gebhart/patrepeval huggingface dataset:
Glycoprotein‐binding site of dystrophin is confined to the cysteine‐rich domain and the first half of the carboxy‐terminal domain (1992)

Dystrophin, a protein product of the Duchenne muscular dystrophy gene, is thought to associate with the muscle membrane by way of a glycoprotein complex which was co-purified with dystrophin. Here, we firstly demonstrate direct biochemical evidence for association of the carboxy-terminal region of dystrophin with the glycoprotein complex. The binding site is found to lie further inward than previously expected and confined to the cysteine-rich domain and the first half of the carboxy-terminal domain. Since this portion corresponds well to the region that, when missing, results in severe phenotypes, our finding may provide a molecular basis of the disease.
Biologically Based Treatment in Head and Neck Squamous Cell Carcinoma (2012)

This article discusses the concept of window-of-opportunity studies in relation to squamous cell cancers of the head and neck. Also discussed are predictors of sensitivity and resistance mechanisms, a review of poly (adenosine diphosphate-ribose) polymerase inhibitors and strategies in chemoradiation.
Overexpression of the robA gene increases organic solvent tolerance and multiple antibiotic and heavy metal ion resistance in Escherichia coli (1995)

Escherichia coli K-12 OST3410 was isolated previously as a stable cyclohexane-tolerant mutant derived from cyclohexane-sensitive strain JA300. A plasmid which provides cyclohexane tolerance to strain JA300 was isolated from the OST3410 genomic library. Subcloning and sequence analysis showed that the plasmid contained the robA gene, whose gene product was reported to bind specifically to the right border of oriC. We observed that the robA gene on the multicopy plasmid generally increased the organic solvent tolerance of several E. coli strains. We also observed an increase in the organic solvent tolerance of JA300 carrying the lac-robA fusion gene on a low-copy plasmid by isopropyl-beta-D-thiogalactopyranoside induction. Strain JA300 carrying the multicopy robA plasmid also showed an increase in resistance to a number of unrelated antibiotics and heavy metal ions, and the spectrum of resistance was significantly similar to that of the soxS-overexpressing strain.
Enhydrazine, 10. Einige aliphatische Enhydrazone (1975)

Abstract Die Enhydrazone 1a – g , 2a , c , d , f , g und 3a – d , f , g werden durch Addition aliphatischer Hydrazone an carbonylaktivierte Acetylenverbindungen dargestellt und ihre NMR‐ und UV‐Spektren verglichen. Einige Thermolyse‐Produkte werden beschrieben.
The Janus kinases (Jaks) (2004)

The Janus kinase (Jak) family is one of ten recognized families of non-receptor tyrosine kinases. Mammals have four members of this family, Jak1, Jak2, Jak3 and Tyrosine kinase 2 (Tyk2). Birds, fish and insects also have Jaks. Each protein has a kinase domain and a catalytically inactive pseudo-kinase domain, and they each bind cytokine receptors through amino-terminal FERM (Band-4.1, ezrin, radixin, moesin) domains. Upon binding of cytokines to their receptors, Jaks are activated and phosphorylate the receptors, creating docking sites for signaling molecules, especially members of the signal transducer and activator of transcription (Stat) family. Mutations of the Drosophila Jak (Hopscotch) have revealed developmental defects, and constitutive activation of Jaks in flies and humans is associated with leukemia-like syndromes. Through the generation of Jak-deficient cell lines and gene-targeted mice, the essential, nonredundant functions of Jaks in cytokine signaling have been established. Importantly, deficiency of Jak3 is the basis of human autosomal recessive severe combined immunodeficiency (SCID); accordingly, a selective Jak3 inhibitor has been developed, forming a new class of immunosuppressive drugs.
TRIPS (2004)

This paper describes the polymorphous TRIPS architecture that can be configured for different granularities and types of parallelism. The TRIPS architecture is the first in a class of post-RISC, dataflow-like instruction sets called explicit data-graph execution (EDGE). This EDGE ISA is coupled with hardware mechanisms that enable the processing cores and the on-chip memory system to be configured and combined in different modes for instruction, data, or thread-level parallelism. To adapt to small and large-grain concurrency, the TRIPS architecture prototype contains two out-of-order, 16-wide-issue grid processor cores, which can be partitioned when easily extractable fine-grained parallelism exists. This approach to polymorphism provides better performance across a wide range of application types than an approach in which many small processors are aggregated to run workloads with irregular parallelism. Our results show that high performance can be obtained in each of the three modes---ILP, TLP, and DLP---demonstrating the viability of the polymorphous coarse-grained approach for future microprocessors.
The Large Fragment of Escherichia coli DNA Polymerase I Can Synthesize DNA Exclusively from Fluorescently Labeled Nucleotides (2001)

