gebhart/patrepeval huggingface dataset:
Microencapsulation: A promising technique for controlled drug delivery. (2010)

MICROPARTICLES OFFER VARIOUS SIGNIFICANT ADVANTAGES AS DRUG DELIVERY SYSTEMS, INCLUDING: (i) an effective protection of the encapsulated active agent against (e.g. enzymatic) degradation, (ii) the possibility to accurately control the release rate of the incorporated drug over periods of hours to months, (iii) an easy administration (compared to alternative parenteral controlled release dosage forms, such as macro-sized implants), and (iv) Desired, pre-programmed drug release profiles can be provided which match the therapeutic needs of the patient. This article gives an overview on the general aspects and recent advances in drug-loaded microparticles to improve the efficiency of various medical treatments. An appropriately designed controlled release drug delivery system can be a foot ahead towards solving problems concerning to the targeting of drug to a specific organ or tissue, and controlling the rate of drug delivery to the target site. The development of oral controlled release systems has been a challenge to formulation scientist due to their inability to restrain and localize the system at targeted areas of gastrointestinal tract. Microparticulate drug delivery systems are an interesting and promising option when developing an oral controlled release system. The objective of this paper is to take a closer look at microparticles as drug delivery devices for increasing efficiency of drug delivery, improving the release profile and drug targeting. In order to appreciate the application possibilities of microcapsules in drug delivery, some fundamental aspects are briefly reviewed.
The vaccinia virus 4c and A-type inclusion proteins are specific markers for the intracellular mature virus particle (1996)

Gel analysis of vaccinia virus particles purified by buoyant [correction of bouyant] density demonstrates a protein with an estimated molecular mass of 59 kDa, which is apparently restricted to the intracellular mature virion (IMV) form. Western blotting (immunoblotting) and immunoprecipitation procedures identify the protein as the vaccinia virus 4c protein, which facilitates occlusion of poxvirus particles within cowpox cytoplasmic inclusions. Western blotting procedures also identify the truncated A-type inclusion protein of vaccinia virus as a specific marker for IMV particles. Kinetic analyses of virion maturation and 4c production suggest that peak enveloped virion production occurs before peak IMV production in the virus replication cycle and that 4c production is concomitant with maturation of IMV. The implications for a distinct and evolutionarily conserved function of IMV in viral pathogenesis are discussed.
Cannabis use improves retention and virological outcomes in patients treated for hepatitis C (2006)

Our results suggest that modest cannabis use may offer symptomatic and virological benefit to some patients undergoing HCV treatment by helping them maintain adherence to the challenging medication regimen.
Target blood pressure in sepsis: between a rock and a hard place (2013)

The optimal target blood pressure in septic shock is still unknown. Therefore, in a long-term, resuscitated porcine model of fecal peritonitis-induced septic shock, Corrêa and colleagues tested whether different titrations of mean arterial pressure (50 to 60 and 75 to 85 mm Hg) would produce different effects on sepsis-related organ dysfunction. The higher blood pressure window was associated with increased needs for fluid resuscitation and norepinephrine support. However, titrating the lower blood pressure range coincided with an increased incidence of acute kidney injury. In contrast, neither the inflammatory response nor tissue mitochondrial activity showed any difference. This research paper in a clinically relevant model elegantly demonstrates that any standard resuscitation strategy may be a double-edged sword with respect to various therapeutic endpoints. Furthermore, it adds an important piece to the puzzle of the complex pathophysiology of sepsis-related acute kidney injury.
Purification, cDNA Cloning, and Characterization of a New Serpin with Megakaryocyte Maturation Activity (1997)

A new member of the serine protease inhibitor (serpin) superfamily with megakaryocyte maturation activity was purified, and its cDNA was cloned and characterized. The predicted amino acid sequence consisting of 380 residues was unique and was 38% identical to the serpin plasminogen activator inhibitor type 2 (PAI-2). The recombinant factor expressed in Chinese hamster ovary cells showed species-specific activity on the induction of megakaryocyte maturation in vitro. When injected into mice, the factor indeed elicited an increase in the number of platelets in plasma. The sequence alignment indicated that the factor possessed a lysine residue at the P1 position, suggesting that it might function as an inhibitor of Lys-specific proteases. Although we could not show any inhibitory activities toward several known Lys-specific proteases, we detected the activity toward protease activity present in the culture supernatant of COLO 201 cells. These results suggested that the protein might influence the maturation of megakaryocytes via action as a serpin.
Transport of macromolecules across microvascular walls: the two-pore theory (1994)

