gebhart/patrepeval huggingface dataset:
Intratumoral Injection of INGN 241, a Nonreplicating Adenovector Expressing the Melanoma-Differentiation Associated Gene-7 (mda-7/IL24): Biologic Outcome in Advanced Cancer Patients (2004)

The mda-7 gene (approved gene symbol IL24) is a novel tumor suppressor gene with tumor-apoptotic and immune-activating properties. We completed a Phase I dose-escalation clinical trial, in which a nonreplicating adenoviral construct expressing the mda-7 transgene (INGN 241; Ad-mda7) was administered intratumorally to 22 patients with advanced cancer. Excised tumors were evaluated for vector-specific DNA and RNA, transgenic MDA-7 expression, and biological effects. Successful gene transfer as assessed by DNA- and RT-PCR was demonstrated in 100% of patients evaluated. DNA analyses demonstrated a dose-dependent penetration of INGN 241 (up to 4 x 10(8) copies/mug DNA at the 2 x 10(12) vp dose). A parallel distribution of vector DNA, vector RNA, MDA-7 protein expression, and apoptosis induction was observed in all tumors, with signals decreasing with distance away from the injection site. Additional evidence for bioactivity of INGN 241 was illustrated via regulation of the MDA-7 target genes beta-catenin, iNOS, and CD31. Transient increases (up to 20-fold) of serum IL-6, IL-10, and TNF-alpha were observed. Significantly higher elevations of IL-6 and TNF-alpha were observed in patients who responded clinically to INGN 241. Patients also showed marked increases of CD3+CD8+ T cells posttreatment, suggesting that INGN 241 increased systemic TH1 cytokine production and mobilized CD8+ T cells. Intratumoral delivery of INGN 241 induced apoptosis in a large volume of tumor and elicited tumor-regulatory and immune-activating events that are consistent with the preclinical features of MDA-7/IL-24.
The Favorskii-type Rearrangement of 3-Bromo-β-ionone with Sodium Ethoxide (1982)

Abstract The reaction of 3-bromo-β-ionone with sodium ethoxide afforded ethyl 4-(2,6,6-trimethyl-2-cyclohexenylidene)butyrate by a Favorskii-type rearrangement, accompanied by double-bond migration, while with sodium phenoxide or diethyl amine, substitution products were primarily obtained.
HLA class II as potential target antigen on malignant B cells for therapy with bispecific antibodies in combination with granulocyte colony-stimulating factor (1996)

We have investigated the capacity of polymorphonuclear phagocytes (PMN) to lyse malignant B-cell lines using antibodies and antibody derivates to a range of different B-cell antigens. PMN were found to mediate lysis of all tested B-cell lines in the presence of HLA class II antibodies L227, L243, F3.3, and CR3/43. Target cell lysis was significantly enhanced when PMN isolated during granulocyte colony-stimulating factor (G-CSF) treatment were compared with PMN from healthy donors. Only G-CSF primed PMN, expressing Fc gamma RI (CD64), lysed B cells in the presence of monoclonal antibody (MoAb) 1D10 or Lym-1 to HLA class II related epitopes. Remarkably, PMN were consistently unable to kill malignant B cells with antibodies to the B-cell related antigens CD19, CD20, CD21, CD37, and CD38. These target antigen restriction was not observed with mononuclear effector cells, which mediated cytotoxicity with antibodies to HLA class II, but also with mouse/human chimeric constructs to CD19, CD37, and CD38. Blocking studies with Fc gamma RI antibodies and reverse antibody-dependent cellular cytotoxicity (ADCC) experiments against Fc gamma R antibody expressing hybridoma targets confirmed the pivotal role of Fc gamma RI in enhanced killing by G-CSF primed neutrophils. Bispecific antibodies (BsAb) with one specificity for Fc gamma RI, and another for a tumor associated antigen, offer an interesting approach to improve effector cell recruitment for immunotherapy. In our studies, very effective lysis was observed with G-CSF primed PMN and an [HLA class II x Fc gamma RI] BsAb. The therapeutic implications of these findings and the possible use of BsAb in combination with G-CSF are discussed.
Human choriogonadotrophin protein core and sugar branches heterogeneity: basic and clinical insights (2008)