A highly sensitive fluorescence-based assay for screening DNA polymerase libraries (see schematic picture) revealed a surprising activity of the wild-type Klenow fragment of Escherichia coli DNA polymerase I: This enzyme, which has emerged during natural evolution as a polymerase “fit” for natural substrates, retains full activity in the sole presence of artificial nucleotides that are labeled with a fluorescent dye of the rhodamine type. This unusual finding opens up the horizon for generating DNA exclusively from rhodamine-labeled analogues—a necessary prerequisite to realizing the idea of “single-molecule sequencing”.
Effect of Invariance Requirements on the Elastic Strain Energy of Crystals with Application to the Diamond Structure (1966)

After demonstrating inconsistencies in some of the better known elasticity calculations, an alternative method of imposing the necessary invariance conditions on the strain energy of a crystal is presented. The new method is equivalent to the Born-Huang procedure but, in addition to providing further insight, also offers one or two operational advantages. For example, it demonstrates that all purely first-neighbor interactions are central only. The method is applied to the calculation of the elasticity of a two-constant model of the diamond type of crystal, and this predicts the relation $2{c}_{44}({c}_{11}+{c}_{12})=({c}_{11}\ensuremath{-}{c}_{12})({c}_{11}+3{c}_{12})$, which is very well satisfied by the experimental data for diamond, silicon, and germanium.
Adenovirus‐mediated RNA interference against collagen‐specific molecular chaperone 47‐KDa heat shock protein suppresses scar formation on mouse wounds (2007)

It has been shown in many investigations that the abnormally increasing production and deposition of collagen is one of the important mechanisms of pathological scars and other fibrotic diseases [Wang Z, Inokuchi T, Nemoto TK, Uehara M, Baba TT. Antisense oligonucleotide against collagen-specific molecular chaperone 47-kDa heat shock protein suppresses scar formation in rat wounds. Plast Reconstr Surg 2003 May; 111(6):1980-7; Obayashi K, Akamatsu H, Okano Y, Matsunage K, Masaki H. Exogenous nitric oxide enhances the synthesis of type I collagen and heat shock protein 47 by normal human dermal fibroblasts. J Dermatol Sci 2006 Feb; 41(2): 121-6 [e pub. 2005 Sep 19]; Kakugawa T, Mukae H, Hayashi T, Ishii H, Nakayama S, Sakamoto N, et-al. Expression of HSP47 in usual interstitial pneumonia and nonspecific interstitial pneumonia. Respir Res 2005 Jun;14(6): 57; Razzaque MS, Taguchi T. The possible role of colligin/HSP47, a collagen-binding protein, in the pathogenesis of human and experimental fibrotic diseases. Histol Histopathol 1999 Oct; 14(4): 1199-1212; Sharp PA. RNA interference - 2001. Genes Dev 2001 Mar 1; 15(5): 485-90; Ohashi S, Abe H, Takahashi T, Yamamoto Y, Takeuchi M, Arai H, et-al. Advanced glycation end products increase collagen-specific chaperone protein in mouse diabetic nephropathy. J Biol Chem 2004 May 7; 279(19): 19816-23 [epub 2004 Mar 5]]. RNA interference is the process that double-stranded RNA induces the homology-dependent degradation of cognate mRNA mediated by 21-23 nucleotide short interfering RNA (siRNA). In this study, we investigated the effect of HSP47-specific siRNA on the fibroblast cells, and then constructed adenovirus containing siRNA against HSP47 to inhibit the formation of scar in animal model. In this pilot study, HSP47 was targeted by this vector. Our results showed that the HSP47-specific siRNA could inhibit the expression of HSP47 at the level of mRNA and protein. Furthermore, adenovirus-mediated transfer of siRNA against HSP47 could inhibit the expression of type I collagen and the formation of scar tissue in animal model. It is likely that the inhibition of HSP47 by RNA interference (RNAi) could be developed as a powerful approach to prevent the scar formation.
The Graft-vs.-Leukemia Effect (1993)

