gebhart/patrepeval huggingface dataset:
Peptide Vectors for the Nonviral Delivery of Nucleic Acids (2012)

Over the past two decades, gene therapy has garnered tremendous attention and is heralded by many as the ultimate cure to treat diseases such as cancer, viral infections, and inherited genetic disorders. However, the therapeutic applications of nucleic acids extend beyond the delivery of double-stranded DNA and subsequent expression of deficient gene products in diseased tissue. Other strategies include antisense oligonucleotides and most notably RNA interference (RNAi). Antisense strategies bear great potential for the treatment of diseases that are caused by misspliced mRNA, and RNAi is a universal and extraordinarily efficient tool to knock down the expression of virtually any gene by specific degradation of the desired target mRNA. However, because of the hurdles associated with effective delivery of nucleic acids across a cell membrane, the initial euphoria surrounding siRNA therapy soon subsided. The ability of oligonucleotides to cross the plasma membrane is hampered by their size and highly negative charge. Viral vectors have long been the gold standard to overcome this barrier, but they are associated with severe immunogenic effects and possible tumorigenesis. Cell-penetrating peptides (CPPs), cationic peptides that can translocate through the cell membrane independent of receptors and can transport cargo including proteins, small organic molecules, nanoparticles, and oligonucleotides, represent a promising class of nonviral delivery vectors. This Account focuses on peptide carrier systems for the cellular delivery of various types of therapeutic nucleic acids with a special emphasis on cell-penetrating peptides. We also emphasize the clinical relevance of this research through examples of promising in vivo studies. Although CPPs are often derived from naturally occurring protein transduction domains, they can also be artificially designed. Because CPPs typically include many positively charged amino acids, those electrostatic interactions facilitate the formation of complexes between the carriers and the oligonucleotides. One drawback of CPP-mediated delivery includes entrapment of the cargo in endosomes because uptake tends to be endocytic: coupling of fatty acids or endosome-disruptive peptides to the CPPs can overcome this problem. CPPs can also lack specificity for a single cell type, which can be addressed through the use of targeting moieties, such as peptide ligands that bind to specific receptors. Researchers have also applied these strategies to cationic carrier systems for nonviral oligonucleotide delivery, such as liposomes or polymers, but CPPs tend to be less cytotoxic than other delivery vehicles.
Comparative evaluation of cell-free tumor DNA in blood and disseminated tumor cells in bone marrow of patients with primary breast cancer (2009)

The detection of LOH on cell-free tumor DNA in blood is unrelated to BM micrometastasis and provides independent information on breast cancer progression.
Stress Reduction during Silicon Thinning Using Thermal Relaxation and 3D Curvature Correction Techniques (2012)

Abstract Backside sample preparation is required by many post silicon validation techniques like FIB (Focused Ion Beam) circuit editing and optical probing using Photon Emission or Laser Stimulus methods [1]. In spite of many conventional methods of silicon thinning and polishing, some challenges remain as new packages are introduced. With large die packages the issue of cracking during backside thinning is arising due to package curvature stress. 3D profile methods will be shown in conjunction with thermal relaxation to alleviate silicon center to edge variance allowing sample prep of large areas with thicknesses below 10μm. Thinning and polishing methods will be shown to be interactive with the device heated; demonstrating both thermal stress reduction coupled with curvature reduction.
Combined physiological effects of bronchodilators and hyperoxia on exertional dyspnoea in normoxic COPD (2006)

By combining the benefits of BD (reduced hyperinflation) and O(2) (reduced ventilatory drive), additive effects on exercise endurance were observed in patients with normoxic COPD.
Trolamine-containing topical emulsion: clinical applications in dermatology. (2008)

Trolamine-containing topical emulsion is used to promote and expedite wound healing. This agent has been shown to recruit macrophages, which serve important functions in the wound healing process, and increase the IL-1:IL-6 ratio, which enhances formation of granulation tissue and collagen synthesis. Therapeutic applications have included acute radiation dermatitis and postoperative wounds, and application after cryotherapy for actinic keratosis (AK). This article reviews the mechanism of action and information on clinical applications of trolamine-containing topical emulsion.
SPINKs in Tumors: Potential Therapeutic Targets (2022)

The serine protease inhibitor Kazal type (SPINK) family includes SPINK1-14 and is the largest branch in the serine protease inhibitor family. SPINKs play an important role in pancreatic physiology and disease, sperm maturation and capacitation, Nager syndrome, inflammation and the skin barrier. Evidence shows that the unregulated expression of SPINK1, 2, 4, 5, 6, 7, and 13 is closely related to human tumors. Different SPINKs exhibit various regulatory modes in different tumors and can be used as tumor prognostic markers. This article reviews the role of SPINK1, 2, 4, 5, 6, 7, and 13 in different human cancer processes and helps to identify new cancer treatment targets.
Synthesis and Characterization of Side Group-Modified Tetradentate Cyclotriphosphazene Derivatives (2012)