Measurement of hCG and/or its related molecules is useful in clinical practice, but greater awareness is needed worldwide regarding the use of new sensitive and specific assays tailored for different clinical applications.
Evaluation of image appeal in consumer photography (2000)

In consumer photography, image appeal may be defined by the interest that a picture generates when viewed by third-party observers. In this paper, the results of a ground truth experiment on human estimation of image appeal are reported, where 11 participants were asked to rank pictures in 30 groups, based on their relative appeal within their group and comment on the factors that influenced their decisions. Based on their responses, a list of both positive and negative influences was compiled and influences were grouped in general categories that include people, composition, subject, and objective metrics. The results of our experiment indicate that image appeal is related to image quality only with respect to the influences in the category of objective metrics, while the majority of influences belong to the categories of people, composition, and subject. The influences in these categories are scene dependent and fundamentally different in nature from traditional image quality metrics. Thus, when evaluating image appeal a new set of metrics needs to be developed. Individual influences and their relative merits are discussed.
Effect of Porous Structure on the Degradation of Freeze-Dried Gelatin Hydrogels (1999)

Porous biodegradable hydrogels were prepared by glutaraldehyde crosslinking of acidic gelatin with an isoelectric point of 5.0, followed by freeze-drying. The inner structures of the freeze-dried hydrogels were strongly dependent on the preliminary freezing temperatures prior to freeze-drying. As the freezing temperature was raised, the pore size of the freeze-dried hydrogels increased while their wall thickness decreased. The hydrogels frozen at -20°C swell more rapidly in water than those at 408 and -196°C. In vivo and in vitro degradations of freeze-dried hydrogels with different inner structures were evaluated subcutis in mice and in a collagenase aqueous solution, respectively. The hydrogels prepared at -20°C were more rapidly degraded both in vitro and in vivo, compared to those at -80° and -196°C. The hydrogels freeze-dried at -196°C had the smallest pore size, thickest gelatin walls, and required a longer time for complete degradation. Basic fibroblast growth factor (bFGF) was impregnated into the gelatin hydrogels and the in vitro bFGF release was evaluated. No influence by the inner structure on the release profile of bFGF was observed. Since bFGF is ionically completed with acidic gelatin, it is possible that it was released from these gelatin hydrogels in a similar fashion, irrespective of the hydrogel inner structure.
CMOS image sensor with organic photoconductive layer having narrow absorption band and proposal of stack type solid-state image sensors (2006)

Digital still cameras overtook film cameras in Japanese market in 2000 in terms of sales volume owing to their versatile functions. However, the image-capturing capabilities such as sensitivity and latitude of color films are still superior to those of digital image sensors. In this paper, we attribute the cause for the high performance of color films to their multi-layered structure, and propose the solid-state image sensors with stacked organic photoconductive layers having narrow absorption bands on CMOS read-out circuits.
Expression of butyrophilin (Btn1a1) in lactating mammary gland is essential for the regulated secretion of milk–lipid droplets (2004)

Butyrophilin 1a1 (Btn1a1), which is a member of the Ig superfamily, is highly expressed in the lactating mammary gland and is secreted into milk in association with lipid droplets. To determine the potential function of Btn1a1 in milk secretion, we ablated Btn1a1 in mice and analyzed the lactation phenotype of homozygous (Btn1a1(-/-)) animals. Two mutant mouse lines were generated in which expression of Btn1a1 was either disrupted or eliminated, respectively. The regulated secretion of milk-lipid droplets was severely compromised in both mutant mouse lines in comparison to wild-type animals. Large pools of triacylglycerol accumulated in the cytoplasm of secretory cells, and lipid droplets escaped from the apical surface with disrupted outer membranes. Luminal spaces became engorged with unstable lipid droplets, which coalesced to form large aggregates. The amount of lipid (wt/vol) was elevated, on average by 50%, during the first 10 days of lactation, and the diameter of the droplets was up to seven times larger than the normal diameter. In contrast, there was no significant difference between wild-type and null animals in the relative amounts of skim-milk proteins secreted from Golgi-derived secretory vesicles. Approximately half the pups suckling Btn1a1(-/-) animals died within the first 20 days, and weaning weights for the surviving pups were 60-80% of those suckling wild-type mice. Thus, expression of Btn1a1 is essential for the regulated secretion of milk-lipid droplets. We speculate that Btn1a1 functions either as a structural protein or as a signaling receptor by binding to xanthine dehydrogenase/oxidase.
Central Nervous System Reactions to Histamine-2 Receptor Blockers (1991)

