Measurement of the Vector and Tensor Asymmetries at Large Missing Momentum in Quasielastic (e[over →],e

We report the measurement of the beam-vector and tensor asymmetries A_{ed}^{V} and A_{d}^{T} in quasielastic (e[over →],e^{'}p) electrodisintegration of the deuteron at the MIT-Bates Linear Accelerator Center up to missing momentum of 500 MeV/c. Data were collected simultaneously over a momentum transfer range 0.1

Long-term safety and efficacy of lentiviral hematopoietic stem/progenitor cell gene therapy for Wiskott-Aldrich syndrome.

Patients with Wiskott-Aldrich syndrome (WAS) lacking a human leukocyte antigen-matched donor may benefit from gene therapy through the provision of gene-corrected, autologous hematopoietic stem/progenitor cells. Here, we present comprehensive, long-term follow-up results (median follow-up, 7.6 years) (phase I/II trial no. NCT02333760 ) for eight patients with WAS having undergone phase I/II lentiviral vector-based gene therapy trials (nos. NCT01347346 and NCT01347242 ), with a focus on thrombocytopenia and autoimmunity. Primary outcomes of the long-term study were to establish clinical and biological safety, efficacy and tolerability by evaluating the incidence and type of serious adverse events and clinical status and biological parameters including lentiviral genomic integration sites in different cell subpopulations from 3 years to 15 years after gene therapy. Secondary outcomes included monitoring the need for additional treatment and T cell repertoire diversity. An interim analysis shows that the study meets the primary outcome criteria tested given that the gene-corrected cells engrafted stably, and no serious treatment-associated adverse events occurred. Overall, severe infections and eczema resolved. Autoimmune disorders and bleeding episodes were significantly less frequent, despite only partial correction of the platelet compartment. The results suggest that lentiviral gene therapy provides sustained clinical benefits for patients with WAS.

Precise measurement of deuteron tensor analyzing powers with BLAST.

We report a precision measurement of the deuteron tensor analyzing powers T(20) and T(21) at the MIT-Bates Linear Accelerator Center. Data were collected simultaneously over a momentum transfer range Q=2.15-4.50 fm(-1) with the Bates Large Acceptance Spectrometer Toroid using a highly polarized deuterium internal gas target. The data are in excellent agreement with calculations in a framework of effective field theory. The deuteron charge monopole and quadrupole form factors G(C) and G(Q) were separated with improved precision, and the location of the first node of G(C) was confirmed at Q=4.19±0.05 fm(-1). The new data provide a strong constraint on theoretical models in a momentum transfer range covering the minimum of T(20) and the first node of G(C).

Retronphage phi R73: an E. coli phage that contains a retroelement and integrates into a tRNA gene.

Some strains of Escherichia coli contain retroelements (retrons) that encode genes for reverse transcriptase and branched, multicopy, single-stranded DNA (msDNA) linked to RNA. However, the origin of retrons is unknown. A P4-like cryptic prophage was found that contains a retroelement (retron Ec73) for msDNA-Ec73 in an E. coli clinical strain. The entire genome of this prophage, named phi R73, is 12.7 kilobase pairs and is flanked by 29-base pair direct repeats derived from the 3' end of the selenocystyl transfer RNA gene (selC). P2 bacteriophage caused excision of the phi R73 prophage and acted as a helper to package phi R73 DNA into an infectious virion. The newly formed phi R73 closely resembled P4 as a virion and in its lytic growth. Retronphage phi R73 lysogenized a new host strain, reintegrating its genome into the selC gene of the host chromosome and enabling the newly formed lysogens to produce msDNA-Ec73. Hence, retron Ec73 can be transferred intercellularly as part of the genome of a helper-dependent retronphage.

The putative pore-forming domain of Bax regulates mitochondrial localization and interaction with Bcl-X(L).

Bax is a proapoptotic member of the Bcl-2 family of proteins which localizes to and uses mitochondria as its major site of action. Bax normally resides in the cytoplasm and translocates to mitochondria in response to apoptotic stimuli, and it promotes apoptosis in two ways: (i) by disrupting mitochondrial membrane barrier function by formation of ion-permeable pores in mitochondrial membranes and (ii) by binding to antiapoptotic Bcl-2 family proteins via its BH3 domain and inhibiting their functions. A hairpin pair of amphipathic alpha-helices (alpha5-alpha6) in Bax has been predicted to participate in membrane insertion and pore formation by Bax. We mutagenized several charged residues in the alpha5-alpha6 domain of Bax, changing them to alanine. These substitution mutants of Bax constitutively localized to mitochondria and displayed a gain-of-function phenotype when expressed in mammalian cells. Furthermore, substitution of 8 out of 10 charged residues in the alpha5-alpha6 domain of Bax resulted in a loss of cytotoxicity in yeast but a gain-of-function phenotype in mammalian cells. The enhanced function of this Bax mutant was correlated with increased binding to Bcl-X(L), through a BH3-independent mechanism. These observations reveal new functions for the alpha5-alpha6 hairpin loop of Bax: (i) regulation of mitochondrial targeting and (ii) modulation of binding to antiapoptotic Bcl-2 proteins.