Abstract A series of novel side group-modified cyclotriphosphazene derivatives were synthesized by the reaction of hexachlorocyclotriphosphazene [N3P3Cl6] with 2,2′-diphenol and the potassium salt of 4-hydroxybenzaldehyde, and subsequent reduction of aldehyde groups to alcohol groups by the use of sodium borohydride. The bromination reaction was carried out with PBr3 to give N3P3(O2C12H8) (p-BrCH2-C6H4-O-)4. This compound was employed in reactions with macrocyclic polyamides, imidazole, or morpholine to produce title compounds. The target compounds were characterized by 1H NMR, 31P NMR, 13C NMR, and electrospray ionization mass spectrometry. Supplemental materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental file.
Cerebrolysin decreases amyloid‐β production by regulating amyloid protein precursor maturation in a transgenic model of Alzheimer's disease (2006)

Cerebrolysin is a peptide mixture with neurotrophic effects that might reduce the neurodegenerative pathology in Alzheimer's disease (AD). We have previously shown in an amyloid protein precursor (APP) transgenic (tg) mouse model of AD-like neuropathology that Cerebrolysin ameliorates behavioral deficits, is neuroprotective, and decreases amyloid burden; however, the mechanisms involved are not completely clear. Cerebrolysin might reduce amyloid deposition by regulating amyloid-beta (Abeta) degradation or by modulating APP expression, maturation, or processing. To investigate these possibilities, APP tg mice were treated for 6 months with Cerebrolysin and analyzed in the water maze, followed by RNA, immunoblot, and confocal microscopy analysis of full-length (FL) APP and its fragments, beta-secretase (BACE1), and Abeta-degrading enzymes [neprilysin (Nep) and insulin-degrading enzyme (IDE)]. Consistent with previous studies, Cerebrolysin ameliorated the performance deficits in the spatial learning portion of the water maze and reduced the synaptic pathology and amyloid burden in the brains of APP tg mice. These effects were associated with reduced levels of FL APP and APP C-terminal fragments, but levels of BACE1, Notch1, Nep, and IDE were unchanged. In contrast, levels of active cyclin-dependent kinase-5 (CDK5) and glycogen synthase kinase-3beta [GSK-3beta; but not stress-activated protein kinase-1 (SAPK1)], kinases that phosphorylate APP, were reduced. Furthermore, Cerebrolysin reduced the levels of phosphorylated APP and the accumulation of APP in the neuritic processes. Taken together, these results suggest that Cerebrolysin might reduce AD-like pathology in the APP tg mice by regulating APP maturation and transport to sites where Abeta protein is generated. This study clarifies the mechanisms through which Cerebrolysin might reduce Abeta production and deposition in AD and further supports the importance of this compound in the potential treatment of early AD.
Ubiquitous commerce - always on, always aware, always pro-active (2003)

The development of the infrastructure for ubiquitous computing is progressing rapidly, yet the applications that will be built on this new infrastructure remain largely ill defined. What will we do with these emerging capabilities? Stock quotes in 3-D on your heads-up display? Sports scores in stereo sound? We believe that the new kinds of services will result from three primary capabilities of ubiquitous devices: (1) to provide a service channel for remote service providers through an "always on" connection, (2) to inform these services about the local context of the user through an array of sensors, and (3) to enable these services to affect things in the user environment through actuators and local communication links. The new services enabled by these capabilities will lead to a new era of ubiquitous commerce, and change all business functions from customer relationship management to enterprise and supply chain management.
Isolation of Two Novel Genes, Down‐regulated in Gastric Cancer (2000)

Using a differential display technique, we identified two genes that are down-regulated in human gastric cancer tissue as compared to normal gastric mucosa. The down-regulated expression of these genes in gastric cancer tissue was confirmed by northern blotting analysis and RT-PCR. One, CA11, was a novel gene expressed predominantly in the stomach and was depleted in all of the gastric cancer cell lines examined. The other gene, GC36, was homologous to the digestive tract-specific calpain gene, nCL-4. The expression of both GC36 and nCL-4 was suppressed or depleted in gastric cancer cell lines of differentiated and poorly differentiated types. This is the first report of genes, the expression of which is down-regulated with considerable frequency in gastric cancer.
Practical operation considerations for memristive integrating sensors (2016)

The effects of key operating parameter on the practical operation of a recently proposed memristor-based neuronal activity sensor are investigated. A test memristor device is repeatedly subjected to a reference neural recording input signal that has been pre-processed using different settings. The resulting changes in the ability of the device to capture and store neuronal activity as resistive state transitions are assessed. It is found that resistive switching saturation is an important performance limiting factor, combatable by resetting the memristor. Higher desired sensitivity (ability to detect less prominent features in the neural waveform) necessitates more frequent resets.
Evaluation of the IEEE 802.11p MAC Method for Vehicle-to-Vehicle Communication (2008)