All H2 blockers are associated with central nervous system reactions. There is no clear evidence of a higher rate of reactions with one H2 blocker compared with another.
The Skill of the Neolithic Bowyers: Reassessing the past through Experimental Archaeology (2000)

An account of the recreation of a working replica of the Neolithic Meare Heath bow that was undertaken utilising tools and materials available to the indigenous Neolithic population of Somerset. The paper assesses how, through re-creation and testing, hypotheses and interpretations previously attributed to the Meare Heath bow, and consequently to Neolithic bow-making in general, can be examined and re-appraised.
Trypsin in colorectal cancer: molecular biological mechanisms of proliferation, invasion, and metastasis (2006)

Trypsin is involved in colorectal carcinogenesis and promotes proliferation, invasion, and metastasis. Although a well-known pancreatic digestive enzyme, trypsin has also been found in other tissues and various cancers, most importantly of the colorectum. Moreover, colorectal cancers with trypsin expression have a poor prognosis and shorter disease-free survival. Biological understanding of how trypsin causes cancer progression is emerging. It seems to act both directly and indirectly through a 'proteinase-antiproteinase-system', and by activation of other proteinase cascades. Invasion of the basal membrane by cancer cells may be promoted directly by trypsin digestion of type I collagen. Trypsin activates, and is co-expressed with matrix metalloproteinases (MMPs), which are known to facilitate invasion and metastasis. MMP-2, MMP-7, and MMP-9 are co-expressed together with trypsin and seem to be of particular importance in proliferation, progression, and invasion. MMPs may play a role in both conversion from adenoma to carcinoma, and in the initiation of invasion and metastasis. Co-segregation of trypsin and MMPs within the tumour environment is important for the activation of MMPs, and may explain the deleterious effect of trypsin on prognosis in colorectal cancer. Trypsin and proteinase-activated receptor 2 (PAR-2) act together in an autocrine loop that promotes proliferation, invasion, and metastasis through various mechanisms, of which prostaglandin synthesis is important. Stimulated by trypsin, both MMP and PAR-2 may activate the mitogenic MAPK-ERK pathway through activation of the epidermal growth factor receptor. Experimental trypsin inhibition is feasible but not very effective, and trypsin as a target for clinical therapy is unlikely to be successful owing to its universal distribution. However, as the pathways of trypsin and co-activated protein cascades emerge, biological understanding of colorectal carcinogenesis will be further illuminated and may pave the way for prognosticators, predictors, and novel targets of therapy.
Hierarchical Robust Control of Oscillating Wave Energy Converters With Uncertain Dynamics (2014)

Energy-maximizing controllers for wave energy devices are normally based on linear hydrodynamic device models. Such models ignore nonlinear effects which typically manifest themselves for large device motion (typical in this application) and may also include other modeling errors. The effectiveness of a controller is, in general, determined by the match between the model the controller is based on and the actual system dynamics. This match becomes especially critical when the controller is highly tuned to the system. In this paper, we present a methodology for reducing this sensitivity to modeling errors and nonlinear effects by the use of a hierarchical robust controller, which shows small sensitivity to modeling errors, but allows good energy maximization to be recovered through a passivity-based control approach.
A 9.6-kb/s DSP Speech Coder (1982)

A digital speech coder has been designed for real-time operation at a data rate of 9.6 kb/s. The design is based on a combination of two speech compression techniques: Time-Domain Harmonic Scaling (TDHS) and Sub-Band Coding (SBC). It is a highly modularized hardware implementation using five Bell Laboratories Digital Signal Processor (DSP) integrated circuits as the key processing elements. Three DSPS are used in the encoder for pitch detection, TDHS compression, and sub-band encoding. Another two DSPS are used in the receiver for sub-band decoding and TDHS expansion. In this paper we describe the overall design of the system and discuss some of the techniques used to realize it in the DSP hardware in real time. General issues of the algorithm design, software implementation, and hardware design are considered.
Oriented nickel-titanium shape memory alloy films prepared by annealing during deposition (1992)