In this review we summarized the evidence favoring the concept that the major plasma proteins are passively transported across vascular walls through water-filled pathways by means of convection and diffusion. With regard to solute transport, a majority of microvascular walls seems to show a bimodal size selectivity. This implies the presence of a high frequency of functional small pores, restricting proteins, and an extremely low number of non-size-selective pathways, permitting the passage of macromolecules from blood to tissue, here denoted large pores. We discussed the general behavior of such a heteroporous system. A major consequence of two-pore heteroporosity is that large-solute transport must mainly occur due to convection through large pores at low filtration rates, that is, at normal or even zero lymph flows. Indeed, convection must be the predominating transport mode for most solutes across large pores when the net filtration rate is zero. Under these (transient) conditions, the convective leak of macromolecules across large pores will be counterbalanced by absorption of essentially protein-free fluid through protein-restrictive pores. In a heteroporous membrane, proteins can thus be transported by solvent drag across vascular walls in the absence of a net convection. Normally the steady-state transcapillary fluid flow (lymph flow) is about equally partitioned among small and large pores, which makes lymph essentially a "half and half" mixture of protein-free ultrafiltrate and plasma. With increasing fluid flows, however, the plasma filtrate will be progressively diluted, eventually reaching a protein concentration largely in proportion to the fractional hydraulic conductance accounted for by the large pores (alpha L). Under these high lymph flow conditions, not only the large-pore transport but also the small-pore transport (of smaller macromolecules) will become convective. At low lymph flows, however, the small-pore transport of smaller macromolecules is usually mostly diffusive. An important implication of capillary heteroporosity is that single-pore formalism is inadequate for correctly evaluating the capillary sieving characteristics. With the use of homoporous transport formalism, the "lumped" macromolecular PS and sigma will therefore vary as a function of transcapillary fluid flow (Jv). However, it is approximately correct to use single-pore formalism for conditions when Jv is very high during steady state. Thus, if minimal sieving coefficients can be measured for macromolecules, then these values will accurately reflect (1 - sigma).(ABSTRACT TRUNCATED AT 400 WORDS)
Evidence that multiple myeloma Ig heavy chain VDJ genes contain somatic mutations but show no intraclonal variation (1992)

To investigate whether somatic hypermutation occurs in multiple myeloma (MM) Ig VH region genes, we have cloned and sequenced the expressed VH genes from five cases of MM. The sequences were obtained after polymerase chain reaction (PCR) on total RNA isolated from the bone marrow, using 5′ VH family-specific leader and 3′ C gamma- or C alpha- specific primers. MM-specific CDR3 oligonucleotides were produced to isolate VH genes expressed by the malignant plasma cells. In all five cases, the productive Ig gene used the VH3 family. Extensive sequence analysis of multiple independent M13 clones showed no intraclonal variation with no evidence for ongoing somatic hypermutation in MM VH region genes. We were able to identify possible germline counterparts of the expressed VH genes in two cases. Comparison of these genes shows that the MM VH region genes have somatic mutations characteristic for an antigen-driven process. In the other three cases, no close homology could be found with published VH3 sequences. These findings implicate that, in MM, clonal proliferation takes place in a cell type that has already passed through the phase of somatic hypermutation.
Attracting the translation machinery to internal ribosome entry sites (2001)

Studies on the control of eukaryotic translation initiation by a cap-independent recruitment of the 40S ribosomal subunit to internal messenger RNA sequences called internal ribosome entry sites (IRESs) have shown that these sequence elements are present in a growing list of viral and cellular RNAs. Here we discuss their prevalence, mechanisms whereby they may function and their uses in regulating gene expression.
Space-frequency-time turbo coded modulation (2001)