In this paper the medium access control (MAC) method of the upcoming vehicular communication standard IEEE 802.11p has been simulated in a highway scenario with periodic broadcast of time-critical packets (so-called heartbeat messages) in a vehicle-to-vehicle situation. The 802.11p MAC method is based on carrier sense multiple access (CSMA) where nodes listen to the wireless channel before sending. If the channel is busy, the node must defer its access and during high utilization periods this could lead to unbounded delays. This well-known property of CSMA is undesirable for time-critical communications. The simulation results reveal that a specific node/vehicle is forced to drop over 80% of its heartbeat messages because no channel access was possible before the next message was generated. To overcome this problem, we propose to use self-organizing time division multiple access (STDMA) for real-time data traffic between vehicles. This MAC method is already successfully applied in commercial surveillance applications for ships (AIS) and airplanes (VDL mode 4). Our initial results indicate that STDMA outperforms CSMA for time-critical traffic safety applications in ad hoc vehicular networks.
Expression of neurotransmitter transport from rat brain mRNA in Xenopus laevis oocytes. (1988)

To permit a molecular characterization of neurotransmitter transporter proteins, we have studied uptake activities induced in Xenopus laevis oocytes after injection of adult rat forebrain, cerebellum, brainstem, and spinal cord poly(A)+ RNA. L-Glutamate uptake could be observed as early as 24 hr after injection, was linearly related to the quantity of mRNA injected, and could be induced after injection of as little as 1 ng of cerebellar mRNA. Transport of radiolabeled L-glutamate, gamma-aminobutyric acid, glycine, dopamine, serotonin, and choline could be measured in single microinjected oocytes with a regional profile consistent with the anatomical distribution of particular neurotransmitter synthesizing soma. Forebrain L-glutamate and dopamine uptake, as well as cerebellar L-glutamate transport, were found to be Na+-dependent. Cerebellar mRNA-induced L-glutamate transport was both time and temperature-dependent, was saturable by substrate, suggesting a single activity with an apparent transport Km of 14.2 microM and a Vmax of 15.2 pmol/hr per oocyte, and was sensitive to inhibitors of brain L-glutamate transport. Thus, the oocyte L-glutamate transport induced by injection of adult rat cerebellar mRNA appears essentially identical to the high-affinity, Na+-dependent L-glutamate uptake found in brain slices and nerve terminals. Experiments with size-fractionated cerebellar mRNA reveal single, comigrating peaks for cerebellar L-glutamate and gamma-aminobutyric acid transport, with peak activity obtained in fractions of approximately 2.7 kilobases, suggesting the presence of single or similarly sized mRNAs encoding each of these activities.
Hippuran transit times in the kidney: a new approach (1978)

Deconvolution of a renogram curve with the Hippuran concentration of the plasma is a procedure for finding the impulse response function H(t), which represents the probability that a Hippuran molecule, entering the kidney at zero time, is still present in the organ at a time t. The initial value of this function is one by definition. It may remain constant for a while but it should never increase and ultimately it should approach zero. Fleming and Goddard (1973) introduced a deconvolution technique for the renogram in which the Laplace transformation of the function I(t), the Hippuran concentration in the plasma, plays a role. This means that a mathematical expression must be found which is not too complicated for the required operations and is nevertheless a sufficiently close approximation of I(t). A three-exponential function I(t) is proposed. Much effort is saved by first computing the integral G(t) of the impulse response function. It is easily differentiated graphically and moreover it provides a simple means for finding the average transit time.
Management of venomous bites and stings (1998)

Many animals are capable of inflicting a bite or sting, particularly when threatened. This article deals with those animals which commonly result in attendance to A&E in the UK. Such animals arc either native species or are relatively common pets. For information on the management of patients who have been bitten or stung by a more exotic or unusual animal, contact a poisons information centre. In all cases where a poisons information centre is contacted, it is helpful if you have the full scientific name, where possible. As the common name may not be specific for a single species.
A study on service data transfer procedure using SCF and SDF (2002)

There has been a rapid increase in the use of mobile telecommunication systems, such as GSM, PDC and PCS, so many people are now using mobile terminal based services. In Japan, the Personal Handy Phone System (PHS) service, which offers a cheaper personal communication service, started in July 1995. Moreover, FPLMTS is being considered as the next generation architecture. As these mobile services become widely used, it will be necessary for a user belonging to one network to be served independently of his location. Therefore, it is important to achieve roaming from one network to another. There are two ways to achieve roaming: one is the HLR (home location register)-based procedure and the other is the VLR (visited location register)-based procedure. In the VLR-based procedure, the visited network can use the data copied from a roaming user's home network, i.e., the VLR. The article discusses VLR-based procedures for roaming and shows which procedure should be applied. Moreover, some message flows are proposed that use the X.500 series recommendation. All of these procedures use the SDF (service data function)-SDF interactions, and it is the agreement between networks that decides the treatment of the copied data.
[Refractory Clostridium difficile infection. Untraditional treatment of antibiotic-induced colitis]. (1991)