Nickel-titanium shape memory alloy films, between 2 and 10 μm thick, were sputter deposited onto (100) silicon substrates. Films deposited onto a substrate at ambient temperature were amorphous; however, several post-deposition annealing procedures produced crystalline films exhibiting the B2-to-B19′ phase transition that gives rise to the shape memory effect. Films that were deposited onto a heated substrate, 350–460 °C, crystallized during deposition, eliminating the need for a separate annealing step. Powder x-ray diffraction indicated that these films were highly oriented, with the NiTi (110)B2 face parallel to the silicon substrate (100) face.
Channel-mediated monovalent cation fluxes in isolated sarcoplasmic reticulum vesicles. (1984)

The permeability of isolated sarcoplasmic reticulum (SR) vesicles to monovalent cations was studied using a stopped-flow fluorescence quenching technique that permits the measurement of ion fluxes on a millisecond time scale. Approximately 70% of the SR vesicles carry a cation conductance pathway mediating fluxes of Tl+, K+, Na+, and Li+, but not of choline. Both K+ and Na+ equilibrate faster than the 3-ms dead time of the apparatus and Li+ equilibrates in approximately 50 ms. These cation fluxes are reduced by a bis-guanidinium blocker of the SR K+ channel previously studied in planar bilayers. The remaining 30% of the vesicles are permeable to these cations on a time scale of seconds. We conclude that the SR K+ channel is present in a major fraction of vesicles and that its properties in the native membrane are similar to those found in planar bilayers. Moreover, the ion fluxes in fractionated SR vesicles suggest that the channels are distributed along the entire surface of the SR membrane, but in higher concentration in vesicles derived from the terminal cisternae region. From the measured rates of K+ movement, we calculate a conductance on the order of 10(-1) S/cm2 for the SR membrane in situ, which implies that this membrane cannot develop a potential of more than a few millivolts under physiological conditions.
Feasibility of Producing Porcine Nuclear Transfer Embryos by Using G2/M-Stage Fetal Fibroblasts as Donors1 (2001)

The type of donor cell most suitable for producing cloned animals is one of the topics under debate in the field of nuclear transfer. To provide useful information to answer this question, G2/M- and G0/G1-stage fetal fibroblasts were used as donor cells for nuclear transfer. In vitro-matured oocytes derived from abattoir ovaries were used as recipient cytoplasts. In both groups, nuclear envelope breakdown and premature chromosome condensation were completed within 1-2 h after donor cells were injected into the cytoplasm of oocytes. Microtubules were organized around condensed chromosomes and formed a spindle within 1-1.5 h after activation. Decondensation of chromosomes could be seen within 2-4 h after activation. Reformation of the new nuclear envelope occurred 4-6 h after activation and was followed by nuclear swelling and formation of a pronucleus-like structure (PN) 8-12 h after activation. Most (80.6%) of the reconstructed oocytes derived from G2/M cells extruded polar body-like structures (PB). However, a much lower frequency of PB (21.7%) was observed in the reconstructed oocytes derived from G0/G1 donors. A variety of PN and PB combinations were observed in reconstructed oocytes derived from G2/M-stage donors, including 1PN+0PB, 1PN+1PB, 1PN+2PB, 2PN+0PB, 2PN+1PB, 2PN+2PB, and 3PN+1PB. Chromosomes of most embryos (10/13) derived from G2/M stage were diploid. The percentage of cleavage and blastocysts and the average nuclear number of blastocysts in the G2/M and G0/G1 groups were not different. These results demonstrate that the G2/M stage can be morphologically remodeled by cytoplasm of MII oocytes in pigs. To maintain normal ploidy, the extra chromosomes derived from G2/M-stage cells could be expelled by oocytes as a second polar body. G2/M-stage fibroblast nuclei could direct reconstructed embryos to develop to the blastocyst stage.
High-Efficient Multi-key Exchange Protocol Based on Three-Party Authentication (2014)