AK2 deficiency compromises the mitochondrial energy metabolism required for differentiation of human neutrophil and lymphoid lineages.

Reticular dysgenesis is a human severe combined immunodeficiency that is primarily characterized by profound neutropenia and lymphopenia. The condition is caused by mutations in the adenylate kinase 2 (AK2) gene, resulting in the loss of mitochondrial AK2 protein expression. AK2 regulates the homeostasis of mitochondrial adenine nucleotides (ADP, ATP and AMP) by catalyzing the transfer of high-energy phosphate. Our present results demonstrate that AK2-knocked-down progenitor cells have poor proliferative and survival capacities and are blocked in their differentiation toward lymphoid and granulocyte lineages. We also observed that AK2 deficiency impaired mitochondrial function in general and oxidative phosphorylation in particular - showing that AK2 is critical in the control of energy metabolism. Loss of AK2 disrupts this regulation and leads to a profound block in lymphoid and myeloid cell differentiation.

Experiments with longitudinally polarized electrons in a storage ring using a siberian snake

We report on first measurements with polarized electrons stored in a medium-energy ring and with a polarized internal target. Polarized electrons were injected at 442 MeV (653 MeV), and a partial (full) Siberian snake was employed to preserve the polarization. Longitudinal polarization at the interaction point and polarization lifetime of the stored electrons were determined with laser backscattering. Spin observables were measured for electrodisintegration of polarized 3He, with simultaneous detection of scattered electrons, protons, neutrons, deuterons, and 3He nuclei, over a large phase space.

Cervical myelopathy from dural substitute.

A case report of cervical spinal cord compression by infolding of a silicone-coated Dacron graft is presented. The possible complications of synthetic dural substitutes are discussed.

Conservative management of aplasia cutis congenita: case report.

A male newborn with a large scalp and skull defect and a cervical meningocele was transferred to the neonatal intensive care unit of the North Carolina Baptist Hospital. The scalp defect measured 8.5 x 9.5 cm, and the sagittal sinus was exposed. Because the defect was considered too large to be covered with a rotation skin flap, it was treated thrice daily with the topical application of bacitracin ointment and circumferential dressings. By the end of 3 months, the skull defect was covered with skin. The cervical meningocele was then removed without incident. At the 9-month follow-up examination, the scalp defect was well healed and the skull defect was closing slowly; the neurological findings were still normal for the patient's age.

Thrombosed aneurysm of the vein of Galen.

Computed tomography in a 3 1/2-year-old boy with ataxia, lethargy, fever, vomiting, and increasing irritability revealed moderate hydrocephalus and a blood density mass lesion lying superior and posterior to the 3rd ventricle. On several of the sections, the blood density was greater in the dependent than in the superior portion of the mass. The average attenuation number within the mass was 40 EMI units. The infusion of contrast agent demonstrated capsular enhancement (a target sign), which was also demonstrated by angiography. The diagnosis, which was confirmed at operation, was thrombosis of an aneurysm of the vein of Galen. The massive thrombus was resected, but the aneurysm was not excised. The patient's recovery was uneventful.

Simulation of a prolactin-secreting adenoma by an intrasellar craniopharyngioma.

We report here an unusual case of a 21-year-old woman who presented with amenorrhea, galactorrhea, and hyperprolactinemia (66 to 81 ng/ml) secondary to an unsuspected intrasellar craniopharyngioma. The results of preoperative endocrine testing were compatible with the presence of a prolactin-secreting adenoma. Moreover, high resolution computed tomographic scanning revealed an uncalcified hypodense sellar mass that did not enhance after contrast administration, a feature shared by many prolactinomas. This report illustrates that amenorrhea, galactorrhea, mild to moderate hyperprolactinemia, and a sellar mass should not automatically be attributed to the presence of a prolactin-secreting adenoma.

Epidermoid tumor presenting as tension pneumocephalus. Case report.

The authors report a patient with an epidermoid tumor that eroded through the frontal sinus, causing an acute neurological deficit secondary to tension pneumocephalus. The historical perspective, radiographic features, and pathophysiological mechanisms are discussed.

Brainstem hemorrhages and increased intracranial pressure: from Duret to computed tomography.

In the late nineteenth century, Henri Duret produced minute brainstem hemorrhage in dogs by rapidly increasing their intracranial pressure. Whether those hemorrhages were the same as those seen today associated with transtentorial herniation is not agreed upon, and the term Duret's hemorrhages is rarely used. Duret's report on his experiments is condensed here and the value of computed tomography for detecting brainstem hemorrhages is illustrated by a case report.