Intestinal Clostridium difficile infections are treated successfully with antibiotics. Relapses can be a problem. We describe a patient who suffered seven relapses after treatment with all the medicaments reported to be efficacious. She was cured only after treatment with faeces administered by duodenal tube.
A Guide to Organophosphorus Chemistry (2000)

The Nature of Organophosphorus Chemistry. Some General Considerations of Organophosphorus Compounds. The Common 3-Coordinate Functions ( ~ 3, ~ 3). The 4-Coordinate Phosphine Oxides, Other Chalcogenides and Phosphonium Salts. The Acids of Organophosphorus Chemistry and Their Derivatives. Phosphorus-31 NMR Spectroscopy. Other Spectroscopic Techniques in Organophosphorus Chemistry. Heterocyclic Phosphorus Compounds. Optically Active Organophosphorus Compounds. The Low- and High-Coordination States of Phosphorus. Organophosphorus Chemistry in Biology, Agriculture, and Technology. Index.
Design of a Retrovirus-Derived Vector for Expression and Transduction of Exogenous Genes in Mammalian Cells (1983)

We have developed a transfection vector for animal cells that contains long terminal repeat (LTR) sequences to promote expression. Plasmid p101/101, a derivative of plasmid pBR322 containing the complete Moloney murine sarcoma virus genome, was cut with restriction enzymes and religated so that both the 5' and 3' LTRs were retained and all but about 700 base pairs of the intervening viral sequences were removed. To test this vector, the Escherichia coli gene gpt was cloned into a unique PstI site, between the two LTRs, with guanine and cytosine tailing, a method that can be generalized for insertion of any DNA segment into this vector. When DNA from recombinant plasmids in which the gpt gene was inserted in the same transcriptional polarity as the LTR sequences was transfected onto murine or rat fibroblast cultures, we obtained a high yield of Gpt(+) colonies. However, plasmid constructs with the gpt gene in the opposite polarity were virtually devoid of activity. With gpt in the proper orientation, restriction enzyme cuts within the LTRs or between the 5' LTR and the gpt gene reduced transfection by more than 98%, whereas a cut between the gpt gene and the 3' LTR gave an 80% reduction in activity. Thus, both 5' and 3' LTR sequences are essential for optimal gpt expression, although the 5' LTR appears to play a more important role. When the LTR-gpt plasmid was transfected onto murine leukemia virus-infected mouse fibroblasts, we obtained evidence that RNA copies became pseudotyped into viral particles which could transfer the Gpt(+) phenotype into rodent cells with extremely high efficiency. This vector should prove useful for high-efficiency transduction of a variety of genes in mammalian cells.
Current status and recent advances of liver transplantation from donation after cardiac death (2011)

The last decade saw increased organ donation activity from donors after cardiac death (DCD). This contributed to a significant proportion of transplant activity. Despite certain drawbacks, liver transplantation from DCD donors continues to supplement the donor pool on the backdrop of a severe organ shortage. Understanding the pathophysiology has provided the basis for modulation of DCD organs that has been proven to be effective outside liver transplantation but remains experimental in liver transplantation models. Research continues on how best to further increase the utility of DCD grafts. Most of the work has been carried out exploring the use of organ preservation using machine assisted perfusion. Both ex-situ and in-situ organ perfusion systems are tested in the liver transplantation setting with promising results. Additional techniques involved pharmacological manipulation of the donor, graft and the recipient. Ethical barriers and end-of-life care pathways are obstacles to widespread clinical application of some of the recent advances to practice. It is likely that some of the DCD offers are in fact probably "prematurely" offered without ideal donor management or even prior to brain death being established. The absolute benefits of DCD exist only if this form of donation supplements the existing deceased donor pool; hence, it is worthwhile revisiting organ donation process enabling us to identify counter remedial measures.
Design and validation of computer protocols (1991)

This text is intended as a comprehensive guide to the design and analysis of computer communications protocols. It introduces a sound discipline for the design of complete and consistent protocol systems, independent of where they are used. This volume discusses the fundamental problems of designing logically consistent methods of communication between multiple computer processes. Standard protocol design problems, such as error control and flow control, are covered in detail, but also structured design methods and the construction of formal validation models. The book contains complete listings and explanations of new protocol validation and design tool called SPIN. Author is in charge of protocol design at Bell Labs. Professionals who bought Tanenbaum's COMPUTER NETWORKS, 2/E and Comer's TCP/IP will buy this. This is the first book to cover automated protocol design and validation tools extensively.