Three-party authenticated key exchange protocol is designed for securing the communication between two users with the help of a trusted server. The users can encrypt data with the exchanged secret keys and then transmit the cipher text to each other. However, the inefficiency, unreliability, and inflexibility problems that can be found in many previous studies should be solved. Therefore, in this paper, we propose a secure multiple key exchange scheme, named the High-efficient Multi-key Exchange protocol based on Three-party Authentication (HeM3A for short), which provides users with a secure method to exchange their encryption keys by utilizing the elliptic curve cryptographic method, the logical XOR operation and the binary addition. The propose is hiding important parameters so as to avoid them from being cracked by hackers easily, and resist known-key, impersonation, replay and eavesdropping attacks. The multi-key exchange process, which provides higher security and performance than previous protocols, is practically useful in securing mobile applications.
Hydroxyl PAMAM dendrimer-based gene vectors for transgene delivery to human retinal pigment epithelial cells (2014)

Ocular gene therapy holds promise for the treatment of numerous blinding disorders. Despite the significant progress in the field of viral and non-viral gene delivery to the eye, significant obstacles remain in the way of achieving high-level transgene expression without adverse effects. The retinal pigment epithelium (RPE) is involved in the pathogenesis of retinal diseases and is a key target for a number of gene-based therapeutics. In this study, we addressed the inherent drawbacks of non-viral gene vectors and combined different approaches to design an efficient and safe dendrimer-based gene-delivery platform for delivery to human RPE cells. We used hydroxyl-terminated polyamidoamine (PAMAM) dendrimers functionalized with various amounts of amine groups to achieve effective plasmid compaction. We further used triamcinolone acetonide (TA) as a nuclear localization enhancer for the dendrimer-gene complex and achieved significant improvement in cell uptake and transfection of hard-to-transfect human RPE cells. To improve colloidal stability, we further shielded the gene vector surface through incorporation of PEGylated dendrimer along with dendrimer-TA for DNA complexation. The resultant complexes showed improved stability while minimally affecting transgene delivery, thus improving the translational relevance of this platform.
Enabling Java mobile computing on the IBM Jikes research virtual machine (2006)

Today's complex applications must face the distribution of data and code among different network nodes. Java is a wide-spread language that allows developers to build complex software, even distributed, but it cannot handle the migration of computations (i.e. threads), due to intrinsic limitations of many traditional JVMs. After analyzing the approaches in literature, this paper presents our research work on the IBM Jikes Research Virtual Machine: exploiting some of its innovative VM techniques, we implemented an extension of its scheduler that allows applications to easily capture the state of a running thread and makes it possible to restore it elsewhere (i.e. on a different hardware or software architecture, but still with a version of JikesRVM installed). Our thread serialization mechanism provides support for both proactive and reactive migration of single- and multi-threaded Java applications. With respect to previous approaches, we implemented the mobility framework without recompiling a previous JVM source code, but simply extending its functionalities with a full Java package.
Reengineered salivary glands are stable endogenous bioreactors for systemic gene therapeutics (2004)

The use of critical-for-life organs (e.g., liver or lung) for systemic gene therapeutics can lead to serious safety concerns. To circumvent such issues, we have considered salivary glands (SGs) as an alternative gene therapeutics target tissue. Given the high secretory abilities of SGs, we hypothesized that administration of low doses of recombinant adeno-associated virus (AAV) vectors would allow for therapeutic levels of transgene-encoded secretory proteins in the bloodstream. We administered 10(9) particles of an AAV vector encoding human erythropoietin (hEPO) directly to individual mouse submandibular SGs. Serum hEPO reached maximum levels 8-12 weeks after gene delivery and remained relatively stable for 54 weeks (longest time studied). Hematocrit levels were similarly increased. Moreover, these effects proved to be vector dose-dependent, and even a dosage as low as 10(8) particles per animal led to significant increases in hEPO and hematocrit levels. Vector DNA was detected only within the targeted SGs, and levels of AAV copies within SGs were highly correlated with serum hEPO levels (r = 0.98). These results show that SGs appear to be promising targets with potential clinical applicability for systemic gene therapeutics.