Clinical evidence for the GVL effect derived from experience in allogeneic bone marrow transplantation (BMT) includes the following: the association of GVHD, both acute and chronic, with a decreased rate of leukemic relapse, the occurrence of a higher relapse rate following identical twin transplants compared to allogeneic major histocompatibility complex-matched sibling transplants, the decrease of GVHD and increase of leukemic relapses with T-cell depletion of donor bone marrow, and that allogeneic marrow transplants without GVHD have a lower leukemic relapse rate compared to identical twin transplants and T-cell depleted transplants. In addition, some reports indicate that modifying the immunosuppressive regimens (consisting of cyclosporine A or methotrexate) that are aimed at prevention of GVHD can affect leukemic relapse rates. Although the mechanism of this GVL effect is poorly understood, there are several favored hypotheses. Cytotoxic T cells, which may mediate GVH effects, could also mediate a GVL effect. There may also be T cells with specificity for destroying leukemic blasts alone. The natural killer/lymphokine-activated killer cytotoxic cell may play a role in the GVL effect. These nonspecific cytotoxic cells can be activated with cytokines induced in the transplant setting. Finally, the GVL effect could be secondary to the in vivo induction of various cytokines that either have direct antileukemic effects or that induce leukemic differentiation. Advances in our basic understanding of the immune system and its activation, and the availability of purified immunoregulatory cytokines, have revealed new ways to induce GVL-like effects. Promising results with therapy based on use of interleukin-2 in solid tumors have been seen. It is hoped that these advances will enable the "antileukemic" components of the GVL effect to be prospectively controlled (as part of the technique of marrow transplant) and intentionally used as leukemic therapy in patients undergoing bone marrow transplantation.
Abdominal Aortic Aneurysm Repair (2001)

Newer, minimally invasive catheter-based endovascular technology utilizing stent grafts are currently being evaluated for abdominal aortic aneurysm (AAA) repair. A retrospective review of all (3 years) consecutive, non-ruptured elective AAA repairs was undertaken to document the results of AAA surgical repair in a modern cohort of patients to allow a contemporary comparison with the evolving endoluminal data. One hundred twenty-one AAAs were identified in a male veteran population. Mean age was 68.5 +/-7.7 years. Medical history review showed hypertension in 55%, heart disease in 73.5%, peripheral vascular disease in 21%, stroke and transient ischemic attacks in 22%, diabetes mellitus in 7%, renal insufficiency in 10%, and smoking history in 80%. The AAA size was documented with ultrasound (5.2 +/-1.3 cm, n=40) and computed tomography (5.6 +/-1.3 cm, n=100). Fifty-nine percent had angiography. Intraoperative end points included an operative time of 165 +/-6.3 minutes from incision to dressing placement. A Dacron tube graft was used in 78%, the remaining were Dacron bifurcated grafts. A suprarenal clamp was used in 8% for proximal aortic control with juxtarenal aneurysms. A pulmonary-artery catheter was placed in 69%. A transverse incision was used in 69% of patients and a midline incision was used in the rest. Estimated blood loss was 1505 +/-103 mL; cell saver blood returned 754 +/-53 mL; crystalloid/Hespan 4771 +/-176 mL; banked packed red blood cells 0.75 +/-0.11 U. Time to extubation was, in the operating room (78.5%), on the day of the operation (5.0%), postoperative day (POD) 1 (12.4%), POD2 (1.7%), POD3 (0.8%), and one case was performed with epidural anesthesia only. Postoperative end points included a 30-day mortality rate of 1.6% (two patients). Postoperative morbidity included wound dehiscence 0.8%; sepsis, urinary tract infection, wound infection, leg ischemia, ischemic colitis, and stroke each had an incidence of 1.6%; myocardial infarction, congestive heart failure, pneumonia, re-operation for suspected bleeding, and ileus or bowel obstruction occurred with an incidence of 3.3%. No significant increase in serum creatinine levels was noted. Time to enteral fluids/nutrition was 3.5 +/-0.08 days. Patients were out of bed to a chair or walking by 1.3 +/-0.06 days postoperatively. The length of stay in the intensive care unit (ICU) was 2.0 +/-0.12 days and postoperative hospital stay was 6.6 +/- 0.33 days. Transfusion requirement for the hospital stay was 1.6 +/-0.2 U per patient. This review highlights a cohort of male veteran patients with significant cardiac co-morbidity who have undergone repair with a conventional open technique and low mortality and morbidity rates. This group had rapid extubation, time to oral intake, and ambulation. In addition, ICU and hospital stays were relatively short.
Invariant or highly conserved TCR alpha are expressed on double-negative (CD3+CD4-CD8-) and CD8+ T cells. (1999)