A new bandwidth and power efficient signaling scheme is proposed that achieves high data rates over wideband radio channels exploiting the bandwidth efficient OFDM modulation, multiple transmit and receive antennas and large frequency selectivity offered in typical low mobility indoor environments. Owing to its maximum transmit diversity gain and large coding gain, space-frequency-time turbo coded modulation strongly outperforms other space-frequency-time coding schemes proposed in literature. A simple way of combining space-frequency-time coding with OFDM delay diversity for cost effective exploitation of more than two transmit antennas is also proposed in this paper.
Transcriptome Studies of Bovine Endometrium Reveal Molecular Profiles Characteristic for Specific Stages of Estrous Cycle and Early Pregnancy (2008)

The endometrium undergoes marked functional changes during estrous cycle and pregnancy. As the adjacent environment of the conceptus, it represents the maternal interface for embryo-maternal communication, which is essential to maintain pregnancy. Transcriptome studies provide the unique opportunity to assess molecular profiles changing in response to endocrine or metabolic stimuli or to embryonic pregnancy recognition signals. Here we review the current state of transcriptome profiling techniques and the results of a series of transciptome studies comparing bovine endometrium samples during the estrous cycle or endometrium samples from pregnant vs. non-pregnant animals. These studies revealed specific mRNA profiles which are characteristic for the functional status of the endometrium. Transcriptome studies of endometrial samples recovered during the pre-attachment period identified many interferon-stimulated genes, genes that are possibly involved in embryo-maternal immune modulation ( C1S, C1R, C4, SERPING1, UTMP, CD81, IFITM1, BST2), as well as genes affecting cell adhesion ( AGRN, CD81, LGALS3BP, LGALS9, GPLD1, MFGE8, and TGM2) and remodeling of the endometrium ( CLDN4, MEP1B, LGMN, MMP19, TIMP2, TGM2, MET, and EPSTI1). The results of these transcriptome studies were compared to those of similar microarray analyses in human, mouse and Rhesus monkey to identify similarities in endometrial biology between mammalian species and species-specific differences. Future studies will cover dynamic transcriptome changes between different stages of early pregnancy, the relationship between metabolic problems in dairy cows and the functionality of reproductive tissues as well as endometrium transcriptome profiles in recipients of somatic cell nuclear transfer embryos.
CORTICOSTEROID INHIBITION OF THE OKT3-INDUCED CYTOKINE-RELATED SYNDROME (1991)

The data presented extend to a larger series of 27 consecutive renal allograft recipients treated prophylactically with OKT3 our previous observation that the acute OKT3-induced clinical syndrome is related to massive release in the circulation of some cytokines, among which are tumor necrosis factor and interferon gamma. In addition, a pilot randomized study was set up including 12 consecutive patients receiving high-dose corticosteroid treatment (0.5 g solumedrol) either before or at the same time as the first OKT3 injection. Results confirm that when corticosteroids are given in sufficient amount and, importantly, 1 hr before the first OKT3 injection, they significantly decrease the release of both tumor necrosis factor and interferon gamma. In addition, the pretreatment with corticosteroids may totally abolish the IL-2 release induced by OKT3. Given the key role the massive although transient cytokine release plays in determining the OKT3-induced acute syndrome, these results provide the biological basis supporting a precise kinetics of administration of high-dose corticosteroids to better decrease the severity of the clinical reaction.
A Scalable Platform for Integrating Horizontal Nanochannels with Known Registries to Microchannels (2008)

Controlling the location and physical orientation of nanobuilding blocks in assemblies of nanodevices become challenging tasks when it comes to the use of “bottom-up” chemical approaches for nanodevice fabrication. Here, a strategy is reported for in situ fabrication of horizontal nanochannels, which allows control over their orientation and average pore size to an unprecedented range of ∼5−20 nm. Using this approach, we selectively fabricated nanochannels with controlled average pore sizes at known positions on a sapphire surface. Equally important, nanochannels, either single or group, are addressable photolithographically and integrable to microchannels without the use of any high resolution lithography. This technique uses horizontal ZnO nanowires (NWs) as a sacrificial template and could provide the capability of fabrication of complex micro- and nanofluidic platforms. Cross-sections of nanowires and nanochannels are prepared via a focused-ion beam and examined by electron microscopy and energy-dispersive X-ray spectroscopy.
A Unifying Genetic Model for Facioscapulohumeral Muscular Dystrophy (2010)

