsible for cell cycle arrest, does not rescue this phenotype; however, deletion of p21 alters the mechanism of cell death from lack of proliferation to apoptosis. Thus, in both examples, deletion of a p53 downstream target gene allows p53 to redirect its efforts, highlighting a high degree of plasticity in p53 function.
Activity of cabozantinib (XL184) in hepatocellular carcinoma patients (pts): Results from a phase II randomized discontinuation trial (RDT). (2012)

261 Background: Cabozantinib is an oral, potent inhibitor of MET and VEGFR2. MET over-expression has been observed in advanced hepatocellular carcinoma (HCC). Anti-VEGF pathway agents have shown clinical benefit in pts w/ HCC. Simultaneous targeting of the MET and VEGF signaling pathways with cabozantinib may therefore be a promising treatment strategy. Methods: HCC pts with progressive measurable disease, per mRECIST received cabozantinib at 100 mg qd PO over a 12 week Lead-in period. Up to one prior regimen was allowed and only pts with Child-Pugh score of A were eligible. Tumor response was assessed every 6 weeks. Treatment beyond Week 12 was based on response: pts with PR continued open-label cabozantinib, those with SD were randomized to cabozantinib vs. placebo, and those with PD discontinued study drug. The primary endpoint was overall response rate (RR) per mRECIST in the Lead-in period, and progression free survival for pts who entered the randomized period. Results: Enrollment has been completed with 41 pts. Results are available for 34 pts. Median age: 61 years (33 to 83). Males: 24/34 (71%). Asian: 13/34 (38%). HCC etiology: Hepatitis B or C 12/34 (35%); alcohol abuse 5/34 (15%); other 17/34 (50%). Extrahepatic spread was observed in 21/34 (62%). The median number of prior systemic treatments was 1; prior sorafenib: 16/34 (47%). Most common related AEs ≥Grade 3 were hand-foot syndrome (15%), diarrhea (9%) and thrombocytopenia (9%). 3/33 pts evaluable for tumor assessment at 12 weeks achieved PR by original RECIST (RR 9%). One additional pt randomized at Week 12 achieved PR at 18 weeks and treatment remains blinded on study for >1 year. 24/30 pts (80%) with ≥1 post-baseline scan had tumor regression (with no apparent relationship to prior sorafenib therapy). The overall disease control rate (DCR = PR+SD) at Week 12: 71% (Asian subgroup: 77%). Median time on study: 6 mos (1 to 15+ mos). AFP responses (defined as reduction from baseline of >50%) in 21 pts with ≥1 post-baseline result: 9/21 (43%). Conclusions: Cabozantinib exhibits clinical activity in HCC pts with advanced disease, regardless of prior sorafenib treatment as reflected by tumor reduction, high DCR and time on study.
Fatigue Damage Monitoring and Remaning Life Assessment using Nonlinear Vibro-Modulation Technique (2008)

Assessment of structural deterioration due to in-service and environmental loads is an essential element in ensuring safety, operability and long life of various structures and structural components. We applied vibro-acoustic modulation technique to monitor material degradation at the micro/meso scale before the onset of the macro-scale fracture. The technique explores nonlinear acoustic interaction of high frequency ultrasound and low frequency structural vibration at the site of the incipient damage. It is shown that micro/meso scale degradation increases the material nonlinearity leading to modulation of the high frequency ultrasonic signal by low frequency vibration, quantified by the nonlinear acoustic Damage Index (DI). Numerous tests with hundreds of test coupons proved high sensitivity of the developed technique to micro/meso scale fatigue damage accumulation. The study further demonstrated that the remaining life of the fatigued material can be predicted using phenomenological damage accumulation rule expressed through measured Damage Index. Work supported by NAVAIR.
Transverse permeability determination and influence in resin flow through an orthotropic medium in the RTM process (2017)

Resin Transfer Molding (RTM) process is commonly used to produce high quality polymeric composites with simple or complex geometries in small to large sizes. In RTM process a preformed reinforcement is positioned inside the mold cavity. This dry reinforcement is actually a fibrous porous media whereby resin will flow. The mold is then closed and resin is injected. After complete impregnation of the reinforcement, resin cure process takes place. Numerical simulation is a very useful tool for mold design and process optimization, however resin and reinforced medium physical properties must be precisely determined. Medium permeability is probably the most important and most difficult parameter to be evaluated. In this work it is proposed a numerical/experimental methodology to determine transverse permeability in reinforcements used within RTM process. PAM-RTM software was chosen to simulate resin flow through the reinforced medium. Proposed methodology uses the inverse parameter estimation method to calculate the unknown permeability. Newton-Raphson method was used to solve the associated algebraic equation system, on which PAM-RTM software is used to calculate resin injection times. Results have shown that with previous knowledge (taken from literature or obtained experimentally) of the in-plane permeabilities (K xx and K yy ), physical properties of the resin (, ), medium porosity () and total filling time (t) it is possible to estimate transverse permeability in thick pieces. It was also performed a numerical study about the influence of transverse permeability in resin flow inside the mold. This study predicted several possible problems that may occur when transverse permeability is much smaller than in-plane permeabilities. Finally, it is possible to state that mold design and proper fibrous reinforcement choice can be optimized when numerical techniques are used.
Antibody-mediated enhancement aggravates chikungunya virus infection and disease severity (2018)