TCR alpha (TCRA) expression was examined in RNA samples from PBMC and isolated populations of CD4+, CD8+, and DN T cells from 15 healthy individuals. The expressed TCR repertoire was surveyed using spectratype analysis, a technique that displays the distribution of complementarity determining region 3 (CDR3) lengths for each TCRAV gene family. The results revealed the presence of unusual populations of double-negative (DN; CD4-CD8-CD3+) T cells that express invariant or conserved TCRAV4A, AV7, AV19, and AV24 chains. Each of the conserved TCRA families was over-represented in >70% of the individuals studied, and all individuals expressed at least one of the over-represented TCRAV families. Over-represented conserved AV4A or AV7 sequences were also present in CD8+ T cells from most donors. The extent of TCRA sequence conservation is unparalleled. TCRAV4A, AV19, and AV24 sequences were invariant, although AV4A and AV19 transcripts contained N region additions. TCRAV24 transcripts derived from the direct juxtaposition of V and J gene segments. TCRAV7 sequences showed some diversity in two amino acids encoded at junctions of V and J gene segments. Although derivation of DN T cells with conserved TCRA chains is puzzling, the wide-spread expression of these unusual cells suggests an important function.
Tumor necrosis factor-alpha enhances platelet activation via cathepsin G released from neutrophils (1991)

In this paper we show that TNF-alpha enhances platelet activation. Experiments were performed on a human polymorphonuclear neutrophil (PMN)-platelet cooperation system in which PMN, stimulated by FMLP, release cathepsin G (Cat.G), a serine proteinase responsible for the activation of nearby platelets. Pretreatment of the mixed cell suspension with 5 ng/ml TNF-alpha resulted in a strong platelet activation (37.7 +/- 3.2% aggregation; 46.0 +/- 14.4% serotonin release) in response to a weak concentration of FMLP (1.25 x 10(-8) M) inducing by itself only 7.7 +/- 4.0% of aggregation and 3.8 +/- 4.1% of serotonin release (mean +/- SD; n = 10). This effect was concentration dependent (maximum between 5 and 10 ng/ml) and was optimal for a brief preincubation time (5 min). Under these experimental conditions the target of TNF-alpha was PMN, as shown by beta-glucuronidase release. The observed potentiation was modified neither by 0.1 mM acetyl salicylic acid (a cyclo-oxygenase inhibitor) nor by 0.1 mM BN 52021 (a platelet-activating factor antagonist), while such a phenomenon was fully inhibited by 20 micrograms/ml eglin C, a strong and specific inhibitor of the human granulocytic proteinases, elastase and Cat.G. In fact, full inhibition was also observed with 300 nM alpha-1-antichymotrypsin, a specific inhibitor of Cat.G. This clear-cut evidence of Cat.G involvement was substantiated by the enhancement of Cat.G release from FMLP-activated PMN primed with TNF-alpha. These results demonstrate that the priming of PMN by TNF-alpha may modulate the activation of other inflammatory cells, particularly of platelets. It is hypothesized that this phenomenon could contribute to pulmonary pathologies, and more specifically to the adult respiratory distress syndrome, a disease for which PMN, platelet and TNF-alpha involvement has been proposed.
The Sequence of Amino Acid Residues in Bovine Pancreatic Ribonuclease: Revisions and Confirmations (1963)