Facioscapulohumeral muscular dystrophy (FSHD) is a common form of muscular dystrophy in adults that is foremost characterized by progressive wasting of muscles in the upper body. FSHD is associated with contraction of D4Z4 macrosatellite repeats on chromosome 4q35, but this contraction is pathogenic only in certain "permissive" chromosomal backgrounds. Here, we show that FSHD patients carry specific single-nucleotide polymorphisms in the chromosomal region distal to the last D4Z4 repeat. This FSHD-predisposing configuration creates a canonical polyadenylation signal for transcripts derived from DUX4, a double homeobox gene of unknown function that straddles the last repeat unit and the adjacent sequence. Transfection studies revealed that DUX4 transcripts are efficiently polyadenylated and are more stable when expressed from permissive chromosomes. These findings suggest that FSHD arises through a toxic gain of function attributable to the stabilized distal DUX4 transcript.
Solving Schrödinger’s equation around a desired energy: Application to silicon quantum dots (1994)

We present a simple, linear-in-size method that enables calculation of the eigensolutions of a Schrödinger equation in a desired energy window. We illustrate this method by studying the near-gap electronic structure of Si quantum dots with size up to Si1315H460(≊37 Å in diameter) using a plane wave pseudopotential representation.
Structure and dynamics of Escherichia coli adenylate kinase (1996)

Escherichia coli adenylate kinase has been studied by X-ray crystallographic and molecular dynamics approaches. The structures of E. coli adenylate kinase complexed with either AMP and AMPPNP, or AMP and ADP are presented. The AMP/AMPPNP complex has been determined to a resolution of 2.0 A, and confirms the location of the AMP and ATP binding sites on the protein. The AMP/ADP complex has been determined to resolution of 2.8 A, and demonstrates the geometry of this inhibitory complex.\nMolecular dynamics studies of E. coli adenylate kinase have been done using the weighted masses technique. Simulations were conducted using two general protocols (CHARMM and X-PLOR) which differ in the nature of the secondary structural constraints applied. Both protocols were successful in simulating the opening of the two mobile domains of the protein. The X-PLOR based trajectories, using a heterogeneous weighting system, were also able to simulate the closing of the mobile domains, resulting in a more Gaussian distribution of conformations than that seen in the CHARMM based method.
Effect of Early Antiretroviral Therapy during Primary HIV-1 Infection on Cell-Associated HIV-1 Dna and Plasma HIV-1 Rna (2010)

Early treatment initiation within 2 months after HIV infection compared with later therapy initiation resulted in reduced levels of plasma viraemia and proviral HIV-1 DNA for ≥1 year after subsequent ART cessation. Plasma HIV-1 RNA levels in early starters were also significantly lower than in untreated controls.
Tolerability and Pharmacokinetics of Delayed-Release Dimethyl Fumarate Administered With and Without Aspirin in Healthy Volunteers (2013)

In healthy volunteers, DR-DMF was well tolerated over 4 days of dosing, with a PK profile consistent with that previously reported and no evidence of accumulation. Aspirin pretreatment reduced the incidence and intensity of flushing without affecting GI events or the DR-DMF PK profile. Elevated levels of PGD2 in some DR-DMF-treated individuals suggest that flushing may be, at least in part, prostaglandin mediated. ClinicalTrials.gov identifier: ID: NCT01281111.
Light-emitting platinum(ii) complexes supported by tetradentate dianionic bis(N-heterocyclic carbene) ligands: towards robust blue electrophosphors (2013)