The arthropod-transmitted chikungunya virus (CHIKV) causes a flu-like disease that is characterized by incapacitating arthralgia. The re-emergence of CHIKV and the continual risk of new epidemics have reignited research in CHIKV pathogenesis. Virus-specific antibodies have been shown to control virus clearance, but antibodies present at sub-neutralizing concentrations can also augment virus infection that exacerbates disease severity. To explore this occurrence, CHIKV infection was investigated in the presence of CHIKV-specific antibodies in both primary human cells and a murine macrophage cell line, RAW264.7. Enhanced attachment of CHIKV to the primary human monocytes and B cells was observed while increased viral replication was detected in RAW264.7 cells. Blocking of specific Fc receptors (FcγRs) led to the abrogation of these observations. Furthermore, experimental infection in adult mice showed that animals had higher viral RNA loads and endured more severe joint inflammation in the presence of sub-neutralizing concentrations of CHIKV-specific antibodies. In addition, CHIKV infection in 11 days old mice under enhancing condition resulted in higher muscles viral RNA load detected and death. These observations provide the first evidence of antibody-mediated enhancement in CHIKV infection and pathogenesis and could also be relevant for other important arboviruses such as Zika virus.
Evolving Models of Biological Sequence Similarity (2008)

For computer scientists the problem of biological data retrieval has become synonymous with homology-based retrieval of primary gene sequence data and their associated protein products. This perspective is accessible to computer scientists, as primary sequence data is modeled as strings and fundamental algorithmic tools can be applied. However, by sticking with this formative foundation, we computer scientists are failing to recognize new challenges and opportunities arising in this rapidly changing arena. Most notably, sequence data represents a polymer; a complex molecule is itself composed of a linear sequence of smaller molecules (monomers). The monomers interact with each other, both with their local neighbors and at long range, forming secondary and tertiary structure. As more sophisticated similarity models incorporate elements of these three-dimensional chemical environments, they have the potential to supplant the use of primary structure homology as the foremost method of data retrieval.
Dyes for the Hydrophobic Fibers1 (1957)

The commercialization of the hydrophohic fibers has necessitated the development of entirely new classes of dyes. This job has been accomplished successfully by the careful tailoring of dye molecules to the chemical and physical requirements of the different fibers. All of the hydrophobic fibers designed for apparel use can be dyed with disperse dyes. Polyamide and acrylic fibers can be dyed with acid dyes. Selected acrylic fibers can be dyed also with basic dyes. The dyeing of hydrophobic fibers with disperse dyes in volves solution of the dye in the fiber : electrostatic interactions are involved in the dyeing of these fibers with ionic dyes. The rate of dyeing with both the disperse and the ionic dyes is largely a function of the specific fiber and the molecular size and geometry of the dye molecules. The polarity of a disperse dye plays a major role in determining the affinity of the dye for a specific fiber. Resistance of both the disperse and the ionic dyes to removal from the fiber by aqueous treatments is directly proportional to the affinity of the dye for the fiber and inversely proportional to the rate of dyeing. The washing fastness of the extremely hydrophobic fibers is excellent with all of the dyes which are applicable. The photochemical decomposition of a dye on a fiber is a reaction of the electronically excited dye molecule with the fiber and or other elements of the environment. Hence, light-fastness is a characteristic of the particular dye fiber system. Many correlations of affinity and fastness properties with molecular structure can be drawn.
Influence of phenobarbital on growth of chick embryo followed by induction of glutathione S-transferase. (1991)

The purpose of the present study was to learn the influence of phenobarbital (PB) on embryonic growth followed by induction of glutathione S-transferase activity (GST) by employing fertilized chicken eggs. A previous single dose (into the air-sac) of 168 μmol of PB killed all embryos tested by day 18. Those surviving when administered a dose of 144 μmol PB grew poorly and their hepatic color was changed to green. A curve of renal GST activity of 18-day-old embryo against PB dose linearly increased up to 120 μmol PB dose, where the activity was 6 times that in the control. A previous single dose (into the air-sac) of 60 μmol PB gave the following daily growth profiles : the whole body, the tibia and femoral bone grew poorly in weight and size after day 11 or 12. The hepatic weight did not differ from that of the control throughout the incubation period of day 7 to 18, however, the GST activity rose at day 14 to reach 2 times that in the control at day 18. The renal weight was slightly elevated compared with the control throughout the period of day 7 to 18, however, the GST activity linearly increased to reach 3 times that in the control at day 18. PB was found to induce hepatic GST activity of chick embryo causing such lesions as changing of the hepatic color to green.