Recent studies (l-3) have led to a revision of the published sequence of residues 11 to 18 in bovine pancreatic ribonuclease (4). In the experiments from this laboratory (1)) the use of improved conditions for the Edman degradation (Konigsberg and Hill (5)) provided an understanding of some of the limitations inherent in the procedure employed by Hirs, Moore, and Stein (4). It was noted that difficulties can be encountered particularly in the determination of sequences of peptides containing glutamine, asparagine, serine, and threonine residues. These observations have stimulated a new examination of the amino acid sequence of the whole molecule to determine whether such complications had affected any of the conclusions drawn in regard to other parts of the chain. Experience with the stepwise degradation has resulted in the following observations: (a) When the cyclization in the Edman degradation is performed in glacial acetic acid-anhydrous HCI, a newly liberated NH*-terminal glutamine residue cyclizes to a pyrrolidone carboxylic acid residue. Since such a peptide has no a-NH2 group, the degradation cannot proceed further. (b) When the process is followed by amino acid analysis of the residual peptide (the subtractive method), an incorrect conclusion can be drawn if any artifactual decomposition of amino acids occurs during hydrolysis, as has been observed for serine and threonine (1) and tyrosine (4). (c) These difficulties are avoided by the modified conditions of Konigsberg and Hill (5), in which the cyclization is performed at 25” in anhydrous trifluoroacetic acid and the residual peptide is purified by passage through a short column of Dowex 50-X2. (d) An internal asparagine or aspartic acid residue may form an imide in glacial acetic acid-HCI at 100” (1). Since the imide opens to give predominantly the P-aspartyl peptide, the stepwise degradation cannot proceed in good yield to the next residue in the sequence. This complication is avoided when the cyclization is performed at 25”. (e) The hydroxyl group of a serine or threonine residue is nearly quantitatively acetylated in acetic acid-HCl. When such an 0-acetylated residue becomes NHe
Effects of transcutaneous tibial nerve stimulation on anorectal physiology in fecal incontinence: a double‐blind placebo‐controlled cross‐over evaluation (2013)

Acute TENS modified anorectal physiology by strengthening the myogenic response to distension rather than increasing muscle relaxation and related rectal compliance in patients with FI.
Time constrained performance of a two channel reservation protocol for local networks (1992)

An efficient reservation-based carrier sense multiple access with collision-detection (CSMA/CD) protocol for two types of priority packets is presented. Type 1 packets are of relatively short duration, need a very quick response time, and have a high arrival rate. Type 2 packets are of longer duration, do not require as fast a response time, and have a low arrival rate. Expressions are developed for both the throughput and delay performance of two channel reservation network (TCRN), two channel reservation network with a preemptive priority, (TCRN/PP), and two channel reservation network with a nonpreemptive priority (TCRN/NPP) protocols. To examine the behavior of the protocols under time-constrained conditions, the authors check the percentage of voice packets which are transmitted within a given amount of time after their generation at a transmitting station and the voice capacity, both under different operating conditions. The results show that the channel is efficiently used to minimize the average delay for the data portion and to maintain as many voice stations as possible.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Global Structural Optimization of Tungsten Borides (2013)

Tungsten borides are among a distinct class of transition-metal light-element compounds with superior mechanical properties that rival those of traditional superhard materials. An in-depth understanding of these compounds, however, has been impeded by uncertainties regarding their complex crystal structures. Here, we examine a wide range of chemical compositions of tungsten borides using a recently developed global structural optimization approach. We establish thermodynamically stable structures and identify a large number of metastable phases. These results clarify and correct previous structural assignments and predict new structures for possible synthesis. Our findings provide crucial insights for understanding the rich and complex crystal structures of tungsten borides, which have broad implications for further exploration of this class of promising materials.
Context‐dependent mutations predominate in an engineered high‐affinity single chain antibody fragment (2006)

A mutational analysis of the femtomolar-affinity anti-fluorescein antibody 4M5.3, compared to its wild-type progenitor, 4-4-20, indicates both context-dependent and -independent mutations are responsible for the 1800-fold affinity improvement. 4M5.3 was engineered from 4-4-20 by directed evolution and contains 14 mutations. The seven mutations identified as present in each of 10 final round affinity maturation clones were studied here. Affinities of the 4-4-20 single mutant addition and 4M5.3 single site reversion mutants were compared. These experiments identified four mutations, of these seven, that were context-dependent in their contribution to higher affinity. A simplified mutant containing only these seven mutations was created to analyze complete double mutant cycles of selected sets of mutations. Specific mutational sets studied included the ligand contact mutations, the heavy chain CDR3 mutations, the heavy chain CDR3 mutations plus the neighboring residue at site H108, and the early and late acquired mutations on the directed evolution pathway. The heavy chain CDR3 mutational set and the ligand-contacting mutations were shown to provide -1.4 and -2.0 kcal/mol, respectively, of the total -3.5 kcal/mol change in free energy of binding of the seven-site consensus mutant. The mutations acquired late in the directed evolution rounds provided much of the change in free energy without the earlier acquired mutations (-3.1 kcal/mol of the total -3.5 kcal/mol). Prior structural data and electrostatic calculations presented several hypotheses for the higher affinity contributions, some of which are supported by these mutational data.