The synthesis, structures and photophysical properties of the charge-neutral Pt(II) complexes (1–6) and their Pd(II) (7) and Ni(II) (8) congeners supported by tetradentate dianionic bis[phenolate-(N-heterocyclic carbene)] ligands are described. The X-ray crystal structures of two solvatomorphs of 2, which has p-F substituents on the tetradentate ligand, have been determined. The photophysical properties of all the complexes were examined. In THF solutions, 1–4 display deep blue phosphorescence (λmax = ∼440–460 nm, Φe = 3–18% and τ = 0.5–3.5 μs). In solutions at room temperature, 5–8 show profoundly different luminescence properties from being virtually non-emissive (Φe < 10−3) for 6–8 to highly emissive (Φe = 15%) with much red-shifted phosphorescence (λmax = ∼530 nm) and a long emission lifetime (τ = 47.2 μs) in the case of 5. Time-dependent density functional theory (TDDFT) calculations reveal that the tetradentate bis(phenolate-NHC) ligands in 1–4 provide a rigid scaffold for preserving a tightly bound Pt(II) in a square-planar coordination geometry in the T1 as in the S0 states and the blue emission is derived from the T1 state having predominant ligand (πAr–O)-to-ligand (π*NHC) charge transfer (LLCT) character. A switch of orbital parentage from LLCT to ligand-centred (LC) π–π* is responsible for the long emission lifetime and vibronically structured emission displayed by 5 when compared to that of 1–4 and 6. Both femtosecond time-resolved fluorescence (fs-TRF) and nanosecond time-resolved emission (ns-TRE) measurements were conducted on 2 and 4 to directly probe the excited-state dynamics after photoexcitation. Excellent thermal stability of the fluorine-free complex 4 and its higher emission quantum yield (relative to 1 and 3), and using 9-(4-tert-butylphenyl)-3,6-bis(triphenylsilyl)-9H-carbazole (CzSi) as host material, led to the fabrication of highly efficient deep blue OLEDs with peak current efficiency of 24 cd A−1 and white organic light-emitting devices (WOLEDs) with peak current efficiency of 88 cd A−1.
Chloride and fluid secretion in polycystic kidney disease. (1998)

Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City 66160, USA.
Multidimensional Ultrasonic Standing Wave Manipulation in Microfluidic Chips (2009)

The use of ultrasonic standing waves for contactless manipulation of microparticles in microfluidic systems is a field with potential to become a new standard tool in lab-on-chip systems. Compared to other contactless manipulation methods ultrasonic standing wave manipulation shows promises of gentle cell handling, low cost, and precise temperature control. The technology can be used both for batch handling, such as sorting and aggregation, and handling of single particles. This doctoral Thesis presents multi-dimensional ultrasonic manipulation, i.e., manipulation in both two and three spatial dimensions as well as time-dependent manipulation of living cells and microbeads in microfluidic systems. The lab-on-chip structures used allow for high-quality optical microscopy, which is central to many bio-applications. It is demonstrated how the ultrasonic force fields can be spatially confined to predefined regions in the system, enabling sequential manipulation functions. Furthermore, it is shown how frequency-modulated signals can be used both for spatial stabilization of the force fields as well as for flow-free transport of particles in a microchannel. Design parameters of the chip-transducer systems employed are investigated experimentally as well as by numerical simulations. It is shown that three-dimensional resonances in the solid structure of the chip strongly influences the resonance shaping in the channel.
Commercial landscape of noninvasive prenatal testing in the United States (2013)

Cell-free fetal DNA-based noninvasive prenatal testing (NIPT) could significantly change the paradigm of prenatal testing and screening. Intellectual property (IP) and commercialization promise to be important components of the emerging debate about clinical implementation of these technologies. We have assembled information about types of testing, prices, turnaround times, and reimbursement of recently launched commercial tests in the United States from the trade press, news articles, and scientific, legal, and business publications. We also describe the patenting and licensing landscape of technologies underlying these tests and ongoing patent litigation in the United States. Finally, we discuss how IP issues may affect clinical translation of NIPT and their potential implications for stakeholders. Fetal medicine professionals (clinicians and researchers), genetic counselors, insurers, regulators, test developers, and patients may be able to use this information to make informed decisions about clinical implementation of current and emerging noninvasive prenatal tests.